INTRODUCTION — Cardiac transplantation is the treatment of choice for many patients with end-stage heart failure (HF) who remain symptomatic despite optimal medical therapy. Risk stratification of patients with end stage HF is pivotal for transplant candidate selection. The primary indications for cardiac transplantation, along with specific inclusion and exclusion criteria, are discussed here.
Treatment of refractory HF and prognosis after cardiac transplantation are discussed separately. (See "Management of refractory heart failure with reduced ejection fraction" and "Heart transplantation in adults: Prognosis".)
CAUSES OF HEART FAILURE LEADING TO CARDIAC TRANSPLANTATION — Nonischemic cardiomyopathy and coronary artery disease are the disease processes leading to the vast majority of cardiac transplants, though increasing numbers of adults with complex congenital heart disease, restrictive cardiomyopathies, hypertrophic cardiomyopathies, and those requiring re-transplantation are represented [1]. For additional information, see the slides Adult Heart Transplantation Statistics.
APPROACH TO EVALUATING POTENTIAL CANDIDATES FOR CARDIAC TRANSPLANTATION — The process of evaluating potential candidates for cardiac transplantation includes the following steps:
●Determining whether an indication for listing for cardiac transplantation is present. Patients with an indication for listing should be referred to a transplant center for cardiac transplantation evaluation. (See 'Indications for cardiac transplantation' below.)
•Determining whether there is a possible indication for combined organ transplantation (eg, heart-kidney transplantation) and, if so, referral to a transplant center experienced in multi-organ transplantation. (See 'Indications for combined organ transplantation' below.)
●Cardiac transplantation evaluation at the transplant center involves reviewing potential indications for transplantation in the individual patient and determining whether any absolute or relative contraindication to cardiac transplantation is present. This determination includes performing baseline and periodic follow-up testing, including right heart catheterization to ascertain if pulmonary hypertension is present. (See 'Contraindications' below and 'Elevated pulmonary vascular resistance' below.)
●The ultimate decision to place a patient on the heart transplant waiting list is made after weighing the potential risks and benefits of treatment options by clinicians at the transplant center based upon a combination of test data and clinical judgment.
●Dynamic listing is a process which involves continually re-evaluating ambulatory patients in the outpatient setting to maximize pharmacologic and device therapy (including implantable cardioverter defibrillator) or biventricular pacing, as indicated [2]. The process includes re-evaluation for response to therapy with cardiopulmonary exercise testing and heart failure survival prognostic scores at three- to six-month intervals. Patients should be considered for delisting if they no longer have an indication for transplantation with maximized therapy.
The International Society for Heart and Lung Transplantation published a consensus statement of listing and management policies for potential cardiac transplantation candidates in 2006 [3]; these guidelines were updated in 2016 [4]. The approach described here is generally consistent with the approach described in the updated guidelines.
INDICATIONS FOR TRANSPLANTATION
Indications for cardiac transplantation — The absolute indications listed below are clinical settings in which cardiac transplantation is generally the treatment of choice [5]. The relative indications are settings in which we suggest weighing the risks and benefits of cardiac transplantation along with other management options. (See 'Contraindications' below.)
The following are absolute indications for referral for cardiac transplantation listing; patients with these conditions should be referred for cardiac transplantation evaluation.
●Cardiogenic shock requiring either continuous intravenous inotropic support or circulatory support with an intraaortic balloon pump counterpulsation device or mechanical circulatory support (such as left ventricular assist device) to maintain adequate organ perfusion.
●Persistent New York Heart Association (NYHA) functional class IV heart failure (HF) symptoms refractory to optimal medical and surgical therapy (including use of devices). Patients with refractory class IV HF should be assessed by cardiopulmonary testing, as well as by HF prognosis score [2].
•The following peak oxygen consumption (VO2) thresholds favor listing, but are not to be used as sole criteria for listing. We agree with the 2015 International Society for Heart Lung Transplantation (ISHLT) listing criteria that these peak VO2 thresholds apply regardless of whether cardiac resynchronization therapy (CRT) is used, although the thresholds are based largely on data in patients not receiving CRT [2]:
-For patients intolerant of beta blocker therapy, a peak VO2 ≤14 mL/kg/min.
-For patients on beta blocker, a peak VO2 ≤12 mL/kg/min.
-An alternative criterion: For patients who are young (<50 years old) or women, peak VO2 <50 percent predicted may be used as an alternative criterion.
•Some experts also use the following additional alternate criterion:
-If a sub-maximal cardiopulmonary exercise test (respiratory exchange ratio [RER] <1.05) is obtained, a ventilation equivalent of carbon dioxide (VE/VCO2) slope of >35 may be used as a criterion for listing.
•The following HF prognosis scores favor listing but are not to be used as sole criteria for listing:
-Seattle Heart Failure Model (SHFM) estimated one-year survival of <80 percent; or
-Heart Failure Survival Score (HFSS) in the high/medium risk range.
●Intractable or severe anginal symptoms in patients with coronary artery disease not amenable to percutaneous or surgical revascularization, including severe transplant coronary artery disease (also known as cardiac allograft vasculopathy). (See "Heart Transplantation: Prevention and treatment of cardiac allograft vasculopathy", section on 'Retransplantation'.)
●Intractable life-threatening arrhythmias unresponsive to medical therapy, catheter ablation, surgery, and/or implantable cardioverter-defibrillator. (See "Electrical storm and incessant ventricular tachycardia".)
●Selected patients with restrictive and hypertrophic cardiomyopathies and NYHA Class III to IV HF [2].
•Evaluation should include work-up to elucidate the etiology of the cardiomyopathy and to exclude constrictive pericarditis. (See "Determining the etiology and severity of heart failure or cardiomyopathy" and "Restrictive cardiomyopathies", section on 'Diagnostic evaluation' and "Differentiating constrictive pericarditis and restrictive cardiomyopathy" and "Restrictive cardiomyopathies", section on 'Differential Diagnosis'.)
•The decision to list a patient with restrictive cardiomyopathy (RCM) for transplantation should include consideration of specific prognostic markers (such as atrial enlargement, left ventricular systolic dysfunction, low cardiac output, and pulmonary hypertension). Patients with restrictive cardiomyopathy with persistent hepatic dysfunction despite relief from congestion should be considered for liver biopsy since findings such as fibrosis and cirrhosis may be helpful in assessing transplant risk.
•Given technical challenges and limited experience with mechanical circulatory support (MCS) in patients with restrictive cardiomyopathy, MCS bridging with a left ventricular assist device or a total artificial heart is an option in only highly selected cases of RCM at experienced centers. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".)
•Selected patients with cardiac amyloidosis are candidates for transplantation [2], noting that severe extracardiac amyloid organ dysfunction is a contraindication to heart transplantation. (See 'Absolute contraindications' below and "Amyloid cardiomyopathy: Treatment and prognosis".):
-Selected patients with HF due to AL amyloidosis who are not candidates for disease-specific therapies due to HF may be considered for cardiac transplantation (with autologous stem cell transplantation following as soon as feasible after recovery from cardiac transplantation) in experienced centers with established cardiovascular and hematology team collaboration.
-Selected patients with transthyretin-related (TTR) cardiac amyloidosis may be considered for heart transplantation. Familial TTR cardiac amyloidosis patients should be considered for combined heart and liver transplantation in experienced centers with established cardiology and hepatology team collaboration.
