Genotype-positive status in patients with hypertrophic cardiomyopathy is associated with higher rates of heart failure events.

Abstract

BACKGROUND:

The aim of the study was to clarify the relationship between genotype status and major cardiovascular outcomes in a large cohort of patients with hypertrophic cardiomyopathy.

METHODS AND RESULTS:

Genetic testing was performed in 558 consecutive proband patients with hypertrophic cardiomyopathy. Baseline and follow-up (mean follow-up 6.3 years) clinical and echocardiographic data were obtained. Pathogenic mutations were identified in 198 (35.4%) patients. Genotype-positive patients were more likely to be women (44% versus 30%; P=0.001), younger (39 versus 48 years; P<0.001), and have a family history of hypertrophic cardiomyopathy (53% versus 20%; P<0.001), as well as family history of sudden cardiac death (17% versus 7%; P=0.002). There were no significant differences in the rates of atrial fibrillation, stroke, or septal reduction procedures. Multivariable analysis demonstrated that genotype-positive status was an independent risk factor for the development of combined heart failure end points (decline in left ventricular ejection fraction to <50%, New York Heart Association III or IV in the absence of obstruction, heart failure-related hospital admission, transplantation, and heart failure-related death; hazards ratio, 4.51; confidence interval, 2.09-9.31; P<0.001). No difference was seen in heart failure events between the myosin heavy chain and myosin-binding protein C genotype-positive patients.

CONCLUSIONS:

The presence of a pathogenic sarcomere mutation in patients with hypertrophic cardiomyopathy was associated with an increase in heart failure events, with no differences in event rates seen between myosin heavy chain and myosin-binding protein C genotype-positive patients. The presence of a disease-causing mutation seems more clinically relevant than the specific mutation itself.

• Authors: Qin Li, Christiane Gruner, Raymond H Chan, Melanie Care, Katherine Siminovitch, Lynne Williams, Anna Woo, Harry Rakowski
• Journal: Circulation. Cardiovascular genetics (Circ Cardiovasc Genet) Vol. 7 Issue 4 Pg. 416-22 (Aug 2014) ISSN: 1942-3268 [Electronic] United States
• PMID: 24909666 (Publication Type: Journal Article)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Carrier Proteins
• myosin-binding protein C
• Myosin Heavy Chains

Topics

• Adult
• Age Factors
• Aged
• Cardiomyopathy, Hypertrophic (genetics, mortality, pathology)
• Carrier Proteins (genetics)
• Cohort Studies
• Death, Sudden, Cardiac (etiology)
• Echocardiography
• Female
• Follow-Up Studies
• Genetic Testing
• Genotype
• Heart Failure (etiology)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multivariate Analysis
• Myosin Heavy Chains (genetics)
• Polymorphism, Single Nucleotide
• Proportional Hazards Models
• Risk Factors
• Sex Factors