Vitamin C Intravenous Treatment In the Setting of Atrial Fibrillation Ablation: Results From the Randomized, Double-Blinded, Placebo-Controlled CITRIS-AF Pilot Study

BackgroundCatheter ablation is an effective treatment for atrial fibrillation (AF), but high levels of post-procedure inflammation predict adverse clinical events. Ascorbic acid (AA) has shown promise in reducing inflammation but is untested in this population. We sought to test the feasibility, safety, and preliminary effects on inflammatory biomarkers in the CITRIS-AF (Vitamin C Intravenous Treatment In the Setting of Atrial Fibrillation Ablation) pilot study. Methods and ResultsPatients scheduled to undergo AF ablation (N=20) were randomized 1:1 to double-blinded treatment with AA (200 mg/kg divided over 24 hours) or placebo. C-reactive protein and interleukin-6 levels were obtained before the first infusion and repeated at 24 hours and 30 days. Pain levels within 24 hours and early recurrence of AF within 90 days were recorded. Median and interquartile range were aged 63 (56–70) years, 13 (65%) men, and 18 (90%) white. Baseline data were similar between the 2 groups except ejection fraction. Baseline C-reactive protein levels were 2.56 (1.47–5.87) mg/L and similar between groups (P=0.48). Change in C-reactive protein from baseline to 24 hours was +10.79 (+6.56–23.19) mg/L in the placebo group and +3.01 (+0.40–5.43) mg/L in the AA group (P=0.02). Conversely, change in interleukin-6 was numerically higher in the AA group, though not statistically significant (P=0.32). One patient in each arm developed pericarditis; no adverse events related to the infusions were seen. There were no significant differences between aggregated post-procedure pain levels within 24 hours or early recurrence of AF (both P\u3e0.05). ConclusionsHigh-dose AA is safe and well tolerated at the time of AF ablation and may be associated with a blunted rise in C-reactive protein, although consistent findings were not seen in interleukin-6 levels. Further studies are needed to validate these findings and explore the potential benefit in improving clinically relevant outcomes

Clarithromycin, QTc interval prolongation and torsades de pointes:the need to study case reports

BACKGROUND: The manufacturers of clarithromycin sought a drug similar in efficacy to erythromycin but with a superior side-effect profile. They generally achieved this outcome, but postmarketing findings identified a series of reports linking clarithromycin to QTc interval prolongation and torsades de pointes (TdP) ultimately leading to a Black Box Warning. We sought to clarify risk factors associated with TdP among case reports of patients receiving clarithromycin linked to QTc interval prolongation and TdP. METHODS AND RESULTS: In a detailed literature search, we found 15 women, five men, and one boy meeting our search criteria. Among the 17 adults with reported clarithromycin dose and concurrent QTc interval measurement, we found no statistically significant relationship between clarithromycin dose and QTc interval duration. This did not change for the adults who developed TdP. Among adults, major risk factors were female sex (15), old age (11) and heart disease (17). A total of eight adult subjects had all three major risk factors and 14 of the 20 adults had at least two major risk factors. All adult subjects had at least two risk factors besides clarithromycin. A total of four of the 20 adults received cisapride and three received disopyramide. Three adults were considered to suffer from some aspect of the congenital long QT syndrome. CONCLUSIONS: We believe that the risk factor description for this drug should be refined to emphasize the major risk factors of (1) female sex, (2) old age and (3) heart disease

Efficacy and Safety of Pulsed Field Ablation in Atrial Fibrillation: A Systematic Review

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with high morbidity and mortality. AF treatment is guided by a patient–provider risk–benefit discussion regarding drug versus ablation or combination. Thermal ablation has a high rate of adverse events compared to pulsed field ablation (PFA). In this systematic review, we aimed to determine the safety and efficacy of PFA. Methods: The electronic search for relevant articles in English was completed in PubMed, PubMed Central, Cochrane library, Scopus, and Embase databases till July 2022. The screening was completed via the use of Covidence software. The risk of bias assessment and data extraction from the included studies was performed, and the narrative synthesis was performed accordingly. Results: A total of six studies were selected for review and 1897 patients receiving PFA were involved in these studies. Our review was focused on pulmonary vein isolation success, major adverse events, and arrhythmia recurrence. Successful pulmonary vein isolation (PVI) was completed in 100% of cases except in two studies. In one of them, six out of seven patients (86%) in the epicardial cohort had successful PVI. In the MANIFEST-PF survey, the acute PVI success rate was 99.9%. The major complications were rare and included pericardial tamponade, vascular complications requiring surgery, and stroke. The atrial arrhythmia recurrence was higher in the thermal group than in the PFA group (39% vs. 11%). Conclusions: The success rate of PVI by PFA is high, and major adverse events are low. PFA is found to decrease the recurrence of atrial arrhythmia compared to thermal ablation. Substantial randomized controlled trials (RCTs) are needed to validate the efficacy and safety of PFA over conventional methods

Methadone, QTc interval prolongation and torsade de pointes:Case reports offer the best understanding of this problem

We reviewed the literature and found 31 adult cases and 1 newborn case of methadone-associated QTc interval prolongation and/or torsade de pointes (TdP). Parametric statistics may not be useful in studying this issue because methadone-associated TdP is a very rare event and, hence, “an extreme outlier” consistent with scalable randomness. We may have to rely upon narrative medicine in the form of case reports with all its limitations and hazards to provide our best understanding. We report risk factors for methadone-associated QTc interval prolongation and TdP based on review of published case reports. We believe both drug manufacturers and the FDA would better serve our patients and inform clinicians if they more readily reported drug-induced outliers such as methadone-associated TdP using a case report format