Citations

AbstractObjectiveIdentify patients undergoing transcatheter mitral valve repair (TMVR) who could potentially benefit from alternative ischemic stroke prophylaxis utilizing a left atrial appendage closure (LAAC) device.BackgroundPatients undergoing TMVR have a high incidence of atrial fibrillation (AF). The co‐morbidities which qualify them to undergo TMVR also increase their risk of stroke and bleeding, making stroke prophylaxis problematic.MethodsWe conducted a single‐center retrospective study, in which the bleeding and stroke risk of all patients undergoing TMVR for degenerative mitral valve disease were reviewed to determine candidacy for a LAAC device for stroke prevention as an alternative to chronic anticoagulation.ResultsAF was present in 122 (62%) of TMVR patients with an average CHA2DS2‐VASc score of 3.99. 23% of TMVR patients had a history of prior major bleeding event, predominately gastrointestinal bleed. Fifty‐three and 47% of TMVR patients were at high or intermediate risk of bleeding, respectively, according to their HAS‐BLED score. 50% of patients undergoing TMVR would qualify for LAAC device based on risk assessments.ConclusionPatients undergoing TMVR represent a high risk group of AF patients that may benefit from a LAAC device.

Background Different approaches to safety event collection influence the determination of liver toxicity within drug development programs. Herein, a description of how fasiglifam-induced liver injury was detected is provided. Methods This eight-trial drug development program was intended to evaluate fasiglifam (25 mg, 50 mg) against placebo or active comparators (glimepiride, sitagliptin) in approximately 11,000 suboptimally controlled patients with type 2 diabetes (terminated Dec 2013 due to liver toxicity). Liver safety had been pre-identified as a concern, and within the phase 3 trials, was measured through (1) adverse event reporting, (2) central predefined liver monitoring schedule with various thresholds for potential drug-induced liver injury, and (3) blinded adjudication of serious liver toxicity by a panel of experts in drug-induced liver injury. A single data monitoring committee provided safety oversight across all trials within the program. Findings Prior to program termination, 7595 of 7602 (99.9%) randomized participants across the eight trials received at least one dose of the study drug (fasiglifam, placebo, or active control). No concerning trends were noted in adverse or serious adverse event frequency, suspected unexpected serious adverse reaction, alanine or aspartate transaminase elevations, or hepatobiliary or gastrointestinal adverse events as reported by local site investigators. However, the predefined central liver safety measurements revealed a greater frequency of possible Hy’s Law cases (5 vs 2) and a 3- to 7-fold greater relative risk in alanine or aspartate transaminase elevation (with respect to upper limit of normal) within fasiglifam recipients compared with placebo/active control: alanine or aspartate transaminase > 3×: relative risk 3.34 (95% confidence interval 2.29–4.90), alanine or aspartate transaminase > 5×: relative risk 6.60 (95% confidence interval 3.03–14.38), alanine or aspartate transaminase > 8×: relative risk 6.14 (95% confidence interval 2.18–17.27), and alanine or aspartate transaminase > 10×: relative risk 6.74 (95% confidence interval 2.05, 22.14). All elevations resolved on study drug discontinuation. Drug-induced liver injury was adjudicated as highly likely or probably related in 0.64% of fasiglifam-treated versus 0.06% placebo or active control-treated patients. Conclusion In spite of clear liver toxicity detected with a systematic surveillance program, liver safety signals were not identified from investigator adverse event reporting alone. By integrating key safety monitoring processes within the randomized design of adequately sized clinical trials, the rare but serious liver toxicity signal became clear, leading to timely program termination.

Abstract Transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke is gaining momentum after the recent publication of four randomized clinical trials suggesting its benefit. This article provides a contemporary overview of the anatomy and pathophysiology of PFO, the available diagnostic tools for the assessment and risk stratification of PFO, and the current and future landscape of PFO closure devices and their optimal utilization. It also summarizes the current data on PFO closure for stroke prevention, and discusses the remaining open issues in the field of PFO closure.

AbstractFibrosing mediastinitis is a rare, often debilitating and potentially lethal disease characterized by an exuberant fibroinflammatory response within the mediastinum. Patients typically present with insidious symptoms related to compression of adjacent structures including the esophagus, heart, airways, and cardiac vessels. Fibrosing mediastinitis is most often triggered by Histoplasmosis infection; however, antifungal and anti‐inflammatory therapies are largely ineffective. While structural interventions aimed at alleviating obstruction can provide significant palliation, surgical interventions are challenging with high mortality and clinical experience with percutaneous interventions is limited. Here, we will review the presentation, natural history, and treatment of fibrosing mediastinitis, placing particular emphasis on catheter‐based therapies.

Objectives The objective was to assess the impact of procedural characteristics on risk of stroke or transient ischaemic attack (TIA) after transcatheter aortic valve replacement (TAVR). Methods We included 370 consecutive patients who underwent balloon-expandable TAVR from 1 November 2008 to 30 June 2014. Procedural characteristics that may be associated with stroke/TIA were assessed. The primary outcome was stroke/TIA at 30 days. A propensity score was constructed using a logistic regression model with 29 parameters. Cox proportional hazards models were used with a propensity score covariate. Results Mean age was 80.9±7.9 years and mean Society of Thoracic Surgeons score was 8.3±5.0. The total number of balloon dilations ranged from 2 to 7. Out of 370 patients, 13 patients (3.5%) suffered stroke/TIA in the first 30 days after TAVR. In univariate analysis, postdeployment balloon dilation (PD) (HR 3.8, 95% CI 1.24 to 11.61; p=0.02) and emergent cardiopulmonary bypass (CPB) (HR 9.66, 95% CI 2.66 to 35.15; p<0.001) were significantly associated with 30-day stroke/TIA. In the multivariable Cox-proportional hazards model, PD (HR 4.95, 95% CI 1.02 to 24.03; p=0.04) and emergent CPB (HR 7.15, 95% CI 1.39 to 36.89; p=0.02) were independently associated with increased risk of 30-day stroke/TIA after adjusting for propensity score, total number of balloon dilations and periprosthetic regurgitation. Conclusion Postdilation as compared with total number of dilations, and emergent CPB were independently associated with increased risk of clinical neurological events in the first 30 days after TAVR. Reduction in balloon postdilation with appropriate valve sizing may reduce the risk of stroke or TIA after TAVR.

The optimal antithrombotic treatment regimen for patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation represents a challenge in clinical practice. In 2016, an updated opinion of selected experts from the United States and Canada on the treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention was reported. After the 2016 North American consensus statement on the management of antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention, results of pivotal clinical trials assessing the type of oral anticoagulant agent and the duration of antiplatelet treatment have been published. On the basis of these results, this focused update on the antithrombotic management of patients with atrial fibrillation undergoing percutaneous coronary intervention recommends that a non–vitamin K antagonist oral anticoagulant be preferred over a vitamin K antagonist as the oral anticoagulant of choice. Moreover, a double-therapy regimen (oral anticoagulant plus single antiplatelet therapy with a P2Y 12 inhibitor) by the time of hospital discharge should be considered for most patients, whereas extending the use of aspirin beyond hospital discharge (ie, triple therapy) should be considered only for selected patients at high ischemic/thrombotic and low bleeding risks and for a limited period of time. The present document provides a focused updated on the rationale for the new expert consensus–derived recommendations on the antithrombotic management of patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention.