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\begin{document}

\title{Heart transplantation at the Peruvian National Heart Institute:
One-decade single-center experience}



\author[1]{Miguel Pinto-Salinas}%
\author[1]{Julio Morón-Castro}%
\author[1]{Fernando Chavarri-Velarde}%
\author[2]{Franz Soplopuco-Palacios}%
\author[3]{Luis Palma-Ortecho}%
\author[4]{Miguel Lescano-Alva}%
\affil[1]{Universidad Nacional Mayor de San Marcos}%
\affil[2]{Department of Cardiovascular Surgery Instituto Nacional Cardiovascular “Carlos Alberto Peschiera Carrillo” Lima Peru}%
\affil[3]{Department of Cardiopediatrics Instituto Nacional Cardiovascular “Carlos Alberto Peschiera Carrillo” Lima Peru}%
\affil[4]{Department of Clinical Cardiology Instituto Nacional Cardiovascular “Carlos Alberto Peschiera Carrillo” Lima Peru}%


\vspace{-1em}



  
  \date{June 14, 2024}


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\selectlanguage{english}
\begin{abstract}
\emph{Background:} Heart transplantations are ideal for most patients
with end-stage heart failure refractory to medical treatment. The
transplantation program at the Peruvian National Heart Institute started
with a 10-year-continuity in 2010. \emph{Objective:} To report the
results of a 10-year heart transplantation experience at the Peruvian
National Heart Institute. \emph{Methods:} We studied 83 patients who
underwent orthotopic heart transplantation at a single center between
January 2010 and December 2019. The recipients' profiles and survival
were analyzed according to sex and age group, ensuring the information's
confidentiality. \emph{Results:} The recipients' mean age was 41.2 \selectlanguage{ngerman}± 17
years, 88\% were adult, and 68.7\% were male. The main indications for
transplantation were idiopathic dilated cardiomyopathy. 85.5\% of
recipients were clinically categorized as INTERMACS Profile 1 to 3
before transplantation. There was a significant difference between sexes
regarding the preoperative left ventricular ejection fraction and
between age groups regarding the waiting time. The average ischemia time
was 3.1 hours, operating time was 6.1 hours, cardiopulmonary bypass time
was 3 hours, and aortic cross-clamp time was 1.7 hours. The principal
early postoperative complications were hematological disorders and acute
kidney failure. The principal late ones were kidney failure and severe
anemia. The postoperative mortality was 15.9\%, and the principal causes
were infection and then acute rejection. The survival at one, five, and
ten years was 87.5\%, 79.8\%, and 79.8\%, respectively. The survival
results were not influenced by sex or age group. \emph{Conclusion:} Our
patients' postoperative complications, mortality, and survival rates
coincided with those reported by the ISHLT registry.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Heart transplantation at the Peruvian National Heart Institute:
One-decade single-center experience}

\textbf{Authors:}

Pinto-Salinas M\textsuperscript{1}, Mor\selectlanguage{ngerman}ón-Castro J\textsuperscript{1,
2}, Chavarri-Velarde F\textsuperscript{1, 3}, Soplopuco-Palacios
F\textsuperscript{2}, Palma-Ortecho L\textsuperscript{3}, Lescano-Alva
M\textsuperscript{4}

\textbf{Affiliation:}

\begin{enumerate}
\tightlist
\item
  Medical School, Universidad Nacional Mayor de San Marcos, Lima, Peru.
\item
  Department of Cardiovascular Surgery, Instituto Nacional
  Cardiovascular ``Carlos Alberto Peschiera Carrillo,'' Lima, Peru.
\item
  Department of Cardiopediatrics, Instituto Nacional Cardiovascular
  ``Carlos Alberto Peschiera Carrillo,'' Lima, Peru.
\item
  Department of Clinical Cardiology, Instituto Nacional Cardiovascular
  ``Carlos Alberto Peschiera Carrillo,'' Lima, Peru.
\end{enumerate}

\textbf{Running title:}

Heart transplantation at Peru

\textbf{Correspondent author}

Miguel Pinto-Salinas MD

Universidad Nacional Mayor de San Marcos

755 Miguel Grau Avenue, Cercado de Lima, 15001 Lima, Peru

e-mail: miguel.pintosal@gmail.com

\textbf{Funding:} None

\textbf{Meeting presentation}

This manuscript was presented as part of Miguel Pinto-Salinas's
undergraduate thesis's support performed at the Universidad Nacional
Mayor de San Marcos Medical School on March 2, 2020 (1)(1).



