impaired relaxation of the heart
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o Hematology & Oncologyo Hepatologyo Infectious Diseaseo Nephrologyo Neurologyo Preventive Medicineo Psychiatry & Psychologyo Pulmonary Diseaseo Rheumatologyo Women's Health
DISEASE MANAGEMENT PROJECT MAINo Chapter Indexo Editorial Boardo Editorial Policy
Text-based CME caseso Disease Management Project Clinical Decisions
Published: August 2010
Heart FailureRobert Hobbs
Andrew Boyle
CHAPTER SECTION LINKS
Definition and etiology
Prevalence and risk factors
Pathophysiology and natural history
Signs and symptoms
Diagnosis
Treatment
Prevention and screening
Considerations in special populations
Summary
References
Definition and etiology
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clinicmeded.com/medicalpubs/diseasemanagement/pulmonary/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry-psychology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/preventive-medicine/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hematology-oncology/ 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Heart failure is a clinical syndrome characterized by systemic perfusion inadequate to meet the body's metabolic
demands as a result of impaired cardiac pump function. This may be further subdivided into systolic or diastolic heart
failure. In systolic heart failure, there is reduced cardiac contractility, whereas in diastolic heart failure there is
impaired cardiac relaxation and abnormal ventricular filling (Fig. 1).
Figure 1: Click to Enlarge
The most common cause of heart failure is left ventricular (LV) systolic dysfunction (about 60% of patients). In this
category, most cases are a result of end-stage coronary artery disease, either with a history of myocardial infarction
or with a chronically underperfused, yet viable, myocardium. In many patients, both processes are present
simultaneously (Fig. 2A). Other common causes of LV systolic dysfunction include idiopathic dilated cardiomyopathy,
valvular heart disease, hypertensive heart disease, toxin-induced cardiomyopathies (e.g., doxorubicin, herceptin,
alcohol), and congenital heart disease (seeFig. 2B).
Figure 2: Click to Enlarge
Right ventricular systolic dysfunction is usually a consequence of LV systolic dysfunction. It can also develop as a
result of right ventricular infarction, pulmonary hypertension, chronic severe tricuspid regurgitation, or arrhythmogenic
right ventricular dysplasia. A less-common cause of heart failure is high-output failure caused by thyrotoxicosis,
arteriovenous fistulae, Paget's disease, pregnancy, or severe chronic anemia.
Diastolic LV dysfunction (impaired relaxation) usually is related to chronic hypertension or ischemic heart disease.
Other causes include restrictive, infiltrative, and hypertrophic cardiomyopathies. Inadequate filling of the right ventricle
can result from pericardial constriction or cardiac tamponade.
Back to Top
Prevalence and risk factors
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Heart failure is a common syndrome, especially in older adults. Although more patients survive acute myocardial
infarction because of reperfusion therapy, most have at least some residual LV systolic dysfunction, which can lead to
heart failure. Currently, 5 million Americans are afflicted with heart failure, approximately 2% of the
population.1Patients with heart failure account for about 1 million hospital admissions annually, and another 2 million
patients have heart failure as a secondary diagnosis. One third of these patients are readmitted within 90 days for
recurrent decompensation.
Patients at high risk for developing heart failure are those with hypertension, coronary artery disease, diabetes
mellitus, family history of cardiomyopathy, use of cardiotoxins, and obesity.
Back to Top
Pathophysiology and natural history
Although much progress has been made in the treatment of heart failure, there is a high overall annual mortality (5%-
20%), particularly in patients with New York Heart Association (NYHA) Class IV symptoms.2Many patients succumb
to progressive pump failure and congestion, although one half die from sudden cardiac death. Some patients die from
end-organ failure resulting from inadequate systemic organ perfusion, particularly to the kidneys. Indicators of poor
cardiac prognosis include renal dysfunction, cachexia, valvular regurgitation, ventricular arrhythmias, higher NYHA
heart failure class, lower LV ejection fraction (LVEF), high catecholamine and B-type natriuretic peptide (BNP) levels,
low serum sodium level, hypocholesterolemia, and marked LV dilation. Patients with combined systolic and diastolic
LV dysfunction also have a worse prognosis than patients with either in isolation.3
In LV systolic dysfunction, the body activates several neurohormonal pathways to increase circulating blood volume.
