What is the most likely cause of death within the next 10 years for a 50-year-old patient diagnosed with Friedreich's Ataxia (FA)?

From the Guidelines

Cardiac complications are the most likely cause of death within the next 10 years for a 50-year-old patient diagnosed with Friedreich's Ataxia (FA). In a 50-year-old patient with FA, cardiac manifestations, including hypertrophic cardiomyopathy and arrhythmias, are the leading causes of mortality [ 1 ]. By age 50, cardiac involvement is typically advanced, with many patients developing heart failure, severe arrhythmias, or sudden cardiac death. According to a study published in Circulation, cardiac dysfunction is the most frequent cause of death in FA [ 1 ].

Key Points to Consider

• Cardiac involvement in FA results from mitochondrial dysfunction and iron accumulation in cardiomyocytes due to frataxin deficiency, leading to progressive myocardial damage [ 1 ].
• The risk of arrhythmias in FA remains unclear but is believed to increase with increasing severity of cardiac hypertrophy [ 1 ].
• Tsou et al reported that arrhythmia was the primary or contributing cause of death in 16% of FA patients [ 1 ].
• While respiratory complications, infections, and falls are all potential causes of morbidity and mortality in FA, cardiac complications remain the predominant cause of death, particularly in middle-aged patients with established disease.

Clinical Implications

• Regular cardiac evaluation is likely warranted for patients with FA, regardless of neurological status [ 1 ].
• Echocardiography has been the mainstay of cardiac morphological and functional imaging in FA, but the use of CMR is potentially appealing due to its ability to recognize iron overload [ 1 ].
• Guidelines for the management of AF are well established, and patients with FA should be monitored closely for signs of arrhythmias [ 1 ].

From the Research

Causes of Death in Friedreich's Ataxia

• The most likely cause of death within the next 10 years for a 50-year-old patient diagnosed with Friedreich's Ataxia (FA) is cardiac dysfunction, which is widely accepted as the most common cause of mortality in FA 2.
• Cardiac dysfunction accounts for 59% of deaths in FA patients, with congestive heart failure and arrhythmia being common causes of cardiac-related death 2.
• The presence of arrhythmia and dilated cardiomyopathy are significantly more common in deceased FA patients compared to living, matched FA controls 2.

Cardiac Involvement in Friedreich's Ataxia

• Nearly all FA patients develop cardiomyopathy at some point in their lives, with the clinical manifestations including ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases 3.
• The cardiac involvement seen in FA is a consequence of mitochondrial proliferation, loss of contractile proteins, and the subsequent development of myocardial fibrosis, leading to thickened left ventricle walls and different phenotypic manifestations, including concentric or asymmetric hypertrophy and dilated cardiomyopathy 3.
• Dilated cardiomyopathy and arrhythmia are associated with mortality in FA patients, whereas hypertrophic cardiomyopathy is not 3.

Clinical Features and Therapeutic Developments

• FA patients should be screened for cardiomyopathy, with a cardiac examination, ECG, and ECHO advised at diagnosis and on the development of any cardiac symptoms 4.
• Treatment is determined by the presence of symptoms, the presence of left ventricular outflow gradient, and the sudden death risk, with institution of aggressive medical therapy early in the course of the disease potentially improving quality of life and providing survival benefit 4.
• Researchers are currently testing targeted therapies for FA, with a centralized database, patient registry, and natural history study launched to support these clinical trials 3.