Management of Patients With Valvular Heart Disease...With Valvular Heart Disease. These guidelines...

Management of Patients With

ValvularHeart Disease

ACC/AHA Pocket Guideline

Based on the ACC/AHA 2006 Guideline Revision

June 2006

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i

Management of Patients With

Valvular Heart DiseaseJune 2006

Writing Committee

Robert O. Bonow, MD, FACC, FAHA, Chair

Blase A. Carabello, MD, FACC, FAHA

Kanu Chatterjee, MD, FACC

Antonio C. de Leon, Jr., MD, FACC, FAHA

David P. Faxon, MD, FACC, FAHA

Michael D. Freed, MD, FACC, FAHA

William H. Gaasch, MD, FACC, FAHA

Bruce Whitney Lytle, MD, FACC

Rick A. Nishimura, MD, FACC, FAHA

Patrick T. O’Gara, MD, FACC, FAHA

Robert A. O’Rourke, MD, MACC, FAHA

Catherine M. Otto, MD, FACC, FAHA

Pravin M. Shah, MD, MACC, FAHA

Jack S. Shanewise, MD

ii

© 2006 American College of

Cardiology Foundation and the

American Heart Association, Inc.

The following material was adapted

from the ACC/AHA 2006 Guidelines

for the Management of Patients With

Valvular Heart Disease (published in

the August 1, 2006, issues of Journal

of the American College of Cardiology

and Circulation). For a copy of the full

report or published executive summary,

visit our Web sites at http://www.acc.org

or http://www.americanheart.org or

call the ACC Resource Center at

1-800-253-4636, ext. 694.

2-D and D

oppler EchocardiographyValve Surgery or Intervention

Managem

ent of Prosthetic Valves

Contents

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

II. Indications for 2-D and Doppler Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

A. Severity of Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

B. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

C. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

D. Bicuspid Aortic Valve With Dilated Ascending Aorta . . . . . . . . . . . . . . . . . 14

E. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

F. Mitral Valve Prolapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

G. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

III. Indications for Valve Surgery or Percutaneous Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

A. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

B. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

C. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

D. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

E. Infective Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

F. Major Criteria for Valve Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

IV. Antithrombotic Management of Prosthetic Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

A. Indications for Anticoagulation in

Patients With Prosthetic Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

B. Embolic Events During

Adequate Antithrombotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

C. Excessive Anticoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

D. Antithrombotic Therapy in Patients Requiring

Noncardiac Surgery/Dental Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

E. Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

F. Thrombosis of Prosthetic Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

3

I. Introduction

Valvular heart disease is one of several cardiac

disorders that affect a large number of people

who require diagnostic procedures and long-term

management. The Pocket Guideline for Management

of Patients With Valvular Heart Disease provides rapid

prompts for 3 specific aspects of the management

of patients with valvular heart disease. The pocket

guide is derived from the full text of the ACC/AHA

2006 Guidelines for the Management of Patients

With Valvular Heart Disease. These guidelines were

first published in 1998 and then revised in 2006.

The full-text guidelines provide a more detailed

explanation of the management of valvular heart

disease, along with appropriate caveats and levels

of evidence. The executive summary of the guide-

lines was published in the Journal of American

College of Cardiology and Circulation. Both

the full guidelines and the executive summary

are available online, at http://www.acc.org or

http://www.americanheart.org. Users of this

pocket guide should consult those documents

for additional information.

4

Scope of the Pocket Guide

The Guidelines for the Management of Patients With Valvular

Heart Disease cannot be reproduced in their entirety in a pocket

guide format. For this reason, the pocket guide focuses on

the 3 aspects of management in the conditions that are most

frequently encountered in the practice of adult cardiology:

■ Indications for echocardiography

■ Indications for valvular surgery or percutaneous intervention

■ Antithrombotic management of prosthetic heart valves

Classification of Recommendations

A classification of recommendation and a level of evidence have

been assigned to each recommendation. Classifications of recom-

mendations and levels of evidence are expressed in the American

College of Cardiology/American Heart Association (ACC/AHA)

format as follows and described in more detail in Figure 1:

Class I Conditions for which there is evidence for and/or

general agreement that the procedure or treatment

is beneficial, useful, and effective.

Class II Conditions for which there is conflicting evidence

and/or a divergence of opinion about the

usefulness/efficacy of a procedure or treatment.

5

Class IIa Weight of evidence/opinion is in favor

of usefulness/efficacy.

Class IIb Usefulness/efficacy is less well established

by evidence/opinion.

Class III Conditions for which there is evidence and/or

general agreement that the procedure/treatment

is not useful/effective and in some cases may

be harmful.

Level of In addition, the weight of evidence in support

Evidence of the recommendation is listed as follows:

Level of Evidence A Data derived from multiple

randomized clinical trials.

Level of Evidence B Data derived from a single

randomized trial or nonrandomized studies.

Level of Evidence C Only consensus opinion

of experts, case studies, or standard-of-care.

6

Figure 1. Applying Classification of Recommendations and Level of Evidence in ACC/AHA Format

LEVEL A

Multiple (3-5) population risk strata evaluated*

General consistency of direction and magnitude of effect

LEVEL B

Limited (2-3) population risk strata evaluated*

LEVEL C

Very limited (1-2) population risk strata evaluated*

CLASS I

Benefi t >>> Risk

Procedure/Treatment SHOULD be performed/ administered

■ Recommendation that procedure or treatment is useful/effective

■ Suffi cient evidence from multiple randomized trials or meta-analyses


■ Limited evidence from single randomized trial or nonrandomized studies


■ Only expert opinion, case studies, or standard-of-care

CLASS IIA

Benefi t >> Risk

Additional studies with focused objectives needed

IT IS REASONABLE to per-form procedure/administer treatment

■ Recommendation in favor of treatment or procedure being useful/effective

■ Some confl icting evidence from multiple randomized trials or meta-analyses


■ Some confl icting evidence from single randomized trial or nonrandomized studies


■ Only diverging expert opinion, case studies, or standard-of-care

should

is recommended

is indicated

is useful/effective/benefi cial

Suggested phrases for writing recommendations†

is reasonable

can be useful/effective/benefi cial

is probably recommended or indicated

S I Z E O F T R E A T M E N T E F F E C T

ES

TIM

AT

E O

F C

ER

TA

INT

Y (

PR

EC

ISIO

N)

OF

TR

EA

TM

EN

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FF

EC

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Class IIb

Benefi t ≥ RiskAdditional studies with broad objectives needed; additional registry data would be helpful

Procedure/Treatment MAY BE CONSIDERED

■ Recommendation’s usefulness/effi cacy less well established

■ Greater confl icting evidence from multiple randomized trials or meta-analyses


■ Greater confl icting evidence from single randomized trial or nonrandomized studies


■ Only diverging expert opinion, case studies, or standard-of-care

Class IIIRisk ≥ Benefi tNo additional studies needed

Procedure/Treatment should NOT be performed/adminis-tered SINCE IT IS NOT HELP-FUL AND MAY BE HARMFUL

■ Recommendation that procedure or treatment is not useful/effective and may be harmful

■ Suffi cient evidence from multiple randomized trials or meta-analyses


■ Limited evidence from single randomized trial or nonrandomized studies


■ Only expert opinion, case studies, or standard-of-care

may/might be considered

may/might be reasonable

usefulness/effectiveness is unknown/unclear/uncertain or not well established

is not recommended

is not indicated

should not

is not useful/effective/benefi cial

may be harmful

* Data available from clinical trials

or registries about the usefulness/

efficacy in different subpopulations,

such as gender, age, history of

diabetes, history of prior myo-

cardial infarction, history of heart

failure, and prior aspirin use. A

recommendation with Level of

Evidence B or C does not imply

that the recommendation is weak.

Many important clinical questions

addressed in the guidelines do not

lend themselves to clinical trials.

Even though randomized trials are

not available, there may be a very

clear clinical consensus that a

particular test or therapy is useful

or effective.

† In 2003 the ACC/AHA Task Force on

Practice Guidelines recently provided

a list of suggested phrases to use

when writing recommendations.

All recommendations in this

guideline have been written in full

sentences that express a complete

thought, such that a recommenda-

tion, even if separated and presented

apart from the rest of the document

(including headings above sets of

recommendations), would still

convey the full intent of the recom-

mendation. It is hoped that this will

increase readers’ comprehension of

the guidelines and will allow queries

at the individual recommenda-

tion level.

8

The following abbreviations are used throughout this pocket guide:

AR aortic regurgitation

AS aortic stenosis

AVR aortic valve replacement

BAV bicuspid aortic valve

CABG coronary artery bypass grafting

ECG electrocardiogram

EF ejection fraction

IE infective endocarditis

INR international normalized ratio

LMWH low-molecular-weight heparin

LV left ventricular

MR mitral regurgitation

MRI magnetic resonance imaging

MS mitral stenosis

MV mitral valve

MVP mitral valve prolapse

NYHA New York Heart Association

PMBV percutaneous mitral balloon valvotomy

RV right ventricular

TEE transesophageal echocardiography

TTE transthoracic echocardiography

TR tricuspid regurgitation

UFH unfractionated heparin

2-D 2-dimensional

2-D and D

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9

II. Indications for 2-D and Doppler Echocardiography

A. Severity of Valve Disease

The severity of valve disease can be determined on the basis

of a detailed, comprehensive 2-dimensional (2-D) and Doppler

echocardiogram. The committee recommends that quantitative

Doppler criteria be used to grade the severity of the valve lesion

(Table 1). In certain situations, cardiac catheterization is required

for further clarification of severity of the valve lesion.

B. Aortic Stenosis

The 2-D echocardiogram is valuable for confirming the

presence of aortic stenosis (AS) and determining left ventricular

(LV) size and function, the degree of hypertrophy, and the

presence of other associated valve disease. In most patients,

the severity of the stenotic lesion can be defined with Doppler

echocardiographic measurements of a Doppler peak velocity,

a mean transvalvular pressure gradient, and derived valve area.

Recommendations for Echocardiography in Aortic Stenosis

Class I 1. Echocardiography is recommended for the following:

A. Diagnosis and assessment of AS severity.

(Level of Evidence: B)

B. Assessment of LV wall thickness, size, and

function. (Level of Evidence: B)continued on page 12

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Table 1. Classification of the Severity of Valve Disease in Adults

A. Left-sided valve disease Aortic Stenosis

Indicator Mild Moderate Severe

Jet velocity (m/s) Less than 3.0 3.0-4.0 Greater than 4.0

Mean gradient (mm Hg)* Less than 25 25-40 Greater than 40

Valve area (cm2) Greater than 1.5 1.0-1.5 Less than 1.0

Valve area index (cm2/m2) Less than 0.6

Mitral Stenosis

Mild Moderate Severe

Mean gradient (mm Hg)* Less than 5 5-10 Greater than 10

Pulmonary artery systolic Less than 30 30-50 Greater than 50pressure (mm Hg)

Valve area (cm2) Greater than 1.5 1.0-1.5 Less than 1.0

Aortic Regurgitation


Qualitative

Angiographic grade 1+ 2+ 3-4+

Color Doppler jet width Central jet, width Greater than Central jet, width less than 25% mild but no signs greater than of LVOT of severe AR 65% LVOT

Doppler vena contracta Less than 0.3 0.3-0.6 Greater than 0.6 width (cm)

Quantitative (cath or echo)

Regurgitant volume (ml/beat) Less than 30 30-59 Greater than or equal to 60

Regurgitant fraction (%) Less than 30 30-49 Greater than or equal to 50

Regurgitant orifice area (cm2) Less than 0.10 0.10-0.29 Greater than or equal to 0.30

Additional Essential Criteria

Left ventricular size Increased

2-D and D


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Mitral Regurgitation


Qualitative

Angiographic grade 1+ 2+ 3-4+

Color Doppler jet area Small, central jet Signs of MR Vena contracta width greater than (less than 4 cm2 greater than mild 0.7 cm with large central MR jet or less than 20% present, but no (area greater than 40% of LA LA area) criteria for area) or with a wall-impinging jet severe MR of any size, swirling in LA

Doppler vena contracta Less than 0.3 0.3 – 0.69 Greater than or equal to 0.70 width (cm)

Quantitative (cath or echo)

Regurgitant volume (ml/beat) Less than 30 30-59 Greater than or equal to 60

Regurgitant fraction (%) Less than 30 30-49 Greater than or equal to 50

Regurgitant orifice area (cm2) Less than 0.20 0.2-0.39 Greater than or equal to 0.40

Additional Essential Criteria

Left atrial size Enlarged

Left ventricular size Enlarged

B. Right-sided valve disease Characteristic

Severe tricuspid stenosis: Valve area less than 1.0 cm2

Severe tricuspid regurgitation: Vena contracta width greater than 0.7 cm and Systolic flow reversal in hepatic veins

Severe pulmonic stenosis: Jet velocity greater than 4 m/s or maximum gradient greater than 60 mm Hg

Severe pulmonic regurgitation: Color jet fills outflow tract Dense continuous wave Doppler signal with a steep deceleration slope

*Valve gradients are flow dependent and when used as estimates of severity of valve stenosis should be assessed with knowledge of cardiac output or forward flow across the valve. Modified from the Journal of the American Society of Echocardiography, 16, Zoghbi WA, Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography, 777–802, Copyright 2003, with permission from American Society of Echocardiography.

AR = aortic regurgitation; cath = catheterization; echo = echocardiography; LA = left atrial/atrium; LVOT = left ventricular outflow tract; MR = mitral regurgitation.

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C. Re-evaluation of patients with known AS and

changing symptoms or signs. (Level of Evidence: B)

D. Assessment of changes in hemodynamic

severity and LV function in patients with known

AS during pregnancy. (Level of Evidence: B)

2. Transthoracic echocardiography (TTE) is

recommended for re-evaluation of asymptomatic

patients every year for severe AS; every 1 to 2 years

for moderate AS; every 3 to 5 years for mild AS.


Class IIa 1. Dobutamine stress echocardiography is

reasonable to evaluate patients with low-

flow/low-gradient AS and LV dysfunction.


In selected patients with low-flow/low-gradient AS and LV

dysfunction, it may be useful to determine the transvalvular

pressure gradient and to calculate valve area during a baseline

state and again during exercise or low-dose pharmacological

(i.e., dobutamine infusion) stress, with the goal of determining

whether stenosis is severe or only moderate in severity. Such

studies can be performed in experienced echocardiographic

or cardiac catheterization laboratories.

C. Aortic Regurgitation

Echocardiography is indicated to confirm the diagnosis of aortic

regurgitation (AR) when it is equivocal on the basis of physical

examination; to assess the cause of AR and valve morphology;

2-D and D


13

to provide a semiquantitative estimate of the severity of

regurgitation; to assess the ventricular response to volume

overload, which includes LV dimension, mass, and systolic

function; and to assess aortic root size.

Recommendations for Echocardiography in Aortic Regurgitation

Class I 1. Echocardiography is indicated for the following:

A. Diagnosis and assessment of severity of acute

or chronic AR. (Level of Evidence: B)

B. Assessment of the cause of chronic AR

(including valve morphology and aortic root

size and morphology) and assessment of

LV hypertrophy, dimension (or volume), and

systolic function. (Level of Evidence: B)

C. Assessment of AR and severity of aortic

dilatation in patients with enlarged aortic roots.


D. Re-evaluation of LV size and function

in asymptomatic patients with severe AR.


E. Re-evaluation of mild, moderate, or

severe AR in patients with new or changing

symptoms. (Level of Evidence: B)

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Radionuclide angiography and magnetic resonance imaging

(MRI) can also be used to assess the ventricular response to

the volume overload, and they are useful in patients with

unsatisfactory echocardiograms. MRI and cardiac computed

tomography may be useful to further evaluate the size of

the aorta. Exercise testing is reasonable for assessment of

functional capacity and symptomatic response in patients

with a history of equivocal symptoms.

Once the chronicity and stability of the process have been

established, the frequency of clinical re-evaluation and repeat

noninvasive testing depends on the severity of AR, degree of

LV dilatation, level of systolic function, and whether previous

serial studies have revealed progressive changes in LV size

or function. Repeat echocardiograms are also recommended

at the onset of symptoms, when there is an equivocal history

of changing symptoms or exercise tolerance, or when there

are clinical findings that suggest worsening AR or progressive

LV dilatation.

D. Bicuspid Aortic Valve With Dilated Ascending Aorta

There is growing awareness that many patients with bicuspid

aortic valves (BAV) have disorders of vascular connective tissue,

which may result in dilatation of the aortic root or ascending

aorta even in the absence of hemodynamically significant AS

or AR. Aortic root or ascending aortic dilatation can progress

with time, and there is a risk of aortic dissection that is related

to the severity and rate of dilatation. Echocardiography remains

the primary imaging technique for identifying and following

2-D and D


15

these patients. More accurate quantification of the diameter

of the aortic root and ascending aorta, as well as full

assessment of the degree of enlargement, can be obtained

with cardiac MRI or computed tomography.

Recommendations for Echocardiography (or Other Imaging Modalities) in Patients With Bicuspid Aortic Valve and Dilated Ascending Aorta

Class I 1. Patients with known BAV should undergo an

initial transthoracic echocardiogram to assess

diameter of the aortic root and ascending aorta.


2. Cardiac MRI or cardiac computed tomography

is indicated in patients with BAV when morph-

ology of the aortic root or ascending aorta cannot

be assessed accurately by echocardiography.

(Level of Evidence: C)

3. Patients with BAV and dilatation of the aortic

root or ascending aorta (diameter greater than

4.0 cm*) should undergo serial evaluation of aortic

root/ascending aorta size and morphology by

echocardiography, cardiac magnetic resonance,

or computed tomography on a yearly basis.


*Consider lower threshold values for patients of small stature of either gender.

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E. Mitral Stenosis

Two-dimensional echocardiography should be used in patients

with mitral stenosis (MS) to assess the morphology of the

mitral valve (MV), including leaflet mobility, leaflet thickness,

leaflet calcification, and subvalvular and commissural fusion.

These features are important in considering the timing and

type of intervention. Doppler echocardiography assesses the

hemodynamic severity of MS, estimates pulmonary artery

systolic pressure from the tricuspid regurgitation (TR) velocity

signal, and assesses severity of concomitant mitral regurgitation

(MR) or AR. Formal hemodynamic exercise testing can be

done using either a supine bicycle or an upright treadmill with

Doppler recordings of transmitral and tricuspid velocities.

Recommendations for Echocardiography in Mitral Stenosis

Class I 1. Echocardiography is indicated for the following:

A. Diagnosis of MS, assessment of severity,

assessment of concomitant valvular lesions, and

assessment of valve morphology (to determine

suitability for percutaneous mitral balloon

valvotomy [PMBV]). (Level of Evidence: B)

B. Re-evaluation in patients with known MS and

changing symptoms or signs. (Level of Evidence: B)

C. Assessment of the hemodynamic response

by exercise Doppler echocardiography when

there is a discrepancy between resting Doppler

echocardiographic findings, clinical findings,

symptoms, and signs. (Level of Evidence: C)

2-D and D


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2. Transesophageal echocardiography (TEE)

is indicated for the following:

A. Assessment of presence or absence of left

atrial thrombus and assessment of severity

of MR in patients considered for PMBV.


B. Assessment of MV morphology and hemo-

dynamics in patients when TTE provides

suboptimal data. (Level of Evidence: C)

Class IIa 1. Echocardiography is reasonable in the

re-evaluation of asymptomatic patients with

MS and stable clinical findings to assess

pulmonary artery pressure (for those with

severe MS, every year; moderate MS, every

1 to 2 years; and mild MS, every 3 to 5 years).


Class III 1. TEE is not indicated in patients with MS

for routine evaluation of MV morphology and

hemodynamics when complete TTE data are

satisfactory. (Level of Evidence: C)

F. Mitral Valve Prolapse

Two-dimensional and Doppler echocardiography constitutes

the most useful noninvasive test for defining MV prolapse

(MVP). On 2-D echocardiography, systolic displacement of

1 or both mitral leaflets in the parasternal long-axis view,

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particularly when they coapt on the atrial side of the annular

plane, indicates a high likelihood of MVP. The diagnosis of

MVP is even more certain when leaflet thickness is greater

than 5 mm. The echocardiographic criteria for MVP should

include structural changes such as leaflet thickening,

redundancy, annular dilatation, and chordal elongation.

Recommendations for Echocardiography in Asymptomatic Mitral Valve Prolapse

Class I 1. Echocardiography is indicated for the diagnosis of

MVP and assessment of MR, leaflet morphology, and

ventricular compensation in asymptomatic patients

with physical signs of MVP. (Level of Evidence: B)

Class IIa 1. Echocardiography can be effective for

A. Excluding MVP in asymptomatic patients who

have been diagnosed without clinical evidence

to support the diagnosis. (Level of Evidence: C)

B. Risk stratification in asymptomatic patients

with physical signs of MVP or known MVP.


Class III 1. Echocardiography is not indicated to exclude

MVP in asymptomatic patients with ill-defined

symptoms in the absence of a constellation

of clinical symptoms or physical findings sugges-

tive of MVP or a positive family history.


2-D and D


19

2. Routine repetition of echocardiography is

not indicated for the asymptomatic patient

who has MVP and no MR or MVP and mild MR

with no changes in clinical signs or symptoms.


G. Mitral Regurgitation

Two-dimensional and Doppler echocardiography is indis-

pensable in the management of patients with MR and

should be used to assess the severity of MR, the LV response

to volume overload (including LV size and systolic function

ejection fraction [EF] and end-systolic dimension), left atrial

size and pulmonary artery systolic pressure. Echocardiography

may also identify the anatomic cause of MR, which is important

for determining the feasibility of successful MV repair.

Recommendations for Echocardiography in Mitral Regurgitation

Class I 1. TTE is indicated for the following:

A. Baseline evaluation of LV size and function,

right ventricular (RV) and left atrial size,

pulmonary artery pressure, and severity of

MR (Table 1) in any patient suspected of having

MR. (Level of Evidence: C)

B. Delineation of the mechanism of MR.


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C. Annual or semiannual surveillance of LV

function (estimated by EF and end-systolic

dimension) in asymptomatic patients with

moderate to severe MR. (Level of Evidence: C)

D. Assessment of the MV apparatus and LV

function after a change in signs or symptoms.


E. Assessment of LV size and function and MV

hemodynamics in the initial evaluation after MV

replacement or MV repair. (Level of Evidence: C)

Class IIa 1. Exercise Doppler echocardiography is reasonable

in asymptomatic patients with severe MR to assess

exercise tolerance and the effects of exercise on

pulmonary artery pressure and MR severity.


Class III 1. TTE is not indicated for routine follow-up

evaluation of asymptomatic patients with mild

MR and normal LV size and systolic function.


Recommendations for Transesophageal Echocardiography in Mitral Regurgitation

Class I 1. Preoperative or intraoperative TEE is indicated

to establish the anatomic basis for severe MR

to assess feasibility of repair and to guide repair

2-D and D


21

in patients in whom surgery is recommended.


2. TEE is indicated for evaluation of MR when

TTE provides nondiagnostic information regarding

severity of MR, mechanism of MR, and/or status

of LV function. (Level of Evidence: B)

Class IIa 1. Preoperative TEE is reasonable in asymptomatic

patients with severe MR who are considered

for surgery to assess feasibility of repair.


Class III 1. TEE is not indicated for routine follow-up

or surveillance of asymptomatic patients with

native valve MR. (Level of Evidence: C)

Asymptomatic patients with mild MR and no evidence of

LV enlargement or dysfunction or pulmonary hypertension

can be monitored clinically on a yearly basis, but yearly

echocardiograms are not necessary unless there is clinical

evidence that regurgitation has worsened. In patients with

moderate MR, clinical evaluations and echocardiograms

should be performed yearly. Patients with severe MR should

be monitored with clinical evaluation and echocardiography

every 6 to 12 months to assess symptoms or transition to

asymptomatic LV dysfunction.

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III. Indications for Valve Surgery or Percutaneous Intervention

A. Aortic Stenosis

Aortic valve replacement (AVR) is clearly indicated in

symptomatic patients with severe AS (Figure 2). Patients with

moderate or severe AS, even without symptoms, who undergo

another cardiac operation should undergo AVR at the time of

surgery. Management decisions are more controversial in

asymptomatic patients with severe AS.

Recommendations for Aortic Valve Replacement in Aortic Stenosis

Class I 1. AVR is indicated for the following patients:

A. Symptomatic patients with severe AS.†


B. Patients with severe AS† undergoing coronary

artery bypass graft surgery (CABG), surgery on

the aorta, or replacement or repair of other heart

valves. (Level of Evidence: C)

C. Patients with severe AS† and LV systolic

dysfunction (EF less than 0.50). (Level of Evidence: C)

Class IIa 1. AVR is reasonable for patients with moderate

AS† undergoing CABG or surgery on the aorta

or other heart valves. (Level of Evidence: B)

Valve Surgery or Intervention

23

Preoperative coronary angiography should be performed routinely, as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography (echo). Modified from Otto CM. Valvular aortic stenosis: disease severity and timing of intervention. J Am Coll Cardiol 2006;47:2141–51.

AVA = aortic valve area; BP = blood pressure; CABG = coronary artery bypass graft surgery; LV = left ventricular; Vmax = maximal velocity across aortic valve by Doppler echocardiography.

Figure 2. Management Strategy for Patients With Severe Aortic Stenosis

Preoperative coronary angiography

No

Exercise test

Symptoms?

Equivocal NoYes

Severe Aortic Stenosis

Vmax greater than 4 m/sAVA less than 1.0 cm2

Mean gradient > 40 mm Hg

Undergoing CABG or other heart surgery?

Reevaluation

Normal LV ejection fraction

Symptoms ↓ BP

Severe valve calcification,rapid progression, and/or

expected delays in surgery

Aortic Valve Replacement Clinical follow-up, patient education, risk factor modification, annual echo

Class I Class I Class I Ib Class I Class I Ib

NormalLess than 0.50

Yes

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Class IIb 1. AVR may be considered for the following patients:

A. Asymptomatic patients with severe AS† and

abnormal response to exercise (e.g., development

of symptoms or asymptomatic hypotension).


B. Adults with severe asymptomatic AS† if there

is a high likelihood of rapid progression (age,

calcification, and coronary artery disease) or if

surgery might be delayed at the time of symptom

onset. (Level of Evidence: C)

C. Patients undergoing CABG who have mild AS†

when there is evidence, such as moderate to

severe valve calcification, that progression may

be rapid. (Level of Evidence: C)

D. Asymptomatic patients with extremely

severe AS (aortic valve area less than 0.6 cm2,

mean gradient greater than 60 mm Hg, and

jet velocity greater than 5.0 m per second)

when the expected operative mortality is 1.0%

or less. (Level of Evidence: C)

Class III 1. AVR is not useful for the prevention of sudden

death in asymptomatic patients with AS who have

none of the findings listed under the Class IIa/IIb

recommendations. (Level of Evidence: B)

†Objective definition of valve severity is provided in Table 1.


25

B. Aortic Regurgitation

AVR is indicated for patients with chronic severe AR who have

cardiac symptoms and for asymptomatic patients with LV

systolic dysfunction at rest, marked LV dilatation, or severely

dilated aortic roots (Figure 3). Patients with BAV may have

dilated aortas; surgery to repair the aortic root or replace the

ascending aorta may be indicated depending on the size of

the aorta.

Recommendations for Aortic Valve Replacement in Chronic Severe Aortic Regurgitation

Class I 1. AVR is indicated for the following patients:

A. Symptomatic patients with severe

AR irrespective of LV systolic function.


B. Asymptomatic patients with chronic severe

AR and LV systolic dysfunction (EF 0.50 or less)

at rest. (Level of Evidence: B)

C. Patients with chronic severe AR while under-

going CABG or surgery on the aorta or other

heart valves. (Level of Evidence: C)

2. Surgery to repair the aortic root or replace

the ascending aorta is indicated in patients with

BAV if the diameter of the aortic root or ascending

aorta is greater than 5.0 cm* or if the rate of

increase in diameter is 0.5 cm per year or more.


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Yes

Clinical eval + Echo

Exercise test

Consider hemodynamic response to exercise

Symptoms?

LV dimensions?

Stable? Stable?

Figure 3. Management Strategy for Patients With Chronic Severe Aortic Regurgitation

Yes

Yes No, or initial study

Clinical eval every 6-12 mo

Echo every 12 mo

Clinical eval every 6 mo Echo every

6 mo

Clinical eval every 6 moEcho every

12 mo

Reevaluate and Echo

3 mo

No

Yes

Chronic Severe Aortic Regurgitation

Equivocal

No symptoms Symptoms

Normal EF EF of 50% or lessEF borderline or uncertain

RVG or MRI

SD >55 mm orDD >75 mm

SD 45-50 mm orDD 60-70 mm

SD 50-55 mm orDD 70-75 mm

Abnormal

Normal

AVR

SD <45 mm orDD <60 mm

Reevaluation

LV function?

Class I

Class I

Class I

Class IIa

Class IIb

Stable?

No, or initial study

Reevaluate and Echo

3 mo

Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography. “Stable” refers to stable echocardiographic measurements. In some centers, serial follow-up may be performed with RVG or MRI rather than echocardiography to assess LV volume and systolic function.

AVR = aortic valve replacement; DD = end-diastolic dimension; Echo = echocardiography; EF = ejection fraction; eval = evalutation; LV = left ventricular; MRI = magnetic resonance imaging; RVG = radionuclide ventriculography; SD = end-systolic dimension.


27

3. In patients with BAV undergoing AVR because

of severe AS or AR (see Sections 3.1.7. and 3.2.3.8.

in the full-text guidelines), repair of the aortic root

or replacement of the ascending aorta is indicated

if the diameter of the aortic root or ascending aorta

is greater than 4.5 cm.* (Level of Evidence: C)

Class IIa 1. AVR is reasonable for asymptomatic patients

with severe AR with normal LV systolic function

(EF greater than 0.50) but with severe LV dilatation

(end-diastolic dimension greater than 75 mm or

end-systolic dimension greater than 55 mm).*


Class IIb 1. AVR may be considered in the following patients:

A. Patients with moderate AR while undergoing

CABG or surgery on the ascending aorta.


B. Asymptomatic patients with severe AR and

normal LV systolic function at rest (EF greater

than 0.50) when the degree of LV dilatation

exceeds an end-diastolic dimension of 70 mm

or end-systolic dimension of 50 mm, when there

is evidence of progressive LV dilatation, declining

exercise tolerance, or abnormal hemodynamic

responses to exercise.* (Level of Evidence: C)

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Class III 1. AVR is not indicated for asymptomatic patients

with mild, moderate, or severe AR and normal

LV systolic function at rest (EF greater than 0.50)

when the degree of dilatation is not moderate or

severe (end-diastolic dimension less than 70 mm,

end-systolic dimension less than 50 mm).*


*Consider lower threshold values for patients of small stature of either gender.

C. Mitral Stenosis

Indications for intervention in patients with MS depend on

symptoms, pulmonary artery pressure, RV function, and

the feasibility of performing PMBV (Figures 4-6). If there is

a discrepancy between symptoms and hemodynamic data,

formal exercise testing with hemodynamics (invasive or

noninvasive) may be useful to differentiate symptoms due

to MS from those due to other causes. Patients who are

symptomatic with a significant elevation of pulmonary artery

pressure (greater than 60 mm Hg), mean transmitral gradient

(greater than 15 mm Hg), or pulmonary artery wedge pressure

(25 mm Hg) with exertion have hemodynamically significant

MS independent of the calculated valve area, and further

intervention should be considered.


29

*The writing committee recognizes that there may be variability in the measurement of mitral valve area (MVA) and that the mean transmitral gradients, pulmonary artery wedge pressure (PAWP), and pulmonary artery systolic pressure (PASP) should also be taken into consideration.

† There is controversy as to whether patients with severe mitral stenosis (MVA < 1.0 cm2) and severe pulmonary hypertension (pulmonary artery pressure > 60 mm Hg) should undergo percutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement to prevent right ventricular failure.

‡ Assuming no other cause for pulmonary hypertension is present.

AF = atrial fibrillation; CXR = chest X-ray; ECG = electrocardiogram; echo = echocardiography; LA = left atrial; MR = mitral regurgitation; 2D = 2-dimensional.

Figure 4. Management Strategy for Patients With Mitral Stenosis

YesNo

YesNo†

Symptoms?

Valve morphologyfavorable for PMBV?

Yearly follow-up

History, physical exam,

CXR, ECG

Mild stenosis MVA>1.5 cm2

Mild stenosis or severe stenosis* MVA ≤1.5 cm2

History, physical exam CXR, ECG, 2D echo/Doppler

Asymptomatic

Mitral Stenosis

PASP > 50 mm Hg?

Yes‡No

Exercise

Poor exercise tolerance or PASP > 60 mm Hg or PAWP ≥ 25 mm Hg

YesNo

New onset AF?

Class I

Class I

ConsiderPMBV

Exclude LA clot,3+ to 4+ MR

Class I Ib

Symptomatic(see Figures 5 and 6)

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† There is controversy as to whether patients with severe mitral stenosis (MVA < 1.0 cm2) and severe pulmonary hypertension (PH; PASP > 60 mm Hg) should undergo percutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement (MVR) to prevent right ventricular failure.

CXR = chest X-ray; ECG = electrocardiogram; echo = echocardiography; LA = left atrial; MR = mitral regurgitation; MVG = mean mitral valve pressure gradient; PAP = pulmonary artery pressure; 2D = 2-dimensional.

Figure 5. Management Strategy for Patients With Mitral Stenosis and Mild Symptoms

History, physical exam, CXR, ECG, 2D echo/Doppler

Mild stenosisMVA >1.5 cm2 *

Moderate or severe stenosis

MVA ≤ 1.5 cm2 *

PASP >60 mm HgPAWP ≥ 25 mm HgMVG >15 mm Hg

Yearly follow-up


No Yes No

6 month follow-up

6 month follow-up

No Yes

Class I Ib Class I

Symptomatic Mitral Stenosis NYHA Functional Class II

Exercise

Consider PMBV

Exclude LA clot,3+ to 4+ MR

Consider commissurotomy

or MVR†


Yes No

Class I Ia

Severe PHPAP > 60 mm Hg

Yes


31


† It is controversial as to which patients with less favorable valve morphology should undergo percutaneous mitral balloon valvotomy (PMBV) rather than mitral valve surgery (see text).

CXR = chest X-ray; ECG = electrocardiogram; echo = echocardiography; LA = left atrial; MR = mitral regurgitation; MVG = mean mitral valve pressure gradient; MVR = mitral valve replacement; NYHA = New York Heart Association; 2D = 2-dimensional.

Class I Exclude LA clot,3+ to 4+ MR

History, physical exam, CXR, ECG, 2D echo/Doppler

Mild stenosisMVA >1.5 cm2

Moderate or severe stenosis

MVA ≤ 1.5 cm2*

PASP >60 mm HgPAWP ≥ 25 mm HgMVG >15 mm Hg

Look for other

etiologies

Yes

YesNo†

Exercise


Class I Ib

High-risk surgical candidate?

YesNo† Consider PMBV

Class I

Class I Ia

Mitral valve repair

or MVR

Symptomatic Mitral Stenosis NYHA Functional Class III-IV

No

Figure 6. Management Strategy for Patients with Mitral Stenosis and Moderate to Severe Symptoms

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Recommendations for Percutaneous Mitral Balloon Valvotomy for Mitral Stenosis

Class I 1. PMBV is indicated for the following patients with

moderate or severe MS† and valve morphology

favorable for PMBV in the absence of left atrial

thrombus or moderate to severe MR:

A. Symptomatic patients (NYHA functional

class II, III, or IV). (Level of Evidence: A)

B. Asymptomatic patients who have pulmonary

hypertension (pulmonary artery systolic pressure

greater than 50 mm Hg at rest or greater than

60 mm Hg with exercise). (Level of Evidence: C)

Class IIa 1. PMBV is reasonable for patients with moderate

or severe MS† who have a nonpliable calcified valve,

are in NYHA functional class III-IV, and are either not

candidates for surgery or are at high risk for surgery.


Class IIb 1. PMBV may be considered for the following

patients in the absence of left atrial thrombus

or moderate to severe MR:

A. Asymptomatic patients with moderate or

severe MS† and valve morphology favorable for

PMBV who have new onset of atrial fibrillation.



33

B. Symptomatic patients (NYHA functional class II,

III, or IV) with MV area greater than 1.5 cm2 if

there is evidence of hemodynamically significant

MS based on pulmonary artery systolic pressure

greater than 60 mm Hg, pulmonary artery wedge

pressure of 25 mm Hg or more, or mean MV

gradient greater than 15 mm Hg during exercise.


C. Patients with moderate or severe MS who have

a nonpliable calcified valve and are in NYHA

functional class III-IV, as an alternative to surgery.


Class III 1. PMBV is not indicated for patients with mild MS.


2. PMBV should not be performed in patients

with moderate to severe MR or left atrial thrombus.


Indications for Surgery for Mitral Stenosis (Valve Repair or Replacement)

Class I 1. MV surgery (repair if possible) is indicated in

patients with symptomatic (NYHA functional class

III-IV) moderate or severe MS† and with acceptable

operative risk when (1) PMBV is unavailable,

(2) PMBV is contraindicated because of left atrial

thrombus despite anticoagulation or because

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concomitant moderate to severe MR is present,

or (3) the valve morphology is not favorable for

PMBV. (Level of Evidence: B)

2. Symptomatic patients with moderate to severe

MS† who also have moderate to severe MR should

receive MV replacement, unless MV repair is

possible at the time of surgery. (Level of Evidence: C)

Class IIa 1. MV replacement is reasonable for patients with

severe MS† and severe pulmonary hypertension

(pulmonary artery systolic pressure greater than

60 mm Hg) with NYHA functional class I-II

symptoms who are not considered candidates for

PMBV or surgical MV repair. (Level of Evidence: C)

Class IIb 1. MV repair may be considered for asymptomatic

patients with moderate or severe MS† who have

had recurrent embolic events while receiving

adequate anticoagulation and who have valve

morphology favorable for repair.


Class III 1. MV repair for MS is not indicated for patients

with mild MS. (Level of Evidence: C)

2. Closed commissurotomy should not be

performed in patients undergoing MV repair;

open commissurotomy is the preferred approach.



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D. Mitral Regurgitation

Factors influencing the timing of surgery for MR include

symptoms, LV EF, LV end-systolic dimension, atrial fibrillation,

and pulmonary hypertension (Figure 7). In most situations,

MV repair is the operation of choice for those patients with

suitable MV anatomy.

Operation is indicated for most patients with severe MR and any

symptoms. Operation is also indicated in asymptomatic patients

who demonstrate mild to moderate LV dysfunction (EF 0.30 to

0.60 and end-systolic dimension 40 to 55 mm). The patient with

severe LV dysfunction (EF less than 0.30 and/or end-systolic

dimension greater than 55 mm) poses a higher risk but may

undergo surgery if chordal preservation is likely.

There is controversy regarding the timing of surgery in the

asymptomatic patient with severe MR and normal LV function.

If MV repair can be performed with a high degree of success

and the operative risk is low, it is reasonable to proceed with

surgery to prevent irreversible LV dysfunction from occurring.

However, this “early” operation should only be performed at

centers in which there is a high likelihood of successful MV

repair because of their demonstrated expertise in this area.

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Figure 7. Management Strategy for Patients With Chronic Severe Mitral Regurgitation

*Mitral valve (MV) repair may be performed in asymptomatic patients with normal left ventricular (LV) function if performed by an experienced surgical team and the likelihood of successful MV repair is greater than 90%.

AF = atrial fibrillation; Echo = echocardiography; EF = ejection fraction; ESD = end-systolic dimension; HT = hypertension; MV = mitral valve; MVR = mitral valve replacement.

Reevaluation

Yes Class I Ia

Chronic Severe Mitral Regurgitation

Clinical evaluation + Echo

Symptoms?

LV function?

YesNo

LV function?

Normal LV function

EF >0.60ESD <40

LV dysfunction EF ≤ 0.60

and/or ESD ≥ 40 mm

EF >0.30 ESD ≤ 55 mm

EF <0.30 and/or

ESD >55 mm

New onset AF? Pulmonary HT?

Chordal preservationlikely?

MV repair likely?*

No

No

Clinical eval every6 mos

Echo every6 mos

MV repair If not possible,

MVR

Yes* Class I Ia MV repair

YesClass I Ia

No

Medical therapy

Class I Class I


37

Recommendations for Mitral Valve Surgery in Nonischemic Severe Mitral Regurgitation

Class I 1. MV surgery is recommended for the following

patients:

A. Symptomatic patients with acute severe MR.†


B. Patients with chronic severe MR† and NYHA

functional class II, III, or IV symptoms in the

absence of severe LV dysfunction (severe LV

dysfunction is defined as EF less than 0.30 and/

or end-systolic dimension greater than 55 mm).


C. Asymptomatic patients with chronic severe

MR† and mild to moderate LV dysfunction,

EF 0.30 to 0.60, and/or end-systolic dimension

greater than or equal to 40 mm.


2. MV repair is recommended over MV replacement

(MVR) in the majority of patients with severe chronic

MR† who require surgery, and patients should

be referred to surgical centers experienced in MV

repair. (Level of Evidence: C)

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Class IIa 1. MV repair is reasonable in experienced surgical

centers for asymptomatic patients with chronic

severe MR† with preserved LV function (EF greater

than 0.60 and end-systolic dimension less than

40 mm) in whom the likelihood of successful repair

without residual MR is greater than 90%.


2. MV surgery is reasonable for the following

patients:

A. Asymptomatic patients with chronic severe

MR†, preserved LV function, and (1) new onset

of atrial fibrillation or (2) pulmonary hypertension

(pulmonary artery systolic pressure greater than

50 mm Hg at rest or greater than 60 mm Hg with

exercise). (Level of Evidence: C)

B. Patients with chronic severe MR† due to a

primary abnormality of the mitral apparatus,

NYHA functional class III-IV symptoms, and

severe LV dysfunction (EF less than 0.30 and/

or end-systolic dimension greater than 55 mm)

in whom MV repair is highly likely.


Class IIb 1. MV repair may be considered for patients with

chronic severe secondary MR† due to severe LV

dysfunction (EF less than 0.30) who have persistent

NYHA functional class III-IV symptoms despite

optimal therapy for heart failure, including

biventricular pacing. (Level of Evidence: C)


39

Class III 1. MV surgery is not indicated for asymptomatic

patients with MR and preserved LV function (EF

greater than 0.60 and end-systolic dimension less

than 40 mm) in whom significant doubt about the

feasibility of repair exists. (Level of Evidence: C)

2. Isolated MV surgery is not indicated for patients

with mild or moderate MR. (Level of Evidence: C)


E. Infective Endocarditis

Surgery is indicated in patients with life-threatening heart

failure or cardiogenic shock due to surgically treatable valvular

heart disease with or without proven infective endocarditis

(IE) if the patient has a reasonable prospect of recovery with

satisfactory quality of life after the operation. In the setting

of acute IE, surgery should not be delayed when heart failure

exists.

Indications for surgery for IE in patients with stable

hemodynamics are less clear. Surgery is recommended

for patients with annular or aortic abscesses, those with

infections resistant to antibiotic therapy, and those with

fungal endocarditis. Prosthetic valve endocarditis and native

valve endocarditis caused by Staphylococcus aureus are almost

always surgical diseases. Early surgery in MV endocarditis

caused by virulent organisms (such as S. aureus or fungi) may

make repair possible.

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When at all possible, MV repair should be performed instead

of MVR in the setting of active infection because of the risk

of infection of prosthetic materials. Aortic valves may often

be repaired as well if there are leaflet perforations, and this

is preferable to AVR for the same reasons.

Indications for Surgery for Native Valve Endocarditis

Class I 1. Surgery of the native valve is indicated in the

following patients with IE:

A. Patients who present with valve stenosis

or regurgitation resulting in heart failure.


B. Patients who present with AR or MR with

hemodynamic evidence of elevated LV end-

diastolic or left atrial pressures (e.g., premature

closure of MV with AR, rapid decelerating MR

signal by continuous-wave Doppler [v-wave

cutoff sign], or moderate or severe pulmonary

hypertension). (Level of Evidence: B)

C. Patients with IE caused by fungal or other

highly resistant organisms. (Level of Evidence: B)

D. Patients with complications of heart block,

annular or aortic abscess, or destructive

penetrating lesions (e.g., sinus of Valsalva to

right atrium, right ventricle, or left atrium fistula;

mitral leaflet perforation with aortic valve

endocarditis; or infection in annulus fibrosa).



41

Class IIa 1. Surgery of the native valve is reasonable in

patients with IE who present with recurrent emboli

and persistent vegetations despite appropriate

antibiotic therapy. (Level of Evidence: C)

Class IIb 1. Surgery of the native valve may be considered

in patients with IE who present with mobile

vegetations in excess of 10 mm with or without

emboli. (Level of Evidence: C)

Indications for Surgery for Prosthetic Valve Endocarditis

Class I 1. Consultation with a cardiac surgeon is indicated

for patients with IE of a prosthetic valve.


2. Surgery is indicated for the following patients

with IE of a prosthetic valve:

A. Patients who present with heart failure.


B. Patients who present with dehiscence evidenced

by cine fluoroscopy or echocardiography.


C. Patients who present with evidence of

increasing obstruction or worsening regurgitation.


D. Patients who present with complications, for

example, abscess formation. (Level of Evidence: C)

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Class IIa 1. Surgery is reasonable for patients with IE

of a prosthetic valve who present with

A. Evidence of persistent bacteremia or recurrent

emboli despite appropriate antibiotic treatment.


B. Relapsing infection. (Level of Evidence: C)

Class III 1. Routine surgery is not indicated for patients

with uncomplicated IE of a prosthetic valve

caused by first infection with a sensitive organism.


F. Major Criteria for Valve Selection

The major advantages of a mechanical valve over a bio-

prosthesis are a low rate of structural deterioration and

a better survival rate in younger patients. Major disadvan-

tages are increased incidence of bleeding due to need for

antithrombotic therapy and the increased risk of thrombosis.

The major advantage of a bioprosthesis over a mechanical

prosthesis is the lack of need for antithrombotic therapy. The

major disadvantage is the increased rate of structural valve

deterioration. The rate of structural valve deterioration in the

aortic position in patients 65 years of age or greater is lower

than for those less than 65 years of age. The final decision

regarding a mechanical valve versus a bioprosthesis is based


43

on multiple factors, including patient age, overall longevity

of the valve, relative contraindications to anticoagulation,

and lifestyle.

In general, MV repair is preferable to MVR, provided it is

feasible and that the appropriate skill level and experience

are available to perform this procedure successfully.

Pregnancy poses a difficult problem. The disadvantages

of a mechanical valve are the complications of warfarin

or UFH therapy that may affect the patient or the fetus.

The disadvantage of a bioprosthesis is the relatively higher

rate of early structural valve deterioration.

If a patient needs antithrombotic therapy for any reason

(i.e., atrial fibrillation or the presence of a mechanical valve

in another position), the major advantage of a biological

valve is reduced.

Recommendations for Aortic Valve Selection

Class I 1. A mechanical prosthesis is recommended

for AVR in patients with a mechanical valve

in the mitral or tricuspid position.


2. A bioprosthesis is recommended for AVR

in patients of any age who will not take warfarin

or who have major medical contraindications

to warfarin therapy. (Level of Evidence: C)

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Class IIa 1. Patient preference is a reasonable consideration

in the selection of aortic valve operation and valve

prosthesis. A mechanical prosthesis is reasonable

for AVR in patients under 65 years of age who

do not have a contraindication to anticoagulation.

A bioprosthesis is reasonable for AVR in patients

under 65 years of age who elect to receive this valve

for lifestyle considerations after detailed discussions

of the risks of anticoagulation versus the likelihood

that a second AVR may be necessary in the future.


2. A bioprosthesis is reasonable for AVR in patients

aged 65 years or older without risk factors for

thromboembolism. (Level of Evidence: C)

3. Aortic valve re-replacement with a homograft is

reasonable for patients with active prosthetic valve

endocarditis. (Level of Evidence: C)

Class IIb 1. A bioprosthesis might be considered for AVR

in a woman of childbearing age. (Level of Evidence: C)


45

Recommendations for Mitral Valve Selection

Class I 1. A bioprosthesis is indicated for MVR in a

patient who will not take warfarin, is incapable

of taking warfarin, or has a clear contraindication

to warfarin therapy. (Level of Evidence: C)

Class IIa 1. A mechanical prosthesis is reasonable for

MVR in patients under 65 years of age with

long-standing atrial fibrillation. (Level of Evidence: C)

2. A bioprosthesis is reasonable for MVR in

patients 65 years of age or older.


3. A bioprosthesis is reasonable for MVR in

patients under 65 years of age in sinus rhythm

who elect to receive this valve for lifestyle

considerations after detailed discussions of the

risks of anticoagulation versus the likelihood

that a second MVR may be necessary in the

future. (Level of Evidence: C)

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IV. Antithrombotic Management of Prosthetic Heart Valves

A. Indications for Anticoagulation in Patients With Prosthetic Heart Valves

All patients with mechanical valves require warfarin therapy,

as indicated in Table 2. The risk of embolization is greater with

the valve in the mitral position than in the aortic position. Other

risk factors for increased risk of embolization include atrial

fibrillation, LV dysfunction, clotting disorder, and prior embolic

events. With either type of prosthesis or valve location, the risk

of emboli is higher in the first few months after valve insertion,

before the valve is fully endothelialized. In most patients with a

mechanical prosthesis, the target international normalized ratio

(INR) is 2.5 to 3.5. The target INR can be reduced to 2.0 to 3.0

in those patients with a new-generation AVR and no other risk

factors for thromboembolic events.

Aspirin is recommended for all patients with prosthetic heart

valves: aspirin alone (75 to 100 mg per day) in patients with

bioprostheses and no risk factors or aspirin (75 to 100 mg per

day) combined with warfarin in patients with mechanical heart

valves and high-risk patients with bioprostheses. In high-risk

patients who cannot take aspirin, the addition of clopidogrel

to warfarin therapy should be considered.

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47

Aspirin Warfarin Warfarin Valve Type (75-100 mg) (INR 2.0-3.0) (INR 2.5-3.5) No Warfarin

Mechanical Prosthetic

A. AVR – Low Risk

■ Less than 3 months Class I Class I Class IIa

■ Greater than 3 months Class I Class I

B. AVR – High Risk Class I Class I

C. MVR Class I Class I

Biological Prosthetic

A. AVR – Low Risk

■ Less than 3 months Class I Class IIa Class IIb

■ Greater than 3 months Class I Class IIa

B. AVR – High Risk Class I Class I

C. MVR – Low Risk

■ Less than 3 months Class I Class IIa

■ Greater than 3 months Class I Class IIa

D. MVR – High Risk Class I Class I

Depending on patients’ clinical status, antithrombotic therapy must be individualized (see special situations in text). In patients receiving warfarin, aspirin is recommended in virtually all situations. Risk factors: atrial fibrillation, LV dysfunction, previous thromboembolism, and hypercoagulable condition. INR should be maintained between 2.5 and 3.5 for aortic disk valves and Starr-Edwards valves. Modified from McAnulty JH, Rahimtoola SH. Antithrombotic therapy in valvular heart disease. In: Schlant R, Alexander RW, editors. Hurst's The Heart. New York, NY: McGraw-Hill, 1998:1867–74. Reprinted with permission from the McGraw-Hill Companies.

AVR = aortic valve replacement; MVR = mitral valve replacement.

Table 2. Recommendations for Antithrombotic Therapy in Patients With Prosthetic Heart Valves

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Recommendations for Antithrombotic Therapy in Patients With Prosthetic Heart Valves

Class I 1. After AVR with bileaflet mechanical or Medtronic

Hall prostheses, warfarin is indicated to achieve

an INR of 2.0 to 3.0 in patients with no risk factors,‡

and to achieve an INR of 2.5 to 3.5 in patients with

risk factors.‡ (Level of Evidence: B)

2. After AVR with Starr-Edwards valves or

mechanical disc valves (other than Medtronic

Hall prostheses), warfarin is indicated to achieve

an INR of 2.5 to 3.5 in patients with no risk factors.‡


3. After MVR with any mechanical valve, warfarin

is indicated to achieve an INR of 2.5 to 3.5.


4. After AVR or MVR with a bioprosthesis and no risk

factors,‡ aspirin is indicated at 75 to 100 mg per day.


5. After AVR with a bioprosthesis in patients with

risk factors,‡ warfarin is indicated to achieve an

INR of 2.0 to 3.0. (Level of Evidence: C)

6. After MVR with a bioprosthesis in patients with

risk factors,‡ warfarin is indicated to achieve an

INR of 2.5 to 3.5. (Level of Evidence: C)

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7. For those patients who are unable to take

warfarin after AVR or MVR, aspirin is indicated

in a dose of 75 to 325 mg per day.


8. The addition of aspirin 75 to 100 mg once daily

to therapeutic warfarin is recommended for all

patients with mechanical heart valves and those

patients with biological valves who have risk

factors.‡ (Level of Evidence: B)

Class IIa 1. During the first 3 months after AVR with

a mechanical prosthesis, it is reasonable to

give warfarin to achieve an INR of 2.5 to 3.5.


2. During the first 3 months after AVR or MVR

with a bioprosthesis in patients with no risk

factors,‡ it is reasonable to give warfarin to

achieve an INR of 2.0 to 3.0.


Class IIb 1. In high-risk patients with prosthetic heart

valves in whom aspirin cannot be used, it may

be reasonable to give clopidogrel (75 mg per day)

or warfarin to achieve an INR of 3.5 to 4.5.


‡ Risk factors include atrial fibrillation, previous thromboembolism, LV dysfunction, and hypercoagulable condition.

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B. Embolic Events During Adequate Antithrombotic Therapy

In the patient who has a definite embolic episode while

undergoing adequate antithrombotic therapy, the dosage

of antithrombotic therapy should be increased, when clinic-

ally safe, as follows:

■ Warfarin, INR 2.0 to 3.0: warfarin dose increased to

achieve INR of 2.5 to 3.5

■ Warfarin, INR 2.5 to 3.5: warfarin dose may need to be

increased to achieve INR of 3.5 to 4.5

■ Not taking aspirin: aspirin 75 to 100 mg per day should

be initiated

■ Warfarin plus aspirin 75 to 100 mg per day: aspirin dose

may also need to be increased to 325 mg per day if the higher

dose of warfarin is not achieving the desired clinical result

■ Aspirin alone: aspirin dose may need to be increased to

325 mg per day, clopidogrel 75 mg per day added, and/or

warfarin added.

C. Excessive Anticoagulation

In most patients with an INR above the therapeutic range,

excessive anticoagulation can be managed by withholding

warfarin and monitoring the level of anticoagulation. Rapid

decreases in INR to less than the therapeutic range will increase

the risk of thromboembolism. Patients with an INR of 5 to 10

who are not bleeding can be treated as follows:

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■ Hold warfarin and administer 1 to 2.5 mg of oral vitamin K1

■ Determine INR after 24 h and subsequently as needed

■ Restart warfarin and adjust dose appropriately to ensure the

INR is in the therapeutic range

■ Emergency use of fresh frozen plasma is preferable to high-

dose vitamin K1, especially parenteral vitamin K1.

D. Antithrombotic Therapy in Patients Requiring Noncardiac Surgery/Dental Care

Antithrombotic therapy should not be stopped for procedures

in which bleeding is either unlikely or would be inconsequential

if it occurred. When bleeding is likely or its potential conse-

quences are severe, antithrombotic therapy should be altered.

The use of “bridging” unfractionated heparin (UFH) or low-

molecular-weight heparin (LMWH) therapy when stopping

the warfarin is dependent on the absence or presence of other

risk factors, which include atrial fibrillation, previous thrombo-

embolism, hypercoagulable condition, LV dysfunction, and the

presence of a mitral prosthesis.

Recommendations for Antithrombotic Therapy in Patients

Class I 1. In patients at low risk of thrombosis, defined as

those with a bileaflet mechanical AVR with no risk

factors,§ it is recommended that warfarin be stopped

48 to 72 h before the procedure (so the INR falls to

less than 1.5) and restarted within 24 h after the

procedure. Heparin is usually unnecessary.


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2. In patients at high risk of thrombosis, defined

as those with any mechanical MVR or a mechanical

AVR with any risk factor,§ therapeutic doses of

intravenous UFH should be started when the INR

falls below 2.0 (typically 48 h before surgery),

stopped 4 to 6 h before the procedure, restarted as

early after surgery as bleeding stability allows, and

continued until the INR is again therapeutic with

warfarin therapy. (Level of Evidence: B)

Class IIa 1. It is reasonable to give fresh frozen plasma

to patients with mechanical valves who require

interruption of warfarin therapy for emergency

noncardiac surgery, invasive procedures, or dental

care. Fresh frozen plasma is preferable to high-

dose vitamin K1. (Level of Evidence: B)

Class IIb 1. In patients at high risk of thrombosis (see above),

therapeutic doses of subcutaneous UFH (15,000 U

every 12 h) or LMWH (100 U per kg every 12 h) may

be considered during the period of a subtherapeutic

INR. (Level of Evidence: B)

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53

Class III 1. In patients with mechanical valves who require

interruption of warfarin therapy for noncardiac

surgery, invasive procedures, or dental care,

high-dose vitamin K1 should not be given routinely,

because this may create a hypercoagulable

condition. (Level of Evidence: B)

§ Risk factors: atrial fibrillation, previous thromboembolism, LV dysfunction, hypercoagulable conditions, older generation thrombogenic valves, mechanical tricuspid valves, or more than 1 mechanical valve.

E. Pregnancy

Anticoagulation for prosthetic valves during pregnancy presents

a difficult problem. Warfarin is probably safe during the first

6 weeks of gestation, but there is a risk of embryopathy if

warfarin is taken between 6 and 12 weeks of gestation.

Warfarin is also relatively safe during the 2nd and 3rd trimester

of pregnancy, but needs to be discontinued and switched to

a heparin compound several weeks before delivery. Several

studies strongly suggest that UFH or LMWH therapy is safe

for the fetus but poses a high incidence of thromboembolic

complications, including fatal valve thrombosis. Thus, warfarin

is more efficacious than UFH for thromboembolic prophylaxis

of women with mechanical heart valves in pregnancy, but with

an increased risk of embryopathy. There are still insufficient

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grounds to make definitive recommendations about optimal

antithrombotic therapy in pregnant patients with mechanical

heart valves because properly designed studies have not been

performed. The final decision on the anticoagulation regimen

requires discussion with the patient regarding the risks and

benefits of each approach. For any anticoagulation, intensive

monitoring is required.

Selection of Anticoagulation Regimen in Pregnant Patients With Mechanical Prosthetic Valves

Class I 1. All pregnant patients with mechanical

prosthetic valves must receive continuous

therapeutic anticoagulation with frequent

monitoring. (Level of Evidence: B)

2. For women requiring long-term warfarin therapy

who are attempting pregnancy, pregnancy tests

should be monitored with discussions about

subsequent anticoagulation therapy, so that

anticoagulation can be continued uninterrupted

when pregnancy is achieved. (Level of Evidence: C)

3. Pregnant patients with mechanical prosthetic

valves who elect to stop warfarin between weeks

6 and 12 of gestation should receive continuous

IV UFH, dose-adjusted UFH, or dose-adjusted

subcutaneous LMWH. (Level of Evidence: C)

4. For pregnant patients with mechanical prosthetic

valves up to 36 weeks of gestation, the therapeutic

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55

choice of continuous intravenous or adjusted-dose

subcutaneous UFH, dose-adjusted LMWH, or

warfarin should be discussed fully. If continuous

IV UFH is used, the fetal risk is lower but the

maternal risks of prosthetic valve thrombosis,

systemic embolization, infection, osteoporosis and

heparin-induced thrombocytopenia are relatively

higher. (Level of Evidence: C)

5. In pregnant patients with mechanical pros-

thetic valves who receive dose-adjusted LMWH,

the LMWH should be administered twice daily

subcutaneously to maintain the anti-Xa level

between 0.7 to 1.2 units 4 h after administration.



thetic valves who receive dose-adjusted UFH,

the aPTT should be at least twice control.



thetic valves who receive warfarin, the INR

goal should be 3.0 (range 2.5 to 3.5).



thetic valves, warfarin should be discontin-

ued and continuous IV UFH given starting at

2 to 3 weeks before planned delivery.


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Class IIa 1. In patients with mechanical prosthetic valves,

it is reasonable to avoid warfarin between weeks

6 and 12 of gestation owing to the high risk of fetal

defects. (Level of Evidence: C)

2. In patients with mechanical prosthetic valves,

it is reasonable to resume heparin 4 to 6 h after

delivery and begin oral warfarin in the absence

of significant bleeding. (Level of Evidence: C)

3. In patients with mechanical prosthetic valves,

it is reasonable to give low-dose aspirin (75 to

100 mg per day) in the second and third trimesters

of pregnancy in addition to anticoagulation with

warfarin or heparin. (Level of Evidence: C)

Class III 1. LMWH should not be administered to pregnant

patients with mechanical prosthetic valves unless

anti-Xa levels are monitored 4 to 6 hours after

administration. (Level of Evidence: C)

2. Dipyridamole should not be used instead

of aspirin as an alternative antiplatelet agent

in pregnant patients with mechanical prosthetic

valves because of its harmful effects on the fetus.


F. Thrombosis of Prosthetic Heart Valves

Obstruction of prosthetic heart valves may be caused by

thrombus formation, pannus ingrowth, or a combination of

both. The cause may be difficult to determine and requires

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57

knowledge of the clinical presentation and findings on

echocardiography, including TEE. Emergency surgery is

indicated for the patient with NYHA functional class III-IV heart

failure or the patient with a large thrombus burden. Fibrinolytic

therapy for a left-sided prosthetic valve obstructed by thrombus

is associated with significant risks (cerebral emboli in 12% to

15%) but may be used in patients at high risk for surgery or

those with stable hemodynamics and a small clot burden.

Recommendations for Thrombosis of Prosthetic Heart Valves

Class I 1. Transthoracic and Doppler echocardiography

is indicated in patients with suspected prosthetic

valve thrombosis to assess hemodynamic severity.


2. TEE and/or fluoroscopy is indicated in patients

with suspected valve thrombosis to assess valve

motion and clot burden. (Level of Evidence: B)

Class IIa 1. Emergency operation is reasonable for the

following patients with a thrombosed left sided

prosthetic valve:

A. Patients with NYHA functional class III-IV

symptoms. (Level of Evidence: C)

B. Patients with a large clot burden.


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2. Fibrinolytic therapy is reasonable for thrombosed

right-sided prosthetic heart valves with NYHA

functional class III-IV symptoms or a large clot

burden. (Level of Evidence C)

Class IIb 1. Fibrinolytic therapy may be considered as

a first-line therapy for the following patients

with a thrombosed left sided prosthetic valve:

A. Patients with NYHA functional class I-II

symptoms, and a small clot burden.


B. Patients with a NYHA functional class III-IV

symptoms, and a small clot burden if surgery

is high risk or not available. (Level of Evidence: B)

C. Patients with an obstructed prosthetic valve

who have NYHA functional class II-IV symptoms

and a large clot burden if emergency surgery

is high risk or not available. (Level of Evidence: C)

2. Intravenous heparin as an alternative to

fibrinolytic therapy may be considered for patients

with a thrombosed valve who are in NYHA

functional class I-II and have a small clot burden.


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UC200700026 EN

ISSN: 1524-4539 Copyright © 2006 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online

72514Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX

DOI: 10.1161/CIRCULATIONAHA.105.561514 2006;113;1622-1632 Circulation

William C. Little and Gregory L. Freeman Pericardial Disease

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Pericardial DiseaseWilliam C. Little, MD; Gregory L. Freeman, MD

In contrast to coronary artery disease, heart failure, valvulardisease, and other topics in the field of cardiology, there

are few data from randomized trials to guide physicians in themanagement of pericardial diseases. Although there are noAmerican Heart Association/American College of Cardiol-ogy guidelines on this topic, the European Society of Cardi-ology has recently published useful guidelines for the diag-nosis and management of pericardial diseases.1 Our reviewfocuses on the current state of knowledge and the manage-ment of the most important pericardial diseases: acute peri-carditis, pericardial tamponade, pericardial constriction, andeffusive constrictive pericarditis.

The Normal PericardiumThe pericardium is a relatively avascular fibrous sac thatsurrounds the heart. It consists of 2 layers: the visceral andparietal pericardium. The visceral pericardium is composedof a single layer of mesothelial cells that are adherent to thecardiac epicardium.2,3 The parietal pericardium is a fibrousstructure that is �2 mm thick and is composed primarily ofcollagen and a lesser amount of elastin. The 2 layers of thepericardium are separated by a potential space that cannormally contain 15 to 35 mL of serous fluid distributedmostly over the atrial-ventricular and interventriculargrooves.

The pericardium surrounds the heart and attaches to thesternum, the diaphragm, and the anterior mediastinum and isinvested around the great vessels and the venae cavae, servingto anchor the heart in the central thorax. Because of itslocation, the pericardium may also function as a barrier toinfection.

The pericardium is well innervated such that pericardialinflammation may produce severe pain and trigger vagallymediated reflexes. The pericardium also secretes prostaglan-dins that modulate cardiac reflexes and coronary tone.4

As a result of its relatively inelastic physical properties, thepericardium limits acute cardiac dilatation and enhancesmechanical interactions of the cardiac chambers.5 In responseto long-standing stress, the pericardium dilates, shifting thepericardial pressure-volume relation substantially to the right(Figure 1).6–8 This allows a slowly accumulating pericardialeffusion to become quite large without compressing thecardiac chambers and for left ventricular remodeling to occurwithout pericardial constriction.

Despite the known important functions of the normalpericardium, congenital absence or surgical resection of thepericardium does not appear to have any major untowardeffects.9

Acute PericarditisEtiologyAcute inflammation of the pericardium with or without anassociated pericardial effusion can occur as an isolatedclinical problem or as a manifestation of systemic diseas-es.1,10–13 Although as many as 90% of isolated cases of acutepericarditis are idiopathic or viral, the list of other potentialcauses is extensive (Table 1). Although formerly common,tuberculous and bacterial infections have become rare causesof pericarditis.14 Other causes of acute pericarditis includeuremia,15 collagen vascular diseases,16 neoplasms, and peri-cardial inflammation after an acute myocardial infarction orpericardial injury.17

Pericarditis after an acute myocardial infarction mostcommonly occurs 1 to 3 days after transmural myocardialinfarction presumably because of the interaction of thehealing necrotic epicardium with the overlying pericardium.A second form of pericarditis associated with myocardialinfarction (Dressler’s syndrome) typically occurs weeks tomonths after a myocardial infarction. It is similar to thepericarditis that may occur days to months after traumaticpericardial injury, after surgical manipulation of the pericar-dium, or after a pulmonary infarction.18 This syndrome ispresumed to be mediated by an autoimmune mechanism andis associated with signs of systemic inflammation, includingfever, and polyserositis. The frequency of pericarditis aftermyocardial infarction has been reduced by the use of reper-fusion therapy.19

Clinical ManifestationsMost patients with acute pericarditis experience sharp retro-sternal chest pain that can be quite severe and debilitating. Insome cases, however, pericarditis may be asymptomatic, as isoften the case with the pericarditis accompanying rheumatoidarthritis. Pericardial pain is usually worse with inspiration andwhen supine and is relieved by sitting forward. Typically,pericardial pain is referred to the scapular ridge, presumablydue to irritation of the phrenic nerves, which pass adjacent to

From the Cardiology Section, Wake Forest University School of Medicine, Winston-Salem, NC (W.C.L.); and Departments of Medicine andPhysiology, University of Texas Health Science Center–San Antonio, South Texas Veteran’s Health Care System, San Antonio, Tex (G.L.F.).

Correspondence to Dr William C. Little, Cardiology Section, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC27157-1045. E-mail [email protected]

(Circulation. 2006;113:1622-1632.)© 2006 American Heart Association, Inc.

Circulation is available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.105.561514

1622

Contemporary Reviews in Cardiovascular Medicine



the pericardium.12 The chest pain of acute pericarditis must bedifferentiated from that of pulmonary embolism and myocar-dial ischemia/infarction (Table 2).10

The pericardial friction rub is the classic finding in patientswith acute pericarditis. It is a high-pitched, scratchy soundthat can have 1, 2, or 3 components. These components occurwhen the cardiac volumes are most rapidly changing: duringventricular ejection, during rapid ventricular filling in earlydiastole, and during atrial systole. Thus, patients with atrialfibrillation have only 1 or 2 component rubs. The pericardialfriction rub can be differentiated from a pleural rub, which isabsent during suspended respiration, whereas the pericardialrub is unaffected. Although it is easy to imagine that thepericardial rub arises from the inflamed visceral and parietallayers of the pericardium rubbing together, most patients withacute pericarditis (including those with audible rubs) have atleast a small pericardial effusion, which should lubricate theinteraction of the 2 layers of the pericardium.12

Early in the course of acute pericarditis, the ECG typicallydisplays diffuse ST elevation in association with PR depres-sion (Figure 2).12 The ST elevation is usually present in allleads except for aVR, but in post–myocardial infarctionpericarditis, the changes may be more localized. Classically,

the ECG changes of acute pericarditis evolve through 4progressive stages: stage I, diffuse ST-segment elevation andPR-segment depression; stage II, normalization of the ST andPR segments; stage III, widespread T-wave inversions; andstage IV, normalization of the T waves.12 Patients withuremic pericarditis frequently do not have the typical ECGabnormalities.19

Patients with acute pericarditis usually have evidence ofsystemic inflammation, including leukocytosis, elevatederythrocyte sedimentation rate, and increased C-reactive pro-tein. A low-grade fever is common, but a temperature �38°Cis unusual and suggests the possibility of purulent bacterialpericarditis.10,20

Troponin is frequently minimally elevated in acute peri-carditis, usually in the absence of an elevated total creatinekinase.21,22 Presumably, this is due to some involvement ofthe epicardium by the inflammatory process. Although theelevated troponin may lead to the misdiagnosis of acutepericarditis as a myocardial infarction, most patients with anelevated troponin and acute pericarditis have normal coronaryangiograms.22 An elevated troponin in acute pericarditistypically returns to normal within 1 to 2 weeks and is notassociated with a worse prognosis.10

Echocardiography usually demonstrates at least a smallpericardial effusion in the presence of acute pericarditis. It isalso helpful in excluding cardiac tamponade (see below).Pericardiocentesis is indicated if the patient has cardiactamponade (see below) or in suspected purulent or malignantpericarditis.1,10,23 In the absence of these situations, when thecause of the acute pericarditis is not apparent on the basis ofroutine evaluation, pericardiocentesis and pericardial biopsyrarely provide a diagnosis and thus are not indicated.23,24

TreatmentIf acute pericarditis is a manifestation of an underlyingdisease, it often responds to the treatment of the primarycondition. For example, uremic pericarditis usually resolveswith adequate renal dialysis.15 Most acute idiopathic or viralpericarditis is a self-limited disease that responds to treatmentwith aspirin (650 mg every 6 hours) or another nonsteroidalantiinflammatory agent (NSAID). The intravenous adminis-tration of ketorolac, a parenteral NSAID, was effective inrelieving the pain of acute pericarditis in 22 consecutivepatients.25 Aspirin may be the preferred nonsteroidal agent totreat pericarditis after myocardial infarction because otherNSAIDs may interfere with myocardial healing.10 Indometh-acin should be avoided in patients who may have coronaryartery disease.

If the pericardial pain and inflammation do not respond toNSAIDs or if the acute pericarditis recurs, colchicine hasbeen observed to be effective in relieving pain and preventingrecurrent pericarditis.26 The routine use of colchicine issupported by recently reported results of the Colchicine forAcute Pericarditis (COPE) Trial.27 One hundred twentypatients with a first episode of acute pericarditis (idiopathic,acute, postpericardiotomy syndrome, and connective tissuedisease) entered a randomized, open-label trial comparingaspirin plus colchicine (1.0 to 2.0 mg for the first dayfollowed by 0.5 to 1.0 mg/d for 3 months) with treatment with

Figure 1. Pericardial pressure-volume relations determined inpericardium obtained from a normal experimental animal andfrom an animal with chronic cardiac dilation produced by vol-ume loading. The pericardial pressure-volume relation is shiftedto the right in the volume-loaded animal, demonstrating that thepericardium can dilate to accommodate slowly increasing vol-ume. Reproduced with permission from Freeman and LeWinter.6Copyright 1984, American Heart Association.

TABLE 1. Causes of Acute Pericarditis

Idiopathic

Infections (viral, tuberculosis, fungal)

Uremia

Acute myocardial infarction (acute, delayed)

Neoplasm

Post–cardiac injury syndrome (trauma, cardiothoracic surgery)

Systemic autoimmune disease (systemic lupus erythematosus, rheumatoidarthritis, ankylosing spondylitis, systemic sclerosing periarteritis nodosa,Reiter’s syndrome)

After mediastinal radiation

Little and Freeman Pericardial Disease 1623



aspirin alone. Colchicine reduced symptoms at 72 hours(11.7% versus 36.7%; P�0.03) and recurrence at 18 months(10.7% versus 36.7%; P�0.004; number needed to treat�5).Colchicine was discontinued in 5 patients because of diar-rhea. No other adverse events were noted. Importantly, noneof 120 patients developed cardiac tamponade or progressed topericardial constriction.28

Although acute pericarditis usually responds dramaticallyto systemic corticosteroids, their use early in the course ofacute pericarditis appears to be associated with increasedincidence of relapse after tapering the steroids.28,29 An obser-vational study strongly suggests that use of steroids increasesthe probability of relapse in patients treated with colchicine.30

Furthermore, in the COPE Trial, steroid use was an indepen-dent risk factor for recurrence (odds ratio�4.3).27 Accord-

ingly, systemic steroids should be considered only in patientswith recurrent pericarditis unresponsive to NSAIDs andcolchicine or as needed for treatment of an underlyinginflammatory disease. If steroids are to be used, an effectivedose (1.0 to 1.5 mg/kg of prednisone) should be given, and itshould be continued for at least 1 month before slowtapering.31 Experts have suggested that a detailed search forthe cause of recurrent pericarditis should be undertakenbefore steroid therapy is initiated in resistant or relapsingcases of pericarditis.1,28

The intrapericardial administration of steroids has beenreported to be effective in acute pericarditis without produc-ing the frequent reoccurrence of pericarditis that complicatesthe use of systemic steroids, but the invasive nature of thisprocedure limits its utility.29,32 A very few patients with

Figure 2. ECG demonstrating typical features seen on presentation of acute pericarditis. There is diffuse ST elevation and PR depres-sion except in aVR, where there is ST depression and PR elevation.

