Heart Failure

James O. Mudd, MD; Michael Field, MD; and Edward Kasper, MD

FAST FACTS

The most common causes of heart failure (HF) in the United States
are ischemic heart disease, hypertension, valvular heart disease, and
idiopathic dilated cardiomyopathy.
HF may result from impaired systolic function, impaired diastolic
function, or a combination of the two.
A patients hemodynamic status can be classified based on the
presence or absence of pulmonary congestion (wet or dry) and the
presence or absence of poor perfusion (cold or warm).
Diuretic therapy is the cornerstone of treatment in both acute and
chronic HF.
Angiotensin-converting enzyme (ACE) inhibitors are indicated in all
cases of left ventricular dysfunction, improving both symptoms and
survival.
Beta-blocker therapy improves survival and symptoms in patients
with New York Heart Association class II to IV HF.
Digoxin therapy improves symptoms and rehospitalization rates but
not mortality in patients with HF.
Aldosterone blockade therapy improves survival and symptoms in
selected patients with HF.
Implantable cardioverter-defibrillators (ICDs) and cardiac
resynchronization therapy provide survival benefit in patients with
reduced left ventricular function.

I. EPIDEMIOLOGY
1. The prevalence of HF continues to grow, resulting in significant
morbidity and mortality. Current estimates suggest that more than 5
million people have this syndrome, and another 400,000 to 700,000
develop HF each year.1
2. HF is a syndrome in which the heart cannot meet the metabolic
demands of the body or fails to maintain adequate cardiac output in the
face of rising filling pressures. Cardiomyopathy, on the other hand, is a
disease of heart muscle that may or may not lead to HF. Box 11-1 lists
the major forms of cardiomyopathy.
3. HF is further subclassified into systolic and nonsystolic (diastolic) HF.
Approximately 30% to 50% of patients with HF have preserved left
ventricular function.2 Nonsystolic HF is defined as a clinical syndrome
with signs and symptoms of HF in the setting of normal left ventricular
ejection fraction (more than 50%) and the absence of valvular disease.
Nonsystolic HF is heterogeneous and is caused by impaired left
131

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132 Cardiology

BOX 11-1
CAUSES OF CARDIOMYOPATHY
Ischemic
Idiopathic and familial
Hypertensive disease
Valvular disease
Tachycardia-induced cardiomyopathy
Sleep apnea
Carcinoid tumor
Infiltrative disorders: amyloid, hemochromatosis, sarcoid
Connective tissue disorders: systemic lupus erythematosus, polyarteritis nodosa,
rheumatoid arthritis, scleroderma, granulomatous disease, dermatomyositis
Endocrine and metabolic: thyrotoxicosis, hypothyroidism, pheochromocytoma,
diabetes, myxedema, uremia, acromegaly, hypocalcemia, hypophosphatemia,
porphyria, gout
Fabrys disease
Gauchers disease
Glycogen storage diseases
Hematologic: polycythemia vera, sickle cell disease, leukemia, Loefflers disease
Infectious and inflammatory: coxsackie B, human immunodeficiency virus,
Chagass disease, Lyme disease, adenovirus, cytomegalovirus
Medications and toxins: alcohol, cocaine, catecholamines, anthracyclines
(doxorubicin), irradiation, cyclophosphamide, bleomycin, 5-fluorouracil, carbon
monoxide, lithium, chloroquine, arsenic, cobalt, antimony, snake venom,
methysergide, lead, antidepressants, disopyramide, phosphorus poisoning, sulfa
drug hypersensitivity
Muscular dystrophies
Nutritional deficiencies: kwashiorkor, selenium, beriberi (thiamine), carnitine
deficiency
Pericardial diseases (pseudocardiomyopathy)
Peripartum
Refsums disease
Transplant rejection
Whipples disease

ventricular relaxation, increased left ventricular stiffness, or impaired

ventricular-arterial coupling. Often, both systolic and nonsystolic HF
coexist. Furthermore, all patients with systolic HF have some degree of
diastolic dysfunction.
II. CLINICAL PRESENTATION
1. The most common presenting symptom of HF is dyspnea.
2. Signs of HF include an accentuated S3, pulmonary rales, pleural
effusions, elevated jugular venous pressure, sustained abdominojugular
reflux, lower extremity edema, Cheyne-Stokes respirations, a pulsatile

