This chapter addresses the following Geriatric Fellowship Curriculum Milestones: #26, #28
Understand the effects of aging on cardiovascular structure and function, and how these changes predispose to the development of heart failure.
Describe the clinical features—including symptoms, signs, and results of diagnostic tests—that distinguish heart failure in older adults from heart failure occurring during middle age.
Describe nonpharmacologic aspects of care for older adults with heart failure.
Understand current treatment of heart failure with reduced and preserved ejection fraction in older adults.
Discuss management of heart failure in patients approaching the end of life.
Key Clinical Points
Cardiovascular aging is associated with extensive changes in cardiac and vascular structure and function that predispose older adults to the development of heart failure.
The clinical features of heart failure, including symptoms, signs, and diagnostic test results, often differ in older adults with heart failure compared to those in younger patients.
Management of heart failure with reduced ejection fraction (HFREF) is generally similar in older and younger patients, but must be individualized in older patients with competing morbidities and in accordance with goals of care.
To date, no pharmacologic agents have been shown to reduce mortality or substantially improve clinical outcome in patients with heart failure and preserved ejection fraction (HFPEF); therefore, treatment of this condition remains empiric.
Nonpharmacologic therapies, including lifestyle changes and multidisciplinary care interventions, play a fundamental role in optimizing care and outcomes for older patients with heart failure.
The overall prognosis for heart failure in older adults is poor, and it is therefore essential to incorporate goals of care and end-of-life planning into the clinical decision-making process, especially as symptoms progress and quality of life declines.
Heart failure may be defined as an inability of the heart to pump sufficient blood to meet the metabolic needs of the body’s tissues or the ability to do so only at the expense of elevated intracardiac pressures. Heart failure represents a clinical syndrome rather than a specific diagnosis, and, to a large extent, it is a geriatric syndrome in much the same way that dementia and incontinence are geriatric syndromes. Indeed, heart failure may be viewed as the quintessential disorder of cardiovascular aging since, as discussed later in this chapter, extensive age-related changes in cardiovascular structure and function, in conjunction with the rising prevalence of cardiovascular diseases with advancing age and declines in premature cardiovascular deaths, all contribute to an exponential rise in heart failure with advancing age. Thus, although the clinical syndrome of heart failure has been recognized by physicians for more than 2000 years, it has only been within the past three decades that it has been identified as a major public health concern, a development that is largely attributable to the aging of the population.
EPIDEMIOLOGY AND ECONOMIC IMPACT
Despite progressive declines in age-adjusted mortality rates from coronary heart disease and hypertensive cardiovascular disease, both the incidence and the prevalence of heart failure are increasing, and it is projected that these trends will continue for the next several decades. As shown in Table 79-1, several factors have contributed to the progressive rise in heart failure. Foremost among these is the increasing number of older adults who, by virtue of advanced age and the high prevalence of hypertension, coronary heart disease, and cardiac valvular disorders in older individuals, are predisposed to the development of heart failure. In addition, advances in the treatment of other acute and chronic cardiac and noncardiac conditions, most notably atherosclerotic heart disease, hypertension, renal failure, cancer, and infectious diseases, have paradoxically contributed to the increasing burden of heart failure. Thus, individuals who 20 years ago might have died in middle age from acute myocardial infarction are now surviving to older age only to develop heart failure in their later years. Similarly, improved blood pressure control has led to a 60% decline in stroke mortality over the last 30 years, yet these same patients remain at risk for the subsequent development of heart failure as a complication of hypertension and left ventricular hypertrophy.
Incident heart failure hospitalizations in the United States by age, gender, and race, 2005–2011: the Atherosclerosis Risk in Communities Study. (National Heart, Lung, and Blood Institute; Circulation. 2015;131:e276.)
Prevalence of heart failure in the United States by age and gender: National Health and Nutrition Examinations Survey, 2009–2012. (National Center for Health Statistics and National Heart, Lung, and Blood Institute; Circulation. 2015;131:e275.)
Distribution of hospitalizations for heart failure in the United States by age, 2000–2010. (National Center for Health Statistics, Data brief no. 108, October 2012.)
TABLE 79-1FACTORS CONTRIBUTING TO THE RISING INCIDENCE AND PREVALENCE OF HEART FAILURE ||Download (.pdf) TABLE 79-1 FACTORS CONTRIBUTING TO THE RISING INCIDENCE AND PREVALENCE OF HEART FAILURE
Aging of the population
Improved therapy for coronary heart disease and hypertension
Improved therapy for other disorders
• End-stage renal disease
• Pneumonia and other infections
Heart failure affects approximately 5.7 million Americans, and it is projected that by 2030 the prevalence of heart failure in the United States will exceed 8 million, largely owing to the aging of the population. In addition, over 850,000 new cases are diagnosed each year. Moreover, both the incidence and the prevalence of heart failure are strikingly age dependent (Figures 79-1 and 79-2). Thus, heart failure is relatively uncommon in individuals younger than 40 years, but the prevalence doubles for each decade thereafter and exceeds 10% in both men and women older than 80 years. Similarly, heart failure mortality rates increase exponentially with advancing age in all major demographic subgroups of the US population.
Heart failure is also a major source of chronic disability and impaired quality of life in older adults, and it is the leading indication for hospitalization in individuals older than 65 years. Moreover, the number of hospital discharges for heart failure increased by more than twofold from 1979 to 2004, primarily owing to the aging of the population. In 2010, there were 1 million hospital admissions in the United States with a primary diagnosis of heart failure (Table 79-2). Of these, 71% were in patients older than 65 years, 53% were in patients 75 years or older, and 25% occurred in the 2% of the population greater than or equal to 85 years (Figure 79-3). The majority of heart failure patients younger than 65 years are males, but women comprise more than half of heart failure admissions after the age of 65, and the proportion of females continues to rise with advancing age. The prevalence of heart failure in older Caucasians and African Americans is similar, but hospital admission rates are lower in Hispanics and Asians. Whether this represents a true difference in population prevalence or a cultural difference in the likelihood that affected individuals will seek medical attention is unknown. Heart failure is also a common reason for ambulatory care visits, with 1.8 million physician office visits with a primary diagnosis of heart failure in 2010. In this regard, heart failure ranks second only to hypertension among cardiovascular causes for outpatient physician visits.
TABLE 79-2EPIDEMIOLOGY OF HEART FAILURE IN THE UNITED STATES ||Download (.pdf) TABLE 79-2 EPIDEMIOLOGY OF HEART FAILURE IN THE UNITED STATES
|POPULATION GROUP ||PREVALENCEa (AGE ≥ 20) ||INCIDENCE (AGE ≥ 55) ||MORTALITYa (2011, ALL AGES) ||HOSPITAL DISCHARGES (2010, ALL AGES) ||COSTb |
|Both sexes ||5.7 million (2.2%) ||870,000 ||58,309 ||1.023 million ||$30.7 |
|Men ||2.7 million (2.3%) ||415,000 ||24,609 (42%) ||501,000 || |
|Women ||3.0 million (2.2%) ||455,000 ||33,700 (58%) ||522,000 || |
|Race/ethnicity || || || || || |
| NH white men ||2.2% ||365,000 ||21,802 || || |
| NH white women ||2.2% ||395,000 ||30,036 || || |
| Black men ||2.8% ||50,000 ||2371 || || |
| Black women ||3.2% ||60,000 ||3143 || || |
| Hispanic men ||2.1% ||NA ||NA || || |
| Hispanic women ||2.1% ||NA ||NA || || |
As a result of its high prevalence and the need for intensive resource use in both the inpatient and the outpatient settings, it is not surprising that the economic burden of heart failure is very high. Heart failure is one of the most costly diagnosis-related groups in the United States, with estimated total annual expenditures in excess of $30 billion. Overall, heart failure accounts for about 6% of Medicare expenditures for inpatient care.
Heart failure represents the prototypical disorder of cardiovascular aging in that age-related changes in the cardiovascular system in concert with an increasing prevalence of cardiovascular diseases at older age conspire to produce an exponential rise in heart failure prevalence with advancing age.
Aging is associated with extensive changes in cardiovascular structure and function (see Chapter 75). However, in the absence of coexistent cardiovascular disease, resting cardiac function is well preserved even at very old age. Thus, the resting left ventricular ejection fraction, an index of left ventricular systolic performance, is unaffected by age in healthy individuals. Similarly, most studies indicate that resting cardiac output is either maintained or declines minimally with normal aging.
From the clinical perspective, the changes associated with cardiovascular aging result in an impaired ability of the heart to respond to stress, whether that stress is physiologic (eg, exercise) or pathologic (eg, hypertension or myocardial ischemia). Four principal changes in the cardiovascular system contribute directly to the heart’s attenuated capacity to augment cardiac output in response to stress. First, aging is associated with reduced responsiveness to β-adrenergic stimulation. The mechanism underlying this change has not been fully elucidated, but is likely related to increased sympathetic nervous system activity and circulating catecholamine levels resulting in β-adrenergic receptor desensitization, rather than decreased β-receptor density on cardiac myocytes or altered responsiveness to intracellular calcium. In any case, the diminished response to β-adrenergic stimulation limits the heart’s capacity to maximally increase heart rate and contractility in response to stress, and β2-mediated peripheral vasodilatation is also impaired.
A second major effect of aging is increased vascular stiffness, primarily because of increased collagen deposition and cross-linking and degeneration of elastin fibers in the media and adventitia of the large- and medium-sized arteries. Increased vascular stiffness results in increased impedance to left ventricular ejection (ie, increased afterload), and it also contributes to the increased propensity of older individuals to develop isolated systolic hypertension.
A third major effect of aging is altered left ventricular diastolic filling. Diastole is characterized by four phases: isovolumic relaxation, early rapid filling, passive filling during mid-diastole, and late filling owing to atrial systole. The first two phases, isovolumic relaxation and early rapid filling, are largely dependent on myocardial relaxation, an active, energy-requiring process, whereas filling during the latter two phases is governed principally by intrinsic myocardial “stiffness,” or compliance. Aging is associated with impaired calcium release from the contractile proteins and reuptake by the sarcoplasmic reticulum at the end of systole, leaving the heart in a state of “partial contraction” at the onset of diastole and inhibiting early diastolic relaxation. In addition, increased interstitial connective tissue content and collagen cross-linking reduce ventricular compliance. Compensatory myocyte hypertrophy in response to increased ventricular afterload and myocyte loss due to apoptosis further compromises left ventricular compliance. Thus, normal aging is associated with important changes that impair both relaxation and compliance, adversely impacting all four phases of diastole and substantially altering the pattern of left ventricular diastolic filling.
Age-related changes in diastolic filling and atrial function can be evaluated noninvasively using Doppler echocardiographic techniques to examine diastolic inflow across the mitral valve (Figure 79-4). In healthy young persons, the transmitral inflow pattern is characterized by a large E-wave, with a rapid upstroke representing rapid filling of the ventricle immediately following the opening of the mitral valve and corresponding to active ventricular relaxation (Figure 79-4A). This is followed by a period in which the rate of filling slows (the downslope of the E-wave), mid-diastolic diastasis (in which left atrial and left ventricular pressures are essentially equal), and a second burst of flow at the end of diastole corresponding to atrial contraction (the A-wave, or atrial “kick”). Importantly, the majority of ventricular filling occurs in the first half of diastole in young individuals, with a relatively small contribution from atrial contraction.
In older persons, alterations in cardiac relaxation and compliance result in characteristic changes in the pattern of diastolic filling (Figure 79-4B). Early filling is impaired, and the upstroke of the E-wave is delayed. Similarly, the downslope of the E-wave is less steep, as it takes a longer time to achieve diastasis. In order to compensate for increased resistance to emptying, the left atrium enlarges and hypertrophies. This results in a more forceful left atrial contraction and an augmented A-wave. As a result of these changes, a greater proportion of filling occurs in the second half of diastole in older individuals, and as much as 30% to 40% of left ventricular end-diastolic volume may be attributable to atrial contraction. Thus, older individuals become increasingly reliant on the atrial “kick” to maximize left ventricular filling.
