Ivabradine: potential clinical applications in critically ill patients

Abstract

It has been extensively demonstrated that an elevated heart rate is a modifiable, independent risk factor for cardiovascular events. A high heart rate increases myocardial oxygen consumption and reduces diastolic perfusion time. It can also increase ventricular diastolic pressures and induce ventricular arrhythmias. Critical care patients are prone to develop a stress induced cardiac impairment and consequently an increase in sympathetic tone. This in turn increases heart rate. In this setting, however, heart rate lowering might be difficult because the effects of inotropic drugs could be hindered by heart rate reducing drugs like beta-blockers. Ivabradine is a new selective antagonist of funny channels. It lowers heart rate, reducing the diastolic depolarization slope. Moreover, ivabradine is not active on sympathetic pathways, thus avoiding any interference with inotropic amines. We reviewed the literature available regarding heart rate control in critical care patients, focusing our interest on the use of ivabradine to assess the potential benefits of the drug in this particular setting.

Reversing dobutamine‐induced tachycardia using ivabradine increases stroke volume with neutral effect on cardiac energetics in left ventricular post‐ischaemia dysfunction

“…That said, ivabradine is also an alternative to β ‐blocker in other critically ill patients with tachycardia, as suggested by De Santis et al . (). Not least, the energetic neutrality of this cotreatment expands the clinical relevance.…”

Opposite diastolic effects of omecamtiv mecarbil versus dobutamine and ivabradine co-treatment in pigs with acute ischemic heart failure

“…This medication does not affect inotropy, and treatment with D+I have been suggested to optimize coronary flow and reduce energy demands in the ischemic heart by optimizing the DT (De Santis et al. ; Gallet et al. ).…”

If blocking potency of ivabradine is preserved under elevated endotoxin levels in human atrial myocytes

“…Therefore further investigations using spontaneously active cardiomyocytes are required to confirm our conclusions and to get a deeper insight in the effect of ivabradine on heart rate under septic conditions in vivo . Such studies are of special interest since currently the clinical MOD I f Y trial studies the benefits of heart rate reduction by ivabradine in patients suffering from MODS [19], where heart rate is usually elevated due to increased oxygen demand and cytokine levels [57] and has been proved to predict survival [3,58]. Pure heart rate reduction by ivabradine could therefore improve the outcome of patients in shock by lowering myocardial oxygen demand, improving diastolic coronary perfusion and acting on the negative force-frequency relationship of the failing heart [57].…”