Pablo García Pavía

Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy

Introduction Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM.

The Scope of Cardiological Competence in New Clinical Settings. Spanish Society of Cardiology Consensus Document

Cardiology is the medical discipline or specialty responsible for the prevention, diagnosis, and treatment of cardiovascular disease. As this is the major cause of morbidity and mortality in Spain and the European Union,1 cardiology professionals have, with respect to other medical specialists, an additional moral authority and responsibility derived from the relevance for society of an excellent performance in combating cardiovascular disease. Hence the importance of keeping up with the rapid transitions that are currently taking place at the social, administrative, educational, health care, and professional levels, transitions that necessarily generate novel contexts for the practice of cardiology and for its professionals. At the end of 2005, the Spanish Society of Cardiology (SSC), by virtue of its leadership role in combating cardiovascular disease, decided to undertake a project, applying a synthetic approach to the process matrix, involving the professionals in cardiology and in other medical specialties, the health care administrations, the pharmaceutical industry, and biotechnology companies, the institutions, the patients and the general population; these processes will ultimately play a role in the development of the field of cardiology, in the work of The Scope of Cardiological Competence in New Clinical Settings

The Scope of Cardiological Competence in New Clinical Settings

Cardiology is the medical discipline or specialty responsible for the prevention, diagnosis, and treatment of cardiovascular disease. As this is the major cause of morbidity and mortality in Spain and the European Union,1 cardiology professionals have, with respect to other medical specialists, an additional moral authority and responsibility derived from the relevance for society of an excellent performance in combating cardiovascular disease. Hence the importance of keeping up with the rapid transitions that are currently taking place at the social, administrative, educational, health care, and professional levels, transitions that necessarily generate novel contexts for the practice of cardiology and for its professionals. At the end of 2005, the Spanish Society of Cardiology (SSC), by virtue of its leadership role in combating cardiovascular disease, decided to undertake a project, applying a synthetic approach to the process matrix, involving the professionals in cardiology and in other medical specialties, the health care administrations, the pharmaceutical industry, and biotechnology companies, the institutions, the patients and the general population; these processes will ultimately play a role in the development of the field of cardiology, in the work of The Scope of Cardiological Competence in New Clinical Settings

The Scope of Cardiological Competence in New Clinical Settings: A Consensus Document of the Spanish Society of Cardiology

Cardiology is the medical discipline or specialty responsible for the prevention, diagnosis, and treatment of cardiovascular disease. As this is the major cause of morbidity and mortality in Spain and the European Union,1 cardiology professionals have, with respect to other medical specialists, an additional moral authority and responsibility derived from the relevance for society of an excellent performance in combating cardiovascular disease. Hence the importance of keeping up with the rapid transitions that are currently taking place at the social, administrative, educational, health care, and professional levels, transitions that necessarily generate novel contexts for the practice of cardiology and for its professionals. At the end of 2005, the Spanish Society of Cardiology (SSC), by virtue of its leadership role in combating cardiovascular disease, decided to undertake a project, applying a synthetic approach to the process matrix, involving the professionals in cardiology and in other medical specialties, the health care administrations, the pharmaceutical industry, and biotechnology companies, the institutions, the patients and the general population; these processes will ultimately play a role in the development of the field of cardiology, in the work of The Scope of Cardiological Competence in New Clinical Settings