Heart Failure

A condition in which cardiac output is insufficient to meet physiologic demands.

Heart failure is common among persons >= 65 years. Its prevalence increases exponentially after age 70 and, unlike that of other cardiac disorders, has been increasing over the past two decades. Heart failure is now the most common diagnosis among hospitalized elderly patients.

Etiology and Pathogenesis

The principal mechanisms of heart failure involve impediments to forward ejection, myocardial failure, impaired cardiac filling, and volume overload (see Table 92-1). In the elderly, heart failure usually results from systemic arterial hypertension, which impedes forward ejection and eventually results in myocardial failure, or from coronary artery disease, which leads directly to myocardial failure. Hypertension and coronary artery disease also impair cardiac filling. Valvular heart disease may lead to heart failure by impeding forward ejection, thereby causing impaired cardiac filling and chronic volume overload, which results in secondary myocardial failure. Heart failure due to idiopathic dilated cardiomyopathy and high-output heart failure due to disorders such as thyrotoxicosis, anemia, arteriovenous fistulas, fever, and thiamine deficiency are less common among the elderly than among younger patients.

Heart failure may result from reduced function of the left and/or right ventricle (reduced stroke volume); combined left- and right-sided heart failure is more common than isolated left- or right-sided heart failure. Reduced ventricular function can result from systolic dysfunction (involving abnormal contractility), from diastolic dysfunction (involving abnormal filling), or from both; combined systolic and diastolic heart failure is more common than isolated systolic or diastolic heart failure.

Diastolic dysfunction, which is relatively uncommon among younger patients, accounts for about 50% of heart failure cases among elderly patients and appears to be particularly common among elderly women. In diastolic dysfunction, prolonged myocardial relaxation and increased myocardial stiffness (which decrease filling rate and volume) increase left ventricular diastolic pressure and reduce stroke volume at rest and during exercise. As a result, heart failure develops, even if systolic function (as indicated by the ejection fraction) is normal or nearly normal.

Age-related changes in the heart and cardiovascular system lower the threshold for expression of heart failure. Interstitial collagen within the myocardium increases, the myocardium stiffens, and myocardial relaxation is prolonged. These changes lead to a significant reduction in diastolic left ventricular function, even in healthy elderly persons. Modest decrements in systolic function also occur with age. An age-related decrease in myocardial and vascular responsiveness to -adrenergic stimulation further impairs the ability of the cardiovascular system to respond to increased work demands.

As a result of these changes, peak exercise capacity decreases significantly (about 8% per decade after age 30), and cardiac output at peak exercise decreases more modestly. Thus, elderly patients are more prone than are younger ones to develop heart failure symptoms in response to the stress of systemic disorders or relatively modest cardiovascular insults. Stressors include infections (particularly pneumonia), hypothyroidism, hyperthyroidism, anemia, myocardial ischemia, hypoxia, hypothermia, hyperthermia, renal failure, nonadherence with drug or diet regimens, and use of certain drugs (including nonsteroidal anti-inflammatory drugs, -blockers, and certain calcium channel blockers).

Symptoms, Signs, and Diagnosis

The cardinal symptoms and signs of heart failure include dyspnea and fatigue (particularly with exertion), orthopnea, and dependent edema. They are common among young and elderly patients. Peripheral edema is less specific as a sign of heart failure in the elderly than in the young. Also, in bedridden patients, edema may occur in the sacral area rather than in the lower extremities. Jugular venous distention and hepatojugular reflux are also common. In patients with advanced, uncompensated heart failure, mild tachycardia occurs. However, elderly patients may also present with nonspecific symptoms and signs (eg, somnolence, confusion, disorientation, weakness, fatigue, failure to thrive).

In elderly persons, a fourth heart sound (S₄ gallop), particularly if soft, does not necessarily indicate clinically significant heart disease. However, a third heart sound (S₃ or early diastolic gallop) usually does. Coarse, wet inspiratory rales can be heard, particularly in the lower lung fields.

Classifying symptom severity according to the New York Heart Association (NYHA) classification (see Table 29-1) aids in selecting therapy, following progress, and determining the prognosis.

