Heart Failure

Case 1

• A 56 year old man with known CAD with NSTEMI x2 and stents in the LAD and LCx presents with 2 months of progressive DOE, LE edema and

Question #1

• Which of the following therapies will improve this patient’s mortality?– A. Lasix– B. Carvedilol– C. Spironolactone– E. Digoxin– D. All of the above

Question #2• PVCs are noted in the hospital. An

echocardiogram has moderatey-severely decreased systolic function (EF 28%). What should you do next?– Increase the lisinopril and carvedilol dose– Implant and AICD– Start amiodarone– Put the defibrilator patches on him– D/C telemetry

Heart Failure Is a Big Problem

• Prevalence: >5,000,000• Incidence: >650,000

new cases/year in the US

• Most common discharge diagnosis

• Most common cause of readmission < 60 days

• Cost: > 34.8 billion annualy

Rosamond. Circulation, 2008.Braunwald. 2007.

Heart Failure Incidence Has Increased, But No By Much

Levy. NEJM, 2002.

Survival has improved, but not dramatically

Levy. NEJM, 2002.

What is Heart Failure?

• Definition: Any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.

• Cardinal manifestations: Dyspnea, fatigue, fluid retention

LV Dysfunction Is Necessary But Not Sufficient For Heart Failure

Acute Compensatory Mechanisms Cause Long Term Damage

• Activation of renin-angiotensin-aldosterone– Salt and water retention– Myocyte hypertrophy,

death and myocardial fibrosis

• Sympathetic nervous system stimulation– Increase contractility

Cardiac Remodeling Following Injury

McMurray. NEJM, 2010.

Activation of the RAS Leads to Remodeling

Etiologies of Heart Failure• Depressed LV Function

– CAD (2/3 of cases of HF)– Pressure overload: HTN, AS– Volume overload: AI, MR, intra/extra cardiac shunt– NICM: Genetic, infiltrative, toxin/drug, metabolic, viral, Chagas’ – Arrythmias

• Preserved LV Function– Hypertrophy: HCM, HTN– Aging– Restrictive: Infiltrative (amyloid, sarcoid), storage dz (hemochromatosis)– Fibrosis– Endomyocardial disorders

• Pulmonary vascular disease• High-Output States

– Metabolic: Thyrotoxicosis, nutrititional (beriberi)– Excessive flow requirements: AV shunt, anemia

Clinical Classification of Heart Failure

Gheorghiade. JACC, 2007.

Initial Evaluation

• Decreased exercise tolerance• Volume overload• Asymptomatic or other complaints

Symptoms To Ask About

• Major Symptoms– Dyspnea – Orthopnea– PND– Ankle edema– Pulmonary edema– Fatigue– Exercise intolerance– Cachexia

• Minor Symptoms– Weight loss– Cough– Nocturia– Palpitations– Peripheral cyanosis– Depression

Physical Exam Findings To Look For

• JVP• Crackles• Pulmonary edema• Displaced PMI, S3 and S4,

Measurement of the JVP

Clinical Methods. Walker. 1990.http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cm&part=A622

5 cm

How To Measure JVP

Clinical Methods. Walker. 1990.http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cm&part=A622

CXR: Pulmonary Edema

www.yale.edu/imaging/contents.html

CXR findings: heart size, congestion, pleural effusion

Brain Natriuretic Peptide

• Natriuretic peptides– ANP- atrium, BNP- ventricles, CNP- endothelial

cells– Increased well stress -> pre-proBNP-> pro-BNP->

BNP+NTproBNP (longer t1/2, higher levels,slower fluctuation)

– From the heart• Induce vasodilation, natriuresis and diuresis

– Useful and systolic and diastolic heart failure

Daniels. JACC, 2007.

Differential Diagnosis BNP Elevation

• LV dysfunction• Previous CHF• Advanced age• Renal dysfunction• ACS• Pulmonary disease• PE• High output• AF

• Lower then expected– Obesity– Flash pulmonary edema– Heart failure upstream

from the LV– Cardiac tamponade– Pericardial constriction

BNP Can Help Differentiate Causes of Dyspnea

Maisel. NEJM, 2002.

Higher BNP Is Associated With Higher Mortality

Braunwald. 2007.

New York Heart Association Functional Classification

• Class I: No symptoms with ordinary activity

• Class II: Some symptoms with ordinary activity

• Class III: Symptoms with minimal activity

• ClassIV: Symptoms at rest

Drugs That May Worsen Heart Failure:Na Retention, Cardiotoxicity, Negative

Inotropy• NSAIDS• Calcium channel blockers- non-dihydropyridine• Metformin• Thiazolidinediones• PDE-3 inhibitors• Antiarrhythmic drugs• Chemotherapy• THF alpha inhibitors• Na Containing drugs• Supplements

Goals Of Therapy Heart Failure

• Relieve symptoms• Slow or reveres deterioration of myocardial

function• Decrease mortality

Heart Failure Therapy: A Timeline

1628William Harvey

describes circulation

1950sThiazide Diuretics

1967 First Heart Transplant

1976 Hydralazine

1994Bisoprolol

reduces mortality

Dietary and Lifestyle Modification: No Randomized Trials

• Sodium Restriction 2-3 gm daily• Weight loss• Smoking cessation• Restriction of alcohol • Daily weight monitoring

Diuretics

• Used to manage volume status

• Dosing is based on response

• Intravenous versus oral therapy

• Agents can be combined for better efficacy

• No effect on mortality

Libby. Braunwald’s Heart Disease. 2007.

Digoxin In Heart Failure

• Inhibits the Na-K-ATPase pump-> increased Ca-> inc LV function

• Inhibition of sympathetic outflow

Digoxin Does Not Improve Mortality

Digitalis Investigation Group. NEJM, 1997.

Digoxin Improves Heart Failure Symptoms and Reduces Hospitalization

Digitalis Investigation Group. NEJM, 1997.

Digoxin Level > 1.2 ng/ml Is Associated With Increased Mortality

Adams. JACC, 2005.

Enalapril Reduces Mortality in NYHA Class IV Heart Failure

Consensus trial study group. NEJM, 1987.

Meta Analysis: ACE-I Improve Mortality After MI

Flather. Lancet, 2000.

Candesartan Is An Reasonable Substitute In Patients Who Cannot

Tolerate ACE-I

Granger.Lancet, 2003.

Mortality Benefit With Hydralazine+ Isordil vs Placebo or Prazosin

Cohn. NEJM, 1986.

Bidil Improved Survival In Blacks With Heart Failure Taking ACE-I

Taylor. NEJM, 2004.

Beta Blockers

• Metoprolol: NYHA II-IV, EF <40%, metop succinate 200 daily

• All cause mortality dec by 34% independent of age, sex etiology of CHF or EF

Merit-HF study group. Lancet, 1999.

Carvedilol Is Superior to Short Acting Metoprolol

Poole-Wilson. L:ancet, 2000.

Improvement of Systolic Function is Related to Beta Blocker Dose

Bristow. Circulation, 1996.

Rales Trial: Spironolactone Improves Mortality In Severe Heart Failure

Pitt. NEJM, 1999.

Ephesus: Epleronone Improves Mortality In Heart Failure Following AMI

Pitt. NEJM, 2003.

Treat With Proven Dosages

McMurray. NJEM, 2010.

Oral Milrinone Causes A 28% Increase In Mortality

Packer. NEJM, 1991.

Take Home Messages About Medical Management of CHF

• Use proven therapies• Treat with proven dosages

How Do I Start These Drugs?

• Diuretic• ACE Inhibitor or ARB• Beta Blocker• Hydralazine and Nitrates• Spironolactone or eplerenone• Digoxin

AICD For Primary Prevention Of Sudden Cardiac Death In Patients With

Heart Failure• Ischemic cardiomyopathy

– EF<30%, prior MI

• Non-ischemic cardiomyopathy– EF < 35%, NYHA II or III– EF<35%, NYHA III or IV and QRS>120 AICD with

CRT– Survival of sudden death or with VT

Mortality Reduction In Patients Post MI: MADIT II

Moss. NEJM, 2002.

Reduction in Mortality in NICM With ICD: ScD Heft

Bardy. NEJM, 2005.