Background-Patients who receive implantable cardioverter defibrillator therapies are at higher risk of death versus those who do not. Programmed settings to reduce nonessential implantable cardioverter defibrillator therapies (therapy reduction programming) have been developed but may have adverse effects. This systematic review and meta-analysis assessed the relationship between therapy reduction programming with the risks of death from any cause, implantable cardioverter defibrillator shocks, and syncope. Methods and Results-MEDLINE, EMBASE, and clinicaltrials.gov databases were searched to identify relevant studies.Those that followed patients for ≥6 months and reported mortality were included. Most (77%) participants were men, had a history of ischemic heart disease (56%), and were prescribed β-blockers (84%). Therapy reduction programming was associated with a 30% relative reduction in mortality (95% confidence interval, 16%-41%; P<0.001). No significant heterogeneity among studies was observed (P=0.6). A similar 26% reduction in mortality was observed when only the 4 randomized trials were included (95% confidence interval, 11%-40%; P=0.002). These results were not significantly altered after adjustment for baseline characteristics. No significant difference in the risk of syncope was observed with conventional versus therapy reduction programming (P=0.5). Conclusions-Therapy reduction programming results in a large, significant, and consistent reduction in mortality, with no apparent increase in the risk of syncope. (Circ Arrhythm Electrophysiol. 2014;7:164-170.)

Rationale Nitrate-rich beetroot juice has been shown to improve exercise capacity in Heart Failure with Preserved Ejection Fraction (HFpEF), but studies using pharmacologic preparations of inorganic nitrate are lacking. Objectives To determine: (1) the dose-response effect of potassium nitrate (KNO3) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO3 in HFpEF. Methods and Results We randomized 12 subjects with HFpEF to oral KNO3 (n=9) or potassium chloride (KCl, n=3). Subjects received 6mmol twice-daily during Week-1, followed by 6mmol thrice-daily during Week-2. Supine cycle ergometry was performed at baseline (Visit 1) and after each week (Visits 2&3). Quality of life (QOL) was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ). The primary efficacy outcome, peak O2-uptake, did not significantly improve (P=0.13). Exploratory outcomes included exercise duration and quality of life. Exercise duration increased significantly with KNO3 (Visit 1: 9.87 [95%CI=9.31–10.43]; Visit 2: 10.73 [95%CI=10.13–11.33]; Visit 3: 11.61 [95%CI=11.05–12.17] minutes, P=0.002). Improvements in the KCCQ total symptom (Visit 1: 58.0 [95%CI=52.5–63.5], Visit 2: 66.8 [95%CI=61.3–72.3]; Visit 3: 70.8 [95%CI=65.3–76.3], P=0.016) and functional status scores (Visit 1: 62.2 [95%CI=58.5–66.0], Visit 2: 68.6 [95%CI=64.9–72.3], Visit 3: 71.1 [95%CI=67.3–74.8]; P=0.01) were seen after KNO3. Pronounced elevations in trough levels of nitric oxide metabolites (NOm) occurred with KNO3 (Visit 2: 199.5 [95%CI=98.7–300.2]; Visit 3: 471.8 [95%CI=377.8–565.8]) versus baseline (Visit 1: 38.0 [95%CI=0.00–132.0] μM; P<0.001). KNO3 did not lead to clinically-significant hypotension or methemoglobinemia. Following 6 mmol of KNO3, systolic blood pressure was reduced by a maximum of 17.9 (95%CI −28.3-[−7.6]) mmHg 3.75 hours later. Peak NOm concentrations were 259.3 (95%CI 176.2–342.4) μM 3.5 hours after ingestion, and the median half-life was 73.0 (IQR 33.4–232.0) minutes. Conclusions KNO3 is potentially well-tolerated and improves exercise duration and QOL in HFpEF. This study reinforces the efficacy of KNO3 and suggests that larger randomized trials are warranted. ClinicalTrials.gov NCT02256345; https://www.clinicaltrials.gov/ct2/show/NCT02256345

Background:The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study.Methods: Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular reentry tachycardia (AVRT), or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, postoperative pacing requirement, arrhythmic recurrence and 1-year all-cause mortality.Results: Among 2260 patients (mean age 45 ± 18 years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT, and AVNRT (p < .001). Periprocedural cardiac tamponade occurred in two AVRT patients. A total of 15 pacemakers (6 within first 30-days, 9 after 30days) were implanted (seven AV block, eight sinus node dysfunction [SND]), with the highest incidence of pacemaker implantation after AT-ablation (5% vs. 0.6% AVNRT vs. 0.1% AVRT, p < .001). Repeat ablations (0.9% AVNRT, 7% AVRT, 4% AT, p < .001) were performed in 78 (3.5%) patients and 13 (0.6%) patients died within a year of ablation. Among outcomes considered adjusting for age, sex, PSVT-type and proceduretime, AT was independently associated with 6-fold increased odds of total (adjusted odds ratio [AOR] 6.32, 95% confidence interval [CI] 1.95-20.53) and late (AOR 6.38, 95% CI 1.39-29.29) pacemaker implantation, while AVRT was associated with higher arrhythmic recurrence with repeat ablations (AOR 4.72, 95% CI 2.36-9.44) compared to AVNRT.Conclusions: Contemporary PSVT ablation is safe with high acute success rates. Longterm outcomes differed by nature of the PSVT.