No test can provide a diagnosis of heart failure. Rather, the diagnosis is based on clinical findings. Diagnosis is complicated because patients often do not perceive substantial, progressive declines or they attribute such declines to old age. Consequently, patients should be encouraged to give concrete examples of their functional abilities, to compare them with those of their peers, and to recall tasks that have become difficult or that are now avoided.

Differentiating systolic heart failure from diastolic heart failure, which is often underdiagnosed, is important because therapy differs. Patients with diastolic heart failure are more often women and tend to be obese. Onset of symptoms may be acute, and clinical deterioration abrupt. This rapid deterioration, commonly known as flash pulmonary edema, is usually related to severe hypertension or acute ischemia. Atrial fibrillation with rapid ventricular response is also a common precipitant. Diastolic dysfunction is typically accompanied by a forceful, minimally displaced apical impulse and a fourth heart sound.

Systolic dysfunction of the left ventricle produces secondary signs of right-sided heart failure (jugular venous distention, pedal edema) more frequently than does diastolic dysfunction of the left ventricle. Systolic dysfunction is typically accompanied by a dilated left ventricle (with a laterally displaced or diffuse point of maximal impulse) and a third heart sound. Onset of symptoms can be rapid but is more often gradual (eg, when due to cardiomyopathy).

Despite these differences, systolic dysfunction and diastolic dysfunction usually cannot be reliably distinguished at bedside. Therefore, evaluation of new-onset heart failure should include an imaging test, usually echocardiography. Echocardiography can evaluate left ventricular systolic function (eg, ejection fraction), help determine the primary etiology of heart failure (eg, cardiac tamponade, aortic stenosis, severe valvular regurgitation), and exclude specific complications (eg, left ventricular aneurysms, mural thrombi).

Typically, patients with primarily diastolic heart failure have a normal (usually 50 to 65%) or high (>= 70%) ejection fraction (stroke volume divided by end-diastolic volume), a normal or small left ventricle, thickened ventricular walls with concentric hypertrophy, and no segmental wall motion abnormalities. Typically, patients with primarily systolic heart failure have a significantly reduced left ventricular ejection fraction (usually <= 40%), a dilated left ventricle, and multiple regional wall motion abnormalities. Patients who have combined systolic and diastolic dysfunction with an ejection fraction of 40 to 50% have mixed heart failure.

Ejection fraction, which can be measured with various imaging tests, provides a relatively reliable measure of systolic function. However, no comparable measure is available for diastolic function. Left ventricular diastolic filling indexes, including early/atrial (E/A) ratio and early deceleration time, can be assessed noninvasively (eg, with Doppler echocardiography). However, because these indexes are affected by factors other than abnormal diastolic function (eg, blood pressure, drugs, aging), they cannot be used to definitively diagnose diastolic dysfunction.

Two relatively inexpensive tests provide important supplemental information: A chest x-ray provides unique information about cardiomegaly, pulmonary vascular congestion, and pleural effusions; and a resting ECG provides information about cardiac rhythm and rate, hypertrophy, and infarction. Measurement of serum electrolytes and creatinine, albumin, and thyroid-stimulating hormone levels; liver function tests; and urinalysis are useful when heart failure is first diagnosed.

Because patients with active myocardial ischemia can present with heart failure, a stress test or, if severe or unstable angina coexists, coronary angiography is often indicated.

Prognosis

Prognosis is determined largely by the primary cause and its severity, the presence of comorbid conditions, and the patient's age. Preliminary data suggest that among community-dwelling elderly persons with a mean age of 70, the annual mortality rate is 9% for diastolic heart failure and 18% for systolic heart failure. However, among hospitalized and very elderly patients, mortality rates for diastolic and systolic heart failure may be similar. Recent hospitalization for heart failure indicates a poor prognosis, whether the heart failure is systolic or diastolic. Other prognostic data regarding diastolic heart failure are scarce.

