Topic 15.1. Emergency department presentation with chest pain in Friedreich ataxia
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
Topic Contents
15.1 Emergency department presentation with chest pain in Friedreich ataxia
15.1.1 Presentations with chest pain
15.1.2 ECG and cardiac troponin in Friedreich ataxia
15.1.3 Non-coronary artery disease causes of chest pain in Friedreich ataxia
Disclaimer / Intended Use / Funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
15.1 Emergency department presentation with chest pain in Friedreich ataxia
Hamed Akhlaghi, Roger E. Peverill, Anne Fournier, Noushin Chini Foroush and Yenni Lie
15.1.1 Presentations with chest pain
Individuals with Friedreich ataxia (FRDA) may present with chest pain due to cardiac or non-cardiac causes. FRDA is commonly accompanied by abnormalities in both cardiac structure and function; however, the finding of coronary artery disease is unusual, and myocardial ischemia may occur in the absence of epicardial coronary artery disease due to abnormal coronary vasculature and/or a mismatch between the thickened LV wall and coronary blood flow (1).
15.1.2 ECG and cardiac troponin in Friedreich ataxia
An abnormal electrocardiogram (ECG or EKG) and elevated serum cardiac troponin levels are common baseline characteristics seen in individuals with FRDA. A retrospective cross-sectional study of a cohort of 239 individuals with FRDA found abnormal electrocardiographic findings in 90%, with common findings being non-specific ST-T wave changes, right axis deviation, left ventricular hypertrophy and right ventricular hypertrophy (2). In another cross-sectional study of 49 asymptomatic individuals with FRDA, 16.3% had raised cardiac troponin I (cTnI) levels typically seen during an acute myocardial infarct and 30.6% had levels above the 99th percentile (3). A prospective study found significantly elevated (³ 14 ng/L) high sensitivity cardiac troponin T (cTnT) in 34% of patients with FRDA, and increased septal wall thickness was significantly associated with increased cTnT levels (4). Therefore, an abnormality of the initial electrocardiogram or an elevation of the initial serum troponin level cannot be assumed to indicate an acute coronary syndrome in FRDA. Serial assessments of the ECG and troponin level are essential components when evaluating chest pain and the possibility of an acute coronary syndrome in FRDA. If there is a lack of change in an initially elevated serial troponin level, then the elevated troponin cannot be used as evidence for an acute coronary syndrome.
15.1.3 Non-coronary artery disease causes of chest pain in Friedreich ataxia
Other non-coronary artery disease-related causes of chest pain should also be considered in individuals with FRDA; for example, angina-like pain may occur during an episode of tachycardia in the setting of left ventricular hypertrophy due to subendocardial ischemia, even in the absence of epicardial coronary artery disease. There is also a possible increased risk of pulmonary embolism due to the sedentary nature of FRDA.
Chest pain management incorporating Friedreich ataxia-specific considerations
QUESTION: Should chest pain management that incorporates Friedreich ataxia-specific considerations versus standard chest pain management without Friedreich ataxia-specific considerations, be used for all people with Friedreich ataxia who present with chest pain?
LEVEL OF EVIDENCE: ⨁⨁◯◯
RECOMMENDATION: We recommend that chest pain assessment in Friedreich ataxia should incorporate the following considerations: coronary artery disease is not more or less common than in the non-Friedreich ataxia population; ECG is usually abnormal in Friedreich ataxia in the absence of coronary disease; troponin can be elevated in patients with Friedreich ataxia for a non-coronary reason and should not be assumed to indicate an acute coronary syndrome; the possibility of increased incidence of pulmonary embolism due to the sedentary nature of the disease. If troponin is elevated, then serial troponin assessment is very important. In the setting of left ventricular hypertrophy an episode of atrial fibrillation can lead to angina-like pain.
JUSTIFICATION: Coronary artery disease in Friedreich ataxia is not more or less common than in the non-Friedreich ataxia population. However, clinical experience of all expert authors is that standard chest pain management without considering the listed caveats can lead to inappropriate investigations and diagnosis of chest pain for individuals with Friedreich ataxia. There is evidence for ECG abnormality in Friedreich ataxia in the absence of coronary disease and elevated troponin levels in people with Friedreich ataxia for non-coronary reasons.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia who present with chest pain.
Evidence to Recommendation Table PDFLay summary of clinical recommendation for chest pain in Friedreich ataxia
Why this recommendation?
People with Friedreich ataxia may present to the hospital emergency department with chest pain. Emergency department staff should consider several important factors when assessing chest pain in people with Friedreich ataxia.
Chest pain in people with Friedreich ataxia
People with Friedreich ataxia may have problems with their heart, but coronary artery disease (when the arteries of the heart become narrow and it is harder for blood to pass through) is not more common than in people without Friedreich ataxia. Besides, people with Friedreich ataxia commonly have baseline abnormal electrocardiogram (ECG/EKG) or blood tests similar to that seen during a heart attack, even when they do not have coronary artery disease.
When a person with Friedreich ataxia presents to the emergency department with chest pain, we recommend that the doctor does not immediately assume that an abnormal ECG or blood tests indicate that the person has had a heart attack. In this situation, obtaining the person’s previous ECG and/or blood test results, if available, and taking a serial blood test assessment would be very important.
In some people with Friedreich ataxia who have a thickened left pumping chamber of the heart, an episode of fast irregular heart rhythm may also lead to chest pain.
Other non-heart related causes of chest pain should also be considered. For example, there is a possible increased risk of blood clot in the lungs due to the sedentary nature of Friedreich ataxia.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
If you or someone you care for present to the emergency department with chest pain, it would be useful to inform the doctor if there have been any heart investigations done previously, such as ECG, blood tests, and/or echocardiogram
Who is this recommendation specifically for?
This recommendation is for all individuals with Friedreich ataxia who present with chest pain.
Hamed Akhlaghi, MD, PhD, FACEM, GradDipClinUSS
Head of Emergency Medicine Research, St Vincent’s Hospital (Melbourne), Melbourne, Victoria, Australia
Email: hamed.akhlaghi@svha.org.au
Noushin Chini Foroush, MD
Neurology Registrar, Monash Medical Centre, Melbourne, Victoria, Australia
Email: noushin.chiniforoush@gmail.com
Anne Fournier, MD, FRCPC
Professor of Pediatrics, University of Montreal, Montreal, Québec, Canada
Email: anne.fournier@umontreal.ca
Yenni Lie, MBBS, FRACP
Neurologist, Monash Health, Melbourne, Victoria, Australia
Email: yenni.lie@monashhealth.org
Roger E. Peverill, MBBS, PhD
Cardiologist, MonashHeart, Monash Health, Clayton, Victoria, Australia
Email: roger.peverill@monash.edu
2. Schadt KA, Friedman LS, Regner SR, Mark GE, Lynch DR, Lin KY. Cross-sectional analysis of electrocardiograms in a large heterogeneous cohort of Friedreich ataxia subjects. J Child Neurol. 2012;27(9):1187-92.
3. Friedman LS, Schadt KA, Regner SR, Mark GE, Lin KY, Sciascia T, et al. Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia. Int J Cardiol. 2013;167(4):1622-4.
4. Legrand L, Maupain C, Monin ML, Ewenczyk C, Isnard R, Alkouri R, et al. Significance of NT-proBNP and high-sensitivity troponin in Friedreich ataxia. J Clin Med. 2020;9(6).
5. Schulz JB, Boesch S, Burk K, Durr A, Giunti P, Mariotti C, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat Rev Neurol. 2009;5(4):222-34.
6. Akhlaghi H, Corben LA, Georgiou-Karistianis N, Bradshaw JL, Storey E, Delatycki MB, et al. Superior cerebellar peduncle atrophy in Friedreich’s ataxia correlates with disease symptoms. Cerebellum. 2011;10:81-7.
7. Maring JR, Croarkin E. Presentation and progression of Friedreich ataxia and implications for physical therapist examination. Phys Ther. 2007;87(12):1687-96.
8. Corben LA, Georgiou-Karistianis N, Bradshaw JL, Evans-Galea M.V, Churchyard AJ, Delatycki MB. Characterising the Neuropathology and Neurobehavioural Phenotype in Friedreich Ataxia In: Hannan A, editor. Tandem Repeat Polymorphisms: Genetic Plasticity, Neural Diversity and Diseas. Texas USA: Landes Bioscience and Springer Science and Business Media 2012.
9. Burtner PA, Woollacott MH, Qualls C. Stance balance control with orthoses in a group of children with spastic cerebral palsy. Dev Med Child Neurol. 1999;41(11):748-57.
10. Pandolfo M. Friedreich Ataxia: the clinical picture. J Neurol. 2009;256:3-8.
11. Eigentler A, Nachbauer W, Donnemiller E, Poewe W, Gasser RW, Boesch S. Low bone mineral density in Friedreich ataxia. Cerebellum. 2014;13(5):549-57.
12. Tsirikos AI, Smith G. Scoliosis in Friedreich’s ataxia. The Journal of Bone and Joint Surgery. 2012;94(B):684-9.
13. Dittmer DK, Teasell R. Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications. Can Fam Physician. 1993;39:1428-32, 35-7.
14. Thompson AJ, Jarrett L, Lockley L, Marsden J, Stevenson VL. Clinical management of spasticity. J Neurol Neurosurg Psychiatry. 2005;76(4):459-63.
15. van Gaalen J, Kerstens FG, Maas RP, Harmark L, van de Warrenburg BP. Drug-induced cerebellar ataxia: a systematic review. CNS Drugs. 2014;28(12):1139-53.
16. Delatycki MB, Paris DB, Gardner RJ, Nicholson GA, Nassif N, Storey E, et al. Clinical and genetic study of Friedreich ataxia in an Australian population. Am J Med Genet. 1999;87(2):168-74.
17. Groen J, Pannek J, Castro Diaz D, Del Popolo G, Gross T, Hamid R, et al. Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology. Eur Urol. 2016;69(2):324-33.
18. Goetz LL, Cardenas DD, Kennelly M, Bonne Lee BS, Linsenmeyer T, Moser C, et al. International Spinal Cord Injury Urinary Tract Infection Basic Data Set. Spinal Cord. 2013;51(9):700-4.
19. Everaert K, Lumen N, Kerckhaert W, Willaert P, van Driel M. Urinary tract infections in spinal cord injury: prevention and treatment guidelines. Acta Clin Belg. 2009;64(4):335-40.
20. Pannek J, Pannek-Rademacher S, Cachin-Jus M. Organ-preserving treatment of an epididymal abscess in a patient with spinal cord injury. Spinal Cord. 2014;52 Suppl 1:S7-8.
21. Cnop M, Mulder H, Igoillo-Esteve M. Diabetes in Friedreich ataxia. J Neurochem. 2013;126 Suppl 1:94-102.
22. Chakraborty PP, Ray S, Bhattacharjee R, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, et al. First Presentation of Diabetes as Diabetic Ketoacidosis in a Case of Friedreich’s Ataxia. Clin Diabetes. 2015;33(2):84-6.
23. Finocchiaro G, Baio G, Micossi P, Pozza G, di Donato S. Glucose metabolism alterations in Friedreich’s ataxia. Neurology. 1988;38(8):1292-6.
24. Cnop M, Igoillo-Esteve M, Rai M, Begu A, Serroukh Y, Depondt C, et al. Central role and mechanisms of beta-cell dysfunction and death in friedreich ataxia-associated diabetes. Ann Neurol. 2012;72(6):971-82.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.