Cardiac involvement in long COVID: echocardiographic, cardiac magnetic resonance, and endomyocardial biopsy findings in previously healthy individuals with persistent chest pain

Abstract Background Long COVID is a poorly understood condition affecting up to 45% of COVID-19 survivors, with chest pain being one of the most common complaints. While viral myocarditis is a well-recognized entity in other infections, the cardiac involvement in Long COVID remains unclear. This study aimed to characterize the clinical presentation, cardiac imaging findings, and endomyocardial biopsy (EMB) results in previously healthy individuals with persistent chest pain after COVID-19. Methods A total of 209 previously healthy patients with post-COVID chest pain were evaluated between January 2021 and January 2024. The diagnostic workup included laboratory biomarkers, echocardiography, 24-hour Holter monitoring, and cardiac magnetic resonance imaging (CMR). EMB was performed in 20 patients with persistent symptoms despite unremarkable or borderline non-invasive testing, or in those with CMR findings suggestive of myocardial involvement. Results Data showed a neutrophil-to-lymphocyte ratio of 2.74 ± 2.6; ultrasensitive Troponin I levels of 47.8 ± 153.2 pg/mL; hypersensitive C-reactive protein of 2.9 ± 5.6µg/mL; brain natriuretic peptide levels of 115.5 ± 236.6pg/mL; D-dimer of 352.4 ± 176.5ng/mL; 25-hydroxy vitamin D at 22.8 ± 5.0ng/mL; SARS-CoV-2 antispike IgG antibody levels of 4546.9 ± 6903.8BAU/mL. The echocardiographic evaluation revealed left ventricular diastolic dysfunction in 10 patients (4.7%) and right ventricular diastolic dysfunction in 11 patients (5.26%). Tricuspid annular plane systolic excursion was 17.17 ± 4.7mm. Global longitudinal strain was 19.6 ± 3.6%, with a global work index of 1844.8 ± 433.7mmHg% and a global work efficiency of 95.0 ± 2.8%. Regional strain analysis revealed decreased values in the basal segments, suggesting microvascular dysfunction and subendocardial involvement. CMR findings, including elevated native T1 (1029.7 ± 4.9 ms) and T2 (56.9 ± 5.9 ms), along with predominant abnormalities in the apical segments, indicate a distinct myocardial injury pattern in Long COVID, differing from classic viral myocarditis. Mean extracellular volume was elevated at 50.28 ± 24.20%. EMB findings revealed diffuse ischemic necrosis in 14 patients (70%), 4 lymphocytic myocarditis, with one demonstrating SARS-CoV-2 antibody positivity, 1 had thrombotic microangiopathy and 1 had AA amyloidosis. Conclusion These findings challenge the assumption that Long COVID-associated cardiac involvement follows the conventional pattern of viral myocarditis. Instead, the predominance of diffuse ischemic necrosis without significant inflammation suggests a novel pathophysiological mechanism distinct from previously recognized post-viral cardiac syndromes. Possible mechanisms include microvascular dysfunction, endothelial injury, and persistent immune dysregulation. These results underscore the need for further research to elucidate the long-term cardiovascular impact of Long COVID and refine diagnostic and therapeutic strategiesimage1