Background/Objectives: Vernakalant is an atrial-selective antiarrhythmic used for rapid pharmacological cardioversion of recent-onset atrial fibrillation. This systematic review and meta-analysis evaluated the efficacy and safety of vernakalant compared with placebo, active antiarrhythmic therapy, and electrical cardioversion. Methods: PubMed, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to August 2026. Randomized clinical trials, clinical trials, and comparative observational studies evaluating vernakalant in adults with atrial fibrillation or atrial flutter were included. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using the Mantel–Haenszel random-effects model in RevMan 5.4. Results: Twenty controlled studies involving 4523 patients were included, of whom 2349 received vernakalant and 2174 received control therapy. Vernakalant significantly increased successful conversion to sinus rhythm compared with all controls (1234/2244 (55%) vs. 991/2147 (46.2%); RR = 1.63; 95% CI [1.34, 1.99]; p < 0.00001). The effect was strongest versus placebo (RR = 5.33; 95% CI [1.95, 14.60]; p = 0.001) and remained significant versus procainamide (111/178 (62.3%) vs. 83/172 (48.2%); RR = 1.29; 95% CI [1.07, 1.57]; p = 0.009) and flecainide (209/280 vs. 209/330 (63.3%); RR = 1.18; 95% CI [1.05, 1.33]; p = 0.007), but non-significant against amiodarone, propafenone, ibutilide, or electrical cardioversion. Safety outcomes did not differ significantly between groups, including all-cause mortality (RR = 1.23), drug discontinuation (RR = 0.98), serious adverse events (RR = 0.87), ventricular tachycardia (RR = 0.68), bradycardia (RR = 1.31), and hypotension (RR = 0.80). Conclusions: Vernakalant was associated with higher rates of conversion to sinus rhythm, while no statistically significant differences were observed in major safety outcomes. These findings support its use as a pharmacological option for rapid rhythm restoration in appropriately selected patients.

Background: Tricuspid regurgitation (TR) increases mortality but remains undertreated due to high surgical risks. Transcatheter tricuspid valve interventions (TTVI) offer safer alternatives, improving functional status and quality of life. However, many candidates for TTVI have trans-tricuspid CIED leads that may interfere with procedural imaging and device deployment and may be exposed to dislodgement, entrapment, or jailing. Evidence regarding both clinical outcomes and postprocedural CIED function in this population remains limited. Existing trial evidence for this population is scarce, requiring further safety analysis. To our knowledge, this is the first meta-analysis to address the comparative risk of complications and residual TR in patients with vs. without CIEDs. Methods: We searched for relevant articles up to March 2026 from PubMed, Scopus, Cochrane Library, and Web of Science. Two independent reviewers extracted data from the selected studies, including baseline information, outcomes, comorbidities, hospitalization metrics, TR severity, and complications. All data analyses were performed using R version 4.4.1. Results: Ten studies comprising 5415 patients were included. Nine comparative studies contributed to the quantitative synthesis, whereas one single-arm study contributed only to the narrative synthesis of CIED-specific mechanical and electrical outcomes. In patients undergoing TTVI, across two studies, patients with CIEDs had a nominally lower risk of single-leaflet device attachment (RR 0.34, 95% CI 0.12–0.94; nominal p = 0.037); however, this exploratory finding should be considered hypothesis-generating. However, no statistically significant differences were observed between groups for cardiovascular death (RR 1.30, p = 0.815), device embolization (RR 1.62, p = 0.666), device malposition (RR 1.10, p = 0.909), stroke (RR 0.52, p = 0.335), hospitalization for heart failure (RR 1.02, p = 0.931), in-hospital mortality (RR 1.02, p = 0.959), major adverse events (RR 0.74, p = 0.635), major bleeding (RR 0.70, p = 0.187), or residual tricuspid regurgitation of mild (RR 0.98, p = 0.686) or moderate severity (RR 1.01, p = 0.646). CIED-specific outcomes were reported heterogeneously. Lead function was generally preserved after T-TEER in carefully selected patients, whereas studies of TTVR with jailed leads reported lead failure or malfunction ranging from 5.8% to 21% in individual cohorts. Conclusions: Among the comparative outcomes available for quantitative pooling, no statistically significant differences were detected between patients with and without CIEDs for most procedural and postprocedural outcomes. However, CIED-specific risks differed according to the intervention. Lead function was generally preserved after T-TEER in carefully selected patients, whereas lead jailing during TTVR was associated with clinically relevant lead malfunction in some cohorts. Therefore, the absence of significant differences in pooled clinical outcomes should not be interpreted as evidence that TTVI does not affect CIED function.