A History of Dropsy:

From Edema to Transplant

Timothy A. Denton, M.D.Attending Cardiologist

High Desert Heart InstituteVictorville, CA

Outline

• History• Physiopathology• Evaluation• Medical therapy• Other therapies

The Time Line

500 20000 500 1000 1500

Socrates (470-399 BC)Hippocrates (460-377 BC)

BC AD

Galen (180)

Harvey (1616)

Laënnec(1700)

dropsy

Heart Failure

~400 B.C. – SOB, edema, rales

First described by HippocratesEar directly on chest

How to drain effusionscaused by excess of “phlegm” (cold humor)

Moving from brain to chest

Dropsy

A morbid condition characterized by the accumulation

of watery fluid in the serous cavitiesor the connective tissue of the body.

Hydrops, Idropsie

First use in 1290 – “Some fullen in-to be dropesie”

OED

DropsyA woman, 50 years of age, had been affected for twelve years with all the symptoms of disease of the heart, in a very high degree, viz. strong and frequent palpitations, habitual dyspnoea, breathlessness on using the least

exercise, sudden startings from sleep, almost constant edema of the lower extremities, and lividity of the cheeks,

nose and lips.

Laennec“A Treatise on the Diseases of the Chest”

1821

Dropsy

Treatment of the Weak and probably Dilated Heart…

During this treatment, and especially when free diuresis is established, it is necessary that wine or some other diffusible

stimulus should be carefully administered, and the system supported by a proper aliment…

Stokes“Diseases of the Heart and the Aorta”

1853

William Harvey

1578-16571639: De Motu Cordis

“We then come to the bloodstream.The blood rushes from the head, down to the feet…gets a look at those feet,and rushes back to the head again.”

Groucho on the Circulation

from “Horse Feathers” 1932(Julius Henry Marx)

William Withering

Born: 1741 - 17991775: Obtained first “tea” from gypsy

From German: Fingerhut (finger hat or thimble)Mid-1500’s: Latinized to “digitalis” – finger (digitus)Digitalis purpurea – a common variety1775 – William Withering

Heart Failure - Etiology

“Pure”LV Heart failure

_________________

Systolic dysfuntionDiastolic dysfunction

IschemicLV Heart failure

_________________

Prior MIOngoing ischemia

Large vessel diseaseSmall vessel disease

MechanicalHeart failure

_________________

ASMR

PericardiumEndocardiumMyocardium

Treat the underlying cause

Definition of Heart Failure

2005 ACC/AHA HF Guidelines

Clinical syndrome resulting from astructural or functional disorder

that impairs the heart fromfilling or ejecting blood

Clinical syndrome includesSymptoms (dyspnea, fatigue) and

Signs (fluid retention)

Heart failure ≠ congestive heart failure

AHA CHF Guidelines

• Stage A – Risk for CHF• Stage B – Heart disease, no symptoms• Stage C – Heart disease, symptoms• Stage D – Heart disease, refractory symptoms

ACC/AHA CHF Guidelines – 2005www.americanheart.org

Heart Failure

Diagnosis• Clinical

SOB, DOEOrthopneaEdema

• CxR• BNP• Echo (or equivalent)• Is there another cause of symptoms?

New York Heart Association Classes

2005 ACC/AHA HF Guidelines

I – symptoms similar to normal patients

II – symptoms with ordinary exertion

III – symptoms at less-than-ordinary exertion

IV – symptoms at rest

Heart Failure

Diagnosis

What is the EF?

Low NormalHigh

• Echo• Echo• Echo• MUGA

Heart Failure

Is there ischemia?

Yes No

Diagnosis

PTCACABGEECP

Heart Failure

Normal Heart Enlarged Heart

Heart Failure

Dilated Normal Hypertrophic

Heart Failure

Systole = contraction (inotropy)

Diastole = relaxation (lusitropy)

Heart Failure

What is diastolic dysfunction?

Heart Failure

Dilated Normal Hypertrophic

Heart FailureSystolic vs Diastolic Failure

Kitzman,et al., Am J Cardiol, 2001;87:413-419

45%

55%Diastolic

Systolic

*No valvular or mechanical causes

LV Systolic Heart Failure

• It’s a hemodynamic diseasePreloadContractilityAfterload

• It’s a neurohormonal disease• Other factors affecting therapy

Heart FailureIt’s a hemodynamic disease !

Preload

Afterload

Contractility

PreloadInpatient and Outpatient Therapy

IV diuretics Lasix (20,40,80,160,320) Lasix drip Combination (Lasix / zaroxolyn)Naturetic peptic (nesiritide)Dialysis / UltrafiltrationNitrates

Control of Volume Status

Patient Responsibilities

• Weight yourself every day• Write it down• 2,000 mg of Sodium per day• 2,000 cc of fluids per day• If your weight goes up by “X”, change your diuretics

DiureticsDrug Dosing Max Duration

Loop

Bumetanide Furosemide Torsemide Ethacrynic acid

0.5 – 1.0 qd BID20 – 40 qd BID

10 – 20 qd25-50 qd BID

10 mg600 mg200 mg200 mg

4-6 h6-8 h

12-16 h6-7 h

Thiazide

Chlorothiazide Chlorthalidone HCTZ Indapamide Metolazone

250 500 qd BID12.5 – 25 qd

25 qd BID1.5 qd2.5 qd

1000 mg100 mg200 mg

5 mg

20 mg

6 – 12 h24-72 h6-12 h36 h

12-24 h

Potassium sparing

Amiloride Spironolactone Triamterene

5 qd12.5 – 25 qd

50 – 75 qd BID

20 mg50 mg

200 mg

24 h2-3 days

7-9 h

Preload

Used into the late 1950’s

Southey’s Tubes

Ultrafiltration

CHF Solutions, Inc.

