All About CHF

7/27/2019 All About CHF

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CHRONIC CONGESTIVE HEART

FAILURE

A Comprehensive Overview on Diagnosis and Treatment

Dr. Cholid Tri Tjahjono, MKes, SpJP

Faculty of Medicine

Brawijaya University Malang


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Introduction


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Definition : Heart Failure

The si tuat ion when the heart is incapable of

maintaining a cardiac ou tpu t adequate to

accommodate metabo l ic requi rements and the

venous return . E. Braunwald

Pathophysiological state in which an

abnormali ty of cardiac funct ion is responsib le

for the fai lure of the heart to pump b lood at arate commensu rate wi th the requ i rements o f

the metabol izing t issues.Euro Heart J ; 2001. 22: 1527-1560


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DEFINITION OF HEART FAILURE.Criteria 1 and 2 should be fulfilled in all cases

1. Symptoms of heart failure(at rest or during exercise)

And

2. Objective evidence of cardiac dysfunction(at rest)

And(in cases where the diagnosis is in doubt)

3. Response to treatment directed towards heartfailure

Task Force Report. Guidelines for the diagnosis and treatment of chronic heart failure.

European Society of Cardiology.2001


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EPIDEMIOLOGY

Europe

The prevalence of symptomatic HF range from 0.4-2%.

10 million HF pts in 900 million total population

USA

nearly 5 million HF pts.

500,000 pts are D/ HF for the 1

st

time each year.Last 10 years number of hospitalizations has increased.

Nearly 300,000 patients die of HF each year.

Guidelines for the diagnosis and treatment of chronic heart failure

European Heart Journal (2001) 22, 1527-1560

ACC/AHA Guidelines for the

Evaluation and Management of Chronic Heart Failure in the Adult 2001


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DESCRIPTIVE TERMS in HEART FAILURE


European Heart Journal (2001) 22, 1528

Acute vs Chronic Heart Failure

Systolic vs Diastolic Heart Failure

Right vs Left Heart Failure

Mild , Moderate, Severe Heart Failure


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New York Heart Association (NYHA)Classification of Heart Failure

Class INo limitation :ordinary physical exercise doesnot cause undue fatigue, dyspnoea or palpita-tions.

Class

II

Slight limitation of physical activity : comfor-

table at rest but ordinary activity results infatigue, dyspnoea, or palpitation.

Class - IIIMarked limitationof physical activity : comfor-table at rest but less than ordinary activityresults in symptoms.

Class - IV

Unable to carry out any physical activitywith-out discomfort : symptoms of heart failure arepresent even at rest with increased discomfortwith any physical activity.


European Heart Journal (2001) 22, 1531

(Adapted from Williams JF et al., Circulation. 1995; 92 : 2764-2784)


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ACC/AHAA New Approach To The Classification of HF

Stage Descriptions Examples

A Patient who is at high risk fordeveloping HFbut has no

structural disorderof the heart.

Hypertension; CAD; DM;rheumatic fever; cardiomyopathy.

B Patient with a structural disorder

of the heart but who has neverdeveloped symptomsof HF.

LV hypertrophy or fibrosis;

LV dilatation; asymptomatic VHD;MI.

C Patient with past or current

symptomsof HF associated with

underlying structural heart

disease.

Dyspnea or fatigue ec LV systolic

dysfunction; asymptomatic

patients with HF.

D Patient with end-stagedisease Frequently hospitalized pts ; pts

awaiting heart transplantation etc

ACC/AHA Guidelines for theEvaluation and Management of Chronic Heart Failure in the Adult 2001


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Stage A Stage B Stage C Stage D

Pts with :

Hypertension

CAD

DM

Cardiotoxins

FHx CM

THERAPY Treat Hypertension

Stop smoking

Treat lipid disorders Encourage regular

exercise

Stop alcohol

& drug use

ACE inhibition

Pts with :

Previous MI

LV systolic

dysfunction

Asymptomatic

Valvular disease

THERAPY All measures under

stage A

ACE inhibitor Beta-blockers


stage A

Drugs for routine use:diuretic

ACE inhibitor

Beta-blockers

digitalis


stage A,B and C

Mechanical assist

device

Heart transplantation

Continuous IV

inotrphic infusions for

palliation

Pts who have

marked symptoms

at rest despite

maximal medical

therapy.

Pts with :

Struct. HD

Shortness of

breath and fatigue,

reduce exercise

tolerance

Struct.

Heart

Disease

Develop

Symp.of

HF

Refract.

Symp.of

HF at rest

Stages in the evolution of HF and recommended therapy by stage



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EVOLUTION OF

CLINICAL STAGES

NORMAL

AsymptomaticLV Dysfunction

CompensatedCHF

DecompensatedCHF

No symptomsNormal exercise

Normal LV fxn

No symptoms

Normal exercise

Abnormal LV fxn

No symptomsExercise

Abnormal LV fxn

Symptoms

Exercise

Abnormal LV fxn

RefractoryCHF

Symptoms not controlled

with treatment


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Evolution of the Concept of Heart Failure

1950 to 20001950 2000

Aetiology Hypertension CHDValvular heart dis Hypertension

Dilated CMP

Natural Course Slowly progressive Slowly progressive (remodelling)

or unpredictable and rapid( coronary event )

Understanding Hemodynamic model Neurohormonal model

Common cause Pulmonary infection Sudden deathof death Pump failure

Arrhythmia Atrial Ventricular

Treatment goal Control edema Improve quality of lifeSlowing Heart Rate + reduce mortality + reduce

hospitalization


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Patophysiology of C H F


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g a b c d e f g a

AO

AorticclosureAortic

pressure

Ventricular

pressure

Cross-over Atrial

pressure

MO

Heartsounds

S4

M1T1

A2P2 S3

Cardiologicsystole

a c

v

JVP

PT

ECG

P

Q S0 800 msec

The Wiggers cycle

Op

ie(2001)

g

a b

iso

c d

isoe

f


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Input

Block diagram of left ventricular pump performance

(Little, 2001)

Output

PULMONARY VENOUSPRESSURE

CARDIAC OUTPUT

Filling Emptying

ED volume x EFeffective =Strokevolume

Heartrate

x

Diastolic function Systolic function

LV Distensibility

RelaxationLeft atriumMitral valvePericardium

Contractility

AfterloadPreloadStructure


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SYSTOLIC FAILURE

Normal

Normaldiastolicchamber

distensibility

Left Ventricular Volume

LeftV

entricularPressure

Left Ventricular Volume

LeftV

entricularPressure

DIASTOLIC FAILURE

Decreaseddiastolicchamberdistensibility

PRESSUREVOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILURE

(Zile & Brutsaert 2002)


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Abnormalrelaxation

A B

Pericardialrestraint

D

Chamberdilation

C

Increasedchamber stiffness

Leftventricularpressure

Left ventricular volume

Mechanisms that cause diastolic dysfunction. (Zile, 1990)


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DETERMINANTS OF

VENTRICULAR FUNCTION

STROKEVOLUME

PRELOAD

CONTRACTILITY

CARDIAC OUTPUT

HEARTRATE

- Synergistic LV contraction- LV wall integrity- Valvular competence

AFTERLOAD

F k St li L


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Frank-Starling Law

Normal

Compensated

CHF

Normal C.O.

