Could thiazolidinediones increase the risk of heart failure in Friedreich's ataxia patients?

2011 ◽  
Vol 26 (5) ◽  
pp. 769-771 ◽  
Author(s):  
José L. García-Giménez ◽  
Fabián Sanchis-Gomar ◽  
Federico V. Pallardó
Keyword(s):  
Heart Failure ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia

Abstract 17263: Pre-Clinical Left Ventricular Myocardial Remodeling in Patients With Friedreich’s Ataxia: A Cardiac MRI Study

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Karen A Takazaki1 ◽  
Thiago Quinaglia A. C. Silva ◽  
Alberto Martinez ◽  
Tomas Neilan ◽  
Ravi SHAH ◽  
...  
Keyword(s):  
Heart Failure ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Extracellular Volume Fraction ◽  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Intracellular Water ◽  
Lv Mass ◽  
Burn Out

Background: Heart Failure (HF) is the most common cause of death in Friedreich’s ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis is a well-documented histopathological feature among FRDA patients with HF. Objectives: In this study we will investigate the myocardial extracellular volume fraction (ECV) and intracellular water lifetime (τ ic ), using T1-weighted CMR imaging, in a cohort of patients with FRDA without signs of heart failure. We will also investigate whether myocardial tissue phenotyping by CMR can highlight particular characteristics of LV remodeling in FRDA’s cardiomyopathy, beyond those currently assessed with imaging-based classification of disease severity. Methods: Twenty-six FRDA’s patients (age 26.6±9.3 years, 15 women) without signs of HF, and 10 healthy controls (32.6±7.3 years, 5 women) underwent cardiac magnetic resonance (CMR) studies for assessment of left ventricular (LV) function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τ ic ) as marker of cardiomyocyte size. Neurological decline was determined using the FRDA rating scale (FARS 3). Results: FRDA patients had normal LV ejection fraction (LVEF: 67.66±11.4 vs. 63.9±9.0, P=0.311), larger LV mass index (LVMASSi: 61.03±22.1 vs. 45±4.2g/m 2 , P<0.001), and decreased LV end-diastolic volume index (LVEDVi 53.42±12 vs. 75.7±16.1, P=0.002), compared with controls. ECV and τ ic , were increased in FRDA patients (ECV: 0.36±0.05 vs. 0.25±0.02, P<0.0001; τ ic : 0.13±0.07 vs. 0.06±0.03, P=0.001). ECV was positively associated with LV mass-to-volume ratio (r=0.628, P<0.001). FARS 3 correlated positively with disease duration (r=0.669, P<0.001), and negatively with τ ic , (r=0.478, P=0.039). LVMASSi and cardiomyocyte mass-index [(1–ECV)LVMASSi] declined with age, indicating that LV hypertrophy may transition to a “burn-out” phase with LV atrophy. Conclusions: LV hypertrophy in FRDA reflects an expansion of the myocardial interstitium and an increase in cardiomyocyte size. In contrast, the neurological decline was more likely with decreasing cardiomyocyte size, possibly an early sign of myocardial “burn-out” in FRDA.

scholarly journals Friedreich’s ataxia-associated childhood hypertrophic cardiomyopathy: a national cohort study

2021 ◽  
pp. archdischild-2021-322455
Author(s):  
Gabrielle Norrish ◽  
Thomas Rance ◽  
Elena Montanes ◽  
Ella Field ◽  
Elspeth Brown ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Hypertrophic Cardiomyopathy ◽  
Cardiac Death ◽  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Atrial Arrhythmia ◽  
Primary Study

