Which specific type of heart failure (hf) is most likely to occur at the beginning of chronic hf

Conventional diuretics (seeTable 108-6 inChapter 108) act by blocking sodium reabsorption in the loop of Henle and distal renal tubule, thereby enhancing urinary excretion of sodium and water.

Although not proven to improve mortality and morbidity in large trials, diuretics are required in nearly all patients with symptomatic heart failure (stages C and D) to relieve dyspnea and the signs of sodium and water retention (“congestion”), that is, peripheral and pulmonary edema.4e No other treatment relieves symptoms and the signs of sodium and water overload as rapidly and effectively. Once a patient needs a diuretic, treatment is usually necessary for the rest of the patient’s life, although the dose and type of diuretic may vary.

The key principle is to prescribe the minimum dose of diuretic needed to maintain an edema-free state (“dry weight”). Excessive use can lead to electrolyte imbalances, such as hyponatremia, hypokalemia (and risk for digitalis toxicity), hyperuricemia (and risk for gout), and uremia. The risk for renal dysfunction is increased by concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs). Diuretic-induced hypovolemia may also cause symptomatic hypotension and prerenal azotemia. Restriction of dietary sodium intake may help reduce but does not eliminate the requirement for diuretics. Diuretic dosing should be flexible, with temporary increases for evidence of fluid retention (e.g., increasing symptoms, weight gain, edema) and decreases for evidence of hypovolemia (e.g., as a consequence of increased electrolyte loss due to gastroenteritis, decreased fluid intake, or both).

In some patients with milder symptoms of heart failure and preserved renal function (stage C), a thiazide diuretic such as chlorthalidone may suffice. In more advanced heart failure (stage D) or in patients with concomitant renal dysfunction, a loop diuretic such as furosemide is often needed. Loop diuretics cause a rapid onset of an intense but relatively short-lived diuresis compared with the longer lasting but gentler effect of a thiazide diuretic. The timing of administration of a loop diuretic, which need not be taken first thing every morning, can be adjusted according to the patient’s social activities. The dose may be postponed or even temporarily omitted if the patient has to travel or has another activity that might be compromised by the prompt action of the diuretic. In severe heart failure (stage D), the effects of long-term administration of a loop diuretic may be diminished by increased sodium reabsorption at the distal tubule. This problem can be offset by use of the combination of a loop diuretic and a thiazide or thiazide-like diuretic (e.g., hydrochlorothiazide or metolazone), which act in synergy with a loop diuretic by blocking sodium reabsorption in different segments of the nephron. This combination requires more frequent monitoring of electrolytes and renal function for diuretic-induced hyponatremia, abnormalities of the serum potassium level, and prerenal azotemia.

A period of intravenous loop diuretic, given either as bolus injections or by continuous infusion, may be required either in the ambulatory setting or as an in-patient in patients who become resistant to the action of oral diuretics. Why this resistance develops is uncertain, but factors thought to be important include impaired absorption of oral diuretics due to gut edema, hypotension, reduced renal blood flow, renal venous congestion, and adaptive changes in the nephron.

Patients with symptomatic heart failure (stages C and D) should be also considered for treatment with a mineralocorticoid receptor (aldosterone) antagonist, such as spironolactone, which increases excretion of sodium but not of potassium (see later). Patients receiving a combination of diuretics requirecareful monitoring of blood chemistry and clinical status. The use of a mineralocorticoid receptor (or, rarely, a potassium-sparing diuretic) along with an ACE inhibitor, ARB, or angiotensin receptor neprilysin inhibitor (ARNI) (treatment with all three is not recommended) requires particular care and surveillance for hyperkalemia.

Although they are highly effective in relieving symptoms and signs, diuretics alone are not sufficient for treatment of heart failure. In cases of severe resistant volume overload, mechanical removal of fluid by ultrafiltration may be considered. The addition of other disease-modifying treatments will slow structural progression, better maintain clinical stability, and reduce the risk for hospital admission and premature death.

ACE inhibitors inhibit the enzyme that converts the inactive decapeptide angiotensin I to the active octapeptide angiotensin II (and that also breaks down bradykinin). In patients with heart failure, excessive angiotensin II is thought to exert myriad harmful actions mediated through stimulation of the angiotensin II type 1 receptor subtype (AT1R), including vasoconstriction (which increases ventricular afterload), excessive growth of myocytes and the extracellular matrix (contributing to maladaptive left ventricular remodeling), activation of the sympathetic nervous system, prothrombotic actions, and augmentation of the release of arginine vasopressin and the retention of sodium (both directly and through stimulation of secretion of aldosterone, which activates the mineralocorticoid receptor). ARBs selectively block the action of angiotensin II at the AT1 receptor. Although pharmacologically distinct from ACE inhibitors, their clinical effects are similar.

