Home Inotropes in Advanced Heart Failure: A Practical Review
Abstract
1. Introduction
2. Evidence on Different Home Inotropes in Advanced Heart Failure
2.1. Levosimendan
2.2. Dobutamine
2.3. Milrinone
2.4. Dopamine
3. Practical Considerations in the Utilization of Home Inotropes
4. Limitations and Future Perspectives
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Dunlay, S.M.; Roger, V.L.; Killian, J.M.; Weston, S.A.; Schulte, P.J.; Subramaniam, A.V.; Blecker, S.B.; Redfield, M.M. Advanced Heart Failure Epidemiology and Outcomes: A Population-Based Study. JACC Heart Fail. 2021, 9, 722–732. [Google Scholar] [CrossRef]
- McDonagh, T.A.; Metra, M.; Adamo, M.; Gardner, R.S.; Baumbach, A.; Böhm, M.; Burri, H.; Butler, J.; Čelutkienė, J.; Chioncel, O.; et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. J. Heart Fail. 2022, 24, 4–131. [Google Scholar]
- Gustafsson, F.; Damman, K.; Nalbantgil, S.; Van Laake, L.W.; Tops, L.F.; Thum, T.; Adamopoulos, S.; Bonios, M.; Coats, A.J.; Crespo-Leiro, M.G.; et al. Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology. Eur. J. Heart Fail. 2023, 25, 457–468. [Google Scholar] [CrossRef]
- McDonagh, T.A.; Metra, M.; Adamo, M.; Gardner, R.S.; Baumbach, A.; Böhm, M.; Burri, H.; Butler, J.; Čelutkienė, J.; Chioncel, O.; et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 2023, 44, 3627–3639. [Google Scholar] [PubMed]
- Heidenreich, P.A.; Bozkurt, B.; Aguilar, D.; Allen, L.A.; Byun, J.J.; Colvin, M.M.; Deswal, A.; Drazner, M.H.; Dunlay, S.M.; Evers, L.R.; et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022, 145, 18. [Google Scholar] [CrossRef] [PubMed]
- Shringi, S.; Joshi, S.; Suffredini, J.M.; Schenk, A.; Rajagopalan, N.; Guglin, M. Long-Term Ambulatory Intravenous Milrinone Therapy in Advanced Heart Failure. Heart Lung Circ. 2022, 31, 1630–1639. [Google Scholar] [CrossRef] [PubMed]
- Silvetti, S.; Pollesello, P.; Belletti, A. Repeated Levosimendan Infusions in the Management of Advanced Heart Failure: Review of the Evidence and Meta-analysis of the Effect on Mortality. J. Cardiovasc. Pharmacol. 2024, 83, 144–157. [Google Scholar] [CrossRef]
- Gentile, P.; Masciocco, G.; Palazzini, M.; Tedeschi, A.; Ruzzenenti, G.; Conti, N.; D’Angelo, L.; Foti, G.; Perna, E.; Verde, A.; et al. Intravenous continuous home inotropic therapy in advanced heart failure: Insights from an observational retrospective study. Eur. J. Intern. Med. 2023, 116, 65–71. [Google Scholar] [CrossRef]
- Pollesello, P.; Ovaska, M.; Kaivola, J.; Tilgmann, C.; Lundström, K.; Kalkkinen, N.; Ulmanen, I.; Nissinen, E.; Taskinen, J. Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C: A molecular modelling, fluorescence probe, and proton nuclear magnetic resonance study. J. Biol. Chem. 1994, 269, 28584–28590. [Google Scholar] [CrossRef]
- Mavrogeni, S.; Giamouzis, G.; Papadopoulou, E.; Thomopoulou, S.; Dritsas, A.; Athanasopoulos, G.; Adreanides, E.; Vassiliadis, I.; Spargias, K.; Panagiotakos, D. A 6-Month Follow-up of Intermittent Levosimendan Administration Effect on Systolic Function, Specific Activity Questionnaire, and Arrhythmia in Advanced Heart Failure. J. Card. Fail. 2007, 13, 556–559. [Google Scholar] [CrossRef]
- Berger, R.; Moertl, D.; Huelsmann, M.; Bojic, A.; Ahmadi, R.; Heissenberger, I.; Pacher, R. Levosimendan and prostaglandin E1 for uptitration of beta-blockade in patients with refractory, advanced chronic heart failure. Eur. J. Heart Fail. 2007, 9, 202–208. [Google Scholar] [CrossRef]
- Kleber, F.X.; Bollmann, T.; Borst, M.M.; Costard-Jäckle, A.; Ewert, R.; Kivikko, M.; Petterson, T.; Pohjanjousi, P.; Sonntag, S.; Wikström, G. Repetitive dosing of intravenous levosimendan improves pulmonary hemodynamics in patients with pulmonary hypertension: Results of a pilot study. J. Clin. Pharmacol. 2009, 49, 109–115. [Google Scholar] [CrossRef] [PubMed]
- Malfatto, G.; Della Rosa, F.; Villani, A.; Rella, V.; Branzi, G.; Facchini, M.; Parati, G. Intermittent levosimendan infusions in advanced heart failure: Favourable effects on left ventricular function, neurohormonal balance, and one-year survival. J. Cardiovasc. Pharmacol. 2012, 60, 450–455. [Google Scholar] [CrossRef] [PubMed]
- Altenberger, J.; Parissis, J.T.; Costard-Jaeckle, A.; Winter, A.; Ebner, C.; Karavidas, A.; Sihorsch, K.; Avgeropoulou, E.; Weber, T.; Dimopoulos, L.; et al. Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: A multicentre randomized trial. Eur. J. Heart Fail. 2014, 16, 898–906. [Google Scholar] [CrossRef]
- Comín-Colet, J.; Manito, N.; Segovia-Cubero, J.; Delgado, J.; García Pinilla, J.M.; Almenar, L.; Crespo-Leiro, M.G.; Sionis, A.; Blasco, T.; Pascual-Figal, D.; et al. Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: The LION-HEART multicentre randomised trial. Eur. J. Heart Fail. 2018, 20, 1128–1136. [Google Scholar] [CrossRef]
- Oliva, F.; Perna, E.; Marini, M.; Nassiacos, D.; Cirò, A.; Malfatto, G.; Morandi, F.; Caico, I.; Perna, G.; Meloni, S.; et al. Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration. Int. J. Cardiol. 2018, 272, 255–259. [Google Scholar] [CrossRef]
- García-González, M.J.; Aldea Perona, A.; Lara Padron, A.; Morales Rull, J.L.; Martínez-Sellés, M.; de Mora Martin, M.; López Díaz, J.; López Fernandez, S.; Ortiz Oficialdegui, P.; Jiménez Sosa, A. Efficacy and safety of intermittent repeated levosimendan infusions in advanced heart failure patients: The LAICA study. ESC Heart Fail. 2021, 8, 4820–4831. [Google Scholar] [CrossRef]
- Pölzl, G.; Altenberger, J.; Comín-Colet, J.; Delgado, J.F.; Fedele, F.; García-González, M.J.; Gustafsson, F.; Masip, J.; Papp, Z.; Störk, S.; et al. Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period: The multinational randomized LeoDOR trial. Eur. J. Heart Fail. 2023, 25, 2007–2017. [Google Scholar] [CrossRef]
- Leier, C.V.; Huss, P.; Lewis, R.P.; Unverferth, D.V. Drug-induced conditioning in congestive heart failure. Circulation 1982, 65, 1382–1387. [Google Scholar] [CrossRef]
- Applefeld, M.M.; Newman, K.A.; Grove, W.R.; Sutton, F.J.; Roffman, D.S.; Reed, W.P.; Linberg, S.E. Intermittent, continuous outpatient dobutamine infusion in the management of congestive heart failure. Am. J. Cardiol. 1983, 51, 455–458. [Google Scholar] [CrossRef]
