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Each month, we will present a challenging Case of the Month for The Green Journal readers, who must use their clinical acumen to arrive at the correct answer. We will also post the case each month on the Journal's web site (http://www.elsevier.com/locate/ajmselect). Several possible answers may be consistent with the case presentation; use your best judgment. Please send your answer (one per respondent) and indicate the case to which you are responding to The Green Journal at editors@amjmed.org or via FAX to (415) 447-2799. Only those answers with a complete mailing address will be considered. The correct answer will appear in the August issue of the Journal. The first five persons who submit correct answers will receive a free one-year subscription to the Journal. Colleagues of Dr. Hirsch in Ann Arbor, Michigan, are not eligible for this month's case. If you would like to contribute a case, please submit a brief synopsis (<250 words) to the editorial office. An individual may win only once per calendar year. [ABSTRACT FROM AUTHOR]

Importance: After the initial disruption from the COVID-19 pandemic, it is unclear how patterns of e-cigarette use in the US have changed., Objective: To examine recent patterns in current and daily e-cigarette use among US adults in 2021., Design, Setting, and Participants: This cross-sectional study used data from the 2021 Behavioral Risk Factor Surveillance System (BRFSS) database. The BRFSS is the largest national telephone-based survey of randomly sampled adults in the US. Adults aged 18 years or older, residing in 49 US states (all except Florida), the District of Columbia, and 3 US territories (Guam, Puerto Rico, and the US Virgin Islands), were included in the data set. Data analysis was performed in January 2023., Main Outcomes and Measures: The main outcome was age-adjusted prevalence of current and daily e-cigarette use overall and by participant characteristics, state, and territory. Descriptive statistical analysis was conducted, applying weights to account for population representation., Results: This study included 414 755 BRFSS participants with information on e-cigarette use. More than half of participants were women (51.3%). In terms of race and ethnicity, 0.9% of participants were American Indian or Alaska Native, 5.8% were Asian, 11.5% were Black, 17.3% were Hispanic, 0.2% were Native Hawaiian or Other Pacific Islander, 62.2% were White, 1.4% were of multiple races or ethnicities, and 0.6% were of other race or ethnicity. Individuals aged 18 to 24 years comprised 12.4% of the study population. The age-standardized prevalence of current e-cigarette use was 6.9% (95% CI, 6.7%-7.1%), with almost half of participants using e-cigarettes daily (3.2% [95% CI, 3.1%-3.4%]). Among individuals aged 18 to 24 years, there was a consistently higher prevalence of e-cigarette use, with more than 18.6% reporting current use and more than 9.0% reporting daily use. Overall, among individuals reporting current e-cigarette use, 42.2% (95% CI, 40.7%-43.7%) indicated former combustible cigarette use, 37.1% (95% CI, 35.6%-38.6%) indicated current combustible cigarette use, and 20.7% (95% CI, 19.7%-21.8%) indicated never using combustible cigarettes. Although relatively older adults (aged ≥25 years) who reported current e-cigarette use were more likely to report former or current combustible cigarette use, younger adults (aged 18-24 years) were more likely to report never using combustible cigarettes. Notably, the proportion of individuals who reported current e-cigarette use and never using combustible cigarettes was higher in the group aged 18 to 20 years (71.5% [95% CI, 66.8%-75.7%]) compared with those aged 21 to 24 years (53.0% [95% CI, 49.8%-56.1%])., Conclusion and Relevance: These findings suggest that e-cigarette use remained common during the COVID-19 pandemic, particularly among young adults aged 18 to 24 years (18.3% prevalence). Notably, 71.5% of individuals aged 18 to 20 years who reported current e-cigarette use had never used combustible cigarettes. These results underscore the rationale for the implementation and enforcement of public health policies tailored to young adults.

