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\begin{document}

\title{Impact of Various Sizing Metrics on Female Donor to Male Recipient Heart
Transplant Outcomes}



\author[1]{Nicholas Hess}%
\author[2]{Gavin Hickey}%
\author[3]{Ibrahim Sultan}%
\author[2]{Yisi Wang}%
\author[2]{Arman Kilic}%
\affil[1]{University of Pittsburgh Medical Center}%
\affil[2]{University of Pittsburgh Medical Center Health System}%
\affil[3]{University of Pittsburgh}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: This study evaluated the impact of various sizing metrics on
outcomes of female donor to male recipient orthotopic heart
transplantation (OHT). Methods: We queried the United Network of Organ
Sharing database to analyze all isolated, primary adult OHTs from
1/12010-3/20/2020. Patients were stratified by donor-recipient sex
pairing. Logistic regression was used to investigate risk-adjusted
effects of current size matching criteria (weight ratio, body mass index
(BMI) ratio, predicted heart mass (pHM) ratio) on one-year
post-transplant mortality. Kaplan-Meier analysis was used to compare
posttransplant survival among cohorts. Results: A total of 22,450
patients were analyzed, of which 3,019 (13.4\%) underwent female-to-male
transplantation. Of sex-matched pairs, female-to-male donation had the
lowest proportion of undersized hearts using weight and BMI ratio
metrics (10.5\% and 5.2\%) but had the highest proportion of undersizing
using pHM metrics (48.1\%) (all P\textless{}0.001). Female-to-male
recipients had the lowest rate of unadjusted one-year survival (90.0\%,
P = 0.0169), and increased hazards of mortality after risk adjustment
(OR 1.17, 95\% CI 1.01-1.36, P=0.034)). Undersizing using pHM
(donor-recipient ratio \textless{} 0.85) was the only metric found to be
associated in increased mortality after risk adjustment (OR 1.32, 95\%
CI 1.02 to 1.71, P=0.035). Conclusions: Female-to-male heart
transplantation has the worst survival of all sex-matching combinations.
Although female donors in this cohort are appropriately sized using
traditional metrics, half are under-sized using pHM. This, combined with
its strong association with mortality, underscores the importance of
routine pHM assessment when evaluating female donors for male
recipients.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Orthotopic heart transplantation (OHT) remains the gold standard
treatment for advanced stage heart failure\textsuperscript{1}. When
selecting an appropriate donor for each intended recipient, it is
paramount that donor-to-recipient sizing is within acceptable standards
in order to meet the cardiac output demands of its
recipient\textsuperscript{2,3}. As a donor heart under consideration
typically cannot be directly inspected prior to the deployment of a
harvesting team, a number of different metrics have been utilized in
clinical practice as a quick tool for sizing. These metrics include
height, weight, and/or body mass index (BMI) ratios, and even predicted
heart mass (pHM) calculations\textsuperscript{2--6}. For weight sizing,
some experts have advocated to finding a donor-recipient match pair with
[?] 30\% weight discrepancy\textsuperscript{7}, but others advocate for a
more conservative [?] 20\% discrepancy\textsuperscript{8,9}. However, the
correlations with some of these measurements to actual heart size have
come into question.

In addition to choosing a donor heart of optimal size, considerations
must also be taken into donor and recipient gender. Prior study has
suggested that female to male (FtoM) donation may be associated with
increased risk of posttransplant mortality\textsuperscript{10--13}. A
possible explanation is that a donor female graft may be more likely to
be under-sized when paired with a male recipient, resulting in a cardiac
supply-demand mismatch in the posttransplant period. As there is no
definitive consensus with regards to how donor-recipient heart sizing
should be conducted, we sought to analyze the distributions of sizing in
the FtoM OHT population using available sizing metrics. We aimed to
investigate the impacts of these metrics on posttransplant survival in
this potentially higher-risk transplant cohort.

\textbf{Patients and Methods}

\emph{Data Source}

The United Network for Organ Sharing (UNOS) database was utilized for
this study, which is a prospectively collected registry of all United
States solid organ transplants since 1987. For this study, we analyzed
patients who underwent isolated, primary 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}

For this analysis, we included adult patients (18 years or older) who
underwent OHT within the aforementioned study period. Patients who
underwent concurrent simultaneous OHT with any other solid organ
transplants, as well as heterotopic heart transplants were excluded.
Patients were stratified based on donor-recipient sex pairing.

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

\emph{Statistical Analysis}

Continuous data are presented as mean (\selectlanguage{ngerman}± standard deviation) for
normally distributed variables or median (interquartile range (IQR)) for
non-normally distributed variables. Categorical data are displayed as
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 non-normally
distributed variables. Categorical variables were compared using chi
square and Fisher's exact test as indicated.

Kaplan Meier survival analysis was used to compare actuarial survival
between patient cohorts. Multivariable logistic regression was performed
to evaluate the risk-adjusted predictors of one-year posttransplant
mortality. Statistical analysis was performed using Stata version 16
(StataCorp, College Station, TX, USA).

