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Left ventricular reverse remodeling is not related to biopsy-detected extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy, regardless of the definition used for LVRR

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Abstract

Left ventricular reverse remodeling (LVRR) is reported in dilated cardiomyopathy (DCM) patients (pts). However, numerous definitions of LVRR exist. Measurements of serum markers of fibrosis provide insight into myocardial fibrosis. The relationship between LVRR and fibrosis is poorly understood. From July 2014 until October 2015, we included 63 consecutive DCM pts (48 ± 12.1 years, EF 24.4 ± 7.4%) with completed baseline and 3-month follow-up echocardiograms. LVRR was assessed on the basis of four differing definitions. Procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, and PIIINP), collagen 1, ostepontin, tumor growth factor beta-1, connective tissue growth factor, and matrix metalloproteinases (MMP-2, MMP-9), and their tissue inhibitor (TIMP-1) were measured in serum. In addition, all pts underwent right ventricular endomyocardial biopsy. Depending on the definition chosen, LVRR could be diagnosed in between 14.3 and 50.8% pts. Regardless of the LVRR definition used, the frequency of LVRR was similar in fibrosis negative and positive DCM. Minor differences of markers of fibrosis were detected between pts with and without LVRR. For every LVRR definition, adjusted and unadjusted models were constructed to evaluate the predictive value of serum fibrosis parameters. Only an increase of TIMP-1 by 1 ng/ml was found to independently increase the probability of LVRR by 0.016%. The choice of a particular definition of LVRR determines the final diagnosis, and this has a profound impact on subsequent management. LVRR is unrelated to biopsy-detected ECM fibrosis. Serum markers of fibrosis are only weakly related to LVRR, and are not of use in the prediction of LVRR.

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References

  1. Cohn JN, Ferrari F, Sharpe N (2000) Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 35:569–582

    Article  CAS  PubMed  Google Scholar 

  2. Gonzalez A, Ravassa S, Beaumont J, Lopez B, Dıez J (2011) New targets to treat the structural remodeling of the myocardium. J Am Coll Cardiol 58:1833–1843

    Article  CAS  PubMed  Google Scholar 

  3. Ikeda Y, Inomata T, Iida Y, Iwamoto-Ishida M, Nabeta T, Ishii S, Sato T, Yanagisawa T, Mizutani T, Naruke T, Koitabashi T, Takeuchi I, Nishii M, Ako J (2016) Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy. Heart Vessels 31:545–554

    Article  PubMed  Google Scholar 

  4. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kühl U, Maisch B, McKenna WJ, Monserrat L, Pankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren A (2007) Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on myocardial and pericardial diseases. Eur Heart J 29:270–277

    Article  PubMed  Google Scholar 

  5. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Eur Heart J 33:1787–1847

    Article  PubMed  Google Scholar 

  6. Merlo M, Pyxaras SA, Pinamonti B, Barbati G, Di Lenarda A, Sinagra G (2011) Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol 57:1468–1476

    Article  PubMed  Google Scholar 

  7. Yu CM, Fung WH, Lin H, Zhang Q, Sanderson JE, Lau CP (2003) Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol 91:684–688

    Article  PubMed  Google Scholar 

  8. Scandura S, Ussia GP, Capranzano P, Caggegi A, Sarkar K, Cammalleri V, Mangiafico S, Chiarandà M, Immè S, Di Pasqua F, Pistritto AM, Millan G, Tamburino C (2012) Left cardiac chambers reverse remodeling after percutaneous mitral valve repair with the MitraClip system. J Am Soc Echocardiogr 25:1099–1105

    Article  PubMed  Google Scholar 

  9. Nabeta T, Inomata T, Iida Y, Ikeda Y, Iwamoto M, Ishii S, Sato T, Watanabe I, Naruke T, Shinagawa H, Koitabashi T, Takeuchi I, Nishii M, Inoue Y, Izumi T (2014) Baseline cardiac magnetic resonance imaging versus baseline endomyocardial biopsy for the prediction of left ventricular reverse remodeling and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy. Heart Vessels 29:784–792

    Article  PubMed  Google Scholar 

  10. Rutschow S, Li J, Schultheiss HP, Pauschinger M (2006) Myocardial proteases and matrix remodeling in inflammatory heart disease. Cardiovasc Res 69:646–656

    Article  CAS  PubMed  Google Scholar 

  11. Timonen P, Magga J, Risteli J, Punnonen K, Vanninen E, Turpeinen A, Tuomainen P, Kuusisto J, Vuolteenaho O, Peuhkurinen K (2008) Cytokines, interstitial collagen and ventricular remodelling in dilated cardiomyopathy. Int J Cardiol 124:293–300

    Article  PubMed  Google Scholar 

  12. Klappacher G, Franzen P, Haab D, Mehrabi M, Binder M, Plesch K, Pacher R, Grimm M, Pribill I, Eichler HG (1995) Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol 75:913–918

    Article  CAS  PubMed  Google Scholar 

  13. Henry WL, Gardin JM, Ware JH (1980) Echocardiographic measurements in normal subjects from infancy to old age. Circulation 62:1054–1061

    Article  CAS  PubMed  Google Scholar 

  14. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (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. Eur Heart J Cardiovasc Imaging 16:233–270

    Article  PubMed  Google Scholar 

  15. Choi JO, Kim EY, Lee GY, Lee SC, Park SW, Kim DK, Oh JK, Jeon ES (2013) Predictors of left ventricular reverse remodeling and subsequent outcome in nonischemic dilated cardiomyopathy. Circ J 77:462–469

    Article  PubMed  Google Scholar 

  16. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 116:2216–2233

    Article  PubMed  Google Scholar 

  17. Steimle AE, Stevenson LW, Fonarow GC, Hamilton MA, Moriguchi JD (1994) Prediction of improvement in recent-onset cardiomyopathy after referral for heart transplantation. J Am Coll Cardiol 23:553–559

    Article  CAS  PubMed  Google Scholar 

  18. Kubanek M, Sramko M, Maluskova J, Kautznerova D, Weichet J, Lupinek P, Vrbska J, Malek I, Kautzner J (2013) Novel predictors of left ventricular reverse remodeling in individuals with recent-onset dilated cardiomyopathy. J Am Coll Cardio 61:54–63

    Article  Google Scholar 

  19. Ishii S, Inomata T, Fujita T, Iida Y, Ikeda Y, Nabeta T, Yanagisawa T, Naruke T, Mizutani T, Koitabashi T, Takeuchi I, Ako J (2016) Clinical significance of endomyocardial biopsy in conjunction with cardiac magnetic resonance imaging to predict left ventricular reverse remodeling in idiopathic dilated cardiomyopathy. Heart Vessels. doi:10.1007/s00380-016-0815-0

    Google Scholar 

  20. Porciani CM, Lilli A, Cappelli F, Pappone A, Perini AP, Pieragnoli P, Ricciardi G, Rao CM, Prinzen FW, Michelucci A, Padeletti L (2010) Echo/Doppler-derived time intervals are able to predict left ventricular reverse remodeling after cardiac resynchronization therapy. J Cardiovasc Med (Hagerstown) 11:157–163

    Article  Google Scholar 

  21. Ceconi C, Freedman SB, Tardif JC, Hildebrandt P, McDonagh T, Gueret P, Parrinello G, Robertson M, Steg PG, Tendera M, Ford I, Fox K, Ferrari R (2011) Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol 146:408–414

    Article  CAS  PubMed  Google Scholar 

  22. Ikeda Y, Inomata T, Fujita T, Iida Y, Nabeta T, Ishii S, Maekawa E, Yanagisawa T, Mizutani T, Naruke T, Koitabashi T, Takeuchi I, Ako J (2016) Cardiac fibrosis detected by magnetic resonance imaging on predicting time course diversity of left ventricular reverse remodeling in patients with idiopathic dilated cardiomyopathy. Heart Vessels. doi:10.1007/s00380-016-0805-2

    PubMed Central  Google Scholar 

  23. Umar S, Bax JJ, Klok M, van Bommel RJ, Hessel MH, den Adel B, Bleeker GB, Henneman MM, Atsma DE, van der Wall EE, Schalij MJ, van der Laarse A (2008) Myocardial collagen metabolism in failing hearts before and during cardiac resynchronization therapy. Eur J Heart Fail 10:878–883

    Article  CAS  PubMed  Google Scholar 

  24. D’Ascia C, Cittadini A, Monti MG, Riccio G, Saccà L (2006) Effects of biventricular pacing on interstitial remodelling, tumor necrosis factor-alpha expression, and apoptotic death in failing human myocardium. Eur Heart J 27:201–206

    Article  PubMed  Google Scholar 

  25. Bruggink AH, van Oosterhout MF, de Jonge N, Ivangh B, van Kuik J, Voorbij RH, Cleutjens JP, Gmelig-Meyling FH, de Weger RA (2006) Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern. J Heart Lung Transplant 25:1091–1098

    Article  PubMed  Google Scholar 

  26. Milting H, Jacob M, Kassner A, Heimann P, Mannherz HG, Becker G, Meyer HE, Böthig D, Arusoglu L, Morshuis M, Körfer R, El Banayosy A (2004) The structural examination of myocardial samples from patients with end-stage heart failure supported by ventricular assist devices using electron microscopy and amino acid analysis reveals low degree of reverse remodeling. J Heart Lung Transplant 23:396–404

    Article  PubMed  Google Scholar 

  27. Francia P, Balla C, Ricotta A, Uccellini A, Frattari A, Modestino A, Borro M, Simmaco M, Salvati A, De Biase L, Volpe M (2011) Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure. Int J Cardiol 153:306–310

    Article  PubMed  Google Scholar 

  28. Polyakova V, Loeffler I, Hein S, Miyagawa S, Piotrowska I, Dammer S, Risteli J, Schaper J, Kostin S (2011) Fibrosis in endstage human heart failure: severe changes in collagen metabolism and MMP/TIMP profiles. Int J Cardiol 151:18–33

    Article  PubMed  Google Scholar 

  29. Sakamuri SS, Takawale A, Basu R, Fedak PW, Freed D, Sergi C, Oudit GY, Kassiri Z (2016) Differential impact of mechanical unloading on structural and nonstructural components of the extracellular matrix in advanced human heart failure. Transl Res 172:30–44

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiac and Vascular Diseases, John Paul II Hospital, 31-202, Krakow, Poland

    Paweł Rubiś, Sylwia Wiśniowska-Śmiałek, Barbara Biernacka-Fijałkowska, Artur Kozanecki, Marta Hlawaty, Agata Leśniak-Sobelga, Magdalena Kostkiewicz, Wojciech Płazak & Piotr Podolec

  2. Department of Pathology, John Paul II Hospital, Pradnicka St. 80, 31-202, Krakow, Poland

    Lucyna Rudnicka-Sosin

  3. Department of Molecular Biology, John Paul II Hospital, Pradnicka St. 80, Krakow, Poland

    Ewa Wypasek

  4. Medical Collage, Jagiellonian University, St. Ann St. 12, 31-008, Krakow, Poland

    Ewa Dziewięcka, Patrycja Faltyn, Aleksandra Karabinowska, Lusine Khachatryan, Wojciech Płazak & Piotr Podolec

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  1. Paweł Rubiś
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Correspondence to Paweł Rubiś.

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Rubiś, P., Wiśniowska-Śmiałek, S., Biernacka-Fijałkowska, B. et al. Left ventricular reverse remodeling is not related to biopsy-detected extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy, regardless of the definition used for LVRR. Heart Vessels 32, 714–725 (2017). https://doi.org/10.1007/s00380-016-0930-y

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