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.