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Cardiac Remodeling: From Concepts to Therapeutics

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Abstract

Cardiac dysfunction in heart failure is widely recognized as a progressive process regardless of clinical signs and symptoms. It is now well accepted that the key to success in reducing the extremely high morbidity and mortality associated with heart failure is slowing or reversing the process of disease progression by favorably altering the course of cardiac remodeling. Thus, a paradigm shift from symptomatic control towards treating the pathophysiologic processes that underlie remodeling has emerged. The shift from traditional concepts that heart failure is merely a 'muscle dysfunction' problem, and hence intervention to support function as remedy to the problem has emanated from the sober recognition that strategies aimed to correct hemodynamic and cardiac contraction dysfunction neither prevent the progression of heart failure nor improve mortality. The only medical interventions that provided some remedy (in the form of reduced morbidity and mortality) are those that affect neurohormonal systems which either directly or indirectly modulate cardiac remodeling. Such systems include the renin-angiotensin-aldosterone and the sympathetic nervous system. This brief review of cardiac remodeling and heart failure provides definitions and concepts that underlie contemporary understanding of heart failure. We also summarize cellular and molecular mechanisms that underwrite the remodeling process and their impact on clinical outcome.

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References

  1. Kostuk KWJ, Kazamias TM, Simon AL, et al. Left ventricular size after acute myocardial infarction: Serial changes and their prognostic significance. Circulation 1973;47:1174–1179.

    Google Scholar 

  2. White HD, Norris RM, Brown MA, et al. Left ventricular end-systolic volume as the major determinant of survival after recovery from endomyocardial infarction. Circulation 1987;76:44–51.

    Google Scholar 

  3. Linzbach AJ. Heart failure from the point of view of quantitative autonomy. Am J Cardiol 1960;5:370–382.

    Google Scholar 

  4. G Ich RW, Jacob R. Geometric and muscle physiological determinants of cardiac stroke volume as evaluation on the basis of model calculation. Basic Res Cardiol 1988;83: 476–485.

    Google Scholar 

  5. Maisch B. Ventricular remodeling. Cardiology 1996;87 (Suppl I):2–10.

    Google Scholar 

  6. Carr A, Prisant M, Watkins L. Detection of hypertensive left ventricular hypertrophy. Hypertension 1985;7:948–954.

    Google Scholar 

  7. Kannel W, Gordon T, Offutt D. Left ventricular hypertrophy by electrocardiogram. Ann Int Med 1969;71:89–106.

    Google Scholar 

  8. Krzesinski JM, Rorive G, Cauwenberge V. Hypertension and left ventricular hypertrophy. Acta Cardiologica 1996; 51:143–154.

    Google Scholar 

  9. Gottdiener J. Left ventricular mass, diastolic dysfunction and hypertension. Adv Int Med 1993;38:31–56.

    Google Scholar 

  10. Casale P, Devereux R, Milner M, et al. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Int Med 1986;105:173–178.

    Google Scholar 

  11. Levy D, Garrison R, Savage D, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study. N Eng J Med 1990;322: 1561–1566.

    Google Scholar 

  12. Ollivier J-P, Bouchet VA. Prospects for cardioreparation. Am J Cardiol 1992;70:27–36C.

    Google Scholar 

  13. Gaudron P, Eilles C, Kugler I, et al. Progressive left ventricular dysfunction and remodeling after myocardial infarction: Potential mechanisms and early predictors. Circulation 1993;87:755–763.

    Google Scholar 

  14. Hammermeister KE. DeRouen TA, Dodge HT. Variables predictive of survival in patients with coronary disease. Selection by univariate and multivariate analyses from the clinical, electrocardiographic, exercise, arteriographic, and quantitative angiographic values. Circulation 1979;59:421–430.

    Google Scholar 

  15. Pfeffer MA, Lamas GA, Vaughan DE, et al. Effect of captopril on progressive ventricular dilation after anterior myocardial infarction. N Engl J Med 1988;319:80–86.

    Google Scholar 

  16. Frank JS, Langer GA. The myocardial interstitium: Its structure and its role in ionic exchange. J Cell Biol 1974; 60:586–601.

    Google Scholar 

  17. Brilla CG, Maisch B, Weber KT. Myocardial collagen matrix remodeling in arterial hypertension. Eur Heart J 1992;13 (Suppl D):24–32.

    Google Scholar 

  18. Weber KT, Brilla CG, Campbell SE. Regulatory mechanisms of myocardial hypertrophy and fibrosis: Results of in vivo studies. Cardiology 1992;81:266–273.

