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REVIEW

Treatment of Systolic and Diastolic


Heart Failure in the Elderly
Wilbert S. Aronow, MD, CMD

Underlying causes, risk factors, and precipitating causes channel blockers should be avoided if systolic HF is
of heart failure (HF) should be treated. Drugs known to present. Digoxin should be avoided in men and
precipitate or aggravate HF should be stopped. Patients women with diastolic HF if sinus rhythm is present and
with HF and an abnormal left ventricular ejection frac- in women with systolic HF. Digoxin should be given to
tion (LVEF) (systolic heart failure) or normal LVEF (dia- men with systolic HF if symptoms persist, but the se-
stolic HF) should be treated with diuretics if fluid reten- rum digoxin level should be maintained between 0.5
tion is present; with an angiotensin-converting enzyme and 0.8 ng/mL. A multidisciplinary approach should be
(ACE) inhibitor or an angiotensin receptor blocker if used with nurse monitoring of the condition. In a
the patient cannot tolerate an ACE inhibitor because home-bound patient, a homemaker should be hired.
of cough, angioneurotic edema, rash, or altered taste (J Am Med Dir Assoc 2006; 7: 29 –36)
sensation; and with a beta blocker unless contraindi-
cated. If severe systolic HF persists, an aldosterone an- Keywords: Heart failure; beta blockers; angiotensin-
tagonist should be added. If HF persists, isosorbide di- converting enzyme inhibitors; diuretics; digoxin; aldo-
nitrate plus hydralazine should be added. Calcium sterone antagonists; isosorbide dinitrate; hydralazine

Approximately 80% of patients hospitalized with heart HF and atrial fibrillation had a higher mortality than those
failure (HF) are older than 65 years.1 HF is not only the most with sinus rhythm.6 This article will discuss the treatment of
common cause of hospitalization in the United States but is HF in the elderly.
also the most costly with annual expenditures of more than
$40 billion spent each year. At 46-month follow-up of 1160
men, mean age 80 years, and of 2464 women, mean age 81
years, in a nursing home (NH), HF developed in 29% of men STAGES OF HEART FAILURE
and in 26% of women.2 The American College of Cardiology (ACC)/American
HF may be associated with an abnormal left ventricular Heart Association (AHA) guidelines for the evaluation and
ejection fraction (LVEF) (systolic HF) or with a normal LVEF management of HF state that there are 4 stages of HF.1
(ⱖ50%) (diastolic HF). The prevalence of diastolic heart Patients with stage A HF are at high risk of developing HF
failure increases with age and is higher in older women than because of the presence of conditions strongly associated with
in older men.3,4 In 674 patients with HF, mean age 81 years, the development of HF.1 These patients have hypertension,
in a NH, 38% of men and 57% of women had diastolic HF.4 coronary artery disease (CAD), diabetes mellitus, a history of
In 566 HF patients in a NH, the 1-year mortality was 19% in cardiotoxic drug therapy, alcohol abuse, a history of rheumatic
patients with diastolic HF and 41% in patients with systolic fever, or a family history of cardiomyopathy.
HF.5 The 5-year mortality was 74% in patients with diastolic Patients with stage B HF have structural heart disease
HF and 92% in patients with systolic HF.5 NH patients with associated with the development of HF but have never shown
symptoms or signs of HF.1 These patients have a prior myo-
cardial infarction (MI), LV hypertrophy or fibrosis, LV dila-
Department of Medicine, Divisions of Cardiology, Geriatrics, and Pulmonary/ tation or hypocontractility, or asymptomatic valvular heart
Critical Care Medicine, Westchester Medical Center/New York Medical Col-
lege, Valhalla, NY. disease.1
Address correspondence to Wilbert S. Aronow, MD, CMD, Cardiology Division,
Patients with stage C HF have current or prior symptoms of
New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595. HF associated with structural heart disease.1 Patients with
E-mail: WSAronow@aol.com stage D HF have advanced structural heart disease and
Copyright ©2006 American Medical Directors Association marked symptoms of HF at rest despite maximal medical
DOI: 10.1016/j.jamda.2005.07.008 therapy and who require specialized interventions.1

REVIEW Aronow 29
TREATMENT OF STAGE A HEART FAILURE Patients with HF should avoid exposure to heavy air pol-
1,7
In patients with stage A HF, treat hypertension ; treat lution. Air conditioning is essential for patients with HF who
lipid disorders1,8; encourage regular exercise; avoid smoking, are in a hot, humid environment. Ethyl alcohol intake should
alcohol consumption, and illicit drug use; control the ventric- be avoided. Medications that precipitate or exacerbate HF
ular rate in patients with supraventricular tachyarrhythmias; should be stopped. Regular physical activity such as walking
and use angiotensin-converting enzyme (ACE) inhibitors in should be encouraged in patients with mild to moderate HF to
patients with atherosclerotic vascular disease, diabetes melli- improve functional status and to decrease symptoms. Patients
tus, or hypertension.1 Patients with diabetes should be treated with HF who are dyspneic at rest at a low work level may
as if they had CAD. benefit from a formal cardiac rehabilitation program.9 A mul-
tidisciplinary approach to care is useful.10
TREATMENT OF STAGE B HEART FAILURE A HF management team usually includes a nurse coordi-
nator or manager, a dietitian, a social worker, a clinical
The ACC/AHA guidelines recommend in patients with
pharmacist, a home health representative, a primary care
stage B HF treatment with all stage A measures, treatment
physician, and a cardiology consultant. In the NH, the nurse
with ACE inhibitors and beta blockers, and valve replace-
manager becomes the caregiver. In home-bound patients, a
ment or repair for patients with hemodynamically significant
hired homemaker becomes the caregiver. Goals of disease
valvular stenosis or regurgitation.1
management are to improve patient compliance with medi-
cations, diet, and exercise by increasing education and self-
GENERAL MEASURES FOR TREATMENT OF
management skills; to provide close follow-up; and to promote
STAGE C HEART FAILURE
physician adherence to recommended HF treatment guide-
Underlying causes of HF should be treated when possible. lines.11
Precipitating causes of HF should be identified and treated.
Common precipitating factors of HF include dietary so- Diuretics
dium excess, excess fluid intake, inadequate treatment,
nonadherence to appropriate drugs, uncontrolled hyperten- Diuretics are the first-line drug in the treatment of older
sion, anemia, infection, fever, hypoxia, a hot and humid patients with HF and volume overload. A thiazide diuretic such
environment, and use of inappropriate drugs such as non- as hydrochlorothiazide may be used to treat older patients with
steroidal anti-inflammatory drugs. Hypertension should be mild HF. However, a thiazide diuretic is ineffective if the glo-
treated with diuretics, ACE inhibitors, and beta blockers. merular filtration rate is less than 30 mL/min. Older patients
Myocardial ischemia should be treated with nitrates and beta with moderate or severe HF should be treated with a loop
blockers. diuretic such as furosemide. Nonsteroidal anti-inflammatory
Older persons with HF without contraindications to coro- drugs should not be taken by these patients because these
nary revascularization who have exercise-limiting angina pec- drugs may inhibit the induction of diuresis by furosemide.
toris, angina pectoris occurring frequently at rest, or recurrent Older patients with severe HF or concomitant renal insuffi-
episodes of acute pulmonary edema despite optimal medical ciency may need the addition of metolazone to the loop
therapy should have coronary angiography. Coronary revas- diuretic. Severe volume overload should be treated with in-
cularization should be performed in selected patients with travenous diuretics and hospitalization.
myocardial ischemia attributable to viable myocardium sub- Older patients with HF treated with diuretics need close
served by severely stenotic coronary arteries. Selected patients monitoring of their serum electrolytes. Hypokalemia and hy-
should have surgical correction of valvular lesions. Infective pomagnesemia, both of which may precipitate ventricular
endocarditus should be treated with intravenous antibiotics arrhythmias and digitalis toxicity, may develop. Hyponatre-
and with surgical replacement of valvular lesions if clinically mia with activation of the renin-angiotensin-aldosterone sys-
indicated. Anemia, infection, bronchospasm, hypoxia, tachy- tem may occur.
arrhythmias, bradyarrhythmias, obesity, hyperthyroidism, and Elderly patients with HF are especially sensitive to volume
hypothyroidism should be treated. depletion. Dehydration and prerenal azotemia may occur if
Oral warfarin should be administered to patients with HF excessive doses of diuretics are given. Therefore, the mini-
who have prior systemic or pulmonary embolism, atrial fibril- mum effective dose of diuretics should be used. Older patients
lation, or cardiac thrombi detected by 2-dimensional echo- with systolic or diastolic HF and volume overload should be
cardiography. The dose of warfarin administered should treated with diuretics (Tables 1 and 2). However, elderly
achieve an International Normalized Ratio of 2.0 to 3.0. patients with systolic HF tolerate higher doses of diuretics
Patients with HF should have their sodium intake de- than do elderly patients with diastolic HF. Elderly patients
creased to 1.6 g of sodium (4 g of sodium chloride) daily. with diastolic HF require high LV filling pressures to maintain
Excessive fluid intake should be avoided. Fluid intake should an adequate stroke volume and cardiac output and cannot
be restricted if dilutional hyponatremia develops and the tolerate intravascular depletion. Therefore, elderly patients
serum sodium concentration falls below 130 mEq/L. Patient with diastolic HF should be treated with a low-sodium diet
compliance should be stressed such as the need for salt re- with cautious use rather than with large doses of diuretics.
striction, fluid restriction, and daily weights through patient The dose of diuretics should be gradually reduced and stopped
education. if possible when fluid retention is not present in patients with

30 Aronow JAMDA – January 2006


Table 1. Treatment of Older Patients With Systolic Heart Failure increased to full therapeutic levels. After the maintenance
1. Therapeutic measures for stages A and B heart failure dose of ACE inhibitors is reached, it may be necessary to
2. Diuretics in patients with fluid retention increase the dose of diuretics. Data indicate that patients with
3. Angiotensin-converting enzyme (ACE) inhibitor or HF should be treated with high doses of ACE inhibitors unless
angiotensin receptor blocker in patients who cannot be
given an ACE inhibitor because of cough, rash, altered
low doses are the only doses that can be tolerated.22
taste sensation, or angioneurotic edema Older patients at risk for excessive hypotension should
4. Beta blockers have their blood pressure monitored closely for the first 2
5. Aldosterone antagonist in patients with class IV weeks of ACE inhibitor therapy and whenever the physician
symptoms, preserved renal function, and normal serum
potassium
increases the dose of ACE inhibitor or diuretic. Renal func-
6. If symptoms persist or if an ACE inhibitor or angiotensin tion should be monitored in patients administered ACE in-
receptor blocker cannot be given because of hibitors to detect increases in blood urea nitrogen and in
hypotension or renal insufficiency, add isosorbide serum creatinine, especially in older patients with renal artery
dinitrate plus hydralazine, especially in African
Americans
stenosis. A doubling in serum creatinine should cause the
7. Digoxin for the treatment of persistent symptoms of physician to consider renal dysfunction caused by ACE in-
heart failure in men hibitors, a need to reduce the dose of diuretics, or exacerba-
8. Exercise training as an adjunctive approach to improve tion of HF. Potassium supplements and potassium-sparing
clinical status in ambulatory patients
9. Avoid calcium channel blockers
diuretics should not be given to patients receiving ACE
inhibitors because ACE inhibitor therapy may cause hyper-
kalemia by blocking aldosterone production.
