Chronic myocarditis in patients with atrial fibrillation of unknown origin: diagnostic challenges and unresolved issues

Aim. To analyze the significance of contrast-enhanced cardiac magnetic resonance imaging (MRI) and endomyocardial biopsy (EMB) in the diagnosis of myocarditis in patients with atrial fibrillation (AF) of unknown origin.

Material and methods. The study included 57 patients with AF of unknown origin aged 45,5 [38,8;53,3] years (men, 77,2%). Paroxysmal AF was observed in 56,1% of patients, while persistent AF — in 22,8%, and long-standing persistent AF — in 21,1%. Thirty-five patients underwent contrast-enhanced cardiac MRI and Lake-Louise criteria assessment. Simultaneously with AF ablation, all patients underwent EMB from the interventricular septum, outflow tract, and right ventricular apex with histological diagnosis of myocarditis based on the Dallas criteria modified by the World Heart Federation.

Results. According to contrast-enhanced cardiac MRI, delayed contrast accumulation was diagnosed in 91,4%. In 17,1% of cases, signs of edema were detected on T2-weighted images, while the average left ventricular (LV) edema level was 1,6±0,3 (reference <2,0). In 25,7% of patients, signs of hyperemia were detected with average LV hyperemia index of 3,4 [2,2;4,0] (reference <4,0). Myocarditis was diagnosed in 12 patients (34,3%) with 3 criteria detected in 2 patients, 2 in 10 patients (6 with hyperemia + fibrosis, 4 with edema + fibrosis), and 1 (fibrosis) in 22 patients. Histological criteria of lymphocytic myocarditis were detected in 28 out of 57 patients (49,1%): focal in 19 (67,9%), diffuse in 6 (21,4%), and diffuse-focal in 3 (10,7%). Edema signs on MRI was the factor most strongly associated with the total number of detected T-lymphocytes in myocardial fragments, assessed using  ROC analysis (AUC 0,782 (95% confidence interval 0,61-0,93) p=0,032). The combined use of MRI and EMB allowed to increase the accuracy of myocarditis diagnosis from 34,3 to 62,9%.

Conclusion. Myocarditis was diagnosed in 34,3% of patients according to MRI and in 49,1% according to EMB. Edema according to MRI data was the only sign that had predictive value for the severity of inflammatory cell infiltration in myocardial fragments. Histological analysis in combination with MRI increased the accuracy of myocarditis diagnosis in patients with AF of unknown origin from 34,3 to 62,9%.

1. Ammirati E, Frigerio M, Adler ED, et al. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ Heart Fail. 2020; 13(11):e007405. doi:10.1161/CIRCHEARTFAILURE.120.007405.

2. De Gaspari M, Rizzo S, Thiene G, et al. Causes of sudden death. Eur Heart J Suppl. 2023;25(Suppl B):B16-B20. doi:10.1093/eurheartjsupp/suad077.

3. Georgiopoulos G, Figliozzi S, Sanguineti F, et al. Prognostic Impact of Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance in Myocarditis: A Systematic Review and Meta-Analysis. Circ Cardiovasc Imaging. 2021;14(1):e011492. doi:10.1161/CIRCIMAGING.120.011492.

4. Domínguez F, Uribarri A, Larrañaga-Moreira JM, et al. Diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Consensus document of the SEC-Working Group on Myocarditis. Rev Esp Cardiol (Engl Ed). 2024;77(8):667-79. doi:10.1016/j.rec.2024.02.022.

5. Batalov RE, Khlynin MS, Rogovskaya YuV, et al. S. Isolated Atrial Fibrillation, Inflammation and Efficacy of Radiofrequency Ablation: Preliminary Insights Based on a Single-Center Endomyocardial Biopsy Study. J. Clin. Med. 2023;12:1254. doi:10.3390/jcm12041254.

6. Arutyunov GP, Paleev FN, Moiseeva OM, et al. 2020 Clinical practice guidelines for Myocarditis in adults. Russian Journal of Cardiology. 2021;26(11):4790. (In Russ.) doi:10.15829/1560-4071-2021-4790.

7. Batalov RE, Rogovskaya YuV, Ryabov VV, et al. Idiopathic form of atrial fibrillation, inflammation and clinical results of radiofrequency ablation. Russian Journal of Cardiology. 2014;(12):7-12. (In Russ.) doi:10.15829/1560-4071-2014-12-7-12.

8. Chauin A. The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis. Vasc Health Risk Manag. 2021;17:601-17. doi:10.2147/VHRM.S327661.

9. O’Brien AT, Gil KE, Varghese J, et al. T2 mapping in myocardial disease: a comprehensive review. J Cardiovasc Magn Reson. 2022;24(1):33. doi:10.1186/s12968-022-00866-0.

10. Gaizauskiene K, Leketaite K, Glaveckaite S, et al. Diagnostic Value of Cardiovascular Magnetic Resonance T1 and T2 Mapping in Acute Myocarditis: A Systematic Literature Review. Medicina (Kaunas). 2024;60(7):1162. doi:10.3390/medicina60071162.

11. Mitrofanova LB. The role of endomyocardial biopsy in diagnostics of inflammatory myocardium diseases. Russian Journal of Cardiology. 2016;(1):73-9. (In Russ.) doi:10.15829/1560-4071-2016-1-73-79.

12. Li ZP, Li GL, Wang RN, et al. Endomyocardial Biopsy: short- and long-term safety in myocarditis patients. Cardiology. 2025:1-26. doi:10.1159/000543593.