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Current concepts for the neurohormonal management of left ventricular dysfunction after myocardial infarction

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Abstract

The importance of addressing neurohormonal activation in patients after a myocardial infarction is now well-appreciated. Inhibition of the renin-angiotensin-aldosterone axis and the sympathetic nervous system can result in improved cardiac function and survival. As we learn more about other systems, we should be able to realize further benefits. In particular, the roles of endothelin, matrix metalloproteinases, and cytokines in remodeling are being investigated, with the potential to result in better outcomes for patients.

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References and Recommended Reading

  1. Weber KT: Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation 1997, 96:4065–4082.

    PubMed  CAS  Google Scholar 

  2. Wolfgang L, Weimer G, Scholkens BA: ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. J Mol Cell Cardiol 1992, 24:909–919.

    Article  Google Scholar 

  3. 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, 342:821–828.

  4. Ambrosioni E, Borghi C, Magnani B: The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. N Engl J Med 1995, 332:80–85.

    Article  PubMed  CAS  Google Scholar 

  5. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group.Lancet 1995, 345:669–685.

  6. Kober L, Torp-Pedersen C, Carlsen JE, et al.: A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 1995, 333:1670–1676.

    Article  PubMed  CAS  Google Scholar 

  7. Swedberg K, Held P, Kjekshus J, et al.: Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction--results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 1992, 327:678–684.

    Article  PubMed  CAS  Google Scholar 

  8. Ryan TJ, Antman EM, Brooks NH, et al.: 1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 1999, 34:890–911.

    Article  PubMed  CAS  Google Scholar 

  9. Dickstein K, Kjekshus J: Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002, 360:752–760. This randomized, controlled trial showed that losartan (50 mg every day) was not superior or noninferior to captopril (50 mg three times daily) for decreasing mortality in patients with q-wave infarcts and resultant heart failure.

    Article  PubMed  CAS  Google Scholar 

  10. Pfeffer MA, McMurray JJ, Velazquez EJ, et al.: Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003, 349:1893–1906. This randomized, controlled trial showed that valsartan (160 mg twice daily) is equivalent to captopril (50 mg three times daily) in reducing mortality in post-MI patients with evidence of heart failure or LV dysfunction. Combining losartan (80 mg twice daily) and captopril (50 mg three times daily) does not provide any additional benefit and increases complications.

    Article  PubMed  CAS  Google Scholar 

  11. Granger CB, McMurray JJ, Yusuf S, et al.: Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensinconverting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003, 362:772–776.

    Article  PubMed  CAS  Google Scholar 

  12. Kim S, Yoshiyama M, Izumi Y, et al.: Effects of combination of ACE inhibitor and angiotensin receptor blocker on cardiac remodeling, cardiac function, and survival in rat heart failure. Circulation 2001, 103:148–154.

    PubMed  CAS  Google Scholar 

  13. McMurray JJ, Ostergren J, Swedberg K, et al.: Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function taking angiotensin-convertingenzyme inhibitors: the CHARM-Added trial. Lancet 2003, 362:767–771.

    Article  PubMed  CAS  Google Scholar 

  14. Hayashi M, Tsutamoto T, Wada A, et al.: Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 2001, 38:1375–1382.

    Article  PubMed  CAS  Google Scholar 

  15. Modena MG, Aveta P, Menozzi A, Rossi R: Aldosterone inhibition limits collagen synthesis and progressive left ventricular enlargement after anterior myocardial infarction. Am Heart J 2001, 141:41–46.

    Article  PubMed  CAS  Google Scholar 

  16. Bauersachs J, Heck M, Fraccarollo D, et al.: Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol 2002, 39:351–358.

    Article  PubMed  CAS  Google Scholar 

  17. Francis J, Weiss RM, Wei SG, et al.: Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am J Physiol Heart Circ Physiol 2001, 281:H2241-H2251.

    PubMed  CAS  Google Scholar 

  18. Bauersachs J, Fraccarollo D, Ertl G, et al.: Striking increase of natriuresis by low-dose spironolactone in congestive heart failure only in combination with ACE inhibition: mechanistic evidence to support RALES. Circulation 2000, 102:2325–2328.

    PubMed  CAS  Google Scholar 

  19. Jorde UP, Vittorio T, Katz SD, et al.: Elevated plasma aldosterone levels despite complete inhibition of the vascular angiotensin-converting enzyme in chronic heart failure. Circulation 2002, 106:1055–1057.

    Article  PubMed  CAS  Google Scholar 

  20. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.

    Article  PubMed  CAS  Google Scholar 

  21. Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321. This is a randomized, controlled trial that showed mortality benefit for initiating eplerenone (titrated to 50 mg every day) within 2 weeks of a MI resulting in a depressed EF and heart failure.

    Article  PubMed  CAS  Google Scholar 

  22. Exner DV, Dries DL, Domanski MJ, Cohn JN: Lesser response to ACE inhibitor therapy in black compared with white patients with left ventricular dysfunction. N Engl J Med 2001, 344:1351–1357.

    Article  PubMed  CAS  Google Scholar 

  23. Hayashi M, Tsutamoto T, Wada A, 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, 107:2559–2565.

    Article  PubMed  CAS  Google Scholar 

  24. Prabhu SD, Chandrasekar B, Murray DR, Freeman GL: Betaadrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling. Circulation 2000, 101:2103–2109.

    PubMed  CAS  Google Scholar 

  25. Zannad F, Alla F, Dousset B, et al.: Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the Randomized Aldactone Evaluation Study (RALES). Circulation 2000, 102:2700–2706.

    PubMed  CAS  Google Scholar 

  26. Vantrimpont P, Rouleau JL, Wun CC, et al.: Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE Investigators. J Am Coll Cardiol 1997, 29:229–236.

    Article  PubMed  CAS  Google Scholar 

  27. Gottlieb SS, McCarter RJ, Vogel RA: Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998, 339:489–497.

    Article  PubMed  CAS  Google Scholar 

  28. Dargie HJ: Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001, 357:1385–1390. This is a randomized, controlled trial proving that in the setting of modern reperfusion therapy and background therapy, a long-term mortality benefit for β-blockade in post-MI patients with LV dysfunction exists.

    Article  PubMed  CAS  Google Scholar 

  29. Chadda K, Goldstein S, Byington R, Curb JD: Effect of propranolol after acute myocardial infarction in patients with congestive heart failure. Circulation 1986, 73:503–510.

    PubMed  CAS  Google Scholar 

  30. Hjalmarson A, Goldstein S, Fagerberg B, et al.: Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). MERIT-HF Study Group. JAMA 2000, 283:1295–1302.

    Article  PubMed  CAS  Google Scholar 

  31. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial.Lancet 1999, 353:9–13.

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

    Article  PubMed  CAS  Google Scholar 

  33. Packer M, Coats AJS, Fowler MB, et al.: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001, 344:1651–1658.

    Article  PubMed  CAS  Google Scholar 

  34. Etoh T, Joffs C, Deschamps AM, et al.: Myocardial and interstitial matrix metalloproteinase activity after acute myocardial infarction in pigs. Am J Physiol Heart Circ Physiol 2001, 281:H987-H994. This study suggests that MMP subtype expression post-MI is temporally and regionally specific.

    PubMed  CAS  Google Scholar 

  35. Peterson JT, Li H, Dillon L, Bryant JW: Evolution of matrix metalloprotease and tissue inhibitor expression during heart failure progression in the infarcted rat. Cardiovasc Res 2000, 46:307–315. This study suggests that MMP subtype expression post-MI is temporally and regionally specific.

    Article  PubMed  CAS  Google Scholar 

  36. Wilson EM, Moainie SL, Baskin JM, et al.: Region- and typespecific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation 2003, 107:2857–2863. This study suggests that MMP subtype expression post-MI is temporally and regionally specific.

    Article  PubMed  CAS  Google Scholar 

  37. Mukherjee R, Brinsa TA, Dowdy KB, et al.: Myocardial infarct expansion and matrix metalloproteinase inhibition. Circulation 2003, 107:618–625.

    Article  PubMed  CAS  Google Scholar 

  38. Omland T, Lie RT, Aakvaag A, et al.: Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction. Circulation 1994, 89:1573–1579.

    PubMed  CAS  Google Scholar 

  39. Cozza EN, Chiou S, Gomez-Sanchez CE: Endothelin-1 potentiation of angiotensin II stimulation of aldosterone production. Am J Physiol 1992, 262:R85-R89.

    PubMed  CAS  Google Scholar 

  40. O’Connor CM, Gattis WA, Adams KF Jr, et al.: Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4). J Am Coll Cardiol 2003, 41:1452–1457. This is a demonstration that the effects of endothelin antagonists are not simple.

