Vol 79, No 12 (2021)
Original article
Published online: 2021-11-16

open access

Page views 6798
Article views/downloads 848
Get Citation

Connect on Social Media

Connect on Social Media

Predictors of mortality and cardiovascular outcomes in Emery-Dreifuss muscular dystrophy in a long-term follow-up

Michał Marchel1, Agnieszka Madej-Pilarczyk2, Roman Steckiewicz1, Przemysław Stolarz1, Michał Peller1, Agata Tymińska1, Ewa Ostrowska1, Krzysztof Ozierański1, Paweł Balsam1, Marcin Grabowski1, Grzegorz Opolski1
Pubmed: 34783354
Kardiol Pol 2021;79(12):1335-1342.

Abstract

Background: Emery-Dreifuss muscular dystrophy (EDMD) is an extremely rare muscular dystrophy due to either emerinopathy (EMD) or laminopathy (LMNA). The main risk for patients is that of cardiovascular complications.
Aims: This study aimed to identify predictors of adverse clinical events in patients with EDMD in a long-term follow-up observation.
Methods: A total of 45 patients with confirmed EMD or LMNA mutation were included in the study. The relationships between clinical parameters, the overall survival rate, and risk factors for disease progression were assessed. The primary endpoint was defined as death, while the secondary endpoint comprised death, resuscitated cardiac arrest (RCA), heart transplant (HTX), stroke, end-stage heart failure (ESHF), and hospitalization due to heart failure (HF).
Results: During a median length of follow-up observation of ten years (interquartile range, 5–15), ten patients (22%) died, one suffered RCA, two had HTX, and six suffered ischemic strokes (13%). Seven patients developed ESHF, and eight were hospitalized due to HF. The secondary endpoint occurred in 16 patients (36%). LMNA mutation (hazard ratio [HR], 6.01; 95% confidence interval [CI], 1.61–22.4; P = 0.008) and higher serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP) concentration (HR, 1.29; 95% CI, 1.06–1.56 per 100 pg/ml; P = 0.01) increased the risk of death. Higher tricuspid annular plane systolic excursion (TAPSE) decreased the risk for the secondary endpoint (HR, 0.78; 95% CI, 0.68–0.90 mm; P <0.001). NT-proBNP >257 pg/ml and TAPSE <21 mm may be assumed as the best cut-off values for the primary and secondary endpoints, respectively.
Conclusions: LMNA mutation and higher NT-proBNP concentration were associated with increased mortality in EDMD. Lower TAPSE was a predictor of a composite secondary endpoint in EDMD.

References

  1. Heller SA, Shih R, Kalra R, et al. Emery-Dreifuss muscular dystrophy. Muscle Nerve. 2020; 61(4): 436–448.
  2. Wang S, Peng D. Cardiac Involvement in Emery-Dreifuss Muscular Dystrophy and Related Management Strategies. Int Heart J. 2019; 60(1): 12–18.
  3. Marchel M, Madej-Pilarczyk A, Tymińska A, et al. Echocardiographic features of cardiomyopathy in emery-dreifuss muscular dystrophy. Cardiol Res Pract. 2021; 2021: 8812044.
  4. Marchel M, Madej-Pilarczyk A, Tymińska A, et al. Cardiac arrhythmias in muscular dystrophies associated with emerinopathy and laminopathy: a cohort study. J Clin Med. 2021; 10(4).
  5. Emery AE, Dreifuss FE. Unusual type of benign x-linked muscular dystrophy. J Neurol Neurosurg Psychiatry. 1966; 29(4): 338–342.
  6. Rowland LP, Fetell M, Olarte M, et al. Emery-Dreifuss muscular dystrophy. Ann Neurol. 1979; 5(2): 111–117.
  7. Bialer MG, McDaniel NL, Kelly TE. Progression of cardiac disease in Emery-Dreifuss muscular dystrophy. Clin Cardiol. 1991; 14(5): 411–416.
  8. Buckley AE, Dean J, Mahy IR. Cardiac involvement in Emery Dreifuss muscular dystrophy: a case series. Heart. 1999; 82(1): 105–108.
  9. Bione S, Maestrini E, Rivella S, et al. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994; 8(4): 323–327.
  10. Bonne G, Di Barletta MR, Varnous S, et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999; 21(3): 285–288.
  11. Bonne G, Mercuri E, Muchir A, et al. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol. 2000; 48(2): 170–180.
  12. Madej-Pilarczyk A, Madej-Pilarczyk A, Kochański A. Emery-Dreifuss muscular dystrophy: the most recognizable laminopathy. Folia Neuropathol. 2016; 54(1): 1–8.
  13. Sakata K, Shimizu M, Ino H, et al. High incidence of sudden cardiac death with conduction disturbances and atrial cardiomyopathy caused by a nonsense mutation in the STA gene. Circulation. 2005; 111(25): 3352–3358.
  14. Steckiewicz R, Stolarz P, Świętoń E, et al. Cardiac pacing in 21 patients with Emery-Dreifuss muscular dystrophy: a single-centre study with a 39-year follow-up. Kardiol Pol. 2016; 74(6): 576–583.
  15. van Rijsingen IAW, Arbustini E, Elliott PM, et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study. J Am Coll Cardiol. 2012; 59(5): 493–500.
  16. Smith GC, Kinali M, Prasad SK, et al. Primary myocardial dysfunction in autosomal dominant EDMD. A tissue doppler and cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2006; 8(5): 723–730.
  17. Madej-Pilarczyk A, Marchel M, Ochman K, et al. Low-symptomatic skeletal muscle disease in patients with a cardiac disease - Diagnostic approach in skeletal muscle laminopathies. Neurol Neurochir Pol. 2018; 52(2): 174–180.
  18. Boriani G, Gallina M, Merlini L, et al. Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study. Stroke. 2003; 34(4): 901–908.
  19. Tesson F, Saj M, Uvaize MM, et al. Lamin A/C mutations in dilated cardiomyopathy. Cardiol J. 2014; 21(4): 331–342.
  20. van Berlo JH, de Voogt WG, van der Kooi AJ, et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med (Berl). 2005; 83(1): 79–83.
  21. Wahbi K, Ben Yaou R, Gandjbakhch E, et al. Development and validation of a new risk prediction score for life-threatening ventricular tachyarrhythmias in laminopathies. Circulation. 2019; 140(4): 293–302.
  22. Hasselberg NE, Haland TF, Saberniak J, et al. Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation. Eur Heart J. 2018; 39(10): 853–860.
  23. Ditaranto R, Boriani G, Biffi M, et al. Differences in cardiac phenotype and natural history of laminopathies with and without neuromuscular onset. Orphanet J Rare Dis. 2019; 14(1): 263.
  24. Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur J Heart Fail. 2021; 23(3): 352–380.
  25. Nikhanj A, Miskew Nichols B, Wang K, et al. Evaluating the diagnostic and prognostic value of biomarkers for heart disease and major adverse cardiac events in patients with muscular dystrophy. Eur Heart J Qual Care Clin Outcomes. 2021; 7(6): 564–573.
  26. Niebroj-Dobosz I, Sokołowska B, Madej-Pilarczyk A, et al. Cardiovascular risk markers in dilated cardiomyopathy in Emery-Dreifuss muscular dystrophy (EDMD). Int J Cardiol. 2014; 173(2): 324–325.
  27. Dobosz I, Sokołowska B. Natriuretic peptides assessment in dilated cardiomyopathy in patients with Emery-Dreifuss muscular dystrophy. Journal of Clinical & Experimental Cardiology. 2012; 03(08).
  28. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018; 17(4): 347–361.
  29. Mączyńska-Mazuruk R, Małek ŁA, Kłopotowski M, et al. Serum N‑terminal pro-brain natriuretic peptide as a prognostic marker in patients with hypertrophic cardiomyopathy. Kardiol Pol. 2019; 77(5): 571–573.
  30. Kaul S, Tei C, Hopkins JM, et al. Assessment of right ventricular function using two-dimensional echocardiography. Am Heart J. 1984; 107(3): 526–531.
  31. Rudski L, Lai W, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography. Journal of the American Society of Echocardiography. 2010; 23(7): 685–713.



Polish Heart Journal (Kardiologia Polska)