Abstract
There have been reports of myocarditis following vaccination against COVID-19. We sought to describe cardiac magnetic resonance (CMR) findings among pediatric patients. Retrospective review at a large academic center of patients clinically diagnosed with post-vaccine myocarditis (PVM) undergoing CMR. Data collected included parametric mapping, ventricular function, and degree of late gadolinium enhancement (LGE). Post-processing strain analysis was performed using feature tracking. Strain values, T1/T2 values, and ventricular function were compared to age- and gender-matched controls with viral myocarditis using a Wilcoxon Signed Rank test. Among 12 patients with presumed PVM, 11 were male and 11 presented after the second vaccination dose, typically within 4 days. All presented with chest pain and elevated troponin. 10 met MRI criteria for acute myocarditis. All had LGE typically seen in the lateral and inferior walls; only five had prolonged T1 values. 10 met criteria for edema based on skeletal muscle to myocardium signal intensity ratio and only 5 had prolonged T2 mapping values. Patients with PVM had greater short-axis global circumferential and radial strain, right ventricle function, and cardiac output when compared to those with viral myocarditis. Patients with PVM have greater short-axis global circumferential and radial strains compared to those with viral myocarditis. LGE was universal in our cohort. Signal intensity ratios between skeletal muscle and myocardium may be more sensitive in identifying edema than T2 mapping. Overall, the impact on myocardial strain by CMR is less significant in PVM compared to more classic viral myocarditis.
Keywords: Myocarditis, Cardiac magnetic resonance, COVID-19, Pediatric, Vaccination
Introduction
Following the Food and Drug Administration’s Emergency Use Authorization (EUA) for the Pfizer-BioNTech BNT1262b2 mRNA vaccine in December 2020, scattered reports emerged of myocarditis temporally associated with vaccine administration. This finding was also reported in the pediatric population after the EUA was extended to patients above age 12 in March 2021 [1–14].
While there are multiple studies detailing the clinical presentation and course of post-vaccine myocarditis, there is little in the way of comparison of these findings with typical viral myocarditis. Cardiac magnetic resonance (CMR) has been used for years for the diagnosis and management of myocarditis [15–19]. However, detailed CMR data on tissue characterization and ventricular function including strain are lacking, especially in the pediatric population. We hypothesized that vaccine myocarditis may have less effect on ventricular function than routine viral myocarditis. The purpose of the current study was to retrospectively leverage granular CMR data from a large-volume academic institution (with consistent imaging protocols and interpretation methodologies for all patients) to compare post-vaccine myocarditis with viral myocarditis.
Methods
This study was a retrospective chart review of patients who were clinically diagnosed with myocarditis after vaccination against COVID-19. Inclusion criteria included age under 21 years and presenting within 30 days of a vaccination dose. Patients who presented with an active viral infection were excluded. Each study subject was age (within 6 months) and gender matched to a control patient diagnosed with presumed viral myocarditis. Potential study subjects with cyanotic and/or symptomatic congenital heart disease, cardiomyopathy, giant cell myocarditis, or a plausible alternate explanation for presentation were not selected. Potential controls who presented with fulminant myocarditis requiring extracorporeal membrane oxygenation, intubation, or mechanical circulatory support were excluded.
Cardiac magnetic resonance (CMR) for patients with suspected myocarditis include cine steady-state-free precession imaging in the 4-chamber, 2-chamber, ventricular short axis, and the left ventricular and right ventricular outflow tract views. Through-plane phase contrast velocity mapping was performed at the aortic root and main pulmonary artery to also assess cardiac output and confirm measurements of ventricular stroke volume. Gadobutrol was used for contrast-enhanced imaging. Angiography including coronary imaging was performed with inversion recovery gradient echo imaging using ECG gating with navigators for respiratory motion adaptation. Multiparametric mapping was performed in the short-axis projection in the basal, mid, and apical views consisting of Modified Look-Locker Inversion recovery sequences for T1 mapping, T2-weighted turbo-inversion recovery magnitude (TIRM) sequences to assess signal intensity ratios of cardiac and skeletal muscle [20], and T2-prepared single-shot steady-state-free precession sequences for T2 mapping. Late gadolinium enhancement assessment was performed in the 4-chamber, long-axis, and short-axis views using respiratory motion-corrected magnitude and phase-sensitive inversion recovery sequences.