\textbf{Results}

This study included a total of 22,450 OHT recipients. Of these, 13,389
(59.6\%) were male and received a heart from a male donor (MtoM), 3,660
(16.3\%) were female and received a heart from a female donor (FtoF). A
total of 2,292 (10.2\%) recipients were female and received a heart from
a male donor (MtoF), and 3,019 (13.4\%) were male and received a heart
from a female donor (FtoM). Baseline recipient, donor, and transplant
characteristics are presented in \textbf{Table 1} . Median age was
highest in the FtoM cohort, and this cohort had both the highest
percentage of patients with ischemic cardiomyopathy and lowest
percentage of patients with nonischemic cardiomyopathy (all
P\textless{}0.001).

Distributions of donor-to-recipient sizing are presented in\textbf{Table
2} . For the weight and BMI metrics, a cutoff of \textgreater{} 20\%
donor-to-recipient discrepancy, or a donor-to-recipient ratio
\textless{} 0.8 were used to define ``undersized''. A \textgreater{}
15\% donor-to-recipient discrepancy, or a donor-to-recipient ratio
\textless{} 0.85 were used to define undersizing using the pHM metric.
These thresholds were based on prior
publications\textsuperscript{6,8,9}. FtoM recipients were least commonly
undersized based on weight and BMI sizing metrics (both
P\textless{}0.001). When using the pHM sizing metric, FtoM recipients
were most commonly undersized (48.1\% undersized, P\textless{}0.001).

Following OHT, the FtoM cohort experienced the highest incidence of
renal failure requiring dialysis (\textbf{Table 3} ) (P=0.039). Rates of
posttransplant stroke and pacemaker placement were equivalent.
Thirty-day mortality was highest in the FtoM cohort and lowest in the
MtoF cohort (4.6\% vs 2.9\%, P=0.003). Drug-treated acute graft
rejection within the first year of transplantation was highest in the
FtoF cohort and lowest in the MtoM cohort (16.5\% vs 9.7\%,
P\textless{}0.001).

Median follow up time was 2.98 years (IQR 1.00 to 5.63 years). At one
year, actuarial survival was greatest in the MtoF cohort (92.0\%).
Actuarial survival was lowest in the FtoM cohort (90.0\%, P=0.0169).
Kaplan Meier survival comparison of all donor-recipient sex pairs are
displayed in \textbf{Figure 1} .

A multivariable analysis was performed to identify independent
risk-adjusted predictors of one-year mortality following OHT. This
analysis adjusted for multiple independent predictors of mortality
including race, heart failure etiology, body mass index, pretransplant
mechanical ventilation or use of intra-aortic balloon pump, ventricular
assist device, donor age, and graft cold ischemia time. Predictors are
presented in \textbf{Table 4} . In this analysis, both FtoF (HR 1.29,
95\% CI 1.14 to 1.62, P=0.001) and FtoM (OR 1.17, 95\% CI 1.01 to 1.36,
P=0.034) donation were associated with increased odds for mortality (in
relation to MtoM).

Because the FtoM cohort was found to have the lowest unadjusted 30-day
and one-year mortality, we investigated the impact of various
donor-recipient sizing metrics on posttransplant outcomes. In a
univariable analysis, donor weight undersizing was associated with a 1\%
increase in odds for one-year mortality for each 1\% undersized in
relation to the recipient, though these findings did not reach
statistical significance (OR 1.01, 95\% CI 1.00 to 1.01, P=0.055). This
relation was also observed with undersizing based on pHM, and did not
meet statistical significance (OR 1.01, 95\% CI 1.00 to 1.02, P=0.170).
Undersizing by BMI was found to have a significant association with
one-year mortality (per 1\% undersized, OR 1.01, 95\% CI 1.00 to 1.01,
P=0.008).

Multivariable logistic regression was performed to identify independent
risk factors of one-year posttransplant mortality in the FtoM cohort. In
this model, donor-recipient sizing metrics were adjusted for recipient
age, year of transplantation, heart failure etiology, total bilirubin
and serum creatinine, pretransplant mechanical ventilation, ventricular
assist device, and waitlist time. Full models are displayed
in\textbf{Supplemental Tables 1 -- 3} . In these models, donor heart
undersizing was significantly associated increased odds of mortality for
all three sizing metrics (\textbf{Table 5} ). For each sizing metric, a
1\% increase in the degree of undersizing was associated with a 1\%
increase in odds of one-year mortality. A large change in
donor-recipient sizing ratio (50\% reduction, or recipient value twice
that of the donor value) was associated with significant increases in
odds of mortality. Of sizing metrics, a 50\% reduction in pHM ratio had
the highest odds of mortality (OR 3.74, 95 CI 1.25 to 11.16, P=0.018).

Donor sizing metrics were also analyzed as categorical variables with
weight and BMI ratios of \textless{} 0.8 considered undersized, and with
a pHM \textless{} 0.85 considered undersized. In these analyses after
risk adjustment, both undersizing based on weight (OR 1.40, 95\% CI 0.94
to 2.07, P=0.095) and BMI (OR 1.47, 95\% CI 0.84 to 2.58, P=0.180) were
not significantly associated with posttransplant mortality. Undersizing
using the pHM metric was associated with a significant increase in
mortality (OR 1.32, 95\% CI 1.02 to 1.71, P=0.035).

\textbf{Discussion}

In this analysis, we found FtoM donation to be associated with the
lowest rate of 30-day and one-year survival in comparison of all
sex-match pairs, and female donation (both FtoF and FtoM) to be
associated with increased risk adjusted hazards for one-year mortality.
There was incremental risk of mortality with incremental degree of donor
heart undersizing using all three donor-to-recipient sizing metrics
within the FtoM cohort. However, based on prior sizing thresholds, only
pHM was found to have significant impacts on mortality. With large
degrees of undersizing, pHM was found to have the strongest associations
with mortality. Additionally, we found that approximately half of FtoM
recipients receive a donor heart with a donor-recipient pHM ratio that
is \textless{} 0.85.

Existing analyses investigating the impacts of donor undersizing based
on weight (donor-recipient weight ratio \textless{} 0.8) have had mixed
conclusions\textsuperscript{7,8,14}. Jayarajan and colleagues did not
find associations with use of weight-undersized donors and survival in
either sex-matched or MtoF recipients. However, in FtoM recipients,
undersizing using weight metrics was associated with decreased median
posttransplant survival (435 days, P=0.0241) and risk adjusted hazards
for mortality (HR 1.201, P=0.0383)\textsuperscript{14}. Bergenfeldt and
colleagues found weight undersizing to be associated with increased
mortality, but these findings did not apply to obese
recipients\textsuperscript{2}. Other studies have identified undersizing
based on weight to be associated with increased mortality in UNOS status
1 patients\textsuperscript{7} and patients with increased pulmonary
vascular resistance\textsuperscript{15}. Other groups have suggested
undersizing based on weight metrics to be associated with early graft
failure\textsuperscript{16,17}. In our analysis, we did not find
donor-recipient weight ratio \textless{} 0.8 to be significantly
associated with survival in the FtoM transplant cohort.

Other groups have advocated the use of pHM as a better means of
donor-recipient heart sizing\textsuperscript{3,6}. Kransdorf \emph{et
al} studied the use of pHM in the general OHT
population\textsuperscript{6}. In their analysis, undersizing based on
pHM (donor-recipient ratio \textless{} 0.86) was associated with
increased hazards for one-year mortality (HR 1.34, 95\% CI 1.13 to 1.59,
P\textless{}0.001). In this analysis, undersizing based on weight, BMI
height, or body surface area metrics were not found to have significant
impacts on posttransplant survival in the general OHT population. They
concluded that a minimum donor-recipient pHM ratio of 0.86 was required
to sustain optimal cardiac output\textsuperscript{18}. When analyzing
the FtoM cohort, we found increased risk adjusted mortality risk in
those who were undersized using pHM metrics, all while no associations
were found using either weight or BMI.

Prior report has suggested increased mortality following sex-mismatched
transplants, but only when the recipient is male\textsuperscript{10}.
This decreased survival in the FtoM cohort was observed at one year, but
longer-term impacts are not as well understood. A possible explanation
for increased mortality in this cohort may be that there is a higher
propensity for female donors to be undersized in relation to their male
recipients. Previous study has suggested that an undersized donor heart
may be able to increase left ventricular mass over time to adapt to
increases in systemic demand\textsuperscript{19}. If true, the impacts
of donor undersizing may be greatest within the first year following
transplantation.

The relationship between sex-pairing and donor sizing has proven rather
complex. When evaluating female donors for male recipients, our study
found this sex-paired combination to have the lowest rates of
undersizing when using weight or BMI metrics. Furthermore, Bergenfeldt
and colleagues have found no associations with FtoM donation and
inappropriate weight matched donors (donor-recipient weight ratio
\textless{}0.7)\textsuperscript{2}. It is possible that this propensity
for undersizing and possibility for decreased survival to be known by
transplanting surgeons, and that precaution is taken to not
``undersize'' a female donor to a male recipient when using BMI or
weight-based metrics. However, when analyzing this population with the
pHM metric, nearly half of the FtoM recipients were undersized
(donor-recipient pHM ratio \textless{} 0.85). Reed and colleagues found
that pHM discrepancies of \textgreater{} 10-15\% to be associated with
increased mortality\textsuperscript{3}. Such findings may account for
decreased survival in the FtoM OHT population. It is possible that
differences in distributions of body fat between males and females may
result in differential relationships between body weight/BMI and heart
size. Therefore, weight or BMI-based sizing in sex-mismatched pairs may
ultimately be inaccurate. It is possible that pHM sizing may result in
more appropriate sizing calculations when evaluating sex-mismatched
donor pairs.