A third pattern of diastolic filling, referred to as the restrictive pattern, occurs when the left ventricle’s ability to accept blood becomes severely compromised. In this situation (Figure 79-4C), very little flow occurs after the rapid filling phase in early diastole. This pattern is characterized by a tall, narrow E-wave with a rapid downslope, as diastasis is achieved early in diastole. Little additional flow occurs during mid-diastole, and the A-wave is typically small, with an amplitude that is less than 50% of the E-wave. A restrictive pattern usually indicates marked elevation of the left ventricular diastolic pressure, and it tends to be associated with a poor prognosis, particularly in patients with concomitant systolic dysfunction. The restrictive pattern almost always occurs in patients with advanced cardiac disease, and it is rarely attributable to aging alone.
Age-related changes in diastolic filling have several important clinical implications. First, inability to distend the cardiac myocytes to an optimal fiber length results in a failure of the Frank-Starling mechanism, one of the cardinal adaptive responses (along with sympathetic activation) to acutely increase cardiac output. Second, impaired diastolic filling results in a shift to the left in the normal ventricular pressure-volume relationship; that is, a small increase in diastolic volume is associated with a greater increase in diastolic pressure in older compared to younger individuals. This increase in diastolic pressure is transmitted back to the left atrium, and left atrial myocytes become “stretched.” This, in turn, increases the likelihood of atrial ectopic beats and atrial arrhythmias, especially atrial fibrillation. This accounts, in part, for the fact that atrial fibrillation, like heart failure, increases in prevalence with advancing age. In addition, atrial fibrillation itself is a common precipitant of heart failure in older adults for two reasons. First, the absence of a coordinated atrial contraction substantially compromises late diastolic filling as a result of loss of the atrial “kick.” Second, the rapid, irregular ventricular rate associated with acute atrial fibrillation shortens the diastolic filling period, which further attenuates ventricular filling.
A third effect of altered diastolic filling is an increased propensity for older adults to develop HFPEF, previously referred to as diastolic heart failure. Because of the altered left ventricular pressure-volume relation, increases in left ventricular pressure owing to ischemia or uncontrolled hypertension may lead to pulmonary congestion and edema. Moreover, individuals with impaired diastolic function are often “volume sensitive”; that is, small increments in intravascular volume, as may occur with a dietary salt load or intravenous fluid administration, are poorly accommodated by the noncompliant ventricle. As a result, intraventricular pressure rises abruptly and heart failure ensues. Conversely, intravascular volume contraction, which may arise from poor oral intake or overdiuresis, can cause a marked fall in left ventricular volume, which in turn leads to a fall in stroke volume and cardiac output.
The fourth major effect of cardiovascular aging is altered myocardial energy metabolism at the level of the mitochondria. Under resting conditions, older cardiac mitochondria are able to generate sufficient quantities of adenosine triphosphate (ATP) to meet the heart’s energy requirements. However, when stress causes an increase in ATP demands, the mitochondria are often unable to respond appropriately. Although the precise mechanism underlying this mitochondrial failure is unclear, the defect adds to the heart’s inability to maintain normal function under stress.
To summarize, four major age-related changes in cardiovascular structure, function, and physiology combine to reduce cardiovascular reserve and greatly increase the risk of heart failure in older adults. Recalling that cardiac output is determined by four primary factors (heart rate, preload, afterload, and contractile state), and recognizing that each of these factors is adversely affected by one or more of the four major effects of aging on the heart, and that superimposed upon these changes is the high prevalence of cardiac disease in older adults, it is indeed not surprising that the incidence and prevalence of heart failure rise exponentially with advancing age.
It is also important to note that aging is associated with significant changes in other organ systems, which impact directly or indirectly on the development and/or management of heart failure. Aging is accompanied by a decline in glomerular filtration rate, and the aging kidney is less able to maintain intravascular volume and electrolyte homeostasis (see Chapter 86). The reduced capacity of the kidneys to respond to intravascular volume overload or dietary sodium excess further increases the risk of heart failure in older individuals. In addition, older patients are less responsive to diuretics and more likely to develop diuretic-induced electrolyte abnormalities than younger patients, factors that may complicate the management of heart failure in the older age group.
Aging is also associated with numerous changes in respiratory function, which serve to diminish respiratory reserve (see Chapter 83). Some of these effects, such as V/Q mismatching and sleep-related breathing disorders, may contribute directly to the development of heart failure by producing hypoxemia or pulmonary hypertension. Other changes reduce the capacity of the lungs to compensate for the failing heart by increasing tidal volume and minute ventilation, thereby contributing to the patient’s sensation of dyspnea. In more severe cases of cardiac failure, such as pulmonary edema, acute respiratory failure may ensue, partly as a consequence of the inability of the lungs to maintain oxygenation and effective ventilation.
Age-related changes in nervous system function include an impaired thirst mechanism, which may contribute to dehydration and intravascular volume contraction in patients treated with diuretics, and reduced capacity of the central nervous system’s autoregulatory mechanisms to maintain cerebral perfusion in the face of changes in systemic arterial blood pressure. The latter effect may contribute to subtle changes in cognitive function in older heart failure patients treated with vasodilators. Aging is also associated with widespread changes in reflex responsiveness. For example, impaired responsiveness of the carotid baroreceptors to acute changes in blood pressure may cause orthostatic hypotension or syncope, and these effects may be further aggravated by many of the drugs used to treat heart failure.
Finally, as is well recognized, aging is associated with significant changes in the pharmacokinetics and pharmacodynamics of almost all drugs. In addition, older patients tend to be at increased risk of both drug-drug and drug-disease interactions as a result of the high prevalence of comorbid conditions and the use of multiple pharmacologic agents. These factors often lead to alterations in drug efficacy and an increased side effect profile, and these effects must be taken into consideration when designing therapy for older heart failure patients (see Chapter 24).
Schematic diagram of Doppler echocardiographic mitral valve inflow patterns. A. Normal pattern. B. Impaired filling pattern. C. Restrictive pattern. AT, acceleration time; DT, deceleration time; IR, isovolumic relaxation; S2, aortic valve closure. (Adapted with permission from Feigenbaum H. Echocardiography. 5th ed. Philadelphia,PA: Lea & Febiger; 1994:152.)
ETIOLOGY AND PRECIPITATING FACTORS
In general, the etiology of heart failure is similar in older and younger patients (Table 79-3), but heart failure in older individuals is more often multifactorial. As in younger patients, hypertension and coronary heart disease are the most common causes of heart failure, accounting for more than 70% of cases. Hypertensive hypertrophic cardiomyopathy represents a more severe form of hypertensive heart disease most commonly seen in older women and often accompanied by calcification of the mitral valve annulus. These patients often manifest severe diastolic dysfunction and may exhibit dynamic left ventricular outflow tract obstruction indistinguishable from that seen in classical hypertrophic cardiomyopathy.
TABLE 79-3COMMON ETIOLOGIES OF HEART FAILURE IN OLDER ADULTS ||Download (.pdf) TABLE 79-3 COMMON ETIOLOGIES OF HEART FAILURE IN OLDER ADULTS
Coronary artery disease
Hypertensive heart disease
Valvular heart disease
|Infective endocarditis |
|Pericardial disease |
|Age-related increase in arterial stiffness and diastolic dysfunction |
Valvular heart disease is an increasingly common cause of heart failure at older age. Calcific aortic stenosis is now the most common form of valvular heart disease requiring invasive treatment, and aortic valve replacement is the second most common major heart procedure performed in patients older than 70 years (after coronary bypass grafting). Mitral regurgitation in older individuals may be caused by myxomatous degeneration of the mitral valve leaflets and chordae tendineae (mitral valve prolapse), mitral annular calcification, valvular vegetations, ischemic papillary muscle dysfunction, or altered ventricular geometry owing to ischemic or nonischemic dilated cardiomyopathy. Importantly, mitral regurgitation may be acute (eg, following acute myocardial infarction), subacute (eg, endocarditis), or chronic (eg, myxomatous degeneration), and the clinical manifestations may vary widely in each of these settings. In the United States, rheumatic mitral stenosis is a less common cause of heart failure in older adults, but it is still occasionally seen. Functional mitral stenosis owing to severe mitral valve annulus calcification with encroachment on the mitral valve orifice is an uncommon cause of heart failure, but it is associated with a poor prognosis. Aortic insufficiency may be either acute (eg, because of endocarditis or type A aortic dissection) or chronic (eg, annuloaortic ectasia or syphilitic aortitis), but it is a relatively infrequent cause of heart failure in older adults. Finally, prosthetic valve dysfunction should be considered as a potential cause of heart failure in any patient who has undergone previous valve repair or replacement.
Cardiomyopathies are classified into three categories: dilated, hypertrophic, and restrictive. In older adults, ischemic heart disease with one or more prior myocardial infarctions is the most common cause of dilated cardiomyopathy. Nonischemic dilated cardiomyopathy is less common in older than in younger individuals; when present, it is most often either idiopathic in origin or attributable to chronic ethanol abuse or cancer chemotherapy (eg, anthracyclines or trastuzumab). Stress cardiomyopathy (also known as takotsubo cardiomyopathy) is a relatively recently recognized cause of acute heart failure usually precipitated by physical or psychological stress. The majority of patients are women and most cases resolve within days to weeks. Classical hypertrophic cardiomyopathy, once thought to be rare in the geriatric age group, has been increasingly recognized in older adults since the advent of echocardiography. Similarly, restrictive cardiomyopathy, most commonly owing to amyloid deposition, is an occasional cause of heart failure. In one autopsy series, cardiac amyloid deposition was thought to be clinically important in approximately 10% of individuals 90 years or older. Recently there has been increased interest in “senile cardiac amyloid,” which has been linked to mutations in the gene coding for the protein transthyretin (previously known as prealbumin). Genetic abnormalities in transthyretin are present in up to 4% of African Americans, who are at increased risk for developing cardiac amyloid. While the genetic defect is present from birth, clinical manifestations typically do not become apparent until after age 60. Novel therapies that inhibit production or promote stabilization of transthyretin amyloid, such as diflunisal and tafamidis, are currently being evaluated in clinical trials.
Infective endocarditis is an uncommon but important cause of heart failure in older patients because it is one of the few etiologies for which curative pharmacologic therapy is available. Endocarditis should be strongly suspected in any patient with persistent fever and either a prosthetic heart valve or a preexisting valvular lesion. It should also be considered in any patient with fever, recent dental work or other procedure, and a new or worsening heart murmur. It is important to recognize, however, that the clinical manifestations of endocarditis are often protean, and the absence of fever or a heart murmur does not exclude this diagnosis in older individuals.
Myocarditis is a relatively rare cause of heart failure in older adults. It may be infectious (eg, postviral) or noninfectious (eg, owing to sarcoid or collagen vascular disease). Pericardial effusions, for which there are numerous etiologies, occasionally present with heart failure symptomatology, including fatigue, exertional dyspnea, and edema. Constrictive pericarditis may be infectious (eg, tuberculous) or noninfectious (eg, postradiation), but it is a rare cause of heart failure in older patients.
High-output failure is an uncommon cause of heart failure in older adults, but when present the diagnosis is frequently overlooked. Potential causes of high-output failure include chronic anemia, hyperthyroidism, thiamine deficiency, and arteriovenous shunting (eg, owing to a dialysis fistula or arteriovenous malformations).
Finally, in a small percentage of older heart failure patients, detailed investigation may fail to identify any primary cardiovascular pathology. In cases with a normal left ventricular ejection fraction, heart failure may be attributed to age-related diastolic dysfunction.
In addition to determining the etiology of heart failure, it is important to identify coexisting factors that may have contributed to the acute or subacute exacerbation (Table 79-4). The most common precipitant in patients with preexisting heart failure is nonadherence to medications and/or diet. Indeed, nonadherence may contribute to as many as two-thirds of heart failure exacerbations. In hospitalized patients, iatrogenic volume overload (eg, in the perioperative period) is also an important precipitant of heart failure.
TABLE 79-4COMMON PRECIPITANTS OF HEART FAILURE IN OLDER ADULTS ||Download (.pdf) TABLE 79-4 COMMON PRECIPITANTS OF HEART FAILURE IN OLDER ADULTS
|Myocardial ischemia or infarction |
|Dietary sodium excess |
|Excess fluid intake |
|Medication nonadherence |
|Iatrogenic volume overload |
Associated medical conditions
Infections, especially pneumonia or sepsis
Hyperthyroidism or hypothyroidism
Hypoxemia from chronic lung disease
Drugs and medications
β-Blockers (including ophthalmologic agents)
Calcium channel blockers
Nonsteroidal anti-inflammatory drugs
Antihypertensive agents (eg, clonidine and minoxidil)
Among cardiac factors, myocardial ischemia or infarction and new-onset atrial fibrillation or flutter are the most common causes of an acute episode of heart failure. Other cardiac causes include ventricular arrhythmias, especially ventricular tachycardia, and bradyarrhythmias, such as marked sinus bradycardia or advanced atrioventricular block. Sick sinus syndrome, which is common in older adults, is a frequent cause of bradyarrhythmias in this population.