LVEDP

Card

iacOutp

ut


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Ventricular Function Curve:

Frank-Starlings

Congestion

SV

Normal

LVEDV


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Factors That Influence Ventricular

Function Curves:

LVEDV

VentricularPerformance

Contractile State of

the Myocardium

Cardiac

GlycosidesCatecholamines

Ca ChannelBlockers (?)

ETOH

Loss of

Myocardium


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The Pathophysiology of Heart Failure

Hurst. The Heart. Diagnosis and Management of Heart Failure.10thed. 688


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Pathophysiological Sequence of

CHF

Heart Failure

Inadequate Cardiac Output

() O2Delivery (rest and/or exercise)Systemic Vasoconstriction

SAS (NE)) RAAS (A-II)

() Flow to Skin, Gut,and Renal Circulations


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Activation ofRAS and ANS

Neurohormonal Activation

Hurst. The Heart. Diagnosis and Management of Heart Failure.10thed. 688


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Frank-Starling Effect

Ventricular dilatation

Wall stress

O2consumption Coronary

perfusion


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SNS

Renin release

Angiotensin II

Vasoconstriction

Growthfactors

Hypertrophy

Apoptosis

ALDO

Fluid

accumulation

Collagen

deposition

Myofibril

necrosis

Preload Afterload


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RBF

Renin release

Angiotensin II

Vasoconstriction

Growth

factors

Hypertrophy

Apoptosis

ALDO

Collagen deposition

Myofibril necrosis

Perfusion of Vital Organs

Na filtered

Afterload

Fluid accumulation


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Sympathetic nervous system up-regulation

IncreasedNorepinephrine levels

DirectMyocardial toxicity

Myocyte dysfunction

Myocytenecrosis

IntracellularCa2+overload/Energy depletion

Apoptosis

DecreasedRenal blood

flow

Activation of theRAA system

Increased HR, PVR &arteriolar vasoconstriction

Increased myocardialoxygen demand

IncreasedAngiotensin II &

Aldosteron

Na+& waterretention

Vasoconstriction Cardiac remodeling

Cesario et.al; Reviews in cardiovascular medicine, vol 3, no.1, 2002


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Causes of Heart Failure

Myocardial Damage or Disease

Infarction (Acute) / Ischemia

Myocarditis Hypertrophic Cardiomyopathy

Excess Load on Ventricle

Volume/ Pressure OverloadResistance to Flow into Ventricle

Cardiac Arrhythmias


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Primary Changes in CHF

Site ofFailure

BackwardFailure

ForwardFailure

Right HeartFailure

() SystemicVenousPressure

() ejectionintoPulmonaryArtery

Left HeartFailure

() PulmonaryVenous

Pressure

() ejectioninto aorta


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MI-INDUCED HEART FAILURE

Myocardial Damage

Contractility

Pump Performance

) SAS DriveVasoconstriction

) Systolic Work Load

RAAS SYSTEM

FLUID RETENTION


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Diagnosis of C H F


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IDENTIFICATIONS OF HF PATIENTS

With a Syndrome of Decrease ExerciseTolerance

With a Syndrome of Fluid Retention

With No Symptoms or Symptoms ofAnother Cardiac or Non Cardiac

Disorder(MI, Arrythmias, Pulmonary orSystemic Thromboembolic Events)


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SYMPTOMS AND SIGN

Breathlessness, Ankle Swelling, Fatique

Characteristic Symptoms

Peripheral Oedema, JVP , Hepatomegaly

Signs of Congestion of Systemic Veins

S3, Pulmonary Rales , Cardiac Murmur

E C G


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E C G

A low Predictive Value

LAH and LVH May Be Associated wit LV Dysfunction Anterior Q-wave and LBBB a good predictors of EF

Detecting Arrhytmias as Causative of HF

CHEST X-RAY

A Part of Initial Diagnosis of HF

Cardiomegaly, Pulmonary CongestionRelationship Between Radiological Signs and

Haemodynamic Findings may Depend on the Duration

and Severity HF

HAEMATOLOGY & BIOCHEMISTRY


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HAEMATOLOGY & BIOCHEMISTRY

A Part of Routine Diagnostic

Hb, Leucocyte, Platelets Electrolytes, Creatinine, Glucose, Hepatic Enzyme,

Urinalysis

TSH, C-RP, Uric Acid

ECHOCARDIOGRAPHY

The Preferred MethodsHelpful in Determining the Aetiology

Follow Up of Patients Heart Failure


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PULMONARY FUNCTIONS

A Little Value in Diagnosis Heart Failure Usefull in Excluding Respiratory Diseases

EXERCISE TESTING

Focused on Functional, Treatment Assessment and

Prognostic

STRESS ECHOCARDIOGRAPHY


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STRESS ECHOCARDIOGRAPHY

For Detecting Ischaemia

Viability Study

NUCLEAR CARDIOLOGY

Not Recommended as a Routine Use

CMR( CARDIAC MAGNETIC RESONANCE IMAGING)

Recommenmded if Other Imaging Techniques not

Provided Diagnostic Answer


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INVASIVE INVESTIGATION

Elucidating the Cause and Prognostic Informations

Coronary Angiography :

in CADs Patients

Haemodynamic Monitoring :

To Assess Diagnostic and Treatment of HF

Endomyocardial Biopsy :

in Patients with Unexplained HF

NATRIURETIC PEPTIDES


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NATRIURETIC PEPTIDES

Cardiac Function (LV Function )

Plasma Natriuretic Peptide Concentration

(Diagnostic Blood Use for HF)

Natriuretic Peptide :

Greatest Risk of CV Events

Natriuretic Peptide :

Improve Outcome in Patients with

Treatment

Identify Pts. With Asymptomatic LVDysfunction (MI, CAD)


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Suspected Heart FailureBecause

of symptoms and signs

Assess Presence of Cardiac Disease by ECG, X-Rayor NatriureticPeptides (Where Available)

Imaging by Echocardiography (NuclearAngiography or MRI Where Available)

Assess Etiology, Degree, PrecipitatingFactors and Type of Cardiac Dysfunction

Tests Abnormal

Tests Abnormal

Choose Therapy

ALGORITHM FOR THE DIAGNOSIS OF THE HF

If NormalHeart Failure

Unlikely

Additional Diagnosis TestsWhere Appropriate (e.g.Coronary Angiography)

If NormalHeart Failure

Unlikely

(ESC, 2001)


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Treatment of C H F


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Aims of Treatment

1. Preventiona) Prevention and/or controlling of diseases leading

to cardiac dysfunction and heart failure

b) Prevention of progression to heart failure once

cardiac dysfunction is established2. Morbidity

Maintenance or improvement in quality of life

3. Mortality

Increased duration of life




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ACC/AHA & EUROPE (ESC) 2001

GUIDELINES FOR THE MANAGEMENT

OF HEART FAILURE

ACE-inhibitor

Use as first line therapy

Should be up titrated to the dosages shown in the large

clinical trial, and not titrated based on symptomatic

improvement

DIURETIC to control fluid overload

-BLOCKER

For all patients with stable mild-severe HF on

standard treatment


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ACC/AHA & EUROPE (ESC) 2001

GUIDELINES FOR THE MANAGEMENT

OF HEART FAILURE

Aldosteron Receptor Antagonis

in advance HF ( NYHA III-IV )

DIGOXIN

in AF

May be added for symptom relief

ARB

Considered in patients not tolerate ACE

inhibitors and not on - blocker


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Management Outline

Establish that the patient has HF.

Ascertain presenting features: pulmonary oedema, exertional

breathlessness, fatigue, peripheral oedema

Assess severity of symptoms

Determine aetiology of heart failure

Identify precipitating and exacerbating factors

Identify concomitant diseases

Estimate prognosis

Anticipate complications

Counsel patient and relatives

Choose appropriate management

Monitor progress and manage accordingly




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TREATMENT

Correction of aggravating factors

MEDICATIONS

Endocarditis

Obesity

Hypertension

Physical activityDietary excess

Pregnancy

Arrhythmias (AF)

Infections

HyperthyroidismThromboembolism

Treatment opt ion s


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Treatment opt ion s

Non-pharmacological management

General advice and measures

Exercise and exercise training

Pharmacological therapy

Angiotensin-converting enzyme (ACE) inhibitors

Diuretics

Beta-adrenoceptor antagonists

Aldosterone receptor antagonists

Angiotensin receptor antagonists

Cardiac glycosidesVasodilator agents (nitrates/hydralazine)

Positive inotropic agents

Anticoagulation

Antiarrhythmic agents

Oxygen

Devices and surgeryRevascularization (catheter interventions and surgery), other forms of surgery

Pacemakers

Implantable cardioverter defibrillators (ICD)

Heart transplantation, ventricular assist devices, artificial heart

Ultrafiltration, haemodialysis

Guidelines for the diagnosis and treatment of chronic heart failureEuropean Heart Journal (2001) 22, 1527-1560


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DRUGSHEMODYNAMIC EFFECTS

AI

A + V

V

D

Ventricular Filling Pressure

StrokeVolume

Normal

CHF


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PHARMACOLOGIC THERAPY

DIURETICS

Improved

symptoms

Decreased

mortality

Prevention

of CHF

yes ? ?

Vasodil.(Nitrates) yes yes ?

DIGOXIN yes = minimal

INOTROPES yes mort. ?

Other neurohormonal

control drugsyes + / - ?

ACEI yes YES yes

Neurohumoral

Control

NO

yes

no

no

YES

YES

TREATMENT


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TREATMENT

Normal

AsymptomaticLV dysfunctionEF


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Pharmacological therapy



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Stage A Stage B Stage C Stage D

Pts with :

Hypertension

CAD

DM

Cardiotoxins

FHx CM

THERAPY Treat Hypertension

Stop smoking

Treat lipid disorders

Encourage regularexercise

Stop alcohol

& drug use

ACE inhibition

Pts with :

Previous MI

LV systolic

dysfunction

Asymptomatic

Valvular disease


stage A

ACE inhibitor

Beta-blockers


stage A

Drugs for routine use:

diureticACE inhibitor

Beta-blockers

digitalis


stage A,B and C

Mechanical assist

device Heart transplantation

Continuous IV

inotrphic infusions for

palliation

Pts who have

marked symptoms

at rest despite

maximal medical

therapy.

Pts with :

Struct. HD

Shortness of

breath and fatigue,

reduce exercise

tolerance

Struct.

Heart

Disease

Develop

Symp.of

HF

Refract.

Symp.of

HF at rest




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1. ACE INHIBITOR


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Angiotens in-con verting enzyme inh ib i tors

Recommended as first-line therapy.

Should be uptitrated to the dosages shown to beeffective in the large, controlled trials, and nottitrated based on symptomatic improvement.

Moderate renal insufficiency and a relatively low bloodpressure (serum creatinine 250 mol.l-1and systolicBP 90 mmHg) are not contraindications.

Absolute contraindications: bilateral renal arterystenosis and angioedema.




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CO

PRELOAD AFTERLOAD

Normal Contractility

DiminishedContractility

Normal Contractility

DiminishedContractility

VV AV

VASODILATOR DRUGS

PRINCIPLES

VASODILATORS


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VenousVasodilatation

MIXEDCalcium antagonistsa-adrenergic Blockers

ACEIAngiotensin II inhibitors

K+channel activatorsNitroprusside

VENOUSNitrates

Molsidomine

ARTERIALMinoxidil

Hydralazine

VASODILATORS

CLASSIFICATION

ArterialVasodilatation

ACEI


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VASOCONSTRICTION VASODILATATION

Kininogen

Kallikrein

Inactive Fragments

Angiotensinogen

Angiotensin I

RENIN

Kininase IIInhibitor

ALDOSTERONE

SYMPATHETIC

VASOPRESSIN

PROSTAGLANDINS

tPA

ANGIOTENSIN II

BRADYKININ

ACEI

MECHANISM OF ACTION

A.C.E.

ACEI


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ACEI

HEMODYNAMIC EFFECTSArteriovenous Vasodilatation

- PAD, PCWP and LVEDP

- SVR and BP

- CO and exercise tolerance

No change in HR / contractility

MVO2

Renal, coronary and cerebral flow

Diuresis and natriuresis


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75

95NoAdditionalTreatment

Necessary

(%)

Quinapril Heart Failure Trial

JACC 1993;22:1557

ACEI

FUNCTIONAL CAPACITY

Quinaprilcontinued

n=114

QuinaprilstoppedPlacebon=110

p


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ACEI

ADVANTAGESInhibit LV remodeling post-MI

Modify the progression of chronic CHF

- Survival- Hospitalizations

-Improve the quality of life

In contrast to others vasodilators,do not produce neurohormonal activationor reflex tachycardia

Tolerance to its effects does not develop

ACEI


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ACEI

UNDESIRABLE EFFECTSInherent in their mechanism of action

-Hypotension

- Hyperkalemia-Angioneurotic edema

Due to their chemical structure

- Cutaneouseruptions- Neutropenia,

thrombocytopenia

-Digestive upset

-Dry cough

-Renal Insuff.

-Dysgeusia

-Proteinuria

ACEI


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ACEI

CONTRAINDICATIONS

Renal artery stenosis

Renal insufficiencyHyperkalemia

Arterial hypotension

Intolerance (due to side effects)


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ACE-Inhibitors in Asymptomatic Heart Failure

Development of symptomatic HF

Hospitalization of HFGuidelines for the diagnosis and treatment of chronic heart failure


SAVE & TRACE Study


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ACE-Inhibitors in Symptomatic Heart Failure

All patientssymptomatic Heart Failure should receive ACE-I.

A) No fluid retention, ACE-I should be given first.

B) With fluid retention,ACE-I + Diuretic

ACE-I : A) improves survival and symptoms.

B) reduces hospitalization.




