Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): A multicenter stepped-wedge cluster randomized controlled trial

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018

Low vulnerability of the right phrenic nerve to electroporation ablation

BACKGROUND Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-3 application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are unknown. OBJECTIVE The purpose of this study was to analyze nerve vulnerability to electroporation ablation in a porcine model. METHODS In 20 animals (60-75 kg), the course of the right PN was pace-mapped inside the superior caval vein (SCV). Thereafter, a single 200-3 circular electroporation ablation was performed via a multipolar circular catheter in firm contact with the inner SCV wall. RESULTS In 19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory above the right atrial contour. Directly after the application, the PN could be captured above the ablation Level in 17 of 19 animals and after maximally 30 minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN functionality was unaffected in all. Histological analysis in 5 animals in which the application had been delivered in the muscular sleeve just above the right atrium showed a transmural circular lesion. However, no lesion was found in the other animals in which the application had been delivered in the fibrous section more cranial in the SCV. CONCLUSIONS Electroporation ablation at an energy Level that may create deep myocardial Lesions may spare the targeted right PN. These animal data suggest that electroporation may be a safe ablation modality near the right PN

Low vulnerability of the right phrenic nerve to electroporation ablation

BACKGROUND Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-3 application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are unknown. OBJECTIVE The purpose of this study was to analyze nerve vulnerability to electroporation ablation in a porcine model. METHODS In 20 animals (60-75 kg), the course of the right PN was pace-mapped inside the superior caval vein (SCV). Thereafter, a single 200-3 circular electroporation ablation was performed via a multipolar circular catheter in firm contact with the inner SCV wall. RESULTS In 19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory above the right atrial contour. Directly after the application, the PN could be captured above the ablation Level in 17 of 19 animals and after maximally 30 minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN functionality was unaffected in all. Histological analysis in 5 animals in which the application had been delivered in the muscular sleeve just above the right atrium showed a transmural circular lesion. However, no lesion was found in the other animals in which the application had been delivered in the fibrous section more cranial in the SCV. CONCLUSIONS Electroporation ablation at an energy Level that may create deep myocardial Lesions may spare the targeted right PN. These animal data suggest that electroporation may be a safe ablation modality near the right PN

Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation : a single-centre cohort study

AIMS: Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence. METHODS AND RESULTS: A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 ± 23 and 55 ± 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% (n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% (n = 297). Additional substrate modification (n = 70) increased success to 62.5% (n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration. CONCLUSION: Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success

Low 30-day Mortality after Atrial Fibrillation Ablation; Results from the Netherlands Heart Registration: NHR-AF Mortality Study

This study presents the 30-day mortality of patients who underwent atrial fibrillation (AF) ablation between 2013 - 2020 and were registered in the Netherlands Heart Registration. In total, 30,197/30,238 (99.9%) patients were analyzed. Fifteen (0.05%) died within 30 days. Nine deaths were considered procedurally related, four were considered non-procedural related, and in two patients the cause of death was unknown