Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals

• Published in: Clinical research in cardiology 2018, Vol.107 (1), p.30-41
• Main Authors: Sedaghat-Hamedani, Farbod, Kayvanpour, Elham, Tugrul, Oguz Firat, Lai, Alan, Amr, Ali, Haas, Jan, Proctor, Tanja, Ehlermann, Philipp, Jensen, Katrin, Katus, Hugo A., Meder, Benjamin
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; Arrhythmia; Cardiac Myosins - genetics; Cardiology; Cardiomyopathy; Cardiomyopathy, Hypertrophic - diagnosis; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - physiopathology; Cardiomyopathy, Hypertrophic - therapy; Cardiovascular diseases; Carrier Proteins - genetics; Case-Control Studies; Clinical outcomes; Conduction; Coronary artery disease; Death, Sudden, Cardiac - etiology; Death, Sudden, Cardiac - prevention & control; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype & phenotype; Genotypes; Health risks; Heart diseases; Heart rate; Heart Transplantation; Humans; Male; Medicine; Medicine & Public Health; Meta-analysis; Middle Aged; Mutation; Myosin Heavy Chains - genetics; Original Paper; Patients; Phenotype; Phenotypes; Risk Factors; Transplantation; Treatment Outcome; Troponin I - genetics; Troponin T - genetics; Ventricle; Young Adult
• ISSN: 1861-0684; 1861-0692
• DOI: 10.1007/s00392-017-1155-5

Background Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, which goes along with increased risk for sudden cardiac death (SCD). Despite the knowledge about the different causal genes, the relationship between individual genotypes and phenotypes is incomplete. Methods and results We retrieved PubMed/Medline literatures on genotype–phenotype associations in patients with HCM and mutations in MYBPC3 , MYH7 , TNNT2, and TNNI3 . Altogether, 51 studies with 7675 HCM patients were included in our meta-analysis. The average frequency of mutations in MYBPC3 (20%) and MYH7 (14%) was higher than TNNT2 and TNNI3 (2% each). The mean age of HCM onset for MYH7 mutation positive patients was the beginning of the fourth decade, significantly earlier than patients without sarcomeric mutations. A high male proportion was observed in TNNT2 (69%), MYBPC3 (62%) and mutation negative group (64%). Cardiac conduction disease, ventricular arrhythmia and heart transplantation (HTx) rate were higher in HCM patients with MYH7 mutations in comparison to MYBPC3 ( p