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ACE INHIBITORS USED TO TREAT HEART FAILURE

DOSE RANGE TARGET DOSE FOR

DRUG (mg) FREQUENCY SURVIVAL BENEFIT*

Captopril 6.25 150 Three times daily 50 mg three times daily

Enalapril 2.5 20 Twice daily 10 mg twice daily

Lisinopril 2.5 40 Daily -

Ramipril 2.5 10 Once or twice daily 5 mg twice daily

Quinapril 5 20 Twice daily -

Zofenopril - - 30 mg twice daily

Trandolapril - - 4 mg daily

Imidapril HCl 5 10 Once daily 10 mg daily

* Target doses are those associated with increased survival in clinical trials

This drug is not approved in the United States


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ACEI SURVIVAL


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Placebo

Enalapril

12111098765

PROBABILITY

OF

DEATH

MONTHS

0.1

0.8

0

0.2

0.3

0.7

0.4

0.5

0.6

p< 0.001

p< 0.002

CONSENSUSN Eng l J Med 1987;316:1429

ACEI SURVIVAL

43210

ACEI SURVIVAL


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50

40

30

20

10

0

Months0 6 12

p = 0.30

2418 30 36 42 48

Enalapriln=2111

Placebon=2117

SOLVD (Prevention)N Eng l J Med 1992;327:685

%MORTALITY

ACEI SURVIVAL

n = 4228No CHF symptomsEF < 35

ACEI SURVIVAL


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50

40

30

20

10

0

Months

0 6 12

p = 0.0036

%MORTALITY

2418 30 36 42 48

Enalapriln=1285

Placebon=1284

SOLVD (Treatment)N Eng l J M 1991;325:293

ACEI SURVIVAL

n = 2589

CHF- NYHA II-III- EF < 35

ACEI SURVIVAL


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Mortality,%

4SAVEN Eng l J Med 1992;327:669

Years

30

20

10

01 2 3

Placebo

Captopril

0

n=1115

n=1116

p=0.019 -19%

ACEI SURVIVAL

n = 2231

3 - 16 days post AMIEF < 4012.5 --- 150 mg / day

Asymptomaticventricular

dysfunction post MI

ACEI


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ISIS-4

GISSI-3

SAVE

SMILE

AIRE

ACEI Benefit Pt Selection

Captopril

Lisinopril

Captopril

Zofenopril

Ramipril

0.5 / 5 wk

0.8 / 6 wk

4.2 / 3.5 yr

4.1 / 1 yr

6 / 1 yr

All with AMI

All with AMI

EF < 40asymptomatic

Ant. AMI, No TRL

Clinical CHF

TRACE Trandolapril 7.6 / 3 yr Vent Dysfx / Clinical CHFEF < 35

ACEI

SURVIVAL POST MI


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2. DIURETICS

Diuret ics


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Diuret ics

Essential for symptomatic treatment when

fluid overloadis present and manifest.

Always be administered in combination

with ACE inhibitorsif possible.



DIURETICS


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Cortex

Medulla

ThiazidesInhibit active exchange of Cl-Na

in the cortical diluting segment of the

ascending loop of Henle

K-sparingInhibit reabsorption of Na in thedistal convoluted and collecting tubule

Loop diuretics

Inhibit exchange of Cl-Na-K inthe thick segment of the ascendingloop of Henle

Loop of HenleCollecting tubule

DIURETICS

THIAZIDES


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THIAZIDES

MECHANISM OF ACTIONExcrete 5 - 10% of filtered Na+

Elimination of KInhibit carbonic anhydrase:increase elimination of HCO3

Excretion of uric acid, Ca and Mg

No dose - effect relationship

LOOP DIURETICS


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LOOP DIURETICS

MECHANISM OF ACTIONExcrete 15 - 20% of filtered Na+

Elimination of K+

, Ca+

and Mg++

Resistance of afferent arterioles

- Cortical flow and GFR- Release renal PGs

- NSAIDs may antagonize diuresis

K-SPARING DIURETICS


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K-SPARING DIURETICS

MECHANISM OF ACTION

Eliminate < 5% of filtered Na+

Inhibit exchange of Na+for K+or H+

Spironolactone = competitive

antagonist for the aldosterone receptor

Amiloride and triamterene blockNa+channels controlled by aldosterone

DIURETIC EFFECTS


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Volume and preload

Improve symptoms of congestion

No direct effect on CO, butexcessive preload reduction may

Improves arterial distensibility

Neurohormonal activation

Levels of NA, Ang II and ARP

Exception: with spironolactone

DIURETIC EFFECTS

DIURETICS


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DIURETICS

ADVERSE REACTIONSThiazide and Loop Diuretics

Changes in electrolytes:

VolumeNa+, K+, Ca++, Mg++metabolic alkalosis

Metabolic changes:glycemia, uremia, goutLDL-C and TG

Cutaneous allergic reactions

DIURETICS


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DIURETICS

ADVERSE REACTIONSThiazide and Loop Diuretics

Idiosyncratic effects:

Blood dyscrasia, cholestatic jaundice andacute pancreatitis

Gastrointestinal effects

Genitourinary effects:Impotence and menstrual cramps

Deafness, nephrotoxicity(Loop diuretics)

DIURETICS


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DIURETICS

ADVERSE REACTIONSK-SPARING DIURETICS

Changes in electrolytes:

Na+, K+, acidosis

Musculoskeletal:

Cramps, weakness

Cutaneous allergic reactions :

Rash, pruritis


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3. ALDOSTERONE

INHIBITORS

ALDOSTERONE INHIBITORS


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ALDOSTERONE

Retention Na+

Retention H2O

Excretion K+

Excretion Mg2+

Collagen

deposition

Fibrosis- myocardium

- vessels

Spironolactone

Edema

Arrhythmias

Competitive antagonist of the

aldosterone receptor

(myocardium, arterial walls, kidney)




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INDICATIONS

FOR DIURETIC EFFECT

Pulmonary congestion (dyspnea)

Systemic congestion (edema)

FOR ELECTROLYTE EFFECTS

Hypo K+, Hypo Mg+

Arrhythmias

Better than K+ supplements

FOR NEUROHORMONAL EFFECTS

Please see RALES results,

N Engl J Med 1999:341:709-717


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Recommended in advanced HF(NYHA III-IV),

in addition to ACE inhibition and diuretics to

improve survival and morbidity

Aldos terone recepto r antagon ists - sp ironolactone




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The RALES mor tali ty tr ial

Low dose spironolactone (12.550 mg) on top

of an ACE inhibitor and a loop diuretic improved survivalof patients in advanced

heart failure (NYHA class III or IV).

A ldos terone recepto r antagon ists - sp ironolactone


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4. -BlockersStart Low Go Slow

Activation and Blockade of Neurohumorali


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System in CHF

RAA System SNS System

Angiotensin II Noradrenalin

Hypertroph y, apopto sis, ischaemia,

arrhytm ia, remodel ing, f ibros is

-BlockerACE-I

ADRENERGIC ACTIVATION


90/180

CNS Sympathetic

Outflow

Sympathetic

activity to kidneys

& blood vessels

Cardiac

Sympathetic activity

1-receptors 2-receptors a1-receptors

Mycocyte hypertrophy & death,

dilatation, ischaemia & arrhytmias

Vasoconstriction

Sodium Retention

Packer, AHA 2000


91/180

Why add-on -blocker,

if HF patient is already stable

on standard therapy with

ACE-I, diuretics digoxin

?

CarvedilolSurvival

1 0

US Carvedilol Study


92/180

Carvedilol

(n=696)

Placebo

(n=398)

Days

0 50 100 150 200 250 300 350 400

1.0

0.9

0.8

0.7

0.6

0.5

Risk reduction = 65%

P


93/180

Short-term :

1. Improvement of symptoms (LVEF )

2. Improvement of NYHA class

3. Improvement of daily activities

4.Reduction of hospitalization rate & length of

hospital stay (financial & psychological burden)

Long-term :

1.Slowing the progression of CHF

2. Increase of survival rate

A Clear Dose-Effect Relationship(MOCHA Study)


94/180

(MOCHA Study)

Plc

0

1

2

3

4

5

6

78

LVEF (EF Units)

*

256.25 12.5

*

* *

mg bid

P < 0.001

- 30

0

30

60

90

* **

mg bidPlc 6.25

* **

%w

orse

%i

mproved

12.5 25

0

0.1

0.2

0.3

0.4

Hospitalization/Pts

* * *

* *

P = 0.01

Plc 256.25 12.5 mg bid 0

4

8

12

16

Mortality (%)

* * *

* *

P < 0.001

Plc 256.25 12.5 mg bidB

ristowetal(1996)

Patient Global Assessment

COPERNICUS


95/180

%S

urvival

00

3 6 9 12 15 18 21Months

100

90

80

60

70

P=0.00013

Carvedilol

Placebo

CO CUS

All-cause mortality

COPERNICUS


96/180

Favors treatment Favorsplacebo

0.50.25 0.75 1.251.0

All

patients

Recent orrecurrentdecompensation

Annual placebo mortality rate

(per patient-year)

19.7%

28.5%

0

Effect of carvedilol on mortality

Beta-adrenoceptor antagon ists


97/180

Recommended for the treatment of all ptswith stable, mild, moderate and severe heart

failure on standard treatment, unless there is

a contraindication.

