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Global cardiac alterations detected by speckle-tracking echocardiography in Fabry disease: left ventricular, right ventricular, and left atrial dysfunction are common and linked to worse symptomatic status

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Abstract

The aim of this study was to test the hypothesis that in patients with Fabry disease, 2D speckle-tracking echocardiography (2DSTE) could detect functional myocardial alterations such as left ventricular (LV), right ventricular (RV), and left atrial (LA) dysfunction, even when conventional cardiac measurements are normal. In addition, we hypothesized that these global cardiac alterations could be linked to worse symptomatic status in these patients. Fifty patients with Fabry disease and a control group of 118 healthy subjects of similar age and gender were included. The myocardial function and structural changes of the LV, RV, and LA were analyzed by 2DSTE and cardiac magnetic resonance imaging. Patients with Fabry disease had significantly lower functional myocardial values of the LV, RV, and LA than healthy subjects (LV, RV, and LA strain −18.1 ± 4.0, −21.4 ± 4.9, and 29.7 ± 9.9 % vs. −21.6 ± 2.2, −25.2 ± 4.0, and 44.8 ± 11.1 %, respectively, P < 0.001) and elevated rates of LV, RV, and LA myocardial dysfunction (24, 20, and 26 %, respectively), even when conventional cardiac measurements such as LVEF, TAPSE, and LAVI were normal. LV septal wall thickness ≥15 mm, RV free wall thickness ≥7 mm, and LV longitudinal dysfunction were the principal factors linked to reduced LV, RV, and LA strain, respectively. In addition, but to a lesser extent, LV and RV fibrosis were linked to reduced LV and RV strain. Patients with reduced LV, RV, and LA strain had worse functional class (dyspnea–NYHA classification) than those with normal cardiac function. In conclusion, in patients with Fabry disease, 2DSTE analyses detect LV, RV, and LA functional myocardial alterations, even when conventional cardiac measurements are normal. These functional myocardial alterations are common and significantly associated with worse symptomatic status in Fabry patients. Therefore, these findings provide important evidence to introduce global myocardial analyses using 2DSTE in the early detection of functional cardiac alterations in Fabry disease.

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References

  1. Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, Bultas J, Lee P, Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR (2006) Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 8:539–548

    Article  PubMed  Google Scholar 

  2. Gambarin FI, Disabella E, Narula J, Diegoli M, Grasso M, Serio A, Favalli BM, Agozzino M, Tavazzi L, Fraser AG, Arbustini E (2010) When should cardiologists suspect Anderson–Fabry disease? Am J Cardiol 106:1492–1499

    Article  PubMed  Google Scholar 

  3. O’Mahony C, Elliott P (2010) Anderson–Fabry disease and the heart. Prog Cardiovasc Dis 52:326–335

    Article  PubMed  Google Scholar 

  4. Zarate YA, Hopkin RJ (2008) Fabry’s disease. Lancet 372:1427–1435

    Article  CAS  PubMed  Google Scholar 

  5. Saccheri MC, Cianciulli TF, Lax JA, Gagliardi JA, Cáceres GL, Quarin AE, Kisinovsky I, Rozenfeld PA, Reisin RC, AADELFA (2013) Two-dimensional speckle tracking echocardiography for early detection of myocardial damage in young patients with Fabry disease. Echocardiography 30:1069–1077

    PubMed  Google Scholar 

  6. Shanks M, Thompson RB, Paterson ID, Putko B, Khan A, Chan A, Becher H, Oudit GY (2013) Systolic and diastolic function assessment in Fabry disease patients using speckle-tracking imaging and comparison with conventional echocardiographic measurements. J Am Soc Echocardiogr 26:1407–1414

    Article  PubMed  Google Scholar 

  7. Sheppard MN, Cane P, Florio R, Kavantzas N, Close L, Shah J, Lee P, Elliott P (2010) A detailed pathologic examination of heart tissue from three older patients with Anderson–Fabry disease on enzyme replacement therapy. Cardiovasc Pathol 19:293–301

    Article  PubMed  Google Scholar 

  8. Chimenti C, Russo MA, Frustaci A (2010) Atrial biopsy evidence of Fabry disease causing lone atrial fibrillation. Heart 96:1782–1783

    Article  CAS  PubMed  Google Scholar 

  9. Fukuzawa K, Yoshida A, Onishi T, Suzuki A, Kanda G, Takami K, Kumagai H, Torii S, Takami M, Fukuda Y, Kawai H, Hirata K (2009) Dilated phase of hypertrophic cardiomyopathy caused by Fabry disease with atrial flutter and ventricular tachycardia. J Cardiol 54:139–143

    Article  PubMed  Google Scholar 

  10. Morris DA, Vaz Pérez A, Blaschke F, Eichstädt H, Ozcelik C, Haverkamp W (2012) Myocardial systolic and diastolic consequences of left ventricular mechanical dyssynchrony in heart failure with normal left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging 13:556–567

    Article  PubMed  Google Scholar 

  11. Morris DA, Boldt LH, Eichstädt H, Ozcelik C, Haverkamp W (2012) Myocardial systolic and diastolic performance derived by 2-dimensional speckle tracking echocardiography in heart failure with normal left ventricular ejection fraction. Circ Heart Fail 5:610–620

    Article  PubMed  Google Scholar 

  12. Morris DA, Parwani A, Huemer M, Wutzler A, Bekfani T, Attanasio P, Friedrich K, Kühnle Y, Haverkamp W, Boldt LH (2013) Clinical significance of the assessment of the systolic and diastolic myocardial function of the left atrium in patients with paroxysmal atrial fibrillation and low CHADS(2) index treated with catheter ablation therapy. Am J Cardiol 111:1002–1011

    Article  PubMed  Google Scholar 

  13. Morris DA, Otani K, Bekfani T, Takigiku K, Izumi C, Yuda S, Sakata K, Ohte N, Tanabe K, Friedrich K, Kühnle Y, Nakatani S, Otsuji Y, Haverkamp W, Boldt LH, Takeuchi M (2014) Multidirectional global left ventricular systolic function in normal subjects and patients with hypertension: multicenter evaluation. J Am Soc Echocardiogr 27:493–500

    Article  PubMed  Google Scholar 

  14. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ (2005) Recommendations for chamber quantification. J Am Soc Echocardiogr 18:1440–1463

    Article  PubMed  Google Scholar 

  15. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22:107–133

    Article  PubMed  Google Scholar 

  16. Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, Galderisi M, Marwick T, Nagueh SF, Sengupta PP, Sicari R, Smiseth OA, Smulevitz B, Takeuchi M, Thomas JD, Vannan M, Voigt JU, Zamorano JL (2011) Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr 24:277–313

    Article  PubMed  Google Scholar 

  17. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB (2010) Guidelines for the echocardiographic assessment of the right heart in adults. J Am Soc Echocardiogr 23:685–713

    Article  PubMed  Google Scholar 

  18. Morris DA, Gailani M, Vaz Pérez A, Blaschke F, Dietz R, Haverkamp W, Özcelik C (2011) Right ventricular myocardial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction. J Am Soc Echocardiogr 24:886–897

    Article  PubMed  Google Scholar 

  19. Verhaert D, Mullens W, Borowski A, Popović ZB, Curtin RJ, Thomas JD, Tang WH (2010) Right ventricular response to intensive medical therapy in advanced decompensated heart failure. Circ Heart Fail 3:340–346

    Article  PubMed Central  PubMed  Google Scholar 

  20. Haugaa KH, Bergestuen DS, Sahakyan LG, Skulstad H, Aakhus S, Thiis-Evensen E, Edvardsen T (2011) Evaluation of right ventricular dysfunction by myocardial strain echocardiography in patients with intestinal carcinoid disease. J Am Soc Echocardiogr 24:644–650

    Article  PubMed  Google Scholar 

  21. Morris DA, Gailani M, Vaz Pérez A, Blaschke F, Dietz R, Haverkamp W, Ozcelik C (2011) Left atrial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction. J Am Soc Echocardiogr 24:651–662

    Article  PubMed  Google Scholar 

  22. Gutberlet M, Spors B, Thoma T, Bertram H, Denecke T, Felix R, Noutsias M, Schultheiss HP, Kühl U (2008) Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence. Radiology 246:401–409

    Article  PubMed  Google Scholar 

  23. Wang J, Buergler JM, Veerasamy K, Ashton YP, Nagueh SF (2009) Delayed untwisting: the mechanistic link between dynamic obstruction and exercise tolerance in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 54:1326–1334

    Article  PubMed  Google Scholar 

  24. Abozguia K, Nallur-Shivu G, Phan TT, Ahmed I, Kalra R, Weaver RA, McKenna WJ, Sanderson JE, Elliott P, Frenneaux MP (2010) Left ventricular strain and untwist in hypertrophic cardiomyopathy: relation to exercise capacity. Am Heart J 159:825–832

    Article  PubMed Central  PubMed  Google Scholar 

  25. Carasso S, Yang H, Woo A, Jamorski M, Wigle ED, Rakowski H (2010) Diastolic myocardial mechanics in hypertrophic cardiomyopathy. J Am Soc Echocardiogr 23:164–171

    Article  PubMed  Google Scholar 

  26. Roşca M, Popescu BA, Beladan CC, Călin A, Muraru D, Popa EC, Lancellotti P, Enache R, Coman IM, Jurcuţ R, Ghionea M, Ginghină C (2010) Left atrial dysfunction as a correlate of heart failure symptoms in hypertrophic cardiomyopathy. J Am Soc Echocardiogr 23:1090–1098

    Article  PubMed  Google Scholar 

  27. D’Andrea A, Caso P, Bossone E, Scarafile R, Riegler L, Di Salvo G, Gravino R, Cocchia R, Castaldo F, Salerno G, Golia E, Limongelli G, De Corato G, Cuomo S, Pacileo G, Russo MG, Calabrò R (2010) Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking two-dimensional strain analysis. Eur J Echocardiogr 11:492–500

    Article  PubMed  Google Scholar 

  28. Kampmann C, Baehner FA, Whybra C, Bajbouj M, Baron K, Knuf M, Wiethoff CM, Trübel H, Beck M (2005) The right ventricle in Fabry disease. Acta Paediatr Suppl 94:15–18

    Article  CAS  PubMed  Google Scholar 

  29. Palecek T, Dostalova G, Kuchynka P, Karetova D, Bultas J, Elleder M, Linhart A (2008) Right ventricular involvement in Fabry disease. J Am Soc Echocardiogr 21:1265–1268

    Article  PubMed  Google Scholar 

  30. Boyd AC, Lo Q, Devine K, Tchan MC, Sillence DO, Sadick N, Richards DA, Thomas L (2013) Left atrial enlargement and reduced atrial compliance occurs early in Fabry cardiomyopathy. J Am Soc Echocardiogr 26:1415–1423

    Article  PubMed  Google Scholar 

  31. Mondillo S, Cameli M, Caputo ML, Lisi M, Palmerini E, Padeletti M, Ballo P (2011) Early detection of left atrial strain abnormalities by speckle-tracking in hypertensive and diabetic patients with normal left atrial size. J Am Soc Echocardiogr 24:898–908

    Article  PubMed  Google Scholar 

  32. Urbano-Moral JA, Rowin EJ, Maron MS, Crean A, Pandian NG (2014) Investigation of global and regional myocardial mechanics with 3-dimensional speckle tracking echocardiography and relations to hypertrophy and fibrosis in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging 7:11–19

    Article  PubMed  Google Scholar 

  33. Prinz C, Van Buuren F, Bogunovic N, Bitter T, Faber L, Horstkotte D (2012) In patients with hypertrophic cardiomyopathy myocardial fibrosis is associated with both left ventricular and left atrial dysfunction. Acta Cardiol 67:187–193

    PubMed  Google Scholar 

  34. Chang SA, Lee SC, Choe YH, Hahn HJ, Jang SY, Park SJ, Choi JO, Park SW, Oh JK (2012) Effects of hypertrophy and fibrosis on regional and global functional heterogeneity in hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 28(Suppl 2):133–140

    Article  PubMed  Google Scholar 

  35. Popović ZB, Kwon DH, Mishra M, Buakhamsri A, Greenberg NL, Thamilarasan M, Flamm SD, Thomas JD, Lever HM, Desai MY (2008) Association between regional ventricular function and myocardial fibrosis in hypertrophic cardiomyopathy assessed by speckle tracking echocardiography and delayed hyperenhancement magnetic resonance imaging. J Am Soc Echocardiogr 21:1299–1305

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank the Department of Nephrology and Radiology of our Institution (Campus Virchow Klinikum, Charité University Hospital) for the excellent assessment and management of patients with Fabry disease.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Cardiology, Charité University Hospital, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Daniel A. Morris, Daniela Blaschke, Sima Canaan-Kühl, Alice Krebs, Gesine Knobloch, Thula C. Walter & Wilhelm Haverkamp

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  1. Daniel A. Morris
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  2. Daniela Blaschke
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Correspondence to Daniel A. Morris.

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Morris, D.A., Blaschke, D., Canaan-Kühl, S. et al. Global cardiac alterations detected by speckle-tracking echocardiography in Fabry disease: left ventricular, right ventricular, and left atrial dysfunction are common and linked to worse symptomatic status. Int J Cardiovasc Imaging 31, 301–313 (2015). https://doi.org/10.1007/s10554-014-0551-4

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