The sympathetic nervous system increases heart rate and contractility, causes arteriolar vasoconstriction in
nonessential vascular beds, and stimulates secretion of renin from the juxtaglomerular apparatus of the kidney.
Unfortunately, catecholamines aggravate ischemia, potentiate arrhythmias, promote cardiac remodeling, and are
directly toxic to myocytes. Stimulation of the renin-angiotensin system as a result of increased sympathetic
stimulation and decreased renal perfusion results in further arteriolar vasoconstriction, sodium and water retention,
and release of aldosterone. An increased aldosterone level, in turn, leads to sodium and water retention, endothelial
dysfunction, and organ fibrosis.
In heart failure, baroreceptor and osmotic stimuli lead to vasopressin release from the hypothalamus, causing
reabsorption of water in the renal collecting duct. Although these neurohormonal pathways initially are compensatory
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and beneficial, eventually they are deleterious, and neurohormonal modulation is the basis for modern treatment of
heart failure.
In contrast, natriuretic peptides are hormones released by secretory granules in cardiac myocytes in response to
myocardial stretching. They have a beneficial influence in heart failure, including systemic and pulmonary
vasodilation, possible enhancement of sodium and water excretion, and suppression of other neurohormones.
With continuous neurohormonal stimulation, the left ventricle undergoes remodeling consisting of LV dilation and
hypertrophy, such that stroke volume is increased without an actual increase in EF. This is achieved by myocyte
hypertrophy and elongation. LV chamber dilation causes increased wall tension, worsens subendocardial myocardial
perfusion, and can provoke ischemia in patients with coronary atherosclerosis. Furthermore, dilation of the LV
chamber can cause mitral annular dilatation and mitral regurgitation, leading to pulmonary congestion.
In diastolic dysfunction, the primary abnormality is impaired LV relaxation, causing high diastolic pressures and poor
filling of the ventricle. To increase diastolic filling, left atrial and pulmonary capillary pressures increase and
pulmonary edema ensues. As a result, patients are often symptomatic with exertion when increased heart rate
reduces LV filling time and circulating catecholamines worsen diastolic dysfunction.++
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+-*
The American College of Cardiology (ACC) and American Heart Association (AHA) have developed a classification of
heart failure based on stages of the syndrome (Table 1).4Stage A includes patients who are at risk for developing
heart failure but who have no structural heart disease at present. The management strategy in this group is
prevention of heart failure. Stage B includes patients with structural heart disease but no symptoms. The
management goal is prevention of LV remodeling leading to heart failure. Stage C includes patients with structural
heart disease with current or prior symptomatic heart failure. Diuretics, digoxin, and aldosterone antagonists may be
added to angiotensin-converting enzyme (ACE)
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inhibitors and beta blockers, depending on the severity of symptoms. Cardiac resynchronization therapy also may be
considered. Stage D includes patients with severe refractory heart failure. Physicians should consider either end-of-
life care or high-technology therapies such as cardiac transplantation or mechanical circulatory support, based on
individual cases.
Table 1: American College of CardiologyAmerican Heart Association Classification of ChronicHeart Failure
Stage Description
A****++ Hypertension, diabetes mellitus, CAD, family history of cardiomyopathy
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: High risk for developing heart failure
B: Asymptomatic heart failure Previous MI, LV dysfunction, valvular heart disease
C: Symptomatic heart failure Structural heart disease, dyspnea and fatigue, impaired exercise tolerance
D: Refractory end-stage heart failure Marked symptoms at rest despite maximal medical therapy
CAD, coronary artery disease; LV, left ventricular; MI, myocardial infarction.
Back to Top
Signs and symptoms
There is a wide spectrum of potential clinical manifestations of heart failure.5Most patients have signs and symptoms
of fluid overload and pulmonary congestion, including dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.
Patients with right ventricular failure have jugular venous distention, peripheral edema, hepatosplenomegaly, and
ascites. Others, however, do not have congestive symptoms but have signs and symptoms of low cardiac output,
including fatigue, effort intolerance, cachexia, and renal hypoperfusion. The NYHA functional classification scheme is
used to assess the severity of functional limitations and correlates fairly well with prognosis (Table 2).
Table 2: New York Heart Association (NYHA) Heart Failure Symptom Classification System
NYHA
ClassLevel of Impairment
I No symptom limitation with ordinary physical activity
II Ordinary physical activity somewhat limited by dyspnea (e.g., long-distance walking, climbing two
flights of stairs)
III Exercise limited by dyspnea with moderate workload (e.g., short-distance walking, climbing one flight
of stairs)
IV Dyspnea at rest or with very little exertion
On physical examination, patients with decompensated heart failure may be tachycardic and tachypneic, with bilateral
inspiratory rales, jugular venous distention, and edema. They often are pale and diaphoretic. The first heart sound
usually is relatively soft if the patient is not tachycardic. An S3 and often an S4 gallop will be present. Murmurs of
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mitral or tricuspid regurgitation may be heard. Paradoxical splitting of S2 may be present because of delayed
mechanical or electrical activation of the left ventricle. Patients with compensated heart failure will likely have clear
lungs but a displaced cardiac apex. Patients with decompensated diastolic dysfunction usually have a loud S4(which
may be palpable), rales, and often systemic hypertension.
Back to Top
Diagnosis
The initial evaluation of new-onset heart failure should include an electrocardiogram, chest radiograph, and BNP
assay. EK6 findings of LV hypertrophy, left bundle branch block, intraventricular conduction delay, and nonspecific
ST-segment and T wave changes support a diagnosis of heart failure. Q waves in contiguous leads strongly implicate
a previous myocardial infarction and coronary atherosclerosis as the cause. Chest radiographic findings of heart
failure include cardiomegaly, pulmonary vascular redistribution, pulmonary venous congestion, Kerley B lines,
alveolar edema, and pleural effusions.
The single most useful diagnostic test is the echocardiogram, which can distinguish between systolic and diastolic
dysfunction. If systolic dysfunction is present, regional wall motion abnormalities or LV aneurysm suggest an ischemic
basis for heart failure, whereas global dysfunction suggests a nonischemic cause. Echocardiography is helpful in
determining other causes, such as valvular heart disease, cardiac tamponade, or pericardial constriction, and
provides useful clues about infiltrative and restrictive cardiomyopathies. Echocardiography can also provide
meaningful prognostic information about diastolic function, severity of hypertrophy, chamber size, and valvular
abnormalities. In many cases, however, the exact cause of the heart failure cannot be discerned from the
echocardiogram.
Cardiac catheterization can detect coronary atherosclerosis as the cause of heart failure. Severe coronary artery
disease is so prevalent that coronary angiography routinely should be performed to exclude this cause and, if found,
should lead to an assessment of myocardial viability, with a goal of revascularization. Coronary computed
tomographic angiography (CTA) might also be a suitable alternative to exclude coronary artery disease in select
patients.
Magnetic resonance imaging (MRI) is useful in assessing for arrhythmogenic right ventricular dysplasia, myocardial
viability, and infiltrative cardiomyopathies.
Objective information about functional capacity can be obtained from metabolic (cardiopulmonary) exercise testing.
This test can distinguish ventilatory from cardiac limitations in patients with exertional dyspnea. A peak oxygen
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consumption higher than 25 mL/kg/min is normal for middle-age adults, but a value lower than 14 mL/kg/min
indicates severe cardiac limitation and poor prognosis.
A useful diagnostic test for the detection of heart failure is the BNP assay.6, 7
BNP levels correlate with severity of
heart failure and decrease as a patient reaches a compensated state. This blood test may be useful for distinguishing
heart failure from pulmonary disease. Because smokers often have both these clinical diagnoses, differentiating
between them may be challenging.
The routine use of invasive hemodynamic monitoring to guide the management of decompensated heart failure has
not proved to be beneficial. However, invasive hemodynamic monitoring may be warranted if unanticipated
responses to therapies are observed or for diagnostic purposes if the diagnosis is uncertain.
Back to Top
Summary
Jugular venous distention is a useful physical sign of heart failure.
The lungs usually are clear in chronic heart failure.
The BNP assay improves the accuracy of diagnosing heart failure.
Echocardiography is the single most useful diagnostic modality.
Coronary angiography confirms or excludes coronary artery disease as the cause.
Back to Top
Treatment
Lifestyle Modifications
Dietary sodium and fluid restrictions should be implemented in all patients with congestive heart failure. Limiting
patients to 2 g/day of dietary sodium and 2 L/day of fluid will lessen congestion and decrease the need for diuretics.
Patient education guidelines are listed in Box 1.
