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.

The Ranger drug-coated balloon: advances in drug-coated technology for treatment of femoropopliteal segment arterial disease.

Paclitaxel drug-coated balloons (DCBs) have been shown to improve patency and lower revascularization rates compared with plain old balloon angioplasty. DCBs continue to evolve by improving balloon-coating techniques that minimize the quantity of particles washed off into the bloodstream while maximizing drug retention and vascular-healing profile. Against this backdrop, it is clear that the future of antiproliferatives for the superficial femoral artery will focus on enhancements in device coating materials that will improve the efficiency of drug delivery. The Ranger DCB system recently gained US FDA approval for use. This review discusses the background of DCBs and how the Ranger DCB builds on these previous platforms based on experimental and clinical data.

Drug-coated balloons are medical devices used to open blocked arteries (a procedure called angioplasty) in patients who have atherosclerotic disease. The drug coating is provided to help keep the arteries open after treatment with the balloon. This is thought to occur through several mechanisms. In this review, we discuss recent advances in technology related to drug-coated balloons focusing on the recently introduced Ranger drug-coated Balloon.

Association of Modified Body Mass Index With In-Hospital Outcomes After Intermediate or High-Risk Pulmonary Embolism.

Background: Pulmonary embolism (PE) outcomes are determined by presentation severity and host-related factors. Limited data exist regarding the association of modified body mass index (mBMI), used as a frailty surrogate, with clinical outcomes after treatment for PE. Therefore, we sought to determine the association of mBMI with mortality and bleeding after treatment for intermediate or high-risk PE. Methods: Patients treated for intermediate-risk or high-risk PE at a large academic center between 2013 and 2019 were studied. PE was characterized as intermediate risk (right ventricular compromise) or high risk (hemodynamic compromise) per European Society of Cardiology guidelines. mBMI was defined as the product of serum albumin concentration and body mass index. Patients were stratified according to mBMI quartiles, with low mBMI defined as ≤79, and evaluated for primary end points of in-hospital mortality and bleeding after treatment. A multivariable logistic regression analysis was performed for primary end points. Results: A total of 843 patients were treated for PE. Low mBMI was associated with increased burden of comorbidities and lower rates of interventional or surgical treatment. mBMI was independently associated with mortality (Q1, 22.8%; Q2, 12.4%; Q3, 10.9%; Q4, 6.6%; P = .005) and bleeding (Q1, 20.1%; Q2, 10.1%; Q3, 13.3%; Q4, 11.0%; P = .006). Compared with the lowest mBMI quartile, the highest mBMI quartile was independently associated with lower rates of mortality (OR, 0.28; 95% CI, 0.13-0.58; P < .001) and bleeding (OR, 0.42; 95% CI, 0.23-0.76; P = .004). Conclusions: Low mBMI is prevalent in patients with intermediate-risk and high-risk PE and is independently associated with in-hospital mortality and bleeding after treatment.

Discovery of Discrete Stages in the Oxidation of exo-Tetrahydrodicyclopentadiene (C10H16) Droplets Doped with Titanium-Aluminum-Boron Reactive Mixed-Metal Nanopowder.

Titanium (Ti), aluminum (Al), and boron (B) reactive mixed-metal nanopowders (Ti-Al-B RMNPs) represent attractive additives to hydrocarbon fuels such as exo-tetrahydrodicyclopentadiene (C10H16; JP-10) enhancing the limited volumetric energy densities of traditional hydrocarbons, but fundamental mechanisms and combustion stages in the oxidation have been obscure. This understanding is of vital significance in the development of next-generation propulsion systems and energy-generation technologies. Here, we expose distinct oxidation stages of single droplets of JP-10 doped with Ti-Al-B-RMNP exploiting innovative ultrasonic levitator technology coupled with time-resolved spectroscopic (UV-vis) and imaging diagnostics (optical and infrared). Two spatially and temporally distinct stages of combustion define a glow flame stage in which JP-10 and nanoparticles combust via a homogeneous gas phase (Al) and heterogeneous gas-surface oxidation (Ti, B) and a slower diffusion flame stage associated with the oxidation of JP-10. These findings enable the development of next-generation RMNP fuel additives with superior payload delivery capabilities.

Electronic Effects of Support Doping on Hydrotalcite-Supported Iridium N-Heterocyclic Carbene Complexes.

The electronic effects of supports on immobilized organometallic complexes impact their activity and lifetime, yet remain poorly understood. Here we describe a systematic study of the support effects experienced by an organometallic complex immobilized on doped hydrotalcite-like materials. To that end, we describe the synthesis and characterization of the first organometallic species immobilized on a palette of doped hydrotalcites via sulfonate linkers. The organometallic species consists of iridium N-heterocyclic carbene (NHC) carbonyl complex ([Na][Ir-(NHC-Ph-SO3)2(CO)2]), a highly active molecular catalyst for transfer hydrogenation of glycerol. The hydrotalcite supports are composed of Al, Mg, and a compatible transition-metal dopant (Fe, Cu, Ni, Zn). The materials were characterized extensively by STEM, XPS, TGA, PXRD, FT-IR, N2 desorption, ICP-AES, TPD, and microcalorimetry to probe the morphology and electronic properties of the support and elucidate structure-property relationships.