For systolic heart failure, prognostic data are relatively plentiful, although few studies have focused on elderly patients. A high NYHA class, low exercise capacity (which can be objectively measured with cardiopulmonary exercise testing), a very low ejection fraction, and ischemic etiology are important indicators of a poor prognosis. Renal failure is a particularly ominous comorbid condition and greatly complicates management. Other indicators of a poor prognosis include hyponatremia, even when mild; conduction abnormalities (eg, left bundle branch block); ventricular ectopy, identifiable on a resting ECG; abnormal liver function test results; and a severely dilated (> 60 mm) left ventricle and circumferential myocardial thinning, both identifiable on an echocardiogram. Shortened deceleration time of the early component of the Doppler mitral filling pattern is an important negative prognostic indicator for patients with dilated cardiomyopathy, who constitute a substantial portion of those with systolic dysfunction. When this filling pattern is accompanied by a restrictive diastolic filling pattern, the 2-year mortality rate appears to be about 50%.

Treatment

Treatment should be aimed at reducing symptoms, improving quality of life, and preventing acute exacerbations and hospitalization. A physician- or nurse-directed interdisciplinary team can help achieve these goals and thereby substantially reduce total health care costs. The team may include a social worker, dietitian, nurse case-manager, and physical therapist. Such a team can provide extensive education for the patient, family members, and other caregivers and can arrange appropriate posthospital support and access to follow-up care.

General measures: Measures include attempts to identify and manage exacerbating factors or disorders; common exacerbating factors include dietary (eg, sodium) indiscretion, drug nonadherence, and inadequate blood pressure control. Management of such factors can frequently prevent acute episodes. Other measures include smoking and alcohol cessation and control of hyperlipidemia and diabetes. Pneumococcal and influenza vaccinations are recommended. Selected elderly patients with heart failure may benefit from cardiovascular rehabilitation. Most patients should be encouraged to engage in light to moderate physical activity regularly so that they can maintain function.

Pharmacotherapy: For the elderly, drugs are generally initiated at a low dose, which is increased gradually to the target maintenance dose. Usually, target maintenance doses are the doses used in clinical studies, but such doses are not always feasible for elderly patients. Therapy should be individualized, because elderly patients, especially those with systolic heart failure, often have limited physiologic reserves and multiple concomitant medical problems.

For patients who have systolic heart failure without significant edema and with only mild symptoms, usual therapy begins with an angiotensin-converting (ACE) inhibitor, which may be the only drug required for some time. If volume overload and edema are present, therapy begins with a diuretic; the dose is adjusted to the lowest dose that maintains euvolemia. Digoxin is added when more severe symptoms or atrial fibrillation develops.

Therapy for patients with diastolic heart failure is largely empiric; data from clinical studies are lacking. Because severe or inadequately controlled hypertension is so common among patients with diastolic heart failure and because increased afterload adversely affects diastolic function, blood pressure control should be a primary goal. ACE inhibitors, angiotensin II receptor blockers, -blockers, and calcium channel blockers are often favored on theoretical grounds. However, no drug has been shown to directly enhance diastolic function in elderly patients with heart failure and a normal left ventricular ejection fraction.

Diuretics are not necessary for all patients or at all stages of the disease. However, most patients with moderate to severe heart failure have symptoms and signs of sodium and volume overload, which warrant cautious use of diuretics. Loop diuretics are most commonly used. For patients with acute pulmonary edema and normal or increased systemic pressure, IV loop diuretics (furosemide, bumetanide) often result in dramatic and rapid reduction of symptoms. Once the acute episode resolves, the dose should be decreased to the lowest dose that maintains the patient in a relatively asymptomatic and euvolemic state; the patient's weight should be noted. Thiazide diuretics are sometimes adequate, particularly for patients with mild heart failure. The potassium-sparing diuretic spironolactone may reduce the mortality rate for patients with systolic heart failure when it is added in low doses to usual therapy, most often consisting of an ACE inhibitor and a loop diuretic, with or without digoxin.

Many patients with heart failure have an intrinsic diuretic dose threshold; doses below this threshold produce minimal diuresis, even when doses are repeated. Usually, a single morning oral dose slightly higher than the threshold can provide effective maintenance diuresis. Multiple daily doses are usually unnecessary, are inconvenient for patients, and can exacerbate urinary incontinence. Dosing can be timed to fit a patient's lifestyle so that incontinence is not precipitated when access to a bathroom is inconvenient. The need to increase the diuretic dose in a previously stable outpatient suggests disease progression, worsening renal dysfunction, poor absorption due to bowel edema, other systemic complications, or nonadherence.