- Applefeld, M.M.; Newman, K.A.; Sutton, F.J.; Reed, W.P.; Roffman, D.S.; Talesnick, B.S.; Grove, W.R. Outpatient dobutamine and dopamine infusions in the management of chronic heart failure: Clinical experience in 21 patients. Am. Heart J. 1987, 114, 589–595. [Google Scholar] [CrossRef] [PubMed]
- Oliva, F.; Latini, R.; Politi, A.; Staszewsky, L.; Maggioni, A.P.; Nicolis, E.; Mauri, F. Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE multicenter trial. Am. Heart J. 1999, 138, 589–595. [Google Scholar] [CrossRef] [PubMed]
- O’Connor, C.M.; Gattis, W.A.; Uretsky, B.F.; Adams KFJr McNulty, S.E.; Grossman, S.H.; McKenna, W.J.; Zannad, F.; Swedberg, K.; Gheorghiade, M.; Califf, R.M. Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: Insights from the Flolan International Randomized Survival Trial (FIRST). Am. Heart J. 1999, 138, 78–86. [Google Scholar] [CrossRef] [PubMed]
- Lang, C.C.; Hankins, S.; Hauff, H.; Maybaum, S.; Edwards, N.; Mancini, D.M. Morbidity and mortality of UNOS status 1B cardiac transplant candidates at home. J. Heart Lung Transplant. 2003, 22, 419–426. [Google Scholar] [CrossRef]
- Martens, P.; Vercammen, J.; Ceyssens, W.; Jacobs, L.; Luwel, E.; Van Aerde, H.; Potargent, P.; Renaers, M.; Dupont, M.; Mullens, W. 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, 562–569. [Google Scholar] [CrossRef]
- Jobbé-Duval, A.; Bochaton, T.; Baudry, G.; Bonnefoy-Cudraz, E.; Hugon-Vallet, E.; Pozzi, M.; Obadia, J.F.; Tomasevic, D.; Amaz, C.; Mewton, N.; et al. Outcome predictors and safety of home dobutamine intravenous infusion in end stage heart failure patients. J. Clin. Med. 2021, 10, 2571. [Google Scholar] [CrossRef]
- Likoff, M.J. Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: A multicenter study. J. Am. Coll. Cardiol. 1987, 9, 711–722. [Google Scholar]
- Packer, M.; Carver, J.R.; Rodeheffer, R.J.; Ivanhoe, R.J.; DiBianco, R.; Zeldis, S.M.; Hendrix, G.H.; Bommer, W.J.; Elkayam, U.; Kukin, M.L.; et al. Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure. N. Engl. J. Med. 1991, 325, 1468–1475. [Google Scholar] [CrossRef]
- Cuffe, M.S.; Califf, R.M.; Adams , K.F., Jr.; Benza, R.; Bourge, R.; Colucci, W.S.; Massie, B.M.; O’Connor, C.M.; Pina, I.; Quigg, R.; et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: A randomized controlled trial. JAMA 2002, 287, 1541–1547. [Google Scholar] [CrossRef]
- Viéitez Flórez, J.M.; Hernández Pérez, F.J.; Mitroi, C.; Lozano Jiménez, S.; Gómez Bueno, M.; Segovia Cubero, J. Usefulness of ambulatory milrinone perfusion in a cohort of advanced heart failure patients. Rev. Española Cardiol. 2023, 76, 386–388. [Google Scholar] [CrossRef]
- Hashim, T.; Sanam, K.; Revilla-Martinez, M.; Morgan, C.J.; Tallaj, J.A.; Pamboukian, S.V.; Loyaga-Rendon, R.Y.; George, J.F.; Acharya, D. Clinical Characteristics and Outcomes of Intravenous Inotropic Therapy in Advanced Heart Failure. Circ. Heart Fail. 2015, 8, 880–886. [Google Scholar] [CrossRef]
- Zewail, A.M.; Nawar, M.; Vrtovec, B.; Eastwood, C.; Kar, M.N.; Delgado, R.M., 3rd. Intravenous milrinone in treatment of advanced congestive heart failure. Tex. Heart Inst. J. 2003, 30, 880–886. [Google Scholar]
