Etiologies and Impact of Exclusion Rates for Transcatheter Mitral and Tricuspid Valve Structural Heart Clinical Trials at a High-Volume Quaternary Care Hospital.

There are various devices under clinical investigation for transcatheter mitral valve intervention and transcatheter tricuspid valve intervention (TTVI); however, the exclusion rates remain high. We aimed to investigate the exclusion rates for transcatheter mitral valve repair (TMVr), transcatheter mitral valve replacement (TMVR), transcatheter tricuspid valve repair (TTVr), and transcatheter tricuspid valve replacement (TTVR). There were 129 patients who were referred to St. Francis Hospital & Heart Center valve clinic and completed screening between January 2021 and July 2022. The causes for exclusion were classified into 4 categories: patient withdrawal, anatomic unsuitability, clinical criteria, and medical futility. In 129 patients, the exclusion rates for TMVr, TMVR, TTVr, and TTVR were 81%, 85%, 91%, and 87%, respectively. Patient withdrawal and medical futility were leading etiologies for exclusion, followed by anatomic unsuitability. TMVr had the highest rate of patient withdrawal (64%) and the lowest anatomic unsuitability (5%) because of short posterior leaflet length. Replacement interventions have a higher anatomic unsuitability (33%) than repair interventions (17%) (p = 0.04). Most exclusions of anatomic unsuitability were because of mitral stenosis or small annulus size for TMVR and large annulus size for TTVR. A total of 50% of exclusions from TTVr were because of the presence of pacemaker/defibrillator leads. In patients excluded from their respective trials, patients being referred for TMVr had the highest recurrent hospitalization and repair group had a higher mortality (p <0.01 and p = 0.01, respectively). In conclusion, the exclusion rates for transcatheter mitral valve intervention and TTVI trials remain high because of various reasons, limiting patient enrollment and treatment. This supports the need for further device improvement or exploring alternative means of therapy.

Probing Liquid-Liquid Phase Separation in Secondary Organic Aerosol Mimicking Solutions Using Articulated Straws.

The presence or absence of liquid-liquid phase separation (LLPS) in aerosol particles containing oxidized organic species and inorganic salts affects particle morphology and influences uptake into, diffusion through, and reactivity within those particles. We report here an accessible method, similar to ice core analyses, using solutions that are relevant for both aerosol chemical systems and aqueous two-phase extraction systems and contain ammonium sulfate and one of eight alcohols (methanol, ethanol, 1-propanol, 2-propanol, 2-butaonol, 3-methyl-2-butanol, 1,2-propanediol, or 1,3-propanediol) frozen in articulated (bendable) straws to probe LLPS. For alcohols with negative octanol-water partitioning coefficient (K OW) values and O/C ratios ≥0.5, no LLPS occurs, while for alcohols with positive K OW values and O/C ratios ≤0.33, phase separation always occurs, both findings consistent with observations using different experimental techniques. When a third species, glyoxal, is added, the glyoxal stays in the aqueous phase, regardless of whether LLPS occurs. When phase separation occurs, the glyoxal forms a strong intermolecular interaction with the sulfate ion, red-shifting the ν3(SO4 2-) peak by 15 cm-1. These results provide evidence of chemical interactions within phase-separated systems that have implications for understanding chemical reactivity within those, and related, systems.

Usefulness of Age (≥85 Years) and Residual Mitral Regurgitation (>1+/4+) for the Prediction of Adverse Outcomes in Patients Receiving the MitraClip.

The goal of this study was to determine the predictors of adverse clinical outcomes in patients treated with the MitraClip for significant mitral regurgitation (MR) with a focus on acute changes in hemodynamics and cardiac function. This retrospective study included 63 patients (mean age 82 ± 8 years, 48% male) with moderate to severe or severe MR. Cardiac catheterization was performed before and immediately after MitraClip repair. Volumetric and functional changes were assessed in both ventricles. A major adverse cardiac event was defined as a composite of cardiac death and readmission for heart failure. Patients were followed up on average for 380 days. MR was improved in 92% of patients after MitraClip therapy from an average grade of 4+ to <2+ (p <0.001). The pulmonary capillary wedge pressure decreased from 22 ± 7 mm Hg to 19 ± 6 mm Hg (p <0.001), and the cardiac stroke volume increased by 28% from 102 ± 53 ml to 131 ± 54 ml (p <0.001). The left ventricular end-diastolic volume was significantly reduced 24 hours after MitraClip therapy compared to that at baseline (p = 0.001). In the multivariate Cox proportion hazard regression model, an age ≥85 years (p <0.001) and residual MR >1+ (p <0.048) were predictors of an adverse prognosis at follow-up. In conclusion, a reduced left ventricular end-diastolic volume and improved hemodynamics occurred early after MitraClip therapy. An advanced age (≥85 years) and residual MR >1+ were associated with an increased risk of mortality and heart failure.

Safety of Same-Day Discharge after Percutaneous Coronary Intervention with Orbital Atherectomy.

BACKGROUND: Severely calcified lesions present many challenges to percutaneous coronary intervention (PCI). Orbital atherectomy (OA) aids vessel preparation and treatment of severely calcified coronary lesions. Same-day discharge (SDD) after PCI has numerous advantages including cost savings and improved patient satisfaction. The aim of this study is to evaluate the safety of SDD among patients treated with OA in a real-world setting. METHODS: This was a single-center retrospective analysis of patients undergoing OA. In-hospital and 30-day outcomes were assessed for major adverse cardiac events (MACE), device-related events and hospital readmissions. RESULTS: There were 309 patients treated with OA of whom 94 had SDD (30.4%). Among SDD patients, there were no acute procedural complications and all patients were safely discharged on the day of the procedure. MACE at 30 days occurred in 1 patient (1.06%) due to major bleeding in the setting of a gastric arteriovenous malformation. There were 8 patients with unplanned 30-day readmissions (8.5%). CONCLUSION: SDD after OA in patients with heavily calcified lesions appears to be safe, with low rates of adverse events and readmissions in select patients. In patients with SDD treated with OA, unplanned readmission occurred at a similar rate to the statewide average 30-day PCI readmission rate. Larger studies are needed to confirm the safety of this treatment paradigm and the potential cost savings.

Combined Flux Chamber and Genomics Approach Links Nitrous Acid Emissions to Ammonia Oxidizing Bacteria and Archaea in Urban and Agricultural Soil.

Nitrous acid (HONO) is a photochemical source of hydroxyl radical and nitric oxide in the atmosphere that stems from abiotic and biogenic processes, including the activity of ammonia-oxidizing soil microbes. HONO fluxes were measured from agricultural and urban soil in mesocosm studies aimed at characterizing biogenic sources and linking them to indigenous microbial consortia. Fluxes of HONO from agricultural and urban soil were suppressed by addition of a nitrification inhibitor and enhanced by amendment with ammonium (NH4(+)), with peaks at 19 and 8 ng m(-2) s(-1), respectively. In addition, both agricultural and urban soils were observed to convert (15)NH4(+) to HO(15)NO. Genomic surveys of soil samples revealed that 1.5-6% of total expressed 16S rRNA sequences detected belonged to known ammonia oxidizing bacteria and archaea. Peak fluxes of HONO were directly related to the abundance of ammonia-oxidizer sequences, which in turn depended on soil pH. Peak HONO fluxes under fertilized conditions are comparable in magnitude to fluxes reported during field campaigns. The results suggest that biogenic HONO emissions will be important in soil environments that exhibit high nitrification rates (e.g., agricultural soil) although the widespread occurrence of ammonia oxidizers implies that biogenic HONO emissions are also possible in the urban and remote environment.

Release of nitrous acid and nitrogen dioxide from nitrate photolysis in acidic aqueous solutions.

