Current diagnostic strategies in heart failure

Current diagnostic strategies in heart failure Manel Ballester-Rode´s, MD,a and Stephen Westaby, MS, PhD, FETS, FESCb In addition to an appropriate history and physical examination, the assessment of patients with congestive heart failure (CHF) often relies on noninvasive imaging techniques. The availability of methods is ample: 2-dimensional echocardiography (2DE) and Doppler techniques, radionuclide imaging techniques, computed axial tomography, and magnetic resonance imaging (MRI) all provide relevant information to the clinician about the nature of the heart failure, the stage of disease evolution, and risk stratification. The heart failure physician is thus faced with the task of deciding which is (are) the most appropriate method(s) by which to obtain relevant clinical data for his or her patients. To allow a precise definition of the patient’s clinical problem, a complete set of data on myocardial and valvular function should be obtained. Information on ventricular morphology, global and regional function, assessment of myocardial viability, innervation, and the presence and severity of myocardial damage may be required in individual patients to understand fully the disease being evaluated and to direct therapy and prognosis. This review focuses on several issues that are of particular relevance in patients with CHF: the assessment of ventricular function, the exclusion of pericardial disease as a cause of CHF, the importance of myocardial viability assessment, the availability of other types of information (innervation, myocardial damage) in the context of CHF, and the combined use of these tools for risk stratification. This review also focuses on the surgeons’ perspective and their expectations from noninvasive diagnosticians. They require distinction of those patients who will respond to revascularization and geometrical restoration and correction of the left ventricle from those who are candidates for long-term mechanical assistance. The merits and scope of tests are critically appraised in the article by Udelson et al in this supplement. From the Service of Cardiology, Hospital Universitari Arnau de Vilanova, Department of Medicine, Faculty of Medicine, University of Lleida (Catalunya), Lleida, Spain,a and Oxford Heart Centre, John Radcliffe Hospital, Headington, Oxford, United Kingdom.b Reprint requests: Manel Ballester-Rode´s, Department of Medicine, Faculty of Medicine, University of Lleida Alcalde Rovira Roure 80, 28198 Lleida (Catalunya), Spain; [email protected]. J Nucl Cardiol 2002;9:S31–S39. Copyright © 2002 by the American Society of Nuclear Cardiology. 1071-3581/2002/$35.00 ⫹ 0 43/0/128462 doi:10.1067/mnc.2002.128462

ASSESSMENT OF VENTRICULAR FUNCTION 2DE and Doppler techniques allow accurate measurement of several variables that are used to analyze left ventricular (LV) systolic and diastolic function. The noninvasive character and optimal cost-effectiveness of 2DE-Doppler make it a satisfactory technique by which to study ventricular function. However, radionuclide imaging methods are an excellent alternative, especially when echocardiography is not feasible or other information (eg, perfusion) is required. MRI has emerged as a useful diagnostic tool in the study of the cardiovascular system. A great deal of the information provided by MRI overlaps with that obtained by ultrasound or nuclear imaging. The limited availability and relatively high cost of this technique should be weighed against the excellent anatomic definition, lack of interference with surrounding structures, and high reproducibility it provides. GLOBAL SYSTOLIC LV FUNCTION: EJECTION FRACTION Ejection fraction (EF) is a nondimensional parameter that expresses the relationship between the maximal (end-diastolic) and minimal (end-systolic) ventricular volumes.1-10 It is the most frequently used variable in clinical practice to indicate the state of global ventricular systolic function, because of the feasibility of its calculation and its recognized prognostic implications. Although EF can be visually estimated with a reasonable degree of accuracy by simple inspection of real-time 2DE by a well-trained observer, a proper quantitative assessment of EF requires measurement of ventricular systolic and diastolic volumes. In the case of a normally shaped left ventricle without regional alterations of wall motion, the morphology of the ventricular cavity is similar to a hemi-ellipsoid; however, the limitations of this assumption are obvious when one is dealing with a dilated (spherical) heart or a heart with regional wall motion abnormalities. In this context, an isotopic study (radionuclide ventriculography) is extremely useful. The strength of this test resides in its high reproducibility; furthermore, compared with other noninvasive modalities, radionuclide ventriculography enables more precise measurements to be made to assess the effects of exercise programs on ventricular performance, exercise capacity, and subsequent outcome of patients with heart failure. In addition, information on perfusion can be obtained siS31

