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Background: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. Methods: We analyzed CAC levels in 324 healthy participants aged 21–45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users ( n = 65), sole e-cigarette users ( n = 19), sole combustible cigarette users ( n = 212), and dual users ( n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. Results: The cohort was 47% female, 51% Black/African American, with a mean (± SD) age of 31 ± 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q ⩽ 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q ⩽ 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q ⩽ 0.05). Conclusion: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Background: Psychosocial stressors may influence tobacco use. Few studies have examined the association of stressors and e-cigarette use in adolescents. Therefore, we examined the associations between psychosocial stressors and e-cigarette use among adolescents in the United States (U.S.). Methods: Using the 2019 Youth Risk Behavior Survey data (YRBS) (N=13,677), students were categorized as non, e-cigarette, and combustible cigarette users based on past 30-day use. The prevalence of use was assessed by participants’ sociodemographic characteristics. Poisson regression models were used to examine the association between stressors and e-cigarette and combustible cigarette use. To estimate the stressor burden score, stressors were grouped into scores: 0, 1-2, 3-4, and 5-7. Results: Overall, 65.0%, 32.7% and 6.0% were non, e-cigarette and combustible cigarettes users, respectively. E-cigarette use prevalence was higher among students who experienced stressors than those who did not ([bullying: 43.9% vs 29.0%]; [skipping school due to safety concerns: 48.0% vs 29.0%]; [depressive symptoms: 43.5% vs 26.5%]; [suicidal thoughts: 47.6% vs 29.3%]; [physical fight: 51.1% vs 28.3%]; [threatened with a weapon56.4% vs 30.9%]). Similar patterns were observed with combustible cigarette use. Students who experienced stressors were more likely to use e-cigarettes (Prevalence Ratio [PR] range: 1.08-1.21) and combustible cigarettes (PR range: 1.34-2.06) than students who did not. Students with higher burden scores had a higher prevalence and PR of e-cigarette use than those with score of zero (1-2 [1.28; 95% CI:1.15-1.42]; 3-4 [1.42; 95% CI:1.23-1.65]; 5-7 [1.45; 95% CI:1.22-1.73]) (ptrends Conclusion: This study demonstrated significant association between psychosocial stressors and e-cigarette use.

Updated data on the patterns of e-cigarette use among adults in the US are needed.To examine recent patterns in current and daily e-cigarette use among US adults.This repeated cross-sectional study used data from the 2017, 2018, and 2020 Behavioral Risk Factor Surveillance System, a nationally representative state-based survey of noninstitutionalized US adults. A total of 994 307 adults 18 years and older who were living in states and territories that provided data on e-cigarette use in 2017 (53 states and territories), 2018 (36 states and Guam), and 2020 (42 states and Guam) were included.The weighted prevalence of current (past 30 days) and daily e-cigarette use was estimated for each year, and changes in prevalence from 2017 to 2020 were assessed, first overall and then stratified by participant characteristics, including state or territory of residence.Among 994 307 adults from states with data on e-cigarette use, 429 370 individuals (weighted 51.3% female) were participants in the 2017 survey, 280 184 (weighted 52.1% female) were participants in the 2018 survey, and 284 753 (weighted 52.1% female) were participants in the 2020 survey. The weighted proportions of young adults aged 18 to 24 years were 12.6% in 2017, 11.8% in 2018, and 11.9% in 2020. Across all 3 years, 17 035 participants (weighted, 1.0%) were American Indian or Alaska Native, 22 313 (weighted, 4.6%) were Asian, 75 780 (weighted, 12.2%) were Black, 72 190 (weighted, 15.1%) were Hispanic, 4817 (weighted, 0.2%) were Native Hawaiian, 757 140 (weighted, 65.1%) were White, 20 332 (weighted, 1.3%) were multiracial, and 6245 (weighted, 0.5%) were of other races and/or ethnicities. The prevalence of current e-cigarette use was 4.4% (95% CI, 4.3%-4.5%) in 2017, which increased to 5.5% (95% CI, 5.4%-5.7%) in 2018 and decreased slightly to 5.1% (95% CI, 4.9%-5.3%) in 2020. The recent decrease, though modest, was observed mainly among young adults aged 18 to 20 years (from 18.9% [95% CI, 17.2%-20.7%] to 15.6% [95% CI, 14.1%-17.1%]; P = .004). However, the prevalence of daily e-cigarette use increased consistently from 1.5% (95% CI, 1.4%-1.6%) in 2017 to 2.1% (95% CI, 2.0%-2.2%) in 2018 and 2.3% (95% CI, 2.2%-2.4%) in 2020. Among young adults aged 21 to 24 years, there was a slight, albeit insignificant, increase in the prevalence of current e-cigarette use (from 13.5% [95% CI, 12.3%-14.7%] to 14.5% [95% CI, 13.2%-15.9%]; P = .28) but a significant increase in the prevalence of daily e-cigarette use (from 4.4% [95% CI, 3.8%-5.1%] to 6.6% [95% CI, 5.6%-7.6%]; P .001) between 2018 and 2020. State-level patterns in the prevalence of current e-cigarette use were heterogeneous, with states like Massachusetts (from 5.6% [95% CI, 4.8%-6.5%] to 4.1% [95% CI, 3.1%-5.3%]; P = .03) and New York (from 5.4% [95% CI, 4.9%-5.9%] to 4.1% [95% CI, 3.5%-4.7%]; P = .001) recording significant decreases between 2018 and 2020. In contrast, Guam (from 5.9% [95% CI, 4.5%-7.9%] to 11.4% [95% CI, 8.7%-14.8%]; P = .002) and Utah (from 6.1% [95% CI, 5.5%-6.7%] to 7.2% [95% CI, 6.5%-8.0%]; P = .02) recorded significant increases in current e-cigarette use over the same period.In this study, a slight decrease in the prevalence of current e-cigarette use was found between 2018 and 2020; this decrease was mainly observed among young adults aged 18 to 20 years. In contrast, daily e-cigarette use consistently increased, particularly among young adults aged 21 to 24 years. This increase in daily use suggests greater nicotine dependence among those who use e-cigarettes, warranting continued surveillance.

In-hospital cardiac arrest during cardiac catheterization is not uncommon. The extent of variation in survival after cardiac arrest occurring in the cardiac catheterization laboratory (CCL) and underlying factors are not well known.The aim of this study was to identify the factors associated with higher survival rates after an index cardiac arrest in the CCL.Within the GWTG (Get With The Guidelines)-Resuscitation registry, patients ≥18 years of age who had index in-hospital cardiac arrest in the CCL between January 1, 2003, and December 31, 2017, were identified. Hierarchical models were used to adjust for demographics, comorbidities, and cardiac arrest characteristics to generate risk-adjusted survival rates (RASRs) to discharge for each hospital with ≥5 cases during the study period. Median OR was used to quantify the extent of hospital-level variation in RASR.The study included 4,787 patients from 231 hospitals. The median RASR was 36% (IQR: 21%) and varied from a median of 20% to 52% among hospitals in the lowest and highest tertiles of RASR, respectively. The median OR was 1.71 (95% CI: 1.52-1.87), suggesting that the odds of survival for patients with identical characteristics with in-hospital cardiac arrest in the CCL from 2 randomly chosen different hospitals varied by 71%. Hospitals with greater annual numbers of cardiac arrest cases in the CCL had higher RASRs.Even in controlled settings such as the CCL, there is significant hospital-level variation in survival after in-hospital cardiac arrest, which suggests an important opportunity to improve resuscitation outcomes in procedural areas.

Background: Circulating Angiogenic Cells (CAC) are known to aid in endothelial repair and are a promising marker of vascular function. Electronic Nicotine Delivery Systems (ENDS) have been hypothesized to impact vascular health, however the association between ENDS and CACs is unknown. Hypothesis: We hypothesize that ENDS use, sole or dual, will be significantly associated with CAC levels. Methods: We analyzed CAC levels of 314 human participants enrolled in the Cardiovascular Injury due to Tobacco Use study, which is a multi-center cross-sectional study of healthy participants 21-45 years age, without known cardiovascular disease or cardiovascular disease risk factors. Four study groups were determined a priori - non-smokers (n=62), sole cigarette users (n=207), sole ENDS users (n=17), and dual users (cigarette and ENDS) (n=28). A total of 15 CACs were measured via a standardized flowcytometry protocol using four cell surface markers - CD146 (endothelial), CD34 (stem cell), CD45 (leukocyte), and ACC133 (early progenitor/stem cell). Regression analysis was conducted using a General Linear Model with gamma distribution and log-link. Model was adjusted for age, sex, race, ethnicity, and enrollment site. Results: Among sole ENDS users, two CACs were significantly higher and four CACs were significantly lower, as compared to referent non-smokers (all P Conclusion: CACs are sensitive to ENDS use, including dual use. Although CACs with endothelial surface markers were most commonly associated with ENDS/dual use, CACs with stem and early progenitor surface markers were also associated with ENDS/dual use. CACs are promising biomarkers of vascular function and further research is needed to quantify the effect of individual CAC on vascular function.

Introduction To implement and evaluate a blended online and in-person training to help mentors of early-career researchers appreciate the complexities of Tobacco Regulatory Science (TRS), refine TRS mentoring skills, and become acquainted with resources for providing effective guidance to TRS mentees. Methods TRS mentors engaged in a two-part pilot test of the training program. Authors evaluated both the online and in-person training using retrospective pre-post evaluations, which measure learning at the conclusion of a training program, and post-program focus groups. Twenty learners completed the online training, and 16 learners attended the in-person training module. Nine participants completed evaluations for the online module, and 12 participants completed evaluations for the in-person module. Results Program assessments revealed that participants found that the training achieved its overall goals. The majority of respondents (87.5%) rated the online portion of the training as valuable. For the in-person training, participants reported statistically significant improvements regarding confidence in: helping mentees to identify skills and training to effectively pursue TRS, assisting mentees in weighing career trajectories, and guiding mentees in conducting research responsive to TRS regulatory priorities. Conclusions The novel mentoring program was well received by faculty seeking to strengthen skills for mentoring early-career TRS researchers to navigate the complex landscape of TRS, explore diverse funding opportunities, and discern potential career trajectories. It provided unique content to address issues outside the traditional tobacco research training curriculum and offered specific information on regulatory policies, priorities, and opportunities. Implications This research documents the deployment and evaluation of a blended online and in-person training program for investigators mentoring early-career researchers working in TRS. Our assessment discovered that participants found the training to be valuable to their overall mentoring objectives. The training comprises a novel curriculum for investigators engaged in mentoring early-career researchers in a unique field, thus filling a deficit in the published literature by presenting a curriculum that has been customized to the unique needs of TRS mentors.

Background The safety and efficacy of supplemental oxygen in acute myocardial infarction (AMI) remains unclear. Study question To evaluate the safety and efficacy of supplemental oxygen in patients who present with AMI. Data sources We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, ISI Web of Science, Scopus, and conference proceedings from inception through January 2016. Study design Eligible studies were randomized trials that evaluated the role of oxygen compared with room air in AMI. The clinical outcome measured was 30-day mortality, and odds ratio (OR) was calculated for the measured outcome. The Mantel-Haenszel method was used to pool 30-day mortality in a random-effects model. Sensitivity analysis was carried out to evaluate the effect of revascularization of the culprit artery on the outcome. Results The pooled analysis suggested no difference in 30-day mortality [OR 1.09; 95% confidence interval (CI), 0.30-4.00; P = 0.89] between oxygen and room air. Metaregression demonstrated that all the between-study variance was because of coronary revascularization (P = 0.01, R = 1.0). A subgroup analysis suggested a trend toward increased mortality with oxygen (OR 3.26; 95% CI, 0.94-11.29; P = 0.06) when less than half of the patient population underwent revascularization. On the other hand, there was a nonsignificant numerical decrease in mortality with oxygen (OR 0.41; 95% CI, 0.14-1.19; P = 0.10) in the presence of coronary revascularization. Metaregression confirmed that all the between-study variance was because of coronary revascularization (P = 0.01, R = 1.0). Conclusions In this meta-analysis, we found that the evidence on the safety and efficacy of oxygen was not only weak and inconsistent but also had modest statistical power. The variation in results was mainly because of the presence or absence of revascularization of the culprit artery. Adequately powered studies are needed to further delineate the role of oxygen in patients undergoing coronary revascularization.

The increasing popularity and prevalence of electronic cigarettes (e-cigarettes) use in the USA necessitates careful evaluation of their proposed benefits and potential public health harms. This report provides a detailed review of current scientific evidence on potential benefits and health risks associated with e-cigarette use. E-cigarettes were introduced as a less harmful alternative to combustible cigarette smoking. However, evidence on their use as effective and safe smoking cessation aids remains inconclusive. Their rapid uptake among tobacco-naive individuals can lead to nicotine addiction and subsequent cigarette smoking. Although e-cigarettes appear to be relatively safer than combustible cigarettes, they expose users to known harmful constituents whose long-term health risks remain unknown. While e-cigarettes have the potential to aid in cessation of cigarette smoking when used as part of a structured cessation program, use among tobacco-naive youth and long-term dual use with combustible cigarettes should be strongly discouraged due to excess risk with dual use.

Our current knowledge about comparative differences in 30-day readmissions and the impact of readmissions on overall costs after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is largely derived from clinical trials. The objectives of this study were to compare readmissions and costs for TAVI and SAVR in a nationally representative population-based sample. The Healthcare Cost and Utilization Project's National Readmission Database was used for the study. Hierarchical multivariable regression analyses were used to examine differences in the propensity score 1:1 matched cohort. The matched cohort included 4,682 patients who survived index procedures done from January through November 2013. Compared with SAVR, the rate of 30-day readmission was not significantly different for endovascular TAVI (16% vs 18%; p = 0.19); and was higher for the transapical TAVI (22% vs 17%; p

OBJECTIVES This study assessed if frequent premature atrial contractions (PACs) were associated with decreased left atrial (LA) strain and adverse remodeling. BACKGROUND Left atrial dysfunction and enlargement increases risk of stroke. If frequent PACs cause LA dysfunction and remodeling, PAC suppressive therapy may be beneficial. METHODS Inclusion criteria were age ≥18 years and sinus rhythm. Exclusion criteria were atrial fibrillation or any etiology for LA enlargement. Hundred and thirty-two patients with frequent PACs (≥100/24 hours) by Holter were matched to controls. Speckle tracking strain of the left atrium was performed from the 4-chamber view. Strain measurements were LA peak contractile, reservoir and conduit strain and strain rates. RESULTS In the frequent PAC vs control group, PACs were more frequent (1959 ± 3796 vs 28 ± 25/24 hours, P

Cardiovascular disease increases incrementally with age and elderly patients concomitantly sustain multimorbidities, with resultant prescription of multiple medications. Despite conforming with disease-specific cardiovascular clinical practice guidelines, this polypharmacy predisposes many elderly individuals with cardiovascular disease to adverse drug events and non-adherence. Patient-centered care requires that the clinician explore with each patient his or her goals of care and that this shared decision-making constitutes the basis for optimization of medication management. This approach to aligning therapies with patient preferences is likely to promote patient satisfaction, to limit morbidity, and to favorably affect healthcare costs.

