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\begin{document}

\title{Nationwide Variability in the Use of Induction Immunosuppression for
Adult Heart Transplantation}



\author[1]{Carlos Diaz-Castrillon}%
\author[2]{Laura Seese}%
\author[2]{Michael Mathier}%
\author[2]{Mary Keebler}%
\author[2]{Gavin Hickey}%
\author[1]{Dennis McNamara}%
\author[1]{Mark SImon}%
\author[1]{Ed Horn}%
\author[2]{Arman Kilic}%
\affil[1]{University of Pittsburgh Medical Center}%
\affil[2]{University of Pittsburgh Medical Center Health System}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Institutional factors have been shown to impact outcomes
following orthotopic heart transplantation (OHT). This study evaluated
center variability in the utilization of induction therapy for OHT and
its implications on clinical outcomes. Methods: Adult OHT patients
between 2010 and 2018 were identified from the UNOS registry. Transplant
centers were stratified based on their rates of induction therapy
utilization. Mixed-effects logistic regression models were created with
drug-treated rejection within 1-year as primary endpoint and individual
centers as random parameter. Risk-adjusted Cox regression was used to
evaluate patient-level mortality outcomes. Results: In 17,524 OHTs
performed at 100 centers, induction therapy was utilized in 48.6\%
(n=8411) with substantial variability between centers (IQR 21.4 --
79.1\%).There were 36, 30, and 34 centers in the low (\textless{}29\%),
intermediate (29-66\%), and high (\textgreater{}67\%) induction
utilization terciles groups, respectively. Induction therapy did not
account for the observed variability in the treated rejection rate at
1-year among centers after adjusting for donor and recipient factors
(p=0.20). No differences were observed in postoperative outcomes among
induction utilization centers groups (all, p\textgreater{}0.05).
Furthermore, there was a weak correlation between the percentage of
induction therapy utilization at the center-level and recipients found
to have moderate (r=0.03) or high (r=0.04) baseline risks for acute
rejection at 1-year. Conclusions: This analysis demonstrates there is
substantial variability in the use of induction therapy among OHT
centers. In addition, there was a minimal correlation with baseline
recipient risk or 1-year rejection rates, suggesting a need for
better-standardized practices for induction therapy use in OHT.%
\end{abstract}%



\sloppy


\textbf{Correspondence and Reprint Requests:}

Arman Kilic, M.D.

Division of Cardiac Surgery

University of Pittsburgh School of Medicine

200 Lothrop St

Suite C700

Pittsburgh, PA 15213

Phone: 412-692-5218

E-mail: kilica2@upmc.edu

\textbf{Abstract}

\textbf{Background:} Institutional factors have been shown to impact
outcomes following orthotopic heart transplantation (OHT). This study
evaluated center variability in the utilization of induction therapy for
OHT and its implications on clinical outcomes.

\textbf{Methods:} Adult OHT patients between 2010 and 2018 were
identified from the UNOS registry. Transplant centers were stratified
based on their rates of induction therapy utilization. Mixed-effects
logistic regression models were created with drug-treated rejection
within 1-year as primary endpoint and individual centers as random
parameter. Risk-adjusted Cox regression was used to evaluate
patient-level mortality outcomes.

\textbf{Results:} In 17,524 OHTs performed at 100 centers, induction
therapy was utilized in 48.6\% (n=8411) with substantially variability
between centers (IQR 21.4 -- 79.1\%).There were 36, 30, and 34 centers
in the low (\textless{}29\%), intermediate (29-66\%), and high
(\textgreater{}67\%) induction utilization terciles groups,
respectively. Induction therapy did not account for the observed
variability in the treated rejection rate at 1-year among centers after
adjusting for donor and recipient factors (p=0.20). No differences were
observed in postoperative outcomes among induction utilization centers
groups (all, p\textgreater{}0.05). Furthermore, there was a weak
correlation between the percentage of induction therapy utilization at
the center-level and recipients found to have moderate (r=0.03) or high
(r=0.04) baseline risks for acute rejection at 1-year.

\textbf{Conclusions:}

This analysis demonstrates that there is substantial variability in the
use of induction therapy among OHT centers. In addition, there was
minimal correlation with baseline recipient risk or 1-year rejection
rates, suggesting a need for better standardized practices for induction
therapy use in OHT.



\textbf{Introduction}

Perioperative high-intensity immunosuppression has the theoretical
benefit of reducing the risk of rejection following orthotopic heart
transplant (OHT) (1--4), where several contemporary randomized trials
that have evaluated the impacts of various induction therapy agents,
have also come to disparate conclusions (5,8). Prior studies have
demonstrated that patients with higher pre-transplant predicted risks of
rejection may garner benefit from receiving induction immunotherapy
(9,10). The current guidelines from the International Society of Heart
and Lung Transplantation (ISHLT) recommend antibody-based induction
immunosuppression as an alternative for patients at high risk of renal
dysfunction or rejection (11), although predicting which patients carry
sufficient risk remains challenging. Considering this uncertainty, many
centers have developed their own protocols for induction therapy
utilization. Institutional factors greatly influence outcomes following
OHT (12, 14) and may also be key determinants in the likelihood of a
patient to receive induction therapy as well as their odds of rejection.
As such, our objective was to evaluate the degree of center variability
in the utilization of induction therapy and its implications on clinical
outcomes following OHT.

\textbf{Methods}

\emph{Data Source}

The United Network for Organ Sharing (UNOS) registry includes
deidentified information on preoperative, intra-operative, and
post-operative variables from all donors, wait-listed candidates, and
transplant recipients in the United States. The University of Pittsburgh
Institutional Review Board granted approval for this study.

\emph{Study Population}

Adults ([?]18 years) within the UNOS data registry who received a
first-time OHT between 2010 and 2018 were included. Exclusion criteria
included recipients of multi-visceral transplants, those undergoing redo
OHT, centers with less than 45 cumulative transplants during the study
period and recipients with more than 20\% missing recipient data. The
types of induction therapy evaluated in the study were interleukin 2
(IL-2) receptor antagonists (basiliximab and daclizumab) as well as
polyclonal and monoclonal anti-thymocyte antibodies (thymoglobulin,
atgam, muromonab OKT3 and alemtuzumab).

\emph{Outcomes}

The primary outcome was drug-treated rejection within the first year
following OHT. The secondary outcomes included rates of new-onset
dialysis, stroke, operative mortality, and survival at 90-days, 1 and
5-years.

\emph{Baseline Characteristics}

Baseline waitlist data included age, gender, body mass index (BMI),
ethnicity, blood type, etiology of heart failure, pulmonary vascular
resistance (PVR), diabetes mellitus status, serum creatinine, dialysis
dependence, ventricular assist device support, mechanical ventilation,
and class I and II panel reactive antibodies. Donor variables included
age, left ventricle ejection fraction, mechanism of death, prior cardiac
arrest, diabetes mellitus status, cocaine usage, and smoking history.
Donor-recipient matching variables included human leukocyte antigen
(HLA) mismatch, ABO blood type match, gender match, race match,
cytomegalovirus match and donor-to-recipient weight ratio. A
pre-existing 13-point risk score for acute rejection within 1-year of
OHT that evaluated the domains of HLA mismatch, ethnicity, age and
gender was used to assign baseline predicted preoperative risk of
post-OHT rejection for each patient in the study (10). Patients were
classified by their cumulative score as low risk (score 0-5 points),
intermediate risk (score 6-9 points) and high risk (score [?]10 points)

