Measuring Intermolecular Excited State Geometry for Favorable Singlet Fission in Tetracene.

Singlet fission (SF) is the process of converting an excited singlet to a pair of excited triplets. Harvesting two charges from a single photon has the potential to increase photovoltaic device efficiencies. Acenes, such as tetracene and pentacene, are model molecules for studying SF. Despite SF being an endoergic process for tetracene and exoergic for pentacene, both acenes exhibit near unity SF quantum efficiencies, raising questions about how tetracene can overcome the energy barrier. Here, we use recently developed instrumentation to measure inelastic neutron scattering (INS) while optically exciting the model molecules using two different excitation energies. The spectroscopic results reveal intermolecular structural relaxation due to the presence of a triplet excited state. The structural dynamics of the combined excited state molecule and surrounding tetracene molecules are further studied using time-dependent density functional theory (TD-DFT), which shows that the singlet and triplet levels shift due to the excited state geometry, reducing the uphill energy barrier for SF to within kT.

Compact, portable, automatic sample changer stick for cryostats and closed-cycle refrigerators.

Beamlines are facilities that produce and deliver highly focused and intense beams of radiation, typically x rays, synchrotron radiation, or neutrons, for scientific research purposes. Millions of dollars are spent annually to maintain and operate these scientific beamlines, oftentimes running continuously between cycles. To reduce human intervention and improve productivity, mechanical sample changers are often commissioned for use. Designing sample changers is difficult because mechanical parts can be bulky, expensive, and challenging to design for instruments with low volume access, high radiation, and cryogenic environments. We present a portable and inexpensive sample changer stick that can hold and manipulate up to four samples, specifically designed for use with cryogenic closed-cycle refrigerators. The sample changer stick enables rapid and efficient exchange of samples without manual intervention, and is compatible with standard sample mounts such as vanadium cans. The sample changer stick includes a motorized rotation and lancing mechanism, which enables the precise positioning of each sample in the neutron beam, while ensuring compatibility with the operating temperatures and vacuum conditions required for closed-cycle refrigerators. The design has been successfully tested at the VISION beamline at the Spallation Neutron Source. The mechanical action and software controls are detailed. The sample changer stick is a valuable tool for scientists working with cryogenic closed-cycle refrigerators.

Photochemistry sample sticks for inelastic neutron scattering.

Every material experiences atomic and molecular motions that are generally termed vibrations in gases and liquids or phonons in solid state materials. Optical spectroscopy techniques, such as Raman, infrared absorption spectroscopy, or inelastic neutron scattering (INS), can be used to measure the vibrational/phonon spectrum of ground state materials properties. A variety of optical pump probe spectroscopies enable the measurement of excited states or elucidate photochemical reaction pathways and kinetics. So far, it has not been possible to study photoactive materials or processes in situ using INS due to the mismatch between neutron and photon penetration depths, differences between the flux density of photons and neutrons, cryogenic temperatures for INS measurements, vacuum conditions, and a lack of optical access to the sample space. These experimental hurdles have resulted in very limited photochemistry studies using INS. Here we report on the design of two different photochemistry sample sticks that overcome these experimental hurdles to enable in situ photochemical studies using INS, specifically at the VISION instrument at Oak Ridge National Laboratory. We demonstrate the use of these new measurement capabilities through (1) the in situ photodimerization of anthracene and (2) the in situ photopolymerization of a 405 nm photoresin using 405 nm excitation as simple test cases. These new measurement apparatus broaden the science enabled by INS to include photoactive materials, optically excited states, and photoinitiated reactions.

A multi-faceted structural, thermodynamic, and spectroscopic approach for investigating ethanol dehydration over transition phase aluminas.

Understanding the role that the surface of a material plays in the mediation of a chemical reaction at the atomic level is paramount to the optimization and improvement of catalytic materials. While this area of research has matured over several decades, few techniques are sensitive enough to directly examine and differentiate the behavior of molecular adsorbates during the course of the chemical reaction with a substrate. In this study, a combined approach which involves structural characterization techniques, volumetric adsorption, temperature programmed desorption, and inelastic neutron scattering (INS) was used to investigate the mechanism of ethanol dehydration on the surface of transition phase aluminas. The alumina samples employed were extensively characterized using X-ray diffraction, solid-state 27Al nuclear magnetic resonance spectroscopy, and thermogravimetric analysis with differential scanning calorimetry. A high-precision volumetric adsorption apparatus was used to characterize the surface area and to controllably dose ethanol onto the surface of the aluminas. A modified temperature programmed desorption (TPD) method which samples the molecular composition of the vapor at discrete temperatures in a closed cell is described. INS results were used to confirm adsorption of ethanol on γ- and θ-alumina and show the reaction of ethanol and subsequent formation of ethylene as a function of temperature. The TPD and INS results affirm that the dehydration reaction and subsequent formation of ethylene on both γ- and θ-aluminas occur rapidly at 300 °C, though ethanol is still observed on θ-alumina indicating fewer active sites. These results demonstrate the value of a multi-faceted characterization approach, featuring INS, towards providing a detailed understanding of the ethanol dehydration mechanism on θ-alumina and further provide the basis for extending this approach to other systems in heterogeneous catalysis and areas where molecule-substrate interactions are poorly understood.

Uncovering the hydride ion diffusion pathway in barium hydride via neutron spectroscopy.

Solid state materials possessing the ability for fast ionic diffusion of hydrogen have immense appeal for a wide range of energy-related applications. Ionic hydrogen transport research is dominated by proton conductors, but recently a few examples of hydride ion conductors have been observed as well. Barium hydride, BaH2, undergoes a structural phase transition around 775 K that leads to an order of magnitude increase in the ionic conductivity. This material provides a prototypical system to understand hydride ion diffusion and how the altered structure produced by the phase transition can have an enormous impact on the diffusion. We employ quasielastic and inelastic neutron scattering to probe the atomic scale diffusion mechanism and vibrational dynamics of hydride ions in both the low- and high-temperature phases. Jump lengths, residence times, diffusion coefficients, and activation energies are extracted and compared to the crystal structure to uncover the diffusion pathways. We find that the hydrogen jump distances, residence times, and energy barriers become reduced following the phase transition, allowing for the efficient conduction of hydride ions through a series of hydrogen jumps of length L = 3.1 Å.

Melting and Re-Freezing Leads to Irreversible Changes in the Morphology and Molecular-Level Dynamics of Pfizer-BioNTech COVID-19 Vaccine.

Background and Objectives: As an mRNA-based vaccine, the Pfizer-BioNTech COVID-19 vaccine has stringent cold storage requirements to preserve functionality of the mRNA active ingredient. To this end, lipid components of the vaccine formulation play an important role in stabilizing and protecting the mRNA molecule for long-term storage. The purpose of the current study was to measure molecular-level dynamics as a function of temperature in the Pfizer-BioNTech COVID-19 vaccine to gain microscopic insight into its thermal stability. Materials and Methods: We used quasielastic and inelastic neutron scattering to probe (1) the vaccine extracted from the manufacturer-supplied vials and (2) unperturbed vaccine in the original manufacturer-supplied vials. The latter measurement was possible due to the high penetrative power of neutrons. Results: Upon warming from the low-temperature frozen state, the vaccine in its original form exhibits two-step melting, indicative of a two-phase morphology. Once the melting is completed (above 0 °C), vaccine re-freezing cannot restore its original two-phase state. This observation is corroborated by the changes in the molecular vibrational spectra. The molecular-level mobility measured in the resulting single-phase state of the re-frozen vaccine greatly exceeds the mobility measured in the original vaccine. Conclusions: Even a brief melting (above 0 °C) leads to an irreversible alteration of the two-phase morphology of the original vaccine formulation. Re-freezing of the vaccine results in a one-phase morphology with much increased molecular-level mobility compared to that in the original vaccine, suggesting irreversible deterioration of the vaccine's in-storage stability. Neutron scattering can be used to distinguish between the vibrational spectra characteristic of the original and deteriorated vaccines contained in the unperturbed original manufacturer-supplied vials.

3D-printed B4C collimation for neutron pressure cells.