TABLE 2. Differentiation of Pericarditis From Myocardial Ischemia/Infarction and Pulmonary Embolism

Myocardial Ischemia or Infarction Pericarditis Pulmonary Embolism

Chest pain

Character Pressure-like, heavy, squeezing Sharp, stabbing, occasionally dull Sharp, stabbing

Change with respiration No Worsened with inspiration In phase with respiration (absentwhen the patient is apneic)

Change with position No Worse when supine; improvedwhen sitting up or leaning forward

No

Duration Minutes (ischemia); hours(infarction)

Hours to days Hours to days

Response to nitroglycerin Improved No change No change

Physical examination

Friction rub Absent (unless pericarditis ispresent)

Present in 85% of patients Rare; a pleural friction rub ispresent in 3% of patients

ECG

ST-segment elevation Localized convex Widespread concave Limited to lead III, aVF, and V1

PR-segment depression Rare Frequent None

Q waves May be present Absent May be present in lead III or aVFor both

T waves Inverted when ST segments arestill elevated

Inverted after ST segments havenormalized

Inverted in lead II, aVF, or V1 to V4

while ST segments are elevated

Adapted with permission from Lange and Hillis.10 Copyright 2004, Massachusetts Medical Society.

1624 Circulation March 28, 2006



frequent, highly symptomatic recurrences of pericarditis de-spite intensive medical therapy may require surgical peri-cardiectomy.32 However, painful relapses can occur evenafter pericardiectomy, especially if the pericardium is notcompletely removed.28

Most patients with acute pericarditis recover without se-quelae. Predictors of a worse outcome include the following:fever �38°C, symptoms developing over several weeks inassociation with immunosuppressed state, traumatic pericar-ditis, pericarditis in a patient receiving oral anticoagulants, alarge pericardial effusion (�20 mm echo-free space orevidence of tamponade), or failure to respond to NSAIDs.20

In a recent series of 300 patients with acute pericarditis, 254(85%) did not have any of the high-risk characteristics andhad no serious complications.20 Of these low-risk patients,221 (87%) were managed as outpatients, and the other 13%were hospitalized when they did not respond to aspirin.20

On the basis of these considerations, we manage patientspresenting with acute pericarditis in the following manner.Patients are hospitalized but are discharged in 24 to 48 hoursif they have no high-risk factors and their pain has improved.Initial therapy includes aspirin (650 to 975 mg every 6 to 8hours) and colchicine (2 g initially followed by 1 g/d). Inaddition, we use a proton pump inhibitor in most patients toimprove the gastric tolerability of the aspirin. We adviseagainst exercise until after the chest pain completely resolves.Even if the pain responds promptly, we continue aspirin for 4weeks and colchicine for 3 months to minimize the risk ofrecurrent pericarditis. If pericarditis reoccurs, we reload withcolchicine and use intravenous ketorolac (30 mg every 6hours) and then continue an oral NSAID and colchicine for atleast 3 more months. We make every effort to avoid the useof steroids, reserving steroids for patients who cannot tolerateaspirin and other NSAIDs or who have a recurrence notresponsive to colchicine and intravenous NSAIDs.

It is important to recognize that there are no clear data toguide this set of recommendations. In general, if a recurrenceof pericarditis is mild it can be treated with intensification ofNSAID therapy; various combinations of aspirin, NSAIDS,and colchicine have been successfully applied in such cases.

Cardiac TamponadePathophysiologyCardiac tamponade occurs when fluid accumulation in theintrapericardial space is sufficient to raise the pressure sur-rounding the heart to the point where cardiac filling is altered.Ultimately, compression of the heart by a pressurized peri-cardial effusion results in markedly elevated venous pressuresand impaired cardiac output producing shock; if untreated, itcan be rapidly fatal.33

Under normal conditions, the space between the parietaland visceral pericardium can accommodate only a smallamount of fluid before the development of tamponade phys-iology. It is not surprising, therefore, that cardiac perforationquickly results in tamponade. With a gradually accumulatingeffusion, however, as is often the case in malignancy, verylarge effusions can be accommodated without tamponade(Figure 1). The key concept is that once the total intraperi-

cardial volume has caused the pericardium to reach thenoncompliant region of its pressure-volume relation, tampon-ade rapidly develops.

Because of its lower pressures, the right heart is mostvulnerable to compression by a pericardial effusion, andabnormal right heart filling is the earliest sign of a hemody-namically significant pericardial effusion. Under these con-ditions, adequate filling of the right heart requires a compen-satory increase in systemic venous pressure, which resultsfrom venoconstriction and fluid retention. Of note, whencardiac tamponade results from hemorrhage into the pericar-dium, there can be rapid circulatory collapse because not onlydoes pericardial pressure rapidly rise but intravascular vol-ume falls, preventing a compensatory increase in venouspressure.

The increased pericardial pressure in cardiac tamponadeaccentuates the interdependence of the cardiac chambers asthe total cardiac volume is limited by the pericardial effu-sion.33–36 The volume in any cardiac chamber can onlyincrease when there is an equal decrease in the volume inother chambers. Thus, venous return and atrial filling pre-dominantly occur during ventricular systole as the ejection ofblood out of the right and left ventricles lowers cardiacvolume and allows blood to enter the atria. Moreover, thenormal effects of respiration are accentuated such that venousreturn and right-sided filling occur during inspiration asintrathoracic pressures fall, providing a pressure gradientfrom the systemic veins to the right atrium. Because the totalintrapericardial volume is fixed by the pressurized effusion,this increased inspiratory right ventricular filling crowds theleft ventricle and impairs its filling. Thus, in tamponade, leftheart filling occurs preferentially during expiration whenthere is less filling of the right heart. The small normalrespiratory variation in left ventricular stroke volume andsystolic arterial pressure is markedly accentuated in cardiactamponade, resulting in the clinical finding of “paradoxicalpulse” (see below).

Clinical PresentationCardiac tamponade is a treatable cause of cardiogenic shockthat can be rapidly fatal if unrecognized. As such, cardiactamponade should be considered in the differential diagnosisof any patients with shock or pulseless electric activity.1

Patients with impending or early tamponade are usuallyanxious and may complain of dyspnea and chest pain.33 Theincreased venous pressure is usually apparent as jugularvenous distension. The X descent (during ventricular systole)is typically the dominant jugular venous wave with little or noY descent. In rapidly developing cardiac tamponade, espe-cially hemorrhagic cardiac tamponade, there may not havebeen time for compensatory increase in venous pressure, andthe jugular veins may not be distended. Such “low-pressure”tamponade may also occur in patients with uremic pericardi-tis who have been volume depleted.37 The heart sounds areclassically soft or muffled, especially if there is a largepericardial effusion.

The hallmark of cardiac tamponade is a paradoxical pulse.This is defined as a �10-mm Hg drop in systolic arterialpressure during inspiration.1 When severe, the paradoxical




pulse can be apparent as an absence of a palpable brachial orradial pulse during inspiration. A paradoxical pulse can alsooccur when there are wide swings in intrathoracic pressureand in other conditions such as pulmonary embolism andhypovolemic shock. It is important to recognize that theparadoxical pulse may be difficult to recognize in the pres-ence of severe shock and may be absent in cardiac tamponadeif there is coexisting aortic insufficiency, atrial septal defect,or preexisting elevated left ventricular end-diastolic pressuredue to left ventricular hypertrophy or dilatation.33,38

EchocardiographyEchocardiography is an important part of the evaluation inpatients with cardiac tamponade and should be performedwithout delay in any patient who is suspected of having thiscondition.39 Echocardiography visualizes pericardial effu-sions as an echo-free space around the heart (Figure 3).Patients with acute hemorrhagic effusions may have pericar-dial thrombus apparent as an echo-dense mass.40 Smallpericardial effusions are only seen posteriorly. Pericardialeffusions large enough to produce cardiac tamponade arealmost always circumferential (both anteriorly andposteriorly).2

Echocardiography can also provide information on thesignificance of the pericardial effusion.41 In the presence ofcardiac tamponade, there is diastolic collapse of the free wallsof the right atrium and/or right ventricle.42,43 This is due tocompression of these relatively low-pressure structures by the

higher-pressure pericardial effusion. The collapse is exagger-ated during expiration when right heart filling is reduced.Right atrial collapse is more sensitive for tamponade, butright ventricular collapse lasting more than one third ofdiastole is a more specific finding for cardiac tamponade. Ofnote, right ventricular collapse may also be present with largepleural effusions in the absence of pericardial effusion orcardiac tamponade.44

There are other echo-Doppler findings that are indicativeof the hemodynamic consequence of cardiac tamponade.41,45

Distention of the inferior vena cavae that does not diminishwith inspiration is a manifestation of the elevated venouspressure in tamponade,46 whereas venous flow predominantlyoccurs in systole, not diastole, because of the limited cardiacvolume.47 In addition, there can be marked reciprocal respi-ratory variation in mitral and tricuspid flow velocities reflect-ing the enhanced ventricular interdependence that is themechanism of the paradoxical pulse (Figure 3).48 Collapse ofright-sided chambers is a sensitive indicator of tamponade,but abnormalities of cardiac filling are a more specificfinding.47

Thus, echocardiography demonstrates the presence andsize of the pericardial effusion and reflects its hemodynamicconsequences. Right atrial and ventricular collapse indicatescardiac compression, whereas enhanced respiratory variationof ventricular filling is a manifestation of increased ventric-ular interdependence. Although echocardiography providesimportant information, it must be emphasized that cardiactamponade is ultimately a clinical diagnosis (see below).47

TreatmentThe treatment of cardiac tamponade is drainage of thepericardial effusion. Medical management is usually ineffec-tive and should be used only while arrangements are made forpericardial drainage. Fluid resuscitation may be of transientbenefit if the patient is volume depleted (hypovolemic cardiactamponade). The use of inotropic agents is usually ineffectivebecause there is already intense endogenous adrenergic stim-ulation. The initiation of mechanical ventilation in a patientwith tamponade may produce a sudden drop in blood pressurebecause the positive intrathoracic pressure will contribute toa further impairment of cardiac filling.39

In the absence of clinical evidence of tamponade, echocar-diographic findings of right-sided diastolic collapse do notmandate emergency pericardiocentesis. For example, we donot recommend emergency pericardial drainage in a patientwho has a nontraumatic pericardial effusion with right-sidedcollapse if there is an adequate stable blood pressure(�110 mm Hg systolic) without a paradoxical pulse (ie,�10 mm respiratory variation in systolic pressure). However,the patient must be observed carefully because the develop-ment of only a small additional amount of pericardial fluidcan result in tamponade. In some patients, the echocardio-graphic signs of cardiac compression will resolve within afew days, and pericardiocentesis can be avoided if there is noother indication.

Traditionally, nonemergent pericardiocentesis has beenperformed in the cardiac catheterization laboratory underfluoroscopic guidance with invasive hemodynamic monitor-

Figure 3. A, Two-dimensional echocardiogram in 4-chamberview from a patient with cardiac tamponade. There is a largepericardial effusion apparent as an echo-free space around theheart. In diastole, there is collapse of the right atrium (arrow). B,Doppler measurement of mitral valve and tricuspid flow veloci-ties in a patient with cardiac tamponade. There is marked recip-rocal respiratory variation: during inspiration, mitral valve flowvelocity decreases, and tricuspid valve flow velocity increases.




ing.1 Performing pericardiocentesis in this setting providesthe option of utilizing right heart catheterization before andafter the procedure to confirm the diagnosis, if necessary, andto detect effusive-constrictive pericardial disease (see below).More recently, echocardiographic-guided pericardiocentesishas been demonstrated to be a safe and effective procedurethat can be performed at the bedside.49 During this procedurethe ideal entry site (minimal distance from skin to pericardialfluid without intervening structures) can be defined. Contin-ued drainage of the pericardial fluid through an indwellingcatheter minimizes the risk of reoccurrence of the effusion. Ifpericardial tissue is required for diagnosis or in the case ofpurulent pericarditis or recurrent effusions, surgical drainagemay be the preferred treatment. Surgery is also the treatmentfor traumatic hemopericardium.1

Surgical drainage of a pericardial effusion is usuallyperformed through a limited subxiphoid incision. This allowsdirect visualization and biopsy of the pericardium. Thediagnosis accuracy can be improved by inserting a pericar-dioscope.50 This provides direct visualization of a muchlarger area of the pericardium and the ability to obtainmultiple biopsies. Recently, a flexible pericardioscope hasbeen developed that can be inserted percutaneously.51

Malignant pericardial effusions frequently reoccur. Suchrecurrent pericardial effusions may necessitate the surgicalcreation of a pericardial window that allows the effusion todrain into the pleural space, preventing reoccurrence ofcardiac tamponade. An attractive alternative in these patients,especially if their overall prognosis is poor from the malig-nancy, is the percutaneous creation of a pericardial windowby balloon dilation.52,53

Pericardial Effusion Without TamponadeAcute pericarditis is often accompanied by a small pericardialeffusion that does not produce tamponade.20 If there is nohemodynamic compromise and the diagnosis can be estab-lished by other means, pericardiocentesis may not be neces-

sary.1,23,54 If it accumulates slowly, a large pericardial effu-sion of a liter or more can be present without cardiactamponade. However, nearly 30% of a series of 28 patientswith large idiopathic pericardial effusions developed cardiactamponade unexpectedly.55 In this series, pericardiocentesiswith catheter drainage alone resulted in resolution of theeffusion without reoccurrence in about half of the patients.Thus, pericardiocentesis may be advisable in patients withvery large pericardial effusions (�20 mm on echocardiogra-phy), even in the absence of tamponade. In contrast, Merce etal47 demonstrated that none of 45 patients with large pericar-dial effusions managed without pericardial drainage subse-quently developed tamponade. It must be recognized thatpericardiocentesis will not yield a diagnosis in most patients,and therefore the reason for draining large effusions is toavoid potential progression to tamponade.47 We believe thatthe risk of progression to tamponade is greatest in patientswith the recent development of large effusions or who haveevidence of diastolic right-sided collapse. Some experts haverecommended routine drainage of pericardial effusions thatpersist for �3 months.54 We do not believe that this isnecessary. A potential algorithm for the management ofpericardial effusions is shown in Figure 4.

Pericardial ConstrictionPathophysiologyPericardial constriction occurs when a scarred, thickened, andfrequently calcified pericardium impairs cardiac filling, lim-iting the total cardiac volume.1,36,56 The pathophysiologicalhallmark of pericardial constriction is equalization of theend-diastolic pressures in all 4 cardiac chambers. This occursbecause the filling is determined by the limited pericardialvolume, not the compliance of the chambers themselves.

Initial ventricular filling occurs rapidly in early diastole asblood moves from the atria to the ventricles without muchchange in the total cardiac volume. However, once the

Figure 4. Potential algorithm for manag-ing patients with a moderate to largepericardial effusion. See the text for adiscussion of methods to drain the peri-cardial effusion. Adapted and redrawnwith permission from Hoit.54 Copyright2002, American Heart Association.




pericardial constraining volume is reached, diastolic fillingstops abruptly. This results in the characteristic dip andplateau of ventricular diastolic pressures. The stiff pericar-dium also isolates the cardiac chambers from respiratorychanges in intrathoracic pressures, resulting in Kussmaul’ssign (see below).

EtiologyPericardial constriction is usually the result of long-standingpericardial inflammation leading to pericardial scarring withthickening, fibrosis, and calcification.56 The most frequentcauses are mediastinal radiation, chronic idiopathic pericar-ditis, after cardiac surgery, and tuberculous pericarditis.1,57–59

Clinical ManifestationsPatients with pericardial constriction typically present withmanifestations of elevated systemic venous pressures and lowcardiac output.58 Because there is equalization of all cardiacpressures (including right and left atrial pressures), systemiccongestion is much more marked than pulmonary congestion.Typically, there will be marked jugular venous distension,hepatic congestion, ascites, and peripheral edema, while thelungs remain clear. The limited cardiac output typicallypresents as exercise intolerance and may progress to cardiaccachexia with muscle wasting. In long-standing pericardialconstriction, pleural effusions, ascites, and hepatic dysfunc-tion may be prominent clinical features.1 Patients with peri-cardial constriction are much more likely to have left-sided orbilateral pleural effusions than solely right-sided effusions.60

The jugular veins are distended with prominent X and Ydescents. The normal inspiratory drop in jugular venousdistention may be replaced by a rise in venous pressure(Kussmaul’s sign). This sign may also be present with severeright heart failure, especially in association with tricuspidregurgitation. The classic auscultatory finding of pericardialconstriction is a pericardial knock. This occurs as a high-pitched sound early in diastole when there is the suddencessation of rapid ventricular diastolic filling.61 When accu-rately recognized, a pericardial knock is a specific butinsensitive indicator of pericardial constriction.

Pericardial calcification seen on the lateral plane chestx-ray is suggestive of pericardial constriction.62 Similarly,most patients with pericardial constriction have a thickenedpericardium (�2 mm) that can be imaged by echocardiogra-phy, CT, and MRI (Figure 5).1,56,63 It is important to recog-nize, however, that pericardial constriction can be presentwithout pericardial calcium and, in some cases, even withoutpericardial thickening. For example, in a series of 143patients from the Mayo Clinic with surgically proven peri-cardial constriction, 26 (18%) had a normal pericardialthickness (�2 mm).64 Finally, the pericardial constrictionmay be predominantly localized to one region of the heart.

Tagged cine MRI has been reported to be able to demon-strate adhesion of the pericardium to the myocardium inpericardial constriction.65 This is recognized by persistentconcordance of tagged signals between the pericardium andmyocardium throughout the cardiac cycle.

Doppler echocardiography is important in the evaluation ofpatients with suspected pericardial constriction. The echocar-

diogram may demonstrate pericardial thickening and calcifi-cation. However, increased pericardial thickness can bemissed on a transthoracic echocardiogram. Transesophagealechocardiography is more sensitive and accurate in determin-ing pericardial thickness.66 Transesophageal echocardiogra-phy can also assess pulmonary venous flow.

Doppler echocardiography frequently demonstrates re-stricted filling of both ventricles with a rapid deceleration ofthe early diastolic mitral inflow velocity (E wave) and smallor absent A wave. In addition, there is substantial (�25%)respiratory variation of the mitral inflow velocity (Figure 6).67

Wide swings in the E wave velocity may also occur inpatients with respiratory disease, but these are associated withmarked respiratory variation in the superior vena caval flowvelocity (typically �20 cm/s), whereas the variation withpericardial constriction is less.46,68 Other findings in constric-tive pericarditis include preserved diastolic mitral annularvelocity, rapid diastolic flow propagation to the apex, anddiastolic mitral regurgitation.69

Differential DiagnosisPericardial constriction should be considered in any patientwith unexplained systemic venous congestion. Echocardiog-raphy is useful in differentiating pericardial constriction fromright heart failure due to tricuspid valve disease and/orassociated pulmonary hypertension.

The most difficult differentiation is between pericardialconstriction and restrictive cardiomyopathy (Table 3). Clini-cal manifestations of restrictive cardiomyopathy most typi-cally due to cardiac amyloid may be very similar to those dueto pericardial constriction.70,71 Doppler echocardiography isthe most useful method to distinguish constriction fromrestriction. Patients with pericardial constriction have markedrespiratory variation (�25%) of mitral inflow, whereas this is

Figure 5. Chest CT from a patient with pericardial constrictionshowing thickened pericardium (arrows) and a left pleural effu-sion. Reproduced with permission from Circulation.2005:111:e364. Copyright 2005, American Heart Association.




not present in restrictive cardiomyopathies.67 In some cases ofpericardial constriction with markedly elevated venous pres-sures, the respiratory variation may only be present afterhead-up tilt.72 The tissue Doppler measurement of mitralannular velocities is useful in distinguishing constriction from

restriction. The early diastolic mitral annular velocity (Ea) isalmost always reduced in patients with myocardial restriction,whereas it remains normal in patients with pericardial con-striction.69,73,74 The optimal discrimination occurs with an Eavelocity of 8 cm/s. Similarly, rapid propagation of earlydiastolic flow to the apex is preserved in constriction andreduced in restriction. A slope �100 cm/s of the first aliasingcontour in the color M-mode best distinguishes the 2.69

It has recently been reported that patients with pericardialconstriction have only minimally elevated B-type natriureticpeptide (�200 pg/mL), whereas the B-type natriuretic pep-tide levels are typically markedly increased in patients withrestrictive cardiomyopathy (�600 pg/mL).75

Traditionally, constriction and restriction were differenti-ated at cardiac catheterization by hemodynamic criteria. Inconstriction, there is usually almost exact equalization of latediastolic pressures in both the right and left heart. Withrestriction, typically left ventricular end-diastolic pressureexceeds right ventricular pressure by at least a few mm Hg.Pulmonary hypertension is frequently seen with restrictionbut is not typically present with constriction. Thus, rightventricular diastolic pressure should be more than one third ofthe right ventricular systolic pressure in pericardialconstriction.

It should be recognized that the aforementioned classichemodynamic criteria have limited specificity (24% to 57%)in distinguishing pericardial constriction from cardiomyopa-thies.76 In contrast, dynamic respiratory variations indicatingincreased ventricular interdependence are superior. In con-striction during inspiration, right ventricular systolic pres-sures increase, while left ventricular systolic pressure de-creases. The inverse occurs during expiration. This finding

Figure 6. Doppler mitral flow and superior vena caval velocity ina patient with pericardial constriction. There is marked (�25%)respiratory variation in the peak early diastolic initial flow veloc-ity E (decreased during inspiration [ins] and increased duringexpiration [exp]). In contrast, there is less respiratory variation ofthe flow velocity in the vena cava. S indicates systole; D, diasto-le. Reproduced with permission from Boonyaratavej et al.68

Copyright 1998, American College of Cardiology Foundation.

TABLE 3. Differentiation of Pericardial Constriction From Restrictive Cardiomyopathy

Pericardial Constriction Restrictive Cardiomyopathy

Physical examination

Pulmonary congestion Usually absent Usually present

Jugular venous pulse Prominent Y descent

Early diastolic sound Pericardial knock S3 (low pitched)

Pericardial thickness �2 mm (but �2 mm in 15%) �2 mm

Echo/Doppler findings

LV myocardium Normal “Sparkling” myocardium in amyloid

Atrial size �/� Atrial enlargement Atrial enlargement

Mitral valve flow pattern Restricted Restricted

Respiratory variation in E wave �25% �20%

Mitral annular diastolic velocity �8 cm/s �8 cm/s

Biomarker

B-type natriuretic peptide �200 pg/mL �600 pg/mL

Hemodynamics

Y descent Prominent Variable

PA systolic pressure �50 mm Hg �60 mm Hg

PCW-RA pressure 0 5 mm Hg

Reciprocal respiratory variationin right ventricular/left ventricular peaksystolic pressure

Present Absent

PA indicates pulmonary arterial; PCW, pulmonary capillary wedge; and RA, right atrial.




had �90% sensitivity and specificity in recognizing constric-tive pericarditis versus restriction in a series of 36 patientsfrom the Mayo Clinic.76

Endomyocardial biopsy performed during catheterizationcan also be utilized in selected cases to distinguish myocar-dial disease from pericardial constriction.77

Bush et al78 first observed that, in some patients, thehemodynamic findings of constriction may only be presentafter rapid volume loading and labeled this syndrome occultconstrictive pericarditis. Some patients with this syndromemay improve after removal of the pericardium. The sensitiv-ity and specificity of the response to volume loading and therole of pericardiectomy in treating this condition are not wellestablished.79 Thus, we do not recommend volume loading aspart of the routine hemodynamic evaluation of patients withsuspected pericardial constriction.

TreatmentIn some patients with relatively acute onset pericardialconstriction, the symptoms and constrictive features mayresolve with medical therapy alone.80 For example, Haley etal81 reported a series of 36 patients with pericardial constric-tion that resolved with treatment with the use of antiinflam-matory agents, colchicine, and/or steroids.

In more chronic pericardial constriction, definitive treat-ment is surgical pericardial decortication, widely resectingboth the visceral and parietal pericardium.1 This operation isa major undertaking with substantial risk (�6% mortalityeven in the most experienced centers).57,58 In some patients, itdoes not immediately restore normal cardiac function, whichmay require some time after removal of the constrictingpericardium to return to normal. The largest surgical seriesfrom the Mayo Clinic and the Cleveland Clinic indicate thatpatients with constriction due to idiopathic or viral pericar-ditis do best and patients with radiation-induced constrictionfare most poorly after surgery.57,58

Effusive Constrictive PericarditisHancock82 first recognized that some patients presenting withcardiac tamponade did not have resolution of their elevatedright atrial pressure after removal of the pericardial fluid. Inthese patients, pericardiocentesis converted the hemodynam-ics from those typical of tamponade to those of constriction(Figure 7). Thus, the restriction of cardiac filling was not onlydue to the pericardial effusion but also resulted from pericar-dial constriction (predominantly the visceral pericardium).

Sagristá-Sauleda et al79 recently reported a consecutiveseries of �1000 patients with pericarditis, 218 of whom hadcardiac tamponade and underwent pericardiocentesis. In 15 ofthese patients, the right atrial and right ventricular diastolicpressures remained elevated with a dip and plateau morphol-ogy after the pericardiocentesis, and thus they were consid-ered to have effusive constrictive pericarditis. The mostcommon cause was idiopathic pericarditis as well as malig-nancies and after radiation. One patient had tuberculouspericarditis. Three of the patients with idiopathic effusiveconstrictive pericarditis had subsequent resolution of theirsymptoms. Others required pericardiectomy, including re-moval of the visceral pericardium. Effusive constrictive

pericarditis most likely represents an intermediate transitionfrom acute pericarditis with pericardial effusion to pericardialconstriction.83

SummaryAcute pericarditis typically is a self-limited disease, usuallyidiopathic or of viral origin, that responds to treatment withNSAIDs. The recent COPE Trial indicates a better outcome ifall patients receive a 3-month course of colchicine. The use ofsteroids to treat acute pericarditis should be avoided because

Figure 7. Effusive pericardial constriction. A, The presence ofpericardial fluid causes tamponade, and a thickened visceralpericardium (epicardium) causes constriction. Pressure tracings(B) show marked and equal elevations of the pericardial andright atrial pressures typical of cardiac tamponade before theremoval of fluid. After fluid removal, the pericardial pressure isnormal (increasing and decreasing with respiration), but the rightatrial pressure remains elevated, indicating the presence of peri-cardial constriction. Reproduced with permission from Han-cock.83 Copyright 2004, Massachusetts Medical Society.




they increase the risk of recurrence. Cardiac tamponade is alife-threatening condition caused by a pressurized pericardialeffusion. Doppler echocardiography plays a key role in itsrecognition, and echocardiogram-guided pericardiocentesishas become the treatment of choice in most instances.Pericardial constriction is a potentially treatable cause ofchronic heart failure that must be distinguished from restric-tive cardiomyopathy. This can be accomplished with acombination of Doppler echocardiography, Doppler tissueimaging, MRI, and cardiac catheterization. In effusive con-strictive pericarditis, the cardiac compression is due to both apressurized pericardial effusion and pericardial restriction.Pericardiocentesis converts the hemodynamics from tampon-ade to constriction.

AcknowledgmentsWe gratefully acknowledge the assistance of Amanda Burnette in thepreparation of this manuscript.

DisclosuresNone.

References1. Maisch B, Seferovic PM, Ristic AD, Erbel R, Rienmuller R, Adler Y,

Tomkowski WZ, Thiene G, Yacoub MH, for the Task Force on theDiagnosis and Management of Pericardial Diseases of the EuropeanSociety of Cardiology. Guidelines on the diagnosis and management ofpericardial diseases: executive summary. Eur Heart J. 2004;25:587–610.

2. LeWinter MM, Kabbani S. Pericardial diseases. In: Zipes DP, Libby P,Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease. 7th ed.Philadelphia, Pa: Elsevier Saunders; 2005:1757–1780.

3. Spodick DH. Macrophysiology, microphysiology, and anatomy of thepericardium: a synopsis. Am Heart J. 1992;124:1046–1051.

4. Miyazaki T, Pride HP, Zipes DP. Prostaglandins in the pericardial fluidmodulate neural regulation of cardiac electrophysiological properties.Circ Res. 1990;66:163–175.

5. Applegate RJ, Johnston WE, Vinten-Johansen J, Klopfenstein HS, LittleWC. Restraining effect of intact pericardium during acute volumeleading. Am J Physiol. 1992;262:H1725–H1733.

6. Freeman GL, LeWinter MM. Pericardial adaptations during chroniccardiac dilation in dogs. Circ Res. 1984;54:294–300.

7. Freeman GL, LeWinter MM. Determinants of the intrapericardialpressure in dogs. J Appl Physiol. 1986;60:758–764.

8. Freeman GL, Little WC. Comparison of in situ and in vitro studies ofpericardial pressure-volume relation in the dog. Am J Physiol. 1986;251:H421–H427.

9. Kansal S, Roitman D, Sheffield LT. Two-dimensional echocardiographyof congenital absence of pericardium. Am Heart J. 1985;109:912–915.

10. Lange RA, Hillis D. Acute pericarditis. N Engl J Med. 2004;351:2195–2202.

11. Troughton RW, Asher CR, Klein AL. Pericarditis. Lancet. 2004;363:717–727.

12. Spodick DH. Acute pericarditis: current concepts and practice. JAMA.2003;289:1150–1153.

13. Zayas R, Anguita M, Torres F, Gimenez D, Bergillos F, Ruiz M, CiudadM, Gallardo A, Valles F. Incidence of specific etiology and role ofmethods for specific etiologic diagnosis of primary acute pericarditis.Am J Cardiol. 1995;75:378–382.

14. Fowler NO. Tuberculous pericarditis. JAMA. 1991;266:99–103.15. Gunukula SR, Spodick DH. Pericardial disease in renal patients. Semin

Nephrol. 2001;21:52–56.16. Mandell BF. Cardiovascular involvement in systemic lupus erythemato-

sus. Semin Arthritis Rheum. 1987;17:126–141.17. Park JH, Choo SJ, Park SW. Acute pericarditis caused by acrylic bone

cement after percutaneous vertebroplasty. Circulation. 2005;111:e98.18. Jerjes-Sanchez C, Ramirez-Rivera A, Ibarra-Perez C. The Dressler

syndrome after pulmonary embolism. Am J Cardiol. 1996;78:343–345.19. Correale E, Maggioni AP, Romano S, Ricciardiello V, Battista R,

Salvarola G, Santoro E, Tognoni G, on behalf of the Gruppo Italiano per

lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI). Com-parison of frequency, diagnostic and prognostic significance of peri-cardial involvement in acute myocardial infarction treated with andwithout thrombolytics. Am J Cardiol. 1993;71:1377–1381.

20. Imazio M, Demichellis B, Parrini I, Gluggia M, Cecchi E, Gaschino G,Demarie D, Ghislo A, Trinchero R. Day-hospital treatment of acutepericarditis: a management program for outpatient therapy. J Am CollCardiol. 2004;43:1042–1046.

21. Bonnefoy E, Gordon P, Kirkorian G, Fatemi M, Chevalier P, Touboul P.Serum cardiac troponin I and ST-segment elevation in patients with acutepericarditis. Eur Heart J. 2000;21:832–836.

22. Imazio M, Demichellis B, Cecchi E, Belli R, Ghisio A, Bobbio M,Trinchero R. Cardiac troponin I in acute pericarditis. J Am Coll Cardiol.2003;42:2144–2148.

23. Permanyer-Miralda G. Acute pericardial disease: approach to theaetiologic diagnosis. Heart. 2004;90:252–254.

24. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acutepericardial disease: a prospective series of 231 consecutive patients.Am J Cardiol. 1985;56:623–630.

25. Arunasalam S, Siegel RJ. Rapid resolution of symptomatic acute peri-carditis with ketorolac tromethamine: a parenteral nonsteroidal antiin-flammatory agent. Am Heart J. 1993;125(pt 1):1455–1458.

26. Adler Y, Finkelstein Y, Guindo J, de la Serna R, Shoenfeld Y,Bayes-Genis A, Sagie A, Bayes de Luna A, Spodick DH. Colchicinetreatment for recurrent pericarditis: a decade of experience. Circulation.1998;97:2183–2185.

27. Imazio M, Bobbio M, Cecchi E, Demarie D, Demichellis B, Pomari F,Moratti M, Gaschino G, Giammaria M, Ghiso A, Belli R, Trinchero R.Colchicine in addition to conventional therapy for acute pericarditis:results of the COlchicine for acute PEricarditis (COPE) Trial. Circu-lation. 2005;112:2012–2016.

28. Shabetai R. Recurrent pericarditis: recent advances and remainingquestions. Circulation. 2005;112:1921–1923.

29. Spodick DH. Intrapericardial treatment of persistent autoreactive pericar-ditis/myopericarditis and pericardial effusion. Eur Heart J. 2002;23:1481–1482.

30. Artom G, Koren-Morag N, Spodick DH, Brucato A, Guindo J, Bayes-de-Luna A, Brambilla G, Finkelstein Y, Granel B, Bayes-Genis A,Schwammenthal E, Adler Y. Pretreatment with corticosteroids attenuatesthe efficacy of colchicine in preventing recurrent pericarditis: a multi-centre all-case analysis. Eur Heart J. 2005;26:723–727.

31. Maisch B. Recurrent pericarditis: mysterious or not so mysterious? EurHeart J. 2005;26:631–633.

32. Maisch B, Ristic D, Pankuweit S. Intrapericardial treatment of autore-active pericardial effusion with triamcinolone. Eur Heart J. 2002;23:1503–1508.

33. Spodick DH. Acute cardiac tamponade. N Engl J Med. 2003;349:684–690.

34. Reddy PS, Curtiss EI, O’Toole JD, Shaver JA. Cardiac tamponade:hemodynamic observations in man. Circulation. 1978;58:265–272.

35. Reddy PS, Curtiss EI, Uretsky BF. Spectrum of hemodynamic changes incardiac tamponade. Am J Cardiol. 1990;66:1487–1491.

36. Shabetai R, Fowler NO, Guntheroth WG. The hemodynamics of cardiactamponade and constrictive pericarditis. Am J Cardiol. 1970;26:480–489.

37. Shabetai R. Pericardial effusion: haemodynamic spectrum. Heart. 2004;90:255–256.

38. Hoit BD, Gabel M, Fowler NO. Cardiac tamponade in left ventriculardysfunction. Circulation. 1990;82:1370–1376.

39. Tsang TS, Barnes ME, Hayes SN, Freeman WK, Dearani JA, Butler SL,Seward JB. Clinical and echocardiographic characteristics of significantpericardial effusions following cardiothoracic surgery and outcomes ofecho-guided pericardiocentesis for management: Mayo Clinic experience,1979–1998. Chest. 1999;116:322–331.

40. Knopf WD, Talley JD, Murphy DA. An echo-dense mass in the peri-cardial space as a sign of left ventricular free wall rupture during acutemyocardial infarction. Am J Cardiol. 1987;59:1202.

41. Tsang TS, Oh JK, Seward JB, Tajik AJ. Diagnostic value of echocardi-ography in cardiac tamponade. Herz. 2000;25:734–740.

42. Singh S, Wann S, Schuchard GH, Klopfenstein HS, Leimgruber PP,Keelan MH, Brooks HL. Right ventricular and right atrial collapse inpatients with cardiac tamponade: a combined echocardiographic andhemodynamic study. Circulation. 1984;70:966–971.

43. Klopfenstein HS, Schuchard GH, Wann LS, Palmer TE, Hartz AJ, GrossCM, Singh S, Brooks HL. The relative merits of pulsus paradoxus and




right ventricular diastolic collapse in the early detection of cardiac tam-ponade: an experimental echocardiographic study. Circulation. 1985;71:829–833.

44. Vaska K, Wann LS, Sagar K, Klopfenstein HS. Pleural effusion as acause of right ventricular diastolic collapse. Circulation. 1992;86:609–617.

45. Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ,Davis JL, Douglas PS, Faxon DP, Gillam LD, Kimball TR, KussmaulWG, Pearlman AS, Philbrick JT, Rakowski H, Thys DM, Antman EM,Smith SC Jr, Alpert JS, Gregoratos G, Russell RO, American College ofCardiology, American Heart Association, American Society of Echocar-diography. ACC/AHA/ASE 2003 guideline update for the clinical appli-cation of echocardiography: summary article: a report of the AmericaCollege of Cardiology/America Heart Association Task Force on PracticeGuidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelinesfor the Clinical Application of Echocardiography). Circulation. 2003;108:1146–1162.

46. Himelman RB, Kircher B, Rockey DC, Schiller NB. Inferior vena cavaplethora with blunted respiratory response: a sensitive echocardiographicsign of cardiac tamponade. J Am Coll Cardiol. 1988;12:1470–1477.

47. Merce J, Sagrista-Sauleda J, Permanyer-Miralda G, Evangelista A,Soler-Soler J. Correlation between clinical and Doppler echocardiograph-ic findings in patients with moderate and large pericardial effusion:implications for the diagnosis of cardiac tamponade. Am Heart J. 1999;138:759–764.

48. Appleton CP, Hatle LK, Popp RL. Cardiac tamponade and pericardialeffusion: respiratory variation in transvalvular flow velocities studied byDoppler echocardiography. J Am Coll Cardiol. 1988;11:1020–1030.

49. Tsang TS, Enriquez-Sarano M, Freeman WK, Barnes ME, Sinak LJ,Gersh BJ, Bailey KR, Seward JB. Consecutive 1127 therapeutic echo-cardiographically guided pericardiocenteses: clinical profile, practicepatterns, and outcomes spanning 21 years. Mayo Clin Proc. 2002;77:429–436.

