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Table of Contents

Revised
September 28, 2004

Robert Hobbs,MD

Department
of Cardiology
The Cleveland Clinic

Andrew Boyle,MD

Division
of Cardiology
University of Minnesota

Print Chapter

DEFINITION

Definition

Etiology

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Therapies and Outcomes

References

Heart failure is a clinical syndrome characterized by inadequate systemic perfusion to meet the body's metabolic demands as a result of impaired cardiac pump function. This may be further subdivided into either 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. The body, sensing inadequate organ perfusion, activates multiple systemic neurohormonal pathways which compensate initially by redistributing blood flow to vital organs, but later exacerbate the patient's symptoms and lead to clinical deterioration.

The most common cause of heart failure is left ventricular 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(s) or chronically underperfused yet viable myocardium. In many patients, both processes are present simultaneously.

Severe coronary artery disease is so prevalent that coronary angiography routinely should be performed to exclude this etiology and, if found, should lead to an assessment of myocardial viability with an aim for revascularization.

Other common causes of left ventricular systolic dysfunction include idiopathic dilated cardiomyopathy, valvular heart disease, hypertensive heart disease, toxin-induced cardiomyopathies (ie, doxorubicin and alcohol), and congenital heart disease.

Right ventricular systolic dysfunction most commonly is a consequence of left ventricular systolic dysfunction. It may also develop as a result of right ventricular infarction, pulmonary hypertension, chronic severe tricuspid regurgitation, and arrhythmogenic right ventricular dysplasia.

Diastolic left ventricular dysfunction usually is related to chronic hypertension or ischemic heart disease. Other etiologies include restrictive, infiltrative and hypertrophic cardiomyopathies. Inadequate filling of the right ventricle may result from either pericardial constriction or cardiac tamponade.

A less common cause of heart failure is high output failure caused by thyrotoxicosis, arteriovenous fistulae, Paget's disease, pregnancy, or severe chronic anemia.

Heart failure is a common syndrome, especially in the elderly. Although more patients survive acute myocardial infarctions because of reperfusion therapy, most have at least some residual left ventricular systolic dysfunction which may lead to heart failure. Currently, 4.7 million Americans are afflicted with heart failure, approximately 1.5% of the population.¹ Patients with heart failure account for about 1,000,000 hospital admissions annually, and another 2,000,0000 hospitalizations occur with heart failure as a secondary diagnosis. One-third of these patients are re-admitted within 90 days for recurrent decompensation.

Although much progress has been made in the treatment of heart failure, there is a 20% overall annual mortality, particularly in patients with New York Heart Association Class IV symptoms.² Many patients succumb to progressive pump failure and congestion, although half die from either tachycardia or bradycardia-induced 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 ventricular arrhythmias, higher NYHA Heart Failure Class, lower left ventricular ejection fraction, high catecholamine and B-type natriuretic peptide levels, low serum sodium, hypocholesterolemia, and marked left ventricular dilatation. Patients with combined systolic and diastolic left ventricular dysfunction also have a worse prognosis than patients with either in isolation.³

In left ventricular systolic dysfunction, regardless of the etiology, cardiac output is low and pulmonary pressures are high, leading to pulmonary congestion. Initially, as a direct result of inadequate cardiac output and systemic perfusion, the body activates several neurohormonal pathways in order to increase circulating blood volume. The sympathetic nervous system increases heart rate and contractility, both of which increase cardiac output. Circulating catecholamines also cause arteriolar vasoconstriction in non-essential vascular beds and stimulate 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. Increased aldosterone, 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. Endothelin levels are elevated in heart failure and correlate with severity of disease and prognosis. Endothelin is an endogenous vasoconstrictor and growth factor. Levels of the pro-inflammatory cytokines also are elevated in heart failure, and contribute to cardiac cachexia and apoptosis. Although these neurohormonal pathways initially are compensatory and beneficial, eventually, they are deleterious, and neurohormonal modulation is the basis for modern treatment for heart failure.

In contrast, natriuretic peptides are hormones released by secretory granules in cardiac myocytes. They have a beneficial influence in heart failure, including systemic and pulmonary vasodilation, enhanced sodium and water excretion, and suppression of other neurohormones.

With continuous neurohormonal stimulation, the left ventricle undergoes remodeling consisting of left ventricular dilatation and hypertrophy, such that stroke volume is increased without an actual increase in ejection fraction. This is achieved by myocyte hypertrophy and elongation.