Patients with LV systolic dysfunction, with or

without symptomatic HF, following an AMI

long-term betablockade is recommendedin addition to ACE inhibitor.



Beta-adrenoceptor antagon ists


98/180

CIB IS II, MERIT HF, US CARVEDILOL AND

COPERNICUS study

Reduction in total mortality, cardiovascularmortality, sudden death and death due to

progression of heart failure in patients in func.class II-IV.

reduces hospitalizations

improves the functional class and leads toless worsening of heart failure.

PHARMACOLOGICAL PROPERTIES OF


99/180

-BLOCKING AGENT FOR HF

AGENT

1-BLOKADE

2-BLOKADE

a-BLOKADE ISA

ANCILLARY

EFFECTS

Carvedilol + + + + + + + + + - + + +

Metoprolol + + + - - - -

Bisoprolol + + + - - - -

THE RECOMMENDED PROCEDURE FOR


100/180

STARTING -BLOCKER

1. Patient should be on standard therapy

(ACE inhibitor +/- diuretic)

2. Patient in stable conditions

No iv inotropic therapy

Without signs of marked fluid retention

3. Start initial low doses and titrate to maintenance dose

(the dose may be doubled every 12 weeks)

(ESC.Gu idelines for HF, 2001)

DOSES OF -BLOCKER


101/180

BLOCKER FIRST DOSE TARGET DOSE TITRATION

PERIOD

Bisoprolol 1.25 mg 10 mg WeeksMonth

Metoprolol

Tartrate

5 mg 150 mg WeeksMonth

Metoprolol

Succinate

12.5 mg 200 mg WeeksMonth

Carvedilol 2 x 3.125 mg 2 x 25 mg WeeksMonth

(Euro pean Heart J ou rnal, vo l. 22, Sept. 2001)

CONTRAINDICATIONS OF


102/180

-BLOCKER IN PATIENT H F

Asthma Bronchial

Severe Bronchial Desease

Symptomatic Bradycardia and

Hypotension

INTOLERANCE OF -BLOCKER


103/180

INTOLERANCE OF -BLOCKER

Symptomatic

Bradycardia

Worsening HF Hypotension

How to Handle Intolerance


104/180

SYMPTOMATIC BRADYCARDIA

Check Blood Digoxin and/or reduce

other AV nodus inhibiting drugs

Reduces -Blockerdoseor if necessary stop it

Consider implantation of

peacemaker



105/180

WORSENING HF

Increase dose of Diuretics

Reduces -Blocker doseor if necessary stop it

If indicated, give inotropic drugs ornitroprusside or nitroglycerin



106/180

HYPOTENSION

Reduces ACE-Iorvasodilator

Take -Blocker :

After meal

At different time than ACE-I

Reduces dose or if necessary stop it

-BLOCKER IN HIGH RISK GROUPS PTS


107/180

WITH CHF

Elderly Patient

Type 2 Diabetes Mellitus

Renal Failure

Digitalis / Aldosteron Antagonist /

Amiodaron

(Pos t-Hoc Analys is o f the CIB IS II)


108/180

5. Angiotensin II receptor

antagonists

ANGIOTENSIN II INHIBITORS


109/180

MECHANISM OF ACTION

RENIN

Angiotensinogen Angiotensin I

ANGIOTENSIN II

ACE

Other paths

Vasoconstriction ProliferativeAction

Vasodilatation AntiproliferativeAction

AT1 AT2

AT1RECEPTORBLOCKERS

RECEPTORS

AT1 RECEPTOR BLOCKERS


110/180

DRUGS

Losartan

ValsartanIrbersartan

Candesartan

Competitive and selective

blocking of AT1 receptors

Angiotensin II recepto r antagonists


111/180

ARBs could be considered in patients who do nottolerateACE inhibitorsfor symptomatictreatment.

It is unclear whether ARBs are as effective asACE inhibitors for mortality reduction.

In combination with ACE inhibition, ARBs may

improve heart failure symptoms and reducehospitalizations for worsening heart failure.



Angiotensin II recepto r antagonists


112/180

VAL-H

Patients were randomized to placebo orvalsartan on top of standard therapy.

The results showed no difference in overallmortality, but a reduction in the combined end-point all-cause mortality or morbidity

expressed as hospitalization because ofworsening heart failure.


113/180

6. Cardiac glycosides

DIGOXIN


114/180

Na+

K+

K+

Na+

Na+ Ca++

Ca++

Na-K ATPase Na-Ca Exchange

Myofilaments

DIGOXIN

CONTRACTILITY

DIGOXIN


115/180

PHARMACOKINETICPROPERTIES

Oral absorption (%)

Protein binding (%)

Volume of distribution (l/Kg)

Half life

EliminationOnset (min)

i.v.

oral

Maximal effect (h)

i.v.

oral

Duration

Therapeutic level (ng/ml)

60 - 75

25

6 (3-9)

36 (26-46) h

Renal

5 - 30

30 - 90

2 - 4

3 - 6

2 - 6 days

0.5 - 2

DIGOXIN


116/180

DIGITALIZATION STRATEGIES

(mg)

0.125-0.5 / d

0.25 / d

i.v

0.5 + 0.25 / 4 h

ILD: 0.75-1

oral 12-24 h

0.75 + 0.25 / 6 h

1.25-1.5

oral 2-5 d

0.25 / 6-12 h

1.5-1.75

Loading dose (mg)Maintenance

Dose

ILD = average INITIAL dose required fordigoxin loading

DIGOXIN


117/180

HEMODYNAMIC EFFECTSCardiac output

LVejection fractionLVEDP

ExercisetoleranceNatriuresis

Neurohormonalactivation

DIGOXIN


118/180

NEUROHORMONALEFFECTS

PlasmaNoradrenaline

Peripheral nervous system activityRAAS activity

VagaltoneNormalizes arterial baroreceptors

DIGOXIN


119/180

%WORSENING

OF CHFp = 0.001DIGOXIN: 0.125 - 0.5 mg /d

(0.7 - 2.0 ng/ml)EF < 35%Class I-III (digoxin+diuretic+ACEI)

Also significantly decreased exercisetime and LVEF.

EFFECT ON CHF PROGRESSION

RADIANCEN Eng l J Med 1993;329:1

Placebo n=93DIGOXINWithdrawal

DIGOXIN n=85

30

10

0

20

10080200 40 60

Days

OVERALL MORTALITY


120/180

50

40

30

20

10

0

Placebon=3403

DIGOXINn=3397

480 12 24 36

%

DIGN Eng l J Med 1997;336:525 Months

p = 0.8

DIGOXIN


121/180

LONG TERM EFFECTS

Survival similar to placebo

Fewer hospital admissions

More serious arrhythmias

More myocardial infarctions

DIGOXIN


122/180

CLINICALUSES

AF with rapid ventricular response

CHF refractory to other drugs

Other indications?