Asymptomatic hypotension with a systolic blood pressure
between 80 and 90 mm Hg and a serum creatinine of less than
systolic or diastolic HF. Patients on high doses of diuretics 2.5 mg/dL are side effects of ACE inhibitors that should not
have an increased mortality.12 necessarily cause discontinuation of this drug but should cause
the physician to reduce the dose of diuretics if the jugular
ACE Inhibitors venous pressure is normal and to consider decreasing the dose
ACE inhibitors improve symptoms, quality of life, and of ACE inhibitor. Contraindications to the use of ACE in-
exercise tolerance in patients with HF. ACE inhibitors also hibitors are symptomatic hypotension, progressive azotemia,
increase survival in patients with systolic HF13–16 and should angioneurotic edema, hyperkalemia, intolerable cough, and
be used to treat patients with systolic HF (Table 1).1 ACE rash.
inhibitors also improve survival and reduce the incidence of There are conflicting data about the importance of the
HF and coronary events in patients with abnormal LVEF negative interaction of aspirin with ACE inhibitors in the
without HF17–19 and should be used to treat these patients.1 treatment of patients with HF. In a study of older patients
At 3-month follow-up of older persons with prior MI and with HF treated with ACE inhibitors, aspirin significantly
diastolic HF treated with diuretics in an NH, patients ran- reduced mortality by 31%.23 Until data from controlled clin-
domized to enalapril had significant improvements in New ical trials are available, a prudent approach to this controversy
York Heart Association (NYHA) functional class (Table 3),
might be to reduce the dose of aspirin to 80 to 100 mg daily
in treadmill exercise time, in LV ejection fraction, and in LV
or substititue clopidogrel as an antiplatelet drug in patients
diastolic function assessed by Doppler echocardiography.20
with HF treated with ACE inhibitors. The dose of ACE
Enalapril also significantly decreased cardiothoracic ratio
inhibitors could also be increased to overcome aspirin-related
measured from chest x-rays and echocardiographic LV mass.20
In an observational study of patients, mean age 75 years, attenuation.
with HF, 65% of 227 patients with an LVEF of 40% to 49%
and 44% of 312 patients with an LVEF of ⱖ50% were treated
with ACE inhibitors.21 At 6-month follow-up, ACE inhibi-
tors significantly decreased mortality by 63% and significantly Table 2. Treatment of Older Patients With Diastolic Heart Failure
improved quality-of-life scores in patients with an LVEF of
1. Treat with cautious use of diuretics and with beta
40% to 49% and insignificantly decreased mortality 39% and blockers
significantly improved quality-of-life scores in patients with 2. If heart failure persists, add angiotensin-converting
an LVEF of ⱖ50%.21 On the basis of these limited data,20,21 enzyme (ACE) inhibitor or angiotensin receptor blocker
persons with diastolic HF should be treated with ACE inhib- if patient cannot tolerate ACE inhibitor because of
itors (Table 2). cough, angioneurotic edema, rash, or altered taste
sensation
ACE inhibitors should be started in older persons with HF 3. Add isosorbide dinitrate plus hydralazine if heart failure
in low doses after correction of hyponatremia or volume persists
depletion. It is important to avoid overdiuresis before initiat- 4. Add calcium channel blocker if heart failure persists
ing treatment with ACE inhibitors because volume depletion 5. Avoid digoxin if sinus rhythm is present
may cause hypotension or renal insufficiency when ACE 6. Exercise training as an adjunctive approach to improve
clinical status in ambulatory patients
inhibitors are started or when the dose of these drugs is

REVIEW Aronow 31
Table 3. Definition of New York Heart Association Functional should be treated with ACE inhibitors plus beta block-
Classes in Patients With Heart Failure ers.1,19,36 An observational prospective study was performed
Class I patients are asymptomatic with ordinary activity in 477 NH patients, mean age 79 years, with prior MI and
Class II patients are symptomatic with ordinary activity abnormal LVEF.19 Compared with no beta blocker or ACE
Class III patients are symptomatic with less than ordinary inhibitor, at 34-month follow-up, ACE inhibitors alone sig-
activity
Class IV patients are symptomatic at rest nificantly reduced new coronary events 17% and new HF
32% and beta blockers alone significantly reduced new coro-
nary events 25% and new HF 41%.19 Compared with no beta
blocker or ACE inhibitor, at 41-month follow-up, ACE in-
Angiotensin Receptor Blockers hibitors plus beta blockers significantly reduced new coronary
events 37% and new HF 61%.19 The significantly longer
The angiotensin II type 1 receptor antagonist losartan follow-up time in patients treated with ACE inhibitors plus
significantly reduced the rate of first hospitalization for HF beta blockers indicates that beta blockers plus ACE inhibitors