As previously discussed, older patients have limited cardiovascular reserve and they are less able to compensate in response to increased demands. As a result, heart failure in older adults is often precipitated by acute or worsening noncardiac conditions. Patients with acute respiratory disorders, such as pneumonia, pulmonary embolism, or an exacerbation of chronic obstructive lung disease, are particularly prone to exhibit deterioration in cardiac function. Other serious infections, such as sepsis or pyelonephritis, may also lead to heart failure exacerbations. In patients with hypertension, inadequate blood pressure control is a common cause of worsening heart failure. Thyroid disease, anemia (eg, owing to gastrointestinal bleeding), and declining renal function may also contribute directly or indirectly to the development of heart failure.
Finally, numerous drugs and medications may contribute to heart failure exacerbations. Alcohol is a cardiac depressant, and it may also precipitate arrhythmias, especially atrial fibrillation. β-Blockers (including ophthalmologic agents) and calcium antagonists are widely used in older individuals with cardiovascular disease, but both classes of agents are negatively inotropic and may exacerbate heart failure. Class Ia (eg, quinidine, procainamide, and disopyramide) and Ic (eg, flecainide and propafenone) antiarrhythmic agents have important myocardial depressant effects that may worsen cardiac function. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are widely used by older adults, impair renal sodium and water excretion and may, therefore, contribute to intravascular volume overload. In addition, NSAIDs antagonize the effects of angiotensin-converting enzyme (ACE) inhibitors, thereby limiting the efficacy of these agents. Corticosteroids and estrogen preparations may cause fluid retention and an increase in total body water. Fluid retention is the most important side effect of the insulin-sensitizing thiazolidinediones (rosiglitazone and pioglitazone), and worsening heart failure may occur with these agents. The antihypertensive agent minoxidil also promotes fluid retention, and several other antihypertensive drugs (eg, clonidine and guanethidine) may have unfavorable hemodynamic effects.
As in younger patients, the most common symptoms of heart failure in older adults are exertional shortness of breath, orthopnea, dependent edema, fatigue, and exercise intolerance. However, there is an increased prevalence of atypical symptomatology in older patients, particularly those older than 80 years (Table 79-5). As a result, heart failure in older adults is paradoxically both over- and underdiagnosed. Thus, shortness of breath and orthopnea in an older individual may be attributed to heart failure when the underlying cause is chronic lung disease, pneumonia, or pulmonary embolism. Similarly, fatigue and reduced exercise tolerance may be caused by anemia, hypothyroidism, depression, or poor physical conditioning. On the other hand, sedentary individuals and those limited by arthritis or neuromuscular conditions may not report exertional dyspnea or fatigue, and atypical symptoms such as those listed in Table 79-5 may be the first and only clinical manifestations of heart failure. In such cases, the physician must maintain a high index of suspicion or the diagnosis of heart failure may be readily overlooked.
TABLE 79-5ATYPICAL MANIFESTATIONS OF HEART FAILURE IN OLDER PERSONS ||Download (.pdf) TABLE 79-5 ATYPICAL MANIFESTATIONS OF HEART FAILURE IN OLDER PERSONS
Nonspecific systemic complaints
As with symptoms, the physical findings in older heart failure patients may be nonspecific or atypical. The classic signs of heart failure include moist pulmonary rales, an elevated jugular venous pressure, abdominojugular reflux, an S3 gallop, and pitting edema of the lower extremities. However, pulmonary rales in older individuals may be due to chronic lung disease, pneumonia, or atelectasis, and peripheral edema may be caused by venous insufficiency, renal disease, or medication (eg, calcium channel blockers). Conversely, older patients may have an essentially normal physical examination despite markedly reduced cardiac performance. Alternatively, impaired sensorium or Cheyne-Stokes respirations may be the only findings to suggest the presence of heart failure.
Heart failure with reduced versus preserved ejection fraction
Current nomenclature distinguishes two forms of heart failure—HFREF, usually defined as ejection fraction less than 40%–50% and HFPEF. The clinical manifestations of both forms of heart failure are similar, and no single clinical feature can reliably distinguish patients with HFREF from those with HFPEF. Nonetheless, certain features tend to favor one form or the other (Table 79-6). Based on the presence or absence of specific features, the probability of normal or reduced systolic function can be estimated, and there have been several attempts to develop algorithms for distinguishing these syndromes. Unfortunately, the predictive accuracy of these algorithms has been modest, and additional testing is essential in order to reliably differentiate HFREF from HFPEF.
TABLE 79-6CLINICAL FEATURES OF HEART FAILURE WITH REDUCED VERSUS PRESERVED EJECTION FRACTION ||Download (.pdf) TABLE 79-6 CLINICAL FEATURES OF HEART FAILURE WITH REDUCED VERSUS PRESERVED EJECTION FRACTION
| ||HFREF ||HFPEF |
|Demographics || |
Age < 60 y
Age > 70 y
|Comorbid illnesses || |
Prior myocardial infarction
|Physical examination || |
May be normotensive or hypotensive
Jugular venous distention
Jugular venous distention often absent
Peripheral edema often absent
|Electrocardiogram ||Q waves due to prior myocardial infarction ||Left ventricular hypertrophy |
Heart failure may be difficult to diagnose in older patients with multiple comorbid conditions and either vague or nonspecific symptoms and signs. Thus, the first task facing the physician is to establish whether or not heart failure is present. This begins with a careful history and physical examination, giving due consideration to potential alternative etiologies for the patient’s findings. As discussed in the previous section, physical signs may be unreliable in older patients. Nonetheless, certain findings, including pulsus alternans, an S3 gallop, and the presence of jugular venous distension at rest or in response to the abdominojugular reflux maneuver, are highly specific signs of heart failure in older patients. In the absence of these findings, the diagnosis often remains in doubt, and additional laboratory studies are required.
To differentiate shortness of breath attributable to heart failure from that owing to other causes, the level of B-type natriuretic peptide (BNP—a 32-amino acid hormone released by the cardiac ventricles in response to increased wall tension) or its precursor N-terminal pro-BNP (NT–pro-BNP) is the single most useful test. However, BNP levels increase modestly with age, especially in women (Figure 79-5), and with declining renal function, but tend to be lower in the presence of obesity. Therefore, the specificity of an elevated BNP level for clinical heart failure declines with age. BNP levels in excess of 500 pg/mL in the appropriate clinical context are highly suggestive of active heart failure, whereas a normal value (< 100 pg/mL) in a nonobese older adult makes the diagnosis of heart failure much less likely. In addition to the BNP level, the chest radiograph remains useful for establishing the presence of active pulmonary congestion. In patients with moderate or severe heart failure, the chest film will usually demonstrate typical findings of cardiomegaly, pulmonary vascular engorgement, parenchymal edema, and pleural effusions. However, in patients with mild heart failure or coexisting pulmonary disease, the chest radiograph may be nondiagnostic.
Once the presence of heart failure has been established, the physician must address two crucial questions, the answers to which will serve as the basis for selecting appropriate therapy:
What is the underlying etiology and pathophysiology of heart failure (see Table 79-3)?
What additional factors, if any, contributed to or precipitated the development of heart failure (see Table 79-4)? Often, one or more precipitating factors can be identified, and alleviating these factors may significantly improve symptoms and reduce the likelihood of subsequent heart failure exacerbations.
In 2013, the American College of Cardiology and American Heart Association Task Force on Practice Guidelines published revised guidelines for the diagnosis and management of heart failure. Table 79-7 outlines an appropriate initial diagnostic assessment for patients with new-onset heart failure. Class I studies are defined as those that are indicated in most patients, class II procedures are acceptable in some patients but are of unproven efficacy and may be controversial, and class III studies are not routinely indicated and in some cases may be harmful. Briefly, basic laboratory studies, a thyroid function test, a chest radiograph, an electrocardiogram, and an echocardiogram with Doppler are recommended in all patients. Cardiac catheterization and coronary angiography are appropriate in patients with angina or significant ischemia on noninvasive testing, and in those who require surgical correction of a noncoronary cardiac lesion (eg, aortic stenosis), unless the patient is not a suitable candidate for coronary revascularization.
TABLE 79-7DIAGNOSTIC EVALUATION OF PATIENTS WITH HEART FAILURE ||Download (.pdf) TABLE 79-7 DIAGNOSTIC EVALUATION OF PATIENTS WITH HEART FAILURE
Class I (indicated in most patients)
Complete blood count
Blood chemistries: electrolytes, creatinine, blood urea nitrogen, glucose, magnesium, calcium, liver function tests, and lipid profile
Thyroid-stimulating hormone (TSH)
B-type natriuretic peptide (BNP) or N-terminal pro-BNP level
Chest radiograph and electrocardiogram (ECG)
Echocardiogram: two-dimensional with Doppler
Cardiac catheterization and coronary angiography in patients with angina or significant ischemia unless the patient is not eligible for revascularization
Class II (acceptable in selected patients; see text)
Serum iron and ferritin
If suspected, assessment for rheumatologic disease, human immunodeficiency virus, amyloidosis, or pheochromocytoma
Screening for sleep-disordered breathing
Stress test to evaluate for ischemia in patients with unexplained heart failure who are potential candidates for revascularization
Coronary angiography if ischemia may be contributing to heart failure in patients who are potential candidates for revascularization
Endomyocardial biopsy when a specific diagnosis is suspected that would influence therapy
Class III (not routinely indicated)
The recommendations outlined in Table 79-7 are targeted toward a broad range of adult heart failure patients, and most are applicable in patients at an advanced age. Nonetheless, in older patients it is appropriate to consider the potential risks and benefits of each diagnostic procedure on an individualized basis, taking into account comorbid conditions, the extent of cardiac and noncardiac disability, and the patient’s goals of care. For example, in a frail 85-year-old individual with diabetic nephropathy, the risk of precipitating dialysis-dependent end-stage renal disease as a complication of coronary angiography must be carefully weighed against the potential benefits to be derived from a successful revascularization procedure. Similarly, patient autonomy must be respected in all cases, and it is inappropriate to exert pressure on an older patient to undergo a procedure that the patient clearly does not desire. In this regard, it is imperative to discuss the therapeutic implications of specific procedures (especially invasive procedures) with respect to the patient’s subsequent care (eg, need for coronary bypass surgery) prior to performing the diagnostic assessment.
B-type natriuretic peptide levels by age and gender (mean values in healthy volunteers). (Adapted with permission from Redfield MM, Rodeheffer RJ, Jacobsen SJ, et al. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002;40:976–982.)
An important goal of the diagnostic evaluation, apart from determining the etiology of heart failure, is differentiating HFREF from HFPEF, since the management of these two syndromes differs. As noted earlier, it is difficult to make this distinction on clinical grounds alone, and it is therefore essential to evaluate left ventricular function directly by echocardiography, radionuclide angiography, magnetic resonance imaging, or contrast ventriculography. In general, transthoracic echocardiography is the most useful technique because it is noninvasive, relatively inexpensive, and, in addition to providing information about systolic and diastolic function, it is helpful in evaluating chamber size, wall thickness and motion, valve function, pulmonary artery pressure, and pericardial disease. Thus, transthoracic echocardiography is appropriate in virtually all older patients with newly diagnosed heart failure and in those with an unexplained change in symptom severity. The principal limitation of echocardiography is that adequate visualization of the heart may be unobtainable in a small percentage of patients, although the availability of echocontrast agents has minimized this problem. Alternatively, radionuclide angiography can provide an accurate assessment of left ventricular function, as well as information about cavity size and regurgitant valvular lesions. Magnetic resonance imaging provides much the same information as echocardiography and radionuclide angiography but is more expensive and contrast administration may be contraindicated in patients with impaired renal function. For those patients who require cardiac catheterization, contrast left ventriculography is an excellent method for evaluating ventricular function.
Based on the results of echocardiography, radionuclide angiography, magnetic resonance imaging, or contrast ventriculography, heart failure may be classified as HFREF or HFREF (in the ensuing discussion HFREF is defined as ejection fraction < 45%, HFPEF is defined as ejection fraction ≥ 45%). However, it must be emphasized that systolic and diastolic dysfunction are not mutually exclusive. Indeed, almost all patients with significant systolic dysfunction also have concomitant diastolic dysfunction. Conversely, systolic dysfunction may play a role in the development of heart failure even when the ejection fraction under resting conditions is normal or near normal. Despite these limitations, the classification of heart failure as HFREF or HFPEF is useful in guiding therapy.
The primary goals of heart failure therapy are to improve quality of life, reduce the frequency of heart failure exacerbations, and extend survival. Secondary goals include maximizing independence and exercise capacity, enhancing emotional well-being, and reducing resource use and the associated costs of care.
To achieve these goals, optimal therapy in older patients comprises three principal components: correction of the underlying etiology whenever possible (eg, aortic valve replacement for aortic stenosis or coronary revascularization for severe ischemia), attention to the nonpharmacologic and rehabilitative aspects of treatment, and the judicious use of medications.
As will be discussed in the section on Prognosis, the outlook for patients with established heart failure is poor. Therefore, the importance of effectively treating the primary etiology and all comorbid conditions predisposing to heart failure cannot be overemphasized. Since coronary heart disease and hypertension are the most common causes of heart failure in older adults, primary and secondary prevention of these conditions are critical if the development of heart failure is to be forestalled. Indeed, it has now been shown in multiple clinical trials that effective treatment of hypertension can reduce the incidence of heart failure by 50% or more. Similarly, appropriate management of other coronary risk factors, particularly hyperlipidemia, sedentary lifestyle, and cigarette smoking, will undoubtedly further reduce the burden of heart failure through the primary prevention of coronary heart disease.
Despite recent advances in the pharmacotherapy of heart failure, repetitive heart failure exacerbations are common and are more often precipitated by behavioral and social factors than by either new cardiac events (eg, ischemia or an arrhythmia) or progressive deterioration in ventricular function. In one study, lack of adherence to prescribed medications and/or diet contributed to 64% of heart failure exacerbations among urban blacks, while emotional and environmental factors contributed to 26% of hospital readmissions. In another study involving 140 patients 70 years or older hospitalized with heart failure, 47% were readmitted at least once during a 90-day follow-up period. Behavioral and social factors contributing to readmission included medication and dietary nonadherence (15% and 18%, respectively), inadequate social support (21%), inadequate discharge planning (15%), inadequate follow-up (20%), and failure of the patient to seek medical attention promptly when symptoms recurred (20%). These findings suggest that interventions directed at behavioral and social factors could potentially reduce readmissions and improve quality of life in patients with heart failure, and this hypothesis has now been confirmed in numerous prospective randomized trials. In a meta-analytic review of 33 such trials, heart failure readmissions were reduced by 42%, all-cause readmissions were reduced by 24%, and mortality was reduced by 20% in patients with heart failure enrolled in a disease management program relative to conventional care.
Components of a comprehensive nonpharmacologic treatment program are listed in Table 79-8. As with other aspects of geriatric care, it is important to structure the treatment program in order to accommodate the needs of each individual patient. Clearly, not every patient will require all of the components listed in the table. Similarly, the optimal intensity of any given component, for example, patient education or follow-up care, will vary substantially. For these reasons, it is desirable to designate a single individual, such as a nurse case manager, to coordinate all aspects of the patient’s care.
TABLE 79-8NONPHARMACOLOGIC ASPECTS OF HEART FAILURE MANAGEMENT ||Download (.pdf) TABLE 79-8 NONPHARMACOLOGIC ASPECTS OF HEART FAILURE MANAGEMENT
Symptoms and signs of heart failure
Detailed discussion of all medications
Emphasize importance of adherence
Specific information about when to contact nurse or physician for worsening symptoms
Daily weight chart
Specific directions on when to contact nurse or physician for changes in weight
Self-management of diuretic dosage based on daily weights in selected patients
Involve family/significant other when feasible
Individualized and consistent with needs/lifestyle
Avoidance of excess sodium intake (> 2.3 g/d)
Avoidance of excess fluid intake (> 2 L/d)
Weight loss, if appropriate
Low fat, low cholesterol, if appropriate
Adequate caloric intake
Emphasize adherence while allowing flexibility
Heart failure therapy in accordance with guidelines
Eliminate unnecessary medications
Simplify regimen whenever possible
Consolidate dosing schedule
Assess social support structure
Evaluate emotional and financial needs
Intervene proactively when feasible
|Palliative care consultation in patients with advanced symptoms or frequent hospitalizations |
Physical Activity and Exercise
Traditionally, patients with heart failure have been advised to restrict physical activity on the grounds that rest is beneficial for the heart and that exercise could potentially worsen cardiac function or precipitate arrhythmias. However, it is now recognized that although some degree of activity restriction may be appropriate, excessive limitation of physical activity may contribute to a progressive decline in functional capacity as a result of cardiovascular and muscular deconditioning. In addition, several studies have demonstrated that participation in an appropriately structured exercise program may result in significant improvements in functional capacity and quality of life in patients with heart failure. In the largest of these trials, HF-ACTION, 2331 patients with stable heart failure and an ejection fraction less than or equal to 35% were randomized to a supervised exercise program or usual care. The mean age was 59 (25% were ≥ 68) and 28% were women. After a median follow-up of 30 months, patients randomized to the exercise intervention experienced a 7% reduction in the primary end point of all-cause mortality or all-cause hospitalization, but the difference was not significant (p = 0.13). After adjusting for highly prognostic baseline characteristics, exercise was associated with an 11% reduction in the primary end point (p = 0.03). In addition, exercise was associated with improved health status beginning at 3 months and persisting for up to 4 years. Based on these findings, current guidelines recommend regular exercise for the majority of patients with heart failure. In addition, in 2014 the Centers for Medicare and Medicaid Services approved structured cardiac rehabilitation and exercise training for heart failure patients similar to those enrolled in the HF-ACTION trial.
While data on exercise training in older adults are limited, a randomized trial involving 200 patients 60 to 89 years (mean 72 years, 66% male) with New York Heart Association (NYHA) class II to III HFREF evaluated the effects of exercise prescription, education, occupational therapy, and psychosocial counseling. At 24 weeks of follow-up, intervention group patients experienced significant improvements in NYHA class, 6-minute walk distance, and quality of life, whereas control-group patients demonstrated no change from baseline in any of these parameters. Patients receiving the intervention also had significantly fewer hospital admissions relative to the control group. In addition, two small randomized trials in older patients with HFPEF have demonstrated that exercise training is safe and results in improved exercise capacity and quality of life. These data provide support for a beneficial effect of exercise and cardiac rehabilitation in older patients with either HFREF or HFPEF. Nonetheless, additional studies are needed to evaluate the safety and efficacy of regular exercise in older heart failure patients, especially those older than 75 years, and patients with frailty or multiple comorbid conditions.
A comprehensive exercise and conditioning program is appropriate for most older patients with mild-to-moderate heart failure symptoms and no contraindications to exercise (Table 79-9). Table 79-10 outlines the basic components of such a program. In general, patients should try to exercise every day. A typical session should include some gentle stretching exercises as well as strengthening exercises using elastic bands or light weights and targeting all of the major muscle groups. Suitable forms of aerobic exercise for older patients include walking, stationary cycling, and swimming. The choice of aerobic exercise should be tailored to the patient’s wishes and abilities. When initiating an exercise program, the duration and intensity of the aerobic activity should be well within the patient’s comfort range. The activity should be enjoyable, not stressful, and after completing the activity the patient should feel “positive” about the experience and not unduly fatigued. For many older patients with heart failure, this may mean starting with as little as 2 to 5 minutes of slow-paced walking. Once the patient feels comfortable exercising, the duration of exercise can be gradually increased over a period of several weeks. Weekly increases of 1 to 2 minutes per session are appropriate for most patients. Once the patient can exercise continuously and comfortably for 20 to 30 minutes, the intensity of exercise may be increased, if desired. For example, if the patient is walking a half-mile in 30 minutes, he or she may gradually reduce the half-mile time to 20 minutes, while maintaining a total exercise duration of 30 minutes. More recently, high-intensity interval training, in which short bursts of higher-intensity exercise are incorporated into the exercise regimen, has been shown to be safe and to result in more rapid increases in exercise capacity in heart failure patients. These findings, while encouraging, should be regarded as preliminary, and high-intensity training should only be initiated in a monitored setting.
TABLE 79-9CONTRAINDICATIONS TO EXERCISE IN OLDER PATIENTS ||Download (.pdf) TABLE 79-9 CONTRAINDICATIONS TO EXERCISE IN OLDER PATIENTS
|Recent myocardial infarction or unstable angina (within 2 wk) |
|Severe, decompensated heart failure (New York Heart Association class IV) |
|Life-threatening arrhythmias not adequately treated |
|Severe aortic stenosis or hypertrophic cardiomyopathy |
|Any acute serious illness (eg, pneumonia) |
|Any condition precluding safe participation in an exercise program |
TABLE 79-10EXERCISE PRESCRIPTION FOR OLDER PATIENTS WITH HEART FAILURE ||Download (.pdf) TABLE 79-10 EXERCISE PRESCRIPTION FOR OLDER PATIENTS WITH HEART FAILURE
Components of conditioning program
|Frequency of exercise: daily, if possible |
|Duration of exercise: individualized; start low, go slow |
|Intensity of exercise: low to moderate (see text for details) |
|Rate of progression: gradual over weeks to months |
|Monitoring: heart rate, perceived exertion (see text) |
The two most common techniques for monitoring exercise intensity are the target heart rate method and the patient’s subjective assessment of perceived exertion. For patients not taking medications that lower heart rate (eg, β-blockers), the maximum attainable heart rate in beats/min can be estimated from the formula: 220 – age. The patient’s resting heart rate is then subtracted from this figure to determine the heart rate reserve. A suitable target heart rate for low-intensity exercise can be calculated as the resting heart rate plus 30% to 50% of the heart rate reserve. For moderate-intensity exercise, the target range is the resting heart rate plus 50% to 70% of the heart rate reserve. For example, an 80-year-old individual has a predicted maximum heart rate of 220 – 80 = 140 beats/min. If the resting heart rate is 80, the heart rate reserve is 60 (ie, 140 – 80). For low-intensity exercise, 30% to 50% of the heart rate reserve would be 18 to 30 beats/min. Adding this to the resting heart rate of 80 would yield a range for the target heart rate of 98 to 110 beats/min.
For many older patients, calculating the target heart rate may be difficult. In addition, it may not be possible to accurately determine heart rate during exercise (unless a heart rate monitor is used). For these reasons, the patient’s subjective assessment of perceived exertion is often the most practical method for monitoring exercise intensity. In addition, perceived exertion correlates reasonably well with exercise heart rate. A simple perceived exertion scale comprises five levels: very light, light, moderate, somewhat heavy, and heavy. Older patients with heart failure should begin with very light exercise, progressing to the light range as tolerated. After several weeks, some patients may wish to increase their perceived exertion level into the moderate range, but more strenuous exercise is not recommended for patients with heart failure.
Treatment of Heart Failure with Reduced Ejection Fraction
In general, the treatment of HFREF in older patients does not differ substantially from that in younger patients.
Numerous prospective randomized clinical trials using multiple different angiotensin-converting enzyme (ACE) inhibitors in a variety of clinical settings have conclusively demonstrated that these agents significantly reduce mortality and hospitalization rates and improve exercise tolerance and quality of life in patients with impaired left ventricular systolic function, even in the absence of clinical heart failure. Although none of these studies included patients older than 80 years, available evidence indicates that ACE inhibitors are as effective in older patients as in younger ones. Based on these findings, ACE inhibitors are now considered first-line therapy for all patients, regardless of age, with left ventricular systolic dysfunction with or without overt heart failure.
ACE inhibitors approved for use in the United States for the treatment of heart failure include captopril, enalapril, lisinopril, ramipril, trandolapril, quinapril, and fosinopril. In older patients, therapy should be initiated with a low dose (eg, captopril 6.25–12.5 mg TID or enalapril 2.5–5 mg BID), and the dose should be gradually increased as tolerated. In hospitalized patients who are hemodynamically stable, the dose may be increased daily; in outpatients, the dose should be increased weekly or biweekly. Throughout the titration period, blood pressure, renal function, and serum potassium levels should be monitored.
