Weight Gain Post Heart Transplantation is Associated with an Increased Risk for Allograft Vasculopathy and Rejection

Purpose: Obesity and overweight have become a global epidemic and are associated with an increased risk for cardiovascular disease. Immunosuppressive medications carry the risk of weight gain and further challenge heart transplantation (HT) patients. Since both fat mass (FM) and fat-free mass (FFM), each with its discrete features, contribute to total body weight (TBW), we aimed to characterize the post-HT change in TBW and its implications for HT outcomes.

Methods: Between 1997 and 2017 we assessed 221 HT patients. Changes in TBW, FM and FFM were reviewed at 1,5, and 10 years after HT. Endpoints included survival, freedom from cardiac allograft vasculopathy (CAV), freedom from any-treated rejection (ATR), and non-fatal major adverse cardiac events (NF-MACE).

Results: Median TBW increased by 7.5% at 1 year after HT, with a significant rise in the obese category (27 vs 12%, p <0.001) and with FM rather than FFM making the main contribution (23 vs 3%, p<0.001). Peak weight gain was reached at 5 years post HT. Multivariate analysis showed that the percent change in weight was independently associated with a significantly increased risk for CAV (HR 1.03; 95% CI 1.01-1.06). When patients were divided according to median TBW percent change (high vs low groups), Kaplan–Meier survival analysis showed that 10-year freedom from CAV and ATR was significantly higher for the low TBW change group (Figure). In addition, 10-year freedom from NF-MACE was significantly higher for the low TBW change group (p=0.044). There was no difference in survival. Consistently, multivariate analyses showed that the high TBW change group was independently associated with a significant 2.8-fold increased risk for CAV (95% CI 1.3-5.9, p=0.01), and >3-fold increased risk for ATR (95% CI 1.4-8.6, p=0.01).

Conclusion: Weight gain at 1 year after HT, contributed mostly by FM, is independently associated with an increased risk for CAV and ATR. In monitoring HT patients, emphasis should be placed on weight gain and on measures to prevent it.