Background and aimsRenin-angiotensin-aldosterone system (RAAS) inhibition is an upstream therapy for managing atrial fibrillation (AF). Of all RAAS-inhibiting agents, only canrenone in the form of potassium canrenoate, a specific inhibitor of mineralocorticoid receptors, is administered intravenously. We evaluated the clinical efficacy of intravenous potassium canrenoate in restoring sinus rhythm in patients with paroxysmal AF episodes.MethodsThis double-center, randomized, double-blind study comprised 52 patients with AF (lasting <48 h) in stable cardiopulmonary conditions who were eligible for cardioversion. The patients were randomly assigned to receive a slow intravenous bolus of 10 ml either as a placebo (0.9% saline) or canrenone (200 mg). The primary endpoint was the return of sinus rhythm within 2 h after drug administration.ResultsOf 52 patients, 27 (51.9%) and 25 (48.1%) were treated with placebo and canrenone, respectively. The median patient age was 68 years, and 27 patients (51.9%) were men. Sinus rhythm restoration during the follow-up period occurred in 3 (11.5%) and 4 (16.0%) patients in the placebo and canrenone arms (P = .477), respectively. Adverse events were observed in 2 (7.4%) and 0 (0.0%) patients in the placebo and canrenone arms, respectively (P = .170).ConclusionsIntravenous canrenone is not effective in the sinus rhythm restoration among the patients with paroxysmal AF.ClinicalTrials.gov. NCT03536806.

Syncope refers to the transient loss of consciousness and the most common type of syncope is vasovagal syncope (VVS), usually occurring when a person is in an upright position, and/or after exposure to intense stress. The sequelae of VVS is caused by an increase in sympathetic tone and heart rate combined with an underfilled left ventricular chamber that leads to stimulation of cardiac afferent C fibers ultimately leading to bradycardia and vasodilation causing a reduction in venous return, cerebral hypoperfusion and VVS. Several treatment options have been tested including physical counter-pressure measures, electrical pacing, cardioneuroblation. Pharmacological interventions and clinical trials for VVS are summarized in this review; however, there is still limited evidence of their efficacy for reducing episodes of VVS. This review will examine studies using animal models of the vasovagal reflex arc to investigate the physiological mechanisms and neurotransmitters associated with VVS, the tilt-table test that induces VVS in patients and the potential sources of cardiac and platelet mediators that can activate cardiac afferent C fibers. This study will also consider how the previously investigated pharmacotherapies provide insight into the multiple mechanisms involved in VVS and propose new targets for the pharmacological treatment of VVS.