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Left ventricular structural and functional changes in Friedreich ataxia – Relationship with body size, sex, age and genetic severity


Autoři: Roger E. Peverill aff001;  Giovanni Romanelli aff001;  Lesley Donelan aff001;  Rhonda Hassam aff001;  Louise A. Corben aff002;  Martin B. Delatycki aff002
Působiště autorů: Monash Cardiovascular Research Centre and Department of Medicine (School of Clinical Sciences at Monash Medical Centre), Monash University and Monash Health, Clayton, Victoria, Australia aff001;  Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia aff002;  Victorian Clinical Genetics Services, Royal Children’s Hospital, Parkville, Victoria, Australia aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225147

Souhrn

Introduction

Although a concentric pattern of left ventricular (LV) geometry appears to be common in Friedreich ataxia (FRDA), there is no accepted method for diagnosing LV abnormalities in FRDA, sex and body size have often not been taken into consideration, and it has not been clear whether children and adults should be classified using the same criteria. The aim of this study was to better define the LV geometric changes in FRDA with respect to sex, body size and subject age, and to investigate the relationship of LV changes with genetic severity, as assessed by GAA repeat length within the shorter allele of the FXN gene (GAA1).

Methods

Echocardiography was performed in 216 subjects (68 children, 148 adults), measurements were made at end-diastole of LV internal diameter (LVEDID), septal wall thickness (SWT), LV length (LVEDL) and LV volume (LVEDV), and calculations were made of relative wall thickness (RWT), LV mass and LV ejection fraction (LVEF).

Results

The most common LV abnormalities in both adults and children with FRDA were increases in RWT and age-normalized RWT. In adults with a normal LVEF, all LV variables other than RWT were larger in males independent of body surface area (BSA), and all LV variables other than SWT and RWT were positively correlated with BSA. After adjustment for sex and BSA, GAA1 was a positive correlate of SWT and RWT (but not of LV mass), and was an inverse correlate of LVEDID, LVEDL and LVEDV. In children with a normal LVEF, SWT, LV mass and LVEDL were larger in males than females after adjusting for BSA, and in combination with sex, BSA was a positive correlate of all the LV variables except SWT and RWT. In children there were no correlations of GAA1 with any of the LV variables.

Conclusion

In FRDA, increases in RWT and age-normalized RWT are the most frequent LV structural abnormalities, sex and body size are important determinants of most other LV structural variables in both children and adults, and increased genetic severity is associated with a smaller left ventricle and increased LV wall thickness in adults, but not associated with LV size or wall thickness in children.

Klíčová slova:

Human genetics – Physiological parameters – Children – Echocardiography – Anthropometry – Adults – Friedreich's ataxia


Zdroje

1. Delatycki MB, Corben LA (2012) Clinical features of Friedreich ataxia. J Child Neurol 27: 1133–1137. doi: 10.1177/0883073812448230 22752493

2. Hewer RL (1968) Study of fatal cases of Friedreich's ataxia. BMJ 3: 649–652. doi: 10.1136/bmj.3.5619.649 5673214

3. Tsou AY, Paulsen EK, Lagedrost SJ, Perlman SL, Mathews KD, Wilmot GR et al. (2011) Mortality in Friedreich ataxia. J Neurol Sci 307: 46–49. doi: 10.1016/j.jns.2011.05.023 21652007

4. Isnard R, Kalotka H, Durr A, Cossee M, Schmitt M, Pousset F et al. (1997) Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreichs ataxia. Circulation 95: 2247–2249. doi: 10.1161/01.cir.95.9.2247 9142000

5. Dutka DP, Donnelly JE, Nihoyannopoulos P, Oakley CM, Nunez DJ (1999) Marked variation in the cardiomyopathy associated with Friedreich's ataxia. Heart 81: 141–147. doi: 10.1136/hrt.81.2.141 9922348

6. Meyer C, Schmid G, Gorlitz S, Ernst M, Wilkens C, Wilhelms I et al. (2007) Cardiomyopathy in Friedreich's ataxia-assessment by cardiac MRI. Mov Disord 22: 1615–1622. doi: 10.1002/mds.21590 17546670

7. Mottram PM, Delatycki MB, Donelan L, Gelman JS, Corben L, Peverill RE (2011) Early changes in left ventricular long-axis function in Friedreich ataxia: relation with the FXN gene mutation and cardiac structural change. J Am Soc Echocardiogr 24: 782–789. doi: 10.1016/j.echo.2011.04.004 21570254

8. Weidemann F, Rummey C, Bijnens B, Stork S, Jasaityte R, Dhooge J et al. (2012) The heart in Friedreich ataxia: Definition of cardiomyopathy, disease severity, and correlation with neurological symptoms. Circulation 125: 1626–1634. doi: 10.1161/CIRCULATIONAHA.111.059477 22379112

9. Regner SR, Lagedrost SJ, Plappert T, Paulsen EK, Friedman LS, Snyder ML et al. (2012) Analysis of echocardiograms in a large heterogeneous cohort of patients with Friedreich ataxia. Am J Cardiol 109: 401–405. doi: 10.1016/j.amjcard.2011.09.025 22078220

