COVID-19 mRNA vaccine-associated myocarditis showed mostly normal cardiac function after 20 months, but 43% had discrete LGE versus 22% in controls (p=0.02).
Does COVID-19 mRNA vaccine-associated myocarditis lead to long-term cardiovascular adverse effects compared to matched controls?
At nearly 2 years follow-up, patients with COVID-19 vaccine-associated myocarditis had normal overall cardiac function but a higher prevalence of discrete late gadolinium enhancement and slightly reduced global longitudinal strain compared to matched controls.
Abstract Background/Introduction Vaccine associated myocarditis (VAM) was an unexpected adverse effect of the COVID-19 mRNA vaccines administered during the COVID-19 pandemic. Long-term cardiac effects of myocarditis cases have not been systematically investigated at a population level. Purpose Our aim was to investigate cardiovascular long-term adverse effects of COVID-19 mRNA VAM in a nationwide follow-up study. Methods Using individually linked national health register data we identified all cases of myocarditis occurring the first 90 days following COVID-19 mRNA vaccination in the total population of Norway, including all ages, between December 2020 and April 2022. VAM cases were identified and validated by thorough medical record review using the Brighton Criteria. All confirmed VAM cases were invited to a follow-up study including clinical examination, blood tests, arrhythmia detection by 24hr ECG, echocardiography and cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE). We recruited an age- and sex-matched control group for a blinded comparison. Results Of 177 validated VAM cases in Norway, 115 (65%) agreed to participate (76% men, median age 33 and 54 years for men and women respectively, p 0.01). The follow-up examinations took place at median 20 (IQR 16-26) months after VAM. In VAM subjects, ECG showed 99% in sinus rhythm, with a median 3 (IQR 1-34) premature ventricular contractions (PVC), per 24 hrs. Troponin and NT-proBNP levels were normal in 99/115 (86%) (p = 0.14 vs. controls 47/50 94%) and 108/115 (94%) (p = 0.08 vs. controls 50/50 100%), respectively. By echocardiography there were no differences in left ventricular (LV) dimensions or function by LV ejection fraction (EF) between VAM subjects and controls (LV end diastolic diameter EDD 49±5 mm vs. 51±4 mm, p = 0.94, LVEF 54±6% vs. 57±4%, p = 0.99) (Figure). Although within normal range, absolute GLS was lower in VAM subjects compared to controls: GLS -18.0% IQR -16.4- -19.7 vs. -18.7% IQR -17.9- -19.5, p = 0.02). CMR (n=65 VAM, n=46 controls) detected discrete LGE in 28 (43%) VAM subjects, compared to 10 (22%) controls, p = 0.02. Conclusion This nationwide, population-based follow-up study of subjects with COVID-19 mRNA VAM found predominantly normal cardiac clinical and imaging findings after ∼2 years follow up. There were no significant differences between VAM subjects and controls regarding LV dimensions, EF, arrhythmic burden, or biomarkers. However, VAM subjects had a higher prevalence of discrete myocardial LGE, as well as subclinically slightly worse LV function as measured by GLS. The long-term clinical significance of LGE findings, which could potentially represent myocardial fibrosis, after Covid-19 VAM remains uncertain and warrants further investigation.Long-term cardiac findings after VAM
Skinningsrud et al. (2025) studied this question. COVID-19 mRNA vaccine-associated myocarditis showed mostly normal cardiac function after 20 months, but 43% had discrete LGE versus 22% in controls (p=0.02).
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