Despite the growing use of electronic cigarettes (EC) in the Unites States, particularly among young people, and their perceived safety, current evidence suggests that EC usage may cause adverse clinical cardiovascular effects. Therefore, we aim to pool all studies evaluating the association of EC exposure with cardiovascular health. Medline, Cochrane CENTRAL, and Scopus were searched for studies from January 1, 2006 until December 31, 2022. Randomized and observational studies reporting cardiovascular outcomes, hemodynamic parameters, and biomarkers of platelet physiology, before and after acute or chronic EC exposure were pooled using a random-effects model. Overall, 27 studies (n = 863) were included. Heart rate increased significantly after acute EC exposure (weighted mean difference [WMD]: 0.76 bpm; 95% confidence interval [CI], 0.48, 1.03; P < 0.00001; I 2 = 92%). Significant increases in systolic blood pressure (WMD: 0.28 mmHg; 95% CI, 0.06, 0.51; P = 0.01; I 2  = 94%), diastolic blood pressure (WMD: 0.38 mmHg; 95% CI, 0.16, 0.60; P = 0.0006; I 2  = 90%), and PWV (WMD: 0.38; 95% CI, 0.13, 0.63; P = 0.003; I 2  = 100%) were also observed. Augmentation index increased significantly (SMD: 0.39; 95% CI, 0.11, 0.67; P = 0.007; I 2 = 90%), whereas reduction in flow-mediated dilation (WMD: -1.48; 95% CI, -2.49, -0.47; P = 0.004; I 2 = 45%) was observed. Moreover, significant rise in both soluble P-selectin (WMD: 4.73; 95% CI, 0.80, 8.66; P = 0.02; I 2  = 98%) and CD40L (WMD: 1.14; 95% CI, 0.41, 1.87; P = 0.002; I 2  = 79%) was observed. Our results demonstrate that smoking EC is associated with a significant increase in cardiovascular hemodynamic measures and biomarkers. Our findings can aid policymakers in making informed decisions regarding the regulation of EC to ensure public safety., Competing Interests: Declaration of Competing Interest Dr Hirsch is supported by National Heart, Lung, and Blood Institute research funding (grant 5U54HL120163-10). Dr. Blaha has received Grants: NIH, Novo Nordisk, Novartis, Speakers Bureau – Esperion, Amgen. Dr. DeFilippis reports grant support from the National Institutes of Health, Private Foundations, Ionis Pharmaceuticals, Astra Zeneca and is on the speaker bureau for Esperion. Other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Surveillance of e-cigarette use among different population groups is important for the timely implementation and evaluation of tobacco regulatory policies. In this review, we identified 13 nationally representative, repeatedly conducted epidemiologic surveys that assess e-cigarette use among U.S. youth and/or adults and have been instrumental in e-cigarette surveillance. These surveys included National Youth Tobacco Survey, Youth Risk Behavior Surveillance System, Monitoring the Future Survey, International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Survey, Behavioral Risk Factor Surveillance System, National Health Interview Survey, Tobacco Use Supplement of the Current Population Survey, Health Information National Trends Survey, Tobacco Products and Risk Perception Surveys, ITC Four Country Smoking and Vaping Survey, National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, and Population Assessment of Tobacco and Health. These surveys vary in scope and detail, with their unique strengths and the regulatory questions that can be answered using each survey data. We also highlighted the gaps in these surveys and made recommendations for improvement., Competing Interests: We declare no competing interests., (© 2023 The Authors.)

Background: This study explores the association between psychosocial stressors and current e-cigarette use among adolescents in the United States., Methods: We used data from 12,767 participants in the 2019 National Youth Risk Behavioral Survey to examine the association between psychosocial stressors (bullying, sexual assault, safety-related absence from school, depressive symptoms, suicidal ideation, physical altercation, and weapon threats) and past-30-day e-cigarette use using multivariable-adjusted logistic regression models. We examined the association for each stressor and then as a burden score (0-7). To compare the strength of the association between stressors and current e-cigarette use to current combustible cigarette use, we additionally examined the association between each stressor and current combustible cigarette use., Results: Approximately 32.7% reported current e-cigarette use. The weighted prevalence of current e-cigarette use was higher among individuals who experienced stressors than those who did not. For example, bullying (43.9% vs. 29.0%). Similar prevalence patterns were seen among other stressors. Individuals who experienced stressors had significantly higher adjusted odds of current e-cigarette use than those who did not (OR [Odds Ratio] range: 1.47-1.75). Similarly, individuals with higher burden scores had a higher prevalence (zero [20.5%], one [32.8%], two [41.4%], three [49.6%], four to seven [60.9%]) and higher odds of current e-cigarette use (OR range: 1.43-2.73) than those with a score of zero. The strength of the association between the stressors and e-cigarette use was similar to that between the stressors and combustible cigarette use., Conclusion: The study demonstrates a significant association between psychosocial stressors and adolescent e-cigarette use, highlighting the potential importance of interventions, such as targeted school-based programs that address stressors and promote stress management, as possible means of reducing adolescent e-cigarette use. Future research directions include exploring underlying mechanisms linking stressors to e-cigarette use and evaluating the effectiveness of interventions addressing stressors in reducing adolescent e-cigarette use., (© 2023. The Author(s).)

