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Hypertrophic cardiomyopathy: A complex disease

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Release date: May 1, 2018
Expiration date: April 30, 2019
Estimated time of completion: 1 hour

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ABSTRACT

Hypertrophic cardiomyopathy (HCM) is a complex cardiovascular disease with wide phenotypic variations. Despite significant advances in imaging and genetic testing, more information is needed about the roles and implications of these resources in clinical practice. Patients with suspected or established HCM should be evaluated at an expert referral center to allow for the best multidisciplinary care. Research is needed to better predict the risk of sudden cardiac death in those judged to be at low risk by current risk-stratification methods.

KEY POINTS

  • Obstruction of the left ventricular outflow tract is a key pathophysiologic mechanism in HCM.
  • Because most of the genetic variants that contribute to HCM are autosomal dominant, genetic counseling and testing are suggested for patients and their first-degree relatives.
  • Transthoracic echocardiography is the first-line imaging test, followed by magnetic resonance imaging.
  • Beta-blockers are the first-line drugs for treating symptoms of HCM.
  • An implantable cardioverter-defibrillator can be considered for patients at risk of sudden cardiac death.
  • When medical therapy fails or is not tolerated in patients with severe symptoms of obstructive HCM, surgery to reduce the size of the ventricular septum can be considered. Alcohol septal ablation is an alternative.


 

References

Hypertrophic cardiomyopathy (HCM) is a complex disease. Most people who carry the mutations that cause it are never affected at any point in their life, but some are affected at a young age. And in rare but tragic cases, some die suddenly while competing in sports. With such a wide range of phenotypic expressions, a single therapy does not fit all.

HCM is more common than once thought. Since the discovery of its genetic predisposition in 1960, it has come to be recognized as the most common heritable cardiovascular disease. 1 Although earlier epidemiologic studies had estimated a prevalence of 1 in 500 (0.2%) of the general population, genetic testing and cardiac magnetic resonance imaging (MRI) now show that up to 1 in 200 (0.5%) of all people may be affected. 1,2 Its prevalence is significant in all ethnic groups.

This review outlines our expanding knowledge of the pathophysiology, diagnosis, and clinical management of HCM.

A PLETHORA OF MUTATIONS IN CARDIAC SARCOMERIC GENES

Figure 1. A, echocardiography, apical 4-chamber view, demonstrates septal hypertrophy (arrow). B, cardiac magnetic resonance imaging of the left ventricular outflow tract also demonstrates septal hypertrophy (arrow). C, echocardiography with continuous-wave Doppler across the left ventricular outflow tract demonstrates a gradient of 70 mm Hg, consistent with obstruction. D, electrocardiography reveals signs of left ventricular hypertrophy by Sokolov-Lynon criteria with S wave depth in V 1 plus R wave height in V 5 > 35 mm (arrows).
The genetic basis of HCM is much more complex than was originally thought, with more than 1,400 mutations in 11 sarcomeric protein genes now known to be associated with the disease. Most of these mutations are autosomal dominant. 3

The genetic differences within HCM result in varying degrees and locations of left ventricular hypertrophy. Any segment of the ventricle can be involved, although HCM is classically asymmetric and mainly involves the septum ( Figure 1 ). A variant form of HCM involves the apex of the heart ( Figure 2 ).

LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION

Figure 2. A, echocardiography, apical 4-chamber view, shows apical hypertrophy (arrows). B, cardiac magnetic resonance imaging (4-chamber view) shows apical hypertrophy (red arrows), as well as an apical aneurysm (blue arrow). C, electrocardiography demonstrates giant T-wave inversions in the left precordial leads, characteristic of apical hypertrophic cardiomyopathy (arrows).
Obstruction of the left ventricular outflow tract is thought to be the pivotal pathophysiologic process of HCM. Other abnormalities may include myocardial ischemia and diastolic dysfunction, believed to be related to narrowing of the intramural coronary arteries. 4 Histopathologic study of heart muscle in HCM demonstrates disarray of the hypertrophied myocyte architecture with variable patterns of interstitial fibrosis.

Only in the last decade has the significance of left ventricular outflow tract obstruction in HCM been truly appreciated. The degree of obstruction in HCM is dynamic, as opposed to the fixed obstruction in patients with aortic stenosis or congenital subvalvular membranes. Therefore, in HCM, exercise or drugs (eg, dobutamine) that increase cardiac contractility increase the obstruction, as do maneuvers or drugs (the Valsalva maneuver, nitrates) that reduce filling of the left ventricle.

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