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Heart Failure Treatment & Management

  • Author: Ioana Dumitru, MD; Chief Editor: Henry H Ooi, MD, MRCPI  more...
Updated: Jan 11, 2016

Approach Considerations

Medical care for heart failure (HF) includes a number of nonpharmacologic, pharmacologic, and invasive strategies to limit and reverse the manifestations of heart failure. Depending on the severity of illness, nonpharmacologic therapies include dietary sodium and fluid restriction; physical activity as appropriate; and attention to weight gain. Pharmacologic therapies include the use of diuretics, vasodilators, inotropic agents, anticoagulants, beta-blockers, and digoxin.

Invasive therapies for heart failure include electrophysiologic intervention such as cardiac resynchronization therapy (CRT), pacemakers, and implantable cardioverter-defibrillators (ICDs); revascularization procedures such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI); valve replacement or repair; and ventricular restoration.

When progressive end-stage heart failure occurs despite maximal medical therapy, when the prognosis is poor, and when there is no viable therapeutic alternative, the criterion standard for therapy has been heart transplantation.[3] However, mechanical circulatory devices such as ventricular assist devices (VADs) and total artificial hearts (TAHs) can bridge the patient to transplantation; in addition, VADs are increasingly being used as permanent therapy.

Comorbidities to consider

Coronary artery disease

Patients with heart failure should be evaluated for coronary artery disease, which can lead to heart failure (see Etiology). Not only may this condition be the underlying cause in up to two thirds of heart failure patients with low ejection fraction, but coronary artery disease may also play a role in the progression of heart failure through mechanisms such as endothelial dysfunction, ischemia, and infarction, among others.[3]

Patients with coronary artery disease with modestly reduced ejection fraction and angina demonstrate symptomatic and survival improvement with coronary artery bypass grafting (CABG) in studies[3] ; however, the studies did not include individuals with heart failure or those with severely reduced ejection fractions.[3] In patients with angina and ventricular dysfunction, evaluation with coronary angiography should not be delayed (see Catheterization and Angiography). Noninvasive cardiac testing is not recommended in patients with significant ischemic chest pain, as revascularization is advised in these patients independent of their degree of ischemia/viability.[3]

Although there are no reports of controlled trials evaluating heart failure without angina and their outcomes with coronary revascularization, surgical revascularization is recommended in those with significant left main stenosis and in those with extensive noninfarcted but hypoperfused and hypocontractile myocardium on noninvasive testing.[3] In patients with heart failure and reduced left ventricular ejection fraction but without angina, it has not yet been determined whether routine evaluation of possible myocardial ischemia/viability and coronary artery disease should be performed.[3]

For patients with heart failure from LV dysfunction without chest pain and without a history of coronary artery disease, coronary angiography may be useful in young patients to exclude congenital coronary anomalies. However, because clinical outcomes have not been shown to improve in patients without angina, coronary angiography may not be as useful in older patients for evaluating the presence of coronary artery disease.[3] Some experts nonetheless suggest excluding coronary artery disease whenever possible, particularly in the presence of diabetes or other states associated with silent myocardial ischemia, because LV function may show improvement with revascularization.[3]

In general, if coronary artery disease has already been excluded as the cause of abnormalities in LV function, it is not necessary to perform repeated evaluations for ischemia (invasive or noninvasive) provided the patient’s clinical status has not changed to suggest the development of ischemic disease.[3]

For more information, see the Medscape Reference articles Primary and Secondary Prevention of Coronary Artery Disease, Risk Factors for Coronary Artery Disease, and Risk Factors for Coronary Artery Disease.

Valvular heart disease may be the underlying etiology or an important aggravating factor in heart failure.[3, 5, 6] For more information, see the Medscape Reference article Valvular Surgery.

Sleep apnea

Sleep apnea has an increased prevalence in patients with heart failure and is associated with increased mortality due to further neurohormonal activation, although randomized, controlled data are lacking. Sleep apnea should be treated aggressively in heart failure patients.

A long-term study involving 283 heart failure patients who had an implanted cardiac resynchronization device with cardioverter-defibrillator concluded that obstructive sleep apnea (OSA) and/or central sleep apnea (CSA) are independently associated with an increased risk for ventricular arrhythmias requiring cardioverter-defibrillator therapies.[108]


Anemia is also common in chronic heart failure. Whether anemia is a reflection of the severity of heart failure or contributes to worsening heart failure is not clear. Potential etiologies of anemia in heart failure involve poor nutrition, ACEIs, the RAAS, inflammatory cytokines, hemodilution, and renal dysfunction. Anemia in heart failure is associated with increased mortality.[109]

The ACC/AHA, HFSA, and ESC make no recommendations regarding the administration of iron to patients with heart failure, although the ACC/AHA noted that several small studies suggested a benefit in mild anemia and heart failure.[3] More and larger studies are needed.

Cardiorenal syndrome

Cardiorenal syndrome reflects advanced cardiorenal dysregulation manifested by acute heart failure, worsening renal function, and diuretic resistance. It is equally prevalent in patients with heart failure with normal ejection fraction (HFNEF) and those with LV systolic dysfunction. Worsening renal function is one of the 3 predictors of increased mortality in hospitalized patients with heart failure regardless of the LVEF.

Cardiorenal syndrome can be classified into the following 5 types[110] :

  • CR1: rapid worsening of cardiac function leading to acute kidney injury (HFNEF, acute heart failure, cardiogenic shock, and RV failure)
  • CR2: worsening renal function due to progression of chronic heart failure
  • CR3: abrupt and primary worsening of kidney function leading to acute cardiac dysfunction (heart failure, arrhythmia, ischemia)
  • CR4: chronic kidney disease leading to progressive cardiac dysfunction, LVH, and diastolic dysfunction
  • CR5: combination of cardiac and renal dysfunction due to acute and chronic systemic conditions

The pathophysiology of CR1 and CR2 is complex and multifactorial, involving neurohormonal activation (RAAS, sympathetic nervous system, arginine vasopressin, natriuretic peptides, adenosine receptor activation), low arterial pressure, and high central venous pressure, leading to lower transglomerular perfusion pressure and decreased availability of diuretics to the proximal nephron. This results in an increased reabsorption of sodium and water and poor diuretic response—hence, diuretic resistance despite escalating doses of oral or intravenous diuretics.

Treatment of cardiorenal syndrome in patients with heart failure is largely empirical, but it typically involves the use of combination diuretics, vasodilators, and inotropes as indicated.[111] Ultrafiltration is recommended for symptomatic relief by the ACC/AHA guidelines for patients with heart failure that is refractory to diuretic therapy.[3]

A sudden increase in creatinine can be seen after initiation of diuretic therapy and is often mistakenly considered evidence of overdiuresis or intravascular depletion (even in the presence of fluid overload). A common error in this situation is to decrease the dose of ACEI/ARB and/or diuretics or to even withdraw one of these agents. In fact, when diuresis or ultrafiltration is continued, patients demonstrate improved renal function, decreased total body fluid, and increased response to diuretics, as central venous pressure falls.

Low-dose dopamine has been used in combination with diuretic therapy, on the supposition that it can increase kidney perfusion. Data have been contradictory, however. In a randomized controlled study, Giamouzis et al found that the combination of low-dose furosemide and low-dose dopamine was equally as effective as high-dose furosemide for kidney function in patients with acute decompensated heart failure. In addition, patients who received dopamine and furosemide were less likely to have worsened renal function or hypokalemia at 24 hours.[112]

Use of nesiritide, a synthetic natriuretic peptide, to increase diuresis in these cases has not been studied. A meta-analysis of several trials using nesiritide suggests the potential of worsening renal function, although this has not been demonstrated in prospective trials. Results of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial suggest that, although nesiritide is safe, it does not provide additional efficacy when added to standard therapy.[113]

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial showed that the addition of the vasopressin antagonist tolvaptan to diuretic therapy facilitates diuresis in acute heart failure. However, tolvaptan had no impact on mortality or hospitalizations in this setting.[114]

Adenosine receptor antagonists have been proposed for protecting renal function in acute heart failure. However, in a double-blind, placebo-controlled trial, the adenosine A1 −receptor antagonist rolofylline demonstrated no benefit for patients hospitalized for acute heart failure with impaired renal function.[115]

A meta-analysis performed by Badve et al suggests that treatment with beta blockers was found to reduce all-cause mortality in patients with chronic kidney disease and systolic heart failure (risk ratio, 0.72).[116]

Atrial fibrillation

Many patients with heart failure also have atrial fibrillation, and the 2 conditions can adversely affect each other. However in the AFFIRM trial, there was no difference in stroke, heart failure exacerbation, or CV mortality in patients treated with rhythm control (amiodarone) and patients treated with rate control.[117] All of these patients require anticoagulation for stroke prevention. This can be achieved by using warfarin or a direct thrombin inhibitor (no need to follow protime).

In a prospective controlled study by Hsu et al, catheter ablation for atrial fibrillation in patients with heart failure and an LVEF of less than 45% resulted in a 21% increase in LVEF and improvement in LV dimensions, exercise capacity, symptoms, and quality of life.[118] At a mean of 12 months, 78% of patients remained in sinus rhythm without antiarrhythmic drugs.

A meta-analysis found that patients with LV systolic dysfunction who underwent catheter ablation for atrial fibrillation demonstrated significant improvements in LVEF, and their risk for recurrent atrial fibrillation or atrial tachycardia after catheter ablation was similar to that in patients with normal LV function after ablation. However, patients with LV systolic dysfunction were more likely to require repeat procedures.[119]

In contrast, MacDonald et al reported that in patients with advanced heart failure and severe LV systolic dysfunction, radiofrequency ablation for persistent atrial fibrillation resulted in long-term restoration of sinus rhythm in only 50% of cases.[120] Radiofrequency ablation also failed to improve such secondary outcomes as walking distance or quality of life, and the rate of related serious complications was 15%.


Nonpharmacologic Therapy

Patients with heart failure can benefit from attention to exercise, diet, and nutrition. Restriction of activity promotes physical deconditioning, so physical activity should be encouraged. However, limitation of activity is appropriate during acute heart failure exacerbations and in patients with suspected myocarditis. Most patients should not participate in heavy labor or exhaustive sports.[3]

A 2012 meta-analysis showed that aerobic exercise training, particularly long-term, can reverse left ventricular remodelling in clinically stable heart failure patients, while strength training had no effect on remodelling.[121]

Because nonadherence to diet and medication can have rapid and profound adverse effects on patients’ clinical status, close observation and follow-up are important aspects of care. Patient education and close supervision, including surveillance by the patient and family, can improve adherence. These measures also facilitate early detection of weight gain or slightly worsened symptoms, which often occur several days before major clinical episodes that require emergency care or hospitalization. Patients can then alert their clinicians, who may be able to prevent such episodes through prompt intervention.[3]

Dietary sodium restriction to 2-3 g/day is recommended. Fluid restriction to 2 L/day is recommended for patients with evidence of hyponatremia (Na < 130 mEq/dL) and for those whose fluid status is difficult to control despite sodium restriction and the use of high-dose diuretics. Caloric supplementation is recommended for patients with evidence of cardiac cachexia.

An analysis of concentrations of plasma eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid, in the Cardiovascular Health Study identified plasma phospholipid EPA concentration as being inversely related to incident congestive heart failure.[122] These results support additional studies on the potential benefits of omega-3 fatty acids for primary prevention of heart failure.

The GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) trial included nearly 7000 patients with systolic heart failure (any LV ejection fraction) who received either 1 g of omega-3 polyunsaturated fatty acids (PUFAs) or placebo daily and demonstrated that the PUFA regimen had a small but significant reduction in both all-cause mortality and all-cause mortality/hospitalization for cardiovascular causes.[123]


Pharmacologic Therapy

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) updated guidelines,[124] 2010 Heart Failure Society of America (HFSA) guidelines,[6] and the 2008 European Society of Cardiology (ESC)[5] guidelines, with varying levels of evidence, recommend the following:

  • Diuretics (to reduce edema by reduction of blood volume and venous pressures) and salt restriction (to reduce fluid retention) in patients with current or previous heart failure symptoms and reduced left ventricular ejection fraction (LVEF) for symptomatic relief
  • Angiotensin-converting enzyme inhibitors (ACEIs) for neurohormonal modification, vasodilatation, improvement in LVEF, and survival benefit
  • Angiotensin receptor blockers (ARBs) for neurohormonal modification, vasodilatation, improvement in LVEF, and survival benefit
  • Hydralazine and nitrates to improve symptoms, ventricular function, exercise capacity, and survival in patients who cannot tolerate an ACEI/ARB or as an add-on therapy to ACEI/ARB and beta-blockers in the black population for survival benefit
  • Beta-adrenergic blockers for neurohormonal modification, improvement in symptoms and LVEF, survival benefit, arrhythmia prevention, and control of ventricular rate
  • Aldosterone antagonists, as an adjunct to other drugs for additive diuresis, heart failure symptom control, improved heart rate variability, decreased ventricular arrhythmias, reduction in cardiac workload, improved LVEF, and increase in survival
  • Digoxin, which can lead to a small increase in cardiac output, improvement in heart failure symptoms, and decreased rate of heart failure hospitalizations
  • Anticoagulants to decrease the risk of thromboembolism
  • Inotropic agents to restore organ perfusion and reduce congestion

In April 2015, the FDA approved the I(f) "funny current" inhibitor, ivabradine (Corlanor). It is indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with an LVEF of 35% or lower, who are in sinus rhythm with a resting heart rate of 70 bpm or higher, and who are either on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.[125, 126] This drug blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) "funny" current, which regulates heart rate without any effect on ventricular repolarization or myocardial contractility.

Approval for ivabradine was based on the international, placebo-controlled SHIFT trial published in 2010, which randomized more than 6500 patients with New York Heart Association (NYHA) class II-IV heart failure and an LVEF of 35% or lower.[125, 126] The trial saw a highly significant 18% drop in risk for cardiovascular death or hospitalization for worsening heart failure over an average of 23 months in patients treated with ivabradine.

In July 2015, the FDA approved the combination tablet sacubitril/valsartan (Ernesto) to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with CHF (NYHA class II-IV) and reduced ejection fraction.[127] The combination drug is the first approved agent in the angiotensin receptor-neprilysin inhibitor (ARNI) class and consists of the angiotensin-receptor blocker valsartan affixed to the neprilysin inhibitor sacubitril. The cardiovascular and renal effects of sacubitril’s active metabolite (LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic peptide). Administration results in increased natriuresis, increased urine cGMP, and decreased plasma mid-regional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP).

The approval was based on the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial.[128] PARADIGM-HF  studied 8442 patients with chronic heart failure treated with either valsartan/sacubitril or enalapril. The combination significantly reduced cardiovascular death or heart-failure hospitalizations (the study's primary end point) by 20% compared with treatment with enalapril alone. All-cause mortality, a secondary end point, was also significantly reduced with the ARNI when compared with enalapril.[128]

The Prospective Comparison of ARNI with ARB on Management of Heart Failure with Preserved Ejection Fraction (PARAMOUNT) trial compared reduction of NP-proBNP levels with sacubitril plus valsartan and valsartan alone over 12 weeks in 149 patients with LVEF of 45% or greater. Sacubitril/valsartan reduced NT-proBNP levels to a significantly greater extent (783 pg/mL at baseline and 605 pg/mL at 12 weeks) compared with valsartan alone (862 pg/mL at baseline and 835 pg/mL at 12 weeks).[129]

Patients with heart failure and depressed LVEF are thought to have an increased risk of thrombus formation due to low cardiac output. Anticoagulation with an international normalized ratio (INR) goal of 2-3 is indicated in the presence of left ventricular (LV) thrombus, thromboembolic event with or without evidence of an LV thrombus, and paroxysmal or chronic atrial arrhythmias.[3, 5]

Routine anticoagulation with warfarin in patients with normal sinus rhythm, heart failure, and LV dysfunction has proven not to be superior to aspirin alone in decreasing death, myocardial infarction (MI), and stroke and was associated with an increased risk of bleeding in the Coumadin arm of the WATCH trial.[130]

The use of regularly scheduled intermittent intravenous infusions of positive inotropic drugs in a supervised outpatient setting has been proposed, but the ACC/AHA guidelines advise against this, given the lack of evidence to support efficacy and concerns about toxicity with an increase in mortality rate. Rather, the guidelines recommend infusion of a positive inotrope only as palliation in patients with end-stage disease who cannot be stabilized with standard medical treatment.[3]

The ACC/AHA guidelines advise that nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and most antiarrhythmic agents may exacerbate heart failure and should be avoided in most patients.[3] NSAIDs can cause sodium retention and peripheral vasoconstriction and can attenuate the efficacy and enhance the toxicity of diuretics and ACEIs.

Antiarrhythmic agents can have cardiodepressant effects and may promote arrhythmia; only amiodarone and dofetilide have been shown not to adversely affect survival. Calcium channel blockers can worsen heart failure and may increase the risk of cardiovascular events; only the vasoselective calcium channel blockers have been shown not to adversely affect survival.[3]

In a community-based cohort study of 2891 digoxin-naive adults with newly diagnosed systolic heart failure, 18% of whom initiated treatment with digoxin, incident digoxin use was associated with significantly higher rates of death (14.2 versus 11.3 per 100 person-years) during a median of 2.5 years of follow-up. Digoxin use was not associated with a significant difference in the risk of hospitalization for heart failure. Results were similar when analyses were stratified by sex and use of beta-blockers. Digoxin currently occupies places in both US and European guidelines as no more than a second-line agent for systolic HF.


Acute Heart Failure Treatment

Most patients who present with acute heart failure have exacerbation of chronic heart failure, with only 15-20% having acute de novo heart failure. Approximately 50% of patients with acute heart failure have a preserved LVEF (>40%).[131, 132] Less than 5% of patients presenting with acute heart failure are hypotensive and require inotropic therapy.[133] Pulmonary edema is a medical emergency, but it is only one of the presentations of acute heart failure.

A systematic and expeditious approach to management of acute heart failure is required, starting in the outpatient setting (eg, emergency department, urgent care center, office), continuing during hospitalization, and extending after discharge to the outpatient setting. The clinician’s agenda in these cases is threefold:

  • Stabilize the patients’ clinical condition
  • Establish the diagnosis, etiology, and precipitating factors
  • Initiate therapies to rapidly provide symptom relief

Administration of oxygen, if oxygen saturation is less than 90%, and noninvasive positive pressure ventilation (NIPPV) provides patients with respiratory support to avoid intubation. NIPPV has been shown to decrease the rate of intubation, hospital morality, and mechanical ventilation.[134, 135, 136, 137, 138] No difference has been noted between continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). A prospective randomized trial that compared the use of noninvasive ventilation (NIV) and standard therapy with the use of standard therapy alone suggested that although NIV may improve dyspnea and respiratory acidosis, it does not appear to improve mortality.[139]

Medical therapy for heart failure patients, the majority who present with normal perfusion and evidence of congestion, focuses on the following goals:

  • Preload and afterload reduction for symptomatic relief using vasodilators (nitrates, hydralazine, nipride, nesiritide, ACEI/ARB) and diuretics
  • Inhibition of deleterious neurohormonal activation (renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system) using ACEI/ARB, beta-blockers, and aldosterone antagonists resulting in long-term survival benefit

Preload reduction results in decreased pulmonary capillary hydrostatic pressure and reduction of fluid transudation into the pulmonary interstitium and alveoli. Preload and afterload reduction provide symptomatic relief. Inhibition of the RAAS and sympathetic nervous system produces vasodilation, thereby increasing cardiac output and decreasing myocardial oxygen demand. While reducing symptoms, inhibition of the RAAS and neurohumoral factors also results in significant reductions in morbidity and mortality rates.[140, 141, 142] Diuretics are effective in preload reduction by increasing urinary sodium excretion and decreasing fluid retention, with improvement in cardiac function, symptoms, and exercise tolerance.[3]

Once congestion is minimized, a combination of 3 types of drugs (a diuretic, an ACEI or an ARB, and a beta-blocker) is recommended in the routine management of most patients with heart failure.[3] This combination can accomplish all of the above goals. ACEIs/ARBs and beta-blockers are generally used together. Beta-blockers are started in the hospital once euvolemic status has been achieved.

If there is evidence of organ hypoperfusion, use of inotropic therapies and/or mechanical circulatory support (eg, intra-aortic balloon pump, extracorporeal membrane oxygenator [ECMO], left ventricular assist device [LVAD]) and continuous hemodynamic monitoring are indicated. If arrhythmia is present and if uncontrolled ventricular response is thought to contribute to the clinical scenario of acute heart failure, either pharmacologic rate control or emergent cardioversion with restoration of sinus rhythm is recommended.

A study of 85 patients with hypertensive acute heart failure found that the IV calcium channel blocker clevidipine (Cleviprex) was safe and more effective than standard IV drugs for rapidly reducing blood pressure and improving dyspnea. In the 32 study patients who received clevidipine, dyspnea resolved completely in 3 hours, compared with 12 hours in the 53 patients who received usual care (mainly IV nitroglycerin or nicardipine). Target blood pressure range was achieved more often in patients receiving clevidipine (71% vs 37% for standard care; P =.002) and was reached sooner.[143]


Diuretics remain the cornerstone of standard therapy for acute heart failure. In such patients, IV administration of a loop diuretic (ie, furosemide, bumetanide, torsemide) is preferred initially because of potentially poor absorption of the oral form in the presence of bowel edema. In patients with hypertensive heart failure who have mild fluid retention, thiazide diuretics may be preferred because of their more persistent antihypertensive effects.[3]

Diuretics can be given by bolus or continuous infusion and in high or low doses. In a study of patients with acute decompensated heart failure, however, Felker et al found that there were no significant differences in effect on symptoms or renal function changes with furosemide given either by bolus or by continuous infusion; additionally, no differences were found with high versus low doses.[144] The dose and frequency of administration depend on the diuretic response 2-4 hours after the first dose is given. If the response is inadequate, then increasing the dose and/or increasing the frequency can help enhance diuresis.

Diuretic resistance is diagnosed if there is persistent pulmonary edema despite the following[145] :

  • Repeated doses of 80 mg of furosemide or
  • Greater than 240 mg of furosemide per day (including continuous furosemide infusion) or
  • Combined diuretic therapy (including loop diuretics with thiazide or an aldosterone antagonist)

Volume status, sodium levels, water intake, and hemodynamic status (for signs of poor perfusion) need to be reevaluated in case of diuretic resistance. Diuretic resistance is a known effect of long-term use of diuretics; some approaches to managing resistance to these agents include increasing the dose and/or frequency of the drug, restricting sodium or water intake, administering the drug as an IV bolus or IV infusion, and combining diuretics.[146, 147] In addition, diuretic resistance is an independent predictor of mortality in patients with chronic heart failure.[148] Eventually, alternative strategies, such as hemodialysis or ultrafiltration,[149] may be used to overcome it. Other agents, such as vasopressin antagonists and adenosine receptor blockers, can be used to assist diuretics.