Left ventricular chamber dilatation causes increased wall tension, worsens subendocardial myocardial perfusion, and may provoke ischemia in patients with coronary atherosclerosis. Furthermore, left ventricular chamber dilatation may cause separation of the mitral leaflets and mitral regurgitation leading to pulmonary congestion. Enhanced neurohormonal stimulation of the myocardium also causes apoptosis or programmed cell death, worsening of ventricular contractility and death.

In diastolic dysfunction, the primary abnormality is impaired left ventricular relaxation causing high diastolic pressures and poor filling of the ventricles. In order to increase diastolic filling, left atrial pressure increases until it exceeds the hydrostatic and oncotic pressures in the pulmonary capillaries and pulmonary edema ensues. As a result, patients are often symptomatic with exertion when increased heart rate reduces left ventricular filling time and circulating catecholamines worsen diastolic dysfunction.

The American College of Cardiology and American Heart Association developed a classification of heart failure based on stages of the syndrome (Table 1).⁴

Stage 1 includes patients at risk of developing heart failure but who have no structural heart disease at present. These include patients with hypertension, diabetes mellitus, coronary artery disease, use of cardiac toxins, and familial history of cardiomyopathy. Strategies to prevent ventricular remodeling, including ACE inhibitors in selected cases, are advised.

Stage 2 includes patients with structural heart disease but no symptoms. The use of ACE inhibitors and beta-blockers is recommended.

Stage 3 includes patients with structural heart disease and symptomatic heart failure. Diuretics, digoxin, and aldosterone antagonists may be added to ACE inhibitors and beta-blockers depending upon the severity of symptoms. Cardiac resynchronization therapy also may be considered in selected patients.

Stage 4 includes patients with severe refractory heart failure. Physicians are urged to consider either end-of-life care or high-tech therapies such as cardiac transplantation, based on individual cases.

There is a wide spectrum of potential clinical presentations with heart failure.⁵ Most patients have signs and symptoms of pulmonary congestion including dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.

Others, however, do not have congestive symptoms but, rather, signs and symptoms of low cardiac output including fatigue, effort intolerance, cachexia, and renal hypoperfusion. Patients with right ventricular failure have jugular venous distention, peripheral edema, hepatosplenomegaly, and ascites.

The NYHA functional classification scheme is used to assess the severity of functional limitations and correlates fairly well with prognosis (Table 2).

On physical examination, a patient with decompensated heart failure may be tachycardic, 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 mitral or tricuspid regurgitation may be heard. Paradoxical splitting of S2 may be present due to 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.

The initial evaluation of new onset heart failure should include an electrocardiogram, chest radiograph, and B-type natriuretic peptide assay. The cardiac rhythm may be normal sinus, sinus tachycardia, or atrial fibrillation. Left ventricular hypertrophy, left bundle branch block, intraventricular conduction delay, and non-specific 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 etiology. Chest radiographic findings of heart failure include cardiomegaly, pulmonary vascular redistribution, pulmonary venous congestion, Kerley B lines, alveolar edema, and pleural effusions.

The most useful diagnostic test is the echocardiogram. Echocardiography can distinguish between systolic and diastolic dysfunction. If systolic dysfunction is present, regional wall motion abnormalities or left ventricular aneurysm suggest an ischemic basis for heart failure, whereas global dysfunction suggests a non-ischemic etiology. Echocardiography is helpful in determining other etiologies such as valvular heart disease, cardiac tamponade, and 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 etiology for heart failure cannot be discerned from the echocardiogram.

Cardiac catheterization may diagnose coronary atherosclerosis as the cause of heart failure. Left ventriculography documents the severity of left ventricular systolic dysfunction and mitral valve regurgitation. Radionuclide ventriculography provides objective data about right and left ventricular systolic function. Because no assessment of diastolic function or valvular function can be obtained, this test is performed less frequently than echocardiography. 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 exercise testing (usually performed at larger centers). This test can distinguish ventilatory from cardiac limitations in patients with exertional dyspnea. A peak oxygen consumption >25 ml/kg/min is normal for middle-age adults, but a value <14 ml/kg/min is indicative of severe cardiac limitation and poor prognosis.

A useful diagnostic test for the detection of heart failure is the B-type natriuretic peptide (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. Since smokers often have both of these clinical diagnoses, differentiating between them may be challenging.

