Medical Policy

This document addresses heart transplantation, a therapeutic modality for individuals with end-stage heart disease, characterized by heart failure (also known as cardiac failure or HF) that does not respond to standard, optimal medical or surgical treatments.

Note: Please see TRANS.00026 Heart/Lung Transplantation for additional information.

Medically Necessary:

Heart transplantation is considered medically necessary in carefully selected individuals when the following Adult or Pediatric Clinical Indications criteria (whichever is applicable) and the General Individual Selection criteria below are met.

Adult Clinical Indications* - Adults with end-stage, irreversible, refractory, symptomatic HF requiring maximal continuous medical or mechanical support must have:

1. A low functional status; and
2. A poor probability of survival; and
3. ONE of the following underlying conditions:
   1. Supported by a mechanical circulatory support (MCS) device; or
   2. Supported by an intra-aortic balloon pump (IABP); or
   3. Refractory cardiogenic shock; or
   4. Dependency on intravenous (IV) inotropic support to maintain adequate organ perfusion; or
   5. Severe ischemia consistently limiting routine activity not amenable to bypass surgery or percutaneous coronary intervention (PCI); or
   6. Recurrent unstable ischemia not amenable to bypass surgery or percutaneous coronary intervention (PCI); or
   7. Recurrent symptomatic ventricular arrhythmias refractory to ALL therapeutic modalities; or
   8. Ischemic cardiomyopathy not amenable to medical therapy or revascularization procedures;
      or
4. Cardiopulmonary exercise testing results including any of the following:
   1. Individuals on beta-blocker maximal VO₂ less than or equal to 12 ml/kg/min; or
   2. Individuals off  beta-blocker maximal VO₂ less than or equal to 14 ml/kg/min; or
   3. Individuals with obesity (BMI greater than or equal to 30kg/m²) with a peak VO₂ adjusted for lean body mass less than or equal to 19 ml/kg/min.
5. In heart transplant candidates with a history of malignancy, documentation of consultation with an oncology specialist that confers suitability of the individual for heart transplantation.

Note: Specific guidance is available within the ISHLT guidelines for individuals with a history of malignancy based on consensus statements from the American Society of Transplant Surgeons (ASTS) with detailed recommendations on transplant candidacy for individuals with a history of skin cancer, hematological malignancies, and solid organ malignancies depending on tumor-grade and stage (Peled, 2024).

Pediatric Clinical Indications* - Heart transplant is an accepted treatment option for selected children with end-stage heart disease characterized by intractable symptoms and HF that cannot be treated with conventional medical or surgical methods. Children must have:

1. Low cardiac output; and
2. ONE of the following conditions:
   1. Intractable HF not amenable to medical or surgical interventions; or
   2. Complex congenital heart disease (CHD) not amenable to surgical repair or palliation or for which the surgical procedure carries a higher risk of mortality than transplantation; or
   3. Heart disease with reactive pulmonary hypertension and a potential of developing fixed, irreversible increased pulmonary vascular resistance (PVR) that would preclude a future orthotopic heart  transplantation; or
   4. PVR indexed to body surface area (PVRI) is less than 9 Wood units m² on initial assessment or after treatment with diuretics, inotropic support, vasodilator therapy, or MCS; or
   5. Heart disease associated with near sudden death; or
   6. Life-threatening arrhythmias untreatable with medications or an implantable defibrillator.

*Note: For multi-organ transplant requests, criteria must be met for each organ requested. In those situations, an individual may present with a concurrent medical condition which would be considered an exclusion or a comorbidity that would preclude a successful outcome but would be treated with the other organ transplant. Such cases will be reviewed on an individual basis for coverage determination to assess the member’s candidacy for transplantation.

Heart Retransplantation

Retransplantation in individuals with graft failure of an initial heart transplant, due to either technical reasons or hyperacute rejection is considered medically necessary.

Retransplantation in individuals with chronic rejection, moderate graft vasculopathy or recurrent disease is considered medically necessary when the individual meets general individual selection criteria as defined below.

Investigational and Not Medically Necessary:

A heart transplantation is considered investigational and not medically necessary when the above criteria are not met.

General Individual Selection Criteria

In addition to having end-stage heart disease, the member must not have a contraindication to transplantation, as defined by the American Society of Transplantation (AST) (Steinman, 2001) and the International Society for Heart and Lung Transplantation (ISHLT) (Mehra 2016, Peled 2024) as listed below.

Relative Contraindications for Transplant Recipients include, but are not limited to, the following:

1. Adult heart transplant candidates with pulmonary artery systolic pressure (PASP) greater than or equal to 50 mmHg; and
   1. A trans pulmonary gradient (TPG) greater than or equal to 5 mmHg while maintaining a systolic arterial blood pressure greater than 85 mmHg; or
   2. PVR greater than or equal to 3 Wood units while maintaining a systolic arterial blood pressure greater than 85 mmHg.

