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CONGESTIVE HEART CONGESTIVE HEART FAILUREFAILURE

EDWARD M. GELTMAN, M.D.EDWARD M. GELTMAN, M.D.PROFESSOR OF MEDICINEPROFESSOR OF MEDICINEWASHINGTON UNIVERSITY WASHINGTON UNIVERSITY

SCHOOL OF MEDICINESCHOOL OF MEDICINE

CHF: DEFINITIONCHF: DEFINITION

Congestive heart failure is a clinical Congestive heart failure is a clinical syndrome in which a patient has insufficient syndrome in which a patient has insufficient cardiac output to meet the oxygen andcardiac output to meet the oxygen andcardiac output to meet the oxygen and cardiac output to meet the oxygen and nutrient requirements of the various organs. nutrient requirements of the various organs. The condition is usually accompanied by The condition is usually accompanied by fluid accumulation in either the pulmonary or fluid accumulation in either the pulmonary or systemic venous beds (or both)systemic venous beds (or both)

Common Symptoms of Heart Common Symptoms of Heart FailureFailure

Dyspnea on exertionDyspnea on exertionParoxysmal nocturnal dyspnea/orthopneaParoxysmal nocturnal dyspnea/orthopneaFatigueFatigueLower extremityLower extremity edemaedema ascitesascitesLower extremity Lower extremity edemaedema, ascites, ascitesCough, usually worsening at nightCough, usually worsening at nightNausea, vomiting, anorexia, RUQ painNausea, vomiting, anorexia, RUQ painNocturiaNocturiaSleep disordersSleep disorders

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Common Physical Findings of Common Physical Findings of Heart FailureHeart Failure

Elevated jugular venous pressureElevated jugular venous pressureHepatojugular refluxHepatojugular refluxDisplaced apical impulseDisplaced apical impulseS3 gallopS3 gallopg pg pPulmonary ralesPulmonary ralesHepatomegalyHepatomegalyAscitesAscitesPeripheral edemaPeripheral edemaCardiac cachexiaCardiac cachexia

Causes of Heart FailureCauses of Heart Failure

Coronary Artery DiseaseCoronary Artery DiseaseHypertensionHypertensionValvular heart disease (rheumatic, Valvular heart disease (rheumatic, d ti it l l ifid ti it l l ifidegenerative, congenital, calcific, degenerative, congenital, calcific, infectious)infectious)Toxins (alcohol, cocaine, chemotherapy)Toxins (alcohol, cocaine, chemotherapy)MyocarditisMyocarditisIdiopathicIdiopathic

Hypertension is the No. 1 risk factor for HFHypertension is the No. 1 risk factor for HF

20

40

60

Population-attributable

risk (%)

Framingham Heart Study

20

0HTN MI Angina VHD LVH Diabetes

Hazard ratio M 2.1 6.3 1.4 2.5 2.2 1.8W 3.3 6.0 1.7 2.1 2.8 3.7

Men Women

Levy D at al. JAMA. 1996;275:1557-62.VHD = valvular heart disease

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Diabetes is the No. 1 risk factor Diabetes is the No. 1 risk factor for HF in women with coronary for HF in women with coronary

diseasediseaseDiabetes

Atrial fibrillationMyocardial infarction >1 event

Creatinine clearance 35

Left bundle branch block

LV hypertrophy

Systolic BP 1402.1

1.91.9

1.61.5

0 0.5 1 1.5 2 2.5 3 3.5

Increasing risk for HF in women with CHD: Increasing risk for HF in women with CHD: Impact of diabetes, renal insufficiency, obesityImpact of diabetes, renal insufficiency, obesity

HERS study; 2391 women with CHD and no HF at baseline

10

12

14 12.8

Annual

Bibbons-Domingo K et al. Circulation.2004;110:1424-30.CrCl (ml/min) = creatinine clearance

0

2

4

6

8

CHD CHD + DM CHD + DM + BMI >36

CHD + DM + CrCl

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Heart Failure HospitalizationsHeart Failure HospitalizationsThe Number of Heart Failure Hospitalizations Is Increasing

in Both Men and Women

scha

rges

400,000

500,000

600,000

CDC/NCHS: hospital discharges include patients both living and dead.American Heart Association. 2002 Heart and Stroke Statistical Update. 2001.