\emph{Statistical analysis}

In order to comparatively assess the effect of center variations, the
induction therapy utilization rate was stratified into equal terciles,
which were classified as low (\textless{}29\%), intermediate (29-66\%)
or high (\textgreater{}67\%) induction therapy utilization. The data is
described as proportions (\%) for categorical variables and as means or
medians for continuous variables, with standard deviation (SD) or
interquartile range (IQR), respectively. Pearson's
Chi\textsuperscript{2} test was used to compare categorical variables
and one-way analysis of variance (ANOVA) or students t-tests were used
to compare continuous data. All statistical tests were 2-sided, and
p\textless{}0.05 was considered significant. Multilevel mixed-effects
logistic regression models were used to estimate the relationship of
induction therapy and post-OHT clinical outcomes accounting for
inter-center variability. The primary endpoint was drug-treated acute
rejection within the first year following OHT. Model A included only the
individual transplant centers as random effect parameters. Model B added
the recipient and donor risk factors identified as fixed effect
parameters to Model A. Finally, Model C, added induction therapy
variable as a fixed effect parameter to Model B. Changes in the estimate
of the between-centers variance may suggest the distribution of
variables across centers. The Variance Partition Coefficient (VPC) was
estimated to evaluate the proportion of variation attributable to
systematic differences between centers characteristics in the context of
a binary dependent variable. This contribution as a percentage was
calculated as {[}X /X+3.29{]} * 100, where X is the variance estimate
from the random effect component of the model (15). Risk-adjusted Cox
proportional hazards models were used to evaluate the adjusted impacts
of induction therapy on mortality. Kaplan-Meier estimates were used to
evaluate the longitudinal impacts of the use of induction therapy on
survival. Pearson's correlation coefficient (R) was utilized to assess
the correlation between pre-OHT risk scores and the use of induction
therapy. All analyses were performed with version 15 STATA statistical
software (StataCorp LP, College Station, TX).

\textbf{Results}

\emph{Study Population -- Center Characteristics}

A total of 100 centers performed 17,524 OHTs with a mean age of 53.8 \selectlanguage{ngerman}±
12.3 years, 27\% (n=4,587) female and 21.3\% (n=3,733) black. The mean
Class I and Class II PRA was 7.04±18.4\% and 5.01±15.8\%, respectively,
78\% (n= 13,690) of patients had more than 3 HLA mismatched, 24.2\%
(n=4,242) gender mismatched and 51.7\% (n=9,068) were CMV matched with
their donors. Approximately 27.1\% (n=4,756) of patients were bridged to
OHT with left ventricular assist devices (LVAD) and the basal median
estimated rejection risk score was 8 points {[}IQR 6,9{]}. The average
donor age was 32.1 ± 11.3 years, the mean ischemic time was 3.1 ± 1.0
hours and the median left ventricle ejection fraction was 60\% (55, 65)
(Supplementary Table 1).

The average rate of induction therapy utilization was 48.6 ± 31.6\%
(Figure 1), and there were 36, 30 and 34 centers at low
(\textless{}29\%), intermediate (29-66\%), and high (\textgreater{}67\%)
induction utilization rates groups (Table 1). There were no significant
differences in age, gender, pre-OHT blood transfusions, calculated PRAs
\textgreater{}20\% or median pre-OHT rejection risk scores among the
groups. Nevertheless, more recipients with elevated creatinine as well
as higher rates of HLA and gender mismatch status were in the high
tercile. On average, these patients had longer ischemic times and
donor-hospital to transplant-center distances. The highest rates of LVAD
support were appreciated in the low tercile (30.2\% vs 22.4\% vs 28.8\%,
p\textless{}0.001).

\emph{Posttransplant outcomes}

At the patient-level there were more 30-day mortalities (4.1\%
non-induction vs 3.1\% induction, p\textless{}0.001) and fewer patients
requiring dialysis after OHT (9.4\% non-induction vs 11.6\% induction,
p\textless{}0.001) in the non-induction therapy group. Nevertheless,
this difference was not sustained when we compared the center-level
outcomes among induction therapy utilization terciles (Figure 2).

Approximately 16.2\% (n=2,845) of patients had an episode of rejection
requiring pharmacological intervention within the first year after OHT.
No differences were observed among the groups with 16.2\% (n=955),
16.3\% (n=951) and 16.1\% (n=939) patients developing drug-treated
rejection within 1-year in the low, intermediate and high induction
terciles, respectively (p=0.47). Overall 25 centers had rates of
rejection above 20\% and these were evenly distributed among the groups
(Figure 3). When patients were stratified by their pre-OHT rejection
risk score, no center-level correlation was observed between the
drug-treated rejection rate and induction therapy utilization (R=0.03
for low, R=0.03 for moderate and r=0.04 for high risk;
p\textless{}0.001) (Figure 4).

\emph{Mixed-Effects Model for 1-year Treated-Acute Rejection Rate}

In model A, which assessed the effect of each center as a random
parameter, the standard deviation for the center effect for drug-treated
rejection within 1-year post OHT was 0.66 {[}95\% confidence interval
(CI) 0.56, 0.78, p\textless{}0.001{]} (Table 2). This variability is
further evidenced by the finding that 42 of the CIs from the 100 centers
did not overlap the average center effect line (Supplementary Figure 1).
After adjusting for year of transplantation and recipient and donor risk
factors as fixed parameters (model B), the standard deviation for the
center effect increased to 0.68 (95\% CI 0.57, 0.79, p\textless{}0.001).
The variables transplant year, recipient age, recipient gender, and HLA
mismatch were significantly associated with 1-year treated rejection. In
Model C, after introducing induction therapy at the patient-level as a
fixed parameter, no significant association was identified between
induction therapy use and 1-year rejection rate (OR 0.93, 95\% CI
0.83-1.03; p=0.20). The VPC for model B and C was 12.5\%, further
suggesting there is substantial center variation in rejection rates
attributable to other unmeasured centers characteristics without any
impact by the inclusion of induction therapy parameter.

\emph{Mortality at 90-days, 1-Year and 5-years}

The overall rates of mortality for the study population were 5.6\%
(n=989), 8.7\% (n=1,529), and 16 \% (n=2,810) at 90-days, 1 and 5-years
from the OHT, respectively. No differences in the center-level mortality
rates at 90-days (5.8\% vs 5.2\% vs 5.9\%, p=0.1), 1 year (8.8\% vs
8.4\% vs 9.0\%, p=0.5) or at 5 years (16.2\% vs 15.4\% vs 16.5\%, p=0.2)
were observed between the low, intermediate and high terciles groups. In
risk-adjusted Cox regression analysis demonstrated a 13\% reduction in
the hazard of death at 90 days (HR 0.87, 95\% CI 0.77-0.99; p=0.04) in
patients who received induction therapy, a relationship that was not
appreciated at longer follow-up times (Supplementary Table 2).

\emph{Impact of Induction Therapy Type}

The most commonly immunosuppressant used was Basiliximab (57.2\%,
n=4,886) followed by thymoglobulin (32.5\%, n=2,775) (Supplementary
Table 3). A sub-analysis that evaluated patients who received induction
therapy with either Thymoglobulin or Basiliximab (n=7,661) indicated
that risk-adjusted odds were comparable between the type of induction
therapy for drug-treated rejection at 1-year, renal failure requiring
dialysis, and mortality at all time intervals (Supplementary Table 4)

\textbf{Discussion}

\emph{Study Findings}

This study confirmed that there is substantial variability in the
utilization of induction therapy among US transplant centers. While this
would ideally suggest that the highest utilization centers would have
recipients with higher baseline risks for post-OHT rejection, instead we
found there is a weak correlation between elevated baseline risk scores
for rejection and the use of induction therapy. Furthermore, in an
average center, induction therapy has no discernible impact on the odds
of developing rejection requiring pharmacologic treatment within 1-year
of OHT, where there is still a substantial proportion of variability
among centers secondary to other unmeasured factors (VPC 17\%). Instead,
we found that HLA-mismatch, recipient age, recipient gender, ischemic
cardiomyopathy, and unbalanced donor/recipient weight ratios were
independent predictors of developing rejection within the first
post-operative year. Likewise, the use of induction therapy did not have
an impact on mortality at any follow-up interval among centers, although
at the patient-level 30- and 90-day mortality was reduced in the
induction therapy group. Another key finding was that patients who were
more than 3 HLA-mismatched, gender mismatched, and black race, were more
concentrated in centers with intermediate or high utilization rates of
induction therapy. However, while these variables were statistically
different among the utilization groups, the absolute magnitude of the
differences were clinically nominal. In addition, taken as a composite
assessment of rejection risk, there were no differences in composite
risk scores for rejection across groups. As such, certain recipients may
have received appropriately risk-stratification for induction therapy,
yet with a weak correlation between the receipt of induction therapy and
recipients at moderate and high pre-OHT baseline risks of rejection,
further emphasis on overall, composite risk-stratification may be
warranted during the pre-OHT evaluation. Additionally, we found that
patients who received induction therapy tended to have higher rates of
acute renal failure requiring dialysis, although this was not sustained
at the center-level comparison. These findings may be less strongly
associated with induction therapy itself and more likely to be
associated with this subset of patients potentially being higher risk
for renal failure pre-OHT and receiving induction therapy as a result.

\emph{Study Implications}

The major implication of this analysis is that the substantial
variability observed in clinical practice across centers with regards to
induction therapy utilization in OHT is not explained by differences in
the estimated composite risks of rejection at the patient-level, further
reflecting the uncertainty behind decision analysis on induction therapy
utilization across U.S.

The data also suggest that there are other unmeasured factors that are
contributing significantly to differences in 1-year rejection that are
not accounted for by induction therapy use. These may include factors
such as educational processes surrounding medication compliance or
staffing and center resources for monitoring, diagnosing and treating
rejection. It is unclear from our analysis what constitutes these
center-level factors, although their importance appears significant in
the preservation of longitudinal, rejection-free outcomes in OHT
recipients.

\emph{Prior Studies}

While this analysis is the first to explore the impacts of center
variability on induction therapy utilization for OHT, similar topics
have been explored in the renal and hepatic transplant populations.
Bittermann et al (16) found that out of 69,349 liver transplants, only
27\% of these patients received induction therapy and that 65.7\% of the
variance in induction therapy utilization was attributed to the
transplant center. Dharnidharka et al (17) analyzed 166,776 kidney
transplants, in which 81.8\% of recipients were treated with induction
therapy although the induction agent utilized was highly variable
(Thymoglobulin 58\% and Alemtuzumab 66\%) and related to center-level
characteristics.

For heart transplant recipients the clinical decision of whether to use
induction therapy, in which patients to use it in, and which agents to
use have been explored without accounting for center variability. A
meta-analysis that included 8 randomized controlled trials (18), using
various induction therapy agents, found the use of induction therapy to
be protective against moderate to severe acute rejection (OR 0.7 95\% CI
0.3 -- 1.7). Unfortunately, the high level of heterogeneity
(I\textsuperscript{2}~= 77\%) somewhat limits the interpretability of
these results. In a separate Cochrane review (19), Penninga \emph{et
al}included 22 RCTs with 1,427 patients and demonstrated that IL\selectlanguage{english}-2
receptor antagonists significantly reduced the risks of rejection (RR
0.73 95\% CI 0.59 to 0.90; I\textsuperscript{2}~57\%) when compared to
no induction therapy, although there were elevated risks of rejection in
patients who received IL-2 antagonists over polyclonal antibody
induction therapy (RR 2.43, 95\% CI 1.01 to 5.86;
I\textsuperscript{2}~28\%). Conversely, our study did not demonstrate
substantial differences in the odds of rejection at 1-year based on the
type of induction therapy utilized. While the studies included in these
meta-analyses have a high degree of bias, it is still important to
consider the potential different efficacies of the available induction
agents. Amin et al investigated the survival of 12,103 OHT recipients
from 2006 to 2015 and reported an increase in mortality associated with
induction therapy, without identifying any benefits in reductions
rejection rates (20). Similarly, a retrospective analysis by Whitson et
al (21) of 17,857 OHT recipients from 1987 to 2012 failed to show an
overall survival benefit from induction therapy. Both of these studies
suggested that the benefit of induction therapy is likely seen in
short-term follow-up rather and is also re-enforced by improved
patient-level survival at 30- and 90-days in induction therapy
recipients in our study, which was mitigated at 1-year and 5-year
follow-up among the groups.

\emph{Limitations}

This study is subject to the biases inherent in retrospective analysis.
We also relied upon the data fidelity of a multicenter registry, which
is susceptible to missing and incorrect data entry. Additionally, the
lack of accurate information about adherence to maintenance
immunosuppression, infections and post-transplant lymphoproliferative
disorders prohibited a thorough analysis. There is also a lack of
information regarding the specific clinical decisions as to why certain
patients may have received induction therapy.

