Preface
This supplement of the European Heart Journal addresses the benefits of heart rate reduction in the cardiovascular continuum based on the presentations at a satellite symposium of the annual congress of the European Society of Cardiology this year in Munich.
The role of heart rate is well established in the development and pathophysiology of myocardial ischaemia. In patients with coronary artery disease (CAD), most ischaemic episodes are triggered by an increase in heart rate that induces the imbalance between myocardial oxygen delivery and consumption. Therefore, reduction in heart rate has been considered an important therapeutic principle in prevention of ischaemia by reducing myocardial oxygen consumption and by improving myocardial perfusion due to prolongation of the diastolic interval. In addition to the beneficial effects of heart rate reduction for the prevention of ischaemia, a lower heart rate is associated with a more favourable prognosis. The association between accelerated resting heart rate and cardiovascular outcomes has been found in general populations and among patients with myocardial infarction, chronic ischaemic heart disease, heart failure, hypertension, and diabetes. Experimental and clinical data suggested that haemodynamic forces, related to increased heart rate, may play an important role in vascular damage, development of endothelial dysfunction favouring both development of atherosclerosis and plaque rupture, and therefore, triggering acute coronary events in patients with CAD.
Over and beyond the beneficial effects of heart rate reduction in the prevention of angina, lower heart rate is associated with a more favourable prognosis in patients with CAD or heart failure. However, the association between heart rate and cardiovascular outcomes has never been tested prospectively. BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction) is the first trial designed to test the hypothesis that heart rate lowering with ivabradine on top of optimal therapy improves cardiovascular outcomes in patients with CAD and left ventricular systolic dysfunction.
In the present issue of the European Heart Journal Supplements, a panel of experts presents a comprehensive overview of the clinical advantages of heart rate reduction as an important therapeutic goal in management of patients with cardiovascular disease.
J. Borer presents observational studies, registries, and trials that have identified heart rate as a risk marker, and suggests that heart rate is evolving from its demonstrated status as a risk marker of cardiovascular events in various populations, to become a risk factor in patients with established CAD. The BEAUTIFUL trial is the first major outcome trial of a selective and specific heart rate reduction with ivabradine to assess the therapeutic value of pure heart rate reduction in populations with CAD and left ventricular dysfunction.
The rationale for heart rate reduction as an important strategy to prevent ischaemia is presented by R. Ferrari, with detailed illustration of the relationship between ischaemic regional myocardial blood flow and contractile function in different haemodynamic situations and the effects of heart rate on this relationship in normal and ischaemic myocardium.
The paper by J.C. Tardif provides evidence that resting heart rate is associated with the severity and rate of progression of coronary arterosclerosis and is an independent predictor of plaque rupture in coronary arteries. Resting heart rate is a simple measurement with important prognostic implications.
Finally, J.L. Zamorano shows in his review that high heart rates intervene along the chain of events that constitutes the cardiovascular continuum promoting cardiovascular disease. Therefore, the reduction in heart rate by the heart rate–lowering agent ivabradine should lead to prevention of atherosclerosis and to prevention of cardiovascular events.
This issue of the European Heart Journal Supplement reviews the available evidence and future perspectives of ivabradine in cardiology.
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