From STEMI to Transplant: Myocarditis Unmasks a Genetic Time Bomb

Description of Clinical Presentation: A 22-year-old man presented with acute chest pain, uneasiness, and vomiting. ECG showed STEMI, and he was thrombolysed. Coronary angiography revealed normal arteries, raising suspicion of a STEMI mimic. Echocardiography demonstrated chamber dilatation, severe biventricular dysfunction, mild mitral and moderate tricuspid regurgitation. He had received a COVID-19 vaccine two weeks earlier but reported no fever or viral prodrome.

Diagnostic Techniques and Their Most Important Findings: Cardiac MRI was performed for further evaluation. It showed global chamber dilatation with severe biventricular systolic dysfunction (LVEF 22%, RVEF 16%) and diffuse hypokinesia. Late gadolinium enhancement (PSIR) imaging demonstrated subepicardial LGE at the LV apex, mid-to-apical inferior wall, and lateral wall, consistent with myocarditis. A presumptive diagnosis of post-vaccination myocarditis was made.

Despite supportive management, the patient’s condition progressively deteriorated, and he eventually required cardiac transplantation. Genetic testing performed post-transplantation identified two variants of uncertain significance (VUS) involving the TTN and OBSCN genes, both associated with dilated cardiomyopathy (DCM). The findings supported a “double-hit” hypothesis—where an underlying genetic predisposition was unmasked or accelerated by an external stressor, in this case myocarditis.

Learning Points from this Case: This case highlights the complex interplay between genetic predisposition and environmental triggers in cardiomyopathy. While vaccination-related myocarditis was suspected as the initial insult, the identification of pathogenic variants associated with DCM suggests a genetic substrate that predisposed the patient to a fulminant course, culminating in transplantation.

The concept of a double-hit mechanism—where external stressors such as viral infections, immune activation, pregnancy, chemotherapy, or intense exercise may unmask latent genetic cardiomyopathies—has significant implications for patient care. This case also underscores the importance of genetic testing in young patients with unexplained or disproportionate myocardial dysfunction. Data such as the Madrid score suggest that genotype-positive patients are at higher risk for adverse outcomes, including progression to end-stage heart failure and ventricular arrhythmias, and demonstrate lower potential for reverse remodeling.

Incorporating genetic evaluation into clinical practice not only aids in risk stratification and management of affected individuals but also facilitates cascade screening of family members, enabling early detection, preventive counseling, and targeted surveillance strategies.

12 lead Electrocardiogram showing ST elevation in lateral and inferior leads
Short axis delayed enhancement images showing subepicardial LGE at lateral and inferior walls
4 Chamber delayed enhancement images showing subepicardial LGE involving the LV apex and lateral wall.