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Home Therapies in Advanced Heart Failure: Inotropes and Diuretics

  • Ethics/Palliative Care (S Fedson, Section Editor)
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Abstract

Purpose of Review

Heart failure (HF) is a significant cause of morbidity, mortality, and decreased quality of life (QOL). Symptoms, including reduced activity tolerance, fatigue, palpitations, and dyspnea, result from volume overload or low output states. Herein, we review the best available literature supporting diuretic and inotropic therapies in advanced HF and how these improve QOL.

Recent Findings

While diuretics and inotropes reduce symptoms and hospitalizations in advanced HF, there is an increased risk of harms with both modalities. While diuretic complications include electrolyte and renal function abnormalities, adverse event data with inotropes is more complex and includes possible arrhythmias and death. Further, inotrope utilization is complicated by required intravenous access, infusion costs, and limited outpatient support.

Summary

Ambulatory use of diuretics and inotropes may improve patients’ QOL through symptom management and reduced hospitalizations. However, risks and limitations of both modalities must be considered as treatment decisions are made.

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References

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

  1. Virani SS, Alonso A, Benjamin EJ, Bittencort MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics--2020 update. A report from the American Heart Association. Circulation. 2020;141(9):e136–596. https://doi.org/10.1161/CIR.0000000000000757.

    Article  Google Scholar 

  2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, 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(16):e147–239. https://doi.org/10.1016/j.jacc.2013.05.019.

    Article  PubMed  Google Scholar 

  3. Verbrugge FH, Tang WHW, Mullens W. Renin-angiotensin-aldosterone system activation during decongestion in acute heart failure. Friend or foe? JACC Heart Fail. 2015;3(2):108–11. https://doi.org/10.1016/j.jchf.2014.10.005.

    Article  PubMed  Google Scholar 

  4. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999;341(8):577–85. https://doi.org/10.1056/NEJM199908193410806.

    Article  CAS  PubMed  Google Scholar 

  5. Blecker S, Herrin J, Li L, Yu H, Grady JN, Horwitz LI. Trends in hospital readmission of Medicare-covered patients with heart failure. J Am Coll Cardiol. 2019;73(9):1004–12. https://doi.org/10.1016/j.jacc.2018.12.040.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lin AH, Chin JC, Sicignano NM, Evans AM. Repeat hospitalizations predict mortality in patients with heart failure. Mil Med. 2017;182(9):e1932–7. https://doi.org/10.7205/MILMED-D-17-00017.

    Article  PubMed  Google Scholar 

  7. Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation. 1986;73(2):257–67. https://doi.org/10.1161/01.cir.73.2.257.

    Article  CAS  PubMed  Google Scholar 

  8. Maeda K, Tsutamoto T, Wada A, Mabuchi N, Hayashi M, Tsutsui T, et al. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol. 2000;36(5):1587–93. https://doi.org/10.1016/s0735-1097(00)00912-8.

    Article  CAS  PubMed  Google Scholar 

  9. Januzzi JL, Troughton R. Are serial BNP measurements useful in heart failure management? Serial natriuretic peptide measurements are useful in heart failure management. Circulation. 2013;127(4):500–7; discussion 508. https://doi.org/10.1161/CIRCULATIONAHA.112.120485.

    Article  PubMed  Google Scholar 

  10. Smith GL, Lichtman JH, Bracken MB, Shlipak MG, Phillips CO, DiCapua P, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol. 2006;47(10):1987–96. https://doi.org/10.1016/j.jacc.2005.11.084.

    Article  PubMed  Google Scholar 

  11. Abraham J, Bharmi R, Jonsson O, Oliveria GH, Artia A, Valika A, et al. Association of ambulatory hemodynamic monitoring of heart failure with clinical outcomes in a concurrent matched cohort analysis. JAMA Cardiol. 2019;4(6):556–63. https://doi.org/10.1001/jamacardio.2019.1384.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ellison DH. Clinical pharmacology in diuretic use. Clin J Am Soc Nephrol. 2019;14(8):1248–57. https://doi.org/10.2215/CJN.09630818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Brater DC. Diuretic therapy. N Engl J Med. 1998;339:387–95. https://doi.org/10.1056/nejm199808063390607.

