Med Clin N Am 90 (2006) 863885

Heart Failure in Older Adults

Michael W. Rich, MD
Department of Medicine, Washington University School of Medicine, 660 South Euclid
Avenue, Campus Box 8086, St. Louis, MO 63110, USA

Heart failure (HF) aects approximately 5 million Americans, and more

than 550,000 new cases are reported each year [1,2]. Additionally, despite recent advances in the diagnosis and treatment of HF, as well as reductions in
age-adjusted mortality from coronary heart disease and hypertensive cardiovascular disease [1,2], the incidence and prevalence of HF are increasing, primarily because of the aging of the population [3]. HF is predominantly
a disorder of the elderly, with prevalence rates increasing exponentially
from less than 1% in the population younger than age 50 years to about
10% in individuals older than age 80 years [4]. Consequently, more than
75% of hospitalizations for HF occur in persons 65 years of age or older
[5], the median age for all HF admissions is 75 years [6], and HF is the leading indication for hospitalization in older adults [5,6].
HF also is a major source of chronic disability and impaired quality of
life in the elderly [7], and it is a common factor that contributes to institutionalization in a chronic care facility. Furthermore, HF is the most costly
medical illness in the United States, with annual expenditures in excess of
$40 billion, which represents 5.4% of the total health care budget [8]. HF
also contributes to more than 250,000 deaths each year [1,2], and 88% of
these deaths are in persons older than 65 years [6]. Thus, HF imposes a striking clinical and economic burden on our society. Given the projected doubling in the number of Americans older than 65 years of age in the next 3
decades, it may be anticipated that the magnitude of this burden will continue to increase and potentially result in a public health crisis.

Pathophysiology
Aging is associated with signicant alterations in cardiovascular structure
and function that diminish homeostatic reserve and predispose older
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individuals to the development of HF (Box 1) [3,9,10]. In general, cardiac

output is determined by four factorsdheart rate, preload, afterload, and
contractile statedand age-related cardiovascular changes impact signicantly on each of these parameters. Thus, diminished b-adrenergic responsiveness and degenerative changes in the sinoatrial node impair the heart
rate response to stress; impaired myocardial relaxation and decreased compliance compromise ventricular lling and alter preload; increased vascular
stiness and a reduction in b2-mediated systemic vasodilation serve to increase afterload; and reduced capacity of mitochondria to generate ATP,
in conjunction with diminished responsiveness to b1-stimulation, lead to
a decrease in contractile reserve. In the absence of cardiovascular disease,
these changes have minimal eect on resting cardiac performance (ie, resting
left ventricular systolic function and cardiac output are reasonably well preserved, even at advanced age). A marked age-dependent reduction in cardiovascular reserve, however, attenuates the hearts ability to respond to
common stressors, such as ischemia, tachycardia (eg, due to atrial brillation), systemic illness (eg, infections), and physical exertion. As a result, clinical events that generally are tolerated well in younger individuals frequently
precipitate HF in older persons.
An important feature that distinguishes HF in the elderly from HF in
middle age is a striking increase in the proportion of cases that occurs in
the setting of normal or near normal left ventricular systolic function
[11,12]. Aging is associated with impaired left ventricular lling that is
due to changes in myocardial relaxation and compliance. These alterations
lead to a shift in the left ventricular pressurevolume relationship, such that
small increments in left ventricular volume result in greater increases in left
ventricular diastolic pressure [13]. This increase in diastolic pressure further

Box 1. Principal effects of aging on cardiovascular structure

and function
Increased vascular stiffness, impedance to ejection, and pulse
wave velocity
Impaired left ventricular early diastolic relaxation and mid-to-late
diastolic compliance
Diminished responsiveness to neurohumoral stimuli, especially
b1 and b2 adrenergic stimulation
Altered myocardial energy metabolism and reduced
mitochondrial ATP-production capacity
Reduced number of sinus node pacemaker cells and impaired
sinoatrial function
Endothelial dysfunction and vasomotor dysregulation
Net effect: Marked reduction in cardiovascular reserve

HEART FAILURE IN OLDER ADULTS

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compromises left ventricular lling, and leads to increases in left atrial, pulmonary venous, and pulmonary capillary pressures, and, thus, predisposes
to pulmonary congestion and HF. Diastolic HF, as it is often called, accounts for less than 10% of HF cases in persons who are younger than age
60, but more than 50% of cases after age 75 [11,12,14]. Diastolic HF also is
more common in women than in men, and accounts for nearly two thirds of
all HF cases among women who are older than age 80 [12].
Clinical features
Symptoms and signs
Exertional dyspnea, orthopnea, lower extremity swelling, and impaired
exercise tolerance are the cardinal symptoms of HF at younger and older
age; however, with increasing age, which often is accompanied by a progressively more sedentary lifestyle, exertional symptoms become less prominent
[15]. Conversely, atypical symptoms, such as confusion, somnolence, irritability, fatigue, anorexia, or diminished activity level, become increasingly
more common manifestations of HF, especially after age 80.
Physical signs of HF include elevated jugular venous pressure, hepatojugular reux, an S3 gallop, pulmonary rales, and dependent edema. Each of
these features occurs less commonly in older patients who have HF, in part
because of the increasing prevalence of diastolic HF, in which signs of rightsided HF are a late manifestation and a third heart sound typically is absent.
Conversely, behavioral changes and altered cognition, which may range
from subtle abnormalities to overt delirium, frequently accompany HF at
elderly age, particularly among institutionalized or hospitalized patients
[16].
Diagnosis
Accurate diagnosis of the HF syndrome at older age is confounded, in
part, by the increasing prevalence of atypical symptoms and signs [15]. Additionally, exertional symptoms may be attributable to noncardiac causes,
such as pulmonary disease, anemia, depression, physical deconditioning,
or aging itself. Likewise, peripheral edema may be due to venous insuciency, hepatic or renal disease, or medication side eects (eg, calcium channel blockers), and pulmonary crepitus may be due to atelectasis or chronic
lung disease. Despite these limitations, careful clinical assessment for the
presence of multiple symptoms and signs should lead to the correct diagnosis in most cases.
Chest radiography is indicated when HF is suspected, and it remains the
most useful diagnostic test for determining the presence of pulmonary congestion; however, chronic lung disease or altered chest geometry (eg, due to
kyphosis) may confound interpretation of the chest radiograph in elderly
individuals.

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Recently, plasma B-type natriuretic peptide (BNP) levels were shown to

be a valuable aid in distinguishing dyspnea that is due to HF from that
which is related to other causes, such as pulmonary disorders [17]. BNP
levels tend to be elevated in systolic and diastolic HF [18,19], and they correlate with response to therapy and prognosis [2022]. BNP levels also increase, however, with age in healthy individuals who do not have HF,
particularly women (Fig. 1), and, as a result, the specicity and predictive
accuracy of BNP levels declines with age [23]. Nonetheless, in cases of diagnostic uncertainty, a low or normal BNP level eectively excludes HF,
whereas a markedly elevated level provides strong evidence in support of
the diagnosis.
Proper management of HF is critically dependent on establishing the
pathophysiology of left ventricular dysfunction (ie, systolic versus diastolic),
determining the primary and any secondary causes (Box 2), and identifying
potentially treatable precipitating or contributory factors (Box 3). Dierentiating systolic from diastolic dysfunction requires an assessment of left ventricular contractility by echocardiography, radionuclide ventriculography,
magnetic resonance imaging (MRI), or contrast angiography. Among these,
echocardiography is the most widely used and clinically useful noninvasive
test for evaluating systolic and diastolic function, and echocardiography is
recommended for all patients who have newly diagnosed HF or unexplained
disease progression [24].
Other diagnostic studies that may be indicated in selected patients include
an assessment of thyroid function (especially in the presence of atrial brillation), an exercise or pharmacologic stress test to evaluate for the presence
and severity of ischemia, and cardiac catheterization if revascularization or
other corrective procedure (eg, valve repair or replacement) is being
contemplated.

70

BNP level, pg/mL

60
50
40
MEN
WOMEN

30
20
10
0
4554

5564

6574

75+

Age, years
Fig. 1. Mean BNP levels in healthy volunteers according to age and gender. (Adapted from
Redeld MM, Rodeheer RJ, Jacobsen SJ, et al. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 2002;40:977; with permission.)

HEART FAILURE IN OLDER ADULTS

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Box 2. Common causes of heart failure in older adults

Coronary artery disease
Acute myocardial infarction
Chronic ischemic cardiomyopathy
Hypertensive heart disease
Hypertensive hypertrophic cardiomyopathy
Valvular heart disease
Aortic stenosis or insufficiency
Mitral stenosis or insufficiency
Prosthetic valve malfunction
Infective endocarditis
Cardiomyopathy
Dilated (nonischemic)
Alcohol
Chemotherapeutic agents
Inflammatory myocarditis
Idiopathic
Hypertrophic
Obstructive
Nonobstructive
Restrictive (esp. amyloid)
Pericardial disease
Constrictive pericarditis
High output syndromes
Chronic anemia
Thiamine deficiency
Hyperthyroidism
Arteriovenous shunting
Age-related diastolic dysfunction

Etiology and precipitating factors

Systemic hypertension and coronary heart disease account for 70% to
80% of cases of HF at older age [25,26]. Hypertension is the most common
cause in older women, particularly those with preserved systolic function
[12,26]. In older men, HF is attributable more often to coronary heart disease [26]. Other common causes include valvular heart disease (especially
aortic stenosis and mitral regurgitation) and nonischemic cardiomyopathy

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Box 3. Common precipitants of heart failure in older adults

Myocardial ischemia or infarction
Uncontrolled hypertension
Dietary sodium excess
Medication noncompliance
Excess fluid intake
Self-induced
Iatrogenic
Arrhythmias
Supraventricular, especially atrial fibrillation
Ventricular
Bradycardia, especially sick sinus syndrome
Associated medical conditions
Fever
Infections, especially pneumonia or sepsis
Hyperthyroidism or hypothyroidism
Anemia
Renal insufficiency
Thiamine deficiency
Pulmonary embolism
Hypoxemia due to chronic lung disease
Drugs and medications
Alcohol
b-Adrenergic blockers (including ophthalmologicals)
Calcium channel blockers
Antiarrhythmic agents
Nonsteroidal anti-inflammatory drugs
Glucocorticoids
Mineralocorticoids
Estrogen preparations
Antihypertensive agents (eg, clonidine, minoxidil)

(see Box 2). HF in the elderly frequently is multifactorial, and, thus, it is essential to identify all potentially treatable causes.
In addition to determining etiology, it is important to identify factors that
precipitate or contribute to HF exacerbations (see Box 3). Noncompliance
with medications and diet is the most common cause of recurrent HF admissions [27,28], and patients should be questioned closely about their dietary
and medication habits. Other common factors that contribute to worsening
symptoms include ischemia, volume overload that is due to excess uid

HEART FAILURE IN OLDER ADULTS

869

intake (self-inicted or iatrogenic) [29], tachyarrhythmias (especially atrial

brillation or utter), intercurrent infections, anemia, thyroid disease, and
various medications or toxins (eg, alcohol).
Comorbidity
A hallmark of aging is the increasing prevalence of multiple comorbid
conditions, many of which impact directly or indirectly on the diagnosis,
clinical course, treatment, and prognosis of HF in the elderly (Table 1)
[30]. As shown in Fig. 2, Medicare beneciaries who are hospitalized with
HF typically have two to six coexisting noncardiac conditions, and many
patients have seven or more such conditions [31]. Additionally, the number
of noncardiac comorbidities is a strong predictor of rehospitalization within
1 year [31]. Although discussion of individual comorbidities is beyond the
scope of this article, it is important to recognize that HF in the elderly virtually never occurs in isolation; therefore, diagnosis and management must
be viewed in the context of the patients other comorbidities and competing
risks [30].

Management
The principal goals of HF therapy are to relieve symptoms, maintain or
enhance functional capacity and quality of life, preserve independence, and
extend survival. Although it often is stated that quality of life is more important than quantity of life in the elderly, this, in fact, is a matter of personal
preference. Furthermore, because the elderly HF population is characterized
by marked heterogeneity in terms of lifestyle, comorbidity, and personal
goals and perspectives, management of HF in the elderly rst and foremost
must be individualized to each patients circumstances and needs.
The basic approach to HF management involves identication and treatment of the underlying etiology and contributing factors, implementation of
an eective therapeutic regimen, and coordination of care through the use of
a multidisciplinary team.
Etiology and precipitating factors
Although HF in the elderly rarely is curable, proper treatment of the
underlying etiology often improves symptoms and delays disease progression. Thus, hypertension should be treated aggressively [32], and coronary
heart disease should be managed appropriately with medications or percutaneous or surgical revascularization. Patients who have severe aortic or mitral valve disease should be considered for surgery in the absence of specic
contraindications [3336]. Atrial brillation, a common precipitant of HF in
older adults, should be treated with rate-controlling agents, warfarin, and,
in some cases, restoration of normal sinus rhythm [37,38]. Anemia, thyroid

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Table 1
Common comorbidities in older patients
Condition

Implications

Renal dysfunction
Anemia
Chronic lung disease
Cognitive dysfunction
Arthritis

Exacerbated by diuretics, ACE inhibitors

Worsens symptoms and prognosis
Contributes to uncertainty about diagnosis/volume status
Interferes with dietary, medication, activity compliance
NSAIDs promote salt and water retention, antagonize HF
and blood pressure medications
Worsens prognosis, interferes with compliance
Exacerbated by vasodilators, diuretics, b-blockers
Aggravated by diuretics, ACE inhibitors (cough)
Interferes with compliance
Exacerbated by dietary restrictions
Compliance issues, drug interactions
Exacerbated by hospitalization; increased fall risk

Depression, social isolation

Postural hypotension, falls
Urinary incontinence
Sensory deprivation
Nutritional disorders
Polypharmacy
Frailty

Abbreviations: ACE, angiotensin-converting enzyme; NSAIDs, nonsteroidal anti-inammatory drugs.

disease, and other systemic illnesses should be identied and treated accordingly. Therapy for diabetes and dyslipidemia should be optimized, smoking
should be discouraged strongly, and a suitable level of regular physical activity should be prescribed. Alcohol intake should be limited to no more
than two drinks per day in men and one drink per day in women, and alcohol use should be proscribed strictly in patients who have suspected alcoholic cardiomyopathy.
The importance of compliance with medications and dietary restrictions,
including avoidance of excessive uid intake, cannot be overemphasized.
Nonsteroidal anti-inammatory drugs are used widely by older individuals
to treat arthritis and relieve chronic pain, but these agents promote sodium

18%
16%
14%
12%
10%
8%
6%
4%
2%
0%

N = 122,630
Mean age 79.6 years
Female = 60%

9 10+

Number of Non-Cardiac Comorbidities

Fig. 2. Prevalence of noncardiac comorbidities in Medicare beneciaries who have heart failure. (Adapted from Braunstein JB, Anderson GF, Gerstenblith G, et al. Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneciaries with
chronic heart failure. J Am Coll Cardiol 2003;42:1228; with permission.)

HEART FAILURE IN OLDER ADULTS

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and water retention, interfere with the actions of angiotensin-converting enzyme (ACE) inhibitors and other anti-hypertensive agents, and may worsen
renal function; their use should be avoided whenever possible [39]. Similarly,
the use of other medications that may aggravate HF should be monitored
closely.
Pharmacotherapy
The design of an eective therapeutic regimen is based, in part, on
whether the patient has predominantly systolic or predominantly diastolic
left ventricular dysfunction. Although these two abnormalities frequently
coexist (virtually all individuals over age 70 have some degree of diastolic
dysfunction), for purposes of this discussion patients with an ejection fraction of less than 45% (ie, moderate or severe left ventricular systolic dysfunction) will be considered as having systolic HF, whereas patients with
an ejection fraction of at least 45% will be considered as having diastolic
HF.
Systolic heart failure
In the past 25 years there has been considerable progress in the treatment
of systolic HF. Although most studies have excluded individuals who were
older than 75 to 80 years of age, or have enrolled too few elderly subjects to
permit denitive conclusions, available data indicate that older patients respond to standard therapies as well or better than do younger patients.
Therefore, current recommendations for drug treatment of systolic HF
are similar in younger and older patients [24].
Angiotensin-converting enzyme inhibitors. ACE inhibitors are the cornerstone of therapy for left ventricular systolic dysfunction, whether or not clinically overt HF is present [24], and there is strong evidence that ACE
inhibitors are as eective in older patients as in younger patients, both in
terms of reducing mortality and improving quality of life [40,41]. Conversely, older patients are more likely to have potential contraindications
to ACE inhibitors (eg, renal dysfunction, renal artery stenosis, orthostatic
hypotension), and they also may be at increased risk for ACE inhibitor
related side eects, such as worsening renal function, electrolyte disturbances, and hypotension. Nonetheless, a trial of ACE inhibitors is indicated
in virtually all older patients who have documented left ventricular systolic
dysfunction. Blood pressure, renal function, and serum potassium levels
should be monitored during the period of drug initiation and dose titration,
and periodically during maintenance therapy.
Angiotensin receptor blockers. Angiotensin receptor blockers (ARBs) have
a more favorable side eect prole than do ACE inhibitors, but there is insucient evidence to conclude that the eects of ARBs on major clinical

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outcomes (eg, death, hospitalizations) are equivalent to those of ACE inhibitors [4244]. Recent studies, however, indicate that ARBs reduce mortality
and hospitalizations in patients who have systolic HF who are intolerant to
ACE inhibitors because of cough or other side eects [45,46]. Additionally,
combining an ARB with an ACE inhibitor improves outcomes compared
with an ACE inhibitor alone [47,48], although in one study triple therapy
with an ACE inhibitor, a b-blocker, and an ARB was associated with increased mortality compared with treatment with only two of these classes
of agents [47]. Based on available evidence, and pending the results of ongoing clinical trials, ACE inhibitors still should be considered rst-line therapy
for HF, but ARBs oer an excellent alternative for patients who are intolerant to ACE inhibitors, and as conjunctive therapy in patients who have
persistent symptoms despite conventional treatment.
Hydralazine and isosorbide dinitrate. The combination of hydralazine, 75
mg four times a day, and isosorbide dinitrate, 40 mg four times a day,
was associated with decreased mortality in a small trial of patients who
had HF who were younger than 75 years of age [49]. Although ACE inhibitors are superior to hydralazine-nitrates in improving survival [50], the
combination provides an additional alternative for patients who are intolerant to ACE inhibitors. Recently, this combination was shown to be of particular benet in men of African descent [51]. Side eects are common with
hydralazine and high-dose nitrates, and the dosing schedule (four times
daily) is a particular disadvantage for older patients.
b-Blockers. b-Blockers, once viewed widely as contraindicated in patients
who have HF, have been shown to improve left ventricular function and decrease mortality in a broad population of patients who have HF, including
those who have New York Heart Association (NYHA) class IV symptoms
and patients who are up to 80 years of age [5255]. As a result, b-blockers
are now considered standard therapy for clinically stable patients without
major contraindications [24]. The use of b-blockers in older patients may
be limited by a higher prevalence of bradyarrhythmias and severe chronic
lung disease, and older patients also may be more susceptible to the development of fatigue and impaired exercise tolerance during long-term
b-blocker administration.
Carvedilol, metoprolol, and bisoprolol have been shown to improve outcomes in patients who have systolic HF, and a recent study found that carvedilol, 25 mg twice daily, was more eective than was metoprolol, 50 mg
twice daily, in reducing mortality [56]. Contraindications to b-blockade include marked sinus bradycardia (resting heart rate !4550 beats per minute), PR interval of at least 0.24 seconds, heart block greater than rst
degree, systolic blood pressure less than 90 to 100 mm Hg, active bronchospastic lung disease, and severe decompensated HF.

