Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy

Circ Cardiovasc Imaging. 2017 Feb;10(2):e005311. doi: 10.1161/CIRCIMAGING.116.005311.

Abstract

Background: The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (β-myosin heavy chain) and MYBPC3 (β-myosin-binding protein C). Phenotypic differences between patients with mutations in these 2 genes have been inconsistent. Scarce data exist on the genotype-phenotype association as assessed by tomographic imaging using cardiac magnetic resonance imaging.

Methods and results: Cardiac magnetic resonance imaging was performed on 358 consecutive genotyped hypertrophic cardiomyopathy probands at 5 tertiary hypertrophic cardiomyopathy centers. Genetic testing revealed a pathogenic mutation in 159 patients (44.4%). The most common genes identified were MYH7 (n=53) and MYBPC3 (n=75); 33.1% and 47% of genopositive patients, respectively. Phenotypic characteristics by cardiac magnetic resonance imaging of these 2 groups were similar, including left ventricular volumes, mass, maximal wall thickness, morphology, left atrial volume, and mitral valve leaflet lengths (all P=non-significant). The presence of late gadolinium enhancement (65% versus 64%; P=0.99) and the proportion of total left ventricular mass (%late gadolinium enhancement; 10.4±13.2% versus 8.5±8.5%; P=0.44) were also similar.

Conclusions: This multicenter multinational study shows lack of phenotypic differences between MYH7- and MYBPC3-associated hypertrophic cardiomyopathy when assessed by cardiac magnetic resonance imaging. Postmutational mechanisms appear more relevant to thick-filament disease expression and outcome than the disease-causing variant per se.

Keywords: cardiomyopathy, hypertrophic; genotype; magnetic resonance imaging; myosin heavy chain; myosin-binding protein C; phenotype.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Canada
  • Cardiac Myosins / genetics*
  • Cardiomyopathy, Hypertrophic, Familial / diagnostic imaging*
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Cardiomyopathy, Hypertrophic, Familial / physiopathology
  • Carrier Proteins / genetics*
  • Contrast Media / administration & dosage
  • Europe
  • Female
  • Gadolinium DTPA / administration & dosage
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Image Interpretation, Computer-Assisted
  • Imaging, Three-Dimensional
  • Magnetic Resonance Imaging, Cine*
  • Male
  • Middle Aged
  • Mutation*
  • Myosin Heavy Chains / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Registries
  • Risk Factors
  • Stroke Volume
  • Tertiary Care Centers
  • United States
  • Ventricular Function, Left
  • Ventricular Remodeling

Substances

  • Carrier Proteins
  • Contrast Media
  • MYH7 protein, human
  • myosin-binding protein C
  • Cardiac Myosins
  • Myosin Heavy Chains
  • Gadolinium DTPA