Rationale and current perspective for early rhythm control therapy in atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia and an important source for mortality and morbidity on a population level. Despite the clear association between AF and death, stroke, and other cardiovascular events, there is no evidence that rhythm control treatment improves outcome in AF patients. The poor outcome of rhythm control relates to the severity of the atrial substrate for AF not only due to the underlying atrial remodelling process but also due to the poor efficacy and adverse events of the currently available ion-channel antiarrhythmic drugs and ablation techniques. Data suggest, however, an association between sinus rhythm maintenance and improved survival. Hypothetically, sinus rhythm may also lead to a lower risk of stroke and heart failure. The presence of AF, thus, seems one of the modifiable factors associated with death and cardiovascular morbidity in AF patients. Patients with a short history of AF and the underlying heart disease have not been studied before. It is fair to assume that abolishment of AF in these patients is more successful and possibly also safer, which could translate into a prognostic benefit of early rhythm control therapy. Several trials are now investigating whether aggressive early rhythm control therapy can reduce cardiovascular morbidity and mortality and increase maintenance of sinus rhythm. In the present paper we describe the background of these studies and provide some information on their design.

Figure 1

Yearly cardiovascular morbidity and mortality rate in the Rate Control Versus Electrical Cardioversion (RACE) I study (published in 2002) and the RAte Control Efficacy in permanent atrial fibrillation (RACE) II study (published in 2010).^,

Figure 2

Flow chart showing the series of events caused by stretch. Hypothetical scheme of stretch induced by hypertension, heart failure and possibly extreme endurance exercise leading to calcium overload, activation of the renin−angiotensin−aldosterone system  and release of different factors, resulting in structural remodelling and finally in atrial fibrillation  (Adapted with permission from De Jong et al.).