\textbf{Conclusions}

In this analysis of 17,524 OHT recipients, we demonstrate that the
institutional utilization of induction therapy is highly variable across
transplant centers and not necessarily attributable to differences in
patients' baseline rejection risk. Furthermore, other unmeasured
center-level factors appear to contribute to differences in 1-year
rejection rates to a higher degree than induction therapy use. The
identification of such factors and efforts to better standardize
induction therapy use in OHT appear prudent.

\textbf{Acknowledgements}

The data reported here have been supplied by the United Network for
Organ Sharing as the contractor for the Organ Procurement and
Transplantation Network. The interpretation and reporting of these data
are the responsibility of the authors and in no way should be seen as an
official policy of or interpretation by the OPTN or the U.S. Government.

\textbf{Disclosures}

Arman Kilic is on the medical advisory board from Medtronic, Inc.

Tables

TABLE 1. Characteristics among induction utilization rate groups centers\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Factor}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Low induction therapy Tercile (n= 5867)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Intermediate induction Tercile (n= 5829)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
High induction therapy Tercile (n= 5828)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
p-value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Recipient Age, mean (SD)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{54.1 (12.1)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{53.5 (12.4))}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{53.9 (12.3)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.05}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Gender, female}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1528 (26.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1532 (26.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1527 (26.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.96}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Rejection Risk score, median (IQR)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{8 (6-9)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{8 (6-10)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{8 (6-9)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Induction therapy}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{767 (13.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{2697 (46.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{5066 (86.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Basiliximab}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{452 (7.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1,120 (41.5\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3,314 (65.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Thymoglobulin}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{256 (4.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1,151 (19.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1,360 (27\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Ethnicity}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Caucasian}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3813 (65.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3819 (65.5\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3954 (67.8\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{African American}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1240 (21.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1210 (20.8\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1283 (22.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Hispanic}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{551 (9.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{509 (8.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{324 (5.6\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Body Mass Index (kg/m2)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{27.4 (4.9)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{27.1 (4.8)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{27.5 (5.1)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Diagnosis}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Non-Ischemic Dilated Cardiomyopathy}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{2987 (50.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3046 (52.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3056 (52.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Ischemic Cardiomyopathy}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{2167 (36.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1989 (34.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{2104 (36.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Congenital}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{127 (2.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{129 (2.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{188 (3.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Restrictive Cardiomyopathy}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{89 (1.5\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{100 (1.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{53 (0.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Hypertrophic Cardiomyopathy}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{122 (2.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{182 (3.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{135 (2.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Valvular}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{179 (3.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{218 (3.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{180 (3.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Status 1A}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3812 (65.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3716 (63.8\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3696 (63.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.18}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Class I PRA \textgreater{} 20\%}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
321 (5.5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
337 (5.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
354 (6.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.38\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Class II PRA \textgreater{} 20\%}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{228 (3.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{263 (4.5\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{242 (4.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.24}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Diabetes Mellitus}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1726 (29.4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1571 (27.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1647 (28.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Intra-Aortic Balloon Pump}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{312 (5.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{201 (3.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{320 (5.5\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Inotropes at listing}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1809 (30.8\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1969 (33.8\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{2083 (35.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Serum Creatinine in mg/dL, mean (SD)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1.20 (.4)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1.22(.4)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1.24(.5)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Pre-Transplant Mechanical Ventilation}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{36 (0.6\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{82 (1.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{83 (1.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Transfusions While Listed}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1350 (23.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1301 (22.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1406 (24.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.06}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Pre-Transplant Dialysis}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{52 (0.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{59 (1.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{39 (0.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.13}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Left Ventricular Assist Device Support}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1774 (30.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1305 (22.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1677 (28.8\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Heartmate 2}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1466 (25.0\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{949 (16.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1246 (21.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Heartmate 3}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{69 (1.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{43 (0.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{51 (0.9\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{HeartWare}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{239 (4.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{313 (5.4\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{380 (6.5\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{HLA mismatch (\textgreater{}3)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{4200 (71.6\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{4761 (81.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{4729 (81.1\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Gender mismatch}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{4359 (74.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{4392 (75.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{4531 (77.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{CMV match}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3062 (52.2\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{3049 (52.3\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{2957 (50.7\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{0.17}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Donor-to-Recipient Weight Ratio, mean (SD)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1.01 (.24)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1.03 (.24)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{1.01 (.23)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}



\emph{Table 2.} \textbf{Mixed effect logistic regression model for
treated acute rejection at 1-year post-OHT.}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Fixed-Effect} \textbf{Parameter-Odds Ratio} \textbf{OR (95\%
CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Random-Effect} \textbf{Parameter-Standard deviation}
\textbf{(95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model A}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model A}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model A}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model A}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Individual center\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.66 (0.56 - 0.78)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model B}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model B}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model B}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model B}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Individual center\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.68 (0.57 - 0.79)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.98 (0.97 -- 0.98)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Gender Female (\emph{Yes/No)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.36 (1.24 -- 1.50)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Transplant year\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.95 (0.93 -- 0.97)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Heart failure diagnosis\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Dilated as reference}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Ischemic Cardiomyopathy\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.13 (1.02 -- 1.25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.01\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Congenital\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.01 (0.78 -- 1.32)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.88\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Restrictive\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.04 (0.69 -- 1.46)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.94\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Hypertrophied\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.91 (0.69 -- 1.20)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.51\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Valvular\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.89 (0.69 -- 1.14)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.37\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
African American (Yes/No)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.04 (0.94 -- 1.16\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.40\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
PRA Class II \textgreater{}20\%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.12 (0.90-1.40)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.29\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
HLA mismatch, 3 or more (Yes/No)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.23 (1.09 -- 1.39)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Donor:Recipient weight ratio\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.80 (0.67 -- 0.96)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.02\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Donor age\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.99 (0.99-1.01)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Average transplant per year\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.00 (0.99 -- 1.01)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.80\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model C}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model C}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model C}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Model C}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Individual center\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.67 (0.57 - 0.79)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.98 (0.97 -- 0.98)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Gender Female (\emph{Yes/No)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.36 (1.24 -- 1.50)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Transplant year\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.95 (0.93 -- 0.97)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Heart failure diagnosis\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Dilated as reference}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Ischemic Cardiomyopathy\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.13 (1.02 -- 1.25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.01\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Congenital\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.02 (0.78 -- 1.32)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.87\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Restrictive\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.01 (0.70 -- 1.48)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.91\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Hypertrophied\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.91 (0.69 -- 1.20)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.53\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Valvular\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.89 (0.69 -- 1.14)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.37\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
African American (Yes/No)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.04 (0.94 -- 1.16\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.39\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
HLA mismatch, \textgreater{} 3 (Yes/No)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.23 (1.01 -- 1.39)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.001\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Donor:Recipient weight ratio\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.79 (0.66 -- 0.95)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.01\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Average transplant per year\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.00 (0.99 -- 1.01)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.79\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Induction Therapy\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.93 (0.83 -- 1.03)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{}

\textbf{Figures}

\textbf{Figure 1.} -- Histogram showing induction therapy use (\%) by
transplant centers

\textbf{Figure 2.} -- Postoperative outcomes stratified by induction
therapy terciles

\textbf{Figure 3.} - Treated-acute rejection rate at 1-year post-OHT
stratified by center-level induction therapy terciles. Each circle
represents an individual center.

\textbf{Figure 4.} -- Center-level correlation between treated-acute
rejection rate at 1 year and induction therapy utilization stratified by
the baseline recipient pre-OHT rejection risk scores. Each circle
represents an individual center.

References

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2. Zuckermann A, Schulz U, Deuse T, Ruhpawar A, Schmitto JD,
Beiras-Fernandez A, et al. Thymoglobulin induction in heart
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3. Wang S-S, Chou N-K, Chi N-H, Huang S-C, Wu I-H, Wang C-H, et al. The
survival of heart transplant recipients using cyclosporine and
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5. Almenar L, Garc\selectlanguage{ngerman}ía-Palomar C, Martínez-Dolz L, Chamorro C, Moro J,
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6. Mehra MR, Zucker MJ, Wagoner L, Michler R, Boehmer J, Kovarik J, et
al. A Multicenter, Prospective, Randomized, Double-Blind Trial of
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7. Hershberger RE, Starling RC, Eisen HJ, Bergh C-H, Kormos RL, Love RB,
et al. Daclizumab to prevent rejection after cardiac transplantation. N
Engl J Med. 2005 Jun 30;352(26):2705--13.