•Patients with refractory severe HF and non-obstructive hypertrophic cardiomyopathy (particularly those with left ventricular dilation and systolic dysfunction) not amenable to other treatment should be considered for heart transplantation.
Other non-dilated cardiomyopathies such as arrhythmogenic right ventricular cardiomyopathy/dysplasia or left ventricular noncompaction are uncommon causes of severe HF requiring cardiac transplantation. The 2016 listing criteria deferred providing specific recommendations for these conditions [2].
●For adults with congenital heart disease (CHD) in the following clinical settings, we suggest referral for possible listing for heart transplantation [2]. Heart transplantation in adults with CHD should be performed only at centers with established medical and surgical experience in both adult CHD and heart transplantation.
•New York Heart Association functional class IV HF not amenable to palliative or corrective surgery.
•Severe symptomatic cyanotic heart disease not amenable to palliation. (See "Medical management of cyanotic congenital heart disease in adults".)
•Post-Fontan procedure with refractory HF, persistent protein-losing enteropathy, and/or plastic bronchitis despite optimal medical and surgical therapy. (See "Management of complications in patients with Fontan circulation".)
•Pulmonary hypertension with the potential risk of developing fixed, irreversible elevation of pulmonary vascular resistance (PVR) that could preclude heart transplantation in the future. (See "Pulmonary hypertension in adults with congenital heart disease: Disease-specific management", section on 'Transplantation'.)
However, heart transplantation should not be performed as routine primary therapy for any specific congenital heart lesion before considering or attempting surgical repair.
Patients with both complex intracardiac abnormalities and significant irreversible pulmonary vascular obstructive disease (such as patients with Eisenmenger syndrome with severe symptoms despite advanced therapy) may require combined heart/lung transplantation. Heart transplantation alone should not be performed in the presence of severe hypoplasia of the central or branch pulmonary arteries or pulmonary veins. (See 'Indications for combined organ transplantation' below and "Heart-lung transplantation in adults", section on 'Indications' and "Pulmonary hypertension in adults with congenital heart disease: Disease-specific management", section on 'Transplantation'.)
Relative indications:
●Patients with HF causing major limitation of daily activities despite medical therapy, including a beta blocker with peak VO2 of 13 to 14 mL/kg per minute (or <55 percent predicted).
●Recurrent unstable ischemia not amenable to other intervention.
●Recurrent instability of fluid balance/renal function not due to patient noncompliance with medical regimen.
Insufficient indications:
●Low left ventricular ejection fraction.
●History of functional class III or IV symptoms of HF.
●Peak VO2 greater than 15 mL/kg per minute (or greater than 55 percent predicted) without other indications.
Indications for combined organ transplantation — In patients with severe irreversible disease of the heart and another organ system, isolated cardiac transplantation should not be performed; multiorgan transplantation may be an option in some of these cases but requires careful consideration given the complex medical issues involved [2]. (See "Heart transplantation in adults: Prognosis", section on 'Heart-kidney transplantation' and "Heart transplantation in adults: Prognosis", section on 'Heart-lung transplantation' and "Heart transplantation in adults: Prognosis", section on 'Heart-liver transplantation'.)
●Patients with end-stage heart disease who also have renal failure with indication for kidney transplantation can be considered for dual organ transplantation. Every effort should be made to determine the reversibility of renal dysfunction. This may include a trial of inotropic agent. In select cases, a renal biopsy may be required.
A separate issue is kidney transplantation in patients who develop renal failure after heart transplantation. (See "Kidney function and non-kidney solid organ transplantation", section on 'Cardiac transplantation'.)
●Patients with end-stage lung disease who also have severe left ventricular dysfunction or other cardiac diseases that would preclude a successful outcome with lung transplantation alone may be candidates for combined heart-lung transplantation. When possible, isolated lung or heart transplantation is preferred to heart-lung transplantation because of several major disadvantages with the combined procedure. (See "Heart-lung transplantation in adults".)
●Combined heart and liver transplantation is an option in select candidates but is rarely performed given the comorbidities frequently involved.
Indications for retransplantation — Retransplantation is indicated for highly selected cardiac transplant recipients who meet criteria for de novo transplantation and have cardiac allograft vasculopathy (CAV) with one or more of the following conditions:
●CAV with one or more of the following:
•ISHLT CAV3 (severe): Left main coronary artery stenosis >50 percent or >70 percent stenosis in two or more primary coronary artery vessels (eg, left anterior descending, left circumflex, or right coronary artery) or >70 percent stenosis in branch coronary artery vessels in three systems.
•Mild or moderate CAV (ISHLT CAV1 or CAV2) plus left ventricular ejection fraction <45 percent:
-ISHLT CAV1 (mild): Left main stenosis <50 percent and primary vessel stenosis <70 percent.
-ISHLT CAV2 (moderate): Left main >50 percent; primary vessel >70 percent or secondary >70 percent branch stenoses in two systems.
•CAV1-3 with restrictive physiology (E to A ratio >2; IVRT <60 ms, RA >12, PCW >25, CI <2).
●Symptomatic graft dysfunction without evidence of active rejection though retransplantation within six months of transplant caused by immunologic mechanisms is associated with poor outcome.
Similar criteria for retransplantation were included in the 2016 ISHLT listing criteria [2].
(See "Heart transplantation in adults: Prognosis", section on 'Repeat cardiac transplantation'.)
Major society guidelines — The above indications for cardiac and combined organ transplantation are in broad agreement with major society guidelines, including the ISHLT listing criteria for cardiac transplantation, which were updated in 2016 [2]. The 2013 American College of Cardiology/American Heart Association HF guidelines and the 2016 European Society of Cardiology guidelines recommend referral for cardiac transplantation in potentially eligible patients with refractory end-stage HF [6,7]. The 2006 Canadian Cardiovascular Society [8] and the 2010 Heart Failure Society of America [9] guidelines recommend cardiac transplantation evaluation for selected patients with severe HF, debilitating refractory angina, or ventricular arrhythmia that cannot be controlled despite drug, device, or alternative surgical therapy.
Evidence supporting indications — Indications for cardiac transplantation are based upon the prognostic value of clinical indices in patients with advanced HF, as well as observational data suggesting improvement in outcomes in patients selected for cardiac transplantation. (See "Heart transplantation in adults: Prognosis".)
Estimation of prognosis is the most important component of the selection process for cardiac transplant recipients. The key prognostic indicators are peak volume of oxygen consumption (VO2) and prognostic scores such as the Heart Failure Survival Score and the Seattle Heart Failure Model. Many other predictors of poor prognosis have been identified, including New York Heart Association functional class III or IV, reduced left ventricular ejection fraction, and hyponatremia. However, use of an individual clinical factor to identify high risk is frequently problematic, given the complexity of HF and the multiple neurohumoral, hemodynamic, and electrophysiologic factors that may contribute to morbidity and mortality. Use of multivariable models has significantly improved our ability to identify high-risk patients. (See "Prognosis of heart failure" and "Predictors of survival in heart failure with reduced ejection fraction".)
Peak VO2 — In general, the peak volume of oxygen consumption (peak VO2 or VO2max) with cardiopulmonary stress testing provides an objective assessment of functional capacity in patients with HF and is one of the best predictors of when to list an individual patient for cardiac transplantation [2,10]. (See "Exercise capacity and VO2 in heart failure" and "Cardiopulmonary exercise testing in cardiovascular disease".)
