Skip to main content
SpringerLink
Log in

Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

End-stage heart failure (HF) frequently needs continuous inotropic support in hospital and has high morbidity and mortality in absence of heart transplantation. This study reports outcome, efficacy, and safety of continuous ambulatory inotropes (AI) and/or periodic levosimendan (LS) infusions in pediatric HF patients. The study included 27 patients, median age 9.4 (0.1–26.1) years, with severe HF (6 myocarditis, 13 dilated cardiomyopathy, 2 restrictive cardiomyopathy, 6 repaired congenital heart disease). Dobutamine and milrinone AI were administered in 21 patients through a permanent central catheter for median duration 1.0 (0.3–3.7) years. Additionally, 14 AI patients and the remaining 6 study patients received periodic LS infusions for median duration 1.1 (0.2–4.2) years. During median follow-up 2.1 (0.3–21.3) years, 4 patients died of worsening HF after 0.8–2.1 years AI, 6 patients underwent heart transplantation with only 3 survivors, while the rest remained stable out of the hospital with complications 4 line infections treated with antibiotics and 4 catheter reinsertions due to dislodgement. Severe pulmonary hypertension was reversed with AI in 2 patients, allowing successful heart-only transplantation. Therapy with AI was discontinued after 1.4–0.4 years in 6 improved myocarditis and 3 cardiomyopathy patients without deterioration. In conclusion, prolonged AI and/or LS infusions in HF are safe and beneficial even in small infants, allowing stabilization and reasonable social and family life out of the hospital. It may provide precious time for heart transplantation or myocardial remodeling, improvement, and possible discontinuation even after long periods of support.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rossano JW, Cherikh WS, Chambers DC, Goldfarb S, Khush K, Kucheryavaya AY et al (2017) The registry of the international society for heart and lung transplantation: twentieth pediatric heart transplantation report-2017; focus theme: Allograft ischemic time. J Heart Lung Transplant 36:1060–1069

    Article  Google Scholar 

  2. Almond CS, Morales DL, Blackstone EH, Turrentine MW, Imamura M, Massicotte MP et al (2013) Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation 127:1702–1711

    Article  CAS  Google Scholar 

  3. Canter CE, Shaddy RE, Bernstein D, Hsu DT, Chrisant MR, Kirklin JK et al (2007) Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on cardiovascular disease in the young; the councils on clinical cardiology, cardiovascular nursing, and cardiovascular surgery and anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 115:658–676

    Article  Google Scholar 

  4. English RF, Janosky JE, Ettedgui JA, Webber SA (2004) Outcomes for children with acute myocarditis. Cardiol Young 14: 488–493

    Article  Google Scholar 

  5. Berg AM, Snell L, Mahle WT (2007) Home inotropic therapy in children. J Heart Lung Transplant 26:453–457

    Article  Google Scholar 

  6. Price JF, Towbin JA, Dreyer WJ, Moffett BS, Kertesz NJ, Clunie SK et al (2006) Outpatient continuous parenteral inotropic therapy as bridge to transplantation in children with advanced heart failure. J Card Fail 12:139–143

    Article  Google Scholar 

  7. Birnbaum BF, Simpson KE, Boschert TA, Zheng J, Wallendorf MJ, Schechtman K et al (2015) Intravenous home inotropic use is safe in pediatric patients awaiting transplantation. Circ Heart Fail 8:64–70

    Article  Google Scholar 

  8. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS et al (2013) 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation 127:e283-352

    Article  Google Scholar 

  9. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH et al (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. J Am Coll Cardiol 62:e147-239

    Article  Google Scholar 

  10. 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 2:320–324

    Article  CAS  Google Scholar 

  11. Cohn JN, Goldstein SO, Greenberg BH, Lorell BH, Bourge RC, Jaski BE et al (1998) A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 339:1810–1816

    Article  CAS  Google Scholar 

  12. Hampton JR, van Veldhuisen DJ, Kleber FX, Cowley AJ, Ardia A, Block P et al (1997) Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators. Lancet 349:971–977

