Mid-term success rate of single stage hybrid ablation of persistent and long-term persistent atrial fibrillation.

INTRODUCTION: Single stage thoracoscopic radiofrequency ablation (RFA) is a treatment method for persistent and long-term persistent atrial fibrillation (AF) offering the possibility for patients otherwise inconsolable by conventional catheter RFA. We present a pilot group of patients after the introduction of the new method at our clinical center. Patients group: A total of 52 patients aged 61.82 ± 9.7 years underwent single stage hybrid ablation (thoracoscopic isolation of pulmonary veins and box lesion followed by catheter verification of the surgical procedure effectivness) for symptomatic persistent and long-term persistent AF with significantly dilated left atrium 57.9 ± 11.0mm in the period September 2016-March 2019. RESULTS: The median duration of the procedure was 232 minutes and the median duration of hospitalization was 10 days. At discharge, 52 patients (100%) had sinus rhythm. 48 of 52 patients (92.3%) had a 6-month follow-up. 41 of 48 (85.4%) and 38 of 44 (86.4%) of patients were AF free at 3-month and 6-month follow-up, respectively. Acute complications were: one left atrial perforation resolved successfully by suture and one transient ischaemic attack without permanent sequelae. Late complications involved one massive pulmonary embolization and an atrioesophageal fistula. There was no periprocedural myocardial infarction or stroke with permanent sequelae. CONCLUSION: Hybrid thoracoscopic-catheter ablation performed during one procedure is an effective and relatively safe mini-invasive method of treatment for long-term persistent atrial fibrillation.

Irreversible electroporation ablation for atrial fibrillation.

Atrial fibrillation (AF) is one of the most important problems in modern cardiology. Thermal ablation therapies, especially radiofrequency ablation (RF), are currently "gold standard" to treat symptomatic AF by localized tissue necrosis. Despite the improvements in reestablishing sinus rhythm using available methods, both success rate and safety are limited by the thermal nature of procedures. Thus, while keeping the technique in clinical practice, safer and more versatile methods of removing abnormal tissue are being investigated. This review focuses on irreversible electroporation (IRE), a nonthermal ablation method, which is based on the unrecoverable permeabilization of cell membranes caused by short pulses of high voltage/current. While still in its preclinical steps for what concerns interventional cardiac electrophysiology, multiple studies have shown the efficacy of this method on animal models. The observed remodeling process shows this technique as tissue specific, triggering apoptosis rather than necrosis, and safer for the structures adjacent the myocardium. So far, proposed IRE methodologies are heterogeneous. The number of devices (both generators and applicators), techniques, and therapeutic goals impair the comparability of performed studies. More questions regarding systemic safety and optimal processes for AF treatment remain to be answered. This work provides an overview of the electroporation process, and presents different results obtained by cardiology-oriented research groups that employ IRE ablation, with focus of AF-related targets. This contribution on the topic aspires to be a practical guide to approach IRE ablation for cardiac arrhythmias, and to highlight controversial features and existing knowledge, to provide background for future improved experimentation with IRE in arrhythmology.

Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading.

The mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells (MSCs). MSC fate decision can be unbalanced by controlling substrate mechanics, in turn altering the transmission of tension through cell cytoskeleton. MSCs have been proposed for orthopedic and reconstructive surgery applications. Thus, a tight control of their adipogenic potential is required in order to avoid their drifting towards fat tissue. Substrate mechanics has been shown to drive MSC commitment and to regulate YAP/TAZ protein shuttling and turnover. The mechanism by which YAP/TAZ co-transcriptional activity is mechanically regulated during MSC fate acquisition is still debated. Here, we design few bioengineering tools suited to disentangle the contribution of mechanical from biological stimuli to MSC adipogenesis. We demonstrate that the mechanical repression of YAP happens through its phosphorylation, is purely mediated by cell spreading downstream of substrate mechanics as dictated by dimensionality. YAP repression is sufficient to prompt MSC adipogenesis, regardless of a permissive biological environment, TEAD nuclear presence or focal adhesion stabilization. Finally, by harnessing the potential of YAP mechanical regulation, we propose a practical example of the exploitation of adipogenic transdifferentiation in tumors.