Transition to oral diuretic therapy is made when the patient reaches a near-euvolemic state. The oral diuretic dose is usually equal to the IV dose. In most cases, 40 mg/day of furosemide is equivalent to 20 mg of torsemide and 1 mg of bumetanide. Weight, signs and symptoms, fluid balance, electrolyte levels, and renal function have to be monitored carefully on a daily basis.


Vasodilators (eg, nitroprusside, nitroglycerin, or nesiritide) may be considered as an addition to diuretics for patients with acute heart failure for relief of symptoms. Vasodilators will decrease preload and/or afterload.

Nitrates are potent venodilators. They decrease preload and therefore decrease LV filling pressure and relieve shortness of breath. They also selectively produce epicardial coronary artery vasodilatation and help with myocardial ischemia. Although nitrates can be used in different forms (sublingual, oral, transdermal, IV), the most common route in acute heart failure is IV. Their use is limited by tachyphylaxis and headache.

Sodium nitroprusside is a potent, primarily arterial, vasodilator resulting in a very efficient afterload reduction and decrease of intracardiac filling pressures. This agent is particularly helpful for patients who present with severe pulmonary congestion in the presence of hypertension and severe mitral regurgitation. Sodium nitroprusside requires not only careful hemodynamic monitoring, often requiring indwelling catheters, but also monitoring for cyanide toxicity, especially in the presence of renal dysfunction. The drug should be titrated to off rather than abruptly stopped because of the potential for rebound hypertension.

Nesiritide (human brain natriuretic peptide analogue) is a vasodilator that was initially thought to alleviate dyspnea faster than nitroglycerin when used in combination with diuretics.[150, 151] This agent reduces pulmonary capillary wedge pressure (PCWP), right atrial pressure, and systemic vascular resistance but has no effect on heart contractility.

Ultrafiltration and refractory heart failure

In ultrafiltration, blood is removed from the body and run through a device that applies hydrostatic pressure across a semipermeable membrane to separate isotonic plasma water. Solutes cross the semipermeable membrane freely, so fluid can be removed without causing significant changes in the concentration of electrolytes and other solutes in serum.[152]

Ultrafiltration was shown to be an effective alternative to intravenous diuretics in the Ultrafiltration Versus Intravenous (IV) Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) trial.[153] The ACC/AHA and ESC recommend the use of ultrafiltration for fluid reduction for patients with refractory heart failure that is not responsive to medical therapy.[3, 5]

Indications for hospitalization

A patient whose condition is refractory to standard therapy will often require hospitalization to receive IV diuretics, vasodilators, and inotropic agents. The 2010 Heart Failure Society of America (HFSA) guidelines recommend hospitalization for acute heart failure in the presence of the following[6] :

  • Severe acute decompensated heart failure (low blood pressure, worsening renal dysfunction, altered mentation)
  • Dyspnea at rest
  • Hemodynamically significant arrhythmia
  • Acute coronary syndrome

Hospitalization should also be considered in the presence of the following[6] :

  • Worsening congestion with or without dyspnea
  • Worsening signs and symptoms of systemic or pulmonary congestion, even in the absence of weight gain
  • Major electrolyte abnormalities
  • Associated comorbid conditions (eg, pneumonia, pulmonary embolism, diabetic ketoacidosis, stroke/strokelike symptoms)
  • Repeat ICD firings
  • New diagnosis of heart failure with signs of active systemic/pulmonary congestion

Most patients requiring hospitalization should be admitted to a telemetry bed or intensive care unit; a small percentage can be admitted to the floor or observation unit. The goal is to continue the diagnostic and therapeutic processes started in the office or emergency department. Treatment includes the following:

  • Volume and hemodynamic status are optimized using careful clinical monitoring, and the heart failure medical regimen is optimized
  • Surgical intervention with a ventricular device has been considered
  • Heart failure education, behavior modification, and exercise and diet recommendation are made
  • Enrollment in heart failure disease management programs for patients with advanced and difficult-to-control heart failure

Invasive hemodynamic monitoring

Invasive hemodynamic monitoring is not indicated for stable patients with heart failure responding appropriately to medical therapy.[3, 107] The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE] trial showed no mortality or hospitalization benefit in such cases.[107] In patients with acute decompensated heart failure, the following are indications for invasive hemodynamic monitoring[3, 154] :

  • Respiratory distress
  • Signs of impaired perfusion
  • Inability to determine intracardiac pressures on the basis of clinical examination
  • No improvement in clinical status despite maximal heart failure therapy

Clinical situations in which invasive hemodynamic monitoring is recommended to guide therapy include the following[3] :

  • Persistent symptomatic hypotension despite initial therapy
  • Worsening renal function despite initial therapy or despite adjustment of recommended therapies
  • Need for parenteral vasoactive agents after initial clinical improvement
  • Presumed cardiogenic shock requiring escalating inotrope and/or pressor therapy and consideration of mechanical support
  • Consideration of advanced device therapy or transplantation

Different monitoring methods have been implemented by physicians in an attempt to reduce hospitalization for heart failure. The results have been equivocal, regardless of the severity of heart failure. No differences in death or hospitalization for heart failure have been found with either standard outpatient monitoring or intense telemonitoring for heart failure.[155, 156]

In May 2014, the FDA approved the first permanently implantable wireless hemodynamic monitoring system (CardioMEMS HF System) for patients with NYHA class III heart failure with a history of hospitalization for heart failure within the past year.[157, 158] The device measures pulmonary artery (PA) pressures (eg, systolic, diastolic, and mean) as well as heart rate, and consists of a sensor/monitor implanted permanently in the PA, a transvenous catheter to deploy the sensor within the distal PA, and an electronics system that acquires and processes the signal from the sensor/monitor and transfers PA measurements to a secure database.[157, 158] This device also permits ambulatory monitoring and is designed to detect early-stage elevations in PA pressure, so that appropriate medical intervention can be provided before worsening elevation leads to congestion.[159]

Approval for the device was based on results from 550 patients from the open-label CHAMPION study (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients), in which the device reduced hospitalizations by 30% compared with standard care.[158, 159]


The patient must be on a stable oral regimen for at least 24 hours before discharge. Patients are ready for discharge when they meet the following criteria:

  • Exacerbating factors have been addressed
  • Volume status has been optimized
  • Diuretic therapy has been successfully transitioned to oral medication, with discontinuation of IV vasodilator and inotropic therapy for at least 24 hours
  • Oral chronic heart failure therapy has been achieved with stable clinical status

Before discharge, patient and family education should be completed, and extensive postdischarge instructions and follow-up in 3-7 days should be arranged. Refractory end-stage heart failure (ACC/AHA stage D, NYHA class IV) is often difficult to manage on an outpatient basis. Therefore, these patients may be referred to a heart failure program with expertise in management of refractory heart failure.[3]

To ensure compliance and understanding of a complex medical regimen, a follow-up phone call can be made 3 days after discharge by a nurse with training in heart failure. Ideally, the patient should be seen in clinic 7-10 days after discharge.


Treatment of Heart Failure with Normal LVEF

Treatment of heart failure with normal left ventricular ejection fraction (HFNEF) is directed toward alleviating symptoms and addressing the underlying condition triggering HFNEF. Evaluation of cardiac ischemia or sleep apnea as potential precipitating factors should also be considered.

There is a paucity of randomized, controlled studies addressing HFNEF. Control of blood pressure, volume, or other risk factors is the mainstay of therapy.[3, 6] Lifestyle modification in important and may include the following:

  • Low-sodium diet
  • Restricted fluid intake
  • Daily measurement of weight
  • Exercise
  • Weight loss

Diuretic therapy is recommended to reduce fluid retention. However, patients must be monitored carefully to avoid hypotension.

ACEI/ARBs are used as indicated for patients with atherosclerotic disease, prior MI, diabetes mellitus, or hypertension. Use of candesartan, irbesartan, or perindopril has not been shown to decrease mortality but has produced a trend toward improved morbidity and decreased hospitalizations.[160] Some evidence shows that losartan and valsartan may promote LV reverse remodeling, with improvement in diastolic function and regression of left ventricular hypertrophy (LVH).

Beta-blockers are indicated for patients with prior MI or hypertension and for control of ventricular rate in those with atrial fibrillation. In the ADHERE registry, the subset of patients with HFNEF not treated with a beta-blocker had a higher mortality, potentially because of the higher incidence of coronary artery disease (CAD) in this population.[161]

Aldosterone receptor blockers are indicated for hypertension and to reduce myocardial fibrosis, although no randomized, controlled studies have been performed to evaluate their role in HFNEF. Calcium channel blockers may improve exercise tolerance via their vasodilatory properties, and nondihydropyridine calcium channel blockers are also used for ventricular rate control in patients with atrial fibrillation. Amlodipine has antianginal properties and is also indicated in hypertension.

Restoration of sinus rhythm should be considered if the patient remains symptomatic despite the above efforts. Use of digitalis or inotropes in patients with HFNEF is not indicated.


Treatment of Right Ventricular Heart Failure

Management of right ventricular (RV) failure includes treatment of the underlying cause; optimization of preload, afterload, and RV contractility; maintenance of sinus rhythm; and atrioventricular synchrony. Hypotension should be avoided, as it can potentially lead to further RV ischemia.

General measures should be applied, as follows:

  • Sodium and fluid restriction
  • Moderate physical activity, with avoidance of isometric exercises
  • Avoidance of pregnancy
  • Compliance with medications
  • Avoidance, or rapid treatment of, precipitating factors

Precipitating factors include the following:

  • Sleep apnea
  • Pulmonary embolism
  • Sepsis
  • Arrhythmia
  • Ischemia
  • High altitude
  • Anemia
  • Hypoxemia

Use of an ACEI/ARB is beneficial if RV failure is secondary to LV failure; the efficacy of these agents in isolated RV failure is not known. The same recommendation applies for use of beta-blockers. The role of nesiritide in RV failure is not well defined. Use of digoxin in RV failure associated with chronic obstructive pulmonary disease (COPD) not associated with LV dysfunction appears not to improve exercise tolerance or RV ejection fraction. Treatment of pulmonary-induced RV failure is to address the correction of a primary pulmonary etiology and a decrease in RV afterload via specific pulmonary artery vasodilatory therapies (please see Primary Pulmonary Hypertension for treatment).

In patients with severe, hemodynamically compromising RV failure, inotropic therapy is administered, using dobutamine (2-5 mcg/kg/min), dobutamine and inhaled nitric oxide, or dopamine alone. Milrinone is preferred if the patient is tachycardic or on beta-blockers.

Anticoagulation indications are standard for evidence of intracardiac thrombus, thromboembolic events, pulmonary arterial hypertension, paroxysmal or persistent atrial fibrillation/flutter, and mechanical right-sided valves. Hypoxemia should be corrected, and positive pressure should be avoided when mechanical ventilation is needed.

Atrial septostomy can be considered as a palliative measure in patients with severe symptoms in whom standard therapy has failed. RV mechanical assist device is indicated only for RV failure secondary to LV failure or post–cardiac transplantation.

The prognosis in patients with RV failure depends on the etiology. Volume overload, pulmonary stenosis, and Eisenmenger syndrome are associated with a better prognosis. Decreased exercise tolerance predicts poor survival.


