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\begin{document}

\title{Waitlist Weight Changes Impact Survival Following Heart Transplantation}



\author[1]{Nicholas Hess}%
\author[2]{Ryan Tedford}%
\author[2]{Brian Houston}%
\author[2]{Nicolas Pope}%
\author[2]{Lucas Witer}%
\author[2]{Marc Katz}%
\author[3]{Arman Kilic}%
\affil[1]{University of Pittsburgh Medical Center}%
\affil[2]{Medical University of South Carolina - College of Medicine}%
\affil[3]{University of Pittsburgh Medical Center Health System}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: This study investigated the impact of weight change in
waitlisted candidates on posttransplant outcomes following orthotopic
heart transplantation (OHT). Methods: The United Network for Organ
Sharing database was queried to identify adult patients undergoing
isolated, primary OHT from 1/1/2010 to 3/20/2020. Patients were
stratified into 3 cohorts based on percent weight change from listing to
OHT. The primary outcome was one-year survival, and multivariable
modeling was used for risk-adjustment. A secondary analysis compared
outcomes of recipients waitlisted [?]90 days. Results: A total of 22,360
patients were included, 18,826 (84.2\%) with stable weight, 1,672
(7.5\%) with [?]5\% weight loss, and 1,862 (8.3\%) with [?]5\% weight gain.
Median age was similar across cohorts. Waitlist time was longest in
patients with weight gain and shortest in those with stable weight (417
vs 74 days, P\textless{}0.001). The weight loss cohort had higher rates
of dialysis dependency, pacemaker, and drug-treated acute rejection at
one year (all P\textless{}0.05). Ninety-day and one-year posttransplant
survival was lowest in the weight loss cohort. Multivariable modeling
identified both [?]5\% weight loss (HR 1.26, 95\% CI 1.07-1.48) and
decreasing weight (per 1\%, HR 1.02, 95\% CI 1.01-1.03) as risk-adjusted
predictors of one-year mortality. In sub-analysis of recipients
waitlisted [?]90 days, [?]5\% weight loss and decreasing weight remained
significant independent predictors for mortality. Conclusion: Waitlisted
OHT candidates with [?]5\% weight loss comprised a small, but higher-risk
population with increased rates of postoperative complications and
decreased survival. Efforts focused on nutritional optimization and
preventing weight loss while awaiting OHT appear warranted.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Orthotopic heart transplantation (OHT) remains the gold standard
treatment for advanced, end-stage heart failure\textsuperscript{1}. As
efforts have focused on improving outcomes following OHT, much research
has aimed at identifying modifiable risk factors that impact
posttransplant outcomes. Of these, recipient weight and body composition
have become of interest. The relationship between weight and heart
failure are complex, as obesity is simultaneously a risk factor for the
development of heart failure and a favorable prognostic marker in
patients with existing heart failure\textsuperscript{2}. In the OHT
population, general consensus has recommended candidates achieve a body
mass index (BMI) of \textless{}35-38 to prevent worse
outcomes\textsuperscript{3,4}. In some instances, OHT candidates may
even undergo bariatric surgery in order to meet this BMI goal and
increase chances of transplantation\textsuperscript{5,6}. Although
higher pretransplant BMI may be associated with longer waitlist times,
several studies have questioned whether increased BMI actually impacts
posttransplant outcomes\textsuperscript{7--9}.

While the impact of pre-OHT BMI remains controversial, even less is
understood about the significance of weight changes on these outcomes.
Among lung transplant recipients, pretransplant weight loss and BMI
reduction, regardless of initial weight, has been shown to be associated
with improved outcomes and survival\textsuperscript{10,11}. However, it
is unknown if these findings are applicable in the heart failure
population. In this study, we aim to investigate the impacts of
pretransplant weight changes on posttransplant outcomes following OHT.

\textbf{Materials and Methods}

\emph{Data Source}

The United Network for Organ Sharing (UNOS) database prospectively
collected database of all thoracic transplants performed in the United
States. We analyzed patients undergoing orthotopic heart transplantation
(OHT) from January 1, 2010 to March 20, 2020. Patient and medical center
identifiers were excluded from the analysis and manuscript. This study
was approved by the Institutional Review Board at the University of
Pittsburgh.

