Discussion
The relationship between weight and pathophysiology of heart failure are complex and remain poorly understood. Obesity is a known risk factor for the development of cardiovascular disease, and alike, heart failure12. Paradoxically, in patients with preexisting heart failure, a higher weight and BMI appears to be a protective when assessing outcomes such as hospital readmission and/or mortality13,14. Such findings have been coined the “obesity paradox”. While this phenomenon may exist within non-transplant patients, less is understood regarding the transplant populations.
The current consensus guidelines recommend that heart transplantation should not be performed in patients with BMI ≥35 kg/m2, and that weight loss should be pursued prior to listing4. Prior analysis has suggested BMI ≥35 kg/m2 is associated with increased mortality, infection, and/or graft rejection following OHT8,15,16. Additionally, post-OHT obesity has been associated with development of cardiac allograft vasculopathy3. However, these findings are controversial, and have been challenged7,9. An analysis of the UNOS database (1998-2007) performed by Weiss et al demonstrated that candidates with BMI ≥35 kg.m2 were half as likely to receive a donor heart (risk-adjusted HR 0.54, 95% CI 0.49 to 0.60, P<0.001). However, following OHT, this cohort did not demonstrate increased one-year mortality7. In our own analysis, we did observe an association between increasing BMI at time of transplant with increased hazards for mortality (HR 1.03, 95% CI 1.02-1.04, P<0.001). Furthermore, this relationship was still observed in our sub-analysis of recipients who were waitlisted at least 90 days prior to OHT (HR 1.03, 95% CI 1.02-1.05, P<0.001).
In light of conflicting evidence regarding the impact of pretransplant BMI on posttransplant outcomes, it is possible that perhaps pretransplant weight change is a better predictor than a static pretransplant measurement. However, it appears that trends in weight change are not uniform across all solid organ transplant recipients. For example, several prior studies have shown that weight loss, regardless of starting weight/BMI, is associated with favorable outcomes and improved survival in the lung transplant population6,10. To our knowledge, this study is the first to examine the effects of pretransplant weight change in the OHT population. In our own analysis of OHT recipients, we found the relationship between pretransplant weight loss and posttransplant outcomes to be opposite that found in lung transplant recipients. In our analysis, we found OHT recipients with ≥5% pretransplant weight loss to have the highest incidence of posttransplant renal failure, drug-treated acute allograft rejection, and one-year mortality. Similar to our findings, weight loss has been associated with worse prognosis in the non-transplant heart failure population. Okuhara et al analyzed a cohort of 242 patients with mild congestive heart failure. In this study, patients with ≥5% weight loss over the course of one year were found to have higher rates of renal failure, and weight loss was an independent predictor of cardiovascular death and/or re-hospitalization (HR 3.22, 95% CI 1.10-8.41, P=0.034)17. While weight loss was found to have these associations, underweight status was not. As a result, changes in weight may offer more prognostic insight into the heart failure population than static BMI or weight measurements.
Although we found pretransplant weight loss to be an independent predictor of worse outcomes following OHT, it is likely these effects are not uniform across patients with different initial BMIs at time of waitlisting. As demonstrated in Figure 2 , the probability of one-year mortality was shown to increase in recipients with >5% weight loss as initial waitlist BMI decreased. However, decreasing initial BMI did not seem to increase probability of mortality in patients with stable weight or weight gain. It also appears the effects of weight loss are less impactful in patients with higher initial BMIs. In our sub-analysis, we did not demonstrate a significant decrease in survival in patients with initial BMI ≥35 who lost weight on the waitlist. It is not uncommon that weight loss in this cohort is intentional, whether through diet, exercise, or bariatric surgery programs, in order to reach a target goal set by providers or increase likelihood of transplant candidacy. For these reasons, it is less likely that reductions in weight in this higher-BMI subpopulation have significant negative impacts on posttransplant outcomes.