Box 1: Patient Education Guidelines
2-g Sodium diet
Monitoring weight daily
2-L Fluid restriction
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Monitoring blood pressure
Medications
Smoking cessation
Light aerobic exercise
Knowing whom to call
Achieving ideal weight
Follow-up visits
Cardiac rehabilitation can improve symptoms and exercise tolerance in patients with heart failure. This will also
reduce or prevent skeletal muscle atrophy that could worsen exercise tolerance. Weight loss is encouraged in obese
patients. Patients should be counseled about smoking cessation.
Medical OptionsAngiotensin-Convert ing Enzyme Inhib i tors
All patients with LV systolic dysfunction should be treated with an ACE inhibitor unless they have a contraindication or
intolerance to the drug (stages B to D). ACE inhibitors are useful in preventing heart failure in patients at high risk
who have atherosclerotic cardiovascular disease, diabetes mellitus, or hypertension with associated cardiovascular
risk factors (stage A). ACE inhibitors and beta blockers should be used for all patients with a history of myocardial
infarction, regardless of LVEF. Vasodilation and neurohormonal modulation with ACE inhibitors improve mortality,
heart failure symptoms, exercise tolerance, and LVEF as well as reduce emergency room visits and
hospitalizations.8-10
The dose of ACE inhibitors should be titrated to the maximum tolerated dose11
or the target dose as listed in Table 3.
Approximately 10% to 20% of patients do not tolerate ACE inhibitors. The main side effect from ACE inhibition is a
dry hacking cough, which can necessitate change to an angiotensin II receptor blocker (ARB). Most patients who
cough on ACE inhibitors have this symptom because of congestive heart failure rather than ACE inhibitor intolerance
and might improve with further diuresis. Two uncommon side effects of ACE inhibitors are angioedema and acute
renal failure (caused by bilateral renal artery stenosis); both necessitate immediate cessation of the drug.
Table 3: Angiotensin-Converting Enzyme Inhibitor Dosing
Agent Target Dose (mg) Frequency
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Captopril* 50 tid
Enalapril* 20 bid
Lisinopril* 40 qd
Ramipril* 5 bid
Quinapril* 20 bid
Fosinopril* 20 bid
Benazepril* 20 qd
Trandolapril 4 qd
*FDA-approved for treatment of heart failure.
FDA-approved for treatment of postmyocardial infarction heart failure.
ACE inhibitors should be used in combination with beta blockers in most patients. Either agent may be started first.
Angiotensin Receptor Blockers
ARBs block the effects of angiotensin II at the receptor level (Table 4). In clinical trials, these agents were found to be
superior to placebo but no better than ACE inhibitors in improving mortality.12
ARBs are recommended as second-line
therapy in patients who do not tolerate ACE inhibitors because of cough or angioedema (stages B to D). ARBs should
not be substituted for ACE inhibitors in cases of hyperkalemia or renal dysfunction. ARBs may have morbidity
benefits for patients with diastolic heart failure.13
Table 4: Angiotensin Receptor Blocker Dosing
Agent Initial Dose (mg) Maximum Dose (mg)
Valsartan* 80 320
Candesartan* 4 32
Losartan 25 100
Irbesartan 75 300
Telmisartan 40 80
Eprosartan 400 800
Olmesartan 20 40
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*FDA-approved for treatment of heart failure.
Beta Blockers
Three beta blockerscarvedilol, metoprolol succinate (Toprol XL), and bisoprololhave been shown to improve
survival in patients with heart failure (Table 5).14-16
Metoprolol tartrate is not U.S Food and Drug Administration (FDA)-
approved for heart failure and was less effective than carvedilol in preventing sudden death.17
The exact mechanism
of beta blocker action is unclear, but it likely involves antiarrhythmic, anti-ischemic, antiremodeling, and antiapoptotic
properties, as well as improved beta receptor pathway function. Myocardial oxygen consumption is reduced wi th beta
blockers, primarily because of a reduction in heart rate.
Table 5: Beta Blocker Dosing
Beta Blocker Initial Dose (mg) Target Dose
Carvedilol* 3.125 mg bid 50 mg bid if >75 kg
25 mg bid if
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should be prescribed to most patients. Digoxin may be prescribed for patients with LV systolic dysfunction who
remain symptomatic while receiving standard medical therapy, particularly if they are in atrial fibrillation.