    Article  CAS  PubMed  Google Scholar 

  14. Oh SW, Han SY. Loop diuretics in clinical practice. Electrolyte Blood Press. 2015;13(1):17–21. https://doi.org/10.5049/ebp.2015.13.1.17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ellison DH. Diuretic therapy and resistance in congestive heart failure. Cardiology. 2001;96(3–4):132–43. https://doi.org/10.1159/000047397.

    Article  CAS  PubMed  Google Scholar 

  16. Asare K. Management of loop diuretic resistance in the intensive care unit. Am J Health Syst Pharm. 2009;66(18):1635–40. https://doi.org/10.2146/ajhp090068.

    Article  PubMed  Google Scholar 

  17. Kaojarern S, Day B, Brater DC. The time course of delivery of furosemide into urine: an independent determinant of overall response. Kidney Int. 1982;22(1):69–74. https://doi.org/10.1038/ki.1982.134.

    Article  CAS  PubMed  Google Scholar 

  18. Brater DC. Pharmacology of diuretics. Am J Med Sci. 2000;319(1):38–50. https://doi.org/10.1097/00000441-200001000-00004.

    Article  CAS  PubMed  Google Scholar 

  19. Vargo DL, Kramer WG, Black PK, Smith WB, Serpas T, Brater DC. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther. 1995;57(6):601–9. https://doi.org/10.1016/0009-9236(95)90222-8.

    Article  CAS  PubMed  Google Scholar 

  20. Bailie GR, Grennan A, Waldek S. Bioavailability of bumetanide in grossly oedematous patients. Clin Pharmacokinet. 1987;12(6):440–3. https://doi.org/10.2165/00003088-198712060-00004.

    Article  CAS  PubMed  Google Scholar 

  21. Vasko MR, Cartwright DB, Knochel JP, Nixon JV, Brater DC. Furosemide absorption altered in decompensated congestive heart failure. Ann Intern Med. 1985;102(3):314–8. https://doi.org/10.7326/0003-4819-102-3-314.

    Article  CAS  PubMed  Google Scholar 

  22. Gehr TW, Rudy DW, Matzke GR, Kramer WG, Sica DA, Brater DC. The pharmacokinetics of intravenous and oral torsemide in patients with chronic renal insufficiency. Clin Pharmacol Ther. 1994;56(1):31–8. https://doi.org/10.1038/clpt.1994.98.

    Article  CAS  PubMed  Google Scholar 

  23. Mentz RJ, Hasselblad V, DeVore AD, Metra M, Voors AA, Armstrong PW, et al. Torsemide versus furosemide in patients with acute heart failure (from the ASCEND-HF trial). Am J Cardiol. 2016;117(3):404–11. https://doi.org/10.1016/j.amjcard.2015.10.059.

    Article  CAS  PubMed  Google Scholar 

  24. Rahhal A, Saad MO, Tawengi K, Assi AAR, Habra M, Ahmed D. Torsemide versus furosemide after acute decompensated heart failure: a retrospective observational study. BMC Cardiovasc Disord. 2019;19(1):127. https://doi.org/10.1186/s12872-019-1112-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. •• Abraham B, Megaly M, Sous M, Fransawyalkomos M, Saad M, Fraser R, et al. Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure. Am J Cardiol. 2020;125(1):92–9. https://doi.org/10.1016/j.jamjcard.2019.09.039. Torsemide was associated with a statistically significant improvement in functional class and lower risk of cardiac mortality in patients with worse NYHA functional class (III/IV) compared with those with better functional class (I/II).

    Article  CAS  PubMed  Google Scholar 

  26. Miles JA, Hanumanthu BK, Patel K, Chen M, Siegel RM, Kokkinidis DG. Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis. J Cardiovasc Med (Hagerstown). 2019;20(6):379–88. https://doi.org/10.2459/JCM.0000000000000794.

    Article  CAS  Google Scholar 

  27. Rao VS, Planavsky N, Hanberg JS, Ahmad T, Brisco-Bacik MA, Wilson FP, et al. Compensatory distal reabsorption drives diuretic resistance in human heart failure. J Am Soc Nephrol. 2017;28(11):3414–24. https://doi.org/10.1681/ASN.2016111178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Loon NR, Wilcox CS, Unwin RJ. Mechanism of impaired natriuretic response to furosemide during prolonged therapy. Kidney Int. 1989;36(4):682–9. https://doi.org/10.1038/ki.1989.246.

    Article  CAS  PubMed  Google Scholar 

  29. Almeshari K, Ahlstrom NG, Capraro FE, Wilcox CS. A volume-independent component to postdiuretic sodium retention in humans. J Am Soc Nephrol. 1993;3(12):1878–83.

    CAS  PubMed  Google Scholar 

  30. • Cox ZL, Hung R, Lenihan DJ, Testani JM. Diuretic strategies for loop diuretic resistance in acute heart failure: the 3T trial. JACC Heart Fail. 2020;8(3):157–68. https://doi.org/10.1016/j.jchf.2019.09.012The addition of metolazone, chlorothiazide, or tolvaptan to loop diuretics aided in diuresis and urine output, but not a statistically significant different.

    Article  PubMed  Google Scholar 

  31. Abdallah JG, Schrier RW, Edelstein C, Jennings SD, Wyse B, Ellison DH. Loop diuretic infusion increases thiazide-sensitive Na(+)/Cl(−)-cotransporter abundance: role of aldosterone. J Am Soc Nephrol. 2001;12(7):1335–41.

    CAS  PubMed  Google Scholar 

  32. Pitt B, Remme W, Zannad F, Nealton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–21. https://doi.org/10.1056/NEJMoa030207.

    Article  CAS  PubMed  Google Scholar 

  33. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, 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(10):709–17. https://doi.org/10.1056/NEJM199909023411001.

    Article  CAS  PubMed  Google Scholar 

  34. Zannad F, McMurray JJV, Krum H, van Veldhusin DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21. https://doi.org/10.1056/NEJMoa030207.

    Article  CAS  PubMed  Google Scholar 

  35. List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009;32(4):650–7. https://doi.org/10.2337/dc08-1863.

    Article  CAS  PubMed  Google Scholar 

  36. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. https://doi.org/10.1056/NEJMoa1504720.

    Article  CAS  PubMed  Google Scholar 

  37. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306. https://doi.org/10.1056/NEJMoa1811744.

    Article  CAS  PubMed  Google Scholar 

  38. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–57. https://doi.org/10.1056/NEJMoa1812389.

    Article  CAS  PubMed  Google Scholar 

  39. • McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. https://doi.org/10.1056/NEJMoa191103Patients receiving dapagliflozin over placebo experienced lower risk of worsening HF or death from cardiovascular causes regardless of whether the patient was diabetic or not.

    Article  CAS  PubMed  Google Scholar 

  40. Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf. 2014;5(6):242–54. https://doi.org/10.1177/2042098614551938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bersoff-Matcha SJ, Chamberlain C, Cao C, Kortepeter C, Chong WH. Fournier gangrene associated with sodium-glucose cotransporter-2 inhibitors: a review of spontaneous postmarketing cases. Ann Intern Med. 2019;170(11):764–9. https://doi.org/10.7326/M19-0085.

    Article  PubMed  Google Scholar 

  42. Heyward J, Mansour O, Olson L, Singh S, Alexander GC. Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: a systematic review and meta-analysis. PLoS One. 2020;15(6):e0234065. https://doi.org/10.1371/journal.pone.0234065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. • Makadia S, Simmons T, Augustine S, et al. The diuresis clinic: a new paradigm for the treatment of mild decompensated heart failure. Am J Med. 2015;128:527–31. https://doi.org/10.1016/j.amjmed.2014.11.028Treatment of mild HF decompensations in an outpatient parenteral diuretic clinic resulted in a “cost-effective decline” in rehospitalization rates.

    Article  PubMed  Google Scholar 

  44. Greene SJ, Wilson LE, Abbasi SA, Yusuf AA, Hammill BG. Outpatient intravenous diuretic therapy for heart failure in the United States. J Am Coll Cardiol. 2019;73(9):1101–3. https://doi.org/10.1016/j.jacc.2018.12.034.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ryder M, Murphy NF, McCaffrey D, O’Loughlin C, Ledwidge M, McDonald K. Outpatient intravenous diuretic therapy; potential for marked reduction in hospitalisations for acute decompensated heart failure. Eur J Heart Fail. 2008;10(3):267–72. https://doi.org/10.1016/j.ejheart.2008.01.003.