Electrophysiologic Intervention

Devices for electrophysiologic intervention in heart failure include pacemakers, cardiac resynchronization therapy (CRT) devices, and implantable cardioverter-defibrillators (ICDs).

The 2010 Heart Failure Society of America (HFSA) guidelines indicate that device therapy is an integral part of the treatment of heart failure and that considerations such as the nature and severity of the condition and any patient comorbidities are essential in optimizing the use of this therapy.[6] The Committee for Practice Guidelines (CPG) of the European Society of Cardiology (ESC) and the ACC/AHA/Heart Rhythm Society (HRS) emphasized the importance of medical devices in heart failure in their respective 2010 and 2012 focused updates on these interventions.[162, 163]

In addition, the AHA has published guidelines on heart device strategies, patient selection, and postoperative care. The guidance focuses on risk stratification and early referral of high-risk patients with heart failure to centers that can implant mechanical circulatory support devices (MCS).[164, 165]

In April 2014, the FDA approved 10 Medtronic biventricular pacemakers, some with defibrillators and some without, for use in patients with less severe systolic heart failure and atrioventricular (AV) block.[166, 167] Approval was based on a study of 691 patients with first-, second-, or third-degree AV block, New York Heart Association (NYHA) class I-III heart failure, and left ventricular ejection fraction (LVEF) less than 50%, in which biventricular pacing over three years reduced all-cause mortality by 26%, reduced heart failure-related urgent care, and increased LV end-systolic volume index by more than 15%.[166, 167]


Maintaining a normal chronotropic response and AV synchrony may be particularly significant for patients with heart failure.[5] Because RV pacing may worsen heart failure due to an increase in ventricular dysynchrony, the current 2010 HFSA Practice Guidelines recommend against placement of a dual-chamber pacemaker in heart failure patients in the absence of symptomatic bradycardia or high-degree AV block.

The ACC/AHA heart failure guidelines recommend consideration of cardiac resynchronization therapy (CRT) for patients with heart failure who have indications for permanent pacing (eg, first implant, upgrading of a conventional pacemaker) and NYHA class III-IV symptoms or those who have an LVEF less than 35% despite being on optimal heart failure therapy and who may have a dependence on RV pacing. These recommendations now also include patients with NYHA class II symptoms and the presence of left-bundle-branch block with a QRS duration that is greater than or equal to 150 ms.[163]

Implantable cardioverter-defibrillators

The role of the ICD has rapidly expanded. Sudden death is 5-10 times more common in patients with heart failure than in the general population. ICD placement results in remarkable reductions in sudden death from ischemic and nonischemic sustained ventricular tachyarrhythmias in heart failure patients. Consequently, current AHA/ACC guidelines recommend an ICD in virtually all patients with an LVEF of less than 35%. (See also the Medscape Reference articles Implantable Cardioverter-Defibrillators and Pacemakers and Implantable Cardioverter Defibrillators.)

The AHA/ACC and ESC recommend ICD placement for the following categories of heart failure patients[3, 5, 52] :

  • Patients with LV dysfunction (LVEF ≤35%) from a previous MI who are at least 40 days post-Ml
  • Patients with nonischemic cardiomyopathy; with an LVEF of 35% or less; in NYHA class II or III; receiving optimal medical therapy; and expected to survive longer than 1 year with good functional status [3, 5]
  • Patients with ischemic cardiomyopathy who are at least 40 days post-MI; have an LVEF of 30% or less; are in NYHA functional class I; are on chronic optimal medical therapy; and are expected to survive longer than 1 year with good functional status
  • Patients who have had ventricular fibrillation (VF)
  • Patients with documented hemodynamically unstable ventricular tachycardia (VT) and/or VT with syncope; with an LVEF less than 40%; on optimal medical therapy; and expected to survive longer than 1 year with good functional status

In moderately symptomatic heart failure patients with an LVEF of 35% or less, primary prevention with an ICD provides no benefit in some cases but substantial benefit in others. A model based on routinely collected clinical variables can be used to predict the benefit of ICD treatment, according to a study by Levy et al.[168] Using data from the placebo arm of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) with their risk prediction model, Levy et al showed that patients could be classified into 5 groups on the basis of predicted 4-year mortality. In the treatment arm, ICD implantation decreased relative risk of sudden cardiac death by 88% in patients with the lowest baseline mortality risk but only by 24% in the highest-risk group. ICD treatment decreased relative risk of total mortality by 54% in the lowest-risk group but only by 2% in the highest-risk group.[168]

It is important to note that use of the SCD-HeFT model has not been prospectively validated for risk stratification in the decision for ICD implantation. More trials are needed.

Cardiac resynchronization therapy/biventricular pacing

Patients with heart failure and interventricular conduction abnormalities (roughly defined as those with a QRS interval >120 ms) are potential candidates for CRT by means of an inserted biventricular pacemaker. CRT aims to improve cardiac performance by restoring the heart’s interventricular septal electrical and mechanical synchrony.[6] Thus, it reduces presystolic mitral regurgitation and optimizes diastolic function by reducing the mismatch between cardiac contractility and energy expenditure.[169]

The ACC/AHA guidelines recommend resynchronization therapy for patients in sinus rhythm or atrial fibrillation with a QRS duration of 120 ms or longer (the greatest benefit is in patients with a QRS >150 ms) and an LVEF of 35% or less with persistent, moderate-to-severe heart failure (NYHA class III and functional NYHA class IV) despite optimal medical therapy.[3] A 2012 update of ACC/AHA/HRS guidelines on CRT expanded Class I indications to patients with NYHA class II symptoms and left-bundle-branch block of ≥150 ms.[163] Biventricular pacing may also be considered in the following patients:

  • Patients with reduced LVEF and a QRS of 150 ms or longer who have NYHA I or II symptoms [6, 170]
  • Patients with reduced LVEF who require chronic pacing and in whom frequent ventricular pacing is expected [3, 6]

The combination of biventricular pacing with ICD implantation (CRT-ICD) may be beneficial for patients with class II heart failure, an LVEF of 30% or less, and QRS duration of more than 150 ms. The MADIT-CRT and Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) investigators reported significant improvement in mortality and morbidity with CRT-ICD treatment versus ICD alone in this group of patients.[170]

Patients with unfavorable coronary sinus anatomy often cannot have a CRT properly placed adjacent to the posterolateral wall of the LV. A study by Giraldi et al suggests that in such patients, a mini-thoracotomy allows for proper lead placement.[171] These patients, when compared with patients who had typical transvenous placement (thus not allowing for preferred posterolateral wall lead placement), had improved outcomes in terms of improved EF and decreased end-systolic volume.[171]

Regarding technique, 3 cardiac leads are placed transvenously: an atrial lead; an RV lead; and an LV lead, which is threaded through the coronary sinus and out one of its lateral wall tributaries. Surgeons have assisted difficult transvenous LV placements by epicardially inserting LV leads using a number of techniques (eg, mini-thoracotomy, thoracoscopy, robotically assisted methods).

Clinical trials of cardiac resynchronization therapy

Several prospective, randomized trials have been performed to evaluate the effectiveness of CRT. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study group demonstrated an improvement in NYHA functional class, quality of life, and LVEF.[172]

A reduction in the risk of heart failure events in patients treated with CRT plus an ICD over that of individuals treated with ICD alone was demonstrated in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). This randomized trial included 1820 patients with an EF of 30% or less, a QRS duration of 130 ms or more, and NYHA class I or II symptoms.[173]

In the MADIT-CRT, during an average follow-up of 2.4 years, death from any cause or a nonfatal heart failure event occurred in 17.2% of patients in the CRT-ICD group versus 25.3% of patients in the ICD-only group. In particular, there was a 41% reduction in the risk of heart failure events in patients in the CRT group, which was evident primarily in patients with a QRS duration of 150 ms or more. CRT was associated with a significant reduction in LV volume and improvement in the EF. No significant difference occurred between the 2 groups in the overall risk of death.[173]

In a follow-up to MADIT-CRT, women seemed to achieve a better response result from resynchronization therapy than men, with a significant 69% reduction in death or heart failure and a 70% reduction in heart failure alone. Those benefits were associated with consistently greater echocardiographic evidence of reverse cardiac remodeling.[174]

Additional findings from MADIT-CRT concerned the relative effects of metoprolol and carvedilol in heart failure patients with devices in place.[175] The key variables were (a) rate of hospitalization for heart failure or death and (b) incidence of ventricular arrhythmia.

Treatment with carvedilol yielded a significantly lower rate of hospitalization for heart failure or death than treatment with metoprolol (23% versus 30%), a reduction that was especially pronounced in patients undergoing CRT with implantable cardioverter-defibrillator (CRT-D), including those with left bundle-branch block (LBBB).[175] The incidence of ventricular arrhythmia was 26% with metoprolol and 22% with carvedilol. There was a clear dose-dependent relation for carvedilol, though not for metoprolol.

In addition to augmenting functional capacity, CRT also appears to favorably affect mortality. The Cardiac Resynchronization-Heart Failure (CARE-HF) trial, which studied CRT placement in patients with NYHA class III or IV heart failure due to LV systolic dysfunction and cardiac dyssynchrony, showed a 36% reduction in death with biventricular pacing.[176]

In the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, biventricular pacing reduced the rate of death from any cause or hospitalization for any cause by approximately 20%. The COMPANION trial was conducted in patients with NYHA class III or IV heart failure due to ischemic or nonischemic cardiomyopathies and a QRS interval of at least 120 ms. The addition of a defibrillator to biventricular pacing incrementally increased the survival benefit, resulting in a substantial 36% reduction in the risk of death compared with optimal pharmacologic therapy.[177]

In both the CARE-HF and the COMPANION studies, mortality was largely due to sudden death.[176, 177]

Noting that high percentages of right ventricular (RV) apical pacing could promote left ventricular (LV) systolic dysfunction, the BLOCK HF trial investigators attempted to determine whether biventricular pacing could improve outcomes in patients with atrioventricular (AV) block and New York Heart Association (NYHA) class I-III heart failure.[178, 179] A total of 691 volunteers received a pacemaker or cardioverter-defibrillator with leads in both ventricles (the LV lead was kept inactive in about half of participants). At follow-up (average, 37 months), 55.6% of the patients in the RV pacing group had died or had worsening heart failure, compared with 45.8% in the biventricular pacing group. The rate of adverse events was comparable in the 2 groups, and most problems occurred during the first month.


Revascularization Procedures

CABG and percutaneous coronary intervention (PCI) are revascularization procedures that should be considered in selected patients with heart failure and CAD. The choice between CABG and PCI depends on the following factors:

  • Patient comorbidities
  • Procedural risk
  • Coronary anatomy
  • Likely extent of viable myocardium in the area to be revascularized
  • Ischemic symptoms
  • LV function
  • Presence of hemodynamically significant valvular disease

In patients who are at low risk for CAD, findings from noninvasive tests such as exercise ECG, stress echocardiography, and stress nuclear perfusion imaging should determine whether subsequent angiography is indicated.[3, 5, 6]

Studies of medical versus surgical therapy for CAD have historically focused on patients with normal LV function. However, a significantly increased survival rate after coronary artery bypass surgery in a subset of patients with an LVEF of less than 50%, in comparison with the survival rate in patients who were randomly selected to receive medical therapy, was demonstrated in the Veterans Affairs Cooperative Study of Surgery. This survival benefit was particularly evident at the 11-year follow-up point (50% vs 38%).