For patients not on beta blocker therapy (due to intolerance), a peak VO2 ≤14 mL/kg/min is a predictor of limited survival (eg, 70 percent at one year versus 94 percent at one year for patients with higher peak VO2) and thus favors transplantation [10]. Peak exercise oxygen consumption is extremely helpful in identifying low-risk patients who can continue on medical therapy.
With evidence-based HF therapy including beta blockers and devices (ie, implantable cardioverter-defibrillator [ICD] and cardiac resynchronization therapy [CRT]), a peak VO2 cut point of ≤12 mL/kg/min appears to be a better threshold than ≤14 mL/kg for identification of high-risk patients [11]. The potential impact of other therapies such as angiotensin receptor-neprilysin inhibitor (ARNI; eg, sacubitril-valsartan) on VO2 threshold has not yet been determined.
Beta blocker therapy has improved survival rates in patients with HF with reduced ejection fraction (HFrEF), including patients with very low peak VO2 to as low as 10 mL/kg per min. The prognostic power of peak VO2 was initially validated prior to the widespread use of beta blockers, but several studies have demonstrated the continued usefulness of VO2 in the modern drug era with beta blocker use [12,13]. In a series of 715 patients with HFrEF referred for heart transplantation, one-year event-free survival was 87 percent in patients with VO2 >14 mL/kg, 77 percent in those with VO2 10.1 to 14 mL/kg, and 65 percent in patients with a VO2 ≤10 mL/kg. (See 'Major society guidelines' above.)
One limitation of the peak VO2 criterion is that it requires a maximal cardiopulmonary exercise test. A maximal cardiopulmonary exercise test is defined as one on optimal pharmacologic therapy with a RER >1.05 and achievement of anaerobic threshold [2]. (See "Exercise physiology".)
If a sub-maximal cardiopulmonary exercise test (RER <1.05) is obtained, some experts use a ventilation equivalent of carbon dioxide (VE/VCO2) slope of >35 as a criterion for listing.
Prognosis scores — Although peak VO2 has often been the major parameter used to guide the selection of heart transplant candidates, a single variable does not provide an optimal risk profile. As a result, several risk models have been developed that use factors identified in multivariable survival analysis to establish a risk score for prognosis in these patients [14-18]. These include the Heart Failure Survival Score (HFSS) [14] and the Seattle Heart Failure Model [18]. (See "Predictors of survival in heart failure with reduced ejection fraction", section on 'Predictive models'.)
For guiding decisions regarding the listing of patients for cardiac transplantation, these scores are most useful in cases where other predictors are ambiguous (eg, peak VO2 12 to 14 mL/kg per min) [3]. Although the prognostic information provided can be helpful when making recommendations about transplantation, cardiac transplantation centers do not base determinations on the results of risk models alone.
Heart Failure Survival Score — One model that has been validated prospectively is the HFSS [14]. This score was derived from a multivariable analysis of 268 ambulatory patients referred for consideration of cardiac transplantation from 1986 to 1991 and validated in 199 similar patients from 1993 to 1995. The predictors of survival in the HFSS include:
●Presence or absence of coronary artery disease
●Resting heart rate
●Left ventricular ejection fraction
●Mean arterial blood pressure
●Presence or absence of an intraventricular conduction delay on electrocardiogram
●Serum sodium
●Peak VO2
The HFSS stratifies patients into low- (HFSS ≥8.10), medium- (HFSS 7.20 to 8.09), and high-risk (HFSS ≤7.19) categories, based upon a sum of the variables above multiplied by defined coefficients. Among the patients in the validation sample, one-year survival rates without transplant for these three strata were 88, 60, and 35 percent, respectively.
Although the prognostic value of the HFSS was initially identified prior to widespread use of beta blockers, its prognostic value has been revalidated since then in patients on beta blocker therapy [11,19]. In a series of 715 patients with HFrEF referred for heart transplantation, one-year event-free survival was 89 percent in patients with low-risk scores, 72 percent in those with VO2 medium-risk scores, and 60 percent in patients with high-risk scores [11].
Seattle Heart Failure Model — The Seattle Heart Failure Model is easier to use than the HFSS as it is available online at https://depts.washington.edu/shfm/?width=1024&height=819.
The model was derived in 1125 HF patients and prospectively validated in five cohorts, including almost 10,000 general outpatients and advanced HF patients who were followed for over 17,000 person-years [18]. The diversity of the patient populations makes the findings more generalizable to clinical practice.
The model provides a relatively accurate estimate of one-, two-, and three-year survival (r values ranging from 0.97 to 0.99) with the use of easily obtained clinical, pharmacologic, device, and laboratory characteristics. It also allows the operator to add in the estimated effect of interventions on an individual patient's prognosis. Unlike the HFSS, the Seattle Heart Failure Model has incorporated the impact of newer HF therapies on survival, including ICDs and CRT.
However, the Seattle Heart Failure model assumes maximum benefit from administered therapy and thus tends to overestimate survival in sicker populations.
Considerations for hypertrophic or restrictive cardiomyopathy — A small percent of patients referred for transplant have hypertrophic or restrictive cardiomyopathies with HF resulting from diastolic abnormalities caused by myocardial abnormalities or infiltration. This group of diseases includes hypertrophic cardiomyopathies, sarcoidosis, amyloidosis, hemochromatosis, glycogen storage diseases, and genetic deficiencies such as Fabry disease. Transplant evaluation in these patients requires a careful work-up to identify the underlying disease, as post-transplant care may need to be modified. Additionally, for infiltrative disorders, the involvement of other organs needs to be assessed. (See "Definition and classification of the cardiomyopathies".)
The post-transplant outcomes of patients with hypertrophic cardiomyopathy are excellent and comparable to patients with dilated cardiomyopathies or coronary artery disease [20]. Patients with sarcoidosis also have excellent post-transplant outcomes, but generally those patients who have been transplanted did not have active extracardiac disease [21]. Patients with hemochromatosis may require combined heart and liver transplant. The infiltrative cardiomyopathy that has generated the most interest in the last few years has been amyloidosis. With amyloid, it is imperative to identify the etiology as either being due to light chain AL amyloid or a transthyretin genetic mutation (TTR). The ISHLT guidelines support cardiac transplantation for AL amyloid patients in conjunction with stem cell transplantation performed as soon as possible after recovery from the heart transplantation [2]. These patients should be carefully selected with predominantly cardiac involvement (51c,D) [22,23]. TTR amyloid patients can be transplanted with or without a liver transplant depending on the age of the candidate.
Congenital heart disease — For adults with CHD, indications for referral for evaluation for heart transplantation include New York Heart Association functional class IV HF not amenable to palliative or corrective surgery; reversible pulmonary hypertension with the potential risk of developing fixed, irreversible elevation of PVR that could preclude heart transplantation in the future; severe symptomatic cyanotic heart disease not amenable to palliation; and failing Fontan physiology with refractory HF, persistent protein-losing enteropathy, and/or plastic bronchitis despite optimal medical and surgical therapy. Thus, heart transplantation is performed for diverse cardiovascular lesions with poor prognosis. Patients with both complex intracardiac abnormalities and significant irreversible pulmonary vascular obstructive disease may require heart/lung transplantation. (See "Management of complications in patients with Fontan circulation" and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis" and "Pulmonary hypertension in adults with congenital heart disease: General management and prognosis".)