Individuals with spinal cord injury develop cardiovascular disease more than age-matched, non-injured cohorts. However, progression of systolic and diastolic dysfunction into cardiovascular disease after spinal cord injury is not well described. We sought to investigate the relationship between systolic and diastolic function in chronic spinal cord injury to describe how biological sex, level, severity, and duration of injury correlate with structural changes in the left ventricle. Individuals with chronic spinal cord injury participated in this study (n = 70). Registered diagnostic cardiac sonographers used cardiac ultrasound to measure dimensions, mass, and systolic and diastolic function of the left ventricle. We found no significant relationship to severity or duration of injury with left ventricle measurements, systolic function outcome, or diastolic function outcome. Moreover, nearly all outcomes measured were within the American Society of Echocardiography-defined healthy range. Similar to non-injured individuals, when indexed by body surface area (BSA) left ventricle mass [-14 (5) g/m2, p < .01], end diastolic volume [-6 (3) mL/m2, p < .05], and end systolic volume [-4 (1) mL/m2, p < .01] were significantly decreased in women compared with men. Likewise, diastolic function outcomes significantly worsened with age: E-wave velocity [-5 (2), p < .01], E/A ratio [-0.23 (0.08), p < .01], and e' velocity [lateral: -1.5 (0.3) cm/s, p < .001; septal: -0.9 (0.2), p < .001] decreased with age while A-wave velocity [5 (1) cm/s, p < .001] and isovolumic relaxation time [6 (3) ms, p < .05] increased with age. Women demonstrated significantly decreased cardiac size and volumes compared with men, but there was no biological relationship to dysfunction. Moreover, individuals were within the range of ASE-defined healthy values with no evidence of systolic or diastolic function and no meaningful relationship to level, severity, or duration of injury. Decreases to left ventricular dimensions and mass seen in spinal cord injury may result from adaptation rather than maladaptive myocardial remodeling, and increased incidence of cardiovascular disease may be related to modifiable risk factors.

Pulmonary arterial hypertension (PAH) leads to progressive increases in pulmonary vascular resistance (PVR), right heart failure, and death if left untreated. This review will summarize and discuss recent updates in the classification and management of patients with PAH. PAH requires careful hemodynamic assessment and is defined by a mean pulmonary artery pressure > 20 mmHg with normal left-sided filling pressures and a PVR ≥ 3 Wood units. Most patients with PAH require targeted pharmacotherapy based on multiparametric risk stratification. Significant improvements in clinical outcome have been realized through the approval of 14 unique pharmacotherapeutic options. The latest clinical recommendations provide the updated hemodynamic definition and clinical classification as well as evidence-based treatment recommendations. An important change is the focus on initial upfront combination therapy for most patients with PAH. Structured follow-up and escalation of treatment for those not achieving low-risk status is paramount.

Background— The association of short-term readmissions after percutaneous coronary intervention (PCI) on healthcare costs has not been well studied. Methods and Results— The Healthcare Cost and Utilization Project National Readmission Database encompassing 722 US hospitals was used to identify index PCI cases in patients ≥18 years old. Hierarchical regression analyses were used to examine the factors associated with risk of 30-day readmission and higher cumulative costs. We evaluated 206 869 hospitalized patients who survived to discharge after PCI from January through November 2013 and analyzed readmissions over 30 days after discharge. A total of 24 889 patients (12%) were readmitted within 30 days, with rates ranging from 6% to 17% across hospitals. Among the readmitted patients, 13% had PCI, 2% had coronary artery bypass surgery, and 3% died during the readmission. The most common reasons for readmission included nonspecific chest pain/angina (24%) and heart failure (11%). Mean cumulative costs were higher for those with readmissions ($39 634 versus $22 058; P 10 cumulative costs by 45% (β: 0.445; P Conclusions— In a national sample of inpatient PCI cases, 30-day readmissions were associated with a significant increase in cumulative costs. The majority of readmissions were because of low-risk chest pain that did not require any intervention. Ongoing effort is warranted to recognize and mitigate potentially preventable post-PCI readmissions.

Nearly 350 000 people in the United States have out-of-hospital cardiac arrest (OHCA) each year.1 Initiation of bystander cardiopulmonary resuscitation (CPR) improves survival after OHCA; however, there is significant geographic variation in the rates of both bystander CPR and OHCA survival in the United States, as much as 5-fold.2 The disparate geographic survival from OHCA was deemed unacceptable by the Institute of Medicine, prompting a call for strategic efforts to educate and train the public in CPR.2 In response, the American Heart Association set the goal to increase the rate of bystander CPR nationally from 31% to 62% of cardiac arrests by 2020.3 Rates of CPR training in the United States are low (median 2.4% of population) and vary by community, with low-income, rural, and minority communities having disproportionately low rates of CPR training.4 The Institute of Medicine identified this low rate of training as a critical barrier to performance of bystander CPR, recognizing that “initiatives designed to increase bystander CPR must overcome existing barriers… and teach the technical skills necessary to perform CPR with confidence.”2 Traditional 4-hour CPR training is costly in terms of time and money, limiting the number of bystanders who are able to be trained by this method. Despite development of alternative CPR training methods, nationwide rates of both CPR training and bystander-initiated CPR remain low. No true gold standard exists for training the public in CPR that is efficient, effective, and leads to retention of CPR skills. The goal of this innovation was to increase the effectiveness and efficiency of public CPR training by creating and implementing a novel, brief, multisensory CPR training method, which we call Alive in Five. In Jefferson County, Kentucky, the rate of bystander CPR in 2015 was 15.4%, below the national average of 31%; additionally, …

