title: Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.
abstract: The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalizes wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the hemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern; and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation.
authors.affiliation: Department of Cardiology, Taunton & Somerset Hospital, Musgrove Park, Taunton, UK; Biological Physics Group, School of Physics & Astronomy, University of Manchester, Manchester, UK; Medical Education, University of Bristol, Senate House, Tyndall Avenue, Bristol BS8 1TH, UK. Electronic address: david.maciver@tst.nhs.uk.
authors.forename: David H
authors.initials: DH
authors.lastname: MacIver
authors.affiliation: Department of Cardiology, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham HU16 5JQ, UK.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Clark
mesh_terms: D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D002423:Cause of Death; D018450:Disease Progression; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D011379:Prognosis; D018570:Risk Assessment; D012518:Sarcomeres / Q000473:pathology*; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D016019:Survival Analysis
keywords: Hypertrophic cardiomyopathy; contractility; diastolic dysfunction; left ventricular hypertrophy; myocardial strain; stress