- Lee, E.C.; McNitt, S.; Martens, J.; Bruckel, J.T.; Chen, L.; Alexis, J.D.; Storozynsky, E.; Thomas, S.; Gosev, I.; Barrus, B.; et al. Long-term milrinone therapy as a bridge to heart transplantation: Safety, efficacy, and predictors of failure. Int. J. Cardiol. 2020, 313, 83–88. [Google Scholar] [CrossRef] [PubMed]
- Harhash, A.A.; Cassuto, J.; Hussein, A.; Achu, E.; Zucker, M.J.; Goldschmidt, M.; Alpert, J.S.; Baran, D.A. Safety of Outpatient Milrinone Infusion in End-Stage Heart Failure: ICD-Level Data on Atrial Fibrillation and Ventricular Tachyarrhythmias. Am. J. Med. 2020, 133, 857–864. [Google Scholar] [CrossRef] [PubMed]
- Sindone, A.P.; Keogh, A.M.; Macdonald, P.S.; McCosker, C.J.; Kaan, A.F. Continuous home ambulatory intravenous inotropic drug therapy in severe heart failure: Safety and cost efficacy. Am. Heart, J. 1997, 134, 889–900. [Google Scholar] [CrossRef]
- Stevenson, L.W.; Miller, L.W.; Desvigne-Nickens, P.; Ascheim, D.D.; Parides, M.K.; Renlund, D.G.; Oren, R.M.; Krueger, S.K.; Costanzo, M.R.; Wann, L.S.; et al. Left ventricular assist device as destination for patients undergoing intravenous inotropic therapy: A subset analysis from REMATCH (Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure). Circulation 2004, 110, 975–981. [Google Scholar] [CrossRef]
- Elsaeidy, A.S.; Abuelazm, M.; Ghaly, R.; Soliman, Y.; Amin, A.M.; El-Gohary, M.; Elshenawy, S.; Seri, A.R.; Abdelazeem, B.; Patel, B.; et al. The Efficacy and Safety of Levosimendan in Patients with Advanced Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials. Am. J. Cardiovasc. Drugs 2024, 24, 775–790. [Google Scholar] [CrossRef]
- Mebazaa, A.; Nieminen, M.S.; Packer, M.; Cohen-Solal, A.; Kleber, F.X.; Pocock, S.J.; Thakkar, R.; Padley, R.J.; Põder, P.; Kivikko, M.; et al. Levosimendan vs. dobutamine for patients with acute decompensated heart failure: The SURVIVE randomized trial. JAMA 2007, 297, 1883–1891. [Google Scholar] [CrossRef]
- Packer, M.; Colucci, W.; Fisher, L.; Massie, B.M.; Teerlink, J.R.; Young, J.; Padley, R.J.; Thakkar, R.; Delgado-Herrera, L.; Salon, J.; et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Heart Fail. 2013, 1, 103–111. [Google Scholar] [CrossRef]
- Vallet, B.; Dupuis, B.; Chopin, C. Dobutamine: Mechanisms of action and use in acute cardiovascular pathology. Ann. Cardiol. Angeiol. 1991, 40, 397–402. [Google Scholar]
- Dobashi, S.; Watanabe, I.; Nakanishi, R.; Hisatake, S.; Kiuchi, S.; Kabuki, T.; Oka, T.; Fujii, T.; Ikeda, T. Comparing the effects of milrinone and olprinone in patients with congestive heart failure. Heart Vessels 2020, 35, 776–785. [Google Scholar] [CrossRef] [PubMed]
- Acharya, D.; Sanam, K.; Revilla-Martinez, M.; Hashim, T.; Morgan, C.J.; Pamboukian, S.V.; Loyaga-Rendon, R.Y.; Tallaj, J.A. Infections, arrhythmias, and hospitalizations on home intravenous inotropic therapy. Am. J. Cardiol. 2016, 117, 952–956. [Google Scholar] [CrossRef] [PubMed]
- Savarese, G.; Becher, P.M.; Lund, L.H.; Seferovic, P.; Rosano, G.M.C.; Coats, A.J.S. Global burden of heart failure: A comprehensive and updated review of epidemiology. Cardiovasc. Res. 2023, 118, 3272–3287. [Google Scholar] [CrossRef] [PubMed]
