Heart Rate Reduction With Ivabradine Protects Against Left Ventricular Remodeling by Attenuating Infarct Expansion and Preserving Remote‐Zone Contractile Function and Synchrony in a Mouse Model of Reperfused Myocardial Infarction

Abstract

BackgroundIvabradine selectively inhibits the pacemaker current of the sinoatrial node, slowing heart rate. Few studies have examined the effects of ivabradine on the mechanical properties of the heart after reperfused myocardial infarction (MI). Advances in ultrasound speckle‐tracking allow strain analyses to be performed in small‐animal models, enabling the assessment of regional mechanical function.Methods and ResultsAfter 1 hour of coronary occlusion followed by reperfusion, mice received 10 mg/kg per day of ivabradine dissolved in drinking water (n=10), or were treated as infarcted controls (n=9). Three‐dimensional high‐frequency echocardiography was performed at baseline and at days 2, 7, 14, and 28 post‐MI. Speckle‐tracking software was used to calculate intramural longitudinal myocardial strain (Ell) and strain rate. Standard deviation time to peak radial strain (SD Tpeak Err) and temporal uniformity of strain were calculated from short‐axis cines acquired in the left ventricular remote zone. Ivabradine reduced heart rate by 8% to 16% over the course of 28 days compared to controls (P<0.001). On day 28 post–MI, the ivabradine group was found to have significantly smaller end‐systolic volumes, greater ejection fraction, reduced wall thinning, and greater peak Ell and Ell rate in the remote zone, as well as globally. Temporal uniformity of strain and SD Tpeak Err were significantly smaller in the ivabradine‐treated group by day 28 (P<0.05).ConclusionsHigh‐frequency ultrasound speckle‐tracking demonstrated decreased left ventricular remodeling and dyssynchrony, as well as improved mechanical performance in remote myocardium after heart rate reduction with ivabradine.

Functional and prognostic implications of cardiac magnetic resonance feature tracking-derived remote myocardial strain analyses in patients following acute myocardial infarction

“…Considering RM as a potential target for treatment strategies, several studies have demonstrated the beneficiary effects of therapeutic approaches, for example inducing a reduced heart rate, [ 22 ], anti-apoptotic effects in RM [ 23 ] or remodeling prevention via an angiotensin–AT1-receptor-dependent mechanism [ 24 ]. Further explorations of RM strain characteristics and their features as targets of pharmacological treatment are necessary in future studies.…”

Effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST‐segment elevation myocardial infarction: A pilot test

“…Animal experiments on AMI (Heusch & skyschally A et al., 2008; Mulder & BarbierS, 2004; O'Connor et al., 2016) showed that ivabradine slowed heart rate to improve the local blood flow in ischemic myocardium and systolic function, and thus reducing myocardial ischemic area. Priti et al (Priti et al., 2017) found that ivabradine is as effective as metoprolol in inferior AMIT patients, reducing the risk of first‐ or second‐degree atrioventricular block.…”

Clinical Study of The Early Application of Lvabradine For Acute Anterior Myocardial Infarction Patients After PCI With Early Heart Failure To Observe Cardiac Function And Prognosis

“…However, the incidences of rst and second degree atrioventricular block were signi cantly higher in the metoprolol group than in the ivabradine group. In the ischemia-reperfusion mouse model, O'Connor DM 8 showed that ivabradine could signi cantly improve ventricular remodeling by reducing the ventricular rate and heart rate variability. In a myocardial infarction and diabetes rat model, Cao X 9 showed that ivabradine could signi cantly reduce the uptake of norepinephrine in the myocardium and the plasma level of brain natriuretic peptide.…”