Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere mutations, resulting in excess myosin-actin cross-bridging and hypercontractility1,2

Normal heart muscle

    In a normal heart muscle unit (sarcomere), myosin binds to actin, forming cross-bridges that regulate the contraction and relaxation of the heart3

Heart with excessive cross-bridging due to HCM

    In HCM, there is an excess of myosin-actin cross-bridging, which can lead to:
  • Increased contractility: The physiological alteration of thickened filament proteins and, indirectly, the cellular metabolic disruption of the sarcomere’s calcium-based regulatory system lead to a state of hypercontractility2-4
  • Decreased relaxation: Increased calcium sensitivity within the myocyte produces deficits in sarcomere relaxation1,2,4
  • Impaired efficiency: More energy is consumed when the sarcomere contracts, resulting in reduced mechanical efficiency1,2

The excessive bridging of myosin and actin increases the heart’s rigidity and can decrease outward blood volume1,2,4

Prevalence

References

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  1. Ommen SR, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25):e558-e631.
  2. Gersh BJ, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. J Thorac Cardiovasc Surg. 2011;142(6):e153-203.
  3. Kamisago M, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000 Dec 7;343(23):1688-96.
  4. Naidu, Srihari S, editor. Hypertrophic Cardiomyopathy. Second ed., Springer International Publishing, 2019.