Paravalvular regurgitation after transcatheter aortic valve replacement in intermediate-risk patients: a pooled PARTNER 2 study.

BACKGROUND: Moderate or worse paravalvular regurgitation (PVR) post transcatheter aortic valve replacement (TAVR) is associated with increased mortality. The mechanisms by which this occurs are not fully understood. AIMS: The aim of this study was to determine the mechanism by which PVR leads to worse outcomes. METHODS: A total of 1,974 intermediate-risk patients who received TAVR in the PARTNER 2 trial and registries were grouped by PVR severity. Clinical and echocardiographic outcomes were compared. RESULTS: Overall 1,176 (60%) patients had none/trace, 680 (34%) had mild, and 118 (6%) had ≥moderate PVR. At two years, ≥moderate PVR patients had increased risks of all-cause (HR 2.33 [1.41-3.85], p-value=0.001) and cardiovascular death (HR 3.30 [1.74-6.28], p-value <0.001), rehospitalisation (HR 2.68 [1.57-4.58], p-value <0.001), and reintervention (HR 14.72 [3.13-69.32], p-value <0.001). Moderate or worse PVR was associated with larger increases in left ventricular (LV) end-diastolic and systolic dimensions and volumes, LV mass indices, and reductions in LV ejection fractions (LVEFs) from 30 days to two years. Mild PVR was not associated with worse outcomes. Adjusting for LV dimensions and LVEF from the one-year echocardiogram, patients with ≥moderate PVR still had an increased risk of all-cause death or rehospitalisation at two years (HR 2.84 [1.25-5.78], p-value=0.009). CONCLUSIONS: Moderate or worse PVR, but not mild PVR, is associated with an increased risk of all-cause and cardiovascular death, rehospitalisation, and reintervention at two years. Moderate or worse PVR is also associated with adverse LV remodelling, which partially mediates how ≥moderate PVR leads to worse outcomes. These results provide dual insights on the deleterious impact of ≥moderate PVR and the contributing mechanisms of poor clinical outcomes.

The "Lollipop" During Catheter-Directed Thrombectomy: 2 Case Examples.

Intraprocedural embolization has been described as a potential complication of catheter thrombectomy for acute pulmonary embolism and may be under-recognized. We describe 2 case examples of "Lollipopping" during thrombectomy, which may be a mechanism of intraprocedural embolization and describe our treatment approach. (Level of Difficulty: Advanced.).

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.

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.

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.

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.

Urologic Complications in Patients Receiving Indwelling Urinary Catheters During Transcatheter Aortic Valve Replacement.

OBJECTIVES: The minimalist approach to transcatheter aortic valve replacement (TAVR) focuses on avoiding extraneous invasive measures. Data describing the clinical impact of routine indwelling urinary catheter (IUC) in TAVR patients is limited. We sought to examine outcomes after IUC placement in patients undergoing TAVR. METHODS: We performed a retrospective analysis of 773 consecutive patients undergoing TAVR between 2011 and 2015. Patients were excluded who did not receive an IUC, had a pre-existing IUC, had renal replacement therapy, or underwent non-transfemoral TAVR. Patients were classified by presence of the composite of in-hospital urologic adverse events (UAEs), defined as urinary retention, IUC reinsertion, discharge with IUC, new hematuria, or urinary tract infection (UTI). The primary study endpoint was all-cause mortality at 1 year. RESULTS: A total of 520 patients met study criteria and were analyzed. The incidence of UAE was 28.6%. Urinary retention after IUC removal occurred in 14.6% of patients. UTIs occurred in 6.5% and acute kidney injury occurred in 13.6% of IUC patients. UAE was associated with an increased rate of 30-day and 1-year all-cause mortality (hazard ratio [HR], 2.84; 95% confidence interval [CI], 1.09-7.35; P=.02 and HR, 1.96; 95% CI, 1.22-3.16; P<.01, respectively). After multivariable adjustment for important baseline differences, UAEs were associated with significantly greater hazard of 1-year mortality (adjusted HR, 1.79; 95% CI, 1.07-2.99; P=.03) but not 30-day mortality (adjusted HR, 1.96; 95% CI, 0.67-5.49; P=.22). CONCLUSION: UAEs were frequent in patients receiving an IUC during TAVR and were associated with substantial morbidity, as well as longer hospital stay. Further research is required to establish whether avoidance of IUC as a component of the minimalist approach will reduce UAEs.