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multaneously, thereby revealing areas of abnormal motion in the presence of myocardial viability (hibernation or stunning). MRI is a particularly well-suited technique for the measurement of both right and left ventricular volumes and their derived calculations. Accurate volume determinations are possible without geometrical assumptions by obtaining multiple contiguous transverse slices of the chamber. In the case of the right ventricle, MRI provides a unique solution to the problem of volume measurement without complex geometrical assumptions. REGIONAL VENTRICULAR FUNCTION An important advantage of 2DE is that it allows assessment of segmental LV function by visualization of the degree of endocardial movement and the increase in wall thickness along the cardiac cycle.11-15 Isotopic assessment with radionuclide ventriculography allows analysis of regional wall motion, which is evaluated qualitatively by viewing the cardiac cycle in closed-loop cine display in multiple projections. Alternatively, quantitation of regional function can be achieved either by measuring regional radial shortening or by assessing regional EF via sector analysis. Functional images such as EF images and amplitude and phase images can be readily calculated. These images have been useful in characterizing regional asynergy and asynchrony. MRI, on the other hand, offers recognized advantages over 2DE in assessing regional ventricular function because of its unrestricted field of view. Cine MRI allows a clear and quantitative study of segmental wall motion and thickening on short-axis views of LV sequences, as well as the possibility of detecting localized complications of myocardial infarction. The technique has been used successfully in combination with a dobutamine infusion to detect perfusion defects and to assess myocardial viability. OTHER METHODS FOR ASSESSING CARDIAC FUNCTION: CARDIAC OUTPUT AND ASSESSMENT OF DIASTOLIC PROPERTIES Calculation of cardiac output has been shown to be feasible and reproducible by 2DE-Doppler or MRI.16-25 Analysis of the Doppler velocity curve of transmitral flow has been shown to be a practical method by which to evaluate the status of LV diastolic function, although variables derived from the shape of this Doppler waveform cannot be considered as a direct measure of diastolic properties. On the other hand, LV relaxation and filling can be evaluated by analysis of ventricular time-activity curves generated from high–temporal-resolution radionuclide angiography: the peak filling rate,

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time to peak filling rate (the time from end systole to the time of peak filling rate), and average filling rate may be reproducibly obtained to assess ventricular filling dynamics in patients with coronary artery disease (CAD), both in the presence and in the absence of active myocardial ischemia, LV hypertrophy, or cardiomyopathies. EXCLUDING PERICARDIAL DISEASE AS A CAUSE OF CHF Diseases of the pericardium may lead to a clinical picture of CHF because of their interference with the process of cardiac filling; for example, pericardial effusion with tamponade and chronic constrictive pericarditis can mimic myocardial abnormalities.26-30 It is of the utmost importance to detect the presence of pericardial disease, because its management may be radically different from that of myocardial disease. In addition to the bedside clinical signs and symptoms of heart failure and specific features of restrictive pericardial disease, 2DEDoppler, MRI, and computed tomography scan have a major role in the differential diagnosis. ASSESSMENT OF MYOCARDIAL PERFUSION AND VIABILITY Patients with extensive CAD and severely reduced LVEF may benefit from myocardial revascularization in terms of survival, as compared with medical therapy.31-39 The concept of myocardial hibernation is at the center of such a consideration: the myocardium is alive (viable) but functionally impaired as the result of a low-flow, usually silent, ischemia. The clinical dilemma is how to predict which myocardial regions that show dysfunction are viable and will improve their systolic function after revascularization, in contrast to those that are dysfunctioning as the result of myocardial tissue scarring. The goal of viability assessment is to identify subgroups who will benefit from revascularization. Myocardial perfusion studies by which to assess myocardial viability and ischemia are usually performed with a series of agents: thallium 201, technetium 99m tetrofosmin, iodine 123 metaiodobenzylguanidine (MIBG), and others. Three-dimensional reconstruction of the ventricular anatomy, function, and perfusion and its cinematic display is now possible with the use of gated single photon emission computed tomography techniques. Patients whose regional systolic dysfunction is chiefly a result of myocardial scarring would not be expected to have improved survival and enhanced functional status after revascularization. In addition, patients with extensive myocardial hibernation who are treated medically have higher rates of cardiac death and nonfatal

