Advertisement

Current Heart Failure Reports

, Volume 12, Issue 1, pp 87–93 | Cite as

Impact of Intravenous Nitroglycerin in the Management of Acute Decompensated Heart Failure

  • Corstiaan A. den UilEmail author
  • Jasper J. Brugts
Management of Heart Failure (TE Meyer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Management of Heart Failure

Abstract

Intravenous nitroglycerin is a well-known, but underused, treatment for acute decompensated heart failure. Nitroglycerin has a rapid onset of action and short half-life and there is a clear dose-response curve on both global hemodynamics and peripheral circulation. IV nitroglycerin reduces LV and RV filling pressures and afterload. In the case of acute decompensated heart failure, there is a typical decreased bioavailability of nitric oxide (NO), which needs to be supplemented by exogenous nitrates. Additionally, there is benefit on clinical endpoints, such as fast optimization of arterial oxygenation, lower rates of mechanical ventilation, and improved survival. Drawbacks of therapy include not only side effects such as headache, resistance, and development of tolerability to nitrates but also free radical production. However, nitrates in combination with diuretics remain the cornerstone of acute decompensated heart failure treatment. We propose a more aggressive use of nitrates and a more limited use of inotropes (due to ischemic demand and pro-arrhythmogenic characteristics) in normo- or hypertensive patients with acute heart failure.