Table 6: Other Heart Failure Drugs
Agent Initial DoseMaximum
DoseGuidelines
Digoxin 0.125 mg
qd
0.25 mg qd Reduce dose in women with renal dysfunction, with amiodarone
Hydralazine 25 mg qid 100 mg qid Use concurrently with nitrates to prevent coronary steal
Isosorbide
dinitrate
20 mg tid 80 mg tid Also useful for angina pectoris
Spironolactone 25 mg qd 50 mg qd Weak diuretic, risk of hyperkalemia, avoid in renal dysfunction;
gynecomastia
Eplerenone 25 mg qd 50 mg qd Risk of hyperkalemia, avoid in renal dysfunction; no
gynecomastia
Diuretics
Diuretics should be used in combination with an ACE inhibitor (or ARB) and a beta blocker. Most patients with heart
failure have some degree of symptomatic congestion and benefit from diuretic therapy.19
Usually, a loop diuretic is
required, with the addition of a thiazide diuretic in patients refractory to the loop diuretic alone (diuretic resistance or
cardiorenal syndrome). Although useful for symptomatic relief, diuretics have not been shown to improve survival,
and they can cause azotemia, hypokalemia, metabolic alkalosis, and elevation of neurohormone levels (Table 7).
Table 7: Diuretic Dosing
Generic Name ClassInitial Dose
(mg)Special Considerations
Furosemide Loop 20 Can be given intravenously; PO equivalent is twice the IV dose
Bumetanide Loop 0.5 Good oral bioavailability; can be given intravenously; oral and IV
doses are the same
Torsemide Loop 5-10 Best oral availability
Ethacrynic acid Loop 50 Only diuretic with no sulfhydryl group; used if allergic to furosemide
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Hydrochlorothiazide Thiazide 12.5 Weak diuretic; used mainly for hypertension
Metolazone Thiazide 2.5 Give1/2 hr before furosemide; only available orally; high risk of
hypokalemia
Aldosterone Antagonists
Two aldosterone antagonists have been approved for patients with heart failure: spironolactone and eplerenone. A
30% reduction in mortality and hospitalizations has been reported when spironolactone is added to standard therapy
for patients with NYHA Class III or IV heart failure and a serum creatinine less than 2.5.20
A 15% reduction in the risk
of death and hospitalization has been reported in patients who had heart failure and an LVEF lower than 40% after a
myocardial infarction and who were treated with eplerenone.21
Aldosterone inhibition can prevent sodium and water retention, endothelial dysfunction, and myocardial fibrosis. With
aldosterone antagonists, diligent monitoring of serum potassium levels is mandatory, because patients can develop
hyperkalemia (see Table 6). These drugs should be avoided in patients with a creatinine level higher than 2.5 mg/dL.
Eight percent of men develop gynecomastia with spironolactone but not with eplerenone. Data from studies of mild
heart failure are lacking, and so these drugs should be reserved for patients with moderately severe to severe heart
failure. Therefore, the addition of an aldosterone antagonist is reasonable for select patients with moderately severe
to severe symptoms of heart failure and reduced LVEF who can be carefully monitored for preserved renal function
and normal potassium concentration.
Hydralazine and Nitrates
Hydralazine is an arterial dilator and nitrates are venous dilators. Hydralazine also prevents nitrate tachyphylaxis
(loss of effect). The combination of hydralazine and nitrate is inferior to an ACE inhibitor in improving survival.22
Once-
daily dosing of ACE inhibitors is easier than giving nitrates three times daily and giving hydralazine four times daily
(see Table 6). The combination of hydralazine and nitrate is reasonable for patients who have current or prior
symptoms of heart failure and reduced LVEF and who cannot be given an ACE or ARB because of drug intolerance,
hyperkalemia, or renal insufficiency. Hydralazine and nitrate also may be added to ACE inhibitors and beta blockers
when additional afterload reduction is needed or pulmonary hypertension is present. A fixed-dose combination tablet
has been approved for treating heart failure in African Americans.
Other Medical Therapies
Patients with known coronary artery disease should be treated with aspirin and a statin to lower the low-density
lipoprotein (LDL) level to 70 mg/dL. Calcium channel antagonists have not been proved beneficial in heart failure
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patients. Dihydropyridines such as amlodipine have a neutral effect on heart failure and may be useful for treating
concomitant hypertension or angina pectoris.23
The use of warfarin to prevent cardioembolic strokes remains controversial in the absence of atrial arrhythmias,
because the risk appears to be relatively low (1%-3% per year). Warfarin therapy is recommended for patients with
atrial arrhythmias, previous embolic event, cardiac thrombi, or LV aneurysms.
Specific therapies for treating atrial fibrillation, sleep apnea, anemia, obesity, and thyroid disease may improve the
symptoms and functional limitations of heart failure.
Intravenous Inotropes and VasodilatorsDobutamine
Dobutamine (Table 8) enhances contractility by directly stimulating cardiac 1 receptors.24
Intravenous (IV)
dobutamine infusions, sometimes guided by hemodynamic monitoring, may be useful for select patients with acute
hypotensive heart failure or shock. The dose of dobutamine should always be titrated to the lowest dose compatible
with hemodynamic stability to minimize adverse events. As with many inotropes, long-term infusions of dobutamine
can increase mortality, principally because of its arrhythmogenic effect. As a result, chronic dobutamine infusions are
reserved for palliative symptom relief or for patients who have an implantable cardioverter-defibrillator (ICD) and are
awaiting heart transplantation. Intermittent outpatient infusions of dobutamine are not recommended for routine
management of heart failure.
Table 8: Intravenous Agents Used for Treatment of Heart Failure
Drug Dose Special Considerations
Dobutamine 2-20 g/kg/min receptor agonist; proarrhythmic; heart rate; ischemia
Milrinone 0.25-0.75 g/kg/min Phosphodiesterase inhibitor; vasodilator; may improve pulmonary
hypertension; used for patients taking beta blockers; proarrhythmic
Nitroglycerin 10-500 g/min Anti-ischemic; vasodilator; limited by vascular headache; hypotension,
tolerance develops rapidly
Nitroprusside 10-500 g/min Thiocyanate accumulation in renal failure; may provoke ischemia by
coronary steal; vasodilator; should be given only in intensive care unit
Nesiritide 2-g/kg bolus; then
0.01 g/kg/min
Fixed weight-based dose; vasodilator; occasional hypotension
Mil r inone
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Milrinone (see Table 8) is a phosphodiesterase inhibitor that enhances contractility. Milrinone is useful for patients
with low-output heart failure and pulmonary hypertension because it is a more potent pulmonary vasodilator than
dobutamine. Milrinone, in contrast to dobutamine, is also useful for patients on chronic oral beta blocker therapy who
develop acute heart failure. The OPTIME (Outcomes of a Prospective Trial of Intravenous Milrinone for
Exacerbations of Chronic Heart Failure) study, involving the routine intravenous infusion of milrinone for 48 hours
during hospitalization for decompensated heart failure, failed to show clinical benefit and was associated with an
increased risk of atrial arrhythmias and hypotension.25
Similar to dobutamine, intermittent outpatient milrinone
infusions are not recommended for routine management of heart failure.
Nitroglycerin
Nitroglycerin (see Table 8) is a nitric oxide donor that causes vasodilation. It is a venodilator at low doses and an
arterial dilator at higher doses, lowering intracardiac pressures and alleviating pulmonary congestion.
Nitroglycerin also dilates coronary arteries, making it useful for patients with heart failure and myocardial ischemia. IV
nitroglycerin requires dose titration to achieve therapeutic goals. The effectiveness of prolonged infusions is limited by
the development of tachyphylaxis (loss of effect) within the first 24 hours.
Sodium Ni troprusside
Sodium nitroprusside (see Table 8) is a nitric oxide donor and a potent short-acting arterial and venous dilator.
Nitroprusside infusions generally are reserved for patients in an intensive care unit. During nitroprusside infusions,
patients should be converted to oral vasodilators such as ACE inhibitors, ARBs, or hydralazine and a nitrate.
Sodium nitroprusside should be infused for a short duration in patients with severe renal disease to prevent
accumulation of thiocyanate, the by-product of hepatic metabolism of nitroprusside, which is excreted by the kidney.
Nitroprusside should be avoided in patients with active ischemia because of its potential for coronary steal syndrome,
which shunts blood away from the ischemic myocardium to well-perfused muscle.