8. Hao W-J, Zong H-T, Cui Y-S, Zhang Y. The Efficacy and Safety of
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9. Higgins R, Kirklin JK, Brown RN, Rayburn BK, Wagoner L, Oren R, et
al. To induce or not to induce: Do patients at greatest risk for fatal
rejection benefit from cytolytic induction therapy? J Hear Lung
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10. Kilic A, Weiss ES, Allen JG, Conte J V., Shah AS, Baumgartner WA, et
al. Simple Score to Assess the Risk of Rejection After Orthotopic Heart
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11. Costanzo MR, Costanzo MR, Dipchand A, Starling R, Anderson A, Chan
M, et al. The International Society of Heart and Lung Transplantation
Guidelines for the care of heart transplant recipients. Vol. 29, The
Journal of Heart and Lung Transplantation. 2010. p. 914--56.

12. Shuhaiber JH, Moore J, Dyke DB. The effect of transplant center
volume on survival after heart transplantation: A multicenter study. J
Thorac Cardiovasc Surg. 2010;

13. Arnaoutakis GJ, George TJ, Allen JG, Russell SD, Shah AS, Conte J
V., et al. Institutional volume and the effect of recipient risk on
short-term mortality after orthotopic heart transplant. J Thorac
Cardiovasc Surg. 2012 Jan;143(1):157-167.e1.

14. Kilic A, Weiss ES, Yuh DD, Shah AS, Cameron DE, Baumgartner WA, et
al. Institutional Factors Beyond Procedural Volume Significantly Impact
Center Variability in Outcomes After Orthotopic Heart Transplantation.
Ann Surg. 2012 Oct;256(4):616--23.

15. Austin PC, Merlo J. Intermediate and advanced topics in multilevel
logistic regression analysis. Stat Med. 2017 Sep 10;36(20):3257--77.

16. Bittermann T, Hubbard RA, Lewis JD, Goldberg DS. The use of
induction therapy in liver transplantation is highly variable and is
associated with posttransplant outcomes. Am J Transplant. 2019 Dec
17;19(12):3319--27.

17. Dharnidharka VR, Naik AS, Axelrod DA, Schnitzler MA, Zhang Z, Bae S,
et al. Center practice drives variation in choice of US kidney
transplant induction therapy: a retrospective analysis of contemporary
practice. Transpl Int. 2018 Feb;31(2):198--211.

18. Briasoulis A, Inampudi C, Pala M, Asleh R, Alvarez P, Bhama J.
Induction immunosuppressive therapy in cardiac transplantation: a
systematic review and meta-analysis. Heart Fail Rev. 2018 Sep
13;23(5):641--9.

19. Penninga L, Møller CH, Gustafsson F, Gluud C, Steinbrüchel DA.
Immunosuppressive T-cell antibody induction for heart transplant
recipients. Cochrane Database Syst Rev. 2013 Dec 2;

20. Amin AA, Araj FG, Ariyamuthu VK, Drazner MH, Ayvaci MUS, Mammen PPA,
et al. Impact of induction immunosuppression on patient survival in
heart transplant recipients treated with tacrolimus and mycophenolic
acid in the current allocation era. Clin Transplant. 2019;

21. Whitson BA, Kilic A, Lehman A, Wehr A, Hasan A, Haas G, et al.
Impact of induction immunosuppression on survival in heart transplant
recipients: a contemporary analysis of agents. Clin Transplant. 2015
Jan;29(1):9--17.

\emph{}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

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\end{figure}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3-Variability-primary-outcome/Figure-3-Variability-primary-outcome}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Figure 4 Risk Stratified Drug-Treated rejection.tiff`  available at \url{https://authorea.com/users/330548/articles/457295-nationwide-variability-in-the-use-of-induction-immunosuppression-for-adult-heart-transplantation}

\selectlanguage{english}
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\end{document}

