Heart failure (HF) affects approximately 5 million persons in the United States each year. HF is predominantly a disease of
the elderly: Approximately 80% of patients hospitalized with HF are older than age 65. Approximately one-half of older adult
patients with CHF have a decreased ejection fraction. Elderly patients with HF and a reduced LVEF have a higher mortality
than elderly patients with HF with a normal LVEF. Despite numerous excellent studies showing the efficacy of appropriate drugs
in reducing mortality in patients with HF and a reduced LVEF, these medications are underutilized in the treatment of HF.
This article discusses the latest guidelines from the American College of Cardiology/American Heart Association for the treatment
of patients with HF and a reduced LVEF.
Aronow WS. ACC/AHA guideline update: Treatment of heart failure with reduced left ventriculat ejection fraction. Geriatrics
2006; 61(Mar): 22-9.
Key words: Heart failure • systolic • guidelines
Drugs discussed: See table 5, page 26-7
Fibonacci + Hockney + A. Baker: Medical illustrator Alexandra Baker married fibonacci numbers with the style of photo collage
artist David Hockney to create a modern take on the aging heart. For links to more on the fibonacci sequence, samples of David
Hockney's famous photo collages, or a discussion of fibonacci and the human heart, visit www.geri.com and click on "cover
details."
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Heart failure (HF) affects approximately 5 million persons in the United States, and more than 550,000 new cases of HF are
reported each year.1 HF is predominantly a disease of the elderly: approximately 80% of patients hospitalized with HF are older than age 65.1 HF is not only the most common cause of hospitalization in the United States, it is also the most costly: An estimated $2.9
billion is spent on drugs for its treatment annually.1 In a recent study that examined the prevalence and incidence of cardiovascular disease in 1,160 men (mean age 80) and 2,464
women (mean age 81), HF was found to have developed in 29% of men and in 26% of women at 46-month follow-up.2 Approximately one-half of older patients with CHF have a decreased ejection fraction (EF).
The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the evaluation and management of
HF define four stages (Stage A, B, C, D) of HF.1,3
Stage A: Patients are at high risk of developing HF because of the presence of conditions strongly associated with the development
of HF.1 These patients have systemic hypertension, coronary artery disease, peripheral arterial disease, diabetes mellitus, dyslipidemia,
history of cardiotoxic drug therapy or alcohol abuse, history of valvular heart disease, history of rheumatic fever, or family
history of cardiomyopathy. These patients have no evidence of structural heart disease.
Stage B: Patients have structural heart disease associated with the development of HF but also have never shown signs or symptoms of
HF.1,3 These patients have a prior MI, left ventricular (LV) hypertrophy or fibrosis, LV dilatation or hypocontractility, or asymptomatic
valvular heart disease.1,3
Stage C: Patients have current or prior symptoms of HF associated with structural heart disease.1,3 Patients with Stage C may have a reduced or normal left ventricular ejection fraction (LVEF).
Stage D: Patients have advanced structural heart disease and marked symptoms of HF at rest, despite maximal medical therapy. These
HF patients require specialized interventions.1,3
Elderly patients with HF and a reduced LVEF have a higher mortality than elderly patients with HF and a normal LVEF.4-8 In one study, the 1-year mortality was 19% in 226 elderly patients with HF and a normal LVEF compared with 41% in 340 elderly
patients with HF and a reduced LVEF.6 The 5-year mortality was 74% in 226 patients with HF and a normal LVEF compared with 92% in 340 elderly patients with a
reduced LVEF.6
Table 1 Class I recommendations for treating persons at high risk for developing heart failure (Stage A)
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Despite numerous excellent studies showing the efficacy of appropriate drugs in reducing mortality in patients with HF and
a reduced LVEF, these medications are underutilized in the treatment of HF. In fact, one recent study in 1418 patients with
HF and an LVEF of ≤ 40% showed that high-risk patients with HF who were at greatest risk for death were least likely (compared
with low-risk patients with HF) to receive angiotensin -converting enzyme (ACE) inhibitors or angiotensin II receptor blockers
(ARBs) and beta blockers .9The ACC/AHA guidelines for treating HF were updated in August 2005.1 This article discusses these latest guidelines for the treatment of patients with HF and a reduced LVEF.