HEART FAILURE IN OLDER ADULTS

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Digoxin. Digoxin improves symptoms and reduces hospitalizations in patients who have symptomatic systolic HF that is treated with ACE inhibitors
and diuretics, but has no eect on total or cardiovascular mortality [57]. The
eects of digoxin are similar in younger and older patients, including octogenarians [58]. Although digoxin is no longer a rst-line agent, it remains
a useful drug for the treatment of systolic HF in patients of all ages who
have limiting symptoms despite standard therapy.
The volume of distribution and renal clearance of digoxin decline with
age. In addition, recent data indicate that the optimal therapeutic concentration for digoxin is 0.5 to 0.8 ng/ml [59] (ie, substantially lower than the traditional therapeutic range of 0.8 to 2.0 ng/mL). Moreover, higher
concentrations of digoxin are associated with increased toxicity but no
greater ecacy [59,60]. For most older patients with preserved renal function (estimated creatinine clearance R60 cm3/min), digoxin, 0.125 mg/d,
provides a therapeutic eect. Lower dosages should be used in patients
who have renal insuciency. Although routine monitoring of serum digoxin
levels is no longer recommended, it seems reasonable to measure the serum
digoxin concentration 2 to 4 weeks after initiating therapy to ensure that the
level does not exceed 0.8 ng/mL. Additionally, a digoxin level should be obtained whenever digoxin toxicity is suspected.
Digoxin side eects include arrhythmias, heart block, gastrointestinal disturbances, and altered neurologic function (eg, visual disturbances). Although older patients often are believed to be at increased risk for
digitalis toxicity, this was not conrmed in a recent analysis from the Digitalis Investigation Group trial [58].
Diuretics. Diuretics are an essential component of therapy for most patients
who have HF, and are the most eective agents for relieving congestion
and maintaining euvolemia. Some patients who have mild HF can be controlled with a thiazide diuretic, but most require a loop diuretic, such as
furosemide or bumetanide. In patients who have more severe HF or significant renal dysfunction (serum creatinine R2.0 mg/dL), the addition of
metolazone, 2.5 to 10 mg daily, may be necessary to achieve eective diuresis. In general, diuretic dosages should be titrated to eliminate signs
of pulmonary and systemic venous congestion. Common side eects include worsening renal function (often due to overdiuresis) and electrolyte
disorders.
Aldosterone antagonists. Spironolactone is a weak, potassium-sparing diuretic that acts by antagonizing aldosterone. Recently, the addition of spironolactone, 12.5 to 50 mg daily, to standard HF therapy was shown to
reduce mortality in patients who had NYHA class IIIIV systolic HF,
with similar benets in older and younger patients [61,62]. Eplerenone, a selective aldosterone antagonist, also was shown to reduce mortality and sudden cardiac death in patients who had left ventricular dysfunction following

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acute myocardial infarction [63]. Spironolactone and eplerenone are contraindicated in patients who have severe renal insuciency or hyperkalemia.
Additionally, up to 10% of patients who are treated with spironolactone develop painful gynecomastia; this side eect occurs less frequently with eplerenone. Older patients who receive spironolactone in combination with an
ACE inhibitor are at increased risk for hyperkalemia, particularly in the
presence of preexisting renal insuciency or diabetes, and at dosages in excess of 25 mg/d [64].
Approach to treatment. Fig. 3 provides a suggested approach to the pharmacologic treatment of systolic HF. All patients who have left ventricular systolic dysfunction, whether asymptomatic or symptomatic, should receive an
ACE inhibitor (or an ARB or alternative vasodilator if ACE inhibitors are
contraindicated or not tolerated). Patients with stable symptoms and no
contraindications also should receive a b-blocker, and diuretics should be
administered in sucient doses to maintain euvolemia. Digoxin or an
ARB should be considered in patients who remain symptomatic despite
the above regimen, and spironolactone should be used in patients who
have persistent NYHA class IIIIV symptoms.
Diastolic heart failure
Despite the fact that more than 50% of elderly patients who have HF
have preserved left ventricular systolic function [11,12], until recently none
of the major HF trials has targeted this disorder specically. As a result,
treatment of diastolic HF remains largely empiric. As with systolic HF,
the underlying cardiac disorder and associated contributing conditions
should be treated appropriately. In particular, hypertension and coronary
heart disease should be managed aggressively. Diuretics should be used judiciously to relieve congestion while avoiding overdiuresis and prerenal azotemia. Topical or oral nitrates may be benecial in reducing pulmonary

Fig. 3. Approach to treatment of systolic heart failure. Shaded areas represent treatments demonstrated to be benecial in prospective randomized clinical trials.

HEART FAILURE IN OLDER ADULTS

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congestion and orthopnea. Based on the results of the Heart Outcomes Prevention Evaluation [65], an ACE inhibitor, such as ramipril, 2.5 to 10 mg
daily, is appropriate for most older adults who have vascular disease, but
the value of ACE inhibitors in the treatment of diastolic HF per se has
not been established. Similarly, the role of ARBs in the management of diastolic HF is evolving. In the recently reported CHARM-preserved trial
(Candesartan in Heart failure: Assessment of Reduction in Mortality and
morbidity), the ARB candesartan reduced HF admissions by 16% but
had no eect on mortality in patients who had HF and a left ventricular
ejection fraction of greater than 40% [66]. The mean age of patients in
the CHARM-preserved trial was 67 years, and 807 patients (27% of the total population) were at least 75 years of age.
b-blockers are indicated in patients who have coronary heart disease (especially previous myocardial infarction), and the recently reported Study of
the Eects of Nebivolol Intervention on Outcomes and Rehospitalization in
Seniors with Heart Failure trial suggested that the b-blocker nebivolol may
be benecial in older patients who have systolic or diastolic HF [67] . Calcium channel blockers are eective antihypertensive agents in the elderly,
and these drugs may provide symptomatic palliation in selected patients
who have diastolic HF [68]. Digoxin, in addition to its inotropic eect,
also facilitates diastolic relaxation, and may improve symptoms and reduce
HF hospitalizations in patients with preserved systolic function [57,58]. In
summary, the physician who is treating diastolic HF is presented with an array of therapeutic options, none of proven benet, and therapy should be
individualized and guided by prevalent comorbidities and the observed response to specic therapeutic interventions.
Device therapy
Although most patients who have HF can be managed eectively with
behavioral interventions and medications, implantable devices are playing
an increasingly important role in the management of selected subgroups
of the HF population.
Cardiac pacemakers
Aging is associated with a progressive decline in the number of functioning sinus nodal pacemaker cells, which often leads to the sick sinus syndrome, characterized by inappropriate sinus bradycardia, sinus pauses,
and chronotropic incompetence (failure to increase heart rate adequately
in response to increased demands) [69]. Because cardiac output is directly
proportional to heart rate (cardiac output heart rate
stroke volume),
age-related bradyarrhythmias may contribute to HF symptoms and impaired exercise tolerance. Because there is no eective medical therapy for
sick sinus syndrome, implantation of a pacemaker is appropriate in symptomatic patients. The use of b-blockers also may precipitate symptomatic

