Advertisement

Pharmacologic Support of the Failing Heart

  • Haifa LysterEmail author
  • Georgios Karagiannis
Chapter
  • 10 Downloads

Abstract

Heart failure (HF), the inability of the heart to achieve adequate blood supply to meet the metabolic needs of the organs, is classified based on the left ventricular ejection fraction (LVEF) into HF with reduced LVEF (HFrEF) and HF with preserved LVEF (HFpEF). The pharmacological treatment of HF mainly consists of medications that suppress the maladaptive mechanisms leading to myocardial dysfunction. In HFrEF the treatment mainly focusses on the inhibition of the sympathetic nervous system and renin-angiotensin-aldosterone system, whereas in HFpEF the main goal is to control the comorbidities. The backbone of treatment of HFrEF is neurohormonal consisting of an angiotensin converting enzyme inhibitor, a beta blocker and a mineralocorticoid receptor antagonist. Randomised controlled clinical trials have shown this approach to be effective in improving both mortality and quality of life and these drugs have been included in current guidelines. Relatively newer drugs, such as ivabradine and sacubitril/valsartan are also important in the conservative treatment algorithm of HFrEF. Certain medications, such as diuretics and digoxin, are used regularly in HF because they improve the patients’ symptoms and reduce the number of hospitalizations for HF. The therapeutic approach of HFpEF includes adequate blood pressure control, the treatment of possible underlying myocardial ischemia and the adequate control of the ventricular response in atrial fibrillation. Inotropes can improve HF haemodynamics in the short-term but are associated in the mid-to long-term with arrhythmias, myocardial ischemia and increased mortality. The pharmacological treatment of acute HF mainly consists of intravenous diuretics, intravenous nitrates and, if there are signs of hypoperfusion, short-term inotropes.

Keywords

Angiotensin converting enzyme inhibitor Heart failure Mineralocorticoid receptor antagonist Renin-angiotensin-aldosterone system Sympathetic nervous system 

References

  1. 1.
    Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol. 2013;62:e147–239.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Kelder JC, Cramer MJ, van Wijngaarden J, et al. The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure. Circulation. 2011;124:2865–73.PubMedCrossRefGoogle Scholar
  4. 4.
    McMurray JJ. Clinical practice. Systolic heart failure. N Engl J Med. 2010;362:228–38.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Vaduganathan M, Fonarow GC. Epidemiology of hospitalized heart failure: differences and similarities between patients with reduced versus preserved ejection fraction. Heart Fail Clin. 2013;9:271–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol. 2004;43:317–27.PubMedCrossRefGoogle Scholar
  7. 7.
    Lam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13:18–28.PubMedCrossRefGoogle Scholar
  8. 8.
    Paulus WJ, Tschope C. A novel paradigm for heart failure with preserved ejection fraction : comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263–71.PubMedCrossRefGoogle Scholar
  9. 9.
    Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137–e61.CrossRefGoogle Scholar
  10. 10.
    NICE chronic-heart-failure-in-adults-diagnosis-and-management 2018.pdf.Google Scholar
  11. 11.
    Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18:891–975.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Lee VC, Rhew DC, Dylan M, Badamgarav E, Braunstein GD, Weingarten SR. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004;141:693–704.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767–71.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Lakhdar R, Al-Mallah MH, Lanfear DE. Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials. J Card Fail. 2008;14:181–8.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kostis JB, Packer M, Black HR, Schmieder R, Henry D, Levy E. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. Am J Hypertens. 2004;17:103–11.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Packer M, Califf RM, Konstam MA, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation. 2002;106:920–6.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9–13.Google Scholar
  19. 19.
    Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–2007.Google Scholar
  20. 20.
    Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol 1996;78:902–907.Google Scholar
  21. 21.
    Pitt B, Williams G, Remme W, et al. The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study. Cardiovasc Drugs Ther. 2001;15:79–87.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    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. N Engl J Med. 1986;314:1547–52.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325:303–10.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049–57.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875–85.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429–1435.Google Scholar
  28. 28.
    Bowling CB, Sanders PW, Allman RM, et al. Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD treatment trial. Int J Cardiol. 2013;167:151–6.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327:669–77.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    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.Google Scholar
  31. 31.
    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;333:1670–6.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349–55.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet 1997;349:375–380.Google Scholar
  34. 34.
    Fagerberg B. The merit of beta(1)-blockade in heart failure. Eur Heart J. 1999;20:1761–3.PubMedCrossRefGoogle Scholar
  35. 35.
    Goldstein S, Fagerberg B, Hjalmarson A, et al. Metoprolol controlled release/extended release in patients with severe heart failure: analysis of the experience in the MERIT-HF study. J Am Coll Cardiol. 2001;38:932–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385–90.PubMedCrossRefGoogle Scholar
  38. 38.
    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;341:709–17.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362:772–6.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893–906.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Brater DC. Diuretic therapy. N Engl J Med. 1998;339:387–95.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Tamargo J, Lopez-Sendon J. Novel therapeutic targets for the treatment of heart failure. Nat Rev Drug Discov. 2011;10:536–55.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Georgiopoulou VV, Kalogeropoulos AP, Giamouzis G, et al. Digoxin therapy does not improve outcomes in patients with advanced heart failure on contemporary medical therapy. Circ Heart Fail. 2009;2:90–7.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Nativi-Nicolau J, Ryan JJ, Fang JC. Current therapeutic approach in heart failure with preserved ejection fraction. Heart Fail Clin. 2014;10:525–38.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    van Veldhuisen DJ, Cohen-Solal A, Bohm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol. 2009;53:2150–8.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777–81.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006;27:2338–45.PubMedCrossRefGoogle Scholar
  48. 48.
    Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–67.PubMedCrossRefGoogle Scholar
  49. 49.
    Edelmann F, Wachter R, Schmidt AG, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA. 2013;309:781–91.PubMedCrossRefGoogle Scholar
  50. 50.
    McMurray JJ, O'Connor C. Lessons from the TOPCAT trial. N Engl J Med. 2014;370:1453–4.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Hashim T, Elbaz S, Patel K, et al. Digoxin and 30-day all-cause hospital admission in older patients with chronic diastolic heart failure. Am J Med. 2014;127:132–9.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol. 1990;66:981–6.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Hung MJ, Cherng WJ, Kuo LT, Wang CH. Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure. Int J Clin Pract. 2002;56:57–62.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Jessup M, Banner N, Brozena S, et al. Optimal pharmacologic and non-pharmacologic management of cardiac transplant candidates: approaches to be considered prior to transplant evaluation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J Heart Lung Transplant. 2006;25:1003–23.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Unverferth DV, Magorien RD, Lewis RP, Leier CV. Long-term benefit of dobutamine in patients with congestive cardiomyopathy. Am Heart J. 1980;100:622–30.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Tacon CL, McCaffrey J, Delaney A. Dobutamine for patients with severe heart failure: a systematic review and meta-analysis of randomised controlled trials. Intensive Care Med. 2012;38:359–67.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Klocke RK, Mager G, Kux A, Hopp HW, Hilger HH. Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition. Am Heart J. 1991;121:1965–73.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Cuffe MS, Califf RM, Adams KF Jr, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002;287:1541–7.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Felker GM, Benza RL, Chandler AB, et al. Heart failure etiology and response tomilrinone in decompensated heart failure. J Am Coll Cardiol. 2003;41:997–1003.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991;325:1468–75.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Nieminen MS, Buerke M, Cohen-Solal A, et al. The role of levosimendan in acute heart failure complicating acute coronary syndrome: a review and expert consensus opinion. Int J Cardiol. 2016;218:150–7.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Follath F, Cleland JGF, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002;360:196–202.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Packer M, Colucci W, Fisher L, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Heart Failure. 2013;1:103–11.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Mebazaa A, Nieminen MS, Packer M, et al. Levosimendan vs. dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA. 2007;297:1883–91.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    failure RAH. addition of vasodilators to diuretic therapy does not improve outcome in acute heart failure. Nat Rev Cardiol. 2014;11:4.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Pharmacy DepartmentHarefield HospitalLondonUK
  2. 2.Royal Brompton & Harefield NHS Foundation TrustHarefield HospitalLondonUK
  3. 3.Cardiology DepartmentHillingdon HospitalLondonUK
  4. 4.Department of Transplantation and Mechanical Circulatory SupportHarefield HospitalLondonUK

Personalised recommendations