Absolute Contraindications for Transplant Recipients include, but are not limited to, the following:

1. Metastatic cancer;
2. Ongoing or recurring infections that are not effectively treated;
3. Serious cardiac or other ongoing insufficiencies that create an inability to tolerate transplant surgery;
4. Serious conditions that are unlikely to be improved by transplantation as life expectancy can be finitely measured;
5. Active, systemic lupus erythematosus or sarcoid with multisystem involvement;
6. Any systemic condition with a high probability of recurrence in the transplanted heart;
7. Demonstrated individual nonadherence, which places the organ at risk by not adhering to medical recommendations;
8. Potential complications from immunosuppressive medications are unacceptable to the individual;
9. Acquired immune deficiency syndrome (AIDS) (diagnosis based on Centers for Disease Control and Prevention [CDC] definition of CD4 count, 200 cells/mm³) unless the following are noted:
   1. CD4 count greater than 200 cells/mm³ for greater than 6 months;
   2. HIV-1 RNA undetectable;
   3. On stable anti-retroviral therapy greater than 3 months;
   4. No other complications from AIDS (for example, opportunistic infection, including aspergillus, tuberculosis, coccidioidomycosis, resistant fungal infections, Kaposi’s sarcoma or other neoplasm);
   5. Meeting all other criteria for heart transplantation.

Heart transplantation is a standard treatment for individuals with refractory end-stage HF that is not amenable to medical or surgical therapies. Heart transplantation has been shown to improve functional status and health-related quality of life.

CHD may be worsened over time with specific anatomic and physiological conditions. Individuals with worsening CHD may be eligible for heart transplantation (Canter, 2007). Conditions associated with worsening CHD include, but are not limited to:

• Severe stenosis or atresia in proximal coronary arteries;
• Moderate to severe stenosis or insufficiency of the atrioventricular or systemic semilunar valve(s);
• Severe ventricular dysfunction;
• Pulmonary hypertension considered to be at potential risk of developing fixed, irreversible elevated PVR that may preclude future orthotopic heart transplant;
• Severe aortic or systemic AV valve insufficiency not amenable to surgical correction;
• Severe arterial oxygen desaturation;
• Persistent protein-losing enteropathy intractable to optimal medical-surgical therapies.

Cardiopulmonary exercise test (CPET) results are routinely used to determine transplant candidacy. Testing is limited to individuals older than 7-8 years of age (Canter, 2007). Maximal VO₂ describes the maximum amount of oxygen used by the body while exerting maximal physical activity. VO₂ is reported per kilogram of body weight per minute. The testing is usually performed on a treadmill or on a cycloergometer. There are different calculators to estimate VO₂ max. Individuals that are physically fit have higher VO₂ max values and can perform more intense exercises. VO₂ max is properly determined by the Fick Equation: VO₂max = Q (CaO₂−CvO₂) where Q is cardiac output, CaO₂ is arterial oxygen content, and CvO₂ is venous oxygen content. The average young untrained natal male will have a VO₂ max of approximately 45 ml/min/kg. The average young untrained natal female will score a VO₂ max of 38 ml/min/kg. These scores can improve with training and generally decrease with age.

Coronary artery vasculopathy (CAV) is a diffuse disease process that results in progressive coronary artery atherosclerosis and is a threat to long-term survival. CAV is the most common cause of complications and death after the first year post-heart transplant. Angiographically confirmed graft vasculopathy results in a poor prognosis. Graft loss or death within 2 years of diagnosis was noted in 24% of individuals with any degree of vasculopathy and 50% of individuals with moderate to severe graft vasculopathy. Canter and colleagues (2007) reported a 2-3% annual risk of death or graft loss, with 70% due to HF resulting from graft vasculopathy, rejection or a combination of both. A pediatric study resulted in similar 3-year survivals of 82% compared with 77% in retransplantations compared to primary transplantations (Canter, 2007). Ongoing clinical studies are focused on preventive therapies to reduce the incidence and severity of CAV (Boucek, 2007; Kobashigawa, 2000; Ross, 2007). There have been various hypotheses and studies to determine the etiology, diagnosis, prevention and treatment of CAV. Despite therapeutic interventions, CAV may result in end-stage HF requiring retransplantation.

Post-transplant morbidity and mortality are frequently caused by right HF. Recommendations by the ISHLT include a pre-transplant vasodilator challenge to be administered if the PVR is greater than 3 Wood units or the TPG is greater than or equal to 15. Despite the lack of absolute cutoff values that would contraindicate transplantation, analyses of the ISHLT registry demonstrated incremental risks as PVR increased. Survival comparison of those with 1-3 Wood units had better outcomes when compared to individuals with a PVR of greater than 5 Wood units. Relative contraindications to heart transplant include PVR greater than 5 Wood units or TPG greater than 16-20 mm Hg or PVR index is greater than 6 (Mehra, 2016).

The previous guidelines for heart transplantation from the ISHLT were developed before the incorporation of β-blocker and device therapies for the treatment of late or end-stage heart disease (Mehra, 2006). Mehra and colleagues (2016) reported early studies showing a significant survival benefit with heart transplantation in adults with a peak VO₂ less than 14 ml/kg/min when compared to individuals who were not considered eligible for transplantation and were maintained on a medical regimen. A subset of individuals with a peak VO₂ less than 10 ml/kg/min who achieved anaerobic threshold had a lower survival rate when compared to individuals with a VO₂ between 10-14 ml/kg/min.