    Article  CAS  Google Scholar 

  13. Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM et al (1991) Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 325:1468–1475

    Article  CAS  Google Scholar 

  14. Metra M, Eichhorn E, Abraham WT, Linseman J, Bohm M, Corbalan R et al (2009) Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials. Eur Heart J 30:3015–3026

    Article  CAS  Google Scholar 

  15. Park SJ, Milano CA, Tatooles AJ, Rogers JG, Adamson RM, Steidley DE et al (2012) Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy. Circ Heart Fail 5:241–248

    Article  Google Scholar 

  16. De Luca L, Colucci WS, Nieminen MS, Massie BM, Gheorghiade M (2006) Evidence-based use of levosimendan in different clinical settings. Eur Heart J 27:1908–1920

    Article  Google Scholar 

  17. Antila S, Sundberg S, Lehtonen LA (2007) Clinical pharmacology of levosimendan. Clin Pharmacokinet 46:535–552

    Article  CAS  Google Scholar 

  18. Nieminen MS, Fruhwald S, Heunks LM, Suominen PK, Gordon AC, Kivikko M et al (2013) Levosimendan: current data, clinical use and future development. Heart Lung Vessel 5:227–245

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Angadi U, Westrope C, Chowdhry MF (2013) Is levosimendan effective in paediatric heart failure and post-cardiac surgeries? Interact Cardiovasc Thorac Surg 17:710–714

    Article  Google Scholar 

  20. Suominen PK (2011) Single-center experience with levosimendan in children undergoing cardiac surgery and in children with decompensated heart failure. BMC Anesthesiol 11:18

    Article  CAS  Google Scholar 

  21. Suominen P, Mattila N, Nyblom O, Rautiainen P, Turanlahti M, Rahkonen O (2017) The hemodynamic effects and safety of repetitive Levosimendan infusions on children with dilated cardiomyopathy. World J Pediatr Congenit Heart Surg 8:25–31

    Article  Google Scholar 

  22. Rhee EK, Canter CE, Basile S, Webber SA, Naftel DC (2007) Sudden death prior to pediatric heart transplantation: would implantable defibrillators improve outcome? J Heart Lung Transplant 26:447–452

    Article  Google Scholar 

  23. Shaddy RE, Boucek MM, Hsu DT, Boucek RJ, Canter CE, Mahony L et al (2007) Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA 298:1171–1179

    Article  Google Scholar 

  24. Vigneswaran TV, Brown JR, Breuer J, Burch M (2016) Parvovirus B19 myocarditis in children: an observational study. Arch Dis Child 101:177–180

    Article  Google Scholar 

  25. De Rita F, Hasan A, Haynes S, Peng E, Gandolfo F, Ferguson L et al (2015) Outcome of mechanical cardiac support in children using more than one modality as a bridge to heart transplantation. Eur J Cardiothorac Surg 48:917–922 (discussion 22)

    Article  Google Scholar 

  26. Kirklin JK (2013) Long-term mechanical circulatory support: could it really have a public health impact? Eur J Cardiothorac Surg 44:198–200

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Cardiology & Adult Congenital Heart Disease, Onassis Cardiac Surgery Center, 356 Syngrou Ave, 176 74, Athens, Greece

    Sotiria C. Apostolopoulou, George A. Vagenakis, Alexandros Tsoutsinos, Felicia Kakava & Spyridon Rammos

Authors
  1. Sotiria C. Apostolopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George A. Vagenakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandros Tsoutsinos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Felicia Kakava
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Spyridon Rammos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sotiria C. Apostolopoulou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with animals performed by any of the authors. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Apostolopoulou, S.C., Vagenakis, G.A., Tsoutsinos, A. et al. Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation. Pediatr Cardiol 39, 1315–1322 (2018). https://doi.org/10.1007/s00246-018-1897-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-018-1897-5

Keywords

Search

Navigation