There was comparable freedom from AT between CB and RF in patients with AF undergoing PVI. Additionally, freedom from AT was similar between CB2 and CF-RF. However, CB was associated with a lower incidence of pericardial effusions or tamponade, albeit with a higher rate of transient phrenic nerve palsies.

Recent studies have demonstrated a clear role for pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of gonadotropin biosynthesis and secretion, both alone and in conjunction with GnRH. First defined as a hypothalamic releasing factor, PACAP subsequently has been identified in the gonadotrope subpopulation of the anterior pituitary gland, suggesting that PACAP may act as an autocrine-paracrine factor in this tissue. In initial studies, we determined that GnRH markedly stimulated endogenous PACAP mRNA levels and promoter-reporter activity in the mature gonadotrope cell line, LbetaT2. GnRH-stimulated rat PACAP promoter activity was blunted with deletion from position -915 to -402 and eliminated with further truncation to position -77 relative to the transcriptional start site. Site-directed mutagenesis demonstrated a functional requirement for a cAMP response element (CRE)-like site at position -205 and an activating protein-1 (AP-1)-like site at position -275, both of which bound CRE binding protein and AP-1 family members on EMSA. Treatment with pharmacological activators or inhibitors of second messenger signaling pathways implicated the protein kinase A, protein kinase C, and MAPK pathways in the GnRH response. In support of these in vitro data, we demonstrate that JunB binds to the rat PACAP gene promoter by chromatin immunoprecipitation assay and that small interfering RNA knockdown of JunB, cFos, and CRE binding protein factors blunts PACAP expression. In summary, these results further elucidate the complex functional interactions between PACAP and GnRH in the anterior pituitary. Specifically, these studies demonstrate that GnRH-stimulated PACAP gene expression is mediated via multiple signaling pathways acting on CRE/AP-1 sites in the proximal gene promoter. Because both PACAP and GnRH regulate gonadotropin biosynthesis and secretion, these results provide important insight into the critical fine tuning of gonadotrope function and, thereby, the maintenance of normal reproductive function.

Introduction: Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP), and RVP for advanced AVB in patients with normal or mildly reduced EF. Methods and Results: MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, Scopus, and Web of Science were searched. Outcomes were all-cause death, heart failure hospitalizations (HFH), EF, left ventricular volumes, 6-minute walk test, and QRS duration. HBP or BiVP was compared with RVP. Subsequently, network metaanalysis compared the three pacing options. Our protocol was registered in PROSPERO (CRD42018094132). Six studies compared BiVP and RVP (704 vs 614 patients) and four compared HBP and RVP (463 vs 568 patients). Follow-up was 6 months to 5 years. There was significantly lower mortality and HFH with HBP or BiVP as compared with RVP (odds ratio [OR], 0.66, [0.51-0.85], P = .002; OR, 0.61 [0.45-0.82], P < .001, respectively]. HBP or BiVP also showed significant increase in EF and decrease in QRS duration (mean difference [MD], 5.27 [3.86-6.69], P < .001; MD −42.2 [−51.2 to −33.3], P < .001, respectively). In network meta-analysis, HBP and BiVP were associated with significantly improved survival compared to RVP,with surface under the cumulative ranking curve (SUCRA) probability of 79.4%, 69.4%, and 1.2% for HBP, BiVP, and RVP, respectively. For HFH, SUCRA probability was 91.5%, 57.2%, and 1.3%, respectively.

Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; p=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; p<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; p<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; p<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; p<0.001).