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Predictors of Left Ventricular Dysfunction in Friedreich’s Ataxia in a 16-Year Observational Study

American Journal of Cardiovascular Drugs volume 20, pages 209–216 (2020)Cite this article

A Letter to the Editor to this article was published on 25 July 2020

A Letter to the Editor to this article was published on 25 July 2020

Abstract

Background

Friedreich’s ataxia (FRDA) is a cerebellar ataxia due to GAA repeat expansions in the FXN gene, and in affected patients, lower left ventricular ejection fraction (LVEF) leads to poorer prognosis. We aimed to identify patients likely to develop worsening LVEF at an early stage.

Methods

We included 115 FRDA patients aged 30 ± 10 years with 620 ± 238 GAA repeats on the shorter allele and disease onset of 15 ± 7 years.

Results

At baseline, left ventricular (LV) hypertrophy was present in 53%, with LVEF 65 ± 7%, LV end diastolic diameter (LVEDD) 43 ± 5 mm, septal wall thickness (SWT) 11.8 ± 2.7 mm, and posterior wall thickness 11.1 ± 2.5 mm. After a mean follow-up of 13 ± 6 years, LVEF ≤ 50% was observed in 12 patients. The main determinants of LVEF ≤ 50% were GAA repeat number on the shorter allele (odds ratio [OR] 1.007, 95% confidence interval [CI] 1.003–1.012, p = 0.002), LVEDD (OR 1.217, 95% CI 1.058–1.399, p = 0.006), and SWT (OR 1.352, 95% CI 1.016–1.799, p = 0.04). High-risk patients were predicted 5 years before LVEF ≤ 50% occurred: area under the curve of 0.91, 95% CI 0.85–0.97. Patients with GAA repeats > 800 were categorized as high risk, patients with 500 < GAA < 800 were high risk if LVEDD was ≥ 52.6 mm and SWT was ≥ 13.3 mm, and patients with GAA < 500 were low risk if LVEDD was < 52.6 mm and SWT was < 13.3 mm.

Conclusions

Echocardiographic follow-up combined with size assessment of GAA repeat expansions is a powerful tool to identify patients at high risk of developing LV systolic dysfunction up to 5 years before clinical symptoms. Further studies are mandatory to investigate if these patients would benefit from cardiac interventions.

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Acknowledgements

The authors would like to thank all patients who participated in the study. Special thanks go to Sandra Benaich and Fabien Lesne, who helped with data handling, and Rachel Peat, for English editing.

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Authors and Affiliations

  1. Cardiology Department, AP-HP, Pitié-Salpêtrière University Hospital, Sorbonne Université, Paris, France

    Lise Legrand, Marie-Lorraine Monin, Richard Isnard, Gilles Montalescot & Francoise Pousset

  2. Genetics Department, AP-HP, Pitié-Salpêtrière University Hospital, Sorbonne Université, Paris, France

    Marie-Lorraine Monin, Claire Ewenczyk, Perrine Charles & Alexandra Durr

  3. ICM (Brain and Spine Institute), INSERM, CNRS, Pitié-Salpêtrière University Hospital, Sorbonne Université, Paris, France

    Alexandra Durr

  4. ICAN (Institute for Cardiometabolism and Nutrition), Pitié-Salpêtrière University Hospital, Paris, France

    Lise Legrand, Richard Isnard & Francoise Pousset

  5. ACTION (Allies in Cardiovascular Trials Initiatives and Organized Networks) Group, URC Lariboisière University Hospital, Paris, France

    Abdourahmane Diallo, Richard Isnard, Eric Vicaut & Gilles Montalescot

  6. Département de Cardiologie, Hôpital de la Salpêtrière, 47 boulevard de l’Hôpital, 75651, Paris Cedex 13, France

    Francoise Pousset

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  1. Lise Legrand
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  2. Abdourahmane Diallo
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  3. Marie-Lorraine Monin
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  4. Claire Ewenczyk
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  6. Richard Isnard
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  7. Eric Vicaut
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  8. Gilles Montalescot
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  9. Alexandra Durr
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  10. Francoise Pousset
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Corresponding author

Correspondence to Francoise Pousset.

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Funding

This study was supported by FP7 (7th Framework Programme) Grant HEALTH-F2-2010-242193 from the European Commission.

Conflict of interest

Lise Legrand, Abdourahmane Diallo, Marie-Lorraine Monin, Claire Ewenczyk, Perrine Charles, Richard Isnard, Eric Vicaut, Gilles Montalescot, Alexandra Durr, and Francoise Pousset declare that they have no potential conflicts of interest that might be relevant to this work.

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Legrand, L., Diallo, A., Monin, ML. et al. Predictors of Left Ventricular Dysfunction in Friedreich’s Ataxia in a 16-Year Observational Study. Am J Cardiovasc Drugs 20, 209–216 (2020). https://doi.org/10.1007/s40256-019-00375-z

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  • DOI: https://doi.org/10.1007/s40256-019-00375-z