\emph{Study Design}

In this study, we included adult patients ([?]18 years) who underwent
isolated, primary OHT within the study period. Multi-visceral
transplants and heterotopic heart transplants were excluded. Percent
waitlist weight change was calculated from time of OHT waitlisting to
time of transplant. Recipients were then divided into three cohorts,
those with [?]5\% weight loss while waitlisted, those with stable weight
(\textless{}\textbar{}5\%\textbar{} weight change), and those with [?]5\%
weight gain. Patient demographic and outcomes data were collected from
the UNOS database.

The primary outcome of this study was one-year posttransplant survival.
Other outcomes included postoperative complications, hospital length of
stay, and rates of drug-treated one-year acute rejection. Predictors of
posttransplant mortality and were modeled in multivariable analysis.

Because patients with short waitlist times are unlikely to experience
significant fluctuations in weight, we performed a sub-analysis. In this
analysis, we excluded patients with waitlist times \textless{}90 days.
One-year survival was compared among cohorts, and multivariable modeling
for mortality was performed in this population. Furthermore, as many
transplanting centers focus on waitlisted candidates achieving a BMI
less than 35 kg/m\textsuperscript{2} prior to transplantation, we
performed a separate sub-analysis to investigate outcomes of patients
with initial waitlist BMI [?] 35 kg/m\textsuperscript{2}.

\emph{Statistical Analysis}

Continuous, normally distributed data are presented as mean (\selectlanguage{ngerman}± standard
deviation), and continuous, nonparametric data are presented as median
{[}interquartile range (IQR){]}. Categorical data are displayed as a
number (percentage). Preoperative baseline characteristics were compared
between groups using Student's t-test for normally distributed
continuous variables and Wilcoxon rank sum test for nonparametric
variables. Categorical variables were compared using either chi square
or Fisher's exact test when appropriate.

Kaplan Meier survival analysis was used to compare one-year survival
among weight change cohorts. Multivariable Cox proportional hazards
modeling was performed to evaluate the risk-adjusted predictors of
one-year posttransplant mortality. B-spline regression was used to model
effects of weight loss across initial waitlisting BMI. Statistical
analysis was performed using Stata version 16.1 statistical software
(StataCorp, College Station, TX, USA).

\textbf{Results}

\emph{Baseline Recipient and Transplant Characteristics}

A total of 22,360 patients were included in this study, 18,826 (84.2\%)
with stable weight (\textless{}\textbar{}5\%\textbar{} weight change),
1,672 (7.5\%) with \selectlanguage{english}[?]5\% weight loss, and 1,862 (8.3\%) with \selectlanguage{english}[?]5\% weight
gain. Distributions of age, race, BMI, and heart failure etiology are
presented in \textbf{Table 1} . Patients with stable weight had the
lowest proportion of recipients with non-ischemic cardiomyopathy (52.0\%
vs 53.1\% vs 55.7\%, P\textless{}0.001). Patients with stable weight
also had the lowest incidence of waitlist transfusion (19.3\% vs 37.8\%
vs 37.5\%, P\textless{}0.001). Recipients with \selectlanguage{english}[?]5\% weight gain had the
lowest incidence of pretransplant mechanical ventilation (1.3\% vs 0.9\%
vs 0.5\%, P=0.004), pretransplant inotrope requirement (37.6\% vs 33.4\%
vs 17.2\%, P\textless{}0.001), intra-aortic balloon pump (10.4\% vs
9.2\% vs 3.2\%, P\textless{}0.001) and extracorporeal membrane
oxygenation support (1.3\% vs 1.3\% vs 0.1\%, P\textless{}0.001).
Patients with \selectlanguage{english}[?]5\% weight gain were also most frequently bridged to
transplant with a left ventricular assist device (39.4\% vs 46.6\% vs
74.9\%, P\textless{}0.001).