\emph{Limitations}

This study was prone to limitations due to its retrospective and
non-randomized design. In choosing a potential donor graft for a
recipient, it is common for surgeons to employ some form of
donor-to-recipient sizing prior to organ acceptance. In this study, the
analysis was conducted on patients who underwent OHT, and therefore,
donor-to-recipient pairing was not randomized. As a result, the true
relationship between donor heart sizing and outcomes may be
underestimated.

\emph{Conclusions}

In this analysis of patients undergoing primary OHT, we found FtoM
recipients to have the lowest unadjusted one-year posttransplant
survival, and both FtoF and FtoM donation to be associated with
increased hazards of mortality after risk adjustment. When looking at
proportions of undersizing in these donor-to-recipient sex matching
cohorts, FtoM had the lowest rates of undersizing using weight and BMI
sizing metrics. However, when looking at distributions of sizing using
the pHM metric, FtoM recipients were actually most frequently
undersized, accounting for nearly half of the population. In this
cohort, increasing degree of undersizing is associated with increased
hazards of mortality using all sizing metrics. However, in large degrees
of undersizing, pHM had the largest associations with increased
mortality. It appears that donor-to-recipient sizing using weight and
BMI may be misleading in this FtoM cohort, and pHM may be the best
sizing metric to use for these higher-risk patient subset.

\textbf{Acknowledgements}

None

\textbf{Disclosures}

IS receives institutional research support from Medtronic and Atricure
and serves as a consultant for Medtronic Vascular. AK is on the medical
advisory board for Medtronic, Inc. These affiliations do not create
direct conflicts with the content of this manuscript.

\textbf{References}

1. Khush KK, Cherikh WS, Chambers DC, et al. The International Thoracic
Organ Transplant Registry of the International Society for Heart and
Lung Transplantation: Thirty-sixth adult heart transplantation report
--- 2019; focus theme: Donor and recipient size match. \emph{J Hear Lung
Transplant} . 2019;38(10):1056-1066. doi:10.1016/j.healun.2019.08.004

2. Bergenfeldt H, Stehlik J, Höglund P, Andersson B, Nilsson J.
Donor--recipient size matching and mortality in heart transplantation:
Influence of body mass index and gender. \emph{J Hear Lung Transplant} .
2017;36(9):940-947. doi:10.1016/j.healun.2017.02.002

3. Reed RM, Netzer G, Hunsicker L, et al. Cardiac Size and Sex-Matching
in Heart Transplantation: Size Matters in Matters of Sex and the
Heart.\emph{JACC Hear Fail} . 2014;2(1):73-83.
doi:10.1016/j.jchf.2013.09.005

4. Rudasill SE, Sanaiha Y, Mardock AL, et al. Height mismatch: An
overlooked component of adult heart transplant outcomes. \emph{Clin
Transplant} . 2020;34(6). doi:10.1111/ctr.13863

5. Shah M, Saeed O, Shin J, et al. Predicted heart mass--based size
matching among recipients with moderate pulmonary hypertension: Outcomes
and sex effect. \emph{J Hear Lung Transplant} . 2020;39(7):648-656.
doi:10.1016/j.healun.2020.01.1339

6. Kransdorf EP, Kittleson MM, Benck LR, et al. Predicted heart mass is
the optimal metric for size match in heart transplantation. \emph{J Hear
Lung Transplant} . 2019;38(2):156-165. doi:10.1016/j.healun.2018.09.017

7. Blackbourne LH, Tribble CG, Langenburg SE, et al. Successful use of
undersized donors for orthotopic heart transplantation-with a
caveat.\emph{Ann Thorac Surg} . 1994;57(6):1472-1476.
doi:10.1016/0003-4975(94)90103-1

8. Sethi GK, Lanauze P, Rosado LJ, et al. Clinical significance of
weight difference between donor and recipient in heart
transplantation.\emph{J Thorac Cardiovasc Surg} . 1993.
doi:10.1016/s0022-5223(19)34077-2

9. Patel ND, Weiss ES, Nwakanma LU, et al. Impact of donor-to-recipient
weight ratio on survival after heart transplantation: analysis of the
United Network for Organ Sharing Database. \emph{Circulation} .
2008;118(14 Suppl). doi:10.1161/CIRCULATIONAHA.107.756866

10. Ayesta A, Urrútia G, Madrid E, Vernooij RWM, Vicent L,
Martínez-Sellés M. Sex-mismatch influence on survival after heart
transplantation: A systematic review and meta-analysis of observational
studies. \emph{Clin Transplant} . 2019. doi:10.1111/ctr.13737

11. Welp H, Spieker T, Erren M, Scheld HH, Baba HA, Stypmann J. Sex
Mismatch in Heart Transplantation Is Associated With Increased Number of
Severe Rejection Episodes and Shorter Long-Term
Survival.\emph{Transplant Proc} . 2009;41(6):2579-2584.
doi:10.1016/j.transproceed.2009.06.098

12. Khush KK, Kubo JT, Desai M. Influence of donor and recipient sex
mismatch on heart transplant outcomes: Analysis of the International
Society for Heart and Lung Transplantation Registry. \emph{J Hear Lung
Transplant} . 2012;31(5):459-466. doi:10.1016/j.healun.2012.02.005

13. Martinez-Selles M, Almenar L, Paniagua-Martin MJ, et al.
Donor/recipient sex mismatch and survival after heart transplantation:
only an issue in male recipients? An analysis of the Spanish Heart
Transplantation Registry. \emph{Transpl Int} . 2015;28(3):305-313.
doi:10.1111/tri.12488

14. Jayarajan SN, Taghavi S, Komaroff E, Mangi AA. Impact of low donor
to recipient weight ratios on cardiac transplantation. \emph{J Thorac
Cardiovasc Surg} . 2013;146(6):1538-1543.
doi:10.1016/j.jtcvs.2013.06.028

15. Russo MJ, Iribarne A, Hong KN, et al. Factors associated with
primary graft failure after heart transplantation.\emph{Transplantation}
. 2010;90(4):444-450. doi:10.1097/TP.0b013e3181e6f1eb

16. D'Alessandro C, Golmard JL, Barreda E, et al. Predictive risk
factors for primary graft failure requiring temporary extra-corporeal
membrane oxygenation support after cardiac transplantation in
adults.\emph{Eur J Cardio-thoracic Surg} . 2011;40(4):962-969.
doi:10.1016/j.ejcts.2011.01.064

17. Kobashigawa J, Zuckermann A, Macdonald P, et al. Report from a
consensus conference on primary graft dysfunction after cardiac
transplantation. \emph{J Hear Lung Transplant} . 2014;33(4):327-340.
doi:10.1016/j.healun.2014.02.027

18. Dewey FE, Rosenthal D, Murphy DJ, Froelicher VF, Ashley EA. Does
Size Matter?-Clinical Applications of Scaling Cardiac Size and Function
for Body Size. \emph{Circulation} . 2008;117(17):2279-2287.
doi:10.1161/CIRCULATIONAHA.107.736785

19. Mather PJ, Jeevanandam V, Eisen HJ, et al. Functional and
morphologic adaptation of undersized donor hearts after heart
transplantation. \emph{J Am Coll Cardiol} . 1995;26(3):737-742.
doi:10.1016/0735-1097(95)00216-Q

\textbf{Table 1.} Baseline donor, recipient, and transplant
characteristics of patients undergoing OHT according to donor-recipient
sex-paired cohorts\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& \textbf{Male to Male} & \textbf{Female to Female} & \textbf{Male to
Female} & \textbf{Female to Male} & \textbf{P-Value}\tabularnewline
\midrule
\endhead
& \textbf{N=13,389} & \textbf{N=3,660} & \textbf{N=2,292} &
\textbf{N=3,019} &\tabularnewline
\textbf{Recipient Characteristics} & & & & &\tabularnewline
Age (years) & 57 (48-64) & 55 (43-62) & 53 (41-61) & 59 (50-65) &
\textless{}0.001\tabularnewline
Race & & & & &\tabularnewline
White & 9,061 (68.0\%) & 2,261 (62.2\%) & 1,352 (59.4\%) & 1,999
(66.6\%) & \textless{}0.001\tabularnewline
Black & 2,748 (20.6\%) & 940 (25.9\%) & 674 (29.6\%) & 444 (14.8\%)
&\tabularnewline
Hispanic & 1,026 (7.7\%) & 298 (8.2\%) & 178 (7.8\%) & 345 (11.5\%)
&\tabularnewline
Asian & 400 (3.0\%) & 112 (3.1\%) & 61 (2.7\%) & 199 (6.6\%)
&\tabularnewline
Other & 84 (0.6\%) & 22 (0.6\%) & 13 (0.6\%) & 16 (0.5\%)
&\tabularnewline
BMI (kg/m\textsuperscript{2}) & 27.99 (4.60) & 26.49 (5.29) & 27.28
(5.34) & 26.38 (4.51) & \textless{}0.001\tabularnewline
Heart Failure Etiology & & & & &\tabularnewline
Non-Ischemic & 6,609 (49.4\%) & 2,299 (63.0\%) & 1,477 (64.6\%) & 1,314
(43.6\%) & \textless{}0.001\tabularnewline
Ischemic & 5,252 (39.3\%) & 656 (18.0\%) & 406 (17.8\%) & 1,329 (44.1\%)
&\tabularnewline
Congenital & 315 (2.4\%) & 161 (4.4\%) & 108 (4.7\%) & 75 (2.5\%)
&\tabularnewline
Restrictive & 418 (3.1\%) & 168 (4.6\%) & 84 (3.7\%) & 125 (4.1\%)
&\tabularnewline
Valvular & 159 (1.2\%) & 64 (1.8\%) & 36 (1.6\%) & 36 (1.2\%)
&\tabularnewline
Hypertrophic & 264 (2.0\%) & 178 (4.9\%) & 96 (4.2\%) & 58 (1.9\%)
&\tabularnewline
Other & 18 (0.1\%) & 10 (0.3\%) & 4 (0.2\%) & 4 (0.1\%) &\tabularnewline
Diabetes Mellitus & 3,954 (29.6\%) & 830 (22.8\%) & 519 (22.7\%) & 886
(29.4\%) & \textless{}0.001\tabularnewline
Total Bilirubin (mg/dL) & 1.00 (1.67) & 0.85 (1.12) & 0.94 (1.65) & 1.00
(1.52) & \textless{}0.001\tabularnewline
Serum Creatinine (mg/dL) & 1.30 (0.59) & 1.08 (0.62) & 1.08 (0.55) &
1.26 (0.45) & \textless{}0.001\tabularnewline
Positive CMV Serology & 6,985 (52.2\%) & 2,308 (63.1\%) & 1,471 (64.2\%)
& 1,721 (57.0\%) & \textless{}0.001\tabularnewline
Pretransplant Infection & 1,457 (11.2\%) & 288 (8.1\%) & 227 (10.2\%) &
224 (7.6\%) & \textless{}0.001\tabularnewline
Transfusion on Waitlist & 3,074 (23.7\%) & 646 (18.2\%) & 462 (20.8\%) &
628 (21.3\%) & \textless{}0.001\tabularnewline
Mechanical Ventilation & 160 (1.2\%) & 41 (1.1\%) & 15 (0.7\%) & 53
(1.8\%) & 0.003\tabularnewline
Intensive Care Unit & 4,108 (30.7\%) & 1,064 (29.1\%) & 806 (35.2\%) &
960 (31.8\%) & \textless{}0.001\tabularnewline
Intravenous Inotropes & 4,371 (32.6\%) & 1,472 (40.2\%) & 908 (39.6\%) &
1,206 (39.9\%) & \textless{}0.001\tabularnewline
Intra-Aortic Balloon Pump & 1,320 (9.9\%) & 325 (8.9\%) & 235 (10.3\%) &
288 (9.5\%) & 0.25\tabularnewline
Extracorporeal Membrane Oxygenation & 172 (1.3\%) & 34 (0.9\%) & 35
(1.5\%) & 34 (1.1\%) & 0.17\tabularnewline
\textbf{Donor Characteristics} & & & & &\tabularnewline
Donor Age (years) & 29 (22-39) & 34 (24-43) & 27 (21-37) & 35 (26-44) &
\textless{}0.001\tabularnewline
Donor Race & & & & &\tabularnewline
White & 8,487 (63.4\%) & 2,506 (68.5\%) & 1,315 (57.4\%) & 2,069
(68.5\%) & \textless{}0.001\tabularnewline
Black & 2,283 (17.1\%) & 522 (14.3\%) & 385 (16.8\%) & 483 (16.0\%)
&\tabularnewline
Asian & 2,204 (16.5\%) & 496 (13.6\%) & 512 (22.3\%) & 374 (12.4\%)
&\tabularnewline
Hispanic & 209 (1.6\%) & 93 (2.5\%) & 38 (1.7\%) & 46 (1.5\%)
&\tabularnewline
Other & 206 (1.5\%) & 43 (1.2\%) & 42 (1.8\%) & 47 (1.6\%)
&\tabularnewline
BMI (kg/m\textsuperscript{2}) & 27.26 (5.43) & 27.98 (6.82) & 25.11
(4.84) & 30.07 (7.17) & \textless{}0.001\tabularnewline
Mechanism of Death & & & & &\tabularnewline
Trauma & 7,387 (55.2\%) & 1,029 (28.1\%) & 1,318 (57.6\%) & 841 (27.9\%)
& \textless{}0.001\tabularnewline
Cardiovascular & 2,061 (15.4\%) & 1,123 (30.7\%) & 339 (14.8\%) & 973
(32.2\%) &\tabularnewline
Drug Overdose & 1,772 (13.2\%) & 616 (16.8\%) & 218 (9.5\%) & 486
(16.1\%) &\tabularnewline
Other & 2,167 (16.2\%) & 889 (24.3\%) & 414 (18.1\%) & 719 (23.8\%)
&\tabularnewline
Diabetes Mellitus & 410 (3.1\%) & 192 (5.3\%) & 64 (2.8\%) & 166 (5.5\%)
& \textless{}0.001\tabularnewline
Hypertension & 4,228 (31.9\%) & 1,169 (32.3\%) & 667 (29.4\%) & 977
(32.6\%) & 0.061\tabularnewline
Serum Creatinine (mg/dL) & 1.60 (1.60) & 1.26 (1.33) & 1.46 (1.50) &
1.28 (1.29) & \textless{}0.001\tabularnewline
Donor LVEF \textless{}50\% & 207 (1.5\%) & 50 (1.4\%) & 33 (1.4\%) & 38
(1.3\%) & 0.63\tabularnewline
Positive CMV Serology & 7,755 (58.2\%) & 2,482 (68.1\%) & 1,406 (61.6\%)
& 2,024 (67.4\%) & \textless{}0.001\tabularnewline
Hepatitis C Positive & 445 (3.3\%) & 140 (3.8\%) & 52 (2.3\%) & 92
(3.0\%) & 0.010\tabularnewline
\textbf{Transplant Characteristics} & & & & &\tabularnewline
Days Listed & 118 (31-335) & 75 (21-232) & 72 (19-237) & 77 (19-249) &
\textless{}0.001\tabularnewline
Donor Distance from Recipient Hospital (nautical miles) & 86 (12-275) &
151 (22-352) & 92.5 (12-281.5) & 123 (22-334) &
\textless{}0.001\tabularnewline
Cold Ischemic Time (hours) & 3.1 (2.4-3.8) & 3.2 (2.5-3.9) & 3.1
(2.3-3.8) & 3.3 (2.5-3.9) & \textless{}0.001\tabularnewline
\bottomrule
\end{longtable}