32% compared with placebo at 3.4-year follow-up of patients delayed as well as reduced the occurrence of new coronary
with type 2 diabetes mellitus and nephropathy.24 Losartan events and HF.19
also significantly decreased hospitalization for HF 41% com-
Patients should be treated with an ACE inhibitor or an-
pared with atenolol at 4.7-year follow-up of patients with
giotensin receptor blocker and be in a relatively stable con-
diabetes with hypertension and electrocardiographic left ven-
dition without the need of intravenous inotropic therapy and
tricular hypertrophy.25
without signs of marked fluid retention before initiating beta
In the Losartan Heart Failure Survival Study II, 3152
blocker therapy in patients with HF.37 Beta blockers should
patients aged 60 years or older with systolic HF were random-
be initiated in a low dose such as carvedilol 3.125 mg twice
ized to receive losartan 50 mg daily or captopril 50 mg 3 times
daily.26 At 555-day follow-up, mortality was 13% insignifi- daily or metoprolol CR/XL 12.5 mg daily if there is NYHA
cantly lower in patients treated with captopril than in patients class III or class IV HF or 25 mg daily if there is NYHA class
treated with losartan, 77% significantly lower in patients II HF. The dose of beta blockers should be doubled at 2 to 3
treated with captopril plus beta blockers than in patients week intervals with the maintenance dose of beta blockers
treated with losartan plus beta blockers, and 5% insignifi- reached over 3 months (carvedilol 25 mg twice daily or 50 mg
cantly lower in patients treated with captopril without beta twice daily if ⬎187 pounds or metoprolol CR/XL 200 mg once
blockers than in patients treated with losartan without beta daily). The patient may experience fatigue during the initia-
blockers.26 Angiotensin receptor blockers have been shown to tion or up-titration of the dose of beta blockers with this effect
reduce mortality plus morbidity in patients with systolic HF dissipating over time. The need to continue beta blockers in
who cannot tolerate ACE inhibitors because of cough, rash, this patient must be stressed because of the importance of beta
altered taste sensation, or angioneurotic edema.27–29 blockers in reducing mortality.
In the Candesartan in Heart Failure Assessment of Reduc- During titration, the patient should be monitored for HF
tion in Mortality and Morbidity–Preserved study, 3023 pa- symptoms, fluid retention, hypotension, and bradycardia.37 If
tients with diastolic HF were randomized to candesartan 32 there is worsening of symptoms, increase the dose of diuretics
mg daily or to placebo.30 At 37-month median follow-up, or ACE inhibitors. Temporarily reduce the dose of beta block-
candesartan insignificantly reduced cardiovascular death or ers if necessary. If there is hypotension, reduce the dose of
hospitalization for HF by 11%. Angiotensin receptor blockers vasodilators and temporarily reduce the dose of beta blockers
should be used to treat older patients with systolic or diastolic if necessary. Reduce or discontinue drugs that may decrease
HF who cannot be treated with an ACE inhibitor because of heart rate in the presence of bradycardia. Contraindications
cough, rash, altered taste sensation, or angioneurotic edema to the use of beta blockers in patients with HF are bronchial
(Tables 1 and 2). asthma, severe bronchial disease, symptomatic bradycardia,
and symptomatic hypotension.37
Beta Blockers
Prospective randomized studies have shown that beta Aldosterone Antagonists
blockers significantly reduce mortality in patients with systolic
HF31–34 or diastolic HF.35 Beta blockers reduce all-cause mor- Spironolactone 25 mg daily has been shown to reduce
tality, cardiovascular mortality, sudden death, and death form mortality and hospitalization for worsening HF in patients
worsening HF in patients with HF.31–35 Beta blockers signif- with severe HF.38 At 16-month follow-up of 6632 patients,
icantly reduce mortality in African-Americans and in whites mean age 64 years, with acute MI complicated by systolic HF,
with HF, in women and in men with HF, in elderly and in eplerenone 50 mg daily significantly reduced mortality 15%
younger patients with HF, in diabetic and in nondiabetic and death from cardiovascular causes or hospitalization for
patients with HF, and in patients with severe HF and with cardiovascular events by 13%.39 The ACC/AHA guidelines
mild or moderate HF.31–35 Beta blockers should be used to recommend using aldosterone antagonists in patients with
treat patients with systolic or diastolic HF unless there are class IV systolic HF despite treatment with diuretics, ACE
contraindications to their use (Tables 1 and 2). inhibitors, beta blockers, and digoxin if there is preserved
Patients with prior MI and asymptomatic abnormal LVEF renal function and a normal serum potassium (Table 1).