Can be combined with other drugs

DIGOXIN


123/180

CONTRAINDICATIONSABSOLUTE:-Digoxin toxicity

RELATIVE

- Advanced A-V block without pacemaker

-Bradycardia or sick sinus without PM

- PVCs and TV

- Markedhypokalemia

- W-P-W with atrial fibrillation

DIGOXIN TOXICITY


124/180

CARDIAC MANIFESTATIONS

ARRHYTHMIAS :

-Ventricular (PVCs, TV, VF)

- Supraventricular (PACs, SVT)

BLOCKS:

- S-A and A-V blocks

CHF EXACERBATION

DIGOXIN TOXICITY


125/180

EXTRACARDIACMANIFESTATIONSGASTROINTESTINAL:

-Nausea, vomiting, diarrheaNERVOUS:

- Depression, disorientation, paresthesias

VISUAL:

-Blurred vision, scotomas and yellow-greenvision

HYPERESTROGENISM:- Gynecomastia, galactorrhea

Cardiac glycosides


126/180

indicated in atrial fibrillation and any degreeof

symptomatic heart failure.

A combination of digoxin and beta-blockadeappears superior than either agent alone.

In sinus rhythm, digoxin is recommended toimprove the clinical statusof patients with

persisting heart failuredespite ACE inhibitor anddiuretic treatment.



Cardiac glycosides


127/180

DIG tr ial

Long-term digoxin did not improve survival.

The primary benefit and indication for digoxinin heart failure is to reduce symptomsand

improve clinical statusdecrease the risk of

hospitalization for heart failure without an

impact on survival.


128/180

7. Vasodilator agents

N ifi l f dil t i th t t t f HF

Vasodi lator agents in chronic heart failure


129/180

No specific role for vasodilators in the treatment of HF

Used as adjunctive therapyfor angina or concomitant

hypertension.

In case of intolerance to ACE inhibitors ARBs are

preferred to the combination hydralazinenitrates.

HYDRALAZINE-ISOSORBIDE DINITRATE

Hydralazine (up to 300 mg) in combination with ISDN (up to 160

mg) without ACE inhibition may have some beneficial effect on

mortality, but not on hospitalization for HF.

Nitratesmay be used for the treatment of concomitant anginaor

relief of acute dyspnoea.




130/180

8. Positive inotropic therapy

POSITIVE INOTROPES


131/180

CARDIAC GLYCOSIDES

SYMPATHOMIMETICS

Catecholamines-adrenergic agonists

PHOSPHODIESTERASE INHIBITORSAmrinoneEnoximone

Others

Milrinone

Piroximone

-ADRENERGIC STIMULANTS


132/180

CLASSIFICATION

B1StimulantsInc rease contract i l i ty

Dobutamine Doxaminol Xamoterol

Butopamine Prenalterol Tazolol

B2StimulantsProdu ce arter ial vasodi latat ion and reduce SVR

PirbuterolCarbuterolRimiterolFenoterol TretoquinolSalbutamolTerbutalineSalmefamolSoterenolQuinterenol

MixedDopamine

DOPAMINE AND DOBUTAMINE


133/180

EFFECTS

Receptors

Contractility

Heart Rate

Arterial Press.Renal perfusion

Arrhythmia

DA (g / Kg / min) Dobutamine

< 2

DA1/ DA2

++

-

2 - 5

1

++

+

++

> 5

1+ a++

++

++

++

1

++

+++

POSITIVE INOTROPES


134/180

CONCLUSIONS

May increase mortality

Safer in lower doses

Use only in refractory CHF

NOT for use as chronic therapy

Posi t ive ino trop ic therapy


135/180

Commonly used to limit severe episodes of

HFor as a bridge to heart transplantationin end-stage HF.

Repeated or prolonged treatment with oral

inotropic agents increases mortality.

Currently, insuffcient data are available torecommend dopaminergic agents for heartfailure treatment.



Posi t ive ino trop ic therapy


136/180

POSITIVE INOTROPHIC AGENTS

DobutaminMilrinone

Levosimendan

DOPAMINERGIC AGENTSIbopamineis not recommended for the treatment of

chronic HF due to systolic LV dysfunction.

Intravenous dopamineis used for the sort-term

correction of haemodynamic disturbancesof severeepisodes of worsening HF.




137/180

9. Antiarrhythmics

ANTIARRHYTHMICS


138/180

Sustained VT, with/without symptoms

- Blockers

-AmiodaroneSudden death from VF

-Consider

implantabledefibrillator

ANTIARRHYTHMICS


139/180

MORTALITY

EMIATAm Coll Cardiol 1996

13.6 13.7

Placebo Amiodarone0

5

10

15

101 / 743 102 / 743

MORTALITY

AT 2 YEARS%

n=14865-21d post MIAmiodarone200 mg/dFollow up 1 - 4 years

ns

N i di ti f th f ti h th i t i HF

Ant iarrhythmics


140/180

No indication for the use of antiarrhythmic agents in HF

Indications for antiarrhythmic drug therapy include AF(rarely flutter), non-sustained or sustained VT.

CLASS I ANTIARRHYTHMICS

should be avoided

CLASS II ANTIARRHYTHMICS

Beta-blockers reduce sudden death in heart failure

CLASS III ANTIARRHYTHMICS

Amiodarone is the only antiarrhythmic drug withoutclinically relevant negative inotropic effects.




141/180

10. Anticoagulation

11. Antiplatelet Drugs

ANTICOAGULANTS


142/180

PREVIOUS EMBOLIC EPISODEATRIAL FIBRILLATION

Identified thrombus

LV Aneurysm (3-6 mo post MI)Class III-IV in the presence of:

-EF < 30

-Aneurysm or very dilated LVPhlebitis

Prolonged bed rest

Ant icoagulat ion


143/180

Recommendation

1. All pts with HF and AFshould be treated with

warfarin unless contraindicated.

2. Patients with LVEF 35%or less.

HFSA Guidelines for Management of Patients With Heart Failure Caused by Left

Ventricular Systolic Dysfunction - Pharmacological Approaches 2000

An t iplatelet Drug s


144/180

Recommendation

There is insufficient evidence concerning thepotential negative therapeutic interactionbetween ASA and ACE inhibitors.

Antiplatelet agent for pts with HF who haveunderlying CAD.

