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(Circulation. 2000;101:1224.)
© 2000 American Heart Association, Inc.

Editorials

Hypertrophic Cardiomyopathy

Do We Have the Algorithm for Life and Death?

Pieter A. Doevendans, MD, PhD

From the Dept of Cardiology, Cardiovascular Research Institute, Academic Hospital Maastricht, Maastricht, The Netherlands.

Correspondence to Pieter A. Doevendans, Dept of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail p.doevendans@cardio.azm.nl

Key Words: Editorials • cardiomyopathy • genetics • hypertrophy

The molecular genetic basis for familial hypertrophic cardiomyopathy (FHC) is being unraveled, but this project is still not complete. All mutations identified thus far affect the function of sarcomeric proteins, and mutations in 8 different genes have been recognized. The mutated genes code for proteins positioned in the thick filament, including the ß-myosin heavy chain (ß-MHC) and essential and regulatory myosin light chains, and in the thin filament, actin, troponin T, troponin I, and -tropomyosin mutations have been identified. In many families, myosin binding protein C, which connects the thick filaments in the A-band, holds the genetic defect.^{1 2} It seems likely that in the next decade, most (if not all) mutations will be known, and the mystery regarding the origin of the disease will be solved.

Ever since the molecular cause of FHC was recognized, studies have attempted to understand the pathophysiology of the disease and discover how the various mutations in functionally different domains of the 8 contractile protein genes lead to myocyte hypertrophy and changes in the architecture of the hypertrophic tissue. This is an arduous task, despite recent advances in molecular biology and physiology. The effect of mutations can be analyzed in vitro by visualizing or measuring the myosin-actin interaction or ex vivo by studying muscle strips from human hearts or skeletal muscle preparations.^{3 4} More recently, interesting mouse models became available; these models carry human-like mutations in mouse genes or true human proteins and develop marked asymmetric cardiac hypertrophy. These mouse models even mimic the typical hemodynamic . . . [Full Text of this Article]

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