Weight Gain Following Heart Transplantation is Associated with Increased Risk of Rejection and Allograft Vasculopathy: An Analysis of the ISHLT Registry

Abstract

Obesity is a risk factor for morbidity and mortality after heart transplant (HT). While rapid and substantial total body weight (TBW) gain is often seen after HT, little is known about the effect of the rate of weight gain on outcomes. We aimed to assess the pattern of post-HT change in TBW, its phenotype [fat mass (FM) vs fat free mass (FFM)], and its impact on outcomes. Post-HT changes in TBW, FM and FFM were examined in 15,182 adult recipients of the ISHLT Transplant Registry transplanted between 1996 and 2016 who survived to 1 year and for whom serial body weight data was recorded. FFM was calculated: FFM=5.1×(height [m]1.14)×(weight [kg]0.41) for men and 5.34×(height [m]1.47)×(weight [kg]0.33) for women, based on height-weight models derived from bioelectrical impedance studies. FM was calculated as TBW minus FFM. Endpoints included cardiac allograft vasculopathy (CAV), treated rejection (TR) and all-cause mortality. Rate of TBW gain was highest during year 1 following HT, such that the proportion of obese patients increased from 23% at HT to 32% at one year after HT (p<0.05), with FM rather than FFM making the main contribution (72%) to TBW change. Figure 1 shows 5-year freedom from TR and 15-year freedom from CAV stratified by the median of 1-year TBW% change. Patients below the median had higher freedom from TR and CAV (p<0.05 for both). Survival was similar in the two groups (p=NS). After adjustment in multivariable analysis, above median TBW% change was associated with increased risk of TR (HR=1.28, p<0.001) and CAV (HR=1.16, p<0.001). Fatness (FM change/TBW change), rather than increase in FFM, was predominantly responsible for the increased risk. A substantial increase in weight is seen in the first year after transplant. The rate of weight gain following HT is independently associated with an increased risk for CAV and TR. Mitigation of the increase of the FM portion of weight gain could reduce post-transplant morbidity.