Skip to main content
SpringerLink
Log in

Structural Remodeling in the Development of Chronic Systolic Heart Failure: Implication for Treatment

  • Chapter
  • First Online:
Congestive Heart Failure and Cardiac Transplantation

  • 3013 Accesses

Abstract

Ventricular remodeling is a complex process that results from interactions between the initial myocardial injury and neurohormonal factors that are capable of modifying the cardiomyocyte phenotype and of inducing changes in the extracellular matrix. At the cellular level, myocyte hypertrophy, necrosis, apoptosis, interstitial fibrosis, and degradation of collagen are the major features of myocardial remodeling. Each of these components of the remodeling process contributes importantly to the development and progression of heart failure (HF). At the level of the ventricular chamber, remodeling is associated with progressive ventricular hypertrophy, enlargement, and cavity distortion that is directly related to deterioration in ventricular performance and to long-term adverse clinical outcomes.

The mechanisms responsible for ventricular remodeling and deterioration of ventricular structure and function are not entirely clear, but are related to neurohormonal and cytokine activation. These factors in combination with increased wall stress and mechanical stretch of the myocytes upregulate a large number of signaling pathways. This leads to structural and functional changes in the myocyte and nonmyocyte compartments, contributing to ventricular dysfunction and the progression of HF.

Although, initially, it may be compensatory in certain pressure and volume-overload conditions, progressive ventricular remodeling is ultimately a maladaptive process. After myocardial infarction, however, progressive hypertrophy and remodeling of noninfarcted myocardium may be harmful from the start.

Ventricular remodeling has emerged as an important therapeutic target and a credible surrogate end point in HF. Agents that have beneficial effects in HF also generally attenuate or reverse ventricular remodeling, whereas agents that fail to improve clinical outcomes either have no effect on remodeling or have been associated with adverse remodeling. An important goal in the treatment of HF is to slow or reverse remodeling to improve long-term outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Eaton LW, Weiss JL, Bulkley BH, Garrison JB, Weisfeldt ML. Regional cardiac dilatation after acute myocardial infarction: recognition by two-dimensional echocardiography. N Engl J Med. 1979;300(2):57–62.

    Article  CAS  PubMed  Google Scholar 

  2. Erlebacher JA, Weiss JL, Eaton LW, Kallman C, Weisfeldt ML, Burkley BH. Late effects of acute infarct dilation on heart size: a two dimensional echocardiographic study. Am J Cardiol. 1982;49(5):1120–6.

    Article  CAS  PubMed  Google Scholar 

  3. McKay RG, Pfeffer MA, Pasternak RC, Markis JE, Come PC, Nakao S, Alderman JD, Ferguson JJ, Safian RD, Grossman W. Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion. Circulation. 1986;74(4):693–702.

    Article  CAS  PubMed  Google Scholar 

  4. Anand IS, Florea VG. Traditional and novel approaches to management of heart failure: successes and failures. Cardiol Clin. 2008;26(1):59–72.

    Article  PubMed  Google Scholar 

  5. Hill JA, Olson EN. Cardiac plasticity. N Engl J Med. 2008;358(13):1370–80.

    Article  CAS  PubMed  Google Scholar 

  6. Flint A. Diseases of the heart. 2nd ed. Philadelphia, PA: HC Lea; 1870.

    Google Scholar 

  7. Osler W. The principles and practice of medicine. New York, NY: Appleton; 1892.

    Google Scholar 

  8. Linzbach AJ. Heart failure from the point of view of quantitative anatomy. Am J Cardiol. 1960;5:370–82.

    Article  CAS  PubMed  Google Scholar 

  9. Hood Jr WP, Rackley CE, Rolett EL. Wall stress in the normal and hypertrophied human left ventricle. Am J Cardiol. 1968;22(4):550–8.

    Article  PubMed  Google Scholar 

  10. Sandler H, Dodge HT. Left ventricular tension and stress in man. Circ Res. 1963;13:91–104.

    Article  CAS  PubMed  Google Scholar 

  11. Meerson FZ. On the mechanism of compensatory hyperfunction and insufficiency of the heart. Cor Vasa. 1961;3:161–77.

    CAS  PubMed  Google Scholar 

  12. Gunther S, Grossman W. Determinants of ventricular function in pressure-overload hypertrophy in man. Circulation. 1979;59(4):679–88.

    Article  CAS  PubMed  Google Scholar 

  13. Huber D, Grimm J, Koch R, Krayenbuehl HP. Determinants of ejection performance in aortic stenosis. Circulation. 1981;64(1):126–34.

    Article  CAS  PubMed  Google Scholar 

  14. Krayenbuehl HP, Hess OM, Ritter M, Monrad ES, Hoppeler H. Left ventricular systolic function in aortic stenosis. Eur Heart J. 1988;9(Suppl E):19–23.

    Article  PubMed  Google Scholar 

  15. 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 evaluations. Circulation. 1979;59(3):421–30.

    Article  CAS  PubMed  Google Scholar 

  16. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114(5):345–52.

    Article  CAS  PubMed  Google Scholar 

  17. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561–6.

    Article  CAS  PubMed  Google Scholar 

  18. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Levy D. Left ventricular dilatation and the risk of congestive heart failure in people without myocardial infarction. N Engl J Med. 1997;336(19):1350–5.

    Article  CAS  PubMed  Google Scholar 

  19. 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(1):44–51.

    Article  CAS  PubMed  Google Scholar 

  20. Florea VG, Mareyev VY, Samko AN, Orlova IA, Coats AJ, Belenkov YN. Left ventricular remodelling: common process in patients with different primary myocardial disorders. Int J Cardiol. 1999;68(3):281–7.

    Article  CAS  PubMed  Google Scholar 

  21. Hutchins GM, Bulkley BH. Infarct expansion versus extension: two different complications of acute myocardial infarction. Am J Cardiol. 1978;41(7):1127–32.

    Article  CAS  PubMed  Google Scholar 

  22. Hochman JS, Bulkley BH. Expansion of acute myocardial infarction: an experimental study. Circulation. 1982;65(7):1446–50.

    Article  CAS  PubMed  Google Scholar 

  23. Weisman HF, Bush DE, Mannisi JA, Bulkley BH. Global cardiac remodeling after acute myocardial infarction: a study in the rat model. J Am Coll Cardiol. 1985;5(6):1355–62.

    Article  CAS  PubMed  Google Scholar 

  24. Erlebacher JA. Ventricular remodeling in myocardial infarction--the rat and the human. Am J Cardiol. 1985;56(13):910.

