Genetic variants identify patients with myocarditis at higher risk for ICD implantation
B Hariharan, R Lim, P Billia, N AleksovaAbstract
Background
Myocarditis affects approximately 1 in 5000 people annually, with clinical outcomes ranging from spontaneous recovery to death. A variety of causes have been implicated; and there is increasing recognition that there is overlap between genetics, immune and infectious causes of myocarditis. Predictors of outcome severity in this population are not well understood and there is growing interest in identifying patients who are at higher risk of disease progression, sudden cardiac death, and heart failure.
Purpose
To evaluate clinical outcomes in patients with myocarditis according to the presence or absence of pathogenic/possibly pathogenic (P/PP) genetic variations.
Methods
We conducted a retrospective, single-centre observational study of patients diagnosed with myocarditis and compared those who did and did not undergo genetic testing until June 2025. The diagnosis of myocarditis was adjudicated in duplicate according to the ESC definition of myocarditis [Caforio 2013]. Outcomes of interest included change in left ventricular ejection fraction (LVEF) by echocardiography, hospitalization for heart failure (HF) or arrhythmia, ICD implantation, heart transplantation and death. Logistic regression was conducted to assess the relationship between P/PP variations and outcomes of interest. A p-value of <0.05 was deemed statistically significant.
Results
There were 161 patients identified with a median follow up time of 7.2 (IQR 3.4-12.1) years: 45 (28%) had genetic testing and 116 (72%) did not have genetic testing. There was no difference in age, sex, late gadolinium enhancement (LGE) on MRI, or LVEF < 30% by echocardiography at initial presentation between patients with and without genetic testing (Table 1). Of the 45 patients diagnosed with myocarditis who underwent genetic testing, 24 (53%) had a P/PP genetic variation and 21 (47%) had no identified variations. Patients with a P/PP genetic variation were younger, more often presented with HF and had LVEF <30% on echocardiogram at the time of diagnosis (Table 2). There was no difference in survival, listing for heart transplantation, or hospitalization for heart failure/cardiogenic shock/arrhythmias at follow up according to the presence or absence of P/PP genetic variations, however ICD implantation at follow-up was more likely in patients diagnosed with myocarditis who also had a P/PP genetic variation (Figure 1).
Conclusions
Genetic testing may be of particular value in younger patients diagnosed with myocarditis with an index presentation of heart failure and severe LV dysfunction. The importance of genetic testing as a predictor of outcomes remains unclear with larger population studies needed, however our study found the odds of ICD implantation were four times greater when patients with a diagnosis of myocarditis also have a P/PP genetic variant present.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.