ACE inhibitors also reduce the breakdown of bradykinin, and the resultant accumulation of bradykinin is directly or indirectly responsible for two of the specific adverse effects of ACE inhibitors: cough and angioedema. ARBs do not inhibit kininase II or the breakdown of bradykinin, so they do not cause cough and are associated with lower rates of angioedema than are ACE inhibitors. This difference between ARBs and ACE inhibitors explains why the combination of neprilysin (which also breaks down bradykinin and may itself cause angioedema)and an ARB is safe (and why the combination of an ACE inhibitor and a neprilysin inhibitor poses a significant risk of angioedema and is not recommended).

Clinical Benefits

Clinical trials have shown that treatment with an ACE inhibitor, when it is used alone or added to diuretics and digoxin, decreases left ventricular size, improves ejection fraction, reduces symptoms and hospital admissions, and prolongs survival. These agents also reduce the risk of developing myocardial infarction and possibly diabetes and atrial fibrillation. Consequently, treatment with an ACE inhibitor is recommended for all patients with left ventricular systolic dysfunction, irrespective of symptoms or etiology. ACE inhibitors are not a substitute for a diuretic but mitigate diuretic-induced hypokalemia.

When used as the sole agent in heart failure, ARBs produce benefits similar to those of ACE inhibitors. An ARB may be used as a substitute in patients who have cough or angioedema with an ACE inhibitor. When they are used in clinically effective doses, other adverse effects such as hypotension, renal dysfunction, and hyperkalemia are encountered as frequently as with an ACE inhibitor.

Practical Use

An ACE inhibitor (or ARB) should be introduced as early as possible in a patient’s treatment. The only contraindications are a history of angioedema (for an ACE inhibitor), current symptomatic hypotension, and bilateral renal artery stenosis (Chapter 116); the latter is often associated with a prompt and marked increase in serum levels of blood urea nitrogen and creatinine when renal perfusion is reduced precipitously by inhibiting the production and actions of angiotensin II. Combined use of an ACE inhibitor and an ARB is contraindicated because it results in increased side effects without an increase in efficacy.

Treatment should be started in a low dose (seeTable 53-2), with the dose gradually increased toward a target dose of proven benefit in a clinical trial. The patient should be evaluated for symptomatic hypotension, uremia, and hyperkalemia after each dose increment; these adverse effects are uncommon and can usually be resolved by reduction in the dose of diuretic (if the patient is edema free) or concomitant hypotensive or nephrotoxic medications (e.g., nitrates, calcium-channel blockers, or NSAIDs). A dry, nonproductive cough occurs in approximately 15% of patients treated with an ACE inhibitor, and if it is troublesome, substitution of an ARB is recommended. In the rare cases of angioedema (Chapter 237), the ACE inhibitor should be stopped and not used again; an ARB can be cautiously substituted (see later).

Mechanism of Action

Heart failure is characterized by excessive activation of the sympathetic nervous system, which causes vasoconstriction and sodium retention, thereby increasing cardiac preload and afterload and often inducing myocardial ischemia or arrhythmias. In addition, norepinephrine can cause hypertrophy of myocytes and augment their apoptosis. β-Blockers counteract many of these harmful effects of the hyperactivity of the sympathetic nervous system. A rapid heart rate is an important prognostic factor in heart failure among patients in sinus rhythm, and β-blockers reduce heart rate.

Clinical Benefits

The long-term addition of a β-blocker to an ACE inhibitor (or an ARB or ARNI) and diuretic, digoxin, and mineralocorticoid receptor antagonist further improves left ventricular function and symptoms, reduces hospital admissions, and strikingly improves survival. Consequently, a β-blocker is recommended for all patients with symptomatic systolic dysfunction, irrespective of etiology and severity, and the combination of a β-blocker with an ACE inhibitor (or ARB or ARNI) is now the cornerstone of the treatment of symptomatic heart failure (seeFig. 53-1). Treatment with a β-blocker, added to an ACE inhibitor (or ARB or ARNI) and a mineralocorticoid receptor antagonist, is generally recommended for all patients with symptoms (NYHA classes II to IV) and left ventricular systolic dysfunction, irrespective of etiology.