    Google Scholar 

  19. Freeman BA, Crapo ID. Biology of disease. Free radicals and tissue injury. Lab Invest 1982;47:412–426.

    Google Scholar 

  20. Saugstad OD, Aasen AO. Plasma hypoxanthine concentrations in pigs: A prognostic aid in hypoxia. Eur Surg Res 1980;12:123–129.

    Google Scholar 

  21. Coker SJ, Parratt JR. Ledingham IM, et al. Thromboxane and prostacyclin release from ischaemic myocardium in relation to arrhythmias. Nature 1981;29:323–324.

    Google Scholar 

  22. Hammond B, Kantos HA, Hess ML. Oxygen radicals in the adult respiratory distress syndrome, in myocardial ischaemia and reperfusion injury, and in cerebral vascular damage. Can J Physiol Pharmacol 1985;63:173–182.

    Google Scholar 

  23. Ferrari R, Ceconi C, Corello S, et al. Intracellular effects of myocardial ischaemia and reperfusion: Role of calcium and oxygen. Eur Heart J 1986;7:3–12.

    Google Scholar 

  24. Ferrari R, Alfieri O, Corello S, et al. Occurrence of oxidative stress during reperfusion of the human heart. Circulation 1990;81:201–211.

    Google Scholar 

  25. Sharov VG, Sabbah HN, Shimoyama H, Goussev AV, Lesch M, Goldstein S. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol 1996; 148:141–149.

    Google Scholar 

  26. Teiger E, Dam T-V, Richard L, et al. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest 1996;97:2891–2897.

    Google Scholar 

  27. James TN, St Martin E, Willis PWI, et al. Apoptosis as a possible cause of gradual development of complete heart block and fatal arrhythmias associated with the absence of the AV node, sinus node, and internodal pathways. Circulation 1996;93:1424–1438.

    Google Scholar 

  28. Hamet P, Moreau P, Dam T-V, et al. The time window of apoptosis: A new component in the therapeutic strategy for cardiovascular remodeling. J Hypertension 1996;14(Suppl 5):S65–S70.

    Google Scholar 

  29. Yue TL, Ma XL, Wang XK, Romanic AM, Liu GL, Loudon C, Gu JL, Poste G, Ruffolo RR, Feuerstein G. Possible involvement of stress activated protein kinase signaling pathway and fas receptor expression in prevention of ischemia reperfusion-induced cardiomyocyte apoptosis by carvedilol. Circ Res 1998;82:166–174.

    Google Scholar 

  30. Shimoyama H, Sabbah HN, Borcak S, Tanimura M, Shevlyagin S, Scieli G, Goldstein S. Short term hemodynamic effects of endothelin receptor blockade in dogs with chronic heart failure. Circulation 1996;94:643–650.

    Google Scholar 

  31. Buttke TM, Sondstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994;15:1–10.

    Google Scholar 

  32. Weber KT, Brilla CG. Pathological hypertrophy and the car-diac interstitium: Fibrosis and the renin-angiotensin-aldosterone system. Circulation 1991;83:1849–1865.

    Google Scholar 

  33. Schelling P, Ganten D, Speck G, et al. Effect of angiotensin II and antagonist saralasin on cell growth and renin in 3T3 and SV 3T3 cells. J Cell Physiol 1979;98:503–514.

    Google Scholar 

  34. Katz AM. Cardiomyopathy of overload: A major determinant of prognosis in congestive heart failure. N Engl J Med 1990;322:100–110.

    Google Scholar 

  35. Zhang J, McDonald KM. Bioenergetic consequences of left ventricular remodeling. Circulation 1995;92:1011–1019.

    Google Scholar 

  36. Apstein CS, Mueller M, Hood WBJ. Ventricular contracture and compliance changes with global ischemia and reperfusion and their effect on coronary resistance in the rat. Cir Res 1977;41:206–217.

    Google Scholar 

  37. Francis GS, McDonald KM. Left ventricular hypertrophy: An initial response to myocardial injury. Am J Cardiol 1992; 69:3–9G.

    Google Scholar 

  38. Sadoshima J, Izumo S. Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the ATI receptor subtype. Circ Res 1993;73:413–423.

    Google Scholar 

  39. Reiss K, Capasso JM, Huang HE, et al. ANG II receptors, c-myc, and c-jun in myocytes after myocardial infarction and ventricular failure. Am J Physiol 1993;264:H760–H769.

    Google Scholar 

  40. Everett AD, Tufro-McReddie A, Fisher A, et al. Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-beta 1 expression. Hypertension 1994;23: 587–592.

    Google Scholar 

  41. Pfeffer JM, Fischer TA, Pfeffer MA. Angiotensin-converting enzyme inhibition and ventricular remodeling after myocardial infarction. Ann Rev Physiol 1995;57:805–826.

    Google Scholar 

  42. Johnston CI. Tissue angiotensin-converting enzyme in cardiac hypertrophy, repair, and remodeling. Hypertension 1994;23:258–268.

    Google Scholar 

  43. Olivetti G, Capasso JM, Sonnenblick EH, et al. Side-toside slippage of myocytes in ventricular wall remodeling acutely after myocardial infarction in rats. Circ Res 1990; 67:23–34.

    Google Scholar 

  44. Weber KT, Brilla CG. Structural basis for pathologic left ventricular hypertrophy. Clin Cardiol 1993;16:1110–1114.

    Google Scholar 

  45. Brilla CG, Reams GP, Maisch B, et al. Renin-angiotensin system and myocardial fibrosis in hypertension: Regulation of the myocardial collagen matrix. Eur Heart J 1993;14 (Suppl):57–61.

    Google Scholar 

  46. Villarreal FJ, Kim NN, Ungab GD, et al. Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation 1993;88:2849–2861.

    Google Scholar 

  47. Brilla CG, Janicki JS, Weber KT. Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy. Circulation 1991;83:1771–1779.

    Google Scholar 

  48. Weber KT, Brilla CG, Cleland JG, et al. Cardioreparation and the concept of modulating cardiovascular structure and function. Blood Pressure 1993;2:6–21.

    Google Scholar 

  49. Schieffer B, Wirger A, Meybrunn M, et al. Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type I receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation 1994;89:2273–2282.

    Google Scholar 

  50. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure: A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation 1990;82:1724–1729.

    Google Scholar 

  51. Dzau VJ. Implications of local angiotensin production in cardiovascular physiology and pharmacology. Am J Cardiol 1987;59:59–65A.

    Google Scholar 

  52. Urata H, Healy B, Steward RW, et al. Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab 1989;69:54–66.

    Google Scholar 

  53. Helin K, Stoll M, Meffert S, et al. The role of angiotensin receptors in cardiovascular diseases. Ann Med 1997;29:v 23–29.

    Google Scholar 

  54. Brilla CG, Zhou G, Matsubara L, et al. Collagen metabolism in cultured adult rat cardiac fibroblasts: Response to angiotensin II and aldosterone. J Mol Cell Cardiol 1994;26:809–820.

    Google Scholar 

  55. MacCumber M, Ross C, Glaser B, et al. Endothelin: Visualization of mRNAs by in situ hybridization provides evidence for local action. Proc Natl Acad Sci USA 1989;86:7258–7259.

    Google Scholar 

  56. Lerman A, Hildebrand F, Aarhus L, et al. Endothelin has biological action at pathophysiological concentrations. Circulation 1991;83:1808–1814.

    Google Scholar 

  57. Shichiri M, Hirata Y, Nakajima T, et al. Endothelin-I is an autocrine/paracrine growth factor for human cancer cells. J Clin Invest 1991;87:1867–1895.

    Google Scholar 

  58. Feldman MD, Copelas L, Gwathmey JK, et al. Deficient production of cyclic AMP: Pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 1987;75:331–339.

    Google Scholar 

  59. Spann JF, Chidsey CA, Pool PE, et al. Mechanism of norepinephrine depletion in experimental heart failure produced by aortic constriction in the guinea pig. Cir Res 1965; 17:312–321.

    Google Scholar 

  60. Bristow MR, Ginsburg R, Minobe W, et al. Decreased catecholamine sensitivity and β-adrenergic receptor density in failing human hearts. N Eng J Med 1982;307:205–211.

    Google Scholar 

  61. Fowler MB, Laser JA, Hopkins GL, et al. Assessment of the fl-adrenergic receptor pathway in the intact failing human heart: Progressive receptor down-regulation and subsensitivity to agonist response. Circulation 1986;74:1290–1302.

    Google Scholar 

  62. Daly PA, Sole MJ. Myocardial catecholamines and the pathophysiology of heart failure. Circulation 1990;82(Suppl I):I-35–I-43.

    Google Scholar 

  63. Ostman-Smith I. Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci 1981;I:265–272.

    Google Scholar 

  64. Simpson P, McGrath A, Savion S. Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines. Cir Res 1982;51:787–801.

    Google Scholar 

  65. Starksen NF, Simpson PC, Bishopric N, et al. Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Pro Nat Acad Sci USA 1986;83:8348–8350.

    Google Scholar 

  66. Rona G, Chappel CI, Balazs T, et al. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. Arch Pathol 1959;67:443–455.

    Google Scholar 

  67. Gilbert PL, Siegel RJ, Melmed S, et al. Cardiac morphology in rats with growth hormone-producing tumours. JMol Cell Cardiol 1985;17:805–811.

    Google Scholar 

  68. Ross J, Hongo M. The role of hypertrophy and growth factors in heart failure. J Cardiac Failure 1996;2:S121–S128.

    Google Scholar 

  69. Fine A, Goldstein RH. The effect of transforming growth factor-fl on cell proliferation and collagen formation by lung fibroblasts. J Biol Chem 1987;262:3897–3902.

    Google Scholar 

  70. Goldstein RH, Poliks CF, Pilch PF, et al. Stimulation of collagen formation by insulin and insulin-like growth factor I in cultures of human lung fibroblasts. Endocrinology 1989; 124:946–970.

    Google Scholar 

  71. Anversa P, Reiss K, Kajstura J, et al. Myocardial infarction and the myocyte IGFI autocrine system. Eur Heart J 1995; 16(Suppl N):37–45.

    Google Scholar 

  72. Botney MD, Bahadori L, Gold LI. Vascular remodeling in primary pulmonary hypertension: Potential role for transforming growth factor-fl. Am J Pathol 1994;144:286–295.

    Google Scholar 

  73. Bahadori L, Milder J, Gold LI, et al. Active macrophage-associated TGF-fl colocalizes with type I procollagen gene expression in atherosclerotic human hypertensive pulmonary arteries. Am J Pathol 1995;146:1140–1149.

    Google Scholar 

  74. Mann DL, Lee-Jackson D, Yokoyama T. Tumor necrosis factor alpha and cardiac remodeling. Heart Failure 1995;11: 166–716.

    Google Scholar 

  75. Suffredini AF, Fromm RE, Parker MM, et al. The cardiovascular response of normal humans to the administration of endotoxin. N Eng J Med 1989;321:280–287.

    Google Scholar 

  76. Dayer JM, Beutler B, Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exper Med 1985;162:2163–2168.

    Google Scholar 

  77. Nakao K, Ogawa Y, Suga S, et al. Molecular biology and biochemistry of the natriuretic peptide system I: Natriuretic peptides. J Hypertension 1992;10:907–912.

    Google Scholar 

  78. Itoh H, Pratt RE, Dzau VJ. Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells. J Clin Invest 1990;86:1690–1697.

    Google Scholar 

  79. Mark AL. Sensitisation of cardiac vagal afferent reflexes at the sensory receptor level: An overview. Federation Proceedings 1987;46:36–40.

    Google Scholar 

  80. Laragh JH. Atrial natriuretic hormone, the renin-angiotensin axis, and blood pressure-electrolyte homeostasis. N Engl J Med 1985;313:1330–1340.

    Google Scholar 

  81. Schafferhans K, Heidbreder E, Grimm D, et al. Norepinephrine-induced acute renal failure: Beneficial effects of atrial natriuretic factor. Nephron 1986;44:240–244.

    Google Scholar 

  82. Itoh H, Nakao K. Antagonism between the vascular reninangiotensin and natriuretic peptide systems in vascular remodeling. Blood Pressure 1994;3:49–53.

    Google Scholar 

  83. Packer M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation 1988;77:721–730.

    Google Scholar 

  84. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109–142.

    Google Scholar 

  85. Oliver JA. Endothelium-derived relaxing factor contributes to the regulation of endothelial permeability. J Cell Physiol 1992;151:506–511.

    Google Scholar 

  86. Oliver JA. Cardiovascular disease and hypertension. Curr Opin Nephrol Hypertension 1993;2:299–306.

    Google Scholar 

  87. Brilla CG, Murphy RLW, Smits JFM, et al. The concept of cardioreparation: Part I. Pathophysiology of remodeling. J Cardiovasc Risk 1996;3:281–285.

    Google Scholar 

  88. Dunn FG, McLenachan JM, Pringle SD. Left ventricular hypertrophy, ventricular arrhythmias and sudden death. In: Cruikshank JM, Messerli FH, eds. Left Ventricular Hypertrophy and Its Regression. London: Science Press, 1992.

    Google Scholar 

  89. McDonagh TA, Morrison CE, Lawrence A, et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet 1997;350:829–833.

    Google Scholar 

  90. Vasan RS, Levy D. The role of hypertension in the pathogenesis of heart failure. Arch Int Med 1996;156:1789–1796.

    Google Scholar 

  91. Hutchins GM, Bulkley BH. Infarct expansion versus extension: Two different complications of acute myocardial infarction. Am J Cardiol 1978;41:1127–1132.

    Google Scholar 

  92. Fishbein MC, MacLean D, Maroko PR. Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Am J Pathol 1978;90: 57–70

    Google Scholar 

  93. Pfeffer JM, Pfeffer MA, Fletcher PJ, et al. Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol 1991;29:H1406–H1414.

    Google Scholar 

  94. Weber KT, Janicki JS. The heart as a muscle-pump system and the concept of heart failure. Am Heart J 1979;98:371–384.

    Google Scholar 

  95. Rumberger JA. Ventricular dilation and remodeling after myocardial infarction. Mayo Clin Proc 1994;69:664–674.

    Google Scholar 

  96. Rumberger JA, Behrenbeck T, Breen JR, et al. Nonparallel changes in global left ventricular chamber volume and muscle mass during the first year after transmural myocardial infarction in humans. J Am Coll Cardiol 1993;21:673–682.

    Google Scholar 

  97. Ertl G, Gaudron P, Neubauer S, et al. Cardiac dysfunction and development of heart failure. Eur Heart J 1993;14(Suppl A):33–37.

    Google Scholar 

  98. Deedwania PC. Prevention of heart failure and postinfarction remodeling. Cardiol Clinics 1994;12:155–164.

    Google Scholar 

  99. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Circulation 1990;81:1161–1172.

    Google Scholar 

  100. Cleland JGF, Dewhurst NG, Murphy RLW, et al. The concept of cardioreparation: Part 2. Medical implications of cardioreparation. J Cardiovasc Risk 1996;3:287–293.

    Google Scholar 

  101. Goldstein RE, Boccuzi SJ, Creuss D, et al. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation 1991;83:52–60.

    Google Scholar 

  102. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: Results of a Veterans Administration Cooperative Study. New Engl J Med 1986;314:1547–1552.

    Google Scholar 

  103. The CONSENSUSTrial Study Group. Effects of enalapril on mortality in severe congestive heart failure: Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). NewEngl J Med 1987;316:1429–1435.

    Google Scholar 

  104. The SOLVD Investigators. The effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. New Engl J Med 1991; 325:293–302.

    Google Scholar 

  105. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. New Engl J Med 1991;325:303–310.

    Google Scholar 

  106. Francis GS, Cohn NJ, Johnson G, et al. Plasma norepinephrine, plasma renin activity, and congestive heart failure. Circulation 1993;87(Suppl VI):VI-40–VI-48.

    Google Scholar 

  107. Waagstein F, Hjälmarson, Varnauskas E, et al. Effect of chronic beta adrenergic receptor blockade in congestive cardiomyopathy. Brit Heart J 1975;37:1022–1036.

    Google Scholar 

  108. Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet 1993;342:1441–1446.

    Google Scholar 

  109. CIBIS Investigators and Committee. A randomized trial of b-blockade in heart failure: The Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation 1994;90:1765–1773.

    Google Scholar 

  110. Packer M, Bristow MR, Cohn JN, for the US Carvedilol Heart Failure Study Group. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. New Engl J Med 1996;334:1349–1355.

    Google Scholar 

  111. Packer M, Colucci WS, Sackner-Bernstein JD, et al. Doubleblind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE trial. Circulation 1996;94:2793–2799.

    Google Scholar 

  112. Gilbert EM, Olsen SL, Renlund DG, et al. Beta-adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy. Am J Cardiol 1993;71: 23C–29C.

    Google Scholar 

  113. Bril A, Slivjak M, DiMartino MJ, et al. Cardioprotective effects of carvedilol, a novel beta adrenoceptor antagonist with vasodilating properties, in anaesthetized minipigs: Comparison with propranolol. Cardiovasc Res 1992;26: 518–525.

    Google Scholar 

  114. Colucci WS, Packer M, Bristow MR, et al. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Circulation 1996;94:2800–2806.

    Google Scholar 

  115. Bristow MR, Gilbert EM, Abraham WT, et al.Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation 1996;94:2807–2816.

    Google Scholar 

  116. Gilbert EM, Abraham WT, Olsen S, et al. Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation 1996;94:2817–2825.

    Google Scholar 

  117. Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet 1997;349:375–380.

    Google Scholar 

  118. Doughty RN, Whalley GA, Gamble G, et al. Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. J Am Coll Cardiol 1997;29:1060–1066.

    Google Scholar 

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Feuerstein, G.Z., Weck, P.K. Cardiac Remodeling: From Concepts to Therapeutics. Heart Fail Rev 4, 7–20 (1999). https://doi.org/10.1023/A:1009847532728

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