Among adolescents, sole use is the most common pattern of e-cigarette use. However, concurrent use of e-cigarettes with other tobacco products is not uncommon and may be associated with high-risk behaviors. We used data from 12,767 participants in the 2019 Youth Risk Behavior Survey to examine the patterns of tobacco product use among youth in the US. First, we examined the prevalence of e-cigarette-specific patterns of tobacco use (nonuse[no tobacco product use], sole use[sole e-cigarette use], dual-use[e-cigarette and one other tobacco product], and poly use[e-cigarette and two or more other tobacco products]). Then, using multivariable Poisson regression, we assessed how the tobacco use patterns were associated with the misuse of nine substances of abuse (alcohol, marijuana, cocaine, ecstasy, hallucinogens, heroin, inhalants, injectables, and methamphetamines). 62.9% of youth reported nonuse of any tobacco product. The weighted prevalence of sole e-cigarette use, dual use, and poly use was 23.2%, 4.2%, and 3.3%, respectively. Across all the substances explored, the prevalence was highest among poly users, followed by dual users, sole users, and non-users. Compared to non-users, sole, dual, and poly users had 7.8(95 %CI:6.1-10.0), 14.3(95 %CI:10.8-18.8), and 19.7(95 %CI:15.0-25.9) times higher adjusted prevalence of reporting past-30-day binge drinking, after adjusting for age, sex, race/ethnicity, sexual orientation, and depressive symptoms. This pattern was seen across all the different substances explored. These findings highlight the high prevalence of substance misuse among youth who use tobacco products and the need to educate and counsel on substances of abuse among this population, particularly among poly-tobacco users., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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: 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., Objectives: The aim of this study was to identify the factors associated with higher survival rates after an index cardiac arrest in the CCL., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Funding Support and Author Disclosures Dr Chan is supported by a grant from the National Heart, Lung, and Blood Institute (R01HL160734); and has received consultancy funding from Optum Rx and the American Heart Association. Dr Hirsch is supported by National Heart, Lung, and Blood Institute research funding (grant 5U54HL120163-10). Dr Drachman has received consulting honoraria from Boston Scientific, Broadview Ventures, Cardiovascular Systems, and Cordis. Dr Hirsch has received consultant funding from Riva Health. Dr Elmariah has received institutional research support from Siemens and Boehringer Ingelheim Pharmaceuticals; and has received consulting fees from Medtronic and Edwards Lifesciences. Dr Bhatt is an advisory board member for Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; is on the boards of directors of AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; is inaugural chair of the American Heart Association Quality Oversight Committee; is a member of data monitoring committees for the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), the Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), the Duke Clinical Research Institute, the Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News and ACC.org; chair, American College of Cardiology Accreditation Oversight Committee), the law firm of Arnold & Porter (for work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee, funded by Boehringer Ingelheim; AEGIS-II executive committee, funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor and associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education steering committees), MJH Life Sciences, Piper Sandler, the Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education steering committees); is deputy editor of Clinical Cardiology; is chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site coinvestigator for Abbott, Biotronik, Boston Scientific, Cardiovascular Systems Inc, St. Jude Medical (now Abbott), Philips, and Svelte; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, Merck, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Detailed description of the prevalence and sources of e-cigarettes among youth is needed to inform effective regulatory policies. We used the Youth Risk Behavior Surveillance System data (2015-2019) to assess trends in current (past-30-day-use) and frequent (≥10 days in past-30-days) e-cigarette use among United States high schoolers before the COVID-19 pandemic. First, we assessed trends overall and then stratified by participants' sociodemographic characteristics, use of other tobacco products, and experiences of psychosocial stress. We also evaluated past year quit attempts and the changing sources of e-cigarettes. Our sample size was 41,021 (15,356-2015; 12,873-2017; 12,792-2019). The prevalence of current e-cigarette use increased from 24.0% (95%CI:21.9%-26.3%) in 2015 to 32.7% (30.4%-35.1%) in 2019. The proportion of current users who reported frequent use also increased significantly from 22.6% (20.4%-24.8%) to 45.4% (42.7%-48.2%). Thus, an increasing proportion of US high school students who use e-cigarettes reported frequent use, indicating greater nicotine dependence. The increase in current and frequent e-cigarette use was more pronounced in youth who reported other substance use and psychosocial stressors such as bullying. Between 2017 and 2019, there was a decline in the proportion of youth who bought e-cigarettes online (6.9% to 3.2%) or from convenience stores (22.0% to 16.6%). Conversely, there was an increase in the proportion who borrowed (34.5% to 40.1%) or purchased e-cigarettes through other people (10.7% to 18.0%), indicating that most youth are evading age-related restrictions by obtaining e-cigarettes from other people. Finally, a considerable proportion of youth tobacco users are making quit attempts; 47.6% (45.1%-50.1%) in 2019., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Importance: Updated data on the patterns of e-cigarette use among adults in the US are needed., Objective: To examine recent patterns in current and daily e-cigarette use among US adults., Design, Setting, and Participants: 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., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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.