    Article  PubMed  CAS  Google Scholar 

  41. Grover GJ, Dzwonczyk S, Parham CS: The endothelin-1 receptor antagonist BQ-123 reduced infarct size in a canine model of coronary occlusion and reperfusion. Cardiovasc Res 1993, 27:1613–1618.

    Article  PubMed  CAS  Google Scholar 

  42. Sakai S, Migauchi T, Kobayashi M, et al.: Inhibition of myocardial endothelin pathway improves long-term survival in heart failure. Nature 1996, 384:353.

    Article  PubMed  CAS  Google Scholar 

  43. Nguyen QT, Cernacek P, Sirois MG, et al.: Long-term effects of nonselective endothelin A and B receptor antagonism in postinfarction rat: importance of timing. Circulation 2001, 104:2075–2081.

    PubMed  CAS  Google Scholar 

  44. Takahashi C, Kagaya Y, Namiuchi S, et al.: Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival. J Cardiovasc Pharmacol 2001, 38:29–38.

    Article  PubMed  CAS  Google Scholar 

  45. Fraccarollo D, Galuppo P, Bauersachs J, Ertl G: Collagen accumulation after myocardial infarction: effects of ETA receptor blockade and implications for early remodeling. Cardiovasc Res 2002, 3:559–567.

    Article  Google Scholar 

  46. Deswal A, Petersen NJ, Feldman AM, et al.: Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone Trial (VEST). Circulation 2001, 103:2055–2059.

    PubMed  CAS  Google Scholar 

  47. Mann DL: Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res 2002, 91:988–998.

    Article  PubMed  CAS  Google Scholar 

  48. Wei GC, Sirois MG, Qu R, et al.: Subacute and chronic effects of quinapril on cardiac cytokine expression, remodeling, and function after myocardial infarction in the rat. J Cardiovasc Pharmacol 2002, 39:842–850.

    Article  PubMed  CAS  Google Scholar 

  49. Anzai T, Yoshikawa T, Takahashi T, et al.: Early use of betablockers is associated with attenuation of serum C-reactive protein elevation and favorable short-term prognosis after acute myocardial infarction. Cardiology 2003, 99:47–53.

    Article  PubMed  CAS  Google Scholar 

  50. Iversen PO, Nicolaysen G, Sioud M: DNA enzyme targeting TNF-alpha mRNA improves hemodynamic performance in rats with postinfarction heart failure. Am J Physiol Heart Circ Physiol 2001, 28:H2211-H2217.

    Google Scholar 

  51. Hwang MW, Matsumori A, Furukawa Y, et al.: Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling. J Am Coll Cardiol 2001, 38:1546–1553.

    Article  PubMed  CAS  Google Scholar 

  52. Mann DL, McMurray JJ: Presentation of the results of the RENAISSANCE, RECOVER and RENEWAL studies. Paper presented at the Heart Failure 2002 Meeting. Oslo, Norway; June 8–11, 2002.

  53. Chung ES, Packer M, Lo KH, et al.: Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the Anti-TNF Therapy Against Congestive Heart Failure. Circulation 2003, 107:3133–3140. This article explains that TNF antagonism may have detrimental effects despite initial promising work and a good theoretical basis.

    Article  PubMed  CAS  Google Scholar 

  54. Tonnessen T, Florholmen G, Henriksen UL, Christensen G: Cardiopulmonary alterations in mRNA expression for interleukin-1beta, the interleukin-6 superfamily and CXCchemokines during development of postischaemic heart failure in the rat. Clin Physiol Funct Imaging 2003, 23:263–268.

    Article  PubMed  CAS  Google Scholar 

  55. de Lemos JA, Morrow DA, Sabatine MS, et al.: Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes. Circulation 2003, 107:690–695.

    Article  PubMed  CAS  Google Scholar 

  56. Damas JK, Gullestad L, Aass H: Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure--modulatory effect of intravenous immunoglobulin. J Am Coll Cardiol 2001, 38:187.

    Article  PubMed  CAS  Google Scholar 

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Shah, K.B., Gottlieb, S.S. Current concepts for the neurohormonal management of left ventricular dysfunction after myocardial infarction. Curr Heart Fail Rep 1, 161–167 (2004). https://doi.org/10.1007/s11897-004-0004-9

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