According to Heidenreich and colleagues (2022), the long-term survival of adult transplant recipients between 2011 and 2013 at 1, 3, and 5 years post-transplant is 90.3%, 84.7%, and 79.6%, respectively. Similarly, heart transplantation has been shown to improve functional status and health-related quality of life.

The medical therapies used for adults with heart disease have also been incorporated into the pediatric population. In addition, there have been significant improvements in overall survival for staged palliative surgeries for left hypoplastic heart disease. Therefore, the heart transplant listing criteria for adults and pediatrics were re-evaluated.

The ISHLT published updated Guidelines for the Evaluation and Care of Cardiac Transplant Candidates in 2024. This update replaced previous documents (Listing Criteria for Heart Transplantation: ISHLT Guidelines for the Care of Cardiac Transplant Candidates 2006, and 2016 ISHLT Listing Criteria for Heart Transplantation: A 10-year Update). The 2024 ISHLT Guidelines highlight that clinical signs or symptoms of advanced HF predict a worse prognosis, therefore, recognition of these clinical indicators should prompt referral and evaluation for heart transplantation (Peled, 2024). **See Background section.

Key takeaways from the 2024 guidelines include:

• In the assessment of heart transplant candidacy, the document focuses on an individualized approach rather than absolute thresholds contraindicating eligibility, specifically for parameters including age and obesity as well as conditions such as cancer, vascular disease, kidney disease, liver disease, and connective tissue diseases.
• With the changing landscape of candidates’ characteristics, particular attention is devoted to assessment of candidacy in individuals with amyloidosis and CHD, as well as to issues of retransplantation. Systematic candidate evaluation should assess the severity and natural history of extra cardiac involvement with a particular focus on the downstream effects of malnutrition and frailty. Retransplantation for CAV, or in highly sensitized individuals with end-organ damage, requires careful planning and emphasis on shared decision-making with individuals and their families.
• A history of malignancy is common in individuals undergoing evaluation for heart transplantation confers a higher risk for post-transplant malignancies. The incidence of de novo malignancy post-transplant in the recent era is also increasing. The document provides extensive recommendations regarding the timing of heart transplantation in individuals with a history or presence of malignancy (skin cancer, hematological, and solid organ malignancies) based on tumor grade and stage at diagnosis, the time from treatment, and cancer screening surveillance.
• The psychosocial evaluation of  heart transplantation candidates is a key component of the multifaceted pre-transplant screening process, aimed at identifying those candidates at increased risk for poor post-transplant outcomes due to inadequate support, substance use, adherence, or optimal mental health. In particular, the evaluation of pediatric candidates warrants careful assessment of cultural considerations, the impact of intellectual and developmental disabilities, and parental refusal of vaccination.
• Given the complexity of the medical and psychosocial issues faced by heart transplantation candidates, a multidisciplinary approach is paramount, including but not limited to a HF cardiologist, cardiac surgeon, transplant nurse coordinator, transplant infectious diseases specialist, transplant pharmacist, immunologist, mental health expert, social worker, registered dietician, physical therapist, occupational therapist, and palliative care specialist, with other specialists included based on the individual’s specific needs. For pediatric heart transplantation candidates, additional specialists may be required, including those with expertise in assessing capacity to assent; child-life specialists to optimize education and participation of the pediatric individual and family in the transplant process; and mental health experts with specific expertise in pediatric mental health.
• Maximally tolerated doses of guideline-directed medical therapy (GDMT) should be maintained while individuals await heart transplantation. For individuals on anticoagulant and/or antiplatelet therapy, a plan for perioperative management should be established at the time of heart transplant listing. For those with worsening HF, optimal support with inotropes and MCS should be considered before the onset of significant end-organ dysfunction. It is also important to consider percutaneous interventional procedures and devices for monitoring [e.g., pulmonary artery pressure monitor] and management [e.g., implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy, transcatheter edge-to-edge repair, transcatheter valve replacement, arrhythmia ablation] in individuals meeting appropriate indications.
• For individuals who are awaiting heart transplantation, it is recommended to continue evaluations at appropriate intervals. These evaluations should include noninvasive testing [cardiopulmonary exercise test, renal and liver function, panel-reactive antibody and ABO titers, biomarker assessment, imaging for malignancy surveillance], invasive testing (hemodynamic assessment), assessment of nutritional and frailty statuses, psychosocial evaluation, and malignancy screening. It is also important to provide recommended vaccinations during the waitlist period. For individuals who are improving, discussion around removal from the list to continue medical therapy may be appropriate for heart transplant candidates who are improving.
• Guideline-directed medical therapy (GDMT) should be maintained while individuals await heart transplantation. For individuals on anticoagulant and/or antiplatelet therapy, a plan for perioperative management should be established at the time of heart transplant listing. For those with worsening HF, optimal support with inotropes and mechanical circulatory support should be considered before the onset of significant end-organ dysfunction. Discussions around care escalation (inotropic support/MCS) or de-escalation may be appropriate for those who are worsening.
• The heart transplant team should establish a preoperative plan focusing on pharmacological therapy adjustment at the time of transplant. This pharmacy management plan should address when to stop select HF medications to avoid vasoplegia, when to reverse anticoagulation, when to initiate antibiotic treatment for methicillin-resistant Staphylococcus aureus (MRSA) colonization, ventricular assist device infections, and antiviral treatment for possible exposure to hepatitis B virus, hepatitis C virus, coronavirus disease 2019 (COVID-19).
• Durable MCS is a useful bridging strategy for transplant-eligible individuals refractory to optimal medical therapy, avoiding further end-organ injury, improving quality of life, and prolonging survival. Given the availability of reliable and lower-risk left ventricular assist devices (LVADs) for clinical use, it is essential to revisit the indications for bridge-to-transplantation LVAD therapy and the optimal timing for MCS support. In individuals with durable MCS, candidacy for heart transplantation must be assessed longitudinally during follow-up regardless of the intended initial strategy. Preoperative planning is vital to ensure successful heart transplantation in this population.
• In transplant candidates supported by MCS, the occurrence of a life-threatening complication refractory to conventional medical or surgical treatment warrants evaluation for urgent heart transplantation. Individuals with severe sepsis secondary to a device-related or device-specific infection should not be transplanted until end-organ functions recover and the sepsis is controlled. The presence of an irreversible clinical condition that might impair post-transplantation survival (e.g., disabling stroke) in individuals supported by MCS should preclude heart transplantation. For individuals in cardiogenic shock refractory to medical therapy, support with temporary MCS is a viable bridging strategy for urgent heart transplantation.

The 2024 ISHLT Guideline provides the following recommendations for heart transplantation.

1. In individuals with HF, when consistent with the individual’s goals of care, the presence of clinical indicators of advanced HF (AvdHF) should trigger evaluation for AdvHF therapies, including heart transplantation. Strong recommendation- Level of evidence: B-NR (Nonrandomized).
2. In ambulatory adult HF individuals referred for transplant evaluation (and pediatric patients when age-appropriate), CPET should routinely be performed to quantify exertional intolerance, inform HF prognosis, and guide transplant listing. Strong recommendation- Level of evidence: B-NR (Nonrandomized).
3. In adult HF individuals evaluated for transplantation, right heart catheterization (RHC) should be performed prior to listing to assess for potentially prohibitive PH and for cardiogenic shock requiring inotropic support and/or temporary MCS. Strong recommendation- Level of evidence: C-LD (limited data).
4. In pediatric heart transplant candidates, RHC may be performed prior to listing. Weak: C-EO (consensus of expert opinion based on clinical experience).
5. In adult heart transplant candidates, HF prognosis scores can be considered in the context of other data collected during transplant evaluation to guide listing decisions. Moderate: Level of evidence: C-LD (limited data).

Additionally, all heart transplantation candidates should be screened for solid organ tumors as recommended for the general population (Peled, 2024).

For heart transplant candidates with established GFR less than 30 ml/min/1.73 m², evaluation for simultaneous heart-kidney transplantation is recommended. In heart transplant candidates with established GFR of 30–44 ml/min/1.73 m² and evidence of chronic kidney disease, such as small kidney size or persistent proteinuria greater than 0.5 g/day in the presence of stable hemodynamics, evaluation for simultaneous heart-kidney transplantation is reasonable (Peled, 2024).

Heart transplants involve the removal of either all or part of a cadaver heart and its implantation into a recipient. There are two types of cardiac transplant: orthotopic and heterotopic. Orthotopic transplant is the more common of the two methods and involves replacing the recipient heart with the donor heart implanting the ventricles of the donor heart onto the right atria and main arteries of the recipient’s heart. Heterotopic transplants involve placing the entire donor heart into the chest cavity and surgically attaching it to the recipient’s entire heart.

In contrast to the 1980s when the majority of heart transplant recipients were sick but stable individuals waiting at home, the majority of heart transplant recipients are now hospitalized Status 1A or 1B individuals at the time of transplant. This shift has occurred due to the increasing demand on the scarce resource of donor organs resulting in an increased waiting time for donor organs. Individuals initially listed as a Status 2 candidate may deteriorate to a Status 1A or 1B candidate before a donor organ becomes available. At the same time, medical therapy of HF has improved (particularly with the advent of ACE inhibitors), making it imperative that heart transplantation be limited to those individuals who have truly exhausted medical therapy and thus are likely to derive the maximum benefit from heart transplantation. Consequently, there has been a search to identify prognostic criteria that could identify such individuals.