- Crespo-Leiro, M.G.; Metra, M.; Lund, L.H.; Milicic, D.; Costanzo, M.R.; Filippatos, G.; Gustafsson, F.; Tsui, S.; Barge-Caballero, E.; De Jonge, N.; et al. Advanced heart failure: A position statement of the Heart Failure Association of the European Society of Cardiology. Eur. J. Heart Fail. 2018, 20, 1505–1535. [Google Scholar] [CrossRef]
- Harjai, K.J.; Mehra, M.R.; Ventura, H.O.; Lapeyre, Y.M.; Murgo, J.P.; Stapleton, D.D.; Smart, F.W. Home inotropic therapy in advanced heart failure: Cost analysis and clinical outcomes. Chest 1997, 112, 1298–1303. [Google Scholar] [CrossRef]
- Chua, D.; Buttar, A.; Kaan, A.; Andrews, H.; Kealy, J.; Lam, S. 453 Development of a home intravenous inotrope program for end-stage heart failure patients awaiting heart transplantation. Can. J. Cardiol. 2011, 27, S226. [Google Scholar] [CrossRef]
- Mathew, R.; Di Santo, P.; Jung, R.G.; Marbach, J.A.; Hutson, J.; Simard, T.; Ramirez, F.D.; Harnett, D.T.; Merdad, A.; Almufleh, A.; et al. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N. Engl. J. Med. 2021, 385, S226. [Google Scholar] [CrossRef]
- Zeitouni, M.; Dorvillius, E.; Sulman, D.; Procopi, N.; Beaupré, F.; Devos, P.; Barthélémy, O.; Rouanet, S.; Ferrante, A.; Chommeloux, J.; et al. Levosimendan in Patients with Cardiogenic Shock Refractory to Dobutamine Weaning. Am. J. Cardiovasc. Drugs 2024, 25, 249–258. [Google Scholar] [CrossRef]
- Nanayakkara, S.; Mak, V.; Crannitch, K.; Byrne, M.; Kaye, D.M. Extended Release Oral Milrinone, CRD-102, for Advanced Heart Failure. Am. J. Cardiol. 2018, 122, 1017–1020. [Google Scholar] [CrossRef]
- Nanayakkara, S.; Byrne, M.; Mak, V.; Carter, K.; Dean, E.; Kaye, D.M. Extended-release oral milrinone for the treatment of heart failure with preserved ejection fraction. J. Am. Heart Assoc. 2020, 9, e015026. [Google Scholar] [CrossRef]
- Nguyen, A.Q.N.; Denault, A.Y.; Théoret, Y.; Varin, F. Inhaled milrinone in cardiac surgical patients: Pharmacokinetic and pharmacodynamic exploration. Sci. Rep. 2023, 13, 3557. [Google Scholar] [CrossRef]
- Cox, Z.L.; Dalia, T.; Goyal, A.; Fritzlen, J.; Gupta, B.; Shah, Z.; Sauer, A.J.; Haglund, N.A. Novel Nebulized Milrinone Formulation for the Treatment of Acute Heart Failure Requiring Inotropic Therapy: A Phase 1 Study. J. Card. Fail. 2024, 30, 329–336. [Google Scholar] [CrossRef]
- Teerlink, J.R.; Diaz, R.; Felker, G.M.; McMurray, J.J.V.; Metra, M.; Solomon, S.D.; Adams, K.F.; Anand, I.; Arias-Mendoza, A.; Biering-Sørensen, T.; et al. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure. N. Engl. J. Med. 2021, 384, 105–116. [Google Scholar] [CrossRef]
- Felker, G.M.; Solomon, S.D.; Claggett, B.; Diaz, R.; McMurray, J.J.V.; Metra, M.; Anand, I.; Crespo-Leiro, M.G.; Dahlström, U.; Goncalvesova, E.; et al. Assessment of Omecamtiv Mecarbil for the Treatment of Patients with Severe Heart Failure: A Post Hoc Analysis of Data from the GALACTIC-HF Randomized Clinical Trial. JAMA Cardiol. 2022, 7, 26–34. [Google Scholar] [CrossRef]
- Van Linthout, S.; Stellos, K.; Giacca, M.; Bertero, E.; Cannata, A.; Carrier, L.; Garcia-Pavia, P.; Ghigo, A.; González, A.; Haugaa, K.H.; et al. State of the art and perspectives of gene therapy in heart failure. A scientific statement of the Heart Failure Association of the ESC, the ESC Council on Cardiovascular Genomics and the ESC Working Group on Myocardial & Pericardial Diseases. Eur. J. Heart Fail. 2024, 27, 5–25. [Google Scholar]
Study | Patients | Type of Study | Administration Scheme | Main Results |
---|---|---|---|---|
Levosimendan | ||||
Mavrogeni et al. (2007) [10] | N = 50 | Single-center, randomized, prospective. | Bolus of 6 μg/kg, followed by 0.1 μg/kg/min, uptitrated to 0.2 μg/kg/min over 24 h. Monthly for 6 months. | Improved LVEF, decrease in MR severity, 6-month mortality 8% in levosimendan arm vs. 32% in placebo arm. |
Berger et al. (2007) [11] | N = 75 | Single-center, randomized, open, parallel group trial. | Loading dose: 12 μg/kg over 10 min (if SBP ≥ 95 mmHg), then 0.1 μg/kg/min for 24 h. Monthly for 3 months. | Facilitated beta-blocker uptitration in refractory patients. 3-month occurrence of death/HT/LVAD 31% in levosimendan arm. |
Kleber et al. (2009) [12] | N = 28 | Single-center, Randomized, prospective. | Initial: 12 μg/kg over 10 min, then 0.1 μg/kg/min for 50 min, followed by 0.2 μg/kg/min for 23 h; subsequent infusions: 0.2 μg/kg/min over 6 h every 2 weeks. | Significant reduction in pulmonary vascular resistance in patients with PH. |
Malfatto et al. (2012) [13] | N = 33 | Single-center, randomized, open-label | 0.1–0.4 μg/kg/min over 24 h, monthly for 1 year. | Improved LVEF, Diastolic function, MR severity, and BNP levels. 1-year CV mortality 18.2% in levosimendan arm vs. 36.4% in furosemide arm. |
Altenberger et al. (2014) (LevoRep) [14] | N = 120 | Multicenter RCT | 0.2 μg/kg/min over 6 h, every 2 weeks for 6 weeks. | No significant improvement in 6 min walk test or QoL; numerically lower number of cardiac deaths, HT, and HF hospitalizations in levosimendan arm. |
Comín-Colet et al. (2018) (LION-HEART) [15] | N = 69 | Multicenter RCT | 0.2 μg/kg/min over 6 h, every 2 weeks for 12 weeks. | Reduced NT-proBNP levels and HF hospitalizations; less decline in HRQoL. |
Oliva et al. (2018) (RELEVANT-HF) [16] | N = 185 | Observational multicenter study | Tailored 0.05–0.2 μg/kg/min over 24–48 h, every 3–4 weeks for ≥6 months. | Lower days in hospital, cumulative number and length of HF hospitalizations. |
García-González et al. (2021) (LAICA) [17] | N = 97 | Multicenter RCT | 0.1 μg/kg/min over 24 h, monthly for 12 months. | Significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 months, and a significant improvement in survival during 12 months of treatment. |
Pölzl et al. (2023) (LeoDOR) [18] | N = 145 | Multinational RCT | Option 1: 0.2 μg/kg/min over 6 h every 2 weeks; Option 2: 0.1 μg/kg/min over 24 h every 3 weeks, for 12 weeks. | No significant effect on primary endpoint; safe with some QoL benefits. |
Dobutamine | ||||
Leier et al. (1982) [19] | N = 26 | Single-center, Randomized controlled trial | 4 h IV infusions weekly for 24 weeks. | Improved exercise tolerance and clinical status; modest improvement in LV function. |