\textbf{ABSTRACT}

Background: Heart transplantations are ideal for most patients with
end-stage heart failure refractory to medical treatment. The
transplantation program at the Peruvian National Heart Institute started
with a 10-year-continuity in 2010.

\emph{Objective:} To report the results of a 10-year heart
transplantation experience at the Peruvian National Heart Institute.

Methods: We studied 83 patients who underwent orthotopic heart
transplantation at a single center between January 2010 and December
2019. The recipients' profiles and survival were analyzed according to
sex and age group, ensuring the information's confidentiality.

Results: The recipients' mean age was 41.2 ± 17 years, 88\% were adult,
and 68.7\% were male. The main indications for transplantation were
idiopathic dilated cardiomyopathy. 85.5\% of recipients were clinically
categorized as INTERMACS Profile 1 to 3 before transplantation. There
was a significant difference between sexes regarding the preoperative
left ventricular ejection fraction and between age groups regarding the
waiting time. The average ischemia time was 3.1 hours, operating time
was 6.1 hours, cardiopulmonary bypass time was 3 hours, and aortic
cross-clamp time was 1.7 hours. The principal early postoperative
complications were hematological disorders and acute kidney failure. The
principal late ones were kidney failure and severe anemia. The
postoperative mortality was 15.9\%, and the principal causes were
infection and then acute rejection. The survival at one, five, and ten
years was 87.5\%, 79.8\%, and 79.8\%, respectively. The survival results
were not influenced by sex or age group.

\emph{Conclusion:} Our patients' postoperative complications, mortality,
and survival rates coincided with those reported by the ISHLT registry.

\emph{Keywords:} Heart transplantation, heart failure, transplant
recipients, cardiac surgery, survival.



\textbf{Introduction}

According to the International Society of Heart and Lung Transplantation
(ISHLT), heart transplantations (HTx) are the ideal treatment for
patients with end-stage heart failure (EHF) refractory to medical
treatment (2). Currently, worldwide survival is favorable, 80\% at one
year and 60\% at five years, mainly due to the development and
improvement of immunosuppressive treatment, the strict selection of
receptors, and the early diagnosis of postoperative complications (3).
Thus, approximately 124 700 HTx have been performed since Barnard's team
performed the first successful HTx in 1967, with approximately 5 000
transplants per year to date (2,4).

These reports include mostly data from Europe and North America (5).
However, the Latin American and Caribbean Transplantation Society
reports a registry of 9 000 patients with HTx by 2016 in Latin America.
In its registry, Peru shows around 97 HTx since 1993, considered one of
the lowest regional rates (6). It was not until 1972 that the first HTx
was carried out in Peru by Molina's team at Hospital Nacional Edgardo
Rebagliati Martins. However, it was an isolated case, and it was until
1993 when the first Peruvian HTx National Program was created with
Pacheco's team with some continuity (7). For a while since the late
1990s, HTxs were not carried out. It is impressive due to changes in
government policy and sociocultural factors, as in other developing
countries of the time, until the program was restarted at the Peruvian
National Heart Institute (INCOR) in 2010 (2,8). Since then, it has been
the only national reference center for HTx in Peru.

Given the lack of systematic reporting of experiences with regional
programs, we sought to compare transplant recipients' profiles and
survival from the Peruvian experience versus international benchmark
results. Furthermore, contributing to the global understanding of these
procedures' performance. Therefore, this study's objective was to report
the results of a 10-year HTX experience at INCOR.



\textbf{Materials and methods}

\textbf{IRB Approval:} This manuscript had an ethics approval by the
hospital Institutional Review Board.

\textbf{Consent Statement:} All research subjects signed and accepted
the institutional informed consent to carry out research work.

\textbf{Clinical trial registration:} N/A

\emph{Population and Study Design}

There were 86 records of patients who underwent human-to-human
orthotopic HTx at INCOR's database from January 2010 to December 2019.
We excluded three patients, two of whom were transplanted in other
centers, and one medical record was unavailable at the study time.
Therefore, we present 83 cases. There was no heart retransplantation,
and none of the recipients had to undergo major cardiac surgery after
the HTx. The profile of the recipients and their survival were analyzed
according to sex and age group. The confidentiality of the data was
ensured.

\emph{Surgical Procedure}

The surgical technique currently performed at INCOR is the
bicaval/unipulmonar described by Sarsam \emph{et al.} (10).