Non-Pharmacological Therapies:

Dietary sodium and fluid restrictions should be implemented in all patients with congestive heart failure. Limiting patients to 2 gm per day of dietary sodium and 2 liters per day of fluid will lessen congestion and lower the need for diuretics.

Cardiac rehabilitation may improve symptoms and exercise tolerance in patients with heart failure. This will also reduce or prevent skeletal muscle atrophy that may worsen exercise tolerance. Weight loss in encouraged in obese patients. Patients should be counseled about smoking cessation.

Standard Medical Therapies:

Angiotensin Converting Enzyme (ACE) Inhibitors
Afterload reduction and neurohormonal modulation with ACE inhibitors improve mortality, heart failure symptoms, exercise tolerance, left ventricular ejection fraction as well as reduce emergency room visits and hospitalizations.^8-10 The dose of ACE inhibitors should be titrated to the maximum that can be tolerated symptomatically¹¹ or the target dose as listed in Table 3. The main side effect from ACE inhibition is cough, which may necessitate change either to an angiotensin-II receptor blocker (ARB) or the combination of hydralazine and nitrate. Of note, most patients who cough on ACE inhibitors have this symptom because of congestive heart failure rather than ACE intolerance, and may improve with further diuresis. Two uncommon side effects of ACE inhibitors are angioedema and acute renal failure (because of bilateral renal artery stenosis), both necessitating immediate cessation of the drug. These recommendations are in agreement with guidelines published by the Heart Failure Society of America (HFSA) and jointly by the American College of Cardiology/American Heart Association (ACC/AHA).

Angiotensin Receptor Blockers (ARBs)
These agents block the effects of angiotensin-II at the receptor level. In clinical trials, these agents were superior to placebo but not better than ACE inhibitors in improving mortality. They improve morbidity when added to ACE inhibitors and have fewer side effects.¹² Angiotensin receptor blockers (ARBs) are recommended as second-line therapy in patients who are intolerant to ACE inhibitors because of cough or angioedema (Table 4). They should not be substituted for ACE inhibitors in cases of hyperkalemia or renal dysfunction. Angiotensin receptor blockers may be useful for the treatment of diastolic heart failure.¹³

Beta-blockers
Three beta-blockers, carvedilol, metoprolol succinate (Toprol XL) and bisoprolol have been shown to improve survival in patients with heart failure (Table 5).^14-16 Metoprolol tartrate is not FDA approved for heart failure and was less effective than carvedilol in preventing sudden death in the COMET Trial.¹⁷ The exact mechanism of beta-blocker action is unclear, but likely involves anti-arrhythmic, anti-ischemic, anti-remodeling, and anti-apoptotic properties as well as improved beta receptor pathway function. Myocardial oxygen consumption is reduced with beta-blockers, primarily due to a reduction in heart rate. In heart failure patients, a beta-blocker should be initiated at a low dose and up titrated slowly as tolerated to target levels.

Guidelines from the HFSA and the ACC/AHA recommend beta-blockers for New York Heart Association (NYHA) Class I - III heart failure. Beta-blockers are now indicated in NYHA Class 4 patients who are euvolemic, based on the findings from the COPERNICUS study.²

Digoxin
Digoxin is a weak oral inotrope whose main effect in heart failure is neurohormonal modulation of centrally mediated sympathetic activity. A large randomized controlled trial showed that the use of digoxin reduces the rate of hospitalization for heart failure, but has no effect on mortality.¹⁸ Digoxin is renally excreted and so dose adjustment is necessary in renal failure (Table 6). A low dose of digoxin (0.125 mg daily) should be prescribed to most patients, especially women. Digoxin currently is recommended in the HFSA and ACC/AHA guidelines for patients with left ventricular systolic dysfunction who remain symptomatic while receiving standard medical therapy, particularly if they are in atrial fibrillation.

Diuretics
Diuretics are useful in relieving congestion and treating hypertension.¹⁹ Most patients with heart failure have some degree of symptomatic congestion and benefit from diuretic therapy. Usually a loop diuretic is required, with the addition of a thiazide diuretic in patients refractory to the loop diuretic alone (Table 7). Although useful for symptomatic relief, diuretics have not been shown to improve survival and may cause azotemia, hypokalemia, metabolic alkalosis and elevation of neurohormones.