A design for an incident-beam collimator for the Paris-Edinburgh pressure cell is described here. This design can be fabricated from reaction-bonded B4C but also through fast turnaround, inexpensive 3D-printing. 3D-printing thereby also offers the opportunity of composite collimators whereby the tip closest to the sample can exhibit even better neutronic characteristics. Here, we characterize four such collimators: one from reaction-bonded B4C, one 3D-printed and fully infiltrated with cyanoacrylate, a glue, one with a glue-free tip, and one with a tip made from enriched 10B4C. The collimators are evaluated on the Spallation Neutrons and Pressure Diffractometer of the Spallation Neutron Source and the Wide-Angle Neutron Diffractometer at the High Flux Isotope Reactor, both at Oak Ridge National Laboratory. This work clearly shows that 3D-printed collimators perform well and also that composite collimators improve performance even further. Beyond use in the Paris-Edinburgh cell, these findings also open new avenues for collimator designs as clearly more complex shapes are possible through 3D printing. An example of such is shown here with a collimator made for single-crystal samples measured inside a diamond anvil cell. These developments are expected to be highly advantageous for future experimentation in high pressure and other extreme environments and even for the design and deployment of new neutron scattering instruments.

Inverse Probability of Treatment Weighting (Propensity Score) using the Military Health System Data Repository and National Death Index.

When randomized controlled trials are not feasible, retrospective studies using big data provide an efficient and cost-effective alternative, though they are at risk for treatment selection bias. Treatment selection bias occurs in a non-randomized study when treatment selection is based on pre-treatment characteristics that are also associated with the outcome. These pre-treatment characteristics, or confounders, can influence evaluation of a treatment's effect on the outcome. Propensity scores minimize this bias by balancing the known confounders between treatment groups. There are a few approaches to performing propensity score analyses, including stratifying by the propensity score, propensity matching, and inverse probability of treatment weighting (IPTW). Described here is the use of IPTW to balance baseline comorbidities in a cohort of patients within the US Military Health System Data Repository (MDR). The MDR is a relatively optimal data source, as it provides a contained cohort in which nearly complete information on inpatient and outpatient services is available for eligible beneficiaries. Outlined below is the use of the MDR supplemented with information from the national death index to provide robust mortality data. Also provided are suggestions for using administrative data. Finally, the protocol shares an SAS code for using IPTW to balance known confounders and plot the cumulative incidence function for the outcome of interest.

Radiation Exposure During Transcatheter Valve Replacement: What Cardiac Surgeons Need to Know.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) and transcatheter mitral valve replacement expose operators to radiation. These procedures differ primarily in whether they are performed via a transfemoral (TF) or an alternative access (AA) approach. This study compared operator radiation exposure during transcatheter valve implantation when performed via a TF vs an AA approach, when performed in a catheterization lab vs a hybrid operating room (OR), and investigated the potential benefit of disposable shielding. METHODS: Dosimeters were worn during TAVR-TF (n = 50) and TAVR-AA (n = 31) procedures by operators. All TAVR-AA procedures were performed in a hybrid OR and TF procedures were performed in either catheterization labs (n = 16) or a hybrid OR (n = 34). Disposable radiation shielding pads (RADPAD; Worldwide Innovations and Technologies, Inc, Kansas City) or a placebo were added in a randomized, blinded fashion. RESULTS: Team radiation exposure was higher after TAVR-AA vs TAVR-TF (median 15.1 mRad [interquartile range: IQR 8.6, 32.4] vs 5.5 mRad [IQR 2.4, 9.8], P < .001). TAVR-TF procedures required the same amount of fluoroscopy time regardless of where they were performed (20.3 ± 7.4 min in hybrid OR vs 19.0 ± 6.4 min in catheterization lab, P = .55). However, radiation exposure for TAVR-TF remained higher when performed in a hybrid OR (median 9.0 mRad [IQR 4.5, 11.9] vs 2.2 mRad [IQR 1.3, 2.8], P < .001). Radiation exposure was greatest for TAVR-AA (median 15.1 mRad [IQR 8.6, 32.4]). The use of RADPAD did not decrease radiation exposure (median 9.0 mRad [IQR 4.5, 14.7] vs 9.4 mRad [IQR 2.8, 19.5], P = .82). CONCLUSIONS: Procedures performed in the hybrid OR were associated with higher operator radiation exposure. In comparison with the TF approach, AA cases had the highest levels of operator radiation. This is particularly important in cases of transcatheter mitral valve replacement that can only be done via an AA approach. The use of disposable radiation shielding in this series did not attenuate operator radiation exposure. Radiation shielding within hybrid ORs should be scrutinized in an effort to remain on par with that found within catheterization labs.

Improved differential diagnosis of intracardiac and extracardiac shunts using acoustic intensity mapping of saline contrast studies.

AIMS: The aim of this study was to test the hypothesis that temporal patterns of saline contrast entry into, and exit from the left heart are significantly different in intra- and extra-cardiac shunts and can be used to differentiate the shunt mechanism when Valsalva manoeuvre cannot be performed, or is of uncertain quality. We propose a novel approach of mapping the temporal changes in acoustic intensity (AI) within the left and right heart to identify and define these unique patterns. METHODS AND RESULTS: We screened cases of right to left shunting on resting agitated saline contrast echocardiograms with clinical criteria that identified the origin of shunting as either a patent foramen ovale or pulmonary arteriovenous malformation. Acoustic time-intensity curves were generated from the right and left heart chambers that reflected the change in saline contrast density over time. Several novel pre-specified parameters were measured from these curves, in addition to the standard heartbeat counting method, to characterize the entrance (wash-in) and exit (wash-out) patterns of saline contrast in the left heart. Statistical analysis showed that AI mapping provided superior differentiation of the two populations than did the traditional beat counting method. CONCLUSION: Diagnosis of shunt mechanism from saline contrast studies can be improved over current methods through the use of AI mapping to define the rapidity that peak contrast effect develops, the speed that the contrast effect decays, and the contrast intensity late in the recording.

Development of a risk score to identify patients with type 2 diabetes mellitus and multivessel coronary artery disease who can defer bypass surgery.

BACKGROUND: Current American College of Cardiology/American Heart Association (ACC/AHA) guidelines provide a class I recommendation for patients with type 2 diabetes mellitus and multivessel coronary artery disease (CAD) to be treated with coronary artery bypass graft surgery (CABG). However, these patients are heterogeneous in terms of the risks and benefits associated with CABG. We sought to develop a risk score to identify low-risk patients with diabetes and multivessel CAD in whom CABG can be safely deferred. METHODS: Patients in the CABG strata randomized to intensive medical therapy (IMT) in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial who experienced death, myocardial infarction (MI), or stroke were compared with those who did not. We developed a risk score for death, MI, or stroke using a Cox proportional hazards model that included the following variables: age, history of heart failure, history of hypercholesterolemia, history of stroke, transient ischemic attack, serum creatinine, insulin use, myocardial jeopardy index, and HbA1c. RESULTS: Among patients with a risk score less than the median, those randomized to IMT or prompt CABG experienced similar rates of event-free survival at 5 years (77.8% vs. 83.2%, logrank P = 0.24). Among patients with a risk score greater than the median, those randomized to IMT experienced worse rates of event-free survival at 5 years than those randomized to prompt CABG (60.3% vs 73.2%, logrank P = 0.01). CONCLUSIONS: A novel risk score identifies low-risk patients with diabetes and stable, symptomatic multivessel CAD in whom CABG can be safely deferred.

Association of High Birth Weight With Incident Heart Failure in the ARIC Study.

Background Traditional risk factors for heart failure--coronary heart disease, hypertension, diabetes mellitus, obesity, and smoking--only account for about 50% of cases. Thus, the identification of novel risk factors is of significant public health importance. As high birth weight infants are at increased risk for obesity and diabetes mellitus later in life, which are both risk factors for the development of heart failure, we sought to assess the association of high birth weight with incident heart failure in the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results The ARIC study is a biracial prospective community-based investigation of 15 792 individuals aged 45 to 64 years at baseline. Study participants who were born premature or born a twin were excluded from this analysis, resulting in 9820 participants who provided either their birth weight category (low, medium, high) or exact birth weight. After adjusting for differences in demographics, risk factors, and comorbidities, compared with medium birth weight, those with high birth weight had a significantly increased risk of incident heart failure (hazard ratio, 1.27; 95% CI , 1.05-1.54 [ P=0.014]). The hazard for all-cause mortality for high birth weight compared with medium birth weight was 1.16 (95% CI , 0.99-1.34; P=0.06). There was no association of high birth weight with myocardial infarction (hazard ratio, 1.06; 95% CI , 0.84-1.34 [ P=0.6]). Conclusions High birth weight was associated with a significantly increased hazard of incident heart failure independent of traditional risk factors and a trend toward an increased hazard of death. A history of high birth weight should be ascertained in young adults for primordial prevention of heart failure and in older adults for primary prevention.

The association of preoperative cardiac stress testing with 30-day death and myocardial infarction among patients undergoing kidney transplantation.

BACKGROUND: Although periodic cardiac stress testing is commonly used to screen patients on the waiting list for kidney transplantation for ischemic heart disease, there is little evidence to support this practice. We hypothesized that cardiac stress testing in the 18 months prior to kidney transplantation would not reduce postoperative death, total myocardial infarction (MI) or fatal MI. METHODS: Using the United States Renal Data System, we identified ESRD patients ≥40 years old with primary Medicare insurance who received their first kidney transplant between 7/1/2006 and 11/31/2013. Propensity matching created a 1:1 matched sample of patients with and without stress testing in the 18 months prior to kidney transplantation. The outcomes of interest were death, total (fatal and nonfatal) MI or fatal MI within 30 days of kidney transplantation. RESULTS: In the propensity-matched cohort of 17,304 patients, death within 30 days occurred in 72 of 8,652 (0.83%) patients who underwent stress testing and in 65 of 8,652 (0.75%) patients who did not (OR 1.07; 95% CI: 0.79-1.45; P = 0.66). MI within 30 days occurred in 339 (3.9%) patients who had a stress test and in 333 (3.8%) patients who did not (OR 1.03; 95% CI: 0.89-1.21; P = 0.68). Fatal MI occurred in 17 (0.20%) patients who underwent stress testing and 15 (0.17%) patients who did not (OR 0.97; 95% CI: 0.71-1.32; P = 0.84). CONCLUSION: Stress testing in the 18 months prior to kidney transplantation is not associated with a reduction in death, total MI or fatal MI within 30 days of kidney transplantation.

Interaction of cardiac implantable electronic device and patent foramen ovale in ischemic stroke: A case-only study.

BACKGROUND: Cardiovascular implantable electronic device (CIED) leads are a nidus for right atrial thrombi. Right-to-left thromboembolism across a patent foramen ovale (PFO) is a putative mechanism for ischemic stroke and PFO has been associated with stroke. We used a novel unbiased case-only study design to assess the effect modification of PFO-associated ischemic stroke risk by presence of CIED. We hypothesized that presence of CIED, as a nidus for right atrial thrombus formation, magnifies the PFO-ischemic stroke relationship; therefore, among hospitalized ischemic stroke patients we would find a higher prevalence of CIED in patients with PFO. METHODS: We included consecutive first ischemic stroke patients admitted to our hospital from 2006 to 2015, who were enrolled in a prospectively maintained stroke registry. PFO was ascertained from documentation on echocardiography, and presence of CIED at time of stroke was determined from chest radiography reports at or prior to hospitalization. We measured distributions of CIED within PFO and control groups and used Fisher's exact test to evaluate the PFO-CIED association among ischemic stroke patients. RESULTS: We included 7089 patients (age: 64.5 ± 14.9 years, 51% female). Echocardiography diagnosed PFO in 760 (10.7%) patients and CIED was reported on chest radiography in 752 (10.6%) patients. Prevalence of CIED was lower in the PFO (61/760, 8.0%) compared to control group (691/6329, 10.9%), P = 0.015. CONCLUSION: Among admitted ischemic stroke patients, we did not find a higher prevalence of CIED in patients with PFO compared to controls. Therefore, in the underlying source population, the presence of CIED did not increase the PFO-associated ischemic stroke risk.

The Combination of Tricuspid Annular Plane Systolic Excursion and HeartMate Risk Score Predicts Right Ventricular Failure After Left Ventricular Assist Device Implantation.

Right ventricular (RV) failure is difficult to predict and is a major determinant of poor outcomes after left ventricular assist device (LVAD) implantation. We evaluated the associations of the following variables with severe RV failure in LVAD patients: tricuspid annular plane systolic excursion (TAPSE), pulmonary artery pulsatility index (PAPi), simplified RV contraction pressure index (sRVCPI), and HeartMate Risk Score (HMRS). We performed a retrospective case-control study on 216 patients who underwent continuous-flow LVAD implantation between 2008 and 2014. The primary analysis assessed the ability of HMRS, PAPi, sRVCPI, and TAPSE to predict severe RV failure. A secondary analysis evaluated the incremental benefit of combining predictive variables. Seventy-four patients developed severe RV failure (24%). Compared with the control group, the severe RV failure group had lower TAPSE (1.30 vs. 1.55; p < 0.001), lower PAPi (1.77 vs. 2.47; p = 0.001), lower sRVCPI (42.71 vs. 57.82; p < 0.001), and higher HMRS (2.12 vs. 1.65; p < 0.001). All four variables had similar receiver operating characteristic curves with modest area under the receiver operating characteristic curve (0.63-0.67, all p values < 0.001). In the evaluation of combined predictive variables, the combination of TAPSE with HMRS was found to be best for predicting severe RV failure. In summary, patients at risk for severe RV failure after LVAD implantation were successfully identified using TAPSE, PAPi, sRCPI, and HMRS. The combination of TAPSE and HMRS-incidentally, the least invasive and most readily available variables-proved to be superior to RV-centric metrics for predicting severe RV failure. The predictive and clinical use of these two variables should be tested prospectively.

Comparison of the Kansas City Cardiomyopathy Questionnaire and Minnesota Living With Heart Failure Questionnaire in Predicting Heart Failure Outcomes.

Patient-reported outcome measures (PROMs) are relevant independent outcomes in heart failure (HF) care and are predictive of subsequent hospitalization and death in HF. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) are the 2 most widely adopted PROMs specific to HF. We compared their prognostic abilities in a prospective cohort of HF patients. A prospective cohort of subjects from a single-center registry was analyzed with regard to baseline KCCQ and MLHFQ scores and the outcomes of death, transplant, or left ventricular assist device implantation and hospitalization. A total of 516 subjects with reduced left ventricular ejection fraction (HFrEF) and 151 subjects with preserved left ventricular ejection fraction (HFpEF) were included. Discrimination was assessed using c-statistics based on time-to-event analyses and receiver-operator curves. The additive contribution of MLHFQ was assessed through the change in c-statistic, incremental discrimination index, and category-free net reclassification index. Overall, KCCQ was superior to MLHFQ for predicting death/transplant/ventricular assist device (c-statistic 0.702 [0.666 to 0.738] and 0.658 [0.621 to 0.695] respectively, p value for difference <0.001) and hospitalization (c-statistic 0.640 [0.613 to 0.666] and 0.624 [0.597 to 0.651], respectively, p value for difference 0.022). However, this difference was statistically nonsignificant in the HFpEF group alone. When analyzing the additional prognostic information afforded by adding MLHFQ to KCCQ in the overall, HFrEF, and HFpEF groups there was no significant improvement, although adding KCCQ to MLHFQ did significantly improve risk stratification. Scoring based upon the abbreviated KCCQ-12 did not reduce the prognostic accuracy of KCCQ. In conclusion, KCCQ is more prognostic of death/transplant/left ventricular assist device and hospitalization than MLHFQ in a combined cohort of patients with HFrEF and HFpEF, although the effect in HFpEF was less pronounced. KCCQ should be the preferred PROM for patients with HF if prognostication is a desired goal of using the PROMs.

Effect of Race on Outcomes Following Early Coronary Computed Tomographic Angiography or Standard Emergency Department Evaluation for Acute Chest Pain.

Objective: To examine racial differences in outcomes with coronary computed tomographic angiography (CCTA) vs standard emergency department (ED) evaluation for chest pain. Design: Retrospective analysis of the prospective, randomized, multicenter Rule Out Myocardial Ischemia/Infarction by Computer Assisted Tomography (ROMICAT-II) trial. Setting: ED at nine hospitals in the United States. Participants: 940 patients who were Caucasian or African American (AA) presenting to the ED with chest pain. Interventions: CCTA or standard ED evaluation. Main Outcome Measures: Length of stay, hospital admission, direct ED discharge, downstream testing and repeat ED visit or hospitalization for recurrent chest pain at 28 days. Safety end points: missed acute coronary syndrome (ACS) and cumulative radiation exposure during the index visit and follow-up period. Results: 659 (66%) patients self-identified as Caucasian and 281 (28%) self-identified as AA. AA were younger and more often female compared with Caucasians, had a higher prevalence of hypertension (64% vs 49%, P<.001) and diabetes (23% vs 14%, P<.001) and a lower prevalence of hyperlipidemia (28% vs 51%, P<.001). ACS was more frequent among Caucasians (10% vs 2%, P<.001). Randomization to CCTA resulted in a reduction in median LOS for Caucasians (7.4 vs 24.7 hours, P<.001) and AA (8.9 vs. 26.3, P<.001; P-interaction=.88). Both AA and Caucasian patients experienced greater radiation exposure and more downstream testing with CCTA compared with standard evaluation. Conclusions: Early CCTA reduced median LOS for both AA and Caucasian patients presenting to the ED with chest pain by approximately 17 hours compared with standard evaluation.

Multimarker Approach to Identify Patients With Higher Mortality and Rehospitalization Rate After Surgical Aortic Valve Replacement for Aortic Stenosis.

OBJECTIVES: This study sought to evaluate whether a multimarker approach might identify patients with higher mortality and hospitalization rates after aortic valve replacement (AVR) for aortic stenosis (AS). BACKGROUND: The society valve guidelines include accepted triggers for AVR in patients with severe asymptomatic AS, but circulating biomarkers do not have a clear role. METHOD: From a prospective registry of patients undergoing cardiac surgery between 2000 and 2012, 665 treated with surgical AVR (441 isolated) were evaluated. Seven biomarkers were measured on blood samples obtained before AVR. Biomarker levels were adjusted to account for the influence of age, sex, body mass index, and renal function; the median was used to determine an elevated value. Endpoints included all-cause mortality and all-cause and cardiovascular hospitalizations. Mean follow-up was 10.7 years and 299 (45%) died. RESULTS: Patients with 0 to 1, 2 to 3, 4 to 6, and 7 biomarkers elevated had 5-year mortality of 10%, 12%, 24%, and 33%, respectively, and 10-year mortality of 24%, 35%, 58%, and 71%, respectively (log-rank p < 0.001). The association between an increasing number of elevated biomarkers and increased all-cause mortality was observed among those with minimal symptoms (New York Heart Association functional class I or II) and those with a low N-terminal pro-B-type natriuretic peptide (p < 0.01 for both). Compared with those with 0 to 1 biomarkers elevated, patients with 4 to 6 or 7 biomarkers elevated had an increased hazard of mortality after adjustment for clinical risk scores (p < 0.01) and a 2- to 3-fold higher rate of all-cause and cardiovascular rehospitalization after AVR. Similar findings were obtained when evaluating cardiovascular mortality. Among patients with no or minimal symptoms, 42% had ≥4 biomarkers elevated. CONCLUSIONS: Among patients with severe AS treated with surgical AVR, an increasing number of elevated biomarkers of cardiovascular stress was associated with higher all-cause and cardiovascular mortality and a higher rate of repeat hospitalization. A multimarker approach may be useful in the surveillance of asymptomatic patients with severe AS to optimize surgical timing.

Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring.

BACKGROUND: Compared with traditional risk factors, coronary artery calcium (CAC) scores improve prognostic accuracy for atherosclerotic cardiovascular disease (ASCVD) outcomes. However, the relative impact of statins on ASCVD outcomes stratified by CAC scores is unknown. OBJECTIVES: The authors sought to determine whether CAC can identify patients most likely to benefit from statin treatment. METHODS: The authors identified consecutive subjects without pre-existing ASCVD or malignancy who underwent CAC scoring from 2002 to 2009 at Walter Reed Army Medical Center. The primary outcome was first major adverse cardiovascular event (MACE), a composite of acute myocardial infarction, stroke, and cardiovascular death. The effect of statin therapy on outcomes was analyzed stratified by CAC presence and severity, after adjusting for baseline comorbidities with inverse probability of treatment weights based on propensity scores. RESULTS: A total of 13,644 patients (mean age 50 years; 71% men) were followed for a median of 9.4 years. Comparing patients with and without statin exposure, statin therapy was associated with reduced risk of MACE in patients with CAC (adjusted subhazard ratio: 0.76; 95% confidence interval: 0.60 to 0.95; p = 0.015), but not in patients without CAC (adjusted subhazard ratio: 1.00; 95% confidence interval: 0.79 to 1.27; p = 0.99). The effect of statin use on MACE was significantly related to the severity of CAC (p < 0.0001 for interaction), with the number needed to treat to prevent 1 initial MACE outcome over 10 years ranging from 100 (CAC 1 to 100) to 12 (CAC >100). CONCLUSIONS: In a largescale cohort without baseline ASCVD, the presence and severity of CAC identified patients most likely to benefit from statins for the primary prevention of cardiovascular diseases.