Dialysis / Ultrafiltration

Heart FailureIt’s a hemodynamic disease !

Preload

Afterload

Contractility

Contractility

• Digoxin• Dobutamine• Milrinone• Epinephrine• Dopamine• LVAD• Heart transplantation

Ambulatory Infusion Pumps

• Dobutamine• Milrinone

LV Assist Devices

• Bridge to Transplant• Destination therapy

Heart Transplantation

• Ejection fraction• Cardiopulmonary exercise testing – VO2 < 14 (???)• Other risk factors• “Risk Score”• Referral to transplant team• Local “work-up”

ISHLT Guidelines – 2006Heart and Lung Transplantation 2006;25:1024

HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2004)

ISHLT 2006

N followed at longest time point: 28,463

J Heart Lung Transplant 2006;25:869-79

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Years

Su

rviv

al (

%)

.

Half-life = 9.9 yearsConditional Half-life = 13 years

N=69,536

Heart FailureIt’s a hemodynamic disease !

Preload

Afterload

Contractility

Afterload• Lowered afterload improves hemodynamics in MR

(Ann Int Med 1975;83:312)• Vasodilator therapy in heart failure

(Ann Int Med 1975;83:421)• Hydralazine / Minoxidil in refractory CHF

(Ann Int Med 1976;85:467)• Lowered afterload improves hemodynamics in AI

(Circulation 1976;53:879)• Lowered afterload improves hemodynamics in CHF

(Ann Rev Physiology 1977;39:277• 1987 - CONSENSUS I

Afterload

• Nitroprusside• ACE inhibitors• ARB’s• Hydralazine / nitrates

Heart Failure

SOLVD NEJM 1991;325:293-302

ACE / ARB

Drug Dosing Max

ACE

CaptoprilEnalaprilFosinoprilLisinoprilPerindoprilQuinaprilRamiprilTrandolapril

6.25 tid2.5 bid5-10 qd2.5-5 qd

2 qd5 bid

1.25-2.5 qd1 qd

50 tid10-20 bid

40 qd20-40 qd8-16 qd20 bid10 qd4 qd

ARB

CandesartanLosartanValsartan

4-8 qd25-50 qd20-40 bid

32 qd50-100 qd

160 bid

Heart Failure

It’s a neurohormonal disease !

• 1963 – Plasma norepinephrine elevated in CHF(NEJM 1963;269:653)

• 1970’s digoxin reduces plasma renin and norepinephrine levels

Neurohormonal

• Beta blocker• Spironolactone / eplerenone• ACE inhibitors• ARB’s

Davies, M K et al. BMJ 2000;320:428-431

Randomised Aldactone Evaluation Study (RALES)

Is there a BEST Beta Blocker?

• Carvedilol• Bisoprolol• Metroprolol succinate

Is there a BEST Beta Blocker?

17% Reduction

Carvedilol or Metoprolol European Trial (COMET) Lancet 2003; 362:7

Beta Blockers

Drug Dosing Max

BisoprololCarvedilolMetoprolol succinate (CR/XL)

1.25 qd3.125 bid

12.5 – 25 qd

10 qd25 bid200 qd

CHF with or without

Dysrhythmia

• ICD• Antiarrhythmics• Beta blockers

ICD’s and Survival

MADIT II SurvivalN Engl J Med. 2002;346:877-883

Dysynchrony

• Bi-V pacing

Heart Failure Clinic

• Central location with ICU nurses• Drug infusion

diureticsdobutaminenesiritide (Fusion II)

• Education• “CAREFUL” follow-up

Medical Therapy

Preload

+ Lasix

+ Ultrafiltration

+ Nitrates

ContractilityDigoxin

Transplant evaluation / LVAD

AfterloadACE / ARB

Hydralazine

Neurohormonal

Beta blocker

ACE / ARB

Spironolactone / eplerinone

DysrhythmiaICD

+ Antiarrhythmics

Dysynchrony BiV Pacing

Therapy of Heart Failure

0 10 20 30 40 50 60 70 80 90 100

Ejection Fraction

NormalRange

Systolic Dysfunction Diastolic Dysfunction

Therapy of Heart Failure

0 10 20 30 40 50 60 70 80 90 100

Ejection Fraction

NormalRange

Systolic Dysfunction Diastolic Dysfunction

• ICD• Heart transplant

• Aggressive MedRx

•BiV pacer

Therapy of Heart Failure

0 10 20 30 40 50 60 70 80 90 100

Ejection Fraction

NYHA

CLASS

I

II

III

IV

Medical therapy

BiV ICD

ICDandTransplant evaluation

The END