Atrial fibrillation (AF) is the most common sustained arrhythmia and its treatment continues to be a challenge. Recently, delayed enhancement (DE)-MRI was introduced in the diagnosis and treatment of AF by the assessment of atrial fibrosis, which is considered the hallmark of the arrhythmogenic substrate in AF. Atrial fibrosis was reported to be an independent predictor of arrhythmia recurrences. Post-ablation DE-MRI allows for assessment of the total scar burden, complete encirclement of pulmonary veins, and the assessment of residual fibrosis, which were all reported to be strong predictors of arrhythmia recurrences post-ablation. Current pathophysiological perspectives for AF are heavily based on the adagium AF begets AF. However, several recent observations, such as atrial fibrosis being present in non-AF patients, do introduce a new pathophysiological perspective for AF. Potentially, atrial fibrosis is a disease process that triggers the initiation and maintenance of the syndrome AF.

Background Late gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation ( AF ) ablation success at 1 year, but the association between left atrial fibrosis and long‐term ablation success has not been studied. Methods and Results Late gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0–10%; II , 10–20%; III , 20–30%; and IV , >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow‐up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57–4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12–12.69). Conclusions The degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow‐up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.

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R enal denervation (RDN) has been reported as a successful treatment of resistant hypertension in multiple trials studying the efficacy of RDN. [1][2][3][4][5][6] The sham-controlled Symplicity Hypertension-3 (HTN-3) trial, however, failed to show significant RDN-induced changes in blood pressure (BP) versus control, 7 raising serious doubts about the efficacy of RDN. 8-11Variable effects of RDN on BP have been reported, with a wide spectrum ranging between nonresponse to marked reduction in BP. 12 The absence of an ablation procedural end point for RDN is a potential explanation for variable responses, and the successful implementation of a reliably predictable end point could improve procedural success and clinical response.Recently, we reported on the feasibility of high-frequency electric renal nerve stimulation (RNS) in patients with resistant hypertension and demonstrated that RNS-induced BP increase was significantly blunted after RDN. 13 We hypothesized that the difference between RNS-induced BP rise before and after RDN could be used as a procedural end point for RDN and may prove a reliable functional test to predict BP response to RDN. The main goal of the current analysis was to investigate the 24-hour ambulatory BP changes after RDN and the relation to RNS before and after RDN. Methods PatientsAll patients with treatment-resistant hypertension referred for RDN between May 2014 and February 2015 were screened for inclusion in the RNS study. Patients were eligible if they were on a stable Abstract-Blood pressure (BP) response to renal denervation (RDN) is highly variable and its effectiveness debated. A procedural end point for RDN may improve consistency of response. The objective of the current analysis was to look for the association between renal nerve stimulation (RNS)-induced BP increase before and after RDN and changes in ambulatory BP monitoring (ABPM) after RDN. Fourteen patients with drug-resistant hypertension referred for RDN were included. RNS was performed under general anesthesia at 4 sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP changes were monitored and correlated to changes in ambulatory BP at a follow-up of 3 to 6 months after RDN. RNS resulted in a systolic BP increase of 50±27

The safety, tolerability, immunogenicity, and pharmacokinetic (PK) profile of an anti‐OX40L monoclonal antibody (KY1005, currently amlitelimab) were evaluated. Pharmacodynamic (PD) effects were explored using keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT) immunizations. Sixty‐four healthy male subjects (26.5 ± 6.0 years) were randomized to single doses of 0.006, 0.018, or 0.05 mg/kg, or multiple doses of 0.15, 0.45, 1.35, 4, or 12 mg/kg KY1005, or placebo (6:2). Serum KY1005 concentrations were measured. Antibody responses upon KLH and TT immunizations and skin response upon intradermal KLH administration were performed. PD data were analyzed using repeated measures analysis of covariances (ANCOVAs) and post hoc exposure‐response modeling. No serious adverse events occurred and all adverse events were temporary and of mild or moderate severity. A nonlinear increase in mean serum KY1005 concentrations was observed (median time to maximum concentration (Tmax) ~ 4 hours, geometric mean terminal half‐life (t½) ~ 24 days). Cutaneous blood perfusion (estimated difference (ED) −13.4 arbitrary unit (AU), 95% confidence interval (CI) −23.0 AU to −3.8 AU) and erythema quantified as average redness (ED −0.23 AU, 95% CI −0.35 AU to −0.11 AU) decreased after KY1005 treatment at doses of 0.45 mg/kg and above. Exposure‐response analysis displayed a statistically significant treatment effect on anti‐KLH antibody titers (IgG maximum effect (Emax) −0.58 AU, 95% CI −1.10 AU to −0.06 AU) and skin response (erythema Emax −0.20 AU, 95% CI −0.29 AU to −0.11 AU). Administration of KY1005 demonstrated an acceptable safety and tolerability profile and PK analyses displayed a nonlinear profile of KY1005. Despite the observed variability, skin challenge response after KY1005 treatment indicated pharmacological activity of KY1005. Therefore, KY1005 shows potential as a novel pharmacological treatment in immune‐mediated disorders.