32 Aronow JAMDA – January 2006


Isosorbide Dinitrate Plus Hydralazine systolic HF in the DIG study showed by multivariate analysis
In the Veterans Administration Cooperative Vasodilator- that digoxin significantly increased the risk of death among
Heart Failure Trial I, compared with placebo, oral isosorbide women by 23% (absolute increase of 4.2%).46 A post hoc
dinitrate plus hydralazine significantly reduced mortality 38% subgroup analysis of data from men with systolic HF in the
at 1 year, 25% at 2 years, and 23% at 3 years in men, mean age DIG study showed that digoxin significantly reduced mortal-
58 years, with systolic HF.40 In 83 patients with diastolic HF ity by 6% if the serum digoxin level was 0.5 to 0.8 ng/mL,
in this study, compared with placebo, isosorbide dinitrate plus insignificantly increased mortality by 3% if the serum digoxin
hydralazine insignificantly decreased mortality by 41%.41 level was 0.8 to 1.1 ng/mL, and significantly increased mor-
The African-American Heart Failure Trial randomized tality by 12% if the serum digoxin level was 1.2 ng/mL or
1040 African Americans with systolic HF (only 23% with higher.47
ischemic heart disease) to isosorbide dinitrate plus hydralazine Another post hoc subgroup analysis of data from all 1926
or to placebo.42 At 10-month follow-up, isosorbide dinitrate women with systolic or diastolic HF in the DIG study showed
plus hydralazine significantly reduced mortality by 43% and that digoxin significantly increased mortality by 20% in wom-
rate of first hospitalization for HF by 33%.42 en.48 This retrospective analysis also showed that higher NYHA
The ACC/AHA guidelines recommend using isosorbide classes were associated with poorer outcomes in patients with
dinitrate plus hydralazine in patients with HF who are being diastolic HF.49
treated with diuretics and beta blockers, and who cannot be On the basis of these data, women with systolic or diastolic
given an ACE inhibitor or angiotensin receptor blocker be- HF and men with diastolic HF (Tables 1 and 2) should not be
cause of hypotension or renal insufficiency (Table 1).1 Oral treated with digoxin. Men with symptoms of persistent HF
nitrates plus hydralazine should also be considered for the despite treatment with diuretics, ACE inhibitors, and beta
treatment of diastolic HF in elderly patients with persistent blockers and systolic HF should be treated with digoxin (Table
symptoms of HF despite diuretics, beta blockers, and ACE 1).1 The maintenance dose of digoxin should be 0.125 mg daily
inhibitors (Table 2). in elderly men, and the serum digoxin level should be between
The initial dose of oral isosorbide dinitrate in elderly pa- 0.5 and 0.8 ng/mL.
tients with HF is 10 mg 3 times daily, with subsequent Digoxin has a narrow therapeutic index, especially in elderly
titration up to a maximum dose of 40 mg 3 times daily. patients. Age-related reduction in renal function increases se-
Nitrates should be given no more than 3 times daily, with rum digoxin levels in older persons. The decrease in skeletal
daily nitrate washout intervals of 12 hours to prevent nitrate muscle mass in elderly patients reduces the volume of distribu-
tolerance from developing. The initial dose of oral hydralazine tion of digoxin, increasing serum digoxin levels. Elderly patients
in elderly patients with HF is 10 mg to 25 mg 3 times daily, are also more likely to be taking drugs that interact with digoxin
with subsequent titration up to a maximum dose of 100 mg 3 by interfering with its bioavailability or excretion. For example,
times daily. spironolactone, triamterene, amiodarone, quinidine, verapamil,
propafenone, erythromycin, tetracycline, propantheline, and
Digoxin other drugs increase serum digoxin levels. Therefore, elderly
patients receiving these drugs are at increased risk for developing
Digoxin reduces the rapid ventricular rate associated with digitalis toxicity.50 In addition, hypokalemia, hypomagnesemia,
supraventricular tachyarrhythmias and may be used to treat myocardial ischemia, hypoxia, acute and chronic lung disease,
older patients with HF and supraventricular tachyarrhythmias acidosis, hypercalcemia, and hypothyroidism may cause digitalis
such as atrial fibrillation. However, digoxin should not be toxicity despite normal serum digoxin levels.50
used to treat patients with HF in sinus rhythm with diastolic
HF. By increasing contractility through increased intracellular
Calcium Channel Blockers
calcium concentration, digoxin may increase LV stiffness in
these patients, increasing LV filling pressure, and aggravating Calcium channel blockers such as nifedipine, diltiazem, and
HF associated with normal LV ejection fraction.43 verapamil exacerbate systolic HF.51 Diltiazem significantly in-
At 37-month follow-up of 7788 patients, mean age 64 creased mortality in patients with pulmonary congestion and
years, with HF (6800 with systolic HF and 988 with diastolic abnormal LVEF after MI.52 The Multicenter Diltiazem Postin-
HF) in the Digitalis Investigator Group (DIG) study, mortal- farction Trial also showed in patients with an LVEF less than
ity was similar in patients treated with digoxin or placebo.44,45 40% that late HF at follow-up was significantly increased in
HF hospitalization was significantly reduced 28% in patients patients randomized to diltiazem (21%) compared with patients
with systolic HF and insignificantly reduced 21% in patients randomized to placebo (12%).53
with diastolic HF.45 Hospitalization for any cause was signif- The vasoselective calcium channel blockers amlodipine54
icantly reduced 8% in patients with systolic HF and insignif- and felodipine55 did not significantly affect survival in patients
icantly increased 4% in patients with diastolic HF.45 Hospi- with systolic HF. In these studies, there was a significantly
talization for suspected digoxin toxicity in patients treated higher incidence of pulmonary edema in patients treated with
with digoxin was 0.67% in patients aged 50 to 59 years, 1.91% amlodipine54 (15%) than in patients treated with placebo
in patients aged 60 to 69 years, 2.47% in patients aged 70 to (10%) and a significantly higher incidence of peripheral edema
79 years, and 4.42% in patients aged 80 years and older.45 in patients treated with amlodipine54 or felodipine55 than in
A post hoc subgroup analysis of data from women with those treated with placebo. On the basis of the available data,

REVIEW Aronow 33
calcium channel blockers should not be administered to patients NESIRITIDE
with systolic HF (Table 1).1 Intravenous nesiritide (human B-type natriuretic peptide)
However, in a double-blind, 5-week crossover trial in 20 men is being used in the treatment of patients with decompensated
with diastolic HF, compared with placebo, verapamil improved HF. However, in 489 patients with dyspnea at rest from
exercise capacity, peak LV filling rate, and a clinicoradiographic decompensated HF in the Vasodilation in the Management of
heart failure score.56 Calcium channel blockers may be given to Acute CHF study, compared with intravenous nitroglycerin,
patients with diastolic HF and symptoms despite diuretics, beta intravenous nesiritide insignificantly increased hospital stay
blockers, ACE inhibitors, and isosorbide dinitrate plus hydral- and 30-day and 6-month mortality.61 A review of Food and
azine (Table 2). Drug Administration files available via the Web site also
SYNCHRONIZED PACING AND showed that nesiritide insignificantly increased mortality 1.8
CARDIOVERTER-DEFIBRILLATORS times in patients with acute decompensated systolic HF.62

Aproximately one third of patients with chronic HF have


electrocardiographic (ECG) evidence of a major intraventric- COMORBIDITIES
ular conduction delay, which may worsen LV systolic dysfunc- Comorbidities have a major role in the progression or
tion through asynchronous ventricular contraction. Cardiac recurrences of HF, and, in turn, can be worsened by HF
resynchronization therapy (CRT) achieved through atrial- itself.63 For example, anemia is emerging as a major risk factor
synchronized biventricular pacing has been shown to cause for poor HF control.64 Anemia also contributes to exercise
significant clinical improvement in patients with moderate- intolerance, which is a major morbidity in patients with
to-severe systolic HF, and a QRS duration on the resting ECG chronic HF. Potential benefits of treating anemia with recom-
of 120 msec or more.57 At 29-month follow-up of 813 patients binant human erythropoeitin include improved oxygen deliv-
with class III or IV systolic HF and cardiac dyssynchrony, ery, improved exercise capacity, attenuation of adverse LV
compared to medical therapy alone, CRT significantly re- remodeling, and reduction of apoptosis.65 Potential risks of
duced death or unplanned hospitalization for a major cardio- this treatment include hypertension, platelet activation, and
vascular event by 37% and mortality by 36%.58 increased thrombosis.
At 46-month follow-up of 2521 patients, mean age 60 Other comorbidities in elderly patients with chronic HF
years, with NYHA class II or III systolic HF and a mean QRS include renal insufficiency, which worsens symptoms and
duration on the resting ECG of 120 msec in the Sudden prognosis and which may be aggravated by diuretics and ACE
Cardiac Death in Heart Failure Trial, compared with placebo, inhibitors. Treatment of older patients with HF with coexis-
amiodarone insignificantly increased mortality by 6%, and tent diabetes mellitus, chronic obstructive lung disease, and
implantable cardioverter-defibrillator (ICD) therapy signifi- arthritis is extensively discussed elsewhere.66
cantly reduced all-cause mortality by 23%.59
On the basis of these data, CRT plus ICD therapy should
be considered in elderly patients with severe systolic CHF PALLIATIVE CARE
despite optimal medical therapy due to ischemic or nonisch- Cardiac transplantation and use of an implantable left
emic heart disease, preferably in sinus rhythm, and with ventricular assist device are not viable options for NH pa-
evidence of ventricular dyssynchrony. However, CRT has tients with end-stage HF. These patients with end-stage HF
been ineffective in treating systolic HF in 35% of patients, should receive palliative care. The major goal of the treat-
and the rate of unsuccessful implants ranges from 8% to 13%. ment of these patients is symptom control. These patients
CRT has not been investigated in patients with diastolic HF should be made as comfortable as possible. Dietary restrictions
and would be unlikely to benefit these patients. should be avoided. The physician should consider that pos-
tural hypotension and falls are exacerbated by diuretics, va-
INOTROPIC THERAPY sodilators, and beta blockers67 and that urinary incontinence
Phosphodiesterase inhibitors such as milrinone, flose- is aggravated by diuretics. If implanted, an ICD should be
quinan, enoximone, vesnarinone, and pimobendan have been discontinued. Continuous intravenous inotropic infusions
demonstrated to significantly increase mortality in patients may be used in these patients to provide relief of symptoms.
with systolic HF. Orally administered adrenergic agents have
not been beneficial in the treatment of patients with systolic
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ceiving continuous intravenous dobutamine in the FIRST to Revise the 1995 Guidelines for the Evaluation and Management of
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