Persistent Chest Pain in Long COVID: Endomyocardial Biopsy Findings in Previously Healthy Individuals

BACKGROUND

This study aimed to characterize the clinical presentation, cardiac imaging findings, and endomyocardial biopsy (EMB) results in previously healthy individuals with persistent chest pain and post-COVID-19.

METHODS

A total of 423 previously healthy patients with post-COVID chest pain were evaluated between January 2021 and March 2025. The diagnostic workup included laboratory biomarkers, echocardiography, 24-hour Holter monitoring, and cardiac magnetic resonance imaging (CMR). EMB was performed in 25 patients with persistent symptoms despite unremarkable or borderline non-invasive testing, or in those with CMR findings sugggestive 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 ± 5.6 ug/mL; brain natriuretic peptide levels of 115.5 ± 236.6 pg/mL; D-dimer of 352.4 ± 176.5 ng/mL; 25-hydroxy vitamin D at 22.8 ± 5.0 ng/mL; SARS-CoV-2 antispike IgG antibody levels of 4546.9 ± 6903.8 BAU/mL. Global longitudinal strain was 19.6 ± 3.6%, with a global work index of 1844.8 ± 433.7 mmHg% and a global work efficiency of 95.0 ± 2.8%. Regional strain analysis revealed decreased values in the basal segments, CMR findings, including elevated native T1 (1029.7 ± 4.9 ms) and T2 (56.9 ± 5.9 ms); mean extracellular volume was elevated at 50.28 ± 24.20%. EMB findings revealed diffuse ischemic necrosis in 19 patients (76%), 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 strategies.