Adult patients with CHD undergoing heart transplantation have lower early survival rates but higher long-term survival rates compared with patients without CHD undergoing heart transplantation. In a systematic review, 30-day survival after heart transplantation was 82.6 for CHD patients versus 92.6 for non-CHD patients [24]. Survival in CHD patients was not significantly different from that in non-CHD patients at one year (79.4 versus 84.6 percent) or five years (69.2 versus 70.5 percent). However, at 10 years, survival was significantly higher in patients with CHD (59.3 versus 51 percent). Prognostic markers for increased mortality in CHD patients undergoing transplantation have been identified such as ≥3 sternotomies and Model for End-Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) score >18 [25], but a comprehensive approach for risk stratification of CHD patients has not been established [2]. (See "Heart transplantation in adults: Prognosis".)
CONTRAINDICATIONS
Approach to evaluating contraindications — Patients with an indication for cardiac transplantation should undergo evaluation to determine if one or more absolute or relative contraindications is present (table 1) [2,5]. Contraindications must be taken into account in judging whether a patient is likely to benefit from heart transplantation since contraindications impact short- and long-term patient and cardiac graft survival.
A key component of the evaluation prior to listing is evaluation (including right heart catheterization) and management of pulmonary hypertension with elevated pulmonary vascular resistance. (See 'Elevated pulmonary vascular resistance' below.)
For patients with a potentially reversible or treatable condition that is considered a contraindication (eg, cancer, obesity, renal failure, tobacco use) or pharmacologically irreversible pulmonary hypertension, mechanical circulatory support may be used as a bridge to decision on transplant candidacy.
Absolute contraindications
Overview of absolute contraindications — The following are considered absolute contraindications to cardiac transplantation:
●Systemic illness with a life expectancy <2 years despite heart transplantation. (See 'Systemic illness with limited life expectancy' below.)
●Irreversible pulmonary hypertension is considered an absolute contraindication, but there is some variation among centers as to the threshold level of pulmonary hypertension above which cardiac transplantation is not performed. Pulmonary hypertension with irreversible pulmonary vascular resistance (PVR) >3 Wood units (>240 dynes-sec/cm5; normal is ≤1.5 Wood units [120 dynes-sec/cm5]) is commonly considered a contraindication to isolated heart transplantation [2]. Heart-lung transplantation may be considered as an alternative when irreversible PVR >3 Wood units is present. However, some centers have successfully performed isolated heart transplantation in patients with irreversible PVR >3 Woods units on a case-by-case basis. (See 'Elevated pulmonary vascular resistance' below.)
●Clinically severe symptomatic cerebrovascular disease [2]. (See 'Clinically severe symptomatic cerebrovascular disease' below.)
●Active substance abuse (drug, tobacco, or alcohol) [2]. (See 'Substance use' below.)
●Multiple demonstrations of inability to comply with drug therapy. (See 'Inadequate social support or cognitive-behavioral disability' below.)
●Multisystem disease with severe extracardiac organ dysfunction (such as some cases of amyloidosis).
Discussion of some absolute contraindications
Systemic illness with limited life expectancy — Cardiac transplantation is contraindicated in patients with a systemic illness which is expected to limit life expectancy to <2 years despite cardiac transplantations. This includes patients with AIDS with frequent opportunistic infections but not HIV-infected patients who have better prognoses. (See 'Infection' below.)
Elevated pulmonary vascular resistance — We suggest the following approach to detection and management of elevated PVR in potential cardiac transplantation candidates (algorithm 1).
●All candidates for cardiac transplantation should undergo right heart catheterization (RHC) prior to listing and repeat RHC until transplantation at intervals adjusted according to patient status [2]:
•In patients with elevated baseline or follow-up PVR, right heart catheterization is repeated at two- to three-month intervals while medications are adjusted to reach the target PVR (≤3 Wood units or 240 dynes-sec/cm5). After target PVR is reached, then right heart catheterization is repeated every six months. This recommendation is similar to the recommendation in the International Society of Heart and Lung Transplantation (ISHLT) listing criteria that right heart catheterization be repeated every three to six months in listed patients in the presence of reversible pulmonary hypertension or worsening heart failure symptoms [2].
•For patients with normal baseline PVR, repeat right heart catheterization is generally performed annually.
●Patients with a pulmonary artery systolic pressure >50 mmHg and either elevated PVR (defined as >3 Wood units), or a transpulmonary pressure gradient >15 mmHg on right heart catheterization should be tested with an acute vasodilator challenge.
Vasodilators used for acute testing of pulmonary hypertension reversibility in this setting include sodium nitroprusside 0.5 to 1.5 mcg/kg/min intravenously, inhaled nitric oxide 20 to 80 ppm, sildenafil 25 to 100 mg po, prostacyclin 50 mg inhaled, PGE1 0.02 to 0.3 mcg/kg/min intravenously, or milrinone 50 mcg/kg infused over one minute. We prefer use of nitroprusside in this setting due to its short duration of action. We generally avoid use of inhaled nitric oxide, sildenafil, prostacyclin, and PGE1 if the pulmonary capillary wedge pressure is elevated, since administration of these agents in this setting may lead to pulmonary edema. We generally avoid use of milrinone bolus in this setting given the risks of inducing persistent hypotension or ventricular tachycardia.
Patients whose PVR can be reduced to ≤3 Wood units (320 dynes-sec/cm5) while maintaining a systolic blood pressure ≥85 mmHg are usually considered acceptable candidates for isolated heart transplantation. If this threshold is not met acutely, some experts suggest hospitalization with continuous hemodynamic monitoring, as the PVR will often decline after 24 to 48 hours of treatment including diuretics, inotropes, and vasoactive agents.
●If acute vasodilator challenge fails to reduce PVR to ≤3 Wood units with systolic blood pressure ≥85 mm Hg, we suggest a two- to eight-week trial of optimized medical therapy, including milrinone (>0.25 mcg/kg/min as tolerated) with or without the addition of a PDE 5 inhibitor (sildenafil 20 mg po TID as tolerated). The dose of these agents is adjusted depending upon patient tolerance in terms of maintaining a systolic blood pressure ≥85 mmHg (with milrinone and/or PDE 5 inhibitor) and arrhythmias (with milrinone).
Patients whose PVR can be reduced to ≤3 Wood units (320 dynes-sec/cm5) while maintaining a systolic blood pressure ≥85 mmHg are usually considered acceptable candidates for isolated heart transplantation.
●If the trial of optimized medical therapy fails to reduce PVR to ≤3 Wood units with systolic blood pressure ≥85 mm Hg, we suggest a three- to six-month trial of mechanical circulatory support (ie, left ventricular assist device [LVAD]) followed by repeat RHC. Patients whose PVR can be reduced to ≤3 Wood units (320 dynes-sec/cm5) while maintaining a systolic blood pressure ≥85 mmHg are usually considered acceptable candidates for isolated heart transplantation.
If PVR fails to fall to ≤3 Wood units with systolic blood pressure ≥85 mmHg, despite pharmacologic measures with mechanical adjuncts, pulmonary hypertension is deemed irreversible [2]. Pulmonary hypertension with irreversible PVR >3 Wood units (dynes-sec/cm5; normal is ≤1.5 Wood units [120 dynes-sec/cm5]) is commonly considered a contraindication to isolated heart transplantation and in this setting, heart-lung transplantation may be considered as an alternative. Patients with an elevated PVR or a transpulmonary gradient (mean pulmonary artery pressure minus mean pulmonary capillary wedge pressure) above 15 mmHg have an increased risk of right ventricular failure in the immediate postoperative period, a time at which the normal donor right ventricle is acutely subjected to a marked increase in workload [2,26,27].