Among 12 patients, 11 studies were performed on a 1.5-Tesla Siemens MRI system (Siemens Medical Solutions, Erlangen, Germany) and 1 study was performed on a 3-Tesla Siemens MRI system. CMR analysis was performed using cvi42 software (Circle Cardiovascular Imaging, Calgary, Canada). All studies were read by a group of six CMR attending who have between 1 and 30 years of experience in reading CMR. Strain analysis was performed by author D.V. and reviewed with M.A.F. Authors were not blinded to clinical information. Per our center’s practice, native T1 values above 1070 ms were considered prolonged and peak regional T2 values above 60 ms were considered abnormal for patients undergoing studies on a 1.5-Tesla scanner [21, 22]. Native T1 values above 1149 ms and peak regional T2 values above 62 ms were considered abnormal for studies performed at 3 Tesla [23]. On T2-weighted imaging, a ratio of 2.0 or higher of signal intensity in myocardium relative to skeletal muscle was considered positive for edema. CMR studies with evidence of both myocardial edema and non-ischemic myocardial injury were considered positive for myocarditis per the updated Lake Louise guidelines [17]. Strain analysis was performed with the feature tracking technique using cines obtained in the short-axis, four-chamber, two-chamber, and three-chamber views.
Statistical analyses were performed using R version 4.0 (R Foundation, Vienna, Austria) and statistical significance was assessed at the 0.05 level. Strain values, T1 values, extracellular volume, T2 values, and ventricular function were compared to age- and gender-matched controls with viral myocarditis using a Wilcoxon Signed Rank test. Spearman’s correlation test was used to determine correlation between strain values, degree of late gadolinium enhancement, and parametric mapping. Patient #4 was excluded from correlation analysis between strain values and parametric mapping as their study was performed on a 3-Tesla MRI scanner. The study protocol was approved by the institutional review board.
Results
Baseline Clinical Information
Among 12 patients with presumed post-vaccine myocarditis, 11 were male, ranging from 12 to 17 years old (median 15.5 years, IQR 13–18 years). No patients had a known history of COVID-19 infection. All patients received the BNT1262b vaccine, as the only COVID-19 vaccine approved for this age group (Table 1) at the time of this study. 11 patients presented after their second vaccine dose and 11 of 12 patients presented within 4 days of receiving the vaccine dose; the remaining patient presented 22 days later without any intervening illness (median = 2.5 days, IQR 1.25–3.75 days). All patients presented with chest pain, and 7 presented with fever or shortness of breath. Patients universally had an elevated troponin, often markedly elevated, and only three patients had mildly elevated B-natriuretic peptide levels. Electrocardiogram (ECG) changes were present in 11 of 12 patients with the most common changes being ST elevation in the inferolateral leads, typically corresponding to regions of late gadolinium enhancement on CMR. Echocardiograms were performed on all patients at the time of admission. 10 patients had normal biventricular ejection. One patient (#6) had mildly depressed left ventricular ejection that normalized two days later and one patient (#5) had mildly depressed left ventricular ejection that was normal 7 days later. No patients had pericardial effusions or wall motion abnormalities.
Table 1.
Study patient characteristics
| Patient | Age (years) | Gender | Vaccine given | Vaccine dose | Symptom onset | Symptoms | Peak Troponin-I | Peak BNP | EKG changes |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 12 | M | BNT1262b2 (Pfizer) | Second | 3 days | Chest pain | 5.87 | 118* | T-wave inversion in inferior leads |
| 2 | 16 | M | BNT1262b2 (Pfizer) | Second | 1 day | Chest pain, fever, myalgias, malaise | 14.6 | 419* | PR depression, nonspecific T-wave changes |
| 3 | 13 | M | BNT1262b2 (Pfizer) | Second | 1 day | Chest pain, fever, headache, nausea | 18.83 | 35 | ST elevation in anterolateral and inferolateral leads |
| 4 | 17 | M | BNT1262b2 (Pfizer) | Second | 2 days | Chest pain, nausea | 25.75 | 87 | None |
| 5 | 17 | M | BNT1262b2 (Pfizer) | Second | 3 days | Chest pain | 8.12 | 30.1 | ST elevation, PR depression in inferolateral leads |
| 6 | 15 | M | BNT1262b2 (Pfizer) | Second | 1 day | Chest pain, fever, nausea | 88.38 | 293.4 | ST elevation in inferolateral leads |
| 7 | 14 | M | BNT1262b2 (Pfizer) | Second | 3 days | Chest pain, malaise, fever, nausea, myalgias | 1.95 | < 10 | Nonspecific T-wave changes |
| 8 | 16 | M | BNT1262b2 (Pfizer) | Second | 22 days | Chest pain | 13.13 | 31 | ST Elevation, T-wave inversion in inferolateral leads |
| 9 | 17 | F | BNT1262b2 (Pfizer) | Second | 2 days | Chest pain, malaise, fever | 7.06 | 20.2 | T-wave inversion in inferior leads |
| 10 | 13 | M | BNT1262b2 (Pfizer) | Second | 2 days | Chest pain, malaise, fever | 15.15 | 56.6 | ST elevation in inferolateral leads, T-wave inversions in inferior leads |
| 11 | 14 | M | BNT1262b2 (Pfizer) | First | 3 days | Chest pain, malaise, fever | 8.48 | 31.2 | ST elevation in inferolateral leads |
| 12 | 16 | M | BNT1262b2 (Pfizer) | Second | 4 days | Chest pain | 22† | Not drawn | Sinus rhythm, premature ventricular complex |
Troponin-I measured in ng/mL
BNP Brain natriuretic peptide, in pg/mL
*NT-proBNP with listed normal values < 125 pg/mL
†High-sensitivity troponin level, with normal values listed as < 14 ng/mL
All 12 patients were admitted and were treated with supportive care consisting of nonsteroidal anti-inflammatory drugs. No patients received corticosteroids or intravenous immunoglobulin. No patients required increased support, such as inotrope infusion, extracorporeal membrane oxygenation, or heart failure medications. All patients were discharged within 96 h of admission.
There were 11 male and 1 female control patients, ranging from 13 to 17 years old (median 15.5 years, IQR 14–16.5 years). All patients presented with chest pain, while 9 of 12 had additional symptoms (Table 2). All 12 patients were admitted and treated with supportive care consisting of NSAIDs. 9 patients had normal ventricular function, 2 patients had mildly depressed function, and 1 patient had moderately depressed function. Two patients had wall motion abnormalities. 11 of 12 patients had abnormal EKGs. 7 of 12 patients presented with ST elevation on EKG.
Table 2.
Control patient characteristics
| Patient | Age (years) | Gender | Symptom onset | Symptoms | Peak Troponin-I | Peak BNP | EKG changes |
|---|---|---|---|---|---|---|---|
| 1 | 13 | M | 2 days | Chest pain, fevers, nausea, fatigue, abdominal pain | 45.96 | 1011.9 | ST Elevation in anterolateral leads, nonspecific T-wave changes |
| 2 | 16 | M | 1 day | Chest pain, recent gastrointestinal illness | 21.42 | Not drawn | Nonspecific ST segment and T-wave changes |
| 3 | 14 | M | 2 days | Chest pain | 6.82 | Not drawn | ST Elevation in lateral leads |
| 4 | 17 | M | 1 day | Chest pain, nausea | 12.23 | 93 | Nonspecific T-wave changes |
| 5 | 17 | M | 1 day | Chest pain, fatigue | 33.03 | 160.5* | ST elevation in inferior leads |
| 6 | 15 | M | 2 days | Fever, dizziness, pre-syncopal symptoms | 7.73 | 1233 | Nonspecific T-wave changes |
| 7 | 14 | M | 3 days | Chest pain, fever, abdominal pain | 28.31 | Not drawn | ST Elevation in lateral leads |
| 8 | 16 | M | 7 days | Chest pain, shortness of breath, headache, fever | 8.27 | 762.2 | ST Elevation and T-wave inversion in lateral precordial leads, T-wave inversion in inferior leads |
| 9 | 17 | F | 1 day | Chest pain | 0.14 | Not drawn | No abnormalities |
| 10 | 14 | M | 1 day | Chest pain | 13.60 | 121.8 | ST Elevation in inferior leads |
| 11 | 14 | M | 10 days | Chest pain, headache, nausea, dizziness | 23.99 | 36.7 | Nonspecific ST changes |
| 12 | 16 | M | 2 days | Chest pain, dizziness, nausea, headache | 25.97 | 100.8 | Diffuse ST segment elevation |
Troponin-I measured in ng/mL
BNP brain natriuretic peptide, in pg/mL
*NT-proBNP with listed normal values < 100 pg/mL
All control patients were discharged home within one week of admission. No patients received intravenous immunoglobulin or steroids, nor did any patients require any mechanical circulatory support, endotracheal intubation, or extracorporeal membrane oxygenation. All control patients had normal ventricular function with no wall motion abnormalities at the time of follow-up and none had disease that progressed to dilated cardiomyopathy or chronic heart failure.
CMR Findings, Vaccine Myocarditis
CMR was obtained between 4 and 41 days after vaccine administration (Table 3). Studies met criteria for myocarditis in 10 patients. All patients had normal biventricular size and ejection fraction on CMR. Every patient met criteria for non-ischemic myocardial injury on the basis of late gadolinium imaging (Table 4, Figs. 1, 2). While the pattern of late gadolinium enhancement was heterogeneous in our cohort, 9 of 12 patients had enhancement in the inferior or inferolateral wall at various levels (Table 4) and the remaining patients had enhancement across the entire lateral free wall at varying short-axis levels. Five patients (#4, 6, 8, 9, 11) also had a prolonged global native T1 time; three patients had a global ECV of 30% or greater. However, six of nine patients with a global ECV less than 30% had regional elevation of the ECV.
Table 3.
Cardiac magnetic resonance imaging findings
| Patient | Vaccine to CMR | Global native T1 | Global Contrast enhanced T1 | Hematocrit (%) | Global ECV (%) | Global PC (%) | Peak T2 | TIRM Ratioa | RV EF (%) | LV EF (%) | Cardiac output | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Base | Mid | Apex | |||||||||||
| 1 | 15 days | 1010 ms | 388 ms | 37 | 27§ | 44 | 63.0 ms | 2.5 | 2.0 | 2.1 | 70 | 80 | 4.0 |
| 2 | 18 days | 1016 ms | 498 ms | 49 | 25 | 49.5 | 52.5 ms | 3.3 | 3.6 | 3.0 | 67 | 69 | 4.8 |
| 3 | 4 days | 1062 ms | 447 ms | 40 | 30 | 50 | 63.0 ms | 2.8 | 2.3 | 2.8 | 66 | 74 | 4.9 |
| 4† | 6 days | 1267 ms | 552 ms | 44 | 23§ | 42 | 47.2 ms | 1.8 | 4.4 | 4.2 | 56 | 86 | 3.7 |
| 5 | 7 days | 1003 ms | 415 ms | 44 | 22 | 39 | 50.4 ms | 1.3 | 1.6 | 2.1 | 63 | 67 | 4.7 |
| 6 | 6 days | 1201 ms | 463 ms | 37 | 33 | 54 | 66.0 ms | 2.0 | 2.3 | 2.9 | 58 | 59 | 4.1 |
| 7 | 9 days | 1022 ms | 491 ms | 39 | 28§ | 46 | 47.0 ms | 1.8 | 1.8 | 2.0 | 71 | 76 | 4.6 |
| 8 | 26 days | 1100 ms | 427 ms | 43 | 30 | 52 | 62.0 ms | 0.6 | 1.9 | 4.1 | 58 | 61 | 4.1 |
| 9 | 41 days | 1293 ms | 441 ms | 40‡ | 28§ | 45 | 46.0 ms | 1.1 | 1.4 | 1.1 | 65 | 66 | 2.4 |
| 10 | 4 days | 1033 ms | 475 ms | 41 | 28§ | 50 | 55.0 ms | 2.0 | 1.8 | 1.7 | 72 | 78 | 5.9 |
| 11 | 6 days | 1089 ms | 425 ms | 34 | 27 | 41 | 61.0 ms | 1.4 | 1.8 | 2.5 | 70 | 72 | 3.8 |
| 12 | 7 days | 1019 ms | 448 ms | 41 | 28§ | 47 | 53.0 ms | 1.8 | 3.2 | 3.1 | 59 | 57 | 4.3 |
| Control 1 | N/A | 1234 ms | 431 ms | 31 | 37 | 52 | 67.0 ms | 2.1 | 2.9 | 3.2 | 43 | 44 | 3.0 |
| Control 2 | N/A | 1028 ms | 378 ms | 34 | 27 | 44 | 55.7 ms | 1.6 | 1.3 | 2.1 | 76 | 61 | 3.6 |
| Control 3 | N/A | 1022 ms | 455 ms | 40 | 25 | 44 | N/A | 2.0 | 2.4 | 1.9 | 68 | 56 | 3.5 |
| Control 4 | N/A | 1101 ms | 412 ms | 43 | 32 | 53 | N/A | 1.0 | 1.7 | 2.6 | 60 | 63 | 3.5 |
| Control 5 | N/A | 1013 ms | 384 ms | 43 | 23 | 43 | 48.6 ms | 2.9 | 2.7 | N/A | 70 | 63 | 3.6 |
