Skip to main content
Top
Published in: Clinical Research in Cardiology 11/2015

01-11-2015 | Original Paper

A single German center experience with intermittent inotropes for patients on the high-urgent heart transplant waiting list

Authors: T. Hübner, T. Nickel, G. Steinbeck, S. Massberg, R. Schramm, B. Reichart, C. Hagl, A. Kiwi, Michael Weis

Published in: Clinical Research in Cardiology | Issue 11/2015

Login to get access

Abstract

Aim

Currently, more than 900 patients with end-stage heart failure are listed for heart transplantation in Germany. All patients on the Eurotransplant high-urgent status (HU) have to be treated in intensive care units and have to be relisted every 8 weeks. Long-term continuous inotropes are associated with tachyphylaxia, arrhythmias and even increased mortality. In this retrospective analysis, we report our single center experience with HU patients treated with intermittent inotropes as a bridging therapy.

Methods and results

117 consecutive adult HU candidates were treated at our intensive care heart failure unit between 2008 and 2013, of whom 14 patients (12 %) were stabilized and delisted during follow-up. In the remaining 103 patients (age 42 ± 15 years), different inotropes (dobutamine, milrinone, adrenaline, noradrenaline, levosimendan) were administered based on the patient’s specific characteristics. After initial recompensation, patients were weaned from inotropes as soon as possible. Thereafter, intermittent inotropes (over 3–4 days) were given as a predefined weekly (until 2011) or 8 weekly regimen (from 2011 to 2013). In 57 % of these patients, additional regimen-independent inotropic support was necessary due to hemodynamic instabilities. Fourteen patients (14 %) needed a left- or biventricular assist device; 14 patients (14 %) died while waiting and 87 (84 %) received heart transplants after 87 ± 91 days. Cumulative 3 and 12 months survival of all 103 patients was 75 and 67 %, respectively.