However, as noted above, some centers have successfully performed heart transplantation in patients with irreversible PVR >3 (up to 5) Woods units on a case-by-case basis.
Fortunately, pulmonary hypertension in most patients with heart failure (HF) is due to neurohumoral vasoconstriction, not structural changes in the pulmonary vasculature, such as calcification or intimal or medial hyperplasia. Accordingly, an elevated PVR often can be reduced acutely or chronically by using agents such as nitroprusside, dobutamine, milrinone, prostaglandin E1, prostacyclin, phosphodiesterase type 3 inhibitors, and inhaled nitric oxide [27-31]. A continuous infusion of milrinone, dobutamine, or prostaglandin E1 for several weeks has been used in some patients as a bridge to transplantation [32,33]. As an example, a study of 68 patients found that prostaglandin E1 was more effective than prostacyclin or dobutamine for preventing worsening of HF [34]. Patients with persistent pulmonary hypertension may be treated with implantation of an LVAD [35,36].
In one report, the three-month mortality rate was higher in patients whose PVR was above 2.5 Wood units compared with those with lower values (17.9 versus 6.9 percent) [27]. However, in patients with initially high PVR that was reduced by nitroprusside, the three-month mortality was only 3.8 percent compared with 41 and 28 percent, respectively, in those who were resistant to nitroprusside or who only responded at a dose that caused systemic hypotension. None of the patients with reversible pulmonary hypertension developed right ventricular failure after transplantation.
Clinically severe symptomatic cerebrovascular disease — Severe symptomatic cerebrovascular disease (CVD) is considered an absolute contraindication given observational evidence suggesting that patients with symptomatic CVD are at increased risk for worse outcomes. An observational study including 1078 patients with symptomatic CVD and 16,765 patients without symptomatic CVD found that patients with symptomatic CVD were at increased risk of stroke (hazard ratio [HR] 2.24; 95% CI: 2.02 to 2.87), and functional decline (HR: 1.21; 95% CI: 1.03 to 1.42) independent of other variables after long-term follow-up after cardiac transplantation [37]. However data are lacking on the effect of treatment such as revascularization and newer LVAD technology on outcomes in this clinical setting.
Relative contraindications
Overview of relative contraindications — The following are relative contraindications to cardiac transplantation [2]:
●Age >70 years old. However, carefully selected patients >70 years old may be considered for transplantation. (See 'Age' below.)
●Obesity (ie, body mass index [BMI] >35 kg/m2). (See 'Obesity' below.)
●Diabetes mellitus with poor glycemic control (glycated hemoglobin [HbA1c]>7.5 percent or 58 mmol/mol) despite optimal effort or end-organ damage other than non-proliferative retinopathy. (See 'Diabetes mellitus' below.)
●Irreversible renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m2) is a relative contraindication for isolated cardiac transplantation. (See 'Irreversible renal dysfunction' below.)
●Neoplasm (requires individualized assessment of severity, treatment options and prognosis). (See 'Neoplasm' below.)
●Infection (requires individualized assessment of severity, treatment options, and prognosis). (See 'Infection' below.)
●Acute pulmonary embolism (within six to eight weeks). (See 'Pulmonary embolism' below.)
●Tobacco use (within six months). (See 'Tobacco use' below.)
●Recent past (eg, within six months) substance (drug or alcohol) abuse. (See 'Substance use' below.)
●Inadequate social support or cognitive-behavioral disability that would prevent compliant care. (See 'Inadequate social support or cognitive-behavioral disability' below.)
●Other conditions that increase the risk of perioperative complications or limit tolerance of immunosuppression, eg, peripheral vascular disease that would limit rehabilitation and is not amenable to revascularization. (See 'Other' below.)
●In addition, frailty may be considered a relative contraindication although further data are needed to define its role is assessing transplant candidacy. (See 'Frailty' below.)
Discussion of some relative contraindications
Age — We agree with the 2016 ISHLT listing criteria that most patients 70 years of age or younger and carefully selected patients over age 70 can be considered for cardiac transplantation [2,3]. Among the relative contraindications to cardiac transplantation, age has historically been a major factor (table 1) [3]. Many programs have routinely excluded patients over the age of 60 to 65, but most feel that physiologic age is more important than chronologic age. Some centers will perform transplants up to age 70 years with the older patients required to meet additional selection criteria such as less than two prior open heart procedures, preserved renal function, no prior cerebrovascular events, and preserved hepatic function.
A report based on United Network of Organ Sharing data for 14,401 first-time transplant recipients between 1999 and 2006 demonstrated that patients ≥60 years of age more frequently had comorbidities than younger patients and that their overall survival post-transplant was lower than in younger patients [38]. However, cumulative five-year survival for patients ≥60 years of age was only slightly lower than that for younger patients (69 versus 75 percent). Multivariate analysis revealed recipient age ≥60 years, donor age, ischemic time, creatinine, hypertension, and diabetes mellitus to be independent predictors of mortality.
Carefully selected patients over 60 years of age have a survival rate comparable to that in younger patients. This was illustrated in a report that compared 63 patients transplanted at 65 years of age or older (mean age 67) with 63 matched younger patients (mean age 48) [39]. Survival was comparable for both groups at 1, 3, 5, and 10 years; there was also no significant difference in the incidence of rejection or infection. As a result of such findings, most centers now focus on the patient's "physiologic" age, with emphasis on the functional integrity of major organ systems and the absence of exclusionary comorbid diseases.
Obesity — Since BMI >35 kg/m2 is associated with worse outcomes after cardiac transplantation, we suggest recommending weight loss to BMI ≤35 kg/m2 prior to listing [2].
Diabetes mellitus — Diabetes mellitus with evidence of significant end-organ damage (eg, neuropathy or nephropathy, but not nonproliferative retinopathy) is a relative contraindication to heart transplantation [2]. Diabetes with persistent poor glycemic control (as evidenced by glycosylated hemoglobin [HbA1c]>7.5 percent or 58 mmol/mol) despite optimal effort also represents a relative contraindication to transplantation.
Single-center studies have reported that carefully selected diabetic patients on insulin or drug therapy can undergo successful cardiac transplantation with similar morbidity and mortality as nondiabetic subjects [40]. Analysis of the United Network of Organ Sharing database confirmed comparable survival in patients with uncomplicated diabetes but not in those diabetics with significant renal insufficiency (creatinine >2.5 mg/dL, obesity, peripheral vascular disease, or past history of stroke) [41]. In diabetics without significant renal dysfunction, the effect of calcineurin inhibitor on renal function was comparable to that in nondiabetics over time [42].
In diabetics with renal dysfunction, combined heart renal transplant can be considered, as the reported outcomes of combined heart-kidney transplant are comparable to heart alone [43]. (See "Heart transplantation in adults: Prognosis" and "Heart transplantation in adults: Prognosis", section on 'Heart-kidney transplantation'.)
Irreversible renal dysfunction — Irreversible renal dysfunction (eGFR <30 ml/min/1.73 m2) is a relative contraindication for isolated cardiac transplantation. Evaluation should be undertaken to detect or exclude intrinsic renal disease and renal artery disease, including renal ultrasound and quantification of proteinuria. The concern in this setting is the superimposed nephrotoxicity of long-term calcineurin inhibitor therapy. (See "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults" and "Cyclosporine and tacrolimus nephrotoxicity".)
Combined kidney-heart transplantation may be offered to those who require transplantation of both organs with expected outcomes in experienced centers that may be similar to those receiving a heart transplant alone. Among such patients, it is essential that reversible impairment of either organ be excluded. These issues are discussed separately. (See "Heart transplantation in adults: Prognosis", section on 'Heart-kidney transplantation'.)
Neoplasm — Given the diverse treatment options and prognosis for neoplasms, appropriate assessment of patients with active neoplasm or past history of neoplasm requires collaboration between oncology and cardiology specialists. Malignancy can be worsened by the immunosuppressive therapy given to prevent transplant rejection. Even without pre-existing disease, the incidence of malignancy (eg, skin cancers, lymphoproliferative disorders, and some solid tumors such as thyroid or cervical cancers) is increased following transplantation [44].
As noted above, an absolute contraindication to transplantation is a condition expected to limit life expectancy to <2 years despite cardiac transplantation; this includes some malignancies with poor prognosis.
Other neoplasms that are not immediately life-limiting may present only a relative contraindication. Cardiac transplantation is an option for patients with low risk of tumor recurrence based upon the tumor type, response to therapy, negative metastatic work-up, and passage of an individualized period of remission (ie, no arbitrary time period for observation in remission) [2]. Thus, patients with past history of malignancy now considered cured who have a cardiomyopathy as a consequence of chemotherapy given for the malignancy are considered reasonable candidates for transplantation. However, these patients do have an increased risk of developing a second malignancy. (See "Malignancy after solid organ transplantation".)
Infection — Depending upon the type and severity of infection, it may be considered an absolute or relative contraindication to transplantation. One concern is that active infection can become fulminant in the setting of introducing immunosuppressive therapy. However, with the increasing use of mechanical device support as a bridge to transplant, it has become accepted practice in some centers to proceed with cardiac transplantation in patients with ongoing controlled device infections; transplantation enables removal of the device, which is essential to eradicate the infection. Whether the survival of infected device patients is comparable to standard recipients is actively being investigated.
COVID-19 — In accord with ISHLT guidance, cardiac transplant candidates with active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are made inactive on the waitlist [45]. For cardiac transplant candidates who recover from coronavirus disease 2019 (COVID-19), criteria for heart transplantation include waiting at least 14 days after initial COVID-19 diagnosis and documenting that the patient is asymptomatic with at least one negative SARS-CoV-2 polymerase chain reaction (PCR)-based test. Although the ISHLT guidance suggested two successive negative PCR-based tests at least 48 hours apart [45], some transplant centers require only one negative PCR-based test.
Management of cardiac transplant recipients with COVID-19 is discussed separately. (See "COVID-19: Evaluation and management of cardiac disease in adults", section on 'Cardiac transplantation'.)
Chronic viral infection — Heart transplantation in patients with clinically important chronic viral infection remains a subject of active debate.
●Hepatitis B or C – Active or fulminant hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a contraindication to heart transplantation.
Evaluation is recommended in patients with chronic or resolved HBV or HCV infection as described in the 2016 listing criteria [2].
•For HCV
-For cardiac transplant candidates with resolved or prior inactive HCV infection, HCV RNA PCR testing should be performed at screening, at three-month intervals while listed, and repeated at the time of transplantation.
-For candidates with chronic HCV infection, HCV genotype should be determined.
Patients with HCV genotype 2 and 3 should be treated with anti-viral treatment. If HCV RNA clears, then liver biopsy is suggested. If the biopsy shows only mild to moderate hepatic pathology, then the candidate can be listed for transplantation. If HCV RNA does not completely clear and a liver biopsy shows no more than mild disease, then some highly specialized centers would proceed with listing for heart transplantation in otherwise acceptable patients.
Patients with HCV non-genotype 2 or 3 should undergo liver biopsy. If the biopsy shows only mild disease, anti-viral treatment is suggested. If the virus clears after antiviral treatment, then the candidate can be listed for transplantation. If the virus does not clear, some centers may still consider transplantation in patients who do not have bridging fibrosis.
•For HBV
-For cardiac transplant candidates with resolved or prior inactive HBV infection, serology (including HBsAg, HBsAb, and HBcAb) and DNA viral load testing should be performed at screening, at three-month intervals while listed, and repeated at the time of transplantation. Complete viral HBV evaluation before transplantation should also include testing serum for HBeAg and anti-HBe, anti-HBc (immunoglobulin [Ig] G and M) and hepatitis delta virus (HDV) RNA, anti-HDV (total and IgG), and alpha-fetoprotein.
-For patients with chronic HBV infection, liver biopsy should be done in all patients to exclude severe disease. Some specialized centers perform heart transplantation in patients with chronic HBV infection with low viral load.
•For patients with chronic HCV or HBV infection, clinical, radiologic, or biochemical signs of cirrhosis, portal hypertension, or hepatocellular carcinoma are contraindications to heart transplantation.
Individuals with chronic hepatitis B or C infections who undergo heart transplantation have an increased frequency of liver disease [46,47]. However, it has been difficult to show that survival after heart transplantation is reduced in the presence of positive hepatitis B or C serology [46,48,49]. As a result, practices of individual centers differ. Since the frequency of progressive liver disease appears to be more common with hepatitis B than with hepatitis C, many transplant programs will accept candidates who are anti-HCV antibody positive, but not those who are HBsAg positive.
Evaluation of such patients usually includes assessment for the level of active viremia and often includes liver biopsy to assess for the presence of cirrhosis. With the development of new oral highly effective therapies for hepatitis C, it is anticipated that ledipasvir-sofosbuvir will be used in place of alpha interferon in patients with hepatitis C either before or after transplant. Pre-transplant therapy would be preferable, but in some cases post-transplant use may be warranted. Many of the novel direct-acting antivirals for hepatitis C are metabolized by the cytochrome P450 system, so interactions with calcineurin inhibitors are anticipated [50]. (See "Overview of the management of chronic hepatitis C virus infection".)
●HIV – Management of patients with HIV infection varies depending upon the patient’s clinical status and prognosis as reflected in the following recommendations from the 2016 guidelines [2]. The advent of combination antiretroviral therapy (ART) has changed the prognosis of HIV, so HIV infection alone is no longer considered an absolute contraindication to transplantation. Given the challenges of managing ART and immunosuppressive therapy, centers performing cardiac transplantation in HIV-positive candidates should have structured protocols with multidisciplinary teams, including access to pharmacologic expertise, immunosuppressant drug monitoring, and antiviral drug resistance testing as needed [2]. (See "Overview of HIV drug resistance testing assays" and "Overview of antiretroviral agents used to treat HIV".)
•Selected HIV positive patients are potential candidates for heart transplantation if they have no active or prior opportunistic infections (progressive multifocal leukoencephalopathy or chronic intestinal cryptosporidiosis >1 month), are clinically stable and compliant on combination antiretroviral therapy (cART) for >3 months, have undetectable HIV RNA, and have CD4 counts >200 cells/microL for >3 months.
•Patients with history of primary central nervous system lymphoma or Kaposi sarcoma should not be considered for cardiac transplantation.
•HIV-positive candidates with other resolved neoplasms, including squamous cell carcinoma of the skin, anogenital carcinoma in situ, and other solid organ tumors considered cured may be considered for transplantation after an appropriate disease-free period.
As an example, a case series from a single institution of seven HIV positive cardiac transplant recipients with low or undetectable viral loads without recent significant infections at the time of transplant reported 100 percent survival over a five-year period without AIDS related infections [51]. Immunosuppressive drugs were well tolerated and HIV remained quiescent in these carefully screened patients. These observations require confirmation by other cardiac transplant centers. Given the use of concomitant antiretroviral therapy, the dosing of calcineurin inhibition must be reduced and carefully monitored.
Chagas disease — Heart transplant is an accepted therapy for patients with refractory heart failure caused by Chagas disease but is associated with risk of reactivation of Trypanosoma cruzi infection. As recommended in the 2016 listing criteria, heart transplant candidates from endemic areas should be screened for T. cruzi infection and surveillance for reactivation is required after transplantation [2]. (See "Chronic Chagas cardiomyopathy: Management and prognosis", section on 'Heart failure'.)
●All heart transplant candidates born in Latin America, who have spent significant time in Latin America, who have a Latin American mother, or have received unscreened blood products, should be screened for T. cruzi infection.
●Testing for the presence of infection should be performed using two serologic assays with different formats and T. cruzi antigen preparations. Thus, an initial positive test should be followed up with a confirmatory test. (See "Chagas disease: Chronic Trypanosoma cruzi infection".)
●Treatment of T. cruzi infection is discussed separately. Patients with evidence of reactivation of T. cruzi infection following cardiac transplantation should be treated with appropriate antimicrobial therapy. (See "Chronic Chagas cardiomyopathy: Management and prognosis" and "Chagas disease: Chronic Trypanosoma cruzi infection".)
Tuberculosis — Screening for tuberculosis (TB) is required prior to heart transplantation given the risk of reactivation in patients with latent TB infection, which is more common than newly acquired infection or transmission from the donor [2].
●All heart transplant candidates should be screened for latent TB infection with a two-step tuberculin skin test (TST) and/or interferon-gamma release assay (IGRA), as appropriate. (See "Tuberculosis in solid organ transplant candidates and recipients", section on 'Screening'.)
●If a heart transplant candidate has had recent exposure to TB or chest radiograph shows old TB (and inadequate or no treatment), three consecutive early morning sputum or bronchoalveolar lavage specimens should be obtained to exclude active tuberculosis. (See "Tuberculosis in solid organ transplant candidates and recipients", section on 'Diagnosis' and "Diagnosis of pulmonary tuberculosis in adults".)
●Heart transplant candidates with a positive IGRA or TST ≥5 mm induration should be treated pre-transplant with isoniazid, if tolerated. Candidates from a TB-endemic area with a positive IGRA or TST ≥5 mm induration require treatment with isoniazid only if they have at least one other risk factor (evidence of a recent seroconversion, evidence of old TB lung disease, history of untreated or inadequately treated TB, close contact with a person with TB). Pyridoxine (25 to 50 mg/day) should be given during isoniazid therapy to avoid peripheral neuropathy. (See "Tuberculosis in solid organ transplant candidates and recipients", section on 'Treatment of latent tuberculosis'.)
●Treatment of latent TB infection should be for six to nine months commencing as soon as possible before transplantation and should not interfere with the timing of cardiac transplantation. Patients should continue treatment after transplant to complete a full course of therapy.
Pulmonary embolism — Recent pulmonary embolism with or without infarction should delay transplantation, because secondary infection in the affected lobe may occur postoperatively [52]. Before putting the patient on the transplant list, most centers treat this disorder with systemic anticoagulants for six to eight weeks or until radiographic evidence of resolution is seen.
Advanced obstructive and/or restrictive lung disease is associated with a higher incidence of postoperative lung complications, including infection associated with immunosuppressive therapy and limited prognosis. Objective exclusion criteria include a forced one-second expiratory volume of less than 1 liter, a forced vital capacity of less than 50 percent of predicted, or a forced expiratory volume-to-vital capacity ratio of less than 1.
Tobacco use — Use of tobacco in the six months prior to transplantation has been identified as a risk factor for poor outcome post-transplant. Accordingly, active tobacco use is a relative contraindication to transplant.
Substance use — Patients must be screened for the use and abuse of alcohol, tobacco, and other recreational drugs [2]. Active drug or alcohol abuse should be considered an absolute contraindication for transplantation. Although post-transplant recidivism is a frequent occurrence in patients in "recovery," survival may not be reduced [53].
There is no uniform approach to guide decision making on the use of marijuana pretransplant. If marijuana is used as a prescribed medication, then theoretically this should not contraindicate transplantation. In contrast, recreational use of marijuana is frequently accompanied by the use of other illicit compounds and raises concerns for medical nonadherence post-transplant [2].
Inadequate social support or cognitive-behavioral disability — All cardiac transplant candidates should undergo a complete psychosocial evaluation during the initial screening process [2]. This may identify social and behavioral factors that cause difficulty during the waiting period, convalescence, and long-term postoperative management [54,55]. The patient must understand that full cooperation and compliance are critical to the safe and effective use of immunosuppressive agents.
Frailty — The use of frailty as a potential contraindication to transplantation is under investigation. Frailty is a prognostic indicator, particularly among candidates referred for transplant who are unable to perform cardiopulmonary stress testing. The most commonly used definition is the Fried Criteria, which includes unintentional weight loss (≥10 lbs in the last year), muscle weakness (<20 percent of predicted hand grip strength), fatigue, slow gait speed (>6 sec to walk 5 meters) and low levels of physical activity. If patients have three or more of five symptoms, they are considered frail [56,57]. Sarcopenia is a key element of frailty. The determination as to whether the frailty is potentially reversible is important in guiding selection of advanced therapies [58].
Other — Other relative exclusion criteria for cardiac transplantation include a number of conditions that increase the rate of perioperative complications or interact poorly with immunosuppressive agents such as advanced peripheral vascular disease (that would limit rehabilitation and is not amenable to revascularization), active peptic ulcer disease, cholelithiasis, diverticulosis, advanced hepatic disease (eg, cirrhosis can limit survival and increase perioperative morbidity, particularly if a coagulopathy is present).
ADDITIONAL CONSIDERATIONS
Role of mechanical circulatory support — Mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) may be used in the following three settings (see "Treatment of advanced heart failure with a durable mechanical circulatory support device", section on 'Indications'):
●Potential candidates for transplantation (with a potentially reversible comorbidity) may require MCS as a bridge to deciding whether transplantation is an option. (See 'Approach to evaluating contraindications' above.)
•Potentially reversible or treatable comorbidities include obesity, tobacco use, renal failure, and some cancers.
•In addition, patients with pharmacologically irreversible pulmonary hypertension who are otherwise candidates for transplantation should receive a three- to six-month trial of MCS. (See 'Elevated pulmonary vascular resistance' above.)
●Candidates for cardiac transplantation may require MCS as a bridge to transplantation.
●Patients with refractory heart failure who are not candidates for heart transplantation may be candidates for MCS as destination therapy.
As noted above, given limited experience with MCS in patients with restrictive or hypertrophic cardiomyopathy, MCS use in such patients is limited to selected cases at experienced centers [2]. (See 'Indications for cardiac transplantation' above.)