For patients with end-stage disease, consultation with a specialist may help optimize diuretic therapy. Use of IV loop diuretics in high, pulsed, and/or intermittent doses can be effective. Oral metolazone 2.5 or 5.0 mg given 30 minutes before the loop diuretic can significantly enhance the diuretic effect. Adjuvant short-term therapy with low-dose dopamine or dobutamine may help promote diuresis by increasing renal flow. Nonsteroidal anti-inflammatory drugs can cause relative diuretic resistance and should be discontinued if possible. During active diuresis, the patient should be closely monitored, and electrolytes, particularly potassium and magnesium, should be replaced; fluid restriction may be needed to prevent or alleviate hyponatremia.

Vasodilators include ACE inhibitors, angiotensin II receptor blockers, hydralazine, and isosorbide dinitrate. Vasodilators can increase stroke volume by reducing impedance to ejection. Nearly all of them can produce short-term improvement in hemodynamics and can reduce symptoms. However, with long-term use, most have minimal benefit. Notable exceptions are ACE inhibitors and angiotensin II receptor blockers, which have multiple therapeutic mechanisms in addition to vasodilation.

ACE inhibitors substantially reduce symptoms, improve exercise tolerance, slow disease progression, and reduce hospitalization and long-term mortality rates for patients with left ventricular ejection fractions of <= 35 to 40%. These benefits occur even if patients have no overt heart failure symptoms and if symptom relief appears to be minimal. Benefits are so compelling that ACE inhibitor therapy, unless contraindicated, should be withheld only from patients who cannot tolerate it despite reasonably aggressive efforts to enable them to do so. With careful management, most patients can start and continue to take an ACE inhibitor. Little information comparing the benefits of different ACE inhibitors is available. Selection is often based on half-life (dose frequency) and cost.

Initially, a low dose (eg, enalapril 2.5 to 5.0 mg po bid, captopril 6.25 mg po tid) is given to avoid hypotension. The dose is slowly increased over several weeks to reach the doses that were shown to be optimally effective in large studies (eg, enalapril 10 to 20 mg bid, captopril 50 mg tid). Although adherence is usually better with once- or twice-daily regimens, dose frequency for captopril should not be reduced to twice daily for patients with heart failure.

Common adverse effects of ACE inhibitors include hypotension, rash, chronic dry cough, and increased serum creatinine and potassium levels. Except for angioedema, which is rare, adverse effects can be minimized by starting with a low dose. When adverse effects occur, they can often be minimized by decreasing the dose or by using a different ACE inhibitor. Patients can often tolerate persistent mild dry cough, particularly when they understand the significant reduction in mortality rate associated with the drug.

Hypotension is common but usually mild and asymptomatic; it is usually most prominent after the first one or two doses. Unless hypotension is unusually severe, the drug should not be discontinued. Patients who are very old and patients who have volume depletion due to excessive diuresis, severe left ventricular dysfunction, a baseline systolic blood pressure of < 100 mm Hg, or hyponatremia are at highest risk of severe first-dose hypotension. Volume depletion should be corrected before ACE inhibitor therapy is initiated.

Angiotensin II receptor blockers directly inhibit angiotensin II at the end-organ receptor level. These drugs have some theoretical advantages and possibly some disadvantages compared with ACE inhibitors. The angiotensin II receptor blocker losartan appears to have no advantage over the ACE inhibitor captopril in terms of mortality rate reduction for patients with systolic heart failure. The incidence of cough seems to be substantially lower with losartan than with captopril, but the incidence of renal dysfunction does not seem to differ. However, until the relative roles of ACE inhibitors and angiotensin II receptor blockers are determined, an ACE inhibitor should probably remain the initial therapy of choice, even for elderly patients with systolic heart failure. An angiotensin II receptor blocker is a rational alternative for patients who cannot tolerate ACE inhibitors, particularly because of cough.