BMI, body mass index

CMV, cytomegalovirus

LVEF, left ventricular ejection fraction

\textbf{Table 2.} Incidence of donor graft undersizing according to
three available sizing metrics

among various donor-recipient sex-paired cohorts\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& \textbf{Male to Male} & \textbf{Female to Female} & \textbf{Male to
Female} & \textbf{Female to Male} & \textbf{P-Value}\tabularnewline
\midrule
\endhead
& \textbf{N=13,389} & \textbf{N=3,660} & \textbf{N=2,292} &
\textbf{N=3,019} &\tabularnewline
\textbf{Weight Ratio} & & & & &\tabularnewline
Normal ([?]0.8) & 11,042 (82.5\%) & 3,274 (89.5\%) & 2,003 (87.4\%) &
2,702 (89.5\%) & \textless{}0.001\tabularnewline
Undersized (\textless{}0.8) & 2,347 (17.5\%) & 386 (10.5\%) & 289
(12.6\%) & 317 (10.5\%) &\tabularnewline
\textbf{BMI Ratio} & & & & &\tabularnewline
Normal ([?]0.8) & 10,955 (81.8\%) & 3,195 (87.3\%) & 1,654 (72.2\%) &
2,861 (94.8\%) & \textless{}0.001\tabularnewline
Undersized (\textless{}0.8) & 2,434 (18.2\%) & 465 (12.7\%) & 638
(27.8\%) & 158 (5.2\%) &\tabularnewline
\textbf{pHM Ratio} & & & & &\tabularnewline
Normal ([?]0.85) & 12,361 (92.3\%) & 3,465 (94.7\%) & 2,287 (99.8\%) &
1,568 (51.9\%) & \textless{}0.001\tabularnewline
Undersized (\textless{}0.85) & 1,028 (7.7\%) & 195 (5.3\%) & 5 (0.2\%) &
1,451 (48.1\%) &\tabularnewline
\bottomrule
\end{longtable}

BMI, body mass index

pHM, predicted heart mass

\textbf{Table. 3.} Posttransplant outcomes among various sex-matched
cohorts\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& \textbf{Male to Male} & \textbf{Female to Female} & \textbf{Male to
Female} & \textbf{Female to Male} & \textbf{P-Value}\tabularnewline
\midrule
\endhead
& \textbf{N=13,389} & \textbf{N=3,660} & \textbf{N=2,292} &
\textbf{N=3,019} &\tabularnewline
Renal Failure Requiring Dialysis & 1,509 (11.5\%) & 404 (11.3\%) & 215
(9.6\%) & 354 (11.9\%) & 0.039\tabularnewline
Stroke & 384 (2.9\%) & 93 (2.6\%) & 77 (3.4\%) & 81 (2.7\%) &
0.29\tabularnewline
Permanent Pacemaker & 388 (3.0\%) & 102 (2.8\%) & 63 (2.8\%) & 82
(2.8\%) & 0.93\tabularnewline
Hospital Length of Stay (days) & 15 (11-22) & 16 (11-24) & 15 (11-22) &
15 (11-23) & \textless{}0.001\tabularnewline
Drug-Treated Acute Rejection & 1,276 (9.7\%) & 597 (16.5\%) & 305
(13.5\%) & 300 (10.1\%) & \textless{}0.001\tabularnewline
30-Day Mortality & 433 (3.3\%) & 126 (3.6\%) & 64 (2.9\%) & 135 (4.6\%)
& 0.003\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4.} Multivariable Logistic Regression for one-year
mortality following OHT.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{Odds Ratio} & \textbf{95\% Confidence Interval} &
\textbf{P-Value}\tabularnewline
\midrule
\endhead
Age, increasing, per year & 1.02 & 1.02, 1.03 &
\textless{}0.001\tabularnewline
Transplant year, increasing, per year & 1.08 & 1.06, 1.10 &
\textless{}0.001\tabularnewline
Race & & &\tabularnewline
White & Ref & Ref & Ref\tabularnewline
Black & 1.03 & 0.90, 1.17 & 0.684\tabularnewline
Hispanic & 1.36 & 1.14, 1.62 & 0.001\tabularnewline
Asian & 1.01 & 0.75, 1.35 & 0.961\tabularnewline
Other & 0.40 & 0.16, 1.00 & 0.051\tabularnewline
Donor-Recipient Sex Match & & &\tabularnewline
MtoM & Ref & Ref & Ref\tabularnewline
FtoF & 1.29 & 1.12, 1.49 & 0.001\tabularnewline
MtoF & 1.19 & 1.00, 1.42 & 0.057\tabularnewline
FtoM & 1.17 & 1.01, 1.36 & 0.034\tabularnewline
BMI, increasing, per 1 kg/m2 & 1.03 & 1.02, 1.04 &
\textless{}0.001\tabularnewline
Heart Failure Etiology & & &\tabularnewline
Non-Ischemic & Ref & Ref & Ref\tabularnewline
Ischemic & 1.11 & 0.99, 1.25 & 0.078\tabularnewline
Congenital & 3.04 & 2.32, 4.00 & \textless{}0.001\tabularnewline
Restrictive & 1.50 & 1.16, 1.94 & 0.002\tabularnewline
Valvular & 0.95 & 0.59, 1.52 & 0.824\tabularnewline
Hypertrophic & 1.11 & 0.79, 1.56 & 0.534\tabularnewline
Other & 5.04 & 2.16, 11.76 & \textless{}0.001\tabularnewline
Diabetes mellitus & 1.09 & 0.98, 1.22 & 0.128\tabularnewline
Total bilirubin, increasing, per 1 mg/dL & 1.16 & 1.12, 1.19 &
\textless{}0.001\tabularnewline
Serum creatinine, increasing, per 1 mg/dL & 1.16 & 1.08, 1.24 &
\textless{}0.001\tabularnewline
Pretransplant mechanical ventilation & 3.10 & 2.20, 4.36 &
\textless{}0.001\tabularnewline
Pretransplant ICU & 1.19 & 1.05, 1.36 & 0.008\tabularnewline
Pretransplant IABP & 1.31 & 1.07, 1.59 & 0.008\tabularnewline
VAD device & & &\tabularnewline
None & Ref & Ref & Ref\tabularnewline
LVAD & 1.34 & 1.19, 1.52 & \textless{}0.001\tabularnewline
RVAD & 2.24 & 0.93, 5.39 & 0.073\tabularnewline
TAH & 4.08 & 2.86, 5.81 & \textless{}0.001\tabularnewline
LVAD + RVAD & 1.86 & 1.35, 2.56 & \textless{}0.001\tabularnewline
Donor age, increasing, per year & 1.01 & 1.00, 1.01 &
\textless{}0.001\tabularnewline
Graft cold ischemia time, increasing, per hour & 1.18 & 1.13, 1.23 &
\textless{}0.001\tabularnewline
Waitlist time, increasing, per day & 1.00 & 1.00, 1.00 &
0.137\tabularnewline
\bottomrule
\end{longtable}

BMI, body mass index

ICU, intensive care unit

LVAD, left ventricular assist device

FtoM, female-to-male

FtoF, female-to-female

MtoF, male-to-female

MtoM, male-to-male

RVAD, right ventricular assist device

TAH, total artificial heart

VAD, ventricular assist device

\textbf{Table 5.} Multivariable logistic regression for one-year
mortality of OHT recipients undergoing female-to-male donation\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{Odds Ratio} & \textbf{95\% Confidence Interval} &
\textbf{P-Value}\tabularnewline
\midrule
\endhead
\textbf{Donor-Recipient Under-Sizing, per 1\%} & & &\tabularnewline
Weight & 1.01 & 1.00, 1.01 & 0.013\tabularnewline
BMI & 1.01 & 1.00, 1.01 & 0.002\tabularnewline
pHM & 1.01 & 1.00, 1.02 & 0.039\tabularnewline
\textbf{Donor-Recipient Ratio, per 50\% reduction} & & &\tabularnewline
Weight & 2.21 & 1.29, 3.78 & 0.004\tabularnewline
BMI & 2.43 & 1.49, 3.99 & \textless{}0.001\tabularnewline
pHM & 3.74 & 1.25, 11.16 & 0.018\tabularnewline
\bottomrule
\end{longtable}

BMI, body mass index

pHM, predicted heart mass

\textbf{Figure Legend}

\textbf{Figure 1.} One-year unadjusted posttransplant survival of all
four sex-paired recipient cohorts following orthotopic heart
transplantation\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure1/Figure1}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