As noted in the American College of Cardiology (ACC) criteria (Hunt, 2009), the VO₂ max serves as a critical objective criterion. The VO₂ max, measured during maximal exercise, reflects the functional reserve of the heart. Studies have suggested that transplantation can be safely deferred in those individuals with a VO₂ max of greater than 14 ml/kg/min. The importance of the VO₂ max has also been emphasized by an American Heart Association (AHA) Scientific Statement addressing heart transplant candidacy (Costanzo, 1995; Mudge, 1995). In past years, a left ventricular ejection fraction of less than 20% or a NYHA Class III or IV status may have been used to determine transplant candidacy. However, as indicated by the ACC criteria, these measurements are no longer considered adequate to identify transplant candidates. These measurements may be used to identify individuals for further cardiovascular workup but should not be the sole criteria for transplant.

The limiting factor for heart transplantation is the short supply of donor organs. The procurement and distribution of heart organs for transplantation in the U.S. is under the direction of United Network for Organ Sharing (UNOS). A national database of transplant candidates, donors, recipients, and donor-recipient matching and histocompatibility is maintained by UNOS. The careful selection of candidates utilizing specific selection criteria has steadily improved the survival rates for those that have undergone heart transplantation. The best available evidence, collected from retrospective registry data on heart transplantation in the United States, is based on UNOS data collected from 2008-2019 which reports 1-year, 3-year and 5-year survival data (90.9%, 87.6%, 77.3%). The number of heart transplant candidates and heart transplants performed in the United States continues to rise annually, with 3552 heart transplants performed in 2019 (Colvin, 2021). Heart transplants are currently the third most common transplant procedure.

In 2021, the ASTS Statement Concerning Eligibility for Solid Organ Transplant Candidacy noted:

The ASTS advocates transplanting as many of these patients, as quickly as possible, while also making the most responsible use of our nation’s organ supply. Limiting a transplanted organ’s life expectancy due to placing it with a patient, or in a situation, in which it cannot be adequately supported can deprive another waitlisted patient of a better outcome with the same organ.

To this end, we feel that any medically eligible patient, with sufficient support in place to allow for their adequate care following surgery, should be supported in their pursuit of transplantation.

When a patient presents to a transplant center for evaluation, the center makes a judgement concerning the patient’s medical fitness to undergo the procedure, and also the patient’s expected ability to capably care for themselves and a new organ.

If the patient has cognitive, physical, or financial limitations that would preclude them from being able to adequately care for themselves, then appropriate social supports or other compensatory mechanisms which would remediate the situation should be identified. If these can be found, then the patient’s candidacy for transplantation should be supported. If, however, they cannot be identified, proceeding with transplantation could threaten both the patient’s health and safety, and the longevity of a donated organ. In such a case, further evaluation should be deferred until the limiting issue can be corrected.

As such it is the recommendation of the ASTS that no patient will be discriminated against or precluded from transplant listing solely due to the presence of a disability or handicap whether physical or psychological. However, if these disabilities lead to a clinical reality where the patient will suffer a great risk of morbidity or mortality from the transplant surgery itself, or the subsequent placement on lifelong immunosuppression, then transplantation would not be recommended. This decision would be made due to the clinical risk benefit analysis for the specific patient, and not on any external factors.

In 2022, the ACC)/AHA/Heart Failure Society of America (HFSA) published guidelines for the management of HF which replaced the 2013 ACC/AHA guidelines for the management of HF and the 2017 ACC/AHA/HFSA focused update of the 2013 guidelines (Heidenreich, 2022). In the 2022 guidelines the committee provided a category 1c recommendation for heart transplant to improve survival and quality of life in eligible individuals with advanced stage D HF refractory to GDMT, device, and surgical management. Heart transplantation provides a mortality and morbidity benefit to selected individuals with stage D HF.

The 2022 Organ Procurement Transplant Network (OPTN)/ Scientific Registry of Transplant Recipients reported that since 2011, pediatric heart transplants have increased 31.7% to 494 and adult heart transplants have increased 85.8% to 3,668 in 2022. The numbers of new candidates for pediatric and adult heart transplants have also increased, with 703 new pediatric candidates and 4,446 new adult candidates in 2022. Adult heart transplantation increased to 122.5 transplants per 100 patient-years in 2022; however, the pediatric heart transplantation rate decreased to its lowest rate in the past decade, 104.2 transplants per 100 patient-years. Since 2011, post-transplant mortality has been stable to slightly better; among recipients who underwent transplant in 2015-2017, the 1-, 3-, and 5-year pediatric survival rates were 93.7%, 89.2%, and 85.0%, respectively, and the adult survival rates were 91.3%, 85.7%, and 80.4%. In 2022, 4,446 new adult heart candidates were added to the heart transplant waiting list; a total of 7,519 candidates aged 18 years and older (Colvin, and colleagues 2023).

A policy for allocation of heart and heart-lung organs prioritizes donor heart organs according to the principles of medical urgency. In March 2023, the OPTN changed the policy to expand the eligibility to pediatric heart status 1A and B candidates, who are registered on the waiting list prior to turning age 2, to accept incompatible blood type (ABOi) donors (UNOS, 2023).

