Heart transplantation is an option for patients who have any of the following and who remain at risk of death and have intolerable symptoms despite optimal use of medications and medical devices:
End-stage heart failure
Hypertrophic cardiomyopathy or other cardiomyopathy
Transplantation may also be indicated for patients who:
Cannot be weaned from temporary cardiac-assist devices after myocardial infarction or nontransplant cardiac surgery
Have cardiac sequelae of a lung disorder requiring lung transplantation
Absolute contraindications for heart transplantation are (1):
Severe pulmonary hypertension that does not respond to preoperative treatments (although heart-lung transplant may be an option)
Anatomic incompatibility of the central pulmonary artery or pulmonary veins (although heart-lung transplant may be an option)
Excessive alcohol use and poor medication adherence
Relative contraindications include (1):
Age > 70 years
Obesity
Life-limiting systemic disease: cancer; diabetes; pulmonary, kidney, cerebrovascular disease
Local or systemic infiltrative disorders (eg, cardiac sarcoma, amyloidosis)
General contraindications to transplantation (eg, active cancer, uncontrolled systemic infection, active substance use disorder, nonadherence to therapy, limited life-expectancy for reasons unrelated to the transplant) should also be considered.
All donated hearts come from brain-dead donors, who are usually required to be < 70 years and have normal cardiac and pulmonary function and no history of coronary artery disease or other heart disorders. Donor and recipient must have compatible ABO blood type and heart size. Pretransplant waitlist mortality was 8.5 deaths per 100 person-years in the United States in 2023 (2).
(See also Overview of Transplantation.)
Bridge and destination ventricular assist devices (VADs)
Left ventricular assist devices and artificial hearts provide interim hemodynamic support for patients waiting for a transplant (bridge-to-transplantation). In addition, ventricular assist devices are used to treat some patients who are not candidates for transplantation (destination therapy). Infection, which may originate at the skin insertion site of the drive lines, is a concern. Other risks include right heart failure (acute or chronic), sepsis, device failure, and thromboembolism. Despite the risks, there are patients who have survived and have been well for several years after these devices were implanted.
General references
1. 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. doi:10.1016/j.healun.2024.05.010
2. Colvin MM, Smith JM, Ahn YS, et al. OPTN/SRTR 2023 Annual Data Report: Heart. Am J Transplant. 2025;25(2S1):S329-S421. doi:10.1016/j.ajt.2025.01.024
Procedure for Heart Transplantation
Donor hearts are preserved by hypothermic storage. They must be transplanted within 4 to 6 hours. Ex situ heart perfusion, an in vitro pump system that perfuses the explanted donor heart with the goal of improving graft survival, and potentially prolonging transplant viability > 4 to 6 hours is in early use and development (1). These systems have also allowed the use of cardiac grafts retrieved from donors after cardiac arrest.
The recipient is placed on a bypass pump, and the recipient's heart is removed, preserving the posterior right atrial wall in situ. The donor heart is then transplanted orthotopically (in its normal position) with aortic, pulmonary artery, and pulmonary vein anastomoses; a single anastomosis joins the retained posterior atrial wall to that of the donor organ.
Immunosuppressive regimens vary but usually include anti-IL-2 receptor monoclonal antibodies, a calcineurin inhibitor, and glucocorticoids (see table Immunosuppressants Used to Treat Transplant Rejection).
Procedure reference
1. Wang L, MacGowan GA, Ali S, Dark JH. Ex situ heart perfusion: The past, the present, and the future. J Heart Lung Transplant. 2021;40(1):69-86. doi:10.1016/j.healun.2020.10.004
Complications of Heart Transplantation
(See also Posttransplantation Complications.)
Rejection
Incidence of acute rejection peaks at 1 month, decreases over the next 5 months, and levels off by 1 year. Approximately 15% of adult heart transplant recipients have an episode of rejection within the first year after transplant (1). Many patients are asymptomatic, but some develop left ventricle dysfunction or atrial arrhythmias.
