Cardiomyopathy of Friedreich's ataxia (FRDA)

Autor: R M Payne, R E Peverill
Rok vydání: 2012
Předmět:
Zdroj: Irish journal of medical science. 181(4)
ISSN: 1863-4362
Popis: We read the review article on the cardiomyopathy of Friedreich’s ataxia (FRDA) by Drs Bourke and Keane with great interest [1]. It nicely summarizes some of the historical findings related to the cardiomyopathy associated with this disease and appropriately emphasizes a multidisciplinary approach to the treatment of FRDA. However, we believe the authors have made a fundamental error in drawing an analogy between the cardiomyopathy of FRDA and that of hypertrophic cardiomyopathy (HCM) [2]. This distinction is very important because the therapeutic recommendations for FA cardiomyopathy contained within the article by Bourke and Keane are based on the assumption of a similarity with HCM. In HCM the basic defect is in the sarcomere, which is the minimal contractile unit of the cardiomyocyte. There is a disorganized expansion of nonfunctional contractile fibers within the cardiomyocyte which leads to hypertrophy [2]. Approximately 30% of subjects with HCM have a resting left ventricular outflow tract (LVOT) pressure gradient [2], but 70% have either a resting or provokable LVOT pressure gradient due to systolic anterior motion of an abnormal anterior mitral leaflet in conjunction with asymmetric septal hypertrophy and vigorous left ventricular contraction [3]. Numerous nonrandomized clinical trials support recommendations for the use of negatively inotropic medications in symptomatic patients with the obstructive form of HCM [2]. Nevertheless, it is recognized that response to treatment in obstructive HCM is variable and that patients who do not respond to one drug may need to be changed to another [2]. The evidence for drug treatment in nonobstructive HCM is even less clear. In contrast with HCM, the basic defect in FRDA is in the mitochondrion and results from a primary deficiency of frataxin. There is both basic and clinical evidence showing uncontrolled proliferation of dysfunctional mitochondria and loss of sarcomeres in the cardiomyocyte [4–6]. Loss of sarcomeres leads to decreased contractile performance and there is an accompanying increase in fibrosis. Asymmetric septal hypertrophy is much less common in FRDA than in HCM and anatomical abnormalities of the mitral valve have not been described in FRDA [7, 8]. In the published literature, and our combined clinical experience of more than 140 subjects with FRDA, resting LVOT obstruction is rare even in those patients with marked hypertrophy. So even if negatively inotropic drugs could be assumed to be beneficial in FRDA patients with LVOT obstruction, such treatment would rarely be indicated. We are not aware of any data regarding provokable LVOT obstruction in FRDA, however, exercise-induced LVOT gradients would not only be difficult to evaluate in this population, given the frequent difficulties with walking, but may also be less clinically relevant for the same reason. In the most common cardiac scenario in FRDA of an asymptomatic subject with a small left ventricle and increased relative wall thickness [8], there is currently no evidence to support the use of any drug treatment. On the other hand, FRDA patients can develop a dilated left ventricle with reduced ejection fraction and this is a progressive condition which leads to heart failure and death. R. M. Payne (&) Indiana University School of Medicine, 1044 W Walnut, R4-302, Indianapolis, IN 46202, USA e-mail: rpayne@iupui.edu
Databáze: OpenAIRE
Externí odkaz: