A, B, C, D, Es of the Management of Heart Failure
Nanette Kass Wenger, MD Emory University School of Medicine Grady Memorial Hospital Atlanta, Georgia
Objectives
Understand the cornerstones of therapy
angiotensin-converting enzyme inhibitors, diuretics, and digitalis
review the role of other therapies: pharmacotherapeutic as well as nonpharmacotherapeutic approaches
Epidemiology
4.7 million patients in the United States are estimated to have heart failure
470,000 new cases recognized annually
Each year, 875,000 hospitalized patients have a primary diagnosis of heart failure. It is the major hospital discharge diagnosis for patients in the Medicare age group.
Epidemiology
heart failure increases with age
half of all heart failure hospitalizations occur in individuals > age 65 years.
In the United States, the estimated costs for the management of patients with heart failure exceed $10 billion annually.
Treatment objectives
Decrease symptoms
Improve exercise capacity
Enhance quality of life
Decrease morbidity
Retard the progression of heart failure
Improve survival
Cornerstones of Therapy
Angiotensin converting enzyme (ACE) inhibitors
diuretics
digitalis
guidelines for the severity-based therapy of heart failure.
Asymptomatic Patients
For asymptomatic patients with left ventricular dysfunction (NYHA class I), typically those with an ejection fraction below 40%, ACE inhibitors are recommended
Symptomatic Patients
NYHA class II
ACE inhibitors, mild diuretics, and digoxin, with or without the use of B-blocker therapy
NYHA class III
add loop diuretics
NYHA class IV
consider positive inotropic agents
surgical therapies may also be applied
A, B, C, D, Es of Heart Failure Therapy
A angiotensin converting enzyme inhibitors anticoagulants, amiodarone, AICD, assist devices
B beta blocking drugs
C calcium channel blocking drugs, coronary revascularization, cardiac transplant, cardiomyoplasty, cardiac reduction surgery
D diet, diuretics, digitalis, dobutamine
E exercise
Angiotensin Converting Inhibitors physiologic benefits
Arteriovenous Vasodilatation
? pulmonary arterial diastolic pressure
? pulmonary capillary wedge pressure
? left ventricular end-diastolic pressure
? systemic vascular resistance
? systemic blood pressure
? maximal oxygen uptake (MVO2)
Angiotensin Converting Inhibitors physiologic benefits
? LV function and cardiac output
? renal, coronary, cerebral blood flow
No change in heart rate or myocardial contractility
no neurohormonal activation
resultant diuresis and natriuresis
Angiotensin Converting Inhibitors clinical benefits
Increases exercise capacity
improves functional class
attenuation of LV remodeling post MI
decrease in the progression of chronic HF
decreased hospitalization
enhanced quality of life
improved survival
Asymptomatic Patients
Enalopril
SOLVD Prevention Trial
EF<35% ? HF progression, ? hospitalization
Captopril
SAVE, GISSI-3, ISIS-4 Post MI, EF <40% ? overall mortality, ? re-infarction ? hospitalization, ? HF progression
Symptomatic Patients
Hydralazine + Isosorbide dinitrate
VHeFT-I ? mortality, improved functional class as compared with use of digoxin and diuretics VHeFT-II proved less effective than enalopril
Symptomatic Patients
Enalopril + digoxin + diuretics
SOLVD Treatment Trial EF<35%, FC III-IV ? mortality, ? hospitalization CONSENSUS-II FC IV ? mortality (40%), ? symptoms, ? hospitalization improved functional class
Symptomatic Patients
Losartan (AT-II inhibitor)
ELITE Trial
losartan improved the survival of elderly heart failure patients treated compared with captopril therapy
Guidelines to ACE Inhibitor Therapy
Contraindications
Renal artery stenosis
Renal insufficiency (relative)
Hyperkalemia
Arterial hypotension
Cough
Angioedema
Alternatives
Hydralazine + ISDN, AT-II inhibitor
Guidelines to ACE Inhibitor Therapy
It is important to titrate to the dosage regimen used in the clinical trials … in the absence of symptoms or adverse effects on end-organ perfusion
in very severe heart failure, hydralazine and nitrates added to ACE inhibitor therapy can further improve cardiac output
Anticoagulant Therapy
Recommended for
patients with NYHA III-IV and EF <30% or ventricular aneurysm or very dilated LV
Indicated for
patients with heart failure who have atrial fibrillation, a prior embolic episode, identified intracardiac thrombus, left ventricular aneurysm, thrombophlebitis, or prolonged bed rest
titrate INR to 2 to 3
Arrhythmias
Sudden death occurs in about 50% of patients with heart failure
Amiodarone
Randomized clinical trials
CHF-STAT NYHA II-III patients with ischemic cardiomyopathy - amiodarone had no affect on survival
GESICA NYHA III-IV patients with more non-ischemic cardiomyopathy - open labeled amiodarone decreased mortality
AICD
Randomized clinical trials
AVID amiodarone vs implantable defibrillator showed the AICD group had lower mortality
AICD should be considered for patients with ventricular fibrillation or prior sudden death
Beta-blockers or amiodarone may be appropriate for patients with sustained VT, with or without symptoms
Assist Devices
a bridge to cardiac transplantation
candidates must meet the inclusion and exclusion criteria for cardiac transplantation
?-blocking Drugs
Physiologic benefits
increase the density of ?-1 receptors
inhibit catecholamine toxicity
decrease neurohormonal activation
decrease heart rate
provide antihypertensive, antianginal, and antiarrhythmic effects
antioxidant and antiproliferative effects
?-blocking Drugs
Clinical benefits
decrease symptoms of HF
improve left ventricular function
improve exercise tolerance
?-blocking Drugs - Clinical Trials
BHAT (? -Blocker Heart Attack Trial)
propranolol decreased cardiovascular mortality, sudden death, and reinfarction in post-MI patients
benefit is greatest in patients who also had left ventricular dysfunction
?-blocking Drugs - Clinical Trials
SAVE (Survival and Ventricular Enlargement)
post-MI patients with an EF <40%
?- blockers reduced mortality both in the ACE inhibitor and the placebo group
lowest mortality occurred in patients receiving both ACE and ?-blocking therapy
?-blocking Drugs - Clinical Trials
MDC (Metoprolol in Dilated Cardiomyopathy)
NYHA II-III with dilated cardiomyopathy
no decrease in mortality
significant decrease in symptoms
significant increase in exercise tolerance, LV ejection fraction, quality of life
?-blocking Drugs - Clinical Trials
MOCHA (Multicenter Oral Carvedilol Heart Failure Assessment Trial)
NYHA II-III heart failure
quadruple therapy (+ACE, diuretic, digoxin)
49% decrease in the combined endpoints of mortality and hospitalization
no improvements in exercise tolerance
?-blocking Drugs - Clinical Trials
PRECISE (Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise)
decrease in mortality from 8% to 3%
40% decrease in hospitalization
decrease in symptoms
improvement in LV ejection fraction
no affect on exercise tolerance
Calci