Introduction: In an era of complex, multi-institutional, team-based science, there is little guidance for the successful creation of effective, collaborative, multisite training programs., Objective: We designed, implemented, and evaluated a multi-institutional Tobacco Regulatory Science (TRS) fellowship representing a scalable program that may be customized for other research areas., Methods: Using a mixed-methods approach, we analyzed program evaluations from trainees enrolled in the first 7 years of the American Heart Association (AHA) Tobacco Regulation and Addiction Center (A-TRAC) fellowship (2014-2021). We also reported the program outcomes, including published TRS manuscripts, independent grant funding, Food and Drug Administration (FDA) Docket comments submitted on TRS topics, TRS oral and poster presentations, research awards, and promotions in the TRS field., Results: Thirty-five unique trainees (49% [n = 17] female, 29% [n = 10] Black) from eight institutions within the A-TRAC network participated in the fellowship since its inception. The trainees reported 74 TRS publications, 78 TRS oral or poster presentations, 25 FDA Docket comment submissions, and 13 funded grant awards. Participant evaluations indicated six areas of programmatic strength: 1) blended instruction medium with webinars and in-person meetings, 2) curricular emphasis on theories of experiential learning, 3) focus on career and professional development, 4) integrated mentorship model, 5) culture of feedback and feedforward to foster successful learning, and 6) focus on recruiting diverse participants. The A-TRAC model stresses experiential education, feedback and feedforward, and peer learning., Conclusions: Our resource-effective, needs-driven program is a reproducible model for institutions interested in developing multisite, virtual research education programs in the era of team science., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2022.)

Cardiac myocyte atrophy and the resulting decreases to the left ventricular mass and dimensions are well documented in spinal cord injury. Therapeutic interventions that increase preload can increase the chamber size and improve the diastolic filling ratios; however, there are no data describing cardiac adaptation to chronic afterload increases. Research from our center has demonstrated that spinal cord epidural stimulation (scES) can normalize arterial blood pressure, so we decided to investigate the effects of scES on cardiac function using echocardiography. Four individuals with chronic, motor-complete cervical spinal cord injury were implanted with a stimulator over the lumbosacral enlargement. We assessed the cardiac structure and function at the following time points: (a) prior to implantation; (b) after scES targeted to increase systolic blood pressure; (c) after the addition of scES targeted to facilitate voluntary (i.e., with intent) movement of the trunk and lower extremities; and (d) after the addition of scES targeted to facilitate independent, overground standing. We found significant improvements to the cardiac structure (left ventricular mass = 10 ± 2 g, p < 0.001; internal dimension during diastole = 0.1 ± 0.04 cm, p < 0.05; internal dimension during systole = 0.06 ± 0.03 cm, p < 0.05; interventricular septum dimension = 0.04 ± 0.02 cm, p < 0.05), systolic function (ejection fraction = 1 ± 0.4%, p < 0.05; velocity time integral = 2 ± 0.4 cm, p < 0.001; stroke volume = 4.4 ± 1.5 ml, p < 0.01), and diastolic function (mitral valve deceleration time = -32 ± 11 ms, p < 0.05; mitral valve deceleration slope = 50 ± 25 cm s -1 , p < 0.05; isovolumic relaxation time = -6 ± 1.9 ms, p < 0.05) with each subsequent scES intervention. Despite the pilot nature of this study, statistically significant improvements to the cardiac structure, systolic function, and diastolic function demonstrate that scES combined with task-specific interventions led to beneficial cardiac remodeling, which can reverse atrophic changes that result from spinal cord injury. Long-term improvements to cardiac function have implications for increased quality of life and improved cardiovascular health in individuals with spinal cord injury, decreasing the risk of cardiovascular morbidity and mortality., (Copyright © 2020 Legg Ditterline, Wade, Ugiliweneza, Singam, Harkema, Stoddard and Hirsch.)

