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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 Conclusions— Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drug-refractory 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.

The use of various pharmacologic agents has been proposed for the preventive treatment of vasovagal syncopal episodes, with conflicting efficacy results from various studies. Angiotensin-converting enzyme inhibitors (ACEIs), although reported in small studies to have a beneficial effect in patients with vasovagal syncope, have not been generally accepted as part of conventional treatment in such patients. Our population consisted of 125 consecutive patients (60 male, mean age 40±15 years), with a positive head-up tilt-table testing (HUTTT) (cardioinhibitory or vasodepressive or mixed response), who were randomized to receive either the ACEI fosinopril (N=63), at a dose of 10 mg qd, or placebo (N=62), for 30 days. They were then submitted to a new HUTTT (80 degrees, before and after infusion of isoproterenol, at a max. rate of 5 mcg/min). Before randomization, the patients were stratified according to the use of other vasoactive agents. Physicians performing the HUTTT were blinded as to each patient’s randomization group. Twenty-eight (44%) of fosinopril-treated patients were positive in the second HUTTT versus 52 (84%) in the placebo group (p=0.015). In a multivariate analysis, entering, apart from the treatment group, patient age, gender, smoking habit, hypertension, the use of beta-blocking agents and various demographic factors, with a negative result in the second HUTTT as the dependent variable, female gender, younger age and the use of fosinopril were independently associated with a negative repeat HUTTT. The present study reports a potential preventive effect of ACEIs in vasovagal syncope and indicates that younger, female patients, taking fosinopril were more likely to have a negative repeat HUTTT. The observed effect may be related to the ability of ACEIs to reduce cardiac wall tension, thus decreasing the activation of C-mechanoreceptors, as well as to their potential to inhibit angiotensin-related catecholamine release.

The regulation of apoptotic processes has been implicated in the evolution of restenosis after percutaneous coronary interventions (PCI) and angiotensin II has been shown to increase proliferation of vascular smooth muscle cells, while its blockade could result in increased apoptosis of the cellular components of restenotic plaques. We studied 60 symptomatic patients with significant obstructive (> 70%) lesions of the left anterior descending artery (LAD), submitted to elective PCI. The patients were randomly assigned to receive 40 mg of quinapril qd, starting one week before PCI and continued for 6 months, or placebo, in addition to standard treatment. Anti-hypertensive treatment (with the exception of angiotensin converting enzyme [ACE] and angiotensin receptor inhibitors) was administered as required to maintain desired blood pressure levels in both groups. Coronary angiography (CAG) was performed 6 months after the PCI to assess restenosis (at least 50% of lumen diameter). Plasma levels of apoptotic mediators soluble Fas and Fas ligand were measured (ELISA) in blood samples drawn during catheterization from the LAD artery (at the time of PCI and 6 months later). Restenosis rates in the quinapril-treated and in the control group were 21.2% and 29.7% respectively (p < 0.05, odds ratio 1.84, 95% CI 1.38 –2.5) and the late loss in minimum lumen diameter was 0.88 ± 0.4 mm and 1,05 ± 0.6 mm, respectively (p = 0.001). Plasma concentrations of Fas and Fas ligand in the LAD blood were significantly increased in the quinapril group at the 6-month CAG compared to baseline (4.8 ± 0.3 ng/ml vs 2.9± ng/ml for Fas and 54.4±3.3 pg/ml vs 32.5±1.9 pg/ml for Fas ligand, respectively), while no significant difference was observed in the control group. We report a potential effect of a relatively high dose of the ACE inhibitor quinapril on apoptotic markers in blood drawn form the LAD, which may be linked to the observed difference of in-stent restenosis, following PCI in the LAD. Increased apoptotic activity may be associated with inhibition of the neo-intimal hyperplasia and the overall atherogenic process, resulting in reduction of in-stent restenosis.