Heart Failure 133

BOX 11-2
NEW YORK HEART ASSOCIATION CLASSIFICATION
Class I: Symptoms of heart failure only at levels that would limit normal individuals
Class II: Symptoms of heart failure with ordinary exertion
Class III: Symptoms of heart failure on less than ordinary exertion
Class IV: Symptoms of heart failure at rest

TABLE 11-1
HEMODYNAMIC PROFILES IN HEART FAILURE

Low Perfusion at Rest?

No
Yes

Congestion at Rest?
No
Yes
Dry-warm
Wet-warm
Dry-cold
Wet-cold

Modified from Nohria A, Lewis E, Stevenson L: JAMA 287:628, 2002.

11
HEART FAILURE

liver, and ascites. Subtle signs and symptoms of fluid overload from HF
include low-grade fevers, slight increases in abdominal girth, nausea,
and anorexia.
3. Elevated jugular venous pressure and an audible S3 in patients with
left ventricular dysfunction are associated with a higher risk of
hospitalizations for HF and death.3
4. Quantification of symptoms is based on the New York Heart Association
(NYHA) classification scheme (Box 11-2).
5. Determining a patients hemodynamic profile is the most important
step in evaluating a patient with suspected HF; the profile is based on
evidence of congestion (wet vs. dry) or evidence of low perfusion (cold
vs. warm). On the basis of this evaluation, patients can be placed into
four hemodynamic profiles, as shown in Table 11-1.
a. Evidence of congestion.
(1) Symptoms of left-sided congestion: dyspnea at rest or early in
exertion, orthopnea, paroxysmal nocturnal dyspnea.
(2) Symptoms of right-sided congestion: lower extremity edema,
abdominal fullness and bloating, and anorexia.
(3) Physical signs: elevated jugular venous pressure, pulmonary rales,
loud P2, new or worsening S3, lower extremity edema, pulsatile
liver. The most useful physical finding is elevation of the jugular
venous pressure both in the acute setting and longitudinally when
treating chronic HF.
b. Evidence of low perfusion.
(1) Symptoms often are protean, including fatigue, somnolence, poor
concentration, and anorexia.
(2) Physical signs include pallor, cool extremities, low volume pulses,
and a narrow pulse pressure.
(3) A proportional pulse pressure ([systolic blood pressure (SBP) diastolic blood pressure (DBP)]/SBP) less than 0.25 is 91%

134 Cardiology

sensitive and 83% specific for a low output state (cardiac index of
2.2 L/min/m2 or less).4
6. Evidence of systolic or diastolic dysfunction. Several features of the
history and physical examination assist in determining whether HF is
caused primarily by systolic or diastolic dysfunction. Clinical findings
can be confirmed with the use of echocardiography.
a. Systolic HF. Evidence of cardiomegaly on chest radiograph, anterior Q
waves on electrocardiogram, left bundle branch block, diffuse soft
apical impulse, pulse greater than 100, and SBP less than 90.5
b. Nonsystolic HF. Hypertension during the HF episode with SBP greater
than 160 mmHg or DBP greater than 100 mmHg. Other suggestive
features include an S4, female sex, history of hypertension,
electrocardiographic evidence of left ventricular hypertrophy, tobacco
use, advanced age, and no prior history of myocardial infarction (MI).
c. Although the aforementioned clinical findings are suggestive, in practice
systolic and nonsystolic HF may be difficult to delineate because there
is significant overlap in their clinical presentations.6
III. DIAGNOSIS
1. Laboratory evaluation should include a complete blood cell count,
comprehensive metabolic panel, coagulation studies, thyroidstimulating hormone, creatine kinase with isozymes, and troponin.
Measurement of brain natriuretic peptide is useful in addressing new
onset HF and potentially in following patients with chronic HF
longitudinally, although such measurements should not be used in
isolation but rather in combination with the history and physical
examination.7,8 In patients with newly diagnosed HF of unclear origin,
assays for ferritin, total iron-binding capacity, antinuclear antibody,
rheumatoid factor, urinary metanephrines, human immunodeficiency
virus antibody testing, and serum and urine protein electrophoresis
should be performed.
2. Electrocardiogram. An electrocardiogram should be obtained on all
patients with new or chronic HF to assess for signs of myocardial
ischemia, new conduction abnormalities, chamber enlargement,
pericarditis, or right heart failure.
3. Chest radiography. Radiographic findings depend on the degree of HF
and may include cardiomegaly, diffuse bilateral infiltrates extending
from the hila, Kerley B lines, and pleural effusions. These findings may
be absent in patients with chronic HF with isolated right heart failure or
those who have adapted to elevated left ventricular filling pressures with
enhanced pulmonary lymphatic clearance.
4. Echocardiography. All patients with a new-onset HF should undergo
transthoracic echocardiography to assess systolic and diastolic function,
valvular abnormalities, filling pressures, and pericardial disease.
5. Right and left heart catheterization. Coronary angiography is indicated
for almost all patients with newly diagnosed HF to exclude ischemic