Conclusion

Intermittent inotropes in HU patients are an adequate strategy as a bridge to transplant; the necessity for assist devices was low. These data provide the basis for a prospective multicenter trial of intermittent inotropes in patients on the HU waiting list.
Literature
1.
go back to reference Felker GM, O’Connor CM (2001) Inotropic therapy for heart failure: an evidence-based approach. Am Heart J 142:393–401CrossRefPubMed Felker GM, O’Connor CM (2001) Inotropic therapy for heart failure: an evidence-based approach. Am Heart J 142:393–401CrossRefPubMed
2.
go back to reference Mortara A, Oliva F, Metra M, Carbonieri E, Di Lenarda A, Gorini M, Midi P, Senni M, Urso R, Lucci D, Maggioni AP, Tavazzi L (2014) Treatment with inotropes and related prognosis in acute heart failure: contemporary data from the italian network on heart failure (in-hf) outcome registry. J Heart Lung Transplant 33:1056–1065CrossRefPubMed Mortara A, Oliva F, Metra M, Carbonieri E, Di Lenarda A, Gorini M, Midi P, Senni M, Urso R, Lucci D, Maggioni AP, Tavazzi L (2014) Treatment with inotropes and related prognosis in acute heart failure: contemporary data from the italian network on heart failure (in-hf) outcome registry. J Heart Lung Transplant 33:1056–1065CrossRefPubMed
3.
go back to reference Gorodeski EZ, Chu EC, Reese JR, Shishehbor MH, Hsich E, Starling RC (2009) Prognosis on chronic dobutamine or milrinone infusions for stage d heart failure. Circ Heart Fail 2:320–324CrossRefPubMed Gorodeski EZ, Chu EC, Reese JR, Shishehbor MH, Hsich E, Starling RC (2009) Prognosis on chronic dobutamine or milrinone infusions for stage d heart failure. Circ Heart Fail 2:320–324CrossRefPubMed
4.
go back to reference Liang CS, Sherman LG, Doherty JU, Wellington K, Lee VW, Hood WB Jr (1984) Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine. Circulation 69:113–119CrossRefPubMed Liang CS, Sherman LG, Doherty JU, Wellington K, Lee VW, Hood WB Jr (1984) Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine. Circulation 69:113–119CrossRefPubMed
5.
go back to reference Hatzizacharias A, Makris T, Krespi P, Triposkiadis F, Voyatzi P, Dalianis N, Kyriakidis M (1999) Intermittent milrinone effect on long-term hemodynamic profile in patients with severe congestive heart failure. Am Heart J 138:241–246CrossRefPubMed Hatzizacharias A, Makris T, Krespi P, Triposkiadis F, Voyatzi P, Dalianis N, Kyriakidis M (1999) Intermittent milrinone effect on long-term hemodynamic profile in patients with severe congestive heart failure. Am Heart J 138:241–246CrossRefPubMed
6.
go back to reference Thackray S, Easthaugh J, Freemantle N, Cleland JG (2002) The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure-a meta-regression analysis. Eur J Heart Fail 4:515–529CrossRefPubMed Thackray S, Easthaugh J, Freemantle N, Cleland JG (2002) The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure-a meta-regression analysis. Eur J Heart Fail 4:515–529CrossRefPubMed
7.
go back to reference Bayram M, De Luca L, Massie MB, Gheorghiade M (2005) Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol 96:47G–58GCrossRefPubMed Bayram M, De Luca L, Massie MB, Gheorghiade M (2005) Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol 96:47G–58GCrossRefPubMed
8.
go back to reference Levin R, Porcile R, Tanus E, Degrange M (2009) The intermittent infusion of levosimendan reduces mortality and re-admisions in patients with advanced heart failure (abstract). Circulation 120:S865CrossRef Levin R, Porcile R, Tanus E, Degrange M (2009) The intermittent infusion of levosimendan reduces mortality and re-admisions in patients with advanced heart failure (abstract). Circulation 120:S865CrossRef
9.
go back to reference Bergh CH, Andersson B, Dahlstrom U, Forfang K, Kivikko M, Sarapohja T, Ullman B, Wikstrom G (2010) Intravenous levosimendan versus dobutamine in acute decompensated heart failure patients on beta-blockers. Eur J Heart Fail 12:404–410PubMedCentralCrossRefPubMed Bergh CH, Andersson B, Dahlstrom U, Forfang K, Kivikko M, Sarapohja T, Ullman B, Wikstrom G (2010) Intravenous levosimendan versus dobutamine in acute decompensated heart failure patients on beta-blockers. Eur J Heart Fail 12:404–410PubMedCentralCrossRefPubMed
10.
