Revisiting risk stratification in hypertrophic cardiomyopathy after the recent guidelines - LGE remains tough to beat

Abstract Background and Objectives Over the last decades, the recommendation for ICD implantation for the primary prevention of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) has been evolving. Late gadolinium enhancement (LGE) has been incorporated in the guidelines as a risk factor to be considered for ICD implantation. The aims of this study were: 1) assess the evolution of accuracy and discriminative ability of the different guidelines (ESC 2014, ESC 2022, ESC 2023, ACC 2011 and ACC 2020) in predicting SCD; and 2) to understand whether LGE can further help in the risk stratification of SCD. Methods We conducted an international multicentric retrospective analysis of HCM patients undergoing cardiac magnetic resonance (CMR) for diagnostic confirmation and/or risk stratification. Eligibility criteria for ICD according to the ESC 2014 (HCM), ESC 2022 (Ventricular arrhythmias VAs), ESC 2023 (Cardiomyopathies), ACC 2011 and ACC 2020 (both HCM guidelines) was determined for each patient. Our primary endpoint was a composite of SCD, appropriate ICD discharge and sustained VT. Results We included a total of 530 patients (median age was 49 (IQR 35-61), 57% male). Over a median follow-up of 3.8 (IQR 1.6 – 7.0) years, 27 events occurred (13 SCDs, 8 appropriate ICD discharges and 6 sustained VAs). The diagnostic accuracy statistics of the European and the American societies guidelines have evolved similarly over time: sensitivity and PPV increased, NPV remained high and discriminative ability also increased (see Figure). However, the concordance in risk assessment is only moderate between the ESC 2022 and ACC 2020 (κ = 0.60 (95%CI: 0.54–0.67); p < 0.001) or the ESC 2023 and ACC 2020 guidelines (κ = 0.56 (95%CI: 0.49–0.62); p < 0.001). LGE was present in 80% of patients. Median LGE% was 3.2% (IQR 0.5 – 8.4%) and remained an independent predictor of arrhythmic events after adjustment to known confounders (aHR of 1.09 per 1% increase in LGE% [95% CI 1.05 – 1.12; p < 0.001]). The Youden test showed a best cut-off for LGE burden of 7.1%. Further risk stratification could be reached by employing LGE% as an arbiter. Irrespectively of the guideline publisher, in patients with any recommendation for ICD (classes IIa and IIb), the absence of LGE identified patients with no arrhythmic events during follow-up (see Figure). Conclusions Current guidelines have shown increased sensitivity, PPV and discriminative power when compared with older counterparts. LGE burden remains an independent risk factor for arrhythmic events and although extensive LGE burden has been included in the risk stratification for ICD implantation, further stratification can be accomplished for ICD recommendation, since this seems to be a predictor stronger than clinical parameters.