Recipients with \selectlanguage{english}[?]5\% weight gain received donor hearts from the lowest
median donor-to-recipient hospital distance (101 miles vs 102 miles vs
86 miles, P=0.004). This cohort also had the longest median waitlist
time, and patients with stable weight had the shortest median waitlist
time (74 days vs 220 days vs 417 days, P\textless{}0.001). Graft cold
ischemic times were similar across cohorts (\textbf{Table 1} ).

\emph{Posttransplant Complications and Survival}

Following transplantation, patients with \selectlanguage{english}[?]5\% weight loss experienced
the highest rate of renal failure requiring dialysis, while those with
\selectlanguage{english}[?]5\% weight gain experienced the lowest (11.2\% vs 14.1\% vs 10.3\%,
P\textless{}0.001). The \selectlanguage{english}[?]5\% weight loss cohort also experienced the
highest incidence of pacemaker requirement (2.9\% vs 3.7\% vs 2.3\%,
P=0.044) and drug-treated acute rejection at one year (11.0\% vs 13.4\%
vs 12.1\%, P=0.005) (\textbf{Table 2} ). Rates of stroke, hospital
length of stay, and 30-day mortality were comparable.

Ninety-day and one-year survival were greatest in recipients with \selectlanguage{english}[?]5\%
weight gain and lowest in those with \selectlanguage{english}[?]5\% weight loss (94.7\% vs 92.8\%
vs 95.8\%; and 91.6\% vs 89.0\% vs 92.3\%, P=0.008) (\textbf{Figure 1}
). In multivariable analysis controlling for both BMI and ventricular
assist device, \selectlanguage{english}[?]5\% weight loss was associated with 26\% increased
hazards for one-year mortality (HR 1.26, 95\% CI 1.07 to 1.48, P=0.005)
and \selectlanguage{english}[?]5\% weight gain was associated with 17\% decrease in mortality (HR
0.83, 95\% CI 0.69 to 1.00, P=0.047) compared to the stable weight
cohort (\textbf{Table 3} ). Decreasing weight modeled as a continuous
variable was also associated with increased hazards for mortality (per
1\% lost, HR 1.02, 95\% CI 1.01 to 1.03, P\textless{}0.001)
(\textbf{Supplemental Table 1} ). Other factors associated with
increased hazards for mortality included increasing BMI, congenital
heart disease, restrictive heart disease, increasing total bilirubin and
serum creatinine, pretransplant mechanical ventilation and
extracorporeal membrane oxygenation, increasing donor age, female donor,
and increasing graft cold ischemia time.

To model the effects of weight loss across initial BMI at waitlisting,
B-spline regression was performed. Probability of one-year
posttransplant mortality was plotted across initial waitlist BMI
in\textbf{Figure 2} . Weight loss \selectlanguage{english}[?] 5\% is shown to have increasing
probability of mortality in waitlist BMI levels below 24
kg/m\textsuperscript{2}. However, in patients with stable weight or
weight gain, decreasing initial waitlist BMI did not appear to increase
probability of one-year posttransplant mortality.

\emph{Sub-analysis}

A sub-analysis was performed which included only patients that had been
waitlisted \selectlanguage{english}[?]90 days prior to OHT. This resulted in a total of 11,623
patients, 8,669 (74.6\%) with stable weight, 1,262 (10.9\%) with \selectlanguage{english}[?]5\%
weight loss, and 1,692 (14.6\%) with \selectlanguage{english}[?]5\% weight gain. Ninety-day
(94.5\% vs 92.9\% vs 95.6\%) and one-year (91.4\% vs 88.9\% vs 92.3\%)
mortality were lowest in patients with \selectlanguage{english}[?]5\% weight loss (\textbf{Figure
3} ) (P =0.0044). In multivariable model, \selectlanguage{english}[?]5\% weight loss was
associated with 33\% increased hazards for posttransplant mortality (HR
1.33, 95\% CI 1.11 to 1.61, P=0.003). \selectlanguage{english}[?]5\% weight gain was not found to
have significant impact on mortality (HR 0.87, 95\% CI 0.72 to 1.06,
P=0.173) (\textbf{Supplemental Table 2} ). When examined as a continuous
variable, decreasing weight was associated with increased hazards for
mortality (per 1\% weight lost, HR 1.02, 95\% CI 1.01 to 1.03,
P\textless{}0.001) (\textbf{Supplemental Table 3} ). Other factors
associated with increased hazards for mortality included increasing BMI,
congenital heart disease, increasing total bilirubin and serum
creatinine, pretransplant mechanical ventilation, extracorporeal
membrane oxygenation, increasing donor age, and increasing graft cold
ischemia time.