Background: Current non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. Aim: The aim of this study is to identify change specific to plaque disruption and pathological thrombosis. Methods: We quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI and 15 stable CAD subjects at two acute phase [time of catheterization (T0), six hours (T6)] and one quiescent (>3 months follow-up) time points. A statistical classifier was constructed utilizing (T0) abundances of a parsimonious set of metabolites that demonstrated a significant change between quiescent phase and the acute phase that was distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects. Results: Nineteen metabolites (Table 1) with an intra-subject fold change from time of acute thrombotic MI presentation to the quiescent state were distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate Conclusions: We have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state and from acute non-thrombotic MI and stable CAD. Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI.

Aims Current non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. The aim of this study was to identify changes specific to plaque disruption and pathological thrombosis that are distinct from acute myocardial necrosis. Methods and results We quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up) time points. A statistical classifier was constructed utilizing baseline (T0) abundances of a parsimonious set of 17 qualifying metabolites. Qualifying metabolites were those that demonstrated a significant change between the quiescent phase and the acute phase and that were distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at presentation. Nineteen metabolites demonstrated an intra-subject change from time of acute thrombotic MI presentation to the quiescent state that was distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate

Background Data are limited regarding transcatheter aortic valve replacement (TAVR)-related thrombocytopenia (TP). We sought to thoroughly characterize the presence, clinical impact, and severity of TP associated with TAVR. Methods and Results Data were collected from 90 patients who underwent TAVR using the Edwards SAPIEN valve (59 TF, 29 TA, 2 Tao). Platelet counts were evaluated peri-procedurally and for 8 days following TAVR. Platelet levels were compared and patients were divided into a no TP (No-TP) group 1, acquired (new) TP (NTP) group 2, pre-existing (pre-TAVR) TP (PTP) group 3, and further stratified based on the severity of TP: mild (M) TP (100–149 × 103 cell/µL) and moderate–severe (MS) TP (

BACKGROUND Access to hand-carried ultrasound technology for noncardiologists has increased significantly, yet development and evaluation of training programs are limited. OBJECTIVE We studied a focused program to teach hospitalists image acquisition of inferior vena cava (IVC) diameter and IVC collapsibility index with interpretation of estimated central venous pressure (CVP). METHODS Ten hospitalists completed an online educational module prior to attending a 1-day in-person training session that included directly supervised IVC imaging on volunteer subjects. In addition to making quantitative assessments, hospitalists were also asked to visually assess whether the IVC collapsed more than 50% during rapid inspiration or a sniff maneuver. Skills in image acquisition and interpretation were assessed immediately after training on volunteer patients and prerecorded images, and again on volunteer patients at least 6 weeks later. RESULTS Eight of 10 hospitalists acquired adequate IVC images and interpreted them correctly on 5 of the 5 volunteer subjects and interpreted all 10 prerecorded images correctly at the end of the 1-day training session. At 7.4 ± 0.7 weeks (range, 6.9–8.6 weeks) follow-up, 9 of 10 hospitalists accurately acquired and interpreted all IVC images in 5 of 5 volunteers. Hospitalists were also able to accurately determine whether the IVC collapsibility index was more than 50% by visual assessment in 180 of 198 attempts (91% of the time). CONCLUSIONS After a brief training program, hospitalists acquired adequate skills to perform and interpret hand-carried ultrasound IVC images and retained these skills in the near term. Though calculation of the IVC collapsibility index is more accurate, coupling a qualitative assessment with the IVC maximum diameter measurement may be acceptable in aiding bedside estimation of CVP. Journal of Hospital Medicine 2013;8:711–714. © 2013 Society of Hospital Medicine

The use of antithrombotic therapy (ATT) (bivalirudin or unfractionated heparin) is a class I recommendation for patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). This survey was conducted to better understand current United States (US) practices in terms of preferences regarding the selection of ATT in STEMI-PPCI, particularly in light of recent clinical trials.An electronic survey consisting of 9 focused questions was forwarded to 2676 US interventional cardiologists who were members of the Society for Cardiovascular Angiography and Interventions (SCAI).Among 390 responders (14.5%), bivalirudin with bail-out glycoprotein IIb/IIIa inhibitor (GPI) was the predominant strategy for 53% of operators, whereas 32% preferred heparin with bail-out GPI and 15% preferred heparin with more routine GPI. The duration of bivalirudin infusion varied widely among operators, and significant variability existed in the bolus dose of heparin that was preferred by operators. About 49% of respondents stated that the choice of ATT was not affected by the bleeding risk of the patient, although access site did appear to affect the choice of ATT for some operators. Notably, 43% of operators reported to have changed their practice regarding ATT in light of recent trial results.There is marked variability in self-reported ATT use in STEMI-PPCI among US interventional cardiologists. Given the patient-related variability in bleeding risk and mixed clinical trial results between the two predominant ATT agents, bivalirudin and unfractionated heparin, more data are needed in order to further inform and potentially unify clinical practice in STEMI-PPCI.

ObjectivesThis study tested the hypothesis that acute administration of the xanthine oxidase (XO) inhibitor allopurinol improves cardiac high-energy phosphate concentrations in human heart failure (HF) and increases the rate of adenosine triphosphate (ATP) synthesis through creatine kinase (CK), the primary myocardial energy reserve.BackgroundStudies of patients and animal models implicate impaired myocardial high-energy phosphate availability in HF. The XO reaction is a critical terminal step in ATP and purine degradation and an important source of reactive oxygen species. Thus, XO inhibition is a potentially attractive means to improve energy metabolism in the failing human heart.MethodsWe randomized 16 patients with nonischemic cardiomyopathy in a double-blind fashion to allopurinol (300 mg intravenously) or placebo infusion, 4-to-1, the latter for purposes of blinding only. The myocardial concentrations of ATP and creatine phosphate (PCr) and the rate of ATP synthesis through CK (CK flux) were determined by 31P magnetic resonance spectroscopy.ResultsAllopurinol infusion increased mean cardiac PCr/ATP and PCr concentration by ∼11% (p < 0.02), and mean CK flux by 39% (2.07 ± 1.27 μmol/g/s to 2.87 ± 1.82 μmol/g/s, p < 0.007). Calculated cytosolic adenosine diphosphate concentration decreased, whereas the free energy of ATP hydrolysis (ΔG∼ATP) increased with allopurinol. The increased CK flux was disproportionate to substrate changes, indicating increased CK enzyme activity.ConclusionsIntravenous administration of the XO inhibitor allopurinol acutely improves the relative and absolute concentrations of myocardial high-energy phosphates and ATP flux through CK in the failing human heart, offering direct evidence that myofibrillar CK energy delivery can be pharmaceutically augmented in the failing human heart. (Intravenous Allopurinol in Heart Failure; NCT00181155)

Prior studies demonstrate an association between specific beta-adrenergic receptor (β-AR) polymorphisms and clinical outcomes in patients with chronic heart failure and following acute coronary syndromes. The underlying mechanism may be due to differences in left ventricular remodeling. This study was undertaken to explore the relationship between LV remodeling after myocardial infarction and polymorphisms in the cardiac β1-AR and β2-AR genes.After first ST-segment elevation myocardial infarction (STEMI), 122 patients on chronic β1 receptor antagonist therapy underwent baseline and 6-month LV volume evaluation. We assessed the relationships between changes in LV volumes and the polymorphisms in β1-AR, β1-Arg389Gly and β1-Ser49Gly, and in β2-AR, β2-Gly16Arg and β2-Gln27Glu.We found that patients homozygous for the β2-Glu27 variant were 5.2 times more likely to be in the group with the highest end systolic volume (ESV) progression (OR 5.2, 95%CI 1.4-19.0). They were also more likely to have the largest progression of end diastolic volume (EDV) and decrease in LV ejection fraction (LVEF). For those with baseline LV dysfunction, being homozygous for Arg at amino acid position 389 in β1-AR was associated with decreases in ESV (-46 mL, CI -3.1, -88) and EDV (-40 mL, CI -1.1, -79) and an increase in LVEF (11%, CI 0.3, 22).We found that polymorphisms of the β1-AR and β2-AR genes are associated with differential LV remodeling in patients treated with a β1 receptor antagonist following STEMI.

Weather emergencies present a multifaceted challenge to residents and residency programs. Both the individual trainee and program may be pushed to the limits of physical and mental strain, potentially jeopardizing core competencies of patient care and professionalism. Although daunting, the task of preparing for these events should be a methodical process integrated into every residency training program.The core elements of emergency preparation with regard to inpatient services include identifying and staffing critical positions, motivating residents to consider the needs of the group over those of the individual, providing for basic needs, and planning activities in order to preserve team morale and facilitate recovery. The authors outline a four-step process in preparing a residency program for an anticipated short-term weather emergency. An example worksheet for emergency planning is included.With adequate preparation, residency training programs can maintain the highest levels of patient care, professionalism, and esprit de corps during weather emergencies. When managed effectively, emergencies may present an opportunity for professional growth and a sense of unity for those involved.

Adriamycin (ADR) is an established, life-saving antineoplastic agent, the use of which is often limited by cardiotoxicity. ADR-induced cardiomyopathy is often accompanied by depressed myocardial high-energy phosphate (HEP) metabolism. Impaired HEP metabolism has been suggested as a potential mechanism of ADR cardiomyopathy, in which case the bioenergetic decline should precede left ventricular (LV) dysfunction. We tested the hypothesis that murine cardiac energetics decrease before LV dysfunction following ADR (5 mg/kg ip, weekly, 5 injections) in the mouse. As a result, the mean myocardial phosphocreatine-to-ATP ratio (PCr/ATP) by spatially localized31P magnetic resonance spectroscopy decreased at 6 wk after first ADR injection (1.79 ± 0.18 vs. 1.39 ± 0.30, means ± SD, control vs. ADR, respectively, P < 0.05) when indices of systolic and diastolic function by magnetic resonance imaging were unchanged from control values. At 8 wk, lower PCr/ATP was accompanied by a reduction in ejection fraction (67.3 ± 3.9 vs. 55.9 ± 4.2%, control vs. ADR, respectively, P < 0.002) and peak filling rate (0.56 ± 0.12 vs. 0.30 ± 0.13 μl/ms, control vs. ADR, respectively, P < 0.01). PCr/ATP correlated with peak filling rate and ejection fraction, suggesting a relationship between cardiac energetics and both LV systolic and diastolic dysfunction. In conclusion, myocardial in vivo HEP metabolism is impaired following ADR administration, occurring before systolic or diastolic abnormalities and in proportion to the extent of eventual contractile abnormalities. These observations are consistent with the hypothesis that impaired HEP metabolism contributes to ADR-induced myocardial dysfunction.

Although cardiac troponin I (cTnI) elevation in patients presenting to the hospital with supraventricular tachycardia (SVT) is well recognized, the prevalence, predictors, and prognostic significance of cTnI elevation associated with SVT presentation are not known. We screened records of all patients presenting to 2 hospitals over a 4-year period with the diagnosis of SVT confirmed by 12-lead electrocardiogram, and who had at least 1 measured cTnI level and at least 1 year of follow-up after discharge. The primary endpoint was the occurrence of 1 of the following outcomes: death, myocardial infarction, or cardiovascular rehospitalization. Seventy-eight patients met the study criteria (54% female; mean age, 62.2 +/- 15.8 yr), and 29 patients (37.2%) had an elevated cTnI level of > or =0.06 ng/mL (range, 0.06-7.78 ng/mL). Univariate predictors of elevated cTnI included left ventricular ejection fraction (LVEF)

Background: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M‐MDD and NonM‐MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro‐inflammatory cytokines via induction of the enzyme indoleamine 2,3‐dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM‐MDD adolescents, adolescents with M‐MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3‐hydroxyanthranilic acid (3‐HAA, neurotoxin) and 3‐HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. Methods: Subjects were 20 adolescents with M‐MDD, 30 adolescents with NonM‐MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale‐Revised (CDRS‐R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high‐performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS‐R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons. Results: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M‐MDD compared to NonM‐MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M‐MDD group between KYN and 3‐HAA/KYN and CDRS‐R. Conclusions: Findings support the notion that adolescent M‐MDD may represent a biologically distinct clinical syndrome.

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD).Materials and Methods.Four healthy subjects (4 men, mean age29 ± 3years and eleven CAD patients (6 women, mean age61±10years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA).Results.LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced.Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30–45 minutes after administration of the contrast agent.

A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-gamma, tumor necrosis factor-alpha, interleukin [IL]-6, IL-1beta, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-gamma/IL-4.Thirty adolescents with MDD (19 females; 13 medication-free/naïve; ages 12-19) of at least 6 weeks duration and a minimum severity score of 40 on the Children's Depression Rating Scale-Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann-Whitney test was used to compare subjects with MDD and controls.Adolescents with MDD had significantly elevated plasma IFN-gamma levels (3.38+/-11.8 pg/ml versus 0.37+/-0.64 pg/ml; p0.003), and IFN-gamma/IL-4 ratio (16.6+/-56.5 versus 1.76+/-2.28; p=0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52+/-2.88 pg/ml versus 0.49+/-0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded.Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow.

Purpose: To develop a computer algorithm to measure myocardial infarct size in gadolinium-enhanced magnetic resonance (MR) imaging and to validate this method using a canine histopathological reference. Materials and Methods: Delayed enhancement MR was performed in 11 dogs with myocardial infarction (MI) determined by triphenyltetrazolium chloride (TTC). Infarct size on in vivo and ex vivo images was measured by a computer algorithm based on automated feature analysis and combined thresholding (FACT). For comparison, infarct size by human manual contouring and simple intensity thresholding (based on two standard deviation [2SD] and full width at half maximum [FWHM]) were studied. Results: Both in vivo and ex vivo MR infarct size measured by the FACT algorithm correlated well with TTC (R 0.95– 0.97) and showed no significant bias on Bland Altman analysis (P not significant). Despite similar correlations (R 0.91– 0.97), human manual contouring overestimated in vivo MR infarct size by 5.4% of the left ventricular (LV) area (equivalent to 55.1% of the MI area) vs. TTC (P 0.001). Infarct size measured by simple intensity thresholdings was less accurate than the proposed algorithm (P 0.001 and P 0.007). Conclusion: The FACT algorithm accurately measured MI size on delayed enhancement MR imaging in vivo and ex vivo. The FACT algorithm was also more accurate than human manual contouring and simple intensity thresholding approaches.

Segmented cine MRI generally requires breath-holding, which can be problematic for many patients. Navigator echo techniques, particularly successful for free-breathing coronary MRA, are incompatible with the acquisition strategies and SSFP pulse sequences commonly used for cine MRI. The purpose of this work is to introduce a new self-gating technique deriving respiratory gating information directly from the raw imaging data acquired for segmented cine MRI. The respiratory self-gating technique uses interleaved radial k-space sampling to provide low-resolution images in real time during the free-breathing acquisition that are compared to target expiration images. Only the raw data-producing images with high correlation to the target images are included in the final high-resolution reconstruction. The self-gating technique produced cine series with no significant differences in quantitative image sharpness to series produced using comparable breath-held techniques. Because of the difficulties associated with breath-holding, the respiratory self-gating technique represents an important practical advance for cardiac MRI. Published 2004 Wiley-Liss, Inc.†

The third Adult Treatment Panel of the National Cholesterol Education Program has recently issued revised guidelines for the treatment of cholesterol in adults. Increased attention to the metabolic syndrome and diabetes, including the inaccuracy of the low-density lipoprotein cholesterol (LDL-C) measurement in these patients because of elevated triglycerides is highlighted. To overcome the inaccuracy of the Friedewald equation in calculating LDL-C when the triglycerides are elevated, measuring non-high-density lipoprotein (non-HDL-C) may provide a better means to follow these patients toward their treatment goals. Recently, non-HDL-C was shown to be a better predictor of cardiovascular death than LDL-C, even in patients with triglyceride levels below 200 mg/dL. The authors review the basis for using non-HDL-C as a treatment target for cholesterol, in comparison with other lipoproteins.

Data are limited regarding transcatheter aortic valve replacement (TAVR)-related thrombocytopenia (TP). We sought to thoroughly characterize the presence, clinical impact, and severity of TP associated with TAVR.Data were collected from 90 patients who underwent TAVR using the Edwards SAPIEN valve (59 TF, 29 TA, 2 Tao). Platelet counts were evaluated peri-procedurally and for 8 days following TAVR. Platelet levels were compared and patients were divided into a no TP (No-TP) group 1, acquired (new) TP (NTP) group 2, pre-existing (pre-TAVR) TP (PTP) group 3, and further stratified based on the severity of TP: mild (M) TP (100-149 × 10(3) cell/µL) and moderate-severe (MS) TP (100 × 10(3) cell/µL). Pre-TAVR point prevalence and post-TAVR incidence of TP were 40% and 79%, respectively (P 0.001); nadir platelet count in all groups occurred day 4 post-TAVR. Baseline predictors for developing MS TP in groups 2-3 included baseline TP, leaner body mass, smaller pre-procedural aortic valve area, higher peak aortic jet velocity, and worsening baseline renal function. Development of "major" TP (nadir platelet count100 × 103 cell/µL, ≥50% decrease) predicted a higher risk of major vascular complications (OR 2.78 [95% CI, 1.58-3.82]) and major bleeding (OR 3.18 [95% CI, 1.33-5.42]) in group 3.TAVR-related TP is predictable and classification by PTP and TP severity prior to TAVR allows for better risk stratification in predicting in-hospital clinical outcomes. Major TP in the presence of worsening TP is predictable and is associated with worse clinical outcomes. © 2014 Wiley Periodicals, Inc.

Morbidity and mortality from heart failure (HF) are high, and current risk stratification approaches for predicting HF progression are imperfect. Adenosine triphosphate (ATP) is required for normal cardiac contraction, and abnormalities in creatine kinase (CK) energy metabolism, the primary myocardial energy reserve reaction, have been observed in experimental and clinical HF. However, the prognostic value of abnormalities in ATP production rates through CK in human HF has not been investigated. Fifty-eight HF patients with nonischemic cardiomyopathy underwent 31P magnetic resonance spectroscopy (MRS) to quantify cardiac high-energy phosphates and the rate of ATP synthesis through CK (CK flux) and were prospectively followed for a median of 4.7 years. Multiple-event analysis (MEA) was performed for HF-related events including all-cause and cardiac death, HF hospitalization, cardiac transplantation, and ventricular-assist device placement. Among baseline demographic, clinical, and metabolic parameters, MEA identified four independent predictors of HF events: New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), African-American race, and CK flux. Reduced myocardial CK flux was a significant predictor of HF outcomes, even after correction for NYHA class, LVEF, and race. For each increase in CK flux of 1 μmol g−1 s−1, risk of HF-related composite outcomes decreased by 32 to 39%. These findings suggest that reduced CK flux may be a potential HF treatment target. Newer imaging strategies, including noninvasive 31P MRS that detect altered ATP kinetics, could thus complement risk stratification in HF and add value in conditions involving other tissues with high energy demands, including skeletal muscle and brain.

Morbidity and mortality from heart failure (HF) are high, and current risk stratification approaches for predicting HF progression are imperfect. Although ATP is required for normal cardiac contraction and abnormalities in energy metabolism have been observed in experimental and clinical HF, the

Objectives Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects. Background Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD). Methods Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period. Results In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: −6.4%±2.0% vs. −5.0%±2.4%, p = 0.22; PDFV: −4.0%±4.6% vs. −4.2%±5.3%, p = 0.83; blood-flow: −9.7%±5.1% vs. −8.7%±6.3%, p = 0.38). Conclusion MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.

We report the case of a 60-year-old man with a history of coronary bypass surgery 20 years prior who had a fever, chest pain, and a mediastinal mass develop after a complicated postoperative course of abdominal aortic aneurysm resection. A mycotic aneurysm of the saphenous vein graft to his left anterior descending coronary artery was diagnosed based on blood culture results and visualization of the aneurysm before resection. A summary of the saphenous vein graft aneurysm and pseudoaneurysm cause, diagnosis, and management is detailed.

The reports on the impact of co-infection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) on the development of cardio-metabolic diseases have been conflicting. We evaluated the impact of HCV co-infection with incidence of diabetes, dyslipidemia, and major adverse cardiac events (