Applefeld et al. (1983) [20] | N = 3 | Single-center, Observational study | Continuous outpatient IV dobutamine via portable infusion pump; dosing individualized. | Improved symptoms and hemodynamics; feasible outpatient management; possible tolerance of long-term infusion. |
Applefeld et al. (1987) [21] | N = 21 | Single-center, Observational study | 48 h IV infusions weekly or continuous infusions; 4 patients also received dopamine infusion. | Improved cardiac index and functional status; feasible outpatient management. |
Oliva et al. (1999) (DICE trial) [22] | N = 38 | Multicenter randomized trial | 2.5 μg/kg/min over 48 h/week for 6 months via portable pump. | Lower number of HF hospitalizations in the dobutamine arm; no improvement in functional status. |
O’Connor et al. (1999) (FIRST trial) [23] | 471 (80 on dobutamine) | Multicenter randomized trial | Continuous IV dobutamine; dosing not specified | Higher 6-month mortality in the dobutamine group; dobutamine emerged as an independent predictor of death. |
Lang et al. (2003) [24] | N = 91 (home group, 39 on dobutamine) | Single-center Observational study | Continuous home IV dobutamine at <7.5 μg/kg/min | Low mortality, high readmission rate, low incidence of arrhythmias |
Martens et al. (2018) [25] | N = 21 | Single-center Observational study | Continuous home IV dobutamine; dosing individualized | Reduced NYHA class and NT-proBNP; reduced HF hospitalizations and healthcare costs |
Jobbé-Duval et al. (2021) [26] | N = 19 | Single-center Retrospective observational study | Continuous home IV dobutamine at 2.6 ± 1.2 μg/kg/min | 32% 1-year survival; catheter-related adverse events in 26%; GFR > 60 mL/min and BNP < 1000 ng/L predicted better survival |
Milrinone | ||||
Anderson et al. (1987) [27] | N = 189 | Multicenter study | 0.25 to 0.75 μg/kg/min over 48 h | Improved cardiac hemodynamics; no significant arrhythmias |
Packer et al. (1991) (PROMISE) [28] | N = 1088 | Multicenter RCT | 40 mg oral daily | Increased all-cause mortality by 28% (95% CI: 1–61%; p = 0.038); cardiovascular mortality increased by 34% (95% CI: 6–69%; p = 0.016) |
Cuffe et al. (2002) [29] | N = 951 | Multicenter RCT | 0.5 μg/kg/min IV for 48 h | No significant difference in 60-day mortality or hospitalization; increased hypotension and arrhythmias |
Viéitez Flórez et al. (2023) [30] | N = 19 | Single-center Observational study | Continuous ambulatory IV milrinone; dosing individualized (0.3 to 0.4 μg/kg/min). | Overall success rate of 74% (78% in BTT, 100% in BTC; 57% in palliative care). |
Hashim et al. (2015) [31] | N = 166 | Retrospective observational study | Continuous IV milrinone; dosing individualized (mean dose 0.296 ± 0.092 μg/kg per minute) | Improved hemodynamics and LVEF; improvement in NYHA Class; 1-year survival of 47.6% in the palliative care group. |
Zewail et al. (2003) [32] | N = 65 | Single-center Observational study | Continuous IV infusion (mean duration 269 days). | 51 patients successfully initiated β-blocker therapy; improved hemodynamics, significant decrease in in-hospital stay, and number of HF hospitalizations. |