Aldosterone Antagonists
The RALES trial was a randomized controlled study that reported a significant mortality benefit of spironolactone, an aldosterone inhibitor, when added to standard therapy in patients with advanced heart failure.²⁰ Aldosterone inhibition may prevent sodium and water retention, endothelial dysfunction and myocardial fibrosis. With spironolactone therapy, diligent monitoring of serum potassium levels is mandatory, as patients may develop hyperkalemia (Table 6). This drug should be avoided in patients with a creatinine >2.5 mg/dl. 8% of men develop gynecomastia with spironolactone. Data in mild heart failure are lacking, and therefore this drug should be reserved for patients with moderately severe-severe heart failure. These recommendations are in agreement with guidelines published by the HFSA. The ACC/AHA guidelines preceded the publication of the RALES trial and do not include these recommendations. The EPHESUS study reported a 15% reduction in the risk of death and hospitalization in patients with heart failure and LVEF <40% after a myocardial infarction, who were treated with the selective aldosterone receptor antagonist, eplerenone.²¹ Gynecomastia was not seen, and the incidence of hyperkalemia was 5.5%.

Hydralazine and Nitrates
Hydralazine and nitrates in combination are effective afterload and preload reducing agents used in ACE-intolerant patients. ACE inhibitors had a mortality benefit over hydralazine and nitrates in a large randomized controlled trial and thus should be the agent of choice.²² The once daily dosing of ACE inhibitors is easier than the TID dosing of nitrates and QID dosing of hydralazine (Table 6). Hydralazine and nitrates may be added to ACE inhibitors when additional vasodilation is needed or pulmonary hypertension is present. These recommendations are in agreement with guidelines published by the HFSA and the ACC/AHA.

Other Medical Therapies
Patients with known coronary artery disease should be treated with aspirin and a statin to lower the low-density lipoprotein (LDL) to 70 mg/dl. Calcium channel antagonists have not been proven to be beneficial in heart failure patients. Short-acting calcium channel antagonists such as nifedipine are contraindicated because they increase mortality, elevate neurohormones, and worsen heart failure. 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, since the risk appears to be relatively low. Warfarin therapy is recommended in patients with atrial arrhythmias, left ventricular thrombi, or left ventricular aneurysms. The INR should be closely monitored in heart failure patients who are taking amiodarone since drug interaction will increase the anticoagulant effect. This recommendation conforms to the published guidelines of the HFSA and the ACC/AHA.

Specific therapies for treating atrial fibrillation, sleep apnea, anemia, obesity, and thyroid diseases may improve the symptoms and functional limitations of heart failure.

Intravenous Inotropes and Vasodilators:

Dobutamine
Dobutamine (Table 8) enhances contractility by directly stimulating cardiac beta-1 receptors.²⁴ Intravenous dobutamine infusions, sometimes guided by hemodynamic monitoring, may be useful in selected patients with acute exacerbations of hypotensive heart failure or shock. The dose of dobutamine should always be titrated to the lowest dose compatible with hemodynamic stability in order to minimize adverse events. As with many inotropes, long-term infusions of dobutamine may increase mortality, principally because of its arrhythmogenic effect. As a result, chronic dobutamine infusions are reserved for palliative symptom relief or for patients with an internal cardioverter defibrillator (ICD) awaiting heart transplantation. Although intermittent outpatient infusions of dobutamine may promote diuresis and temporary relief of congestion, patients may have an inadequate cardiac output and poor exercise tolerance between infusions. Intermittent outpatient infusions of dobutamine are not recommended for routine management of heart failure.

Milrinone
Milrinone (Table 8) is a phosphodiesterase-III inhibitor that increases intracellular cyclic adenosine monophosphate (cAMP) and enhances contractility. Milrinone is useful in patients with hypotensive, low output heart failure and pulmonary hypertension, since it is a more potent pulmonary vasodilator than dobutamine. Milrinone, in contrast to dobutamine, is also useful in patients on chronic oral beta-blocker therapy who develop decompensated heart failure. The OPTIME study, involving the intravenous infusion of milrinone for 48 hours during hospitalization for decompensated heart failure, failed to show symptomatic benefit, and was associated with an increased risk of atrial arrhythmias and hypotension.²⁵ Chronic milrinone infusions may increase mortality due to arrhythmogenicity, similar to other inotropes, and is more costly than dobutamine. Similar to dobutamine, intermittent outpatient milrinone infusions are not recommended for routine management of heart failure.

Nitroglycerin
Nitroglycerin (Table 8) is a nitric oxide donor that increases the intracellular concentration of cGMP in endothelial and smooth muscle cells causing vasodilation. It is predominantly a venodilator, and to a lesser extent, an arterial vasodilator that reduces cardiac preload and alleviates pulmonary congestion.

