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\begin{document}

\title{Post-Cardiac Injury Syndrome after Surgical Repair of Atrial Septal
Defect: Reporting a Rare Occurrence}



\author[1]{Beni Verma R}%
\author[1]{Ashwin Kumar}%
\author[1]{Muhammad Furqan}%
\author[1]{Abdullah Yesilyaprak}%
\author[1]{Ankit Agrawal}%
\author[1]{Gauranaga Mahalwar}%
\author[1]{Muhammad Majid}%
\author[1]{Harjit Singh}%
\author[1]{Bo Xu}%
\author[1]{Allan Klein}%
\affil[1]{Cleveland Clinic Tomsich Family Department of Cardiovascular Medicine}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
A 16-year-old male with past medical history of congenital atrial septal
defect surgical repair presented with recurrent pericarditis secondary
to post-cardiotomy injury syndrome (PCIS). After failing medical
therapy, he ultimately underwent pericardiectomy for symptom resolution.
PCIS is underdiagnosed in children and should be considered in patients
with recurrent chest pain.%
\end{abstract}%



\sloppy


\textbf{Post-Cardiac Injury Syndrome after Surgical Repair of Atrial
Septal Defect: Reporting a Rare Occurrence}

Beni R Verma, MD\textsuperscript{1,2}, Ashwin Kumar,
MD\textsuperscript{1,4}, Muhammad Furqan, MBBS\textsuperscript{1},
Abdullah Yesilyaprak, MD\textsuperscript{1,3}, Ankit Agrawal,
MD\textsuperscript{1}, Gauranaga Mahalwar, MD\textsuperscript{1},
Muhammad Majid, MD\textsuperscript{1}, Harjit Singh,
MD\textsuperscript{1}, Bo Xu, MD\textsuperscript{1}, Allan L Klein,
MD\textsuperscript{1}

Institutional Affiliations: 1. Center for the Diagnosis and Treatment of
Pericardial Diseases, Department of Cardiovascular Medicine, Heart and
Vascular Institute, Department of Cardiovascular Medicine, Cleveland
Clinic, Cleveland, Ohio, USA

2. MetroHealth System, Department of Cardiology, Cleveland, Ohio, USA

3. Wayne State University, Department of Internal Medicine, Detroit,
Michigan, USA

4. Department of Internal Medicine, MedStar Georgetown University
Hospital, Washington, DC, USA

\emph{Corresponding Author:}

Allan L Klein, MD Director, Pericardial Disease Center Department of
Cardiovascular Medicine Cleveland Clinic 9500 Euclid Ave., Desk J1-5~
Cleveland, OH 44195~ Tel:~(216) 444-3932 Fax \# (216) 445-6145 Email:
KLEINA@ccf.org Twitter: @AllanLKleinMD1

\emph{Word Count:} \textbf{1425}

\emph{Disclosures:} A. Klein: research grant, scientific advisory board
Kiniksa Pharmaceuticals, Ltd; scientific advisory board Swedish Orphan
Biovitrum AB; scientific advisory board Pfizer, Inc.; scientific
advisory board Cardiol Therapeutics All other authors have no
disclosures.

\emph{Funding:} None

\emph{Data Availability:} Data available upon reasonable request.

\emph{Abstract:}

A 16-year-old male with past medical history of congenital atrial septal
defect surgical repair

presented with recurrent pericarditis secondary to post-cardiotomy
injury syndrome (PCIS).

After failing medical therapy, he ultimately underwent pericardiectomy
for symptom resolution.

PCIS is underdiagnosed in children and should be considered in patients
with recurrent chest

pain.

\emph{Key Words:} recurrent pericarditis, multimodality imaging, atrial
septal defect, post-cardiac injury syndrome, pericardiectomy

\emph{Abbreviations:}

ASD: atrial septal defect

CRP: C-reactive protein

ESR: erythrocyte sedimentation rate

hs-CRP: high-sensitive C-reactive protein

NSAIDs: non-steroid anti-inflammatory drugs

PCIS: post-cardiac injury syndrome

RP: recurrent pericarditis CMR: cardiac magnetic resonance imaging Echo:
Echocardiography

\emph{Introduction:}

Post cardiac injury syndrome (PCIS) is the development of pericardial
diseases in patients with prior history of cardiac surgery,
electrophysiology procedures, myocardial infarction, or percutaneous
coronary intervention. The incidence of PCIS varies and is dependent on
underlying cause.\textsuperscript{1} Cardiac surgery is the most common
cause (10-40\%) followed by electrophysiology procedures (1-2\%), and
coronary intervention (0.1-1\%).\textsuperscript{1} The clinical
presentation is varied as symptoms may develop even after a few years
therefore making diagnosis and associated management difficult. Here, we
present a case of an adolescent male who developed PCIS induced
recurrent pericarditis (RP) after surgical repair of an atrial septal
defect (ASD).

