\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Bench valvular surgery in donor hearts before transplantation: Choice
versus Necessity}



\author[1]{Magdy  El-Sayed Ahmed}%
\author[2]{Anthony Pham}%
\author[3]{Basar Sareyyupoglu}%
\author[4]{Si  Pham}%
\affil[1]{Mayo Clinic in Florida}%
\affil[2]{Lake Erie College of Osteopathic Medicine}%
\affil[3]{Mayo Clinic Florida}%
\affil[4]{Mayo Clinic's Campus in Florida}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Severe shortage of donor hearts has increased the mortality of patients
on the transplant waiting list. However, donor hearts with valvular
dysfunction are rarely used. Utilizing donor hearts with valvular
lesions that can be repaired or replaced at the time of transplant will
decrease waitlist mortality and offer many patients a second chance in
life.%
\end{abstract}%



\sloppy


Title: \textbf{Bench valvular surgery in donor hearts before
transplantation: Choice versus Necessity}

Magdy M. El-Sayed Ahmed, MD, MS\textsuperscript{1,2}; Anthony Pham,
MS\textsuperscript{1,3}; Basar Sareyyupoglu, MD\textsuperscript{1}; Si M
Pham, MD, FACS\textsuperscript{1}

Short Running Title: Valvular surgery in donor hearts

\textsuperscript{1}Department of Cardiothoracic Surgery, Mayo Clinic,
Jacksonville, Florida, USA

\textsuperscript{2}Department of Surgery, Zagazig University Faculty of
Medicine, Egypt

\textsuperscript{3}Lake Erie College of Osteopathic Medicine, Lake Erie,
Pennsylvania, USA

Corresponding author:

Si M Pham, MD, FACS

Mail address: 4500 San Pablo Rd S, Jacksonville, FL 32224

e-mail: pham.si@mayo.edu

Phone: 904-956-3212

Fax: 904-953-7368

\textbf{Word Count:} 1728

\textbf{Conflict of Interests} : None

\textbf{Funding sources:} None

\textbf{Disclosure:} None

\textbf{Abstract}

Severe shortage of donor hearts has increased the mortality of patients
on the transplant waiting list. However, donor hearts with valvular
dysfunction are rarely used. Utilizing donor hearts with valvular
lesions that can be repaired or replaced at the time of transplant will
decrease waitlist mortality and offer many patients a second chance in
life.

Heart transplantation is the gold standard treatment for patients with
terminal end-stage heart diseases, however this option is limited by the
discrepancy between the number of transplant candidates on the waiting
list and the number of available organs.(1) As a result, many patients
die waiting for donors. According the 2020 OPTN/SRTR (Organ Procurement
and Transplantation Network/Scientific Registry of Transplant
Recipients) report, the overall mortality rate among patients on the
heart waitlist in the U.S.A was 9 per 100 waitlist-years, and status 1A
patients had pretransplant mortality rate of 29.5 deaths per 100
waitlist-years.(2) To alleviate the death on waitlist, efforts have been
focused on expanding the donor pool by multiple approaches, including
the expansion of the donor criteria. Structural valve diseases have been
considered an absolute contraindication for accepting a donor heart.
However, several reports have documented successful outcomes after bench
(ex-vivo) repair or replacement of valves before heart
transplantation.(3-6)

In this issue of the Journal, Rend\selectlanguage{ngerman}ón et al., (7) described bench aortic
valve replacement before heart transplantation in a 39 year-old
critically ill patient. They reported a bicuspid calcified aortic valve
during back table examination of the donor heart before transplant.
Giving the critical condition of the recipient and the lack of proper
mechanical circulatory support device, replacing this incidentally
discovered calcified valve was the only option to save this patient's
life. In developing countries, proper equipment, and medical specialists
to adequately evaluate the heart before procurement are not always
available, hence, it is possible to discover valvular or coronary artery
disease during procurement or during back table organ examination. More
importantly, the lack of an advanced mechanical circulatory support
program does not give the surgeon other alternatives but utilizing this
marginal heart with aortic valve disease. The authors used a
bioprosthetic valve instead of mechanical valve to avoid anticoagulation
with potential bleeding during posttransplant cardiac biopsies.
Structural deterioration of bioprosthesis in young patients is a known
risk, however catheter-based valve-in- valve or mechanical valve
replacements are options in the future, when the patient is in better
condition, should aortic valve stenosis occur.

Utilizing hearts with valvular diseases that need repair or replacement
has been reported as case reports or small case series, with acceptable
outcomes. In a case series from Portugal, Prieto et al., (5) performed
bench repair of the mitral valve on 4 donor hearts before transplant
with short total ischemic time. These repairs included one
posterio-medial commissurotomy and posterior annuloplasty, one
reimplantation of a torn head of the posterior papillary muscle, and two
posterior annuloplasties. All repairs and transplant were successful,
but one die from persistent profound thrombocytopenia resulting in
intracerebral bleeding and death. In another case series Fiore et al.,
reported successful use of 4 hearts with valvular lesions that underwent
repair or replacement at the time of transplantation.(3) Three of them
had moderate-severe mitral regurgitation that each required the
following: annuloplasty, annuloplasty and chordal replacement, and cleft
repair. The 4th showed aortic valve stenosis requiring an aortic valve
replacement with a bioprosthesis. They reported no residual mitral
regurgitation or aortic stenosis post-operatively. These cumulative
experiences along with other case reports showed a total of at least 11
cases of bench mitral valve surgery before transplant with good
outcomes. (4, 5, 8-10)

For aortic valve repair or replacement, in addition to the case reported
in this current issue of the Journal, (7) there are other 7 cases in the
literatures. Of these 8 cases, 1 was repaired with Cabrol commissural
annular plication technique (11) the other were replacement with either
bioprosthetic (3, 12-14) or mechanical (6, 15) valves. All had excellent
outcomes. The mechanical aortic valve is more durable but its need for
chronic systemic anticoagulation will complicate posttransplant care,
especially during the first year with frequent surveillance
endomyocardial biopsy. Besides the advantage of avoiding long term
anticoagulation, aortic valve bioprosthesis may outlast the heart
recipient, especially those at age 60 years or higher. Bourguignon et
al., reported that the freedom from reoperation due to structural valve
deterioration for the Carpentier-Edwards Perimount pericardial
bioprosthesis~at 15 year were 70.8\% ± 4.1\% and 82.7\% ± 2.9\%, for the
patients with the age of 60 years or younger, and for those of 60 to 70
years of age, respectively. (16) This freedom from structural
deterioration compares very favorable with the long-term survival of the
heart recipients of 53\% at 10 years.(17) Moreover, available data
suggest that immunosuppression may slow down the process of structural
valve deterioration. Eishi et al., reported that aortic bioprosthesis in
patients with aortitis who received chronic steroid treatment showed
lower degree of structural valve degeneration. (18)

In general bench valve surgery in donor hearts at the time of heart
transplantation are performed either by choice of by necessity. In the
former, the transplant team is aware of the valvular dysfunction in the
donor but elects to use it, while in the latter, the valvular
abnormality is discovered right before implantation of the donor heart.

Because the valve repair or replacement in donor hearts at the time of
transplant potentially increase the risk of complications, it is prudent
to select both the recipient and donor carefully. One needs to balance
the risk of death on the waitlist versus the increased risk of
complications, such as primary graft failure due to prolonged ischemic
time (due to the valve repair or replacement), endocarditis, bleeding
from systemic anticoagulation for mechanical valves, structural failure
of the prosthesis, durability and success of the repair. One technique
that will reduce the ischemic time of the donor heart is to perform the
bench valvular repair or replacement then implant the heart by
anastomosing the left atrial cuffs and the ascending aortas. After these
anastomoses are completed, unclamp the aorta to reperfuse the heart
while the pulmonary arterial, the inferior and superior vena caval
anastomoses are carried out.

For critically ill patients when advanced therapies including mechanical
circulatory supports is not available (in developing countries) or is
contraindicated (such as infected durable left ventricular assist
devices) the decision is usually straightforward. In more stable
patients, the decision to use these marginal donors requires thoughtful
discussion with, and consent from, patients and their health care
surrogates.

In conclusions, the use of donor hearts that require valvular repair or
replacement, either by choice or by necessity, will reduce waitlist
mortality and may offer many people with a second chance in life,
especially for those in areas where resources are limited or where
donors are in severe shortage.

\textbf{Author contributions} Concept/design: MA, BS, SMP. Drafting
article: MA; Critical revision of article: ANP, BS, SMP; Approval of
article: MA, ANP, BS, SMP.



\section*{}

{\label{section-1}}

1. Singh TP, Milliren CE, Almond CS, Graham D. Survival benefit from
transplantation in patients listed for heart transplantation in the
United States. J Am Coll Cardiol. 2014;63(12):1169-78.

2. Colvin M, Smith JM, Ahn Y, Skeans MA, Messick E, Bradbrook K, et al.
OPTN/SRTR 2020 Annual Data Report: Heart. Am J Transplant. 2022;22 Suppl
2:350-437.

3. Fiore A, Grande AM, Gatti G, Youssari A, Piscitelli M, Bergoend E, et
al. Valvular surgery in donor hearts before orthotopic heart
transplantation. Arch Cardiovasc Dis. 2020;113(11):674-8.

4. Massad MG, Smedira NG, Hobbs RE, Hoercher K, Vandervoort P, McCarthy
PM. Bench repair of donor mitral valve before heart transplantation. Ann
Thorac Surg. 1996;61(6):1833-5.

5. Prieto D, Antunes P, Antunes MJ. Donor mitral valve repair in cardiac
transplantation. Transplant Proc. 2009;41(3):932-4.

6. Saito S, Matsumiya G, Ueno T, Sakaguchi T, Kuratani T, Ichikawa H, et
al. Bench replacement of donor aortic valve before orthotopic heart
transplantation. J Heart Lung Transplant. 2009;28(9):981-3.

7. Rendón JC, Vinck EE, Gómez AQ, Escobar JJ, Suárez S, Echeverri DA.
Bench Bioprosthetic Aortic Valve Replacement in a Donor Heart Before. J
Card Surg. 2022;(In Press).

8. Michler RE, Camacho DR. Ex-vivo mitral valve repair prior to
orthotopic cardiac transplantation. Ann Thorac Surg. 2002;73(3):962-3.

9. Pawale A, Tang GH, Milla F, Pinney S, Adams DH, Anyanwu AC. Bench
mitral valve repair of donor hearts before orthotopic heart
transplantation. Circ Heart Fail. 2012;5(6):e96-7.

10. Sprengel A, Skwara W, Ziegelhöffer T, Cetinkaya A, Schönburg M,
Richter M. Combined mitral valve repair and heart transplantation. Clin
Case Rep. 2018;6(4):564-8.

11. Navia JL, Atik FA, Marullo A, Starling RC, Garcia M, Vega PR, et al.
Bench repair of donor aortic valve with minimal access orthotopic heart
transplantation. Ann Thorac Surg. 2005;80(1):313-5.

12. Patel M, Vahdat KK, Nathan S, Petrovic M, Loyalka P, Kar B, et al.
Bioprosthetic Aortic Valve Replacement in a Donor Heart before
Orthotopic Heart Transplantation. Tex Heart Inst J. 2017;44(2):135-7.

13. Sultan I, Seese L, Lagazzi L, Gleason TG. Concomitant aortic valve
replacement with orthotopic heart transplantation. J Thorac Cardiovasc
Surg. 2018;155(5):e151-e2.

14. Rao JN, Prendergast B, Dark JH. Orthotopic heart transplantation
with concurrent aortic valve replacement and coronary artery bypass
grafting. J Heart Lung Transplant. 2000;19(9):897-9.

15. Larobina ME, Mariani JA, Rowland MA. Aortic valve replacement for
aortic stenosis during orthotopic cardiac transplant. Ann Thorac Surg.
2008;86(6):1979-82.

16. Bourguignon T, Bouquiaux-Stablo AL, Candolfi P, Mirza A, Loardi C,
May MA, et al. Very long-term outcomes of the Carpentier-Edwards
Perimount valve in aortic position. Ann Thorac Surg. 2015;99(3):831-7.

17. Suarez-Pierre A, Lui C, Zhou X, Giuliano K, Etchill E,
Almaraz-Espinoza A, et al. Long-term Survival After Heart
Transplantation: A Population-based Nested Case-Control Study. Ann
Thorac Surg. 2021;111(3):889-98.

18. Eishi K, Ishibashi-Ueda H, Nakano K, Kosakai Y, Sasako Y, Kobayashi
J, et al. Calcific degeneration of bioprosthetic aortic valves in
patients receiving steroid therapy. J Heart Valve Dis. 1996;5(6):668-72.

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