Nitroglycerin is also a coronary artery vasodilator and is useful in patients with heart failure and myocardial ischemia. IV nitroglycerin requires dose-titration in order to achieve therapeutic goals, and the effectiveness of prolonged infusions is limited by the development of tolerance (loss of effect) within the first 24 hours. Intravenous nitroglycerin is recommended in the ACC/AHA guidelines for the management of patients with acute pulmonary edema.

Sodium Nitroprusside
Sodium nitroprusside (Table 8) is a nitric oxide donor and a potent short-acting arterial and venous vasodilator. It is useful as an afterload reducing agent in patients with acute decompensated heart failure and adequate systemic blood pressure. During nitroprusside infusions, patients are converted to oral vasodilators such as ACE inhibitors, ARBs, or hydralazine/nitrates. Nitroprusside should be avoided in patients with active ischemia due its potential for "coronary steal syndrome" which shunts blood away from the ischemic myocardium to well-perfused muscle.

Nitroprusside infusions are generally reserved for patients in an intensive care unit and require invasive hemodynamic monitoring. Sodium nitroprusside should be infused for a short duration in patients with severe renal disease to avoid accumulation of thiocyanate, the byproduct of hepatic metabolism of nitroprusside, which is excreted by the kidney. Sodium nitroprusside is recommended by the ACC/AHA guidelines for the management of patients with acute pulmonary edema.

Nesiritide
Nesiritide (Table 8), synthetic B-type natriuretic peptide, is an arterial and venous vasodilator with modest diuretic and natriuretic properties.²⁶ Nesiritide increases cardiac output by reflex vasodilation without increasing heart rate or oxygen consumption. It modulates the vasoconstrictor and sodium retaining effects of other neurohormones. Nesiritide is administered as a bolus followed by a continuous intravenous infusion for 1 to 3 days as treatment for decompensated heart failure with fluid overload. 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. Nesiritide probably is more effective than nitroglycerin in normalizing hemodynamic abnormalities and improving symptoms.

Electronic Therapies for Heart Failure:

Cardiac Resynchronization Therapy
Multiple clinical trials have shown the potential benefit of cardiac resynchronization therapy in patients with severe symptomatic heart failure, and a wide QRS complex.^27,28 Symptomatic improvement is achieved in approximately 70% of patients due to improved ventricular contraction and reduction of mitral regurgitation. With cardiac resynchronization therapy, a third electrode is implanted in a left cardiac vein via the coronary sinus so that the right and left ventricles can be activated simultaneously. Optimal synchronization of atrial and ventricular contraction is achieved with echocardiographic guidance. Cardiac resynchronization therapy may be considered in patients with Class 3-4 heart failure with wide QRS (>120ms), usually LBBB, who remain symptomatic despite an optimal medical regimen.

Defibrillator Therapy
Approximately half of the patients with heart failure die suddenly. Implantation of an internal cardioverter defibrillator (ICD) may improve survival in certain subsets of heart failure patients and has been shown to be superior to anti-arrhythmic drug therapy in preventing sudden death.^29,30 Current indications for defibrillator therapy include survivors of a cardiac arrest, patients with sustained ventricular tachycardia, inducible ventricular tachycardia, and LVEF <30% following a myocardial infarction. An ICD implanted in patients with dilated cardiomyopathy and at least NYHA Class II CHF may improve survival over optimal medical care and/or anti-arrhythmic drug therapy.³¹ Cardiac resynchronization therapy can be combined with an ICD as a single device if a patient meets criteria for both devices, as often is the case.

Surgical Therapies for Heart Failure:

Left Ventricular Assist Devices (LVAD)
Certain patients with cardiogenic shock unresponsive to intra-aortic balloon counterpulsation and intravenous inotrope therapy are referred to a tertiary care center for mechanical circulatory support.^32,33 At the present time, LVADs are best used as a bridge to cardiac transplantation in patients who are appropriate transplant candidates. The inflow cannula for 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. FDA-approved LVADs include the Heartmate, Novacor, Thoratec, and Abiomed devices. Complications following LVAD implantation are common and often life-threatening: stroke, infection, peri-operative coagulopathy and bleeding, multi-system organ failure and bioprosthetic valve insufficiency. LVADs may be used as permanent implants (destination therapy), but many obstacles prevent widespread implementation at the present time.

Ventricular Reconstruction Surgery
Ventricular reconstruction surgery, also called ventricular remodeling surgery or a Dor procedure, is performed for heart failure secondary to ischemic cardiomyopathy.³⁴ It consists of several components: coronary artery bypass grafting, mitral and tricuspid valve repair, resection of left ventricular scar or aneurysm, reshaping the left ventricle from an spherical to an elliptical shape, and epicardial left ventricular pacing lead placement. Patients suitable for this procedure have coronary artery disease, extensive ischemia or hibernating myocardium, severe left ventricular dysfunction with akinetic or dyskinetic ventricular segments, and mitral/tricuspid regurgitation.

Cardiac Transplantation
Cardiac transplantation is reserved for otherwise healthy patients with end-stage congestive heart failure with severely impaired function despite optimal medical therapy.³⁵ Patients are excluded for transplantation if they have chronic medical co-morbidities, pulmonary hypertension, active infection, psychosocial contraindications, or medical non-compliance. Survival after cardiac transplantation is about 85% at 1 year and then declines by 4% annually thereafter. Complications that limit survival include rejection, infection, transplant coronary vasculopathy, and malignancy. Following cardiac transplantation, patients are subjected to lifelong immunosuppression to prevent rejection that renders them susceptible to various opportunistic infections and malignancies.

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1. American Heart Association. Heart Disease and Stroke Statistics-2004 Update. Dallas Tex.: American Heart Association 2003.
   
   
2. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651-1658.
   
   
3. Hansen A, Haass M, Zugck, C, et al. Prognostic value of Doppler echocardiographic mitral inflow patterns: implications for risk stratification in patients with chronic congestive heart failure. J Am Coll Cardiol. 2001;37:1049-1055.
   
   
4. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committtee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Circulation. 2001; 104:2996-3007.
   
   
5. Remme WJ, Swedberg K. Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J. 2001;22:1527-1560.
   
   
6. Dao Q, Krishnaswamy P, Kazanegra R, et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol. 2001;37:379-385.
   
   
7. Kazanegra R, Cheng V, Garcia A, et al. A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study. J Card Fail. 2001;7:21-29.
   
   
8. Pitt B, Cohn JN, et al. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure (SOLVD). N Engl J Med. 1991;325:293-302.
   
   
9. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986;314:1547-1552.
   
   
10. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145-153.
    
    
11. Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999;100:2312-2318.
    
    
12. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667-1675.
    
    
13. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003;362:777-781.
    
    
14. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349-1355.
    
    
15. 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.
    
    
16. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9-13.
    
    
17. Poole-Wilson PA, Swedberg K, Cleland JGF, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomized controlled trial. Lancet 2003; 362:7-13.
    
    
18. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group. N Engl J Med. 1997;336:525-533.
    
    
19. Brater DC. Diuretic Therapy. New Engl J Med. 1997;336:525-33.
    
    
20. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709-717.
    
    
21. 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.
    
    
22. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325:303-310.
    
    
23. Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med. 1996;335:1107-1114.
    
    
24. Felker GM, O'Conner CM, Ghali JK, et al. Inotropic therapy for heart failure: An evidence-based approach. Am Heart J. 2001;142:393-401.
    
    
25. Cuffe MS, Califf RM, Adams KF, et al. Short-term intravenous milirinone for acute exacerbation of chronic heart failure. A randomized controlled trial. JAMA. 2002;287:1541-1547.
    
    
26. Iyengar S, Feldman DS, Trupp R, Abraham WT. Nesiritide for the treatment of congestive heart failure. Expert Opin Pharmacother. 2004;5:901-907.
    
    
27. Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001;344:873-880.
    
    
28. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346:1845-1853.
    
    
29. Gollob MH, Seger JJ. Current status of the implantable cardioverter-defibrillator. Chest. 2002:119:1210-1221.
    
    
30. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-883.
    
    
31. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350:2151-2158.
    
    
32. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345:1435-1443.
    
    
33. Delgado DH, Rao V, Ross HJ, et al. Mechanical circulatory assistance: state of the art. Circulation. 2002;106:2046-2050.
    
    
34. Mickleborough LL, Merchant N, Ivanov J, et al. Left ventricular reconstruction: Early and late results. J Thorac Cardiovasc Surg. 2004:128:27-37.
    
    
35. Hunt SA. Current status of cardiac transplantation. JAMA. 1998;280:1692-1698.

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