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\begin{document}

\title{An unusual story of electrical storm on the graft.}



\author[1]{etienne charbonneau}%
\author[2]{Bernard Lelong}%
\author[1]{celine chabanne}%
\author[1]{vincent galand}%
\author[2]{Erwan Flecher}%
\affil[1]{CHU Pontchaillou}%
\affil[2]{Pontchaillou Hospital}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: Cancers, and specifically lymphomas, are one of the main
causes of morbidity and mortality after heart transplant. We encountered
this complication on a 54-year-old male patient, which brought to our
attention the lack of a specific and appropriate treatment for a primary
cardiac lymphoma on the graft. Objective: This case report highlights
the challenging management of primitive heart transplant lymphoma and
its treatment. Method: electronic medical record literature reviewed
through Pubmed interface of Medline. Result: We report the case of an
Epstein-Barr Virus (EBV) induced primary cardiac lymphoma on the graft.
The lymphoma spread quickly in spite of the numerous treatments we tried
and resulted in rhythmic complication. Endocavitary implantable
cardioverter defibrillator was implanted but quickly removed due to
local complications. The patient died from a sudden death at home
shortly after. Conclusions: Primary cardiac lymphoma on the graft is
highly rare with poor prognosis and rhythmic complications. Further
studies are needed to assess the benefits of other treatment approaches,
such as radiofrequency ablation techniques.%
\end{abstract}%



\sloppy


An unusual story of electrical storm on the graft.

Etienne Charbonneau\selectlanguage{ngerman}¹\textsuperscript{,} ², MD, Céline
Chabanne¹\textsuperscript{,} ², MD, Bernard Lelong¹\textsuperscript{,}²,
MD, Vincent Galand ², MD, Erwan Flécher¹, MD, PhD.

¹Department of cardiothoracic and vascular surgery, Rennes University
Hospital, Rennes, France

²Department of cardiology, Rennes University Hospital, Rennes, France.

The data that support the findings of this study are openly available in
Journal of Cardiac Surgery at http://doi.org/{[}doi{]}, reference number
{[}reference number{]}.

Corresponding Author:

Dr Etienne Charbonneau

Departement of Cardiology

CHU Pontchaillou

2 henri Le Guilloux St

35 000 Rennes, France

Tel : +33648883662

Email :~\emph{echarbonneau@hotmail.fr}

Declarations of interest: none

Funding~: none

\textbf{Abstract}Background: Cancers, and specifically lymphomas, are
one of the main causes of morbidity and mortality after heart
transplant. We encountered this complication on a 54-year-old male
patient, which brought to our attention the lack of a specific and
appropriate treatment for a primary cardiac lymphoma on the graft.

Objective: This case report highlights the challenging management of
primitive heart transplant lymphoma and its treatment.

Method: electronic medical record literature reviewed through Pubmed
interface of Medline.

This study was approved by the CHU Rennes Ethics Committee.

Written informed consent was obtained from the patient for the
publication of this case report.

Result: We report the case of an Epstein-Barr Virus (EBV) induced
primary cardiac lymphoma on the graft. The lymphoma spread quickly in
spite of the numerous treatments we tried and resulted in rhythmic
complication. Endocavitary implantable cardioverter defibrillator was
implanted but quickly removed due to local complications. The patient
died from a sudden death at home shortly after.

Conclusions: Primary cardiac lymphoma on the graft is highly rare with
poor prognosis and rhythmic complications. Further studies are needed to
assess the benefits of other treatment approaches, such as
radiofrequency ablation techniques.

\textbf{Keywords:} lymphoma, heart transplant, ventricular arythmia,
electrical storm.

Abbreviations; ICD: implantable cardioverter defibrillator, EBV: ebstein
bar virus, TV: ventricular tachycardia, CICU: Cardiac Intensive Care
Unit.

\textbf{Introduction}

Cancers remain one of the main causes of long-term mortality after heart
transplantation. According to the International Society of Heart and
Lung Transplantation (ISHLT), 16\% of the transplant recipients develop
a cancer within five years and almost 30\% within ten years (1,2). Among
this population, 50\% develop cutaneous cancers but lymphomas are
frequent as well, representing 10\% of these patients (2).
Interestingly, the incidence of lymphoma does not regularly increase
during follow-up but is more important during the 5 years following
transplantation (3). Notably, post-cardiac transplant lymphomas are more
likely extranodal with lesions of the central nervous system, lungs, or
liver (3). However, isolated cardiac graft lymphomas are extremely
unusual and have been poorly reported so far. We aimed at describing the
case of a patient who developed an isolated graft lymphoma after
receiving heart transplantation.

\textbf{Case report}

In 2017, a 52-year-old man was successfully transplanted for acute
advanced heart failure due to massive myocardial infarction, going
through a step of left ventricular assistance device complicated by
thromboembolic accident. Serology was mismatched, the donor was EBV
positive and the patient EBV negative. After transplant no adverse event
occur except an moderate chronic renal failure. For protect the renal
function we treated him by prednisolone, mycophénolate mofétil,
éverolimus and ciclosporine in order to use low dose of calcineurine
inhibitor. In December 2019, he was admitted to our hospital for severe
but well-tolerated palpitations. The ECG showed a ventricular
tachycardia (Fig.1) that was reduced by beta blocker (Atenolol ®).
Echocardiographic parameters showed no myocardial dysfunction and no
sign of graft rejection. Further investigations did not bring any
biological abnormalities beside an Epstein-Barr Virus (EBV) high
replication - 30 4000 IU/ml. Cardiac computed tomography and cardiac
magnetic resonance imaging revealed two nodular images developed in the
antero-medium and apical wall of the right ventricle and extending
intracavitary and to epicardial area (Fig. 1). Endomyocardial biopsies
were performed and ruled out an acute rejection. Nonetheless, the
microscopic appearance revealed a post-transplantation monomorphic
lymphoproliferative disorder, EBV induced, high grade B cell lymphoma
type Diffuse large B-cell lymphoma (DLBCL). As illustrated in Figure 1,
the 18FDG-PET indicated an important lymphoma extension with three
hypermetabolic pericardial tumors. Of note, a coronary angiography ruled
out an additionnaly underlying ischemic cardiomyopathy but
hypervascularization was observed in the intramyocardial tumoral masses.
We proceed with an initial therapy of four cycles of rituximab and a
reduction of the immunosuppressive drug in order to decrease the EBV
replication. Unfortunately, despite pursing beta-blockers treatment
ventricular arrhythmias still occurred including ventricular premature
beats and sustained ventricular tachycardia (VT). Due to the sporadic
nature of the arrhythmia, we decided not to implant an implantable
cardioverter-defibrillator (ICD) as the first line therapy but to
optimize the antiarrhythmic therapy by inflating beta-blockers to the
maximum tolerated dose. Despite optimal medical therapy including
amiodarone and beta-blockers, the patient presented an electrical storm
associated with hemodynamic instability and was hospitalized in the
Cardiac Intensive Care Unit (CICU). In CICU, the VT recurrences were
controlled using Esmolol infusion. After 2 days, the patient was free
from VT recurrence and Nadolol was introduced with a good tolerance,
authorizing the continuation of the chemotherapy. Fourth cycles of
Rituximab were consequently completed and a PET reevaluation was
realized showing the persistence of an intense hypermetabolism in the
three pericardial tumors\emph{.} A new therapy using Doxorubicin,
Cyclophosphamide and Vincristine was implemented as an emergency
treatment with regular PET reevaluations and a minimized
immunosuppression. In order to prevent the sudden cardiac death, the
patient was implanted with an endocavitary ICD (Medtronic, Dublin,
ireland). The first cycle of chemotherapy caused a pancytopenia with a
profound thrombocytopenia resulting in the formation of an ICD pocket
hematoma. The hematoma spontaneously progressed to fistula, leading to a
revision surgery with device removal. Before hospital discharge, the
patient received a life-vest (Zoll, Chelmsford, USA) that was badly
tolerated. Successive chemotherapy cycles were ineffective with a
tachyphylaxis situation and a quick progression of the tumoral lesions
assessed by cardiac imaging and significant EBV replication. The patient
died from a sudden death at home 3 month after the diagnosis, not
wearing his life-vest anymore because of the bone pain caused by
chemotherapy.

\textbf{Discussion}

Isolated primary cardiac lymphoma is an exceptional post-transplant
complication with only very rare cases previously reported to the best
of our knowlegde (4). The appropriate treatment strategy remains
challenging. We decided not to propose a second heart transplantation
taking account the uncertain risk of recurrence on the graft. Indeed,
only few papers suggested such therapeutic option for primary cardiac
tumors but with heterogeneous results (5,6).

Considering the immunosuppressive strategy, we chose an
immunosuppressive quadritherapy (Prednisolone, mycophénolate mofétil,
éverolimus, ciclosporine), before the lymphoma, in order to use lower
dose of calcineurin inhibitors. However this strategy may be associated
with an increase in infectious and neoplastic complications and place
and benefits of such quadritherapy remain matter of debate.

To prevent sudden death in this case, we implanted an endocavitary ICD.
The arrhythmia triggering factor was obvious but its persistence and the
eventuality of a post-treatment fibrosis area was uncertain. Moreover,
we considered that the rhythmic risk would remain high even at a
distance from the lymphoma. Radiofrequency catheter ablation might be an
interesting option for such patients but the procedure seems associated
with high risks including tumor spreading or ventricular
hyperexcitability. Additionally, the penetration of the radiofrequency
current would be probably insufficient due to the large tumoral masses.
More recently few teams developed non-invasive ablation methods of the
VT using external radiation (7). This procedure might have been
interesting in this case as it presents the double benefit of enhanced
security of the procedure and of transmural ablation that might have
been beneficial to the lymphoma treatment.

\textbf{Conclusion} :

Primary cardiac lymphoma of the graft is a very rare complication with a
very poor prognosis. Its management and treatment remain discussed in
this population. Adaptation of immunosuppression and development of
non-invasive radiofrequency ablation techniques might be interesting
research track in the future.

\textbf{References:}

\begin{enumerate}
\tightlist
\item
  Khush KK, Cherikh WS, Chambers DC, et al. The international thoracic
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  lung transplantation: thirty-fifth adult heart transplantation
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  Trans. 2018;37:1155. https://doi.org/10.1016/J.HEALUN.2018.07.022
\item
  Crespo-Leiro MG, Alonso-Pulpón L, Vázquez de Prada JA, et al.
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\item
  Salla Jäämaa-Holmberg, Birgitta Salmela, Karl Lemström, Eero Pukkala
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  https://doi.org/10.1080/0284186X.2019.1580385
\item
  Burtin P, Guerci A, Boman F, Dopff C, Pinelli G, Haberer JP, Villemot
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  Eur Heart J. 1993 Aug;14(8):1143-5. doi: 10.1093/eurheartj/14.8.1143.
\item
  Yuh DD, Kubo SH, Francis GS, Bank A, McDonald KM, Jessurun J,
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\item
  Gowdamarajan A, Michler RE. Therapy for primary cardiac tumors: is
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\item
  Cuculich PS, Schill MR, Kashani R, Mutic S, Lang A, Cooper D, Faddis
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\end{enumerate}

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