Neither ACE inhibitors nor angiotensin II receptor blockers have been extensively studied in patients with diastolic heart failure. However, both drug classes decrease blood pressure, left ventricular hypertrophy, and interstitial myocardial collagen; all of these effects are theoretically beneficial for patients with diastolic heart failure. In animal models of heart failure, diastolic dysfunction is ameliorated after antagonism of angiotensin II. In one small study of elderly patients with heart failure and a normal left ventricular ejection fraction, enalapril, an ACE inhibitor, improved exercise tolerance. In another study, losartan, an angiotensin II receptor blocker, improved exercise tolerance and quality of life and reduced exercise blood pressure in elderly patients with mild diastolic dysfunction.

Compared with ACE inhibitors, the combination of hydralazine and isosorbide dinitrate--the first vasodilator regimen shown to reduce the mortality rate in patients with systolic heart failure--has a more cumbersome dosing regimen, is less well tolerated, and reduces the mortality rate less. However, this combination is useful for patients who cannot tolerate ACE inhibitors or angiotensin II receptor blockers, usually because of renal dysfunction or allergy, and has been used in patients with advanced systolic heart failure.

Calcium channel blockers have little, if any, role in primary therapy for patients with systolic left ventricular dysfunction. In some analyses, use of these drugs has been associated with an increased mortality rate for such patients. Calcium channel blockers with negative inotropic properties, including verapamil and diltiazem, can precipitate or exacerbate heart failure symptoms. A possible exception is the dihydropyridine calcium channel blocker amlodipine. Among patients with severe systolic left ventricular dysfunction, the addition of amlodipine to usual therapy seems to decrease the mortality rate for those without known coronary artery disease and not to increase the mortality rate for those with coronary artery disease.

In patients with diastolic heart failure, verapamil may reduce symptoms and improve exercise tolerance. In addition, verapamil can reduce symptoms in patients with hypertrophic cardiomyopathy, which is present in a subset of patients with diastolic heart failure.

-Blockers have intrinsic negative inotropic properties that can precipitate or exacerbate heart failure symptoms in patients with significant systolic left ventricular dysfunction. However, these drugs, when added cautiously to usual therapy, may significantly reduce symptoms as well as hospitalization and mortality rates for selected patients with systolic left ventricular dysfunction and mild to moderate symptoms of heart failure. The greatest effect on mortality reduction appears to be in patients with heart failure after acute myocardial infarction. -Blockers are important in the treatment of coronary artery disease (including myocardial infarction) and of ventricular arrhythmia, which are common concomitant disorders in patients with systolic heart failure. Carvedilol, bisoprolol, and metoprolol have been studied the most extensively. Carvedilol, a nonselective -blocker, is approved for the treatment of systolic heart failure.

-Blockers may be considered additive therapy for selected patients who have symptomatic systolic heart failure and have been stabilized with diuretics, ACE inhibitors, and possibly digoxin. -Blockers should not be used in patients who are acutely symptomatic, who have severe (NYHA class IIIS or IV) heart failure, or who have contraindications to -blockers (eg, bronchospastic chronic obstructive pulmonary disease, significant conduction abnormalities).

-Blockers should be initiated in very low doses (typically, carvedilol 3.125 mg bid, bisoprolol 1.25 mg once daily, or sustained-release metoprolol 12.5 mg once daily). The patient should be directly observed for at least 1 to 2 hours after administration of the first dose, or longer depending on the patient's condition. If tolerated, the initial dose should be continued at least 2 weeks before the dose is gradually increased. Generally, target maintenance doses are similar to the doses used in studies (eg, carvedilol 25 mg bid, bisoprolol 10 mg once daily, sustained-release metoprolol 50 to 100 mg once daily). Patients must be closely monitored during therapy.

-Blockers can have substantial adverse effects; most occur early in therapy. Experience with -blocker therapy in very elderly or debilitated patients with heart failure is relatively limited.

-Blockers have been recommended as therapy for diastolic heart failure, because they have the theoretical benefits of heart rate reduction and negative inotropism. However, supportive data from clinical studies are lacking.

