Interstitial fibrosis, the renin-angiotensin-aldosterone system and biomarkers in the cardiac disease of Friedreich ataxia
The large gaps in our knowledge regarding the nature and causes of the heart involvement in Friedreich ataxia (FRDA) limit our ability to investigate potential treatments in this condition. Increased thickness of the heart walls, a common feature in FRDA, is a predictor of symptomatic heart disease and premature mortality. Based on this information alone, a reduction in wall thickness has been considered to be a valid clinical endpoint in some clinical trials. It is suspected that the increase in wall thickness involves both loss of heart muscle cells and an increase in scar tissue. It is critical we further our understanding of the mechanisms that contribute to increased wall thickness in FRDA, as this will help determine if reduction in wall thickness is a valid outcome measure. A new CMR technique has shown promise in detecting early scarring but has not yet been studied in FRDA. In this collaborative study between the Melbourne and Philadelphia CCRN sites we propose to perform CMR on 105 individuals with FRDA to determine the frequency and extent of scarring in the heart muscle wall. An important part of this study is the investigation of the relationship of heart changes in FRDA with one of the body’s natural hormonal systems, already to known to play a role in other types of heart disease. A second important part of the study will be measuring a number of blood markers of heart function in individuals with and without FRDA, as a means of trying to understand the mechanisms which may contribute to the heart muscle changes. Some individuals with FRDA will undergo repeat CMR and blood testing at 12 months to determine changes in these markers. This aspect is critical in addressing their potential usefulness in future clinical trials in FRDA. The findings arising from this study will provide vital information regarding the nature of heart involvement in FRDA and help us to identify the best techniques to use when testing drugs in FRDA in the future.