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

Introduction

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. A secondary analysis was performed in centers two centers, using a composite outcome of cardiovascular 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).

In the secondary analysis, Septal LGE was associated with cardiovascular death (HR 9.21, [95% CI 3.42–24.8], p<0.001), as was the LGE extent (HR 5.22, [95% CI 2.18–12.5], p<0.001), whereas LGE distribution pattern did not reach statistical significance (HR 2.39, [95% CI 0.32–17.7], p=0.33).

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.Figure 1Figure 2