Heart Failure 135

IV. TREATMENT
A. ACUTE HF
A systematic search for precipitating causes must be performed in every
patient with new-onset or worsening HF (Box 11-3). Therapy should be
directed at the underlying cause (if identified and treatable) and standard
HF therapy initiated on the basis of one of four clinical hemodynamic
profiles (Table 11-1).
1. Treatment goals by hemodynamic profile.
a. Wet and warm. This is the most common hemodynamic profile in HF.
These patients have congestion resulting from elevated filling pressures
and volume overload. Congestion can be relieved with intravenous loop
diuretics, and patients may benefit from intravenous or oral vasodilators
such as nitroglycerin. Positive inotropic agents often are unnecessary
and may be detrimental in patients who do not have evidence of low
perfusion.

BOX 11-3
PRECIPITANTS OF ACUTE DECOMPENSATED HEART FAILURE
Myocardial ischemia
Hypertension
Infection (myocarditis)
Arrhythmia
Noncompliance with medication
Sodium and fluid indiscretion (dietary noncompliance)
Excessive alcohol intake
Pulmonary embolism
Thyrotoxicosis
High output (thyrotoxicosis, arteriovenous fistula, pregnancy, anemia)

11
HEART FAILURE

heart disease if a readily apparent explanation does not exist. Right

heart catheterization (Swan-Ganz catheter) provides information about
right- and left-sided filling pressures, pulmonary artery pressures,
cardiac output, and systemic vascular resistance.
6. Endomyocardial biopsy. Some investigators have found right-sided
endomyocardial biopsy helpful as it may help facilitate the diagnosis in
80% of patients with unexplained cardiomyopathy.9
7. Exercise testing. Exercise testing can be used to detect ischemic heart
disease and provides an estimate of functional capacity for risk
stratification and prognosis in patients with known HF. Measurement
of maximal oxygen uptake is an objective index of functional severity
and the best index of prognosis, and it can be used to determine the
necessity and timing of cardiac transplantation in patients with chronic
HF. The 6-minute walk test (distance the patient can walk in 6
minutes) is a simpler test used in clinical practice that correlates with
maximal oxygen uptake.