Additional sub-analysis investigated the outcomes of patients with
initial waitlist BMI \selectlanguage{english}[?]35 kg/m\textsuperscript{2}. This subgroup was
comprised of 1,470 patients, 1,205 (82.0\%) who were transplanted with a
BMI \selectlanguage{english}[?] 35 kg/m\textsuperscript{2}, and 265 (18.0\%) who dropped to a BMI
\textless{} 35 kg/m\textsuperscript{2} prior to OHT. Comparison of
baseline characteristics are shown in \textbf{SupplementalTable 4} .
Patients who were transplanted at a BMI \textless{} 35
kg/m\textsuperscript{2} had a higher utilization of left ventricular
assist device as a bridge to OHT (66.9\% vs 56.9\%, P\textless{}0.001),
and also had a longer median waitlist time (397 days {[}IQR 172 to
727{]} vs 111 days {[}IQR 31 to 343{]}, P\textless{}0.001) compared
those who were transplanted with a BMI \selectlanguage{english}[?] 35
kg/m\textsuperscript{2}.\textbf{Figure 4a} displays Kaplan Meier
posttransplant survival between groups. Additionally, recipients with
waitlist BMI \selectlanguage{english}[?] 35 kg/m\textsuperscript{2} were stratified into weight
change while on waitlist (stable weight, \selectlanguage{english}[?]5\% weight loss, \selectlanguage{english}[?]5\% weight),
and Kaplan Meier survival comparisons are shown in \textbf{Figure 4b} .
In both comparisons, there were no differences in one-year survival
among groups.

\textbf{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
failure\textsuperscript{12}. 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
mortality\textsuperscript{13,14}. 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 \selectlanguage{english}[?]35
kg/m\textsuperscript{2,} and that weight loss should be pursued prior to
listing\textsuperscript{4}. Prior analysis has suggested BMI \selectlanguage{english}[?]35
kg/m\textsuperscript{2} is associated with increased mortality,
infection, and/or graft rejection following
OHT\textsuperscript{8,15,16}. Additionally, post-OHT obesity has been
associated with development of cardiac allograft
vasculopathy\textsuperscript{3}. However, these findings are
controversial, and have been challenged\textsuperscript{7,9}. An
analysis of the UNOS database (1998-2007) performed by Weiss et al
demonstrated that candidates with BMI \selectlanguage{english}[?]35 kg.m\textsuperscript{2} were
half as likely to receive a donor heart (risk-adjusted HR 0.54, 95\% CI
0.49 to 0.60, P\textless{}0.001). However, following OHT, this cohort
did not demonstrate increased one-year mortality\textsuperscript{7}. 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\textless{}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\textless{}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
population\textsuperscript{6,10}. 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 \selectlanguage{english}[?]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 \emph{et al} analyzed a
cohort of 242 patients with mild congestive heart failure. In this
study, patients with \selectlanguage{english}[?]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)\textsuperscript{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 \textbf{Figure 2} , the probability of
one-year mortality was shown to increase in recipients with
\textgreater{}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 \selectlanguage{english}[?]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.