    Article  CAS  PubMed  Google Scholar 

  25. Chanutin A, Ludewig S. Experimental renal insufficiency produced by partial nephrectomy. Arch Intern Med. 1939;64(3):513–25.

    Article  CAS  Google Scholar 

  26. Pfeffer JM, Pfeffer MA, Fishbein MC, Frohlich ED. Cardiac function and morphology with aging in the spontaneously hypertensive rat. Am J Physiol. 1979;237(4):H461–8.

    CAS  PubMed  Google Scholar 

  27. Pfeffer J, Pfeffer M, Fletcher P, Braunwald E. Alterations of cardiac performance in rats with established spontaneous hypertension. Am J Cardiol. 1979;44(5):994–8.

    Article  CAS  PubMed  Google Scholar 

  28. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol. 2000;35(3):569–82.

    Article  CAS  PubMed  Google Scholar 

  29. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation. 2000;101(25):2981–8.

    Article  CAS  PubMed  Google Scholar 

  30. Doughty RN, Whalley GA, Gamble G, MacMahon S, Sharpe N. Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group. J Am Coll Cardiol. 1997;29(5):1060–6.

    Article  CAS  PubMed  Google Scholar 

  31. Doughty RN, Whalley GA, Walsh HA, Gamble GD, Lopez-Sendon J, Sharpe N, CAPRICORN Echo Substudy Investigators. Effects of carvedilol on left ventricular remodeling after acute myocardial infarction: the CAPRICORN Echo Substudy. Circulation. 2004;109(2):201–6.

    Article  CAS  PubMed  Google Scholar 

  32. Greenberg B, Quinones MA, Koilpillai C, Limacher M, Shindler D, Benedict C, Shelton B. Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy. Circulation. 1995;91(10):2573–81.

    Article  CAS  PubMed  Google Scholar 

  33. Groenning BA, Nilsson JC, Sondergaard L, Fritz-Hansen T, Larsson HB, Hildebrandt PR. Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure. J Am Coll Cardiol. 2000;36(7):2072–80.

    Article  CAS  PubMed  Google Scholar 

  34. St. John Sutton M, Pfeffer MA, Moye L, Plappert T, Rouleau JL, Lamas G, Rouleau J, Parker JO, Arnold MO, Sussex B, Braunwald E. Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial. Circulation. 1997;96(10):3294–9.

    Article  CAS  PubMed  Google Scholar 

  35. Konstam MA, Udelson JE, Anand IS, Cohn JN. Ventricular remodeling in heart failure: a credible surrogate endpoint. J Card Fail. 2003;9(5):350–3.

    Article  PubMed  Google Scholar 

  36. Anand IS, Florea VG, Fisher L. Surrogate end points in heart failure. J Am Coll Cardiol. 2002;39(9):1414–21.

    Article  PubMed  Google Scholar 

  37. Harris P. Evolution and the cardiac patient. Cardiovasc Res. 1983;17(6):313–9. 373-8, 437-45.

    Article  CAS  PubMed  Google Scholar 

  38. Olivetti G, Capasso JM, Sonnenblick EH, Anversa P. Side-to-side slippage of myocytes participates in ventricular wall remodeling acutely after myocardial infarction in rats. Circ Res. 1990;67(1):23–34.

    Article  CAS  PubMed  Google Scholar 

  39. Weisman HF, Bush DE, Mannisi JA, Weisfeldt ML, Healy B. Cellular mechanisms of myocardial infarct expansion. Circulation. 1988;78(1):186–201.

    Article  CAS  PubMed  Google Scholar 

  40. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Sonnenblick EH, Olivetti G, Anversa P. The cellular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol. 1995;27(1):291–305.

    Article  CAS  PubMed  Google Scholar 

  41. Anversa P, Kajstura J, Olivetti G. Myocyte death in heart failure. Curr Opin Cardiol. 1996;11(3):245–51.

    Article  CAS  PubMed  Google Scholar 

  42. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest. 1996;74(1):86–107.

    CAS  PubMed  Google Scholar 

  43. Gupta S, Prahash AJ, Anand IS. Myocyte contractile function is intact in the post-infarct remodeled rat heart despite molecular alterations. Cardiovasc Res. 2000;48(1):77–88.

    Article  CAS  PubMed  Google Scholar 

  44. Linzbach A. Hypertrophy, hyperplasia and structural dilation of the human heart. Adv Cardiol. 1976;18:1–14.

    Article  CAS  PubMed  Google Scholar 

  45. Komamura K, Shannon RP, Ihara T, Shen YT, Mirsky I, Bishop SP, Vatner SF. Exhaustion of Frank-Starling mechanism in conscious dogs with heart failure. Am J Physiol. 1993;265(4 Pt 2):H1119–31.

    CAS  PubMed  Google Scholar 

  46. Zhao MJ, Zhang H, Robinson TF, Factor SM, Sonnenblick EH, Eng C. Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional (“stunned”) but viable myocardium. J Am Coll Cardiol. 1987;10(6):1322–34.

    Article  CAS  PubMed  Google Scholar 

  47. Yamamoto S, James TN, Sawada K, Okabe M, Kawamura K. Generation of new intercellular junctions between cardiocytes. A possible mechanism compensating for mechanical overload in the hypertrophied human adult myocardium. Circ Res. 1996;78(3):362–70.

    Article  CAS  PubMed  Google Scholar 

  48. Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, Braunwald E. Myocardial infarct size and ventricular function in rats. Circ Res. 1979;44(4):503–12.

    Article  CAS  PubMed  Google Scholar 

  49. Fletcher PJ, Pfeffer JM, Pfeffer MA, Braunwald E. Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction. Effects on systolic function. Circ Res. 1981;49(3):618–26.

    Article  CAS  PubMed  Google Scholar 

  50. Picard MH, Wilkins GT, Gillam LD, Thomas JD, Weyman AE. Immediate regional endocardial surface expansion following coronary occlusion in the canine left ventricle: disproportionate effects of anterior versus inferior ischemia. Am Heart J. 1991;121(3 Pt 1):753–62.

    Article  CAS  PubMed  Google Scholar 

  51. Pirolo JS, Hutchins GM, Moore GW. Infarct expansion: pathologic analysis of 204 patients with a single myocardial infarct. J Am Coll Cardiol. 1986;7(2):349–54.

    Article  CAS  PubMed  Google Scholar 

  52. Weisman HF, Healy B. Myocardial infarct expansion, infarct extension, and reinfarction: pathophysiologic concepts. Prog Cardiovasc Dis. 1987;30(2):73–110.

