Reversal of Right Ventricular Hypertrophy and Dysfunction by Prostacyclin in a Rat Model of Severe Pulmonary Arterial Hypertension.

Prostacyclin analogs are among the most effective and widely used therapies for pulmonary arterial hypertension (PAH). However, it is unknown whether they also confer protection through right ventricle (RV) myocardio-specific mechanisms. Moreover, the use of prostacyclin analogs in severe models of PAH has not been adequately tested. To further identify underlying responses to prostacyclin, a prostacyclin analogue, treprostinil, was used in a preclinical rat Sugen-chronic hypoxia (SuCH) model of severe PAH that closely resembles the human disease. Male Sprague-Dawley rats were implanted with osmotic pumps containing vehicle or treprostinil, injected concurrently with a bolus of Sugen (SU5416) and exposed to 3-week hypoxia followed by 3-week normoxia. RV function was assessed using pressure-volume loops and hypertrophy by weight assessed. To identify altered mechanisms within the RV, tissue samples were used to perform a custom RNA array analysis, histological staining, and protein and transcript level confirmatory analyses. Treprostinil significantly reduced SuCH-associated RV hypertrophy and decreased the rise in RV systolic pressure, mean pulmonary arterial (mPAP), and right atrial (RAP) pressure. Prostacyclin treatment was associated with improvements in RV stroke work, maximum rate of ventricular pressure change (max dP/dt) and the contractile index, and almost a complete reversal of SuCH-associated increase in RV end-systolic elastance, suggesting the involvement of load-independent improvements in intrinsic RV systolic contractility by prostacyclin treatment. An analysis of the RV tissues showed no changes in cardiac mitochondrial respiration and ATP generation. However, custom RNA array analysis revealed amelioration of SuCH-associated increases in newly identified TBX20 as well as the fibrotic markers collagen1α1 and collagen 3α1 upon treprostinil treatment. Taken together, our data support decreased afterload and load-independent improvements in RV function following prostacyclin administration in severe PAH, and these changes appear to associate with improvements in RV fibrotic responses.

Yes-Associated Protein (Yap) Is Up-Regulated in Heart Failure and Promotes Cardiac Fibroblast Proliferation.

Left ventricular (LV) heart failure (HF) is a significant and increasing cause of death worldwide. HF is characterized by myocardial remodeling and excessive fibrosis. Transcriptional co-activator Yes-associated protein (Yap), the downstream effector of HIPPO signaling pathway, is an essential factor in cardiomyocyte survival; however, its status in human LV HF is not entirely elucidated. Here, we report that Yap is elevated in LV tissue of patients with HF, and is associated with down-regulation of its upstream inhibitor HIPPO component large tumor suppressor 1 (LATS1) activation as well as upregulation of the fibrosis marker connective tissue growth factor (CTGF). Applying the established profibrotic combined stress of TGFß and hypoxia to human ventricular cardiac fibroblasts in vitro increased Yap protein levels, down-regulated LATS1 activation, increased cell proliferation and collagen I production, and decreased ribosomal protein S6 and S6 kinase phosphorylation, a hallmark of mTOR activation, without any significant effect on mTOR and raptor protein expression or phosphorylation of mTOR or 4E-binding protein 1 (4EBP1), a downstream effector of mTOR pathway. As previously reported in various cell types, TGFß/hypoxia also enhanced cardiac fibroblast Akt and ERK1/2 phosphorylation, which was similar to our observation in LV tissues from HF patients. Further, depletion of Yap reduced TGFß/hypoxia-induced cardiac fibroblast proliferation and Akt phosphorylation at Ser 473 and Thr308, without any significant effect on TGFß/hypoxia-induced ERK1/2 activation or reduction in S6 and S6 kinase activities. Taken together, these data demonstrate that Yap is a mediator that promotes human cardiac fibroblast proliferation and suggest its possible contribution to remodeling of the LV, opening the door to further studies to decipher the cell-specific roles of Yap signaling in human HF.