For maintenance therapy, ACE inhibitor dosages should be commensurate with those used in the clinical trials. Recommended “target” doses for selected ACE inhibitors are as follows: captopril 50 mg TID, enalapril 10 to 20 mg BID, lisinopril 20 to 40 mg daily, ramipril 10 mg daily, trandolapril 4 mg daily, quinapril 40 mg BID, and fosinopril 40 mg daily. In patients unable to tolerate full therapeutic doses of ACE inhibitors, lower doses may be used; however, it must be recognized that clinical benefits may be attenuated. In addition, although captopril is an excellent agent for use during the titration phase, once the maintenance dose has been reached, it may be desirable to change to a once-daily ACE inhibitor at equivalent dosage for reasons of convenience, adherence, and cost.
The most common side effect from ACE inhibitors is a dry, hacking cough, which may be severe enough to require discontinuation of therapy in 5% to 10% of patients during long-term use. Less common but more serious side effects include hypotension, a decline in renal function, and hyperkalemia. These side effects tend to occur shortly after initiation of therapy and may be aggravated by intravascular volume contraction as a result of overdiuresis. Indications for downward titration or discontinuation of an ACE inhibitor include symptomatic hypotension, persistent increase in serum creatinine of 1 mg/dL or greater, or a rise in the serum potassium level above 5.5 mEq/L. Note that asymptomatic low blood pressure does not mandate dosage reduction.
Although ACE inhibitors are generally well tolerated and can be taken safely in combination with most other medications, it is important to recognize that NSAIDs, which are widely used by older adults (both by prescription and over the counter), are potent ACE inhibitor antagonists. In addition, NSAIDs promote sodium and water retention and may adversely affect renal function. Therefore, NSAIDs should be avoided whenever possible in patients with heart failure. The use of low-dose aspirin in combination with an ACE inhibitor appears to be safe and does not attenuate the beneficial effects of the ACE inhibitor. Therefore, patients with a clear indication for aspirin therapy, such as coronary artery disease, peripheral arterial disease, cerebrovascular disease, or diabetes mellitus, should receive aspirin according to current treatment guidelines for these conditions. The value of prophylactic aspirin in older patients with heart failure without known vascular disease or diabetes is unknown, and additional study of this issue is needed.
Angiotensin II receptor blockers
Angiotensin II receptor blockers (ARBs) bind directly to angiotensin II receptors on the cell membrane. Unlike ACE inhibitors, ARBs do not inhibit the breakdown of bradykinins, thus eliminating bradykinin-mediated side effects, including cough.
The use of ARBs for the treatment of heart failure, either alone or in combination with an ACE inhibitor, has been evaluated in several studies. In the second Evaluation of Losartan in the Elderly trial (ELITE-II), losartan 50 mg once daily was compared to captopril 50 mg TID in 3152 patients 60 years or older (mean age 71) with moderate heart failure and an ejection fraction of 40% or less. After a mean follow-up of 18 months, there was no statistically significant difference in mortality between the two treatments, although there were 12% more deaths in the losartan group (280 vs 250). As in the smaller ELITE-I trial, losartan was better tolerated than the ACE inhibitor captopril.
In the Valsartan Heart Failure Trial (Val-HEFT), 5010 patients with heart failure and an ejection fraction of less than 40% were randomized to valsartan or placebo in addition to standard care, which included an ACE inhibitor in 93% of patients and a β-blocker in 35%. During a 2-year follow-up period, mortality did not differ between patients treated with valsartan or placebo, but there was a significant 24% reduction in rehospitalizations for heart failure in the valsartan group, with similar effects in younger and older patients. However, patients receiving both an ACE inhibitor and a β-blocker as background therapy experienced an unexplained increase in mortality when valsartan was added.
In the Valsartan in Acute Myocardial Infarction trial, 14,703 patients with clinical heart failure and/or an ejection fraction less than 35% within 10 days of experiencing an acute myocardial infarction were randomly assigned to receive valsartan, captopril, or both drugs. More than 70% of patients were also receiving β-blockers. During a median follow-up of 24.7 months, there were no differences between groups with respect to all-cause mortality or the composite end point of fatal or nonfatal cardiovascular events. Median age was 65, and results were similar in older and younger patients. Hypotension and renal dysfunction were more common with valsartan, whereas cough, rash, and taste disturbances were more common with captopril. Limiting side effects were more common in patients receiving both drugs than in those receiving either drug alone.
The use of candesartan for the treatment of patients with heart failure and an ejection fraction of 40% or less has been evaluated in two large trials. In the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)—Alternative study, 2028 patients intolerant to ACE inhibitors were randomized to candesartan or placebo and followed for a median of 33.7 months. Compared to patients in the placebo group, patients randomized to candesartan experienced a significant 30% reduction in the composite end point of cardiovascular death or hospitalization for heart failure. All-cause mortality was reduced by 17%, which was of borderline statistical significance. Hypotension, worsening renal function, and hyperkalemia, but not cough or angioedema, were more common in the candesartan group. The mean age of patients in the CHARM-Alternative study was approximately 66.5, and nearly one-fourth of patients were 75 years or older; however, subgroup analysis by age has not been reported.
In the CHARM-Added trial, 2548 symptomatic patients with heart failure and an ejection fraction of 40% or less who were receiving an ACE inhibitor were randomized to candesartan or placebo and followed for a median of 41 months. Compared to the placebo group, there was a significant 15% reduction in the composite end point of cardiovascular death or hospitalization for heart failure in patients randomized to candesartan. All-cause mortality was 11% lower in the candesartan group, but the difference was not significant. The mean age of patients in the CHARM-Added trial was 64, 19% of patients were 75 years or older, and similar results were reported in older and younger patients.
Combining the results of these two trials with a third study that compared candesartan with placebo in patients with HFPEF, a total of 7599 patients were enrolled, of whom 1736 (22.8%) were 75 years or older. Among the latter group, candesartan was associated with a significant 13.7% reduction in all-cause mortality or first admission for heart failure.
Based on these studies, ARBs are indicated for treatment of symptomatic heart failure in patients intolerant to ACE inhibitors and in patients with heart failure or left ventricular systolic dysfunction following acute myocardial infarction. In the United States, valsartan and candesartan are approved for the treatment of heart failure. The recommended starting dose of valsartan is 20 to 40 mg BID, and the dose should be titrated to 160 mg BID as tolerated. The starting dose of candesartan is 4 to 8 mg once daily, with titration to 32 mg once daily as tolerated. The major side effects of ARBs include hypotension, renal insufficiency, and hyperkalemia.
In patients who are unable to tolerate an ACE inhibitor or ARB, the combination of hydralazine with oral or topical nitrates provides an acceptable alternative. In the first Veteran’s Administration Heart Failure trial (V-HeFT-I), the hydralazine/nitrate combination was associated with a 36% mortality reduction compared to prazosin and placebo in patients with HFREF. In a follow-up study (V-HeFT-II), patients with HFREF were randomized to receive hydralazine/nitrates or enalapril. Although hydralazine/nitrates and enalapril had similar effects on exercise tolerance and quality of life, mortality was lower in the enalapril group.
More recently, the African-American Heart Failure Trial (A-HeFT) randomized 1050 black patients with NYHA class III or IV heart failure to a fixed-dose combination of isosorbide dinitrate plus hydralazine or to placebo in addition to standard heart failure therapy. The study was stopped after an average follow-up of 10 months because of a significantly lower mortality rate in patients randomized to the intervention. Heart failure hospitalizations were also lower and quality of life was improved in patients randomized to hydralazine-nitrates relative to placebo. Based on the results of A-HeFT, the fixed-dose combination of isosorbide dinitrate and hydralazine has been approved for treatment of heart failure in black patients in the United States. Although there was no upper-age restriction for the A-HeFT study, the average age of patients enrolled in the trial was 57, so the efficacy of this therapy in older blacks remains unknown.
The dose of hydralazine used in the V-HeFT trials was 75 mg QID, and nitrates were administered as isosorbide dinitrate 40 mg QID. In A-HeFT, the total daily dose of hydralazine was 225 mg and of isosorbide dinitrate 120 mg. For older patients, treatment should begin with lower dosages (eg, hydralazine 12.5–25 mg TID–QID; isosorbide dinitrate 10 mg TID–QID), followed by gradual upward titration to achieve the doses used in the trials. The most common side effects associated with hydralazine/nitrates in the V-HeFT and A-HeFT studies included headache and dizziness. A small percentage of patients in V-HeFT developed arthralgias or other symptoms suggestive of hydralazine-induced lupus.
As recently as 20 years ago, β-adrenergic blocking agents were considered contraindicated in patients with heart failure owing to their negative inotropic and chronotropic effects, both of which serve to diminish cardiac output. However, it is now recognized that persistent activation of the sympathetic nervous system is detrimental in patients with heart failure because it exacerbates ischemia, aids in arrhythmogenesis, promotes β-receptor desensitization, and contributes to a progressive decline in ventricular function. Furthermore, several large prospective randomized clinical trials have now confirmed that long-term β-blockade improves left ventricular function and reduces both total mortality and sudden cardiac death in a broad spectrum of patients with HFREF.
In the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure trial (SENIORS), 2128 patients 70 years or older (mean age 76, 37% women) were randomized to nebivolol or placebo. During a mean follow-up of 21 months, the primary composite outcome of death or cardiovascular hospitalization was significantly lower in patients randomized to nebivolol, with similar results in younger and older patients, including those older than 85 years. Based on these studies, β-blockers are now recommended as a standard therapy, along with ACE inhibitors, in almost all patients with symptomatic HFREF in the absence of contraindications.
In the United States, carvedilol and metoprolol succinate have been approved for the treatment of heart failure. Starting dosages are carvedilol 3.125 mg BID and metoprolol succinate 25 mg once daily. The dose should be gradually increased at approximately 2-week intervals as tolerated to achieve maintenance dosages of carvedilol 25 to 50 mg BID or metoprolol 100 to 200 mg daily.
Contraindications to the use of β-blockers include severe decompensated heart failure, significant bronchospastic lung disease, marked bradycardia (resting heart rate < 50/min), systolic blood pressure less than 90 to 100 mm Hg, advanced heart block (> first degree), and known intolerance to β-blockade. In addition, as a result of the potential for significant adverse effects, it is important to monitor heart rate, blood pressure, clinical symptoms, and the cardiorespiratory examination during initiation and titration of therapy. Patients should be advised that they may experience a modest deterioration in heart failure symptoms during the first few weeks of β-blocker therapy, but that in most cases these symptoms resolve and the long-term tolerability of β-blockers is excellent. However, if severe adverse effects occur, dosage reduction or discontinuation of treatment may be necessary.
The mineralocorticoid antagonists spironolactone and eplerenone are relatively weak potassium-sparing diuretics that interfere with the effect of the neurohormone aldosterone. In the Randomized Aldactone Evaluation of Survival trial, spironolactone 12.5 to 50 mg once daily reduced mortality by 30% and heart failure hospitalizations by 35% in patients with NYHA class III or IV heart failure and a left ventricular ejection fraction less than or equal to 35%, in addition to therapy with an ACE inhibitor, digoxin, and loop diuretic. Moreover, the beneficial effects of spironolactone were at least as great in older as in younger patients. In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival study, eplerenone 25 to 50 mg once daily significantly reduced mortality by 15% over a mean follow-up period of 16 months in patients with clinical evidence for heart failure and an ejection fraction of 40% or less within 3 to 16 days following acute myocardial infarction. Sudden death from cardiac causes and cardiovascular hospitalizations were also reduced in the eplerenone group. Compared to placebo, hyperkalemia occurred more commonly but hypokalemia occurred less frequently with eplerenone. The average age of patients in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival study was 64, and although the relative benefit of eplerenone was somewhat less in older compared to younger patients, the difference was not statistically significant.
More recently, the EMPHASIS-HF trial randomized 2737 patients with NYHA class II heart failure and a left ventricular ejection fraction less than or equal to 35% to eplerenone at a dose of up to 50 mg or matching placebo. The mean age was 68.7 and 24% of patients were 75 years or older. The primary outcome was death from cardiovascular causes or hospitalization for heart failure. The study was stopped prematurely after a median follow-up of 21 months because eplerenone was associated with a marked reduction in the primary end point relative to placebo (18.3% vs 25.9%, hazard ratio 0.63, p < 0.001). Results were similar in patients over or under age 75. Eplerenone was also associated with significant reductions in all-cause mortality, all-cause hospitalizations, and heart failure hospitalizations (hazard ratios 0.76, 0.77, and 0.58, respectively).
