Cardiac dysfunction remains the most common cause of death in patients with Friedreich’s ataxia, according to the findings of a retrospective study.
The majority (59%) of 61 deceased patients studied died as a result of cardiac dysfunction, most often congestive heart failure or arrhythmia; another 3% died of probable cardiac dysfunction, Dr. Amy Y. Tsou of the University of Pennsylvania, Philadelphia, and her colleagues found (J. Neurol. Sci. 2011;307:46-9).
Cardiac dysfunction is widely accepted as the leading cause of death in patients with Friedreich’s ataxia (FRDA), but this has not been well studied in the years since clinical and genetic diagnostic criteria were developed and led to improved diagnostic accuracy for this inherited ataxia, Dr. Tsou and her associates said.
FRDA is characterized by dysarthria, areflexia, and loss of vibratory and proprioceptive sensation. Systemic manifestations of the disease can include cardiomyopathy, diabetes, and scoliosis.
Noncardiac deaths accounted for 28% of the 61 deaths, and unknown causes accounted for the remaining 10%, the investigators reported.
In a comparison with patients who suffered noncardiac deaths, patients who died from cardiac causes died at younger ages (median of 26 years vs. 41 years) and with shorter disease duration (mean of 19.6 years vs. 30.1 years). Those with a disease duration of 20 years or more had significantly lower odds of death from cardiac dysfunction, compared with a disease duration of less than 20 years (odds ratio 0.19). Patients who died from cardiac dysfunction also had a significantly longer mean GAA triplet repeat length than did patients who died from a noncardiac cause (687 vs. 508).
In a case-control analysis of 20 of the deceased patients whose records were particularly detailed and 40 living age- and sex-matched control patients with FRDA, deceased patients were significantly more likely to have arrhythmia (75% vs. 15%), dilated cardiomyopathy (65% vs. 5%), congestive heart failure (65% vs. 5%), stroke (20% vs. 0%), or be wheelchair bound (75% vs. 48%). However, the presence of hypertrophic cardiomyopathy did not differ significantly between the groups.
"As cardiac hypertrophy in FRDA is common but not associated with mortality in our study, further investigation to identify factors that predict development of dilatation may allow improved prognostication and targeting of future research. In addition, while hypertrophy has been used as a primary endpoint in several clinical trials, our results suggest that other manifestations of cardiac dysfunction such as a dilated cardiomyopathy or arrhythmia are more relevant indicators of clinical significance," the investigators wrote.
They noted that because their cohort had a young mean age of onset (12 years) and mean age of death (37 years) in comparison with large living cohorts, the study may not be "entirely representative of the general FRDA population," despite the fact that they drew patients from a wide geographical area that included patients from a community group as well as multiple academic medical centers. "The difficulties with selection in our study highlight how relevant the problem of selection bias in FRDA studies continues to be, particularly when working with smaller numbers of patients."
This study was supported by a grant to coauthor David R. Lynch from the Friedreich’s Ataxia Research Alliance.