Abstract
Background: Intravenous inotropic intervention in congestive heart failure is generally associated with a poor prognosis and is largely used as a “bridge” to mechanical support or heart transplantation.
Hypothesis: We hypothesized that the inotropic support afforded by dobutamine may serve as a bridge to the introduction and intensification of angiotensin‐converting enzyme (ACE) inhibitor‐nitrate therapy.
Methods: We studied the efficacy of transitioning inotrope‐dependent patients in endstage heart failure from intravenous dobutamine to high‐dose ACE inhibitor‐nitrates, with 1‐year follow‐up. Forty‐nine sequential dobutamine‐dependent patients with left ventricular ejection fraction (LVEF) 17 ± 17% were treated with increasing lisinopril (1.9 ± 1.5 to 46 ± 28 mg/day) and isosorbide dinitrate (7 ± 6 to 229 ± 161 mg/day). Outpatient dobutamine was continued or repeat infusions pursued, as indicated, and dobutamine was tapered when feasible.
Results: During the following year, 14 of 49 patients required repeat dobutamine, with home treatment with dobutamine for 6.3 ± 3.7 months (n = 5). At 1 year, New York Heart Association (NYHA) classification improved from 3.6 ± 0.5 to 1.9 ± 1.0, p < 0.0001; yearly hospitalizations fell from 2.7 ± 2.3 to 1.2 ± 3.0, p = 0.02; and LVEF rose from 17 ± 7% to 24 ± 11%, p < 0.0001. At 1 year, 14 patients who remained dobutamine dependent had significantly more severe symptoms than dobutamine‐independent patients (n = 35). Transplant or death occurred in 7 of 14 patients with follow‐up dobutamine, and in 5 of 35 patients free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n = 10, death n = 12) continued to be more limited (NYHA 2.7 ± 0.9 vs. 1.7 ± 0.9, p = 0.0002), with more follow‐up hospitalizations (3.6 ± 5.4 vs. 0.6 ± 0.8, p = 0.0004), and no improvement in LVEF (17 ± 8 vs. 28 ± 11%, p = 0.003).
Conclusions: Of the patients on dobutamine inotropic support, 70% were successfully transitioned to ACE inhibitor‐nitrate therapy, with improved symptoms and LVEF, and with reduced hospitalizations and follow‐up dobutamine or transplant. Thirty percent of patients with continued need for dobutamine had a significantly poorer 1‐year clinical outcome.
Keywords: parenteral inotropic therapy, dobutamine, angiotensin‐converting enzyme inhibitor, vasodilators, decompensated heart failure, prognosis
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References
- 1. Packer M: The neurohormonal hypothesis: A theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 1992; 20: 248–254 [DOI] [PubMed] [Google Scholar]
- 2. Cohn JN: Structural basis for heart failure: Ventricular remodeling and its pharmacological inhibition. Circulation 1995; 91: 2504–2507 [DOI] [PubMed] [Google Scholar]
- 3. Sabbah HN, Kono T, Stein PD, Mancini J, Goldstein S: Left ventricular shape changes during the course of evolving heart failure. Am J Physiol (Heart Circ Physiol 32) 1992; 263: H266–H270 [DOI] [PubMed] [Google Scholar]
- 4. The CONSENSUS Trial Study Group : Effects of enalapril on mortality in severe congestive heart failure: Results of the Cooperative North Scandinavian Enalapril Survival Study. N Engl J Med 1987; 316: 1429–1435 [DOI] [PubMed] [Google Scholar]
- 5. Captopril Multicenter Research Group : A placebo‐controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol 1983; 2: 755–763 [DOI] [PubMed] [Google Scholar]
- 6. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman B, Loeb H, Wong M, Bhat G, Goldman S, Fletcher RD, Doherty J, Hughes CV, Carson P, Cintron G, Shabetai R, Haakenson C: A comparison of enalapril with hydralazine‐isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991; 325: 303–310 [DOI] [PubMed] [Google Scholar]
- 7. The SOLVD Investigators : Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293–302 [DOI] [PubMed] [Google Scholar]