Because graft damage can be irreversible and catastrophic, surveillance endomyocardial biopsy is usually done once per year; degree and distribution of mononuclear cell infiltrate and presence of myocyte injury in specimens are determined. Differential diagnosis includes perioperative ischemia, cytomegalovirus infection, and idiopathic B-cell infiltration (Quilty lesions).
Clinical manifestations of rejection can be classified according to onset, duration (see table Manifestations of Heart Transplant Rejection by Category). Histologic classification of rejection is graded from 1 to 4. Mild rejection (grade 1) without detectable clinical sequelae requires no treatment; moderate or severe rejection (grades 2 to 4) or mild rejection with clinical sequelae is treated with glucocorticoid pulses (eg, methylprednisolone) and antithymocyte globulin as needed. The grading scale for rejection reflects progressive degrees of abnormality on histologic examination of biopsy specimens.). Histologic classification of rejection is graded from 1 to 4. Mild rejection (grade 1) without detectable clinical sequelae requires no treatment; moderate or severe rejection (grades 2 to 4) or mild rejection with clinical sequelae is treated with glucocorticoid pulses (eg, methylprednisolone) and antithymocyte globulin as needed. The grading scale for rejection reflects progressive degrees of abnormality on histologic examination of biopsy specimens.
Manifestations of Heart Transplant Rejection by Category*
Rejection Category | Manifestations |
|---|---|
Hyperacute | Cardiogenic shock |
Accelerated | Atrial arrhythmia, cardiogenic shock |
Acute | Heart failure, atrial arrhythmia |
Chronic | Dyspnea during exertion, low stress tolerance |
* Most patients with heart transplant rejection are asymptomatic. | |
Cardiac allograft vasculopathy
The main long-term complication of heart transplantation is cardiac allograft vasculopathy, a form of atherosclerosis that diffusely narrows or obliterates vessel lumina. Approximately 30% of adult heart transplant patients develop some degree of cardiac allograft vasculopathy within 5 years of transplantation (2). Its cause is probably multifactorial and relates to donor age, cold and reperfusion ischemia, dyslipidemia, immunosuppressants, chronic rejection, and viral infection (adenovirus in children, cytomegalovirus in adults).
For early detection, surveillance stress testing or coronary angiography with or without intravascular ultrasound is often done at the time of endomyocardial biopsy.
Treatment is aggressive lipid lowering with statins and control of hypertension with calcium channel blockers or other agents (2).
Complications references
1. 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 [published correction appears in J Am Coll Cardiol. 2023 Apr 18;81(15):1551. doi: 10.1016/j.jacc.2023.03.002]. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012
2. Mallah SI, Atallah B, Moustafa F, et al. Evidence-based pharmacotherapy for prevention and management of cardiac allograft vasculopathy. Prog Cardiovasc Dis. 2020;63(3):194-209. doi:10.1016/j.pcad.2020.03.007
Prognosis for Heart Transplantation
Survival rates at 1 year after heart transplantation are estimated at approximately 90%; they are approximately 80% at 5 years (1).
Within 1 year, death most often results from acute rejection or infection; after 1 year, death most often results from cardiac allograft vasculopathy or a lymphoproliferative disorder.
Functional status of heart transplant recipients alive at > 1 year is excellent; exercise capacity remains below normal but is sufficient for daily activities and may increase over time with sympathetic reinnervation. More than 90% of patients reach New York Heart Association class I cardiac status, and the majority return to employment by 1 year after transplant (2, 3).
Prognosis references
1. 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 [published correction appears in J Am Coll Cardiol. 2023 Apr 18;81(15):1551. doi: 10.1016/j.jacc.2023.03.002]. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012
2. Cramer CL, Marsh K, Krebs ED, et al. Long term employment following heart transplantation in the United States. J Heart Lung Transplant. 2023;42(7):880-887. doi:10.1016/j.healun.2022.12.025
3. Grady KL, Jalowiec A, White-Williams C. Patient compliance at one year and two years after heart transplantation. J Heart Lung Transplant. 1998;17(4):383-394.
Key Points
Heart transplant is indicated for refractory heart failure.
Heart transplant requires lifelong immunosuppression and care, but has a reasonable prognosis.
Drugs Mentioned In This Article