In recent years, the discussion of heart transplantation as a treatment for cardiomyopathy caused by amyloidosis has garnered interest. Cardiac amyloidosis causes restrictive cardiomyopathy, progressive HF, and death. Heart transplantation outcomes have been poorer in individuals with cardiac amyloidosis due to the systemic nature of the condition. Suppressive therapies for light chain amyloidosis (AL) may improve outcomes.

Barrett and colleagues (2020) reported a retrospective, single center study of heart transplantation outcomes in 31 individuals with cardiac amyloidosis (13 with AL, and 18 with transthyretin [ATTR] amyloidosis). Screening included evaluation for extracardiac amyloidosis with organ specific biopsies, and extracardiac amyloid deposits constituted an absolute contraindication. In individuals with vascular or mucosal amyloid positive gastrointestinal biopsy, transplantation candidacy was evaluated by clinical symptoms. Individuals were considered for transplantation if there was no evidence of dysmotility, bleeding, or malabsorption. Pre-transplantation response to light chain reducing therapies in AL amyloidosis was not an absolute requirement for transplantation. Post-transplantation immunosuppression regimens were followed. Autologous stem cell transplants were performed in select participants with AL amyloidosis once they achieved clinical stability following the transplant, but no sooner than 6 months post-heart transplantation. The results demonstrated that post-transplantation outcomes were similar between the AL and ATTR groups, including post-transplantation infection and organ rejection. Two participants had difficulty with post-transplantation hemostasis, and 5 developed post-transplantation renal dysfunction that required renal replacement therapy. One participant with gastrointestinal amyloid deposits developed a post-operative ileus, which resolved. Of the 2 participants with renal amyloidosis, 1 developed progressive renal dysfunction that required dialysis 7 years after transplantation. There were 4 deaths after transplantation, but none were determined to be due to amyloidosis or amyloidosis therapy complications. There were no differences in mortality between the 31 participants and 599 individuals without amyloidosis who underwent heart transplantation for all other indications at the same facility. The authors concluded that in carefully selected individuals with AL and ATTR cardiac amyloidosis, the results were similar in both post-transplantation outcomes and survival compared to individuals without amyloidosis who received transplantation for all other conditions. These results are promising; however, the study was limited by its small size and single center transplant practices. Treatment practices and transplant eligibility policies can vary between institutions and could lead to different results, therefore larger studies are needed to confirm the outcomes.

In 2023, the ACC published the “Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient with Cardiac Amyloidosis.” The consensus supports heart transplant in some individuals with cardiac amyloidosis: 

In select patients with ATTR-CM and AL-CM with advanced/stage D HF, heart transplantation may be an option, and the current adult donor allocation system provides priority as Status 4 to amyloid CM, given the lack of durable (MCS) support options. The traditional signs of advanced HF apply in patients with cardiac amyloidosis and should be recognized as triggers for a discussion of prognosis and advanced HF therapies that incorporates the patient’s goals, values, and preferences.

In 2024 the AHA, ACC, American Medical Society for Sports Medicine, Heart Rhythm Society, Pediatric and Electrophysiology Society and the Society for Cardiovascular Magnetic Resonance published updated Guidelines for the Management of Hypertrophic Cardiomyopathy (Ommen, 2024). The update states:

In patients with nonobstructive HCM and advanced HF (NYHA functional class III to class IV despite GDMT), CPET should be performed to quantify the degree of functional limitation and aid in selection of patients for heart transplantation or MCS.

In patients with nonobstructive HCM and advanced HF (NYHA functional class III to class IV despite GDMT) or with life-threatening ventricular arrhythmias refractory to maximal GDMT, assessment for heart transplantation in accordance with current listing criteria is recommended.

In patients with nonobstructive HCM and advanced HF (NYHA functional class III to class IV despite GDMT) who are candidates for heart transplant, continuous-flow LVAD therapy is reasonable as a bridge to heart transplantation.

In patients with HCM and recurrent, poorly tolerated life-threatening ventricular tachyarrhythmias refractory to maximal antiarrhythmic drug therapy and ablation, heart transplantation is indicated in accordance with current listing criteria.

The ACC acknowledges that no single test can identify which individuals may be candidates for advanced HF therapies; multiple factors including the history, physical examination, laboratory testing, and imaging studies must be considered together to identify those at greatest risk of future decompensation and those who will derive the greatest benefit.

The 2024 ISHLT guideline identifies pulmonary hypertension as a potential contraindication to heart transplantation. The recommendations state:

In adult heart transplant candidates with pulmonary artery systolic pressure (PASP) ≥ 50 mmHg and either a TPG ≥ 15 mmHg or PVR ≥ 3 Wood units while maintaining a systolic arterial blood pressure > 85 mmHg, the following stepwise evaluation is recommended to assess transplant candidacy:
1) An acute vasodilator challenge to assess for reversibility of PH (Class 1);
2) Hospitalization with continuous hemodynamic monitoring as often the PVR will decline after 24 to 48 hours of treatment consisting of diuretics, inotropic support, and vasodilators (Class I); and
3) Temporary or durable MCS for unloading of the left ventricle (Class 2a).
Condition of recommendation: Strong, Level of evidence: Level C-D (limited data).