Ann

ual D

is

0

100,000

200,000

300,000

'79 '81 '83 '85 '87 '89 '91 '93 '95 '97

WomenMen

Year'99

Heart Failure Severity in the United Heart Failure Severity in the United StatesStates

Class INo limitations of physical activityClass IISlight limitations of physical

Class IV240 K(5%)

Class III1.20 M(25%)

Class I1.68 M(35%)

activityClass IIIMarked limitations of physical activityClass IVInability to carry out physical activities without discomfort and/or symptoms at rest

Class II1.68 M(35%)

AHA Heart and Stroke Statistical Update 2001

Pathogenesis of Myocardial DysfunctionPathogenesis of Myocardial Dysfunction

Oxidative stressOxidative stressApoptosisApoptosis

Injury to myocytesand extracellular matrix

VentricularRemodeling

Neurohormonal activationNeurohormonal activationIncreased cytokineIncreased cytokineexpressionexpression

Electrical, vascular,renal, pulmonary,

muscle, and other effects

Altered geneAltered geneexpressionexpressionEnergy starvationEnergy starvation

Inflammatory changesInflammatory changesAltered fibrinolysisAltered fibrinolysis

HFModified from McMurray and PfefferModified from McMurray and Pfeffer. . Circulation. Circulation. 2002:105:20992002:105:2099--2106.2106.

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The RAAS in HFAngiotensinogen Kininogens

Angiotensin I Bradykinin

ACEinhibitors

Bradykinin receptor Norepinephrine Vasodilation Vessel permeability tPA/prostaglandin release

Nonspecific chymases ACE/kininase II

Inactive peptidesAngiotensin II

RAAS = renin-angiotensin-aldosterone system Jamali AH et al. Arch Intern Med. 2001;161:667-72.

Nitric oxide

AldosteroneAldosteroneantagonists Increased afterload disease progression

Improvedendothelial function

ARB

Sympatheticactivity

AT2 receptor Myocardial fibrosis Adrenal catechols? Apoptosis

AT1 receptor Myocardial fibrosis Norepinephrine Vasoconstriction PAI/endothelin

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Pathogenesis of Hyponatremia in HFPathogenesis of Hyponatremia in HF

NaNa++ RetentionRetention1. Renal perfusion2. Activation of RAAS3. Impaired natriuretic

responses

Water RetentionWater Retention1.1. Proximal tubular Proximal tubular

reabsorptionreabsorption2.2. AVP secretionAVP secretion3.3. AngiotensinAngiotensin--mediated thirstmediated thirst

Modified from Leier. Modified from Leier. Am Heart JAm Heart J. 1994;128:564. 1994;128:564--574.574.

Total Body NaTotal Body Na++Total Body WaterTotal Body Water

HYPONATREMIAHYPONATREMIA

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Renal Effects of Neurohormonal Activation With Renal Effects of Neurohormonal Activation With HFHF

HighHigh--Output Output Cardiac FailureCardiac Failure

Peripheral Vascular Peripheral Vascular ResistanceResistance

LowLow--Output Output Cardiac FailureCardiac Failure

Cardiac OutputCardiac OutputPeripheral Vascular ResistancePeripheral Vascular Resistance

Arterial UnderfillingArterial UnderfillingArterial UnderfillingArterial Underfilling

Modified from Schrier Modified from Schrier et al. et al. Mt Sinai J Med.Mt Sinai J Med. 2001;68:3502001;68:350--361.361.

Nonosmotic Nonosmotic AVP ReleaseAVP Release

ReninRenin--AngiotensinAngiotensin--Aldosterone SystemAldosterone System

Sympathetic Sympathetic Nervous SystemNervous System

Decreased Renal Perfusion and Decreased Renal Perfusion and Impaired Sodium & Water ExcretionImpaired Sodium & Water Excretion

Renal Effects of Neurohormonal Activation With Renal Effects of Neurohormonal Activation With HFHF

Abnormal LV FunctionAbnormal LV Function

Nonosmotic Nonosmotic AVP ReleaseAVP Release

ReninRenin--AngiotensinAngiotensin--Aldosterone SystemAldosterone System

Sympathetic Sympathetic Nervous SystemNervous System

Modified from Schrier Modified from Schrier et al. et al. Mt Sinai J Med.Mt Sinai J Med. 2001;68:3502001;68:350--361.361.

yyyy

Decreased Renal Perfusion and Decreased Renal Perfusion and Impaired Sodium & Water ExcretionImpaired Sodium & Water Excretion

Renal Effects of Neurohormonal Activation With Renal Effects of Neurohormonal Activation With HF and CirrhosisHF and Cirrhosis

Cirrhosis or HighCirrhosis or High--Output Cardiac Output Cardiac

FailureFailure

Peripheral Vascular Peripheral Vascular ResistanceResistance

LowLow--Output Output Cardiac FailureCardiac Failure

Cardiac OutputCardiac Output

Arterial UnderfillingArterial Underfilling

Schrier Schrier et al. et al. Mt Sinai J Med.Mt Sinai J Med. 2001;68:3502001;68:350--361.361.

Nonosmotic Nonosmotic AVP ReleaseAVP Release

ReninRenin--AngiotensinAngiotensin--Aldosterone SystemAldosterone System

Sympathetic Sympathetic Nervous SystemNervous System

Decreased Renal Perfusion and Decreased Renal Perfusion and Impaired Sodium & Water ExcretionImpaired Sodium & Water Excretion

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Left Ventricular Remodeling After Myocardial InfarctionLeft Ventricular Remodeling After Myocardial Infarction

Zouein et al Congest Heart Fail. 2012,18: 284-290

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Assessment of LV Remodeling Post MI by MRI

ORegan et al J. of Cardovascular Mag. Res. 2012: 1441

Changes in Ventricular Geometry Post MI

Carrabba et al Atherosclerosis 2012, 222: 123-128

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Randomized AldactoneRandomized AldactoneEvaluation Study (RALES)Evaluation Study (RALES)

1.00

of S

urvi

val

Spironolactone*

0.95

0.90

0.85

0.80

0.75

1663 patients with recent or 1663 patients with recent or current NYHA class IV heart failure current NYHA class IV heart failure (already receiving an ACE (already receiving an ACE inhibitor) inhibitor) Randomized to placebo or Randomized to placebo or spironolactone* (spironolactone* ( 25 mg daily) for 25 mg daily) for mean of 24 monthsmean of 24 months

Pitt B., et al. N Engl J Med. 1999;341:709717.

Placebo

Months

Prob

abili

ty o

0.70

0.65

0.60

0.55

0.50

0.45

0.000 3 6 9 12 15 18 21 24 27 30 33 36

P

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Case StudyCase Study

22 Y.O. male, new onset CHF, no clear precipitant, normal coronary 22 Y.O. male, new onset CHF, no clear precipitant, normal coronary arteries, RV 45/5, PA 50/18, PCW 25, RA 8, 3+ MR, LVEF 15% arteries, RV 45/5, PA 50/18, PCW 25, RA 8, 3+ MR, LVEF 15% (Sept. 1999)(Sept. 1999)Aggressive medical therapy, sequential titration of quinapril, Aggressive medical therapy, sequential titration of quinapril, carvedilol, spironolactone, digoxin, furosemide (titrated downward)carvedilol, spironolactone, digoxin, furosemide (titrated downward)Sequential improvement in LVEFSequential improvement in LVEF LVIDdLVIDd and PASPand PASPSequential improvement in LVEF, Sequential improvement in LVEF, LVIDdLVIDd and PASPand PASPSept. 2000 LVEF