Elsevier

Journal of Cardiac Failure

Volume 22, Issue 9, September 2016, Pages 731-737
Journal of Cardiac Failure

Review Article
Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy

https://doi.org/10.1016/j.cardfail.2016.03.020Get rights and content

Highlights

  • •

    Contractile abnormalities are common and progressive in hypertrophic cardiomyopathy (HCM).

  • •

    Abnormal cardiomyocyte disarray results in reduced contractile stress.

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    The development of hypertrophy helps normalize resting contractile forces.

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    The normal or increased ejection fraction is explained by the presence of hypertrophy.

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    The different phenotypes of HCM may be explained by the distribution of contractile stresses and strains.

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.

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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