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.
This Viewpoint discusses aspects of the organ transplant waiting list, transplant technology, and the expansion of graft availability.
Importance One in 5 heart transplant candidates in the US die or are delisted without transplant. Donor hearts are currently allocated by a 6-status therapy-based system criticized for limited risk stratification and susceptibility to gaming. Objective To develop a new heart allocation policy based on an objective medical urgency score that ranks candidates based on the interaction between physiology and mechanical circulatory support. Design, Setting, and Participants Registry-based observational study using data from the US organ transplant system. All adult (aged ≥18 years) heart transplant candidates from January 2019 to August 2025 were included, split into training (2019-2023), validation (2023-2024), and test (2024-2025) datasets. Main Outcomes and Measures A marginal structural model of 6-week mortality without transplant was estimated (the US Candidate Risk Score [US-CRS]). Eight models were compared in held-out data by weighted time-dependent area under the curve (AUC) and calibration by status. Finally, US-CRS was converted into an allocation policy and a match-run simulation of waitlist reordering was performed compared with the current 6-status system. Results Adult heart transplant candidates were partitioned into consecutive training (n = 21 859), validation (n = 7897), and test (n = 8256) datasets (mean [SD] age, 53 [13] years; 74% male). The chosen US-CRS model included 5 laboratory values and 4 therapeutic devices (durable left ventricular assist device, intra-aortic balloon pump, microaxial flow pump, and advanced mechanical circulatory support). In test-set cross-sections of candidates actively waiting on the same calendar date, US-CRS had similar or significantly higher time-dependent AUC than the current 6-status system (mean AUC, 0.807 vs 0.693, respectively) and acceptable calibration by status, especially for candidates who received their status by exception. In match-run analysis (n = 45 530 donor hearts), a US-CRS–based system led to 67% of transplant recipients moving down in rank order and increased observed 6-week transplant-censored mortality for the first candidate on the match run from 11.2% (95% CI, 10.1%-12.5%) under the current system to 15.7% (95% CI, 13.9%-17.6%) under the US-CRS–based system. Conclusions and Relevance In this registry-based study of US heart transplant candidates, a US-CRS–based allocation system prioritized sicker candidates with higher mortality without transplant compared with the current medical urgency statuses.