Surgical revascularization prolonged survival to a greater degree than did medical therapy in most clinical and angiographic subgroups in the Coronary Artery Surgery Study (CASS) of patients with left main equivalent disease.[180] Of importance, this study demonstrated that surgical therapy markedly improved the 5-year cumulative survival rate in patients with an EF of less than 50% (80% vs 47%).[181]

These early randomized trials were limited by their inclusion of patients who had what is currently considered a good EF. That is, many patients referred for coronary revascularization live with EFs of less than 35%.

According to a number of studies, surgical revascularization can benefit patients who have ischemic heart failure and substantial areas of viable myocardium in the following ways:

  • Reduced mortality rates
  • Improved NYHA classification
  • Favorable alteration of LV geometry
  • Increased LVEFs

For example, surgical revascularization confers a dramatic survival benefit in patients with a substantial amount of hibernating myocardium (ie, regions of the heart that are dysfunctional under ischemic conditions but that can regain normal function after blood flow is restored).[182, 183] For patients with at least 5 of 12 segments showing myocardial viability, revascularization has been found to result in a cardiac mortality of 3%, versus 31% for medically treated patients with viable myocardium.

Coronary artery bypass grafting

The role of CABG in patients with CAD and heart failure has been unclear. Clinical trials from the 1970s that established the benefit of CABG for patients with CAD excluded patients with an EF of less than 35%. In addition, major advances in medical therapy and cardiac surgery have taken place since these trials.[184]

Investigators from Yale and the University of Virginia, among many others, have published their results of CABG in patients with extremely poor LV function who were on the transplant waiting list. Elefteriades et al reported that in patients with EFs of less than 30% who had CABG, the survival rate was 80% at 4.5 years.[185] This figure approaches that of cardiac transplantation. Kron et al reported a similar 3-year survival rate, of 83%, in patients who underwent coronary artery bypass with an EF of less than 20%.[186]

STICH trial

The Surgical Treatment of Congestive Heart Failure (STICH) study found no significant difference between medical therapy alone and medical therapy plus CABG with respect to death from any cause (the primary study outcome).[184, 187, 188] STICH included 1212 patients with an EF of 35% or less and CAD amenable to CABG. Patients were randomized to either CABG with intensive medical therapy or medical therapy alone and followed up for a median of 56 months.

There was no difference between the treatment groups for all-cause mortality.[184] Owing to the lack of significant difference in the primary endpoint, the secondary endpoints should be viewed cautiously. Except for 30-day mortality, secondary study results favored CABG; compared with study patients assigned to medical therapy alone, patients assigned to CABG had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.[184] Surprisingly, the presence of viable, hibernating myocardium was not predictive of improved outcomes from CABG.[106]

Taken together, these findings suggest that in the absence of severe angina or left main disease, medical therapy alone remains a reasonable option for patients with an EF of 35% or less and CAD. Furthermore, current methods of assessing myocardial viability/hibernating myocardium may not accurately predict benefit from revascularization, although cardiac magnetic resonance imaging offers a promise of accuracy in identifying viable myocardium and predicting the success of revascularization in patients with low EFs.[103]

The adoption of techniques on and off cardiopulmonary bypass, as well as beating-heart techniques for revascularization, highlight the aim of treating high-risk patients.[189] The surgery in the STICH trial was performed with these modern surgical advantages. Preventive strategies include the increased use of bilateral mammary and arterial grafting.[190]


Valvular Surgery

Valvular heart disease may be the underlying etiology or an important aggravating factor in heart failure.[3, 6, 5] The ACC/AHA recommends that valve repair or replacement in patients with hemodynamically significant valvular stenosis or regurgitation and asymptomatic heart failure should be based on contemporary guidelines. In addition, the ACC/AHA indicates that such surgery should be considered for patients with severe aortic or mitral valve stenosis or regurgitation, even when ventricular function is impaired.

The ESC notes that although impaired LVEF is an important risk factor for higher perioperative and postoperative mortality, surgery may be considered in symptomatic patients with poor LV function.[5] However, it is essential that optimal conservative management of the patient's heart failure and any comorbidities be undertaken before surgery, with a thorough clinical and echocardiographic assessment that focuses on cardiovascular and noncardiovascular comorbidities.

Aortic valve replacement

Diseases of the aortic valve can frequently lead to the onset and progression of heart failure. Although the natural histories of aortic stenosis and aortic regurgitation are well known, patients are often followed up conservatively after they present with clinically significant heart failure.

Heart failure is a common indication for aortic valve replacement (AVR), but one must be cautious in patients with a low LVEF and possible aortic stenosis. Assessment of contractile reserve with dobutamine has been demonstrated as a reliable method to determine which patients with low EF and aortic stenosis may benefit from AVR.[191]

If no contractile reserve is present (a finding that suggests some ventricular reserve), the outcome with standard AVR is poor. In this situation, transplantation might be the only option, although the use of percutaneous valves, an apical aortic conduit, or a left ventricular assist device (LVAD) may offer an intermediate solution.


Decision making regarding valve surgery should not be delayed by medical treatment. Be cautious in using vasodilators (ACEIs, ARBs, and nitrates) in patients with severe aortic stenosis, as these agents may cause significant hypotension.[5]

Surgery is recommended in selected patients with symptomatic heart failure and severe aortic stenosis or severe aortic regurgitation, as well as in asymptomatic patients with severe aortic stenosis or severe aortic regurgitation and impaired LVEF (< 50%). This intervention may be considered in patients with a severely reduced valve area and LV dysfunction.

Patient survival

Of the 3 classic symptoms of aortic stenosis—syncope, angina, and dyspnea—dyspnea is the most robust risk factor for death. Only 50% of patients with dyspnea in this setting are still alive within 2 years.[192] Angina is associated with a mortality risk of 50% within 5 years, whereas syncope confers a 50% mortality risk in 3 years.

In contrast, the age-corrected survival rate for patients undergoing AVR for aortic stenosis is similar to that for the normal population.[193] Once patients develop severe LV dysfunction, however, the results of AVR are somewhat guarded.[194] Because of poor LV function, these patients are unable to develop significant transvalvular gradients (ie, low-output, low-gradient aortic stenosis).

A critical aspect of the decision for or against AVR is whether the ventricular dysfunction is truly valvular or reflects other forms of cardiomyopathy, such as ischemia or restrictive processes. Valvular dysfunction improves with AVR; other forms do not.

Precise measurement of the area of the aortic valve is difficult, because the calculated area is directly proportional to cardiac output. Also, the Gorlin constant varies at lower outputs. Therefore, in this situation, valvular areas might be considered critically small when at surgery the valve is found to be only moderately diseased.

Preoperative evaluation with dobutamine testing to increase contractile reserve or with vasodilator-induced stress echocardiography by using the continuity equation rather than the Gorlin formula can be helpful in making this distinction. The results can guide the physician or surgeon in determining whether the patient is a candidate for the relatively high-risk procedure.[195] Nevertheless, because of the possibility of ventricular recovery and lengthened patient survival, most patients with heart failure and aortic stenosis are offered valve replacement.[196]

Surgical timing

Timing of surgical intervention for aortic insufficiency is more challenging in patients just described than in patients with aortic stenosis. However, as before, once symptoms occur and once evidence of LV structural changes become apparent, morbidity and mortality due to aortic insufficiency increase.[197]

As with aortic stenosis, early intervention before the onset of severe LV dysfunction is crucial to improving the survival of patients with aortic insufficiency, as was shown in a retrospective review from the Mayo Clinic. In this study, 450 patients receiving AVR for aortic insufficiency were compared according to ranges of EF (< 35%, 35-50%, >50%). Although the group with severe dysfunction had an operative mortality of 14%, the EF improved, and the group's 10-year survival rate was 41%.[198, 199]

Mitral valve repair

Mitral valve regurgitation can either cause or result from chronic heart failure. Its presence is an independent risk factor for cardiovascular morbidity and mortality.[200] In addition to frank rupture of the papillary muscle in association with acute MI, chronic ischemic cardiomyopathies result in migration of the papillary muscle as the ventricle dilates. This dilation causes tenting of the mitral leaflets, restricting their coaptation.

Dilated cardiomyopathies can have similar issues, as well as annular dilatation. In addition to mitral regurgitation, the alteration in LV geometry contributes to volume overload, increases LV wall tension, and leaves patients susceptible to exacerbations of heart failure.[201]

Mitral valve surgery in patients with heart failure has gained favor, because it abolishes the regurgitant lesion and decreases symptoms. The pathophysiologic rationales for repair or replacement are to reverse the cycle of excessive ventricular volume, to allow for ventricular unloading, and to promote myocardial remodeling.

Among other researchers, a group from Michigan has advocated mitral repair in the population with heart failure. Bolling and colleagues demonstrated that mitral valve repair increased the EF, improved NYHA classes from 3.9 to 2.0, and decreased the number of hospitalizations, although the results have not been able to be reproduced by other centers.[202] Additional effects with repair in these patients are the increase in coronary blood flow reserve afforded by the reduction in LV volume.[203]

Despite the potential benefits of mitral reconstruction surgery, a retrospective review showed no decrease in long-term mortality among patients with severe mitral regurgitation and significant LV dysfunction who underwent mitral valve repair.[204] Mitral valve annuloplasty was not predictive of clinical outcomes and did not improve mortality. Factors associated with lower mortality were ACEI use, beta-blockade, normal mean arterial pressures, and normal serum sodium concentrations. The results of this analysis were not overly surprising. For example, in most patients in this situation, heart failure is not due to flail leaflets but is secondary to ventricular dysfunction.

In evaluating studies of heart failure with mitral regurgitation, it is important to separate the etiology (eg, ischemic vs dilated) as well as the surgical approaches. Future trials must be designed to distinguish differences between various surgical strategies, such as annuloplasty, resuspension of the papillary muscle, secondary chordal transection, ventricular reconstruction, passive restraints, and chordal-sparing valve replacement. A paramount goal with these procedures is for the patient to have little or no residual mitral regurgitation.[205]


The ESC recommends considering mitral valve surgery in patients with heart failure and severe mitral valve regurgitation whenever coronary revascularization is an option.[5] Candidates would include the following[5] :

  • Patients with severe mitral regurgitation due to an organic structural abnormality or damage to the mitral valve in whom symptoms of heart failure develop
  • Patients with an LVEF greater than 30%
  • Patients with severe ischemic mitral regurgitation and an LVEF greater than 30% when CABG is planned

The HFSA indicates that isolated mitral valve repair or replacement for severe mitral regurgitation secondary to ventricular dilatation in the presence of severe LV systolic dysfunction is not generally recommended.[6]

CRT should be considered in eligible patients with functional mitral regurgitation, as it may improve LV geometry and papillary muscle dyssynchrony and may reduce mitral regurgitation.[5]


Treatment of cardiomyopathy-associated mitral regurgitation most commonly involves the insertion of either a complete or a partial band attached to the annulus of the mitral valve. Thus, mitral repair deals with only 1 aspect of the patient's overall pathophysiologic condition. That is, annuloplasty rings may assist with tenting of the leaflet, but they do not address displacement of the papillary muscle with ventricular scarring.[206] In many patients, the underlying problem (ie, primary myopathy) continues unabated.

In general, ischemic mitral regurgitation is a ventricular problem. Many operations allow for coaptation and no mitral regurgitation when the patient leaves the operating room. However, as the left ventricle continues to dilate, mitral regurgitation often recurs. Therefore, it is overambitious to say that annuloplasty cures this condition. As a result, many other approaches have been attempted (eg, chordal cutting, use of restraint devices, papillary relocation). However, results have been mixed.