Identifying the most important ECG predictors of reduced ejection fraction in patients with suspected acute coronary syndrome.

BACKGROUND: Non-invasive screening tools of cardiac function can play a significant role in the initial triage of patients with suspected acute coronary syndrome. Numerous ECG features have been previously linked with cardiac contractility in the general population. We sought to identify ECG features that are most predictive for real-time screening of reduced left ventricular ejection fraction (LVEF) in the acute care setting. METHODS: We performed a secondary analysis of a prospective, observational cohort study of patients evaluated for suspected acute coronary syndrome. We included consecutive patients in whom an echocardiogram was performed during indexed encounter. We evaluated 554 automated 12-lead ECG features in multivariate linear regression for predicting LVEF. We then used regression trees to identify the most important predictive ECG features. RESULTS: Our final sample included 297 patients (aged 63 ± 15, 45% females). The mean LVEF was 57% ± 13 (IQR 50%-65%). In multivariate analysis, depolarization dispersion in the horizontal plane; global repolarization dispersion; and abnormal temporal indices in inferolateral leads were all independent predictors of LVEF (R2 = 0.452, F = 6.679, p < 0.001). Horizontal QRS axis deviation and prolonged ventricular activation time in left ventricular apex were the most important determinants of reduced LVEF, while global QRS duration was of less importance. CONCLUSIONS: Poor R wave progression in precordial leads with dominant QS pattern in V3 is the most predictive feature of reduced LVEF in suspected ACS. This feature constitutes a simple visual marker to aid clinicians in identifying those with impaired cardiac function.

The role of heart rate variability, heart rate turbulence, and deceleration capacity in predicting cause-specific mortality in chronic heart failure.

BACKGROUND: The volume of regional denervated myocardium (D-M) on positron emission tomography has been recently suggested as a strong independent predictor of cause-specific mortality from sudden cardiac arrest (SCA) in chronic heart failure. We sought to evaluate whether ECG indices of global autonomic function predict risk of SCA to a similar degree as regional D-M. METHODS: Subjects enrolled in the Prediction of Arrhythmic Events using Positron Emission Tomography (PAREPET) study were included in this study. Patients completed a 24-hour Holter ECG at enrollment and were followed up at 3-month intervals. SCA events were adjudicated by two board-certified cardiologists. Other cardiovascular death events were classified as nonsudden cardiac death (NSCD). Eight measures of heart rate variability were analyzed: SDNN, RMSSD, low-frequency (LF) and high-frequency (HF) power, heart rate turbulence onset and slope, and acceleration and deceleration capacity. We used competing risk regression to delineate cause-specific mortality from SCA versus NSCD. RESULTS: Our sample included 127 patients (age 67 ±â€¯12, 92% male). After a median follow-up of 4.1 years, there were 22 (17%) adjudicated SCA and 18 (14%) adjudicated NSCD events. In multivariate Cox-regression, LF power was the only HRV parameter to predict time-to-SCA. However, in competing risk analysis, reduced LF power was preferentially associated with NSCD rather than SCA (HR = 0.92 [0.85-0.98], p = 0.019). CONCLUSION: Depressed LF power might indicate impaired vagal reflex, which suggests that increasing vagal tone in these patients would have a protective effect against NSCD beyond that achieved by the mere slowing of heart rate using ß-blockers.

Seismic Performance and Cost Analysis of UHPC Tall Buildings in UAE with Ductile Coupled Shear Walls.

The superior mechanical characteristics of ultra-high-performance concrete (UHPC) have attracted the interest of many researchers worldwide. Researchers have attempted to perform comparative analyses on the behavior of UHPC versus conventional and high-strength concrete, with their aim being to gain more insights into the difference between different types of concrete. However, the current state-of-the-art revealed no direct comprehensive comparisons between their behaviors in ductile coupled shear walls under seismic loading. This paper explores a comprehensive side-by-side comparison in terms of seismic behavior and cost analysis for four 60-story archetype buildings. The reference building was designed using high-strength concrete with a strength of 60 MPa. The other three archetype variations incorporated three different UHPC grades: 150 MPa, 185 MPa, and 220 MPa. The plan configuration and the lateral force-resisting system (LFRS) were chosen according to the most common practice in the UAE. The main objective is to report the effect of UHPC on the LFRS (ductile coupled shear walls). Moreover, a simplified initial cost analysis (materials and labor) design was performed. The findings of this paper indicate that the use of UHPC is capable of improving the seismic performance behavior of the lateral system as well as reducing the total initial costs.

