Combined Spectroscopic and Computational Investigation on the Oxidation of exo-Tetrahydrodicyclopentadiene (JP-10; C10H16) Doped with Titanium-Aluminum-Boron Reactive Metal Nanopowder.

We report the results on the combustion of single, levitated droplets of exo-tetrahydrodicyclopentadiene (JP-10) doped with titanium-aluminum-boron (Ti-Al-B) reactive metal nanopowders (RMNPs) in an oxygen (60%)-argon (40%) atmosphere by exploiting an ultrasonic levitator with droplets ignited by a carbon dioxide laser. Ultraviolet-visible (UV-vis) emission spectroscopy revealed the presence of gas-phase aluminum (Al) and titanium (Ti) atoms. These atoms can be oxidized in the gas phase by molecular oxygen to form spectroscopically detected aluminum monoxide (AlO) and titanium monoxide (TiO) transients. Analysis of the optical ignition videos supports that the nanoparticles are ignited before JP-10. The detection of boron monoxide (BO) further proposes an active surface chemistry through the oxidation of the RMNPs and the release of at least BO into the gas phase. The oxidation of gas-phase BO by molecular oxygen to boron dioxide (BO2) plus atomic oxygen might operate in the gas phase, although the involvement of surface oxidation processes of RMNPs to BO2 cannot be discounted. The UV-vis emission spectra also revealed the key reactive intermediates (OH, CH, C2, and HCO) of the oxidation of JP-10. Electronic structure calculations reveal that the presence of reactive radicals has a profound impact on the oxidation of JP-10. Although titanium monoxide (TiO) reacts to produce titanium dioxide (TiO2), it does not engage in an active JP-10 chemistry as all abstraction pathways are endoergic by more than 217 kJ mol-1. This is similar for atomic aluminum and titanium, whose hydrogen abstraction reactions from JP-10 were revealed to be endoergic by at least 77 kJ mol-1. Therefore, aluminum and titanium react preferentially with molecular oxygen to produce their monoxides. However, the formation of BO, AlO, and BO2 supplies a pool of highly reactive radicals, which can abstract hydrogen from JP-10 via transition states ranging from only 1 to 5 kJ mol-1 above the separated reactants, forming JP-10 radicals along with the hydrogen abstraction products (boron hydride oxide, aluminum monohydroxide, and metaboric acid) in the overall exoergic reactions. These abstraction barriers are well below the barriers of abstractions for ground-state atomic oxygen and molecular oxygen. In this sense, gas-phase BO, AlO, and BO2 catalyze the oxidation of gas-phase JP-10 via hydrogen abstraction, forming highly reactive JP-10 radicals. Overall, the addition of RMNPs to JP-10 not only provides a higher energy density fuel but is also expected to lead to shorter ignition delays compared to pure JP-10 due to the highly reactive pool of radicals (BO, AlO, and BO2) formed in the initial stage of the oxidation process.

Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.

AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Impact of renin-angiotensin system inhibitors on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: an analysis of from the PARTNER 2 trial and registries.

AIMS: Left ventricular pressure overload is associated with activation of the cardiac renin-angiotensin system, which may contribute to myocardial fibrosis and worse clinical outcomes. We sought to assess the association between treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) at baseline and clinical outcomes in patients with symptomatic, severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) in the PARTNER 2 trial and registries. METHODS AND RESULTS: A total of 3979 intermediate, high, or prohibitive risk patients who underwent TAVR in the PARTNER 2 trial and registries (excluding the valve in valve registry) were included in the study. Clinical outcomes at 2 years were compared according to baseline ACEI/ARB treatment status using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models. Sensitivity analysis was conducted using propensity score matching. Of 3979 patients who were included in the current analysis, 1736 (43.6%) were treated and 2243 (56.4%) were not treated with ACEI/ARB at baseline. Treatment with ACEI/ARB was associated with lower 2-year all-cause mortality (18.6% vs. 27.5%, P < 0.0001), cardiovascular mortality (12.3% vs. 17.9%, P < 0.0001), and non-cardiovascular mortality (7.2% vs. 11.7%, P < 0.0001). Angiotensin-converting enzyme inhibitor/ARB treatment at baseline remained independently associated with a lower hazard of 2-year all-cause and cardiovascular mortality after multivariable adjustment, and propensity score matching. CONCLUSION: In a large cohort of patients with severe symptomatic AS from the PARTNER 2 trial and registries, ACEI/ARB treatment at baseline was independently associated with a lower risk of 2-year all-cause and cardiovascular mortality.

Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry.

