Faculty Bibliography

New evidence suggests that closure of a patent foramen ovale (PFO) plus medical therapy (MT; antiplatelet or anticoagulation) is superior to MT alone to prevent recurrent cryptogenic stroke. We performed a meta-analysis of randomized controlled trials that compared PFO closure plus MT with MT alone in patients with cryptogenic stroke. The efficacy end points were recurrent stroke, transient ischemia attack, and death. The safety end points were major bleeding and newly detected atrial fibrillation. Trials were pooled using random effects and fixed effects models. A trial sequential analysis was performed to assess if the current evidence is sufficient. Risk ratios (RR) were calculated for pooled estimates of risk. Five randomized controlled trials (3,440 patients) were included. Mean follow-up was 4.1 years. PFO closure reduced the risk of recurrent stroke by 58% (RR 0.42, 95% CI 0.20 to 0.91, p = 0.03). The number needed to treat was 38. The cumulative Z-line crossed the trial sequential boundary, suggesting there is adequate evidence to conclude that PFO closure reduces the risk of recurrent stroke by 60%. PFO closure did not reduce the risk of transient ischemia attack (RR 0.78, 95% CI 0.53 to 1.15, p = 0.21), mortality (RR 0.74, 95% CI 0.35 to 1.60, p = 0.45), or major bleeding (RR 0.96, 95% CI 0.42 to 2.20, p = 0.93); it did increase the risk of atrial fibrillation (RR 4.69, 95% CI 2.17 to 10.12, p <0.0001).

Recently, several randomized controlled trials (RCT) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) have compared a strategy of routine multivessel percutaneous coronary intervention (PCI) performed either as a single procedure or as staged procedures to culprit-only PCI. All of these trials have been underpowered for clinical end points. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCT comparing multivessel PCI with culprit-only PCI in patients with STEMI and MVD. The primary efficacy outcome was the composite rate of death or MI. Other efficacy outcomes included death, MI, and repeat revascularization. Safety outcomes were contrast-associated acute kidney injury, stroke, and major bleeding. Pairwise direct comparison and mixed-treatment comparison network meta-analyses were performed. Eleven trials that enrolled 3,150 patients with a total of 5,296 patient-years of follow-up were included. In direct comparison meta-analysis, single-procedure multivessel PCI was associated with a reduction in the risk of death or MI (rate ratio [RR] = 0.52; 95% confidence interval [CI] 0.37 to 0.73; p <0.001), due to less death (RR = 0.64; 95% CI 0.40 to 1.02; p = 0.06) and MI (RR = 0.42; 95% CI 0.25 to 0.69; p <0.0001) compared with culprit-only PCI. No heterogeneity (I2 = 0) was present between studies. In contrast, staged multivessel PCI did not significantly reduce death or MI compared with culprit-only PCI. Both multivessel PCI strategies reduced the risk of repeat revascularization without significant differences in safety outcomes. Results were consistent in the mixed-treatment comparison meta-analysis. In conclusion, the present meta-analysis suggests that single-procedure multivessel PCI may be the preferred strategy in patients with STEMI and MVD.

BACKGROUND:Device-related thrombus (DRT) after left atrial appendage occlusion is a worrisome finding with little knowledge about when to expect it and how to prevent it. This study sought to investigate correlates of DRT after left atrial appendage occlusion, its time of diagnosis, and particularly, association with postimplantation dual antiplatelet therapy duration. METHODS AND RESULTS/RESULTS:=0.77). CONCLUSIONS:In this real-world series, DRT was observed early, late, and very late after left atrial appendage occlusion. It was related to patient and procedural characteristics but not to postimplantation dual antiplatelet therapy duration.

BACKGROUND:Higher visit-to-visit variability in risk factors such as blood pressure and low-density lipoprotein (LDL)-cholesterol are associated with an increase in cardiovascular (CV) events. OBJECTIVE:The purpose of this study was to determine whether variability in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels predicted coronary and CV events in a clinical trial population with known coronary disease. METHODS:We assessed intraindividual variability in fasting high-density lipoprotein (HDL)-cholesterol, triglyceride, and LDL-cholesterol measurements among 9572 patients in the Treating to New Targets trial and correlated the results with coronary events over a median follow-up of 4.9 years. RESULTS:In the fully adjusted Cox model, 1 standard deviation of average successive variability, defined as the average absolute difference between successive values, was associated with an increased risk of a coronary event for HDL-cholesterol (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.11-1.21, P < .0001), for triglycerides (HR 1.09, 95% CI 1.04-1.15, P = .0005), and for LDL-cholesterol (HR 1.14, 95% CI 1.09-1.19, P < .0001). Similar results were found for the 3 other measures of variability, standard deviation, coefficient of variability, and variability independent of the mean. Similar results were seen for CV events, stroke, and nonfatal myocardial infarction. Higher variability in triglyceride and LDL-cholesterol, but not HDL-cholesterol, was predictive of incident diabetes. The correlation among the variability of the 3 lipid measurements was weak. CONCLUSION/CONCLUSIONS:Visit-to-visit variability in fasting measurements of HDL-cholesterol, triglycerides, and LDL-cholesterol are predictive of coronary events, CV events, and for triglyceride and low-density lipoprotein cholesterol variability, incident diabetes. The mechanisms accounting for these associations remain to be determined.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is typically performed under general anesthesia (GA). However, there is increasing data supporting the safety of performing TAVR under local anesthesia/conscious sedation (LA). We performed a meta-analysis to gain better understanding of the safety and efficacy of LA versus GA in patients with severe aortic stenosis undergoing TAVR. METHODS AND RESULTS: We comprehensively searched EMBASE, PubMed, and Web of Science. Effect sizes were summarized using risk ratios (RRs) difference of the mean (DM), and 95% CIs (confidence intervals) for dichotomous and continuous variables respectively. Twenty-six studies and 10,572 patients were included in the meta-analysis. The use of LA for TAVR was associated with lower overall 30-day mortality (RR, 0.73; 95% CI, 0.57-0.93; P = 0.01), use of inotropic/vasopressor drugs (RR, 0.45; 95% CI, 0.28-0.72; P < 0.001), hospital length of stay (LOS) (DM, -2.09; 95% CI, -3.02 to -1.16; P < 0.001), intensive care unit LOS (DM, -0.18; 95% CI, -0.31 to -0.04; P = 0.01), procedure time (DM, -25.02; 95% CI, -32.70 to -17.35; P < 0.001); and fluoroscopy time (DM, -1.63; 95% CI, -3.02 to -0.24; P = 0.02). No differences were observed between LA and GA for stroke, cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, acute kidney injury, paravalvular leak, vascular complications, major bleeding, procedural success, conduction abnormalities, and annular rupture. CONCLUSION: Our meta-analysis suggests that use of LA for TAVR is associated with a lower 30-day mortality, shorter procedure time, fluoroscopy time, ICU LOS, hospital length of stay, and reduced need for inotropic support.

OBJECTIVES: This study sought to examine long-term outcomes with transcatheter aortic valve replacement (TAVR) in women versus men. BACKGROUND: TAVR is commonly performed in women. Previous studies have shown conflicting results with respect to sex differences in outcomes with TAVR. In addition, short-term outcomes have primarily been reported. METHODS: Electronic search was performed until March 2017 for studies reporting outcomes with TAVR in women versus men. Random effects DerSimonian-Laird risk ratios were calculated. Outcomes included all-cause mortality and major cardiovascular events at short- (30 days) and long-term (>1 year) follow-up. RESULTS: Seventeen studies (8 TAVR registries; 47,188 patients; 49.4% women) were analyzed. Women were older but exhibited fewer comorbidities. At 30 days, women had more bleeding (p < 0.001), vascular complications (p < 0.001), and stroke/transient ischemic attack (p = 0.02), without difference in all-cause (p = 0.19) or cardiovascular mortality (p = 0.91) compared with men. However, female sex was associated with lower all-cause mortality at 1 year (risk ratio: 0.85; 95% confidence interval: 0.79 to 0.91; p < 0.001), and longest available follow-up (mean 3.28 +/- 1.04 years; risk ratio: 0.86; 95% confidence interval: 0.81 to 0.92; p < 0.001), potentially caused by less moderate/severe aortic insufficiency (p = 0.001), and lower cardiovascular mortality (p = 0.009). The female survival advantage remained consistent across multiple secondary analyses. The risk of stroke, moderate/severe aortic insufficiency, and all-cause mortality seemed to vary based on the type of valve used; however, without significant subgroup interactions. CONCLUSIONS: Despite a higher upfront risk of complications, women derive a better long-term survival after TAVR compared with men.