    Article  CAS  PubMed  Google Scholar 

  53. Meizlish JL, Berger HJ, Plankey M, Errico D, Levy W, Zaret BL. Functional left ventricular aneurysm formation after acute anterior transmural myocardial infarction. Incidence, natural history, and prognostic implications. N Engl J Med. 1984;311(16):1001–6.

    Article  CAS  PubMed  Google Scholar 

  54. Hammerman H, Kloner RA, Alker KJ, Schoen FJ, Braunwald E. Effects of transient increased afterload during experimentally induced acute myocardial infarction in dogs. Am J Cardiol. 1985;55(5):566–70.

    Article  CAS  PubMed  Google Scholar 

  55. Nolan SE, Mannisi JA, Bush DE, Healy B, Weisman HF. Increased afterload aggravates infarct expansion after acute myocardial infarction. J Am Coll Cardiol. 1988;12(5):1318–25.

    Article  CAS  PubMed  Google Scholar 

  56. Rabkin SW, Mathewson FA, Tate RB. Prognosis after acute myocardial infarction: relation to blood pressure values before infarction in a prospective cardiovascular study. Am J Cardiol. 1977;40(4):604–10.

    Article  CAS  PubMed  Google Scholar 

  57. Jugdutt BI, Khan MI. Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction. Circulation. 1994;89(5):2297–307.

    Article  CAS  PubMed  Google Scholar 

  58. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Lancet. 1986;1(8478):397–402.

    Google Scholar 

  59. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J, Overlie P, Donohue B, Chelliah N, Timmis GC, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med. 1993;328(10):673–9.

    Article  CAS  PubMed  Google Scholar 

  60. Hochman JS, Lamas GA, Buller CE, Dzavik V, Reynolds HR, Abramsky SJ, Forman S, Ruzyllo W, Maggioni AP, White H, Sadowski Z, Carvalho AC, Rankin JM, Renkin JP, Steg PG, Mascette AM, Sopko G, Pfisterer ME, Leor J, Fridrich V, Mark DB, Knatterud GL, Occluded Artery Trial Investigators. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med. 2006;355(23):2395–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Dzavik V, Buller CE, Lamas GA. Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function: the Total Occlusion Study of Canada (TOSCA)-2 trial. Circulation. 2006;114(23):2449–57.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E, Quaini F, Sonnenblick EH, Olivetti G, Anversa P. Structural basis of end-stage failure in ischemic cardiomyopathy in humans. Circulation. 1994;89(1):151–63.

    Article  CAS  PubMed  Google Scholar 

  63. 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(1):141–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Teiger E, Than VD, Richard L, Wisnewsky C, Tea BS, Gaboury L, Tremblay J, Schwartz K, Hamet P. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest. 1996;97(12):2891–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Di Loreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P. Apoptosis in the failing human heart. N Engl J Med. 1997;336(16):1131–41.

    Article  CAS  PubMed  Google Scholar 

  66. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA. Apoptosis in myocytes in end-stage heart failure. N Engl J Med. 1996;335(16):1182–9.

    Article  CAS  PubMed  Google Scholar 

  67. Kostin S, Heling A, Hein S, Scholz D, Klovekorn W-P, Schaper J. The protein composition of the normal and diseased cardiac myocyte. Heart Fail Rev. 1998;2:245–60.

    Article  CAS  Google Scholar 

  68. Schaper J, Froede R, Hein S, Buck A, Hashizume H, Speiser B, Friedl A, Bleese N. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation. 1991;83(2):504–14.

    Article  CAS  PubMed  Google Scholar 

  69. Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975;56(1):56–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Gerdes AM, Onodera T, Wang X, McCune SA. Myocyte remodeling during the progression to failure in rats with hypertension. Hypertension. 1996;28(4):609–14.

    Article  CAS  PubMed  Google Scholar 

  71. Onodera T, Tamura T, Said S, McCune SA, Gerdes AM. Maladaptive remodeling of cardiac myocyte shape begins long before failure in hypertension. Hypertension. 1998;32(4):753–7.

    Article  CAS  PubMed  Google Scholar 

  72. Gerdes AM. The use of isolated myocytes to evaluate myocardial remodeling. Trends Cardiovasc Med. 1992;2(4):152–5.

    Article  CAS  PubMed  Google Scholar 

  73. Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000;102(4):470–9.

    Article  CAS  PubMed  Google Scholar 

  74. Urabe Y, Mann DL, Kent RL, Nakano K, Tomanek RJ, Carabello BA, Cooper 4th G. Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation. Circ Res. 1992;70(1):131–47.

    Article  CAS  PubMed  Google Scholar 

  75. Olivetti G, Capasso JM, Meggs LG, Sonnenblick EH, Anversa P. Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. Circ Res. 1991;68(3):856–69.

    Article  CAS  PubMed  Google Scholar 

  76. Zimmer HG, Gerdes AM, Lortet S, Mall G. Changes in heart function and cardiac cell size in rats with chronic myocardial infarction. J Mol Cell Cardiol. 1990;22(11):1231–43.

    Article  CAS  PubMed  Google Scholar 

  77. Gerdes AM, Kellerman SE, Moore JA, Muffly KE, Clark LC, Reaves PY, Malec KB, McKeown PP, Schocken DD. Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy. Circulation. 1992;86(2):426–30.

    Article  CAS  PubMed  Google Scholar 

  78. Anand IS, Liu D, Chugh SS, Prahash AJ, Gupta S, John R, Popescu F, Chandrashekhar Y. Isolated myocyte contractile function is normal in postinfarct remodeled rat heart with systolic dysfunction. Circulation. 1997;96(11):3974–84.

    Article  CAS  PubMed  Google Scholar 

  79. Tamura T, Onodera T, Said S, Gerdes AM. Correlation of myocyte lengthening to chamber dilation in the spontaneously hypertensive heart failure (SHHF) rat. J Mol Cell Cardiol. 1998;30(11):2175–81.

    Article  CAS  PubMed  Google Scholar 

  80. Spinale FG, Ishihra K, Zile M, DeFryte G, Crawford FA, Carabello BA. Structural basis for changes in left ventricular function and geometry because of chronic mitral regurgitation and after correction of volume overload. J Thorac Cardiovasc Surg. 1993;106(6):1147–57.

    CAS  PubMed  Google Scholar 

  81. Wisenbaugh T, Spann JF, Carabello BA. Differences in myocardial performance and load between patients with similar amounts of chronic aortic versus chronic mitral regurgitation. J Am Coll Cardiol. 1984;3(4):916–23.