Purpose of Review: 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., Recent Findings: 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.

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., Competing Interests: The authors have declared that no competing interests exist.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: 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., Recent Findings: 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.

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 < .0001). LA peak contractile strain was reduced in the group with frequent PACs vs controls (-7.85 ± 4.12% vs -9.33 ± 4.45%, P = .006). LA peak late negative contractile strain rate was less negative in the frequent PAC vs control group (-0.63 ± 0.27 s -1 vs -0.69 ± 0.32 s -1 , P = .051). LA reservoir and conduit strain and strain rates did not differ. LA volume index (LAVI) was larger in the frequent PAC vs control group (26.6 ± 7.8 vs 24.6 ± 8.8 mL/m 2 , P < .05). Frequent PACs were an independent predictor of reduced LA peak contractile strain and reduced LA peak late negative contractile strain rate., Conclusions: Patients with frequent PACs have reduced LA peak contractile strain and strain rates and larger LAVI compared to controls. Frequent PACs are an independent predictor of reduced LA peak contractile strain and strain rate. These findings support the hypothesis that frequent PACs impair LA contractile function and promote adverse LA remodeling., (© 2018 Wiley Periodicals, Inc.)

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 <0.01) group. The 30-day cumulative costs were higher for the 2 endovascular TAVI ($51,025 vs $46,228; p = 0.03) and transapical TAVI ($59,575 vs $45,792; p <0.01). In multivariable analyses, the risk of 30-day readmission was similar for endovascular TAVI (odds ratio [OR] 0.93; 95% confidence interval [CI] 0.78 to 1.12) and was 27% higher for transapical TAVI (OR 1.27; 95% CI 1.02 to 1.57). Cumulative costs (index plus readmission costs) were 13% (β 0.13; 95% CI 0.10 to 0.15) and 19% (β 0.19; 95% CI 0.16 to 0.23) higher for the endovascular TAVI and transapical TAVI, respectively. In conclusion, the rate of readmissions was similar for endovascular TAVI and SAVR but the costs were 26% higher for TAVI than for SAVR., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chronic low blood pressure and orthostatic hypotension remain challenging clinical issues after severe spinal cord injury (SCI), affecting health, rehabilitation, and quality of life. We previously reported that targeted lumbosacral spinal cord epidural stimulation (scES) could promote stand and step functions and restore voluntary movement in patients with chronic motor complete SCI. This study addresses the effects of targeted scES for cardiovascular function (CV-scES) in individuals with severe SCI who suffer from chronic hypotension. We tested the hypothesis that CV-scES can increase resting blood pressure and attenuate chronic hypotension in individuals with chronic cervical SCI. Four research participants with chronic cervical SCI received an implant of a 16-electrode array on the dura (L1-S1 cord segments, T11-L1 vertebrae). Individual-specific CV-scES configurations (anode and cathode electrode selection, voltage, frequency, and pulse width) were identified to maintain systolic blood pressure within targeted normative ranges without skeletal muscle activity of the lower extremities as assessed by electromyography. These individuals completed five 2-h sessions using CV-scES in an upright, seated position during measurement of blood pressure and heart rate. Noninvasive continuous blood pressure was measured from a finger cuff by plethysmograph technique. For each research participant there were statistically significant increases in mean arterial pressure in response to CV-scES that was maintained within normative ranges. This result was reproducible over the five sessions with concomitant decreases or no changes in heart rate using individual-specific CV-scES that was modulated with modest amplitude changes throughout the session. Our study shows that stimulating dorsal lumbosacral spinal cord can effectively and safely activate mechanisms to elevate blood pressures to normal ranges from a chronic hypotensive state in humans with severe SCI with individual-specific CV-scES.

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 <0.001). The multivariable analyses showed that readmission increased the log 10 cumulative costs by 45% (β: 0.445; P <0.001). There was no significant difference in cumulative costs by the type of insurance., 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., (© 2017 American Heart Association, Inc.)

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.

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 <5%)., Conclusions: We have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state after MI, from acute non-thrombotic MI, and from 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.

Background: 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., Methods: 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)., Results: 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., Conclusion: 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.