In pediatric heart transplant candidates, heart transplantation is reasonable if PVR indexed to body surface area (PVRI) is less than 9 Wood units m2 on initial assessment or after treatment with diuretics, inotropic support, vasodilator therapy, or MCS.
Condition of recommendation: Moderate, Level of evidence: Level B-NR (Nonrandomized).

** The ISHLT 2024 Guidelines for the Evaluation and Care of Cardiac Transplant Candidates notes that the presence of one or more clinical signs or symptoms of advanced HF is associated with a worse prognosis, recognition of these clinical indicators should prompt referral and evaluation for heart transplantation. The mnemonic “I NEED HELP” encapsulates clinical clues for all proven risk factors that increase all-cause mortality in HF.

I: Inotropes- Previous or ongoing requirement for dobutamine, milrinone, dopamine, or levosimendan
N: NYHA class/Natriuretic peptides- Persisting NYHA class III or IV and/or persistently high BNP or NT-pro-BNP E: End-organ dysfunction -Worsening renal or liver dysfunction in the setting of HF
E: Ejection fraction -Very low LVEF < 20%
D: Defibrillator shocks - Recurrent appropriate defibrillator shocks
H: Hospitalizations - More than 1 hospitalization with HF in the last 12 months
E: Edema/Escalating diuretics - Persisting fluid overload and/or increasing diuretic requirement
L: Low blood pressure - Consistently low blood pressure with systolic < 90-100 mm Hg
P: Prognostic medication - Inability to up-titrate (or need to decrease/cease) GDMP.

End-stage heart failure: In people with HF, the body does not receive an adequate supply of oxygen. As a result, they can feel weak, fatigued or short of breath resulting in limited functional capacity. Everyday activities such as walking, climbing stairs, carrying groceries and yard work can become quite difficult. In end-stage HF, the heart is so weakened the individual will die without a heart transplant.

Heart transplant: Removal of an individual's heart and replacing it with a donor heart.

Mechanical circulatory support device (MCSD): An implanted ventricular assist device or percutaneous ventricular assist device.

New York Heart Association (NYHA) definitions:

The NYHA classification of HF is a tiered system that categorizes individuals based on subjective impression of the degree of functional compromise; the class III and IV NYHA functional classes are as follows:

• Class III. Individuals with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea (difficulty breathing) or anginal (chest) pain.
• Class IV. Individuals with cardiac disease resulting in the inability to carry on any physical activity without discomfort. Symptoms of HF or the anginal (chest) syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
• Wood unit: A measure of pulmonary vascular resistance (PVR) expressed in mmHg/L/min where mmHg = (mean pulmonary artery pressure – capillary wedge pressure) and L/min = cardiac output. Normal PVR values are 0.5 – 1.1. Named for the Australian cardiologist Paul Wood.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Barrett CD, Alexander KM, Zhao H, et al. Outcomes in patients with cardiac amyloidosis undergoing heart transplantation. JACC Heart Fail. 2020; 8(6):461-468.
2. Bauer J, Thul J, Kramer U, et al. Heart transplantation in children and infants: short-term outcome and long-term follow-up. Pediatr Transplant. 2001; 5(6):457-462.
3. Boucek MM, Waltz DA, Edwards LB, et al. International Society for Heart and Lung Transplantation. Registry of the International Society for Heart and Lung Transplantation: ninth official pediatric heart transplantation report--2006. J Heart Lung Transplant. 2006; 25(8):893-903.
4. Canter CE, Shaddy RE, Bernstein D, et al. Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007; 115(5):658-676.
5. Costanzo MR, Augustine S, Bourge R, et al. Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association. Circulation. 1995; 92(12):3593-3612.
6. Dearani GA, Razzouk AJ, Gundry SR, et al. Pediatric cardiac retransplantation: intermediate-term results. Ann Thorac Surg. 2001; 71(1):66-70.
7. Dellgren G, Koirala B, Sakopoulus A, et al. Pediatric heart transplantation: improving results in high-risk patients. J Thorac Cardiovasc Surg. 2001; 121(4):782-791.
8. Gandhi SK, Canter CE, Kulikowska A, Huddleston CB. Infant heart transplantation ten years later – where are they now? Ann Thorac Surg. 2007; 83(1):169-171.
9. Gronda E, Bourge RC, Costanzo MR, et al. Heart rhythm considerations in heart transplant candidates and considerations for ventricular assist devices: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates – 2006. J Heart Lung Transplant. 2006; 25(9):1043-1056.
10. Hosenpud JD, Pamidi SR, Fiol BS, et al. Outcomes in patients who are hepatitis B surface antigen-positive before transplantation: an analysis and study using the joint ISHLT/UNOS thoracic registry. J Heart Lung Transplant. 2000; 19(8):781-785.
11. Jessup M, Banner N, Brozena S, et al. Optimal pharmacologic and non-pharmacologic management of cardiac transplant candidates: approaches to be considered prior to transplant evaluation: International Society for Heart and Lung Transplantation Guidelines for the care of cardiac transplant candidates – 2006. J Heart Lung Transplant. 2006; 25(9):1003-1023.
12. Kobashigawa, J. What is the optimal prophylaxis treatment of cardiac allograft vasculopathy? Curr Control Trials Cardiovasc Med. 2000; 1(3):166-171.
13. Mudge GH, Goldstein S, Addonizio LJ, et al. 24th Bethesda Conference: Cardiac transplantation. Task Force 3: Recipient guidelines/prioritization. J Am Coll Cardiol. 1993; 22(1):21-31.
14. Rosenthal D, Chrisant MR, Edens E, et al. International Society for Heart and Lung Transplantation: Practice guidelines for management of heart failure in children. J Heart Lung Transplant. 2004; 23(12):1313-1333.
15. Ross M, Kouretas P, Gamberg P, et al. Ten- and 20-year survivors of pediatric orthotopic heart transplantation. J Heart Lung Transplant. 2006; 25(3):261-270.
16. Srivastava R, Keck BM, Bennett LE, Hosenpud JD. The results of cardiac retransplantation: an analysis of the Joint International Society for Heart and Lung Transplantation/United Network for Organ Sharing Thoracic Registry. Transplantation. 2000; 70(4):606-612.
17. Steinman TI, Becker BN, Frost AE, et al. Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation. 2001; 71(9):1189-1204.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Society of Transplant Surgeons. ASTS Statement Concerning Eligibility for Solid Organ Transplant Candidacy. Available at: https://www.asts.org/docs/default-source/position-statements/asts-statement-concerning-eligibility-for-solid-organ-transplant-candidacy.pdf?sfvrsn=1a6b4ed3_3. Accessed on September 24, 2024.
2. Centers for Medicare and Medicaid Services. National Coverage Determination for Heart Transplants. NCD #260.9. Effective May 1, 2008. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=112&ncdver=3&DocID=260.9&SearchType=Advanced&bc=IAAAABAAAAAA&. Accessed on August 23, 2024.
3. Dew MA, DiMartini AF, Dobbels F, et al. ISHLT Consensus. The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support. J Heart Lung Transplant. 2018; 37(7):803-823.
4. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Amer Coll Cardiol. 2022; 79(17): e263-e403.
5. Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
6. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023; 81:1076-1126.
7. Lorts A, Conway J, Schweiger M, et al. ISHLT consensus statement for the selection and management of pediatric and congenital heart disease patients on ventricular assist devices. Endorsed by the American Heart Association. J Heart Lung Transplant. 2021; 40(8):709-732.
8. Medicare/HCFA. Heart Transplants. Medicare Medical Policy Guidelines. 1999;2.
9. Mehra MR, Canter CE, Hannan MM, et al.; International Society for Heart Lung Transplantation (ISHLT) Infectious Diseases Council; International Society for Heart Lung Transplantation (ISHLT) Pediatric Transplantation Council; International Society for Heart Lung Transplantation (ISHLT) Heart Failure and Transplantation Council. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. J Heart Lung Transplant. 2016; 35(1):1-23. Available at: http://www.jhltonline.org/article/S1053-2498(15)01484-9/pdf. Accessed on September 18, 2023.
10. Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates – 2006. J of Heart and Lung Transplantation. 2006; 25(9):1024-1042. Available at: http://www.jhltonline.org/article/S1053-2498(06)00460-8/fulltext. Accessed on August 23, 2024.
11. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2024; 149(23): e1239-e1311. Available at: 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines | Circulation (ahajournals.org). Accessed on August 23, 2024.
12. Peled Y, Ducharme A, Kittleson M, et al. International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024. J Heart Lung Transplant. 2024; 43(10):1529-1628.e54.
13. Steinman TL, Becker BN, Frost AE, et al. Clinical Practice Committee, American Society of Transplantation. Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation. 2001; 71(9):1189-1204.
14. United Network for Organ Sharing (UNOS). Policy 6 Organ Distribution: Allocation of Hearts and Heart-Lungs. Updated September 14, 2023. Available at: optn_policies.pdf (hrsa.gov)Accessed on September August 23, 2024.
15. United Network for Organ Sharing. Expanded Intended Incompatible Blood Type Eligibility to All Pediatric Status 1A and 1B Heart and Heart-Lung Candidates. Available at: https://optn.transplant.hrsa.gov/media/dt1nv0op/policy-notice-modify-heart-policy-for-aboi.pdf. Accessed on August 23,  2024.
16. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 128: e240-e327.

1. American Heart Association. Available at: https://www.heart.org/en/health-topics. Accessed on August 23, 2024.
2. National Heart, lung, And Blood Institute. Heart transplantation. Last updated March 24, 2022. Available at: https://www.nhlbi.nih.gov/health-topics/heart-transplant. Accessed on August 23, 2024.
3. Scientific Registry of Transplant Recipients. Available at: Heart (hrsa.gov). Accessed on August 23, 2024.

Heart Transplantation
Human Heart Transplantation
Transplantation, Human Heart