https://orcid.org/0000-0002-1976-0785
Abstract
Presently, the association between myocarditis and messenger ribonucleic acid (mRNA) COVID-19 vaccination is well established. From the most current data, cases of myocarditis following COVID-19 vaccination seem to be mild with fast clinical recovery. Nevertheless, the complete resolution of the inflammatory process is still unclear.
We report the case of a 13-year-old boy who developed chest pain following the second dose of the Pfizer-BioNTech COVID-19 vaccine with long-term follow-up of cardiac magnetic resonance (CMR) imaging. An electrocardiogram (ECG) revealed progressively ST-segment elevation on the 2nd day of admission with a rapid improvement within 3 hours where only mild ST-segment elevation remained. The peak level of high-sensitivity cardiac troponin T was 1546 ng/L with rapid reduction. Echocardiogram revealed depressed left ventricular septal wall motion. CMR mapping techniques showed myocardial oedema with an increase in native T1 and extracellular volume (ECV). On the other hand, T1-weighted and T2-weighted images and late gadolinium enhancement (LGE) did not detect inflammation. The patient’s symptoms were relieved by oral ibuprofen. After 2 weeks, ECG and echocardiogram were unremarkable. However, the inflammation process was still present based on the CMR by mapping technique. During the 6-month follow-up, CMR returned to normal.
In our case, the subtle myocardial inflammation was diagnosed by mapping technique with only a T1-based marker according to the updated Lake Louise Criteria and the inflammation of the myocardium returned to normal within 6 months after the onset of the disease. Further follow-up and larger studies are needed to determine the complete resolution of the disease.
Cardiac magnetic resonance (CMR) parametric mapping technique might be needed to diagnose subtle myocardial inflammation.
The inflammation of the myocardium in myocarditis after messenger ribonucleic acid (mRNA) vaccination can return to normal within 6 months after the onset of the disease.
The recommendation to avoid competitive sports for 3–6 months with the re-evaluation of ECG, echocardiogram, and CMR imaging should be considered after myocarditis.
Introduction
After the emergency use authorization for the BNT162b2 messenger ribonucleic acid (mRNA) (Pfizer-BioNTech) vaccine to adolescents by the Food and Drug Administration of the United States (US) to prevent COVID-19 infection, cases of myopericarditis have been reported to the Vaccine Adverse Event Reporting System (VAERS) primarily in adolescent males after the second dose in the US.1 There were several case reports of confirmed myocarditis following the mRNA vaccine in the US and Israel.2 The most current data of short-term and mid-term follow-up suggest that the complete resolution of the inflammatory process may last over 3 months.3–5 However, long-term follow-up data are still limited.6,7 The Centre for Disease Control and Prevention (CDC) has started active follow-up surveillance to assess cardiac outcomes at 3 to 6 months in cases of myocarditis after COVID-19 vaccination.8 In this case report, we report a long-term follow-up case of confirmed myocarditis after the Pfizer-BioNTech COVID-19 vaccine with a focus on the dynamic changes in electrocardiography (ECG) and cardiac magnetic resonance (CMR) mapping techniques.
Timeline
PTA, prior to admission; ECG, electrocardiogram; CMR, cardiac magnetic resonance; IRBBB, incomplete right bundle branch block.
Case presentation
A previously healthy 13-year-old boy presented to an emergency department with chest pain and shortness of breath 20 h after receiving the second dose of Pfizer-BioNTech COVID-19 following the first dose 3 weeks ago. The symptoms started with fever, followed by chest pain and shortness of breath.
Initially, the patient had stable vital signs, normal oxygen saturation, and normal physical examination. However, ECG demonstrated diffuse ST-segment elevation (Figure 1A). C-Reactive protein (CRP) was slightly elevated (16.8 mg/L, normal range < 5 mg/L) but the erythrocyte sedimentation rate (ESR) and ferritin were normal. N-Terminal pro-brain natriuretic peptide (NT-proBNP) was normal (90 pg/mL, normal range < 125 pg/mL). High-sensitivity cardiac troponin T (hsTnT) was initially elevated (506 ng/L, normal range 0–16 ng/L) with a peak level on day 3 (Table 1). A nasopharyngeal polymerase chain reaction (PCR) for COVID-19 and another respiratory viral panel test were negative. Furthermore, the result for SARS-CoV-2 spike protein antibody was positive, and anti-nucleocapsid IgG was negative. Chest radiograph was normal. Echocardiogram revealed normal global cardiac function except mildly depressed left ventricular septal regional longitudinal strain (Figure 2) and no pericardial effusion.
Electrocardiogram (ECG). (A) ECG on day 1 shows diffuse ST elevation in lead I, II, aVL, aVF, and V2–V6 with ST depression in lead V1. (B) ECG on day 2 shows progressive ST elevation. (C) ECG on day 2 after 3 h shows significant improvement in ST-segment elevation. (D) ECG after 1-week follow-up shows ST elevation in lead V2–V5, the biphasic T waves in lead I, II, III, aVL, and V4–V6 with incomplete right bundle branch block.
Strain imaging echocardiography: regional longitudinal strain shows mildly depressed left ventricular function at anteroseptal and inferoseptal area.
Laboratory and imaging findings of the patient at presentation and follow-up
| Time from admission date | Admission day | 2 weeks | 3 months | 6 months | ||||
|---|---|---|---|---|---|---|---|---|
| Cardiac enzyme | ||||||||
| hsTnT (ng/L) | Day1 | Day2 | Day3 | Day4 | Day5 | 5 | - | - |
| (normal < 16) | 506 | 1405 | 1546 | 1136 | 538 | |||
| Electrocardiogram | ||||||||
| ECG findings | ST elevation in I, II, aVL, aVF, and V2–V6 with ST depression in V1 | ST elevation in V2–V4, biphasic T waves in I, II, III, aVL, and V4–V6 with incomplete RBBB | No ST elevation with incomplete RBBB | No ST elevation with incomplete RBBB | ||||
| Echocardiography | ||||||||
| LVEF (%) regional wall motion changes | 61 depressed left ventricular septal regional longitudinal strain | 63 normal | — | 64 normal | ||||
| CMR imaging | ||||||||
| T2 weighted and T1 weighted with LGE images | No myocardial oedema or necrosis | No myocardial oedema or necrosis | — | No myocardial oedema or necrosis | ||||
| Native T1 (ms) | 1031 ± 23.7 | 1060 ± 21.3 | 997 ± 33.8 | |||||
| Native T2 (ms) | 54.1 ± 2.96 | 49.8 ± 2.61 | 45.3 ± 2.66 | |||||
| ECV (%) | 32.3 | 26.1 | 24.2 | |||||
| Time from admission date | Admission day | 2 weeks | 3 months | 6 months | ||||
|---|---|---|---|---|---|---|---|---|
| Cardiac enzyme | ||||||||
| hsTnT (ng/L) | Day1 | Day2 | Day3 | Day4 | Day5 | 5 | - | - |
| (normal < 16) | 506 | 1405 | 1546 | 1136 | 538 | |||
| Electrocardiogram | ||||||||
| ECG findings | ST elevation in I, II, aVL, aVF, and V2–V6 with ST depression in V1 | ST elevation in V2–V4, biphasic T waves in I, II, III, aVL, and V4–V6 with incomplete RBBB | No ST elevation with incomplete RBBB | No ST elevation with incomplete RBBB | ||||
| Echocardiography | ||||||||
| LVEF (%) regional wall motion changes | 61 depressed left ventricular septal regional longitudinal strain | 63 normal | — | 64 normal | ||||
| CMR imaging | ||||||||
| T2 weighted and T1 weighted with LGE images | No myocardial oedema or necrosis | No myocardial oedema or necrosis | — | No myocardial oedema or necrosis | ||||
| Native T1 (ms) | 1031 ± 23.7 | 1060 ± 21.3 | 997 ± 33.8 | |||||
| Native T2 (ms) | 54.1 ± 2.96 | 49.8 ± 2.61 | 45.3 ± 2.66 | |||||
| ECV (%) | 32.3 | 26.1 | 24.2 | |||||
CMR data are reported as mean ± SD (range); cutoff value for the quantitative parameter of CMR9: T1 native > 1000 ms, T2 native > 55.9 ms, and ECV fraction > 28.8%. The normal values at our centre: T1 native = 998 ± 23.9 ms, T2 native = 54.6 ± 8.64 ms, and ECV = 25.4 ± 4%. hsTnT, high sensitivity cardiac troponin T; ECG, electrocardiogram; RBBB, right bundle branch block; LVEF, left ventricular ejection fraction; CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement; ms, milliseconds; ECV, extracellular volume; -, not applicable.
Laboratory and imaging findings of the patient at presentation and follow-up
| Time from admission date | Admission day | 2 weeks | 3 months | 6 months | ||||
|---|---|---|---|---|---|---|---|---|
| Cardiac enzyme | ||||||||
| hsTnT (ng/L) | Day1 | Day2 | Day3 | Day4 | Day5 | 5 | - | - |
| (normal < 16) | 506 | 1405 | 1546 | 1136 | 538 | |||
| Electrocardiogram | ||||||||
| ECG findings | ST elevation in I, II, aVL, aVF, and V2–V6 with ST depression in V1 | ST elevation in V2–V4, biphasic T waves in I, II, III, aVL, and V4–V6 with incomplete RBBB | No ST elevation with incomplete RBBB | No ST elevation with incomplete RBBB | ||||
| Echocardiography | ||||||||
| LVEF (%) regional wall motion changes | 61 depressed left ventricular septal regional longitudinal strain | 63 normal | — | 64 normal | ||||
| CMR imaging | ||||||||
| T2 weighted and T1 weighted with LGE images | No myocardial oedema or necrosis | No myocardial oedema or necrosis | — | No myocardial oedema or necrosis | ||||
| Native T1 (ms) | 1031 ± 23.7 | 1060 ± 21.3 | 997 ± 33.8 | |||||
| Native T2 (ms) | 54.1 ± 2.96 | 49.8 ± 2.61 | 45.3 ± 2.66 | |||||
| ECV (%) | 32.3 | 26.1 | 24.2 | |||||
| Time from admission date | Admission day | 2 weeks | 3 months | 6 months | ||||
|---|---|---|---|---|---|---|---|---|
| Cardiac enzyme | ||||||||
| hsTnT (ng/L) | Day1 | Day2 | Day3 | Day4 | Day5 | 5 | - | - |
| (normal < 16) | 506 | 1405 | 1546 | 1136 | 538 | |||
| Electrocardiogram | ||||||||
| ECG findings | ST elevation in I, II, aVL, aVF, and V2–V6 with ST depression in V1 | ST elevation in V2–V4, biphasic T waves in I, II, III, aVL, and V4–V6 with incomplete RBBB | No ST elevation with incomplete RBBB | No ST elevation with incomplete RBBB | ||||
| Echocardiography | ||||||||
| LVEF (%) regional wall motion changes | 61 depressed left ventricular septal regional longitudinal strain | 63 normal | — | 64 normal | ||||
| CMR imaging | ||||||||
| T2 weighted and T1 weighted with LGE images | No myocardial oedema or necrosis | No myocardial oedema or necrosis | — | No myocardial oedema or necrosis | ||||
| Native T1 (ms) | 1031 ± 23.7 | 1060 ± 21.3 | 997 ± 33.8 | |||||
| Native T2 (ms) | 54.1 ± 2.96 | 49.8 ± 2.61 | 45.3 ± 2.66 | |||||
| ECV (%) | 32.3 | 26.1 | 24.2 | |||||
CMR data are reported as mean ± SD (range); cutoff value for the quantitative parameter of CMR9: T1 native > 1000 ms, T2 native > 55.9 ms, and ECV fraction > 28.8%. The normal values at our centre: T1 native = 998 ± 23.9 ms, T2 native = 54.6 ± 8.64 ms, and ECV = 25.4 ± 4%. hsTnT, high sensitivity cardiac troponin T; ECG, electrocardiogram; RBBB, right bundle branch block; LVEF, left ventricular ejection fraction; CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement; ms, milliseconds; ECV, extracellular volume; -, not applicable.
First CMR imaging on admission revealed normal biventricular volumes and systolic function. Coronary artery abnormalities were excluded by coronary magnetic resonance angiography (see Supplementary material online, Figure S1). A conventional qualitative analysis of signal intensities on T2-weighted and late gadolinium enhancement (LGE) images did not show oedematous change or myocardial necrosis (Figure 3). On the other hand, a quantitative analysis of myocardial tissue showed an increase in all segments of the native T1 by mapping technique (Figure 4), and extracellular volume (ECV) (1031 ± 23.7 ms and 0.32, respectively) (Table 1). The native T1 value was highest at the inferolateral and anterior segments (1092 ± 41.8 and 1039 ± 74.8 ms, respectively), which indicated myocardial oedema and fibrosis. CMR imaging was performed on a 1.5-T MR unit (Ingenia Philips Medical Systems, Best, The Netherlands) using a body and phased array coils. Myocardial T1 mapping was assessed by the modified Look-Locker inversion recovery (MOLLI) sequence.
Serial cardiac magnetic resonance (CMR) imaging performed on admission day (1), 2 weeks (2), and 6 months (3). The figure shows steady-state free precession imaging (SSFP CINE), T1-weighted imaging (T1W), T2-weighted imaging (T2W), T2-weighted short-tau inversion recovery imaging (T2W STIR), late gadolinium enhancement imaging (LGE), native T1 mapping (nT1 mapping), enhanced T1 mapping (eT1 mapping), and T2 mapping.
(A) Native T1 mapping and postcontrast images showing a region of interest (ROI) draw in the six basal segments with increased T1 native in all segments (1031 ± 23.7 ms) and postcontrast T1 mapping (469 ± 20.3 ms), and (B) T2 mapping image with value (54.1 ± 2.96 ms). Data are reported as mean ± SD (range). Cutoff value9: T1 native > 1000 ms, T2 native > 55.9 ms. The normal values at our centre: native T1 mapping = 998 ± 23.9 ms, enhanced T1 mapping = 420 ± 9 ms, T2 mapping = 54.6 ± 8.64 ms. ms, milliseconds. Cardiac magnetic resonance (CMR) acquisition protocol included balanced steady-state free precession cine-MR (SSFP cine MR) images. Oedema CMR was performed by black–blood T2-weighted short tau inversion recovery (STIR) and T2 mapping. A dose of 0.2 mmol/kg Gadobutrol (Gd-DO3A-butrol, Gadovist; Bayer Healthcare, Leverkusen, Germany) was injected with a rate of 2.5 mL/s.
The patient required only an oxygen cannula for respiratory support during this admission. On day 2 of admission, he developed severe chest pain but stable vital signs. ECG showed progression of ST elevation (Figure 1B), hsTnT elevated to 1405 ng/L. However, his symptom was relieved by oral ibuprofen 400 mg once daily without any other medications and ECG was significantly improved within 3 h (Figure 1C). He was discharged on day 5. After a 1-week follow-up, he had no symptoms, normal troponin T level, mild ST elevation, and incomplete right bundle branch block (RBBB) on ECG (Figure 1D). He did not receive any medications at the follow-up.
Subsequently, the patient’s clinical condition and ECG were assessed at week 2, month 3, and month 6. The echocardiogram and CMR were done at week 2 and month 6 until CMR returned to normal (Figure 3 and Table 1). After the normalization of CMR, the last follow-up schedule was at month 12 to ensure that there is no additional change in clinical and ECG including advising any concerns about the booster vaccine before discharging the patient from our clinic.
Discussion
We reported a case of a 13-year-old boy with confirmed myocarditis following the CDC Working Case Definitions with 2018 Lake Louise criteria (LLC) for CMR10,11 after receiving the 2nd dose of the Pfizer-BioNTech COVID-19 vaccine with the long-term follow-up.
Possible mechanisms for myocarditis after mRNA-based vaccination include a nonspecific innate inflammatory response or a molecular mimicry mechanism between viral spike protein and cardiac protein.12 Nevertheless, the long-term effect of post-mRNA vaccine myocarditis is unclear.
Our case report showed the long-term follow-up and striking dynamic change of ECG and CMR. After the resolution of symptoms and normalized cardiac enzyme, we found an incomplete RBBB on the ECG that might be residual inflammation of the myocardium at the conduction system, compatible with mildly depressed left ventricular septal regional longitudinal strain. However, long-term follow-up of ECG at 3 months and 6 months still showed incomplete RBBB, while the result of CMR showed improvement in inflammation and returned to normal at 6 months. Therefore, the RBBB on ECG might be a pre-existing condition.
We emphasized long-term follow-up on CMR to explain the course and recovery pattern of COVID-19 vaccine–induced myocarditis. Shiyovich et al.6 performed a follow-up on CMR at a median time of 212 days (IQR: 105–274 days) in seven patients with a relatively older age compared to our study’s population. The results showed complete resolution of LGE in one patient and some improvement of LGE in the remaining patients.
In our study, we skipped CMR at 3 months and chose the 6-month follow-up to reduce unnecessary exposure to contrast and ensured that there was a higher chance that the myocardium would return to normal. In our case report, we recognized that the inflammation of the myocardium can return to normal within 6 months after the onset of the disease.
Unlike the previous studies,3–7 we found that the myocardial oedema was detected using T1 mapping and ECV without evidence of positive LGE. Thus, myocarditis can be diagnosed based only on T1-based criteria relying on the updated LLC,10 though with less specificity. Therefore, to confirm the diagnosis, we suggest performing the T1-mapping in cases of suspected myocarditis with negative results of T2-weighted image and LGE.
Based on our results and the recommendation to avoid competitive sports for 3–6 months after myocarditis13 and multisystem inflammatory syndrome in children (MIS-C),14 we suggest re-evaluation with ECG, echocardiogram, exercise test, and CMR with the quantitative analysis in those with abnormalities on the baseline before a resumption of sports to confirm that there is no subtle myocardial inflammation.
In terms of a booster vaccine in the patient, the patient’s perspective is also concerned about a booster vaccine during follow-up. Our suggestion relies on the current US Centre for Disease Control advice on vaccine boosters in postvaccination myocarditis.15 Since the patient has no risk of severe acute COVID-19, a booster vaccine should be avoided until additional safety data are available.
Based on the current data, the benefits of vaccination still outweigh the risk. However, our single case represents only mild clinical severity. Therefore, further studies with larger numbers of cases and various severities for long-term follow-up data are required.
Lead author biography
Pakaparn Kittichokechai is a paediatric cardiologist in the Department of Paediatrics, Panyananthaphikkhu Chonprathan Medical Centre, Srinakharinwirot University, Nonthaburi, Thailand—initial date submitted: Oct 05, 2022; date of final disposition set: 11 May 2023; date of revision being submitted: 05 May 2023.
Supplementary material
Supplementary material is available at European Heart Journal – Case Reports online.
Acknowledgements
The authors would like to acknowledge the paediatricians and emergency physicians at Panyananthaphikkhu Chonprathan Medical Centre for taking care of the patient. We would like to thank Professor Anant Khositseth for the comprehensive language review and editing of this manuscript and Dr. Kitchawan Hengkrawi for the data on COVID-19 mRNA vaccines. The study has been approved by the Committee on Human Rights Related Research Involving Human Subjects, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University (EC 018/64).
Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.
Consent: The authors confirm that written consent for the submission and publication of this case has been obtained from the patient in line with COPE guidance.
Funding: There is no source of financial grants and other funding.
Data availability
The data underlying this article are available in the article and in its online Supplementary material.
References
Author notes
Conflict of interest: None declared.
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