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bradyarrhythmias in elderly patients who have HF. Because b-blockers

improve ventricular function and reduce mortality and hospitalizations in
patients who have systolic HF [5255], placement of a pacemaker often is
preferable to discontinuation of b-blocker therapy.
Cardiac resynchronization therapy
Recently, a new role has evolved for pacemakers in treating selected patients who have advanced HF. Approximately 30% of patients who have
HF have left bundle branch block or an intraventricular conduction abnormality that results in signicant prolongation of the QRS interval (R120
milliseconds). In these patients, left ventricular contraction often is dysynchronous and out of phase with right ventricular contraction. Biventricular
pacing, with one lead pacing the right ventricle and a second lead pacing the
left ventricle through retrograde insertion into the coronary sinus, can resynchronize ventricular contraction, and, thus, improve ejection fraction
and cardiac output [70,71]. The addition of atrial pacing may provide further benet by optimizing the timing of atrial and ventricular contraction.
The benets of cardiac resynchronization therapy in improving ejection
fraction, reducing left ventricular cavity size, enhancing exercise tolerance
and quality of life, and decreasing mortality have been well documented
in several randomized trials that involved patients who had advanced HF
symptoms (NYHA class IIIIV), reduced ejection fractions, and prolonged
QRS durations [7276]. Although the use of biventricular pacemakers in
older patients must be individualized, cardiac resynchronization therapy is
a reasonable option for carefully selected older patients who have advanced
HF symptoms despite conventional therapies.
Implantable cardioverter debrillators
Approximately 40% of all deaths in patients who have HF are attributable to ventricular tachycardia (VT) and ventricular brillation (VF). Implantable cardioverter debrillators (ICDs) have the capacity to recognize
VT and VF, and to restore normal rhythm by pacing techniques (in the
case of VT) or by delivering an intracardiac electrical shock (refractory
VT or VF). Moreover, these devices improve survival signicantly in certain
high-risk subgroups of the HF population, including those who have symptomatic sustained VT, ischemic or nonischemic cardiomyopathy with ejection fraction less than 35% or restricted cardiac arrest [7780]. The
survival benet of ICDs is greatest in patients who are older than 70 years
of age with ejection fractions of less than 35% and NYHA class III or IV
HF symptoms [81].
In the United States, more than half of ICDs are implanted in patients 65
years of age or older; however, despite the established benets of ICDs in
appropriately selected patients, the clinical role of ICDs in elderly patients
who have HF remains a subject of debate [8284]. These devices are expensive, with a total cost of approximately $40,000 to $50,000 per device,

HEART FAILURE IN OLDER ADULTS

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although a $10,000 generic version recently has gained approval. Additionally, the societal cost burden is likely to increase substantially as the indications for these devices continue to expand. There also are ethical
questions, such as how and when to turn o the device in the terminal stages
of HF, or in cases where another life-threatening illness develops (eg, stroke
or cancer). In part for these reasons, many older patients may elect to forego
ICD implantation, even though survival may be enhanced. Although additional study is needed, it is clear that the use of ICDs must be individualized,
and that older age should not constitute the sole grounds for withholding
ICD therapy.
Multidisciplinary care
The presence of multiple comorbid conditions, polypharmacy, dietary
concerns, and a host of psychosocial and nancial issues frequently complicate the management of HF in older patients. Moreover, these factors often
contribute to poor outcomes in older adults, including recurrent hospitalizations [28,85]. To address these issues, and to provide comprehensive, yet
individualized, care for older patients who have HF, a coordinated multidisciplinary approach is recommended. Several recent studies have documented the ecacy of multidisciplinary HF disease management
programs in reducing hospitalizations and improving quality of life in older
patients, and these interventions also were reported to decrease overall medical costs [8688].
Elements of an eective HF disease management program include patient
and caregiver education, enhancement of self-management skills, optimization of pharmacotherapy (including consideration of polypharmacy issues),
and close follow-up. The structure of an HF disease management team is
similar to that of a multidisciplinary geriatric assessment team, and typically
includes a nurse coordinator or case manager, dietitian, social worker, clinical pharmacist, home health representative, primary care physician, and
cardiology consultant. Specic goals of disease management are to improve
patient compliance with medications, diet, and exercise recommendations
by enhancing education and self-management skills; to provide close
follow-up and improved health care access through telephone contacts,
home health visits, and nurse or physician oce visits; and to optimize
the medication regimen by promoting physician adherence to recommended
HF treatment guidelines [24], simplifying and consolidating the regimen
when feasible, eliminating unnecessary medications, and minimizing the
risks for drugdrug and drugdisease interactions.
Exercise
HF and normal aging are associated with reduced exercise capacity, in
part due to sarcopenia (loss of muscle mass) and alterations in skeletal