- 8. Waagstein F, Bristow MR, Swedberg K, Caprerini F, Folwer MB, Silver MA, Gilbert EM, Johnson MR, Goss FG, Hjalmarson A, for the Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group : Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet 1993; 342: 1441–1446 [DOI] [PubMed] [Google Scholar]
- 9. CIBIS‐II Investigators and Committees : The Cardiac Insufficiency Bisoprolol Study II (CIBIS‐II): A randomized trial. Lancet 1999; 353: 9–13 [PubMed] [Google Scholar]
- 10. MERIT‐HF Study Group : Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT‐HF). Lancet 1999; 353: 2001–2007 [PubMed] [Google Scholar]
- 11. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J, for the Randomized Aldactone Evaluation Study Investigators : The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709–717 [DOI] [PubMed] [Google Scholar]
- 12. Levine TB, Levine AB, Keteyian SJ, Narins B, Lesch M: Reverse remodeling in heart failure with intensification of vasodilator therapy. Clin Cardiol 1997; 20: 697–702 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Levine TB, Levine AB, Goldberg AD, Tobes M, Narins B, Lesch M: Clinical status of patients removed from a transplant waiting list rivals that of transplant recipients at significant cost savings. Am Heart J 1996; 132: 1189–1194 [DOI] [PubMed] [Google Scholar]
- 14. Leier CV, Webel J, Bush CA: The cardiovascular effects of the continuous infusion of dobutamine in patients with severe cardiac failure. Circulation 1997; 56: 468–472 [DOI] [PubMed] [Google Scholar]
- 15. Akhtar N, Mikulic E, Cohn J, Chaudhry MH: Hemodynamic effect of dobutamine in patients with severe heart failure. Am J Cardiol 1975; 36: 202–205 [DOI] [PubMed] [Google Scholar]
- 16. Hawkins ET, Levine TB, Goss SJ, Moosvi A, Levine AB: Hypersensitivity myocarditis in the explanted hearts of transplant recipients—reappraisal of pathologic criteria and their clinical implications. Pathology Annual 1995; 30 (Part I): 287–304 [PubMed] [Google Scholar]
- 17. Spear GS: Eosinophilic explant carditis with eosinophilia: Hypersensitivity to dobutamine infusion. J Heart & Lung Transplant 1995; 14: 755–761 [PubMed] [Google Scholar]
- 18. Mills RM, Cunningham MS: Long‐term hemodynamic responses to vasodilator therapy in patients with severe left ventricular dysfunction. Am J Cardiol 1999; 84 (8): 939–941, A7 [DOI] [PubMed] [Google Scholar]
- 19. Milfred‐LaForest SK, Shubert J, Mendoza B, Flores I, Eisen HJ, Pina IL: Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oral angiotensin‐converting enzyme inhibitors. Am J Cardiol 1999; 84 (8): 894–899 [DOI] [PubMed] [Google Scholar]
- 20. Katz AM: Cyclic adenosine monophosphate effects on the myocardium: A man who blows hot and cold with one breath. J Am Coll Cardiol 1983; 2: 143–149 [DOI] [PubMed] [Google Scholar]
- 21. Bristow MR, Hershberger RE, Port JD, Rasmussen R, Cates AE, Feldman AM: Adrenergic pathways in non‐failing and failing human ventricular myocardium. Circulation 1990; 82 (suppl I): I‐12–25 [PubMed] [Google Scholar]
- 22. Colluci WS: In‐vivo studies of myocardial b̃‐adrenergic receptor pharmacology in patients with congestive heart failure. Circulation 1990; 82 (suppl I): I‐44–51 [PubMed] [Google Scholar]
- 23. Grose R, Strain J, Greenberg M, LeJemtel TH: Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure. J Am Coll Cardiol 1986; 7: 1107–1113 [DOI] [PubMed] [Google Scholar]
- 24. Monrad ES, Baim DS, Smith HS, Lanoue AS: Milrinone, dobutamine, and nitroprusside: Comparative effects on hemodynamics and myocardial energetics in patients with severe congestive heart failure. Circulation 1986; 73 (suppl III): III–168 [PubMed] [Google Scholar]
- 25. Biddle TL, Benotti JR, Creager MA, Faxon DP, Firth BG, Fitzpatrick PG, Konstam MA, Krebs C, Walton L, Kershner RP, Jacobson J, Luczkowec CA, Montenaro MJ, Tandon PK, Fitzpatrick S, Schwarz RP: Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy. Am J Cardiol 1987; 59: 1345–1350 [DOI] [PubMed] [Google Scholar]
- 26. Binkley PF, Van Fossen DB, Haas GJ, Leier CV: Increased ventricular contractility is not sufficient for effective positive inotropic intervention. Am J Physiol 1996; (Heart Circ Physiol 40) 271: H1635–H1642 [DOI] [PubMed] [Google Scholar]
- 27. Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB: Decreased catecholamine sensitivity and b̃‐adrenergic‐receptor density in failing human hearts. N Engl J Med 1982; 307: 205–211 [DOI] [PubMed] [Google Scholar]
- 28. Stiles GL, Caron MG, Lefkowitz RJ: b̃‐adrenergic receptors: Biochemical mechanisms of physiological regulation. Physiol Rev 1984; 64 (2): 661–741 [DOI] [PubMed] [Google Scholar]
- 29. March JD, Barry WH, Smith TW: Desensitization to the inotropic effect of isoproterenol in cultured ventricular cells. J Pharm Exper Ther 1982; 223 (1): 60–67 [PubMed] [Google Scholar]
- 30. Levine TB, Francis GS, Goldsmith SR, Simon AB, Cohn JN: Activity of the sympathetic nervous system and renin‐angiotensin system assessed by plasma hormone levels and their relationship to hemodynamic abnormalities in congestive heart failure. Am J Cardiol 1982; 49: 1659–1666 [DOI] [PubMed] [Google Scholar]
- 31. Benedict CR, Francis G, Shelton BJ, Johnstone D, Kubo S, Kirlin PC, Nicklas J, Liang C‐S, Konstarn MA, Greenberg B, Yusuf S, for the SOLVD Investigators : Effect of long‐term enalapril therapy on neurohormones in patients with left ventricular dysfunction. Am J Cardiol 1995; 75: 1151–1157 [DOI] [PubMed] [Google Scholar]
- 32. Sanbe A, Takeo S: Long‐term treatment with angiotensin I‐converting enzyme inhibitors attenuates the loss of cardiac b̃‐adrenoceptor responses in rats with chronic heart failure. Circulation 1995; 92: 2666–2675 [DOI] [PubMed] [Google Scholar]
- 33. Spinale FG, Holzgrefe HH, Mukherjee R, Hird RB, Walker JD, Arnim‐Barker A, Powell JR, Koster WH: Angiotensin converting enzyme inhibition and the progression of congestive cardiomyopathy: Effects on the left ventricular and myocyte structure and function. Circulation 1995; 92: 562–578 [DOI] [PubMed] [Google Scholar]
- 34. Levine TB, Levine AB, Kathawala M, Narins B, Kaminski P: Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy. Am J Hypertens 1998; 11: 1041–1047 [DOI] [PubMed] [Google Scholar]
- 35. Cusick DA, Pfeifer PB, Quigg RJ: Effects of intravenous milrinone followed by titration of high‐dose oral vasodilator therapy on clinical outcome and rehospitalization rates in patients with severe heart failure. Am J Cardiol 1998; 82: 1060–1065 [DOI] [PubMed] [Google Scholar]
- 36. Cintron G, Johnson G, Francis G, Cobb F, Cohn JN, for the V‐HeFT VA Cooperative Studies Group : Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. Circulation 1993; 87 (suppl VI): VI‐17–VI‐23 [PubMed] [Google Scholar]
- 37. Wong M, Johnson G, Shabetai R, Highes V, Bhat G, Lopez B, Cohn JN, for the V‐HeFT VA Cooperative Studies Group : Echocardiographic variables as prognostic indicators and therapeutic monitors in chronic congestive heart failure: Veterans Affairs Cooperative Studies V‐HeFT I and II. Circulation 1993; 87 (suppl VI): VI‐65–VI‐70 [PubMed] [Google Scholar]
- 38. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, Kubo SH, Nahara KA, Ingersoll H, Krueger S, Young S, Shusterman N, for the MOCHA Investigators : Carvedilol produces dose‐related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation 1996; 94: 2807–2816 [DOI] [PubMed] [Google Scholar]
- 39. Lechat P, Escolano S, Golmard JL, Lardoux H, Witchitz S, Henneman JA, Maisch B, Hetzel M, Jaillon P, Boissel JP, Mallet A, on behalf of the CIBIS Investigators : Prognostic value of bisoprolol‐induced hemodynamic effects in heart failure during the Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation 1997; 96: 2197–2205 [DOI] [PubMed] [Google Scholar]