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Cited by 31Cardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic ControlHeart rate and cardiovascular health

The effect of ivabradine on the heart rate and sympathovagal balance in postural tachycardia syndrome patients

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Barzilai, Merav, Giris, Jacob·2015·Rambam Maimonides Medical Journal
DOI 10.5041/rmmj.10213PMC PMC4524401
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Abstract

BACKGROUND: Postural tachycardia syndrome (POTS) is a common form of chronic orthostatic intolerance. The remarkable increase in heart rate (HR) upon standing is the hallmark of this syndrome. Treatment of POTS patients is challenging and includes drugs that slow the HR. Ivabradine is a selective If channel blocker designed to slow the HR, as an anti-anginal agent. In view of its ability to slow the HR, we posited that ivabradine may be an ideal medication for treating POTS patients. This report provides the results of an investigation in which we studied ivabradine's effect on the hemodynamics and sympathovagal balance in POTS patients. METHODS: An open-label trial, without a placebo control, was performed in eight patients with POTS of two years' standing. Characterization of symptoms, hemodynamics, autonomic function tests, and HR and blood pressure (BP) variability were determined while patients were in a supine position and during a 20-minute head-up tilt before and after a single oral dose of 7.5 mg ivabradine. RESULTS: Ivabradine slowed the HR of POTS patients at rest by 4±1 bpm (P<0.05). During a 5-minute head-up tilt, the HR decreased from 118±4 bpm to 101±5 bpm (P<0.01). Ivabradine did not affect the BP when patients were at rest in a supine position or in head-up tilt position. Cardiovascular vagal and sympathetic tone, extrapolated from the time and frequency domains of the HR and BP variability, were also not affected by ivabradine. CONCLUSIONS: Ivabradine is an effective drug for slowing the HR of POTS patients at rest and during tilting, without producing significant adverse effects. Moreover, ivabradine exerts its effects without influencing the sympathovagal balance.

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  • In limited studies, ivabradine has also been shown to reduce HR in POTS.

    “In limited studies, ivabradine has also been shown to reduce HR in POTS (112,113).”

    From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [113]

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Research works printed but not linked: 27

  1. [4]Streeten DH Orthostatic intolerance. A historical introduction to the pathophysiological mechanisms Am J Med Sci 1999 317 78 87 10.1097/00000441-199902000-00002 10037111 · DOI
  2. [6]Streeten DH Scullard TF Excessive gravitational blood pooling caused by impaired venous tone is the predominant non-cardiac mechanism of orthostatic intolerance Clin Sci (Lond) 1996 90 277 85 8777834
  3. [7]Bohora S Joint hypermobility syndrome and dysautonomia: expanding spectrum of disease presentation and manifestation Indian Pacing Electrophysiol J 2010 10 158 61 20376182 PMC2847865
  4. [10]Kanjwal K Karabin B Kanjwal Y Grubb BP Postpartum postural orthostatic tachycardia syndrome in a patient with the joint hypermobility syndrome Cardiol Res Pract 2009 2009 187543 10.4061/2009/187543 19946638 PMC2778448 · DOI
  5. [11]Kanjwal K Saeed B Karabin B Kanjwal Y Grubb BP Comparative clinical profile of postural orthostatic tachycardia patients with and without joint hypermobility syndrome Indian Pacing Electrophysiol J 2010 10 173 8 20376184 PMC2847867
  6. [12]Keller NR Robertson D Familial orthostatic tachycardia Curr Opin Cardiol 2006 21 173 9 10.1097/01.hco.0000221577.41125.c8 16601453 · DOI
  7. [15]Bohm M Swedberg K Komajda M Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial Lancet 2010 376 886 94 10.1016/S0140-6736(10)61259-7 20801495 · DOI
  8. [16]Colin P Ghaleh B Monnet X Hittinger L Berdeaux A Effect of graded heart rate reduction with ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs J Pharmacol Exp Ther 2004 308 236 40 10.1124/jpet.103.059717 14569053 · DOI
  9. [17]DiFrancesco D Camm JA Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease Drugs 2004 64 1757 65 10.2165/00003495-200464160-00003 15301560 · DOI
  10. [18]Fox K Ford I Steg PG Tendera M Ferrari R 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 10.1016/S0140-6736(08)61170-8 18757088 · DOI · Paper page
  11. [19]Gupta A Sharma YP Ivabradine and outcomes in chronic heart failure Lancet 2010 376 2069 70 10.1016/S0140-6736(10)62285-4 21168044 · DOI
  12. [20]Kang SM Won H Hong N Oh J Ivabradine and outcomes in chronic heart failure Lancet 2010 376 2069 70 10.1016/S0140-6736(10)62286-6 21168043 · DOI
  13. [21]Monnet X Colin P Ghaleh B Hittinger L Giudicelli JF Berdeaux A Heart rate reduction during exercise-induced myocardial ischaemia and stunning Eur Heart J 2004 25 579 86 10.1016/j.ehj.2003.10.010 15120055 · DOI
  14. [22]Reil JC Bohm M BEAUTIFUL results--the slower, the better? Lancet 2008 372 779 80 10.1016/S0140-6736(08)61172-1 18757092 · DOI
  15. [23]Sulfi S Timmis AD Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina Int J Clin Pract 2006 60 222 8 10.1111/j.1742-1241.2006.00817.x 16451297 PMC1448693 · DOI
  16. [24]Swedberg K Komajda M Bohm M Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study Lancet 2010 376 875 85 10.1016/S0140-6736(10)61198-1 20801500 · DOI · Paper page
  17. [26]Tardif JC Ford I Tendera M Bourassa MG Fox K Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina Eur Heart J 2005 26 2529 36 10.1093/eurheartj/ehi586 16214830 · DOI
  18. [27]Bois P Bescond J Renaudon B Lenfant J Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells Br J Pharmacol 1996 118 1051 7 10.1111/j.1476-5381.1996.tb15505.x 8799581 PMC1909508 · DOI
  19. [28]DiFrancesco D Funny channels in the control of cardiac rhythm and mode of action of selective blockers Pharmacol Res 2006 53 399 406 10.1016/j.phrs.2006.03.006 16638640 · DOI
  20. [30]DiFrancesco D The role of the funny current in pacemaker activity Circ Res 2010 106 434 46 10.1161/CIRCRESAHA.109.208041 20167941 · DOI
  21. [31]Thollon C Cambarrat C Vian J Prost JF Peglion JL Vilaine JP Electrophysiological effects of S 16257, a novel sinoatrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49 Br J Pharmacol 1994 112 37 42 10.1111/j.1476-5381.1994.tb13025.x 8032660 PMC1910295 · DOI
  22. [32]Thollon C Bedut S Villeneuve N Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity Br J Pharmacol 2007 150 37 46 10.1038/sj.bjp.0706940 17128289 PMC2013855 · DOI
  23. [33]Sutton R Salukhe T Ivabradine in the treatment of orthostatic intolerance Europace 2011 13 306 7 10.1093/europace/euq497 21345925 · DOI
  24. [34]Sutton R Salukhe TV Franzen-McManus AC Collins A Lim PB Francis DP Ivabradine in treatment of sinus tachycardia mediated vasovagal syncope Europace 2014 16 284 8 10.1093/europace/eut226 24072450 · DOI
  25. [35]McDonald C Frith J Newton JL Single centre experience of ivabradine in postural orthostatic tachycardia syndrome Europace 2011 13 427 30 10.1093/europace/euq390 21062792 PMC3043639 · DOI · Paper page
  26. [36]Joannides R Moore N Iacob M Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise Br J Clin Pharmacol 2006 61 127 37 10.1111/j.1365-2125.2005.02544.x 16433867 PMC1884997 · DOI
  27. [37]Nerla R Di FA Milo M Differential effects of heart rate reduction by atenolol or ivabradine on peripheral endothelial function in type 2 diabetic patients Heart 2012 98 1812 16 10.1136/heartjnl-2012-302795 23086971 · DOI

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Authors
Barzilai, M., & Giris, J.
Affiliations
Tel Aviv Sourasky Medical Center (IL)
ORCID
Barzilai, Merav
Venue
Rambam Maimonides Medical Journal
Publisher
Rambam Health Corporation
Published
2015-07-30
Volume
6
Issue
3
Pages
e0028
ISSN
2076-9172 (ISSN-L)
DOI
10.5041/rmmj.10213
PMC
PMC4524401
OpenAlex
W1551524043
Cited by
31
References
10
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 1
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Rambam Maimonides Medical Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
Keywords
ivabradine, postural orthostatic tachycardia syndrome, heart rate reduction, sympathovagal balance, autonomic function, head-up tilt, orthostatic intolerance, blood pressure variability, heart rate variability

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