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muscle blood ow and metabolism. Regular physical activity improves exercise performance in healthy older adults, as well as in those who have HF,
and regular exercise is now recommended for most older patients who have
HF [24,8993]. Although supervised exercise programs have been associated
with the greatest improvements in exercise performance, such programs are
not feasible for most older patients because of the lack of availability, travel
concerns, and cost constraints. Therefore, most older patients who have HF
should be encouraged to engage in a self-monitored home exercise program
that includes stretching exercises, strengthening exercises, and aerobic activities. Stretching increases or maintains muscle exibility and decreases the
risk for injury. Strength training increases muscle mass and reduces the
risk for falls and frailty [94]. Aerobic exercise leads to improved physical
performance and quality of life, and may increase the likelihood that older
adults will remain independent in activities of daily living [9093].
Contraindications to exercise in elderly patients who have HF include decompensated HF, unstable coronary disease or arrhythmias, neurologic or
muscular disorders that preclude participation in an exercise program, or
any other condition that would render exercise unsafe. Additionally, patients should be instructed to stop exercising and contact their physician if
they develop chest pain, undue shortness of breath, dizziness or syncope,
or any other symptom that may indicate clinical instability.
End of life
The overall 5-year survival rate for older patients who have established
HF is less than 50% (ie, the prognosis is worse than for most forms of cancer) [9597]. Clinical features that portend a less favorable outcome include
older age, more severe symptoms and functional impairment, lower left ventricular ejection fraction, underlying coronary heart disease, and impaired
renal function [98]. Older patients who have advanced HF, as evidenced
by NYHA class IIIIV symptoms, have a 1-year mortality of 25% to
50%; for these patients, HF can be considered a terminal illness. Additionally, all patients who have HF are at risk for sudden arrhythmic death,
which may occur during periods of apparent clinical stability. For these reasons, it is appropriate to address end-of-life issues early in the course of HF
care, and to reconsider these issues periodically as the disease progresses or
when changes in clinical status occur.
Patients should be encouraged to develop an advance directive and to appoint a durable power of attorney. The advance directive should be as explicit as possible in dening circumstances under which the patient does
not want to be hospitalized, intubated, subjected to other life-sustaining interventions (eg, a feeding tube), or resuscitated. Because patients often
change their minds about these issues as clinical circumstances evolve [99],
it is important to maintain open communication throughout the disease
process.

HEART FAILURE IN OLDER ADULTS

879

End-stage HF is accompanied frequently by considerable discomfort and

anxiety, and data from the Study to Understand Prognoses and Preferances
for Outcomes and Risks of Treatments indicate that most patients and
families express concerns about the quality of end-of-life care [100,101].
A cardinal principal of end-of-life care is to provide adequate relief of pain
and suering through the judicious use of conventional therapies in conjunction with narcotics (eg, morphine), sedatives (eg, benzodiazepines), and other
comfort measures. Equally important is the provision of emotional support
for the patient and family, assisted by nurses, members of the clergy, social
service representatives, and other qualied health care professionals.

Future directions
In light of the high prevalence and poor prognosis that are associated
with HF in the elderly, it is evident that more eective means for the prevention and treatment of this disorder are needed. The most eective preventive strategies involve aggressive treatment of established risk factors
for the development of HF (ie, hypertension and coronary heart disease)
[102108]. Similarly, it is likely that smoking cessation, weight control in
obese patients, and aggressive control of diabetes will lead to a reduction
in HF.
In addition to existing therapies, several new pharmacologic and technologic treatments for HF are under active investigation (Box 4). Although it

Box 4. New approaches to the treatment of chronic heart failure

Pharmacologic agents
Neutral endopeptidase inhibitors
Endothelin receptor antagonists
Cytokine inhibitors
Calcium sensitizers
Therapeutic angiogenesis and antiangiogenesis
Inhibition of apoptosis
Gene therapy and pharmacogenomics
Hereditary disorders (eg, cardiomyopathies, dyslipidemias)
Modulation of signaling pathways
Targeted therapy based on specific genetic profile
Biventricular pacing
Implantable assist devices
Cell transplantation and growth factor therapy
Xenotransplantation
Prevention of cardiovascular aging

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RICH

is dicult to project which of these new therapies will come into widespread
clinical use, it is likely that the management of HF will undergo substantial
evolution over the course of the next several decades.

References
[1] Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statisticsd2006 update.
A report from the American Heart Association Statistics Committee and Stroke Statistics
Subcommittee. Circulation 2006;113:85151.
[2] National Institutes of Health. National Heart, Lung, and Blood Institute Fact Book, 2005.
Available at: http://www.nhlbi.nih.gov/about/05factbk.pdf. Accessed March 28, 2006.
[3] Rich MW. Epidemiology, pathophysiology, and etiology of congestive heart failure in older
adults. J Am Geriatr Soc 1997;45:96874.
[4] Kannel WB, Belanger AJ. Epidemiology of heart failure. Am Heart J 1991;121:9517.
[5] DeFrances CJ, Hall MJ, Podgornik MN. 2003 National Hospital Discharge Survey. Advance data from vital and health statistics; no. 359. Hyattsville (MD): National Center
for Health Statistics; 2005.
[6] Popovic JR. 1999 National Hospital Discharge Survey: annual summary with detailed diagnosis and procedure data. National Center for Health Statistics. Vital Health Stat 2001;
13(151):1206.
[7] Hobbs FDR, Kenkre JE, Roalfe AK, et al. Impact of heart failure and left ventricular systolic dysfunction on quality of life. A cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population. Eur Heart J 2002;23:
186776.
[8] OConnell JB. The economic burden of heart failure. Clin Cardiol 2000;23(Suppl III):
III-610.
[9] Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a set up for vascular disease. Circulation 2003;107:
13946.
[10] Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation 2003;
107:34654.
[11] Vasan RS, Larson MG, Benjamin EJ, et al. Congestive heart failure in subjects with normal
versus reduced left ventricular ejection fraction: prevalence and mortality in a populationbased cohort. J Am Coll Cardiol 1999;33:194855.
[12] Kitzman DW, Gardin JM, Gottdiener JS, et al. Importance of heart failure with preserved
systolic function in patients R65 years of age. CHS Research Group. Cardiovascular
Health Study. Am J Cardiol 2001;87:4139.
[13] Gaasch WH, Levine HJ, Quinones MA, et al. Left ventricular compliance: mechanisms and
clinical implications. Am J Cardiol 1976;38:64553.
[14] Wong WF, Gold S, Fukuyama O, et al. Diastolic dysfunction in elderly patients with congestive heart failure. Am J Cardiol 1989;63:15268.
[15] Tresch DD. Clinical manifestations, diagnostic assessment, and etiology of heart failure in
elderly patients. Clin Geriatr Med 2000;16:44556.
[16] Rockwood K. Acute confusion in elderly medical patients. J Am Geriatr Soc 1989;37:
1504.
[17] Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic
peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347:1617.
[18] Krishnaswamy P, Lubien E, Clopton P, et al. Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction. Am J Med 2001;111:
2749.