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infarction during follow-up than do patients who are treated with coronary revascularization. Positron emission tomography has become a fine tool, albeit of limited availability, for identifying viable myocardium in patients with impaired LV function. ASSESSMENT OF SYMPATHETIC INNERVATION In addition to imaging anatomy and assessing function or metabolism, other methods provide potentially useful information by which to assess patients with heart failure.40-44 One example is the use of MIBG, which is taken up by myocardial sympathetic nerves, enabling changes in myocardial adrenergic neuron integrity and function to be detected. In patients with CHF, MIBG uptake has been shown to be reduced. In addition, MIBG studies may define patients with CHF at risk of an adverse event, based up the presence of excessive sympathetic nervous system stimulation of the myocardium and depressed neuronal catecholamine uptake. MIBG studies have been conducted to assess adrenergic innervation impairment due to doxorubicin cardiotoxicity. In these studies, decreased myocardial MIBG uptake preceded EF deterioration. Furthermore, correlation with parameters derived from radionuclide angiocardiography suggested a global process of myocardial adrenergic derangement. IMAGING MYOCYTE NECROSIS AND APOPTOSIS IN MYOCARDIAL DISEASE In a patient with heart failure, myocardial uptake of labeled monoclonal antimyosin antibodies allows in vivo detection of the presence of myocardial damage.45-59 Antibodies directed to human cardiac myosin and injected in vivo bind to the antigen only if sarcolemmal disruption (ie, myocyte damage) has occurred. Designed to detect patients with acute myocardial infarction, it has been useful in the identification of diffuse myocardial damage— either acute or chronic, as in myocarditis, dilated cardiomyopathy, drug-induced cardiotoxicity, heavy alcohol consumption, cardiac allograft rejection, or systemic diseases. The noninvasive nature of the procedure and the possibility of performing repeat studies in individual patients have prompted its use in several clinical settings in which endomyocardial biopsy could not be performed or repeated (eg, myocarditis, cardiac rejection). Detection of myocyte damage by antimyosin antibodies has been reported in patients with dilated cardiomyopathy associated with known diseases or toxic agents: alcohol; tricyclic antidepressant drugs, such as amitryptyline; or several systemic diseases, such as hyperthyroidism, amyloidosis, and systemic sclerosis. In a recent series, enteroviruses were found to be associated

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with myocardial damage. In the context of heart failure due to alcoholic dilated cardiomyopathy, antimyosin studies reflect the activity of alcohol consumption and can be useful to monitor reduction or disappearance of damage after alcohol withdrawal. Patients with heart failure due to doxorubicin cardiotoxicity can also benefit from early diagnosis with this technique. Similarly, myocardial damage can be detected in patients receiving amitryptyline as part of a chronic tricyclic antidepressant drug therapy, even at a time when ventricular function is normal. Long-term persistence of this damage could explain the occurrence of overt heart failure described in these patients, which may be reversed after drug withdrawal. Annexin V imaging of apoptosis will open the way to newer forms of evaluation in CHF. The recent suggestion that the outcome of certain diseases (dilated cardiomyopathy, hypertension) could be related to apoptosis opens the way to risk stratification and to improved evaluation of therapy in individual patients. RISK STRATIFICATION There is no single test that accurately predicts prognosis in CHF. However, combined information from a number of variables does allow precise risk stratification in individual patients.60 This is especially critical when the decision to include a patient in a heart transplantation program is being considered.61 It may seem obvious that a very ill patient with CHF should be recommended for transplant immediately and that the decision should be delayed in a patient without symptoms, but this might not be the case. In the former, spontaneous or treatment-induced improvement might follow and the need for transplant might be delayed or prevented; in the latter, the risk of death based on mathematical models could prompt a quick referral for transplantation (Table 1). In summary, several tools are now available to address specific questions relating to the evaluation of a patient with CHF. Along with a thorough clinical evaluation, the most appropriate test or combinations of tests—ideally noninvasive, easily accessible, and inexpensive—should be selected for each individual patient.62 Tests that have recently become available offer new information (myocardial damage or innervation) may open the way to better understand the pathogenesis of the disease63 and thus improve therapy and prognosis. A SURGEON’S PERSPECTIVE The major economic consequences of advanced heart failure emanate from repeated hospital admissions in patients with dysrhythmia or pulmonary edema. In the

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Table 1. Risk in dilated cardiomyopathy: Probability of death due to heart failure/heart transplantation within a 2-year period