10. St John Sutton M, Ky B, Regner SR, Schadt K, Plappert T, He J et al. (2014) Longitudinal strain in Friedreich Ataxia: a potential marker for early left ventricular dysfunction. Echocardiography 31: 50–57. doi: 10.1111/echo.12287 23834395

11. Peverill RE, Donelan L, Corben LA, Delatycki MB (2018) Differences in the determinants of right ventricular and regional left ventricular long-axis dysfunction in Friedreich ataxia. PLoS ONE 13: e0209410. doi: 10.1371/journal.pone.0209410 PONE-D-18-20195 [pii]. 30596685

12. Weidemann F, Liu D, Hu K, Florescu C, Niemann M, Herrmann S et al. (2015) The cardiomyopathy in Friedreich's ataxia—New biomarker for staging cardiac involvement. Int J Cardiol 194: 50–57. S0167-5273(15)01131-6 [pii]; doi: 10.1016/j.ijcard.2015.05.074 26005806

13. Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C, Jiralerspong S et al. (1997) Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 6: 1771–1780. doi: 10.1093/hmg/6.11.1771 9302253

14. Deutsch EC, Santani AB, Perlman SL, Farmer JM, Stolle CA, Marusich MF et al. (2010) A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia. Mol Genet Metab 101: 238–245. doi: 10.1016/j.ymgme.2010.07.001 20675166

15. Durr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C et al. (1996) Clinical and genetic abnormalities in patients with Friedreichs ataxia. N Engl J Med 335: 1169–1175. doi: 10.1056/NEJM199610173351601 8815938

16. Bit-Avragim N, Perrot A, Schols L, Hardt C, Kreuz FR, Zuhlke C et al. (2001) The GAA repeat expansion in intron 1 of the frataxin gene is related to the severity of cardiac manifestation in patients with Friedreich's ataxia. J Mol Med 78: 626–632. doi: 10.1007/s001090000162 11269509

17. Pousset F, Legrand L, Monin ML, Ewenczyk C, Charles P, Komajda M et al. (2015) A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia. JAMA Neurol 1–8. 2444310 [pii]; doi: 10.1001/jamaneurol.2015.1855

18. Raman SV, Phatak K, Hoyle JC, Pennell ML, McCarthy B, Tran T et al. (2011) Impaired myocardial perfusion reserve and fibrosis in Friedreich ataxia: a mitochondrial cardiomyopathy with metabolic syndrome. Eur Heart J 32: 561–567. doi: 10.1093/eurheartj/ehq443 21156720

19. Rajagopalan B, Francis JM, Cooke F, Korlipara LV, Blamire AM, Schapira AH et al. (2010) Analysis of the factors influencing the cardiac phenotype in Friedreich's ataxia. Mov Disord 25: 846–852. doi: 10.1002/mds.22864 20461801

20. Ribai P, Pousset F, Tanguy ML, Rivaud-Pechoux S, Le B, I, Gasparini F et al. (2007) Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up. Arch Neurol 64: 558–564. doi: 10.1001/archneur.64.4.558 17420319

21. Filla A, De Michele G, Cavalcanti F, Pianese L, Monticelli A, Campanella G et al. (1996) The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am J Hum Genet 59: 554–560. 8751856

22. Lamont PJ, Davis MB, Wood NW (1997) Identification and sizing of the GAA trinucleotide repeat expansion of Friedreich's ataxia in 56 patients. Clinical and genetic correlates. Brain 120 (Pt 4): 673–680.

23. Montermini L, Richter A, Morgan K, Justice CM, Julien D, Castellotti B et al. (1997) Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion. Ann Neurol 41: 675–682. doi: 10.1002/ana.410410518 9153531

24. Monros E, Molto MD, Martinez F, Canizares J, Blanca J, Vilchez JJ et al. (1997) Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat. Am J Hum Genet 61: 101–110. doi: 10.1086/513887 9245990

25. Colan SD (2013) The why and how of Z scores. J Am Soc Echocardiogr 26: 38–40. doi: 10.1016/j.echo.2012.11.005 23261367

26. de Simone G, Daniels SR, Kimball TR, Roman MJ, Romano C, Chinali M et al. (2005) Evaluation of concentric left ventricular geometry in humans: evidence for age-related systematic underestimation. Hypertension 45: 64–68. doi: 10.1161/01.HYP.0000150108.37527.57 15557389

27. de Simone G, Devereux RB, Daniels SR, Meyer RA (1995) Gender differences in left ventricular growth. Hypertension 26: 979–983. doi: 10.1161/01.hyp.26.6.979 7490158

28. Carroll JD, Carroll EP, Feldman T, Ward DM, Lang RM, McGaughey D et al. (1992) Sex-associated differences in left ventricular function in aortic stenosis of the elderly. Circulation 86: 1099–1107. doi: 10.1161/01.cir.86.4.1099 1394918

29. Hees PS, Fleg JL, Lakatta EG, Shapiro EP (2002) Left ventricular remodeling with age in normal men versus women: novel insights using three-dimensional magnetic resonance imaging. Am J Cardiol 90: 1231–1236. doi: 10.1016/s0002-9149(02)02840-0 12450604

30. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L et al. (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28: 1–39. S0894-7317(14)00745-7 [pii]; doi: 10.1016/j.echo.2014.10.003 25559473

31. Stoylen A, Molmen HE, Dalen H (2016) Importance of length and external diameter in left ventricular geometry. Normal values from the HUNT Study. Open Heart 3: e000465. doi: 10.1136/openhrt-2016-000465 openhrt-2016-000465 [pii]. 27752332

32. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I et al. (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57: 450–458. 0002-9149(86)90771-X [pii]. doi: 10.1016/0002-9149(86)90771-x 2936235

33. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O et al. (1992) Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol 20: 1251–1260. doi: 10.1016/0735-1097(92)90385-z 1401629

34. Kampmann C, Wiethoff CM, Wenzel A, Stolz G, Betancor M, Wippermann CF et al. (2000) Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart 83: 667–672. doi: 10.1136/heart.83.6.667 10814626

35. Peverill RE, Chou B, Donelan L, Mottram PM, Gelman JS (2016) Possible mechanisms underlying aging-related changes in early diastolic filling and long axis motion—Left ventricular length and blood pressure. PLoS ONE 11: e0158302. doi: 10.1371/journal.pone.0158302 PONE-D-16-02781 [pii]. 27351745

36. Evans-Galea MV, Carrodus N, Rowley SM, Corben LA, Tai G, Saffery R et al. (2012) FXN methylation predicts expression and clinical outcome in Friedreich ataxia. Ann Neurol 71: 487–497. doi: 10.1002/ana.22671 22522441

37. Pfaffenberger S, Bartko P, Graf A, Pernicka E, Babayev J, Lolic E et al. (2013) Size matters! Impact of age, sex, height, and weight on the normal heart size. Circ Cardiovasc Imaging 6: 1073–1079. CIRCIMAGING.113.000690 [pii]; doi: 10.1161/CIRCIMAGING.113.000690 24014823

38. Kou S, Caballero L, Dulgheru R, Voilliot D, De SC, Kacharava G et al. (2014) Echocardiographic reference ranges for normal cardiac chamber size: results from the NORRE study. Eur Heart J Cardiovasc Imaging 16: 680–690. jet284 [pii]; doi: 10.1093/ehjci/jet284 24451180

39. Pettersen MD, Du W, Skeens ME, Humes RA (2008) Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. J Am Soc Echocardiogr 21: 922–934. doi: 10.1016/j.echo.2008.02.006 18406572

40. Cantinotti M, Scalese M, Murzi B, Assanta N, Spadoni I, De Lucia V et al. (2014) Echocardiographic nomograms for chamber diameters and areas in Caucasian children. J Am Soc Echocardiogr 27: 1279–1292. S0894-7317(14)00586-0 [pii]; doi: 10.1016/j.echo.2014.08.005 25240494

41. Rinaldi C, Tucci T, Maione S, Giunta A, De Michele G, Filla A (2009) Low-dose idebenone treatment in Friedreich's ataxia with and without cardiac hypertrophy. J Neurol 256: 1434–1437. doi: 10.1007/s00415-009-5130-6 19363628

42. Plehn JF, Hasbani K, Ernst I, Horton KD, Drinkard BE, Di Prospero NA (2018) The Subclinical Cardiomyopathy of Friedreich's Ataxia in a Pediatric Population. J Card Fail 24: 672–679. S1071-9164(17)31221-6 [pii]; doi: 10.1016/j.cardfail.2017.09.012 28986271

43. Haland TF, Hasselberg NE, Almaas VM, Dejgaard LA, Saberniak J, Leren IS et al. (2017) The systolic paradox in hypertrophic cardiomyopathy. Open Heart 4: e000571. doi: 10.1136/openhrt-2016-000571 openhrt-2016-000571 [pii]. 28674623

44. Sacca F, Puorro G, Antenora A, Marsili A, Denaro A, Piro R et al. (2011) A combined nucleic acid and protein analysis in Friedreich ataxia: implications for diagnosis, pathogenesis and clinical trial design. PLoS ONE 6: e17627. doi: 10.1371/journal.pone.0017627 21412413

45. Peverill RE (2019) Aging and the relationships between long-axis systolic and early diastolic excursion, isovolumic relaxation time and left ventricular length-Implications for the interpretation of aging effects on e`. PLoS ONE 14: e0210277. doi: 10.1371/journal.pone.0210277 PONE-D-18-21676 [pii]. 30615676

46. Cheng S, Fernandes VR, Bluemke DA, McClelland RL, Kronmal RA, Lima JA (2009) Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging 2: 191–198. doi: 10.1161/CIRCIMAGING.108.819938 19808592


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