Prognostic impact of late gadolinium enhancement granularity using cardiovascular magnetic resonance in end-stage hypertrophic cardiomyopathy

Background: End-stage hypertrophic cardiomyopathy (HCM) is a distinct and advanced form of HCM, defined by a left ventricular ejection fraction (LVEF) < 50% and associated with a markedly poor prognosis. Evidence on the prognostic relevance of LGE and its key features in end-stage HCM remains limited. We aim to evaluate the prognostic value of the LGE granularity model including its location, extent and pattern in end-stage HCM patients.Methods: All patients referred for cardiovascular magnetic resonance (CMR) assessment of HCM at three French university hospitals between 2008 and 2024 were retrospectively screened. All patients with HCM and LVEF < 50% were included. The “LGE granularity model” was defined as a model combining LGE extent (focal vs. multifocal involvement), location (septal vs. other), and pattern (subepicardial vs. midwall). The primary endpoint was all-cause mortality using the National Registry of Death.Results: Among 2,873 patients with HCM, 691 (24%) with end-stage HCM were included (53±7 years, 54% male). At the time of CMR, 30% of patients presented with heart failure symptoms classified as NYHA > II and 26% had a history of atrial fibrillation. After a median follow-up of 9 years (IQR 6–11), 226 patients died (32%). LGE was observed in 259 patients (37%) and was strongly associated with mortality (HR: 3.37, [95% CI: 2.57-4.42], p< 0.001), even after adjustment for traditional prognostic factors (HR: 1.52, [95% CI: 1.07-2.18], p=0.02). In sub-group analysis, LGE presence was associated with all-cause mortality in patients with LVEF >40% (HR: 3.32 [95% CI: 1.61-6.45], p< 0.001) but was not in patients with LVEF < 40% (HR: 0.98 [95% CI: 0.73-1.32], p=0.90). Each LGE granularity component was independently associated with mortality after adjustment with traditional prognostic factors: LGE extent (HR: 2.85, [95% CI: 1.03-7.85], p=0.02), septal location (HR: 1.73, [95% CI: 1.10-2.73], p< 0.001), and midwall pattern (HR: 4.15, [95% CI: 1.79-9.61], p< 0.001). The LGE granularity model improved risk reclassification and discrimination compared to traditional prognostic factors (NRI: 32%; IDI: 10%, both p< 0.001; global Chi-square: 139 to 167, p< 0.001).Conclusion: In this large multicenter cohort of end-stage HCM patients, the LGE granularity model integrating the LGE extent, location, and pattern provided strong and independent prognostic value beyond traditional prognostic factors.