Randomized Feasibility Trial of Prophylactic Radiofrequency Ablation to Prevent Atrial Fibrillation after Cardiac Surgery.

OBJECTIVE: Evaluate the feasibility of prophylactic radiofrequency isolation of the pulmonary veins, with left atrial appendage amputation, to reduce the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery in patients aged 70 and older. METHODS: The Federal Food and Drug Administration granted an investigational device exemption to utilize a bipolar radiofrequency clamp for prophylactic pulmonary vein isolation in a limited, feasibility trial. Sixty-two patients without prior dysrhythmias, were prospectively randomized to undergo either their index cardiac surgical procedure, or bilateral pulmonary vein isolation and left atrial appendage amputation during their cardiac operation. The primary outcome was occurrence of in-hospital POAF. Subjects were on 24-hour telemetry until discharge. Dysrhythmias, any episode of atrial fibrillation > 30 seconds, were confirmed by electrophysiologists blinded to the study. RESULTS: Sixty patients, mean age 75 years and mean CHA2DS2-VASc score 4, were analyzed. Thirty-one patients randomized to control and twenty-nine to the treatment group. Majority of cases in each group were isolated CABG. No perioperative complications related to the treatment procedure, need for permanent pacemaker, or mortality occurred. The in-hospital incidence of POAF was 55% (17/31) in the control group and 7% (2/29) in the treatment group. (p<0.001) The control group had a significantly higher requirement for antiarrhythmic medications at discharge, 45% (14/31) vs 7% (2/29) in the treatment group (p<0.001). CONCLUSIONS: Prophylactic radiofrequency isolation of the pulmonary veins with left atrial appendage amputation, during the primary cardiac surgical operation, reduced the incidence of POAF in patients 70 years and older with no history of atrial arrhythmias.

Surgical Explantation of Transcatheter Aortic Valve Bioprostheses: A Statewide Experience.

BACKGROUND: Despite the rapid adoption of transcatheter aortic valve replacement (TAVR) since its initial approval in 2011, the frequency and outcomes of surgical explantation of TAVR devices (TAVR-explant) is poorly understood. METHODS: Patients undergoing TAVR-explant between January 2012 and June 2020 at 33 hospitals in Michigan were identified in the Society of Thoracic Surgeons Database and linked to index TAVR data from the Transcatheter Valve Therapy Registry through a statewide quality collaborative. The primary outcome was operative mortality. Indications for TAVR-explant, contraindications to redo TAVR, operative data, and outcomes were collected from Society of Thoracic Surgeons and Transcatheter Valve Therapy databases. Baseline Society of Thoracic Surgeons Predicted Risk of Mortality was compared between index TAVR and TAVR-explant. RESULTS: Twenty-four surgeons at 12 hospitals performed TAVR-explants in 46 patients (median age, 73). The frequency of TAVR-explant was 0.4%, and the number of explants increased annually. Median time to TAVR-explant was 139 days and among known device types explanted, most were self-expanding valves (29/41, 71%). Common indications for TAVR-explant were procedure-related failure (35%), paravalvular leak (28%), and need for other cardiac surgery (26%). Contraindications to redo TAVR included need for other cardiac surgery (28%), unsuitable noncoronary anatomy (13%), coronary obstruction (11%), and endocarditis (11%). Overall, 65% (30/46) of patients underwent concomitant procedures, including aortic repair/replacement in 33% (n=15), mitral surgery in 22% (n=10), and coronary artery bypass grafting in 16% (n=7). The median Society of Thoracic Surgeons Predicted Risk of Mortality was 4.2% at index TAVR and 9.3% at TAVR-explant (P=0.001). Operative mortality was 20% (9/46) and 76% (35/46) of patients had in-hospital complications. Of patients alive at discharge, 37% (17/37) were discharged home and overall 3-month survival was 73±14%. CONCLUSIONS: TAVR-explant is rare but increasing, and its clinical impact is substantial. As the utilization of TAVR expands into younger and lower-risk patients, providers should consider the potential for future TAVR-explant during selection of an initial valve strategy.

Early Outcomes for Valve-in-valve Transcatheter Aortic Valve Replacement in Degenerative Freestyle Bioprostheses.

Transcatheter aortic valve replacement (TAVR) is used increasingly to treat bioprosthetic valve failure. A paucity of data exists regarding valve-in-valve (ViV) TAVR in degenerated Freestyle stentless bioprostheses (FSBs). This study sought to evaluate the feasibility and short-term outcomes of ViV TAVR in previously placed FSB. From October 2014 to September 2016, 22 patients at a single institution underwent ViV TAVR with a self-expanding transcatheter valve for a failing FSB. Patient baseline characteristics and clinical outcomes data were collected retrospectively and entered into a dedicated database. The mean patient age was 74 ± 9 years, and the mean Society of Thoracic Surgeons' Risk score was 9.0 ± 7.4%. Ten patients presented with acute heart failure requiring urgent intervention. The most common mode of failure of the FSB was regurgitation caused by a flail or malcoapting leaflet. Seventeen (77%) patients had a modified subcoronary implantation, 3 (14%) had a full root replacement, and 2 (9%) had a root inclusion. Device success using a self-expanding transcatheter valve was 95%, all via transfemoral approach. The mean implant depth was 7 ± 3 mm. Thirty-day survival was 100%. No patient had more than mild paravalvular regurgitation at 30 days, and the permanent pacemaker rate was 9%. The mean hospital stay after intervention was 5 ± 2 days. ViV TAVR using a self-expanding transcatheter valve is safe, feasible, and can be used successfully to treat a failed FSB. Procedural challenges suggest referral to valve centers of excellence.

Penetratin and related cell-penetrating cationic peptides can translocate across lipid bilayers in the presence of a transbilayer potential.

Fluorescent-labeled derivatives of the Antennapedia-derived cell-penetating peptide penetratin, and of the simpler but similarly charged peptides R(6)GC-NH(2) and K(6)GC-NH(2), are shown to be able to translocate into large unilamellar lipid vesicles in the presence of a transbilayer potential (inside negative). Vesicles with diverse lipid compositions, and combining physiological proportions of neutral and anionic lipids, are able to support substantial potential-dependent uptake of all three cationic peptides. The efficiency of peptide uptake under these conditions is strongly modulated by the vesicle lipid composition, in a manner that suggests that more than one mechanism of peptide uptake may operate in different systems. Remarkably, peptide uptake is accompanied by only minor perturbations of the overall barrier function of the lipid bilayer, as assessed by assays of vesicle leakiness under the same conditions. Fluorescence microscopy of living CV-1 and HeLa cells incubated with the labeled peptides shows that the peptides accumulate in peripheral vesicular structures at early times of incubation, consistent with an initial endosomal localization as recently reported, but gradually accumulate in the cytoplasm and nucleus during more extended incubations (several hours). Our findings indicate that these relatively hydrophilic, polybasic cell-penetrating peptides can translocate through lipid bilayers by a potential- and composition-dependent pathway that causes only minimal perturbation to the overall integrity and barrier function of the bilayer.