HFSA Guidelines for Management of Patients With Heart Failure Caused by Left

Ventricular Systolic Dysfunction - Pharmacological Approaches 2000

Chron ic heart fai lure cho ice of

pharmacological therapyA


145/180

LV systolic dysfunction ACE inhibitor Diuretic Beta-blocker AldosteroneAntagonist

Asymptomatic LV

dysfunctionIndicated Not indicated Post MI Not indicated

Symptomatic HF (NYHA II) Indicated

Indicated if

Fluid retention Indicated Not indicated

Worsening HF (NYHA III-IV) IndicatedIndicated

comb. diuretic

IndicatedIndicated

End-stage HF (NYHA IV) Indicated

Indicated

comb. diuretic

Indicated

Indicated



Chronic heart fai lure cho ice ofpharmacological therapy

B


146/180

LV systolic dysfunction

Angiotensin

II receptor

antagonists

Cardiac glycosides

Vasodilator

(hydralazine/

isosorbide

dinitrate)

Potassium -sparing

diuretic

Asymptomatic LV

dysfunctionNot indicated With AF Not indicated Not indicated

Symptomatic HF (NYHA II)

If ACE inhibitors

are not tolerated

and not on beta-

blockade

(a) when AF

(b) when improved

from more severe

HF in sinusrhythm

If ACE inhibitors

and angiotensin

II antagonists

are not

tolerated

If persisting

hypokalaemia

Worsening HF (NYHA III-IV)

If ACE inhibitors

are not tolerated

and not on beta-

blockade

indicated

If ACE inhibitors

and angiotensin

II antagonists

are not

tolerated

If persisting

hypokalaemia

End-stage HF (NYHA IV) If ACE inhibitorsare not tolerated

and not on beta-

blockade

indicated

If ACE inhibitors

and angiotensinII antagonists

are not

tolerated

If persistinghypokalaemia




147/180

Intervention

RevascularizationSurgical


148/180

Pts with heart failure of ischaemicorigin revascularization symtomatic improvement.

A strong negative correlation of operative mortality and LVEF,

a low LVEF (


149/180

Recommended components of programs

use a team approachvigilant follow-up, first follow-up within 10 days ofdischarge

discharge planning

increased access to health careoptimizing medical therapy with guidelines

intense education and counselling inpatient andoutpatient

strategies address barriers to compliance

early attention to signs and symptoms

flexible diuretic regimen



Future treatment


150/180

1. Sympathetic nervous system

2. The RAA system3. Atrial and brain natriuretic peptides

4. Arginin vasopressin

5. Endothelin

6. Growth hormone

7. Calcitonin gene related peptide

Neurohormonal modulation

Cardiac reparation: fixing the heartwith cells, new vessels and genes (1)


151/180

1. Multiplication of residual myocytes(forcing the cells to enter mytotic cycle)

2. Transforming fibrablasts in the scar

3. Implanting exogenous contractiles cells(foetal cardiomyocites, skeletalmyoblasts, stem cells)

Aims:to repopulate fibrous scars with new

contractile cells

Cell based

interventions

Eur Heart J 2002;4: D73-81

CONT (2)


152/180

1. Administration of angiogenic growth factors

VEGF, basic FGF

2. Problems: nature of compound , dose,

route, and adverse events (abnormal bloodvessels, proliferative retinopathy, etc)

AngiogenesisAims:to provides new blood supply to

the diseased heart

Eur Heart J2002;4: D73-81

CONT(3)


153/180

1. Gene manipulation of 3 majors areas: Ca

handling, beta-adenergic signalling and

apoptosis

2. Inducing expression of silent genes

Gene therapy

Aims:to improve the function of the failing

heart

Safety problems:control of targeted proteinexpression, inflammation, autoimmunity

and oncogenesis (basically irreversible)

Eur Heart J 2002;4: D73-81

Dual-chamber pacemakers arebeneficial


154/180

Drug-resistant CHF

Intact sinus rhythm

Absence of chronic atrial dysrhythmias

EF , MR and TR, QRS >, QRS

PR + QRS > 350 ms. QRS >140 ms, MR > 450 ms, and LV filling

time


155/180

py Reason:

Patients with CHF frequently exhibitedQRS prolongation with diseaseprogression. The delayed ventricular

activation leads to asynchronousventricular contraction with negativeeffects on LV performance

Aim:

To normalize AV activation sequenceand disturbed ventricular contractionpatterns

Cardiac resynchronizationtherapy


156/180

StudyNYHA QRS (ms) EF (%)

0 mo 3 mo 0 mo 3 mo 0 mo 3 mo

Path-CHF

(n=42)

3.0 2.0 - - - -

In Sync(n=81)

3.4 2.2 179 143 21 24

Alouco

(n=26)

3.3 2.0 179 159 - -

MUSTIC(n=67)

- - 176 - 23 -

J Inv Cardiol2002; 14: 48-53

Resume


157/180

Pharmacological Treatment :

I. Asymptomatic Systolic LV dysfunction: ACE Inhibitor

-Blocker (in CAD)

II. Symptomatic Systolic LV dysfunction

A. No fluid retentionACE Inhibitor

-BlockerIf ischaemia (+) nitrate / revascularization

B. Fluid retention

Diuretic

ACE Inhibitor (ARBs if not tolerated)

-BlockerDigitalis

Resume


158/180

III. Worsening HF

Standard treatment : ACE Inhibitor, -BlockerDiuretic : doses + loop diureticLow dose spironolactone

Digitalis

Consider :

Revascularization

Valve surgery

Heart transplant

IV. End-stage HF

Intermittent inotrophic support

Circulatory support (IABP, Ventr.Assist Devices)Haemofiltration on dialysis

briddging to heart transplantation

Conclusion


159/180

Management of HF must be starting fromtheearlier stage(AHA/ACC stage A).

Treatment at each stage can reduce

morbidity and mortality.

Before initiatingtherapy:

Established the correct diagnose.

Consider management outline.

Conclusion

Non pharmacolgical intervention are helpfull in :


160/180

Non pharmacolgical intervention are helpfull in:

improving quality of lifereducing readmission

lowering cost.

Organize multi-disciplinary care:

HF clinic, HF nurse specialist, pts telemonitoring.

Health care system.

To optimize HF management

Treatment should be according to the Guidelines,intensive education, and behavioral change efforts.


161/180

Thank YoU


162/180


163/180

DIASTOLIC HEART

FAILURE

SCOPE OF THE PROBLEM


164/180

Epidemiological studies of HF havesuggested that 30-50% of cases of HF

have preserved LV systolic function.

DHF has mortality rate equal assystolic heart failure

No guideline yet regarding the

treatment of DHF

Greenberg & Hermann 2004

Defining Diastolic Heart Failure


165/180

Diastolic dysfunction refers to a condition in which

abnormalities in mechanical function are presenting

during diastole.

Diastolic dysfunction is a condition in which higherthan normal LV filling pressure are needed to maintain

a normal cardiac output.

Diastolic heart failure is a clinical syndrome

characterized by the symptoms and signs of heartfailure, a preserved EF and abnormal diastolic

function.

(Vasan & Levy 2000)

Normal diastolic

function

Mild diastolic

dysfunction

Pseudonormal

stage

Restrictive-

filling stage

Echo-Doppler and Diastolic Dysfunction


166/180

function dysfunction stage filling stage

Left ventricular relaxation Normal Left ventricular stiffness Normal Left atrial contractility Normal Normal Preload Normal Normal

Electrocardiogram

Mitral flow

Pulmonary venousflow

E wave

A wave

QRST P

Diastole

Systole

Atrial reversal

( Garcia, 2000 )

Diastolic Heart Failure : Effects of

Age on Prevalence and Prognosis


167/180

Age, y

70

Prevalence 15 33 50

Mortality 15 33 50

Morbidity 25 50 50

( Zile & Brutsaert, 2002 )

CHARACTERISTICS

Age

Sex

DIASTOLIC HEART

FAIURE

Frequently elderly

Frequently female

SYSTOLIC HEART

FAILURE

All ages,typically 50-70 yr

More often male


168/180

Sex

Left ventricle EF

Left ventricle cavity size

LVH on echo

Chest radiography

Gallop rhythm present

Coexisting conditions

Hypertension

Diabetes mellitus

Previous MCI

Obesity

Chronic lung disease

Sleep apnea

Long term dialysis

Atrial fibrillation

Frequently female

Preserved or normal (+ > 40%)