HEART FAILURE IN OLDER ADULTS

881

[19] Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting

diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 2002;105:
595601.
[20] Kazanegra R, Cheng V, Garcia A, et al. A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot
study. J Card Fail 2001;7:219.
[21] Anand IS, Fisher LD, Chiang YT, et al. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial
(Val-HeFT). Circulation 2003;107:127883.
[22] de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular
disease. Lancet 2003;362:31622.
[23] Redeld MM, Rodeheer RJ, Jacobsen SJ, et al. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 2002;40:97682.
[24] Hunt SA, for the ACC/ AHA Task Force on Practice Guidelines. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult. J Am
Coll Cardiol 2005;46(6):e182.
[25] Gottdiener JS, Arnold AM, Aurigemma GP, et al. Predictors of congestive heart failure in
the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2000;35:162837.
[26] Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive
heart failure. JAMA 1996;275:155762.
[27] Ghali JK, Kadakia S, Cooper R, et al. Precipitating factors leading to decompensation of
heart failure: traits among urban blacks. Arch Intern Med 1988;148:20136.
[28] Vinson JM, Rich MW, Shah AS, et al. Early readmission of elderly patients with congestive
heart failure. J Am Geriatr Soc 1990;38:12905.
[29] Rich MW, Freedland KE, Shah AS, et al. Iatrogenic congestive heart failure in older adults:
clinical course and prognosis. J Am Geriatr Soc 1996;44:63843.
[30] Rich MW. Heart failure in the oldest patients: the impact of comorbid conditions. Am J
Geriatr Cardiol 2005;14:13441.
[31] Braunstein JB, Anderson GF, Gerstenblith G, et al. Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneciaries with chronic heart
failure. J Am Coll Cardiol 2003;42:122633.
[32] Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure:
the JNC 7 report. JAMA 2003;289:256072.
[33] Slaughter MS, Ward HB. Surgical management of heart failure. Clin Geriatr Med 2000;16:
56792.
[34] Geholt A, Mullany CJ, Ilstrup D, et al. Aortic valve replacement in patients aged eighty
years and older: early and long-term results. J Thorac Cardiovasc Surg 1996;111:102636.
[35] Bolling SF, Deeb GM, Bach DS. Mitral valve reconstruction in elderly, ischemic patients.
Chest 1996;109:3540.
[36] Marzo K, Prigent FM, Steingart RM. Interventional therapy in heart failure management.
Clin Geriatr Med 2000;16:54966.
[37] Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control
in patients with atrial brillation. N Engl J Med 2002;347:182533.
[38] Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm
control in patients with recurrent persistent atrial brillation. N Engl J Med 2002;347:
183440.
[39] Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure
in elderly patients. An underrecognized public health problem. Arch Intern Med 2000;160:
77784.
[40] Garg R, Yusuf S, for the Collaborative Group on ACE Inhibitor Trials. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in
patients with heart failure. JAMA 1995;273:14506.

882

RICH

[41] Flather MD, Yusuf S, Kber L, et al. Long-term ACE-inhibitor therapy in patients with
heart failure or left-ventricular dysfunction: a systematic overview of data from individual
patients. Lancet 2000;355:157581.
[42] Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients
over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet
1997;349:74752.
[43] Pitt B, Poole-Wilson PA, Segal R, et al. Eect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trialdthe Losartan Heart
Failure Survival Study ELITE II. Lancet 2000;355:15827.
[44] Dickstein K, Kjekshus J, for the OPTIMAAL Steering Committee of the OPTIMAAL
Study Group. Eects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomized trial. Optimal Trial
in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002;360:
75260.
[45] Maggioni AP, Anand I, Gottlieb SO, et al. Eects of valsartan on morbidity and mortality
in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am
Coll Cardiol 2002;40:141421.
[46] Granger CB, McMurray JJV, Yusuf S, et al. Eects of candesartan in patients with chronic
heart failure and reduced left-ventricular systolic function intolerant to angiotensinconverting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362:7726.
[47] Cohn JN, Tognoni G. and the Valsartan Heart Failure Trial Investigators. A randomized
trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med
2001;345:166775.
[48] McMurray JJV, Ostergren J, Swedberg K, et al. Eects of candesartan in patients with
chronic heart failure and reduced left-ventricular systolic function taking angiotensinconverting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362:76771.
[49] Cohn JN, Archibald DG, Ziesche S, et al. Eect of vasodilator therapy on mortality in
chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.
N Engl J Med 1986;314:154752.
[50] Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazineisosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;
325:30310.
[51] Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine
in blacks with heart failure. N Engl J Med 2004;351(20):204957.
[52] Packer M, Bristow MR, Cohn JN, et al. The eect of carvedilol on morbidity and mortality
in patients with chronic heart failure. N Engl J Med 1996;334:134955.
[53] CIBIS-II Investigators and Committees. The Cardiac Insuciency Bisoprolol Study II
(CIBIS II): a randomized trial. Lancet 1999;353:913.
[54] MERIT-HF Study Group. Eect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERITHF). Lancet 1999;353:20017.
[55] Packer M, Coats AJS, Fowler MB, et al. Eect of carvedilol on survival in severe chronic
heart failure. N Engl J Med 2001;344:16518.
[56] Poole-Wilson PA, Swedberg K, Cleland JGF, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:713.
[57] The Digitalis Investigation Group. The eect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:52533.
[58] Rich MW, McSherry F, Williford WO, et al, for the Digitalis Investigation Group. Eect of
age on mortality, hospitalizations, and response to digoxin in patients with heart failure:
The DIG Study. J Am Coll Cardiol 2001;38:80613.
[59] Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003;289:8718.

HEART FAILURE IN OLDER ADULTS

883

[60] Slatton ML, Irani WN, Hall SA, et al. Does digoxin provide additional hemodynamic and
autonomic rhythm? J Am Coll Cardiol 1997;29:120613.
[61] Pitt B, Zannad F, Remme WJ, et al. The eect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:70917.
[62] Pitt B, Perez A. for the Randomized Aldactone Study Investigators. Spironolactone in
patients with heart failure. N Engl J Med 2000;342:1334.
[63] Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients
with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:
130921.
[64] Wrenger E, Muller R, Moesenthin M, et al. Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: analysis of 44 cases. BMJ 2003;327:1479.
[65] Yusuf S, Sleight P, Pogue J, et al. Eects of an angiotensin-converting-enzyme inhibitor,
ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention
Evaluation Study Investigators. N Engl J Med 2000;342:14553.
[66] Yusuf S, Pfeer MA, Swedberg K, et al. Eects of candesartan in patients with chronic
heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial.
Lancet 2003;362:77781.
[67] Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the eect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart
failure (SENIORS). Eur Heart J 2005;26(3):21525.
[68] Setaro JF, Zaret BL, Schulman DS, et al. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic lling and normal left ventricular
systolic performance. Am J Cardiol 1990;66:9816.
[69] Adan V, Crown LA. Diagnosis and treatment of sick sinus syndrome. Am Fam Phys 2003;
67:172532.
[70] Kerwin WF, Botvinick EH, OConnell JW, et al. Ventricular contraction abnormalities in
dilated cardiomyopathy: eect of biventricular pacing to correct interventricular dyssynchrony. J Am Coll Cardiol 2000;35:12217.
[71] Bakker P, Meijburg H, de Bries J, et al. Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function. J Interv Card Electrophysiol 2000;
4:395404.
[72] Abraham WT, Fisher WG, Smith AL, et al, for the MIRACLE Study Group. Cardiac
resynchronization in chronic heart failure. N Engl J Med 2002;346:184553.
[73] Linde C, Leclercq C, Rex S, et al. Long-term benets of biventricular pacing in congestive
heart failure: results from the Multisite STimulation in Cardiomyopathy (MUSTIC) Study.
J Am Coll Cardiol 2002;40:1118.
[74] Bradley DJ, Bradley EA, Braughman KL, et al. Cardiac resynchronization and death from
progressive heart failure: a meta-analysis of randomized controlled trials. JAMA 2003;289:
73040.
[75] Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion debrillation in advanced chronic heart failure: the MIRACLE
ICD Trial. JAMA 2003;289:268594.
[76] Cleland JG, Daubert JC, Erdmann E, et al. The eect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352(15):153949.
[77] Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a debrillator in patients
with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:87783.
[78] Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted debrillator in
patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Debrillator Implantation Trial Investigators. N Engl J Med 1996;335:193340.
[79] Ezekowitz JA, Armstrong PW, McAlister FA. Implantable cardioverter debrillators in
primary and secondary prevention: a systematic review of randomized, controlled trials.
Ann Intern Med 2003;138:44552.

