Despite sustained pressure overload, inhibition of mTOR by a 4-week period of Rapamune treatment attenuates chronically established LVH and cardiac fibrosis with preserved contractile function.
ImportancePulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison.ObjectiveTo compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation.Design, Setting, and ParticipantsInvestigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022.InterventionsThe PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone.Main Outcomes and MeasuresPrimary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications.ResultsAmong 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, –1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone.Conclusions and RelevanceIn patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF.Trial Registrationanzctr.org.au Identifier: ACTRN12616001436460
OBJECTIVES:Current guidelines recommend topical steroids as first-line treatment for patients with eosinophilic esophagitis (EoE). However, the evidence for this approach has been inconsistent in earlier reports. This meta-analysis aimed to clarify the efficacy of topical steroid treatment in active EoE using updated evidence.METHODS:CENTRAL, MEDLINE and EMBASE databases were searched for randomized controlled trials (RCTs) published up to May 2014 that compared topical steroids with control treatments for active EoE. Study bias was assessed using the Cochrane Collaboration Tool, and outcomes were pooled using random effects models. The primary outcome was the mean change in eosinophil counts. Secondary outcomes were symptom responses and adverse events.RESULTS:In total, seven RCTs (226 patients) were included. Topical steroids were associated with a significant reduction in esophageal mucosal eosinophil counts compared with control therapy although substantial heterogeneity between studies was observed (weighted mean difference (WMD) −27.2, 95% confidence interval (CI) −45.3 to −9.1, I2=56.2%). Subgroup analysis indicated the reduction in eosinophil counts was only present in studies where a proton pump inhibitor (PPI) trial was used to exclude other diagnoses (WMD −46.3, 95% CI −61.3 to −31.4, I2=0.0%). Subdivision of studies on the use of a PPI trial also accounted for the majority of heterogeneity among RCTs. No clear trends in symptom resolution were observed. Eleven out of 127 patients who received topical steroids developed asymptomatic esophageal candidiasis.CONCLUSIONS:These data provide updated high-quality evidence that support current guidelines for first-line EoE treatment with topical steroids after an initial PPI trial to exclude non-EoE pathologies (PROSPERO ID: CRD42014008828).
Idiopathic ventricular arrhythmias commonly originate from the right ventricular and left ventricular outflow tracts (OTs). Advances in real-time imaging have refined our understanding of the intimate anatomic structures implicated in the genesis of OT arrhythmias, making catheter ablation for arrhythmias beyond the right ventricular OT a feasible option for cure—indeed ablation is now a class I indication in recent guidelines. The surface 12-lead ECG is routinely used to localize the anatomic site of origin before catheter ablation. However, the intimate and complex anatomy of the OT limits predictive value ECG criteria alone for localization for these arrhythmias. Multiple ECG algorithms have been developed to assist preprocedural localization, and hence predict safety and efficacy for catheter ablation of OT ventricular arrhythmias. This review will summarize all of the published 12-lead ECG algorithms used to guide localization of OT ventricular arrhythmias.
Aims: Obesity is associated with higher electrical cardioversion (ECV) failure in persistent atrial fibrillation (PeAF). For ease-of-use, many centers prefer patches over paddles. We assessed the optimum modality and shock vector, as well as the safety and efficacy of the Manual Pressure Augmentation (MPA) technique. Methods: Patients with obesity (BMI ≥ 30) and PeAF undergoing ECV using a biphasic defibrillator were randomized into one of four arms by modality (adhesive patches or handheld paddles) and shock vector (anteroposterior [AP] or anteroapical [AA]). If the first two shocks (100 and 200 J) failed, then patients received a 200-J shock using the alternative modality (patch or paddle). Shock vector remained unchanged. In an observational substudy, 20 patients with BMI of 35 or more, and who failed ECV at 200 J using both patches/paddles underwent a trial of MPA.Results: In total, 125 patients were randomized between July 2016 and March 2018. First or second shock success was 43 of 63 (68.2%) for patches and 56 of 62 (90.3%) for paddles (P = 0.002). There were 20 crossovers from patches to paddles (12 of 20 third shock success with paddles) and six crossovers from paddles to patches (three of six third shock success with patches). Paddles successfully cardioverted 68 of 82 patients compared with 46 of 69 using patches (82.9% vs 66.7%; P = 0.02). Shock vector did not influence first or second shock success rates (82.0% AP vs 76.6% AA; P = 0.46). MPA was successful in 16 of 20 (80%) who failed in both (patches/paddles), with 360 J required in six of seven cases.
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