Strength curve data for slender geopolymer concrete columns with GFRP, steel and hybrid reinforcement.

This article provides a wide range of circular columns strength values under different loading conditions. The provided strength values are dependent on various parameters including the longitudinal and transverse reinforcement ratios. Results for GFRP, steel and hybrid reinforcement configurations are provided. The results were collected from analysis output files of more than 60,000 columns, and tabulated in a form that is suitable for generating analytical strength curves. The provided data format allows the generation of strength curves for a wide range of slenderness ratios and the applied load eccentricities. Inspecting the analytical strength curves could provide insights on the slenderness limits for maintaining specific strength thresholds. Also, further investigations of data could provide a group of recommendations to avoid longitudinal and transverse reinforcement underutilization. Additional data processing could provide axial load-bending moment interaction diagrams for different columns` configurations taking into consideration the slenderness effects. The use of interaction diagrams in inspecting slender columns behavior is a ubiquitous subject that has been utilized in many recent research papers. Moreover, the results of a sensitivity analysis are provided within the article.

Experimental quantification of punching shear capacity for large-scale GFRP-reinforced flat slabs made of synthetic fiber-reinforced self-compacting concrete dataset.

This article provides experimental data on the punching shear behavior of synthetic fiber-reinforced slabs reinforced with glass fiber reinforced polymer (GFRP) bars and cast from self-consolidating concrete (SCC). The data was collected from tests performed on six full-scale specimens centrically loaded until failure as indicated by penetration of the column stub into the slab and achieving a sharp drop in the load carrying capacity. Three different reinforcement bar spacings were used to consider the effect of reinforcement ratio on punching shear resistance. Three of the specimens tested were reinforced by 1.25% of volume of synthetic fiber, and three were control specimens cast from regular SCC. Applied load, central deflections, and bar strain were monitored during the experiment and are provided in the supplementary data. Any future models for analyzing the punching shear behavior and capacity of flat slabs reinforced with GFRP rebars will find this data valuable for model validation, and for establishing suitable safety factors for design. Numerical studies on the simulation of fiber-reinforced concrete would also find value in this data to validate the numerical model and enable it to be used for further studies.

Seismic risk quantification and GIS-based seismic risk maps for Dubai-UAE_Dataset.

The data provided in this article quantifies the potential seismic losses in multi-story buildings located in Dubai, UAE. Besides, it developed GIS-based seismic risk maps, which form essential inputs towards the seismic resilience of buildings. The GIS data described herein come from different sources. The base map including the major roads, key land use classes, and administrative boundaries are from the ArcMap maps library. The Dubai districts were digitized in ArcMap from a rectified Worldview imagery of Dubai. The seismic risk analysis data are represented as attributes of the centroids of Dubai districts, which is the main data layer. The GIS-based seismic risk maps are raster GIS layers, which are created in ArcGIS using the Inverse Distance Weighted (IDW) interpolation method. The base map template is from the ArcMap maps library.

Up-to-date earthquake and focal mechanism solutions datasets for the assessment of seismic hazard in the vicinity of the United Arab Emirates.

This article presents updated and unified Poissonian earthquake and focal mechanism catalogs for the United Arab Emirates and its surroundings. Data were compiled from different local, regional, and international sources. Several magnitude-conversion relationships have been applied to obtain the unified moment magnitude estimates for the final datasets. Dependent earthquakes were identified and removed from the compiled data via a declustering process to ensure a time independent Poissonian distribution of seismicity. The final compiled earthquake catalog is comprised of 1464 mainshocks, which span the time period of 658-2019 [1]. The range of their spatial region is 21°-31°N on the latitude and 47° to 66°E on the longitude. Additionally, an overall number of 583 focal mechanism solutions spanning the time period of 1923-2015 were acquired [1]. Such datasets are compatible with other published catalogs from across the globe which provide a basis for the estimation of seismic hazard and risk, as well as, the establishment of a unified seismic action representation in the building codes for the United Arab Emirates. This paper and its dataset are a companion for a published article in the Journal of Asian Earth Sciences under the title "A State-Of-The-Art Seismic Source Model for the United Arab Emirates" [2].

A Novel Non-Invasive Assessment of Cardiac Hemodynamics in Patients With Heart Failure and Atrial Fibrillation.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) often coexist. The hemodynamic alterations induced by AF in patients with HF are well studied; however we lack reliable and non-invasive means to study these hemodynamic alterations in ambulatory patients. We sought to evaluate the clinical utility of impedance cardiography (ICG) as a novel and non-invasive tool to evaluate cardiac hemodynamics in ambulatory patients with HF and AF. METHODS: This was a single-center observational study. A convenient sample of ambulatory patients with chronic HF underwent non-invasive electrocardiogram (ECG) and hemodynamic monitoring using BioZ Dx impedance cardiographer. Hemodynamics were automatically computed and ECG data were interpreted by an independent reviewer. RESULTS: A total of 32 patients (62 ± 14 years of age; 66% male; ejection fraction 33±13%) were enrolled. There were no baseline demographic or clinical differences between those with AF (28%) and those without AF (72%). However, patients with AF exhibited lower stroke volume (60 ± 7 vs. 89 ± 29, P = 0.008), left ventricular work (33 ± 9 vs. 45 ± 13, P = 0.016), cardiac contractility (30 ± 8 vs. 40 ± 13, P = 0.037), and arterial elasticity (13 ± 5 vs. 21 ± 5, P = 0.012), as well as higher cardiac afterload (203 ± 57 vs. 151 ± 49, P = 0.015). CONCLUSIONS: Using non-invasive ICG, we have shown that it is feasible to characterize hemodynamics in ambulatory HF patients. We show that AF compromises left ventricular function in patients with HF and is associated with excess afterload and reduced arterial elasticity.

Nonspecific electrocardiographic abnormalities are associated with increased length of stay and adverse cardiac outcomes in prehospital chest pain.

BACKGROUND: Nonspecific ST-T repolarization (NST) abnormalities alter the ST-segment for reasons often unrelated to acute myocardial ischemia, which could contribute to misdiagnosis or inappropriate treatment. We sought to define the prevalence of NST patterns in patients with chest pain and evaluate how such patterns correlate with the eventual etiology of chest pain and course of hospitalization. METHODS: This was a prospective observational study that included consecutive prehospital chest pain patients from three tertiary care hospitals in the U.S. Two independent reviewers blinded from clinical data audited the prehospital 12-lead ECG for the presence or absence of NST patterns (i.e., right or left bundle branch block, left ventricular hypertrophy with strain pattern, ventricular pacing, ventricular rhythm, or coarse atrial fibrillation). The primary outcome was 30-day major adverse cardiac events (MACE) defined as cardiac arrest, acute heart failure, post-discharge infarction, or all-cause death. RESULTS: The final sample included 750 patients (age 59 ± 17, 58% males). A total of 40 patients (5.3%) experienced 30-MACE and 131 (17.5%) had NST patterns. The presence of NST patterns was an independent multivariate predictor of 30-day MACE (9.9% vs. 4.4%, OR = 2.2 [95% CI = 1.1-4.5]. Patients with NST patterns had increased median length of stay (1.0 [IQR 0.5-3] vs. 2.0 [IQR 1-4] days, p < 0.05) independent of the etiology of chest pain. CONCLUSIONS: One in six prehospital ECGs of patients with chest pain has NST patterns. This pattern is associated with increased length of stay and adverse cardiac outcomes, suggesting the need of preventive measures and close follow up in such patients.