Mitral valve replacement

If repair is deemed improbable, mitral replacement should be performed. Traditional mitral valve replacement includes complete resection of the leaflets and the chordal attachments. This destruction of the subvalvular apparatus results in ventricular dysfunction. In patients with mitral regurgitation and heart failure, preservation of the chordal attachments to the ventricle with valve replacement might provide results similar to, or even better than, those of annuloplasty.[207, 208]

Although the benefits in terms of quality of life (decreased heart failure) might not portend increased survival in these high-risk patients,[209, 210] they likely keep low-EF mitral valve interventions in the armamentarium of surgeons who manage heart failure.

An emerging approach to functional and degenerative mitral valve regurgitation is percutaneous mitral valve repair, using devices such as the MitraClip system. The EVEREST (Endovascular Valve Edge-to-Edge Repair Study II) randomized trial reported low rates of morbidity and mortality and reduction of acute mitral regurgitation to less than 2+ in the majority of patients, with sustained freedom from death, surgery, or recurrent mitral regurgitation in a substantial proportion of patients.[211]


Ventricular Restoration

After a transmural MI occurs, the ventricle pathologically remodels from its normal elliptical shape to a spherical shape. This change in geometry is in part responsible for the constellation of symptoms associated with HF and decreased survival.[212, 213]

Several ventricular restoration techniques exist. All aim to correct the above-described pathologic alteration in geometry. Most approaches involve incising and excluding nonviable myocardium with either patch or primary reconstruction to decrease ventricular volume.

The Batista procedure (reduction left ventriculoplasty) was designed with the intent of providing ventricular restoration, but it was associated with high failure rates. Although the initial enthusiasm for ventricular resection to treat nonischemic dilated cardiomyopathies has faded, a long-established finding is that resection of dyskinetic segments associated with LV aneurysms can increase patients' functional status and prolong life.[214, 215]

The success of early lytic and percutaneous therapy for acute MI has decreased the incidence of true LV aneurysms. As such, ventricular restoration now focuses on excluding relatively subtle regions of akinetic myocardium.

Benefits from ventricular restoration using the technique Dor described were reported in 2004 by the International Reconstructive Endoventricular Surgery Returning Torsion Original Radius Elliptical Shape to the Left Ventricle (RESTORE) group.[216] The investigators reported that among the patients studied, EFs increased from 29.6% to 39.5%, the end-systolic volume index decreased, and NYHA functional classes improved from 67% class III/IV before surgery to 85% class I/II after surgery.

The major study of ventricular reconstruction has been the STICH trial. The major study of ventricular reconstruction has been the STICH trial.[217] One thousand patients with an ejection fraction of less than 35%, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone or CABG with surgical ventricular reconstruction (SVR). The median follow-up was 48 months. SVR reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved to a similar degree in both groups. However, no significant difference was observed in death from any cause and hospitalization for cardiac causes. On the basis of these results, SVR cannot be recommended for routine use in patients with ischemic cardiomyopathy and dominant anterior left ventricular dysfunction.


Extracorporeal Membrane Oxygenation

In some cases of extreme cardiopulmonary failure (ie, ACC/AHA stage D), the only recourse is complete support with extracorporeal membrane oxygenation (ECMO). ECMO provides both oxygenation and circulation of blood, allowing the lungs and heart time to recover. Unlike cardiopulmonary bypass, whose duration of use is measured in hours, ECMO can be used for 3-10 days.

For ECMO, one cannula is placed percutaneously via the right jugular vein or femoral vein into the right atrium, or it is placed surgically into the right atrial appendage, and another cannula is placed arterially either in the femoral artery or in the aortic arch. The drained venous blood is pumped through the ECMO device, where it is oxygenated, warmed, and anticoagulated. It is then returned to the arterial circulation.

ECMO devices can be used for short-term circulatory support in patients who are expected to recover from a major cardiac insult. Despite encouraging results with ECMO for the management of cardiogenic shock, most patients requiring circulatory assistance can be helped with ventricular support alone.


Ventricular Assist Devices

Ventricular assist devices (VADs) are invaluable tools in the treatment of heart failure. A number of these devices are available to support the acutely or chronically decompensated heart (ie, ACC/AHA stage D). Depending on the particular device used, the right ventricle and left ventricle can be assisted with a left ventricular assist device (LVAD), a right VAD (RVAD), or a biventricular assist device (BiVAD). An alternative term for a VAD is a ventricular assist system (VAS).[218, 219]

In concept, LVADs, RVADs, and BiVADs are similar. Blood is removed from the failing ventricle and diverted into a pump that delivers blood to either the aorta (in the case of an LVAD) or the pulmonary artery (in the case of an RVAD). An exception is the Impella (Abiomed, Inc). This device is inserted percutaneously into the left ventricle; it draws blood from the left ventricle and expels it into the ascending aorta.

LVADs can often be placed temporarily. In patients with acute, severe myocarditis or those who have undergone cardiotomy, this approach can serve as a bridge to recovery, unloading the dysfunctional heart and perhaps allowing reverse remodeling; in patients with end-stage heart failure, it can serve as a bridge to heart transplantation,[5, 6, 162] allowing them to undergo rehabilitation and possibly go home before transplantation.

Long-term use (ie, destination therapy rather than bridge therapy) may be a consideration when no definitive procedure is planned.[5] Patients with severe heart failure who are not transplant candidates and who otherwise would die without treatment are candidates for lifetime use of VADs. Destination therapy with LVADs is superior to medical therapy in terms of quantity and quality of life, according to the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial and several later studies.[220, 221]

In the United States, several Food and Drug Administration (FDA)–approved options are available for bridging the patient to recovery and transplantation. These options continue to change and evolve. Some examples include are as follows:

  • Abiomed AB5000 Ventricle (Abiomed, Inc)
  • AB Portable Driver (Abiomed, Inc)
  • Thoratec CentriMag Blood Pump (Thoratec Corp)
  • Thoratec PVAD (Paracorporeal Ventricular Assist Device) (Thoratec Corp)
  • Thoratec IVAD (Implantable Ventricular Assist Device) (Thoratec Corp)
  • HeartMate XVE LVAD (also known as HeartMate I) (Thoratec Corp)
  • HeartMate II LVAS (Thoratec Corp)
  • TandemHeart Percutaneous LVAD (CardiacAssist Inc)
  • HeartAssist 5 Pediatric VAD (MicroMed Technology)

The HeartMate LV assist systems are the only LVADs that are approved by the US Food and Drug Administration (FDA) for destination therapy. Several other devices are actively being studied in the United States for use as destination therapy, such as the DeBakeyVAD (MicroMed Cardiovascular, Inc) and the Impella Recover (Abiomed, Inc).

In addition, Jarvik 2000 Flowmaker (Jarvik Heart, Inc), MiFlow VAD (WorldHeart Inc), and PediaFlow VAD (WorldHeart Inc) are actively involved in clinical trials.

The HeartMate XVE LVAD (Thoratec) does not require warfarin anticoagulation, unlike another well-known first-generation pulsatile pump, the Novacor LVAD (WorldHeart). The newer axial-flow pumps (eg, HeartMate II LVAS, Jarvik 2000, HeartAssist 5 Pediatric VAD) are relatively small and easy to insert, and they decrease morbidity; however, they do require anticoagulation.

Potential complications of VADs include mechanical breakdown, infection, bleeding, and thromboembolic events. Despite these potential drawbacks, however, the survival rate for patients receiving VADs is roughly 70%. This rate is impressive given the severity of illness in this cohort of patients. Furthermore, the evolving technology raises a host of clinical and physiologic questions that, when studied and answered, continue to advance the field.

Selected trials

In the REMATCH study, survival rates of medically treated and LVAD-treated patients were, respectively, 25% and 52% at 1 year and 8% and 23% at 2 years.[222] The study offered the first prospective, randomized data of very ill, non–transplant-eligible patients with heart failure receiving optimal medical therapy versus an early-generation HeartMate LVAD. In addition to survival advantage, LVAD patients had improvements in several measures of quality of life.

Modifications in technique and perioperative care have decreased the rates of LVAD-related morbidity and mortality observed in the REMATCH trial.[223] Although REMATCH was a single study in very high risk patients, the data serve as proof of concept for the future development of VAD technologies.

Despite the need for an external energy source, most patients can use mechanical circulatory devices in the outpatient setting. Many patients have lived productive lives for longer than 4-6 years with their original device (depending on the device).

Starling et al used INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) data to determine that following postmarket approval by the FDA, the HeartMate II LVAS, a continuous-flow LVAD, continues to have excellent results as a bridge to heart transplantation relative to other types of LVADs in the following measures[224] :

  • The 30-day operative mortality was 4% for the group receiving the HeartMate II compared with 11% for other LVADs
  • Ninety-one percent of the group receiving the HeartMate II reached transplant, cardiac recovery, or ongoing LVAD support by 6 months, compared with 80% for the group receiving other LVADs
  • Renal function test levels such as creatinine and blood urea nitrogen were lower in the HeartMate II group
  • For all adverse events, the rates were similar or lower for the group that received the HeartMate II, with bleeding being the most frequent adverse event for both groups
  • Survival for patients remaining on support at 1 year was 85% for the HeartMate II group, versus 70% for the group with other LVADs
  • Relative to baseline, both groups had significant improvement of quality of life at 3 months of support, which was sustained through 12 months

In another study, Ventura et al used a large national data registry to compare posttransplant outcomes between pulsatile-flow (HeartMate XVE [HeartMate I]) and continuous-flow (HeartMate II) LVADs as bridges to transplantation and found similar 1- and 3-year survival rates but less risk of early allograft rejection and sepsis with the HeartMate II device.[225]

Patients with class IV stage D heart failure who are symptomatic despite optimal medical heart failure therapy for 45 of 60 days or who require inotropic support for 14 days or IABP support for 7 days and have no contraindication for anticoagulation are eligible for implantation on LVAD HM II as destination therapy if they are not eligible or if they do not desire cardiac transplantation. The INTERMACS registry (a national database for patients with advanced heart failure receiving mechanical circulatory support) has established a patient profile (1-7) that determines urgency to implantation and assesses risk and survival at 90 days.

Recommendations for clinical management of continuous-flow LVAD were published in 2010, assisting providers with standardized care for this patient population.[226] Bleeding, infection, and stroke are postimplant complications, and death may occur due to right heart failure, sepsis, or stroke. A multidisciplinary approach to LVAD implantation is needed, as destination therapy identifies patients at high risk for complications and the need to optimize these patients medically before surgery. In a recent report from INTERMACS, 1-year survival for destination-therapy patients was 61% for pulsatile devices and 74% for continuous-flow devices.[227]


Heart Transplantation

Selected patients with severe heart failure, debilitating refractory angina, ventricular arrhythmia, or congenital heart disease that cannot be controlled despite pharmacologic, medical device, or alternative surgical therapy should be evaluated for heart transplantation.[6] The patient must be well informed, motivated, and emotionally stable; have a good social support network; and be capable of complying with intensive medical treatment.[5]

Since Christiaan Barnard performed the first orthotopic heart transplantation in 1967, the world has seen tremendous advancement in the field of cardiac transplantation. For patients with progressive end-stage heart failure despite maximal medical therapy who have a poor prognosis and no viable alternative form of treatment,[5] heart transplantation has become the criterion standard for therapy.[3]

Compared with patients who receive only medical therapy, transplant recipients have fewer rehospitalizations; marked functional improvements; enhanced quality of life; more gainful employment; and longer survival, with 50% surviving 10 years postoperatively.[228] Heart transplantation is associated with a 1-year survival rate of 83%; subsequently, survival decreases in a linear manner by approximately 3.4% per year.

Careful selection of donors and recipients is critical for ensuring good outcomes. In addition, transplant teams must strive to minimize potential perioperative dangers, including ischemic times, pulmonary hypertension, mechanical support, and cardiogenic shock.

For more information, see the Medscape Reference article Heart Transplantation.


According to the ACC/AHA, absolute indications for heart transplantation include hemodynamic compromise following heart failure, including the following scenarios[3] :

  • Refractory cardiogenic shock
  • Dependence on IV inotropic support for adequacy of organ perfusion
  • Peak oxygen consumption per unit time (VO 2) less than 10 mL/kg/min
  • Severe ischemic symptoms with consistent limitations of routine activity that are not amenable to revascularization procedures (CABG, percutaneous coronary intervention)
  • Recurrent symptomatic ventricular arrhythmias despite all therapeutic interventions

Relative indications for heart transplantation include the following[3] :

  • Peak VO 2 between 11 and 14 mL/kg/min (or 55% of predicted) with major limitation of routine activities
  • Recurrent unstable ischemia that is not amenable to other treatment
  • Recurrent instability of fluid balance/renal function despite patient compliance with medical therapy

In the absence of other indications, however, the following are not sufficient indications for heart transplantation[3] :

  • Low LVEF
  • History of NYHA class III/IV heart failure symptoms
  • Peak VO 2 >15 mL/kg/min (and >55% predicted)


The ESC indicates that heart transplantation is contraindicated in patients with the following conditions[5] :

  • Current alcohol and/or drug abuse
  • Lack of compliance
  • Uncontrolled or mental health disease
  • Active malignancy
  • Multiorgan systemic disease
  • Active infection except for LVAD infection
  • Significant renal failure (creatinine clearance < 50 mL/min), significant hepatic dysfunction, or pulmonary disease (FEV 1 < 50% of predicted or < 1 L)
  • Irreversible high pulmonary vascular resistance (6-8 Wood units and mean transpulmonary gradient >15 mmHg)
  • Recent thromboembolic complications
  • Unhealed peptic ulcer
  • Other serious comorbidity with a poor prognosis

Note that the HFSA and ESC indicate that cardiomyoplasty and partial left ventriculectomy (Batista operation) is not recommended to treat heart failure, nor should it be used as an alternative to heart transplantation.[5, 6]

Coronary graft atherosclerosis

The Achilles heel of the long-term success of heart transplantation is the development of coronary graft atherosclerosis, the cardiac version of chronic rejection. Coronary graft atherosclerosis is uniquely different from typical coronary artery disease in that it is diffuse and is usually not amenable to revascularization.

Shortage of donor hearts

In the United States, fewer than 2500 heart transplantation procedures are performed annually.[229] Each year, an estimated 10-20% of patients die while awaiting a heart transplant. Of the 5 million people with heart failure, approximately 30,000 to 100,000 have such advanced disease that they would benefit from transplantation or mechanical circulatory support.[230] This disparity between the number of patients needing transplants and the availability of heart donors has refocused efforts to find other ways to support severely failing hearts.


Total Artificial Heart

The creation of a suitable total artificial heart (TAH) for orthotopic implantation has been the subject of intense investigation for decades.[231] In 1969, Dr. Denton Cooley implanted the Liotta TAH (which is no longer made) into a high-risk patient after failing to wean the patient off cardiopulmonary bypass after LV aneurysm repair. The patient was sustained until, after 3 days, a donor heart became available, but the patient subsequently died of pneumonia and multiple organ failure.[232]

Compared with LVADs, the TAH has several potential advantages, including the ability to assist patients with severe biventricular failure; a lack of device pocket and thus a lessened risk of infection; and the opportunity to treat patients with systemic diseases (eg, amyloidosis, malignancy) who are not otherwise candidates for transplantation.[233, 234, 235, 236, 237]

At present, 2 TAHs are receiving the most attention:

  • SynCardia (formerly CardioWest) TAH (SynCardia Systems, Inc)
  • AbioCor TAH (Abiomed, Inc)

The SynCardia TAH is a structural cousin of the original Jarvik-7 TAH (Jarvik Heart, Inc) that was implanted into patient Barney Clark with great publicity in 1982. In 2004, investigators reported data that allowed this device to receive FDA approval for use as a bridge to transplantation.

The AbioCor TAH involves a novel method of transcutaneous transmission of energy, freeing the patient from external drivelines. The patient exchanges the external battery packs, which can last as long as 4 hours. This TAH is unique in that it is the first TAH to use coils to transmit power across the skin; therefore, no transcutaneous conduits are needed. This feature allows for the advantages of a closed system, which potentially reduces sources of infection, a known complication of earlier devices.

The first clinical implantation of this TAH was performed in July 2001. Before the end of 2004, 14 patients had received this device as part of a trial in patients whose expected survival was less than 30 days. Although all subsequently died, 4 patients were ambulatory after surgery, and 2 were discharged from the hospital to a transitional-care setting. One of the discharged patients was discharged on postoperative day 209. A limitation of the AbioCor TAH is its large size, which permits its implantation in only 50% of men and 20% of women. In 2006, the FDA approved the Abiocor TAH as a permanent TAH for humanitarian uses.

The SynCardia and AbioCor TAHs require recipient cardiectomy before implantation. The devices are similar in that they are sewn to atrial cuffs and to the great vessels after the native heart is explanted.

Despite more than 40 years of effort, the clinical application of artificial-heart technology is still immature. However, with the approval of the SynCardia device and with new efforts to create small pumps, TAHs will ultimately be routine components of heart failure surgery for very sick patients with heart failure and biventricular failure.

Contributor Information and Disclosures

Ioana Dumitru, MD Associate Professor of Medicine, Division of Cardiology, Founder and Medical Director, Heart Failure and Cardiac Transplant Program, University of Nebraska Medical Center; Associate Professor of Medicine, Division of Cardiology, Veterans Affairs Medical Center

Ioana Dumitru, MD is a member of the following medical societies: American College of Cardiology, International Society for Heart and Lung Transplantation, Heart Failure Society of America

Disclosure: Nothing to disclose.


Mathue M Baker, MD Cardiologist, BryanLGH Heart Institute and Saint Elizabeth Regional Medical Center

Mathue M Baker, MD is a member of the following medical societies: American College of Cardiology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Henry H Ooi, MD, MRCPI Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville Veterans Affairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine

Disclosure: Nothing to disclose.


Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York AcademyofSciences,and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital

David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Joseph Cornelius Cleveland Jr, MD Associate Professor, Division of Cardiothoracic Surgery, University of Colorado Health Sciences Center

Joseph Cornelius Cleveland Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American College of Cardiology, American College of Chest Physicians, American College of Surgeons, American Geriatrics Society, American Physiological Society, American Society of Transplant Surgeons, Association for Academic Surgery, Heart Failure Society of America, International Society for Heart and Lung Transplantation, Phi Beta Kappa, Society of Critical Care Medicine, Society of Thoracic Surgeons, and Western Thoracic Surgical Association

Disclosure: Thoratec Heartmate II Pivotal Tria; Grant/research funds Principal Investigator - Colorado; Abbott Vascular E-Valve E-clip Honoraria Consulting; Baxter Healthcare Corp Consulting fee Board membership; Heartware Advance BTT Trial Grant/research funds Principal Investigator- Colorado; Heartware Endurance DT trial Grant/research funds Principal Investigator-Colorado

Shamai Grossman, MD, MS Assistant Professor, Department of Emergency Medicine, Harvard Medical School; Director, The Clinical Decision Unit and Cardiac Emergency Center, Beth Israel Deaconess Medical Center

Shamai Grossman, MD, MS is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

John D Newell Jr, MD Professor of Radiology, Head, Division of Radiology, National Jewish Health; Professor, Department of Radiology, University of Colorado School of Medicine

John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians, American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association of University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology

Disclosure: Siemens Medical Grant/research funds Consulting; Vida Corporation Ownership interest Board membership; TeraRecon Grant/research funds Consulting; Medscape Reference Honoraria Consulting; Humana Press Honoraria Other

Craig H Selzman, MD, FACS Associate Professor of Surgery, Surgical Director, Cardiac Mechanical Support and Heart Transplant, Division of Cardiothoracic Surgery, University of Utah School of Medicine

Craig H Selzman, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Thoracic Surgery, American College of Surgeons, American Physiological Society, Association for Academic Surgery, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons, Southern Thoracic Surgical Association, and Western Thoracic Surgical Association

Disclosure: Nothing to disclose.

Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; Royalty Other

Brett C Sheridan, MD, FACS Associate Professor of Surgery, University of North Carolina at Chapel Hill School of Medicine

Disclosure: Nothing to disclose.

George A Stouffer III, MD Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director of Interventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology, University of North Carolina Medical Center

George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.
Cardiac cirrhosis. Congestive hepatopathy with large renal vein.
Cardiac cirrhosis. Congestive hepatopathy with large inferior vena cava.
This electrocardiogram (ECG) is from a 32-year-old female with recent-onset congestive heart failure and syncope. The ECG demonstrates a tachycardia with a 1:1 atrial:ventricular relationship. It is not clear from this tracing whether the atria are driving the ventricles (sinus tachycardia) or the ventricles are driving the atria (ventricular tachycardia).At first glance, sinus tachycardia in this ECG might be considered with severe conduction disease manifesting as marked first-degree atrioventricular block with left bundle branch block. Looking more closely, electrocardiographic morphology gives clues to the actual diagnosis of VT. These clues include the absence of RS complexes in the precordial leads, a QS pattern in V6, and an R wave in aVR. The patient proved to have an incessant VT associated with dilated cardiomyopathy.
This is a posteroanterior view of a right ventricular endocardial activation map during ventricular tachycardia in a patient with a previous septal myocardial infarction. Earliest activation is recorded in red; late activation shows as blue to magenta. Fragmented low-amplitude diastolic local electrocardiograms were recorded adjacent to the earliest (red) breakout area, and local ablation in this scarred zone (red dots) resulted in termination and noninducibility of this previously incessant arrhythmia.
A 28-year-old woman presented with acute heart failure secondary to chronic hypertension. The enlarged cardiac silhouette on this anteroposterior (AP) radiograph is caused by acute heart failure due to the effects of chronic high blood pressure on the left ventricle. The heart then becomes enlarged, and fluid accumulates in the lungs (ie, pulmonary congestion).
Epsilon wave on an electrocardiogram in a patient with arrhythmogenic right ventricular dysplasia (ARVD). ARVD is a congenital cardiomyopathy that is characterized by infiltration of adipose and fibrous tissue into the right ventricle wall and loss of myocardial cells. Primary injuries usually are at the free wall of right ventricular and right atria, resulting in ventricular and supraventricular arrhythmias. The most significant of all rhythms associated with heart failure are the life-threatening ventricular arrhythmias.
Electrocardiogram depicting ventricular fibrillation in a patient with a left ventricular assist device (LVAD). Ventricular fibrillation is often due to ischemic heart disease and can lead to myocardial infarction and/or sudden death.
The rhythm on this electrocardiogram (ECG) is sinus with borderline PR prolongation. There is evidence of an acute/evolving anterior ischemia/myocardial infarction (MI) superimposed on the left bundle branch block–like (LBBB) pattern. Note the primary T wave inversions in leads V2-V4, rather than the expected discordant (upright) T waves in the leads with a negative QRS. Although this finding is not particularly sensitive for ischemia/MI with LBBB, such primary T wave changes are relatively specific. The prominent voltage with left atrial abnormality and leftward axis in concert with the left ventricular intraventricular conduction delay (IVCD) are consistent with underlying left ventricular hypertrophy. This ECG is an example of "bundle branch block plus." Image courtesy of .
This electrocardiogram (ECG) shows evidence of severe left ventricular hypertrophy (LVH) with prominent precordial voltage, left atrial abnormality, lateral ST-T abnormalities, and a somewhat leftward QRS axis (–15º). The patient had malignant hypertension with acute heart failure, accounting also for the sinus tachycardia (blood pressure initially 280/180 mmHg). The ST-T changes seen here are nonspecific and could be due to, for example, LVH alone or coronary artery disease. However, the ECG is not consistent with extensive inferolateral myocardial infarction. Image courtesy of .
The rhythm on this electrocardiogram is atrial tachycardia (rate, 154 beats/min) with a 2:1 atrioventricular (AV) block. Note the partially hidden, nonconducted P waves on the ST segments (eg, leads I and aVL). The QRS is very wide with an atypical intraventricular conduction defect (IVCD) pattern. The rSR' type complex in the lateral leads (I, aVL) is not due to a right bundle branch block (RBBB) but to an atypical left ventricular conduction defect. These unexpected rSR' complexes in the lateral leads (El-Sherif sign) correlate with underlying extensive myocardial infarction (MI) and, occasionally, ventricular aneurysm. (El-Sherif. Br Heart J. 1970;32:440-8.) The notching on the upstroke of the S waves in lead V4 with a left bundle branch block-type pattern also suggests underlying MI (Cabrera sign). This patient had severe cardiomyopathy secondary to coronary artery disease, with extensive left ventricular wall motion abnormalities. Image courtesy of .
On this electrocardiogram, baseline artifact is present, simulating atrial fibrillation. Such artifact may be caused by a variety of factors, including poor electrode contact, muscle tremor, and electrical interference. A single premature ventricular complex (PVC) is present with a compensatory pause such that the RR interval surrounding the PVC is twice as long as the preceding sinus RR interval. Evidence of a previous anterior myocardial infarction is present with pathologic Q waves in leads V1-V3. Borderline-low precordial voltage is a nonspecific finding. Cardiac catheterization showed a 90% stenosis in the patient's proximal portion the left anterior descending coronary artery, which was treated with angioplasty and stenting. Broad P waves in lead V1 with a prominent negative component is consistent with a left atrial abnormality. Image courtesy of .
This electrocardiogram (ECG) is from a patient who underwent urgent cardiac catheterization, which revealed diffuse severe coronary spasm (most marked in the left circumflex system) without any fixed obstructive lesions. Severe left ventricular wall motion abnormalities were present, involving the anterior and inferior segments. A question of so-called takotsubo cardiomyopathy (left ventricular apical ballooning syndrome) is also raised (see Bybee et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Int Med 2004:141:858-65). The latter is most often reported in postmenopausal, middle-aged to elderly women in the context of acute emotional stress and may cause ST elevations acutely with subsequent T wave inversions. A cocaine-induced cardiomyopathy (possibly related to coronary vasospasm) is a consideration but was excluded here. Myocarditis may also be associated with this type of ECG and the cardiomyopathic findings shown here. No fixed obstructive epicardial coronary lesions were detected by coronary arteriography. The findings in this ECG include low-amplitude QRS complexes in the limb leads (with an indeterminate QRS axis), loss of normal precordial R wave progression (leads V1-V3), and prominent anterior/lateral T wave inversions. Image courtesy of .
This electrocardiogram shows an extensive acute/evolving anterolateral myocardial infarction pattern, with ST-T changes most apparent in leads V2-V6, I, and aVL. Slow R wave progression is also present in leads V1-V3. The rhythm is borderline sinus tachycardia with a single premature atrial complex (PAC) (4th beat). Note also the low limb lead voltage and probable left atrial abnormality. Left ventriculography showed diffuse hypokinesis as well as akinesis of the anterolateral and apical walls, with an ejection fraction estimated at 33%. Image courtesy of
This electrocardiogram shows a patient is having an evolving anteroseptal myocardial infarction secondary to cocaine. There are Q waves in leads V2-V3 with ST segment elevation in leads V2-V5 associated with T-wave inversion. Also noted are biphasic T-waves in the inferior leads. These multiple abnormalities suggest occlusion of a large left anterior descending artery that wraps around the apex of the heart (or multivessel coronary artery disease). Image courtesy of .
A color-enhanced angiogram of the heart left shows a plaque-induced obstruction (top center) in a major artery, which can lead to myocardial infarction (MI). MIs can precipitate heart failure.
Emphysema is included in the differential diagnosis of heart failure. In this radiograph, emphysema bubbles are noted in the left lung; these can severely impede breathing capacity.
Cervicocephalic fibromuscular dysplasia (FMD) can lead to complications such as hypertension and chronic kidney failure, which can lead to heart failure. In this color Doppler and spectral Doppler ultrasonographic examination of the left internal carotid artery (ICA) in a patient with cervicocephalic FMD, stenoses of about 70% is seen in the ICA.
Cervicocephalic fibromuscular dysplasia (FMD) can lead to complications such as hypertension and chronic kidney failure, which, in turn, can lead to heart failure. Nodularity in an artery is known as the string-of-beads sign, and it can be seen this color Doppler ultrasonographic image from a 51-year-old patient with low-grade stenosing FMD of the internal carotid artery (ICA).
Electrocardiogram from a 46-year-old man with long-standing hypertension showing left atrial abnormality and left ventricular hypertrophy with strain.
Electrocardiogram from a 46-year-old man with long-standing hypertension showing left atrial abnormality and left ventricular hypertrophy with strain.
Apical 4-chamber echocardiogram in a 37-year-old man with arrhythmogenic right ventricular dysplasia (ARVD), a congenital cardiomyopathy. Note the prominent trabeculae and abnormal wall motion of the dilated right ventricle.ARVD can result in ventricular and supraventricular arrhythmias. The most significant of all rhythms associated with heart failure are the life-threatening ventricular arrhythmias.
Cardiac magnetic resonance image (CMRI), short axis view. This image shows right ventricular dilatation, trabucular derangement, aneurysm formation and dyskinetic free wall in a patient with arrhythmogenic right ventricular dysplasia.
Transthoracic echocardiogram demonstrating severe mitral regurgitation with heavily calcified mitral valve and prolapse of the posterior leaflet into the left atrium.
Echocardiogram of a patient with severe pulmonic stenosis. This image shows a parasternal short axis view of the thickened pulmonary valve. Pulmonic stenosis can lead to pulmonary hypertension, which can result in hepatic congestion and in right-sided heart failure.
Echocardiogram of a patient with severe pulmonic stenosis. This image shows a Doppler scan of the peak velocity (5.2 m/s) and gradients (peak 109 mm Hg, mean 65 mm Hg) across the valve.
Echocardiogram of a patient with severe pulmonic stenosis. This image shows that moderately severe pulmonary insufficiency (orange color flow) is also present.
This video is an echocardiogram of a patient with severe pulmonic stenosis. The first segment shows the parasternal short axis view of the thickened pulmonary valve. The second segment shows the presence of moderate pulmonary insufficiency (orange color flow). AV = aortic valve, PV = pulmonary valve, PA = pulmonary artery, PI = pulmonary insufficiency.
Transesophageal echocardiogram with continuous wave Doppler interrogation across the mitral valve demonstrating an increased mean gradient of 16 mm Hg consistent with severe mitral stenosis.
Table 1. Framingham Diagnostic Criteria for Heart Failure
Major Criteria Minor Criteria
Paroxysmal nocturnal dyspnea Nocturnal cough
Weight loss of 4.5 kg in 5 days in response to treatment Dyspnea on ordinary exertion
Neck vein distention A decrease in vital capacity by one third the maximal value recorded
Rales Pleural effusion
Acute pulmonary edema Tachycardia (rate of 120 bpm)
Hepatojugular reflux Hepatomegaly
S3 gallop Bilateral ankle edema
Central venous pressure > 16 cm water  
Circulation time of 25 sec  
Radiographic cardiomegaly  
Pulmonary edema, visceral congestion, or cardiomegaly at autopsy  
Source:  Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol. 1993 Oct;22(4 suppl A):6A-13A.[1]
Table 2. NYHA Functional Classification of Heart Failure
Class Functional Capacity
I Patients without limitation of physical activity
II Patients with slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, dyspnea, or anginal pain; they are comfortable at rest
III Patients with marked limitation of physical activity, in which less than ordinary activity results in fatigue, palpitation, dyspnea, or anginal pain; they are comfortable at rest
IV Patients who are not only unable to carry on any physical activity without discomfort but who also have symptoms of heart failure or the anginal syndrome even at rest; the patient's discomfort increases if any physical activity is undertaken
Source:  American Heart Association. Classes of heart failure. Available at: Accessed: September 6, 2011.[2]
Table 3. ACC/AHA Stages of Heart Failure Development
level Description Examples Notes
A At high risk for heart failure but without structural heart disease or symptoms of heart failure Patients with coronary artery disease, hypertension, or diabetes mellitus without impaired LV function, hypertrophy, or geometric chamber distortion
  • Patients with predisposing risk factors for developing heart failure
  • Corresponds with patients with NYHA class I heart failure
B Structural heart disease but without signs/symptoms of heart failure Patients who are asymptomatic but who have LVH and/or impaired LV function
C Structural heart disease with current or past symptoms of heart failure Patients with known structural heart disease and shortness of breath and fatigue, reduced exercise tolerance
  • The majority of patients with heart failure are in this stage
  • Corresponds with patients with NYHA class II and III heart failure
D Refractory heart failure requiring specialized interventions Patients who have marked symptoms at rest despite maximal medical therapy
  • Patients in this stage may be eligible to receive mechanical circulatory support, receive continuous inotropic infusions, undergo procedures to facilitate fluid removal, or undergo heart transplantation or other procedures
  • Corresponds with patients with NYHA class IV heart failure
Sources:  (1) Hunt SA, American College of Cardiology, and the American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). 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. J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82.[4] ; and (2) Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol. Apr 14 2009;53(15):e1-e90.[3]
Table 4. Evidence-Based BNP and NT-proBNP Cutoff Values for Diagnosing HF
Criterion BNP, pg/mL NT-proBNP, pg/mL
HF Unlikely (LR-Negative) HF Likely (LR-Positive) HF Unlikely (LR-Negative) HF Likely (LR-Positive)
Age, y >17 < 100 (0.13)* >500 (8.1)* - -
>21 - - < 300 (0.02) -
21-50 - - - >450 (14)
50-75 - - - >900 (5.0)
>75 - - - >1800 (3.1)
Estimated GFR, < 60 mL/min < 200 (0.13) >500 (9.3) - -
BNP = B-type natriuretic peptide; GRF = glomerular filtration rate; HF = heart failure; LR = likelihood ratio; NPV = negative predictive value; NT-pro-BNP = N-terminal proBNP; PPV = positive predictive value; – = not specifically defined.

* Derived from Breathing Not Properly data (1586 emergency department [ED] patients, prevalence of HF = 47%).[61]

Derived from PRIDE data (1256 ED patients, prevalence of HF = 57%).[62, 68]

Derived from subset of Breathing Not Properly data (452 ED patients, prevalence of HF = 49%).[67]

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