Based on the results of these studies, a mineralocorticoid antagonist is recommended in patients with NYHA class II to IV heart failure symptoms and left ventricular ejection fraction less than or equal to 35%, and in patients with heart failure and an ejection fraction of 40% or less following myocardial infarction. These agents are contraindicated in patients with significant renal dysfunction (creatinine ≥ 2.5 mg/dL) or preexisting hyperkalemia. Older patients are at increased risk of adverse effects, and renal function as well as serum potassium levels should be monitored closely during initiation and titration of therapy. In addition, up to 10% of patients receiving long-term treatment with spironolactone may experience painful gynecomastia requiring discontinuation of the drug; this side effect occurs rarely with eplerenone.
Diuretics are the most effective agents for relieving pulmonary congestion and edema, and for this reason they remain a key component of heart failure management. However, neither thiazide nor loop diuretics have been shown to alter the natural history of heart failure, and their beneficial effects are primarily palliative.
In patients with mild chronic heart failure, a thiazide diuretic may be sufficient for relieving congestive symptoms and maintaining fluid homeostasis. However, most patients will require a more potent agent, and the “loop” diuretics, including furosemide, bumetanide, and torsemide, are the drugs most widely used. For optimal effectiveness, patients should be instructed to maintain a low sodium diet (< 2.3 g/day) and to avoid excessive fluid intake. Typical daily doses of “loop” diuretics range from 20 to 160 mg for furosemide, 0.5 to 5 mg for bumetanide, and 5 to 100 mg for torsemide. In patients hospitalized with an acute episode of heart failure, intravenous administration may be more effective than the oral route in promoting diuresis, in part due to bowel wall edema which may decrease the drug’s absorption. In patients who fail to respond adequately to a loop diuretic, the addition of metolazone 2.5 to 10 mg daily often leads to a brisk diuresis.
The most common and important side effects of diuretics are electrolyte disturbances, including hypokalemia, hyponatremia, hypomagnesemia, and increased bicarbonate levels indicative of metabolic alkalosis. Owing to age-related changes in renal function as well as a higher prevalence of comorbid illnesses such as diabetes, older patients are at increased risk of serious diuretic-induced electrolyte abnormalities. For this reason, electrolytes should be monitored closely when diuretic therapy is being adjusted. This is particularly true when using metolazone, which can cause life-threatening hyponatremia after relatively short-term use.
Digoxin inhibits the sodium-potassium exchange pump located within the myocyte membrane, producing a rise in intracellular sodium concentration. This facilitates sodium-calcium exchange, leading to an increase in intracellular calcium. Calcium binds with troponin C, which initiates the process of contraction by allowing myosin to bind with actin. By increasing calcium availability, digoxin induces a modest increase in the force of myocardial contraction (positive inotropic effect). This effect occurs whether or not heart failure is present, and it does not appear to be affected by age.
In 1997, the Digitalis Investigation Group (DIG) reported the results of a prospective randomized trial involving 6800 patients with HFREF. Patients were randomized to receive digoxin or placebo in addition to diuretics and an ACE inhibitor, and the average duration of follow-up was 37 months. Overall mortality did not differ between digoxin and placebo (34.8% vs 35.1%), but there were 28% fewer hospitalizations for heart failure in the digoxin group, and the combined end point of death or hospitalization for heart failure was significantly reduced. In addition, the beneficial effects of digoxin were similar in younger and older patients, including octogenarians. Subsequent analyses based on data from the DIG trial suggest that digoxin administered at low dosages to achieve serum concentrations in the range of 0.5 to 0.9 ng/mL may be associated with improved survival as well as a reduction in all-cause hospitalizations. These findings confirm that digoxin is beneficial in controlling heart failure symptoms and support the use of low-dose digoxin in patients who remain symptomatic despite appropriate dosages of an ACE inhibitor, β-blocker, mineralocorticoid antagonist, and diuretic.
Side effects from digoxin fall into three major categories: cardiac, neurologic, and gastrointestinal. In the DIG study, side effects that occurred more frequently in patients receiving digoxin included nausea and vomiting, diarrhea, visual disturbances, supraventricular and ventricular arrhythmias, and advanced atrioventricular heart block. Although not reported in the DIG trial, older patients may be at increased risk of digoxin toxicity, especially cardiac toxicity, in part owing to a decreased volume of drug distribution. Patients with chronic lung disease, amyloid heart disease, and other conditions may also be at increased risk of digoxin toxicity.
In most older patients with relatively normal renal function, a digoxin dose of 0.125 mg daily is usually sufficient to achieve a therapeutic effect. Patients with renal impairment or small body habitus may require a lower dose. Serum digoxin concentration should be measured 2 to 4 weeks after initiating therapy, and periodically thereafter, to ensure that the level is in the therapeutic range of 0.5 to 0.9 ng/mL. It is also appropriate to measure the digoxin level whenever digitalis intoxication is suspected. In addition, since diuretic-induced hypokalemia and hypomagnesemia potentiate digoxin’s cardiotoxic effects, including proarrhythmia, it is important to maintain normal serum concentrations of these electrolytes in all patients receiving digoxin.
First-generation calcium channel blockers, including nifedipine, diltiazem, and verapamil, are contraindicated in patients with systolic heart failure because each of these agents has been associated with adverse clinical outcomes. The third-generation calcium channel blockers amlodipine and felodipine have been studied in prospective randomized trials involving patients with HFREF. Although the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) suggested that amlodipine might be beneficial in patients with nonischemic HFREF, this was not confirmed in PRAISE-2. Similarly, the V-HeFT-3 trial failed to demonstrate a significant benefit in patients with HFREF treated with felodipine. Thus, there are no approved indications for the use of calcium channel blockers in patients with heart failure, and their use in this condition is not recommended. However, in patients with heart failure and active anginal symptoms not controlled with β-blockers and nitrates, the addition of a long-acting calcium channel blocker is reasonable. Similarly, diltiazem or verapamil may be used in heart failure patients with rapid atrial fibrillation who do not respond adequately to β-blockers and other interventions.
Patients with left ventricular systolic dysfunction are at increased risk for thromboembolic events, including stroke. However, in the absence of atrial fibrillation, rheumatic mitral valve disease, or a history of prior embolization, the value of antithrombotic treatment for the prevention of embolic events is unproven. In the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial, 1587 patients with NYHA class II or III HFREF were randomized to receive aspirin 162 mg/day, clopidogrel 75 mg/day, or warfarin to maintain an international normalized ratio (INR) of 2.5 to 3.0. After a mean follow-up of 23 months, there were no differences between the three groups in the primary composite end point of death, myocardial infarction, or stroke. Hospitalizations for heart failure occurred more frequently in the aspirin group than with either clopidogrel or warfarin, whereas bleeding complications were more common with warfarin. The mean age of patients in the WATCH trial was 63; subgroup analysis by age has not been reported.
In the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) study, 2305 patients with heart failure, a left ventricular ejection fraction less than or equal to 35%, and sinus rhythm were randomized to warfarin (target INR 2.0–3.5) or to aspirin 325 mg daily. The primary outcome was all-cause mortality, ischemic stroke, or intracerebral hemorrhage. The mean age was 61 and 80% of participants were men. After a mean follow-up of 3.5 years, there was no difference between groups in the primary outcome. Warfarin was associated with fewer ischemic strokes but more major bleeding events. Intracranial hemorrhage was infrequent and did not differ between groups. As with WATCH, subgroup analysis by age has not been reported.
Based on currently available data, anticoagulation with warfarin to achieve an INR of 2 to 3 is recommended in heart failure patients with chronic or paroxysmal atrial fibrillation or atrial flutter, rheumatic mitral valve disease with left atrial enlargement, prior stroke or unexplained arterial embolus, a mobile left ventricular thrombus (as demonstrated by echocardiography or other imaging modality), or a left atrial appendage thrombus identified by transesophageal echocardiography. Routine use of warfarin in other circumstances is not recommended. In patients with nonvalvular atrial fibrillation, one of the newer oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) may be used as an alternative to warfarin.
Aspirin is justified in patients with known coronary heart disease, particularly those with recent myocardial infarction, unstable angina, percutaneous coronary intervention, or bypass surgery. Aspirin is also recommended for older patients with peripheral arterial disease or diabetes. In addition, aspirin is appropriate in high-risk patients (as listed earlier) who are not suitable candidates for warfarin. As noted previously, additional study is needed to determine the value of aspirin in older patients with heart failure without established vascular disease or diabetes. The need for “triple therapy” with aspirin, clopidogrel, and warfarin in patients with indications for both dual anti-platelet therapy and systemic anticoagulation has recently been questioned, with at least one randomized trial showing that eliminating aspirin from the regimen reduces bleeding without increasing ischemic events.
Statins reduce mortality and nonfatal cardiovascular events in patients up to age 82 with coronary artery disease, peripheral arterial disease, or diabetes. However, the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA), in which 5011 patients 60 years or older (mean age 73, 24% female) with ischemic cardiomyopathy and an ejection fraction of 40% or less were randomized to rosuvastatin or placebo and followed for an average of 33 months, failed to show a significant benefit of rosuvastatin on either the primary outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, or on total mortality. Hospitalizations for cardiovascular causes occurred less frequently in patients randomized to rosuvastatin. Based on these findings, rosuvastatin is not recommended for older patients with HFREF. The role of other statins in this population requires further investigation.
Device therapy, including implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT), is playing an increasing role in the management of patients with HFREF. ICDs reduce mortality from sudden cardiac death in patients with NYHA class II to III HFREF and a left ventricular ejection fraction less than or equal to 35% (primary prevention), and in patients resuscitated from cardiac arrest attributable to ventricular tachyarrhythmias (secondary prevention). However, although current HF guidelines do not incorporate age into the recommendations for ICD therapy, very few patients greater than or equal to 75 years were enrolled in clinical trials evaluating these devices. In addition, a comprehensive meta-analysis suggested that the benefit of ICDs declines with age, most likely due to competing risks for mortality. Patients with life expectancies of less than 12 to 18 months are unlikely to benefit from an ICD, and patients greater than or equal to 80 years are twice as likely as younger patients to experience major complications related to device implantation. Thus, the benefit-to-risk relationship is modified by age, and consideration of ICD therapy must be individualized based on life expectancy, prevalent comorbidities, and patient goals of care using a process of shared decision making. In patients who choose to undergo placement of an ICD, management of the ICD at end of life, including circumstances under which the patient would want to have the device disabled in order to avoid painful shocks, should be clearly articulated prior to implantation. Similarly, if a generator change is needed due to battery depletion, the option of foregoing the procedure, along with the implications of this decision, should be discussed.
In contrast to ICDs, which reduce the risk of sudden death but do not improve quality of life, CRT improves symptoms, exercise tolerance, quality of life, and survival in carefully selected patients with HFREF, including octogenarians. CRT involves placement of a biventricular pacemaker with one lead in the right ventricle and a second lead inserted into the coronary sinus in a retrograde fashion to pace the left ventricle. As the name implies, the goal of CRT is to “resynchronize” myocardial contraction, thereby increasing stroke work, ejection fraction, and cardiac output. CRT is indicated in patients with NYHA class II to IV HFREF, left ventricular ejection fraction less than or equal to 35%, and QRS duration greater than or equal to 150 milliseconds by electrocardiogram. Patients with left bundle branch block, which is present in 20% to 30% of patients with HFREF, derive the greatest benefit from CRT, and there is evidence that the benefits tend to be greater in women than in men. CRT can be performed with or without concomitant ICD therapy (CRT-D and CRT-P, respectively), and patients greater than or equal to 80 years are proportionately more likely than younger patients to receive a CRT-P device. As with ICDs, selection of patients for CRT should involve shared decision making with appropriate consideration of the potential salutary effects on quality of life in older patients who are significantly limited by persistent heart failure symptoms despite optimal medical therapy.
Treatment of Heart Failure With Preserved Ejection Fraction
Despite the fact that approximately 50% of older patients with heart failure have preserved left ventricular systolic function (ie, HFPEF), no large-scale clinical trials have documented major beneficial effects for any pharmacologic agents (Table 79-11). As a result, therapy for HFPEF remains largely empiric.
