Skip to main content
SpringerLink
Log in

Ivabradine in Postural Orthostatic Tachycardia Syndrome: Preliminary Experience in Children

  • short communication
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Objective

Ivabradine is a selective and specific inhibitor of the I(f) current in the sinoatrial and atrioventricular nodes. It decreases heart rate and myocardial oxygen consumption at rest and during exercise. It is used in adults for management of heart failure and angina, but promising results have been obtained in postural orthostatic tachycardia syndrome (POTS). There is little experience of ivabradine in childhood, although it is used on a compassionate basis. Our aim was to review our experience of ivabradine in a retrospective evaluation of pediatric patients with POTS.

Methods

We evaluated all patients younger than 18 years for whom ivabradine had been prescribed for this indication, from February 2008 to June 2014.

Results

Twenty-two patients were identified (15 female). Median age was 14.5 years (11–17 years). The ivabradine dosage after up-titration was 0.1 mg/kg per dose twice daily. In 15 (68%) symptoms improved. Ivabradine was suspended in five, but only in one for worsening of symptoms. There was a reduction in heart rate on resting electrocardiogram (EKG) from a mean (standard deviation) of 82.5 (13.6) bpm to a mean of 71 (16.5) bpm (p = 0.007). No patient had increased duration of QTc (p = 0.44). One (4.5%) experienced phosphenes.

Conclusions

From this initial experience, ivabradine is safe in patients younger than 18 years with POTS. We observed improvement of symptoms in 68% and phosphenes in less than 5%. Further studies are needed to assess the safety in a randomized control setting.

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

References

  1. Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.

    Article  CAS  PubMed  Google Scholar 

  2. Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875–85.

    Article  CAS  PubMed  Google Scholar 

  3. McDonald C, Frith J, Newton JL. Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. Europace. 2011;13:427–30.

    Article  PubMed  Google Scholar 

  4. Sutton R, Salukhe TV, Franzen-McManus AC, et al. Ivabradine in treatment of sinus tachycardia mediated vasovagal syncope. Europace. 2014;16:284–8.

    Article  PubMed  Google Scholar 

  5. Bonnet D, Berger F, Jokinen E, et al. Ivabradine in children with dilated cardiomyopathy and symptomatic chronic heart failure. J Am Coll Cardiol. 2017;70(10):1262–72.

    Article  CAS  PubMed  Google Scholar 

  6. Carew S, Connor MO, Cooke J, et al. A review of postural orthostatic tachycardia syndrome. Europace. 2009;11:18–25.

    Article  PubMed  Google Scholar 

  7. Bucchi A, Baruscotti M, DiFrancesco D. Current-dependent block of rabbit sino-atrial node if channels by ivabradine. J Gen Physiol. 2002;120:1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fox K, Ford I, Steg PG et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372:817–21.

    Article  PubMed  Google Scholar 

  9. Montalescot G, Sechtem U, Achenbach S, et al. ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013;34:2949–3003.

    Article  PubMed  Google Scholar 

  10. Fox K, Ford I, Steg PG et al (SIGNIFY investigators). Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371:1091–9.

    Article  PubMed  Google Scholar 

  11. Fox K, Ford I, Steg PG et al. Rationale, design, and baseline characteristics of the Study assessInG the morbidity–mortality benefits of the If inhibitor Ivabradine in patients with coronarY artery disease (SIGNIFY trial): a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654–61.

    Article  CAS  PubMed  Google Scholar 

  12. Fox KM, Ferrari R. Heart rate: a forgotten link in coronary artery disease? Nat Rev Cardiol. 2011;8:369–79.

    Article  PubMed  Google Scholar 

  13. Fox K, Ford I, Steg PG et al (BEAUTIFUL investigators). Relationship between ivabradine treatment and cardiovascular outcome in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized controlled BEAUTIFUL trial. Eur Heart J. 2009;30:2337–45.

    Article  CAS  PubMed  Google Scholar 

  14. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. ESC Committee for Practice Guidelines. Eur J Heart Fail. 2012;14:803–69.

    Article  CAS  PubMed  Google Scholar 

  15. Fox K, Komajda M, Ford I, et al. Effect of ivabradine in patients with left-ventricular systolic dysfunction: a pooled analysis of individual patient data from the BEATIFUL and SHIFT trial. Eur Heart J. 2013;34:2263–70.

    Article  CAS  PubMed  Google Scholar 

  16. Oliphant CS, Owens RE, Bolorunduro OB, et al. Ivabradine: a review of labelled and off-labeled uses. Am J Cardiovasc Drugs. 2016;16:337–47.

    Article  PubMed  Google Scholar 

  17. Khan S, Hamid S, Rinaldi C. Treatment of inappropriate sinus tachycardia with ivabradine in a patient with postural orthostatic tachycardia syndrome and a dual chamber pacemaker. Pacing Clin Electrophysiol. 2009;32:131–3.

    Article  PubMed  Google Scholar 

  18. Al-Ghamdi S, Al-Fayyadh MI, Hamilton RM. Potential new indication for ivabradine: treatment of a patient with congenital junctional ectopic tachycardia. J Cardiovasc Electrophysiol. 2013;24:822–4.

    Article  PubMed  Google Scholar 

  19. Romeo E, Grimaldi N, Sarubbi B, et al. A pediatric case of cardiomyopathy induced by inappropriate sinus tachycardia: efficacy of ivabradine. Pediatr Cardiol. 2011;32:842–5.

    Article  PubMed  Google Scholar 

  20. Cervetto L, Demontis GC, Gargini C. Cellular mechanisms underlying the pharmacological induction of phosphenes. Br J Pharmacol. 2007;150:383–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Savelieva I, Camm AJ. If inhibition with ivabradine: electophysiological effect and safety. Drug Saf. 2008;31:95–107.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Khola Khan, Senior Pharmacist at the Royal Brompton Hospital for her input and help.

Author information

Authors and Affiliations

  1. Royal Brompton Hospital, Sydney St, London, SW3 6NP, UK

    Grazia Delle Donne, Ferran Rosés Noguer, Jan Till, Tushar Salukhe, Sanjay K. Prasad & Piers E. F. Daubeney

  2. Imperial College, London, UK

    Sanjay K. Prasad & Piers E. F. Daubeney

  3. Vall d’Hebron University Hospital, Barcelona, Spain

    Ferran Rosés Noguer

Authors
  1. Grazia Delle Donne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ferran Rosés Noguer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Till
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tushar Salukhe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sanjay K. Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Piers E. F. Daubeney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Piers E. F. Daubeney.

Ethics declarations

This study was supported by the Clinical Research Unit of the Royal Brompton Hospital.

Conflict of interest

Grazia Delle Donne, Ferran Rosés Noguer, Jan Till, Tushar Salukhe, Sanjay K. Prasad and Piers E. F. Daubeney declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Delle Donne, G., Rosés Noguer, F., Till, J. et al. Ivabradine in Postural Orthostatic Tachycardia Syndrome: Preliminary Experience in Children. Am J Cardiovasc Drugs 18, 59–63 (2018). https://doi.org/10.1007/s40256-017-0248-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-017-0248-x

Search

Navigation