\emph{Study Implications}

This study findings add to the growing knowledge regarding the complex
relationship between weight and heart failure. This study and others
have demonstrated higher pretransplant BMI to be associated with higher
risk of posttransplant mortality. However, we suggest that perhaps
examination of weight changes in the pretransplant period may offer
better prognostic potential than weight measurements alone. In this
study, we found an inverse relationship between pretransplant weight
loss and posttransplant mortality, with a 2\% increase in risk-adjusted
hazards for mortality for every 1\% of initial weight lost. Furthermore,
the impacts of pretransplant weight loss are likely the highest in
patients with lower initial BMI. Patients with \selectlanguage{english}[?]5\% weight loss account
for 7.5\% of all OHT recipients, and 11\% of recipients who are
waitlisted for 90 or more days and represent a vulnerable and high-risk
subset. Further efforts are needed to identify these patients and
investigate the underlying mechanisms by which weight loss impact
long-term outcomes. Such understanding of these mechanism may help
promote future interventions such as patient-tailored nutritional
optimization prior to OHT.

\emph{Limitations}

This study was subject to limitations. First, this was a retrospective
study and thus subject to selection bias that true randomization would
eliminate. It is possible that pretransplant weight loss may serve as a
surrogate for other disease processes and illness that influence
posttransplant outcomes. In order to adjust for these possible
confounding variables, we performed a multivariable analysis to adjust
for pretransplant risk factors that were found to have influence on
posttransplant mortality. However, it is possible that further
unmeasured variables exist and may influence the findings of this study.
Additionally, we recognize that weight changes are gradual, and patients
who are transplanted after short waitlisting times are not likely to
experience significant weight change. To address this, we performed a
secondary analysis and included only patients who were waitlisted at
least 90 days prior transplantation. Finally, we cannot determine from
this analysis if weight loss was intentional or unintentional, or how
volume overload and subsequent diuresis may have impacted our
categorization.

\emph{Conclusions}

In this analysis of 22,360 adult patients undergoing isolated OHT, we
identified significant impacts of pretransplant weight changes on
posttransplant outcomes. Patients with \selectlanguage{english}[?]5\% loss in weight from time of
OHT listing were found to have higher incidence of renal failure
requiring dialysis and drug-treated acute rejection at one year.
Furthermore, one-year survival was significantly reduced in comparison
to recipients with stable pretransplant weight, and the negative effects
of pretransplant weight loss are likely higher in patients with lower
initial waitlist BMI levels. This cohort represents a small (7.5\%), but
high-risk subset of OHT recipients. As a result, efforts should be made
to identify these at-risk patients and focus on nutritional optimization
and weight loss prevention prior to OHT.

\textbf{Disclosures}

None of the following disclosures are in direct conflict with this
manuscript

\textbf{AK:} advisory board for Medtronic, Inc.

\textbf{RT:} consulting, Medtronic, Abbott, Aria CV Inc., Arena
Pharmaceuticals, Acceleron, Eidos Therapeutics, Gradient and United
\selectlanguage{english}Therapeutics.

-steering committee for Medtronic, Acceleron, Itamar and Abbott

-research advisory board for \selectlanguage{english}Abiomed

-hemodynamic core lab work for Actelion and Merck

\textbf{BH:} received research grant funding from and is on the medical
advisory board for Medtronic, Inc.

\textbf{MK:} consulting for Abbott, Boston Scientific, Edwards, and
Medtronic.

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doi:10.1016/j.cardfail.2018.11.003

\textbf{Table 1} . Baseline recipient and transplant characteristics of
OHT recipients stratified by waitlist weight change\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& \textbf{Stable Weight} & \textbf{[?]5\% Weight Loss} & \textbf{[?]5\%
Weight Gain} & \textbf{P-Value}\tabularnewline
\midrule
\endhead
& \textbf{N=18,826} & \textbf{N=1,672} & \textbf{N=1,862}
&\tabularnewline
Recipient Characteristics & & & &\tabularnewline
Recipient Age (years) & 57 (47-63) & 56 (46-63) & 56 (45-62) &
\textless{}0.001\tabularnewline
Female & 5,142 (27.3\%) & 397 (23.7\%) & 413 (22.2\%) &
\textless{}0.001\tabularnewline
Race & & & &\tabularnewline
White & 12,427 (66.4\%) & 1,122 (67.5\%) & 1,124 (60.8\%) &
\textless{}0.001\tabularnewline
Black & 3,930 (21.0\%) & 371 (22.3\%) & 505 (27.3\%) &\tabularnewline
Hispanic & 1,557 (8.3\%) & 132 (7.9\%) & 158 (8.5\%) &\tabularnewline
Asian & 693 (3.7\%) & 29 (1.7\%) & 50 (2.7\%) &\tabularnewline
Other & 115 (0.6\%) & 8 (0.5\%) & 12 (0.6\%) &\tabularnewline
BMI at Waitlisting (kg/m\textsuperscript{2}) & 27.32 (4.82) & 30.02
(5.24) & 26.01 (4.39) & \textless{}0.001\tabularnewline
BMI at Transplant (kg/m\textsuperscript{2}) & 27.32 (4.81) & 26.76
(4.64) & 29.39 (4.84) & \textless{}0.001\tabularnewline
Recipient Blood Type & & & &\tabularnewline
A & 7,747 (41.2\%) & 595 (35.6\%) & 662 (35.6\%) &
\textless{}0.001\tabularnewline
AB & 1,156 (6.1\%) & 67 (4.0\%) & 58 (3.1\%) &\tabularnewline
B & 2,878 (15.3\%) & 231 (13.8\%) & 240 (12.9\%) &\tabularnewline
O & 7,045 (37.4\%) & 779 (46.6\%) & 902 (48.4\%) &\tabularnewline
Heart Failure Etiology & & & &\tabularnewline
Non-Ischemic & 9,775 (52.0\%) & 887 (53.1\%) & 1,037 (55.7\%) &
\textless{}0.001\tabularnewline
Ischemic & 6,450 (34.3\%) & 528 (31.6\%) & 665 (35.7\%) &\tabularnewline
Congenital & 559 (3.0\%) & 50 (3.0\%) & 50 (2.7\%) &\tabularnewline
Restrictive & 695 (3.7\%) & 69 (4.1\%) & 31 (1.7\%) &\tabularnewline
Valvular & 257 (1.4\%) & 22 (1.3\%) & 16 (0.9\%) &\tabularnewline
Hypertrophic & 512 (2.7\%) & 57 (3.4\%) & 27 (1.5\%) &\tabularnewline
Other & 30 (0.2\%) & 5 (0.3\%) & 1 (0.1\%) &\tabularnewline
Diabetes Mellitus & 5,172 (27.6\%) & 503 (30.2\%) & 514 (27.6\%) &
