Endothelin is a potent vasoconstrictor substance that also can exert proliferative, inflammatory, and fibrotic changes in blood vessels and other organs. It acts on tissues in a paracrine and autocrine fashion, with local production and regulation occurring in both endothelial and nonendothelial cells. Endothelin stimulation of ETA and ETB receptors results in different and often opposing effects, which under physiologic conditions, establishes a balance that contributes to the regulation of vascular tone and blood pressure. Dysregulation of the endothelin system can induce or mediate endothelial dysfunction and organ damage in systemic hypertension (HTN), effects which may be ameliorated by endothelin antagonists. Endothelin receptor antagonists are currently being used in the treatment of pulmonary HTN. Both selective and dual-acting endothelin receptor blockers can also reduce systemic blood pressure in animal models and in hypertensive patients. Clinical trials evaluating the efficacy and safety of these agents are underway, and show potential as a new class of antihypertensives. Studies are also in progress with a single moiety dual angiotensin-endothelin A receptor antagonist, which is being evaluated in HTN. Issues that need to be addressed include the net contribution of endothelin in the pathophysiology of HTN, its interaction with other neurohormonal systems such as the renin-angiotensin-aldosterone system, and the clinical demonstration of the effect of endothelin receptor antagonism on end-organ damage in hypertensive patients.

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Background: National registries have provided data on in-hospital outcomes for several cardiac procedures. The available data on in-hospital outcomes and its predictors after pericardiocentesis are mostly derived from single center studies.Furthermore, the outcomes after pericardiocentesis for iatrogenic pericardial effusion and the impact of procedural volume on in-hospital outcomes in the United States are largely unknown.Methods: We used national inpatient database files for the years 2009-2013 to estimate the inpatient outcomes after pericardiocentesis in all-comers and in the subgroups with iatrogenic effusion. We also studied the impact of hospital procedural volume, among other predictors, on inpatient mortality.Results: About 64,070 (95%CI 61 008-67 051) pericardiocentesis were performed in the United States during 2009-2013. Of these, 57.15% (56.02-58.26%) of the pericardiocentesis were in hemodynamically unstable patients. Percutaneous cardiac procedures were performed in 17.7% of patients (percutaneous coronary intervention (PCI) 4.02%, electrophysiologic procedures 13.58%, and structural heart intervention (SHI) 0.76%). Overall inpatient mortality was 12.30% (95%CI 11.66-12.96%). Inpatient mortality after PCI, electrophysiologic procedures, SHI and cardiac surgery were 27.67% (95%CI 24-31.67%), 7.8% (95%CI 6.67-9.31%), 22.36% (95%CI 15.06-31.85%) and 18.97% (95%CI 15.84-22.57%), respectively. There was an inverse association between hospital procedural volume and inpatient mortality, with a mortality of 14.01% (12.84-15.26%) at the lowest and 10.82% (9.44-12.37%) at highest quartile hospitals by procedure volume (p trend = 0.001). Conclusion:The inpatient mortality after pericardiocentesis is high, particularly when associated with PCI and SHI. K E Y W O R D S iatrogenic effusion, inpatient mortality, pericardiocentesis 1 | BACKGROUND Pericardiocentesis, the percutaneous drainage of the pericardial sac, is a procedure performed in contemporary cardiovascular practice in both the elective and emergent setting. A timely pericardiocentesis can be lifesaving in tamponade; else, a pericardiocentesis is done for large effusions for diagnostic and therapeutic reasons. The current European Society of Cardiology guidelines gives pericardiocentesis a J Interv Cardiol. 2018;31:815-825.wileyonlinelibrary.com/journal/joic

Rab GTPases are essential for vesicular transport. Rab GDP dissociation inhibitor (GDI) binds to GDP-bound rabs, removes rabs from acceptor membranes and delivers rabs to donor membranes. We isolated lethal GDI mutations in Drosophila and analyzed their developmental phenotypes. To learn how these mutations affect GDI structure, the crystal structure of Drosophila GDI was determined by molecular replacement to a resolution of 3.0 A. Two hypomorphic, missense mutations are located in domain II of GDI at highly conserved positions, but not in previously identified sequence conserved regions. The mutant GDIs were tested for ability to extract rabs from membranes and showed wild-type levels of rab membrane extraction. The two missense alleles showed intragenic complementation, indicating that domain II of GDI may have two separable functions. This study indicates that GDI function is essential for development of a complex, multicellular organism and that puparium formation and pole cell formation are especially dependent on GDI function.

The presence of LISA at a follow up of 6-18 months after stent implantation is associated with a higher risk of late/very late ST and MI. Additional studies are required to establish a cause and effect, and inform the management strategy. © 2017 Wiley Periodicals, Inc.

Inadvertent lead misplacement in the left ventricle can lead to thromboembolic events, valvular damage, and endocarditis. We present a case of an inadvertently placed transarterial pacemaker lead in the left ventricle in a patient who underwent percutaneous lead removal. After a multidisciplinary team discussion involving cardiac electrophysiology and interventional cardiology as well as a discussion of treatment options with the patient, it was decided to proceed with pacemaker lead removal with the Sentinel™ Cerebral Protection System (Boston Scientific, Marlborough, MA, USA) to prevent thromboembolic events. The patient tolerated the procedure well without post-procedural complications and was discharged the next day on oral anticoagulation. We also present a step-by-step approach to perform lead removal with the use of Sentinel™, emphasizing mitigating the stroke and bleeding risks in this patient setting.

Objective To examine the clinical outcomes with catheter-directed thrombolysis (CDT) vs. catheter-directed embolectomy (CDE) for high-risk pulmonary embolism (PE). Background Comparative data on the short-term outcomes for CDE vs. CDT among patients with high-risk PE are scarce. Methods The Nationwide Readmissions Database was utilized to identify hospitalizations with high-risk PE undergoing CDE or CDT from 2016 to 2019. The main outcome of interest was all-cause in-hospital mortality. Propensity score matching was used to compare the outcomes in both groups. Results Among 3,216 high-risk PE hospitalizations undergoing catheter-directed interventions, 868 (27%) received CDE, 1,864 (58%) received CDT and 484 (15%) received both procedures. In the unadjusted analysis, the rate of all-cause in-hospital mortality was not between both CDE and CDT (39.6% vs. 34.2%, P = 0.07). After propensity score matching, CDE was not associated with higher mortality (adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 0.95, 1.72, P = 0.10), intracranial hemorrhage (ICH) (adjusted OR 1.57, 95% CI 0.75, 3.29, P = 0.23) or non-ICH bleeding (adjusted OR 1.17, 95% CI 0.85, 1.62, P = 0.33). There were no differences in the length of stay, cost and 30-day unplanned readmissions between both groups. Conclusions In this contemporary observational analysis of patients admitted with high-risk PE undergoing CDT or CDE, the rates of in-hospital mortality, ICH and non-ICH bleeding events were not different.

Background: Mitral regurgitation (MR) is commonly encountered in patients with severe aortic stenosis (AS). However, its independent impact on mortality in patients undergoing transcatheter aortic valve implantation (TAVI) has not been established. Methods: We performed a systematic search for studies reporting characteristics and outcome of patients with and without significant MR and/or adjusted mortality associated with MR post-TAVI. We conducted a meta-analysis of quantitative data. Results: Seventeen studies with 20,717 patients compared outcomes and group characteristics. Twenty-one studies with 32,257 patients reported adjusted odds of mortality associated with MR. Patients with MR were older, had a higher Society of Thoracic Surgeons score, lower left ventricular ejection fraction, a higher incidence of prior myocardial infarction, atrial fibrillation, and a trend towards higher NYHA class III/IV, but had similar mean gradient, gender, and chronic kidney disease. The MR patients had a higher unadjusted short-term (RR =