136 Cardiology

b. Wet and cold. Patients with congestion and critically limited

hypoperfusion often must be warmed up before they can be dried
out.10 Perfusion may be improved through the use of vasodilators
alone, although these patients may have therapy-limiting hypotension
necessitating inotropic agents such as dopamine, milrinone, or
dobutamine. In cases unresponsive to inotropic support, mechanical
circulatory support with left ventricular assist devices or intraaortic
balloon pump may be necessary as a lifesaving measure and a bridge
to heart transplantation.
c. Dry and warm. This hemodynamic profile represents compensated HF,
and many patients with this form do not need inpatient management.
Efforts should be aimed at maintaining stable volume status and
preventing disease progression, as outlined later in this chapter.
d. Dry and cold. This small subgroup of patients has a low cardiac output and
evidence of poor perfusion but no clinical evidence of elevated filling
pressures. Patients may respond transiently to inotropes, but long-term use
has produced adverse effects. Careful management with ACE inhibitors,
beta-blockers, and digoxin may lead to improvement in some patients,
whereas others with unrecognized congestion may benefit from diuresis.
2. Pharmacologic agents in acute HF.
a. Morphine is a m-opioid receptor agonist with both vascular and central
effects providing symptomatic relief in acute pulmonary edema through
venodilation and a decreased perception of dyspnea. Potential side
effects include hypotension, somnolence, and respiratory depression.
b. Diuretics.
(1) Loop diuretics, such as furosemide, are the cornerstone of
therapy in acute decompensated HF. Furosemide produces acute
venodilation and increases sodium excretion, thereby reducing
preload and pulmonary vascular congestion.
(a) In acute HF, patients who have been taking oral loop diuretics
should be switched to intravenous therapy because intestinal
absorption of oral agents may be limited by bowel wall edema.
Patients with renal insufficiency may need higher dosages of
loop diuretics, and some may respond better to a continuous
infusion than intermittent doses.
(b) The starting intravenous dosage typically is half of the home
oral dosage. If there is not an adequate response (100 to
200 ml urine output) within 30 minutes, the dosage should be
doubled until the patient responds. Once an effective dosage is
identified, further diuresis can be accomplished by increasing
the frequency of administration.
(c) The diuretic effect of furosemide lasts 6 hours. Afterward, the
kidneys are highly sodium avid, and diuretic efficacy will be lost
if the patient is not maintained on a low-sodium diet as well.
(d) Markers of adequate diuresis include resolution of dyspnea,
decrease in jugular venous pressure, decrease in intensity of S3,

Heart Failure 137

11
HEART FAILURE

elevation of serum creatinine level, and attainment of dry

weight. Side effects of loop diuretics include hypokalemia,
hypomagnesemia, hyponatremia or hypernatremia, volume
depletion, renal failure, and reversible ototoxicity.
(2) Adding a thiazide diuretic such as chlorothiazide can potentiate the
effect of loop diuretics by preventing compensatory distal tubular
reabsorption of sodium. Thiazide diuretics should be given
approximately 30 minutes before a loop diuretic is administered.11
c. Nesiritide, or recombinant B-type natriuretic peptide, is a natriuretic
peptide with potent vasodilator and natriuretic effects that reduce
pulmonary capillary wedge pressure, right atrial pressure, and systemic
vascular resistance and increase cardiac index.12 Nesiritide is associated
with a lower incidence of arrhythmias than that of other inotropes and
may be particularly useful in patients with decompensated HF and
tachyarrhythmias. The most common adverse effect of nesiritide is
hypotension.
d. Vasodilators.
(1) ACE inhibitors are started at low dosages with short-acting agents
such as captopril and titrated to the maximum tolerated dosage.
Blood pressure response, symptoms, and serum potassium and
creatinine levels should be monitored closely. Once short-acting
agents are tolerated, patients should be transitioned to long-acting
agents. About 10% to 30% of patients with advanced HF cannot
tolerate ACE inhibitors because of hypotension or renal dysfunction.8
(2) Organic nitrates such as nitroglycerin are vasodilators (particularly
of the systemic veins), resulting in decreased preload. Nitrates have
a role in the management of acute pulmonary edema and HF in
the setting of hypertension or angina. Contraindications include
concurrent sildenafil use and severe aortic stenosis.
(3) Hydralazine is a potent short-acting arterial vasodilator that can be
used alone or in combination with nitrates for rapid afterload
reduction. It is often considered as an alternative to ACE inhibitors
and angiotensin II receptor blockers (ARBs) in patients with acute
renal failure and other conditions in which ACE inhibitors are
contraindicated.
(4) Nitroprusside is a potent intravenous arterial vasodilator that may
be warranted if further vasodilation and afterload reduction are
necessary. Adverse effects include thiocyanate toxicity, particularly
in patients with hepatic or renal dysfunction, and coronary steal
phenomenon in patients with ischemic heart disease.
e. Beta-blockers should be used with caution in acute HF exacerbations.
Patients naive to beta-blockade should be euvolemic and tolerating a
stable dosage of ACE inhibitors before beginning beta-blocker therapy.
Patients already on beta-blockers may have to have their dosage
temporarily reduced, but beta-blockers should not be withdrawn unless
hypotension or cardiogenic shock is present.

138 Cardiology

f. Inotropes may be used for the temporary treatment of diuretic-refractory

acute HF (i.e., cold and wet) and as a bridge to definitive treatment
such as revascularization or cardiac transplantation. Inotropes may also
be appropriate as a palliative measure in patients with end-stage HF.
The routine use of inotropes is not indicated in either acute or chronic
HF.13
(1) Dopamine is an endogenous catecholamine that has distinct
cardiovascular effects at escalating dosages: Low-dose dopamine
(1 to 3 mg/kg/min) acts through dopaminergic receptors, leading to
increased renal blood flow and natriuresis; intermediate dosages
(2 to 10 mg/kg/min) result in predominant beta-adrenergic receptor
stimulation, increasing cardiac output by augmenting contractility
and heart rate; higher dosages (10 to 20 mg/kg/min) result in
increased afterload through alpha-adrenergic stimulation, which
may be detrimental in HF. Dopamine should be used primarily to
stabilize hypotensive patients. Tachycardia may be an undesirable
side effect, particularly in those with ischemic heart disease or
diastolic dysfunction who depend on filling time. Low-dose
dopamine in critically ill patients has not been shown to improve
diuresis and does not provide renal protection in patients with renal
dysfunction.14
(2) Dobutamine is a beta-adrenergic agonist with a predominant
hemodynamic effect of direct inotropic stimulation with reflex
arterial vasodilation, resulting in afterload reduction and increased
cardiac output. Side effects include hypotension, ventricular
arrhythmias, and potentially worsening ischemic heart disease by
increasing myocardial oxygen demand.
(3) Milrinone, a phosphodiesterase inhibitor, increases contractility
and produces vasodilation. As with dobutamine, hypotension and
arrhythmias may occur.
3. Response to therapy. Once treatment has begun, careful attention
should be paid to daily weights, urine output, jugular venous pressure,
and pulse pressure. Use of Swan-Ganz catheters in patients with acute
HF exacerbations who do not otherwise have an indication for a SwanGanz catheter is safe but does not alter length of stay, rehospitalization
rates, or mortality.15
B. CHRONIC HF
1. Systolic HF.
Staging: HF is a continuum of stages progressing from asymptomatic to
advanced disease (Fig. 11-1).
Stage A: Patients at high risk for left ventricular dysfunction.
The leading risk factor for HF is ischemic heart disease, accounting
for approximately 60% of new cases.16 Other risk factors include
hypertension, diabetes mellitus, familial history, and presence of
cardiotoxins such as excessive alcohol, radiation, and chemotherapy.
Interventions include controlling hypertension17 and hyperlipidemia;

Heart Failure 139

Stage A:
At high risk for HF:
No structural heart
disease and
No HF symptoms

Stage B:
Structural
heart disease
and No HF
symptoms

Stage C:
Structural heart
disease and
Prior or current
HF symptoms

Stage D:
Advanced HF
Refractory to
maximum
therapy

Structural heart

Development of

Refractory

disease

symptoms

symptoms

Patients with:
Hypertension
Diabetes
Exposure to
cardiotoxins
Family history
of
cardiomyopathy

Therapy:
Treat
hypertension
Treat lipid
disorders
Stop smoking
Avoid alcohol
ACE inhibitors
in patients with
vascular
disease,
diabetes, or
hypertension
and
cardiovascular
risk factors

Patients with:
Patients with:
Previous MI
Known structural
heart disease
Left ventricular
hypertrophy
Shortness of
Left ventricular
breath and
fatigue, reduced
systolic
exercise tolerance
dysfunction
Asymptomatic
due to left
valvular disease
ventricular systolic
dysfunction

Therapy:
Stage A
measures and
ACE inhibitors
if history of MI
or reduced EF
b-Blockers if
history of MI
or reduced EF
Valve surgery
if indicated

Therapy:
Stage A
measures and
Diuretics
ACE inhibitors
b-Blockers
Digoxin
Salt restriction
Spironolactone

Patients with:
Marked
symptoms at
rest despite
maximal
medical
therapy

Therapy:
Stage A, B,
and C
measures
and
Mechanical
assist devices
Heart
transplantation
Continuous
intravenous
inotropic
infusions
for palliation
Hospice care

FIG. 11-1
Stages in the evolution of heart failure and recommended therapy by stage.9 ACE,
angiotensin-converting enzyme; EF, ejection fraction; HF, heart failure; MI, myocardial
infarction.

HEART FAILURE

11

140 Cardiology

discouraging smoking, excessive alcohol intake, and illicit drug use; and
encouraging exercise and weight loss. ACE inhibitors are indicated for
patients with atherosclerotic vascular disease (MI, cerebrovascular
accident, peripheral vascular disease) or diabetes with associated risk
factors.18
Stage B: Patients with structural heart disease in whom symptoms
have not yet developed. Asymptomatic patients with a prior MI, evidence
of left ventricular hypertrophy, left ventricular dysfunction, or valvular
disease are at very high risk for HF. In addition to the recommendations
for stage A, all patients with systolic dysfunction, regardless of symptoms,
should receive ACE inhibitors. ACE inhibitors and beta-blockers are
indicated for patients with a history of MI regardless of the ejection
fraction. Beta-blockers may be used for patients with asymptomatic
systolic dysfunction, although the evidence is not as strong as it is for
symptomatic patients. Valvular repair or replacement should be performed
according to published guidelines (see Chapter 12).19
Stage C: Patients with left ventricular dysfunction with current or
prior symptoms. Readmission for HF occurs at a high rate (30% to 50%)
in the 6 months after discharge. A number of criteria should be met
before discharge, including transition to oral medications for 24 hours,
achievement of dry weight, stable or improving renal function, and
ambulation with decreased dyspnea and without symptomatic
hypotension. During hospitalization patients should receive education
about sodium and fluid restriction and recommendations for exercise.
Patients should monitor their weight at home and may benefit from a
sliding scale outpatient diuretic regimen based on their daily weight.
Vaccination for pneumococcal infection and influenza is recommended.
Use of nonsteroidal antiinflammatory drugs for patients with advanced
HF should be avoided because it may lead to fluid retention and renal
dysfunction. Recommendations listed under stage A and B apply as well.
Stage D: Patients with refractory end-stage HF. Recommendations
include meticulous control of fluid retention with diuretics. ACE inhibitors
and beta-blockers are beneficial, but these patients are at particular
risk of developing hypotension and renal failure with ACE inhibitors and
worsening HF with beta-blockers. Cardiac transplantation should be
considered in eligible patients. Left ventricular assist devices provide
hemodynamic support for patients awaiting heart transplantation and
may be beneficial even for patients who are not candidates for heart
transplantation.20 Continuous intravenous inotropic infusions and hospice
may be used as palliative measures in patients with end-stage HF.
2. Pharmacologic agents in chronic HF.
a. ACE inhibitors are indicated for all patients with systolic dysfunction as
they improve survival, relieve symptoms, prevent hospitalization, and
halt the progression of left ventricular remodeling.21,22 They may have
added benefit at higher dosages,23 and attempts should be made to
achieve target dosages reported in major clinical trials (lisinopril 20 to

Heart Failure 141

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HEART FAILURE

40 mg/day, enalapril 10 mg twice a day, or captopril 50 mg three

times a day). The benefit of ACE inhibitors in HF is independent of
their blood pressurelowering effect. Cough and angioedema are
adverse effects most commonly associated with ACE inhibitors.
Contraindications include symptomatic hypotension, acute renal failure,
bilateral renal artery stenosis, hyperkalemia, and pregnancy.
b. ARBs. When patients are intolerant of ACE inhibitors, use of an ARB
results in a significant reduction in mortality and HF hospitalizations.24
As with ACE inhibitors, however, ARBs should not be used in the
presence of acute renal failure or hyperkalemia and may produce
symptomatic hypotension. Studies directly comparing ARBs and ACE
inhibitors have shown no greater survival with use of ARBs.25,26
Addition of an ARB to a regimen with an ACE inhibitor shows a trend
toward improvement in mortality and reduced hospitalizations.27 Given
the greater experience with ACE inhibitors, they should be used as firstline agents, and ARBs should be reserved for patients who cannot
tolerate ACE inhibitors.
c. Nitrates and hydralazine. Isosorbide dinitrate (40 mg four times a day)
combined with hydralazine (75 mg four times a day) has been shown
to improve survival in chronic HF.28 Although inferior to ACE inhibitors,
this combination should be considered for patients who cannot tolerate
ACE inhibitors and ARBs.29 A nitrate-free interval should be allowed to
prevent the development of nitrate tolerance in patients on long-term
therapy. This combination may be especially useful in African American
patients with HF.30
d. Beta-blockers. Several beta-blockers have been shown to reduce
mortality in patients with symptomatic HF and systolic dysfunction,
including metoprolol, carvedilol, and bisoprolol.31,32 All stable,
euvolemic patients with NYHA class II to IV HF resulting from left
ventricular dysfunction should receive a beta-blocker unless they cannot
tolerate beta-blockers or have a contraindication. Usually an ACE
inhibitor is titrated first, and the beta-blocker is added sequentially in
the outpatient setting. Metoprolol extended release (metoprolol
succinate) can be initiated at 25 mg per os (PO) daily (12.5 mg PO
daily in NYHA class IV) and titrated slowly (monthly) to a maximum
dosage of 200 PO daily. Carvedilol is begun at 3.125 mg PO twice
daily and titrated (every 2 weeks) to a maximum dosage of 25 to 50
mg PO twice daily. Bisoprolol is begun at a dosage of 1.25 PO
daily and titrated to 10 mg PO daily. Carvedilol has been shown to
have a survival advantage over short-acting metoprolol33 and better
ejection fraction compared with extended-release metoprolol in a
meta-analysis.34 Contraindications to beta-blockade include acute
decompensated HF, symptomatic bradycardia, advanced heart block,
and severe bronchospastic disease. Although many patients take
atenolol, no studies evaluating the use of atenolol in chronic HF have
been presented.

142 Cardiology

e. Diuretics.
(1) Loop diuretics. In addition to their role in acute management of
HF, loop diuretics have a central role in long-term management to
attenuate progressive volume overload caused by compensatory
sodium avidity. Diuretics are indicated for patients with
symptomatic HF even after they have been rendered free of edema
and generally are necessary indefinitely. Serum electrolytes should
be monitored closely given the concern for increased risk of
arrhythmic death in patients with HF taking nonpotassiumsparing diuretics.35
(2) Aldosterone antagonism. Aldosterone blockade provides a diuretic
effect and modulates the harmful effects of aldosterone on the
heart. Spironolactone, a potassium-sparing diuretic, has been
shown to decrease both mortality and rehospitalization by one third
in patients with primarily NYHA class III to IV HF.36 Spironolactone
is given as a once-daily dose of 25 mg to those without renal
insufficiency or hyperkalemia. Patients should have stable serum
creatinine levels less than 2.5 mg/dl and serum potassium less
than 5 mmol/L, should undergo frequent electrolyte monitoring
for hyperkalemia, and should not receive daily potassium
supplementation.37 Gynecomastia, breast pain, menstrual
irregularities, and impotence are troubling side effects in about
10% of patients. Eplerenone is another alternative shown to reduce
all-cause mortality in patients with reduced left ventricular ejection
fraction after an MI.38
f. Digoxin. Digoxin is a glycoside shown to improve symptoms and
prevent hospitalization in patients with systolic dysfunction.39 It is
indicated for patients with HF symptoms despite optimal therapy with
ACE inhibitors and diuretics or for patients with coexisting atrial
fibrillation. Toxic effects are more likely to occur in patients with
renal insufficiency, electrolyte abnormalities, advanced age, and
coadministration of other antiarrhythmic drugs (e.g., amiodarone,
quinidine, verapamil, propafenone). Toxic manifestations include
confusion, nonspecific gastrointestinal complaints, vision and color
disturbances, and arrhythmia.
g. Warfarin. Anticoagulation with warfarin is warranted for patients with
concomitant atrial fibrillation, visible thrombus on echocardiogram, or a
previous cardioembolic event.40 Although many consider anticoagulation
for patients with a very low ejection fraction (< 20%), recent data from
the Warfarin and Antiplatelet Therapy in Heart Failure (WATCH) trial
suggest no short-term (23 months) benefit in reducing the incidence of
nonfatal stroke, death, or nonfatal MI in patients with an ejection
fraction of 35% or less randomized to aspirin, clopidogrel, or
Coumadin.41
h. Exercise. A prescription for exercise may improve functional capacity
and quality of life and prevent death from cardiovascular disease.42

Heart Failure 143

11
HEART FAILURE

i. Maintenance of sinus rhythm. Patients with HF benefit from normal

sinus rhythm. Achieving this goal can be difficult with antiarrhythmic
drugs in HF given potential drug interactions. Recent literature has
shown an improvement in ejection fraction, symptoms, exercise
capacity, and quality of life when patients are maintained in sinus
rhythm by means of catheter ablation.43
3. Nonsystolic HF.
Acute exacerbations of nonsystolic HF generally are treated in a similar
fashion as acute exacerbations of systolic HF. Few large trials have
evaluated long-term treatment for nonsystolic HF. Based on the
pathophysiology of diastolic dysfunction, four principles may be used to
guide management.9,44
a. Control of blood pressure. Beta-blockers, ACE inhibitors, ARBs, and
calcium channel blockers may be used to control SBP and DBP
according to published guidelines. In the largest treatment trial for
nonsystolic HF, the ARB candesartan, when added to traditional
medical therapy, was associated with fewer hospitalizations for HF.45
b. Control of tachycardia. Patients with atrial fibrillation need rate control
and may benefit from an attempt at cardioversion to optimize left
ventricular filling.
c. Control of pulmonary congestion and edema. Patients may have rales
and evidence of volume overload (elevated neck veins and peripheral
edema). Loop diuretics such as furosemide decrease filling pressures
and relieve pulmonary congestion. Care must be taken with diuresis
because patients with diastolic HF are sensitive to preload reduction,
and hypotension or prerenal azotemia may develop.
d. Assessment and control of ischemia. Revascularization should be
considered for patients with evidence of ischemia.
4. Device therapy for HF. Patients with HF and reduced left ventricular
function are at a higher risk for sudden cardiac death caused by
ventricular arrhythmias. The Multicenter Automatic Defibrillator
Implantation Trial II (MADIT II) showed a lower all-cause mortality for
the use of ICDs as primary prevention in patients with a left ventricular
ejection fraction less than 30% in cardiomyopathy of ischemic origin.46
ICDs also provide a mortality benefit when used in patients with
cardiomyopathy of nonischemic origin.47 Combining ICD therapy with a
biventricular pacemaker, known as cardiac resynchronization therapy,
has also been shown to reduce all-cause mortality and hospitalizations
in patients with ischemic or nonischemic cardiomyopathies.48 Given
these trials, ICDs with and without cardiac resynchronization therapy
have become additional tools in the management of HF (see Chapter
15).
PEARLS AND PITFALLS
Patients already on beta-blocker therapy with HF exacerbations should
remain on their current dosage (hemodynamics permitting) without
escalation, whereas those who are naive to beta-blockers should not

144 Cardiology

receive beta-blockade until clinically euvolemic and on a stable ACE

inhibitor dosage.
Accurate bedside determination of jugular venous pressure is crucial to
successful management of HF.
Frequent outpatient evaluation in chronic HF management helps to
reduce hospitalizations.
Care should be taken with the use of nonsteroidal antiinflammatory
drugs, metformin, thiazolidinediones, sildenafil, and antiarrhythmic drugs
because these medications may precipitate exacerbations of HF.
Daily weight measurement at home allows patients to titrate diuretics to
a goal weight.
Atrial fibrillation can be deleterious to patients with systolic and
nonsystolic HF.
Patients who need positive inotropic support with dobutamine or
dopamine may not receive the full benefit of these agents if on betablockers.

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