Idiopathic NYHA class 1 and 2 Acute DD ⬍75 HLR ⬍1.9 LVEF ⬍29 LVEF ⬎29 HLR ⬎1.9 LVEF ⬍29 LVEF ⬎29 DD ⬎75 HLR ⬍1.9 LVEF ⬍29 LVEF ⬎29 HLR ⬎1.9 LVEF ⬍29 LVEF ⬎29

Chronic

Alcoholic

NYHA class 3 and 4 Acute

Chronic

NYHA class 1 and 2 Acute

Chronic

NYHA class 3 and 4 Acute

Chronic

14.6 8.4

35.0 22.4

44.4 29.9

71.6 57.4

4.9 2.7

14.0 8.0

19.4 11.4

43.2 28.9

19.9 11.7

44.0 29.6

53.8 38.3

78.6 66.2

7.0 3.9

19.1 11.2

25.9 15.8

52.5 37.1

33.7 21.4

61.6 46.2

70.4 56.0

88.2 80.1

13.3 7.6

32.6 20.6

41.8 27.7

69.3 54.7

42.6 28.4

70.0 55.6

77.6 64.9

91.6 85.4

18.2 10.7

41.3 27.4

51.1 35.8

76.7 63.8

Alcoholic, More than 100 g daily for 10 years or more than 70 g daily and total cumulative doses totaling more than 360 kg; NYHA, New York Heart Association; Acute, disease duration less than 12 months; Chronic, disease duration more than 12 months; DD, LV end-diastolic diameter; HLR, heart-to-lung ratio of antimyosin uptake.60

study by the Consensus Trial Study Group, patients randomized to enalapril spent 15% (30 days) of their mean 6.5-month follow-up time in the hospital.64 Readmission rates ranged from 29% to 47% in the first 6 months after discharge. Up to one third of New York Heart Association class 4 patients gained no symptomatic relief from combination medical therapy. To date, heart transplantation has been the only treatment to provide consistent improvement in quality of life and survival for patients in end-stage heart failure. Whereas 80,000 patients in the United States have end-stage heart failure, only 2184 patients underwent heart transplantation in 1999, representing less than half of the patients on the waiting list. These patients were carefully selected and were predominantly under age 65 years; 700 died while waiting for a donor, and 676 were withdrawn from consideration because of intervening illness. During 2001, only 217 heart transplants were undertaken in the United Kingdom. Most heart failure patients cannot be considered because of age limitations, concomitant disease (diabetes, chronic obstructive airways disease, renal impairment, or malignancy), or elevated pulmonary vascular resistance. Another difficulty is the prediction of outcome for any individual patient without transplantation. Although the degree of LV dysfunction is a prognostic indicator for death, many

patients with markedly reduced LVEF can survive for years with reasonable functional capacity. Deng et al65 showed that in the German transplant experience (1997), patients on the waiting list with ischemic heart disease who did not receive a donor organ had 3- and 4-year survival rates similar to those who received transplants. The survival benefit of heart transplantation over continued medical management has never been tested in a prospective randomized trial. Transplant listing of more critically ill patients and the use of so-called marginal donor hearts have limited improvement in outcomes after transplantation. In the meantime the medical and nontransplant surgical treatment for these patients has improved. Among the surgical options are revascularization of hibernating myocardium, surgical LV remodeling, and the use of long-term LV assist devices (LVADs).66,67 Consequently, there has been a shift away from the practice of placing patients with heart failure on transplant lists until alternative methods have been considered. This reasoning is in line with the current reassessment of treatment options for patients with end-stage liver, lung, and kidney disease. CAD is responsible for 75% of heart failure cases. LV dysfunction results from acute myocardial ischemia, myocardial infarction, or hibernating myocardium.68 Myocardial stunning, which is a short- term phenome-

