CONGRESS ABSTRACT

Introduction Genetic testing identifies a pathogenic variant, typically involving sarcomeric genes, in about 40-60% of patients with Hypertrophic Cardiomyopathy (HCM). When no pathogenic variant is found, clinical presentation may differ from that of genetic-positive individuals. The aim of this study was to investigate clinical and demographic characteristics of HCM patients followed at our Center, focusing on the relation between these features and genetic testing results. Methods We conducted a retrospective observational study on the cohort of all consecutive patients with a confirmed diagnosis of HCM followed at our center, divided into 3 groups based on the genetic test result: positive, negative, and variant of uncertain significance (VUS). We compared their demographic, clinical, and instrumental features. Results Of the 147 patients analyzed,74 (50.3%) had a pathogenic variant, 65 (44.2%) a negative test, and 8 (5.5%) a VUS. Genetic-negative patients had lower family history of HCM than positive ones (37% vs. 86%, p<0.0001) and VUS (88%, p=0.008)–Tab 1. The median age at diagnosis was significantly younger in the genetic-positive group than in the negative one (43.5, IQR 27-55 vs 56, IQR 47-63 years, p<0.0001), as was the percentage of patients with hypertension (32% vs 54%, p=0.008). Conversely, the genetic-negative group was more frequently prescribed beta-blockers (80% vs 58%, p=0.004) or RAAS inhibitors (49% vs 30%, p=0.02) compared to the one with a pathogenic variant. Additionally, patients with negative genetic result more often presented with an obstructive form of HCM (55% vs 24%, p=0.0002), had a higher outflow gradient at baseline (27.5, IQR 15-42 vs 15, IQR 10-20 mmHg, p=0.007) and during Valsalva maneuver (50, IQR 34.5-72.5 vs 22, IQR 14.5-36.5 mmHg, p=0.0004), and a larger left ventricle end-diastolic diameter (45±5 vs 43±5 mm, p=0.004)–Tab 2 Conclusions This monocentric retrospective analysis confirmed that, in patients with HCM, distinct characteristics are associated with the presence of a pathogenic genetic variant. Patients with negative or uncertain genetic results tend to be older and present with an obstructive form of the disease. Based on these preliminary findings, further studies are needed to assess the prognostic significance of these differences, investigate the underlying causes of HCM with negative genetic results, and better define potential management and therapeutic strategies tailored to the different subgroups.