Heart Transplant for Advanced Heart Failure: A Review

Importance: Heart failure affects more than 6 million US adults; approximately 4% to 5% progress to advanced disease despite optimal therapy. Heart transplant is a class I guideline-recommended therapy for select individuals with advanced heart failure. Observations: Early referral for heart transplant is guided by the "I NEED HELP" mnemonic, a tool that identifies patients with advanced heart failure based on criteria such as use of inotropes, persistent symptoms (New York Heart Association class III or IV), end-organ dysfunction, left ventricular ejection fraction, defibrillator shocks, hospitalizations for heart failure, persistent edema or escalating use of diuretics, and low blood pressure. Each criterion is associated with higher risk of death or first heart failure hospitalization over a median follow-up of 260 days (adjusted hazard ratio, 1.19 [95% CI, 1.11-1.27] for each additional criterion). Typical absolute contraindications to heart transplant include active systemic infection, malignancy with limited life expectancy, severe and irreversible end-organ dysfunction (eg, cirrhosis, severe pulmonary hypertension), active substance use, major untreated psychiatric illness, inadequate social support, and severe frailty. Approximately 4600 heart transplants are performed annually in the US. The mortality rate was 8.5 deaths/100 patient-years for adults on the transplant waiting list in 2023. Leading causes of early death after transplant include primary graft dysfunction (39.5%), multiorgan failure (18.5%), and infection (13.9%). Among adults, contemporary survival rates after heart transplant are 91.5% at 1 year and 80.3% at 5 years. Lifelong maintenance immunosuppression typically combines a calcineurin inhibitor, antiproliferative agents (typically mycophenolate mofetil or azathioprine) and corticosteroids, with selective use of induction therapy (intensive immunosuppression immediately after transplant). Acute rejection requiring treatment occurs in 20% to 25% of recipients within a year, and may be treated with high-dose corticosteroids, antithymocyte globulin, and B-cell-targeted therapies (such as rituximab or bortezomib). Rejection surveillance with endomyocardial biopsies of the right ventricular septum is performed 5 to 10 times within the first year after transplant. Cardiac allograft vasculopathy (chronic rejection that causes diffuse coronary narrowing) affects 29% of heart transplant recipients within 5 years and 46.8% by 10 years and is the leading cause of late mortality. Cardiac allograft vasculopathy is treated with statins, mechanistic target of rapamycin inhibitors (such as sirolimus or everolimus), and retransplant for severe cases. Infections (62.5% are bacterial, 30.0% are viral, 6.7% are fungal, and 0.8% are parasitic) and malignancy (10.7% within 5 years after heart transplant) are other leading causes of late mortality. Conclusions and Relevance: Heart transplant is the definitive therapy for carefully selected patients with advanced heart failure despite receiving optimal, guideline-directed therapy. After heart transplant, lifelong multidisciplinary care is necessary to manage immunosuppression, prevent and treat rejection and cardiac allograft vasculopathy, and monitor for infection and malignancy.