\emph{Antibiotic Prophylaxis Protocol}

Intravenous cefepime is included as antibiotic prophylaxis before
transplantation. If cephalosporin allergy is present, vancomycin is
chosen. It is prescribed at discharge oral trimethoprim/sulfamethoxazole
once daily, oral nystatin three times daily, after meals, rinsing and
swallowing, and topical clotrimazole twice daily. Oral valganciclovir is
added on intermediate to high-risk patients once daily.

\emph{Immunosuppression Protocol}

Our immunosuppressive protocol has been based on triple therapy:
corticosteroids, a calcineurin inhibitor, and an antiproliferative
agent. Induction therapy consisted of intravenous thymoglobulin (1.5
mg/kg/day) during the first five postoperative days and was preceded by
acetaminophen, methylprednisolone, and chlorphenamine. Thymoglobulin
dose was decreased (1 mg/kg/day) if leukocytes \textless{}3000
cells/mm\textsuperscript{3} or platelets \textless{}75000
cells/mm\textsuperscript{3}, and discontinued if leukocytes
\textless{}2000 cells/mm\textsuperscript{3} or platelets
\textless{}50000 cells/mm\textsuperscript{3}. Basiliximab (20 mg) is
also administrated, one drug regimen two hours preoperatively, and
another on the fourth postoperative day. The corticosteroid regimen
started with intravenous methylprednisolone (500 mg) in the preoperative
period and upon release of the aortic clamp, and 125 mg 3 times daily on
the first postoperative day. Prednisone (1 mg/kg/day) was continued
twice daily, with the dose being decreased 5 mg every three days until
reaching approximately 0.2 mg/kg/day by the sixth week. After six months
of treatment, it was tapered at 5 mg/day. Our institute currently
employs oral tacrolimus (0.05 -- 0.1 mg/kg/day) twice daily as a
calcineurin inhibitor and adjusted according to renal function. It is
titrated to achieve a serum level between 15 ng/mL and 20 ng/mL for the
first month, between 10 ng/mL and 15 ng/mL from months one to nine, and
between 5 ng/mL and 10 ng/mL after nine months from transplantation.
Cyclosporine is only considered in the presence of tacrolimus
intolerance. As an antiproliferative agent, we considered mycophenolate
mofetil 1g pre-transplant if there was no induction therapy and 1g twice
on the first day. Then it is tapered from 0.5g to 2g twice daily.
Indications for discharge consisted of oral prednisone twice daily in
descending doses of 5mg every three days until reaching 10 mg/day, oral
tacrolimus twice daily with serum controls at regular time intervals,
mycophenolate mofetil twice daily, and, eventually, everolimus.
Endomyocardial biopsies were performed before discharge, in the second
month, the third month, the sixth month, and one year after
transplantation.

\emph{Statistical Analysis}

Frequencies and percentages of qualitative variables were calculated,
and arithmetic means and standard deviations of quantitative variables.
Averages were compared using the Student's test for independent samples,
verifying the variables' normality using the Shapiro-Wilk test. In the
absence of normal distribution, the Mann-Whitney U test was used. The
value of p \textless{} 0.05 was accepted to determine the significant
differences in the statistical tests. Kaplan-Meier survival analysis was
performed with the log-rank test to compare the survival distributions
of the samples. The analysis was performed using SPSS Statistics 24.

\textbf{Results}

\emph{Recipients' Age and Sex}

The mean age at HTx was 41.2 ± 17 years (5 - 69 years), 73 (88\%) were
adult, and 57 (68.7\%) were male. The number of HTx performed according
to the recipients' sex and age group per year is shown in Figure 1. It
was observed an average of 8.3 HTx per year. A consecutive increase from
1 HTx in 2010 HTx to 13 in 2014. Then, it decreased to 5 by 2016, and a
maximum of 14 in 2019. Recipients' characteristics at HTx are shown in
Table 1.

\emph{Surgical Indications, Clinical Profile, and Comorbidities}

The main indications for HTx included idiopathic dilated cardiomyopathy
(DCM) in 55 (66.3\%) patients and ischaemic cardiomyopathy in 15
(18.1\%) patients. The other indications are also shown in Table 1.

The general preoperative left ventricular ejection fraction (LVEF) was
22.9 ± 14.5\% (6 - 70\%). In male, the LVEF was 19.9 ± 10.6\% (6 -
67\%), compared with 29.3 ± 19.3\% (10 - 70\%) in female. As for adults,
the LVEF was 22.4 ± 14.6\% (6 - 70\%), compared with 26.2 ± 13.6\% (10 -
57\%) in pediatric patients. Overall, 74 (89.2\%) patients had a reduced
LVEF (\textless{}40\%). There was a significant difference between sexes
(p = 0.04) but not between age groups (p = 0.19) regarding the
preoperative LVEF.

According to their clinical profile and condition, 61 recipients
(73.5\%) were clinically categorized as Interagency Registry for
Mechanically Assisted Circulatory Support (INTERMACS) Profile 3 before
transplantation (11). Thus, 45 (54.2\%) were on intravenous inotropic
support, of which 12 (14.5\%) required mechanical assist device support:
5 of them with intra-aortic balloon pump (IABP), 4 had an implanted left
ventricular assist device (VAD), and 3 had an implanted bi-VAD (Thoratec
Corporation, CA, USA).

Among comorbidities, the most frequent were pulmonary hypertension
(25.3\%), hypothyroidism (19.3\%), chronic kidney disease (15.7\%),
arterial hypertension (14.5\%), and diabetes mellitus (8.4\%).

\emph{Catheterization variables}

From the recipients' preoperative catheterization evaluation, the
averages of a mean pulmonary artery pressure (mPAP) of 35.2 ± 10.1 mmHg
(13 - 55 mmHg), a pulmonary vascular resistance (PVR) of 3.2 ± 2.1 uW
(0.3 - 11.1 uW), and a transpulmonary pressure gradient (TPG) of 10.7 ±
5.4 mmHg (1 - 25 mmHg). The differences in the means between sexes and
age groups were not significant in mPAP (p = 0.26) (p = 0.37), PVR (p =
0.19) (p = 0.90), nor TPG (p = 0.19) (p = 0.07), respectively.

\emph{Surgical Procedure and Times}

The most performed surgical technique was the bicaval/unipulmonar
(96.4\%); however, in 3 (3.6\%) cases, biatrial surgery was performed
before institutional surgical consensus. Thirteen patients (15.7\%) had
a previous sternotomy. An extension of the inferior vena cava with a
bovine pericardial patch and another with a dacron tube had to be
performed in 2 children. Two patients underwent combined simultaneous
heart and kidney transplantation from the same donor. Three patients
(3.6\%) left the operating room with extracorporeal membrane oxygenation
(ECMO) support.

Mean recipients' waiting time was 12.7 ± 28 weeks (0 - 232 weeks), mean
ischemia time was 3.1 ± 1.2 hours (1.3 -- 6.4 hours), mean operating
time was 6.1 ± 1.9 hours (3.1 -- 15.2 hours), mean cardiopulmonary
bypass (CPB) time was 3 ± 1.5 hours (1.3 -- 11.1 hours), and mean aortic
cross-clamp time was 1.7 ± 0.8 hours (0.8 -- 6.8 hours). Regarding the
waiting time, there were no significant differences between sexes (p =
0.57) but there were between age groups (p = 0.01) with an average time
in adults of 8.9 ± 13.2 weeks, compared with 40.6 ± 69.3 weeks in
children. On the other hand, there were no significant differences
between sexes and age groups of ischemia (p = 0.18) (p = 0.12),
operating (p = 0.41) (p = 0.94), CPB (p = 0.41) (p = 0.30), nor aortic
cross-clamp (p = 0.42) (p = 0.52) times, respectively.

\emph{Postoperative Complications and Times}

The postoperative complications after HTx are shown in Table 2. The
early complications were considered during the first 72 hours
postoperative and the late after that period. During follow-up, three
patients developed arterial hypertension, three diabetes mellitus, and 1
case of ascending aortic pseudoaneurysm in a child treated successfully
with an endovascular stents placement (12). Neoplasms were not
documented.

Mean postoperative intensive care unit (ICU) stay was 14.2 ± 14.1 days
(1 - 84 days), mean postoperative hospital stay was 37.1 ± 26.3 days (1
- 165 days), and mean total hospital stay was 56.1 ± 41.7 days (3 - 178
days). In the evaluation of the postoperative ICU stay, the readmission
cases were not considered. The postoperative hospital stay ranged from
admission to the ICU until discharge, and the total hospital stays from
admission to INCOR until discharge. There were no significant
differences between sexes and age groups of postoperative ICU (p = 0.15)
(p = 0.53), postoperative hospital (p = 0.61) (p = 0.98), nor total
hospital (p = 0.59) (p = 0.54) stays, respectively.

\emph{Causes of Death}

One patient died during surgery due to cardiogenic shock. In this case,
the surgical indication was EHF due to Fontan failure, and it had 6.8
and 11.5 hours of ischemia and surgical time, respectively. There were
82 surviving recipients. The postoperative mortality was 15.9\% (13
patients), and the principal causes of death were infection in 6
patients and acute rejection in 5. Hospital mortality was 7.3\%; 2 died
in the post-HTx 72-hours, one from cardiogenic shock, and one during
reoperation due to revision of hemostasis. After the post-HTx 72-hours,
three patients died from septic shock and one from acute humoral
rejection. During the follow-up after hospital discharge, three patients
died from cardiogenic shock due to 3R acute cellular rejection, two from
septic shock, one from massive pulmonary thromboembolism, and one from
septic and cardiogenic shock due to 3R acute cellular rejection. One of
the recipients, who died from cardiogenic shock due to 3R acute cellular
rejection, had blood type O- while the heart donor was O+. Causes of
death after HTx are shown in Table 3.

\emph{Survival and the Influence of Recipients' Sex and Age Group}

The global survival at one, five, and ten years was 87.5\%, 79.8\%, and
79.8\%, respectively (Figure 2). Separately, survival per recipient's
sex at one, five, and ten years in male were 87.3\%, 83,1\%, and 83.1\%,
respectively, compared with 1-year's 87.9\% and 5-year's 73.3\%, in
female (p = 0.66) (Figure 3). Besides, pediatric patients' survival was
100\% in all years, and in adults, 85.\% in 1-year and 77.4\% in five
and ten years (p = 0.17) (Figure 4).

\textbf{Discussion}

Through scientific development, ongoing training, and spreading program
formation, HTx is now, to a greater extent, a better opportunity for the
treatment of EHF patients around the world (5,13--16). However, only 102
countries report their numbers annually to the International Registry in
Organ Donation and Transplantation (IRODaT) database (5). Given this
development, some Latin American countries have reported their results,
showing that HTx programs are feasible in developing countries (6--8).
Approximately nine transplants were performed in Peru during the 1990s
in different national centers in Lima (1,7). Although this initiative
was bringing unhurried but worthy results, it declined due to the lack
of funding and political interest (1). For this reason, it was not until
2010 that the INCOR's Program was reactivated without interruption until
this study was carried out.

In this first decade, a total of 83 HTx were studied. Despite the
program's effort, according to the IRODaT database in 2019, Peru is one
of the countries with the lowest rate of HTx, with 14 HTx per year (5).
The USA, France, Brazil, Spain, and Argentina led with 3587, 434, 381,
300, and 123 HTx per year, respectively (5). From another perspective,
the average HTx frequency in these ten years in Peru was 8.3 HTx per
year. In this regard, from 2013 to date, we reported a number greater
than or equal to 9 HTx per year. According to Bocchi \emph{et al.} ,
this frequency is sufficient not to be associated with an increased risk
of death (19). Nevertheless, in 2016 only 5 HTx were performed in total
due to institutional management changes. Additionally, Peru had a 0.5
HTx per million population (pmp) rate while the USA, Croatia, Spain,
Uruguay, and Argentina had 10.9, 9.3, 6.5, 3.9, and 2.8 HTx pmp,
respectively (5). This data also placed us as one of the countries with
the lowest HTx pmp regionally and globally in 2019.

In our study, 68.7\% were male. Although 76.9\% of women had reduced
LVEF, there was a significant difference between preoperative LVEF
between the sexes. This could be related to the lower number of female
recipients and the higher percentage (94.7\%) of males with EHF with
reduced LVEF. In addition, the low percentage of pediatric HTx is
related to the lower rate of pediatric donors, and it is reflected in
the significant difference regarding the waiting time, in which adults'
average was 8.9 weeks, and children's, 40.9 weeks. This phenomenon is
widely reported (15,16,18). In our experience, most of them have been
children due to the lack of donors and the slowly growing number of HTx
in developing countries, coinciding with regional experiences (17,20).

Like ISHLT reports, our main indications were idiopathic DCM in 66.3\%
of HTx and ischaemic cardiomyopathy in 18.1\% (21). Although Chagas
disease continues to be a Latin American public health problem, we have
no indications for HTx due to Chagas cardiomyopathy (7,22). We consider
that this is related to the underreporting of cases, and this local
factor should be reevaluated since we are still a Chagas endemic country
(23). Regarding pretransplant clinical status, 85.5\% had an INTERMACS
Profile 1 to 3, similar to ISHLT reports (24). It is a progressive
increase of urgent HTx from 36.2\% to 46.8\% in the last decade in
Spain; in our program, the average was 54.2\% due to longer waiting
times (15). On the contrary, 54.2\% of recipients required inotropic
support pretransplant, lower than ISHLT's (24). Since the REMATCH trial,
it is well-known that mechanical circulatory support potentially reduces
mortality, increases survival, and improves the quality of life of
transplanted recipients (25). Consequently, the ISHLT reports a gradual
increase in VADs as bridge-to-transplant in 23\% by 2005 and 50.3\% by
2019 (24). Likewise, Gonzales \emph{et al.} describe an inverse
relationship in the use of IABPs and VADs (15). Our program utilized
mechanical support in 14.5\% of patients: 6\% with IABP and 9.6\% with
VADs.

Even though having elevated catheterization values and pulmonary
hypertension in 25.3\% of cases, reversibility of these values was
achieved through pretransplant pharmacological and mechanical support
avoiding high incidences of graft failure (18). Furthermore, the world's
average waiting time is 10 weeks; our recipients expected an adequate
average of 12.7 weeks compared to 25, 22.6, and 4.1 weeks in the USA,
Australia-New Zealand, and Chile, respectively (8,26,27). The optimal
ischemia time is a maximum of 4 to 6 hours, and we had a mean of 3.1
hours (28). We associate this result with the speed of the system when
the National Donor Alert is activated.

Our mean postoperative stays in ICU and hospital were higher than
reported in the USA, Brazil, and Chile (8,14,28). Consistent with most
reports, infection was the first cause of death after HTx; however, the
second cause was acute rejection, unlike other series, which was primary
graft failure (2,13,15). Our overall survival rate was slightly higher
than that described by the ISHLT at one, five, and ten years after HTx,
and the analysis by age group was also higher, especially in children,
as they still have a 100\% survival (3). Consistently, we neither found
significant differences in survival rates between the sexes. These
results are subject to a limited number of HTx performed and a still
short follow-up, especially in children, so future analyses are
required. Although the ISHLT describes significant differences between
the survival rates of adults recipients by sex, we did not found them,
but a notable decrease in the females' from 87.9\% at one year to 73.3\%
at five years, while in males, the difference was minor from 87.3\% to
83.1\% (3). Indeed, Bocchi \emph{et al.} describe female recipients, in
experimental models, may require increased immunosuppression due to
higher frequency of rejection, and this may not be related to sex as
such but to a previous pregnancy, a variable not considered in this
study (19).

The study's limitations include the lack of data in the clinical
histories on the profile of the donors and the short follow-up time
concerning the appearance of complications. We agree and suggest that
with well-selected donors, a careful evaluation of recipients, and a
strict follow-up by a multidisciplinary team, suitable results can be
reached in developing countries (18,28).



\textbf{Conclusion}

In summary, HTx remains the treatment of choice for most EHF patients.
Our patients' postoperative complications, mortality, and survival rates
coincided with those reported by the ISHLT registry. However, no
survival adjustment was made according to postoperative complications or
multivariate analysis of the profiles. The careful receptor and donor
selection, advancement in immunosuppression protocol, and the early
detection of postoperative complications have allowed us to perform HTx
in our institution with acceptable results compared to others worldwide.

\textbf{Acknowledgments}

The authors would like to thank all the people involved in the Peruvian
National Heart Institute's Heart Transplantation Program. We would also
like to highlight and appreciate the decision of donors and their
families.

\textbf{Conflict of Interest:} None



\textbf{Data Availability Statement}

The data underlying this article will be shared on reasonable request to
the corresponding author.

\textbf{ORCID iD}

Miguel Pinto-Salinas https://orcid.org/0000-0001-5789-3960

Julio Morón-Castro https://orcid.org/0000-0002-7964-7311

Fernando Chavarri-Velarde https://orcid.org/0000-0003-2524-0003

Franz Soplopuco-Palacios https://orcid.org/0000-0003-2100-3537

Luis Palma-Ortecho https://orcid.org/0000-0002-5874-127X

Miguel Lescano-Alva https://orcid.org/0000-0001-8177-9965



\textbf{References}

1. Pinto-Salinas M. Características Clínico-Quirúrgicas de los
Trasplantes Cardiacos del Instituto Nacional Cardiovascular ``Carlos
Alberto Peschiera Carrillo'' 1993 -- 2019 {[}Tesis para optar el Título
Profesional de Médico Cirujano{]}. {[}Facultad de Medicina, Escuela
Profesional de Medicina Humana{]}: Universidad Nacional Mayor de San
Marcos; 2020.

2. Lund LH, Khush KK, Cherikh WS, Goldfarb S, Kucheryavaya AY, Levvey
BJ, et al. The Registry of the International Society for Heart and Lung
Transplantation: Thirty-fourth Adult Heart Transplantation Report-2017;
Focus Theme: Allograft ischemic time. J Heart Lung Transplant Off Publ
Int Soc Heart Transplant. 2017;36(10):1037--46.

3. Khush KK, Cherikh WS, Chambers DC, Harhay MO, Hayes D, Hsich E, 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. J Heart Lung Transplant. 2019 Oct;38(10):1056--66.

4. Barnard CN. A human cardiac transplant: An interim report of a
successful operation performed at Groote Schuur Hospital, Cape Town.
SAMJ South Afr Med J. 1967;41(48):1271--4.

5. International Registry on Organ Donation and Transplantation
(IRODaT). Donations in 2019 (Database).

6. Sociedad de Trasplante de America Latina y el Caribe. Registros -
Latin America Transplantation Registry Report 2015-2016.

7. Aguilar C, Alarco W, Soplopuco F, Morón J, Lescano M, Morales J, et
al. Patología del trasplante cardiaco en el Perú: Experiencia con 61
casos en un centro de referencia nacional. Rev Peru Med Exp Salud
Pública. 2018 Jun;35:241--9.

8. Villavicencio M, Rossel V, Larrea R, Peralta JP, Larraín E, Sung Lim
J, et al. Experiencia clínica con 53 trasplantes cardiacos consecutivos.
Rev Médica Chile. 2013 Dec;141(12):1499--505.

9. Rojas-Contreras C, De la Cruz-Ku G, Valcarcel-Valdivia B.
Noninfectious and Infectious Complications and Their Related
Characteristics in Heart Transplant Recipients at a National Institute.
Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2018
Apr;16(2):191--8.

10. Sarsam MA, Campbell CS, Yonan NA, Deiraniya AK, Rahman AN. An
alternative surgical technique in orthotopic cardiac transplantation. J
Card Surg. 1993 May;8(3):344--9.

11. Stevenson LW, Pagani FD, Young JB, Jessup M, Miller L, Kormos RL, et
al. INTERMACS profiles of advanced heart failure: the current picture. J
Heart Lung Transplant Off Publ Int Soc Heart Transplant. 2009
Jun;28(6):535--41.

12. Skrabonja\selectlanguage{english}-Crespo A, Chavarri\selectlanguage{english}-Velarde F, Pinto\selectlanguage{english}-Salinas M, Tauma\selectlanguage{english}-Arrue
A. Percutaneous endovascular management of ascending aortic
pseudoaneurysm after heart transplantation in a pediatric patient.
Pediatr Transplant. 2020;25(3):e13958.

13. Udovicic M, Grizelj D, Mihajlovi\selectlanguage{polish}ć \selectlanguage{english}V, Falak H, Jordan A, Rudez I, et
al. Heart transplantation results from the Department of Cardiology at
Dubrava University Hospital. Cardiol Croat. 2021 Jan;16:33--33.

14. Awad M, Czer LSC, Mirocha J, Ruzza A, de Robertis M, Rafiei M, et
al. Similar Mortality and Morbidity of Orthotopic Heart Transplantation
for Patients 70 Years of Age and Older Compared With Younger Patients.
Transplant Proc. 2016 Oct;48(8):2782--91.

15. Gonz\selectlanguage{ngerman}ález-Vilchez F, Almenar-Bonet L, Crespo-Leiro MG, Gómez-Bueno M,
González-Costello J, Pérez-Villa F, et al. Spanish Heart Transplant
Registry. 31th Official Report of the Heart Failure Association of the
Spanish Society of Cardiology. Rev Esp Cardiol Engl Ed. 2020
Nov;73(11):919--26.

16. Khush KK, Potena L, Cherikh WS, Chambers DC, Harhay MO, Hayes D, et
al. The International Thoracic Organ Transplant Registry of the
International Society for Heart and Lung Transplantation: 37th adult
heart transplantation report---2020; focus on deceased donor
characteristics. J Heart Lung Transplant. 2020 Oct;39(10):1003--15.

17. Avila MS, Belfort D de SP. Progress in Heart Transplantation in
Brazil: is it Time to Build a National Database? Arq Bras Cardiol. 2021
Apr;116:754--5.

18. Peradejordi M, Favaloro L, Vigliano C, Renedo M, Martínez L,
Moscoloni S, et al. Resultados del trasplante cardíaco según el perfil
clínico del receptor: 21 años de experiencia. Rev Argent Cardiol. 2016
Jun;84.

19. Bocchi EA, Fiorelli A, First Guideline Group for Heart
Transplantation of the Brazilian Society of Cardiology. The Brazilian
experience with heart transplantation: a multicenter report. J Heart
Lung Transplant Off Publ Int Soc Heart Transplant. 2001
Jun;20(6):637--45.

20. Javier M, Delmo E, Hetzer R. Evolution of heart transplantation
since Barnard's first. Cardiovasc Diagn Ther. 2021 Feb 1;11:171--82.

21. Lund LH, Edwards LB, Dipchand AI, Goldfarb S, Kucheryavaya AY,
Levvey BJ, et al. The Registry of the International Society for Heart
and Lung Transplantation: Thirty-third Adult Heart Transplantation
Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant.
J Heart Lung Transplant Off Publ Int Soc Heart Transplant.
2016;35(10):1158--69.

22. Vieira J, Tavora F, Sobral M, Vasconcelos G, Almeida G, Fernandes J,
et al. Chagas Cardiomyopathy in Latin America Review. Curr Cardiol Rep.
2019 Feb;21(2):8.

23. Vega S, Cabrera R, Alvarez C, Uribe-Vilca I, Guerrero-Quincho S,
Ancca J, et al. Clinical and epidemiological characteristic of cases of
Acute Chagas Disease in the Peruvian Amazon Basin, 2009-2016. Rev perú
med exp salud publica. 2021 Feb;38(1):70--6.

24. Goldstein D, Meyns B, Xie R, Cowger J, Pettit S, Nakatani T, et al.
Third Annual Report From the ISHLT Mechanically Assisted Circulatory
Support Registry: A comparison of centrifugal and axial continuous-flow
left ventricular assist devices. J Heart Lung Transplant. 2019 Apr
1;38:352--63.

25. Rose E, Moskowitz A, Packer M, Sollano J, Williams D, Tierney A, et
al. The REMATCH trial: rationale, design, and end points. Randomized
Evaluation of Mechanical Assistance for the Treatment of Congestive
Heart Failure. Ann Thorac Surg. 1999 Mar;67(3):723--30.

26. Goldstein BA, Thomas L, Zaroff JG, Nguyen J, Menza R, Khush KK.
Assessment of heart transplant waitlist time and pre- and
post-transplant failure: A mixed methods approach. Epidemiol Camb Mass.
2016 Jul;27(4):469--76.

27. Ruygrok P, Pettersson R, Keogh A, Bergin P, Weintraub R, Dembo L, et
al. Factors Influencing Waiting Time on the Heart Transplant Waiting
List in Australia and New Zealand. J Heart Lung Transplant. 2014
Apr;33(4):S262.

28. Bruschi G, Colombo T, Oliva F, Botta L, Morici N, Cannata A, et al.
Heart transplantation: 25 years' single-centre experience. J Cardiovasc
Med Hagerstown Md. 2013 Sep;14(9):637--47.

\textbf{Figures}

\textbf{Figure 1.} Number of heart transplantations performed per
year.\textbf{A,} According to the recipients' sex. \textbf{B,} According
to the recipients' age group.

\textbf{Figure 2.} Kaplan-Meier survival curve after heart
transplantations.

\textbf{Figure 3.} Kaplan-Meier survival curve after heart
transplantations according to the recipients' sex.

\textbf{Figure 4.} Kaplan-Meier survival curve after heart
transplantations according to the recipients' age group.

\textbf{Tables}

\textbf{Table 1.} Recipients' characteristics at heart transplantation.

\textbf{Table 2.} Causes of death after heart transplantation.\selectlanguage{english}
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\verb`Table 3.docx`  available at \url{https://authorea.com/users/356470/articles/543155-heart-transplantation-at-the-peruvian-national-heart-institute-one-decade-single-center-experience}

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