Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband's risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers. We performed an observational study of patients with HCM due to the novel p.Arg652Lys variant in the MYH7 gene. Eight families and 59 patients are described in the follow-up for a median of 63 months, among whom 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator discharge, an embolic event, or admission for heart failure) was observed in five (20%) patients. Given the finding of the p.Arg652Lys variant in patients with HCM, but not in controls, with evident segregation in patients with HCM from eight families and the location in an active site of the protein, we can define this variant as likely pathogenic and associated with the development of HCM.

Diastolic dysfunction and exercise capacity in patients with metabolic syndrome and overweight/obesity.

BACKGROUND: Left ventricle diastolic dysfunction (LVDD) is a common finding in high risk individuals, its presence being associated with reduced exercise capacity (EC). We assessed the prevalence of LVDD, applying the 2016 guidelines of the American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI), in a population with overweight/obesity and metabolic syndrome and its association with EC. METHODS AND RESULTS: This was a prospective, cross-sectional study of a cohort of 235 patients (mean age of 65 ±â€¯5 years old and 33% female) without heart disease and an ejection fraction >50% who underwent a complete echocardiographic assessment and cardiopulmonary exercise testing. Individuals meeting three or more criteria of the 2016 ASE/EACVI guidelines are considered to have LVDD, while tests are considered indeterminate in those meeting only two. Overall, 178 (76%) of our patients met one echocardiographic cutoff value for LVDD, 91 (39%) met two and 7 (3%) three or more. Patients meeting three cutoffs values showed a significant reduction in maximal oxygen uptake (16 ±â€¯3 vs. 19.6 ±â€¯5 ml/kg/min, p < .05), unlike those with indeterminate tests. In multiple regression analysis, meeting three cutoffs was associated with number of METS (ß = -2.2, p = .018). In exploratory analysis, using two criteria based on cutoffs different from those proposed in the guidelines, we identified groups with different EC. CONCLUSIONS: The application of 2016 ASE/EACVI guidelines limited the prevalence of LVDD to 3%. This group showed a clear reduction of the EC. New echocardiographic cutoff values proposed in this study allow us to establish subgroups with different levels of EC.