AIMS: B-type natriuretic peptide (BNP) is a cardiac neurohormone that is secreted in response to ventricular volume expansion and pressure overload. There are conflicting data regarding the association between BNP levels and outcomes after transcatheter aortic valve replacement (TAVR). We therefore sought to assess the association between baseline BNP and adverse outcomes in patients with symptomatic, severe aortic stenosis (AS), and left ventricular ejection fraction (LVEF) ≥50%, undergoing TAVR in the PARTNER 2 Trial and Registry. METHODS AND RESULTS: A total of 1782 patients were included in the analysis, and BNP was evaluated both as a continuous log-transformed value and by a priori categories: low (<50 pg/mL), normal (≥50 and <100 pg/mL), moderately elevated (≥100 and <400 pg/mL), or markedly elevated (≥400 pg/mL). Clinical outcomes from discharge to 2 years were compared between patients according to their baseline BNP level, using Kaplan-Meier event rates and multivariable Cox proportional hazards regression models. After adjustment, spline curves revealed a non-linear association between log-transformed BNP and all-cause and cardiovascular mortality in which both the lowest and highest values were associated with increased mortality. Two-year all-cause mortality rates for those with low (n = 86), normal (n = 202), moderately elevated (n = 885), and markedly elevated (n = 609) baseline BNP were 20.0%, 9.8%, 17.7%, and 26.1%, respectively. In adjusted models, compared to a normal baseline BNP, low [adjusted hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.3-5.0, P-value 0.005], moderately elevated (adjusted HR 1.6, 95% CI 1.0-2.6, P-value 0.06), and markedly elevated (adjusted HR 2.1, 95% CI 1.3-3.5, P-value 0.003) BNP were associated with increased all-cause mortality, driven by cardiovascular mortality. CONCLUSIONS: In a large cohort of patients with severe symptomatic AS and preserved LVEF undergoing TAVR, all-cause and cardiovascular mortality rates at 2 years were higher in patients with low and markedly elevated BNP levels. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ unique identifier #NCT01314313, #NCT02184442, #NCT03222128, and #NCT03222141.

Adverse events in patients with high platelet reactivity following successful chronic total occlusion PCI: The Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) study.

BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) typically requires a greater number of stents and longer stent length than non-CTO PCI, placing these patients at greater risk for adverse ischemic events. We sought to determine whether the association between high platelet reactivity (HPR) and the risk of ischemic events is stronger after CTO than non-CTO PCI. METHODS: Patients undergoing successful PCI in the multicenter ADAPT-DES study were stratified according to whether they underwent PCI of a CTO. HPR was defined as VerifyNow platelet reaction units >208. The study primary endpoint was the 2-year risk target vessel failure ([TVF] defined as cardiac death, myocardial infarction, or target lesion revascularization). RESULTS: CTO PCI was performed in 400 of 8448 patients. HPR was present in 34.5% of CTO PCI patients and 43.1% of non-CTO PCI patients (P = .0007). Patients undergoing CTO PCI with versus without HPR had significantly higher 2-year rates of TVF (15.0% versus 8.3%, P = .04) without significant differences in bleeding. HPR was an independent predictor of 2-year TVF (adjusted HR 1.16, 95% CI 1.02-1.34, P = .03) whereas CTO PCI was not (adjusted HR 0.89, 95% CI 0.65-1.22, P = .48). There was a significant interaction between CTO versus non-CTO PCI and PRU as a continuous variable for 2-year TVF (Pinteraction = 0.02). CONCLUSIONS: In ADAPT-DES, HPR was associated with an increased 2-year risk of TVF after PCI, an association that was at least as strong after CTO PCI compared with non-CTO PCI.

Intravascular ultrasound analysis of intraplaque versus subintimal tracking in percutaneous intervention for coronary chronic total occlusions: One year outcomes.

OBJECTIVES: We sought to determine the 1-year outcomes of patients receiving successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedures comparing subintimal versus intraplaque wire tracking patterns. BACKGROUND: CTO PCI utilizes both intraluminal and subintimal wire tracking to achieve successful percutaneous revascularization. Intravascular ultrasound (IVUS) can be used to precisely determine the path of wire tracking. METHODS: From 2014 to 2016, data from patients undergoing CTO PCI were collected in a single-center database. The primary composite endpoint was target vessel failure (TVF) defined as cardiovascular death, target vessel myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS: In total 157 patients with successful CTO PCI and concomitant IVUS imaging completed 1-year follow-up. Subintimal tracking was detected in 53.5% of cases and those patients had a higher incidence of prior PCI, prior coronary artery bypass grafting, and higher J-CTO score. At 1-year, the unadjusted rate of TVF in the subintimal tracking group was higher than the intraplaque group (17.9 vs. 6.9%, HR 2.74, 95% CI 1.00-7.54, P = 0.04), driven by numerically higher rates of TVR and peri-procedural MI. After multivariable adjustment, no significant differences in the rates of the TVF between subintimal vs. intraplaque groups were present at 1-year (TVF: HR 1.51, 95% CI 0.38-6.00, P = 0.55). Landmark analysis excluding in-hospital events showed no significant differences in TVF to 1-year. CONCLUSIONS: IVUS-detected subintimal tracking was observed in over half of successful CTO PCI cases and correlated with baseline and angiographic factors that contributed to the overall rate of TVF at 1-year.

Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis.

BACKGROUND: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. OBJECTIVES: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). METHODS: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. RESULTS: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). CONCLUSIONS: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.