    Article  PubMed  Google Scholar 

  46. •• Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797–805. https://doi.org/10.1056/NEJMoa1005419No improvement in global symptom burden or change in renal function when parenteral loop diuretics were administered either by intermittent bolus over continuous infusion or by high dose compared with low dose.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sica DA, Muntendam P, Myers RL, Ter Maaten JM, Sale ME, de Boer RA, et al. Subcutaneous furosemide in heart failure: pharmacokinetic characteristics of a newly buffered solution. JACC Basic Transl Sci. 2018;3(1):25–34. https://doi.org/10.1016/j.jacbts.2017.10.001.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gilotra NA, Princewill O, Marino B, Okwuosa IS, Chasler J, Almansa J, et al. Efficacy of intravenous furosemide versus a novel, pH-neutral furosemide formulation administered subcutaneously in outpatients with worsening heart failure. JACC Heart Fail. 2018;6(1):65–70. https://doi.org/10.1016/j.jchf.2017.10.001.

    Article  PubMed  Google Scholar 

  49. Jozwiak R, Marks S. Subcutaneous diuretics for end-of-life management of heart failure #353. J Palliat Med. 2018;21(6):879–80. https://doi.org/10.1089/jpm.2018.0199.

    Article  PubMed  Google Scholar 

  50. Afari ME, Aoun J, Khare S, Tsao L. Subcutaneous furosemide for the treatment of heart failure: a state-of-the art review. Heart Fail Rev. 2019;24(3):309–13. https://doi.org/10.1007/s10741-018-9760-6.

    Article  CAS  PubMed  Google Scholar 

  51. • Abraham WT, Adams KF, Fonarow GC, Costanza MR, Berkowitz RL, LeJemtel TH, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005;46(1):57–64. https://doi.org/10.1016/j.jacc.2005.03.051Positive inotropic therapy was associated with a significantly higher in-hospital mortality for patient with acute decompensated HF versus those who received vasodilator or natriuretic peptide treatments.

    Article  PubMed  Google Scholar 

  52. Cuffe MS, Califf RM, Adams KF Jr, Benza R, Bourge R, Colucci WS, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002;287(12):1541–7. https://doi.org/10.1001/jama.287.12.1541.

    Article  CAS  PubMed  Google Scholar 

  53. Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005;96(6A):47g–58g. https://doi.org/10.1016/j.amjcard.2005.07.021.

    Article  CAS  PubMed  Google Scholar 

  54. Rossinen J, Harjola VP, Siirila-Waris K, Lassus J, Melin J, Peuhkurinen K, et al. The use of more than one inotrope in acute heart failure is associated with increased mortality: a multi-centre observational study. Acute Card Care. 2008;10(4):209–13. https://doi.org/10.1080/17482940802262376.

    Article  PubMed  Google Scholar 

  55. Khush KK, Cherikh WS, Chambers DC, Goldfarb S, Hayes D Jr, Kucheryavaya AY, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-fifth adult heart transplantation report-2018; focus theme: multiorgan transplantation. J Heart Lung Transplant. 2018;37(10):1155–68. https://doi.org/10.1016/j.healun.2018.07.022.

    Article  PubMed  Google Scholar 

  56. Gosev I, Kiernan MS, Eckman P, Soleimani B, Kilic A, Uriel N, et al. Long-term survival in patients receiving a continuous-flow left ventricular assist device. Ann Thorac Surg. 2018;105(3):696–701. https://doi.org/10.1016/j.athoracsur.2017.08.057.

    Article  PubMed  Google Scholar 

  57. • Hashim T, Sanam K, Revilla-Martinez M, Morgan CJ, Tallaj JA, Pamboukian SV, et al. Clinical characteristics and Outcomes of intravenous inotropic therapy in advanced heart failure. Circ Heart Fail. 2015;8(5):880–6. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001778Median survival for patients with AHF who are not candidates for transplantation or LVAD who receive palliative inotropic therapy remains low at 9 months; 1-year survival 47.6%, 2-year survival 38.4%.

