Low QRS voltages and risk stratification in acute myocarditis : insights from the AMPHIBIA registry

Background Acute myocarditis (AM) is associated with a non-negligible risk of mortality, heart transplantation, and major ventricular arrhythmias. While low QRS voltages (LQRSV) have shown prognostic value in other cardiac diseases, their role in AM remains poorly investigated. The aim of this study was to assess the prevalence of LQRSV and its association with clinical outcomes in this population. Methods This analysis included patients hospitalized for AM between 2015 and 2024 at our Hospital (France) and enrolled in the AMPHIBIA registry (an observational ambispective cohort study). ECGs recorded at hospital admission were analyzed, and LQRSV was defined as an R-to-S peak-to-peak amplitude ≤0.5 mV in all limb leads. The primary endpoint was a composite of all-cause mortality, heart transplantation, temporary mechanical circulatory support (MCS), or sustained ventricular tachycardia/ventricular fibrillation (sVT/VF) at 5 years. Secondary endpoints included arrhythmic events and all-cause mortality analyzed separately. Cox proportional hazards models were used to assess associations with outcomes. Results Of the 439 patients enrolled in the AMPHIBIA registry after January 2015, 78 were excluded due to the absence of an available admission ECG, resulting in 361 patients included in the analysis. LQRSV was present in 9.9% of patients. Those with LQRSV had a more severe clinical presentation, with lower LVEF at admission (45% vs 56%) and a greater need for temporary mechanical circulatory support (30.6% vs 8.6%). At 5 years, the primary endpoint occurred in 50% of patients with LQRSV versus 13.5% without LQRSV (Figure 1). This difference was consistent across secondary outcomes, including all-cause mortality (16.7% vs 1.2%) and incidence of sVT/VF (19.4% vs 3.7%). Findings remained consistent after excluding patients with pericardial effusion. In multivariable analysis including established prognostic factors, LQRSV was independently associated with the composite endpoint (HR 2.20, 95% CI 1.23-3.93), together with LVEF <50%, sVT/VF at presentation, and female sex. A second model using best-subset selection confirmed LQRSV as an independent factor associated with worse clinical outcomes (HR 2.27, 95% CI 1.29-3.99). Conclusions In this large real-world AM cohort, LQRSV at admission identified a distinct high-risk phenotype characterized by greater hemodynamic compromise, increased need for intensive therapies, and markedly worse arrhythmic and survival outcomes at 5 years. As a simple and readily available ECG marker, LQRSV may improve early risk stratification in AM and support closer monitoring of affected patients. Further studies integrating genetic data may clarify its relationship with underlying cardiomyopathy substrates.