Abstract
BackgroundHeart Failure (HF) is the most common cause of death in Friedreich’s ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis and myocardial hypertrophy are well-documented autopsy features among FRDA patients with HF.ObjectivesTo leverage the unique tissue characterization features of cardiac magnetic resonance (CMR) for characterizing myocardial remodeling in patients with genetically confirmed FRDA without HF and preserved left ventricular ejection fraction (LVEF > 55%).MethodsTwenty-seven FRDA’s patients (age 27.6 ± 9.7 years, 15 women) and 10 healthy controls (32.6±7.3 years, 5 women) underwent a CMR for assessment of LV function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τic), a marker of cardiomyocyte size.ResultsAs compared to controls, FRDA patients had a preserved LVEF (LVEF: 70.5±7.4% vs. 63.9±9.0%, P<0.058), larger LV mass index (LVMASSi: 61±21.7 vs. 45±4.2g/m2, P<0.02), and decreased LV end-diastolic volume index (LVEDVi 53.1±12.0 vs. 75.7±16.1ml/m2, P<0.001), compared with controls. Additionally, ECV and cardiomyocyte size (τic,) were larger in FRDA patients (ECV: 0.36 ±0.05 vs. 0.25±0.02, P<0.001; τic: 0.15±0.08 vs. 0.06±0.03 s, P = 0.02). ECV and τic were positively associated with LV mass-to-volume ratio (ECV: r = 0.57, P = 0.003; τic: r = 0.39; P = 0.05). LVMASSi and cardiomyocyte mass-index [(1−ECV)·LVMASSi] declined with age at the CMR exam, independent of the age at initial diagnosis.ConclusionsLV hypertrophy and concentric LV remodeling in FRDA are associated at the tissue level with an expansion of the ECV and an increase in cardiomyocyte size. The adverse tissue remodeling assessed by ECV and τic is associated with more severe cardiomyopathy classification, suggesting a role for these markers in tracking disease progression.
Highlights
Friedreich’s ataxia (FRDA) is the most frequent autosomal recessive ataxia worldwide with a prevalence of approximately 1 in 50,000 [1]
left ventricular (LV) hypertrophy and concentric LV remodeling in FRDA are associated at the tissue level with an expansion of the extracellular volume fraction (ECV) and an increase in cardiomyocyte size
The adverse tissue remodeling assessed by ECV and τic is associated with more severe cardiomyopathy classification, suggesting a role for these markers in tracking disease progression
Summary
Friedreich’s ataxia (FRDA) is the most frequent autosomal recessive ataxia worldwide with a prevalence of approximately 1 in 50,000 [1]. It is caused by homozygous GAA expansions in intron 1 of the FXN gene on chromosome 9q13 [2]. The mutation results in a severe deficiency of frataxin, a mitochondrial protein that plays a key role in iron homeostasis [3]. This leads to nervous system, endocrine and cardiac damage. Myocardial fibrosis and myocardial hypertrophy are welldocumented autopsy features among FRDA patients with HF
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