open access

Vol 27, No 1 (2020)
Original articles — Basic science and experimental cardiology
Published online: 2018-08-14
Get Citation

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial

Marina Pascual Izco, Rafael Ramírez-Carracedo, Ignacio Hernández Navarro, Álvaro Osorio Ruiz, Borja Castejón Navarro, Irene Cuadrado Berrocal, Carlota Largo Aramburu, Gonzalo Luis Alonso Salinas, Javier Díez, Marta Saura Redondo, José Luis Zamorano, Carlos Zaragoza, Marcelo Sanmartín
DOI: 10.5603/CJ.a2018.0078
·
Pubmed: 30155868
·
Cardiol J 2020;27(1):62-71.

open access

Vol 27, No 1 (2020)
Original articles — Basic science and experimental cardiology
Published online: 2018-08-14

Abstract

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure.

Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period.

Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. –19.7% variation, p < 0.01).

Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.

Abstract

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure.

Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period.

Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. –19.7% variation, p < 0.01).

Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.

Get Citation

Keywords

acute heart failure, heart rate, ivabradine, swine model, porcine model

About this article
Title

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial

Journal

Cardiology Journal

Issue

Vol 27, No 1 (2020)

Pages

62-71

Published online

2018-08-14

DOI

10.5603/CJ.a2018.0078

Pubmed

30155868

Bibliographic record

Cardiol J 2020;27(1):62-71.

Keywords

acute heart failure
heart rate
ivabradine
swine model
porcine model

Authors

Marina Pascual Izco
Rafael Ramírez-Carracedo
Ignacio Hernández Navarro
Álvaro Osorio Ruiz
Borja Castejón Navarro
Irene Cuadrado Berrocal
Carlota Largo Aramburu
Gonzalo Luis Alonso Salinas
Javier Díez
Marta Saura Redondo
José Luis Zamorano
Carlos Zaragoza
Marcelo Sanmartín

References (25)
  1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016; 18(8): 891–975.
  2. Hastillo A, Taylor DO, Hess ML. Secific ositiv inotroic agents. In: Messerli FH,ed. Cardiovascular drug theray. 2nd Ed. W G Saunders Company; Philadelphia. 1996: 1151–1161.
  3. Tisdale JE, Patel R, Webb CR, et al. Electrophysiologic and proarrhythmic effects of intravenous inotropic agents. Prog Cardiovasc Dis. 1995; 38(2): 167–180.
  4. Vasquez A, Kern KB, Hilwig RW, et al. Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction. Resuscitation. 2004; 61(2): 199–207.
  5. Roubille F, Lattuca B, Busseuil D, et al. Is ivabradine suitable to control undesirable tachycardia induced by dobutamine in cardiogenic shock treatment? Med Hypotheses. 2013; 81(2): 202–206.
  6. Akodad M, Lim P, Roubille F. Does ivabradine balance dobutamine effects in cardiogenic shock? A promising new strategy. Acta Physiol (Oxf). 2016; 218(2): 73–77.
  7. Fox K, Ford I, Steg P, 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(9641): 807–816.
  8. Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010; 376(9744): 875–885.
  9. Gallet R, Ternacle J, Damy T, et al. Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction. Int J Cardiol. 2014; 176(2): 450–455.
  10. Bonadei I, Sciatti E, Vizzardi E, et al. Ivabradine during cardiogenic shock: A clinical case and review of the literature. Heart Lung J Crit Care. 2015; 44(1): 57–58.
  11. Hidalgo FJ, Anguita M, Castillo JC, et al. Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced left ventricular ejection fraction (ETHIC-AHF): A randomised study. Int J Cardiol. 2016; 217: 7–11.
  12. Pascual Izco M, Alonso Salinas GL, Sanmartín Fernández M, et al. Clinical Experience with Ivabradine in Acute Heart Failure. Cardiology. 2016; 134(3): 372–374.
  13. Heusch G, Skyschally A, Gres P, et al. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction. Eur Heart J. 2008; 29(18): 2265–2275.
  14. Verrier RL, Silva AFG, Bonatti R, et al. Combined actions of ivabradine and ranolazine reduce ventricular rate during atrial fibrillation. J Cardiovasc Electrophysiol. 2015; 26(3): 329–335.
  15. Verrier RL, Bonatti R, Silva AFG, et al. If inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation. Heart Rhythm. 2014; 11(12): 2288–2296.
  16. Camm AJ, Lau CP. Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology. Drugs R D. 2003; 4(2): 83–89.
  17. Lie RH, Hasenkam JM, Nielsen TT, et al. Post-conditioning reduces infarct size in an open-chest porcine acute ischemia-reperfusion model. Acta Anaesthesiol Scand. 2008; 52(9): 1188–1193.
  18. Abraham WT, Adams KF, Fonarow GC, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005; 46(1): 57–64.
  19. Takahama H, Yokoyama H, Kada A, et al. Extent of heart rate reduction during hospitalization using beta-blockers, not the achieved heart rate itself at discharge, predicts the clinical outcome in patients with acute heart failure syndromes. J Cardiol. 2013; 61(1): 58–64.
  20. Morelli A, Ertmer C, Westphal M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013; 310(16): 1683–1691.
  21. Sargento L, Satendra M, Longo S, et al. Heart rate reduction with ivabradine in patients with acute decompensated systolic heart failure. Am J Cardiovasc Drugs. 2014; 14(3): 229–235.
  22. Cavusoglu Y, Mert U, Nadir A, et al. Ivabradine treatment prevents dobutamine-induced increase in heart rate in patients with acute decompensated heart failure. J Cardiovasc Med (Hagerstown). 2015; 16(9): 603–609.
  23. Barillà F, Pannarale G, Torromeo C, et al. Ivabradine in patients with ST-elevation myocardial infarction complicated by cardiogenic shock: a preliminary randomized prospective study. Clin Drug Investig. 2016; 36(10): 849–856.
  24. Nuding S, Schröder J, Presek P, et al. Reducing elevated heart rates in patients with multiple organ dysfunction syndrome with the if (funny channel current) inhibitor ivabradine. Shock. 2018; 49(4): 402–411.
  25. Bakkehaug JP, Naesheim T, Torgersen Engstad E, et al. Reversing dobutamine-induced tachycardia using ivabradine increases stroke volume with neutral effect on cardiac energetics in left ventricular post-ischaemia dysfunction. Acta Physiol (Oxf). 2016; 218(2): 78–88.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl