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Cardiac Remodeling: The Course Towards Heart Failure-II. Diagnostic and Therapeutic Approaches

  • Dennis V. CokkinosEmail author
Chapter

Abstract

The diagnosis of cardiac remodeling (REM) is based on echocardiographic, radionuclide, and cardiac magnetic resonance imaging. With all of these three modalities, molecular imaging investigating various processes can be implemented. With regard to therapy, pharmaceutical treatment is still evolving: angiotensing converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, aldosterone inhibitors and statins are the big 4 of therapy. Revascularization is an option if viability is found. In cases of left bundle branch block (LBBB), resynchronization therapy can be effective, especially in nonischemic etiology. Gene therapy by SERCA-2 gene transfer has been investigated but the results of CUPID 2 were disappointing. Progenitor cell therapy still remains under evaluation. Finally, with left ventricular assist device (LVAD) placement, improved results are reported with regard to both weaning from mechanical circulation support and overall survival.

Keywords

Radionuclide echocardiography Cardiac magnetic resonance imaging LBBB Resynchronization therapy Mechanical circulation Support 

References

  1. 1.
    Yang XW, Hua W, Wang J, Liu ZM, Ding LG, Chen KP, et al. Regression of fragmented QRS complex: a marker of electrical reverse remodeling in cardiac resynchronization therapy. Ann Noninvasive Electrocardiol. 2015;20:18–27.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Poole JE, Singh JP, Birgersdotter-Green U. QRS duration or QRS morphology: what really matters in cardiac resynchronization therapy? J Am Coll Cardiol. 2016;67:1104–17.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Azevedo PS, Polegato BF, Minicucci MF, Paiva SA, Zornoff LA. Cardiac remodeling: concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arq Bras Cardiol. 2016;106:62–9.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Bhatt AS, Ambrosy AP, Velazquez EJ. Adverse remodeling and reverse remodeling after myocardial infarction. Curr Cardiol Rep. 2017;19:71.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Migrino RQ, Young JB, Ellis SG, White HD, Lundergan CF, Miller DP, et al. End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute myocardial infarction is a strong predictor of early and late mortality. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I Angiographic Investigators. Circulation. 1997;96:116–21.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987;76:44–51.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Kapetanakis S, Bhan A, Murgatroyd F, Kearney MT, Gall N, Zhang Q, et al. Real-time 3D echo in patient selection for cardiac resynchronization therapy. JACC Cardiovasc Imaging. 2011;4:16–26.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Lepper W, Kamp O, Vanoverschelde JL, Franke A, Sieswerda GT, Pasquet A, et al. Intravenous myocardial contrast echocardiography predicts left ventricular remodeling in patients with acute myocardial infarction. J Am Soc Echocardiogr. 2002;15:849–56.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Na HM, Cho GY, Lee JM, Cha MJ, Yoon YE, Lee SP, et al. Echocardiographic predictors for left ventricular remodeling after acute ST elevation myocardial infarction with low risk group: speckle tracking analysis. J Cardiovasc Ultrasound. 2016;24:128–34.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Gorcsan J, Kanzaki H, Bazaz R, Dohi K, Schwartzman D. Usefulness of echocardiographic tissue synchronization imaging to predict acute response to cardiac resynchronization therapy. Am J Cardiol. 2004;93:1178–81.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Mollema SA, Liem SS, Suffoletto MS, Bleeker GB, van der Hoeven BL, van de Veire NR, et al. Left ventricular dyssynchrony acutely after myocardial infarction predicts left ventricular remodeling. J Am Coll Cardiol. 2007;50:1532–40.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Yeh J Nihoyannopoulos P. Molecular imaging of inflammation using echocardiography. Advances with the use of microbubbles. Introduction to translational cardiovascular research. Springer 2015. p. 465–50.Google Scholar
  13. 13.
    Hoffmann R, von Bardeleben S, Kasprzak JD, Borges AC, ten Cate F, Firschke C, et al. Analysis of regional left ventricular function by cineventriculography, cardiac magnetic resonance imaging, and unenhanced and contrast-enhanced echocardiography: a multicenter comparison of methods. J Am Coll Cardiol. 2006;47:121–8.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Fieno DS, Kim RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing. J Am Coll Cardiol. 2000;36:1985–91.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Tarantini G, Razzolini R, Cacciavillani L, Bilato C, Sarais C, Corbetti F, et al. Influence of transmurality, infarct size, and severe microvascular obstruction on left ventricular remodeling and function after primary coronary angioplasty. Am J Cardiol. 2006;98:1033–40.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation. 1999;100:1992–2002.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Bulluck H, Go YY, Crimi G, Ludman AJ, Rosmini S, Abdel-Gadir A, et al. Defining left ventricular remodeling following acute ST-segment elevation myocardial infarction using cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2017;19:26.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Bhat A, Gan GC, Tan TC, Hsu C, Denniss AR. Myocardial viability: from proof of concept to clinical practice. Cardiol Res Pract. 2016;2016:1020818.  https://doi.org/10.1155/2016/1020818.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Thornhill RE, Prato FS, Wisenberg G. The assessment of myocardial viability: a review of current diagnostic imaging approaches. J Cardiovasc Magn Reson. 2002;4:381–410.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Anagnostopoulos CD, Cokkinos DV. Prediction of left ventricular remodelling by radionuclide imaging. Eur J Nucl Med Mol Imaging. 2011;38:1120–3.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Berti V, Sciagrà R, Acampa W, Ricci F, Cerisano G, Gallicchio R, et al. Relationship between infarct size and severity measured by gated SPECT and long-term left ventricular remodelling after acute myocardial infarction. Eur J Nucl Med Mol Imaging. 2011;38:1124–31.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging. 2011;4:98–108.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Paschali A. Non invasive imaging modalities for cardiovascular translational research-technical considerations. Introduction to Translational Cardiovascular Research Springer 2015. p. 413–431.Google Scholar
  24. 24.
    Curley D, Lavin Plaza B, Shah AM, Botnar RM. Molecular imaging of cardiac remodelling after myocardial infarction. Basic Res Cardiol. 2018;113:10.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Kasama S, Toyama T, Sumino H, Nakazawa M, Matsumoto N, Sato Y, et al. Prognostic value of serial cardiac 123I-MIBG imaging in patients with stabilized chronic heart failure and reduced left ventricular ejection fraction. J Nucl Med. 2008;49:907–14.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Bengel FM. Imaging of post-infarct inflammation: moving forward toward clinical application. Circ Cardiovasc Imaging. 2016;9:e004713.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Fukushima K, Bravo PE, Higuchi T, Schuleri KH, Lin X, Abraham MR, et al. Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors. J Am Coll Cardiol. 2012;60:2527–34.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Verjans JW, Lovhaug D, Narula N, Petrov AD, Indrevoll B, Bjurgert E, et al. Noninvasive imaging of angiotensin receptors after myocardial infarction. JACC Cardiovasc Imaging. 2008;1:354–62.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Jerosch-Herold M, Kwong R. Magnetic resonance imaging in the assessment of ventricular remodeling and viability. Curr Heart Fail Rep. 2008;5:5–10.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113:2335–62.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.CrossRefGoogle Scholar
  32. 32.
    Zannad F. What is measured by cardiac fibrosis biomarkers and imaging? Circ Heart Fail. 2014;7:239–42.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Ellims AH, Taylor AJ, Mariani JA, Ling LH, Iles LM, Maeder MT, et al. Evaluating the utility of circulating biomarkers of collagen synthesis in hypertrophic cardiomyopathy. Circ Heart Fail. 2014;7:271–8.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Azuaje F, Devaux Y, Wagner DR. Integrative pathway-centric modeling of ventricular dysfunction after myocardial infarction. PLoS One. 2010;5:e9661.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Yang J, Liu Y, Fan X, Li Z, Cheng Y. A pathway and network review on beta-adrenoceptor signaling and beta blockers in cardiac remodeling. Heart Fail Rev. 2014;19:799–814.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Funaro S, La Torre G, Madonna M, Galiuto L, Scarà A, Labbadia A, et al. Incidence, determinants, and prognostic value of reverse left ventricular remodelling after primary percutaneous coronary intervention: results of the Acute Myocardial Infarction Contrast Imaging (AMICI) multicenter study. Eur Heart J. 2009;30:566–75.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Rosenblatt-Velin N, Badoux S, Liaudet L. Pharmacological therapy in the heart as an alternative to cellular therapy: a place for the brain natriuretic peptide? Stem Cells Int. 2016;2016:5961342.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Ruvinov E, Harel-Adar T, Cohen S. Bioengineering the infarcted heart by applying bio-inspired materials. J Cardiovasc Transl Res. 2011;4:559–74.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Hausenloy DJ, Erik Bøtker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, et al. Translating cardioprotection for patient benefit: position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2013;98:7–27.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Hausenloy DJ, Garcia-Dorado D, Bøtker HE, Davidson SM, Downey J, Engel FB, et al. Novel targets and future strategies for acute cardioprotection: position paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart. Cardiovasc Res. 2017;113:564–85.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Newton N, Croisille P, Gahide G, Rioufol G, Bonnefoy E, Sanchez I, et al. Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction. J Am Coll Cardiol. 2010;55:1200–5.CrossRefGoogle Scholar
  42. 42.
    Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, et al. Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J Med. 2015;373:1021–31.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Ottani F, Latini R, Staszewsky L, La Vecchia L, Locuratolo N, Sicuro M, et al. Cyclosporine a in reperfused myocardial infarction: the multicenter, controlled, open-label CYCLE trial. J Am Coll Cardiol. 2016;67:365–74.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Monassier L, Ayme-Dietrich E, Aubertin-Kirch G, Pathak A. Targeting myocardial reperfusion injuries with cyclosporine in the CIRCUS trial—pharmacological reasons for failure. Fundam Clin Pharmacol. 2016;30:191–3.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Ishii H, Amano T, Matsubara T, Murohara T. Pharmacological intervention for prevention of left ventricular remodeling and improving prognosis in myocardial infarction. Circulation. 2008;118:2710–8.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Xie M, Burchfield JS, Hill JA. Pathological ventricular remodeling: therapies: part 2 of 2. Circulation. 2013;128:1021–30.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Cokkinos D. Le remodelage cardiaque après un infarctus: nouvelles données sur la prévention et le traintment. Bull Acad Natl Med 2015;199:1383–94.Google Scholar
  48. 48.
    Belogianneas C, Cokkinos DV. Left ventricular remodeling: a problem in search of solutions. European Cardiology Review 2016;11:29–35.CrossRefGoogle Scholar
  49. 49.
    Tarone G, Balligand JL, Bauersachs J, Clerk A, De Windt L, Heymans S, et al. Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology. Eur J Heart Fail. 2014;16:494–508.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Miura T, Miki T. Limitation of myocardial infarct size in the clinical setting: current status and challenges in translating animal experiments into clinical therapy. Basic Res Cardiol. 2008;103:501–13.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Khattar RS. Effects of ACE-inhibitors and beta-blockers on left ventricular remodeling in chronic heart failure. Minerva Cardioangiol. 2003;51:143–54.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel JP. Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation. 1998;98:1184–91.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Madamanchi A. Beta-adrenergic receptor signaling in cardiac function and heart failure. Mcgill J Med. 2007;10:99–104.Google Scholar
  54. 54.
    Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006;355:1873–84.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Spanou D, Perimenis P, Mantzouratou P, Gomatos C, Cokkinos D, Mourouzis I, et al. Clenbuterol favorably remodels neonatal cardiac cells via activation of p38 MAPK signalling pathway. J Cardiovasc Surg. 2012;53:789–95.Google Scholar
  56. 56.
    Moens AL, Leyton-Mange JS, Niu X, Yang R, Cingolani O, Arkenbout EK, et al. Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor. J Mol Cell Cardiol. 2009;47:576–85.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Kajstura J, Cigola E, Malhotra A, Li P, Cheng W, Meggs LG, et al. Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol. 1997;29:859–70.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Jugdutt BI. Apoptosis after reperfused myocardial infarction: role of angiotensin II. Exp Clin Cardiol. 2004;9:219–28.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Albuquerque FN, Brandão AA, Silva DA, Mourilhe-Rocha R, Duque GS, Gondar AF, et al. Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling. Arq Bras Cardiol. 2014;102:70–9.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, et al. Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation. 1994;89:2273–82.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    von Lueder TG, Wang BH, Kompa AR, Huang L, Webb R, Jordaan P, et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ Heart Fail. 2015;8:71–8.CrossRefGoogle Scholar
  63. 63.
    Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Iraqi W, Rossignol P, Angioi M, Fay R, Nuée J, Ketelslegers JM, et al. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study. Circulation. 2009;119:2471–9.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, et al. Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2003;41:574–81.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, et al. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001;37:1228–33.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Hayashi M, Tsutamoto T, Wada A, Tsutsui T, Ishii C, Ohno K, et al. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation. 2003;107:2559–65.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Beygui F, Cayla G, Roule V, Roubille F, Delarche N, Silvain J, et al. Early aldosterone blockade in acute myocardial infarction: the ALBATROSS randomized clinical trial. J Am Coll Cardiol. 2016;67:1917–27.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Bell RM, Yellon DM. Atorvastatin, administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by up-regulating a pro-survival pathway. J Am Coll Cardiol. 2003;41:508–15.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Kinlay S, Schwartz GG, Olsson AG, Rifai N, Leslie SJ, Sasiela WJ, et al. High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation. 2003;108:1560–6.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Nahrendorf M, Sosnovik D, Chen JW, Panizzi P, Figueiredo JL, Aikawa E, et al. Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia–reperfusion injury. Circulation. 2008;117:1153–60.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Cheng CF, Juan SH, Chen JJ, Chao YC, Chen HH, Lian WS, et al. Pravastatin attenuates carboplatin-induced cardiotoxicity via inhibition of oxidative stress associated apoptosis. Apoptosis. 2008;13:883–94.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Lee TM, Lin MS, Tsai CH, Chang NC. Effects of pravastatin on ventricular remodeling by activation of myocardial KATP channels in infarcted rats: role of 70-kDa S6 kinase. Basic Res Cardiol. 2007;102:171–82.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Krum H, Ashton E, Reid C, Kalff V, Rogers J, Amarena J, et al. Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. J Card Fail. 2007;13:1–7.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248–61.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1231–9.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Kjekshus J. Are statins failing in heart failure? Eur Heart J. 2015;36:1502–4.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Preiss D, Campbell RT, Murray HM, Ford I, Packard CJ, Sattar N, et al. The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials. Eur Heart J 2015;36:1536–1546.Google Scholar
  79. 79.
    Oerlemans MI, Liu J, Arslan F, den Ouden K, van Middelaar BJ, Doevendans PA, et al. Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia-reperfusion in vivo. Basic Res Cardiol. 2012;107:270.  https://doi.org/10.1007/s00395-012-0270-8.
  80. 80.
    Luedde M, Lutz M, Carter N, Sosna J, Jacoby C, Vucur M, et al. RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction. Cardiovasc Res. 2014;103:206–16.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Letavernier E, Zafrani L, Perez J, Letavernier B, Haymann JP, Baud L. The role of calpains in myocardial remodelling and heart failure. Cardiovasc Res. 2012;96:38–45.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Portbury AL, Willis MS, Patterson C. Tearin' up my heart: proteolysis in the cardiac sarcomere. J Biol Chem. 2011;286:9929–34.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Spaeth CS, Boydston EA, Figard LR, Zuzek A, Bittner GD. A model for sealing plasmalemmal damage in neurons and other eukaryotic cells. J Neurosci. 2010;30:15790–800.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, et al. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2011;13:1–10.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Gao R, Zhang J, Cheng L, Wu X, Dong W, Yang X, et al. A phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. J Am Coll Cardiol. 2010;55:1907–14.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Jabbour A, Hayward CS, Keogh AM, Kotlyar E, McCrohon JA, England JF, et al. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail. 2011;13:83–92.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Fan GC, Kranias EG. Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure. J Mol Cell Cardiol. 2011;51:574–7.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    De Acetis M, Notte A, Accornero F, Selvetella G, Brancaccio M, Vecchione C, et al. Cardiac overexpression of melusin protects from dilated cardiomyopathy due to long-standing pressure overload. Circ Res. 2005;96:1087–94.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Willis MS, Patterson C. Into the heart: the emerging role of the ubiquitin-proteasome system. J Mol Cell Cardiol. 2006;41:567–79.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Lee DI, Kass DA. Phosphodiesterases and cyclic GMP regulation in heart muscle. Physiology (Bethesda). 2012;27:248–58.Google Scholar
  91. 91.
    Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011;4:8–17.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309:1268–77.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Tocchetti CG, Stanley BA, Murray CI, Sivakumaran V, Donzelli S, Mancardi D, et al. Playing with cardiac “redox switches”: the “HNO way” to modulate cardiac function. Antioxid Redox Signal. 2011;14:1687–98.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Fraccarollo D, Widder JD, Galuppo P, Thum T, Tsikas D, Hoffmann M, et al. Improvement in left ventricular remodeling by the endothelial nitric oxide synthase enhancer AVE9488 after experimental myocardial infarction. Circulation. 2008;118:818–27.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Greenberg B, Butler J, Felker GM, Ponikowski P, Voors A, Desai AS, et al. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet. 2016;387:1178–86.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation. 2011;124:304–13.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Hajjar R. Resilient course of gene therapy in cardiovascular diseases. Lecture presented at the 1st Olympiad in Cardiovascular Medicine. International Symposium on Experimental & Clinical Cardiology, 17 May 2018, Athens.Google Scholar
  98. 98.
    Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, et al. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011;378:676–83.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Teerlink JR, Clarke CP, Saikali KG, Lee JH, Chen MM, Escandon RD, et al. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet. 2011;378:667–75.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Teerlink JR, Felker GM, McMurray JJ, Solomon SD, Adams KF Jr, Cleland JG, et al. Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016;388:2895–903.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Gustafsson F, Guarracino F, Schwinger RHG. The inodilator levosimendan as a treatment for acute heart failure in various settings. Eur Heart J Suppl. 2017;19(Suppl C):C2–7.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Mavrogeni S, Giamouzis G, Papadopoulou E, Thomopoulou S, Dritsas A, Athanasopoulos G, et al. A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure. J Card Fail. 2007;13:556–9.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Silvetti S, Nieminen MS. Repeated or intermittent levosimendan treatment in advanced heart failure: an updated meta-analysis. Int J Cardiol. 2016;202:138–43.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Tarkia M, Stark C, Haavisto M, Kentala R, Vähäsilta T, Savunen T, et al. Effect of levosimendan therapy on myocardial infarct size and left ventricular function after acute coronary occlusion. Heart. 2016;102:465–71.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Louhelainen M, Vahtola E, Kaheinen P, Leskinen H, Merasto S, Kytö V, et al. Effects of levosimendan on cardiac remodeling and cardiomyocyte apoptosis in hypertensive Dahl/Rapp rats. Br J Pharmacol. 2007;150:851–61.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Tardif JC, O'Meara E, Komajda M, Böhm M, Borer JS, Ford I, et al. Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy. Eur Heart J. 2011;32:2507–15.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Cittadini A, Napoli R, Monti MG, Rea D, Longobardi S, Netti PA, et al. Metformin prevents the development of chronic heart failure in the SHHF rat model. Diabetes. 2012;61:944–53.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Xiao H, Ma X, Feng W, Fu Y, Lu Z, Xu M, et al. Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway. Cardiovasc Res. 2010;87:504–13.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.CrossRefGoogle Scholar
  110. 110.
    Byme NJ. Basic to translational science. JACC. 2017;2:347–54.Google Scholar
  111. 111.
    Verma S, Garg A, Yan AT, Gupta AK, Al-Omran M, Sabongui A, et al. Effect of empagliflozin on left ventricular mass and diastolic function in individuals with diabetes: an important clue to the EMPA-REG OUTCOME trial? Diabetes Care. 2016;39:e212–3.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Rastogi S, Sharov VG, Mishra S, Gupta RC, Blackburn B, Belardinelli L, et al. Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Am J Physiol Heart Circ Physiol. 2008;295:H2149–55.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Das S, Aiba T, Rosenberg M, Hessler K, Xiao C, Quintero PA, et al. Pathological role of serum- and glucocorticoid-regulated kinase 1 in adverse ventricular remodeling. Circulation. 2012;126:2208–19.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Wang S, Fan Y, Feng X, Sun C, Shi Z, Li T, et al. Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1. Biochem Biophys Res Commun. 2018;495:292–9.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Lee TM, Lin MS, Chang NC. Inhibition of histone deacetylase on ventricular remodeling in infarcted rats. Am J Physiol Heart Circ Physiol. 2007;293:H968–77.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N. Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochim Biophys Acta. 1813;2011:1323–32.Google Scholar
  117. 117.
    Varela A, Mavroidis M, Katsimpoulas M, Sfiroera I, Kappa N, Mesa A, et al. The neuroprotective agent rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction. ESC Heart Fail. 2017;4:331–40.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Hughes BG, Schulz R. Targeting MMP-2 to treat ischemic heart injury. Basic Res Cardiol. 2014;109:424.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Yabluchanskiy A, Li Y, Chilton RJ, Lindsey ML. Matrix metalloproteinases: drug targets for myocardial infarction. Curr Drug Targets. 2013;14:276–86.PubMedPubMedCentralGoogle Scholar
  120. 120.
    Cerisano G, Buonamici P, Valenti R, Moschi G, Taddeucci E, Giurlani L, et al. Effects of a timely therapy with doxycycline on the left ventricular remodeling according to the pre-procedural TIMI flow grade in patients with ST-elevation acute myocardial infarction. Basic Res Cardiol. 2014;109:412.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Ago T, Sadoshima J. Thioredoxin and ventricular remodeling. J Mol Cell Cardiol. 2006;41:762–73.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Li HL, Liu C, de Couto G, Ouzounian M, Sun M, Wang AB, et al. Curcumin prevents and reverses murine cardiac hypertrophy. J Clin Invest. 2008;118:879–93.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Raj P, Aloud BM, Louis XL, Yu L, Zieroth S, Netticadan T. Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats. J Nutr Biochem. 2016;28:155–63.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Ashrafian H, Czibik G, Bellahcene M, Aksentijević D, Smith AC, Mitchell SJ, et al. Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway. Cell Metab. 2012;15:361–71.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Nguyen B, Luong L, Naase H, Vives M, Jakaj G, Finch J, et al. Sulforaphane pretreatment prevents systemic inflammation and renal injury in response to cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2014;148:690–697.e3.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Engberding N, Spiekermann S, Schaefer A, Heineke A, Wiencke A, Müller M, et al. Allopurinol attenuates left ventricular remodeling and dysfunction after experimental myocardial infarction: a new action for an old drug? Circulation. 2004;110:2175–9.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Xu X, Hu X, Lu Z, Zhang P, Zhao L, Wessale JL, et al. Xanthine oxidase inhibition with febuxostat attenuates systolic overload–induced left ventricular hypertrophy and dysfunction in mice. J Card Fail. 2008;14:746–53.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Gibson CM, Giugliano RP, Kloner RA, Bode C, Tendera M, Jánosi A, et al. EMBRACE STEMI study: a phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J. 2016;37:1296–303.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P, et al. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur Heart J. 2015;36:112–9.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    López B, González A, Hermida N, Valencia F, de Teresa E, Díez J. Role of lysyl oxidase in myocardial fibrosis: from basic science to clinical aspects. Am J Physiol Heart Circ Physiol. 2010;299:H1–9.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    López B, Querejeta R, González A, Beaumont J, Larman M, Díez J. Impact of treatment on myocardial lysyl oxidase expression and collagen cross-linking in patients with heart failure. Hypertension. 2009;53:236–42.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    TORAFIC Investigators Group. Effects of prolonged-release torasemide versus furosemide on myocardial fibrosis in hypertensive patients with chronic heart failure: a randomized, blinded-end point, active-controlled study. Clin Ther. 2011;33:1204–1213.e3.CrossRefGoogle Scholar
  133. 133.
    Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, et al. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation. 2003;107:1359–65.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Rajagopalan S, Mohler E 3rd, Lederman RJ, Saucedo J, Mendelsohn FO, Olin J, et al. Regional angiogenesis with vascular endothelial growth factor (VEGF) in peripheral arterial disease: design of the RAVE trial. Am Heart J. 2003;145:1114–8.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Iwasaki H, Kawamoto A, Tjwa M, Horii M, Hayashi S, Oyamada A, et al. PLGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors. PLoS One. 2011;6:e24872.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Talan MI, Ahmet I, Lakatta EG. Did clinical trials in which erythropoietin failed to reduce acute myocardial infarct size miss a narrow therapeutic window? PLoS One. 2012;7:e34819.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Brüel A, Christoffersen TE, Nyengaard JR. Growth hormone increases the proliferation of existing cardiac myocytes and the total number of cardiac myocytes in the rat heart. Cardiovasc Res. 2007;76:400–8.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Lee TM, Lin MS, Chou TF, Tsai CH, Chang NC. Adjunctive 17beta-estradiol administration reduces infarct size by altered expression of canine myocardial connexin43 protein. Cardiovasc Res. 2004;63:109–17.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Wang XF, Qu XQ, Zhang TT, Zhang JF. Testosterone suppresses ventricular remodeling and improves left ventricular function in rats following myocardial infarction. Exp Ther Med. 2015;9:1283–91.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Zaruba MM, Huber BC, Brunner S, Deindl E, David R, Fischer R, et al. Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival. Cardiovasc Res. 2008;77:722–31.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Bodyak N, Ayus JC, Achinger S, Shivalingappa V, Ke Q, Chen YS, et al. Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals. Proc Natl Acad Sci U S A. 2007;104:16810–5.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Rafacho BP, Santos P, Assalin HB, Ardisson LP, Roscani MG, Polegato BF, et al. Role of vitamin D in the cardiac remodeling induced by tobacco smoke exposure. Int J Cardiol. 2012;155:472–3.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Park M, Sweeney G. Direct effects of adipokines on the heart: focus on adiponectin. Heart Fail Rev. 2013;18:631–44.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Soeki T, Kishimoto I, Schwenke DO, Tokudome T, Horio T, Yoshida M, et al. Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. Am J Physiol Heart Circ Physiol. 2008;294:H426–32.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Cokkinos DV, Chryssanthopoulos S. Thyroid hormones and cardiac remodeling. Heart Fail Rev. 2016;21:365–72.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Pantos C, Mourouzis I, Markakis K, Dimopoulos A, Xinaris C, Kokkinos AD, et al. Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats. Eur J Cardiothorac Surg. 2007;32:333–9.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Pantos C, Mourouzis I, Markakis K, Tsagoulis N, Panagiotou M, Cokkinos DV. Long-term thyroid hormone administration reshapes left ventricular chamber and improves cardiac function after myocardial infarction in rats. Basic Res Cardiol. 2008;103:308–18.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Pantos C, Mourouzis I, Tsagoulis N, Markakis K, Galanopoulos G, Roukounakis N et al. Thyroid hormone at supra-physiological dose optimizes cardiac geometry and improves cardiac function in rats with old myocardial infarction. J Physiol Pharmacol 2009;60:49–56.Google Scholar
  149. 149.
    Kalofoutis C, Mourouzis I, Galanopoulos G, Dimopoulos A, Perimenis P, Spanou D, et al. Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction. Mol Cell Biochem. 2010;345:161–9.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Henderson KK, Danzi S, Paul JT, Leya G, Klein I, Samarel AM. Physiological replacement of T3 improves left ventricular function in an animal model of myocardial infarction–induced congestive heart failure. Circ Heart Fail. 2009;2:243–52.PubMedCrossRefPubMedCentralGoogle Scholar
  151. 151.
    Mahaffey KW, Raya TE, Pennock GD, Morkin E, Goldman S. Left ventricular performance and remodeling in rabbits after myocardial infarction. Effects of a thyroid hormone analogue. Circulation. 1995;91:794–801.PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Chen YF, Weltman NY, Li X, Youmans S, Krause D, Gerdes AM. Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats. J Transl Med. 2013;11:40.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Chen YF, Pottala JV, Weltman NY, Ge X, Savinova OV, Gerdes AM. Regulation of gene expression with thyroid hormone in rats with myocardial infarction. PLoS One. 2012;7:e40161.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Chen YF, Kobayashi S, Chen J, Redetzke RA, Said S, Liang Q, et al. Short term triiodo-L-thyronine treatment inhibits cardiac myocyte apoptosis in border area after myocardial infarction in rats. J Mol Cell Cardiol. 2008;44:180–7.CrossRefGoogle Scholar
  155. 155.
    Mourouzis I, Mantzouratou P, Galanopoulos G, Kostakou E, Roukounakis N, Kokkinos AD, et al. Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings. Mol Cell Biochem. 2012;363:235–43.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia–reperfusion injury in mouse heart. Circulation. 2000;101:660–7.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Matsui T, Tao J, del Monte F, Lee KH, Li L, Picard M, et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation. 2001;104:330–5.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Matsui T, Li L, Wu JC, Cook SA, Nagoshi T, Picard MH, et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem. 2002;277:22896–901.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Nagoshi T, Matsui T, Aoyama T, Leri A, Anversa P, Li L, et al. PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest. 2005;115:2128–38.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Rajagopalan V, Gerdes AM. Role of thyroid hormones in ventricular remodeling. Curr Heart Fail Rep. 2015;12:141–9.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Goglia F, Moreno M, Lanni A. Action of thyroid hormones at the cellular level: the mitochondrial target. FEBS Lett. 1999;452:115–20.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Maity S, Kar D, De K, Chander V, Bandyopadhyay A. Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion. J Endocrinol. 2013;217:215–28.PubMedCrossRefPubMedCentralGoogle Scholar
  163. 163.
    De Sibio MT, Luvizotto RA, Olimpio RM, Corrêa CR, Marino J, de Oliveira M, et al. A comparative genotoxicity study of a supraphysiological dose of triiodothyronine (T3) in obese rats subjected to either calorie-restricted diet or hyperthyroidism. PLoS One. 2013;8(2):e56913.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Chen S, Shauer A, Zwas DR, Lotan C, Keren A, Gotsman I. The effect of thyroid function on clinical outcome in patients with heart failure. Eur J Heart Fail. 2014;16:217–26.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Lymvaios I, Mourouzis I, Cokkinos DV, Dimopoulos MA, Toumanidis ST, Pantos C. Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association? Eur J Endocrinol. 2011;165:107–14.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Pingitore A, Nicolini G, Kusmic C, Iervasi G, Grigolini P, Forini F. Cardioprotection and thyroid hormones. Heart Fail Rev. 2016;21:391–9.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Iervasi G. THIRST. Thyroid hormone replacement therapy in ST elevation myocardial infarction (the PONTE study). Cambridge; January 31, 2012.Google Scholar
  168. 168.
    Pantos C, Mourouzis I. Translating thyroid hormone effects into clinical practice: the relevance of thyroid hormone receptor α1 in cardiac repair. Heart Fail Rev. 2015;20:273–82.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 169.
    Pantos C, Mourouzis I, Paizis I, Malliopoulou V, Xinaris C, Moraitis P, et al. Pharmacological inhibition of TRalpha1 receptor potentiates the thyroxine effect on body weight reduction in rats: potential therapeutic implications in controlling body weight. Diabetes Obes Metab. 2007;9:136–8.PubMedCrossRefPubMedCentralGoogle Scholar
  170. 170.
    Kubin T, Pöling J, Kostin S, Gajawada P, Hein S, Rees W, et al. Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell. 2011;9:420–32.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Garza MA, Wason EA, Zhang JQ. Cardiac remodeling and physical training post myocardial infarction. World J Cardiol. 2015;7:52–64.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004;18:1150–2.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 173.
    Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, et al. Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation. 2005;111:1763–70.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Hammett CJ, Prapavessis H, Baldi JC, Varo N, Schoenbeck U, Ameratunga R, et al. Effects of exercise training on 5 inflammatory markers associated with cardiovascular risk. Am Heart J. 2006;151:367.e7–367.e16.CrossRefGoogle Scholar
  175. 175.
    Giannuzzi P, Temporelli PL, Corrà U, Tavazzi L, ELVD-CHF Study Group. Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure: results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) trial. Circulation. 2003;108:554–9.CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Dubach P, Myers J, Dziekan G, Goebbels U, Reinhart W, Vogt P, et al. Effect of exercise training on myocardial remodeling in patients with reduced left ventricular function after myocardial infarction: application of magnetic resonance imaging. Circulation. 1997;95:2060–7.PubMedCrossRefPubMedCentralGoogle Scholar
  177. 177.
    Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. J Am Coll Cardiol. 2007;49:2329–36.PubMedCrossRefPubMedCentralGoogle Scholar
  178. 178.
    Adamopoulos S, Gouziouta A, Mantzouratou P, Laoutaris ID, Dritsas A, Cokkinos DV, et al. Thyroid hormone signalling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices: potential physiological consequences? Interact Cardiovasc Thorac Surg. 2013;17:664–8.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 179.
    Wei M, Xin P, Li S, Tao J, Li Y, Li J, et al. Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Circ Res. 2011;108:1220–05.PubMedCrossRefPubMedCentralGoogle Scholar
  180. 180.
    Hausenloy D, Yellon D. Ischemic conditioning and reperfusion injury. Nat Rev Cardiol. 2016;13:193–209.PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    Clarke CL, Grunwald GK, Allen LA, Barón AE, Peterson PN, Brand DW, et al. Natural history of left ventricular ejection fraction in patients with heart failure. Circ Cardiovasc Qual Outcomes. 2013;6:680–6.PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Goldfinger JZ, Nair AP. Myocardial recovery and the failing heart: medical, device and mechanical methods. Ann Glob Health. 2014;80:55–60.PubMedCrossRefPubMedCentralGoogle Scholar
  183. 183.
    Shah AM, Mann DL. In search of new therapeutic targets and strategies for heart failure: recent advances in basic science. Lancet. 2011;378:704–12.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Kramer DG, Trikalinos TA, Kent DM, Antonopoulos GV, Konstam MA, Udelson JE. Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a meta-analytic approach. J Am Coll Cardiol. 2010;56:392–406.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA 3rd, et al. ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012;60:1297–313.PubMedCrossRefPubMedCentralGoogle Scholar
  186. 186.
    European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA), Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on Cardiac Pacing and Resynchronization Therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace. 2013;15:1070–118.CrossRefGoogle Scholar
  187. 187.
    Sze E, Daubert JP. Left bundle branch block: is it "unsafe at any speed"? JACC Heart Fail. 2016;4:904–6.PubMedCrossRefPubMedCentralGoogle Scholar
  188. 188.
    Hessel MH, Bleeker GB, Bax JJ, Henneman MM, den Adel B, Klok M, et al. Reverse ventricular remodelling after cardiac resynchronization therapy is associated with a reduction in serum tenascin-C and plasma matrix metalloproteinase-9 levels. Eur J Heart Fail. 2007;9:1058–63.PubMedCrossRefPubMedCentralGoogle Scholar
  189. 189.
    Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, et al. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005;112:1580–6.PubMedCrossRefPubMedCentralGoogle Scholar
  190. 190.
    St John Sutton MG, Plappert T, Abraham WT, Smith AL, Delurgio DB, Leon AR, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation. 2003;107:1985–90.PubMedCrossRefPubMedCentralGoogle Scholar
  191. 191.
    Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, et al. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009;54:1837–46.PubMedCrossRefPubMedCentralGoogle Scholar
  192. 192.
    Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352:1539–49.PubMedCrossRefPubMedCentralGoogle Scholar
  193. 193.
    Cleland JGF. Should we be trying to define responders to cardiac resynchronization therapy? J Am Coll Cardiol 2010;2010:04.003.Google Scholar
  194. 194.
    Solomon SD, Foster E, Bourgoun M, Shah A, Viloria E, Brown MW, et al. Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy. Circulation. 2010;122:985–92.PubMedCrossRefPubMedCentralGoogle Scholar
  195. 195.
    St John Sutton M, Cerkvenik J, Borlaug BA, Daubert C, Gold MR, Ghio S, et al. Effects of cardiac resynchronization therapy on cardiac remodeling and contractile function: results from resynchronization reverses remodeling in systolic left ventricular dysfunction (REVERSE). J Am Heart Assoc. 2015;4:e002054.PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Gold MR, Daubert C, Abraham WT, Ghio S, St John Sutton S, Hudnall JH, et al. The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: results of the REVERSE study. Heart Rhythm. 2015;12:524–30.PubMedCrossRefPubMedCentralGoogle Scholar
  197. 197.
    Waring AA, Litwin SE. Redefining reverse remodeling: can echocardiography refine our ability to assess response to heart failure treatments? J Am Coll Cardiol. 2016;68:1277–80.PubMedCrossRefPubMedCentralGoogle Scholar
  198. 198.
    Sekaran NK, Crowley AL, de Souza FR, Resende ES, Rao SV. The role for cardiovascular remodeling in cardiovascular outcomes. Curr Atheroscler Rep. 2017;19:23.PubMedCrossRefPubMedCentralGoogle Scholar
  199. 199.
    Mathias A, Moss AJ, McNitt S, Zareba W, Goldenberg I, Solomon SD, et al. Clinical implications of complete left-sided reverse remodeling with cardiac resynchronization therapy: a MADIT-CRT substudy. J Am Coll Cardiol. 2016;68:1268–76.PubMedCrossRefPubMedCentralGoogle Scholar
  200. 200.
    St John Sutton M, Plappert T, Adamson PB, Li P, Christman SA, Chung ES, et al. Left ventricular reverse remodeling with biventricular versus right ventricular pacing in patients with atrioventricular block and heart failure in the BLOCK HF trial. Circ Heart Fail. 2015;8:510–8.PubMedCrossRefPubMedCentralGoogle Scholar
  201. 201.
    Vanderheyden M, Mullens W, Delrue L, Goethals M, de Bruyne B, Wijns W, Geelen P, et al. Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy responders versus nonresponders. J Am Coll Cardiol. 2008;51:129–36.PubMedCrossRefPubMedCentralGoogle Scholar
  202. 202.
    Krenz M, Robbins J. Impact of beta-myosin heavy chain expression on cardiac function during stress. J Am Coll Cardiol. 2004;44:2390–7.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Liu X, Yang HJ, Ping HQ, Qiu S, Shi S, Yang B. The safety and efficacy of cardiac contractility modulation in heart failure: a meta-analysis of clinical trials. Herz. 2017;  https://doi.org/10.1007/s00059-016-4514-5.PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Puehler T, Ensminger S, Schoenbrodt M, Börgermann J, Rehn E, Hakim-Meibodi K, et al. Mechanical circulatory support devices as destination therapy—current evidence. Ann Cardiothorac Surg. 2014;3:513–24.PubMedPubMedCentralGoogle Scholar
  205. 205.
    Imamura T, Kinugawa K, Nitta D, Hatano M, Kinoshita O, Nawata K, et al. Advantage of pulsatility in left ventricular reverse remodeling and aortic insufficiency prevention during left ventricular assist device treatment. Circ J. 2015;79:1994–9.PubMedCrossRefPubMedCentralGoogle Scholar
  206. 206.
    Krabatsch T, Schweiger M, Dandel M, Stepanenko A, Drews T, Potapov E, et al. Is bridge to recovery more likely with pulsatile left ventricular assist devices than with nonpulsatile-flow systems? Ann Thorac Surg. 2011;91:1335–40.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Torre-Amione G, Stetson SJ, Youker KA, Durand JB, Radovancevic B, Delgado RM, et al. Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support: a potential mechanism for cardiac recovery. Circulation. 1999;100:1189–93.PubMedCrossRefPubMedCentralGoogle Scholar
  208. 208.
    Hall JL, Birks EJ, Grindle S, Cullen ME, Barton PJ, Rider JE, et al. Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy. Eur Heart J. 2007;28:613–27.PubMedCrossRefPubMedCentralGoogle Scholar
  209. 209.
    Blaxall BC, Tschannen-Moran BM, Milano CA, Koch WJ. Differential gene expression and genomic patient stratification following left ventricular assist device support. J Am Coll Cardiol. 2003;41:1096–106.PubMedCrossRefPubMedCentralGoogle Scholar
  210. 210.
    Mitchell A, Guan W, Staggs R, Hamel A, Hozayen S, Adhikari N, et al. Identification of differentially expressed transcripts and pathways in blood one week and six months following implant of left ventricular assist devices. PLoS One. 2013;8:e77951.PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Ambardekar AV, Buttrick PM. Reverse remodeling with left ventricular assist devices: a review of clinical, cellular, and molecular effects. Circ Heart Fail. 2011;4:224–33.PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Topkara VK, Chambers KT, Yang KC, Tzeng HP, Evans S, Weinheimer C, et al. Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling. JCI Insight. 2016;1:e86038.PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    Jacobs S, Geens J, Rega F, Burkhoff D, Meyns B. Continuous-flow left ventricular assist devices induce left ventricular reverse remodeling. J Heart Lung Transplant. 2013;32:466–8.PubMedCrossRefPubMedCentralGoogle Scholar
  214. 214.
    Marinescu KK, Uriel N, Mann DL, Burkhoff D. Left ventricular assist device-induced reverse remodeling: it's not just about myocardial recovery. Expert Rev Med Devices. 2017;14:15–26.PubMedCrossRefPubMedCentralGoogle Scholar
  215. 215.
    Basuray A, French B, Ky B, Vorovich E, Olt C, Sweitzer NK, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation. 2014;129:2380–7.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Basuray A, Fang JC. Management of patients with recovered systolic function. Prog Cardiovasc Dis. 2016;58:434–43.PubMedCrossRefPubMedCentralGoogle Scholar
  217. 217.
    de Groote P, Fertin M, Duva Pentiah A, Goéminne C, Lamblin N, Bauters C. Long-term functional and clinical follow-up of patients with heart failure with recovered left ventricular ejection fraction after β-blocker therapy. Circ Heart Fail. 2014;7:434–9.PubMedCrossRefPubMedCentralGoogle Scholar
  218. 218.
    Givertz MM, Mann DL. Epidemiology and natural history of recovery of left ventricular function in recent onset dilated cardiomyopathies. Curr Heart Fail Rep. 2013;10:321–30.PubMedCrossRefPubMedCentralGoogle Scholar
  219. 219.
    Pan S, Aksut B, Wever-Pinzon OE, Rao SD, Levin AP, Garan AR, et al. Incidence and predictors of myocardial recovery on long-term left ventricular assist device support: results from the United Network for Organ Sharing database. J Heart Lung Transplant. 2015;34:1624–9.PubMedCrossRefPubMedCentralGoogle Scholar
  220. 220.
    Drakos SG, Mehra MR. Clinical myocardial recovery during long-term mechanical support in advanced heart failure: insights into moving the field forward. J Heart Lung Transplant. 2016;35:413–20.PubMedCrossRefPubMedCentralGoogle Scholar
  221. 221.
    Selzman CH, Madden JL, Healy AH, McKellar SH, Koliopoulou A, Stehlik J, et al. Bridge to removal: a paradigm shift for left ventricular assist device therapy. Ann Thorac Surg. 2015;99:360–7.PubMedCrossRefPubMedCentralGoogle Scholar
  222. 222.
    Klotz S, Danser AH, Foronjy RF, Oz MC, Wang J, Mancini D, et al. The impact of angiotensin-converting enzyme inhibitor therapy on the extracellular collagen matrix during left ventricular assist device support in patients with end-stage heart failure. J Am Coll Cardiol. 2007;49:1166–74.PubMedCrossRefPubMedCentralGoogle Scholar
  223. 223.
    Soucy KG, Smith EF, Monreal G, Rokosh G, Keller BB, Yuan F, et al. Feasibility study of particulate extracellular matrix (P-ECM) and left ventricular assist device (HVAD) therapy in chronic ischemic heart failure bovine model. ASAIO J. 2015;61:161–9.PubMedCrossRefPubMedCentralGoogle Scholar
  224. 224.
    Zavadzkas JA, Stroud RE, Bouges S, Mukherjee R, Jones JR, Patel RK, et al. Targeted overexpression of tissue inhibitor of matrix metalloproteinase-4 modifies post-myocardial infarction remodeling in mice. Circ Res. 2014;114:1435–45.PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    Felkin LE, Lara-Pezzi E, George R, Yacoub MH, Birks EJ, Barton PJ. Expression of extracellular matrix genes during myocardial recovery from heart failure after left ventricular assist device support. J Heart Lung Transplant. 2009;28:117–22.PubMedCrossRefPubMedCentralGoogle Scholar
  226. 226.
    Markham DW, Fu Q, Palmer MD, Drazner MH, Meyer DM, Bethea BT, et al. Sympathetic neural and hemodynamic responses to upright tilt in patients with pulsatile and nonpulsatile left ventricular assist devices. Circ Heart Fail. 2013;6:293–9.PubMedCrossRefPubMedCentralGoogle Scholar
  227. 227.
    Westman PC, Lipinski MJ, Luger D, Waksman R, Bonow RO, Wu E, et al. Inflammation as a driver of adverse left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol. 2016;67:2050–60.PubMedCrossRefPubMedCentralGoogle Scholar
  228. 228.
    Grosman-Rimon L, Jacobs I, Tumiati LC, McDonald MA, Bar-Ziv SP, Fuks A, et al. Longitudinal assessment of inflammation in recipients of continuous-flow left ventricular assist devices. Can J Cardiol. 2015;31:348–56.PubMedCrossRefPubMedCentralGoogle Scholar
  229. 229.
    Grosman-Rimon L, McDonald MA, Jacobs I, Tumiati LC, Pollock Bar-Ziv S, Shogilev DJ, et al. Markers of inflammation in recipients of continuous-flow left ventricular assist devices. ASAIO J. 2014;60:657–63.PubMedCrossRefPubMedCentralGoogle Scholar
  230. 230.
    Baskin KK, Taegtmeyer H. Taking pressure off the heart: the ins and outs of atrophic remodelling. Cardiovasc Res. 2011;90:243–50.PubMedPubMedCentralCrossRefGoogle Scholar
  231. 231.
    Cao DJ, Jiang N, Blagg A, Johnstone JL, Gondalia R, Oh M, et al. Mechanical unloading activates FoxO3 to trigger Bnip3-dependent cardiomyocyte atrophy. J Am Heart Assoc. 2013;2:e000016.PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    Barbone A, Holmes JW, Heerdt PM, The’ AH, Naka Y, Joshi N, et al. Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure: a primary role of mechanical unloading underlying reverse remodeling. Circulation. 2001;104:670–5.PubMedCrossRefPubMedCentralGoogle Scholar
  233. 233.
    Ahmad T, Wang T, O'Brien EC, Samsky MD, Pura JA, Lokhnygina Y, et al. Effects of left ventricular assist device support on biomarkers of cardiovascular stress, fibrosis, fluid homeostasis, inflammation, and renal injury. JACC Heart Fail. 2015;3:30–9.PubMedCrossRefPubMedCentralGoogle Scholar
  234. 234.
    Matkovich SJ, Van Booven DJ, Youker KA, Torre-Amione G, Diwan A, Eschenbacher WH, et al. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation. 2009;119:1263–71.PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Lok SI, de Jonge N, van Kuik J, van Geffen AJ, Huibers MM, van der Weide P, et al. MicroRNA expression in myocardial tissue and plasma of patients with end-stage heart failure during LVAD support: comparison of continuous and pulsatile devices. PLoS One. 2015;10:e0136404.PubMedPubMedCentralCrossRefGoogle Scholar
  236. 236.
    Schipper ME, van Kuik J, de Jonge N, Dullens HF, de Weger RA. Changes in regulatory microRNA expression in myocardium of heart failure patients on left ventricular assist device support. J Heart Lung Transplant. 2008;27:1282–5.PubMedCrossRefPubMedCentralGoogle Scholar
  237. 237.
    Topkara VK, Garan AR, Fine B, Godier-Furnémont AF, Breskin A, Cagliostro B, et al. Myocardial recovery in patients receiving contemporary left ventricular assist devices: results from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Circ Heart Fail 2016;9. doi: 10.1161/CIRCHEARTFAILURE.116.003157.Google Scholar
  238. 238.
    Drakos SG, Pagani FD, Lundberg MS, Baldwin TJ. Advancing the science of myocardial recovery with mechanical circulatory support: a working group of the National Heart, Lung, and Blood Institute. J Thorac Cardiovasc Surg. 2017;154:165–70.PubMedCrossRefPubMedCentralGoogle Scholar
  239. 239.
    Gustafsson F, Rogers JG. Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes. Eur J Heart Fail. 2017;19:595–602.PubMedCrossRefPubMedCentralGoogle Scholar
  240. 240.
    Starling RC, Estep JD, Horstmanshof DA, Milano CA, Stehlik J, Shah KB, et al. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: the ROADMAP study 2-year results. JACC Heart Fail. 2017;5:518–27.PubMedCrossRefPubMedCentralGoogle Scholar
  241. 241.
    Mehra MR, Goldstein DJ, Uriel N, Cleveland JC, Yuzefpolskaya M, Salerno C, Walsh MN, Milano CA, Patel CB, Ewald GA, Itoh A, Dean D, Krishnamoorthy A, Cotts WG, Tatooles AJ, Jorde UP, Bruckner BA, Estep JD, Jeevanandam V, Sayer G, Horstmanshof D, Long JW, Gulati S, Skipper ER, O’Connell JB, Heatley G, Sood P, Naka Y. Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure. N Eng J Med. 2018;378(15):1386–95.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Heart and Vessel DepartmentBiomedical Research Foundation, Academy of Athens - Gregory SkalkeasAthensGreece

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