In a retrospective analysis of pooled data from 11 randomized trials in patients with heart failure, β-blockers improved the left ventricular ejection fraction but did not appear to reduce all-cause mortality in patients with atrial fibrillation, whereas they reduced mortality by 27% in patients who were in sinus rhythm.A8 Although the interpretation of these results is controversial, β-blockers remain the preferred treatment for control of the ventricular rate in patients who have both atrial fibrillation and heart failure with a reduced ejection fraction because of their excellent safety profile.

Practical Use

The major contraindications to use of a β-blocker are asthma (although it is important to note that the dyspnea caused by pulmonary congestion can be confused with reactive airway disease) and second- or third-degree atrioventricular block. Initiation of treatment during an episode of acute decompensated heart failure should also be avoided until the patient is stabilized. In addition, caution is advised in patients with a heart rate below 60 beats per minute or a systolic blood pressure below 90 mm Hg. It is recommended that a β-blocker shown to produce benefits in a randomized trial be used.

Like an ACE inhibitor (or an ARB or ARNI), β-blockers should be introduced as early as possible in a patient’s treatment, started in a low dose (seeTable 53-3), and increased gradually toward a target dose used in a clinical trial (the “start low–go slow” approach). The patient should be checked for symptomatic hypotension and excessive bradycardia after each dose increment, but both ofthese side effects are uncommon, and hypotension can often be resolved by reduction in the dose of other nonessential blood pressure–lowering medications (e.g., nitrates and calcium-channel blockers). Bradycardia is more likely in patients who are also taking digoxin or amiodarone, and the simultaneous use of these agents should be reviewed if excessive bradycardia occurs. On occasion, symptomatic worsening and fluid retention (e.g., weight gain or edema) may occur after initiation of a β-blocker or during dose up-titration; these side effects usually can be resolved by a temporary increase in the diuretic dose without necessitating discontinuation of the β-blocker.

Treatment with a β-blocker should be given for life, although the dose may need to be decreased (or, rarely, treatment discontinued) temporarily during episodes of acute decompensation if the patient shows signs of circulatory underperfusion or refractory congestion.

Mechanism of Action

Aldosterone, which is the second effector hormone in the renin-angiotensin-aldosterone cascade, has detrimental vascular, renal, autonomic, and cardiac actions when it is produced in excess in patients with heart failure. Excessive aldosterone promotes sodium retention and hypokalemia, and it is believed to contribute to myocardial fibrosis, all of which predispose to arrhythmias. Aldosterone mediates its effects by activating the mineralocorticoid receptor, which is also stimulated by other endogenous corticosteroids. Mineralocorticoid receptor antagonists block these undesirable actions and, at high doses, also act as potassium-sparing diuretics.

Clinical Benefits

The mineralocorticoid receptor antagonist spironolactone improves symptoms, reduces hospital admissions, and increases survival when it is added to an ACE inhibitor (and diuretics and digoxin) in patients with a reduced left ventricular ejection fraction and severely symptomatic heart failure. Eplerenone, another mineralocorticoid receptor antagonist, reduces mortality and morbidity when it is added to both an ACE inhibitor and β-blocker in patients with a reduced left ventricular ejection fraction and heart failure with mild symptoms (NYHA class II). Consequently, a mineralocorticoid receptor antagonist should be considered in all patients who remain symptomatic (class II to IV) despite treatment with a diuretic, ACE inhibitor (or ARB or ARNI), and β-blocker.A9 When begun, a mineralocorticoid receptor antagonist should be given indefinitely.

Practical Use

Treatment with a mineralocorticoid receptor antagonist should be initiated with a low dose (Table 53-5) with careful monitoring of serum electrolytes and renal function. Hyperkalemia and uremia are the adverse effects of greatest concern (as with ACE inhibitors, ARBs, or an ARNI), and a mineralocorticoid receptor antagonist should not be given to patients with a serum potassium concentration of more than 5.0 mmol/L, serum creatinine concentration above 2.5 mg/dL (>221 µmol/L), or other evidence of markedly impaired renal function. The importance of selection of patients and dose is underscored by reports of a worrisome incidence of serious hyperkalemia in community practice settings. Spironolactone can have antiandrogenic effects, especially painful gynecomastia, in men; because eplerenone has less of an action on the androgen receptor, it is a reasonable substitute in patients who experience this adverse effect.

Mechanism of Action

The SGLT2 is found in the renal proximal tubule, where it is responsible for the reabsorption of glucose filtered at the glomerulus. Inhibition of SGLT2 results in increased urinary excretion of glucose and sodium, along with an osmotic diuresis. Whether this action completely or partly explains the benefit of these drugs in patients with heart failure (and chronic kidney disease) is unknown. In addition to increased glycosuria and a resultant reduction in blood glucose, the other consistent effects of SGLT2 inhibitors are an increase in hematocrit, reduced rate of long-term decline in glomerular filtration rate (after an initial dip in this measure), and a modest decrease in blood pressure.4f Many other actions of SGLT2 have been speculated but not confirmed in humans.

Clinical Benefits

Clinical trials have shown that adding an SGLT2 inhibitor to a renin-angiotensin system blocker (or ARNI), β-blocker, a mineralocorticoid receptor antagonist, and a neprilysin inhibitorA8b decreases left ventricular size, improves ejection fraction, reduces symptoms and hospital admissions, and prolongssurvival in men and women regardless of whether or not they have type 2 diabetes, chronic renal disease, or a recent worsening of their heart failure.A9b–A9h These agents also reduce the risk of worsening kidney functionA9d and possibly of developing diabetes. Consequently, treatment with an SGLT2 inhibitor is recommended for all symptomatic patients with left ventricular systolic dysfunction, irrespective of diabetes status. SGLT2 inhibitors also may mitigate MRA-induced hyperkalemia.

Practical Use

Although only recently shown to be effective in heart failure, their consistent and large benefits, ease of use, and generally good tolerability means SGLT2 inhibitors are likely to become a standard therapy for most patients with a reduced LVEF. The only contraindications are type 1 diabetes, a history of diabetic ketoacidosis, and severe renal dysfunction (estimated glomerular filtration rate <20 mL/min/1.73m2). In patients with type 2 diabetes (Chapter 216), other glucose-lowering therapy may need to be adjusted, especially if there is a recent history of hypoglycemia. The dose of insulin should not be decreased by more than 25%, and it is prudent to discuss changes in insulin dosage with an endocrinologist before commencing an SGLT2 inhibitor.

Unlike other treatments for heart failure, SGLT2 inhibitors are prescribed as a single dose, and no up-titration is required (Table 53-5A). Treatment may lead to a modest initial, but short-lived, diuresis and small decline in estimated glomerular filtration rate, although neither of these is usually a clinical problem. It is advisable to check kidney function within a month of starting treatment, especially in patients with a very low baseline estimated glomerular filtration rate. A clinically meaningful change in blood pressure is rare. Genital skin fungal infections may occur in 5-10% of patients, are rarely troublesome, and can usually be treated with an antifungal cream. In the rare cases of ketoacidosis (Chapter 216), the SGLT2 inhibitor should be discontinued immediately. Patients at greatest risk of ketoacidosis are those who are concurrently taking insulin or who may be insulin-deficient (e.g., as a result of previous pancreatitis). SGLT2 inhibitors should be temporary withheld in situations that might trigger ketoacidosis (i.e., illness leading to decreased food and fluid intake or stopping or reducing the dose of insulin), including elective surgery, for which SGLT2 inhibitors should be discontiued 3 days pre-operatively.

Mechanism of Action

Ivabradine is the first of a new class of drugs developed to inhibit the mixed sodium-potassium channel or current (also known as the funny channel, abbreviated as If or Ikf) in the sinoatrial node and, in so doing, reduce heart rate. Reduction in heart rate is the only known cardiac action of ivabradine, which has this effect only in patients in sinus rhythm.

Clinical Benefits

In patients with symptomatic heart failure (NYHA class II to IV), a reduced ejection fraction (≤35%), and sinus rhythm with a rate of 70 beats per minute or higher, ivabradine improves symptoms and ejection fraction and reduces the risk for hospitalization for heart failure (but not mortality) when added to an ACE inhibitor (or ARB or, presumably, ARNI), a β-blocker, and a mineralocorticoid receptor antagonist.A9i

Practical Use

Ivabradine should be considered in patients who have persistent symptoms (NYHA class II to IV) despite treatment with a diuretic and other disease-modifying therapies (i.e., an ACE inhibitor [or ARB or ARNI], β-blocker, and a mineralocorticoid receptor antagonist) and who are in sinus rhythm with a heart rate of 70 beats per minute or greater. Ivabradine is not a substitute for a β-blocker and is not effective in atrial fibrillation. Treatment should be started at 5 mg twice daily, increased to 7.5 mg twice daily after 14 days unless the heart rate is 60 beats per minute or less, and reduced usually to 2.5 mg twice daily if the rate is less than 50 beats per minute. Symptomatic bradycardia and visual disturbance (phosphenes) are uncommon but require the dose be reduced or ivabradine be discontinued. Ivabradine also may increase the risk of developing atrial fibrillation, which should prompt discontinuation of the drug. Ivabradine should not be used in combination with agents that prolong the QT interval (e.g., amiodarone) and must be used cautiously with inhibitors (including grapefruit juice) or inducers of CYP3A4.