Keywords

Acute heart failure Critical care Emergency care Hemodynamics Inodilators Intensive care Microcirculation Nitrates Nitroglycerin Perfusion Vasodilators 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Corstiaan A. den Uil and Jasper J. Brugts declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.•
    Singer AJ, Skopicki H, Thode HC, Peacock WK. Hemodynamic profiles of ED patients with acute decompensated heart failure and their association with treatment. Am J Emerg Med. 2014;32:302–5. This study is an example of the fact that less than 50 % of patients with acute decompensated heart failure is currently treated with vasodilators.PubMedCrossRefGoogle Scholar
  2. 2.
    Collins SP, Pang PS, Lindsell CJ, Kyriacou DN, Storrow AB, et al. International variations in the clinical, diagnostic, and treatment characteristics of emergency department patients with acute heart failure syndromes. Eur J Heart Fail. 2010;12:1253–60.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Mentz RJ, Cotter G, Cleland JG, Stevens SR, Chiswell K, et al. International differences in clinical characteristics, management, and outcomes in acute heart failure patients: better short-term outcomes in patients enrolled in Eastern Europe and Russia in the PROTECT trial. Eur J Heart Fail. 2014;16:614–24.PubMedCrossRefGoogle Scholar
  4. 4.•
    Tarvasmäki T, Harjola VP, Tolonen J, Siirilä-Waris K, Nieminen MS, et al. Management of acute heart failure and the effect of systolic blood pressure on the use of intravenous therapies. Eur Heart J Acute Cardiovasc Care. 2013;2:219–25. This study is an example of the fact that less than 50 % of patients with acute decompensated heart failure is currently treated with vasodilators.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Elkayam U, Janmohamed M, Habib M, Hatamizadeh P. Vasodilators in the management of acute heart failure. Crit Care Med. 2008;36:S95–105.PubMedCrossRefGoogle Scholar
  6. 6.
    Forstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, et al. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension. 1994;23:1121–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Katz SD, Khan T, Zeballos GA, Matthew L, Potharlanka P, et al. Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure. Circulation. 1999;99:2113–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Mohri M, Egashira K, Tagawa T, Kuga T, Tagawa H, et al. Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure. Hypertension. 1997;1(Pt 1):50–6.CrossRefGoogle Scholar
  9. 9.
    Smith CJ, Sun D, Hoegler C, Roth BS, Zhang X, et al. Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. Circ Res. 1996;78:58–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Kubo SH, Rector TS, Bank AJ, Williams RE, Heifetz SM. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation. 1991;84:1589–96.PubMedCrossRefGoogle Scholar
  11. 11.
    Katz SD, Krum H, Khan T, Knecht M. Exercise-induced vasodilation in forearm circulation of normal subjects and patients with congestive heart failure: role of endothelium-derived nitric oxide. J Am Coll Cardiol. 1996;28:585–90.PubMedCrossRefGoogle Scholar
  12. 12.
    Schwarz M, Katz SD, Demopoulos L, Hirsch H, Yuen JL, et al. Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure. Circulation. 1994;89:1609–14.PubMedCrossRefGoogle Scholar
  13. 13.
    Hornig B, Arakawa N, Kohler C, Drexler H. Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation. 1998;97:363.PubMedCrossRefGoogle Scholar
  14. 14.
    Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature. 2002;416:337–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Simon JN, Duglan D, Casadei B, Carnicer R. Nitric oxide synthase regulation of cardiac excitation-contraction coupling in health and disease. J Mol Cel Cardiol. 2014;73C:80–91.CrossRefGoogle Scholar
  16. 16.
    Stein B, Eschenhagen T, Rudiger J, Scholz H, Forstermann U, et al. Increased expression of constitutive nitric oxide synthase III, but not inducible nitric oxide synthase II, in human heart failure. J Am Coll Cardiol. 1998;32:1179–86.PubMedCrossRefGoogle Scholar
  17. 17.
    Damy T, Ratajczak P, Shah AM, Camors E, Marty I, et al. Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet. 2004;363:1365–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Comini L, Bachetti T, Agnoletti L, Gaia G, Curello S, et al. Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-alpha. Eur Heart J. 1999;20:1503–13.PubMedCrossRefGoogle Scholar
  19. 19.•
    Munzel T, Daiber A, Gori T. Good review article on the current evidence for mode of action of nitrates and the development of tolerance. Circulation. 2011;123:2132–44. Good review article on the current evidence for mode of action of nitrates and the development of tolerance.PubMedCrossRefGoogle Scholar
  20. 20.
    Fung HL. Pharmacokinetic determinants of nitrate action. Am J Med. 1984;76:22–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Den Uil CA, Lagrand WK, Spronk PE, van der Ent M, Jewbali LS, et al. Low-dose nitroglycerin improved microcirculation in hospitalized patients with acute heart failure. Eur J Heart Fail. 2009;11:386–90.CrossRefGoogle Scholar
  22. 22.
    Den Uil CA, Caliskan K, Lagrand WK, Van der Ent M, Jewbali LS, et al. Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure. Intensive Care Med. 2009;35:1893–9.CrossRefGoogle Scholar
  23. 23.
    Den Uil CA, Lagrand WK, Van der Ent M, Jewbali LS, Cheng JM, et al. Impaired microcirculation predicts poor outcome of patients with acute myocardial infarction complicated by cardiogenic shock. Eur Heart J. 2010;31:3032–9.CrossRefGoogle Scholar
  24. 24.
    Den Uil CA, Lagrand WK, Valk SD, Spronk PE, Simoons ML. Management of cardiogenic shock: focus on tissue perfusion. Curr Probl Cardiol. 2009;34:330–49.CrossRefGoogle Scholar
  25. 25.
    Wakai A, McCabe A, Kidney R, Brooks SC, Seupaul RA, et al. Nitrates for acute heart failure syndromes. Cochrane Database Syst Rev. 2013;8, CD005151.PubMedGoogle Scholar
  26. 26.
    Nelson GI, Silke B, Ahuja RC, Hussain M, Taylor SH. Haemodynamic advantages of isosorbide dinitrate over furosemide in acute heart failure following myocardial infarction. Lancet. 1983;1:730–3.PubMedCrossRefGoogle Scholar
  27. 27.
    Verma SP, Silke B, Hussain M, Nelson GI, Reynolds GW, et al. First-line treatment of left ventricular failure complicating acute myocardial infarction: a randomised evaluation of immediate effects of diuretic, venodilator, arteriodilator, and positive inotropic drugs on left ventricular function. J Cardiovasc Pharmacol. 1987;10:38–46.PubMedCrossRefGoogle Scholar
  28. 28.
    Beltrame JE, Zeitz CJ, Unger SA, Brennan RJ, Hunt A, et al. Nitrate therapy is an alternative to furosemide/morphine therapy in the management of acute cardiogenic pulmonary edema. J Card Fail. 1998;4:271–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Webster MW, Sharpe DN, Coxon R, et al. Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy. Am J Cardiol. 1989;63:217–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Dupuis J, Lalonde G, Lemieux R, et al. Tolerance to intravenous NTG in patients with congestive heart failure: role of increased intravascular volume, neurohumoral activation and lack of prevention with N-acetylcysteine. J Am Coll Cardiol. 1990;16:923–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Dakak N, Makhoul N, Merdler A, et al. Haemodynamic and neurohumoral effects of flosequinan in severe heart failure: Similarities and differences compared with intravenous NTG therapy. Eur Heart J. 1993;14:836–44.PubMedCrossRefGoogle Scholar
  32. 32.
    Chow SL, O'Barr SA, Peng J, Chew E, Pak F, et al. Renal function and neurohormonal changes following intravenous infusions of nitroglycerin versus nesiritide in patients with acute decompensated heart failure. J Card Fail. 2011;17:181–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Chow SL, O'Barr SA, Peng J, Chew E, Pak F, et al. Modulation of novel cardiorenal and inflammatory biomarkers by intravenous nitroglycerin and nesiritide in acute decompensated heart failure. Circ Heart Fail. 2011;4:450–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Aziz EF, Kukin M, Javed F, Pratap B, Sabharwal MS, et al. Effect of adding nitroglycerin to early diuretic therapy on the morbidity and mortality of patients with chronic kidney disease presenting with acute decompensated heart failure. Hosp Pract. 1995;39:126–32.CrossRefGoogle Scholar
  35. 35.
    Cotter G, Metzkort E, Kaluski E, Faigenberg Z, Miller R, et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet. 1998;351:389–93.PubMedCrossRefGoogle Scholar
  36. 36.
    Sharon A, Shpirer I, Kaluski E, Moshkovitz Y, Milovanov O, et al. High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema. J Am Coll Cardiol. 2000;36:832–7.PubMedCrossRefGoogle Scholar
  37. 37.
    VMAC. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287:1531–40.Google Scholar
  38. 38.
    Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications. J Am Coll Cardiol. 2005;46:57–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Costanzo MR, Johannes RS, Pine M, Gupta V, Saltzberg M, et al. The safety of intravenous diuretics alone versus diuretics plus parenteral vasoactive therapies in hospitalized patients with acutely decompensated heart failure: a propensity score and instrumental variable analysis using the Acutely Decompensated Heart Failure National Registry (ADHERE) database. Am Heart J. 2007;154:262–77.CrossRefGoogle Scholar
  40. 40.
    Katz SD, Biasucci L, Sabba C, et al. Impaired endothelium mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol. 1992;19:918–25.PubMedCrossRefGoogle Scholar
  41. 41.
    Elkayam U, Mehra A, Shotan A. Nitrate resistance and tolerance: potential limitations in the treatment of congestive heart failure. Am J Cardiol. 1992;70:98B–104.PubMedCrossRefGoogle Scholar
  42. 42.
    Elkayam U, Kulick D, McInthosh N, Roth A, Hsueh W, et al. Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure. Circulation. 1987;76:577–84.PubMedCrossRefGoogle Scholar
  43. 43.
    Gori T, Mak SS, Kelly S, Parker JD. Evidence supporting abnormalities in nitric oxide synthase function induced by nitroglycerin in humans. J Am Coll Cardiol. 2001;38:1096–101.PubMedCrossRefGoogle Scholar
  44. 44.
    Mehra A, Ostrzega E, Shotan A, Johnson JV, Elkayam U. Persistent hemodynamic improvement with short-term nitrate therapy in patients with chronic congestive heart failure already treated with captopril. Am J Cardiol. 1992;70:1310–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Daiber A, Oelze M, Coldewey M, Kaiser K, Huth C, et al. Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure. Biochem Biophys Res Commun. 2005;338:1865–74.PubMedCrossRefGoogle Scholar
  46. 46.
    Muunzel T, Kurz S, Rajagopalan S, Thoenes M, Berrington WR, et al. Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase: a new action for an old drug. J Clin Invest. 1996;98:1465–70.CrossRefGoogle Scholar
  47. 47.
    Cohn JN. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Eur Heart J. 1988;9:171–3.PubMedCrossRefGoogle Scholar
  48. 48.
    Cohn JN, Tam SW, Anand IS, Taylor SH, Sabolinski ML, et al. 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;13:331–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Watanabe H, Kakihana M, Ohtsuka S, Sugishita Y. Preventive effects of carvedilol on nitrate tolerance: a randomized, double-blind, placebo-controlled comparative study between carvedilol and arotinolol. J Am Coll Cardiol. 1998;32:1201–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Liuni A, Luca M, Uxa A, Mariani J, Gori T, et al. Coadministration of atorvastatin prevents nitroglycerin-induced endothelial dysfunction and nitrate tolerance in humans in vivo. J Am Coll Cardiol. 2011;3:93–8.CrossRefGoogle Scholar
  51. 51.
    O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365:32–43.PubMedCrossRefGoogle Scholar
  52. 52.
    Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013;310:2533–43.PubMedCentralPubMedGoogle Scholar
  53. 53.
    Unverzagt S, Wachsmuth L, Hirsch K, Thiele H, Buerke M, et al. Inotropic agents and vasodilator strategies for acute myocardial infarction complicated by cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev. 2014;1, CD009669.PubMedGoogle Scholar
  54. 54.
    Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, et al. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial. Eur Heart J. 2014;35:1041–50.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of CardiologyErasmus Medical Center, ThoraxcenterCE RotterdamThe Netherlands

Personalised recommendations