Pre-Transplant Amiodarone and Long-Term Heart Transplant Survival

Quick Takes

  • Amiodarone use pre-transplant was associated with increased short-term mortality and graft dysfunction, but this was not translated into an effect on long-term mortality.
  • The role amiodarone dose-reduction or discontinuation pre-heart transplant listing on short-term mortality post-transplant needs to be further evaluated.

Study Questions:

Does pre-heart transplant amiodarone use affect post-heart transplant outcomes?

Methods:

This was a retrospective cohort analysis of adult patients in the United States undergoing heart transplant between January 2000–August 2018, as reported in the Scientific Registry of Transplant Recipients. Patients were excluded if they received combined heart-lung or heart-kidney transplant. Patients were stratified by amiodarone use at the time of heart transplant listing, and propensity scores were calculated based on recipient and donor characteristics. Two analyses were conducted. The first included all eligible patients listed for heart transplant and evaluated mortality on the waiting list and the incidence of heart transplant. The second analysis evaluated 30-day, 1-year, 3-year, 5-year, and 10-year mortality, primary graft failure, drug-treated rejection, and post-heart transplant dialysis requirement in heart transplant recipients.

Results:

Amiodarone users at the time of listing made up 31.3% of the 57,285 patients listed for heart transplant during the study period. Amiodarone users were found to have a higher risk of dying while on the waitlist compared to nonusers (13.1% vs. 11.03%; subhazard ratio [SHR], 1.24; 95% confidence interval [CI], 1.14-1.35; p < 0.0001). A total of 25,394 listed patients received a heart transplant, with similar proportions of amiodarone users and nonusers (68% vs. 67.5%, respectively; SHR, 1.03; 95% CI, 0.99-1.06; p = 0.11). Of those patients who underwent heart transplant, 31.6% were receiving amiodarone at the time of transplant listing. Amiodarone-treated patients were older (54 vs. 57 years), more often men (81.2% vs. 72.9%), with higher frequency of history of sudden death, ventilator support, cardiac surgery, drug-treated hypertension or chronic obstructive pulmonary disease, prior intra-aortic balloon pump, and left ventricular assist device use compared to nonusers (p < 0.0001 for all groups).

An association between pre-transplant amiodarone use and post-transplant mortality was suggested in the adjusted mortality at 30 days (HR, 1.25; 95% CI, 1.11-1.41; p = 0.0002) and 1 year (HR, 1.13; 95% CI, 1.04-1.22; p = 0.0029); however, 3-year (HR, 1.05; 95% CI, 0.98-1.12; p = 0.15), 5-year (HR, 1.01; 95% CI, 0.96-1.07; p = 0.68), and 10-year (HR, 1.05; 95% CI, 0.98-1.13; p = 0.14) mortality was similar in amiodarone users and nonusers. Amiodarone users had higher odds of primary graft failure (OR, 1.3; 95% CI, 1.07-1.57; p = 0.007), lower odds of drug-treated rejection (OR, 0.81; 95% CI, 0.7-0.93; p = 0.0032), and higher odds of post-transplant dialysis (OR, 1.23; 95% CI, 1.16-1.31; p < 0.0001) compared to nonusers.

Conclusions:

This study found that while pre-heart transplant amiodarone use was associated with higher short-term mortality, this was not translated to an effect on long-term survival. Pre-heart transplant amiodarone use was associated with an increased risk of primary graft dysfunction and post-transplant dialysis, but lower risk of drug-treated rejection.

Perspective:

This large multicenter contemporary cohort of heart transplant patients evaluated clinical outcomes, including a thorough assessment of mortality at different time points post-transplant in amiodarone users and nonusers. The authors were able to demonstrate that an increased risk of short-term mortality did not appear to translate into an effect on long-term (5- or 10-year) mortality. The study findings of increased risk of primary graft dysfunction and post-transplant dialysis may have been related or correlated with the patient population more likely to be receiving amiodarone prior to transplant. Similarly, increased risk of post-transplant dialysis and decreased drug-treated rejection may have been related to a persistent drug-drug interaction between amiodarone and calcineurin inhibitors. Further characterization of the mechanisms by which amiodarone may directly affect post-transplant outcomes and whether these are dose-dependent or even avoidable by discontinuation prior to heart transplant listing are needed.

Keywords: Amiodarone, Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Calcineurin Inhibitors, Cardiac Surgical Procedures, Death, Sudden, Drug Interactions, Heart Failure, Heart Transplantation, Heart-Assist Devices, Hypertension, Patient Care Team, Primary Graft Dysfunction, Pulmonary Disease, Chronic Obstructive, Renal Dialysis, Transplant Recipients, Ventilators, Mechanical


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