Nitrate (NO3(-)) is an abundant component of aerosols, boundary layer surface films, and surface water. Photolysis of NO3(-) leads to NO2 and HONO, both of which play important roles in tropospheric ozone and OH production. Field and laboratory studies suggest that NO3¯ photochemistry is a more important source of HONO than once thought, although a mechanistic understanding of the variables controlling this process is lacking. We present results of cavity-enhanced absorption spectroscopy measurements of NO2 and HONO emitted during photodegradation of aqueous NO3(-) under acidic conditions. Nitrous acid is formed in higher quantities at pH 2-4 than expected based on consideration of primary photochemical channels alone. Both experimental and modeled results indicate that the additional HONO is not due to enhanced NO3(-) absorption cross sections or effective quantum yields, but rather to secondary reactions of NO2 in solution. We find that NO2 is more efficiently hydrolyzed in solution when it is generated in situ during NO3(-) photolysis than for the heterogeneous system where mass transfer of gaseous NO2 into bulk solution is prohibitively slow. The presence of nonchromophoric OH scavengers that are naturally present in the environment increases HONO production 4-fold, and therefore play an important role in enhancing daytime HONO formation from NO3(-) photochemistry.

Uptake of gas phase nitrous acid onto boundary layer soil surfaces.

Nitrous acid (HONO) is an important OH radical source that is formed on both ground and aerosol surfaces in the well-mixed boundary layer. Large uncertainties remain in quantifying HONO sinks and determining the mechanism of HONO uptake onto surfaces. We report here the first laboratory determination of HONO uptake coefficients onto actual soil under atmospheric conditions using a coated-wall flow tube coupled to a highly sensitive chemical ionization mass spectrometer (CIMS). Uptake coefficients for HONO decrease with increasing RH from (2.5 ± 0.4) × 10(-4) at 0% RH to (1.1 ± 0.4) × 10(-5) at 80% RH. A kinetics model of competitive adsorption of HONO and water onto the particle surfaces fits the dependence of the HONO uptake coefficients on the initial HONO concentration and relative humidity. However, a multiphase resistor model based on the physical and chemical processes affecting HONO uptake is more flexible as it accounts for the pH dependence of HONO uptake and bulk diffusion in the soil matrix. Fourier transform infrared (FTIR) spectrometry and cavity-enhanced absorption spectroscopy (CEAS) studies indicate that NO and N2O (16% and 13% yield, respectively) rather than NO2 are the predominant gas phase products, while NO2(-) and NO3(-) were detected on the surface post-exposure. Results are compared to uptake coefficients inferred from models and field measurements, and the atmospheric implications are discussed.

Relationship of phasic left atrial volume and emptying function to left ventricular filling pressure: a cardiovascular magnetic resonance study.

BACKGROUND: Left atrial volume (LAV) and emptying fraction (LAEF) are phasic during cardiac cycle. Their relationships to left ventricular end diastolic pressure (LVEDP) have not been fully defined. METHODS: Forty one patients undergoing clinically indicated left heart catheterization were recruited for same day cardiovascular magnetic resonance (CMR). LAV and LAEF were assessed in cine images using biplane area and length method. Three phasic LAV was assessed at LV end systole (LAV(max)), LV end diastole (LAV(min)) and late LV diastole prior to LA contraction (LAV(ac)). LAEF was assessed as global LAEF (LAEF(Total)), passive (LAEF(Passive)) and active LAEF (LAEF(Contractile)). The relationships of phasic LAV and LAEF to LVEDP were assessed using Receiver operating characteristic comparing areas under the curves (AUC). RESULTS: The mean age of the patients was 59 years. A history of heart failure was present in 16 (39%) with NYHA functional class III or IV in 8 (20%) patients. Average LV ejection fraction was 49 ± 16% ranging from 10% to 74% and LVEDP by catheterization 14 ± 8 mmHg ranging from 4 mmHg to 32 mmHg. LAV(min) had the strongest association with LVEDP elevation (>12 mmHg) (AUC 0.765, p = 0.002), as compared to LAV(max) (AUC 0.677, p = 0.074) and LAV(ac) (AUC 0.735, p = 0.008). Among three phasic LAEF assessed, LAEF(Total) had the closest association with LVEDP elevation (AUC 0.780, p = 0.001), followed by LAEF(Contractile) (AUC 0.698, p = 0.022) and LAEF(Passive) (AUC 0.656, p = 0.077). CONCLUSIONS: Increased LAV(min) and decreased LAEF(Total) have the best performance in identifying elevated LVEDP among three phasic LAV and LAEF analyzed. Future studies should further characterize LA phasic indices in clinical outcomes.

The influence of translational and vibrational energy on the reaction of Cl with CH3D.

The reaction of Cl atoms with CH3D proceeds either by abstraction of hydrogen to produce HCl + CH2D or by abstraction of deuterium to produce DCl + CH3. Using Cl atoms with different amounts of translational energy, produced by photolysis of Cl2 with 309, 355, or 416 nm light, reveals the influence of translational energy on the relative reaction probability for the two channels. These measurements give an estimate of the energy barrier for the reaction for comparison to theory and indicate that tunneling is the dominant reaction mechanism at low collision energies. Adding two quanta of C-H stretching vibration causes the reaction to proceed readily at all collision energies. Detecting the vibrational state of the CH2D product shows that vibrational energy initially in the surviving C-H bond appears as vibrational excitation of the product, an example of spectator behavior in the reaction. The reaction produces both stretch and stretch-bend excited products except at the lowest collision energy. A subtle variation in the reaction probability of the lowest energy rotational states with translational energy may reflect the presence of a van der Waals well in the entrance channel.

Effects of hemodynamics on global and regional lung perfusion: a quantitative lung perfusion study by magnetic resonance imaging.

BACKGROUND: Cardiac hemodynamics affect pulmonary vascular pressure and flow, but little is known of the effects of hemodynamics on lung perfusion at the tissue level. We sought to investigate the relationship between hemodynamic abnormalities in patients with left heart failure and global and regional lung perfusion using lung perfusion quantification by magnetic resonance imaging. METHODS AND RESULTS: Lung perfusion was quantified in 10 normal subjects and 28 patients undergoing clinically indicated left and right heart catheterization and same day research cardiac magnetic resonance imaging. A total of 228 lung slices were evaluated. Global lung perfusion, determined as the average of 6 coronal lung slices through the anterior, mid, and posterior left and right lungs, was significantly lower in patients with reduced cardiac index (<2.5 L/min per m(2)): 94±30 mL/100 mL per minute versus 132±40 mL/100 mL per minute in those with preserved cardiac index (≥2.5 L/min per m(2); P=0.003). The gravitational anterior to posterior perfusion gradient was inversely associated with left ventricular end-diastolic pressure (r=-0.728; P<0.001), resulting in a blunted perfusion gradient in patients with elevated left ventricular end-diastolic pressure, a finding largely attributed to the perfusion reduction in posterior lung regions. In a multivariate regression analysis adjusting for all hemodynamic variables, altered lung perfusion gradient was most closely associated with increased mean pulmonary arterial pressure (P=0.016). CONCLUSIONS: Increased left ventricular filling pressure and the resultant increase in pulmonary arterial pressure are associated with disruption of the normal gravitational lung perfusion gradient. Our findings underscore the complexity of heart-lung interaction in determining pulmonary hemodynamics in left heart failure.

Left ventricular filling pressure assessment using left atrial transit time by cardiac magnetic resonance imaging.

BACKGROUND: Left atrial (LA) size and function reflect left ventricular (LV) hemodynamics. In the present study, we developed a novel method to determine LA circulation transit time (LATT) by MRI and demonstrated its close association with LV filling pressure. METHODS AND RESULTS: All subjects were prospectively recruited and underwent contrast-enhanced MR dynamic imaging. Mean LATT was determined as the time for contrast to transit through the LA during the first pass. In an invasive study group undergoing clinically indicated cardiac catheterization (n=25), LATT normalized by R-R interval (nLATT) was closely associated with LV early diastolic pressure (r=0.850, P=0.001), LV end-diastolic pressure (r=0.910, P<0.001), and mean diastolic pressure (r=0.912, P<0.001). In a larger noninvasive group (n=56), nLATT was prolonged in patients with LV systolic dysfunction (n=47) (10.1±3.0 versus 6.6±0.7 cardiac cycles in normal control subjects, n=9; P<0.001). Using a linear regression equation derived from the invasive group, noninvasive subjects were divided into 3 subgroups by estimated LV end-diastolic pressure: ≤10 mm Hg, 11 to 14 mm Hg, and ≥15 mm Hg. There were graded increases from low to high LV end-diastolic pressure subgroups in echocardiographic mitral medial E/e' ratio: 9±5, 11±4, and 13±3 (P=0.023); in B-type natriuretic peptide (interquartile range): 44 (60) pg/mL, 87 (359) pg/mL, and 371 (926) pg/mL (P=0.002); and in N-terminal pro-B-type natriuretic peptide: 57 (163) pg/mL, 208 (990) pg/mL, and 931 (1726) pg/mL (P=0.002), demonstrating the ability of nLATT to assess hemodynamic status. CONCLUSIONS: nLATT by cardiac MR is a promising new parameter of LV filling pressure that may provide graded noninvasive hemodynamic assessment.

Effect of percutaneous mitral repair with the MitraClip device on mitral valve area and gradient.

AIMS: Percutaneous repair of mitral regurgitation (MR) by leaflet apposition using a clip deployed via transseptal catheterisation is undergoing evaluation. METHODS AND RESULTS: In order to detect the potential for clinically significant left ventricular inflow obstruction after percutaneous repair, we measured mitral valve area (MVA) and mean transmitral gradient (MVG) echocardiographically in 96 patients implanted with a clip followed for up to 24 months. By planimetry, the mean MVA decreased from 6.0 +/- 1.3 cm2 to 3.6 +/- 1.2 cm2 (p < 0.05) (range 1.9 to 7.6 cm2) after clip placement, and remained unchanged after 24 months of follow-up (3.5 +/- 0.8 cm2). The mean MVG increased after clip placement from 1.7 +/- 0.9 mmHg to 4.1 +/- 2.2 mmHg (p < 0.05), and did not increase further to 24 months (3.8 +/- 1.9 mmHg). There were no differences in MVA or MVG between patients who received 1-clip (69%) and those receiving 2-clips (31%). Patients with functional MR (23%) had a slightly smaller MVA, both at baseline and after clip placement, but did not differ from degenerative MR patients at later follow-up. After 2 years of follow-up, no patient required surgery for LV inflow obstruction. CONCLUSIONS: Mitral repair with the MitraClip device for MR decreases MVA without significant mitral obstruction. After 2 years of follow-up, no patient required surgery for LV inflow obstruction, and these results were not influenced by the use of more than 1 clip or the aetiology of MR.

Reaction dynamics and vibrational spectroscopy of CH3D molecules with both C-H and C-D stretches excited.

State-resolved reactions of CH3D molecules containing both C-H and C-D stretching excitation with Cl atoms provide new vibrational spectroscopy and probe the consumption and disposal of vibrational energy in the reactions. The vibrational action spectra have three different components, the combination of the C-H symmetric stretch and the C-D stretch (nu1 + nu2), the combination of the C-D stretch and the C-H antisymmetric stretch (nu2 + nu4), and the combination of the C-D stretch and the first overtone of the CH3 bend (nu2 + 2nu5). The simulation for the previously unanalyzed (nu2 + nu4) state yields a band center of nu0 = 5215.3 cm(-1), rotational constants of A = 5.223 cm(-1) and B = 3.803 cm(-1), and a Coriolis coupling constant of zeta = 0.084. The reaction dynamics largely follow a spectator picture in which the surviving bond retains its initial vibrational excitation. In at least 80% of the reactive encounters of vibrationally excited CH3D with Cl, cleavage of the C-H bond produces CH2D radicals with an excited C-D stretch, and cleavage of the C-D bond produces CH3 radicals with an excited C-H stretch. Deviations from the spectator picture seem to reflect mixing in the initially prepared eigenstates and, possibly, collisional coupling during the reaction.