ObjectiveHypertrophic cardiomyopathy (HCM) is an important predictor of long-term outcomes in Friedreich’s ataxia (FA), but the clinical spectrum and survival in childhood is poorly described. This study aimed to describe the clinical characteristics of children with FA-HCM.Design and settingRetrospective, longitudinal cohort study of children with FA-HCM from the UK.Patients78 children (<18 years) with FA-HCM diagnosed over four decades.InterventionAnonymised retrospective demographic and clinical data were collected from baseline evaluation and follow-up.Main outcome measuresThe primary study end-point was all-cause mortality (sudden cardiac death, atrial arrhythmia-related death, heart failure-related death, non-cardiac death) or cardiac transplantation.ResultsThe mean age at diagnosis of FA-HCM was 10.9 (±3.1) years. Diagnosis was within 1 year of cardiac referral in 34 (65.0%) patients, but preceded the diagnosis of FA in 4 (5.3%). At baseline, 65 (90.3%) had concentric left ventricular hypertrophy and 6 (12.5%) had systolic impairment. Over a median follow-up of 5.1 years (IQR 2.4–7.3), 8 (10.5%) had documented supraventricular arrhythmias and 8 (10.5%) died (atrial arrhythmia-related n=2; heart failure-related n=1; non-cardiac n=2; or unknown cause n=3), but there were no sudden cardiac deaths. Freedom from death or transplantation at 10 years was 80.8% (95% CI 62.5 to 90.8).ConclusionsThis is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly.

Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia

2013 ◽  
Vol 453 (3) ◽  
pp. 321-336 ◽  
Author(s):  
Darius J. R. Lane ◽  
Michael Li-Hsuan Huang ◽  
Samantha Ting ◽  
Sutharshani Sivagurunathan ◽  
Des R. Richardson
Keyword(s):  
Heart Failure ◽  
Stress Response ◽  
Mitochondrial Disease ◽  
Mitochondrial Disorder ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Comprehensive Understanding ◽  
Disease Pathogenesis ◽  
Common Cause ◽  
Biochemical Mechanisms

FRDA (Friedreich's ataxia) is a debilitating mitochondrial disorder leading to neural and cardiac degeneration, which is caused by a mutation in the frataxin gene that leads to decreased frataxin expression. The most common cause of death in FRDA patients is heart failure, although it is not known how the deficiency in frataxin potentiates the observed cardiomyopathy. The major proposed biochemical mechanisms for disease pathogenesis and the origins of heart failure in FRDA involve metabolic perturbations caused by decreased frataxin expression. Additionally, recent data suggest that low frataxin expression in heart muscle of conditional frataxin knockout mice activates an integrated stress response that contributes to and/or exacerbates cardiac hypertrophy and the loss of cardiomyocytes. The elucidation of these potential mechanisms will lead to a more comprehensive understanding of the pathogenesis of FRDA, and will contribute to the development of better treatments and therapeutics.

scholarly journals Electrocardiographic and Vectocardiographic Findings in Friedreich's Ataxia

1976 ◽  
Vol 3 (4) ◽  
pp. 323-328 ◽  
Author(s):  
S. Malo ◽  
Y. Latour ◽  
M. Cote ◽  
G. Geoffroy ◽  
B. Lemieux ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Right Ventricular ◽  
Neurological Disorder ◽  
Ventricular Hypertrophy ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Right Ventricular Hypertrophy ◽  
Serial Examination

SUMMARY:Electrocardiographic and vectocardiographic changes are frequent in Friedreich's ataxia. In one of 35 patients both tests were normal. The vectocardiogram is more explicit in demonstrating the severity of the QRS changes with a right ventricular hypertrophy pattern present in 60% of cases. Serial examination and ECG tracings are recommended to monitor the cardiomyopathy in this progressive neurological disorder, in order to detect the onset of congestive heart failure, significant tachyarrythmias, or obstructive cardiomypathy.

scholarly journals Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich’s ataxia cardiomyopathy

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0178354 ◽  
Author(s):  
Amanda R. Stram ◽  
Gregory R. Wagner ◽  
Brian D. Fogler ◽  
P. Melanie Pride ◽  
Matthew D. Hirschey ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Protein ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Lysine Acetylation ◽  
Protein Lysine Acetylation
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