Optimization of pretransplant amiodarone therapy to prevent primary graft dysfunction following heart transplantation

Despite its side effects, amiodarone remains widely used for arrhythmias in patients awaiting heart transplantation (HT). We evaluated the impact of pretransplant amiodarone use and the timing of its discontinuation on the risk of primary graft dysfunction (PGD), graft survival, and recipient outcomes.

We retrospectively analyzed adults undergoing primary isolated HT from the United Network for Organ Sharing registry (October 2018-December 2024). Patients were categorized by amiodarone use on the waitlist: never used, continued until HT, or discontinued within 5 days before HT. Recipient and donor characteristics were balanced using 1:1 propensity score matching between continued and discontinued groups. Kaplan-Meier methods evaluated survival, while multivariate Cox and logistic regression models identified predictors of mortality and PGD, respectively.

The matched cohort included 7,040 recipients (continued: n = 3,520; discontinued: n = 3,520). Continued amiodarone therapy significantly increased severe PGD (4.1% vs 2.9%; p = 0.037; adjusted odds ratios 1.63, 95% confidence intervals [1.31-2.01]), pacemaker implantation (2.6% vs 1.6%; p = 0.035), dialysis (20.8% vs 18.7%; p = 0.024), and length of hospital stay (27 vs 25.4 days; p = 0.043). No significant differences in mortality were observed (p = 0.916), nor in overall graft failure rates (p = 0.051). Discontinuation of amiodarone was associated with significant reduction in severe PGD compared to continued use (3.1% vs 4.3%, p = 0.012). Subgroup analysis demonstrated significantly reduced PGD in recipients discontinuing amiodarone 5 to 30 days before HT compared to continued users (2.2% vs 4.1%; p < 0.0001).

Discontinuing amiodarone closer to HT significantly reduces severe PGD without compromising long-term recipient or graft survival. This timing strategy may further optimize perioperative outcomes in donation after circulatory death recipients.