Treatment of heart failure
Table 2 Class I recommendations for treating persons with cardiac structural abnormalities or remodeling but without heart
failure symptoms (Stage B)
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Recommendations for treatment, dependent on New York Heart Association (NYHA) Classification in relation to the ACC/AHA staging
system, are summarized in the tables included herein. Table 1 lists the Class I recommendations for treatment of Stage A.1 Table 2 lists the Class I recommendations for treatment of Stage B.1 Table 3 lists the Class I recommendations for treatment of Stage C with a reduced LVEF.1 Finally table 4 lists the Class IIa recommendations for treatment of Stage C with a reduced LVEF.1 .
Table 3 Class I recommendations for treating persons with current or prior symptoms of heart failure (Stage C) with reduced
left ventricular ejection fraction
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Diuretics. Diuretics and salt restriction should be used in treating patients with HF and fluid retention including edema or pleural
effusions (table 3).1 Sodium intake should be reduced to 1.6-2.0 g sodium (4-5 g sodium chloride daily). Inappropriately high doses of diuretics
will lead to volume depletion, which increases the risk of hypotension with ACE inhibitors, ARBs, and vasodilators, and the
risk of renal insufficiency with ACE inhibitors and ARBs.1,10 The use of diuretics in the treatment of elderly patients with HF is discussed in detail elsewhere.10 .
Angiotensin-converting enzyme inhibitors. ACE inhibitors should be used in the treatment of patients with HF to reduce mortality unless there are contraindications
to the use of these drugs (table 3).1 Numerous studies have demonstrated that ACE inhibitors improve symptoms, quality of life, and exercise tolerance, as well
as reduce mortality in elderly patients with HF and a reduced LVEF.10-15 The initial and maximum doses of oral antihypertensive drugs (ACE inhibitors, ARBs, aldosterone antagonists, and beta blockers)
used for treating HF can be found in table 5.1
Beta blockers. Beta blockers should be used in the treatment of patients with HF to reduce mortality unless there are contraindications to
the use of these drugs (table 3).1 Beta blockers have been demonstrated to reduce mortality in patients with HF and a reduced LVEF16-18 or normal LVEF.19 The initial and maximum doses of bisoprolol, carvedilol, and extended-release metoprolol succinate (which is given once
daily) for treating HF can be found in table 5.1 Carvedilol and extended-release metoprolol succinate are approved by the U.S. Food and Drug Administration for treating
HF; bisoprolol is approved for treating HF in Europe.
Angiotensin receptor blockers. If a patient cannot tolerate ACE inhibitors because of cough, rash, or angioneurotic edema, ARBs should be used in the treatment
of patients with HF to reduce mortality, unless there are contraindications to their use (table 3).1,20 The initial and maximum doses of candesartan, losartan, and valsartan for treating HF can be found in table 5. Candesartan
and losartan can be given once daily.
Avoidance of drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) (table 3) should be avoided because these drugs precipitate and aggravate HF;
contribute to renal insufficiency in patients with HF; cause sodium and fluid retention, vasoconstriction, and hypertension;
interfere with the efficacy of antihypertensive drugs, such as diuretics, ACE inhibitors, beta blockers, and vasodilators;
and interfere with the efficacy of diuretics in patients with HF.1,10 These adverse effects of NSAIDs apply to cyclooxygenase-2 specific inhibitors as well as cyclooxygenase-1 inhibitors.
Calcium channel blockers (all classes) worsen HF by activating neurohormonal systems and therefore should be avoided (table
3).1,10
Antiarrhythmic drugs, except for beta blockers, digoxin, and amiodarone, should be avoided because their negative inotropic
effects worsen HF (table 3).1,10
Exercise training. Regular physical activity, such as walking, should be encouraged in patients with mild to moderate HF to improve functional
status and decrease symptoms (table 3).1 Patients with HF who are dyspneic at rest or at a low work level may benefit from a formal cardiac rehabilitation program.21 A multidisciplinary approach to care is useful.22
A home walking program is useful for most elderly patients with HF. Segmental training, limb by limb, may offer the local
benefits of walking on the peripheral circulation and skeletal muscles without stressing the heart. Patients can only be monitored
in a formal cardiac rehabilitation program.