Usually normal,often LVH

concentric

Usually present

Congestion with/out cardiomegali

Fourth heart sound

+++

+++

+

+++

++

++

++

+

Usually paroxismal

More often male

Depressed,+ < 40%

Usually dilated

Sometimes present

Congestion & cardiomegali

Third heart sound

++

++

+++

+

0

++

0

+

Usually persistent(NEJM 2003)

Conditions Associated with Diastolic

Dysfunction


169/180

Condition

Coronary artery disease

Hypertensive heart disease

Valvular heart disease

Normal aging

Hypertrophic cardiomyopathy

Infiltrative disease of the

myocardium

(amyloid,sarcoid,haemocromatosis,

lympoma)

Possible Contributory Mechanism :

Asynchronous myocardial relaxation

secondary,to ischemia or scar and

altered mechanical loading

LVH

AS leading to LVH , MS leading to reduced

filling

Impaired early filling due to reduced

compliance with associated increase in late

filling

Hypertrophy,fibrosis, and asynchronous

regional lengthening, hence impairedrelaxation.

Reduced LVED distensibility (increased

LVEDP)

(Vasan & Levy 1998)


170/180

(Mandinov,Eberli,Seiler,Hess.Cardiosvasc Res 2000)

Diagnostic Criteria for Diastolic Heart Failure

Signs or symptoms of congestive heart failure

Exertional dyspnoea [eventually objective evidence by reduced peak exercise oxygen consumption(


171/180

( European Study Group on DHF, 1998 )

and

Normal or mildly reduced left ventricular systolic function:

LVEF45% and LVEDIDI105 ms

and/or >48 msand/or slow early left ventricular filling:

PFR12 mmHg

and/or PV A Flow > 35 cm.s-1

and/or PV A t>MV A t+ 30 ms

and/or A/H>0.20

and/or increased left ventricular chamber or muscle stiffness:

b>0.27

and/or b>16

Criteria for Definite DHF

Criterion Objective Evidence


172/180

Definite evidence of CHF

AND

Objective evidence of normal LVsystolic function in proximity to

the CHF event

AND

Objective evidence of LV diastolicdysfunction

Includes clinical symptoms and signs, supporting

laboratory tests (such as chest X-ray), and a typicalclinical response to treatment with diuretics, with or

without documentation of elevated LV filling pressure

(at rest, on exercise, or in response to a volume load)

or a low cardiac index

Abnormal LV relaxation /filling/distensibility indices on

cardiac catheterization

LV EF > 0.50 within 72 h of event

( Vasan & Levy, 2000 )

Criteria for Probable DHF


Definitive evidence of CHF Includes clinical symptoms and signs, supporting laboratory tests

(such as chest X-ray), and a typical clinical response to treatment

with diuretics with or without documentation of elevated LV filling


173/180

Objective evidence of normal LV systolic

function in proximity to the CHF event

Objective evidence of LV diastolic

dysfunction is lacking

AND

BUT

with diuretics, with or without documentation of elevated LV filling

pressure (at rest, on exercise, or in response to a volume load) or a

low cardiac index

LV EF > 0.50 within 72 h of CHF event

No conclusive information on LV diastolic function

Criteria for Possible DHF


Definitive evidence of CHF

Objective evidence of normal LV systolic

function, but not at the time of the CHF event

Objective evidence of LV diastolic dysfunction

is lacking

Includes clinical symptoms and signs, supporting laboratory test (such

as chest X-ray), and a typical clinical response to treatment with

diuretics, with or without documentation of elevated LV filling pressure

(at rest, on exercise, or in response to a volume load) or a low cardiac index

LV EF > 0.50

No conclusive information on LV diastolic function

AND

AND

( Vasan & Levy, 2000 )

Other Methods in diagnosing DHF

Plasma Brain Natriuretic Peptide


174/180

Plasma Brain Natriuretic Peptide

Doppler tissue imaging

Magnetic resonance imaging

Radionuclide angiography

Cardiac catheterization

Greenberg & Hermann 2004

Treatment of Diastolic Heart Failure


175/180

Clinical investigations in relatively small

groups of patients Clinical experience

Concepts based on pathophysiology

mechanisms

The guidelines are based on :

Treatment of Diastolic Heart failure


176/180

Treatment of Diastolic Heart failure

symptom targeted treatment

disease / pathological targeted treatment

the underlying mechanism targeted

treatment

( Zile & Brutsaert, 2002 )

Diastolic Heart Failure: Treatment


177/180

Symptom targeted treatment

Decrease pulmonary venous pressure

Reduce LV volumeMaintain atrial contraction

Prevent tachycardia

Improve exercise tolerance

Use positive inotropic agents with caution( Zile & Brutsaert, 2002 )

Diastolic Heart Failure: Treatment

N h l i l t t t

Symptom targeted treatment


178/180

Nonpharmacological treatment

Restrict sodium to prevent volume overload

Restrict fluid to prevent volume overload

Perform moderate aerobic exercise to improve cardiovascular

conditioning, decrease heart rate and maintain skeletal muscle

function

Pharmacological treatment

Diuretics including loop diuretics thiazides, spironolactone

Long-acting nitrates, -Adrenergic blockersCalcium channel blockers

Renin angiotensin-aldosterone antagonists including ACE

inhibitors, angiotensin II receptor blockers and aldosterone

antagonists ( Zile & Brutsaert, 2002 )

Disease-targeted treatment

Prevent/treat myocardial ischemia

Diastolic Heart Failure


179/180

Prevent/treat myocardial ischemia

Prevent/regress ventricular hypertrophy

Mechanisms targeted treatment

Modify myocardial and extramyocardial mechanisms

Modify intracellular and extracellular mechanisms

An ideal therapeutic agent.

- Should target the underlying mechanisms

- Improve calcium homeostasis and energetics

- Blunt neurohumoral activation

- Prevent and regress fibrosis( Zile & Brutsaert, 2002 )

Trials of Diastolic Heart Failure

Trial Comparison Follow-up (n) Diagnostic Criteria

for DHF

Other Important

Inclusion/ Exclusion

Main Outcomes


180/180

Criteria

PEP-CHF

CHARM-2

I-PRESERVE

SENIORS

(diastolic subset)

Hong Kong

SWEDIC

Placebo

Perindopril

Placebo

Candesartan

Placebo

IrbesartanPlacebo

Nebivolol

Placebo

Ramipril

Irbesartan

Placebo

Carvedilol

1.000

Minimum 18 months

2.500

Minimum 24 months

3.600

Approx 48 months2.000

(% DHF uncertain)

450

Minimum 12 months

140

9 months

3 of 9 clinical and

2 of 4 echocardiographic

criteria

EF > 40%

EF > 45%

EF > 35% and a cardiac

abnormality

Doppler criteria

Doppler criteria

Age > 70 years

Diuretics

Hospital admission in last

3 months

None

Clinical diagnosis of HF

Aged > 70 years

Hospital admission within

last 12 months

Diuretics

AF excluded

Death or HF-related

hospitalization

Death or hospitalization

for HF

Death and hospitalization

cardiovascular disease

Death or hospitalization

for HF

Quality of life 6-minute

walk test

Regression of diastolic

dysfunction

All About CHF

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