Figure 3: Click to Enlarge
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Nesir i t ide
Nesiritide (see Table 8), synthetic BNP, is an arterial and venous vasodilator with modest diuretic and natriuretic
properties.26
Nesiritide increases cardiac output by afterload reduction without increasing heart rate or oxygen
consumption. It modulates the vasoconstrictor and sodium-retaining effects of other neurohormones. Nesiritide is
administered as a weight-based bolus followed by continuous IV infusion in patients who have acutely
decompensated heart failure and who have dyspnea at rest or with minimal activity. It may be started in the
emergency department and does not require invasive hemodynamic monitoring or frequent titration. Tolerance to the
drug does not occur and it is not arrhythmogenic. Intermittent outpatient infusions of nesiritide are not recommended
for the routine management of heart failure.
Device Therapies for Heart FailureCardiac Resynch ronization Therapy
Several clinical trials have shown the potential benefit of cardiac resynchronization therapy (CRT) for patients with
severe symptomatic heart failure and a wide QRS complex.27, 28
Symptomatic improvement is achieved in
approximately 70% of patients because of improved ventricular contraction, ventricular reverse-remodeling, and
reduction of mitral regurgitation. With cardiac resynchronization therapy (biventricular pacing), a third electrode is
implanted in a left cardiac vein via the coronary sinus so that the right and left ventricles are paced in a synchronous
fashion (Fig. 3). Optimal synchronization of atrial and ventricular contraction is achieved with echocardiographic
guidance. Guidelines for resynchronization therapy are listed in Box 2.
Box 2: Guidelines for Resynchronization Therapy
NYHA Class III or IV heart failure symptoms
Symptomatic despite medications
Left ventricular ejection fraction 35% (consider cardiac resynchronization therapy-defibrillator)
Wide QRS (>120 msec; left bundle branch block, intraventricular conduction delay)
Evidence of dyssynchrony
Defibri l lator Therapy
Approximately 50% of patients with heart failure die suddenly. Implantation of an ICD can improve survival in certain
subsets of heart failure patients and has been shown to be superior to antiarrhythmic drug therapy in preventing
sudden death.29-32
Current indications for defibrillator therapy are listed in Box 3. Cardiac resynchronization therapy
can be combined with an ICD as a single device if the patient meets criteria for both therapies, as is often the case.
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Box 3: Indications for an Implantable Cardioverter-Defibrillator
Cardiac arrest survivor
Sustained ventricular tachycardia
Inducible ventricular tachycardia
Ischemic cardiomyopathy,*LVEF 35%
Dilated cardiomyopathy, LVEF 35% with symptoms
*40-day waiting period after myocardial infarction, stenting, bypass surgery.
9-month waiting period after diagnosis.
LVEF, left ventricular ejection fraction.
Ultrafi l trat ion Therapy
Ultrafiltration therapy is an effective method for extracting sodium and fluid from volume overloaded heart failure
patients with resistance to diuretic therapy. A reduction in rehospitalization has been observed compared with
intravenous diuretic therapy.33
Figure 4: Click to Enlarge
Surgical OptionsLeft Ventr icu lar Assist Devices (LVADs )
Certain patients with end-stage heart failure and NYHA Class IV symptoms are referred to a tertiary care center for
mechanical circulatory support.34, 35
At present, LV assist devices (LVADs) are used either as a bridge to cardiac
transplantation in patients who are appropriate transplantation candidates or as destination therapy in patients
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ineligible for transplantation. The inflow cannula of an LVAD is connected to the apex of the left ventricle. Blood is
mechanically pumped by the device via the outflow cannula to the aorta (Fig. 4). Complications following LVAD
implantation are common and often life threatening; these include stroke, infection, perioperative coagulopathy and
bleeding, and multisystem organ failure. Newer rotary continuous flow LVADs have proven to be more durable and
are associated with fewer complications.36
Ventr icu lar Reconstruct ion Surgery
Ventricular reconstruction surgery, also called ventricular remodeling surgery or a Dor procedure, has been
performed for heart failure secondary to ischemic cardiomyopathy.37
It consists of several components: coronary
artery bypass grafting, mitral and tricuspid valve repair, resection of LV scar or aneurysm, reshaping the left ventricle
from a spherical to an elliptic shape, and epicardial LV pacing lead placement (Fig. 5). The STICH trial failed to show
benefit over standard bypass or value surgery. Thus, the future of ventricular reconstruction surgery is uncertain.