TABLE 79-11PHARMACOTHERAPY TRIALS FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION ||Download (.pdf) TABLE 79-11 PHARMACOTHERAPY TRIALS FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION
|TRIALa ||PATIENTS ||TREATMENT ||LVEFb ||AGE ||OUTCOMES COMPARED TO PLACEBOc |
|PEP-CHF ||850 ||Perindopril ||65 (56–66) ||75 (72–79) ||Death/hospitalization by 1 y—HR 0.69 (0.47–1.01, p = 0.055). HF hospitalization by 1 y—HR 0.63 (0.41–0.97, p = 0.033) |
|CHARM-Preserved ||3023 ||Candesartan ||54 ± 9 ||67 ± 11 ||CV death/HF admission—HR 0.89 (0.77–1.03, p = 0.118). HF admission—HR 0.85 (0.72–1.01, p = 0.072) |
|I-PRESERVE ||4128 ||Irbesartan ||60 ± 9 ||72 ± 7 ||Death/hospitalization—HR 0.95 (0.86–1.05, p = 0.35) |
|SENIORS (EF > 35% subgroup) ||643 ||Nebivolol ||49 ± 10 ||76 ± 5 ||All cause death/CV hospitalization—HR 0.81 (0.63–1.04) |
|TOPCAT ||3445 ||Spironolactone ||56 (51–62) ||69 (61–76) || |
CV death/HF hospitalization/aborted SCD—HR 0.89 (0.77–1.04, p = 0.14).
HF hospitalization—HR 0.83 (0.69–0.99, p = 0.04)
|Aldo-DHF ||422 ||Spironolactone ||67 ± 8 ||67 ± 8 ||Reduced E/e’ avg 1.5 (p < 0.001) |
|RELAX ||216 ||Sildenafil ||60 (56–65) ||69 (62–77) ||No difference in Δ VO2 peak at 24 wk |
|ESS-DHF ||192 ||Sitaxsentan ||61 ± 12 ||65 ± 10 ||Median 43 s relative increase in Naughton treadmill time (p = 0.03) |
|DIG Ancillary ||988 ||Digoxin ||55 ± 8 ||67 ± 10 ||HF hospitalization—HR 0.79 (0.59–1.04, p = 0.09). Hospitalization for unstable angina—HR 1.37 (0.99–1.91, p = 0.06) |
|SWEDIC ||113 ||Carvedilol ||> 45 ||66 (48–84) ||No effect on primary composite end point of diastolic function; improved E/A with carvedilol |
|RAAM-PEF ||44 ||Eplerenone ||62 ||70 ||No effect on 6-min walk distance; collagen turnover and E/e’ improved with eplerenone |
|ELANDD ||116 ||Nebivolol ||62.6 ||66 ||No effect on 6-min walk distance, peak VO2, or quality of life |
At least 70% to 80% of older persons with HFPEF have hypertension, and coronary and valvular heart diseases are also highly prevalent in this population. Treatment for HFPEF begins with aggressive management of hypertension to target levels; that is, systolic blood pressure less than 140 mm Hg for most patients 60 to 79 years, less than 150 mm Hg for most patients greater than or equal to 80 years, and diastolic blood pressure less than 90 mm Hg for all older adults. Myocardial ischemia should be treated with antianginal medications and/or coronary revascularization as indicated. Resting and exercise heart rate should be adequately controlled in patients with atrial fibrillation. Patients with severe valvular heart disease should be considered for valve repair or replacement, and less severe regurgitant valvular lesions should be treated with unloading agents, such as ACE inhibitors. As with HFREF, nonpharmacologic aspects of therapy, including regular physical activity and exercise as described earlier, should be appropriately addressed.
Diuretics are an essential component of therapy for the relief of pulmonary and systemic venous congestion in most patients with HFPEF. However, such patients are often “volume sensitive.” As a result, overly zealous diuresis can lead to a reduction in left ventricular diastolic volume, with a resultant decline in stroke volume and cardiac output, often manifested by increased fatigue, relative hypotension, and worsening prerenal azotemia. Thus, diuretics must be prescribed judiciously in order to relieve congestion while avoiding overdiuresis.
β-Blockers have little or no direct effect on diastolic function, but they may improve symptoms in patients with HFPEF by slowing heart rate and lengthening the diastolic filling period. In patients with left ventricular hypertrophy, long-term β-blockade and effective blood pressure control may aid in the regression of left ventricular hypertrophy, which in turn may be associated with improved diastolic function. In the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure trial, more than 20% of patients had relatively preserved left ventricular systolic function (ejection fraction ≥ 40%), and the benefits of nebivolol were similar in this group compared to those with ejection fractions less than 40%. These data provide some support for the use of β-blockers in patients with HFPEF.
The goal of β-blocker therapy in HFPEF is to reduce the resting heart rate to less than 65 beats/min. The initial β-blocker dose should be low and titration should be gradual. In the event that symptoms and exercise tolerance do not improve, alternative therapy should be considered.
ACE inhibitors may improve symptoms in HFPEF both directly (by improving diastolic function) and indirectly (by promoting regression of left ventricular hypertrophy). The use of ACE inhibitors for the treatment of HFPEF in patients of advanced age is supported by findings from the Perindopril in Elderly People with Chronic Heart Failure study, in which 850 patients greater than or equal to 70 years (mean age 76, 55% women) with heart failure and relatively preserved left ventricular systolic function (estimated ejection fraction ≥ 40%) were randomized to perindopril 4 mg once daily or placebo and followed for an average of 2.1 years. Overall, there was no significant difference between groups with respect to the primary outcome of death or unplanned hospitalization for heart failure. However, heart failure hospitalizations were significantly reduced by 78% during the first 12 months of follow-up in patients randomized to perindopril. Relative to placebo, perindopril-treated patients also experienced significant improvements in NYHA class and exercise tolerance during the first year of therapy. Perindopril is not approved for the treatment of heart failure in the United States, and none of the other ACE inhibitors are approved for the treatment of HFPEF.
Angiotensin II receptor blockers
ARBs lower blood pressure and may have salutary effects on diastolic function similar to those observed with ACE inhibitors. In the CHARM-Preserved Trial, 3024 patients with NYHA class II to IV heart failure and an ejection fraction greater than 40% were randomized to candesartan or placebo and followed for a median of 36.6 months. The mean age was 67, 27% were 75 years or older, and 40% were women. Mortality did not differ between groups, but patients randomized to candesartan experienced a significant 16% reduction in the risk of hospitalization for heart failure and 29% fewer total heart failure admissions. Subgroup analysis by age was not reported. Hypotension, hyperkalemia, and worsening renal function occurred more frequently in the candesartan group.
Taken together, the findings of Perindopril in Elderly People with Chronic Heart Failure and CHARM-Preserve suggest that some ACE inhibitors and ARBs may reduce hospitalizations and improve symptoms in patients with HFPEF but have little or no effect on mortality. In contrast, the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial, which enrolled over 4000 patients greater than or equal to 60 years with HFPEF, showed that the ARB irbesartan was of no benefit in the treatment of this condition. Thus, the value of ACE inhibitors and ARBs in the management of patients with HFPEF remains uncertain.
The mineralocorticoid antagonists spironolactone and eplerenone reduce myocardial hypertrophy and fibrosis in laboratory animals and small studies indicate that they have a favorable effect on left ventricular diastolic function in humans. In addition, as discussed previously, both of these agents have been shown to improve mortality and other outcomes in patients with HFREF. In a recently published trial, 3445 patients with symptomatic heart failure and an ejection fraction greater than or equal to 45% were randomized to spironolactone or placebo and followed for a mean of 3.3 years. The average age was 68.7 and 52% were women. The primary outcome, a composite of cardiovascular death, aborted cardiac arrest, or hospitalization for heart failure, did not differ between patients randomized to spironolactone versus placebo. Similarly, total mortality and all-cause hospitalizations were not different between groups. However, hospitalizations for heart failure were reduced 17% among patients randomized to spironolactone (p = 0.04). In addition, in a post hoc analysis of patients enrolled in North or South American (vs Russia or Georgia), spironolactone was associated with a significant 18% reduction in the primary end point, as well as a 26% reduction in cardiovascular mortality and 18% reduction in heart failure rehospitalization. Thus, although additional research is needed, this study suggests that spironolactone may be beneficial for patients with HFPEF.
Calcium channel blockers decrease intracellular calcium and may have a modest beneficial effect on diastolic function. However, there have been no large clinical trials evaluating calcium channel blockers for the treatment of HFPEF, and calcium channel antagonists are not recommended for the treatment of this condition.
In addition to relieving ischemia, nitrates are effective venodilators and thus lower pulmonary capillary wedge pressure. For these reasons, nitrates may serve as a useful adjunct to diuretics in relieving symptoms of pulmonary congestion, particularly orthopnea. However, nitrates have the potential for decreasing venous return to the heart, thereby reducing left ventricular diastolic volume and stroke volume. In addition, tolerance to the hemodynamic effects of nitrates occurs in the majority of patients. As a result, the value of nitrates in the long-term management of HFPEF is uncertain, and further study of these agents, alone or in combination with other drugs, is needed.
Digoxin is usually considered contraindicated in patients with heart failure and normal systolic function. However, digoxin, as well as other inotropic agents, may exert a favorable effect on diastolic function by accelerating calcium reuptake by the sarcoplasmic reticulum at the onset of diastole. In the original DIG trial, 988 patients with heart failure and an ejection fraction of more than 45% were randomized to digoxin or placebo in an ancillary study. As in the main trial, digoxin had no effect on mortality. Hospitalizations for heart failure were reduced in patients with HFPEF receiving digoxin, but this effect was counterbalanced by increased hospitalizations for acute coronary syndromes. Thus, digoxin does not appear to be beneficial in patients with HFPEF and is not recommended except as an adjunct for controlling heart rates in patients with atrial fibrillation.
Preliminary studies of phosphodiesterase 5 inhibitors suggested that these agents may have favorable effects on exercise capacity in patients with HFPEF. In the RELAX trial, 216 patients (mean age 69, 48% women) with heart failure and a left ventricular ejection fraction greater than or equal to 50% were randomized to sildenafil or placebo and followed for 24 weeks. The primary end point was change in peak oxygen consumption; secondary outcomes included change in 6-minute walk distance and a composite clinical status score. The main findings were that sildenafil did not result in significant improvements in exercise capacity or clinical status compared to placebo.
Endothelin type A receptor antagonists have also shown promise for treating HFPEF in preliminary studies. In the Effectiveness of Sitaxsentan Sodium in Patients with Diastolic Heart Failure (ESS-DHF) trial, 192 patients (mean age 65, 63% women) with HFPEF and a left ventricular ejection fraction greater than or equal to 50% were randomly assigned in a 2:1 ratio to receive sitaxsentan or placebo for 24 weeks. The primary outcome was change in treadmill exercise time; secondary outcomes included changes in left ventricular mass, diastolic function, symptom severity, and quality of life. Sitaxsentan therapy was associated with a modest improvement in treadmill exercise time relative to placebo (37 seconds; p = 0.03), but there was no effect on any of the secondary outcomes.
Studies published to date indicate that ACE inhibitors, ARBs, mineralocorticoid antagonists and β-blockers may have favorable effects on some outcomes in patients with HFPEF, but none of these agents are of proven benefit and none are recommended as standard therapy in current practice guidelines. Management of HFPEF should include aggressive treatment of the underlying cardiac disease, and a diuretic should be administered at low-to-moderate doses to relieve congestion and edema. The addition of an ACE inhibitor, ARB, mineralocorticoid antagonist, or β-blocker to improve symptoms and reduce the risk of hospitalization seems reasonable. However, if the patient fails to respond to initial therapy, alternative treatment should be considered. Additional studies are needed to evaluate novel therapies for this condition.
Isolated Right Heart Failure
While the most common cause of chronic right-sided heart failure is one or more abnormalities of left heart function, a small proportion of patients present with isolated right heart failure. Etiologies of isolated right heart failure in older adults include pulmonary arterial hypertension due to chronic lung disease, chronic pulmonary thromboembolic disease, sleep-disordered breathing, or primary pulmonary vascular disease, and disorders of the tricuspid or (less commonly) pulmonic valve (eg, infectious endocarditis, carcinoid heart disease). Rarely, right heart failure in older patients may be attributed to congenital heart disease (eg, atrial septal defect), neoplasm (eg,. right atrial myxoma or rhabdomyosarcoma), or a primary cardiomyopathy involving the right ventricle (eg, arrhythmogenic right ventricular dysplasia). Acute right heart failure may be due to right ventricular infarction, massive or submassive pulmonary embolism, or severe lung disease (eg, pneumonia, acute respiratory distress syndrome). Symptoms of right heart failure include dyspnea, impaired exercise tolerance, dependent edema, and, in severe cases, abdominal discomfort and swelling. The physical examination is notable for signs of elevated right-sided pressures (jugular venous distension, abdominojugular reflux, right ventricular heave, hepatomegaly), lower extremity edema, and possibly ascites. Depending on the etiology, other symptoms and signs may be present. Treatment is directed primarily at the underlying cause(s) and secondarily at alleviating systemic congestion through the judicious use of diuretics. The value of other pharmacologic agents, such as β-blockers and renin-angiotensin system inhibitors, for the treatment of isolated right heart failure is unknown.
Refractory heart failure may be defined as heart failure not amenable to primary corrective measures (eg, valve replacement or revascularization) and not responsive to aggressive nonpharmacologic and pharmacologic therapy as described earlier. However, before designating heart failure as refractory, it is important to perform a careful search for potentially treatable causes, to carefully review the patient’s medication regimen to ensure that therapy is optimal, and to discuss the patient’s diet and medication habits in detail with the patient and family to ensure that an appropriate level of adherence is being maintained. The latter issue is of particular importance, since many cases of refractory heart failure can be traced to nonadherence to dietary restrictions, medications, or both.
In most cases, refractory heart failure simply represents the final common pathway of end-stage heart disease. Under these circumstances, the value of highly aggressive treatment is questionable, and decisions regarding the appropriateness of specific therapeutic interventions must be made on an individualized basis (see also Chapters 9 and 55).
Table 79-12 lists treatment options for refractory heart failure. In patients with systolic heart failure, intensifying the vasodilator regimen by using high doses of ACE inhibitors (eg, up to 400 mg/day of captopril or 80 mg/day of enalapril), either alone or in combination with hydralazine/nitrates or an angiotensin II receptor blocker, may result in significant symptomatic improvement. This can often be accomplished in the outpatient setting, but titration must be very gradual, with frequent follow-up contacts to avoid adverse events. In patients who fail to respond to these measures, intravenous vasodilator therapy with nitroglycerin, nitroprusside, or nesiritide (recombinant BNP) may be considered and may lead to significant clinical and hemodynamic improvements.
TABLE 79-12TREATMENT OPTIONS FOR REFRACTORY HEART FAILURE ||Download (.pdf) TABLE 79-12 TREATMENT OPTIONS FOR REFRACTORY HEART FAILURE
|Heart failure with reduced ejection fraction |
Intensive vasodilator therapy
Intensive diuretic therapy
Chronic or intermittent inotropic therapy
|Cardiac resynchronization therapy |
|Left ventricular assist device |
|Heart transplantation |
|Heart failure with preserved ejection fraction |
|Intensive diuretic therapy |
In patients with persistent pulmonary congestion or peripheral edema, high-dose oral diuretics (eg, furosemide 200 mg BID or bumetanide 10 mg daily), alone or in combination with metolazone, may be effective. Alternatively, a continuous intravenous infusion of furosemide 5 to 40 mg/h or bumetanide 0.5 to 1 mg/h may facilitate diuresis.
The use of intravenous inotropic agents in the management of chronic heart failure is somewhat controversial, since these agents have not been shown to improve outcomes and they may increase the risk of life-threatening arrhythmias. Nonetheless, extensive clinical experience indicates that intermittent or continuous infusions of dobutamine or milrinone may reduce symptoms and improve quality of life in selected patients with refractory heart failure.
As noted earlier, cardiac resynchronization therapy has been shown to improve symptoms, quality of life, and survival in patients with advanced heart failure and left bundle branch block or marked intraventricular conduction delay on the 12-lead electrocardiogram. This procedure should, therefore, be considered in appropriately selected patients with persistent class III or IV heart failure symptoms.
An emerging therapy for patients with end-stage refractory heart failure (primarily HFREF) is mechanical circulatory support through implantation of a left ventricular assist device (LVAD). LVADs improve symptoms, exercise tolerance, quality of life, and survival in selected patients with severe heart failure, including patients in their 70s and early 80s. Although LVADs were originally developed as a bridge to heart transplantation, with technological advances they are now commonly implanted as “destination therapy” in patients who are not transplant candidates. As a result, an increasing number of older adults are receiving LVADs, and this trend is likely to continue as the technology evolves. Older adults are at increased risk for gastrointestinal bleeding following LVAD implantation; other potential complications include infection, stroke, and pump thrombosis. Optimal patient selection is critical, and patients with advanced comorbidities or frailty may not be suitable candidates. To this end, a thorough discussion of goals of care, perhaps facilitated by a palliative care team consultation, is recommended as an integral component of the evaluation for LVAD therapy.
Heart transplantation is a highly effective therapy for patients with advanced heart failure, but its use is limited by the paucity of donor hearts. As a result, the number of heart transplants performed in the United States has remained stable at about 2000 to 2500 per year for more than a decade. In part due to limited availability, most transplant centers exclude patients over 70 to 75 years of age. Nonetheless, among patients greater than or equal to 65 years undergoing heart transplantation, outcomes are favorable and generally similar to those in younger patients.
For patients with refractory HFPEF, therapeutic options are limited (see Table 79-12). Intensive diuretic therapy may be attempted, but efficacy is often confounded by the development of progressive prerenal azotemia and/or worsening renal function. If satisfactory symptom control and an acceptable quality of life cannot be achieved, transition to a palliative care approach should be considered (see later).
The long-term prognosis in patients with established heart failure is poor, and the 5-year survival rate among older adults is less than 50%. In patients greater than or equal to 80 years hospitalized with heart failure, fewer than 25% survive more than 5 years. In general, the prognosis is worse in men than in women, in patients with HFREF rather than HFPEF, and in patients with an ischemic rather than nonischemic etiology. Patients with more severe symptoms or exercise intolerance, as defined by the NYHA functional class or as assessed by a 6-minute walk test, also have a less favorable outlook. Other markers of an adverse prognosis include elevated plasma norepinephrine, BNP, tumor necrosis factor alpha (TNF-α), and endothelin 1 levels; low systolic blood pressure; hyponatremia; renal insufficiency; anemia; peripheral arterial disease; cognitive dysfunction; reduced heart rate variability; and the presence of atrial fibrillation or high-grade ventricular arrhythmias. In patients with chronic heart failure, 40% to 50% die from progressive heart failure, 40% die from arrhythmias, and 10% to 20% die from other causes (eg, myocardial infarction or noncardiac conditions). Notably, the proportion dying from noncardiac causes is much higher among patients with HFPEF compared to those with HFREF.
ADVANCE CARE PLANNING AND END-OF-LIFE DECISIONS
Overall survival rates for patients with heart failure are lower than for most forms of cancer. In addition, once heart failure symptoms have reached an advanced stage (eg, NYHA class III or IV), quality of life is often severely compromised and therapeutic options are limited. Moreover, even patients with relatively mild or well-compensated heart failure are continually at risk of experiencing sudden cardiac arrest, and, if initial resuscitative efforts are successful, questions regarding life support and related issues may arise.
For these reasons, it is incumbent upon the physician to discuss the patient’s wishes regarding the intensity of treatment and end-of-life care at a time when the patient is still capable of understanding the issues and making informed choices. In addition, since the patient’s views may evolve over the course of illness, these issues should be readdressed at periodic intervals. The development of an advance directive and appointment of durable power of attorney should also be encouraged (see Chapters 9 and 12).
A related concern is the extent to which clinicians should offer aggressive or investigational therapeutic options that are unlikely to substantially alter the natural history of disease or significantly improve quality of life. This concern applies not only to many of the treatment modalities discussed in the Refractory Heart Failure section earlier, but also to such procedures as admission to an intensive care unit and endotracheal intubation. In many cases, these interventions not only fail to modify the clinical course but actually contribute to the patient’s pain and suffering in the terminal stages of disease. Moreover, the suggestion that a given intervention may help stabilize the patient and slow disease progression may create false hopes in the minds of the patient and family, and subsequent failure of the intervention may compound the emotional suffering that both the patient and the family are forced to endure. For these reasons, it is essential that the clinician realistically appraise the potential benefits and attendant risks, both physical and emotional, prior to offering aggressive therapeutic options that may provide little or no hope of improving the patient’s quality of life over a clinically important period of time. In this context, it is often appropriate to offer transition to a palliative care approach and to obtain consultation from a palliative care specialist.
Finally, as the patient approaches the terminal stages of disease, there should be discussions with the patient and family regarding where the patient would like to spend his or her final days. For many patients, the idea of dying at home surrounded by close family is comforting, and this desire should be honored whenever possible. Often home hospice affords optimal end-of-life care in the home environment by providing effective symptom control, as well as emotional, spiritual, and caregiver support. Home hospice is also associated with higher levels of patient and family satisfaction with care in most cases. For some patients, the hospital or an inpatient hospice may be the preferred environment for terminal care, but an attempt should be made to secure a private room with open visitation hours. The intensive care unit, with its austere, “high-tech” facade, may be the least desirable place to die, and this should be avoided whenever possible.
In view of the exceptionally poor prognosis associated with established heart failure in older adults, it is essential to develop and implement preventive strategies. Appropriate treatment of hypertension has been repeatedly shown to reduce the incidence of heart failure by 50% or more. In the Hypertension in the Very Elderly Trial, for example, treatment of hypertension was associated with a 64% reduction in incident heart failure among patients 80 years or older (additional details in Chapter 82). Treatment of hyperlipidemia has also been shown to reduce the incidence of heart failure, most likely through prevention of myocardial infarction and other ischemic events. Likewise, smoking cessation and regular exercise reduce the risk of myocardial infarction and stroke in older adults and likely have similar effects on the development of heart failure. Unfortunately, despite abundant evidence that heart failure prevention is feasible through risk factor modification, such strategies are underused, especially in persons older than 80 years.
Heart failure is an exceedingly common and important clinical problem in older adults, owing, in large part, to the complex interplay between age-related changes in the cardiovascular system, the high prevalence of cardiovascular and noncardiovascular diseases in the older population, and the widespread use of certain drugs and other therapies that may adversely affect cardiovascular physiology. As the world population continues to age, heart failure will exact a progressively greater toll on health care delivery systems. In addition, the impact of heart failure on quality of life and independence in the large number of older adults with this disorder is incalculable. Clearly, there is a compelling need to develop more effective strategies for the prevention and treatment of heart failure, with particular emphasis on the geriatric population.
et al. Clinical strategies and outcomes in advanced heart failure patients older than 70 years of age receiving HeartMate II left ventricular assist device. J Am Coll Cardiol
et al. Cardiac rehabilitation exercise and self-care for chronic heart failure. JACC Heart Fail
et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med
HM. Geriatric conditions and subsequent mortality in older patients with heart failure. J Am Coll Cardiol
J. The perindopril
in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J
et al. Transitional care interventions to prevent readmissions for persons with heart failure. A systematic review and meta-analysis. Ann Intern Med
et al. Randomized trial to determine the effect of nebivolol
on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J
LA. Frailty and the selection of patients for destination therapy left ventricular assist device. Circ Heart Fail
et al. Contemporary prevalence and correlates of incident heart failure with preserved ejection fraction. Am J Med
et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail
et al. Warfarin
in patients with heart failure and sinus rhythm. N Engl J Med
et al. Heart failure management in skilled nursing facilities: a scientific statement from the American Heart Association and the Heart Failure Society of America. Circ Heart Fail
JP, von Lueder
et al. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol
et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation
et al. Patterns of comorbidity in older adults with heart failure: the Cardiovascular Research Network PRESERVE study. J Am Geriatr Soc
P, Di Blase
L, Dello Russo
et al. Meta-analysis: age and effectiveness of prophylactic implantable cardioverter-defibrillators. Ann Intern Med
et al. End-of-life care in patients with heart failure. J Cardiac Fail. 2014;20:121–134.
et al. 2013 ACCF/AHA guideline for the management of heart failure. J Am Coll Cardiol
et al. Effects of candesartan
in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet