Although prior studies have shown that cardiovascular complications, such as myocardial infarction, myocarditis, ventricular arrhythmias, and stress cardiomyopathy, were prevalent in hospitalized patients with COVID-19 [4-6] , cardiovascular complications of the mRNA-based vaccines have not yet been reported in the literature, and are likely to be very rare. In this case series, we describe two patients with clinically suspected myocarditis, one patient with stress cardiomyopathy, and two patients with pericarditis after receiving an mRNA-based COVID-19 vaccine. None of these patients had previously tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

In December 2020, the Food and Drug Administration issued an Emergency Use Authorization (EUA) for two mRNA-based vaccines developed by Pfizer-BioNTech and Moderna for the prevention of coronavirus disease 2019 (COVID-19) [1] . In the clinical trials assessing the safety of these two-dose vaccines, patients who received the vaccines more commonly experienced higher rates of local injection site reactions, fatigue, and headaches, and there were very few serious adverse events [2,3] . Furthermore, there were no reports of serious cardiovascular events.

Myocarditis

Case 1

A 19-year-old male student with no significant past medical history presented to our hospital with acute substernal chest pressure and shortness of breath four days after receiving the second dose of the Pfizer-BioNTech vaccine.

On presentation, he was afebrile, with a heart rate of 71 beats per minute (bpm), and blood pressure of 145/95 mmHg. Physical exam was unremarkable. His electrocardiogram (ECG) was notable for diffuse ST elevations (Figure 1A), and laboratory studies demonstrated evidence of myocardial injury and elevated inflammatory markers (Table 1). There was no evidence of coronary artery disease (CAD) on coronary angiography, and echocardiography showed a mildly reduced left ventricular (LV) ejection fraction (EF) of 47% with no regional wall motion abnormalities.

Figure 1: Electrocardiogram (ECG) and cardiac magnetic resonance imaging (CMR) findings corresponding to Case 1 A. ECG shows diffuse ST elevations. B. Short axis cine in diastole. C. T1 imaging demonstrates regional elevation in the lateral wall (between the arrows). D. T2 mapping shows elevated T2 values in the lateral wall (between the arrows). E. Late gadolinium enhancement imaging shows subepicardial enhancement (between the arrows) in the same areas of T1 and T2 elevations.

Cardiovascular Adverse Event Age (years) Gender Viral serologies Cardiac Biomarkers Inflammatory Markers Transthoracic Echocardiogram Cardiac MRI Coronary Evaluation Myocarditis Patient 1 19 Male HIV, influenza, RSV, and SARS-CoV-2 negative Troponin T: 1.37 ng/mL (reference range: <0.03 ng/mL) CRP: 1.8 mg/dL (reference range: <0.80 mg/dL); ESR: 26 mm/hour (reference range: < 20 mm/hour) LVEF: 47%; LVIDd: 4.7 cm; Normal RV size and function; No valvular disease LVEF: 56%; LVEDVi: 84 mL/m2; RVEF: 54%; RVEDVi: 86 mL/m2; Subepicardial LGE involving the basal to mid lateral wall, with corresponding elevated native T1 and T2 values Coronary angiography: No coronary artery disease or anomalies Patient 2 18 Male HIV, influenza, RSV, and SARS-CoV-2 negative High-sensitivity troponin: 7,206 ng/L \(\rightarrow\) 32,140 ng/L (reference range: <15 ng/L) CRP: 74.2 mg/L (reference range: <10 mg/L); ESR: 29 mm/hour (reference range: <15 mm/hour) LVEF: 59% \(\rightarrow\) 50%, LVIDd: 4.8 cm; Normal RV size and function; No valvular disease LVEF: 53%; LVEDVi: 101 mL/m2; RVEF: 49%; RVEDVi: 118 mL/m2; Subepicardial LGE involving the mid lateral wall, with corresponding elevated native T1 and T2 values Coronary computed tomography angiography: No coronary artery disease or anomalies Stress Cardiomyopathy Patient 1 60 Female SARS-CoV-2, influenza, and RSV negative Troponin T: 0.129 ng/mL (reference range: <0.03 ng/mL) Not checked LVEF: 44%; LVIDd: 3.5 cm; Normal RV size and function; Apical akinesis Not performed Coronary angiography: Patent LAD stent Pericarditis Patient 1 21 Female SARS-CoV-2, HIV negative Troponin T: undetectable CRP: 72.6 mg/L (reference range: <3 mg/L); ESR: 9 mm/hour (reference range: <19 mm/hour) LVEF: 60%; LVIDd: 4.5 cm; Normal RV size and function; Small pericardial effusion Not performed Not performed Patient 2 61 Female SARS-CoV-2 negative Troponin T: undetectable CRP: 23.1 mg/dL (reference range: <0.80 mg/dL); ESR: 81 mm/hour (reference range: <15 mm/hour) LVEF: 65%; LVIDd: 3.6 cm; Normal RV size and function; Small to moderate circumferential pericardial effusion Not performed Not performed Table 1: Summary of diagnostic testing. CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HIV, human immunodeficiency virus; LAD, left anterior descending artery; LGE, late gadolinium enhancement; LVEDVi, left ventricular end-diastolic volume index; LVEF: left ventricular ejection fraction; LVIDd: left ventricular end-diastolic internal dimension; MRI, magnetic resonance imaging; RSV, respiratory syncytial virus; RVEDVi, right ventricular end-diastolic volume index; RVEF: right ventricular ejection fraction

Cardiac magnetic resonance imaging (CMR) identified mild hypokinesis of the basal to mid lateral wall, with corresponding elevated native T1 values (1070-1160 ms; reference range: 950-1050 ms), elevated T2 values (57-59 ms; reference range: 40-50 ms), and subepicardial delayed enhancement (Figure 1B-1E) in the lateral wall. Based on the clinical presentation and updated Lake Louise Criteria for myocardial inflammation by CMR [7], the patient was diagnosed with acute myocarditis. Subsequent viral studies were negative for human immunodeficiency virus (HIV), influenza, respiratory syncytial virus (RSV), and SARS-CoV-2. The patient’s chest pain resolved, and he was discharged on lisinopril and metoprolol succinate.

Case 2

An 18-year-old male student with no significant past medical history was transferred to our hospital for management of worsening LV function following the second dose of the Moderna vaccine.

He initially presented to another hospital, where he reported fevers, myalgias, and acute substernal chest pain one day after receiving the second dose. On presentation, his temperature was 101°F, heart rate was 120 bpm, and blood pressure was 110/59 mmHg. Physical examination was unremarkable. ECGs demonstrated diffuse ST elevations (Figure 2A), and laboratory studies were notable for an elevated high-sensitivity troponin. LV systolic function on the initial echocardiogram was normal, but a subsequent echocardiogram demonstrated a mild reduction in LVEF to 50%. At our hospital, coronary computed tomography angiography revealed normal coronaries.

Figure 2: Electrocardiogram (ECG) and cardiac magnetic resonance imaging (CMR) findings corresponding to Case 2 A. ECG shows diffuse ST elevations. B. 4 chamber cine. C. T1 imaging demonstrates regional elevation in the lateral wall (between the arrows). D. T2 mapping shows elevated T2 values in the lateral wall (between the arrows). E. Late gadolinium enhancement imaging shows subepicardial enhancement (between the arrows) in the same areas of T1 and T2 elevations.

CMR revealed mild hypokinesis of the mid lateral wall, with corresponding elevated native T1 values (1089-1097 ms; reference range: 950-1050 ms) and T2 values (64-72 ms; reference range: 40-50 ms), and subepicardial delayed enhancement (Figure 2B-2E) in the lateral wall. Viral serologies for HIV, influenza, RSV, and SARS-CoV-2 were negative. The patient’s hospital course was complicated by brief episodes of non-sustained ventricular tachycardia, and he was discharged on metoprolol succinate and a course of colchicine and ibuprofen.

Stress cardiomyopathy

A 60-year-old woman with a history of a stent placed in the left anterior descending artery (LAD) three years ago, and normal LV function and wall motion on echocardiography five months ago, presented to clinic four days after receiving her second dose of the Pfizer-BioNTech vaccine, with exertional chest pain and new inferolateral T wave inversions (Figure 3A). She was admitted to the hospital for further evaluation, and echocardiography revealed mildly reduced LV function with apical akinesis (Figure 3B-3C). Coronary angiography demonstrated a patent LAD stent and no obstructive disease. Based on these findings, the patient was diagnosed with a stress cardiomyopathy, and she was discharged on metoprolol succinate and lisinopril.

Figure 3: Electrocardiogram (ECG) and echocardiography findings in a patient with stress cardiomyopathy A. ECG demonstrating T wave abnormalities in the inferolateral leads (II, III, aVF, V3-V6). B. Apical 3 chamber view in diastole. C. Apical 3 chamber view in systole. The arrows denote the hinge points of apical akinesis.

Pericarditis

The first patient was a 21-year-old woman with a history of idiopathic thrombocytopenic purpura, who presented three weeks after her first dose of the Pfizer-BioNTech vaccine with chest pain that worsened during inspiration and while supine. She was found to have sinus tachycardia, a small pericardial effusion on echocardiogram, and elevated inflammatory markers without evidence of myocardial injury. Based on the clinical presentation, the patient was diagnosed with pericarditis [8]. Her symptoms improved significantly with initiation of colchicine.

The second patient was a 61-year-old woman with a history of hypertension who developed low-grade fevers, night sweats, chest discomfort and palpitations four weeks after her second dose of the Pfizer-BioNTech vaccine. She noted that her symptoms improved when leaning forward. On exam, she was found to have a friction rub. ECG revealed new-onset atrial fibrillation (Figure 4A) and echocardiography demonstrated a small to moderate circumferential pericardial effusion (Figure 4B-4C). Inflammatory markers were significantly elevated and viral serologies were negative. Based on these clinical features, the patient was diagnosed with pericarditis [8]. The patient was started on colchicine with improvement in her symptoms. Both patients tested negative for SARS-CoV-2.