Use of a LVAD as a mechanical bridge to heart transplantation has grown substantially since its inception in 1990 [59]. LVAD support is offered to transplant candidates who are rapidly deteriorating despite maximal medical therapy, or are developing end-organ damage despite maximal medical therapy or are inotrope dependent with an anticipated long waitlist time, ie, large size blood type O recipients. These categories correspond to the Interagency Registry for Mechanically Assisted Circulatory Support Levels 1 to 3 . Use of the LVAD as a bridge to transplantation requires that LVAD recipients be accepted for cardiac transplantation and thus meet the same inclusion criteria previously detailed. (See 'Indications for transplantation' above and 'Contraindications' above.)
The number of patients treated with mechanical support continues to increase. The 2015 International Society for Heart and Lung Transplantation (ISHLT) registry report indicated that 50 percent of transplant recipients required MCS as a bridge to transplantation [1]. Increased device use has salvaged many transplant candidates but concerns have been raised by reports of decreased post-transplant survival in device-supported patients [60]. Multivariate analysis of data from registry of the ISHLT has shown mechanical support to be associated with increased mortality post-transplant but this analysis includes biventricular support, short-term support, and left ventricular support with long-term devices [1]. Some single-center studies have actually shown improved survival after transplant in patients with device support prior to transplant [61]. For the first time, the 2014 ISHLT registry report did not find an association of worse post-transplant prognosis with the use of continuous flow left ventricular support devices [1].
Vaccination — After evaluation of vaccination history and serologic evidence of protection, heart transplant candidates should receive any indicated vaccinations prior to transplantation. Since live viral vaccination is not recommended following transplantation, live viral vaccinations such as varicella, herpes zoster, mumps measles rubella, and yellow fever should be performed prior to transplantation (suggested >4 weeks prior to transplantation).
The patient’s close contacts including family members and health care workers should receive all routine vaccinations including yearly influenza vaccine.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Heart transplant (The Basics)")
●Beyond the Basics topics (see "Patient education: Heart transplantation (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The process of evaluating potential candidates for cardiac transplantation includes determining if there is an indication for cardiac transplantation, determining if combined organ transplantation is required, identifying and assessing contraindications to cardiac transplantation, and performing an assessment of potential risks and benefits of therapeutic options. The ultimate decision to place a patient on the heart transplant waiting list is made after weighing the potential risks and benefits of treatment options by clinicians at the transplanting center based upon a combination of test data and clinical judgment. (See 'Approach to evaluating potential candidates for cardiac transplantation' above.)
●The following are absolute indications for cardiac transplantation listing; patients with these conditions should be referred for cardiac transplantation evaluation (see 'Indications for cardiac transplantation' above):
•Cardiogenic shock requiring either continuous intravenous inotropic support or circulatory support with an intraaortic balloon pump counterpulsation device or mechanical circulatory support (such as left ventricular assist device) to maintain adequate organ perfusion.
•Persistent New York Heart Association (NYHA) functional class IV heart failure (HF) symptoms refractory to optimal medical and surgical therapy (including use of devices). Patients with refractory class IV HF should be assessed by cardiopulmonary testing as well as by HF prognosis score.
-The following peak oxygen consumption (VO2) thresholds favor listing but are not to be used as sole criteria for listing:
-For patients intolerant of beta blocker therapy, a peak VO2 ≤14 mL/kg/min
-For patients on beta blocker, a peak VO2 ≤12 mL/kg/min
As an alternative: For patients who are young (<50 years old) or women (with or without beta blocker therapy), peak VO2 <50 percent predicted may be used as an alternative criterion.
-The following HF prognosis scores favor listing but are not to be used as sole criteria for listing:
-Seattle Heart Failure Model estimated one-year survival of <80 percent or
-Heart Failure Survival Score in the high/medium risk range
•Intractable or severe anginal symptoms in patients with coronary artery disease not amenable to percutaneous or surgical revascularization including severe transplant coronary artery disease (also known as cardiac allograft vasculopathy). (See "Heart Transplantation: Prevention and treatment of cardiac allograft vasculopathy", section on 'Retransplantation'.)
•Intractable life-threatening arrhythmias unresponsive to medical therapy, catheter ablation, surgery, and/or implantable cardioverter-defibrillator. (See "Electrical storm and incessant ventricular tachycardia".)
•Selected patients with restrictive and hypertrophic cardiomyopathies and NYHA Class III to IV HF as described above, including selected patients with cardiac amyloidosis and patients with refractory HF and non-obstructive hypertrophic cardiomyopathy, as described above. (See 'Indications for cardiac transplantation' above.)
•Congenital heart disease in the following clinical settings [2]:
-NYHA functional class IV HF not amenable to palliative or corrective surgery.
-Severe symptomatic cyanotic heart disease not amenable to palliation. (See "Medical management of cyanotic congenital heart disease in adults".)
-Post-Fontan procedure with refractory HF, persistent protein-losing enteropathy, and/or plastic bronchitis despite optimal medical and surgical therapy. (See "Management of complications in patients with Fontan circulation".)
-Pulmonary hypertension with the potential risk of developing fixed, irreversible elevation of pulmonary vascular resistance (PVR) that could preclude heart transplantation in the future (See "Pulmonary hypertension in adults with congenital heart disease: General management and prognosis", section on 'Introduction'.)
●Patients with both complex intracardiac congenital abnormalities and significant irreversible pulmonary vascular obstructive disease (such as patients with Eisenmenger syndrome with severe symptoms despite advanced therapy) may require heart/lung transplantation. Heart transplantation alone should not be performed in the presence of severe hypoplasia of the central or branch pulmonary arteries or pulmonary veins. (See 'Indications for combined organ transplantation' above and "Heart-lung transplantation in adults", section on 'Indications' and "Pulmonary hypertension in adults with congenital heart disease: Disease-specific management", section on 'Transplantation'.)
●Since the major indication for cardiac transplantation is to improve survival, the ability to estimate prognosis in patients with severe HF is the most important component of the selection process. (See 'Evidence supporting indications' above.)
●Absolute contraindications to cardiac transplantation include systemic illness with a life expectancy <2 years despite heart transplantation, irreversible pulmonary hypertension (with PVR >3 Wood units; although some experts allow selected exceptions) (algorithm 1), clinically severe symptomatic cerebrovascular disease, active substance (drug or alcohol) abuse, multiple demonstrations of inability to comply with drug therapy, and multisystem disease with severe extracardiac organ dysfunction. (See 'Absolute contraindications' above.)
●Relative contraindications include age >70 years old, obesity (ie, body mass index [BMI] >35 kg/m2), diabetes mellitus with poor glycemic control or end organ damage other than nonproliferative retinopathy, acute pulmonary embolism (within six to eight weeks), recent past substance abuse, psychosocial impairment that would jeopardize post-transplant survival, and other conditions that increase the risk of perioperative complications or limit tolerance of immunosuppression. Neoplasm and infection require individualized assessment of severity, treatment options and prognosis. Irreversible renal dysfunction (estimated glomerular filtration rate <30 mL/min/1.73 m2) is a relative contraindication for isolated cardiac transplantation. (See 'Relative contraindications' above.)
●In patients with refractory HF, mechanical circulatory support may be used as a bridge to cardiac transplantation, a bridge to decision on whether to proceed with cardiac transplantation, or as destination therapy for patients who are not candidates for heart transplantation. (See 'Role of mechanical circulatory support' above and "Treatment of advanced heart failure with a durable mechanical circulatory support device", section on 'Indications'.)
