Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.
Author: Pascual Izco, Marina; Ramírez Carracedo, Rafael; Hernández Navarro, Ignacio; Osorio Ruiz, Álvaro; Castejón Navarro, Borja; Cuadrado Berrocal, Irene; Largo Aramburu, Carlota; Alonso Salinas, Gonzalo Luis; Díez, Javier; Saura Redondo, Marta; Zamorano Gómez, José Luis; Zaragoza Sánchez, Carlos; Sanmartín, Marcelo
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.
Universal identifier: http://hdl.handle.net/10641/1507
Date: 2018
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