Central Sympathetic Inhibition to Reduce Postablation Atrial Fibrillation Recurrences in Hypertensive Patients

Abstract

The objective of this prospective, randomized, controlled study was to test the hypothesis that central sympathetic inhibition, using the centrally acting agent moxonidine, can lead to reduced postablation recurrence risk in patients with hypertension who are undergoing pulmonary vein isolation for drug-refractory paroxysmal AF.Background-The autonomic system is an important determinant of atrial arrhythmogenesis. Current evidence indicates that a combined sympathovagal drive is most commonly responsible for eliciting atrial fibrillation (AF) episodes. The purpose of this study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, can lead to a reduction in postablation AF recurrence. Methods and Results-This was a prospective, double-blinded, randomized study of 291 hypertensive patients with symptomatic paroxysmal AF who were scheduled to undergo pulmonary vein isolation. Patients were randomly assigned to receive either moxonidine (0.2-0.4 mg daily) or placebo, along with standard antihypertensive treatment. No significant differences in blood pressure levels were observed between the 2 groups. In the primary outcome analysis, mean recurrence-free survival was 467 days (95% CI, 445-489 days) in the moxonidine group as compared with 409 days (95% CI, 381-437 days) in control subjects (log rank test, P=0.006). The calculated 12-month recurrence rate estimates were 36.9% in the control group and 20.0% in the moxonidine group (P=0.007). Moxonidine treatment was associated with lower recurrence risk after adjustment for age, body mass index, number of AF episodes in the previous year, and left atrial diameter (adjusted hazard ratio, 0.35 [95% CI, 0.22-0.55]; P<0.001). Conclusions-Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drugrefractory AF in patients with hypertension. The observed effect does not appear to depend on the antihypertensive action of this agent. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791699.

Sympathetic Nervous System Activation and Its Modulation: Role in Atrial Fibrillation

“…Moreover, moxonidine induced sympathetic inhibition decreased the AF burden in hypertensive patients with paroxysmal AF without any side effects (Deftereos et al, 2013). Furthermore, moxonidine reduced post-ablation recurrence of AF in hypertensive patients who underwent pulmonary vein isolation for drug-refractory paroxysmal AF (Giannopoulos et al, 2014).…”

Catheter ablation in patients with persistent atrial fibrillation

“…Initial results also suggest that antihypertensive therapies that modulate central sympathetic tone (moxonidine) reduce recurrent AF after catheter ablation. 31 Angiotensin converting enzyme inhibitors or sartans, while not effective in preventing recurrent AF in patients without structural heart disease in the short term, 32,33 may have long-term beneficial effects for the primary prevention of AF. 34 It has also been suggested that evidence-based therapy of heart failure with reduced ejection fraction can help to prevent AF.…”

Effect of catheter ablation on pre-existing abnormalities of left atrial systolic, diastolic, and neurohormonal functions in patients with chronic heart failure and atrial fibrillation

“…LA remodelling leads to loss of normal sympathoinhibition; the resulting increase in autonomic activity to the LA can trigger AF, whereas restoration of central sympathetic inhibition ameliorates the risk of AF 16 . Heart failure also disrupts the adaptive neurohormonal response to LA stretch, such that chamber distension no longer leads to reflex sympathoinhibition, 16 but instead, causes paradoxical sympathetic activation, leading to AF 17 . In addition, circulating natriuretic peptides are increased in heart failure, particularly in patients with AF, but heart failure impairs the cleavage of prohormones in the LA, thus limiting the release of biologically active peptides 18 .…”