Genetic characterization and genotype-phenotype associations in a large cohort of patients with hypertrophic cardiomyopathy – An ancillary study of the Portuguese registry of hypertrophic cardiomyopathy. (1st March 2019)

• Record Type: Journal Article
• Authors: Lopes, Luis Rocha; Brito, Dulce; Belo, Adriana; Cardim, Nuno
• Is Part Of: International journal of cardiology. Volume 278(2019)
• Page Start: 173
• Page End: 179
• Publication Date: 2019-03-01
• Subjects: Hypertrophic cardiomyopathy -- Genetics -- Genotype-phenotype -- Registry -- LV systolic dysfunction -- Sudden cardiac death; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2018.12.012
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: We present an ancillary study of the Portuguese Registry of Hypertrophic Cardiomyopathy (PRo-HCM). This is one of the largest HCM genetic studies based on a registry. Methods and results: Collected genetic variants were re-analysed for pathogenicity. Demographic, clinical, imaging and outcome data were analysed for associations with genotype, focusing on comparisons between patients with (G+) vs without (G−) a pathogenic/likely pathogenic (P/LP) variant in one the 9 main causal sarcomeric genes. From the 1042 patients in the registry, 528 (51%) had genetic testing. 152 (28%) were G+ and 98 pts. (19%) had variants of unknown significance. From the patients with the 9 mentioned genes sequenced (424 pts), 14.6% had P/LP variants in MYBPC3, 8.7% MYH7, 4.5% TNNT2, 1.7% TNNI3 . Patients were 51 ± 16 years-old, 59% males. Genotype was associated with the following: birthplace ( p = 0.005); age ( p < 0.001); family history of HCM ( p < 0.0005); hypertension ( p < 0.0005); chest pain ( p = 0.015); pattern of hypertrophy ( p = 0.006); left ventricular hypertrophy on the ECG (p < 0.0005); family history of sudden cardiac death (SCD) ( p = 0.002). G+ patients more frequently had more than one risk factor for SCD (p = 0.002) and a higher ESC-SCD risk score ( p = 0.003). In survival analysis, G+ was associated with SCD ( p = 0.017) and MYH7 + with LV systolic dysfunction ( p = 0.038). Conclusion: Half of the registry patients had genetic testing. Sarcomere-positive patients had distinct demographics, ECG, imaging characteristics and family history and are at increased risk of SCD. The presence of a MYH7 mutation was associated with evolution towards LV systolic dysfunction. Highlights: This is one of the largest HCM genetic studies based on a registry. Collected genetic variants were thoroughly re-analysed for pathogenicity. Sarcomere-positive patients had distinct demographics, ECG, imaging and family history. Sarcomere-positive patients are at increased risk of sudden death. MYH7 was associated with evolution towards systolic dysfunction.