ICD for secondary prevention of sudden death. Patients with HF and a history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia
are at high risk for sudden cardiac death and should have an implantable cardioverter-defibrillator (ICD) inserted (table
3).1,23
ICD for primary prevention of sudden death. An ICD should be inserted in persons with ischemic heart disease ≥ 40 days post MI or non-ischemic cardiomyopathy, an LVEF
≤ 30%, NYHA Class II or III symptoms on optimal medical therapy, and an expectation of survival of ≥ 1 year to reduce mortality
(table 3).1,24 In the Sudden Cardiac Death in Heart Failure Trial, 2,521 patients (mean age 60) with Class II or III HF, an LVEF of ≤ 35%,
and a mean QRS duration on the resting electrocardiogram (ECG) of 120 msec, were randomized to placebo, amiodarone, or an
ICD.24 At 46-month median follow-up, compared with placebo, amiodarone insignificantly increased mortality by 6%.24 At 46-month median follow-up, compared with placebo, ICD therapy significantly reduced all-cause mortality by 23%.24
Cardiac resynchronization therapy. Cardiac resynchronization therapy (CRT) should be used in persons with an LVEF ≤ 35%, NYHA Class III or IV symptoms despite
optimal therapy, and a QRS duration on an ECG of > 120 msec (table 3).1,25,26 At 29-month follow-up of 813 patients with Class III or IV HF, a low LVEF, and cardiac dyssynchrony, compared to medical
therapy alone, CRT significantly reduced death or unplanned hospitalization for a major cardiovascular event by 37% and mortality
by 36%.26
Table 4 Class IIa recommendations for treating persons with current or prior symptoms of heart failure (Stage C) with reduced
left ventricular ejection fraction
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Class IIa indications for reduced ejection fraction. Table 4 lists the Class IIa indications for treating HF with a reduced LVEF.1 If a patient with HF is receiving an ARB for another indication, the ARB may be used instead of an ACE inhibitor with
a Class IIa indication.1 Hydralazine plus a nitrate may be used if HF symptoms persist despite treatment with Class I measures.1,27,28 Noting that "race is an imprecise concept," the guidelines do not distinguish between drug use in blacks and whites.
Table 5 Oral antihypertensive drugs*
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Aldosterone antagonists. An aldosterone antagonist (ie, spironolactone, eplerenone) should be used in selected patients with moderately severe to severe
symptoms of HF who can be carefully monitored for renal function and potassium concentration to reduce mortality.1,30,31 The serum creatinine should be ≤ 2.5 mg/dL in men and ≤ 2.0 mg/dL in women.1 The serum potassium should be < 5.0 mEq/L.1 The initial and maximum doses of spironolactone and of eplerenone for treating HF can be found in table 5.1ICD in reduced LVEF. An ICD may be used in persons with an LVEF of 30% to 35% of any origin with NYHA Class II or III symptoms on optimal medical
therapy and a life expectancy of >1 year to reduce mortality with a Class IIa indication.1,24
Table 5 (continued)
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Digoxin. Digoxin may be used in persons with HF, a reduced LVEF, and persistent symptoms despite optimum therapy (ie, ACE inhibitors,
diuretics, beta blockers) to reduce hospitalization for HF with a Class IIa indication.1 The serum digoxin concentration should be maintained between 0.5-0.8 mg/dL in all ages. A post-hoc subgroup analysis of
data from women with an LVEF ≤ 45% in the Digitalis Investigation Group (DIG) study showed by multivariate analysis that digoxin
significantly increased the risk of death among women by 23% (absolute increase of 4.2%; number needed to harm: 24).31 Another post-hoc subgroup analysis of data from all 1,926 women with HF and a reduced or normal LVEF in the DIG study showed
that digoxin significantly increased mortality by 20% in women.32 On the basis of this data, the author does not use digoxin to treat HF in women;31,32 the updated guidelines do not differentiate between treatment of men and women. Conclusion
Heart failure remains a major health problem in the United States. Given that the condition mainly affects the older patient,
the incidence of HF will continue to increase as our older patient population continues to grow over the coming decades.
This discussion has focused on the treatment of patients with HF and reduced LVEF, an HF patient subset that has shown a higher
mortality in older HF patients than that seen in older HF patients with a normal LVEF. To effectively manage this group as
well as all patients with HF, the primary care physician needs to be familiar with the ACC/AHA guidelines and any updated
changes to the guidelines as these occur. An understanding of the efficacy of appropriate drugs for HF, avoidance of other
drugs that may worsen the condition, role of exercise training in its management, and finally the utility of such technological
advances as the ICD and CRT will help avert unplanned hospitalizations and reduce mortality in these vulnerable older patients.
Dr. Aronow is clinical professor of medicine, department of medicine, divisions of cardiology, geriatrics, and pulmonary/critical care
medicine, New York Medical College, Valhalla, NY.
Disclosures: Dr. Aronow has no real or apparent conflicts of interest relating to the subject under discussion.
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