go back to reference Bonios MJ, Terrovitis JV, Drakos SG, Katsaros F, Pantsios C, Nanas SN, Kanakakis J, Alexopoulos G, Toumanidis S, Anastasiou-Nana M, Nanas JN (2011) Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure. Int J Cardiol 159:225–229CrossRefPubMed Bonios MJ, Terrovitis JV, Drakos SG, Katsaros F, Pantsios C, Nanas SN, Kanakakis J, Alexopoulos G, Toumanidis S, Anastasiou-Nana M, Nanas JN (2011) Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure. Int J Cardiol 159:225–229CrossRefPubMed
11.
go back to reference Nanas JN, Kontoyannis DA, Alexopoulos GP, Anastasiou-Nana MI, Tsagalou EP, Stamatelopoulos SF, Moulopoulos SD (2001) Long-term intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure. Chest 119:1173–1178CrossRefPubMed Nanas JN, Kontoyannis DA, Alexopoulos GP, Anastasiou-Nana MI, Tsagalou EP, Stamatelopoulos SF, Moulopoulos SD (2001) Long-term intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure. Chest 119:1173–1178CrossRefPubMed
12.
go back to reference Nanas JN, Tsagalou EP, Kanakakis J, Nanas SN, Terrovitis JV, Moon T, Anastasiou-Nana MI (2004) Long-term intermittent dobutamine infusion, combined with oral amiodarone for end-stage heart failure: a randomized double-blind study. Chest 125:1198–1204CrossRefPubMed Nanas JN, Tsagalou EP, Kanakakis J, Nanas SN, Terrovitis JV, Moon T, Anastasiou-Nana MI (2004) Long-term intermittent dobutamine infusion, combined with oral amiodarone for end-stage heart failure: a randomized double-blind study. Chest 125:1198–1204CrossRefPubMed
13.
go back to reference Mavrogeni S, Giamouzis G, Papadopoulou E, Thomopoulou S, Dritsas A, Athanasopoulos G, Adreanides E, Vassiliadis I, Spargias K, Panagiotakos D, Cokkinos DV (2007) 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 13:556–559CrossRefPubMed Mavrogeni S, Giamouzis G, Papadopoulou E, Thomopoulou S, Dritsas A, Athanasopoulos G, Adreanides E, Vassiliadis I, Spargias K, Panagiotakos D, Cokkinos DV (2007) 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 13:556–559CrossRefPubMed
14.
go back to reference Lilleberg J, Laine M, Palkama T, Kivikko M, Pohjanjousi P, Kupari M (2007) Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure. Eur J Heart Fail 9:75–82CrossRefPubMed Lilleberg J, Laine M, Palkama T, Kivikko M, Pohjanjousi P, Kupari M (2007) Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure. Eur J Heart Fail 9:75–82CrossRefPubMed
15.
go back to reference Malfatto G, Della Rosa F, Villani A, Rella V, Branzi G, Facchini M, Parati G (2007) Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival. J Cardiovasc Pharmacol 60:450–455CrossRef Malfatto G, Della Rosa F, Villani A, Rella V, Branzi G, Facchini M, Parati G (2007) Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival. J Cardiovasc Pharmacol 60:450–455CrossRef
16.
go back to reference Silvetti S, Greco T, Licia Di Prima A, Mucchetti M, Maria de Lurdes C, Pasin L, Scandroglio M, Landoni G, Zangrillo A (2014) Intermittent levosimendan improves mid-term survival in chronic heart failure patients: meta-analysis of randomised trials. Clin Res Cardiol 103:505–513CrossRefPubMed Silvetti S, Greco T, Licia Di Prima A, Mucchetti M, Maria de Lurdes C, Pasin L, Scandroglio M, Landoni G, Zangrillo A (2014) Intermittent levosimendan improves mid-term survival in chronic heart failure patients: meta-analysis of randomised trials. Clin Res Cardiol 103:505–513CrossRefPubMed
17.
go back to reference Tuomainen P, Magga J, Timonen P, Miettinen K, Kurttila M, Vanninen E, Laitinen T, Timonen K, Punnonen K, Parviainen I, Uusaro A, Vuolteenaho O, Kivikko M, Peuhkurinen K (2013) Intermittent levosimendan treatment in patients with severe congestive heart failure. Clin Res Cardiol 102:485–493CrossRefPubMed Tuomainen P, Magga J, Timonen P, Miettinen K, Kurttila M, Vanninen E, Laitinen T, Timonen K, Punnonen K, Parviainen I, Uusaro A, Vuolteenaho O, Kivikko M, Peuhkurinen K (2013) Intermittent levosimendan treatment in patients with severe congestive heart failure. Clin Res Cardiol 102:485–493CrossRefPubMed
18.
go back to reference Zobel C, Dörpinghaus M, Reuter H, Erdmann E (2012) Mortality in a cardiac intensive care unit. Clin Res Cardiol 101:521–524CrossRefPubMed Zobel C, Dörpinghaus M, Reuter H, Erdmann E (2012) Mortality in a cardiac intensive care unit. Clin Res Cardiol 101:521–524CrossRefPubMed
19.
go back to reference Adamopoulos S, Piepoli M, Qiang F, Pissimissis E, Davies M, Bernardi L, Forfar C, Sleight P, Coats A (1995) Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure. Lancet 345:344–349CrossRefPubMed Adamopoulos S, Piepoli M, Qiang F, Pissimissis E, Davies M, Bernardi L, Forfar C, Sleight P, Coats A (1995) Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure. Lancet 345:344–349CrossRefPubMed
20.
go back to reference Leier CV, Binkley PF (1998) Parenteral inotropic support for advanced congestive heart failure. Prog Cardiovasc Dis 41:207–224CrossRefPubMed Leier CV, Binkley PF (1998) Parenteral inotropic support for advanced congestive heart failure. Prog Cardiovasc Dis 41:207–224CrossRefPubMed
21.
go back to reference Unverferth DV, Magorien RD, Altschuld R, Kolibash AJ, Lewis RP, Leier CV (1983) The hemodynamic and metabolic advantages gained by a three-day infusion of dobutamine in patients with congestive cardiomyopathy. Am Heart J 106:29–34CrossRefPubMed Unverferth DV, Magorien RD, Altschuld R, Kolibash AJ, Lewis RP, Leier CV (1983) The hemodynamic and metabolic advantages gained by a three-day infusion of dobutamine in patients with congestive cardiomyopathy. Am Heart J 106:29–34CrossRefPubMed
22.
go back to reference Colombo PC, Banchs JE, Celaj S, Talreja A, Lachmann J, Malla S, DuBois NB, Ashton AW, Latif F, Jorde UP, Ware JA, LeJemtel TH (2005) Endothelial cell activation in patients with decompensated heart failure. Circulation 111:58–62CrossRefPubMed Colombo PC, Banchs JE, Celaj S, Talreja A, Lachmann J, Malla S, DuBois NB, Ashton AW, Latif F, Jorde UP, Ware JA, LeJemtel TH (2005) Endothelial cell activation in patients with decompensated heart failure. Circulation 111:58–62CrossRefPubMed
23.
go back to reference Binkley PF, Van Fossen DB, Nunziata E, Unverferth DV, Leier CV (1990) Influence of positive inotropic therapy on pulsatile hydraulic load and ventricular-vascular coupling in congestive heart failure. J Am Coll Cardiol 15:1127–1135CrossRefPubMed Binkley PF, Van Fossen DB, Nunziata E, Unverferth DV, Leier CV (1990) Influence of positive inotropic therapy on pulsatile hydraulic load and ventricular-vascular coupling in congestive heart failure. J Am Coll Cardiol 15:1127–1135CrossRefPubMed
24.
go back to reference Unverferth DV, Leier CV, Magorien RD, Croskery R, Svirbely JR, Kolibash AJ, Dick MR, Meacham JA, Baba N (1980) Improvement of human myocardial mitochondria after dobutamine: a quantitative ultrastructural study. J Pharmacol Exp Ther 215:527–532PubMed Unverferth DV, Leier CV, Magorien RD, Croskery R, Svirbely JR, Kolibash AJ, Dick MR, Meacham JA, Baba N (1980) Improvement of human myocardial mitochondria after dobutamine: a quantitative ultrastructural study. J Pharmacol Exp Ther 215:527–532PubMed
25.
go back to reference Jessup M, Banner N, Brozena S, Campana C, Costard-Jackle A, Dengler T, Hunt S, Metra M, Rahmel A, Renlund D, Ross H, Warner Stevenson L (2006) 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 25:1003–1023CrossRefPubMed Jessup M, Banner N, Brozena S, Campana C, Costard-Jackle A, Dengler T, Hunt S, Metra M, Rahmel A, Renlund D, Ross H, Warner Stevenson L (2006) 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 25:1003–1023CrossRefPubMed
26.
go back to reference Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 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. Circulation 128:e240–e327CrossRefPubMed Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 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. Circulation 128:e240–e327CrossRefPubMed
27.
go back to reference Teerlink JR, Metra M, Zaca V, Sabbah HN, Cotter G, Gheorghiade M, Cas LD (2009) Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond. Heart Fail Rev 14:243–253PubMedCentralCrossRefPubMed Teerlink JR, Metra M, Zaca V, Sabbah HN, Cotter G, Gheorghiade M, Cas LD (2009) Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond. Heart Fail Rev 14:243–253PubMedCentralCrossRefPubMed
28.
go back to reference De Luca L (2014) Inotropic agents in advanced heart failure: repetita iuvant? Int J Cardiol 176:6–7CrossRefPubMed De Luca L (2014) Inotropic agents in advanced heart failure: repetita iuvant? Int J Cardiol 176:6–7CrossRefPubMed
Metadata
Title
A single German center experience with intermittent inotropes for patients on the high-urgent heart transplant waiting list
Authors
T. Hübner
T. Nickel
G. Steinbeck
S. Massberg
R. Schramm
B. Reichart
C. Hagl
A. Kiwi
Michael Weis
Publication date
01-11-2015
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 11/2015
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-015-0852-1

Other articles of this Issue 11/2015

Clinical Research in Cardiology 11/2015 Go to the issue