Lee et al. (2020) [33] | N = 150 | Single-center, Retrospective observational study | Long-term IV milrinone as a bridge to transplant; dosing individualized. | Safe and effective as bridge therapy (78% of success); predictors of failure included male sex, no ICD, and lack of GDMT (especially beta-blockers). |
Harhash et al. (2020) [34] | N = 98 | Single-center, Retrospective observational study | Outpatient IV milrinone; dosing individualized | Median survival 581 ± 96 days; higher incidence of ICD shocks in those with previous ventricular arrhythmias. |
Dopamine | ||||
Sindone et al. (2020) [35] | N = 20 (13 pts on dopamine alone) | Single-center. Retrospective observational study | Outpatient IV dopamine; average dose 4.4 ± 1.1 mcg/kg/min | 71% of survival at 3 months; 70% of the time spent outside the hospital; 11 patients received HT. |
Stevenson L. et al. (2004) [36] | N = 61 on inotropes (16 on dopamine) | Randomized clinical trial | Outpatient or inpatient setting | 25% 1-year survival in patients on inotropes. |
Gentile et al. (2023) [8] | N = 14 | Single-center retrospective observational study | Outpatient IV dopamine, average dose 2.9 ± 0.56 mcg/kg/mi | Decrease in HF hospitalizations (from 1.93 ± 0.99 per patient to 0.93 ± 0.958 per year) |
Indications | Contraindications |
---|---|
Persistently highly symptomatic (NYHA IV) despite optimized medical/device therapy | Uncontrolled or life-threatening ventricular arrhythmias |
Refractory congestion not responsive to diuretics | Severe uncontrolled hypertension |
Signs of systemic hypoperfusion | Inability to ensure safe venous access |
Multiorgan dysfunction | Inability to guarantee adequate monitoring and follow-up |
Bridge to advanced therapies (LVAD or HT) | |
Palliative option when advanced therapies are not feasible |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Manca, P.; Matassini, M.V.; Fazzini, L.; Bianco, M.; Di Nora, C.; Rizzello, V.; Carigi, S.; De Gennaro, L.; Tinti, M.D.; De Maria, R.; et al. Home Inotropes in Advanced Heart Failure: A Practical Review. J. Clin. Med. 2025, 14, 7018. https://doi.org/10.3390/jcm14197018
Manca P, Matassini MV, Fazzini L, Bianco M, Di Nora C, Rizzello V, Carigi S, De Gennaro L, Tinti MD, De Maria R, et al. Home Inotropes in Advanced Heart Failure: A Practical Review. Journal of Clinical Medicine. 2025; 14(19):7018. https://doi.org/10.3390/jcm14197018
Chicago/Turabian StyleManca, Paolo, Maria Vittoria Matassini, Luca Fazzini, Matteo Bianco, Concetta Di Nora, Vittoria Rizzello, Samuela Carigi, Luisa De Gennaro, Maria Denitza Tinti, Renata De Maria, and et al. 2025. "Home Inotropes in Advanced Heart Failure: A Practical Review" Journal of Clinical Medicine 14, no. 19: 7018. https://doi.org/10.3390/jcm14197018
APA StyleManca, P., Matassini, M. V., Fazzini, L., Bianco, M., Di Nora, C., Rizzello, V., Carigi, S., De Gennaro, L., Tinti, M. D., De Maria, R., Colivicchi, F., Grimaldi, M., Oliva, F., & Gori, M. (2025). Home Inotropes in Advanced Heart Failure: A Practical Review. Journal of Clinical Medicine, 14(19), 7018. https://doi.org/10.3390/jcm14197018