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\begin{document}

\title{Perimyocarditis after COVID-19 mRNA Vaccine: The Role of Cardiac
Magnetic Resonance Imaging}



\author[1]{Ashwin Kumar}%
\author[1]{Evan Harmon}%
\author[2]{Abdullah Yesilyaprak}%
\author[1]{Ankit Agrawal}%
\author[3]{Sayan Manna}%
\author[4]{Paul Schoenhagen}%
\author[1]{Allan Klein}%
\affil[1]{Cleveland Clinic}%
\affil[2]{Wayne State University}%
\affil[3]{Mt. Carmel Health System}%
\affil[4]{Cleveland Clin}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
A 22-year-old male presented with chest pain 3 days after his second
dose of the COVID-19 vaccine. Cardiac magnetic resonance imaging
demonstrated myocardial and pericardial enhancement. Given imaging and
clinical findings, he was diagnosed with perimyocarditis. He was treated
with a multitude of medications including NSAIDs, colchicine, and
steroids. Fortunately, he was able to achieve symptom improvement. Due
to COVID-19 vaccination novelty, further research is needed to identify
side effects.%
\end{abstract}%



\sloppy


\textbf{Perimyocarditis after COVID-19 mRNA Vaccine: The Role of Cardiac
Magnetic Resonance Imaging}

Ashwin Kumar, BS\textsuperscript{1*}, Evan Harmon,
MD\textsuperscript{1*}, Abdullah Yesilyaprak, MD\textsuperscript{1},
Ankit Agrawal, MD\textsuperscript{1}, Sayan Manna,
MD\textsuperscript{2}, Paul Schoenhagen, MD\textsuperscript{3}, Allan L.
Klein, MD\textsuperscript{1}

*Contributed Equally

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. Mt. Carmel Health System, Columbus, Ohio, USA

3. Imaging Institute, Cleveland Clinic, Cleveland, Ohio, USA

\textbf{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

\textbf{Word Count: 1288}

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

\textbf{Funding:} None

\textbf{ABSTRACT:}

A 22-year-old male presented with chest pain 3 days after his second
dose of the COVID-19 vaccine. Cardiac magnetic resonance imaging
demonstrated myocardial and pericardial enhancement. Given imaging and
clinical findings, he was diagnosed with perimyocarditis. He was treated
with a multitude of medications including NSAIDs, colchicine, and
steroids. Fortunately, he was able to achieve symptom improvement. Due
to COVID-19 vaccination novelty, further research is needed to identify
side effects.

\textbf{KEY WORDS:} pericarditis, multimodality imaging, COVID-19, mRNA
vaccine, cardiac magnetic resonance imaging

\textbf{Presentation}

A 22-year-old male with past medical history of Coxsackie myocarditis in
2019 presented to the emergency department with acute chest pressure and
diaphoresis. He described his chest pain as squeezing with radiation to
the back. The patient denied dyspnea, edema, and lightheadedness.
Physical examination and vital signs were within normal limits.
Cardiovascular exam showed regular rate, normal rhythm, S1, S2 sounds,
and no pericardial rub. He was taking no medications and had received
his second dose of the Pfizer (BNT162b2) mRNA Coronavirus-19 disease
(COVID-19) vaccine 3 days prior to symptoms onset. Laboratory
examination showed high sensitivity C-reactive protein (hs-CRP) (3.15
mg/L), troponin (126 ng/mL) and brain natriuretic peptide (105 pg/mL)
levels were all elevated. Severe acute respiratory
syndrome-Coronavirus-2 (SARS-CoV-2) IgG test was positive indicative of
prior infection with COVID-19. Electrocardiogram (ECG) showed diffuse
ST-segment elevation suggestive of pericarditis. CXR was negative.
Bedside echocardiography (Echo) demonstrated mildly reduced ejection
fraction (EF) (45\%). Cardiac magnetic resonance imaging (CMR)
identified a small pericardial effusion, and profound basal
inferolateral and lateral myocardial involvement \textbf{(Figure
1A).}Given his clinical and imaging findings, he was diagnosed with
perimyocarditis secondary to COVID-19 vaccination. He was prescribed
Aspirin 650 mg TID, colchicine 0.6 mg BID, and 1 month prednisone taper
(30 mg). At 6 week follow-up, the patient noted his pain was
significantly improved. The patient had completed his steroid taper and
discontinued aspirin therapy due to gastrointestinal distress.
Laboratory markers and ECG were normal. Echo showed EF
recovery\textbf{(Video 1).} Repeat CMR demonstrated interval improvement
in pericardial effusion and delayed enhancement \textbf{(Figure 1B)} .
His colchicine was tapered to 0.6 mg daily and he was told to follow up
in 4 months.

\textbf{Discussion}

COVID-19 vaccination efforts have been increasing resulting in many
receiving mRNA vaccines. The COVID-19 mRNA vaccine encodes for the spike
glycoprotein of the virus. The vaccine's liquid suspension particles
allow for direct delivery of mRNA into host cells. Once intracellular,
the mRNA upregulates ribosomal activity to create the spike
glycoprotein.\textsuperscript{1} The spike glycoprotein is then
presented on the surface of the cell, this subsequently triggers the
immune system to produce antibodies specific to the spike
protein.\textsuperscript{1,2} COVID-19 vaccine side effects are
typically mild and may involve local injection site pain, myalgia, and
fatigue. Serious adverse effects are rare, but recent reports have
suggested that mRNA COVID-19 vaccines may cause myocarditis,
pericarditis, and myopericarditis. As of June 11th 2021, the Centers for
Disease Control (CDC) have identified 323 cases of myocarditis,
pericarditis, and myopericarditis in the United
States.\textsuperscript{3} CDC findings suggest that afflicted patients
are more likely to be male, younger with a median age of 19 years, and
experience symptoms within two days after
vaccination.\textsuperscript{3} The most common presenting symptoms
include chest pain (85\%-95\%), fever (65\%) dyspnea (19\%-49\%), and
syncope (6\%).\textsuperscript{4} The CDC also determined that patients
were more likely to be hospitalized, but clinical course was mild as
most patients recover fully .\textsuperscript{3,5} While no consensus
mechanism has been elucidated, vaccine component hypersensitivity,
inflammatory reaction, and inappropriate immune system activation have
been mentioned as potential causes.\textsuperscript{4} Perimyocarditis
diagnosis requires fulfillment of 2 out of 4 major criteria: pleuritic
chest pain, auscultation of pericardial rub, ECG changes, and effusion
on imaging.\textsuperscript{6} Additionally, patients must also have
elevated biomarkers suggestive of myocardial injury (troponin) and
reduced left ventricular function.\textsuperscript{4} Our patient
presented with pleuritic chest pain, characteristic ECG changes,
effusion on imaging, minor LV dysfunction, and biomarker elevation.
Imaging with Echo and CMR are useful for diagnosis and informing
clinical course. Echo can identify the presence of effusion as well as
be used for risk stratification in patients with cardiac
tamponade.\textsuperscript{7} Findings of pericarditis on CMR include
T1-weighted enhancement of the thickened pericardium, T2-weighted
increased pericardial intensity, and presence of pericardial edema on
delayed hyperenhancement (DHE).\textsuperscript{8} Notably, CMR findings
of DHE in patients who develop non-vaccine myocarditis is associated
with increased risk of cardiac
complications.\textsuperscript{9}Therefore, assessing the long term risk
of complications in patients who have DHE on CMR after vaccination is
paramount.\textsuperscript{9} While much is still unknown about
management of perimyocarditis in patients after COVID-19 vaccination,
patients are treated using current guidelines for pericarditis
management (non-steroidal anti-inflammatory drugs, colchicine, and/or
steroids). Luckily, our patient was able to achieve clinical improvement
on this regimen alone. Biologics (rilonacept) are indicated in patients
who develop dependence on NSAIDs, colchicine, and
steroids.\textsuperscript{10}To our knowledge, this is one of the first
reports of perimyocarditis after COVID-19 vaccination. Fortunately,
these patients seem to experience mild disease courses. However, further
observational studies are required to understand the side effects
associated with COVID-19 vaccination.

\textbf{Conclusion:}

Perimyocarditis after COVID-19 mRNA vaccination is a rare occurrence.
Patients present rapidly after vaccination, but overall have mild
clinical courses. Diagnosis requires high clinical suspicion and proper
clinical assessment. Multi-modality imaging especially CMR imaging is
also helpful for diagnosis and management.

\textbf{Author Contributions:} Ashwin Kumar: Drafting article, critical
revision of article, approval of article Evan Harmon: Drafting article,
critical revision of article, approval of article Abdullah Yesilyaprak:
Drafting article, critical revision of article, approval of article
Ankit Agrawal: Drafting article, critical revision of article, approval
of article Sayan Manna: Drafting article, critical revision of article,
approval of article Paul Schoenhagen: Drafting article, critical
revision of article, approval of article Allan Klein: Drafting article,
critical revision of article, approval of article

\textbf{References:}

1. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against
SARS-CoV-2 --- Preliminary Report. \emph{N Engl J Med} .
2020;383(20):1920-1931. doi:10.1056/NEJMoa2022483

2. Hendaus MA, Jomha FA. mRNA Vaccines for COVID-19: A Simple
Explanation. \emph{Qatar Med J} . 2021;2021(1). doi:10.5339/qmj.2021.7

3. Gargano JW, Wallace M, Hadler SC, et al. Use of mRNA COVID-19 Vaccine
After Reports of Myocarditis Among Vaccine Recipients: Update from the
Advisory Committee on Immunization Practices --- United States, June
2021. \emph{MMWR Morb Mortal Wkly Rep} . 2021;70(27):977-982.
doi:10.15585/mmwr.mm7027e2

4. Hudson B, Mantooth R, DeLaney M. Myocarditis and pericarditis after
vaccination for COVID-19. \emph{J Am Coll Emerg Physicians Open} .
2021;2(4). doi:10.1002/emp2.12498

5. Lazaros G, Klein AL, Hatziantoniou S, Tsioufis C, Tsakris A,
Anastassopoulou C. The Novel Platform of mRNA COVID-19 Vaccines and
Myocarditis: Clues into the Potential Underlying
Mechanism.\emph{Vaccine} . 2021;39(35):4925-4927.
doi:10.1016/j.vaccine.2021.07.016

6. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the
diagnosis and management of pericardial diseases. \emph{Eur Heart J} .
2015;36(42):2921-2964. doi:10.1093/eurheartj/ehv318

7. Chetrit M, Xu B, Verma BR, Klein AL. Multimodality Imaging for the
Assessment of Pericardial Diseases. \emph{Curr Cardiol Rep} .
2019;21(5):41. doi:10.1007/s11886-019-1115-y

8. Imazio M, Pivetta E, Palacio Restrepo S, et al. Usefulness of Cardiac
Magnetic Resonance for Recurrent Pericarditis. \emph{Am J Cardiol} .
2020;125(1):146-151. doi:10.1016/j.amjcard.2019.09.026

9. Dionne A, Sperotto F, Chamberlain S, et al. Association of
Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case
Series of Children. \emph{JAMA Cardiol} . Published online August 10,
2021. doi:10.1001/jamacardio.2021.3471

10. Klein AL, Imazio M, Cremer P, et al. Phase 3 Trial of Interleukin-1
Trap Rilonacept in Recurrent Pericarditis. \emph{N Engl J Med} .
2021;384(1):31-41. doi:10.1056/NEJMoa2027892

\textbf{Figures:}

\textbf{Figure 1. Timeline of Disease Course}

A. Initial CMR with basal inferolateral and lateral myocardial
involvement \emph{(arrows)} and associated pericardial effusion

\emph{(star)}

B. Follow up CMR with interval improvement in pericardial effusion and
delayed enhancement \emph{(arrows)}

\emph{BNP: Brain Natriuretic Peptide}

\emph{CMR: Cardiac Magnetic Resonance Imaging DHE: Delayed Enhancement
Hs-CRP: High Sensitivity C - reactive protein}

\emph{LV: Left Ventricle}

\emph{RV: Right Ventricle}

\emph{RV: Right Ventricle Outflow Tract}

\textbf{Figure 2. Follow-Up Echocardiographic Findings}

Four chamber apical view demonstrating normal biventricular function
after symptom resolution.

\emph{LA: Left Atrium LV: Left Ventricle RA: Right Atrium RV: Right
Ventricle}\selectlanguage{english}
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