View Full Version : Hypertrophic cardiomyopathy

26-05-09, 05:49 AM
Hypertrophic cardiomyopathy is a complex cardiac disease with unique pathophysiologic characteristics and a great diversity of morphologic, functional, and clinical features. The heterogeneity of the disease is accentuated by the fact that it afflicts patients of all ages. During the past few years, technological developments in implantable defibrillators and pacemakers have provided new therapeutic options for patients with the disease. In addition, rapid advances in our knowledge of the molecular defects responsible for hypertrophic cardiomyopathy have deepened our understanding of the disorder and have suggested new approaches to the assessment of prognosis. These recent developments, however, have also generated considerable uncertainty and raised new questions about the optimal management of hypertrophic cardiomyopathy. In this article we critically reexamine and place in perspective the most appropriate therapeutic strategies for these patients.

Heterogeneity of Clinical and Genetic Features

Recent observations suggest that the prevalence of hypertrophic cardiomyopathy in the general population is higher (about 1 in 500) than previously thought. The condition therefore appears to be a common genetic malformation of the heart. The clinical course varies markedly; some patients remain asymptomatic throughout life, some have severe symptoms of heart failure, and others die suddenly, often in the absence of previous symptoms. The heterogeneous natural history of the disease and the fact that patients with severe symptoms are preferentially referred to tertiary care centers have been major impediments to assembling large study populations that truly represent the overall spectrum of the disease. Indeed, because most of the literature on hypertrophic cardiomyopathy is derived from investigations performed at tertiary care centers, the clinical picture of the disease that has emerged from published studies is profoundly influenced by referral bias. This is evident in the fact that the annual mortality figures for hypertrophic cardiomyopathy from such institutions (3 to 4 percent overall and up to 6 percent in children) are substantially higher than those recently reported in unselected populations (1 percent or less). These observations suggest that in a substantial proportion of patients the disease has a more favorable clinical course than previously believed. Strategies for treatment should therefore rely on data from relatively unselected populations, as well as from studies at tertiary care referral centers, and on the clinical experience of physicians who have focused their investigative efforts on this disease and acquired particular expertise in its management.

Molecular studies of the genetic alterations responsible for hypertrophic cardiomyopathy also provide insight into the heterogeneity of its clinical features. The disease can be caused by a mutation in one of four genes that encode proteins of the cardiac sarcomere: the β-myosin heavy-chain, cardiac troponin T, α-tropomyosin, and myosin-binding protein C genes (Fig. 1). In addition, mutations in the two genes encoding the myosin light chains have been reported in what appears to be a rare form of hypertrophic cardiomyopathy, and other genes that cause the disease are likely to be found. This etiologic complexity is further compounded by intragenic heterogeneity; more than 50 disease-causing mutations have been identified in these genes of the sarcomere. Hence, the precise molecular defect responsible for hypertrophic cardiomyopathy often differs in unrelated patients.


Figure 1. Components of the Sarcomere.

Cardiac contraction occurs when calcium binds the troponin complex (subunits C, I, and T) and α-tropomyosin, making possible the myosin-actin interaction. Actin stimulates ATPase activity in the globular myosin head and results in the production of force along actin filaments. Cardiac myosin-binding protein C, arrayed transversely along the sarcomere, binds myosin and, when phosphorylated, modulates contraction. In hypertrophic cardiomyopathy, mutations may impair these and other protein interactions, result in ineffectual contraction of the sarcomere, and produce hypertrophy and disarray of myocytes. Percentages represent the estimated frequency with which a mutation on the corresponding gene causes hypertrophic cardiomyopathy. Modified from Seidman and Seidman.

The diverse clinical and genetic features of hypertrophic cardiomyopathy make it impossible to define precise guidelines for management. As in many diseases, it is often necessary to individualize therapy. In hypertrophic cardiomyopathy, the treatment of symptoms to improve quality of life and the identification of patients who are at high risk for sudden death and require aggressive therapy are two distinct issues that must be addressed by largely independent strategies.

at :gilead.org

29-06-09, 12:24 AM
bài này "thúi ùm" luôn rồi mà không ai dịch hết. lâu lâu ghé chơi bà con ơi.

06-07-09, 01:47 AM
Same ơi. Bài này dài quá mình mới dịch 50% là gần chết rùi. Để CN tuần này mình dịch chơi nhe. :)

08-07-09, 12:20 AM
same ơi bạn giỏi anh văn lắm mà, same dịch cho mấy bạn tham khảo với ha, bài này hay đó, (nghĩa đen chứ ko có y xấu).thân