0.076\tabularnewline
Total Bilirubin (mg/dL) & 0.98 (1.62) & 0.99 (1.48) & 0.86 (1.12) &
0.006\tabularnewline
Serum Creatinine (mg/dL) & 1.23 (0.61) & 1.24 (0.48) & 1.24 (0.40) &
0.94\tabularnewline
Positive CMV Serology & 10,514 (55.8\%) & 899 (53.8\%) & 1,072 (57.6\%)
& 0.075\tabularnewline
Transfusion on Waitlist & 3,527 (19.3\%) & 608 (37.8\%) & 675 (37.5\%) &
\textless{}0.001\tabularnewline
Pretransplant Mechanical Ventilation & 245 (1.3\%) & 15 (0.9\%) & 9
(0.5\%) & 0.004\tabularnewline
Pretransplant Intensive Care Unit & 6,148 (32.7\%) & 555 (33.2\%) & 235
(12.6\%) & \textless{}0.001\tabularnewline
Intravenous Inotropes & 7,078 (37.6\%) & 559 (33.4\%) & 320 (17.2\%) &
\textless{}0.001\tabularnewline
Pretransplant Intra-Aortic Balloon Pump & 1,954 (10.4\%) & 154 (9.2\%) &
60 (3.2\%) & \textless{}0.001\tabularnewline
Pretransplant Extracorporeal Membrane Oxygenation & 253 (1.3\%) & 21
(1.3\%) & 1 (0.1\%) & \textless{}0.001\tabularnewline
Ventricular Assist & & & &\tabularnewline
None & 10,729 (57.7\%) & 747 (45.2\%) & 413 (22.4\%) &
\textless{}0.001\tabularnewline
LVAD & 7,329 (39.4\%) & 770 (46.6\%) & 1,379 (74.9\%) &\tabularnewline
RVAD & 35 (0.2\%) & 4 (0.2\%) & 3 (0.2\%) &\tabularnewline
TAH & 159 (0.9\%) & 58 (3.5\%) & 16 (0.9\%) &\tabularnewline
LVAD + RVAD & 330 (1.8\%) & 74 (4.5\%) & 31 (1.7\%) &\tabularnewline
Transplant Characteristics & & & &\tabularnewline
Sex Matched & 14,267 (75.8\%) & 1,314 (78.6\%) & 1,468 (78.8\%) &
\textless{}0.001\tabularnewline
Race Matched & 9,696 (51.5\%) & 861 (51.5\%) & 920 (49.4\%) &
0.22\tabularnewline
HLA Matched & 2,428 (12.9\%) & 231 (13.8\%) & 239 (12.8\%) &
0.56\tabularnewline
ABO Matched & 15,761 (83.7\%) & 1,448 (86.6\%) & 1,688 (90.7\%) &
\textless{}0.001\tabularnewline
CMV Matched & 9,946 (53.1\%) & 857 (51.4\%) & 989 (53.5\%) &
0.40\tabularnewline
Donor Distance (nautical miles) & 101 (14-303) & 102 (15-289) & 86
(12-271) & 0.004\tabularnewline
Cold Ischemic Time (hours) & 3.2 (2.4-3.8) & 3.2 (2.5-3.8) & 3.1
(2.4-3.8) & 0.15\tabularnewline
Days Listed & 74 (21-230) & 220 (91-504) & 417 (212-758) &
\textless{}0.001\tabularnewline
\bottomrule
\end{longtable}

BMI, body mass index, CMV, cytomegalovirus; HLA, human leukocyte
antigen; LVAD, left ventricular assist device; RVAD, right ventricular
assist device; TAH, total artificial heart; VAD, ventricular assist
device

\textbf{Table 2} . Post-transplant outcomes stratified by waitlist
weight change\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& \textbf{Stable Weight} & \textbf{[?]5\% Weight Loss} & \textbf{[?]5\%
Weight Gain} & \textbf{P-Value}\tabularnewline
& \textbf{N=18,826} & \textbf{N=1,672} & \textbf{N=1,862}
&\tabularnewline
Renal Failure Requiring Dialysis & 2,061 (11.2\%) & 232 (14.1\%) & 189
(10.3\%) & \textless{}0.001\tabularnewline
Stroke & 532 (2.9\%) & 44 (2.7\%) & 59 (3.2\%) & 0.61\tabularnewline
Pacemaker & 532 (2.9\%) & 61 (3.7\%) & 42 (2.3\%) & 0.044\tabularnewline
Hospital Length of Stay (days) & 15 (11-22) & 16 (11-25) & 16 (11-23) &
\textless{}0.001\tabularnewline
Drug-Treated Acute Rejection at One Year & 2,034 (11.0\%) & 222 (13.4\%)
& 222 (12.1\%) & 0.005\tabularnewline
30-Day Mortality & 651 (4.3\%) & 59 (4.5\%) & 48 (3.2\%) &
0.102\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3} . Multivariable Cox Proportional Hazards model for
one-year mortality.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{Hazard Ratio} & \textbf{95\% Confidence Interval} &
\textbf{P-Value}\tabularnewline
\midrule
\endhead
Recipient Age (increasing, per year) & 1.02 & 1.02, 1.03 &
\textless{}0.001\tabularnewline
Weight Change & & &\tabularnewline
Stable Weight & Reference & Reference & Reference\tabularnewline
[?]5\% Weight Loss & 1.26 & 1.07, 1.48 & 0.005\tabularnewline
[?]5\% Weight Gain & 0.83 & 0.69, 1.00 & 0.047\tabularnewline
Body Mass Index (increasing, per kg/m\textsuperscript{2}) & 1.03 & 1.02,
1.04 & \textless{}0.001\tabularnewline
Heart Failure Etiology & & &\tabularnewline
Non-Ischemic & Reference & Reference & Reference\tabularnewline
Ischemic & 1.08 & 0.97, 1.20 & 0.172\tabularnewline
Congenital & 2.74 & 2.14, 3.51 & \textless{}0.001\tabularnewline
Restrictive & 1.45 & 1.14, 1.83 & 0.002\tabularnewline
Valvular & 0.90 & 0.58, 1.42 & 0.661\tabularnewline
Hypertrophic & 1.07 & 0.77, 1.47 & 0.699\tabularnewline
Other & 4.79 & 2.38, 9.63 & \textless{}0.001\tabularnewline
Diabetes Mellitus & 1.10 & 0.99, 1.22 & 0.084\tabularnewline
Total Bilirubin (increasing, per mg/dL) & 1.06 & 1.05, 1.07 &
\textless{}0.001\tabularnewline
Serum Creatinine (increasing, per mg/dL) & 1.10 & 1.07, 1.14 &
\textless{}0.001\tabularnewline
Pretransplant Mechanical Ventilation & 2.37 & 1.75, 3.23 &
\textless{}0.001\tabularnewline
Pretransplant Intensive Care Unit & 1.16 & 1.04, 1.30 &
0.010\tabularnewline
Pretransplant Extracorporeal Membrane Oxygenation & 1.78 & 1.26, 2.52 &
0.001\tabularnewline
Ventricular Assist & & &\tabularnewline
None & Reference & Reference & Reference\tabularnewline
LVAD & 1.33 & 1.19, 1.49 & \textless{}0.001\tabularnewline
RVAD & 1.89 & 0.94, 3.81 & 0.076\tabularnewline
TAH & 3.41 & 2.50, 4.65 & \textless{}0.001\tabularnewline
LVAD + RVAD & 1.71 & 1.28, 2.30 & \textless{}0.001\tabularnewline
Heartmate III & 1.64 & 1.05, 2.55 & 0.030\tabularnewline
Donor Age (increasing, per year) & 1.01 & 1.01, 1.01 &
\textless{}0.001\tabularnewline
Female Donor & 1.21 & 1.10, 1.35 & \textless{}0.001\tabularnewline
Graft Cold Ischemic Time (increasing, per hours) & 1.13 & 1.08, 1.18 &
\textless{}0.001\tabularnewline
Waitlist Time (increasing, per day) & 1.00 & 1.00 1.00 &
0.016\tabularnewline
\bottomrule
\end{longtable}

LVAD, left ventricular assist device; RVAD, right ventricular assist
device; TAH, total artificial heart

\textbf{Figure Legend}

\textbf{Figure 1.} Kaplan Meier survival analysis of primary, isolated
orthotopic heart transplant recipients. Patients stratified by percent
change in weight from time of waitlisting to transplantation.

\textbf{Figure 2.} Probability of one-year mortality modeled across
initial body mass index at time of waitlisting. Comparison of [?] 5\%
weight loss and less than 5\% weight loss.

\textbf{Figure 3.} Sub-analysis\textbf{.} Kaplan Meier survival analysis
of primary, isolated orthotopic heart transplant recipients who were
waitlisted [?]90 days. Patients stratified by percent change in weight
from time of waitlisting to transplantation.

\textbf{Figure 4.} Sub-analysis\textbf{.} Kaplan Meier one-year survival
of OHT recipients with initial waitlisting BMI [?] 35
kg/m\textsuperscript{2}. \textbf{Figure 4a} compares recipients with a
BMI lower than 35 kg/m\textsuperscript{2} at time of transplant with
those with BMI [?]35 kg/m\textsuperscript{2}. \textbf{Figure 4b} compares
recipients based on weight change while on transplant waitlist.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure1/Figure1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure2/Figure2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure3/Figure3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure4/Figure4}

\end{center}
\end{figure}

\selectlanguage{english}
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