The cardiomyopathy in Friedreich's ataxia — New biomarker for staging cardiac involvement

BACKGROUND: Patients with autosomal-recessively inherited Friedreich's ataxia (FA) may develop a hypertrophic cardiomyopathy (CM), which potentially progresses towards a life-limiting problem. The typical features of this CM and the sequence of progression are widely unknown. METHODS: Thirty-two consecutive patients with genetically confirmed FA were included. All patients received resting electrocardiogram (ECG), 24-hour Holter-ECG, echocardiography with speckle tracking imaging, cardiac magnetic resonance imaging (cMRI) with late enhancement imaging (for replacement fibrosis), and measurement of high-sensitive troponin-T (hsTNT). In addition, morphological parameters were retrospectively compared to data obtained five years before. RESULTS: Based on criteria comprising ejection fraction (<55%), left ventricular end-diastolic posterior wall thickness (LVPWT ≥ 11 mm), fibrosis on cMRI, hsTNT ≥ 14 ng/ml, or T-wave-inversion, in all but two patients a CM could be detected (94%). Using these criteria we propose the following staging: a) mild CM (n=5, 16%; T-wave-inversion only); b) intermediate CM (n=4, 13%; T-wave-inversion with hypertrophy but no fibrosis); c) severe CM (n=13, 41%; fibrosis with raised hsTNT); and d) end-stage CM (n=8; 25%; ejection-fraction<55%). All patients with end-stage CM also showed fibrosis on cMRI, T-wave-inversion, marked elevation in hsTNT, and a decrease in LVPWT during the last five years (from 10.7 ± 1.2mm to 9.5 ± 1.3mm, p=0.025). In addition, 38% suffered from supraventricular tachycardia on Holter-ECG. CONCLUSIONS: A comprehensive cardiac assessment will unravel established CM in almost all patients with FA with electrocardiographic abnormalities as earliest signs. Advanced stages can be characterized by elevated hsTNT and replacement fibrosis leading to recession of hypertrophy, reduction of global myocardial function, and electrical instability.