Inflammation of conduction tissue in patients with arrhythmic phenotype of myocarditis

Background Manifestation of arrhythmias in otherwise normal heart suggests a possible compromise of conduction tissue. It, however, remains, usually, a supposition with limited therapeutical implications. Purpose Reporting histology of inflammation/infection of conduction tissue as a cause of arrhythmic phenotype of myocarditis. Material and methods Among 420 patients with a biopsy proven myocarditis diagnosed from 2009 to 2019, 42 presented with an arrhythmic phenotype and normal cardiac anatomy and function (LVEF >50%). Of the latter, 12 subjects (28.5%; M 9; F 3; mean age 44,75±14.9 years) had included in a left ventricular endomyocardial biopsy sections of conduction tissue (CT). CT was identified by recognition of morphological Aschoff and Monckeberg criteria and positive immunostaining for HCN4. CT inflammation was defined by ≥7 CD3+ T lymphocytes with focal necrosis of adjacent cells. Cause of CT inflammation was investigated by polymerase chain reaction (PCR) of 2 frozen endomyocardial samples, immunohistochemistry for the identified viral antigens and for Tall like receptor 4 (TLR4). Results Four pts presented with non-sustained ventricular tachycardia (nsVT), seven pts with sustained (S) VT, 1 died during hospitalization because of ventricular fibrillation (VF). Inflammatory involvement of CT was documented in all 12 pts. PCR was positive for Influenza A virus in 2 pts and HHV2 in 1 with positive CT immunostaining for related antigens. In the remaining 8 pts negative PCR for viral genomes and overexpression of TLR4 suggested an immune-mediated pathway of CT inflammation. Pts with Influenza A myocarditis and CT infection responded to tamiflu (1 cp bid for 5 days) with ECG normalization while the pt with HHV2 infection died. The 8 pts with virus-negative myocarditis and TLR4 overexpession were treated with steroids and azathioprine based on TIMIC protocol. Seven of them had no more repetitive ventricular ectopic beats at Holter of 2 weeks follow-up. Conclusions Arrhythmic phenotype of myocarditis is caused by elective inflammation/infection of CT. Molecular characterization of CT damage may bring to pharmacologic control of arrhythmias in up to 75% of cases. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Project ERA-CVD “Transnational Research Projects on Cardiovascular Diseases”