Review ArticleContractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy
Section snippets
A Disorder of Cardiomyocyte Morphology and Remodeling
In HCM, the cells are often obliquely angled with a swirling pattern.3 Individual cells are hypertrophied and the myofibril architecture is disorganized with disrupted myotubes. The arteriolar density is reduced, the capillaries are structurally abnormal, and there is increased interstitial fibrosis.3 An important observation is that different individuals with the identical mutation have different phenotypic patterns, suggesting that there is a nongenetic influence over the phenotype.
The route
A Disorder of Exercise
One of the most common manifestations of HCM is exertional breathlessness. This may be due to inotropic incompetence, limited filling during diastole, worsening mitral regurgitation, or increasing left ventricular outflow obstruction.6 Failure to augment stroke volume could be related to impaired diastolic filling because of the thicker ventricular wall. Exercise intolerance in HCM is related to an inability to increase the stroke volume appropriately and results from reduced inotropic reserve.
A Disorder of Contractile Stress
Contractile “function” is difficult to define and therefore we will avoid the term hereafter. Contractile stress is the active force per unit area produced by the myocytes. Contractile stress is not a passive consequence of the systemic blood pressure, but an active process that determines aortic pressure development and flow. Contraction of myofibrils results in contractile stress along the cells' axes that is transformed into a stress in an orthogonal radial direction. The cardiomyocyte
The Consequences of HCM When Viewed as a Disorder of Contractile Stress
The wall of the left ventricle must be thicker to achieve a normal wall force in the presence of reduced contractile stress.36 The direction of myocardial stresses can be determined from the direction (Fig. 2) of the cardiomyocytes (Fig. 3). The cumulative force may then be calculated using the wall thickness (Fig. 4).
We view HCM as a primary abnormality of contractile stress and hypertrophy as a compensatory response which helps normalizes contractile wall forces.
Conclusions
There are important contractile abnormalities at the organ level in patients with HCM that coincide with the severity of the hypertrophy both regionally and globally. Ejection fraction may be normal or increased despite reduced myocardial contraction (and radial strain) because the hypertrophy increases absolute mural thickening. The different phenotypes seen in HCM might be determined by differences in systolic myocardial wall stresses. Measures of “diastolic dysfunction” are common in HCM but
Disclosures
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgments
We would like to thank Dr Garth N. Wells and Quang-Thinh Ha of the Engineering Department, University of Cambridge for their discussions and contribution to the engineering aspects of this article.
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Funding: Nil.