884

RICH

[80] Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-debrillator for congestive heart failure. N Engl J Med 2005;352(3):22537.
[81] Sheldon R, Connolly S, Krahn A, et al. Gardner M. Identication of patients most likely to
benet from implantable cardioverter-debrillator therapy: the Canadian Implantable
Debrillator Study. Circulation 2000;101:16604.
[82] Camm AJ, Nisam S. The utilization of the implantable debrillatorda European enigma.
Eur Heart J 2000;21:19982004.
[83] Exner DV, Klein GJ, Prystowsky EN. Primary prevention of sudden death with implantable debrillator therapy in patients with cardiac disease: can we aord to do it? (can we
aord not to?). Circulation 2001;104:156470.
[84] Weiss JP, Saynina O, McDonald KM, et al. Eectiveness and cost-eectiveness of implantable cardioverter debrillators in the treatment of ventricular arrhythmias among Medicare
beneciaries. Am J Med 2002;112:51927.
[85] Krumholz HM, Butler J, Miller J, et al. Prognostic importance of emotional support for
elderly patients hospitalized with heart failure. Circulation 1998;97:95864.
[86] McAlister FA, Stewart S, Ferrua S, et al. Multidisciplinary strategies for the management
of heart failure patients at high risk for admission. A systematic review of randomized trials.
J Am Coll Cardiol 2004;44:8109.
[87] Phillips CO, Wright SM, Kern DE, et al. Comprehensive discharge planning with postdischarge support for older patients with congestive heart failure. A meta-analysis. JAMA
2004;291:135867.
[88] Rich MW, Nease RF. Cost-eectiveness analysis in clinical practice: the case of heart failure. Arch Intern Med 1999;159:1690700.
[89] Pina IL, Apstein CS, Balady GJ, et al. Exercise and heart failure: a statement from the
American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation 2003;107:121025.
[90] McKelvie RS, Teo KK, Roberts R, et al. Eects of exercise training in patients with heart
failure: the Exercise Rehabilitation Trial (EXERT). Am Heart J 2002;144:2330.
[91] Hambrecht R, Gielen S, Linke A, et al. Eects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial.
JAMA 2000;283:3095101.
[92] Belardinelli R, Georgiou D, Cianci G, et al. Randomized controlled trial of long-term moderate exercise training in chronic heart failure: eects on functional capacity, quality of life,
and clinical outcome. Circulation 1999;99:117382.
[93] Keteyian SJ, Levine AB, Brawner CA, et al. Exercise training in patients with heart failure:
a randomized, controlled trial. Ann Intern Med 1996;124:10517.
[94] Hare DL, Ryan TM, Selig SE, et al. Resistance exercise training increases muscle strength,
endurance, and blood ow in patients with chronic heart failure. Am J Cardiol 1999;83:
16747.
[95] Croft JB, Giles WH, Pollard RA, et al. Heart failure survival among older adults in the
United States: a poor prognosis for an emerging epidemic in the Medicare population.
Arch Intern Med 1999;159:50510.
[96] MacIntyre K, Capewell S, Stewart S, et al. Evidence of improving prognosis in heart failure.
Trends in case fatality in 66,547 patients hospitalized between 1986 and 1995. Circulation
2000;102:112631.
[97] Stewart S, MacIntyre K, Hole DJ, et al. More malignant than cancer? Five-year survival
following a rst admission for heart failure. Eur J Heart Fail 2001;3:31522.
[98] Krumholz HM, Chen YT, Vaccarino V, et al. Correlates and impact on outcomes of worsening renal function in patients R65 years of age with heart failure. Am J Cardiol 2000;85:
11103.
[99] Krumholz HM, Phillips RS, Hamel MB, et al. Resuscitation preferences among patients
with severe congestive heart failure: results from the SUPPORT project. Study to

HEART FAILURE IN OLDER ADULTS

[100]
[101]
[102]
[103]
[104]
[105]

[106]

[107]
[108]

885

Understand Prognoses and Preferences for Outcomes and Risks of Treatments. Circulation
1998;98:64855.
Levenson JW, McCarthy EP, Lynn J, et al. The last six months of life for patients with congestive heart failure. J Am Geriatr Soc 2000;48:S1019.
Baker R, Hyg MS, Wu AW, et al. Family satisfaction with end-of-life care in seriously ill
hospitalized adults. J Am Geriatr Soc 2000;48:S619.
Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet 1985;I:134954.
Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients
in primary care. BMJ 1986;293:114551.
Dahlof B, Lindholm LH, Hannson L, et al. Morbidity and mortality in the Swedish Trial in
Old Patients with Hypertension (STOP-Hypertension). Lancet 1991;338:12815.
The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group.
Prevention of stroke by antihypertensive drug treatment in older persons with isolated
systolic hypertension: nal results of SHEP. JAMA 1991;265:325564.
Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and
active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997;350:75764.
Gong L, Zhang W, Zhu Y, et al. Shanghai Trial of Nifedipine in the Elderly (STONE).
J Hypertens 1996;14:123745.
Kjekshus J, Pedersen TR, Olsson AG, et al. The eects of simvastatin on the incidence of
heart failure in patients with coronary heart disease. J Card Fail 1997;3:24954.