Abstract 11009: A Novel Patient-Patient Network Medicine Approach to Refine Hypertrophic Cardiomyopathy Subgrouping: Implications for Risk Stratification

Abstract

Introduction: In hypertrophic cardiomyopathy (HCM), the presence of left ventricular (LV) apical aneurysm warrants implantable cardioverter defibrillator (ICD) therapy consideration for primary prevention of sudden death (SD). However, a significant proportion of these patients may never experience an SD event. Thus, identifying parameters that modify SD risk in this population may be important clinically, but likely requires phenotyping methods that include robust patient-level information. Methods: Clinical, demographic and echocardiographic parameters were compiled for a large HCM referral population. Variables (N=52) were normalized to the cohort and the Pearson’s correlation was calculated between patients using r>0.6 (after Benjamini-Hochberg correction), selected to maximize the patient:edge ratio. The SD event/risk profile was defined as: SD event/ ≥ 1 major HCM SD risk factor. Results: From N=3,412 HCM patients (male, 62%; 49 17 years at diagnosis) in the network, the clinical profile included maximum LV thickness, 18 4 mm; left atrial diameter, 41 7 mm; LV outflow tract gradient 30 mmHg, and N=68 (3%) patients with LV apical aneurysm. We identified N=17 distinct patient modules (range, N=19-483 patients/module). Module #15 was highly enriched for LV apical aneurysm (N=56/56); however, the SD event rate was significantly less compared to LV apical aneurysm patients in all other modules (N=12; 4% vs. 75%; P<0.0001). Lower blood pressure and smaller left atrial size delineated LV apical aneurysm patient in module #15. Conclusions: This proof-of-concept patient-patient network analysis suggests that lower blood pressure and smaller left atrial size may contribute to a favorable SD risk profile among HCM LV apical aneurysm patients.