Among patients with persistent atrial fibrillation, we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01203748.).

P ulmonary vein (PV) isolation is an effective therapy to alleviate symptoms and restore sinus rhythm in patients with atrial fibrillation (AF).1 However, recent reports have shown that ablation in the left atrium (LA) is associated with new asymptomatic cerebral emboli (ACE) visible on postprocedural diffusion-weighted cerebral MRI.2 The largest such study reported an ACE incidence of 14.2% using openirrigation radiofrequency (RF) catheters.3 Although no patient parameters were correlated with ACE, procedural parameters, such as cardioversion and activated clotting time (ACT) level, were associated with new silent lesions. Smaller subsequent reports with rates ranging from 7% to 12% have similarly implicated procedural factors to increasing ACE incidence, including concomitant diagnostic coronary angiography, 4 total RF duration, 5 and non-PV ablation.6 Editorial see p 827 Clinical Perspective on p 842Two nonrandomized studies found that use of multielectrode RF (MER) ablation was associated with elevated ACE incidence compared with irrigated RF and cryoablation, with a rate as high as 38%. 7,8 Subsequent animal studies showed that both gaseous and solid emboli were generated during both irrigated and MER ablation in the swine LA. 9 Specifically with the circular MER catheter, increased gas emboli were observed during catheter insertion into transseptal sheaths while both embolic and gaseous © 2013 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-This prospective, multicenter study sought to evaluate the incidence of asymptomatic cerebral emboli (ACE) during ablation of atrial fibrillation (AF) using a multielectrode radiofrequency (MER) system when specific procedural changes were applied. Methods and Results-Sixty subjects (age 60±10 years; 87% paroxysmal; CHADS 2 score, 0.6±0.7) undergoing AF ablation with a circular MER catheter were studied. Three procedural changes were specified: (1) ablation was performed under therapeutic vitamin K antagonist and heparin to maintain activated clotting time >350 seconds; (2) submerged loading of the catheter into the introducer before sheath insertion to minimize air ingress; and (3) either the distal or proximal electrode of the circular MER catheter was deactivated to prevent inadvertent bipolar radiofrequency interaction. MRI was performed <7 days preablation and 2 days postablation. Subjects with new cerebral findings after ablation underwent repeat MRI after 1 month. An acute ACE lesion was defined by a new hyperintensity on diffusion-weighted and fluidattenuated inversion recovery cerebral MRI sequences. Neurological function was evaluated at baseline, postablation, and 1 month. All target pulmonary veins were isolated. In 60% (36/60) of patients, pre-existing cerebral lesions were seen on the preprocedure MRI (8 lesions per subject; interquartile range, 3-22). New postprocedural ACE occurred in only 1/60 patients (incidence, 1.7%; 95% confidence interval, 0.04-8.9), which was no longer visible on MRI after 1 month. Conclusi...

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Background-Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). Methods and Results-We treated 251 consecutive patients with paroxysmal (nϭ179) or permanent (nϭ72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (nϭ124) or AF (nϭ127) using 3D electroanatomic guidance. Procedures lasted 148Ϯ26 minutes. Among 980 lesions surrounding individual PVs (nϭ956) or 2 ipsilateral veins with close openings or common ostium (nϭ24), 75% were defined as complete by a bipolar electrogram amplitude Ͻ0.1 mV inside the lesion and a delay Ͼ30 ms across the line. The amount of low-voltage encircled area was 3594Ϯ449 mm 2 , which accounted for 23Ϯ9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4Ϯ4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (PϽ0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; PϽ0.001). Conclusions-Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).