| Control 6 | N/A | 1047 ms | 435 ms | 40‡ | 25 | 41 | 53.5 ms | 2.0 | 3.0 | 3.0 | 64 | 61 | 3.1 |
| Control 7 | N/A | 1018 ms | 438 ms | 45 | 26§ | 48 | N/A | 1.6 | 2.2 | 2.4 | 71 | 59 | 3.6 |
| Control 8 | N/A | 1173 ms | 362 ms | 40 | 35 | 59 | 74.5 ms | 3.9 | 4.4 | 4.1 | 53 | 62 | 2.7 |
| Control 9 | N/A | 1009 ms | 369 ms | 44 | 24 | 47 | 52.7 ms | 2.3 | 2.4 | 2.9 | 66 | 65 | 2.6 |
| Control 10 | N/A | 1032 ms | 484 ms | 42 | 30 | 52 | N/A | 1.8 | 3.0 | 3.5 | 77 | 46 | 4.8 |
| Control 11 | N/A | 1022 ms | 454 ms | 38 | 30 | 49 | 54.1 ms | 3.7 | 2.5 | 2.2 | 66 | 57 | 3.8 |
| Control 12 | N/A | 1089 ms | 411 ms | 40 | 32 | 54 | 50.8 ms | 2.1 | 2.6 | 3.4 | 66 | 47 | 3.7 |
CMR cardiac magnetic resonance, ECV extracellular volume, PC partition coefficient, RV right ventricle, LV left ventricle, EF ejection fraction
aRatio of signal intensity on T2-weighted Turbo Inversion Recovery Magnitude Imaging (TIRM) between myocardium and skeletal muscle
†Study performed on a 3-Tesla MRI scanner
‡Study done with assumed hematocrit of 40%
§Although global ECV was within normal limits, regional ECV over 30% were noted
Table 4.
Late gadolinium enhancement findings in patients with post-vaccine myocarditis
| Patient | Regions of enhancement |
|---|---|
| 1 | Basal inferior and inferolateral walls |
| 2 | Mid to apical lateral wall |
| 3 | Basal, mid, and apical anterior, anterolateral, inferolateral, and inferior walls; mid inferolateral wall |
| 4 | Mid inferolateral and anterolateral walls, apical and basal anterior and lateral walls, tip of apex |
| 5 | Mid and apical anterolateral and inferolateral extending into the inferior wall |
| 6 | Lateral wall from base to apex, basal inferior septum |
| 7 | Basal inferior septum |
| 8 | Lateral wall of the apex extending to the mid ventricle, apical inferior wall |
| 9 | Lateral wall at the apex |
| 10 | Basal inferior lateral wall |
| 11 | Mid lateral free wall, extending into the apical, and basal lateral free wall |
| 12 | Mid to apical anterolateral free wall |
Fig. 1.
Four- chamber late gadolinium enhancement imaging of patient 8 demonstrating enhancement along the lateral wall of the mid left ventricle and apex as indicated by arrows
Fig. 2.
Short-axis late gadolinium enhancement imaging of patient 8 demonstrating enhancement along the inferolateral wall as indicated by arrows
Ten patients had signal intensity ratios of cardiac and skeletal muscle equal to or greater than 1.9 on T2-weighted TIRM sequences and five patients had prolonged T2 relaxation values. (Fig. 3) Even using a cut-off of > 55 ms, this finding would not have changed. Two patients, #9 and 10, did not meet criteria for myocardial edema for either TIRM ratio or T2 relaxation times.
Fig. 3.
Native T2 mapping of patient 8 in the short- axis projection in the apex demonstrating increased signal intensity in the lateral wall
One of these patients (#9) underwent her CMR 39 days after the onset of symptoms and was asymptomatic at the time of her study. She did undergo an echocardiogram one day after symptom onset that demonstrated normal biventricular function with no wall motion abnormalities or effusions.
One patient (#4) was incidentally diagnosed with partial anomalous pulmonary venous connection of the left upper pulmonary vein to the innominate vein and right upper pulmonary vein as well as right middle pulmonary vein to the right superior vena cava; his Qp:Qs was roughly 1.9:1 by CMR. Another patient (#6) had a history of a bicuspid aortic valve; his echocardiogram and CMR demonstrated insignificant aortic insufficiency and stenosis.
CMR Findings, Viral Myocarditis
CMR was obtained within 10 days after symptoms onset in 11 of 12 patients with viral myocarditis. One patient had CMR performed three months later that definitively met criteria for myocarditis. Eleven patients met criteria for myocarditis; one patient was felt to be borderline positive on the basis of very minimal late gadolinium enhancement. Three patients had mildly depressed left ventricular function, although as a whole the left ventricular function was not significantly different from the study cohort. One patient had mildly depressed right ventricular function. Late gadolinium enhancement was universal in the control patients. Six of 12 patients had increased global ECV; one additional patient had a normal global ECV but increased regional ECV. All control patients met criteria for edema on the basis of signal intensity on T2-weighted TIRM sequences. Only two of eight patients who underwent T2 mapping had prolonged T2 values.
Comparison Between CMR Findings of Vaccine and Viral Myocarditis
Compared to age-matched controls with viral myocarditis, patients with post-vaccine myocarditis had a higher right ventricular ejection fraction (RVEF) and cardiac index (Table 6). They also had more favorable short-axis global circumferential and radial strain (Tables 5 and 6). There was no difference between the two cohorts in long-axis strain, T1 values and left ventricular function. Among patients with post-vaccine myocarditis, there was no correlation between strain values and quantification of late gadolinium enhancement nor strain values and T1 values or extracellular volume (Tables 6 and 7).
Table 6.
Comparison of study patients to age-matched controls
| Study patients | Age-matched controls | p value | |||
|---|---|---|---|---|---|
| Median | IQR | Median | IQR | ||
| LV ejection fraction (%) | 70.5 | 63.5, 77.0 | 66 | 62.0, 70.5 | 0.28 |
| RV ejection fraction (%) | 65.7 | 58.0, 69.8 | 60 | 51.5, 62.5 | 0.042 |
| Indexed cardiac output (L/min)/m2) | 4.2 | 3.9, 4.8 | 3.6 | 3.1, 3.7 | 0.024 |
| Short-axis global circumferential strain (%) | − 21.3 | − 22.5, − 20.5 | − 19.5 | − 21.0, − 17.1 | 0.006 |
| Short-axis global radial strain (%) | 40.9 | 37.8, 45.8 | 34.4 | 28.6, 39.1 | 0.007 |
| Long-axis global longitudinal strain (%) | − 19.1 | − 20.7, − 17.9 | − 17.8 | − 19.9, − 15.6 | 0.18 |
| Long-axis global radial strain (%) | 33.8 | 32.2, 39.0 | 33.5 | 25.9, 36.0 | 0.18 |
| Native T1 (ms)a | 1033 | 1018, 1094 | 1028 | 1020, 1068 | 0.97 |
| Contrast T1 (ms)a | 447 | 426, 469 | 431 | 381, 446 | 0.10 |
| ECV (%) | 28% | 25.35, 30.65 | 30 | 23.25, 36.75 | 0.27 |
| Peak T2 (ms) (n = 8) | 54 | 41.35, 66.65 | 49.5 | 41.75, 57.25 | 0.44 |
aPatient 4 was excluded from T1 value analysis as his study was done with a 3.0 − Tesla scanner
Table 5.
Cardiac magnetic resonance strain data
| Study patients | Control patients | |||||||
|---|---|---|---|---|---|---|---|---|
| SAX global circ strain | SAX global radial strain | LAX global long strain | LAX global radial strain | SAX global circ strain | SAX global radial strain | LAX global long strain | LAX global radial strain | |
| 1 | − 22.7 | 46.6 | − 20.8 | 41.4 | − 11.2 | 15.3 | − 13.5 | 21.8 |
| 2 | − 21.1 | 38 | − 19.3 | 33.1 | − 21.6 | 40.6 | − 22.9 | 51.3 |
| 3 | − 21.5 | 41.6 | − 20.5 | 36.6 | − 20.3 | 37 | − 17.6 | 32.9 |
| 4 | − 21.3 | 45 | − 18.6 | 32.9 | − 16.7 | 28 | − 19.9 | 37.3 |
| 5 | − 21.1 | 39.5 | − 18.4 | 34.4 | − 19.6 | 34.2 | − 19.9 | 35.6 |
| 6 | − 18.5 | 30.6 | − 15.5 | 24.2 | − 19.4 | 34.6 | − 15.3 | 24.3 |
| 7 | − 24.3 | 52.7 | − 24.4 | 55.1 | − 20.3 | 37.6 | − 18.9 | 34.1 |
| 8 | − 19.3 | 33.5 | − 15.7 | 25.5 | − 13.4 | 19.8 | − 13.5 | 20.6 |
| 9 | − 22.3 | 43.1 | − 19.4 | 35.4 | − 17.7 | 29.2 | − 17.9 | 30.8 |
| 10 | − 24.4 | 55.2 | − 21.4 | 41.7 | − 23.1 | 47.4 | − 15.8 | 35.8 |
| 11 | − 21.3 | 40.1 | − 17.3 | 31.5 | − 22.2 | 42.4 | − 20 | 36.2 |
| 12 | − 19.8 | 37.6 | − 18.9 | 33 | − 17.4 | 29.8 | − 16.9 | 27.4 |
SAX short axis, LAX long axis
†All strain data are expressed in percentages
Table 7.
Correlation between strain and parametric mapping in study patients
| Native T1a | Contrast enhanced T1a | Extracellular volume | Partition coefficient | Mass of myocardium with late enhancement | Percentage of myocardium with late enhancement | |
|---|---|---|---|---|---|---|
| Short-axis global circumferential strain |
r = 0.17 p = 0.67 |
r = − 0.07 p = 0.84 |
r = 0.11 p = 0.73 |
r = 0.27 p = 0.40 |
r = 0.33 p = 0.30 |
r = 0.14 p = 0.66 |
| Short-axis global radial strain |
r = − 0.18 p = 0.59 |
r = 0.03 p = 0.94 |
r = − 0.22 p = 0.49 |
r = − 0.34 p = 0.24 |
r = − 0.22 p = 0.48 |
r = − 0.12 p = 0.72 |
|
Long-Axis global Longitudinal Strain |
r = 0.33 p = 0.33 |
r = − 0.27 p = 0.42 |
r = 0.04 p = 0.91 |
r = 0.05 p = 0.86 |
r = 0.45 p = 0.14 |
r = 0.36 p = 0.24 |
|
Long-axis global Radial Strain |
r = − 0.37 p = 0.26 |
r = 0.15 p = 0.67 |
r = − 0.10 p = 0.76 |
r = − 0.16 p = 0.62 |
r = − 0.53 p = 0.07 |
r = − 0.44 p = 0.15 |
aPatient 4 was excluded from T1 value analysis as his study was done with a 3.0- Tesla scanner
Discussion
In this study comparing pediatric patients with post-vaccine myocarditis and viral myocarditis, we found that patients with post-vaccine myocarditis have more favorable short-axis global circumferential and radial strain as well an increased right ventricular ejection fraction and cardiac index. However, there was no correlation of myocardial strain to either the burden of late gadolinium enhancement nor extracellular volume or T1 values.
Post-vaccine myocarditis is a rare phenomenon and has been reported in vaccinations previously, including oral polio, influenza, and smallpox vaccination [24–26]. In cases not directly caused by infection of the myocardium [24], the suspected pathogenesis of post-vaccine myocarditis is “molecular mimicry” between antigens involved in producing vaccination response and those on the myocardium. [25, 27]
CMR parametric mapping data in cases of pediatric post-COVID-19 vaccine myocarditis in the literature are limited. Shaw et al. described two pediatric patients with T1 values, T2 values, and extracellular volume ranging from 1122 to 1172 ms (normal 950-1050 ms), 56 to 74 ms (normal < 55 ms), and 38 to 42% (normal < 28%), respectively. [5] Dionne et al. described 15 patients, with 4 of 15 patients showing borderline or elevated T1 values, 1 of 15 with borderline elevated T2 values, and 2 of 15 with regional hyperintensity on T2-weighted imaging [14]. Vidula et al. described an 18 year old who had a T1 time and T2 time of 1089–1097 ms, respectively. [2] McLean et al. and Park reported hyperemia and early enhancement, respectively, but without reporting T1 values [1, 4]. There was no comparison in any of these studies with viral myocarditis.
All 12 patients had late gadolinium enhancement, predominantly in the lateral and inferior walls of the left ventricle. This pattern is consistent with cases of pediatric post-COVID-19 vaccination myocarditis reported in the literature. Similar patterns have also been found after smallpox vaccination [28]. Early data suggest that this late gadolinium enhancement may improve over time [13], but long-term CMR data and clinical outcomes for post-vaccine myocarditis are still to be determined.
We found that patients with post-vaccine myocarditis had more favorable short-axis longitudinal and radial strain compared to patients with viral myocarditis. This finding has not been previously reported in the pediatric population. Myocardial strain can be more sensitive in identifying decreased myocardial deformation than ejection fraction as a normal global ejection fraction can mask diseased and hypokinetic segments. Less favorable strain is associated with adverse events, such as all-cause mortality, ventricular tachycardia of longer than 30 s, and hospitalization for heart failure in adult patients with myocarditis [29]. In addition, adult patients with fulminant myocarditis have less favorable strain than those with non-fulminant myocarditis [30]. Our study cohort had normal values for strain [31] and more favorable strain for previously published strain values in children with myocarditis [32]. This suggests that post-vaccine myocarditis represents a milder variant of myocarditis.
We failed to find any correlation between parametric mapping values and the amount of discrete fibrosis with strain values (Table 5). This may be due to our cohort’s small sample size; a larger sample size to determine this would be needed. Previous studies in other diseases such as tetralogy of Fallot has found a correlation between T1 mapping and left ventricular strain; however, DENSE was used to measure myocardial deformation in that study [33].
A relatively low proportion of patients both reported in the literature as well as in this case series have had elevated T2 relaxation times. Using the myocardial to skeletal muscle signal intensity ratio may have increased sensitivity to identify patients with myocardial edema. Alternatively, further work may be needed to identify a more appropriate cut-off for myocardial T2 values to help increase the sensitivity of T2 mapping.
We also found that although the RVEF was normal in both cohorts, patients with post-vaccine myocarditis had a greater RVEF. Previous studies have shown that depressed right ventricular function has been associated with adverse events [34].
Despite the findings in this study, the benefits of vaccination far outweigh the risks [35]. The rate of myocarditis is far higher in patients with COVID-19 than in patients receiving the COVID-19 vaccine [36]. In addition, children with COVID-19 are at risk for the subsequent multisystem inflammatory syndrome in children (MIS-C), in which children present with severe multi-organ inflammation about 2–6 weeks after the initial infection, sometimes in shock and requiring intensive care with decreased ventricular function [37].
This study was limited due to its retrospective nature and relatively small cohort as patients were enrolled from a single center. However, these limitations allow for consistent CMR scanning techniques, sequence analysis, and imaging interpretation. Each patient’s diagnosis was felt to be consistent with post-vaccine myocarditis by the clinical providers, but causation cannot necessarily be proved.
Conclusion
Post-vaccine myocarditis has more favorable short-axis global circumferential and radial myocardial strain than those with viral myocarditis, lending to the notion that this illness affects ventricular function less than viral myocarditis. Typical CMR findings in our cohort consisted of late gadolinium enhancement in the lateral and free walls of the left ventricle. Overall, the impact on myocardial strain by CMR is less significant in post-vaccine myocarditis compared to more classic viral myocarditis.
Author Contributions
All authors contributed to the study conception and design. Material preparation and data collection were performed by DV and MDE. All authors drafted, read, critically revised, and approved the final manuscript.
Funding
This project was not funded by any internal or external funds.
Declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval
This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and the national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed Consent
Not obtained due to retrospective study design.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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