    Article  CAS  PubMed  Google Scholar 

  58. Hershberger RE, Nauman D, Walker TL, Dutton D, Burgess D. Care processes and clinical outcomes of continuous outpatient support with inotropes (COSI) in patients with refractory endstage heart failure. J Card Fail. 2003;9(3):180–7. https://doi.org/10.1054/jcaf.2003.24.

    Article  PubMed  Google Scholar 

  59. Guglin M, Kaufman M. Inotropes do not increase mortality in advanced heart failure. Int J Gen Med. 2014;7:237–51. https://doi.org/10.2147/IJGM.S62549.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Vallet B, Dupuis B, Chopin C. Dobutamine: mechanisms of action and use in acute cardiovascular pathology (French). Ann Cardiol Angeiol (Paris). 1991;40(6):397–402.

    CAS  Google Scholar 

  61. Puddu PE, Papalia U, Schiariti M, Usta C. Dobutamine effects on spontaneous variability of ventricular arrhythmias in patients with severe chronic heart failure: the Italian multicenter study. Ital Heart J. 2004;5(9):693–701.

    PubMed  Google Scholar 

  62. Tisdale JE, Patel R, Webb CR, Borzak S, Zarowitz BJ. Electrophysiologic and proarrhythmic effects of intravenous inotropic agents. Prog Cardiovasc Dis. 1995;38(2):167–80. https://doi.org/10.1016/s0033-0620(05)80005-2.

    Article  CAS  PubMed  Google Scholar 

  63. • Martens P, Vercammen J, Ceyssens W, Jacobs L, Luwel E, Van Aerde H, et al. Effects of intravenous home dobutamine in palliative end-stage heart failure on quality of life, heart failure hospitalization, and cost expenditure. ESC Heart Fail. 2018;5(4):562–9. https://doi.org/10.1002/ehf2.12248Small study demonstrating home intravenous dobutamine improved symptom severity, HF hospitalizations, and healthcare-related costs.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Scholz H, Dieterich HA, Schmitz W. Mechanism of the positive inotropic effect of phosphodiesterase inhibitors (German). Z Kardiol. 1991;80 Suppl 4:1–6.

    CAS  PubMed  Google Scholar 

  65. Cesario D, Clark J, Maisel A. Beneficial effects of intermittent home administration of the inotrope/vasodilator milrinone in patients with end-stage congestive heart failure: a preliminary study. Am Heart J. 1998;135(1):121–9. https://doi.org/10.1016/S0002-8703(98)70352-7.

    Article  CAS  PubMed  Google Scholar 

  66. Hatzizacharias A, Makris T, Krespi P, Triposkiadis F, Voyatzi P, Dalianis N, et al. Intermittent milrinone effect on long-term hemodynamic profile in patients with severe congestive heart failure. Am Heart J. 1999;138(2 Pt 1):241–6. https://doi.org/10.1016/s0002-8703(99)70107-9.

    Article  CAS  PubMed  Google Scholar 

  67. Loh E, Elkayam U, Cody R, Bristow M, Jaski B, Colucci WS. A randomized multicenter study comparing the efficacy and safety of intravenous milrinone and intravenous nitroglycerin in patients with advanced heart failure. J Card Fail. 2001;7(2):114–21. https://doi.org/10.1054/jcaf.2001.24136.

    Article  CAS  PubMed  Google Scholar 

  68. Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al. Effect of oral milrinone on mortality in severe chronic heart failure. the PROMISE Study Research Group. N Engl J Med. 1991;325(21):1468–75. https://doi.org/10.1056/NEJM199111213252103.

    Article  CAS  PubMed  Google Scholar 

  69. DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989;320(11):677–83. https://doi.org/10.1056/NEJM198903163201101.

    Article  CAS  PubMed  Google Scholar 

  70. Kass DA, Solaro RJ. Mechanisms and use of calcium-sensitizing agents in the failing heart. Circulation. 2006;113(2):305–15. https://doi.org/10.1161/CIRCULATIONAHA.105.542407.

    Article  PubMed  Google Scholar 

  71. Nanayakkava S, Byrne M, Mak V, Carter K, Dean E, Kaye DM. Extended-release oral milrinone for the treatment of heart failure with preserved ejection fraction. J Am Heart Assoc. 2020;9:e015026. https://doi.org/10.1161/JAHA.119.015026.

    Article  Google Scholar 

  72. Packer M, Colucci W, Fisher L, Massie BM, Teerlink JR, Young J, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Heart Fail. 2013;1(2):103–11. https://doi.org/10.1016/j.jchf.2012.12.004.

    Article  PubMed  Google Scholar 

  73. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA. 2007;297(17):1883–91. https://doi.org/10.1001/jama.297.17.1883.

    Article  CAS  PubMed  Google Scholar 

  74. Effects of pimobendan on adverse cardiac events and physical activities in patients with mild to moderate chronic heart failure: the effects of pimobendan on chronic heart failure study (EPOCH study). Circ J. 2002;66(2):149–57. https://doi.org/10.1253/circj.66.149.

  75. Lubsen J, Just H, Hjalmarsson AC, la Framboise D, Remme WJ, Heinrich-Nols J, et al. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart. 1996;76(3):223–31. https://doi.org/10.1136/hrt.76.3.223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Papp Z, Agostoni P, Alvarez J, Bettex D, Bouchez S, Brito D, et al. Levosimendan efficacy and safety: 20 years of SIMDAX in clinical use. J Cardiovasc Pharmacol. 2020;7(1):4–22. https://doi.org/10.1097/FJC.0000000000000859.

    Article  CAS  Google Scholar 

  77. Harjola V-P, Giannakoulas G, von Lewinski D, Matskeplishvili S, Mebazaa A, Papp Z, et al. Use of levosimendan in acute heart failure. Eur Heart J Suppl. 2018;20(Suppl I):I2–I10. https://doi.org/10.1093/eurheartj/suy039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Smith TW. Digitalis. Mechanisms of action and clinical use. N Engl J Med. 1988;318(6):358–65. https://doi.org/10.1056/NEJM198802113180606.

    Article  CAS  PubMed  Google Scholar 

  79. Patel N, Ju C, Macon C, Thadani U, Schulte PJ, Hernandez AF, et al. Temporal trends of digoxin use in patients hospitalized with heart failure: analysis from the American Heart Association Get With The Guidelines-Heart Failure Registry. JACC Heart Fail. 2016;4(5):348–56. https://doi.org/10.1016/j.jchf.2015.12.003.

    Article  PubMed  Google Scholar 

  80. Gheorghiade M, Patel K, Filippatos G, Anker SD, van Veldhuisen DJ, Cleland JGF, et al. Effect of oral digoxin in high-risk heart failure patients: a pre-specified subgroup analysis of the DIG trial. Eur J Heart Fail. 2013;15(5):551–9. https://doi.org/10.1093/eurjhf/hft010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Turakhia MP, Santangeli P, Winkelmayer WC, Xu X, Ullall AJ, Than CT, et al. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study. J Am Coll Cardiol. 2014;64(7):660–8. https://doi.org/10.1016/j.jacc.2014.03.060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chong LYZ, Satya K, Kim B, Berkowitz R. Milrinone dosing and a culture of caution in clinical practice. Cardiol Rev. 2018;26(1):35–42. https://doi.org/10.1097/CRD.0000000000000165.

    Article  PubMed  Google Scholar 

  83. Groninger H, Gilhuly D, Walker KA. Getting to the heart of the matter: a regional survey of current hospice practices caring for patients with heart failure receiving advanced therapies. Am J Hosp Palliat Care. 2019;36(1):55–9. https://doi.org/10.1177/1049909118789338.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA

    Jason P. Graffagnino, Leslie C. Avant & Keith M. Swetz

  2. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Jason P. Graffagnino, Leslie C. Avant & Keith M. Swetz

  3. Western New York Veterans Affairs Medical Center, Department of Medicine, Jacobs School of Medicine at University of Buffalo, Buffalo, NY, USA

    Bethany C. Calkins

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  1. Jason P. Graffagnino
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  2. Leslie C. Avant
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  3. Bethany C. Calkins
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  4. Keith M. Swetz
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Correspondence to Keith M. Swetz.

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Graffagnino, J.P., Avant, L.C., Calkins, B.C. et al. Home Therapies in Advanced Heart Failure: Inotropes and Diuretics. Curr Heart Fail Rep 17, 314–323 (2020). https://doi.org/10.1007/s11897-020-00482-y

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