PO84
When Myocarditis Returns: Viral Relapse, Genetic Substrate, or Both?

Although acute myocarditis is often linked to viral causes, recent studies suggest a predisposing genetic component.

A 42-year-old woman with a history of hypertension experienced suspected acute myocarditis at age 25, complicated by cardiogenic shock, left ventricular (LV) systolic dysfunction, and complete atrioventricular block (CAVB), requiring inotropes and temporary pacing. She was treated with non-steroidal anti-inflammatory therapy and later corticosteroids, with recovery of LV function and sinus rhythm at discharge. Serological and immunological studies were negative, and she remained asymptomatic without LV or conduction abnormalities. At the time cardiac MRI and endomyocardial biopsy were not performed. There was no family history of sudden cardiac death, cardiomyopathy, or early device implantation.

Seventeen years later, after a respiratory infection, she developed exertional fatigue and pleuritic chest pain. On admission, she was stable (118/85 mmHg, afebrile). ECG showed CAVB with ventricular escape at 68 bpm. Echocardiography revealed septal hypertrophy (∼15 mm) and mild global LV dysfunction (LVEF 50%). Laboratory tests showed elevated C-reactive protein 18 mg/L (ref <5), hs-troponin T 1032 pg/ml (ref <14) and NT-proBNP 2457 pg/ml (ref <450). Coronary angiography excluded obstructive disease. She improved with high-dose aspirin; serologies and immunology remained negative. By day 7, she recovered sinus rhythm.

Cardiac MRI supported myocarditis, showing mildly dilated LV (End Diastolic LV Volume 100 ml/m²), LVEF 51%, septal hypertrophy (∼14 mm), subtle T2 hyperintensity, and subepicardial/intramural late gadolinium enhancement. Endomyocardial biopsy revealed lymphocytic myocarditis with viral PCR positive for Epstein–Barr virus. Genetic testing showed two variants of uncertain significance: CACNA1C c.76G>A p.(Ala26Thr) and CTNNA3 c.2493G>T p.(Lys831Asn), the latter with potential functional impact.

This case highlights the challenge of differentiating viral myocarditis from an underlying cardiomyopathy. Genetic testing can be decisive and guide management, but often, as here, reveals variants of uncertain significance that do not explain the phenotype and instead raise questions for patient and family follow-up. The variants detected lack sufficient evidence to be considered causative. This underscores the need for long-term surveillance, periodic reassessment of genetic data, and a multidisciplinary approach. Ultimately, both viral and genetic contributions should be considered, with close monitoring to determine whether such episodes represent isolated myocarditis or early inherited cardiomyopathy.