0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia

Francoise Pousset, MD1; Lise Legrand, MD1; Marie-Lorraine Monin, MD2,3; Claire Ewenczyk, MD2; Perrine Charles, MD, PhD2; Michel Komajda, MD1,4; Alexis Brice, MD2,3; Massimo Pandolfo, MD5; Richard Isnard, MD, PhD1,4,6; Sophie Tezenas du Montcel, MD, PhD7,8,9; Alexandra Durr, MD, PhD2,3
[+] Author Affiliations
1Department of Cardiology, Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France
2Department of Genetics and Cytogenetics, Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France
3Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, Université Pierre et Marie Curie, University Paris 06, Unité Mixte de Recherche (UMR) 1127, Institut National de la Santé et de la Récherche Médicale (INSERM) Unité 1127, Centre National de la Recherche Scientifique UMR 7225, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France
4Sorbonne Universités, Université Pierre et Marie Curie, University Paris 06, UMR 1166, INSERM, Paris, France
5Department of Neurology, Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium
6Institute for Cardiometabolism and Nutrition, Paris, France
7Sorbonne Universités, Université Pierre et Marie Curie, University Paris 06, UMR 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France
8INSERM, UMR 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France
9Biostatistics Unit, Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
JAMA Neurol. 2015;72(11):1334-1341. doi:10.1001/jamaneurol.2015.1855.
Text Size: A A A
Published online

Importance  Friedreich ataxia (FRDA) is the most common genetic sensory ataxia, and myocardial involvement is a major determinant of survival.

Objective  To assess FRDA survival and cardiac outcome to adapt future therapeutic trials.

Design, Setting, and Participants  In a longitudinal follow-up study, all patients with genetically confirmed FRDA seen in the reference center and referred for cardiac evaluation (standard 12-lead electrocardiogram and transthoracic echocardiography) to the cardiology department were enrolled and followed up from April 27, 1990, to July 31, 2013. The setting was the French National Reference Center for Rare Diseases and the Department of Cardiology, Salpêtrière University Hospital, Paris, France. In total, 138 patients with FRDA were followed up. Among 133 patients homozygous for expanded GAA repeats, the mean (SD) age was 31 (10) years (age range, 11-62 years), with a mean (SD) age at disease onset of 16 (8) years (age range, 3-50 years) and a mean (SD) age at first wheelchair use of 26 (9) years (age range, 11-64 years). Cardiac hypertrophy was present in 57.9% (77 of 133), and electrocardiography was normal in 6.8% (9 of 133).

Main Outcomes and Measures  Long-term cardiac outcome and predictors of survival in FRDA.

Results  After a mean (SD) follow-up of 10.5 (5.5) years (range, 0.6-23.0 years), the 10-year survival rate was 88.5%. In 80.0% of patients (12 of 15), death was due to cardiac causes. Predictors of survival were a shorter GAA repeat length on the smaller allele of the frataxin gene (hazard ratio [HR], 1.85; 95% CI, 1.28-2.69), left ventricular ejection fraction (HR, 0.42; 95% CI, 0.20-0.89), and left ventricular mass index (HR, 1.19; 95% CI, 1.04-1.36). Two cardiac evolutions were distinguished with a group-based trajectory model, including a low-risk cardiac group (78.6% [81 of 103] with normal ejection fraction at baseline that declined slightly over time but remained within the normal range) and a high-risk cardiac group (21.4% [22 of 103] in which the ejection fraction progressively declined during follow-up). The patients with the worse cardiac evolution had longer GAA repeats. Neurological impairment was not predictive of cardiac change over time.

Conclusions and Relevance  Survival in FRDA is determined by cardiac complications, which are dependent on the mutation (ie, the size of the expanded GAA repeat). Patients with progressive decline of the left ventricular ejection fraction had a worse prognosis. This finding demonstrates that cardiac follow-up is important in FRDA to identify individuals at risk for further cardiac complications.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure 1.
Survival Curve in 133 Patients With Friedreich Ataxia

The mean age at death was 39 years, and survival was 88.7% (118 of 133) after 10 years of follow-up.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Trajectory Groups of Left Ventricular Ejection Fraction During Follow-up in 103 Patients With Friedreich Ataxia

Trajectories of left ventricular ejection fraction (LVEF) during follow-up (bold lines) were calculated using the model’s coefficient estimates and 95% CIs (dotted lines). Two cardiac evolutions were distinguished, including a low-risk cardiac group (78.6% [81 of 103]), with a normal ejection fraction at baseline that declined slightly over time but remained in the normal range, and a high-risk cardiac group (21.4% [22 of 103]), which started with a lower ejection fraction and had a progressively decreasing ejection fraction.

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

644 Views
1 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Quick Reference

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Quick Reference

brightcove.createExperiences();