    Article  CAS  PubMed  Google Scholar 

  82. Sutton M, Plappert T, Spiegel A, Raichlen J, Douglas P, Reichek N, Edmunds L. Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: a prospective two-dimensional echocardiographic study. Circulation. 1987;76(1):77–89.

    Article  CAS  PubMed  Google Scholar 

  83. Carabello BA. The relationship of left ventricular geometry and hypertrophy to left ventricular function in valvular heart disease. J Heart Valve Dis. 1995;4 Suppl 2:S132–8. discussion S138-9.

    PubMed  Google Scholar 

  84. Feiring AJ, Rumberger JA. Ultrafast computed tomography analysis of regional radius-to-wall thickness ratios in normal and volume-overloaded human left ventricle. Circulation. 1992;85(4):1423–32.

    Article  CAS  PubMed  Google Scholar 

  85. Bing OH, Brooks WW, Robinson KG, Slawsky MT, Hayes JA, Litwin SE, Sen S, Conrad CH. The spontaneously hypertensive rat as a model of the transition from compensated left ventricular hypertrophy to failure. J Mol Cell Cardiol. 1995;27(1):383–96.

    Article  CAS  PubMed  Google Scholar 

  86. Mann DL, Kent RL, Parsons B, Cooper 4th G. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation. 1992;85(2):790–804.

    Article  CAS  PubMed  Google Scholar 

  87. Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT. Cardiac myocyte necrosis induced by angiotensin II. Circ Res. 1991;69(5):1185–95.

    Article  CAS  PubMed  Google Scholar 

  88. Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, Angelici L, Barlera S, Parrinello G, Maggioni AP, Tognoni G, Cohn JN, Val-HeFT Investigators. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation. 2007;116(11):1242–9.

    Article  CAS  PubMed  Google Scholar 

  89. Missov E, Calzolari C, Pau B. Circulating cardiac troponin I in severe congestive heart failure. Circulation. 1997;96(9):2953–8.

    Article  CAS  PubMed  Google Scholar 

  90. Narula J, Haider N, Arbustini E, Chandrashekhar Y. Mechanisms of disease: apoptosis in heart failure--seeing hope in death. Nat Clin Pract Cardiovasc Med. 2006;3(12):681–8.

    Article  CAS  PubMed  Google Scholar 

  91. Garg S, Narula J, Chandrashekhar Y. Apoptosis and heart failure: clinical relevance and therapeutic target. J Mol Cell Cardiol. 2005;38(1):73–9.

    Article  CAS  PubMed  Google Scholar 

  92. Laugwitz KL, Moretti A, Weig HJ, Gillitzer A, Pinkernell K, Ott T, Pragst I, Stadele C, Seyfarth M, Schomig A, Ungerer M. Blocking caspase-activated apoptosis improves contractility in failing myocardium. Hum Gene Ther. 2001;12(17):2051–63.

    Article  CAS  PubMed  Google Scholar 

  93. Moretti A, Weig HJ, Ott T, Seyfarth M, Holthoff HP, Grewe D, Gillitzer A, Bott-Flügel L, Schömig A, Ungerer M, Laugwitz KL. Essential myosin light chain as a target for caspase-3 in failing myocardium. Proc Natl Acad Sci U S A. 2002;99(18):11860–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, Hintze TH, Olivetti G, Anversa P. Stretch-induced programmed myocyte cell death. J Clin Invest. 1995;96(5):2247–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Colucci WS, Sawyer DB, Singh K, Communal C. Adrenergic overload and apoptosis in heart failure: implications for therapy. J Card Fail. 2000;6(2 Suppl 1):1–7.

    CAS  PubMed  Google Scholar 

  96. Cigola E, Kajstura J, Li B, Meggs LG, Anversa P. Angiotensin II activates programmed myocyte cell death in vitro. Exp Cell Res. 1997;231(2):363–71.

    Article  CAS  PubMed  Google Scholar 

  97. Kajstura J, Cigola E, Malhotra A, Li P, Cheng W, Meggs LG, Anversa P. Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol. 1997;29(3):859–70.

    Article  CAS  PubMed  Google Scholar 

  98. Ferrari R, Agnoletti L, Comini L, Gaia G, Bachetti T, Cargnoni A, Ceconi C, Curello S, Visioli O. Oxidative stress during myocardial ischaemia and heart failure. Eur Heart J. 1998;19(Suppl B):B2–11.

    CAS  PubMed  Google Scholar 

  99. DeLong MJ. Apoptosis: a modulator of cellular homeostasis and disease states. Ann N Y Acad Sci. 1998;842:82–90.

    Article  CAS  PubMed  Google Scholar 

  100. Condorelli G, Morisco C, Stassi G, Notte A, Farina F, Sgaramella G, de Rienzo A, Roncarati R, Trimarco B, Lembo G. Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. Circulation. 1999;99(23):3071–8.

    Article  CAS  PubMed  Google Scholar 

  101. Li Z, Bing OH, Long X, Robinson KG, Lakatta EG. Increased cardiomyocyte apoptosis during the transition to heart failure in the spontaneously hypertensive rat. Am J Physiol. 1997;272(5 Pt 2):H2313–9.

    CAS  PubMed  Google Scholar 

  102. Matturri L, Milei J, Grana DR, Lavezzi AM. Characterization of myocardial hypertrophy by DNA content, PCNA expression and apoptotic index. Int J Cardiol. 2002;82(1):33–9.

    Article  PubMed  Google Scholar 

  103. Baldi A, Abbate A, Bussani R, Patti G, Melfi R, Angelini A, Dobrina A, Rossiello R, Silvestri F, Baldi F, Di Sciascio G. Apoptosis and post-infarction left ventricular remodeling. J Mol Cell Cardiol. 2002;34(2):165–74.

    Article  CAS  PubMed  Google Scholar 

  104. Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM, Tikkanen I. Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol. 2001;280(6):H2726–31.

    CAS  PubMed  Google Scholar 

  105. Sam F, Sawyer DB, Chang DL, Eberli FR, Ngoy S, Jain M, Amin J, Apstein CS, Colucci WS. Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart. Am J Physiol Heart Circ Physiol. 2000;279(1):H422–8.

    CAS  PubMed  Google Scholar 

  106. Lowes BD, Minobe W, Abraham WT, Rizeq MN, Bohlmeyer TJ, Quaife RA, Roden RL, Dutcher DL, Robertson AD, Voelkel NF, Badesch DB, Groves BM, Gilbert EM, Bristow MR. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest. 1997;100(9):2315–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Labeit S, Kolmerer B. Titins: giant proteins in charge of muscle ultrastructure and elasticity. Science. 1995;270(5234):293–6.

