Abstract 14514: Hypertrophic Cardiomyopathy - Genotype Distribution and Genotype-Phenotype Correlations - A Unique Perspective From a Single Center Study

Abstract

Background: The role of genotype in risk stratification of hypertrophic cardiomyopathy (HCM) is unclear. Hypothesis: Genotype status affects phenotype and associated outcomes. Aims: To evaluate genotype-phenotype correlations in all adult HCM patients seen at our Cardiac Specialty Center over 13 years and associated outcomes. Methods: We evaluated genotype-phenotype correlations, all-cause mortality, and a composite outcome, including mortality, stroke, implantable cardioverter-defibrillator placement, heart failure hospitalization, LV assist device implantation, heart transplant, septal myectomy, and alcohol septal ablation. Results: Of 827 HCM patients, genotyping was completed in 754 (91.2%), which included 27% genotype-positive (Gen-P), 22% variants of unknown significance (VUS), and 51% genotype-negative (Gen-N) patients with a mean age of 47, 57, and 58 years, respectively. The most common gene implicated was MYBPC3 (63%). LV hypertrophy on electrocardiogram was more frequent in Gen-N than Gen-P patients. Gen-P patients had more frequent non-sustained ventricular tachycardia on Holter monitoring (25% vs 10%), grade III diastolic dysfunction (12% vs 7%), elevated ProBNP (71% vs 61%), and lower ejection fraction (66% vs 69%) than Gen-N patients (P <.05 for all comparisons). All heart transplantations (N=5) were performed in Gen-P patients. LVOT obstruction was more frequent in Gen-N than Gen-P patients (48% vs 26%, P <.01). Distribution of outcomes is shown in Panels A-H. The composite outcome was worse in Gen-P vs Gen-N patients (HR 1.84, P <.01). The other independent predictors of poor composite outcome were old age, male sex, obesity, and atrial fibrillation. A separate analysis of mortality showed similar survival in all groups. Conclusion: Differences exist in phenotype and outcomes based on the genotype status, with more severe phenotype and poorer outcomes in Gen-P patients in our single-state single-center experience.