Mortality in Friedreich's Ataxia

This letter was referred to Drs. Giugliano and Sethi, who reply in this manner:

We would like to thank Dr. Lynch and colleagues for their interest in our paper. They highlight several interesting issues with regard to patients with Friedreich's ataxia (FA).

First, we agree that coronary artery disease in FA may be under-recognized, but, more important, it is probably under-reported in the literature. Friedreich's ataxia is a rare disorder, and we encourage those with extensive experience with such patients to publish their findings, in order to expand physician awareness and to counter misconceptions about this disease.

Second, with regard to the mortality rate in FA, our findings were drawn from the available, peer-reviewed literature. Although there may be anecdotal evidence of improved mortality using a wide array of therapies in patients with FA and in selected subsets of FA clinics, the literature does not support any significant change in survival since the report in 2000 by Delatycki and colleagues,¹ in which the average age of death was at 37.5 years (range, 5–71 years). The wide range of life expectancy highlights the limited data and also the genotypic variability of this disorder.^1–4 Certainly, patients with less-severe phenotypes will likely outlive the more severely impaired patients. While there have been several advances in medical therapy that improve survival in patients with coronary artery disease and heart failure, it is unclear if this survival benefit will be realized in patients with FA. We agree that advances in medical therapy, most notably in the area of antioxidants, may lead to some improvement in neurologic function,⁵ and to a delay in disease progression,⁶ but there are still no definitive data on the mortality benefit. We could not identify any quality-of-life studies in patients with FA and cardiomyopathy, although it is conceivable that better management of heart failure and angina could translate into improved quality of life. The assertion by Dr. Lynch and colleagues that patients with FA “usually attend college, are employed as professionals and paraprofessionals, and lead lives that are successful and productive” may be the consequence of selection bias, tilted towards those patients who survived longer than the mean and had less-severe phenotypes, without cardiac compromise.

We recognize that some patients with FA have received cardiac transplants and left ventricular assist devices (LVADs), although these aggressive treatments may not be warranted. Because we do not understand the predictors of survival in patients with FA, it is difficult to justify at this time the allocation of limited and expensive resources such as cardiac transplantation, LVADs, and defibrillators. After all, it has only recently been demonstrated that LVADs improve survival in patients with congestive heart failure.⁷

It is true that if the prognosis and quality of life in patients with FA improve with innovative medical and gene therapy, the cardiology community will need to become proactive in the early diagnosis and management of the cardiovascular manifestations. To that end, further research needs to be directed towards identifying predictors or markers of survival, so that patients may be appropriately selected for destination therapy and for primary prevention of sudden cardiac death with automated implantable cardioverter-defibrillator therapy. Until that time comes, let us not lose sight of the simple and relatively inexpensive therapies, such as aspirin, statins, β-blockers, and angiotensin-converting enzyme inhibitors, which will improve heart failure and symptomatic angina.

Gregory R. Giugliano, MD, SM
Prabhdeep S. Sethi, MD, MPh
Division of Cardiology, Baystate Medical Center, Springfield, Massachusetts