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Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy
- Source :
- Journal of the American College of Cardiology. (10):1776-1782
- Publisher :
- American College of Cardiology Foundation. Published by Elsevier Inc.
-
Abstract
- OBJECTIVES: We investigated cardiac energetics in subjects with mutations in three different familial hypertrophic cardiomyopathy (HCM) disease genes, some of whom were nonpenetrant carriers without hypertrophy, using phosphorus-31 magnetic resonance spectroscopy. BACKGROUND: Familial hypertrophic cardiomyopathy is caused by mutations in sarcomeric protein genes. The mechanism by which these mutant proteins cause disease is uncertain. A defect of myocyte contractility had been proposed, but in vitro studies of force generation have subsequently shown opposing results in different classes of mutation. An alternative hypothesis of "energy compromise" resulting from inefficient utilization of adenosine triphosphate (ATP) has been suggested, but in vivo data in humans with genotyped HCM are lacking. METHODS: The cardiac phosphocreatine (PCr) to ATP ratio was determined at rest in 31 patients harboring mutations in the genes for either beta-myosin heavy chain, cardiac troponin T, or myosin-binding protein C, and in 24 controls. Transthoracic echocardiography was used to measure left ventricular (LV) dimensions and maximal wall thickness. RESULTS: The PCr/ATP was reduced in the HCM subjects by 30% relative to controls (1.70 +/- 0.43 vs. 2.44 +/- 0.30; p < 0.001), and the reduction was of a similar magnitude in all three disease-gene groups. The PCr/ATP was equally reduced in subjects with (n = 24) and without (n = 7) LV hypertrophy. CONCLUSIONS: Our data provide evidence of a bioenergetic deficit in genotype-confirmed HCM, which is present to a similar degree in three disease-gene groups. The presence of energetic abnormalities, even in those without hypertrophy, supports a proposed link between altered cardiac energetics and development of the disease phenotype.
- Subjects :
- Adult
Male
medicine.medical_specialty
Magnetic Resonance Spectroscopy
Heart disease
Adolescent
Phosphocreatine
Cardiomyopathy
Mutation, Missense
030204 cardiovascular system & hematology
Gene mutation
medicine.disease_cause
Article
Muscle hypertrophy
Ventricular Myosins
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Adenosine Triphosphate
Troponin complex
Troponin T
Internal medicine
Medicine
Humans
Child
030304 developmental biology
Aged
0303 health sciences
Mutation
business.industry
Myocardium
Hypertrophic cardiomyopathy
Cardiomyopathy, Hypertrophic
Middle Aged
medicine.disease
Endocrinology
chemistry
Female
business
Cardiology and Cardiovascular Medicine
Carrier Proteins
Energy Metabolism
Cardiac Myosins
Echocardiography, Transesophageal
Subjects
Details
- Language :
- English
- ISSN :
- 07351097
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of the American College of Cardiology
- Accession number :
- edsair.doi.dedup.....f17b21914e4cf5aa0057d6e563e4e223
- Full Text :
- https://doi.org/10.1016/S0735-1097(02)03009-7