Mechanism of Action

Digitalis glycosides inhibit the cell membrane Na+, K+-ATPase pump, thereby increasing intracellular calcium and myocardial contractility. In addition, digoxin is thought to enhance parasympathetic and reduce sympathetic nervous activity as well as to inhibit renin release.

Clinical Benefits

In the only large RCT that examined the effects of starting (as opposed to withdrawing) digoxin, digoxin did not reduce mortality but did decrease the risk for admission to hospital for worsening heart failure and improve quality of life when it was added to a diuretic and an ACE inhibitor. In patients in sinus rhythm, the addition of digoxin can be considered if heart failure remains symptomatic despite standard treatment with a diuretic and three disease-modifying drugs (i.e., an ACE inhibitor [or ARB or ARNI], a β-blocker, and a mineralocorticoid receptor antagonist). However, digoxin has not been as well studied and may not be as safe as ivabradine when used in conjunction with contemporary therapies. In patients with atrial fibrillation, digoxin may be used at an earlier stage if a β-blocker fails to control the ventricular rate during exercise (Chapter 58). Digoxin can also be used to control the ventricular rate when β-blocker treatment is being initiated or up-titrated.

If the effect of digoxin is needed urgently, loading with 10 to 15 µg/kg lean body weight, given in three divided doses 6 hours apart, may be used. The maintenance dose should be one third of the loading dose. Smaller maintenance doses (e.g., one fourth of the loading dose and not more than 62.5 µg/day) should be used in elderly patients and in patients with reduced renal function as well as in patients with a low body mass. Monitoring of the serum digoxin concentration is recommended because of the narrow therapeutic window. A steady state is reached 7 to 10 days after treatment is started; blood should be collected at least 6 hours (and ideally 8 to 24 hours) after the last dose. The currently recommended therapeutic range is 0.5 to 1.0 ng/mL).

Digoxin can cause anorexia, nausea, arrhythmias, confusion, and visual disturbances, especially if the serum concentration is above 2.0 ng/mL. Hypokalemia increases susceptibility to the adverse effects. The dose of digoxin should be reduced in elderly patients and in patients with renal dysfunction. Certain drugs increase serum digoxin concentration, including amiodarone.

Mechanism of Action

Hydralazine is a powerful direct-acting arterial vasodilator. Its mechanism of action is not understood, although it may inhibit enzymatic production of superoxide, which neutralizes nitric oxide and may induce nitrate tolerance. Nitrates dilate both veins and arteries, thereby reducing preload and afterload by stimulating the nitric oxide pathway and increasing cyclic guanosine monophosphate in vascular smooth muscle. Neither drug on its own nor any other direct-acting vasodilator has been demonstrated to be beneficial in heart failure.

Clinical Benefits

The addition of hydralazine and isosorbide dinitrate reduces mortality, hospital admissions for heart failure, and heart failure symptoms when added to standard disease-modifying drugs (i.e., an ACE inhibitor [or presumably an ARB or ARNI, a β-blocker, and a mineralocorticoid receptor antagonist) in African American patients with NYHA class III or IV symptoms and an ejection fraction of 45% or less. The dose is a fixed combination of 37.5 mg of hydralazine and 20 mg of isosorbide dinitrate; if one tablet is tolerated, a second is given 12 hours later. Then the tablet is given three times daily for 3 to 5 days, at which point the dose is increased to the target maintenance of two tablets three times daily (i.e., a daily dose of 225 mg hydralazine and 120 mg isosorbide dinitrate). It is uncertain whether hydralazine/isosorbide dinitrate is an effective addition to standard therapy in non-African American patients.

Practical Use

Other than for African Americans, the main indication for hydralazine and isosorbide dinitrate is as a substitute in patients who are intolerant to an ACE inhibitor, an ARB, and an ARNI. However, many patients who cannot tolerate these three drugs also do not tolerate hydralazine and isosorbide dinitrate. Hydralazine and isosorbide dinitrate can also be used as additional treatment in non-African Americans who remain symptomatic with other proven therapies. The main dose-limiting adverse effects of hydralazine and isosorbide dinitrate are headache and dizziness. A rare adverse effect of higher doses of hydralazine, especially in slow acetylators, is a systemic lupus erythematosus–like syndrome (Chapter 250).

Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting

Percutaneous coronary intervention or coronary artery bypass grafting (Chapter 65), as appropriate, is indicated for relief of angina. The extent of ischemia and residual myocardial viability can be determined by noninvasive assessments such as dobutamine echocardiography (Chapter 49), magnetic resonance imaging (Chapter 50), and positron emission tomographic scanning (Chapter 50) in patients with impaired left ventricular ejection fraction. Coronary artery bypass grafting reduces the risk for cardiovascular death and cardiovascular hospitalization (including heart failure hospitalization) in patients with ischemic cardiomyopathy, an ejection fraction of 35% or less, and coronary artery disease amenable to coronary-artery bypass grafting (although the trial excluded individuals with left main disease and Canadian Cardiovascular Society angina classes III-IV).A19 The net benefit was not apparent until approximately 2 years after randomization because of the perioperative mortality related to surgery. Coronary artery bypass grafting is therefore recommended in such patients who are otherwise fit for surgery and have an anticipated life expectancy of 2 years or more. Whether percutaneous coronary intervention has a similar prognostic benefit is unknown.

Cardiac Transplantation

Cardiac transplantation remains the most accepted (Table 53-7) surgical intervention in end-stage heart failure. Selection criteria usually focus on patients with refractory heart failure, that is, those with severe symptoms and functional limitations (peak oxygen consumption of less than 12 mL/kg per minute), as well as a particularly worrisome clinical course and prognosis attributed to their cardiac condition. These patients are often dependent on intravenous inotropic agents and mechanical support.

About 3000 heart transplant procedures are performed annually in the United States (compared with about 4000 ventricular assist device implantations). The major limitation is the scarcity of donor organs. Absolute and relative exclusion criteria for heart transplantation (Table 53-8) include advanced age, serious comorbid conditions, and nonreversible pulmonary vascular resistance of more than 6 Wood units.

To diagnose allograft rejection, which can be antibody-mediated or cell-mediated, transjugular endomyocardial biopsies are usually performed weekly for one month, every other week for 2 months, and then every 1 to 2 months for the first year. In patients who are asymptomatic on low doses of corticosteroids, a gene expression profile of peripheral blood10 can provide equivalent clinical outcomes despite fewer biopsies.A20 Cellular rejection is usually easily treated with high-dose corticosteroids, but humoral rejection may require more aggressive immunosuppression (Chapter 43).

Another form of chronic rejection is transplant vasculopathy, which occurs at an annual rate of 5 to 10%.11 Patients are more likely to present with fatigue, heart failure, myocardial infarction, ventricular arrhythmia, or sudden death than with exertional angina. Patients are typically screened with annual coronary angiography, stress echocardiography, or positron emission tomography. Treatment emphasizes high-dose statins (seeTable 195-3 inChapter 195) and mTOR inhibitors (e.g., sirolimus or everolimus),A21 but repeat transplantation may be required.

The survival rate after heart transplantation is currently about 85 to 90% at one year, 70 to 75% at 5 years, and 20% at 20 years. Transplant vasculopathy and malignancies account for about one third of deaths among patients who survive for ten or more years.

Mechanical Circulatory Support

Given the scarcity of organ donors, mechanical circulatory support using a left ventricular (or biventricular) assist device (LVAD) may be used as a “bridge to transplantation” or, in some centers, as a permanent and definitive alternative to transplantation (“destination therapy”).12 Mechanical circulatory support may also be used as “bridge to candidacy” (i.e., to try to improve a patient’s clinical status sufficiently to become eligible for transplantation).13 A continuous axial-flow device can provide a 46% 2-year survival free of repeat device surgery or disabling stroke. A newer ventricular magnetically levitated centrifugal-flow pump may provide better short-term and two-year outcomes than the axial-flow pump.A22,A22b

Because not every hospital could or should be expected to offer all these levels of support for patients with advanced heart failure, there is a general recognition that such services should be concentrated in a limited number of tertiary centers. Centers implanting these devices use criteria such as persistent (>2 months) severe symptoms despite optimal drug and device therapy and other features placing patients at high risk for death (e.g., left ventricular ejection fraction <25%, three or more heart failure hospitalizations in the prior 12 months, peak oxygen consumption <12 mL/kg per minute, dependence on intravenous inotropic therapy, progressive end-organ dysfunction, and deteriorating right ventricular function) to decide who should be considered for mechanical circulatory support.