Digoxin therapy for symptomatic heart failure remains important. Regardless of whether sinus rhythm is normal, a third heart sound is present, or left ventricular ejection fraction is reduced, digoxin can improve exercise tolerance, alleviate symptoms, and reduce the incidence of heart failure exacerbations and the risk and duration of hospitalization.

For elderly patients with a wide range of left ventricular ejection fractions, digoxin seems to have a neutral effect on the overall mortality rate: A slight reduction in the number of deaths related to heart failure is balanced by a similar increase in the number of deaths due to other conditions, particularly sudden cardiac death. Thus, digoxin is indicated for relief of heart failure symptoms that persist despite ACE inhibitor and diuretic therapy, usually in patients with NYHA class III or IV heart failure.

For most patients > 70, digoxin should be initiated and maintained at 0.125 mg daily. For large patients with normal renal function (especially if they are < 70), the dose may be 0.25 mg/day. For elderly patients with renal dysfunction, 0.125 mg every other day or twice a week may be adequate. One assay may be performed shortly after initiation of therapy (ie, after at least 5 doses or half-lives), but thereafter, patients can usually be monitored clinically without routine assays.

Inotropic drugs such as IV dopamine and milrinone may help markedly symptomatic hospitalized patients who do not respond adequately to usual measures. These drugs can reduce symptoms and improve quality of life. For highly selected patients with severe, refractory end-stage systolic heart failure, IV dobutamine is appropriate as compassionate-use therapy or can be used as a bridge to surgical treatment. Oral inotropic drugs that initially showed promise, sometimes with dramatic reduction in symptoms, have been shown to increase mortality rates and have been abandoned in the USA.

Antiarrhythmic therapy, including drugs and electrical cardioversion, is often warranted to restore and maintain sinus rhythm in patients with atrial fibrillation. Elderly persons, in particular, depend on atrial contraction for adequate ventricular filling.

Use of amiodarone and/or an automatic implantable defibrillator can reduce the risk of sudden cardiac death, which is common among patients with systolic heart failure. High-risk patients who may benefit from such therapy include those with a history of sustained ventricular tachycardia, ventricular fibrillation, or resuscitated sudden cardiac death. -Blockers may also provide protection. Type I antiarrhythmic drugs should generally be avoided in patients with heart failure and an ejection fraction <= 40% unless they have an automatic implantable defibrillator, because mortality risk is increased.

Warfarin is indicated for patients with systolic heart failure and atrial fibrillation or prior embolism. Its use in other patients with systolic heart failure is controversial. Warfarin has also been used in patients who have a markedly dilated left ventricle, who have an unstable cardiac thrombus or a ventricular aneurysm at high risk of rupture, who are at increased risk of thrombophlebitis, or who require prolonged bed rest. During bed rest, mechanical devices and leg and toe exercises can also help prevent venous thrombosis. The elderly are at increased risk of adverse effects from warfarin and other anticoagulants.

Surgical treatment: Coronary revascularization should be considered if patients have severe coronary artery disease and manifest myocardial ischemia. Valve replacement surgery is warranted for many patients with heart failure due to primary valvular disease.

Survival rates after heart transplantation have improved steadily because of improved medical supportive posttransplant care and immunotherapy. However, because the availability of donor organs is limited, transplantation is rarely performed in elderly patients. Ventricular assist devices are generally appropriate only as a bridge to transplantation. New ventricular remodeling surgeries are considered experimental and should be performed only in highly selected patients.

Patient and Caregiver Issues

The patient, family members, and other caregivers must thoroughly understand the drug regimen, diet (including moderate sodium restriction), and need for regular moderate physical activity. Patients with heart failure should have a scale, weigh themselves regularly, and know what steps to take if weight unexpectedly increases more than a specified amount, usually 3 to 5 pounds (1.4 to 2.2 kg). Nurses can communicate diuretic dose adjustments to patients by telephone, or patients may be able to adjust the dose themselves, using individualized algorithms.

End-of-Life Issues

When heart failure reaches a terminal stage, quality of life may be poor and therapeutic options may become limited; comfort issues and home services are important. There should be timely discussion of advance directives with patients.