Figure 5: Click to Enlarge
Cardiac Transplantation
Cardiac transplantation is reserved for otherwise healthy patients who have end-stage heart failure with severely
impaired functional capacity despite optimal medical therapy (Fig. 6).38
Patients are excluded from transplantation if
they have chronic medical comorbidities, pulmonary hypertension, active infection, psychosocial contraindications, or
medical noncompliance. Survival after cardiac transplantation is about 85% at 1 year, and median life expectancy is
approximately 10 years. Complications limiting survival include rejection, infection, transplant coronary vasculopathy,
and malignancy. Following cardiac transplantation, patients are subjected to lifelong immunosuppression to prevent
rejection, which in turn renders them susceptible to various opportunistic infections and malignancies.
Back to Top
Summary
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All heart failure patients should receive an ACE inhibitor and a beta blocker.
Diuretics are needed in most patients to manage fluid retention.
Digoxin is reserved for patients with signs and symptoms of heart failure.
Aldosterone antagonists are used in patients with Class III or IV heart failure.
ARBs or a hydralazine plus nitrate may be added to standard therapy for additional benefit.
Back to Top
Prevention and screening
Patients classified as stage A are at high risk for heart failure but without structural heart disease or heart failure
symptoms. They include patients with hypertension, diabetes mellitus, obesity, coronary artery disease, or use of
cardiotoxins and those with a family history of cardiomyopathy. Preventive therapies include treatment of lipid
disorders and hypertension, smoking cessation, regular exercise, avoidance of excess alcohol and illicit drugs, and
ACE inhibitors in appropriate patients. Patients with stage B heart failure have structural heart disease, but no
symptoms of heart failure. These include patients with previous myocardial infarction, LV systolic dysfunction, and
asymptomatic valvular disease. Therapies are prescribed to prevent LV remodeling. These include all preventive
strategies for stage A, as well as ACE inhibitors and beta blockers for appropriate patients.
Figure 6: Click to Enlarge
Back to Top
Considerations in special populations
Heart failure is slightly more common in women than men. In women, heart failure occurs later in life, is often related
to hypertension, and is often associated with preserved LV systolic function. Women tend to have more prominent
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heart failure manifestations and more hospitalizations but better overall survival (except with coronary artery disease)
than men. Heart failure therapeutic agents are not gender specific.
African Americans appear to benefit from a combination of hydralazine and nitrates when added to conventional heart
failure therapy.39
Back to Top
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Back to Top
Suggest Readings
Adams KF, Lindenfeld J, Arnold JMO, et al: Executive summary: HFSA 2006 comprehensive heart failure
practice guideline. J Cardiac Failure. 2006, 12: 10-38.
American Heart Association. Heart Disease and Stroke Statistics-2008 Update. Dallas: American Heart
Association, 2008.
Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive
heart failure. N Engl J Med. 2005, 352: 225-237.
Brater DC. Diuretic therapy. N Engl J Med. 1998, 339: 387-395.
Cleland JGF, Daubert JC, Erdman E, et al: The effect of cardiac resynchronization on morbidity and
mortality in heart failure. N Engl J Med. 2005, 352: 1539-1549.
Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N
Engl J Med. 1997, 336: 525-533.
Hjalmarson A, Goldstein S, Fagerberg B, et al: Effects of controlled-release metoprolol on total mortality,
hospitalizations, and well-being in patients with heart failure: The Metoprolol CR/XL Randomized
Intervention Trial in congestive heart failure (MERIT-HF). JAMA. 2000, 283: 1295-1302.
Hunt SA, Abraham WT, Chin MH, et al: American College of Cardiology; American Heart Association Task
Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and
Lung Transplantation; Heart Rhythm Society: ACC/AHA 2005 Guideline Update for the Diagnosis and
Management of Chronic Heart Failure in the Adult: A report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for
the Evaluation and Management of Heart Failure): Developed in collaboration with the American College of
Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart
Rhythm Society. Circulation. 2005, 112: e154-e235.
Mueller C, Scholer A, Laule-Kilian K, et al: Use of B-type natriuretic peptide in the evaluation and
management of acute dyspnea. N Engl J Med. 2004, 350: 647-654.
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: 1309-1321.
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#top -
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Pitt B, Zannad F, Remme WJ, et al: The effect of spironolactone on morbidity and mortality in patients with
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