The spatial ventricular gradient is associated with adverse outcomes in acute pulmonary embolism.

BACKGROUND: The spatial ventricular gradient (SVG) is a vectorcardiographic measurement that reflects cardiac loading conditions via electromechanical coupling. OBJECTIVES: We hypothesized that the SVG is correlated with right ventricular (RV) strain and is prognostic of adverse events in patients with acute pulmonary embolism (PE). METHODS: Retrospective, single-center study of patients with acute PE. Electrocardiogram (ECG), imaging, and outcome data were obtained. SVG components were regressed on tricuspid annular plane systolic excursion (TAPSE), qualitative RV dysfunction, and RV/left ventricular (LV) ratio. Odds of adverse outcomes (30-day mortality, vasopressor requirement, or advanced therapy) after PE were regressed on demographics, RV/LV ratios, traditional ECG signs of RV dysfunction, and SVG components using a logit model. RESULTS: ECGs from 317 patients (48% male, age 63.1 ± 16.6 years) with acute PE were analyzed; 36 patients (11.4%) experienced an adverse event. Worse RV hypokinesis, larger RV/LV ratio, and smaller TAPSE were associated with smaller SVG X and Y components, larger SVG Z components, and smaller SVG vector magnitude (p < .001 for all). In multivariable logistic regression, odds of adverse events after PE decreased with increasing SVG magnitude and TAPSE (OR 0.32 and 0.54 per standard deviation increase; p = .03 and p = .004, respectively). Receiver operating characteristic (ROC) analysis showed that, when combined with imaging, replacing traditional ECG criteria with the SVG significantly improved the area under the ROC from 0.70 to 0.77 (p = .01). CONCLUSION: The SVG is correlated with RV dysfunction and adverse outcomes in acute PE and has a better prognostic value than traditional ECG markers.

Ventricular Flutter and Pleomorphic Ventricular Tachycardia-Induced Syncope in Borderline Arrhythmogenic Right Ventricular Cardiomyopathy.

A 20-year-old female competitive collegiate swimmer presented after 2 postexercise syncopal episodes and 1 episode while actively swimming. Ambulatory monitoring and exercise testing revealed nonsustained ventricular tachycardia. Electroanatomic mapping demonstrated multifocal premature ventricular contractions and ventricular flutter originating from the right ventricular outflow tract, consistent with borderline arrhythmogenic right ventricular cardiomyopathy. (Level of Difficulty: Intermediate.).

Changes in Care for Acute Pulmonary Embolism Through A Multidisciplinary Pulmonary Embolism Response Team.

BACKGROUND: Optimal management of acute pulmonary embolism requires expertise offered by multiple subspecialties. As such, pulmonary embolism response teams (PERTs) have increased in prevalence, but the institutional consequences of a PERT are unclear. METHODS: We compared all patients that presented to our institution with an acute pulmonary embolism in the 3 years prior to and 3 years after the formation of our PERT. The primary outcome was in-hospital pulmonary embolism-related mortality before and after the formation of the PERT. Sub-analyses were performed among patients with elevated-risk pulmonary embolism. RESULTS: Between August 2012 and August 2018, 2042 patients were hospitalized at our institution with acute pulmonary embolism, 884 (41.3%) pre-PERT implementation and 1158 (56.7%) post-PERT implementation, of which 165 (14.2%) were evaluated by the PERT. There was no difference in pulmonary embolism-related mortality between the two time periods (2.6% pre-PERT implementation vs 2.9% post-PERT implementation, P = .89). There was increased risk stratification assessment by measurement of cardiac biomarkers and echocardiograms post-PERT implementation. Overall utilization of advanced therapy was similar between groups (5.4% pre-PERT implementation vs 5.4% post-PERT implementation, P = 1.0), with decreased use of systemic thrombolysis (3.8% pre-PERT implementation vs 2.1% post-PERT implementation, P = 0.02) and increased catheter-directed therapy (1.3% pre-PERT implementation vs 3.3% post-PERT implementation, P = 0.05) post-PERT implementation. Inferior vena cava filter use decreased after PERT implementation (10.7% pre-PERT implementation vs 6.9% post-PERT implementation, P = 0.002). Findings were similar when analyzing elevated-risk patients. CONCLUSION: Pulmonary embolism response teams may increase risk stratification assessment and alter application of advanced therapies, but a mortality benefit was not identified.

Structural and mechanistic basis of zinc regulation across the E. coli Zur regulon.

Commensal microbes, whether they are beneficial or pathogenic, are sensitive to host processes that starve or swamp the prokaryote with large fluctuations in local zinc concentration. To understand how microorganisms coordinate a dynamic response to changes in zinc availability at the molecular level, we evaluated the molecular mechanism of the zinc-sensing zinc uptake regulator (Zur) protein at each of the known Zur-regulated genes in Escherichia coli. We solved the structure of zinc-loaded Zur bound to the P(znuABC) promoter and show that this metalloregulatory protein represses gene expression by a highly cooperative binding of two adjacent dimers to essentially encircle the core element of each of the Zur-regulated promoters. Cooperativity in these protein-DNA interactions requires a pair of asymmetric salt bridges between Arg52 and Asp49' that connect otherwise independent dimers. Analysis of the protein-DNA interface led to the discovery of a new member of the Zur-regulon: pliG. We demonstrate this gene is directly regulated by Zur in a zinc responsive manner. The pliG promoter forms stable complexes with either one or two Zur dimers with significantly less protein-DNA cooperativity than observed at other Zur regulon promoters. Comparison of the in vitro Zur-DNA binding affinity at each of four Zur-regulon promoters reveals ca. 10,000-fold variation Zur-DNA binding constants. The degree of Zur repression observed in vivo by comparison of transcript copy number in wild-type and Δzur strains parallels this trend spanning a 100-fold difference. We conclude that the number of ferric uptake regulator (Fur)-family dimers that bind within any given promoter varies significantly and that the thermodynamic profile of the Zur-DNA interactions directly correlates with the physiological response at different promoters.