50. Nugue O, Millaire A, Porte H, de Groote P, Guimer P, Wurtz A, DuclouxG. Pericardioscopy in the etiologic diagnosis of pericardial effusion in141 consecutive patients. Circulation. 1996;94:1635–1641.

51. Seferovic PM, Ristic AD, Maksimovic R, Tatic V, Ostojic M, Kanjuh V.Diagnostic value of pericardial biopsy: improvement with extensivesampling enabled by pericardioscopy. Circulation. 2003;107:978–983.

52. Ziskind AA, Pearce AC, Lemmon CC, Burstein S, Gimple LW, HermannHC, McKay R, Block PC, Waldman H, Palacios IF. Percutaneous balloonpericardiotomy for the treatment of cardiac tamponade and large peri-cardial effusions: description of technique and report of the first 50 cases.J Am Coll Cardiol. 1993;21:1–5.

53. Wang HJ, Hsu KL, Chiang FT, Tseng CD, Tseng YZ, Liau CS. Technicaland prognostic outcomes of double-balloon pericardiotomy for largemalignancy-related pericardial effusions. Chest. 2002;122:893–899.

54. Hoit BD. Management of effusive and constrictive pericardial heartdisease. Circulation. 2002;105:2939–2942.

55. Sagrista-Sauleda J, Angel J, Permanyer-Miralda G, Soler-Soler J.Long-term follow-up of idiopathic chronic pericardial effusion. N EnglJ Med. 1999;341:2054–2059.

56. Oh KY, Shimizu M, Edwards WD, Tazelaar HD, Danielson GK. Surgicalpathology of the parietal pericardium: a study of 344 cases (1993–1999).Cardiovasc Pathol. 2001;10:157–168.

57. Bertog SC, Thambidorai SK, Parakh K, Schoenhagen P, Ozduran V,Houghtaling PL, Lytle BW, Blackstone EH, Lauer MS, Klein AL. Con-strictive pericarditis: etiology and cause-specific survival after pericardi-ectomy. J Am Coll Cardiol. 2004;2004:1445–1452.

58. Ling LH, Oh JK, Schaff HV, Danielson GK, Mahoney DW, Seward JB,Tajik AJ. Constrictive pericarditis in the modern era: evolving clinicalspectrum and impact on outcome after pericardiectomy. Circulation.1999;100:1380–1386.

59. Ling LH, Oh JK, Breen JF, Schaff HV, Danielson GK, Mahoney DW,Seward JB, Tajik AJ. Calcific constrictive pericarditis: is it still with us?Ann Intern Med. 2000;132:444–450.

60. Weiss JM, Spodick DH. Association of left pleural effusion with peri-cardial disease. N Engl J Med. 1983;308:696–697.

61. Tyberg TI, Goodyer AV, Langou RA. Genesis of pericardial knock inconstrictive pericarditis. Am J Cardiol. 1980;46:570–575.

62. Cavendish JJ, Linz PE. Constrictive pericarditis from a severely calcifiedpericardium. Circulation. 2005;112:e137–e139.

63. Pohost GM, Hung L, Doyle M. Clinical use of cardiovascular magneticresonance. Circulation. 2003;108:647–653.

64. Talreja DR, Edwards WD, Danielson GK, Schaff HV, Tajik AJ, TazelaarHD, Breen JF, Oh JK. Constrictive pericarditis in 26 patients with his-tologically normal pericardial thickness. Circulation. 2003;108:1852–1857.

65. Kojima S, Yamada N, Goto Y. Diagnosis of constrictive pericarditis bytagged cine magnetic resonance imaging. N Engl J Med. 1999;341:373–374.

66. Ling LH, Oh JK, Tei C, Click RL, Breen JF, Seward JB, Tajik AJ.Pericardial thickness measured with transesophageal echocardiography:feasibility and potential clinical usefulness. J Am Coll Cardiol. 1997;29:1317–1323.

67. Oh JK, Hatle LK, Seward JB, Danielson GK, Schaff HV, Reeder GS,Tajik AJ. Diagnostic role of Doppler echocardiography in constrictivepericarditis. J Am Coll Cardiol. 1994;23:154–162.

68. Boonyaratavej S, Oh JK, Tajik AJ, Appleton CP, Seward JB. Comparisonof mitral inflow and superior vena cava Doppler velocities in chronicobstructive pulmonary disease and constrictive pericarditis. J Am CollCardiol. 1998;32:2043–2048.

69. Rajagopalan N, Garcia MJ, Rodriguez L, Murray RD, Apperson-HansenC, Stugaard M, Thomas JD, Klein AL. Comparison of new Dopplerechocardiographic methods to differentiate constrictive pericardial heartdisease and restrictive cardiomyopathy. Am J Cardiol. 2001;87:86–94.

70. Kushwaha SS, Fallon JR, Fuster V. Restrictive cardiomyopathy. N EnglJ Med. 1997;336:267–276.

71. Falk RH. Diagnosis and management of the cardiac amyloidoses. Circu-lation. 2005;112:2047–2060.

72. Oh JK, Tajik AJ, Appleton CP, Hatle LK, Nishimura RA, Seward JB.Preload reduction to unmask the characteristic Doppler features of con-strictive pericarditis: a new observation. Circulation. 1997;95:796–799.

73. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL.Differentiation of constrictive pericarditis from restrictive cardiomyopa-thy: assessment of left ventricular diastolic velocities in longitudinal axisby Doppler tissue imaging. J Am Coll Cardiol. 1996;27:108–114.

74. Ha JW, Ommen SR, Tajik AJ, Barnes ME, Ammash NM, Gertz MA,Seward JB, Oh JK. Differentiation of constrictive pericarditis fromrestrictive cardiomyopathy using mitral annular velocity by tissue Dopp-ler echocardiography. Am J Cardiol. 2004;94:316–319.

75. Leya FS, Arab D, Joyal D, Shioura KM, Lewis BE, Steen LH, Cho L. Theefficacy of brain natriuretic peptide levels in differentiating constrictivepericarditis from restrictive cardiomyopathy. J Am Coll Cardiol. 2005;45:1900–1902.

76. Hurrell DG, Nishimura RA, Higano ST, Appleton CP, Danielson GK,Holmes DR, Tajik AJ. Value of dynamic respiratory changes in left andright ventricular pressures for the diagnosis of constrictive pericarditis.Circulation. 1996;93:2007–2013.

77. Schoenfeld MH, Supple EW, Dec GW, Fallon JT, Palacios IF. Restrictivecardiomyopathy versus constrictive pericarditis: role of endomyocardialbiopsy in avoiding unnecessary thoracotomy. Circulation. 1987;75:1012–1017.

78. Bush CA, Stang JM, Wooley CF, Kilman JW. Occult constrictive peri-cardial disease. Circulation. 1977;56:924–930.

79. Sagristá-Sauleda J, Angel J, Sanchez A, Permanyer-Miralda G,Soler-Soler J. Effusive-constrictive pericarditis. N Engl J Med. 2004;350:469–475.

80. Tom CW, Oh JK. Images in cardiovascular medicine: a case of transientconstrictive pericarditis. Circulation. 2005;111:e364.

81. Haley JH, Tajik J, Danielson GK, Schaff HV, Mulvagh SL, Oh JK.Transient constrictive pericarditis: causes and natural history. J Am CollCardiol. 2004;43:271–275.

82. Hancock EW. Subacute effusive-constrictive pericarditis. Circulation.1971;43:183–192.

83. Hancock EW. A clearer view of effusive-constrictive pericarditis. N EnglJ Med. 2004;350:435–437.

KEY WORDS: cardiac tamponade � pericarditis � pericardium




In the Contemporary Review article “Pericardial Disease,” by Little and Freeman (Circulation.2006;113:1622-1632), the dose of colchicine in paragraph 3 on page 1625 is incorrectly stated as“colchicine (2 g followed by 1 g/d).” It should say “colchicine (2 mg followed by 1 mg/d).” Thedose of colchicine on page 1623 is correct.

This correction has been made to the current online version of the article, available athttp://circ.ahajournals.org/cgi/content/full/113/12/1622. The authors regret the error.

DOI: 10.1161/CIRCULATIONAHA.107.182028

(Circulation. 2007;115:e406.)© 2007 American Heart Association, Inc.

Circulation is available at http://www.circulationaha.org

e406

Correction



http://infection.thelancet.com Vol 8 April 2008 225

Review

Prophylaxis of infective endocarditis: current tendencies, continuing controversiesXavier Duval, Catherine Leport

Infective endocarditis is a severe disease with high mortality, and results most often from the combination of bacteraemia (sometimes provoked) and a predisposing cardiac condition. Prophylaxis for infective endocarditis has been recommended by diff erent countries on the basis of the supposed pathophysiology of the disease, although no randomised clinical trial has confi rmed its effi cacy. We review the data presented over the past few decades, challenge the principles underlying prophylaxis recommendations, and analyse the arguments that explain the general tendency in very recent years to decrease prophylaxis indications. Such arguments include the probable important role of everyday-life bacteraemia in the occurrence of infective endocarditis, the estimated huge number of prophylaxis doses to be given to avoid a single case of infective endocarditis, and the lack of scientifi c evidence to identify those procedures that should lead to prophylaxis. Recommendations for prophylaxis are now essentially focused on patients with high-risk predisposing cardiac conditions before dental procedures.

IntroductionInfective endocarditis is a rare but severe disease, with 100% mortality in the pre-antibiotic area. Its incidence seems to have been stable over the past few decades and has a range of 25–50 cases per million inhabitants per year.1,2 The epidemiology of infective endocarditis is complex to assess because diagnosis is diffi cult and referral bias has a large impact on the clinical characteristics of the population studied in diff erent clinical settings. However, the profi le of patients presenting with infective endocarditis seems to have changed during the past few decades, with an increased proportion of elderly patients, a decrease in patients with rheumatic heart disease, and a decrease in infective endocarditis caused by oral streptococci, although this latter point is the subject of controversy.1–3 Valve surgery for infective endocarditis is done in about one patient in two, with a perioperative mortality that remains high. Overall, in-hospital mortality is around 20%. Since 1954, prophylaxis of infective endocarditis has been recommended by diff erent countries based on the supposed pathophysiology of the disease. Over time, various arguments have arisen to support a trend towards a reduction in prophylaxis and how this should be achieved in practice. The aim of our Review is to summarise recent data that support such a reduction, and to outline the current general principles of infective endocarditis prophylaxis. This Review will concentrate mainly on infective endocarditis prophylaxis for dental procedures, the most widely studied situation in which antibiotic prophylaxis is used.

Data supporting the current prophylaxis recommendationsThe link between dental hygiene and infective endocarditis was made in 1909 by Horder,4 who observed that, “infection is grafted upon a previously sclerosed endocardium…the source of infecting agent, in most of the cases, is the mouth”. In 1935, Okell and Elliott5 reported the occurrence of bacteraemia after tooth

extraction in 84 (61%) of 138 patients. Infective endocarditis is a condition that lends itself well to strategies that aim to prevent the development of bacteria on the endocardium of patients with a previously identifi ed predisposing cardiac condition (PCC; panel). A preventive strategy targeting such patients is based not only on the screening and treatment of potential points of entry, but also on antibiotic prophylaxis given before invasive procedures that could potentially induce bacteraemia. Although its effi cacy has not been shown in human beings, antibiotic prophylaxis of infective endocarditis has been recommended since 1954 for patients with PCC.7,8 The recommendations for prophylaxis are based in part on the results of animal studies that showed the eff ectiveness of antibiotics in preventing the development of infective endocarditis after experimental inoculation of bacteria,9 and in part on

Lancet Infect Dis 2008; 8: 225–32

APHP, Department of Infectious and Tropical Diseases, Paris 7 Diderot University, Paris, France (X Duval MD, C Leport MD)

Correspondence to: Dr Xavier Duval, Université Paris 7 Denis Diderot, Service des Maladies Infectieuses et Tropicales, Centre d’Investigation Clinique, Hôpital Bichat Claude Bernard, 46 rue Henri Huchard, 75877 Paris Cedex 18, France.Tel +33 140 257 803;fax +33 140 258 860;[email protected]

Panel: PCCs according to the risk of developing infective endocarditis (consensual classifi cation)

High risk Previous infective endocarditisMechanical or biological prosthetic valvesSurgically constructed systemic or pulmonary shunt or conduitComplex cyanotic congenital heart disease (single ventricle states, transposition of the great arteries, tetralogy of Fallot)Cardiac transplantation recipients who develop cardiac valvulopathy*

Moderate riskMost other congenital cardiac malformations (except isolated secundum atrial septal defect)Acquired valvular dysfunction†Hypertrophic cardiomyopathy Mitral-valve prolapse with valvular regurgitation and/or thickened leafl ets

*In the 2007 American Heart Association recommendations.6 †With echocardiographic documentation of substantial leafl et pathology and regurgitation.

226 http://infection.thelancet.com Vol 8 April 2008

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common practice. However, a Cochrane review concluded that there was little evidence to support the published guidelines.10 A randomised controlled trial should be implemented to assess the eff ectiveness of prophylaxis for infective endocarditis; however, the number of patients necessary to enrol (more than 6000 patients per group), has thus far discouraged any attempt. Furthermore, use of a testing strategy that runs counter to current guidelines would raise ethical and legal issues.11

In the context of habitual application of weakly supported guidelines, several issues have been raised over the past decade that challenge the principles underlying prophylaxis recommendations and that explain the general tendency observed in very recent years to reduce prophylaxis indications.12 Transient repeated bacteraemia from everyday life activities (eg, tooth brushing, chewing, etc) might pose a greater risk for infective endocarditis than intermittent bacteraemia after occasional procedures.13,14 A theoretical study of cumulative bacteraemia over 1 year postulated that everyday bacteraemia is 6 million times greater than bacteraemia from a single dental extraction (fi gure 1).14 However, the concept of cumulative bacteraemia is only relevant if the magnitude of everyday bacteraemia is above a theoretical cut-off needed to seed cardiac valves and induce infective endocarditis. This could explain why, of infective endocarditis cases presented in large studies, only a small number are preceded by a dental procedure (2·7–5% of cases in epidemiological series).16–18 However, even in the case of a close temporal relation between a dental procedure and the development of infective endocarditis, it is not possible to determine with certainty whether bacteraemia that caused the condition was induced by the procedure, was caused by the dental disease treated by the procedure, or was the result of a daily activity. Therefore, under the hypothesis of cumulative bacteraemia, the number of cases of infective endocarditis preventable through antibiotic prophylaxis given for occasional invasive procedure is probably very low.14

The prevalence of PCCs for which prophylaxis is generally recommended is much higher than previously believed. Previously unknown PCCs detected with

systematic echocardiography have been estimated to exist in 2·5% (95% CI 2·2–2·7) of the US general population.19 This prevalence reaches 13·3% (95% CI 11·7–15·0) in individuals aged over 75 years. Prevalence of previously known PCCs has been estimated to be 1·8% in the US general population and 3·3% in the 25–84-year-old French population.16,19 An estimate of at-risk dental procedures is 2·1 per patient per year in patients with PCC.16 Given that the proportion of patients who are treated in accordance with the prophylaxis recommendations is low (~40%), a very large number of dental procedures are probably done each year on at-risk patients without any prophylaxis (so-called unprotected procedures).16,17,20,21

The risk of developing infective endocarditis in patients with PCC after an unprotected at-risk dental procedure seems to be extremely low. A French study estimated that one in 10 700 adults with prosthetic valves and one in 54 300 adults with native-valve PCC developed infective endocarditis as a result of such a procedure.16 The risks reported in the USA are even lower (one in 114 000 adults with prosthetic valves, and one in 142 000 adults with rheumatic heart disease).22 Thus, a huge number of prophylaxis doses would be necessary to prevent a very small number of infective endocarditis cases.

This very low risk probably explains why case-control studies did not identify a clear relation between the onset of infective endocarditis and preceding at-risk dental procedures. Van der Meer and colleagues17 published a prospective study exploring the possibility of a causal relation between dental procedures and infective endocarditis, and assessed the effi cacy of antibiotic prophylaxis to prevent infection in patients with native or prosthetic cardiac valves. They concluded that dental or other procedures probably caused only a small number of infective endocarditis cases and that prophylaxis would prevent only a small number of cases, even if it were 100% eff ective. The same investigators also did a 2-year case-control study.23 Because fi ve of eight infective endocarditis cases occurred despite prophylaxis, they concluded that prophylaxis was not eff ective.23

Strom and colleagues18 assessed dental prophylaxis and cardiac risk factors in a case-control study. Controls without infective endocarditis were more likely to have undergone a dental procedure than were patients with infective endocarditis (adjusted odds ratio [OR] 0·2 [95% CI 0·04–0·7] over 3 months; p=0·03). They concluded that dental procedures were not a risk factor, even in patients with PCCs, and that only a few cases of infective endocarditis could be prevented with prophylaxis, even if it were 100% eff ective.

In another case-control study, Lacassin and co-workers24 found that the mean number of procedures was signifi cantly higher in cases than in controls (2·0 vs 1·5, p<0·05). In their multivariate analysis, the only procedure associated with a risk for infective endocarditis caused by Streptococcus viridans was tooth scaling (OR 5·25; p=0·025).24

Prophylaxis

Procedure-related bacteraemia

Everyday-lifebacteraemia

Time

Figure 1: Current concept of the limited role of antibiotic prophylaxis against everyday versus procedures related bacteraemiaAdapted from reference 15.


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In a study by Imperiale and Horwitz,25 cases were eight patients with high-risk lesions whose fi rst episode of native-valve infective endocarditis occurred within 12 weeks of a dental procedure. For each case, three controls were chosen from patients who underwent echocardiographic assessment, and who were matched for the specifi c high-risk lesion and age. Antibiotic prophylaxis was used in only one (13%) of the eight cases compared with 15 (63%) of 24 controls (OR 0·09; p=0·025).25

The estimation of the benefi t of prophylaxis must be weighed against the adverse eff ects of prophylaxis and the prognosis of the disease. Antibiotic prophylaxis is not risk free. β-lactam exposes patients to the risk of anaphylactic reaction (15–40 per 100 000 uses), which is potentially fatal in 1–3 per 100 000 uses.26–29 Furthermore, the widespread use of antibiotic therapy promotes the emergence of resistant microorganisms most likely to cause infective endocarditis, such as S viridans and enterococci. However, the extent to which a single dose of antibiotic prophylaxis could be implicated in the selection of resistant microorganisms is unknown.

Infective endocarditis caused by oral microorganisms (ie, streptococci) has the best prognosis, with a mortality of 10% in the French epidemiological survey on infective endocarditis, compared with 35% for Staphylococcus

aureus.1 From this mortality and the risk of developing infective endocarditis (one in 54 300 unprotected oral procedures) for patients with native-valve PCC, the risk of death after an unprotected procedure in such patients can be estimated at one in 543 000 patients. Thus, it might be that prophylaxis with β-lactams could induce more deaths than the infection itself would in patients with native-valve PCC.

Several studies have estimated the cost-eff ectiveness of antibiotic prophylaxis and have found confl icting results.30–32 Agha and colleagues30 estimated that clarithromycin prophylaxis was cost eff ective in patients with moderate or high risk for infective endocarditis, whereas amoxicillin and ampicillin prophylaxis resulted in a loss of lives because of the occurrence of severe adverse drug reactions.

As the eff ectiveness of preventive antibiotic treatment remains to be proven, recommendations originating from diff erent countries diverge according to the patient population to whom preventive antibiotic should be administered.6,33–35 Additionally, diff erences in the medicolegal context between diff erent countries also infl uence recommendations and the way in which they are followed. Given the high mortality of infective endocarditis, fear of medicolegal consequences has been shown to lead practitioners in some countries to overuse prophylaxis compared with the use recommended in current guidelines.36 Recommendations for prophylaxis require the identifi cation of the highest risk situations: those cardiac conditions at high risk for infective endocarditis, and those procedures most likely to induce bacteraemia and infective endocarditis.

Identifi cation of cardiac conditions at risk for occurence or mortality from endocarditisThe risk of occurrence of infective endocarditis in any given case of PCC is most often very indirectly estimated by comparing the frequency of diff erent cardiac diseases in patients with infective endocarditis to its estimated frequency in the overall population.18 This risk can also be estimated by monitoring cohorts of cardiac patients and calculating the incidence of infective endocarditis cases, thus determining the lifetime risk of acquisition of infective endocarditis associated with a specifi c PCC.37–42 Choice of the threshold above which risk for infective endocarditis can be considered too high is subjective. Therefore, any attempt at classifi cation has only informational value. According to this risk gradation, patients with a history of infective endocarditis, a mechanical or a biological prosthetic valve, or a surgically constructed systemic or pulmonary shunt or conduit, are the patients with the highest incidence of infective endocarditis and are therefore considered at highest risk of developing infective endocarditis during their lifetime. This risk gradation is consensual.6,33–35

The prognosis of infective endocarditis occurring in a given case of PCC must also be taken into account in the choice of PCC to be covered. Patients with infective endocarditis on prosthetic valves and those with a previous history of infective endocarditis are generally at higher risk of death than others. Other characteristics of patients’ general health background have also been associated with in-hospital death during infective endocarditis: older age, diabetes mellitus (mainly insulin-dependent diabetes mellitus), immunodefi ciency, dialysis, and hepatic insuffi ciency.43–46 In most

Proportion of positive blood cultures

References

Mastication 17–51% 47–51

Toothbrushing or irrigation 0–50% 47–51

Flossing 20–60% 47–51

Dental examination 17% 47–51

Dental polishing 24% 47,51–53

Intraligamentary local anaesthetic injection 97% 47,51–53

Matrix band placement 32% 47,51–53

Rubber dam placement 30% 47,51–53

Slow drill 12% 47,51–53

Fast drill 4% 47,51–53

Single dental extraction 18–94% 54–61

Multiple dental extraction 10–85% 54–61

Scaling 17–70% 60

Periodontal surgery 32–88% 60

Endodontic instrumentation 20–42% 60,62

Post-operative suture removal 5% 63

Endodontic treatment 42% 62,63

Table 1: Proportion of positive blood samples reported after various oral procedures


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recommendations, these considerations have led to the identifi cation of patients at moderate and high risk of infective endocarditis (panel). According to these

classifi cations, infective endocarditis prophylaxis involves both groups or is limited to the patients at highest risk. To date, only the 2002 French recommendations take into consideration the patient’s health background in modulating the indication of prophylaxis.33

Identifi cation of at-risk proceduresThe identifi cation of at-risk procedures for infective endocarditis include the consideration of diff erent characteristics: (1) the number of identifi ed infective-endocarditis-inducing pathogens (inoculum) colonising the area that could enter the bloodstream in case of an invasive procedure; (2) the amount of the bleeding induced by the procedure; (3) the proportion of bacteria-positive blood cultures after a given procedure (table 1); (4) the magnitude of bacteraemia after the procedure; (5) the duration of the bacteraemia; and (6) the number of reported cases of infective endocarditis after a given procedure. However, there is wide variation in reported frequencies of these characteristics after procedures. For example, bacteraemia is noted in 10–95% of patients after tooth extraction, which probably indicates the heterogeneity of these procedures, of the host, and of the experimental methods used (table 1).54–59 Because of the disparity of these data, it is diffi cult to clearly establish criteria for defi ning risk factors. A better knowledge of the factors that predispose a patient to infective endocarditis is necessary. Given the existence of everyday-life cumulative bacteraemia, and despite the high prevalence of PCC in the general population, the incidence of infective endocarditis is astonishingly low. Genetic host susceptibility that promotes attachment of microorganisms to the valvular endothelium probably exists; its identifi cation could allow better focusing of prophylactic measures on the patients at highest risk.

Meanwhile, the proportion of patients with bacteraemia after an at-risk procedure has been used as a surrogate measure of the risk of infective endocarditis to identify procedures requiring antibiotic prophylaxis. However, bacteraemia does not respond to the prerequisite of a pertinent (appropriate) surrogate measure. There is no evidence-based method to decide which procedure should require prophylaxis because no data show that either the incidence, the magnitude, or the duration of bacteraemia after a procedure increase the risk of infective endocarditis. Thus, any attempt to identify the procedures that need prophylaxis is artifi cial. However, this identifi cation method has resulted in a detailed and complex list of procedures for which prophylaxis is and is not recommended.

Recent guidelines that suggest reduction in use of prophylaxisTable 2 and table 3 summarise and compare the current and previous recommendations for the prophylaxis of infective endocarditis. French guidelines that challenge the accepted practice were published in 2002,33,78 and

Recommended drug

Prophylaxis for adults

AHA (1972)64 Penicillin 600 000 units procaine penicillin G with 200 000 units crystalline penicillin G IM 1 h before procedure and once daily for 2 days after the procedure

AHA (1977)65 Penicillin Aqueous crystalline penicillin G (1×10⁶ units IM) with procaine penicillin G (600 000 units IM), 30 min to 1 h before the procedure and then penicillin V 500 mg orally every 6 h for two doses

BSAC (1982)66 Amoxicillin 3 g 1 h before procedure

AHA (1984)67 Penicillin V 2 g orally 30 min to 1 h before procedure; then 1 g 6 h after initial dose

BSAC (1986)68,69 Amoxicillin 3 g 1 h before procedure

AHA (1990)70 Amoxicillin 3 g orally 1 h before procedure; then 1·5 mg 6 h after initial dose


BSAC (1992)72,73 Amoxicillin 3 g 1 h before procedure

France (1992)74 Amoxicillin 3 g 1 h before procedure

European Infectious Diseases Society consensus (1995)75

Amoxicillin 3 g 1 h before procedure

AHA (1997)8 Amoxicillin 2 g 1 h before procedure

New Zealand (1999)76 Amoxicillin 2 g 1 h before procedure; then 1 g 6 h after initial dose

Switzerland (2000)34 Amoxicillin 2·25 g (3×750 mg) 1 h before procedure then 750 mg 6 h after initial dose

France (2002)33 Amoxicillin 3 g or 2 g (if weight <60 kg) 1 h before procedure

European Society of Cardiology consensus (2004)77

Amoxicillin 2 g 1 h before procedure


AHA (2007)6 Amoxicillin 2 g 1 h before procedure

AHA=American Heart Association. BSAC=British Society for Antimicrobial Chemotherapy. IM=intramuscularly.

Table 2: Recommended prophylaxis guidelines (by year) for adults for dental procedures since 1972 (general use)

Procedures listed Predisposing cardiac conditions*

High risk Moderate risk

Dental procedures

French (2002)33,78

Several dental procedures—eg, dental extraction, scaling

Prophylaxis recommended

Prophylaxis optional

BSAC (2006)35

All dental procedures involving dento-gengival manipulation or endodontics


Prophylaxis not recommended

AHA (2007)6

Any dental procedure that involves manipulation of the oral mucosa



Extra-dental procedures

French (2002)33,78

Several procedures—eg, colonoscopy Prophylaxis recommended or optional (depending on the procedure)

Prophylaxis optional or not recommended (depending on the procedure)

BSAC (2006)35

Several procedures—eg, oesophageal laser therapy



AHA (2007)6

.. Prophylaxis not recommended


*See panel. BSAC=British Society of Antimicrobial Chemotherapy. AHA=American Heart Association.

Table 3: Comparison of recent guidelines that have reduced indications for prophylaxis of infective endocarditis


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proposed that prophylaxis should be restricted to “cases that have the highest ratio of individual benefi t to individual and collective risk” (fi gure 2).33 Prophylaxis is suggested for many invasive dental, respiratory, gastrointestinal, and genito urinary procedures in the high-risk PCC group, but is optional in the moderate risk group (panel). The decision to use prophylaxis became based on the subsequent risks “from” infective endocarditis, by taking patients’ back-ground characteristics into consideration, rather than on the direct risk “of” infective endocarditis from the procedure itself. Importantly, post-hoc prophylaxis may be administered in the event of unanticipated procedural complexity. Furthermore, limiting the number of patients with PCCs who are candidates for prophylaxis could improve overall adherence to prophylaxis among the most critical patients.

In the 2006 British Society for Antimicrobial Chemotherapy (BSAC) guidelines, prophylaxis is suggested for “all dental procedures involving dento-gengival manipulation or endodontics” only for those patients with previous infective endocarditis, a cardiac valve replacement, or a prosthetic systemic or pulmonary shunt or conduit.35 Prophylaxis is extended to all at-risk cardiac patients for extra-dental procedures. The guidelines include a detailed list of gastrointestinal, genitourinary, gynaecological, and respiratory procedures for which prophylaxis is recommended, on the basis of anecdotal associations and the risk of bacteraemia.35 This recommendation and those previously proposed (and diametrically opposed) by the UK and the European cardiology societies have led to vigorous exchanges between infectious diseases specialists, cardiologists, and dentists.77,79–83

The most recent guidelines were established by the American Heart Association (AHA) in 2007.6 These new recommendations represent a radical change from the previous ones: antibiotic prophylaxis is no longer recommended before a dental procedure, except for patients with the highest risk of adverse outcome resulting from infective endocarditis (panel), and who are due to undergo “any dental procedure that involves manipulation of the oral mucosa”.6 Prophylaxis is thus abandoned in patients at moderate cardiac risk of infective endocarditis, such as those with a history of aortic regurgitation or mitral regurgitation who undergo a dental procedure (as in the BSAC recommendations), but also in all cardiac at-risk patients before extra-oral procedures (eg, colonoscopy), irrespective of their PCCs.

General preventive measuresBecause of the limits of the data that support the current guidelines and the uncertainties of the eff ectiveness of antibiotic prophylaxis, early recognition and treatment of the source of infective endocarditis is essential. All at-risk patients should be educated to seek medical advice in case of fever or other symptoms, and for their physician to understand the importance of assessing blood cultures

before any antibiotic administration. The patient should then remain under medical supervision until a diagnosis of infective endocarditis is excluded. Furthermore, patients and physicians should be informed that all localised infections, whatever the site, particularly those caused by Staphylococcus and Streptococcus spp, represent a potential portal of entry for infective endocarditis in at-risk cardiac patients and should be treated accordingly. Health practitioners should be instructed to limit catheters in both frequency and duration in at-risk cardiac patients.84 To improve the identifi cation of at-risk patients and to increase the proportion of those following the

Oral regimen (1 h before procedure)

Regimen for those unable to take oral medication*

Drugs for general use

Amoxicillin 2–3 g† 1–2 g IM or IV†‡

Ampicillin .. 1–2 g IM or IV†‡

Drugs for use in patients with allergy to penicillin

Clindamycin 600 mg 300–600 mg IV

Azithromycin§ 500 mg ..

Clarithromycin§ 500 mg ..

Cephalexin¶ 2 g ..

Cefazolin¶ .. 1 g IM or IV

Vancomycin|| .. 1 g (slow IV infusion over 1–2 h)

Teicoplanin|| .. 400 mg IV or IM

*Or who are unable to take other oral fi rst or second generation cephalosporin; cephalosporins should not be used in individuals with immediate-type hypersensitivity reaction to penicillins. †Additional dose 6 h later (Switzerland). ‡1 g orally 6 h later in some guidelines (France). §Not recommended in French guidelines. ¶Just before the procedure or at induction of anaesthesia. ||Not recommended in US guidelines. IM=intramuscularly. IV=intravenously.

Table 4: Commonly recommended antibiotics for dental procedures in adults6,33–35,78

Time

Num

ber o

f pro

cedu

res French*

2002

British†2006

US‡2007

Figure 2: Diagrammatic representation of the number of procedures recommended for prophylaxis: evolution of guidelines during recent yearsDark green columns indicate the regular increase in the recommended number of procedures in the diff erent guidelines until 2002 (see table 2). *2002 French guidelines.33 †2006 British Society for Antimicrobial Chemotherapy guidelines.35 ‡2007 American Heart Association guidelines.6


Review

prophylactic recommendations, the use of infective endocarditis preventive cards have been proposed in several countries.

Because of the frequency of everyday bacteraemia and its postulated primary role in infective endocarditis, the main preventive strategy is to limit spontaneous bacteraemia (through chewing, brushing) by reducing the global oral burden of bacteraemia via improved oral hygiene. This strategy requires regular systematic dental check-ups of at least twice a year in high-risk patients.

The benefi ts and risks of silver-coated prosthetic valves, which were developed to decrease the rate of infection, were assessed in a clinical trial (AVERT study) because of the high risk of infective endocarditis in patients with prosthetic valves.85 This trial was prematurely suspended because of the occurrence of major paravalvular leakage in patients receiving silver-coated valves.86

Antibiotic choice and route of administrationAntibiotics should act on the primary bacteraemia responsible for infective endocarditis: oral streptococci for dental procedures, and enterococcus and group D streptococci for digestive or urinary-tract procedures. The main antibiotics to have proved eff ective in experimental models are amoxicillin, vancomycin, teicoplanin, clindamycin, synergistins, azithromycin, and clarithromycin.

When antibiotic prophylaxis is recommended before dental and upper respiratory procedures, amoxicillin is used in most countries, at doses varying from 2 g to 3 g (table 2 and table 4). For patients allergic to β-lactams, clindamycin or a glycopeptide are substituted; azithromycin or clarithromycin are recommended in some guidelines.6,34,35 For dental procedures, antibiotic prophylaxis is generally administered as a single dose in the hour before the procedure. Streptococci or enterococci originating from the digestive and urinary tract are less susceptible to antibiotics, and therefore the use of an ampicillin–gentamicin or glycopeptide–aminoglycoside synergistic combination is preferable.

The possible association between gastrointestinal and genitourinary procedures and infective endocarditis has not been studied as extensively as has the possible association with dental procedures. The determination of those requiring antibiotic prophylaxis is currently based

on the risk of a procedure causing a bacteraemia and whether such a procedure has been anecdotally linked to cases of infective endocarditis. Current guidelines determine the procedure for which prophylaxis is or is not recommended based on assessment of the risks. For general intravenous prophylaxis just before the procedure or at induction of anaesthesia, 1–2 g amoxicillin or ampicillin plus 1·5 mg/kg gentamicin is recommended, with an additional 1 g amoxicillin or ampicillin given orally 6 h later in some guidelines (ie, France).33,35 Patients who are allergic to penicillin are recommended to receive 400 mg teicoplanin or 1 g vancomycin (at more than 60 min), plus 1·5 mg/kg gentamicin.33,35 However, prophylaxis is no longer recommended before extra-dental procedures in the 2007 AHA guidelines.6

In patients who are due to undergo cardiac surgery, a careful preoperative dental assessment is recommended and dental treatment given before surgery whenever possible. Preoperative antibiotic prophylaxis is recommended and should be eff ective against microorganisms responsible for early post-operative infective endocarditis (ie, S aureus and coagulase-negative staphylococci). The choice of antibiotic should be determined based on the susceptibility of these microorganisms to antimicrobials in the institution where surgery is done.

ConclusionsTo date, there is no evidence for the effi cacy and the lack of adverse eff ects of prophylactic strategies for infective endocarditis. The current tendency is to limit prophylaxis to the procedures and populations with the highest risks. This process culminated with the 2007 AHA guidelines that limit infective endocarditis prophylaxis to the highest risk cardiac patients who are due to undergo dental procedures. Energy should be focused on the population with the highest risk to improve the adherence rate to prophylaxis recommendations. In all patients, oral and general hygiene should be reinforced, and regular preventive dental check-ups done. In case of fever, infective endocarditis should be excluded before prescribing antimicrobials. Patients should be educated about this point, and the reasons leading to the modifi cation of the infective endocarditis prophylactic strategy explained. The strategy of targeting indications might be improved by a better analysis of factors associated with an increased risk of death from infective endocarditis or an increased risk of infective endo-carditis from certain medico-surgical conditions, including staphylococcus bacteraemia. Epidemiological surveys must be done to monitor the potential consequences of guideline modifi cations on the profi le of infective endocarditis epidemiology (ie, incidence and type of microorganisms).Confl icts of interestWe declare that we have no confl icts of interest.

Search strategy and selection criteria

Data for this Review were identifi ed by research on Medline, Current Contents, and references from relevant articles. Search terms used were “endocarditis”, “prophylaxis”, “procedures”, “risk factors”, and “bacteremia”. All English and French papers published since 1992 were assessed for potential inclusion in this review. Papers were fi rst selected based on the abstract analysis. Then, only papers bringing new data or understanding on infective endocarditis pathophysiology or prophylaxis were kept for this Review.


Review

References1 Hoen B, Alla F, Selton-Suty C, et al. Changing profi le of infective

endocarditis: results of a 1-year survey in France. JAMA 2002; 288: 75–81.

2 Tleyjeh IM, Steckelberg JM, Murad HS, et al. Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA 2005; 293: 3022–28.

3 Moreillon P, Que YA. Infective endocarditis. Lancet 2004; 363: 139–49.

4 Horder TJ. Infective endocarditis with analysis of 150 cases and with special reference to the chronic form of the disease. Q J Med 1909; 2: 289–24.

5 Okell CC, Elliott SD. Bacteraemia and oral sepsis with special reference to the aetiology of subacute endocarditis. Lancet 1935; 2: 869–72.

6 Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis. Guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 116: 1736–54.

7 American Heart Association. Prevention of rheumatic fever and bacterial endocarditis through control of streptococcal infections. Circulation 1955; 11: 317–20.

8 Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 1997; 277: 1794–801.

9 Glauser MP, Bernard JP, Moreillon P, Francioli P. Successful single-dose amoxicillin prophylaxis against experimental streptococcal endocarditis: evidence for two mechanisms of protection. J Infect Dis 1983; 147: 568–75.

10 Oliver R, Roberts GJ, Hooper L. Penicillins for the prophylaxis of bacterial endocarditis in dentistry. Cochrane Database Syst Rev 2004; 2: CD003813.

11 Durack DT. Prevention of infective endocarditis. N Engl J Med 1995; 332: 38–44.

12 Durack DT. Antibiotics for prevention of endocarditis during dentistry: time to scale back? Ann Intern Med 1998; 129: 829–31.

13 Drangsholt MT. A new causal model of dental diseases associated with endocarditis. Ann Periodontol 1998; 3: 184–96.

14 Roberts GJ. Dentists are innocent! “Everyday” bacteremia is the real culprit: a review and assessment of the evidence that dental surgical procedures are a principal cause of bacterial endocarditis in children. Pediatr Cardiol 1999; 20: 317–25.

15 Moreillon P, Dargère S, Piroth L, Entenza JM. Infective endocarditis prophylaxis: lessons from the experimental model. Med Mal Infect 2002; 32: 605–12 (in French).

16 Duval X, Alla F, Hoen B, et al. Estimated risk of endocarditis in adults with predisposing cardiac conditions undergoing dental procedures with or without antibiotic prophylaxis. Clin Infect Dis 2006; 42: e102–07.

17 van der Meer JT, Thompson J, Valkenburg HA, Michel MF. Epidemiology of bacterial endocarditis in The Netherlands. II. Antecedent procedures and use of prophylaxis. Arch Intern Med 1992; 152: 1869–73.

18 Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study. Ann Intern Med 1998; 129: 761–69.

19 Nkomo V, Gardin J, Skelton T, Gottdiener J, Scott C, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet 2006; 368: 1005–11.

20 Stucki C, Mury R, Bertel O. Insuffi cient awareness of endocarditis prophylaxis in patients at risk. Swiss Med Wkly 2003; 133: 155–59.

21 Seto TB, Kwiat D, Taira DA, Douglas PS, Manning WJ. Physicians’ recommendations to patients for use of antibiotic prophylaxis to prevent endocarditis. JAMA 2000; 284: 68–71.

22 Pallasch TJ. Antibiotic prophylaxis: problems in paradise. Dent Clin North Am 2003; 47: 665–79.

23 Van der Meer JT, Van Wijk W, Thompson J, Vandenbroucke JP, Valkenburg HA, Michel MF. Effi cacy of antibiotic prophylaxis for prevention of native-valve endocarditis. Lancet 1992; 339: 135–39.

24 Lacassin F, Hoen B, Leport C, et al. Procedures associated with infective endocarditis in adults. A case control study. Eur Heart J 1995; 16: 1968–74.

25 Imperiale TF, Horwitz RI. Does prophylaxis prevent postdental infective endocarditis? A controlled evaluation of protective effi cacy. Am J Med 1990; 88: 131–36.

26 Idsoe O, Guthe T, Willcox RR, de Weck AL. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ 1968; 38: 159–88.

27 Ahlstedt S. Penicillin allergy—can the incidence be reduced? Allergy 1984; 39: 151–64.

28 Little P, Williamson I. Sore throat management in general practice. Fam Pract 1996; 13: 317–21.

29 Lin RY. A perspective on penicillin allergy. Arch Intern Med 1992; 152: 930–37.

30 Agha Z, Lofgren RP, VanRuiswyk JV. Is antibiotic prophylaxis for bacterial endocarditis cost-eff ective? Med Decis Making 2005; 25: 308–20.

31 Devereux RB, Frary CJ, Kramer-Fox R, Roberts RB, Ruchlin HS. Cost-eff ectiveness of infective endocarditis prophylaxis for mitral valve prolapse with or without a mitral regurgitant murmur. Am J Cardiol 1994; 74: 1024–29.

32 Gould IM, Buckingham JK. Cost eff ectiveness of prophylaxis in dental practice to prevent infective endocarditis. Br Heart J 1993; 70: 79–83.

33 Danchin N, Duval X, Leport C. Prophylaxis of infective endocarditis: French recommendations 2002. Heart 2005; 91: 715–18.

34 Moreillon P. Endocarditis prophylaxis revisited: experimental evidence of effi cacy and new Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis. Schweiz Med Wochenschr 2000; 130: 1013–26.

35 Gould FK, Elliott TS, Foweraker J, et al. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006; 57: 1035–42.

36 Lockhart PB, Brennan MT, Fox PC, Norton HJ, Jernigan DB, Strausbaugh LJ. Decision-making on the use of antimicrobial prophylaxis for dental procedures: a survey of infectious disease consultants and review. Clin Infect Dis 2002; 34: 1621–26.

37 Morris CD, Reller MD, Menashe VD. Thirty-year incidence of infective endocarditis after surgery for congenital heart defect. JAMA 1998; 279: 599–603.

38 Gersony WM, Hayes CJ, Driscoll DJ, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation 1993; 87 (suppl 2): I121–26.

39 Spirito P, Rapezzi C, Bellone P, et al. Infective endocarditis in hypertrophic cardiomyopathy: prevalence, incidence, and indications for antibiotic prophylaxis. Circulation 1999; 99: 2132–37.

40 Zuppiroli A, Rinaldi M, Kramer-Fox R, Favilli S, Roman MJ, Devereux RB. Natural history of mitral valve prolapse. Am J Cardiol 1995; 75: 1028–32.

41 Horstkotte D. Prosthetic valve endocarditis. In: Bodnar E, Horstkotte D, eds. Infective endocarditis. London: IRC Publishers, 1991: 229–61.

42 Moller JH, Anderson RC. 1000 consecutive children with a cardiac malformation with 26- to 37-year follow-up. Am J Cardiol 1992; 70: 661–67.

43 Duval X, Alla F, Docco-Lecompte T, et al. Diabetes mellitus and infective endocarditis: the insulin factor in patient morbidity and mortality. Eur Heart J 2007; 28: 59–64.

44 Chu VH, Cabell CH, Benjamin DK, et al. Early predictors of in-hospital death in infective endocarditis. Circulation 2004; 109: 1745–49.

45 Thuny F, Disalvo G, Belliard O, et al. Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study. Circulation 2005; 112: 69–75.

46 Strom BL, Abrutyn E, Berlin JA, et al. Risk factors for infective endocarditis: oral hygiene and nondental exposures. Circulation 2000; 102: 2842–48.

47 Roberts GJ, Holzel HS, Sury MR, Simmons NA, Gardner P, Longhurst P. Dental bacteremia in children. Pediatr Cardiol 1997; 18: 24–27.

48 Longman LP, Martin MV. A practical guide to antibiotic prophylaxis in restorative dentistry. Dent Update 1999; 26: 7–14.


Review

49 Seymour RA, Lowry R, Whitworth JM, Martin MV. Infective endocarditis, dentistry and antibiotic prophylaxis; time for a rethink? Br Dent J 2000; 189: 610–16.

50 Lucas V, Roberts GJ. Odontogenic bacteremia following tooth cleaning procedures in children. Pediatr Dent 2000; 22: 96–100.

51 Al-Karaawi ZM, Lucas VS, Gelbier M, Roberts GJ. Dental procedures in children with severe congenital heart disease: a theoretical analysis of prophylaxis and non-prophylaxis procedures. Heart 2001; 85: 66–68.

52 Roberts GJ, Gardner P, Longhurst P, Black AE, Lucas VS. Intensity of bacteraemia associated with conservative dental procedures in children. Br Dent J 2000; 188: 95–98.

53 Roberts GJ, Lucas VS, Omar J. Bacterial endocarditis and orthodontics. J R Coll Surg Edinb 2000; 45: 141–45.

54 Hall G, Heimdahl A, Nord CE. Eff ects of prophylactic administration of cefaclor on transient bacteremia after dental extraction. Eur J Clin Microbiol Infect Dis 1996; 15: 646–49.

55 Lockhart PB. An analysis of bacteremias during dental extractions. A double-blind, placebo-controlled study of chlorhexidine. Arch Intern Med 1996; 156: 513–20.

56 Szontágh E, Méray J, Nagy E, Füzesi H. Incidence of transient bacteremia following tooth extraction and antibiotic sensitivity of isolated bacteria. Fogorv Sz 1994; 87: 165–71 (in Hungarian).

57 Roberts GJ, Watts R, Longhurst P, Gardner P. Bacteremia of dental origin and antimicrobial sensitivity following oral surgical procedures in children. Pediatr Dent 1998; 20: 28–36.

58 Roberts HW, Tahn C, Nevins S. Clinical consideration for infective endocarditis antibiotic prophylaxis. Gen Dent 1998; 46: 89–91.

59 Okabe K, Nakagawa K, Yamamoto E. Factors aff ecting the occurrence of bacteremia associated with tooth extraction. Int J Oral Maxillofac Surg 1995; 24: 239–42.

60 Boy-Lefevre ML. Buccodental procedures at-risk for infective endocarditis. Med Mal Infect 1992; 22: 1023–30 (in French).

61 Lockhart PB, Brennan MT, Kent ML, Norton HJ, Weinrib DA. Impact of amoxicillin prophylaxis on the incidence, nature, and duration of bacteremia in children after intubation and dental procedures. Circulation 2004; 109: 2878–84.

62 Debelian GJ, Olsen I, Tronstad L. Bacteremia in conjunction with endodontic therapy. Endod Dent Traumatol 1995; 11: 142–49.

63 Hall G, Heimdahl A, Nord CE. Bacteremia after oral surgery and antibiotic prophylaxis for endocarditis. Clin Infect Dis 1999; 29: 1–8.

64 American Heart Association. Prevention of bacterial endocarditis. Circulation 1972; 46 (suppl A): S3–6.

65 Kaplan EL. Prevention of bacterial endocarditis. Circulation 1977; 56: 139A–43A.

66 Simmons NA, Cawson RA, Clarke C, et al. The antibiotic prophylaxis of infective endocarditis. Report of a working party of the British Society for Antimicrobial Chemotherapy. Lancet 1982; 2: 1323–26.

67 Shulman ST, Amren DP, Bisno AL, et al. Prevention of bacterial endocarditis. A statement for health professionals by the Committee on Rheumatic Fever and Infective Endocarditis of the Council on Cardiovascular Disease in the Young. Circulation 1984; 70: 1123A–27A.

68 Simmons NA, Cawson RA, Clarke CA, et al. Prophylaxis of infective endocarditis. Lancet 1986; 1: 1267.

69 Anon. Infective endocarditis. Based on a scientifi c meeting of the British Society for Antimicrobial Chemotherapy. London, 29–30 April 1986. J Antimicrob Chemother 1987; 20 (suppl A): 1–192.

70 Dajani AS, Bisno AL, Chung KJ, et al. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 1990; 264: 2919–22.

71 Simmons NA, Cawson RA, Eykyn SJ, et al. Antibiotic prophylaxis of infective endocarditis. Recommendations from the Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy. Lancet 1990; 335: 88–89.

72 Simmons NA, Ball AP, Cawson RA, et al. Antibiotic prophylaxis and infective endocarditis. Lancet 1992; 339: 1292–93.

73 Littler WA, McGowan DA, Shanson DC. Changes in recommendations about amoxycillin prophylaxis for prevention of endocarditis. British Society for Antimicrobial Chemotherapy Endocarditis Working Party. Lancet 1997; 350: 1100.

74 Anon. Infective endocarditis prophylaxis: guidelines and experts’ reports. Med Mal Infect 1992; 22: 1119–41 (in French).

75 Leport C, Horstkotte D, Burckhardt D. Antibiotic prophylaxis for infective endocarditis from an international group of experts towards a European consensus. Group of Experts of the International Society for Chemotherapy. Eur Heart J 1995; 16 (suppl B): 126–31.

76 Ellis-Pegler RB, Hay KD, Lang SD, Neutze JM, Swinburn BA. Prevention of infective endocarditis associated with dental treatment and other medical interventions. National Heart Foundation. N Z Dent J 1999; 95: 85–88.

77 Horstkotte D, Follath F, Gutschik E, et al. Guidelines on prevention, diagnosis and treatment of infective endocarditis executive summary; the task force on infective endocarditis of the European society of cardiology. Eur Heart J 2004; 25: 267–76.

78 Danchin N, Duval X, Leport C. Update of the infective endocarditis prophylaxis guidelines. Med Mal Infect 2002; 32: 562–95 (in French).

79 Royal College of Surgeons of England. Dental aspects of endocarditis prophylaxis: new recommendations from the British Cardiac Society Guidelines and the Royal College of Physicians Clinical Eff ectiveness and Evaluation Unit. 19 April 2004. http://www.rcseng.ac.uk/fds/docs/ie_recs.pdf (accessed Jan 10, 2008).

80 Ashrafi an H, Bogle RG. Antimicrobial prophylaxis for endocarditis: emotion or science? Heart 2007; 93: 5–6.

81 Chalmers JA, Pullan DM. Antimicrobial prophylaxis for endocarditis: emotion or science? Heart 2007; 93: 753.

82 Longman LP, Martin NV, Field EA, et al. Cause for concern? Br Dent J 2004; 197: 115.

83 Ramsdale DR, Palmer ND. Antimicrobial prophylaxis for endocarditis: emotion or science? Heart 2007; 93: 753.

84 Fowler VG, Miro JM, Hoen B, et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 2005; 293: 3012–21.

85 Schaff H, Carrel T, Steckelberg JM, Grunkemeier GL, Holubkov R. Artifi cial Valve Endocarditis Reduction Trial (AVERT): protocol of a multicenter randomized trial. J Heart Valve Dis 1999; 8: 131–39.

86 Schaff HV, Carrel TP, Jamieson WR, et al. Paravalvular leak and other events in silzone-coated mechanical heart valves: a report from AVERT. Ann Thorac Surg 2002; 73: 785–92.

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alvular Heart Disease: A Century of Progressanjay Sharma, MD, Anilkumar Mehra, MD, Shahbudin H. Rahimtoola, MB, FRCP, DSc (Hon)

he Griffith Center, Division of Cardiovascular Medicine, Department of Medicine, LAC�USC Medical Center, Keck School of
edicine at University of Southern California, Los Angeles, Calif.
Ta©

E-mail address

002-9343/$ -see foi:10.1016/j.amjm

ABSTRACT

he 20th century witnessed amazing advances in the diagnosis and treatment of valvular heart disease. Thedvances and our hopes for future progress are described.

2008 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2008) 121, 664-673

KEYWORDS: Cardiac catheterization; Doppler echocardiography; Percutaneous catheter intervention; Valve surgery

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How can you understand the world if you don’t know whatappened in it?”

—John W. Kirklin, MD1

Since the turn of the 20th century, extraordinary ad-ances have been made in the diagnosis and treatment ofalvular heart disease. Some of the major achievementsnderlying these advances have received due recognitionTable 1).2 Breakthroughs in medicine are a culmination ofmall advances3 in valvular heart disease. Different smalldvances occurred in both halves of the century (Tablesand 3).

HE FIRST HALF OF THE LAST CENTURY

etting the Stageuring World War I, Lewis,4 charged with the care of

ombatants with heart disease, noted the inadequate under-tanding of cardiac disease and its prognosis. In a report to

Dr Rahimtoola has received honoraria for educational lectures from themerican College of Cardiology Foundation (Washington, DC); Americanollege of Physicians (Philadelphia, Pa); University of California Losngeles; University of California Irvine; Cornell University (New York,Y); Creighton University (Omaha, Neb); Thomas Jefferson University

Philadelphia, Pa); Cedars-Sinai Medical Center (Los Angeles, Calif);arvard Medical School (Boston, Mass); University of Wisconsin (Mil-aukee Campus, Wis); University of Hawaii (Honolulu, Hawaii); Cardi-logists Association of Hong Kong, China; ATS (New York, NY); St Judeedical (St Paul, Minn); Carbomedics (Austin, Tex); Merck (Whitehouse

tation, NJ); Pfizer (New York, NY); and Edwards Life Sciences (Irvine,alif).

Requests for reprints should be addressed to Shahbudin H. Rahimtoola,D, University of Southern California, 2025 Zonal Avenue, GNH 7131,

os Angeles, CA 90033.
e: [email protected]
ront matter © 2008 Elsevier Inc. All rights reserved.ed.2008.03.027

he Medical Research Council, he advocated prospectiveollow-up studies, or “after-histories,” of patients. Thesefter-histories5 were the predecessors of databases and reg-stries in use today.

According to Feinstein,6 the first randomized controlledtudy in scientific literature was reported in agriculturalxperiments carried out by T. Eden in 1923 on the effect ofanure on potato crops. The first randomized clinical trial

n valvular heart disease began in 1954.7 The 5-year resultsre shown in Table 4.8

heumatic Fever and Carditisn the first half of the 20th century, rheumatic heart diseaseas a major problem; for example, in Britain, rheumaticeart disease accounted for 20% of all heart disease and0,000 deaths annually.9

The observations that led to the conquering of thiscourge merit a brief review.10 From an epidemiologic sur-ey, Newsholme11 correctly deduced that an active infectivegent and conditions of environmental and personal factorsere required for the development of rheumatic fever.schoff described the specific rheumatic lesion (Aschoffody).10 In the late 1920s, Griffith and Lancefield identifiedroup A hemolytic streptococcus as the causative organ-

sm.10 Centers were established in New York, Boston, andondon for the long-term care of these patients. In 1944,ones12 published his seminal work on the diagnosis of rheu-atic fever. In Denmark, improvements in socioeconomic

onditions and housing dramatically reduced the incidencef rheumatic fever before the antibiotic era (Figure 1).10

heumatic carditis and valve disease have been virtually
liminated from developed countries, similar to the virtual

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limination of smallpox and poliomyelitis in the world byaccines.

HE SECOND HALF OF THE TWENTIETH CENTURY

atient Assessmentressure Measurement. Efforts

o quantify the severity of valvulareart disease began in 1945 withttempts to measure intracardiacressures. In landmark studies,ellems et al13 and Lagerlöf anderkö14 documented that pres-

ures recorded with a cardiac cathe-er wedged into the distal pulmonaryrtery reflected left atrial pressure.oss15 developed the transseptalpproach to the left ventricle. Per-utaneous transthoracic puncturef the left ventricle was used toeasure left ventricular pressure in

ortic stenosis. Subsequently, theeldinger16 technique for percuta-eous entry into a systemic arteryevolutionized retrograde accesso the ascending aorta and leftentricle.

alve Area Calculations. By comparing hydraulic systemsnd cardiac physiology, Gorlin and Gorlin17 derived theollowing formula for calculating mitral and aortic valvereas:

mitral valve area �CO/HR � DFP

37'.9'�gradient

aortic valve area �CO/HR � SEP'

44'.3'�gradient'

here CO � cardiac output, HR � heart rate, DFP �iastolic filling period, and SEP � systolic ejection period.

ngiography. The first angiocardiogram in humans waserformed by Castellanos and colleagues.18 Aortographynd left ventricular angiography were essential to assessingortic and mitral regurgitation. Dodge and colleagues19 ac-urately calculated the left ventricular volumes and ejectionraction from left ventricular angiograms using Arvidsson’sechnique.

ormal Values. Values for right-sided heart pressures, pul-onary artery wedge pressure, and cardiac output were

ocumented in healthy volunteers.20 Another study inealthy subjects documented right and left-sided heart pres-ures and left ventricular volumes and ejection fraction.21

he normal cardiac index was found to be 3.6 � 0.9

CLINICAL SIGNIF

● The diagnosis anverity of valve steare at an advance

● Interventional thvalvular heart diprovement of symleft ventricular fuhypertension. Sumany patients.

● All patients shoutial candidates foand should undeevaluation and di

/min/m2. d

oronary Arteriography. Sones and colleagues22 obtainedselective coronary arteriogram by inadvertently engaging

he right coronary artery during an aortogram. Subse-uently, coronary arteriography became routine in clinicalractice but required arterial cutdown. The development of

a percutaneous arterial accesstechnique by Seldinger16 and ofpreformed catheters by Judkins23

made coronary arteriography fea-sible for widespread use. The dataobtained by catheterization, ven-tricular and aortic angiography,and selective coronary arteriogra-phy are the foundation for evalu-ation of valvular heart disease.

Doppler Echocardiography andUltrasonography. Edler andHertz,24 using ultrasonography,first recorded the movement ofcardiac structures in 1953. EarlyM-mode echocardiography waseffective in the diagnosis of mitralstenosis; 2-dimensional echocar-diography allowed for real-timevisual morphologic evaluation ofcardiac structure and function. Su-

erimposition of Doppler by Hatle and colleagues25 allowedor indirect hemodynamic measurement. Transesophagealchocardiography increased the clarity and accuracy of aumber of valvular heart diseases.

Echocardiography/Doppler permitted the rapid initial as-essment of patients with mild, moderate, or severe valvulareart disease. It also was of great value not only in diag-osing unsuspected lesions but also in excluding disease.long with the chest x-ray and the electrocardiogram, echo-

ardiography/Doppler has become an essential componentf the clinical evaluation of patients with valvular heartisease. Computed tomography, electron beam computedomography, and cardiac magnetic resonance imaging haveot been proven superior to echocardiography/Doppler forhis purpose.

NDIVIDUAL LESIONS

itral Stenosisn 1954, the outstanding clinical cardiologist and scholaraul Wood26 described the clinical features, pathophysiol-gy, complications, and outcomes of mitral stenosis. Heocumented that, on average, the symptoms of mitral ste-osis began 19 years after rheumatic carditis.

As early as the 1920s, but mainly in the early 1950s,itral commissurotomy was performed by manual dilata-

ion (“finger fracture”).27 Later in the 1950s, the resultsere improved by using the Tubbs’ dilator, which is intro-

CE

ssment of the se-and regurgitation

el of accuracy.

in patients withresults in an im-

s, functional class,n, and pulmonaryl is improved in

considered poten-rventional therapyppropriate clinicaltic testing.

ICAN

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ld ber intergo a

uced from the left ventricular apex. Both of these proce-

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ures were “blind” (closed). When performed by a skilled,xperienced surgeon on an appropriate patient, closed mitralommissurotomy had an excellent outcome; the survivalas better than that of medical therapy (Figure 2),28 and the4-year survival was 84%.27 The next development wasopen” mitral commissurotomy, which incorporated extra-orporeal circulation. However, in skilled surgical hands,he results of closed and open mitral commissurotomiesere similar.29 In the early 1960s, mitral valve replacementrovided excellent results for those patients who were poorandidates for surgical commissurotomy.30

The 1980s ushered in the era of catheter balloon com-issurotomy; the double balloon technique was followed by

he Inoue balloon (Toray Medical Co, Ltd), which is still inurrent use. In randomized trials, catheter balloon commis-urotomy yielded outcomes at least as good as those ob-ained from closed or open surgical commissurotomy.31

ll 3 procedures yield the best results for mobile and

Table 1 Nobel Prize and Lasker Award-winningAchievements Relevant to Valvular Heart Disease

ilhelm Conrad Röntgen The Nobel Prize in Physics 1901“In recognition of the extraordinary

services he has rendered by thediscovery of the remarkable rayssubsequently named after him”

lexis Carrel The Nobel Prize in Physiology orMedicine 1912

“In recognition of his work onvascular suture and thetransplantation of blood vesselsand organs”

illem Einthoven The Nobel Prize in Physiology orMedicine 1924

“For his discovery of the mechanismof the electrocardiogram”

erhard Domagk The Nobel Prize in Physiology orMedicine 1939

“for the discovery of the antibacterialeffects of prontosil”*

ir Alexander Fleming,rnst Boris Chain, Siroward Walter Florey

The Nobel Prize in Physiology orMedicine 1945

“for the discovery of penicillin and itscurative effect in various infectiousdiseases”

ndré Frédéricournand, Wernerorssmann, Dickinson W.ichards

The Nobel Prize in Physiology orMedicine 1956

“for their discoveries concerningheart catheterization andpathological changes in thecirculatory system”

lbert Starr, Alainarpentier

Albert Lasker Clinical Research Award2007

“Surgeon-scientists whorevolutionized the treatment ofheart disease”

*Protonsil was the first synthetic drug used for treatment of general
bacterial infections in humans.
Table 2 Procedural Advances in Valvular Heart Disease

iscoveries by 6 Nobel Laureates who have had an impact onvalvular heart disease

dentification of the infecting organism of rheumatic feverstablishment of databaseserformance of randomized clinical trialseasurement of intracardiac pressures and calculation of valve

areaseft ventricular angiography, aortography, coronary

arteriographychocardiography/Dopplerotal cardiopulmonary bypass for intracardiac surgeryardiac Surgery:

CommissurotomyProsthetic heart valvesValve repairRobotic surgeryCoronary artery bypass graft surgeryPercutaneous catheter intervention for coronary artery

diseaseCatheter balloon commissurotomy

Table 3 Accomplishments in Valvular Heart Disease

irtual elimination of rheumatic valve disease in developedcountries

eduction of rheumatic fever, rheumatic fever recurrences, andrheumatic valve disease in developing countries

ecognition of drug-induced valve diseaseore accurate diagnosis of valve disease and assessment of

their severityignificantly better assessment of severity of valve diseasesefinition of valvular abnormality/pathologyorrection of valve abnormality/pathologyelief of mitral stenosis by percutaneous catheter techniqueppropriate selection of valve replacement device and procedure

resulting in improvement of symptoms, functional status,left ventricular function, pulmonary hypertension, andsurvival

Table 4 Recurrence of Rheumatic Fever*

PerYear, %

ComplianceRate, %

enzathine penicillin, 1.2 million(intramuscular) every 4 wk

0.4 94

ral penicillin G, 200,000 U once daily 5.5 50ulfadiazine, 1 g/d 2.8 50

*Data from Alban B, Epstein JA, Feinstein AR. Rheumatic fever inchildren and adolescents: a long-term epidemiologic study of subsequentprophylaxis, streptococcal infection and clinical sequelae. Ann Intern
Med. 1964;60(Suppl 5):1-129.

nlm

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onthickened or mildly thickened valves. Catheter bal-oon commissurotomy is now the first-line treatment foritral stenosis.30

ortic Regurgitationost patients described in the after-histories of Lewis4 had

hronic aortic regurgitation. There were 3 eras.32 The era ofyphilis: The data are largely from the preantibiotic era;yphilitic cardiovascular disease is now rare. The era of rheu-

101860 ‘70 ‘80 ‘90 1900 ‘10 ‘20 ‘30 ‘40 ‘50 ‘60 ‘70

YEAR

MO

RB

IDIT

Y P

ER

100

,000

50

100

200

20

300

Penicillin

Reported Rheumatic Fever, Denmark, 1862-1962

Figure 1 Incidence of rheumatic fever in Denmark from 1862to 1962. From the Public Health Board of Denmark, Copenha-gen, Denmark. This is a log scale; from 1860 to 1945 morbiditydecreased by approximately 75%. The time when penicillin wasavailable for clinical use (arrow). Adapted from Stollerman GH.Rheumatic Fever and Streptococcal Infections. New York:Grune & Stratton, Inc. 1975;21-146.

MITRAL STENOSISMITRAL STENOSIS(Functional Class II)(Functional Class II)

Figure 2 Closed mitral commissurotomtherapy in patients with severe mitral steseverely symptomatic (right). Adapted fro
lation. 1968;38(suppl V):68-76.
atic fever and carditis: On average, symptoms of aortic re-urgitation began 20 years after the occurrence of carditis.he incidence of death, angina, or heart failure was 87% atyears in the high-risk group and 8% at 15 years in the

ow-risk group.32 In the current era, aortic regurgitation issually the result of aortic root dilation with echocardiog-aphy/Doppler used to study the natural history.31 Ofsymptomatic patients with normal left ventricular ejectionraction, approximately 3% to 6% per year become symptom-tic or progress to left ventricular dysfunction; more than oneuarter of patients with left ventricular dysfunction becomeymptomatic per year; and the mortality for symptomaticatients is more than 10% per year. In addition, echocar-iographic data for left ventricular dimensions show that annd-diastolic dimension of �70 mm (�35 mm/m2) or annd-systolic dimension of �50 mm (�25 mm/m2) increaseshe chance that a patient will become symptomatic or de-elop left ventricular dysfunction.31 Left ventricular dys-unction precedes the development of symptoms in morehan half of asymptomatic patients.31,33

Arteriolar dilators were shown to have beneficial effectsn hemodynamics and left ventricular size during 1 year ofollow-up. These data set the stage for a randomized trialocumenting that long-acting nifedipine reduced or de-ayed the need for aortic valve replacement in asymp-omatic patients with normal left ventricular ejectionraction (Figure 3).33 In all symptomatic patients, aorticalve replacement was shown to have beneficial effects onymptoms, as well as left ventricular size and function, evenhen baseline left ventricular systolic function was abnor-al;34 minimally symptomatic and asymptomatic patientsith mild left ventricular dysfunction have the best out-

omes from the procedure.35

MITRAL STENOSISMITRAL STENOSIS(Functional Class III & IV)(Functional Class III & IV)

ociated with better survival than medicalwho were mildly symptomatic (left) and

SB, Gopinath N. Mitral stenosis. Circu-

y is assnosism Roy

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ortic Stenosisost cases of severe aortic stenosis currently seen in de-

eloped countries are calcific (so-called degenerative) and

Figure 3 Long-acting nifedipine administered twice daily re-sults in a lower incidence of the need for aortic valve replace-ment in asymptomatic patients with chronic severe aortic regur-gitation and normal left ventricular ejection fraction. FromScognamiglio R, Rahimtoola SH, Fasoli G, et al. Nifedipine inasymptomatic patients with severe aortic regurgitation and nor-mal left ventricular function. N Engl J Med. 1994;331:689-695.PTS � patients; AR � aortic regurgitation; LV � left ventricular.

operated

non-operated

AFigure 4 Survival is better after aortictherapy (non-operated) in patients with sevBanmann P, Manthey J, et al. The effectlation. 1982;66:1105-1110. B: Adapted fr
of aortic valve stenosis. Eur Heart J. 1988;9(su
ccur in older patients. Atherosclerosis and inflammationre important factors in the complex cause of calcific aortictenosis.36,37 The life expectancy of patients has markedlyncreased; calcific aortic stenosis is now the most commoneason for valve replacement.

In 1968, an analysis of autopsy data showed a 3-yearverage life expectancy for symptomatic patients with se-ere aortic stenosis.38 Twenty years later, a follow-up studyfter cardiac catheterization confirmed the short life expect-ncy.39 In both studies, life expectancy after the onset ofeart failure was only 1 to 2 years.

In the 1970s, the importance of correcting aortic valvereas for body size was recognized.40 Severe aortic stenosisas diagnosed as aortic valve areas of 1.0 cm2 or less (�0.6

m2/m2);41 more recently, severe aortic stenosis was defineds an aortic valve area of 0.7 cm2 or less (�0.4 cm2/m2). Aean aortic valve gradient of 50 mm Hg or more is usuallyreliable indicator of severe aortic stenosis.42

In symptomatic patients with severe aortic stenosis, aor-ic valve replacement has a beneficial effect on symptoms,eft ventricular function, left ventricular hypertrophy, andurvival (Figure 4).39,43 It also markedly improves symp-oms in patients with severe aortic stenosis and clinical heartailure; if patients have no history of myocardial infarctionnd the procedure is performed early, the left ventricularjection fraction normalizes in one half to two thirds ofatients (Figure 5).44 These positive outcomes also occur inatients with aortic stenosis, low aortic valve gradients, and

operatedoperated

nonnon--operatedoperated

Beplacement (operated) than with medicalrtic stenosis. A: Adapted from Schwarz F,ic valve replacement on survival. Circu-rstkotte D, Loogen F. The natural history

valve rere aoof aortom Ho

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evere left ventricular dysfunction if they have severe aortictenosis.45

itral Regurgitationn the early 1900s, mitral regurgitation was the mostommonly diagnosed valve lesion. At that time, physi-ians were strongly discouraged from overdiagnosingrganic mitral regurgitation, thus saving healthy subjectsrom invalidism.9

Mackenzie46 was well aware of the spectrum of thelinical aspects of mitral regurgitation, writing, “The reallyerious trouble in connexion with mitral regurgitation arises

mean ± SE

EJE

CT

ION

FR

AC

TIO

N

P<0.001

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0Pre-Op Post-Op

Peri-Op MI and late CHBPost-Op: Perivalvular Aortic Regurgitation

AVR FOR AS IN HEART FAILURE

Figure 5 Left ventricular ejection fraction improves and evennormalizes after aortic valve replacement in approximately twothirds of patients with severe aortic stenosis and clinical heartfailure. Adapted from Smith N, McAnulty JH, Rahimtoola SH.Severe aortic stenosis with impaired left ventricular functionand clinical heart failure. Results of valve replacement. Circu-lation. 1978;58:255-264. AVR � aortic valve replacement; SE� standard error; MI � myocardial infarction; CHB � com-plete heart block.

hen the muscle is impaired and the regurgitation is due to s

complication of the dilated orifice and diseased valve. Theubsequent results depend on the degree of the exhaustionf the muscle of the heart. The backward pressure resultingrom the regurgitation embarrasses the left auricle, pulmo-ary circulation, and right heart.” These observations, maden 1908, are valid even now.

The incidence of mitral regurgitation in patients withheumatic valve disease was documented to be 34%.9 Inhe late 1950s, ruptured chordae tendineae were recog-ized as the cause of acute mitral regurgitation. At the958 Goulstonian Lecture, Leatham47 gave his classicresentation on auscultation of the heart. However, hehought that late systolic sounds were pericardial/pleuraln origin and that the accompanying murmur wasinnocent” (Figure 16 in his article).47 Also in 1958,cKusick48 wrote a treatise on cardiovascular sounds,

escribing in considerable detail a “musical pleural peri-ardial murmur” often preceded by a click. He noted thathis sound had been described earlier, first in 1843 inatients with valves later determined at autopsy to benormal,” and then in 1880 by Osler.48

In 1963, on the basis of autopsy findings, Barlow andolleagues49 described mitral valve prolapse as a cause ofhese sounds. Subsequently, mitral valve prolapse wasiagnosed clinically by left ventricular angiography.chocardiography/Doppler represented a major advance

hat not only provided evidence of the causes of mitralegurgitation, including mitral valve prolapse, and theathophysiologic changes associated with mitral regurgi-ation, but also showed that mitral valve prolapse isommon and the most common cause of ruptured chordaeendineae, which became known as “flail leaflets.” Mitralegurgitation also can be caused by coronary artery dis-ase because of its effect on the left ventricle. Recently,ome drugs also have been shown to cause valvularegurgitation.50

Symptomatic patients with severe mitral regurgitationenefited from mitral valve replacement or repair. In asymp-omatic patients, mitral valve replacement or repair can beeferred until the onset of symptoms or evidence of leftentricular dysfunction, pulmonary hypertension, or atrialbrillation.51

ricuspid Valve Diseasen 1908 Mackenzie46 observed, “Although actual diseasef the valves is rare, incompetence of the tricuspid orifices extremely common . . . It should never be concludedhat no tricuspid regurgitation occurs because of the ab-ence of a murmur . . . A weak muscular wall and widerifice may give rise to no murmur.” These observationsemain relevant even today, and good methods for repair-ng or replacing tricuspid valves are still lacking. There is

great need for improvements in surgical techniques,eplacement valves, and assessment of patients for
urgery.

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URGERY

pen Heart Surgeryn 1954, John Gibbon Jr52 described the use of total cardio-ulmonary bypass for intracardiac surgery. This had annormous impact on valve surgery and completely changedts performance. Valve surgery has been the most importantdvance in the treatment of symptomatic patients with se-ere valve disease. Valve surgery markedly improves func-ional class, hemodynamics, and left ventricular function. Itlso has improved survival in patients with severe aortic oritral valve stenosis (Figures 2 and 4), and probably has

mproved survival in symptomatic patients with severe aor-ic or mitral regurgitation.

alve Replacementrosthetic heart valves are mechanical or biological. Bio-

ogical valves can be derived from patient tissues (au-ografts) or donor tissues (allografts, called homografts), oran be valves taken from another species (xenografts, calledbioprosthesis”).