    Article  CAS  PubMed  Google Scholar 

  108. Gregorio CC, Trombitas K, Centner T, Kolmerer B, Stier G, Kunke K, Suzuki K, Obermayr F, Herrmann B, Granzier H, Sorimachi H, Labeit S. The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J Cell Biol. 1998;143(4):1013–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Obermann WM, Gautel M, Weber K, Fürst DO. Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin. EMBO J. 1997;16(2):211–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Hein S, Scholz D, Fujitani N, Rennollet H, Brand T, Friedl A, Schaper J. Altered expression of titin and contractile proteins in failing human myocardium. J Mol Cell Cardiol. 1994;26(10):1291–306.

    Article  CAS  PubMed  Google Scholar 

  111. Hein S, Kostin S, Heling A, Maeno Y, Schaper J. The role of the cytoskeleton in heart failure. Cardiovasc Res. 2000;45(2):273–8.

    Article  CAS  PubMed  Google Scholar 

  112. Gregorio CC, Granzier H, Sorimachi H, Labeit S. Muscle assembly: a titanic achievement? Curr Opin Cell Biol. 1999;11(1):18–25.

    Article  CAS  PubMed  Google Scholar 

  113. Gelfand VI, Bershadsky AD. Microtubule dynamics: mechanism, regulation, and function. Annu Rev Cell Biol. 1991;7:93–116.

    Article  CAS  PubMed  Google Scholar 

  114. Lockard VG, Bloom S. Trans-cellular desmin-lamin B intermediate filament network in cardiac myocytes. J Mol Cell Cardiol. 1993;25(3):303–9.

    Article  CAS  PubMed  Google Scholar 

  115. Heling A, Zimmermann R, Kostin S, Maeno Y, Hein S, Devaux B, Bauer E, Klövekorn WP, Schlepper M, Schaper W, Schaper J. Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium. Circ Res. 2000;86(8):846–53.

    Article  CAS  PubMed  Google Scholar 

  116. Rappaport L, Samuel JL. Microtubules in cardiac myocytes. Int Rev Cytol. 1988;113:101–43.

    Article  CAS  PubMed  Google Scholar 

  117. Tsutsui H, Ishihara K, Cooper 4th G. Cytoskeletal role in the contractile dysfunction of hypertrophied myocardium. Science. 1993;260(5108):682–7.

    Article  CAS  PubMed  Google Scholar 

  118. Tsutsui H, Tagawa H, Kent RL, McCollam PL, Ishihara K, Nagatsu M, Cooper 4th G. Role of microtubules in contractile dysfunction of hypertrophied cardiocytes. Circulation. 1994;90(1):533–55.

    Article  CAS  PubMed  Google Scholar 

  119. Tagawa H, Wang N, Narishige T, Ingber DE, Zile MR, Cooper 4th G. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy. Circ Res. 1997;80(2):281–9.

    Article  CAS  PubMed  Google Scholar 

  120. Wang X, Li F, Campbell SE, Gerdes AM. Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: II. Cytoskeletal remodeling. J Mol Cell Cardiol. 1999;31(2):319–31.

    Article  CAS  PubMed  Google Scholar 

  121. Milner DJ, Taffet GE, Wang X, Pham T, Tamura T, Hartley C, Gerdes AM, Capetanaki Y. The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function. J Mol Cell Cardiol. 1999;31(11):2063–76.

    Article  CAS  PubMed  Google Scholar 

  122. Kostin S, Scholz D, Shimada T, Maeno Y, Mollnau H, Hein S, Schaper J. The internal and external protein scaffold of the T-tubular system in cardiomyocytes. Cell Tissue Res. 1998;294(3):449–60.

    Article  CAS  PubMed  Google Scholar 

  123. Ohlendieck K. Towards an understanding of the dystrophin-glycoprotein complex: linkage between the extracellular matrix and the membrane cytoskeleton in muscle fibers. Eur J Cell Biol. 1996;69(1):1–10.

    CAS  PubMed  Google Scholar 

  124. Ortiz-Lopez R, Li H, Su J, Goytia V, Towbin JA. Evidence for a dystrophin missense mutation as a cause of X-linked dilated cardiomyopathy. Circulation. 1997;95(10):2434–40.

    Article  CAS  PubMed  Google Scholar 

  125. Towbin JA. The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol. 1998;10(1):131–9.

    Article  CAS  PubMed  Google Scholar 

  126. Towbin JA, Bowles KR, Bowles NE. Etiologies of cardiomyopathy and heart failure. Nat Med. 1999;5(3):266–7.

    Article  CAS  PubMed  Google Scholar 

  127. Klietsch R, Ervasti JM, Arnold W, Campbell KP, Jorgensen AO. Dystrophin-glycoprotein complex and laminin colocalize to the sarcolemma and transverse tubules of cardiac muscle. Circ Res. 1993;72(2):349–60.

    Article  CAS  PubMed  Google Scholar 

  128. Kaprielian RR, Stevenson S, Rothery SM, Cullen MJ, Severs NJ. Distinct patterns of dystrophin organization in myocyte sarcolemma and transverse tubules of normal and diseased human myocardium. Circulation. 2000;101(22):2586–94.

    Article  CAS  PubMed  Google Scholar 

  129. Severs NJ. The cardiac gap junction and intercalated disc. Int J Cardiol. 1990;26(2):137–73.

    Article  CAS  PubMed  Google Scholar 

  130. Smith JH, Green CR, Peters NS, Rothery S, Severs NJ. Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. Am J Pathol. 1991;139(4):801–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Emdad L, Uzzaman M, Takagishi Y, Honjo H, Uchida T, Severs NJ, Kodama I, Murata Y. Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade. J Mol Cell Cardiol. 2001;33(2):219–31.

    Article  CAS  PubMed  Google Scholar 

  132. Gutstein DE, Morley GE, Tamaddon H, Vaidya D, Schneider MD, Chen J, Chien KR, Stuhlmann H, Fishman GI. Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Circ Res. 2001;88(3):333–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Lerner DL, Yamada KA, Schuessler RB, Saffitz JE. Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in Cx43-deficient mice. Circulation. 2000;101(5):547–52.

    Article  CAS  PubMed  Google Scholar 

  134. Weber KT, Brilla CG, Janicki JS. Myocardial fibrosis: functional significance and regulatory factors. Cardiovasc Res. 1993;27(3):341–8.

    Article  CAS  PubMed  Google Scholar 

  135. Weber KT, Sun Y, Tyagi SC, Cleutjens JP. Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. J Mol Cell Cardiol. 1994;26(3):279–92.

    Article  CAS  PubMed  Google Scholar 

  136. Rossi MA, Abreu MA, Santoro LB. Images in cardiovascular medicine. Connective tissue skeleton of the human heart: a demonstration by cell-maceration scanning electron microscope method. Circulation. 1998;97(9):934–5.

    Article  CAS  PubMed  Google Scholar 

  137. Weber KT, Pick R, Janicki JS, Gadodia G, Lakier JB. Inadequate collagen tethers in dilated cardiopathy. Am Heart J. 1988;116(6 Pt 1):1641–6.

    Article  CAS  PubMed  Google Scholar 

  138. Gunja-Smith Z, Morales AR, Romanelli R, Woessner Jr JF. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol. 1996;148(5):1639–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Spinale FG, Tomita M, Zellner JL, Cook JC, Crawford FA, Zile MR. Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia. Am J Physiol. 1991;261(2 Pt 2):H308–18.

    CAS  PubMed  Google Scholar 

  140. Florea VG, Anand IS. Troponin T and plasma collagen peptides in heart failure. Circ Heart Fail. 2012;5(4):394–7.

    Article  CAS  PubMed  Google Scholar 

  141. Abrahams C, Janicki JS, Weber KT. Myocardial hypertrophy in Macaca fascicularis. Structural remodeling of the collagen matrix. Lab Invest. 1987;56(6):676–83.

    CAS  PubMed  Google Scholar 

  142. Weber KT, Janicki JS, Shroff SG, Pick R, Chen RM, Bashey RI. Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circ Res. 1988;62(4):757–65.

    Article  CAS  PubMed  Google Scholar 

  143. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation. 1991;83(6):1849–65.

    Article  CAS  PubMed  Google Scholar 

  144. Schaper J, Speiser B. The extracellular matrix in the failing human heart. Basic Res Cardiol. 1992;87 Suppl 1:303–9.

    PubMed  Google Scholar 

  145. Kato S, Spinale FG, Tanaka R, Johnson W, Cooper 4th G, Zile MR. Inhibition of collagen cross-linking: effects on fibrillar collagen and ventricular diastolic function. Am J Physiol. 1995;269(3 Pt 2):H863–8.

    CAS  PubMed  Google Scholar 

  146. Stroud JD, Baicu CF, Barnes MA, Spinale FG, Zile MR. Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment. Am J Physiol Heart Circ Physiol. 2002;282(6):H2324–35.

    Article  CAS  PubMed  Google Scholar 

  147. Katz AM, Zile MR. New molecular mechanism in diastolic heart failure. Circulation. 2006;113(16):1922–5.

    Article  PubMed  Google Scholar 

  148. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004;350(19):1953–9.

    Article  CAS  PubMed  Google Scholar 

  149. Dell’italia LJ, Balcells E, Meng QC, Su X, Schultz D, Bishop SP, Machida N, Straeter-Knowlen IM, Hankes GH, Dillon R, Cartee RE, Oparil S. Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs. Am J Physiol. 1997;273(2 Pt 2):H961–70.

    PubMed  Google Scholar 

  150. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev. 2007;87(4):1285–342.

    Article  CAS  PubMed  Google Scholar 

  151. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta. 2000;1477(1-2):267–83.

    Article  CAS  PubMed  Google Scholar 

  152. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006;69(3):562–73.

    Article  CAS  PubMed  Google Scholar 

  153. Sundstrom J, Evans JC, Benjamin EJ, Levy D, Larson MG, Sawyer DB, Siwik DA, Colucci WS, Wilson PW, Vasan RS. Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study. Eur Heart J. 2004;25(17):1509–16.

    Article  CAS  PubMed  Google Scholar 

  154. Cavusoglu E, Ruwende C, Chopra V, Yanamadala S, Eng C, Clark LT, Pinsky DJ, Marmur JD. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction. Am Heart J. 2006;151(5):1101.e1–8.

    Article  CAS  Google Scholar 

  155. Marino TA, Kent RL, Uboh CE, Fernandez E, Thompson EW, Cooper 4th G. Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle. Am J Physiol. 1985;249(2 Pt 2):H371–9.

    CAS  PubMed  Google Scholar 

  156. Apstein CS, Lecarpentier Y, Mercadier JJ, Martin JL, Pontet F, Wisnewsky C, Schwartz K, Swynghedauw B. Changes in LV papillary muscle performance and myosin composition with aortic insufficiency in rats. Am J Physiol. 1987;253(5 Pt 2):H1005–11.

    CAS  PubMed  Google Scholar 

  157. Silver MA, Pick R, Brilla CG, Jalil JE, Janicki JS, Weber KT. Reactive and reparative fibrillar collagen remodelling in the hypertrophied rat left ventricle: two experimental models of myocardial fibrosis. Cardiovasc Res. 1990;24(9):741–7.

    Article  CAS  PubMed  Google Scholar 

  158. Brilla CG, Maisch B. Regulation of the structural remodelling of the myocardium: from hypertrophy to heart failure. Eur Heart J. 1994;15(Suppl D):45–52.

    Article  PubMed  Google Scholar 

  159. Brilla CG, Matsubara LS, Weber KT. Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol. 1993;25(5):563–75.

    Article  CAS  PubMed  Google Scholar 

  160. Weber KT, Sun Y, Campbell SE. Structural remodelling of the heart by fibrous tissue: role of circulating hormones and locally produced peptides. Eur Heart J. 1995;16(Suppl N):12–8.

    Article  CAS  PubMed  Google Scholar 

  161. Sabbah HN, Goldstein S. Ventricular remodelling: consequences and therapy. Eur Heart J. 1993;14(Suppl C):24–9.

    Article  PubMed  Google Scholar 

  162. Douglas PS, Morrow R, Ioli A, Reichek N. Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1989;13(2):311–5.

    Article  CAS  PubMed  Google Scholar 

  163. Saks VA, Belikova YO, Kuznetsov AV, Khuchua ZA, Branishte TH, Semenovsky ML, Naumov VG. Phosphocreatine pathway for energy transport: ADP diffusion and cardiomyopathy. Am J Physiol. 1991;261(4 Suppl):30–8.

    CAS  PubMed  Google Scholar 

  164. Kono T, Sabbah HN, Rosman H, Alam M, Jafri S, Goldstein S. Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure. J Am Coll Cardiol. 1992;20(7):1594–8.

    Article  CAS  PubMed  Google Scholar 

  165. Florea VG, Henein MY, Anker SD, Francis DP, Gibson DG, Coats AJ. Relation of changes over time in ventricular size and function to those in exercise capacity in patients with chronic heart failure. Am Heart J. 2000;139(5):913–7.

    Article  CAS  PubMed  Google Scholar 

  166. Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T, Smith R, Fletcher R. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. Circulation. 1993;87(6 Suppl):VI5–16.

    CAS  PubMed  Google Scholar 

  167. Meerson FZ. Compensatory hyperfunction of the heart and cardiac insufficiency. Circ Res. 1962;10:250–8.

    Article  CAS  PubMed  Google Scholar 

  168. Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors. Circulation. 1993;87(3):755–63.

    Article  CAS  PubMed  Google Scholar 

  169. Sharpe N, Smith H, Murphy J, Greaves S, Hart H, Gamble G. Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition. Lancet. 1991;337(8746):872–6.

    Article  CAS  PubMed  Google Scholar 

  170. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357(9266):1385–90.

    Article  CAS  PubMed  Google Scholar 

  171. Doughty RN, Whalley GA, Walsh H, et al. Effects of carvedilol on left ventricular remodeling in patients following acute myocardial infarction: the CAPRICORN echo substudy. Circulation. 2001;104 (Suppl.)(17):II-517. Abstract.

    Google Scholar 

  172. The ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. Circulation. 1998;97(22):2202–12.

    Article  Google Scholar 

  173. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342(8875):821–8.

    Google Scholar 

  174. Buch P, Rasmussen S, Abildstrom SZ, Kober L, Carlsen J, Torp-Pedersen C, TRACE investigators. The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years. Eur Heart J. 2005;26(2):145–52.

    Article  CAS  PubMed  Google Scholar 

  175. Grossman W. Cardiac hypertrophy: useful adaptation or pathologic process? Am J Med. 1980;69(4):576–84.

    Article  CAS  PubMed  Google Scholar 

  176. Katz AM. Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure. N Engl J Med. 1990;322(2):100–10.

    Article  CAS  PubMed  Google Scholar 

  177. Raya TE, Fonken SJ, Lee RW, Daugherty S, Goldman S, Wong PC, Timmermans PB, Morkin E. Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. Am J Hypertens. 1991;4(4 Pt 2):334S–40.

    Article  CAS  PubMed  Google Scholar 

  178. Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, Drexler H. 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(5):2273–82.

    Article  CAS  PubMed  Google Scholar 

  179. McDonald KM, Rector T, Carlyle PF, Francis GS, Cohn JN. Angiotensin-converting enzyme inhibition and beta-adrenoceptor blockade regress established ventricular remodeling in a canine model of discrete myocardial damage. J Am Coll Cardiol. 1994;24(7):1762–8.

    Article  CAS  PubMed  Google Scholar 

  180. Tamura T, Said S, Harris J, Lu W, Gerdes AM. Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by targeting of the renin-angiotensin system. Circulation. 2000;102(2):253–9.

    Article  CAS  PubMed  Google Scholar 

  181. Xu X, Wan W, Ji L, Lao S, Powers AS, Zhao W, Erikson JM, Zhang JQ. Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodelling in rats. Cardiovasc Res. 2008;78(3):523–32.

    Article  CAS  PubMed  Google Scholar 

  182. Konstam MA, Kronenberg MW, Rousseau MF, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, Howe DM, Kilcoyne L, Metherall J, Benedict C, Yusuf S, Pouleur H; for the SOLVD Investigators. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators. Circulation. 1993;88(5 Pt 1):2277–83.

    Google Scholar 

  183. Konstam MA, Rousseau MF, Kronenberg MW, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. Circulation. 1992;86(2):431–8.

    Article  CAS  PubMed  Google Scholar 

  184. St. John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moyé LA, Dagenais GR, Lamas GA, Klein M, Sussex B, Goldman S, et al. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation. 1994;89(1):68–75.

    Article  CAS  PubMed  Google Scholar 

  185. Hall SA, Cigarroa CG, Marcoux L, Risser RC, Grayburn PA, Eichhorn EJ. Time course of improvement in left ventricular function, mass and geometry in patients with congestive heart failure treated with beta-adrenergic blockade. J Am Coll Cardiol. 1995;25(5):1154–61.

    Article  CAS  PubMed  Google Scholar 

  186. Sabbah HN, Sharov VG, Gupta RC, Todor A, Singh V, Goldstein S. Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure. J Am Coll Cardiol. 2000;36(5):1698–705.

    Article  CAS  PubMed  Google Scholar 

  187. Hayashi M, Tsutamoto T, Wada A, Tsutsui T, Ishii C, Ohno K, Fujii M, Taniguchi A, Hamatani T, Nozato Y, Kataoka K, Morigami N, Ohnishi M, Kinoshita M, Horie M. 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(20):2559–65.

    Article  CAS  PubMed  Google Scholar 

  188. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Matsui T, Kinoshita M. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001;37(5):1228–33.

    Article  CAS  PubMed  Google Scholar 

  189. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation. 2003;108(15):1831–8.

    Article  CAS  PubMed  Google Scholar 

  190. Chan AK, Sanderson JE, Wang T, Lam W, Yip G, Wang M, Lam YY, Zhang Y, Yeung L, Wu EB, Chan WW, Wong JT, So N, Yu CM. Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure. J Am Coll Cardiol. 2007;50(7):591–6.

    Article  CAS  PubMed  Google Scholar 

  191. Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345(23):1667–75.

    Article  CAS  PubMed  Google Scholar 

  192. Maggioni AP, Anand I, Gottlieb SO, Latini R, Tognoni G, Cohn JN, Val-HeFT Investigators (Valsartan Heart FailureTrial). Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol. 2002;40(8):1414–21.

    Article  CAS  PubMed  Google Scholar 

  193. Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, Benza RL, Gottlieb SO, Kleemann TD, Rosconi F, Vandervoort PM, Cohn JN, Val-HeFT Heart Failure Trial Investigators. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002;40(5):970–5.

    Article  CAS  PubMed  Google Scholar 

  194. Wong M, Staszewsky L, Latini R, Barlera S, Glazer R, Aknay N, Hester A, Anand I, Cohn JN. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J Am Coll Cardiol. 2004;43(11):2022–7.

    Article  PubMed  Google Scholar 

  195. Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristiansson K, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S, LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):1004–10.

    Article  CAS  PubMed  Google Scholar 

  196. Cintron G, Johnson G, Francis G, Cobb F, Cohn JN. Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87(6 Suppl):VI17–23.

    CAS  PubMed  Google Scholar 

  197. Cohn JN, Tam SW, Anand IS, Taylor AL, Sabolinski ML, Worcel M, A-HeFT Investigators. Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: results from A-HeFT. J Card Fail. 2007;13(5):331–9.

    Article  CAS  PubMed  Google Scholar 

  198. Taylor AL, Ziesche S, Yancy C, Carson P, D’Agostino Jr R, Ferdinand K, Taylor M, Adams K, Sabolinski M, Worcel M, Cohn JN, African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351(20):2049–57.

    Article  CAS  PubMed  Google Scholar 

  199. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49.

    Article  CAS  PubMed  Google Scholar 

  200. Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S, McKenna W, Fitzgerald M, Deharo JC, Alonso C, Walker S, Braunschweig F, Bailleul C, Daubert JC. Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol. 2002;40(1):111–8.

    Article  PubMed  Google Scholar 

  201. Molhoek SG, Bax JJ, van Erven L, Bootsma M, Boersma E, Steendijk P, van der Wall EE, Schalij MJ. Comparison of benefits from cardiac resynchronization therapy in patients with ischemic cardiomyopathy versus idiopathic dilated cardiomyopathy. Am J Cardiol. 2004;93(7):860–3.

    Article  PubMed  Google Scholar 

  202. Sutton MG, Plappert T, Hilpisch KE, Abraham WT, Hayes DL, Chinchoy E. Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circulation. 2006;113(2):266–72.

    Article  PubMed  Google Scholar 

  203. Sutton MS, Keane MG. Reverse remodelling in heart failure with cardiac resynchronisation therapy. Heart. 2007;93(2):167–71.

    Article  PubMed  Google Scholar 

  204. Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, Daubert J-C, Cleland JGF. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J. 2007;28(13):1592–7.

    Article  CAS  PubMed  Google Scholar 

  205. Chaudhry PA, Mishima T, Sharov VG, Hawkins J, Alferness C, Paone G, Sabbah HN. Passive epicardial containment prevents ventricular remodeling in heart failure. Ann Thorac Surg. 2000;70(4):1275–80.

    Article  CAS  PubMed  Google Scholar 

  206. Saavedra WF, Tunin RS, Paolocci N, Mishima T, Suzuki G, Emala CW, Chaudhry PA, Anagnostopoulos P, Gupta RC, Sabbah HN, Kass DA. Reverse remodeling and enhanced adrenergic reserve from passive external support in experimental dilated heart failure. J Am Coll Cardiol. 2002;39(12):2069–76.

    Article  CAS  PubMed  Google Scholar 

  207. Sabbah HN, Sharov VG, Gupta RC, Mishra S, Rastogi S, Undrovinas AI, Chaudhry PA, Todor A, Mishima T, Tanhehco EJ, Suzuki G. Reversal of chronic molecular and cellular abnormalities due to heart failure by passive mechanical ventricular containment. Circ Res. 2003;93(11):1095–101.

    Article  CAS  PubMed  Google Scholar 

  208. Blom AS, Mukherjee R, Pilla JJ, Lowry AS, Yarbrough WM, Mingoia JT, Hendrick JW, Stroud RE, McLean JE, Affuso J, Gorman RC, Gorman 3rd JH, Acker MA, Spinale FG. Cardiac support device modifies left ventricular geometry and myocardial structure after myocardial infarction. Circulation. 2005;112(9):1274–83.

    Article  PubMed  Google Scholar 

  209. Blom AS, Pilla JJ, Arkles J, Dougherty L, Ryan LP, Gorman 3rd JH, Acker MA, Gorman RC. Ventricular restraint prevents infarct expansion and improves borderzone function after myocardial infarction: a study using magnetic resonance imaging, three-dimensional surface modeling, and myocardial tagging. Ann Thorac Surg. 2007;84(6):2004–10.

    Article  PubMed  Google Scholar 

  210. Pilla JJ, Blom AS, Gorman 3rd JH, Brockman DJ, Affuso J, Parish LM, Sakamoto H, Jackson BM, Acker MA, Gorman RC. Early postinfarction ventricular restraint improves borderzone wall thickening dynamics during remodeling. Ann Thorac Surg. 2005;80(6):2257–62.

    Article  PubMed  Google Scholar 

  211. Mann DL, Acker MA, Jessup M, Sabbah HN, Starling RC, Kubo SH, Acorn Trial Principal Investigators and Study Coordinators. Clinical evaluation of the CorCap Cardiac Support Device in patients with dilated cardiomyopathy. Ann Thorac Surg. 2007;84(4):1226–35.

    Article  PubMed  Google Scholar 

  212. Starling RC, Jessup M, Oh JK, Sabbath HN, Acker MA, Mann DL, Kubo SH. Sustained benefits of the CorCap Cardiac Support Device on left ventricular remodeling: three year follow-up results from the Acorn clinical trial. Ann Thorac Surg. 2007;84(4):1236–42.

    Article  PubMed  Google Scholar 

  213. Klodell Jr CT, Aranda Jr JM, McGiffin DC, Rayburn BK, Sun B, Abraham WT, Pae Jr WE, Boehmer JP, Klein H, Huth C. Worldwide surgical experience with the Paracor HeartNet cardiac restraint device. J Thorac Cardiovasc Surg. 2008;135(1):188–95.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiology Section, VA Medical Center, University of Minnesota, 1 Veterans Drive, Minneapolis, MN, 55417, USA

    Inder S. Anand MD, FRCP, D Phil (Oxon.)

  2. Minneapolis VA Health Care System, Cardiology 111 C, One Veterans Drive, Minneapolis, MN, 55417, USA

    Viorel G. Florea MD, PhD, DSc, FACC, FAHA

Authors
  1. Inder S. Anand MD, FRCP, D Phil (Oxon.)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Viorel G. Florea MD, PhD, DSc, FACC, FAHA
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Inder S. Anand MD, FRCP, D Phil (Oxon.) .

Editor information

Editors and Affiliations

  1. Lillehei Heart Institute, Department of Medicine, University of Minnesota Medical Center, University of Minnesota, Minneapolis, Minnesota, USA

    Daniel J. Garry

  2. Division of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota, USA

    Robert F. Wilson

  3. Division of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota, USA

    Zeev Vlodaver

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Anand, I.S., Florea, V.G. (2017). Structural Remodeling in the Development of Chronic Systolic Heart Failure: Implication for Treatment. In: Garry, D., Wilson, R., Vlodaver, Z. (eds) Congestive Heart Failure and Cardiac Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-44577-9_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-44577-9_17

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44575-5

  • Online ISBN: 978-3-319-44577-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation