Enhancing risk prediction for sudden cardiac death: quantitative late gadolinium enhancement analysis in hypertrophic cardiomyopathy

OBJECTIVES: To assess the prognostic value of multiple late gadolinium enhancement (LGE) quantification methods for sudden cardiac death (SCD) prediction in hypertrophic cardiomyopathy (HCM). MATERIALS AND METHODS: In this single-center retrospective study, 617 HCM patients who underwent cardiac magnetic resonance (CMR) examinations were consecutively enrolled. LGE was quantified using the n-standard deviation (SD) technique (with multiple thresholds) and the full width at half maximum method. "Gray zone" was defined as the myocardium with signal intensity between two predefined thresholds on LGE images. The primary outcome was SCD or aborted SCD. RESULTS: Among 617 HCM patients, 424 (68.7%) were male, mean age was 49.1 ± 14.0 years, and LGE was identified in 438 (71.0%). During 67.9 ± 21.0 months of follow-up, 24 patients (3.9%) reached the primary endpoint. All dual-threshold gray zone measures and five single-threshold LGE quantifications (2-6 SDs) independently predicted SCD (HR range: 1.031-1.220, all adjusted p < 0.05). Gray zone (HR range: 1.091-1.220) showed stronger associations than single-threshold LGE measures (HR range: 1.031-1.046). Both approaches improved discrimination beyond the composite American Heart Association (AHA)/American College of Cardiology (ACC) model, with increased net reclassification improvement (0.321 and 0.397, respectively) and comparable C-statistics (0.794-0.871 vs 0.794-0.898, p = 0.155). CONCLUSION: While conventional single-threshold LGE quantification predicts SCD in HCM, dual-threshold gray-zone analysis demonstrates stronger associations. Both approaches provide incremental prognostic value beyond the AHA/ACC guideline-based risk model. These findings underscore the importance of standardizing LGE quantification to improve SCD risk stratification in patients with HCM. KEY POINTS: Question: The optimal LGE quantification approach for SCD risk stratification in HCM remains uncertain. FINDINGS: Both single- and dual-threshold LGE quantification independently predict SCD in patients with HCM, while dual-threshold gray zone metrics demonstrate stronger prognostic associations. Critical Relevance: By systematically comparing multiple LGE quantification approaches, this study highlights the impact of methodological variability on SCD risk stratification in HCM, underscores the need for standardized LGE assessment, and informs clinical radiology practice.