\emph{Case Presentation:}

A 16-year-old male with past medical history of pericarditis that
developed after surgically repaired ASD presented for recurrent episodes
of chest pain. He described his chest pain as 7/10, pleuritic, sharp,
mid-sternal, and worse when supine. Pain was non-radiating without any
associated shortness of breath, fever or chills. Physical examination
and vital signs were within normal limits. Cardiovascular exam showed
regular rate, normal rhythm, S1, S2 sounds, and no pericardial rub. His
chest pain began a few months after surgery, and at that time he was
diagnosed with acute idiopathic pericarditis. After diagnosis, he
frequently experienced flares limiting his daily activities. During
these episodes, he was intermittently treated with a combination of
non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and
prednisone.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

The patient underwent further workup. Chest x-ray (CXR) showed no focal
pulmonary consolidation, cardiac enlargement or pericardial
calcification. Inflammatory markers including erythrocyte sedimentation
rate (ESR), C-reactive protein (CRP), and high-sensitive C-reactive
protein (hs-CRP) were elevated. High-sensitivity troponin and brain
natriuretic peptide (BNP) levels were within normal limits. A 12-lead
electrocardiogram (ECG) demonstrated normal sinus rhythm. Echocardiogram
displayed diastolic septal bounce and the presence of mild constrictive
physiology with annular reversal \textbf{(Figure 1)} .

\textbf{(Figure 1)}.

Cardiac magnetic resonance imaging (CMR) identified mild pectus
deformity (Haller Index: 3.6) and mild late gadolinium enhancement (LGE)
in the absence of pericardial edema \textbf{(Figures 2,3,4)} .\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{(Figure 2)}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{(Figure 3)}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{(Figure 4)}

Based on his clinical and imaging findings, he was diagnosed with
recurrent pericarditis complicated by constrictive physiology. Given his
frequent recurrences, he was treated with ibuprofen 800 mg three times a
day, colchicine 0.6 mg twice a day and prednisone 40 mg daily. He was
counseled on the need for strict exercise restriction and adherence to
medication. Additionally, the criteria for advancing the therapy to
biologics (anakinra) or pericardiectomy was also discussed.
Unfortunately, 4 months after his visit, he developed another
recurrence. Given his significant limitation in quality of life (QoL),
he elected to undergo pericardiectomy. Surgical pathology revealed
organized pericarditis without any evidence of necrosis or necrobiosis.

At 6-month follow-up, he reported significant improvement in his
functional capacity, and QoL He reported no further flares. ESR, CRP,
and hs-CRP were normal. ECG demonstrated normal sinus rhythm. Repeat
transthoracic echocardiogram revealed no constrictive physiology but
displayed development of new mild tricuspid regurgitation. His
colchicine was tapered from 0.6 mg to 0.3 mg daily and was instructed to
follow up in 6 months for further tapering.

\emph{Discussion:}

PCIS is well reported in adults, however it is rare in children. The
proposed pathophysiological mechanism of PCIS includes release of
cardiac antigens in the pericardial space precipitating chemokines and
anti-myocardial antibodies production. Ongoing inflammation at the
epicardial level results in an inflammatory cascade \textbf{(Figure 5)}
.\textsuperscript{1,2}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

\textbf{(Figure 5)}

Indications for ASD closure in childhood are well documented, and
treatment is known to be effective.\textsuperscript{3} Complications
including development of cardiac tamponade, recurrent pericardial
effusion or pericardial effusions requiring drainage after ASD closure
are rare.\textsuperscript{1,4--6} Furthermore, these pericardial
complications are usually reported in the peri-procedure period, as
compared to our patient who developed symptoms several months after
surgery.\textsuperscript{7} RP concomitantly with constrictive
physiology in these patients after a latent period has been sporadically
reported in the literature. A prior study of 15 cases on RP in children
and adolescents concluded that surgical ASD closure (n=6) was the
predominant underlying etiology .\textsuperscript{6} Interestingly, the
risk of development of PCIS presenting as RP is similar between
pediatric and adult populations.\textsuperscript{8}

Echocardiogram and CMR supplemented clinical information to attain
diagnosis in our patient. CMR findings: mild LGE, right ventricular
tethering, diastolic septal bounce, and respirophasic shift supported
the diagnosis of recurrent pericarditis complicated by constrictive
physiology in our case.\textsuperscript{1} Short courses or abrupt
cessation of anti-inflammatory therapy without adequate tapering may
have resulted in residual pericardial inflammation, increasing his risk
of further flares. Treatment of pericarditis requires NSAIDs and
colchicine (as first line), steroids (second line), biologics such as
interleukin-1 receptor blockers or disease modifying anti-rheumatic
drugs (third line) and pericardiectomy (fourth line in refractory
cases).\textsuperscript{9,10}

Our case represents a rare occurrence of RP with constrictive physiology
treated with pericardiectomy in an adolescent patient with prior
surgical ASD repair. Medical management of PCIS can be complicated due
to its prolonged duration and notable side effects. Further, it can be
an underdiagnosed or under-reported condition among adolescents.
Patients with ASD repair are living longer and require monitoring for
complications.\textsuperscript{11} Therefore, in order to improve their
outcomes it is imperative to timely identify the development of PCIS and
adequately manage it.

\emph{Conclusion:}

Recurrent pericarditis along with constrictive physiology may occur in
adolescent patients with prior ASD repair after a prolonged symptom free
interval. Therefore, adolescents with repaired congenital heart defects
should be carefully screened for development of PCIS. Management can be
challenging and often requires advanced imaging (CMR) to guide
appropriate therapy. Treatment may necessitate addition of biologics to
anti-inflammatory therapy or further escalation to pericardiectomy in
refractory cases. Further research is needed to identify at-risk
patients and design preventive strategies.

\emph{References:}

1. Verma BR, Chetrit M, Gentry Iii JL, Noll A, Bafadel A, Khayata M, et
al. Multimodality imaging in patients with post-cardiac injury syndrome.
Heart. 2020 May;106(9):639--46.

2. Ramjee V, Li D, Manderfield LJ, Liu F, Engleka KA, Aghajanian H, et
al. Epicardial YAP/TAZ orchestrate an immunosuppressive response
following myocardial infarction. J Clin Invest. 2017 Mar
1;127(3):899--911.

3. Bialkowski J, Karwot B, Szkutnik M, Banaszak P, Kusa J, Skalski J.
Closure of atrial septal defects in children: surgery versus Amplatzer
device implantation. Tex Heart Inst J. 2004;31(3):220--3.

4. Han Y, Zhang X, Zhang F. Transcatheter and intraoperative device
closure of atrial septal defect in infants under three years of age. J
Cardiothorac Surg. 2020 Jan 8;15(1):9.

5. Kim BJ, Ma JS. Constrictive pericarditis after surgical closure of
atrial septal defect in a child. J Korean Med Sci. 1998
Dec;13(6):658--61.

6. Raatikka M, Pelkonen PM, Karjalainen J, Jokinen EV. Recurrent
pericarditis in children and adolescents: report of 15 cases. J Am Coll
Cardiol. 2003 Aug 20;42(4):759--64.

7. Abaci A, Unlu S, Alsancak Y, Kaya U, Sezenoz B. Short and long term
complications of device closure of atrial septal defect and patent
foramen ovale: meta-analysis of 28,142 patients from 203 studies.
Catheter Cardiovasc Interv. 2013 Dec 1;82(7):1123--38.

8. Tombetti E, Giani T, Brucato A, Cimaz R. Recurrent Pericarditis in
Children and Adolescents. Front Pediatr. 2019;7:419.

9. Adler Y, Charron P, Imazio M, Badano L, Bar\selectlanguage{ngerman}ón-Esquivias G, Bogaert J,
et al. 2015 ESC Guidelines for the diagnosis and management of
pericardial diseases. European Heart Journal. 2015 Nov
7;36(42):2921--64.

10. Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, et al.
Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent
Pericarditis. N Engl J Med. 2021 Jan 7;384(1):31--41.

11. Nyboe C, Karunanithi Z, Nielsen-Kudsk JE, Hjortdal VE. Long-term
mortality in patients with atrial septal defect: a nationwide
cohort-study. Eur Heart J. 2018 Mar 21;39(12):993--8.

\emph{Figures:}

Figure 1: Mitral annular early diastolic velocities ((lateral (A) and
medial (B)) demonstrating annulus reversus.

Figure 2: Black blood imaging demonstrates no overt pericardial
thickening \emph{(arrow).}

Note additional finding of mild pectus chest wall deformity \emph{(*).}

\emph{LA=Left Atrium}

\emph{LV=Left Ventricle}

\emph{RA=Right Atrium}

\emph{RV=Right Ventricle}

Figure 3: T1-weighted (fat suppressed) phase sensitive inversion
recovery sequence showing mild, predominantly basal pericardial delayed
enhancement \emph{(arrows).}

\emph{LV=Left Ventricle}

\emph{RV=Right Ventricle}

Figure 4: T2-weighted short-tau inversion recovery sequence, showing
absence of significant pericardial edema \emph{(arrow).} In contrast,
there is increased signal detected within the adjacent gastrointestinal
tract \emph{(*).}

\emph{LV=Left Ventricle}

\emph{RV=Right Ventricle}

Figure 5: Pictorial representation of pathophysiology of post cardiac
injury syndrome. \emph{Figure created using BioRender.}

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