Mechanical prosthetic heart valves were used in 1960 byarken and Starr. It was the initial results obtained by Starr

nd Edwards53,54 that changed the scene. Of Starr anddwards’ first 8 patients, all of whom were in advanced

StarrStarr--EdwardsEdwards

0 1 2 3 4 5 6 7 80

10

20

30

40

50

60

70

80

90

100

Time after operation (years)

Sur

viva

l (%

)

n=122

n=118

n=113

n=110

n=104

n=102

n=93

n=90

n=75

n=78

n=59

n=60

n=38

n=44

n=21

n=24

Figure 6 Survival (left) and event-free survival (right) after aoIrvine, Calif) and St Jude valve (St Jude Medical Inc, St Paul, Mpermission from Murday AJ, Hochstizky A, Mansfield J, et al. Amitral valve prostheses. Ann Thorac Surg. 203;76:66-74.

eart failure, 6 survived to leave the hospital and several b

esumed an active life; 1 patient is known to have survivednother 31 years. This epochal event was followed in 1963nd 1964 by an astounding surgical accomplishment dem-nstrating that valve replacement could be “safe.” McGoont al55 replaced native aortic valves with Starr-Edwardsalves (Edwards Life Sciences, Irvine, Calif) in 100 con-ecutive patients, most of whom were in severe heart fail-re, and all of the patients survived. Since 1960, Starr andolleagues have used the Starr-Edwards valve in 3653 pa-ients, 1 of whom survived 41 years.56 After improvementso the original model in 1965, the Starr-Edwards valve hasemained virtually unchanged, and no structural valve de-erioration has yet been observed. A randomized trial hashown that Starr-Edwards and newer St Jude (St Jude Med-cal Inc, St Paul, Minn) valves yield equally favorableutcomes up to 8 years of follow-up (Figure 6).57

Xenografts (heterografts) were first used in 1965 byarpentier et al,58 who coined the term “bioprosthesis.”59

oss60 used autografts in 1967.Procedures involving stentless bioprostheses, homografts,

r the “Ross principle” require aortic root replacement witheimplantation of coronary arteries, which poses a problemf reoperation is needed. Furthermore, data from morehan 400,000 patients from the Society of Thoracic Sur-ery database have shown that the operative mortality forhese procedures is approximately twice that for stented

St. Jude St. Jude

0 1 2 3 4 5 6 7 80

10

20

30

40

50

60

70

80

90

100

Time after operation (years)E

vent

-fre

e S

urv

ival

(%

)

n=112

n=106

n=101

n=92

n=85

n=83

n=75

n=72

n=55

n=59

n=42

n=45

n=25

n=32

n=12

n=17

lve replacement with Starr-Edwards valve (Carpentier-Edwards,Data with mitral valve replacement were similar. Adapted withctive controlled trial of St. Jude versus Starr Edwards aortic and

rtic vainn).

prospe

ioprosthesis.61

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The 2 largest randomized trials, the Edinburgh Heartalve trial62 and the Veterans Administration trial,63 com-ared a mechanical valve (original Delron-ring Bjork-hiley valve [Shiley Labs, Irvine, Calif]) with a porcineioprosthesis (Figures 7 and 8). The findings were similar:here was no significant difference in survival over 20ears with 1 exception (discussed below); there were noignificant differences in thromboembolism, infective en-ocarditis, or all-cause complications; the mechanicalalves did not deteriorate, but they had a higher rate ofleeding; and the bioprosthetic valves deteriorated at anncreasing rate. Only the Veterans Administration trial, inhich a larger number of patients underwent aortic valve

eplacement, showed a higher mortality for the porcinealve because of structural deterioration; however, noeterioration was observed in patients who were at least5 years old at the time of valve replacement.

The current choice is usually a mechanical valve ortented bioprosthesis.64 The choice between the 2 types ofrosthetic heart valves is a choice between which compli-ation is a greater problem for an individual patient and toe avoided: anticoagulants and its complications with aechanical valve or the structural valve deterioration and its

omplications with the use of a bioprosthesis. Patients un-ergoing aortic valve replacement who are at least 60 to 65ears of age should receive a bioprosthesis. Current datandicate that the Carpentier-Edwards pericardial valve has aower rate of structural deterioration than a porcine pros-hetic heart valve.64 In the Veterans Administration trial,nly 40% to 50% of the deaths after valve replacementere related to the prosthetic valve, confirming that sur-

0

20

40

60

80

100

Pat

ien

ts s

urv

ivin

g w

ith

o

rig

inal

pro

sth

esis

inta

ct (

%)

0 2 4 6 8 10 12 14 16 18 20Years after randomization

MechanicalBioporosthesis

AVR

MVR

Figure 7 Survival with original valve after aortic valve re-placement and mitral valve replacement in the Edinburgh HeartValve trial. Adapted from Oxenham H, Bloomfield P, WheatleyDJ, et al. Twenty year comparison of a Bjork-Shiley mechanicalheart valve with porcine bioprostheses. Heart. 2003;89:715-721.AVR � aortic valve replacement; MVR � mitral valve

sreplacement.

ival after valve replacement depends largely on patient-elated factors.63,65

All prosthetic heart valves are smaller in area than theative human valve and thus have the problem of valverosthesis–patient mismatch.40 After aortic valve replace-ent, severe mismatch (valve area � 0.6 cm2/m2) is asso-

iated with significant morbidity and increased mortality.64

alve Repairortic Valve. Aortic valve repair is performed most often

or congenital aortic stenosis with mobile, noncalcified aor-ic valves. Many of these valves are suitable for catheteralloon commissurotomy. Repair also is performed in se-ected patients with severe aortic regurgitation.

itral Valve. After Lillehei performed mitral valve repairo treat mitral regurgitation in 1957,65 many more surgeons,ncluding McGoon and Kay, advocated and practiced therocedure. It became even more popular in the 1970s, withhe elegant repair methods of Carpentier and Duran,65 andgain after 1983, when Carpentier66 described his sophisti-ated “French correction.” A major advantage to mitralalve repair, as opposed to replacement, is that it circum-ents both the complications of prosthetic valves and theeed for anticoagulation therapy associated with mechanicalrosthetics.

alve Surgery and Coronary Artery Disease. A combi-ation of valve surgery and coronary artery bypass graft

Figure 8 Department of Veterans Affairs trial of valvularheart disease. Fifteen-year survival after aortic valve replace-ment is better with a mechanical valve than with a bioprostheticporcine valve because of structural valve deterioration of theporcine bioprosthetic valve. With permission from Hammer-meister KE, Sethi GK, Henderson WG, et al. Outcomes 15 yearsafter valve replacement with a mechanical versus a bioprostheticvalve: final report of the VA randomized trial. J Am Coll Car-diol. 2000;36:1152-1158. DVA � developmental venous anom-aly; VHD � valvular heart disease; AVR � aortic valvereplacement.

urgery is the routine procedure in these patients.

FOe

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1

1

11

1

1

1

1

1

1

2

2

2

2

2

2

2

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3

3

3

3

3

3

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UTURE DIRECTIONSur hopes for further advancements in valvular heart dis-

ase are summarized in Table 5.

eferences1. Luderitz B. Book review. N Engl J Med. 2002;347:2175.2. LeRoy F. A Century of Nobel Prize Recipients, Chemistry Physics and

Medicine. New York, NY: Marcel Dekker, Inc; 2003;229-360.3. Comroe JH, Jr. Exploring the Heart. New York: WW Norton & Co;

1983;3-21.4. Lewis T (Sir). Special Report Series to the National Health Insurance

Joint Committee, Medical Research Committee. 1917:8.5. Grant RT. After-histories for 10 years of a thousand men suffering

from heart disease. Heart. 1933;16:275-334.6. Feinstein AR. Current problems and future challenges in randomized

clinical trials. Circulation. 1984;70:767-774.7. Fisher RA, Mackenzie WA. Studies in crop variation. II The manorial

response to different potato varieties. J Agric Sci. 1923;13:315.8. Alban B, Epstein JA, Feinstein AR. Rheumatic fever in children and

adolescents: a long-term epidemiologic study of subsequent prophy-laxis, streptococcal infection and clinical sequelae. Ann Intern Med.1964;60(Suppl 5):1-129.

9. Wood P. Disease of the Heart and Circulation. Eyre & Spottiswoode2nd Edition. 1956:471-604.

0. Stollerman GH. Rheumatic Fever and Streptococcal Infections. NewYork: Grune & Stratton, Inc. 1975;21-146.

1. Newsholme A. The Milroy lectures on the natural history and affinitiesof rheumatic fever: a study in epidemiology. Lancet. 1895;1:589-595,657-665.

2. Jones TD. Diagnosis of rheumatic fever. JAMA. 1944;126:481-484.3. Hellems HK, Haynes FW, Dexter L. Pulmonary ‘capillary’ pressure in

Table 5 Some Desirable Progress in the Future of ValvularHeart Disease

limination, or at least marked reduction, of rheumatic heartdisease in developing countries

etter knowledge of the development and growth of nativevalves, including the role of genetics and other factors

ore accurate and complete knowledge of the causes of valvedisease

etter assessment of severity of valve stenosisore accurate measured quantitative assessment of valveregurgitation

ore precise and accurate documentation of the natural historyof all asymptomatic patients with severe, moderate, and mildvalve disease

etter therapeutic options:harmacologic agents for primary and secondary preventionptimal timing of invasive proceduresetter PHV, including tissue-engineered (including stem cell)PHV

ercutaneous therapeutic proceduresetter therapeutic options for tricuspid valve diseaseybrid procedures (valve replacement � CABG/PCI), performedin a combined catheterization laboratory � operating room

arly diagnosis and treatment of emergencies in valvular heartdisease

PHV � prosthetic heart valve; CABG � coronary bypass graft surgery;PCI � percutaneous catheter intervention.

man. J Appl Physiol. 1949;2:24-29.

4. Lagerlöf H, Werkö L. Studies on the circulation of blood in man VI.The pulmonary capillary venous pressure pulse in man. Scand J ClinLab Invest. 1949;1:147-161.

5. Ross J, Jr. Transseptal left heart catheterization: a new method of leftarterial puncture. Ann Surg. 1959;149:395-401.

6. Seldinger SI. Catheter replacement of the needle in percutaneousarteriography; a new technique. Acta Radiol. 1953;39:368-376.

7. Gorlin R, Gorlin SG. Hydraulic formula for the calculation of thestenotic mitral valve, other cardiac valves, and central circulatoryshunts. Am Heart J. 1951;41:1-29.

8. Castellanos A, Pereiras R, Garcia AA. L’angio-cardiogra radio-opacachez l’enfant. Arch Estud Clin Habana. 1937;31:523-527.

9. Dodge HT, Sandler H, Ballew DW, et al. The use of biplane angio-cardiography for the measurement of left ventricular volume in man.Am Heart J. 1960;60:762-776.

0. Barrat-Boyes B, Wood EH. Cardiac output and related measurementand pressure values in the right heart and associated vessels, responseto the inhalation of high oxygen mixtures in healthy subjects. J LabClin Med. 1958;51:72-90.

1. Ehsani, Rahimtoola SH, Sinno MZ, et al. Left ventricular performanceduring convalescent phase of myocardial infection. Arch Int Med.1975;135:1539-1575.

2. Sones FM, Jr, Shirey EK, Prondfit WL, et al. Cinecoronary arteriog-raphy. Circulation. 1959;20:773.

3. Judkins MP. Selective coronary arteriography: a percutaneous trans-femoral technique. Radiology. 1967;89:815-824.

4. Edler I, Hertz CH. Use of ultrasonic reflectoscope for the continuousrecording of the movements of heart walls. Kunglia FysiografskaSallskapets I Lund Frohandlingar. 1954;24:1-19.

5. Hatle L, Angelsen BA, Tromsdal A. Non-invasive assessment of aorticstenosis by Doppler ultrasound. Br Heart J. 1980;43:284-292.

6. Wood P. An appreciation of mitral stenosis. Br Med J. 1954;1:1051-1063, 1113-1124.

7. John S, Bashi VV, Jairaj PS, et al. Closed mitral valvotomy: earlyresults and long term follow-up of 3724 consecutive patients. Circu-lation. 1983;68:891-896.

8. Roy SB, Gopinath N. Mitral stenosis. Circulation. 1968;38(supplV):68-76.

9. Hickey MSJ, Blacksone E, Kirklin JW, et al. Outcome probabilitiesafter surgical commissurotomy: implication for balloon commissurot-omy. J Am Coll Cardiol. 1991;17:29-42.

0. Rahimtoola SH, Durairaj A, Mehra N, Nuno I. Current evaluation andmanagement of patients with mitral stenosis. Circulation. 2002;106:1183-1188.

1. Bonow RO, Carabello B, de Leon AC. Task Force on practice guide-lines (Committee on management of patients with a report of theAmerican College of Cardiology/American Heart Association ACC/AHA guidelines for the management of patients with valvular heartdisease. J Am Coll Cardiol. 1998;32;1486-1582.

2. Rahimtoola SH. Indications for surgery in aortic valve disease. In:Yusuf S, Cairns J, Camm J, Gallen E, Gersh B, eds. Evidence BasedCardiology. London: BMJ Publishing Books; 1998:811-832.

3. Scognamiglio R, Rahimtoola SH, Fasoli G, et al. Nifedipine in asymp-tomatic patients with severe aortic regurgitation and normal left ven-tricular function. N Engl J Med. 1994;331:689-695.

4. Clark DG, McAnulty JH, Rahimtoola SH. Valve replacement in aorticinsufficiency with left ventricular dysfunction. Circulation. 1980;61:411-421.

5. Tornos P, Sambola A, Permanyar-Miralda C, et al. Long-term outcomeof surgically treated aortic regurgitation. J Am Coll Cardiol. 2006;46:1012-1017.

6. Freeman RV, Otto CM. Spectrum of calcific aortic valve disease:pathogenesis, disease progression, and treatment strategies. Circula-tion. 2005;111:3316-3326.

7. Rajamannan N, Bonow RO, Rahimtoola SH. Calcific aortic stenosis:an update. Nat Clin Pract Cardiovasc Med. 2007;4:254-262.

8. Ross J, Jr, Braunwald E. Aortic stenosis. Circulation. 1968;36(suppl
IV):61-67.

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9. Horstkotte D, Loogen F. The natural history of aortic valve stenosis.Eur Heart J. 1988;9(suppl E):57-64.

0. Rahimtoola SH. The problem of valve prosthesis-patient mismatch.Circulation. 1978;58:20-24.

1. Rahimtoola SH. Perspective on valvular heart-disease: an update. J AmColl Cardiol. 1989;14:1-23.

2. Griffith MJ, Carey C, Coltart DJ, et al. Inaccuracies of using aorticvalve gradients alone to grade severity of aortic stenosis. Br Heart J.1989;62:372-378.

3. Schwarz F, Banmann P, Manthey J, et al. The effect of aortic valvereplacement on survival. Circulation. 1982;66:1105-1110.

4. Smith N, McAnulty JH, Rahimtoola SH. Severe aortic stenosis withimpaired left ventricular function and clinical heart failure. Results ofvalve replacement. Circulation. 1978;58:255-264.

5. Connolly HM, Oh JK, Schaff HV, et al. Severe aortic stenosis with lowtransvalvular gradient and severe left ventricular dysfunction: results ofaortic valve replacement in 52 patients. Circulation. 2000;101:1940-1946.

6. Mackenzie J. Diseases of the Heart. Oxford University Press; 1908;220-234.

7. Leatham A. Auscultation of the heart. Lancet. 1958;2:703-708, 757-765.

8. McKusick VA. Cardiovascular Sound in Health and Disease. Balti-more, MD: Williams & Wilkins Co; 1958;202-212.

9. Barlow JB, Pocock WA, Marchand P, et al. The significance of latesystolic murmurs. Am Heart J. 1963;66:443-452.

0. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart diseaseassociated with fenfluramine-phentermine. N Engl J Med. 1997;337:581-588.

1. Rosenhek R, Rader F, Klaar H, et al. Outcome of watchful waiting inasymptomatic severe mitral regurgitation. Circulation. 2006;113:2238-2244.

2. Gibbon JH, Jr. Application of a mechanical heart and lung apparatusto cardiac surgery. Minn Med. 1954;37;171-180.

3. Starr A, Edwards ML. Mitral replacement: clinical experience with a
ball-valve prosthesis. Ann Surg. 1961;154:726-740.
4. Rahimtoola SH. The twenty-fifth anniversary of valve replacement: atime for reflection. Circulation. 1985;71:1-3.

5. McGoon DC, Pestana C, Moffitt EA. Decreased risk of aortic valvesurgery. Arch Surg. 1965;91:779-786.

6. Gao G, Wu YX, Grunkemeier GL, Starr A. Forty year survival withthe Starr-Edwards heart valve prosthesis. J Heart Valv Dis. 2004;13:91-96.

7. Murday AJ, Hochstizky A, Mansfield J, et al. A prospective controlledtrial of St. Jude versus Starr Edwards aortic and mitral valve prosthe-ses. Ann Thorac Surg. 203;76:66-74.

8. Carpentier A, Lemaigre G, Robert L. Biological factors affectinglong-term results of valvular homografts. J Thorac Cardiovasc Surg.1969;58:467-483.

9. Carpentier A, Dubost C. From xenograft to bioprosthesis. In: IonescuMI, Ross DN, Wooler GH, eds. Biological Tissue in Heart ValveReplacement. London: Butterworth; 1971:515-541.

0. Ross DN. Replacement of aortic and mitral valves with a pulmonaryautograft. Lancet. 1967;2:956-958.

1. Rankin JS, Hammill BG, Ferguson TB, Jr, et al. Determinants ofoperative mortality in valvular heart surgery. J Thorac CardiovascSurg. 2006;131:547-557.

2. Oxenham H, Bloomfield P, Wheatley DJ, et al. Twenty year compar-ison of a Bjork-Shiley mechanical heart valve with porcine biopros-theses. Heart. 2003;89:715-721.

3. Hammermeister KE, Sethi GK, Henderson WG, et al. Outcomes 15years after valve replacement with a mechanical versus a bioprostheticvalve: final report of the VA randomized trial. J Am Coll Cardiol.2000;36:1152-1158.

4. Rahimtoola SH. Choice of prosthetic heart valve for adult patients.J Am Coll Cardiol. 2003;41:893-894.

5. Rahimtoola SH. Lessons learned about the determinants of the resultsof valve surgery. Circulation. 1988;78:1503-1507.

6. Carpentier A. Cardiac valve surgery—“the French correction.” J Tho-
rac Cardiovasc Surg. 1983;86:323-337.

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Review

The Diagnosis and Management of ChronicRheumatic Heart Disease—An

Australian Guideline�

Warren Walsh, FRACP, FACC a,∗, Alex Brown, MPH, FCSANZ b andJonathan Carapetis, PhD, FRACP, FAFPHM c

a Department of Cardiovascular Medicine, The Prince of Wales Hospital, Sydney, Australiab Centre for Indigenous Vascular and Diabetes Research, Baker Heart Research Institute, Alice Springs, Australia

c Menzies School of Health Research, Darwin, Australia

Keywords. Heart valve disease; Valvular heart disease; Rheumatic heart disease; Aortic regurgitation; Mitral regurgita-tion; Mitral valve stenosis

Introduction

Chronic rheumatic valvular heart disease is the long-term result of recurrent acute rheumatic fever. It

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vices and major hospitals. (2) Follow-up care often posesmany difficulties because of geographical, cultural andother barriers. (3) Medication adherence is often difficultbecause of the many other daily problems facing Aborig-

©A

s a disease of poverty and disadvantage. In Australiahe burden of rheumatic heart disease is confined almostxclusively to our Indigenous population. The continuingigh burden of rheumatic heart disease contrasts greatlyith the virtual elimination of this problem from theon-Indigenous population. Australian Aboriginal andorres Strait Islander people have the distinction of hav-ng the highest per capita incidence of rheumatic fever andheumatic heart disease in the world.

This unacceptable situation prompted the Nationaleart Foundation of Australia and the Cardiac Society

f Australia and New Zealand to sponsor the prepara-ion of the first review of the diagnosis and managementf chronic rheumatic heart disease for Australia. Theiagnosis and management of chronic rheumatic valvu-

ar heart disease in the Indigenous population presentsany unique challenges compared to the non-Indigenous

opulation. For example: (1) A large number of Aborigi-al and Torres Strait Islander people live in communities

n rural and remote regions of central and northernustralia, which are at some distance from specialist ser-

inal and Torres Strait Islander families—for instance, insome situations long-term warfarin therapy may be prob-lematic and this will have a significant impact on the typeof valve surgery that can be performed.

This evidence-based review of chronic rheumatic heartdisease has been written primarily for health professionalsdealing with Aboriginal and Torres Strait Islander peoplebut the principles of diagnosis and management applyequally to the non-Indigenous population. The unac-ceptable health status of our Indigenous population canbe greatly improved by application of evidence-basedmedicine. Knowledge is available to diagnose, manageand control the high burden of rheumatic heart diseasein Australian Aboriginal and Torres Strait Island people.

Background and Management Principles

In Australia the vast majority of people with chronicrheumatic heart disease (RHD) are Aboriginal and Tor-res Strait Islander people, many of whom live in remoteareas of Western Australia, the Northern Territory and

eceived 9 May 2007; received in revised form 30 November007; accepted 3 December 2007; available online 1 April 2008

Queensland.1 It is difficult and expensive for Aboriginaland Torres Strait Islander people to travel to major centresfctr

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The Guideline was prepared by the RF/RHD Guidelineevelopment Working Group on behalf of the National Heart

oundation of Australia and the Cardiac Society of Australiand New Zealand. Other members of the Working Group werer. Keith Edwards, Royal Darwin Hospital, Darwin; Dr. Cliveadfield, Cairns Base Hospital, Cairns; Professor Diana Lennon,niversity of Auckland, Auckland, Ms Lynette Burton, Northest Tasmania Division of General Practice, Burnie; Dr. Gavinheaton, Adelaide Children’s Hospital, Adelaide; Dr. Nigel Wil-

on, Starship Children’s Hospital, Auckland.Corresponding author. Tel.: +61 2 9382 0770; fax: +61 2 9382 0792.-mail address: [email protected] (W. Walsh).

2007 Australasian Society of Cardiac and Thoracic Surgeustralia and New Zealand. Published by Elsevier Inc. Al

or cardiac services, often hospital based. Although spe-ialist outreach services are improving in many regions,he access to specialist care is suboptimal in rural andemote areas.2

The implementation of guidelines for chronic RHDas major implications for Aboriginal and Torres Strait

slanders health care services, especially in rural andemote regions. In addition to access to appropriate pri-

ary care services, best practice for RHD prescribes:

1) Secondary prevention with penicillin prophylaxis.

and the Cardiac Society ofts reserved.

1443-9506/04/$30.00doi:10.1016/j.hlc.2007.12.002

mailto:[email protected]

dx.doi.org/10.1016/j.hlc.2007.12.002

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272 Walsh et al. Heart, Lung and CirculationThe Diagnosis and Management of Chronic Rheumatic Heart Disease—An Australian Guideline 2008;17:271–289

Table 1. Levels of Evidence for Clinical Interventions and Grades of Recommendation

Level of Evidencea Study Design Grade of Recommendationb

I Evidence obtained from a systematic review of allrelevant randomised controlled trials (RCTs).

A—rich body of high-quality RCT data.

II Evidence obtained from at least one properly designedRCT.

B—limited body of RCT data orhigh-quality non-RCT data.

III-I Evidence obtained from well-designed pseudo-RCTs(alternate allocation or some other method).

C—limited evidence.

III-2 Evidence obtained from comparative studies withconcurrent controls and allocation not randomised(cohort studies), case-control studies, or interruptedtime series with a control group.

D – no evidence available – panelconsensus judgement.

III-3 Evidence obtained from comparative studies withhistorical control, two or more single-arm studies, orinterrupted time series without a parallel control group.

IV Evidence obtained from case series, either post-test orpre-test and post-test.

a Adapted from National Health and Medical Research Council. A guide to the development, implementation and evaluation of clinical practiceguidelines. Canberra: NHMRC, 1999.b Adapted from US National Institutes of Health. Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults:executive summary. Expert Panel on the identification, evaluation and treatment of overweight in adults. Am J Clin Nutr 1998;68:899–917. (Details can befound at www.nhlbi.nih.gov/guidelines/obesity/ob home.htm).

(2) Access to a specialist physician and/or cardiologist,preferably the same specialist over a prolonged time.

(3) Access to echocardiography.(4) Adequate monitoring of anticoagulation therapy in

patients with atrial fibrillation and/or mechanicalprosthetic valves.

The increasing availability of specialist outreach ser-vices and portable echocardiography should mean thatall RHD patients in Australia, regardless of location, haveaccess to most of these requirements.3,4

Secondary Prevention with Penicillin ProphylaxisThe fundamental goal in long-term management ofchronic RHD is to avoid, or at least delay, valve surgery.Therefore, penicillin prophylaxis for prevention of recur-rent ARF is a crucial strategy in the management ofpatients with chronic RHD. Where adherence to secondaryprevention is poor, there is greater need for surgical inter-vention and long-term surgical outcomes are not as good.5

Importance of EchocardiographyAll patients with murmurs suggestive of valve disease,or a past history of acute rheumatic fever (ARF), requireechocardiography (Level of evidence: Grade D—seeTable 1). This will detect any valvular lesion, and allowassessment of its severity and of left ventricular (LV) sys-tolic function. Many patients with chronic RHD do not

artery pressure. These objective echocardiographic dataare crucial in helping to determine the timing of any sur-gical intervention.

Monitoring Anticoagulation TherapyThe ability to adequately monitor and achieve thera-peutic anticoagulation levels may be difficult becauseof language and cultural differences, mobility of thepopulation and remoteness from pathology services.6

For these reasons there may be difficulties in achievinggood adherence to anticoagulation and other medica-tions in remote communities.6 Point-of-care internationalnormalised ratio (INR) testing is now available, and itsapplication needs to be systematically tested in remoteregions.7

Local RHD registers may also be useful in identifyingpatients requiring recall for INR monitoring. Despite thedifficulties, many Aboriginal and Torres Strait Islanderpatients requiring anticoagulant therapy achieve con-sistency of INR readings, as required in patients withmechanical prosthetic valves.

The specific valvular lesions in chronic RHD are dis-cussed in subsequent sections. Many patients (e.g. 47%of Top End Northern Territory RHD patients)8 will haveinvolvement of two or more valves, most commonly mitraland aortic, although pathology in one is usually domi-nant. The assessment of severity of each valvular lesion

have a past history of ARF, and it may be difficult tojudge their symptomatic status by standard clinical cri-teria (e.g. New York Heart Association Functional Class;NYHA FC) because of communication difficulties and cul-tural barriers. For example, many Aboriginal and TorresStrait Islander patients, especially those from remote com-munities, report few symptoms, even in the presence ofadvanced valvular disease.

Serial echocardiography plays a critical role in the diag-nosis and follow-up of rheumatic valve disease, allowingobjective monitoring of the severity of valve lesions, LVchamber size, LV function and any increase in pulmonary

can be made by echocardiography. Management is usu-ally focused on the most severe valve lesion, especiallywith regard to timing of intervention.

Mitral Regurgitation

Natural HistoryMitral regurgitation is the most common valvular lesionin RHD, and is particularly frequent in young patients,who have not yet developed scarred and stenotic valvesfrom persistent or recurrent valvulitis. In Aboriginal RHDpatients in the Northern Territory, 41% had pure mitral

http://www.nhlbi.nih.gov/guidelines/obesity/ob_home.htm

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Heart, Lung and Circulation Walsh et al. 2732008;17:271–289 The Diagnosis and Management of Chronic Rheumatic Heart Disease—An Australian Guideline

regurgitation while in children aged under 10 years, over90% of mitral valve lesions were pure regurgitation. Inpatients aged between 10 and 39 years, the proportion was60–70%.8

In chronic mitral regurgitation, volume overload ofthe left ventricle and left atrium occurs.9 This leads toincreased mitral regurgitant flow into the low pressureleft atrium, especially during the earliest phase of systole.LV and left atrial size increases in response to large vol-umes of regurgitant mitral blood flow. LV systolic functionmay remain within normal limits for many years, despitethe presence of severe mitral regurgitation. Eventually thisdegree of volume overload results in a progressive declinein systolic contractile function.

In mitral regurgitation, LV outflow resistance (after-load) is decreased by ejection into the low pressure leftatrium, so that the LV function may appear to be nor-mal or low normal, even when myocardial contractilityis impaired. Therefore, LV dysfunction is less likely to bereversible following mitral valve surgery than it is with aor-tic valve surgery for aortic regurgitation. The developmentof significant pulmonary vascular disease and pulmonaryhypertension is much less common in mitral regurgitationthan in mitral stenosis.

There is wide individual variation in the rate of progres-sion of mitral regurgitation, although many cases tend toprogress over the next 5–10 years especially if there is ar 10–12

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and radiological signs of pulmonary congestion in moreadvanced cases.

EchocardiographyEchocardiography allows accurate assessment of left ven-tricular (LV) size and systolic function, as well as leftatrial size.9,13,14 The two-dimensional (2D) images of therheumatic mitral valve are quite characteristic and canhelp confirm a diagnosis of RHD, even without previousdocumentation of ARF in patients from high-risk popula-tions.

The main features of pure mitral regurgitation is over-riding or prolapse of the anterior mitral valve leaflet due toelongation of the chordae to the anterior leaflet and, in themore severe cases, dilation of the posterior mitral annu-lus. This results in an eccentric posteriorly directed jet ofvariable severity depending on the degree of prolapse.15

There may be some thickening and tethering of either orboth leaflets, even in mild valvular disease. This resultsin an “elbow” (or “dog leg”) appearance of the anteriorleaflet and reduced mobility of the posterior leaflet. Thisabnormality is especially common if there is mild mitralstenosis. Leaflet and annular calcification tends to be a latedevelopment and is unusual in young patients.

Accurate measurement of LV end systolic and end dias-tolic dimensions and systolic function by M mode and 2Dechocardiography must be obtained. Patients with moder-aa

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ecurrence of ARF.

ymptomsatients with mild to moderate mitral regurgitation mayemain asymptomatic for many years.10 Patients withoderate to severe mitral regurgitation may also be

symptomatic or mildly symptomatic. Initial symptomsnclude dyspnoea on exertion, fatigue and weakness,13

nd these may progress slowly over time. Patients oftenecome symptomatic if they develop atrial fibrillation,articularly with a rapid ventricular rate. Worseningymptoms may also result from a recurrence of ARF orhordal rupture, both of which can cause an acute changen the severity of regurgitation.

xaminationn patients with mild to moderate mitral regurgitation,he LV apex will not be displaced, and there will be a

id- or pansystolic murmur heard best at the apex, whichay radiate laterally or medially, depending on the direc-

ion of the regurgitant jet.13 Patients with moderate orore severe mitral regurgitation will have an apex beat

isplaced to the anterior or mid-axillary line and a loudansystolic murmur maximal at the apex. There may ben associated diastolic murmur of mitral stenosis, or aid-diastolic murmur from increased transmitral flow.

CG/Chest X-RayCG and chest X-ray are not usually helpful in diagnosis of

his condition. In more severe degrees of mitral regurgita-ion, especially in older patients, atrial fibrillation may beresent. Chest X-ray will show an enlarged left ventricle

te or greater mitral regurgitation almost always have LVnd left atrial enlargement.Pulse Doppler and colour flow mapping in the left

trium allows a semi-quantitative estimate of the sever-ty of the mitral regurgitant jet. This is done by gradinghe area of the regurgitant jet in relation to the area ofhe left atrium and by examining the spectral intensityf the jet by pulse Doppler. Milder degrees of regurgi-ation may be missed, unless “sweeping” scans of the lefttrium and mitral valve from parasternal and apical win-ows are used. An experienced echocardiographer may beequired to distinguish physiological (trivial) from patho-ogical mitral regurgitation.

Quantitative grading of mitral regurgitation usingoppler echocardiography to calculate effective regurgi-

ant orifice area has been proposed as a more accurateethod to assess mitral regurgitation severity.16 How-

ver, this measurement is time consuming and technicallyemanding and therefore has not yet been widely used.Due to higher quality imaging, transoesophageal

chocardiography (TOE) provides more optimal evalua-ion of mitral valve morphology and is commonly usedre-operatively to help assess suitability for valve repairnd intra-operatively to assess adequacy of surgical repair.t is also useful in patients yielding poor image quality withransthoracic echocardiography, such as obese patients.

owever, TOE is usually only performed in urban or largeegional centres limiting its availability.

ardiac Catheterisationardiac catheterisation is only necessary when there isneed to exclude coronary artery disease. In Aborigi-

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nal and Torres Strait Islander people this may need to beconsidered in patients aged over 30 years because of thepremature onset of coronary artery disease in this popula-tion. Left ventriculography is another method of assessingthe degree of mitral regurgitation, but the radiographicassessment may be affected by catheter-induced ventric-ular ectopy.

Medical ManagementVasodilator drug therapy (e.g. dihydropyridines, ACEinhibitors) has been suggested as potentially beneficialfor volume-overloaded ventricles by decreasing the workof the overloaded left ventricle, potentially minimisingmyocardial damage and deferring the need for surgery.In contrast to aortic regurgitation, there are limited dataavailable on the efficacy of chronic vasodilator therapy forpatients with mitral regurgitation.

The absence of increased afterload in mitral regurgita-tion (instead there is a low resistance leak into the leftatrium) suggests that vasodilator therapy would not bebeneficial in improving outcome.17 Therefore, this drugtherapy is not recommended in the medical managementof mitral regurgitation, unless there is associated heartfailure, LV dysfunction or hypertension (Level IV, GradeC).

Medical therapy of complications, such as atrial fibrilla-tion, is described in ‘Mitral Stenosis’ section. Patients who

long-term results of mitral valve repair are superior tothose of mitral valve replacement in RHD. In a reportfrom Toronto, the 10-year survival rate for mitral valverepair was 88%, compared with 70% for bioprosthesesand 73% for mechanical prostheses.19 The superior sur-vival rate was statistically significant, even after correctionfor baseline differences between patient groups. The 10-year freedom from thromboembolic events was 93% forvalve repair, 93% for bioprostheses and 72% for mechani-cal valve replacement.

Valve repair for rheumatic mitral valve regurgitationis more technically demanding than repair of myxoma-tous mitral valves and the long-term results are not asgood. Nevertheless, very acceptable results have beenobtained centres that perform these operations regularly.In a French series of 951 patients, who had repair fordominant rheumatic mitral regurgitation, the in-hospitalmortality was 2% and the actuarial survival was 89% at 10years and 82% at 20 years.20 Freedom from re-operationwas 82% at 10 years and 55% at 20 years. Whether thesegood results for mitral valve repair can be extrapolatedto Aboriginal and Torres Strait Islander people is uncer-tain. Long-term results depend on the population studiedand therefore will be affected by the public health andgeneral social and geographical environments in whichpeople live.

For example, in a mitral valve surgical series from Barag-

develop evidence of clinical heart failure with symptomsand signs of fluid retention (e.g. elevated venous pressure)require diuretic therapy and ACE inhibitors.

In asymptomatic or mildly symptomatic patients withmoderate or more severe mitral regurgitation, echocardio-graphy should be performed at least every 6–12 months(Grade D). Measurement of LV dimensions, assessmentof systolic function, Doppler assessment of the degree ofregurgitation and estimation of pulmonary artery systolicpressure are essential with every study. Comparison withprevious studies is an important part of the process.

Surgical ManagementCHOICE OF OPERATION. The operation of choice for domi-nant or pure rheumatic mitral regurgitation is mitral valverepair, rather than replacement (Level II, Grade B).18,19

Mitral valve repair has a lower operative risk, and pro-vides better preservation of LV systolic function and abetter late clinical outcome than mitral valve replacement.In patients who are in sinus rhythm, it avoids the need forlong-term anticoagulation with warfarin. Stable, reliableanticoagulation requires a high level of engagement withthe health service. It is often difficult to achieve this in Abo-riginal and Torres Strait Islander patients, and warfarin isalso highly undesirable in women of childbearing age andyoung physically active men. Valve repair avoids the riskof many of the complications of prosthetic valves, includ-ing thromboembolic and bleeding events, infection, andstructural deterioration of bioprosthetic valves in youngerpatients.

Although there have been no randomised comparativetrials, more recent surgical experience has shown that the

wanath Hospital in Soweto, South Africa of predominantlyyoung patients, one-third of whom had active carditis, thelong-term results of repair were less satisfactory. The free-dom from valve failure was 66% after five years and 27%of patients required re-operation during that period.15,21

These authors concluded active carditis at the time ofsurgery was the major predictor of late valve failure.

Therefore, strict adherence to a prophylactic antibi-otic program post surgery is vital to prevent progressionof valvular disease due to recurrence of ARF. Regularechocardiographic studies are required in all patients postrepair to monitor the degree of any residual regurgitationand detect any increase in its severity that might suggestvalve failure.

The re-operation rate is higher with mitral valve repairthan replacement, but in experienced centres re-operationcan be carried out at low risk. This may require mitral valvereplacement, but initial valve repair should delay the needfor long-term anticoagulation for many years.

If the mitral valve is not suitable for repair, the optionsare valve replacement, either with a mechanical valveprosthesis or a bioprosthetic valve. The advantage ofmechanical valve prostheses is their long-term durabilitywith extremely low rates of failure. The major disad-vantage is the need for long-term anticoagulation withwarfarin. Patients with tilting disc or bileaflet valves in themitral position require a slightly higher target INR of 3.0(range 2.5–3.5), compared to those in the aortic position(2.5).22

The pros and cons of mechanical versus bioprostheticvalves are discussed in pages 9, 10. However, the majordisadvantage of bioprosthetic valves is their limited dura-bility, and it has been clearly documented that structural

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valve degeneration occurs earlier and is more commonwith mitral bioprosthetic valves than aortic bioprostheticvalves in younger patients.23 Nevertheless, a woman ofchildbearing years, who is in sinus rhythm but is notsuitable for repair, may need to be considered for bio-prosthetic valve replacement in order to avoid the hazardsof anticoagulation during pregnancy. After bioprostheticvalve replacement, most patients in sinus rhythm can bemanaged without long-term anticoagulation.22

The need for re-do valve surgery is higher in the Abo-riginal and Torres Strait Islander population than in otherpopulations.23 All patients need a careful pre-operativeassessment of the likelihood of adherence to anticoagula-tion therapy and monitoring before a decision regardingtype of operation is made. Poor adherence with antico-agulation is associated with less favourable long-termoutcomes, especially after mechanical valve replacement.

Other important factors influencing choice of operationare age, gender, adherence to other medications and socialcircumstance.

Indications for SurgeryPatients with severe mitral regurgitation should bereferred for mitral valve surgery if they become symp-tomatic, or if they have echocardiographic indicatorssuggesting LV systolic dysfunction (Level III-2, Grade B).These include evidence of reduced LV systolic function(≥Ai

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replacement, and thromboembolic sequelae are rarebecause there is usually no need for anticoagulation.

The arguments against early mitral valve surgery are:

(1) Up to 10% of patients develop significant mitralregurgitation after mitral valve repair, requiring re-operation within two years;

(2) In some patients initially thought to be suitable, themitral valve cannot be repaired, necessitating valvereplacement.

As indications for surgery in asymptomatic patientsare still evolving it is important that physicians car-ing for patients with asymptomatic moderate to severemitral regurgitation consult cardiac surgeons early, so thatappropriate care plans can be organised, taking into con-sideration the clinical and echocardiographic findings andthe patient’s individual circumstance.

Patients with mitral regurgitation and associated mitralstenosis, who have severely fibrotic, calcified valves,may require mitral valve replacement. Because of the

Table 2. Key Points in Managing Rheumatic MitralRegurgitation

Symptoms May be asymptomatic for manyyearsExertional dyspnoea and fatigue

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Indications for surgery Moderate/severe mitral reguritationwith symptoms NYHA FC II, III, IVAsymptomatic severe mitralregurgitation in childrenAsymptomatic severe mitralregurgitation in adults when:Reduced LVEF (<60%)LVESD ≥40 mmPulmonary hypertension (PAS>50 mmHg)

Choice of operation

Notes: LVEF, left ventricular ejection fraction; LVESD, left ventricular endsystolic diameter (Echo); NYHA FC, New York Hear AssociationFunctional Class; PAS, pulmonary artery systolic pressure.

ejection fraction <60%), or an LV end systolic diameter40 mm determined by echocardiography in the adult.25

critical LV end systolic dimension has not been identifiedn children.

In addition patients with severe mitral regurgitationho are asymptomatic or mildly symptomatic, should be

eferred for early surgical consultation.17 This is becauseompared to those with normal LV function, patients whoevelop reduced LV systolic function have increased sur-ical risk, less likelihood of restoring normal LV functionnd increased risk of late heart failure and death. Earlyeferral is particularly important in children. Additionalndicators favouring early referral for surgical consultationre progressive but rapid LV enlargement, the presence ofignificant pulmonary hypertension (PA systolic pressure50 mmHg) and chronic or recurrent atrial fibrillation.Nevertheless there is controversy about timing of

urgery in patients who are asymptomatic or mildly symp-omatic and have severe mitral regurgitation and normalV systolic function (ejection fraction ≥60%).17,26,27 Therguments for early valve repair in these patients include:

1) Borderline systolic function (LVEF 50–60%) may indi-cate LV dysfunction in severe mitral regurgitation, dueto the relatively low impedance to LV outflow;

2) In most cases mitral regurgitation slowly worsens, withmost patients becoming symptomatic during the next5–10 years10; and

3) These patients are very likely to be suitable for mitralvalve repair since younger patients tend to havepreservation of the anterior leaflet and chordae andrelatively pliable valve leaflets. The operative risk isvery low in patients repaired early compared to valve

xamination Pansystolic murmur at leftventricular apex

chocardiography Over-riding or prolapse of anteriormitral valve leafletThickened “dog leg” anterior mitralvalve leaflet, especially if associatedmitral stenosisRetrograde colour (mosaic)regurgitant jet into left atrium, oftenposteriorly directedSeverity graded by area of colourregurgitant jet in left atriumLeft ventricular chamberdimensions enlarged if moderate orgreater mitral regurgitationAssess left ventricular systolicfunction

ardiac catheterisation Only to exclude coronary arterydisease

edical management No role for vasodilators, e.g.nifedipineDiuretics and ACE inhibitors ifheart failure

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long-term morbidity accompanying prosthetic valvereplacement in many Aboriginal and Torres Strait Islanderpeople, and the frequent requirement for anticoagula-tion, it is often preferable to wait until the patient is moresymptomatic despite medical therapy (NYHA FC II-III),provided that LV systolic function is preserved (Table 2).

Mitral Stenosis

Natural historyThe natural history of mitral stenosis varies accordingto the population being studied. In the non Aboriginaland Torres Strait Islander population there is often alatent period of 20–40 years between episodes of ARFand presentation with mitral stenosis.28,29 However, in theAboriginal and Torres Strait Islander population, mitralstenosis progresses more rapidly and patients becomesymptomatic at a younger age. In some developing coun-tries, such as India, this trend is more marked wheremitral stenosis is not uncommon in children aged under10 years.

Approximately 30% of Aboriginal RHD patients in theNorthern Territory aged 10–19 years have mitral stenosis,and the mean age of all those with mitral stenosis is 33years.8 At the time of diagnosis, the majority of patientswith mitral stenosis do not recall having had ARF.

The progression of mitral stenosis is variable, and best30

left lateral position. It may be difficult to hear especially ifthe ventricular rate is rapid. An inexperienced health careprovider may miss this murmur in the resting patient. Itcan be accentuated by increasing the heart rate throughmild exercise. The duration of the murmur correlates withthe severity of mitral stenosis. If the patient is in sinusrhythm there will be pre-systolic accentuation, but this islost once atrial fibrillation occurs.

ECG/Chest X-RayECGs are not particularly helpful in diagnosing mitralstenosis, although they may show evidence of left atrialenlargement. However, an ECG shows whether the heartis in sinus rhythm or atrial fibrillation.

A chest X-ray may show left atrial enlargement andredistribution of pulmonary vascular flow to the upperlung fields. Calcification of the mitral valve apparatus maybe visible in lateral projections. If the patient has devel-oped heart failure, pulmonary congestion will be visibleon the chest X-ray.

EchocardiographyDoppler echocardiography is used to accurately charac-terise the severity of mitral stenosis and associated valvelesions, and assess LV function and left atrial size.13,31,34

Two-dimensional echocardiography can demonstrate thethickened, restricted anterior and posterior mitral valve

monitored with serial Doppler echocardiography. Morerapid progression may be due to undetected recurrencesof ARF. Secondary pulmonary hypertension results fromthe elevated pressures in the pulmonary vascular bed,leading to right ventricular (RV) hypertension, dilatationand tricuspid regurgitation.

SymptomsProgressive obstruction to LV inflow develops, leading toa diastolic gradient between the left atrium and ventri-cle. This gradient is accentuated by faster heart rates, forexample during exercise, or in the presence of atrial fibril-lation with rapid ventricular rates. Patients usually do notdevelop symptoms until the mitral valve orifice decreasesto <2 cm2.

The initial symptom is exertional dyspnoea, whichworsens slowly over time, with progressive fibrosis andnarrowing of the mitral valve orifice. Symptoms of heartfailure (orthopnoea, paroxysmal dyspnoea and occasion-ally haemoptysis) develop as the mitral valve orificedecreases to <1.0–1.5 cm2.31 Less commonly, patients maypresent with signs of arterial embolism from the leftatrium, such as a stroke or peripheral arterial occlusion.The occurrence of systemic embolism does not correlatewith the severity of mitral stenosis32,33 but is related to thepresence of atrial fibrillation.

Physical ExaminationIt may be possible to palpate a RV heave in the left paraster-nal region due to RV systolic hypertension.

The murmur of mitral stenosis is a low-pitched, dias-tolic rumble heard best at the apex, with the patient in the

leaflets, the doming motion of the anterior leaflet (elbow ordog leg deformity), involvement of subvalvular apparatusand any associated valvular calcification.

Estimation of the severity of mitral stenosis requires acontinuous wave Doppler study. When the flow is sampledacross the stenotic mitral valve, the mean velocity can bemeasured and mean gradient calculated. The mitral orificearea can be calculated, using either the pressure half-timemethod based on the slope of the mitral inflow velocity, orby direct planimetry of the stenotic orifice in the short axisif the image quality is good. The extent of any associatedmitral regurgitation can be assessed by examining the areaof regurgitant colour flow within the left atrium duringsystole. LV systolic function is usually preserved, althoughin some cases it may be reduced, particularly if the patienthas developed chronic atrial fibrillation with inadequatelycontrolled ventricular rate.

If tricuspid regurgitation is present, the pulmonaryartery systolic pressure can be estimated by measuringthe peak velocity across the tricuspid valve. This can beconverted into a pressure gradient using the Bernoulliequation (gradient = 4 × velocity2). By adding an estimateof right atrial pressure to the pressure gradient, RV sys-tolic pressure can then be calculated. In the absence ofpulmonary valve disease, RV systolic pressure is the sameas pulmonary artery systolic pressure.

Cardiac CatheterisationDoppler echocardiography has replaced cardiac catheter-isation as the gold standard for determining the severity ofmitral stenosis.31 Cardiac catheterisation is only requiredto identify associated coronary artery disease. Therefore,

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younger patients can be referred for interventional ther-apy without diagnostic cardiac catheterisation.

Medical ManagementPatients who develop congestive heart failure, with ele-vated venous pressure and/or pulmonary congestion,respond to oral or intravenous diuretic therapy (e.g.frusemide). In general, the treatment of symptomaticmitral stenosis is interventional therapy.

Atrial FibrillationThe most common complication of mitral stenosis is atrialfibrillation.32 Initially, this may be paroxysmal but even-tually it becomes chronic, as mitral stenosis and leftatrial dilatation progress. Approximately 40% of patientswith mitral stenosis will exhibit chronic atrial fibrillation,and the incidence increases with age and left atrial size.Atrial fibrillation may lead to systemic embolism fromleft atrial thrombi, which form predominantly in the leftatrial appendage (the area of lowest velocity). Patientswith mitral stenosis and chronic or paroxysmal atrialfibrillation should receive long-term prophylactic antico-agulation with warfarin (Level III-3, Grade C).22 However,left atrial thrombus can occur in mitral stenosis, even whensinus rhythm is present, due to left atrial dilatation, lowblood velocity and disorganised blood flow. Therefore,ppr

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Percutaneous Balloon Mitral ValvuloplastyThe treatment of choice for dominant or pure mitral steno-sis is percutaneous balloon mitral valvuloplasty (PBMV)(Level III, Grade B).37–40 The balloon catheter is insertedvia the femoral vein and placed in the left atrium, usingthe transeptal technique. The balloon is positioned acrossthe stenotic mitral valve and inflated, thereby separatingthe stenotic leaflets along the commissures.

The short-term and medium-term results are com-parable to surgical valvuloplasty.40,41 However, PBMVusually requires only one night in hospital, is consid-erably cheaper and has less associated morbidity thanmitral valve surgery.31 Mitral orifice area usually increasesto 1.5–2.0 cm2 or more following balloon valvuloplasty,with corresponding reduction in left atrial pressure andincrease in cardiac output. Symptoms of pulmonary con-gestion are relieved. Long-term results have been goodwith 65% of patients being free of restenosis 10 yearsafter the procedure.37–39 Repeat valvuloplasty can be per-formed, if restenosis leads to recurrence of symptoms,especially if the predominant mechanism of restenosis iscommissural fusion.

The most serious complication of the procedure istearing of the mitral valve leaflets and/or subvalvularapparatus, causing severe mitral regurgitation. Of 528patients with rheumatic mitral stenosis (mean age 56.1years) treated at the Prince of Wales Hospital in Sydney(oure

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rophylactic anticoagulation should also be considered foratients with mitral stenosis, a large left atrium and sinushythm.

Patients who develop atrial fibrillation with a rapidentricular rate may develop heart failure, includingulmonary oedema, and require intravenous diuretic

herapy. The ventricular rate in atrial fibrillation is bestlowed with beta-blockers, digoxin, rate-slowing cal-ium channel blockers (e.g. diltiazem), or combinationsf these medications. Anti-arrhythmics, such as amio-arone or sotalol, should not be used for long-termate or rhythm control of atrial fibrillation in youngeratients, because of long-term adverse effects includ-

ng pulmonary, thyroid (amiodarone) and pro-arrthymiasotalol).

When new onset atrial fibrillation is symptomatic, con-ideration should be given to direct current cardioversiono restore sinus rhythm (Grade B). Anticoagulation is indi-ated prior to this procedure22,35 and long term. Patientsan be anticoagulated initially with intravenous or lowolecular weight heparin to minimise the time required

efore performing cardioversion. The exclusion of atrialhrombus by transoesophageal echocardiography allowsardioversion to be performed within a few days, ratherhan after the previously recommended three weeks ofherapeutic anticoagulation.36

If sinus rhythm is achieved, the most effective medi-ations for maintenance are the Class III agents, sotalolr amiodarone. These are not recommended in youngeratients, as mentioned above. Anti-arrhythmic Class Igents, such as quinidine, procainamide or disopyramide,re also not recommended due to their pro-arrhythmicotential.

RM McCredie, personal communication, August 2005)nly 4% developed mitral regurgitation requiring semi-rgent mitral valve surgery, usually valve repair. Otherare complications are cardiac tamponade and systemicmbolism.

atient Selectionhe indication for PBMV is progressive exertional dysp-oea (NYHA FC II, III or IV), associated with documentedvidence of moderate or severe mitral stenosis (mitral ori-ce area <1.5 cm2) (Grade B).31,42 Asymptomatic patientssually do not need intervention, unless there is aistory of thromboembolism, paroxysmal atrial fibrilla-

ion or significant pulmonary hypertension (pulmonaryrtery systolic pressure >50 mmHg). Patients with pliable,obile, relatively thin valves with no or minimal cal-

ification and without significant thickening and fusionf the subvalvular apparatus, are the best candidates.his comprises the majority of symptomatic youngeratients. However, experienced operators can obtaincceptable results in older patients with less favourablenatomy.Patients with pure or dominant mitral stenosis requiring

ntervention should be referred for PBMV to a cen-re with considerable experience in the technique andocumented low complication rates, regardless of thenatomy of their mitral valves.31,40 Early referral is rec-mmended for younger patients as they have the mostavourable valve morphology and have the best long-termesults.

A large left atrial thrombus is a contraindication toBMV.40 However, it can often be performed safely in

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the presence of a small, stable thrombus in the left atrialappendage. Mild regurgitation is acceptable, but patientswith moderate or greater mitral regurgitation are not suit-able, and should be referred for surgery if symptoms aresignificant. Most patients do not develop worsening ofmitral regurgitation over time after successful PBMV.

Surgical ManagementPBMV has largely replaced surgical mitral commissuro-plasty and commissurotomy.40,41 In the relatively fewpatients who are not suitable for PBMV, every effort shouldbe made to repair the mitral valve rather than replace it, ifpatients are in sinus rhythm (Grade D). The goal of surgicalrepair is to restore the pliability of the mitral valve leafletsby excising fibrous tissue, secondary chordae and areas ofcalcification, and to increase the orifice area by performingtwo commissurotomies extended deep into the respectivefused papillary muscles.

Mitral valve replacement may be necessary in heavilycalcified valves, especially with subvalvular involvement.The choice of mitral valve prosthesis has been discussed

Table 3. Key Points in Managing Rheumatic Mitral Stenosis

Symptoms May be asymptomaticExertional dyspnoea, fatigue,palpitations

in ‘Mitral Regurgitation’ section. In the presence of parox-ysmal or chronic atrial fibrillation, replacement with amechanical prosthesis is usually recommended, sincelong-term anticoagulation is already required.

Replacement with a bioprosthesis may be necessary forfemales in the childbearing years (especially those in sinusrhythm), to avoid anticoagulation during pregnancy.

Surgery for Atrial FibrillationPatients with paroxysmal or chronic atrial fibrillation,who require mitral valve surgery, can have sinus rhythmrestored in more than 80% of cases with atrial ablationprocedures at the time of surgery using radiofrequencyand other modalities.43,44 In most cases, the mechanicalcontractile function of the atria returns. Since it is nowbelieved that most atrial fibrillation focal circuits origi-nate around the origin of the pulmonary veins, this siteis the main target of ablation. The addition of an abla-tion procedure usually prolongs the cross clamp time ofthe operation by 10–15 min. Not all surgical units are per-forming this procedure as it is a relatively new techniqueand long-term results are not yet available (Table 3).

Aortic Regurgitation

Natural HistoryModerate or more severe aortic regurgitation results in

Examination Low-pitched mid diastolic“rumble” at left ventricular apex

Echocardiography Thickened restricted “dog leg”anterior mitral valve leafletRestricted posterior leafletMeasure mean mitral gradientfrom continuous wave DopplersignalCalculate MVA from slope ofDoppler mitral inflow velocityCalculate PAS pressure frompeak tricuspid regurgitant jetvelocity (4V2)

Cardiac catheterisation Only to exclude coronary arterydisease

Atrial fibrillation CommonRate control using beta-blockersor digoxin, or considercardioversion if recent onsetNeed anticoagulation to preventthromboembolic complications

Indications for intervention Symptoms NYHA FC II-IVMVA <1.5 cm2 orPAS >50 mmHg
No left atrial thrombusMild or no mitral regurgitation
Procedure of choice Percutaneous balloon mitralvalvuloplasty by high volumeoperator/centre65% of patients free of restenosisafter 10 yearsMitral valve repair orreplacement if valve leafletsheavily calcified

Notes: MVA, mitral valve area; NYHA FC, New York Heart AssociationFunctional Class, PAS, pulmonary artery systolic; V, velocity.

LV overload with an increase in LV end diastolic volume,which helps maintain the increased total stroke volume.45

As the severity of regurgitation increases, the left ventri-cle undergoes progressive dilatation and hypertrophy. Inchronic aortic regurgitation there is often a long compen-sated phase with preserved systolic function, despite thepressure and volume overload. However, over time LVcontractile dysfunction occurs in the more severe cases.The rate of progression to symptoms and/or systolic dys-function is approximately 6% per year.17,46

Symptoms and Examination FindingsIn the chronic situation, many patients remain asymp-tomatic, despite having moderate or severe regurgitation.Eventually, dyspnoea on exertion occurs, sometimesaccompanied by orthopnoea and, in advanced cases,symptoms of frank congestive heart failure, such as parox-ysmal nocturnal dyspnoea and oedema.

Patients may also experience episodes of angina, despitehaving normal coronary arteries, probably due to hypoten-sion in diastole, when most coronary flow occurs. In severeaortic regurgitation, the pulse pressure is widened and theKorotkoff sounds are heard almost down to the pressureof zero. Examination usually reveals a forceful LV apicalimpulse, which may be displaced laterally and down-wards. An obvious waterhammer pulse at the brachialartery and a collapsing carotid pulse are clinical indica-tions of at least moderate aortic regurgitation.

The typical murmur of aortic regurgitation is a diastolic,blowing decrescendo murmur best heard at the left ster-nal border, with the patient sitting upright. In general, thelength of the murmur correlates with severity, with more

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severe cases producing a pan-diastolic murmur. There isusually an associated systolic murmur, even in the absenceof aortic stenosis, due to the increased antegrade flowacross the aortic valve and, in occasional cases, a mitraldiastolic murmur.

ECG/Chest X-rayWith severe aortic regurgitation, the ECG often showsnon-specific ST-T wave changes, with or without increasedLV voltages. Chest X-ray may show an enlarged left ven-tricle and a dilated ascending aorta.

EchocardiographyLV function is assessed quantitatively by measuring LVend systolic and end diastolic diameters. The degree of LVdilatation is usually greater in severe aortic than in severemitral regurgitation. The aortic valve is usually thickenedand the aortic root is dilated in more severe cases.

The extent of aortic regurgitation is examined withcolour flow mapping in the left ventricle.47,48 The spa-tial extent of the colour flow jet in the LV outflow tractis an approximate guide to the severity of aortic regur-gitation. If the area is at least two-thirds or more of theLV outflow tract, the regurgitation is in the moderate tosevere range. The depth of the jet in the left ventricle isalso of some value, although it may be obscured by turbu-lent mitral valve inflow, particularly in cases of associatedm

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the potential for slowing progression of LV dilatation, andhence delaying the need for surgery. These drugs mayalso be beneficial as these patients usually have systolichypertension. Most of the publications describe expe-rience with the dihydropyridine, nifedipine,49 althoughsmaller studies have shown that ACE inhibitors are alsoeffective.50 However, there is some recent evidence thatprior treatment with nifedipine or an ACE inhibitor doesnot reduce or delay the need for aortic valve replacementin patients with asymptomatic severe aortic regurgita-tion and normal LV function.51 Nevertheless until thereis more trial data, vasodilator therapy with nifedipine orACE inhibitors is still recommended for asymptomaticor mildly symptomatic patients with preserved systolicfunction and moderate or greater degrees of aortic regur-gitation (Level III-3, Grade C) especially when systolichypertension is present.

Patients with symptoms of pulmonary congestion willbenefit from diuretic therapy but should be referredfor surgery even if symptoms subside. Atrial fibrilla-tion is uncommon in aortic regurgitation, but may leadto symptomatic deterioration due to a rapid ventricularrate. Treatment comprises digoxin and rate slowing beta-blockers or calcium channel blockers, as described formitral valve disease. Cardioversion may need to be con-sidered.

Serial echocardiography is essential for monitoring LVsMyio

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itral stenosis.A useful method for assessing the severity of aortic

egurgitation is to sample diastolic flow in the descendinghoracic aorta from the suprasternal notch position. Theength and velocity of the reversed flow is proportional tohe severity of regurgitation. Pan-diastolic reversed flow,articularly with increased velocity, is indicative of mod-rate or severe regurgitation, while in more severe caseshere is reversal of diastolic flow in the abdominal aorta.

pressure half-time of <400 ms usually indicates at leastoderate aortic regurgitation. However, additional fac-

ors, such as heart rate and LV end diastolic pressure, canffect pressure half-time.47,48

ardiac Catheterisationardiac catheterisation is not required for diagnosis orssessment of the severity of aortic regurgitation. It shouldnly be carried out if coronary artery disease must bexcluded. Since coronary artery disease presents mucharlier in Aboriginal and Torres Strait Islander patients,oronary angiography may be required in those over0 years of age. Aortography may be carried out at theame procedure allowing assessment of the degree ofegurgitation and the dimensions of the ascending aorta.ncreasingly dense opacity due to contrast medium in theeft ventricle and slower clearance of contrast, correlates

ith greater degrees of aortic regurgitation.

edical Managementn asymptomatic patients with significant aortic regur-itation, vasodilator therapy has been demonstrated toeduce LV dilatation and regurgitant fraction.17 This has

ize and function and severity of aortic regurgitation.ild regurgitation usually requires evaluation every two

ears, whereas more severe regurgitation should be stud-ed every 6–12 months, depending on the extent and ratef serial change.

urgical Managementatients with moderate/severe aortic regurgitation, whoecome symptomatic, should be referred for surgery

Level III-2, Grade B).9,17,52 Without surgery symptomaticatients have a significantly impaired prognosis, the mor-

ality rate being over 20% per year. Patients with reducedystolic function (LVEF <50%) should be referred as soons possible for valve surgery, as long-term studies suggestrogression of heart failure and death occurs in up to 25%f these patients per year.53,54

SYMPTOMATIC AND MILDLY SYMPTOMATIC PATIENTS WITH SEVERE

ORTIC REGURGITATION. In patients with normal LV systolicunction and few or no symptoms, the aim is to delayurgery as long as possible, but before onset of LV sys-olic dysfunction.17 If serial echocardiography shows thathe LV end systolic diameter is approaching 55 mm, or theystolic ejection fraction is <55%, these patients shoulde referred for aortic valve surgery (Grade C).46 In addi-

ion, an LV end diastolic diameter >70 mm may be a signf increased cardiovascular risk and the need to considerurgery. More long-term outcome data are required beforeV end diastolic diameter can become a definitive criterionor surgical intervention.17

HOICE OF OPERATION. The options for aortic valve surgeryre replacement with either a mechanical valve, atented or a stentless bioprosthesis valve, or an aortic

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homograft.24,55 Other surgical options are either aorticvalve repair or the Ross procedure (pulmonary autograftwith homograft replacement of pulmonary valve).24 It isimportant that the choice of operation be fully discussedwith the patient and his or her family and, if possible, withthe patient’s primary health care provider before a finaldecision is made.

Replacement with a bioprosthesis has the advantage ofavoiding long-term anticoagulation. The main disadvan-tages of bioprostheses are their limited durability24,56 inyounger patients (15–50 years). Structural deteriorationof bioprostheses, such as the Hancock valve, has beenreported to be 50% at 10 years and 90% at 15 years.57

Newer, stentless bioprosthetic valves appear to have a sim-ilar rate of structural deterioration, at least up to 10 yearsfollow-up,58 but long-term outcome studies are not yetavailable.

Structural deterioration usually results in prostheticregurgitation, although some degree of prosthetic stenosismay also occur. It is important that bioprosthetic valves beregularly monitored by echocardiography to detect earlymanifestations of deterioration with regurgitation and/orstenosis. Late re-operation will be required in the major-ity of younger patients because of valve degeneration andrecurrence of symptoms.

Homografts are also subject to structural deterioration,often with associated calcification.59–61 Homografts have

in the Northern Territory, who had aortic or mitralvalve replacement with predominantly older generationmechanical prostheses, the number of major bleedingevents was higher at 2.2 per 100 patient-years, and therisk of embolism was also high at 3.9 per 100 patient-years, reflecting difficulties with anticoagulation.7,63,66 Inthis series, complications were most common in the firstfour years after surgery.

As with all prostheses, other complications such asendocarditis, prosthetic valve thrombosis, valve dehis-cence and haemolysis may occur.

Experience with repair of rheumatic aortic valves islimited.67 The Carpentier group in Paris has pioneeredthis approach, and has recently reported 92% freedomfrom re-operation at five years with cusp augmentationtechniques.68 Long-term results are not yet available.Repair is best in the early stages of rheumatic valvulardisease when the cusps are thin and pliable. Patients donot require warfarin but most receive antiplatelet therapy.However, there is little experience with aortic valve repairin Australia, and its role remains limited in the local envi-ronment. Patients at risk of recurrence of ARF, because ofpoor adherence with antibiotic prophylaxis, are not suit-able, as rheumatic activity can lead to valve dysfunction.

Another alternative for aortic valve surgery is theRoss procedure,69,70 which uses a pulmonary autograftfor aortic valve replacement and a homograft for pul-

the advantage of haemodynamics identical to that of anative aortic valve and the avoidance of anticoagulanttherapy if the patient is in sinus rhythm. However, lim-ited donor supply means that valves may not always beavailable. The largest follow-up study of aortic homograftsfound a 10 and 20-year freedom from tissue failure (devel-opment of significant regurgitation or stenosis) of 62%and 18%.62 Difficulties in obtaining donor homografts andthe significantly increased complexity of re-operation inmany of these patients, has led to this procedure becomingmuch less favoured in recent years, especially in youngerrheumatic patients.

Mechanical tilting disc/bileaflet prostheses have excel-lent long-term durability with favourable long-termoutcome if good warfarin adherence can be achieved. Ifpatients already have chronic atrial fibrillation requiringanticoagulation, the valve of choice is a mechanical valveprothesis. The main complications of mechanical valvesare bleeding and thromboembolic events, usually dueto problems with anticoagulation adherence.7,63 Patientswith newer disc/bileaflet mechanical aortic valves canusually be anticoagulated to a lower INR (2.0–3.0) thanwas needed with the earlier generation caged ball/discvalves, because these newer prostheses appear to havea lower risk of thromboembolism,22,64,65 especially inthe aortic position. However, there is still a risk ofembolism and bleeding complications occurring, espe-cially in some patients where stable anticoagulation isdifficult to achieve.

The incidence of major bleeding in non Aboriginaland Torres Strait Islander populations is approximately1.4 per 100 patient-years, and the risk of stroke is 0.6per 100 patient-years.64 In a series of Aboriginal patients

monary valve replacement. The surgery is more complexand consequently has a slightly higher operative risk.It is best suited for aortic valves in the later stagesof rheumatic disease when leaflets are thickened andretracted. It has the theoretical advantages of the valve“growing” in younger patients, anticoagulation not beingrequired and pregnancy not resulting in structural valvedegeneration.

However, recurrence of ARF can involve the neo-aorticvalve (pulmonary autograft) causing regurgitation. Latefollow-up has also shown that patients may develop signif-icant aortic regurgitation, especially after five years. The10-year freedom from re-operation was 75% in a recentsurgical series.71 Also in younger patients, structuraldegeneration of the pulmonary homograft, manifestingusually as pulmonary stenosis, remains a problem.72 Theneed for late reoperation is the principal limitation of theRoss procedure.

RecommendationsA careful pre-operative assessment of the likelihood ofmedication adherence, especially warfarin, is essential indetermining the choice of valve surgery. If stable antico-agulation is unlikely to be achieved, serious considerationshould be given to the use of an aortic bioprosthesis.Patients who demonstrate good adherence with medica-tions are suitable for replacement with the newer bileafletmechanical valve prosthesis, since they have the best long-term durability and highest freedom from re-operation.However, in young female patients every effort must bemade to avoid a mechanical prothesis, because of the sig-nificant risk to mother and foetus posed by anticoagulationduring pregnancy.

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Table 4. Key Points in Managing Rheumatic Aortic Regurgitation

Symptoms May be asymptomatic for many yearsExertional dyspnoea and fatigue

Signs Diastolic blowing, decrescendo murmur at left sternal border, usually associatedwith systolic ejection murmur

Echocardiography Retrograde diastolic regurgitant colour jet in LVOT and left ventricular chamberArea of jet in LVOT correlates with severityLeft ventricular chamber dimensions enlarged if moderate or greater aorticregurgitationMay have associated mitral valve diseasePan-diastolic reversed diastolic flow in descending thoracic aorta ifmoderate/severe aortic regurgitation (Doppler)Assess left ventricular systolic function

Cardiac catheterisation Only to exclude coronary artery disease

Medical management Vasodilator therapy with dihydropyridines (e.g. nifedipine), especially if systolichypertension in asymptomatic, moderate or greater aortic regurgitationDiuretics and ACE inhibitors if heart failure

Indications for surgery Moderate/severe aortic regurgitation with symptoms NYHA FC II-IVAsymptomatic moderate/severe aortic regurgitation if:LVEF <55%LVESD ≥55 mmLVEDD >70 mm

Choice of surgery Valve replacementBioprosthesis or homograft

-No warfarin if in sinus rhythm-Limited durability in younger patients

Mechanical valve-Warfarin required

Aortic valve repair: limited experienceRoss procedure:

Aortic Homograft (pulmonary valve) and pulmonary homograft replacementreplacement.

Ross procedure, aortic valve repair only in selected cases with experiencedsurgeons.

Notes: LVEDD, left ventricular end diastolic diameter; LVOT, left ventricular outflow tract; LVEF, left ventricular ejection fraction; LVESD, left ventricularend systolic diameter; NYHA, New York Heart Association.

Aortic homograft replacement is also a possible option,but is currently not favoured because of technical diffi-culties of late re-operation for valve degeneration. Aorticvalve repair or Ross procedure is another option inselected cases where the surgeon is skilled in the tech-nique (Table 4).

Aortic Stenosis

Natural HistoryRHD is an uncommon cause of aortic stenosis. Isolatedaortic stenosis is a very rare manifestation of RHD.73,74

It almost always occurs in the presence of associatedrheumatic mitral valve disease. As with rheumatic mitralstenosis, aortic stenosis results from progressive fibrosisand commissural fusion of valve cusps with eventual cal-cification. The obstruction to the LV outflow tract resultsin a significant systolic gradient between the left ventricleand aorta. A 50% reduction in aortic valve orifice resultsonly in a small gradient across the aortic valve, but >50%reduction results in a substantial increase in the gradient,LV pressure overload and the development of concentricventricular hypertrophy to compensate for the increasedsystolic wall stress. The natural history of aortic steno-

sis is variable in the individual patient, but it is generallyprogressive.

SymptomsThe classic symptoms of aortic stenosis are dyspnoea onexertion, angina and syncope. Symptoms are gradual inonset, but are usually slowly progressive over time, espe-cially if there is associated mitral valve disease.

ExaminationThe characteristic clinical finding in aortic stenosis isa loud, low pitched mid-systolic ejection murmur bestheard in the aortic area, radiating to the neck and theapex.75 In patients with haemodynamically significant aor-tic stenosis, useful physical signs are a slowed and reducedcarotid pulse upstroke, and the presence of a thrill in thesuprasternal notch. The murmur of aortic stenosis is some-times difficult to distinguish from mitral regurgitation.

ECG/Chest X-rayECG usually shows sinus rhythm and may demonstratevoltage criteria for LV hypertrophy. Sometimes there aresecondary repolarisation abnormalities. A chest X-rayusually shows normal heart size, unless there is associ-

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ated mitral regurgitation. Calcification of the aortic valvemay be visible in the lateral chest X-ray.

EchocardiographyTwo-dimensional echocardiography demonstrates thick-ened and restricted aortic valve leaflets. Left ventricularsize and systolic function can be assessed quantitatively.The peak and mean velocity across the aortic valve is mea-sured by continuous wave Doppler and converted to agradient using the simplified Bernoulli equation of gra-dient = 4 × velocity2. The aortic valve orifice area can alsobe calculated to help determine severity, and is especiallyuseful when the LV function is reduced, making the aor-tic gradient less reliable.45 In these circumstances an aorticvalve orifice area <1.0 cm2 usually indicates severe disease.

Cardiac CatheterisationCardiac catheterisation is usually not needed to measurethe severity of aortic stenosis, but may be required to doc-ument coronary artery disease if anginal symptoms aredisproportionate to the severity of aortic stenosis. Coro-nary angiography should also be considered in Aboriginaland Torres Strait Islander patients 30 years or older, dueto the high incidence of premature coronary artery dis-ease in this population group. If there is uncertainty aboutthe Doppler-derived gradients, it is important to measurethe trans-valvular aortic gradient at the time of cardiac

Table 5. Key Points in Management of Rheumatic AorticStenosis

Symptoms May be asymptomaticExertional dyspnoea, angina,syncope

Signs Low-pitched, systolic ejectionmurmur in aortic area

Echocardiography Thickened, restricted aortic valveleafletsMeasure peak and mean systolicgradient from Doppler velocityacross aortic valve (4V2)Access left ventricular systolicfunction

Cardiac catheterisation Only to exclude coronary arterydisease

Indications for surgery Symptoms plus mean systolicgradient >50 mmHg or AVA<1.0 cm2

Choice of surgery Valve replacement:Bioprosthesis or homograft

-Limited durability-No warfarin if in sinus

rhythmMechanical valve

-Long-term warfarin required

Notes: AVA, aortic valve area; V, velocity.

some patients with normal LV function have a gradient<50 mmHg and symptoms clearly due to aortic stenosis.Aortic valve surgery involves replacement with either amechanical valve, a bioprosthetic valve or a homograft24

(Table 5).

Multivalvular Disease

In patients with chronic rheumatic heart disease, boththe mitral and aortic valves may be involved (e.g. aor-tic regurgitation and mitral stenosis or aortic and mitralregurgitation). The management is usually that of thedominant lesion. However, the proximal valve lesion maymodify the effects of the distal lesion—e.g. severe mitralstenosis may prevent the development of significant LVdilation secondary to aortic regurgitation.

The progression of the milder valve lesion is variable.However, an Israeli follow-up study (mean 13 ± 7 years) ofrheumatic valvular disease patients (mean age 61 years)with mild aortic valve disease who had required mitralvalve surgery showed that in the vast majority of cases,the aortic valve disease remained stable without dis-ease progression.78 In younger patients, the degree ofadherence to antibiotic prophylaxis would be the majordeterminant of the progression of the non-operated valvedisease.

The combination of significant mitral and aortic regur-79

catheterisation and calculate the aortic orifice area.

Medical ManagementPatients usually do not become symptomatic until a mod-erate or severe systolic gradient develops (mean gradient>40–50 mmHg). Initially, symptoms are exertional dysp-noea and fatigue. However, many patients may remainasymptomatic, despite having evidence of haemodynam-ically significant aortic stenosis. Once symptoms develop,prognosis is poor without surgery.

Aortic ValvuloplastyPercutaneous aortic valvuloplasty76 may reduce severeaortic stenosis to moderate stenosis, but usually leavesa significant residual gradient. The procedure mayentail substantial morbidity and mortality, particularly inolder patients. Follow-up studies have shown that ini-tial improvement is usually not maintained after a fewmonths. There is a high restenosis rate, particularly in verydeformed valves.76 Aortic valvuloplasty is now reservedfor patients who are not candidates for surgery and there-fore, it has a limited application in patients with rheumaticaortic stenosis.

Surgical ManagementAortic valve replacement is a definitive therapy for symp-tomatic aortic stenosis (Level III-2, Grade B). It should beperformed in all patients with significant gradients and areduced valve orifice (mean gradient >50 mm, aortic valveorifice <1 cm2), once they develop exertional symptoms.77

It should also be considered in patients with significant LVdysfunction but with a lower aortic gradient. Occasionally,

gitation is a surgical challenge and carries a high risk ofventricular dysfunction.

Surgical intervention is indicated at the onset ofsymptoms, or if LV dysfunction is identified by echocardio-graphy. The preferred surgery for Aboriginal and TorresStrait Islander patients would depend on the likelihood

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of maintaining optimal anticoagulation. If significant dif-ficulties are anticipated the preferred surgery would bemitral valve repair, accompanied by aortic valve repair orbioprosthetic aortic replacement to minimise the likeli-hood of the need for long-term anticoagulation.

Pregnancy in Patients with Rheumatic HeartDisease

Normal pregnancy is associated with a 20–100% increasein blood volume, reduction in systemic vascular resis-tance and corresponding increase in cardiac output. Thesechanges begin during the first trimester, peaking at 28–30weeks of pregnancy and are then sustained until term. Theincrease in blood volume is associated with an increasein heart rate by 10–15 beats per minute. Because ofthe hyperdynamic circulation, innocent, soft mid-systolicmurmurs are common during pregnancy, particularlyalong the left sternal border. These circulatory changesof pregnancy will exacerbate any pre-existing valvulardisease. Sometimes RHD, especially mitral stenosis, isfirst diagnosed during pregnancy, through the detec-tion of a heart murmur or the development of heartfailure.80

Ideally, patients with known rheumatic valvular dis-ease should be properly assessed before pregnancy. Thisshould include a full history and examination, with func-tIrbnomctf

RTt(mtvwcmd2criw

MIwi

increases LV volume overload, but the decrease in sys-temic vascular resistance partly compensates for this.

Some patients may develop congestive heart failure,especially during the third trimester. These patientsmay need diuretics and vasodilator therapy. Angiotensinreceptor antagonists and ACE inhibitors are contraindi-cated during pregnancy. Therefore hydralazine andnitrates, or dihydropyridine calcium channel blockers(e.g. nifedipine), should be used if vasodilator therapy isneeded (Level IV, Grade C).

Vaginal delivery is usually possible in most patients withcongestive heart failure controlled with medication. Everyeffort should be made to avoid cardiac valve surgery dur-ing pregnancy because of the high risk of foetal loss.

Mitral StenosisMitral stenosis is the most commonly encountered valvu-lar lesion in pregnancy.31,82 The increase in blood volumeand cardiac output causes a significant increase in themitral valve gradient, especially during the second andthird trimesters. Pregnancy-associated tachycardia mayalso shorten diastolic filling and accentuate the gradient.In patients with moderate or severe mitral stenosis (mitralvalve orifice <1.5 cm2) symptoms of heart failure, includ-ing breathlessness due to pulmonary oedema, frequentlydevelop.

pbplcdpCs

tawonoslbcmcs

udiwiupw

ional assessment and a detailed echocardiographic study.f patients are already symptomatic due to significantheumatic valvular disease, serious consideration shoulde given to interventional therapy or surgery prior to preg-ancy, to avoid life-threatening complications which mayccur in these patients. In patients with moderate or severeitral stenosis (orifice area <1.5 cm2), PBMV should be

onsidered, even for the asymptomatic or mildly symp-omatic woman, because of the high risk of maternal andoetal complications during pregnancy.

isk Factorshe predictors of increased maternal and foetal risk in

he pregnant patient with rheumatic valvular disease are1) reduced LV systolic function, (2) significant aortic or

itral stenosis, (3) moderate or severe pulmonary hyper-ension, (4) a history of heart failure, and (5) symptomaticalvular disease before pregnancy.80 During pregnancy,omen with valvular heart disease should have serial

ardiac evaluations, the frequency of which is deter-ined by the severity of disease. Women with severe

isease may require specialist clinical evaluation every–3 weeks after 20 weeks gestation. Whenever there is ahange in symptoms, maternal cardiac status should beeviewed. A multidisciplinary approach to managements an important principle for care of the pregnant patient

ith rheumatic valvular disease.

itral/Aortic Regurgitationn general, pregnancy is well-tolerated in patientsith moderate or severe valvular regurgitation.81,82 The

ncrease in blood volume and cardiac output in pregnancy

In patients with mild or moderate symptoms duringregnancy, medical therapy with diuretics, digoxin and/oreta-blockers to slow heart rate is usually sufficient torovide symptomatic relief. Development of atrial fibril-

ation with a rapid ventricular rate requires initial rateontrol with the use of beta-blockers (e.g. metoprolol) andigoxin. A higher dose of digoxin is usually required inregnancy (e.g. 250 mcg bd). Diltiazem should be avoided.ardioversion should be considered if the patient remains

ymptomatic, or if rate control is inadequate.If the patient remains symptomatic despite medical

herapy, there is significant risk to both mother and foetus,nd relief of mitral stenosis is usually required. Patientsith NYHA Class III or IV symptoms with a mitral valverifice of <1.0–1.5 cm2, suitable valve characteristics ando atrial thrombus should undergo PBMV83,84 at the endf the second trimester or the beginning of the third. Theafety of this procedure in pregnancy has been well estab-ished in more than 250 patients.85 Cardiac surgery shoulde avoided because of the 30% foetal loss that occurs withardiopulmonary bypass.83 There is a small risk of trau-atic mitral regurgitation resulting from PBMV, but this

an usually be managed medically, without the need forurgery until after pregnancy.

In patients with mitral stenosis, vaginal delivery is thesual approach, with the use of assisted delivery devicesuring the second stage to avoid the need for push-

ng and shorten the second stage. Severe mitral stenosisith severe pulmonary hypertension is associated with

ncreased maternal and foetal risk during labour. This sit-ation requires multidisciplinary team care and carefullylanned delivery, usually by elective caesarean sectionith invasive haemodynamic monitoring.

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Aortic StenosisSevere rheumatic aortic stenosis in pregnancy is far lesscommon than mitral stenosis. Suspected aortic stenosisshould be accurately assessed by Doppler echocardiogra-phy. Most patients with mild or moderate aortic stenosiscan usually be safely followed during pregnancy. Rarecases with severe aortic stenosis (gradient over 50 mmHgand/or valve orifice <1.0 cm2) are at significant risk ofadverse maternal and foetal outcomes. In experiencedcentres, severely symptomatic patients can have percu-taneous balloon aortic valvuloplasty in order to avoid therisks of cardiac surgery.

Prosthetic Heart Valves in PregnancyIn the childbearing age group, tissue valves have the majoradvantage of not requiring anticoagulation if the patient isin sinus rhythm. However, the vast majority of patients willrequire re-operation later in life because of structural valvedegeneration. The choice of valve prosthesis in the child-bearing age group requires careful judgement of the needfor later re-operation weighed against the hazards of anti-coagulation in pregnancy required for mechanical pros-theses. There are also some reports of accelerated struc-tural valve degeneration of bioprosthetic valves duringpregnancy but his has not been confirmed in other stud-ies. Most patients with normally functioning prostheticvalves who are asymptomatic or only mildly symptomatic

valve thrombosis occurred with older generation pros-thetic valves (e.g. caged ball) often with unmonitored lowmolecular weight heparin or inadequate levels of anti-coagulation with unfractionated heparin.89 Therefore ifheparin (usually low molecular weight heparin) is used, itis essential that anticoagulation levels be regularly moni-tored with measurement of antifactor Xa (anti-Xa) levels.Anti-Xa monitoring may be difficult to obtain outside anurban environment. The addition of low-dose aspirin toheparin may reduce the risk of valve thrombosis.

The problems with heparin have led to the use ofwarfarin in pregnancy, especially in higher thromboticrisk patients with first generation mechanical valves inthe mitral position, atrial fibrillation or a history ofthromboembolism. Warfarin use in pregnancy is moreefficacious in preventing valve thrombosis, but is associ-ated with a high rate of foetal loss (up to 30%) and warfarinembryopathy (approximately 5–29%).86 The risk of embry-opathy is greatest during the first trimester, especiallybetween 6 and 12 weeks. This has led to a recommen-dation of using low molecular weight heparin for thefirst trimester to avoid the risk of embryopathy and thenswitching to warfarin until the 36th week of pregnancy.However, there is recent evidence that if the warfarin dosecan be ≤5 mg, the risk of foetal loss or embryopathy islow.81 This is usually possible with lower risk bi-leafletprostheses in the aortic position where an INR of 2.0–3.0

tolerate the haemodynamic changes of pregnancy well.However, heart failure may develop, especially if LV func-tion is already impaired. Treatment of symptomatic heartfailure requires digoxin, diuretics, hydralazine, nitratesand beta-blockers. ACE inhibitors and angiotensin antag-onists are contraindicated in pregnancy.

Mechanical Prosthetic Valves: Management ofAnticoagulation TherapyPregnant women with mechanical valves are a veryhigh-risk group in whom all anticoagulation optionspose maternal and/or foetal risks.85–90 Therefore,patients with mechanical prosthetic valves should begiven appropriate contraceptive advice and counselledabout the risks to mother and foetus with pregnancy(Grade D).

The high risk is due to the hypercoagulable state thatexists throughout pregnancy and the adverse effects ofanticoagulation on mother and foetus. Warfarin crossesthe placenta, increasing the risk of early abortion, embry-opathy and late foetal loss. Both unfractionated and lowmolecular weight heparin do not cross the placenta, andhave been suggested as alternatives to warfarin dur-ing pregnancy.91,92 However, the rate of prosthetic valvethrombosis in patients treated with heparin has beenreported as high as 20%.86,93 The risk of maternal throm-boembolism and maternal death also more than doublein the first trimester with the use of heparin, especiallywhen more aggressive therapeutic anticoagulation mustbe used with older generation mechanical valves, such ascaged ball or tilting disc in the mitral position.93 Mostof the reported cases of heparin-associated prosthetic

is usually adequate.It is important that the choice of anticoagulant regimens

be fully discussed with the pregnant patient and family,preferably before pregnancy and certainly early in the firsttrimester. After the patient agrees to the use of an anticoag-ulant regimen, written consent should be obtained, or thedecision fully documented in the patient’s health record(Grade D).

Recommendations for Anticoagulation in Pregnancy inPatients with Mechanical ValvesThere is limited published data available on anticoagu-lant options and no randomised comparative studies havebeen or are likely to be performed. There is a choice ofthree different anticoagulant regimens during pregnancyfor patients with mechanical prostheses (Level IV, GradeC).86,89

1. LOW MOLECULAR WEIGHT HEPARIN (LMWH) THROUGHOUT

PREGNANCY.

Weight-adjusted dose LMWH throughout pregnancy,administered subcutaneously every 12 h with anti-Xamonitoring.The dose must be adjusted to maintain a trough (pre-dose) level of anti-Xa heparin level of 0.6 U/ml in casesat lower risk (aortic valve prosthesis) and at 0.7 U/mlin higher risk patients (older generation prostheticvalve in mitral position). Peak levels should not exceed1.5 U/ml. Anti-Xa levels should be measured every2 weeks.The addition of low dose aspirin daily (75–100 mg) mayadd additional antithrombotic efficacy.

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LMWH ceased 36 h before delivery or at onset oflabour. Unfractionated heparin used until onset oflabour.

2. LMWH/WARFARIN.

LMWH as above up to 13 weeks of gestation with moni-toring of anti Xa levels as above.Warfarin for weeks 13–36.Switch to LMWH or intravenous unfractionated heparinat 36 weeks of gestation.Addition of low dose aspirin (75–100 mg) may add addi-tional antithrombotic efficacy.Reversal of warfarin with vitamin K and caesarean sectionif onset of labour prior to cessation of warfarin.LMWH—should be ceased 36 h before elective deliv-ery or at onset of labour and UFH used until onset oflabour.

3. WARFARIN THROUGHOUT PREGNANCY (ESPECIALLY OLDER

PROSTHESES).

Maintain target INR with as low a dose of warfarin aspossible.Switch to LMWH or UFH at 36 weeks because about 30%of patients have premature labour.Addition of low-dose aspirin daily (75–100 mg) may addadditional antithrombotic efficacy.Reversal of warfarin with vitamin K and caesarean sectionif onset of labour prior to cessation of warfarin.LMWH ceased 36 h before delivery or at onset of labour.UFH used until onset of labour.

Because of risk of prosthetic thrombosis with heparinand the difficulty in obtaining anti-Xa monitoring, theEuropean Society of Cardiology has recently stronglyrecommended regimen 3 as the preferred anticoagu-lation approach in patients with mechanical prosthetic

Table 6. Key Points in Management of Pregnancy in Patients with Chronic Rheumatic Heart Disease

Blood volume increases 20–100%Will exacerbate any pre-existing rheumatic valvular heart disease

Factors that put pregnancy and mother at increased risk Decreased left ventricular systolic functionSignificant aortic and mitral stenosisPulmonary hypertensionHeart failureSymptoms before pregnancy

C EavaPl

M UTrin

M MMpetri>5Be

A MDBeAv

M HRiEm

C

L

Na

ardiac assessment

itral/aortic regurgitation

itral stenosis

ortic stenosis (rare)

echanical/prosthetic valves and anticoagulation in pregnancy

hoice of three antithrombotic regimens 1.an2.INof3.wle

abour HvaAmAAp

otes: Anti-Xa, anti-factor Xa; AVA, aortic valve areas; INR, international normarea; PAS, pulmonary artery systolic; UFH, unfractionated heparin.

rly comprehensive assessment with echocardiography to assesslves and left ventricular functionan multidisciplinary management

sually well toleratedeat medically with diuretics, vasodilators (no ACEhibitors/angiotensin II receptor blockers) for heart failure

ild to moderate mitral stenosis—manage medicallyoderate to severe mitral stenosis (MVA < 1.5 cm2)—considerrcutaneous balloon mitral valvuloplasty during late secondmester if patient remains symptomatic and PAS pressure0 mmHg.ta-blockers, digoxin for rate control of atrial fibrillation

ild to moderate well tolerated.iuretics for heart failureta-blockers, digoxin for rate control of atrial fibrillationoid cardiac surgery, as high risk of foetal loss

igh maternal and foetal risksk of warfarin embryopathy in first trimester

bryopathy may be avoided if warfarin dose ≤5 mg

LMWH throughout pregnancy, weight adjusted dose withti-Xa level monitoringWarfarin throughout pregnancy if can keep warfarin ≤5 mg, e.g.R 2.0–3.0 in aortic prosthesis, sinus rhythm; change to LMWHUFH at 36 weeksLMWH until 13 weeks and then warfarin and aspirin until 36eeks; change to LMWH or UFH until labour. Monitor anti-Xavels with LMWH

aemodynamic monitoring—non invasive if mild to moderatelve disease

ntibiotic prophylaxis if prolonged labour and/or rupturedembranesim for short second stage, multidisciplinary management

proach with low threshold for obstetric intervention

lised ratio; LMWH, low molecular weight heparin; MVA, mitral valve

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valves—i.e. warfarin throughout pregnancy until the 36thweek.94

Management of DeliveryPatients on low molecular weight heparin at the end ofpregnancy should be switched to unfractionated heparinat least 36 h prior to elective delivery in the 38th week.Patients receiving warfarin should be switched to hep-arin at 36 weeks, since about 30% experience prematurelabour.88 Labour is induced and IV heparin ceased oncelabour is established, or 4–6 h before caesarean section,and resumed 6–12 h after delivery. Vaginal delivery is rec-ommended if the patient is not on warfarin at the onsetof labour and there is no significant prosthetic dysfunc-tion or other significant cardiac disease. Careful titrationof the IV heparin over the first 3–4 days postpartumis necessary, particularly following caesarean section, toavoid major bleeding. Warfarin is recommenced 24–48 hafter delivery, and the heparin ceased once INR isover 2. Breastfeeding can be encouraged in women tak-ing anticoagulants, as heparin is not secreted in breastmilk and the amount of warfarin in breast milk is low(Grade C).

Endocarditis ProphylaxisPatients with prosthetic valves or with a history ofinfective endocarditis are at higher risk and there-fore should receive prophylactic antibiotics prior to

2. Australian Institute of Health and Welfare. The health and wel-fare of Australia’s Aboriginal and Torres Strait Islander Peoples.Canberra: Australian Institute of Health and Welfare; 2005.

3. Gruen RL, Bailie RS, d’Abbs PH, O’Rourke IC, O’Brien MM,Verma N. Improving access to specialist care for remoteAboriginal communities: evaluation of a specialist outreachservice. Med J Aust 2001;174(10):507–11.

4. Salustri A, Trambaiolo P. Point-of-care echocardiography:small, smart and quick. Eur Heart J 2002;23(19):1484–7.

5. Carapetis JR, Powers JR, Currie BJ, Sangster JF, Begg A, FisherDA, Kilburn CJ, Burrow JNC. Outcomes of cardiac valvereplacement for rheumatic heart disease in Aboriginal Aus-tralians. Asia Pacific Heart J 2000;8(3):138–47.

6. Smyth T. Anticoagulation in patients with metallic valvu-lar prosthesis in the Top End of the Northern Territory. In:39th CARPA Conference Central Australian Rural PractitionersAssociation in conjunction with the Royal Australasian College ofPhysicians NT Annual Scientific Meeting. 2003.

7. Gill JM, Landis MK. Benefits of a mobile, point-of-care anti-coagulation therapy management program. Jt Comm J QualImprov 2002;28(11):625–30.

8. Carapetis JR. Ending the heartache: the epidemiology andcontrol of acute rheumatic fever and rheumatic heart diseasein the top end of the northern territory, 1998. UnpublishedDoctor of Philosophy thesis, University of Sydney, Sydney.

9. Carabello BA, Crawford FA. Valvular heart disease. New EnglJ Med 1997;337(1):32–41.

10. Enriquez-Sarano M, Basmadjian AJ, Rossi A, Bailey KR,Seward JB, Tajik AJ. Progression of mitral regurgitation—aprospective Doppler echocardiographic study. J Am Coll Car-

delivery.89 The role of prophylactic antibiotics at thetime of delivery in patients with valvular heart dis-ease is controversial. Recent reports have suggested ahigher rate of bacteraemia than previously thought. This,together with the seriousness of endocarditis in theperipartum period, has led to some major centres rec-ommending prophylactic antibiotics for all patients withvalvular heart disease having a vaginal or abdominaldelivery.82 However, antibiotics are certainly recom-mended if labour is prolonged or if there is prematurerupture of the membranes. The recommended regimeis ampicillin 2.0 g IV plus gentamycin (1.5 mg/kg not toexceed 120 mg) given at the start of labour or within30 min of caesarean section. A second dose of IV ampi-cillin or oral amoxicillin should be given 6 h later(Table 6).

Acknowledgments

The working group wishes to acknowledge the financialsupport provided for the preparation of this review bythe National Heart Foundation of Australia and the Car-diac Society of Australia and New Zealand. Content of thismanuscript is copyright of the National Heart Foundationof Australia and reproduced in this article with permis-sion

References

1. Australian Institute of Health and Welfare. Rheumatic heartdisease: all but forgotten in Australia except among Aboriginals andTorres Strait Islander Peoples. Canberra: Australian Institute ofHealth and Welfare; 2004.

diol 1999;34(4):1137.11. Marcus RH, Sareli P, Pocock WA, Barlow JB. The spectrum

of severe rheumatic mitral valve disease in a developingcountry. Correlations among clinical presentation, surgicalpathologic findings, and hemodynamic sequelae. Ann Int Med1994;120(3):177–83.

12. Meira ZMA, Goulart EMA, Colosimo EA, Mota CCC. Longterm follow up of rheumatic fever and predicators of severerheumatic valvular disease in Brazilian children and adoles-cents. Heart 2005;91:1019–22.

13. Rodriguez L, Gillinov AR. Mitral valve disease. In: Topol EJ,Califf RM, editors. Textbook of Cardiovascular Medicine. Lippin-cott Williams & Wilkins; 2006.

14. Otto CM. Evaluation and management of chronic mitralregurgitation. N Eng J Med 2001;345(10):740–6.

15. Essop MR, Nkomo VT. Rheumatic and non-rheumatic valvu-lar heart disease: epidemiology, management and preventionin Africa. Circulation 2005;112(23):3584–91.

16. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, DetaintD, Capps M, Nkomo V, Scott C, Schaff HV, Tajik AJ. Quanti-tative determinants of the outcome of asymptomatic mitralregurgitation. N Engl J Med 2005;352(9):875–83.

17. Borer JS, Bonow RO. Contemporary approach to aortic andmitral regurgitation. Circulation 2003;108(20):2432–8.

18. Thourani VH, Weintraub WS, Guyton RA, Jones EL, WilliamsWH, Elkabbani S, Craver JM. Outcomes and long-term sur-vival for patients undergoing mitral valve repair versusreplacement. Effects of age and concomitant coronary arterybypass grafting. Circulation 2003;108(3):298–304.

19. Yau T, El-Ghoneimi YA, Armstrong S, Ivanov J, David TE.Mitral valve repair and replacement for rheumatic heart dis-ease. J Thorac Cardiovasc Surg 2000;119(1):53–61.

20. Chauvaud S, Fuzellier JF, Berrebi A, Deloche A, Fabiani JN,Carpentier A. Long term(29 years) results of reconstructivesurgery in rheumatic mitral valve insufficiency. Circulation2001;104(12 Suppl. 1):I12–5.

RE

VIE

W


21. Skoularigis J, Sinovich V, Joubert G, Sareli P. Evaluation of thelong-term results of mitral valve repair in 254 young patientswith rheumatic mitral regurgitation. Circulation 1994;90(5 Pt2):167–74.

22. Salem DN, Stein PD, Al-Ahmad A, Bussey HI, HorstkotteD, Miller N, Pauker SG. Antithrombotic therapy in valvu-lar heart disease—native and prosthetic. Chest 2004;126(3Suppl.):457S–82S.

23. McLean A, Waters M, Spencer E, Hadfield C. Experience withcardiac valve operations in Cape York Peninsula and TorresStrait Islanders, Australia. MJA 2007;186(11):560–3.

24. Rahimtoola SH. Choice of prosthetic heart valve for adultpatients. J Am Coll Cardiol 2003;41(6):893–904.

25. Wisenbaugh T, Skudicky D, Sareli P. Prediction of outcomeafter valve replacement for rheumatic mitral regurgitation inthe era of chordal preservation. Circulation 1994;89(1):191–7.

26. Otto CM, Salerno CT. Timing of surgery in asymptomaticmitral regurgitation. N Engl J Med 2005;352(9):928–9.

27. Bonow RO, Carabello BA, Chatterjee K, de Leon Jr AC,Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishirmura RA,O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS.ACC/AHA 2006 guidelines for the management of patientswith valvular heart disease: a report of the American Col-lege of Cardiology/American Heart Association Task Force onPractical Guidelines (Writing Committee to Develop Guide-lines for the Management of Patients with Valvular HeartDisease). Circulation 2006;114:e84–231.

28. Rowe JC, Bland EF, Sprague HB, White PD. The course ofmitral stenosis without surgery: ten-and twenty-year perspec-tives. Ann Intern Med 1960;52:741–9.

37. Turi ZG, Reyes VP, Raju BS, Raju AR, Kumar DN, RajagopalP, Sathyanarayana PV, Rao DP, Srinath K, Peters P. Percuta-neous balloon versus surgical closed commissurotomy formitral stenosis. A prospective randomized trial. Circulation1991;83(4):1179–85.

38. Hernandez R, Banuelos C, Alfonso F, Goicolea J, Fernandez-Ortiz A, Escaned J, Azcona L, Almeria C, Macaya C.Long-term clinical and echocardiographic follow-up afterpercutaneous valvuloplasty with the Inoue balloon. Circula-tion 1999;99(12):1580–6.

39. Iung B, Garbarz E, Michaud P, Helou S, Farah B, Berdah P,Michel PL, Cormier B, Vahanian A. Late results of percuta-neous mitral commissurotomy in a series of 1024 patients.Analysis of late clinical deterioration: frequency, anatomicfindings, and predictive factors. Circulation 1999;99(25):3272–8.

40. Vahanian A, Palacios IF. Percutaneous approaches to valvulardisease. Circulation 2004;109(13):1572–9.

41. Reyes VP, Raju BS, Wynne J, Stephenson LW, Raju R, FrommBS, Rajagopal P, Mehta P, Singh S, Rao DP, Satyanarayana PV,Turi ZG. Percutaneous balloon valvuloplasty compared withopen surgical commissurotomy for mitral stenosis. N Engl JMed 1994;331(15):961–7.

42. Pendergast BD, Shaw TR, Iung B, Vahanian A, Northridge DB.Contemporary criteria for the selection of patients for percu-taneous balloon mitral valvuloplasty. Heart 2002;87(5):401–4.

43. Doukas G, Samani NJ, Alexiou C, Oc M, Chin DT, Stafford PG,Ng LL, Spyt TJ. Left atrial frequency ablation during mitralvalve surgery for continuous atrial fibrillation: a randomizedcontrolled trial. JAMA 2005;294(18):2323–9.

44. Lee JW, Park NH, Choo SJ, Jo MS, Song H, Song MG. Surgical
29. Olesen KH. The natural history of 217 patients with mitral
stenosis under medical treatment. Brit Heart J 1962;24:349.30. Sagie A, Freitas N, Padial LR, Leavitt M, Morris E, Weyman AE,

Levine RA. Doppler echocardiographic assessment of long-term progression of mitral stenosis in 103 patients: valve areaand right heart disease. J Am Coll Cardiol 1996;28(2):472–9.

31. Carabello BA. Modern management of mitral stenosis. Circu-lation 2005;112(3):432–7.

32. Keren G, Etzion T, Sherez J, Zelcer AA, Megidish R, MillerHI, Laniado S. Atrial fibrillation and atrial enlargement inpatients with mitral stenosis. Am Heart J 1987;114(5):1146–55.

33. Chiang CW, Lo SK, Ko YS, Cheng NJ, Lin PJ, Chang CH. Pre-dictors of systemic embolism in patients with mitral stenosis.A prospective study. Ann Intern Med 1998;128(11):885–9.

34. Lutas EM, Devereux RB, Borer JS, Goldstein JE. Echocardio-graphic evaluation of mitral stenosis: a critical appraisal ofits clinical value in detection of severe stenosis and valvularcalcification. J Cardiovasc Ultrasound 1983;2:131.

35. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, FryeRL, Halperin JL, Kay GN, Klein WW, Levy S, McNamaraRL, Prystowsky EN, Wann LS, Wyse DG. ACC/AHA/ESCguidelines for the management of patients with atrial fibrilla-tion; executive summary; a report of the American Collegeof Cardiology/American Heart Association Task Force onPractice Guidelines and the European Society of CardiologyCommittee for Practice Guidelines and Policy Conferences(Committee to Develop Guidelines for the Management ofPatients With Atrial Fibrillation). Circulation 2001;104:2118–50.

36. Klein AL, Grimm RA, Murray RD, Apperson-Hansen C,Asinger RW, Black IW, Davidoff R, Erbel R, HalperinJL, Orsinelli DA, Porter TR, Stoddard MF. Assessmentof cardioversion using transesophageal echocardiographyinvestigators. Use of transoesophageal echocardiography toguide cardioversion in patients with atrial fibrillation. N EnglJ Med 2001;344(19):1411–20.

outcome of the maze procedure for atrial fibrillation in mitralvalve disease: rheumatic versus degenerative. Ann Thorac Surg2003;75(1):57–61.

45. Stewart WJ, Carabello B. Chronic aortic valve disease. In:Topol EJ, editor. Textbook of cardiovascular medicine. Philadel-phia: Lippincott, Williams and Wilkins; 2003.

46. Enriquez-Sarano M, Tajik AJ. Aortic regurgitation. N Engl JMed 2004;351(15):139–46.

47. Jaffe WM, Roche AH, Coverdale HA, McAlister HF, OrmistonJA, Greene ER. Clinical evaluation versus Doppler echocar-diography in the quantitative assessment of valvular heartdisease. Circulation 1988;78(2):267–75.

48. Perry GL, Helmcke F, Nanda NC, Byard C, Soto B. Evaluationof aortic insufficiency by Doppler color flow mapping. J AmColl Cardiol 1987;9(4):952–9.

49. Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla VoltaS. Nifedipine in asymptomatic patients with severe aorticregurgitation and normal left ventricular function. N Engl JMed 1994;331(11):689–94.

50. Wisenbaugh T, Sinovich V, Dullabh A, Sareli P. Six-monthpilot study of captopril for mildly symptomatic severe iso-lated mitral and isolated aortic regurgitation. J Heart Valve Dis1994;3(2):197–204.

51. Evangelista A, Tornos P, Sambola A, Permanyer-MiraldaG, Soler-Soler J. Long term vasodilator therapy inpatients with severe aortic regurgitation. New Engl JMed 2005;353(13):1342–9.

52. Tarasoutchi F, Grinberg M, Spina GS, Sampaio RO, CardosoLF, Rossi EG, Pomerantzeff P, Laurindo F, da Luz PL, RamiresJA. Ten-year clinical laboratory follow-up after application ofa symptom-based therapeutic strategy to patients with severechronic aortic regurgitation of predominant rheumatic etiol-ogy. J Am Coll Cardiol 2003;41(8):1316–24.

53. Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR,Seward JB, Tajik AJ. Mortality and morbidity of aortic regur-

RE

VIE

W


gitation in clinical practice. A long-term follow-up study.Circulation 1999;99(14):1851–7.

54. Ishii D, Hirota Y, Suwa M, Kita Y, Onaka H, Kawamura K.Natural history and left ventricular response in chronic aorticregurgitation. Am J Cardiol 1996;78(3):357–61.

55. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic heartvalves. New Engl J Med 1996;335(6):407–16.

56. Hammermeister K, Sethi GK, Henderson WG, Grover FL,Oprian C, Rahimtoola SH. Outcomes 15 years after valvereplacement with a mechanical versus a bioprosthetic valve:final report of the Veterans Affairs randomized trial. J Am CollCardiol 2000;36(4):1152–8.

57. Yun KL, Miller DC, Moore KA, Mitchell RS, Oyer PE, Stin-son EB, Robbins RC, Reitz BA, Shumway NE. Durabilityof the Hancock MO bioprosthesis compared with the stan-dard aortic valve bioprosthesis. Ann Thorac Surg 1995;60(2Suppl.):S221–8.

58. David TE, Feindel CM, Scully HE, Bos J, Rakowski H. Aorticvalve replacement with stentless porcine aortic valves: a ten-year experience. J Heart Valve Dis 1998;7(3):250–4.

59. Barratt-Boyes BG, Roche AH, Subramanyan R, PembertonJR, Whitlock RM. Long-term follow-up of patients withantibiotic-sterilized aortic homograft inserted freehand in theaortic position. Circulation 1987;75(4):768–77.

60. Clarke DR, Campbell DN, Hayward AR, Bishop DA. Degen-eration of aortic valve allografts in young recipients. J ThoracCardiovasc Surg 1993;105(5):934–41.

61. Yap CH, Yii M. Allograft aortic valve replacement in the adult:a review. Heart Lung Circ 2004;13(1):41–51.

62. Lund O, Chandrasekaran V, Grocott-Mason R, Elwidaa H,

71. Kouchoukos NT, Masetti P, Nickerson NJ, Castner CF, Shan-non WD, Davila-Roman VG. The Ross procedure: long-termclinical and echocardiographic follow-up. Ann Thorac Surg2005;78(3):773–81.

72. Feier H, Collart F, Ghez O, Riberi A, Caus T, Kreitmann B,Metras D. Factors, dynamics and cutoff values for homo-graft stenosis after the Ross procedure. Ann Thorac Surg2005;79(5):1669–75.

73. Matsumura T, Ohtaki E, Misu K, Tohbaru T, Asano R,Nagayama M, Kitahara K, Umemura J, Sumiyoshi T, KawaseM, Ida T, Kasegawa H, Hosoda S. Etiology of aortic valvedisease and recent changes in Japan: a study of 600 valvereplacement cases. Int J Cardiol 2000;86(2–3):217–23.

74. Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natu-ral history and rate of progression of aortic stenosis. Chest1998;113(4):1109–14.

75. Munt B, Legget ME, Kraft CD, Miyake-Hull CY, Fujioka M,Otto CM. Physical examination in valvular aortic stenosis:correlation with stenosis severity and prediction of clinicaloutcome. Am Heart J 1999;137(2):298–306.

76. Lieberman EB, Bashore TM, Hermiller JB, Wilson JS, PieperKS, Keeler GP, Pierce CH, Kisslo KB, Harrison JK, David-son CJ. Balloon aortic valvuloplasty in adults: failure ofprocedure to improve long-term survival. J Am Coll Cardiol1995;26(6):1522–8.

77. Carabello BA. Timing of valve replacement in aortic stenosis:moving closer to perfection. Circulation 1997;95(9):2241–3.

78. Vaturi M, Porter A, Adler Y, Shapira Y, Sahar G, Vidne B, SagieA. The natural history of aortic valve disease after mitral valvesurgery. J Am Coll Cardiol 1999;33(7):2003–8.

Mazhar R, Khaghani A, Mitchell A, Ilsley C, Yacoub MH. Pri-mary aortic valve replacement with allografts over twenty-fiveyears: valve related and procedure related determinants ofoutcome. J Thorac Cardiovasc Surg 1999;117(1):77–90 [discus-sion 90-1].

63. Kejiriwal NK, Tan JT, Vasudevan A, Ong M, Newman MA,Alvarez JM. Follow-up of Australian Aboriginal patients fol-lowing open-heart surgery in Western Australia. Heart LungCirc 2004;13(1):70–3.

64. Fihn SD. Aiming for safe anticoagulation. New Engl J Med1995;333(1):54–5.

65. Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ,Vandenbroucke JP, Briet E. Optimal oral anticoagulant ther-apy in patients with mechanical heart valves. New Engl J Med1995;333(1):11–7.

66. McDonald M, Currie B. Outcomes of cardiac surgery in Abo-riginal Australians: what are the problems and what’s to bedone? Heart Lung Circ 2004;13(2):129–31.

67. Carr JF, Savage EB. Aortic valve repair for aortic insuffi-ciency in adults: a contemporary review and comparisonwith replacement techniques. Eur J Cardiothorac Surg2004;25(1):6–15.

68. Grinda JM, Latremouille C, Berrebi AJ, Zegdi R, ChauvaudS, Carpentier AF, Fabiani JN, Deloche A. Aortic cusp exten-sion valvuloplasty for rheumatic aortic valve disease: midtermresults. Ann Thorac Surg 2002;74(2):438–43.

69. Gerosa G, Ross DN, Brucke PE, Dziatkowiak A, MohammadS, Norman D, Davies J, Sbarbati A, Casarotto D. Aortic valvereplacement with pulmonary homografts; early experience. JThorac Cardiovasc Surg 1994;107(2):424–36.

70. Aklog L, Carr-White GS, Birks EJ, Yacoub MH. Pulmonaryautograft versus aortic homograft for aortic valve replace-ment: interim results form a prospective randomized trial. JHeart Valve Dis 2000;9(2):176–88.

79. Skudicky D, Essop MR, Sareli P. Time-related changes in leftventricular function after double valve replacement for com-bined aortic and mitral regurgitation in a young rheumaticpopulation. Circulation 1997;95(4):899–904.

80. Reimold SC, Rutherford JD. Valvular heart disease in preg-nancy. New Engl J Med 2003;349(1):52–9.

81. Task Force on the Management of Cardiovascular DiseasesDuring Pregnancy of the European Society of Cardiology.Expert consensus document on management or cardiovascu-lar diseases during pregnancy. Eur Heart J 2003;24(8):761–81.

82. Elkayam U, Bitar F. Valvular heart disease and pregnancy partI: native valves. J Am Coll Cardiol 2005;46(2):223–30.

83. De Souza JA, Martinez Jr EE, Ambrose JA, Alves CM, BornD, Buffolo E, Carvalho AC. Percutaneous balloon mitralvalvuloplasty in comparison with open mitral valve com-missurotomy for mitral stenosis during pregnancy. J Am CollCardiol 2001;37(3):900–3.

84. Martinez-Reding J, Cordero A, Kuri J, Martinez-Rios MA,Salazar E. Treatment of severe mitral stenosis with percu-taneous balloon valvuloplasty in pregnant patients. J ClinCardiol 1998;21(9):659–63.

85. Routray SN, Mishra TK, Swain S, Patnaik UK, Behera M. Bal-loon mitral valvuloplasty during pregnancy. Int J GynaecolObstet 2004;85(1):18–23.

86. Ginsberg JS, Chan WS, Bates SM, Kaatz S. Anticoagulation ofpregnant women with mechanical heart valves. Arch Int Med2003;163(6):694–8.

87. Elkayam U, Singh H, Irani A, Akhter MW. Anticoagulationin pregnant women with prosthetic heart valves. J CardiovascPharmaco Therapeut 2004;9(2):107–15.

88. Hung L, Rahimtoola SH. Prosthetic heart valves and preg-nancy. Circulation 2003;107(9):1240–6.

89. Elkayam U, Bitar F. Valvular heart disease and pregnancy partII: prosthetic valves. J Am Coll Cardiol 2005;46(3):403–10.

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90. Sadler L, McCowan L, White H, Stewart A, Bracken M, NorthR. Pregnancy outcomes and cardiac complications in womenwith mechanical, bioprosthetic and homograft valves. Brit JObstet Gynaecol 2000;107(2):245–53.

91. Rowan JA, McCowan LM, Raudkivi PJ, North RA. Enoxaparintreatment in women with mechanical valves during preg-nancy. Am J Obstet Gynecol 2001;185(3):663–7.

92. Leyh RG, Fischer S, Ruhparwar A, Haverich A. Antico-agulation for prosthetic heart valves during pregnancy: islow-molecular-weight heparin an alternative? Eur J Cardiotho-rac Surg 2002;21(3):577–9.

93. Salazar E, Izaguirre R, Verdejo J, Mutchinick O. Failure ofadjusted doses of subcutaneous heparin to prevent throm-boembolic phenomena in pregnant patients with mechanicalcardiac valve prostheses. J Am Coll Cardiol 1996;27(7):698–703.

94. Butchart EG, Gohlke-Barwolf C, Antunes MJ, Tornos P, DeCaterina R, Cormier B, Prendergast B, Lung B, Bjornstad H,Leport C, Hall RJ, Vahanian A, Working Groups on ValvularHeart Disease, Thrombosis, and Cardiac Rehabilitation andExercise Physiology. European Society of Cardiology. Recom-mendations for the management of patients after heart valvesurgery. Eur Heart J 2005;26(22):2463–71.

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