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non, may be superimposed on any of these situations and may eventually lead to heart failure.69 CAD also causes mechanical problems such as mitral regurgitation or ventricular septal defect that result in clinical heart failure without significant LV systolic dysfunction. LV dysfunction from any cause results in, or contributes to, myocardial ischemia by increasing myocardial oxygen need and reducing coronary blood flow. Structural changes commonly occur in LV dysfunction and, when persistent, may cause heart failure. Hibernating myocardium can be partially or completely restored to normal with reperfusion, after which systolic dysfunction may improve.68 The extent of and the time to improvement of LV function are dependent on the adequacy of revascularization and the extent and severity of myocardial changes that were present before intervention (percutaneous transluminal coronary angioplasty or coronary artery bypass grafting [CABG]). In the absence of revascularization, repetitive ischemia may progress to myocyte necrosis or apoptosis, which indicates that hibernating myocardium is not fully adapted to chronic underperfusion. Cellular degeneration and myocyte loss are accompanied by reparative fibrosis. They combine to cause degeneration in the structural and functional integrity of the left ventricle. Consequently, if revascularization is to succeed, it should be applied early, before functional hibernation progresses to structural hibernation. Changes in the Remote Myocardium After Infarction The components of postinfarction ventricular remodeling include infarct expansion, neurohormonal activation, myocardial hypertrophy, and global LV dilation. The left ventricle progressively dilates and assumes a more spherical, as opposed to elliptical, contour. The workload of the myocardium remote from the infarction is increased both by loss of contraction in the scar and by dysfunctional changes. Increased wall stress results in lengthening and thinning of the LV wall through lateral slippage of myocardial planes. In the early stages ventricular dilation serves to maintain stroke volume through the Starling curve. The changes in ventricular geometry, local wall strain, and filling pressures combine to increase the metabolic requirements of the remote myocardium, which plays a crucial part in maintaining cardiac output. These working segments undergo compensatory hypertrophy. When the infarcted region occupies more than 10% of the total myocardial mass (40% of all transmural myocardial infarctions), the left ventricle progressively enlarges with the onset of symptomatic heart failure.70 When more than 50% of the myocardium is impaired,

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increased wall tension causes subendocardial ischemia in the remote myocardium. This triggers LV failure. The relationship between the extent of myocardial infarction, degree of LV dysfunction, and late mortality was defined by Yoshida and Gould.71 They showed that a myocardial infarction of greater than 23% of the LV circumference caused impaired LVEF (⬍43%) and a 3-year mortality rate of 43%. This contrasted with less extensive myocardial infarctions, which carried a 3-year mortality rate of only 5%. In those patients in whom LVEF was less than 43%, the 3- year mortality rate was 38%, in contrast to only 6% when LVEF was greater than 43%. However, LVEF alone was a poor predictor of late mortality in patients with hibernating myocardium. The presence of viable myocardium is an independent predictor of survival, as well as an identifier of those with impaired LVEF who are most likely to benefit from revascularization. The 3-year mortality rate in patients with an LVEF of less than 43% and no viable myocardium was 63%, in contrast to 13% for those with viable myocardium submitted for revascularization. For patients with only fixed scar in the territory at risk from coronary occlusion, the mortality rate of 50% at 3 years was no different with or without revascularization, thereby suggesting no benefit of CABG in this subgroup. Less than 10% of potential heart transplant candidates will eventually receive a donor organ. In an attempt to lower waiting- list mortality and provide an alternative to transplantation, many centers now select outpatients for high-risk coronary bypass surgery, with or without surgical LV remodeling. Remodeling operations such as the procedure of Dor et al67 aim to change the globular remodeled LV cavity shape back to a more favorable elliptical configuration. Mitral regurgitation resulting from annular dilation, altered LV geometry, or papillary muscle dysfunction is also corrected by annuloplasty. These procedures reduce both systolic and diastolic wall stress through their physical relationship with diameter and intracavitary pressure. Myocardial Viability Assessment for Possible Revascularization Currently, percutaneous transluminal coronary angioplasty and CABG are applied predominantly on the basis of symptoms and angiographic findings. In the presence of poor LV function without angina or knowledge of myocardial viability, it is unlikely that more than 50% of patients will achieve benefit.72 Revascularization does not improve the function of scar tissue, and it is difficult or impossible on the basis of the electrocardiography, coronary angiography, or ventriculography to determine which areas of the myocardium might benefit from enhanced perfusion. From the now-historic Coro-

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Table 2. Decision making with regard to surgery for end-stage ischemic heart disease

Condition Reversible ischemia, LVESVI ⬍60 mL/m2 Full-thickness scar and ventricular aneurysm Akinetic/dyskinetic left ventricle LVESVI ⬎60 mL/m2 with reversible ischemia Class III/IV mitral regurgitation No reversible ischemia LVESVI ⬎ 100 mL/m2 Pulmonary hypertension (PAP ⬎70 mm Hg) Right ventricular failure

Intervention CABG alone Linear resection ⫾ CABG CABG ⫹ LV restoration surgery Mitral valve repair ⫾ CABG LVAD or transplantation (no conservative option)

Adapted by permission of the publisher from Hausmann et al. Survival predictors in patients with a left ventricular ejection fraction of 10-30% receiving a coronary bypass: analysis of preoperative variables, Cardiovasc Surg, Vol. 1, No. 5, pp. 558-62, Copyright 1993 by Elsevier Science Inc. LVESVI, LV end-systolic volume index (normal, ⬍30 mL/m2); PAP, pulmonary artery pressure.

nary Artery Surgery Study (CASS) registry, the 5-year survival rate for medically treated patients with an LVEF of less than 25% was only 41%, as compared with 62% for those treated with CABG.73 For many of these patients, fatigue and breathlessness are the predominant symptoms and prognosis is poor despite medical therapy. The goal of myocardial viability assessment is to identify prospectively potentially reversible LV dysfunction together with areas of dyskinesia amenable to LV restoration surgery in heart failure patients whose prognosis may be favorably altered by nontransplant surgery. Differentiation between reversible ischemia and scar can sometimes be made on clinical grounds, for instance, in the presence of angina, which responds to sublingual nitrate therapy. In the absence of anginal symptoms, more objective evidence is required to differentiate between those who will and those who will not derive benefit from improved myocardial blood flow. (See review by Udelson et al in this supplement.) Up to 50% of ischemic patients submitted for transplantation, and many more who are deemed unsuitable to undergo transplantation, have hibernating myocardium and may respond favorably to CABG with or without surgical LV remodeling or mitral valve repair. Those without viable muscle derive limited or no benefit from CABG at high operative risk. The long-term outlook for those with initial improvement after CABG is uncertain but limited by myocardial fibrosis in nonischemic segments after the native LV remodeling process. Nevertheless, the medium-term outcome is considerably better than the prospect of a transplant waiting list. Consequently, a more aggressive approach to investigation and treatment is warranted for patients with advanced ischemic heart disease and poor LV function. Guidelines for surgical decision making in end-stage ischemic heart disease are summarized in Table 2.

Use of Blood Pumps as an Alternative to Transplantation As the heart failure population increases in tandem with a global decrease in donor availability, the use of long-term LVAD support seems a logical alternative. The first and only prospective randomized trial of LVAD support versus continued medical therapy began in 1998 and was reported in November 2000. The Randomised Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure study (REMATCH) used the vented electric Thermocardio Systems (TCI) (Thoratec Corp., Pleasanton, Calif.) LVAD in New York Heart Association class 4 heart failure patients on maximum medical therapy. Entry criteria were LVEF of less than 25%, peak oxygen consumption of less than 25%, peak oxygen consumption of less than 12 mL/kg per minute, or a continued need for intravenous inotropic therapy for symptomatic hypotension, decreasing renal function, or worsening pulmonary congestion. The investigating transplant centers had to overcome major ethical, logistic, and economic hurdles in order to recruit 129 patients who were unsuitable for transplantation and willing to be randomized. The all-cause mortality rate (the primary endpoint) was 38% lower in the LVAD group. Median survival was 408 days in the device group and only 150 days in the medical therapy group. However, only 23% of LVAD patients survived for 2 years. Anticipated improvement in quality of life was limited by a 28% incidence of device infection by 3 months, a 42% incidence of bleeding by 6 months, and a 35% probability of pump failure by 2 years. Of the 68 patients who received the TCI LVAD, 10 had the device replaced. However, the 75% 1-year mortality rate for medically treated patients exceeded that for patients with acquired immunodeficiency syndrome and breast, lung,

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and colon cancer. The use of an LVAD was associated with a 48% relative reduction in the risk of death during the follow-up period and a 27% absolute reduction in mortality rate at 1 year. The REMATCH study is a landmark in the evolution of mechanical circulatory support. These findings established mechanical support as an alternative to medical treatment for selected transplant-ineligible patients or those who prefer not to undergo heart transplantation. However, it is clear that long-term mechanical support will only gain widespread acceptance with the use of more user-friendly LVADS. Acknowledgment The authors have indicated they have no financial conflicts of interest.

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