Background: In accordance with the 2007 American College of Cardiology and American Heart Association infective endocarditis (IE) guideline update, antibiotic prophylaxis is now being restricted to a smaller number of cardiac conditions with very high risk for adverse outcomes from IE. However, there is scant data on IE trends since this major practice change in the United States., Objectives: The aim of this study was to compare temporal trends in IE incidence, microbiology, and outcomes before and after the change in the 2007 IE prophylaxis guideline in the United States., Methods: The NIS (Nationwide Inpatient Sample) database was used to investigate IE hospitalization rates in the United States from 2000 through 2011. The mean annual rates of IE before and after the 2007 guideline change were compared using segmented regression analysis., Results: There were 457,052 IE-related hospitalizations in the United States from 2000 to 2011, with a steady increase in incidence (p < 0.001). The trend in IE hospitalization rates from 2000 to 2007 and from 2008 to 2011 was not significantly different (p = 0.74). The increases in the number of Staphylococcus IE cases per million population during the study periods 2000 to 2007 and 2008 to 2011 were similar (p = 0.13), but Streptococcus IE hospitalization rates were significantly higher after the release of new guidelines (p = 0.002). Finally, valve replacement rates for IE steadily increased from 2000 to 2007 (p = 0.03) but showed a plateau from 2007 to 2011. Overall, there was no significant difference in the rates of valve replacement for IE before and after the release of new guideline (p = 0.23)., Conclusions: These results show that IE incidence has increased in the United States over the past decade. With regard to the microbiology of IE, there has been a significant rise in the incidence of Streptococcus IE since the 2007 guideline revisions. However, the rates of hospitalization and valve surgery for IE have not increased since the change in IE prophylaxis guideline in 2007., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 × 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 count <100 × 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., Conclusion: 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., (© 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.

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., (© 2013 Society of Hospital Medicine.)

Background: Asymptomatic left ventricular systolic dysfunction is an important risk factor for heart failure and death. Given the availability of patients, trained personnel, and equipment, the hospital is an ideal setting to identify and initiate treatment for left ventricular systolic dysfunction. The purpose of this study was to determine the prevalence of asymptomatic left ventricular systolic dysfunction in patients 45 years of age or older with at least one clinical heart failure risk factor admitted to a general medical service., Methods: Bedside, hand-carried echocardiography provided quantitative assessment of left ventricular systolic function in 217 medical inpatients 45 years of age or older who had at least one heart failure risk factor. Patients with known or suspected heart failure or with an assessment of left ventricular function in the past 5 years were excluded. We measured the prevalence of asymptomatic left ventricular systolic dysfunction, defined by left ventricular ejection fraction of 50% or lower, and its association with heart failure risk factors., Results: Of 207 patients with interpretable images, 11 (5.3%) had a left ventricular ejection fraction of 50% or lower. Patients with left ventricular systolic dysfunction had more heart failure risk factors than those without left ventricular systolic dysfunction (3.09±0.8 vs 2.5±1.0, P=.04). The total number of heart failure risk factors trended towards an association with a greater prevalence of asymptomatic left ventricular systolic dysfunction, but this did not reach significance (odds ratio 1.74; 95% confidence interval, 0.97-3.12, P=.06)., Conclusions: Asymptomatic left ventricular systolic dysfunction is present in about 1 of every 20 general medical inpatients with at least one risk factor for heart failure. Because treatment of asymptomatic left ventricular systolic dysfunction may reduce morbidity, further studies examining the costs and benefits of using hand-carried ultrasound to identify this important condition in general medical inpatients are warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Adulterants "cut into" street heroin are common and often not detected by standard urine toxicology screening; however, their unwitting co-injection may have clinical consequences. We report a case of accelerated atrioventricular junctional arrhythmia that we determined to have been caused by quinine/quinidine cut into heroin. While identification and discontinuation of the offending agent helps confirm the diagnosis and is the treatment of choice, this is often complicated by the individual's dependence on the street drug in which the adulterant is mixed. This case highlights the need for clinicians to be aware of common adulterants, to know how to test for them, and to consider them as possible causes of medical complications in individuals who use drugs.

Background: Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness., Methods and Results: Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008)., Conclusions: There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.

Objectives: This 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., Background: Studies 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., Methods: We 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 (31)P magnetic resonance spectroscopy., Results: Allopurinol 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., Conclusions: Intravenous 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)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary vessel distensibility is reduced with atherosclerosis and normal aging, but direct measurements have historically required invasive measurements at cardiac catheterization. Therefore, we sought to assess coronary artery distensibility noninvasively using 3.0 Telsa coronary magnetic resonance imaging (MRI) and to test the hypothesis that this noninvasive technique can detect differences in coronary distensibility between healthy subjects and those with coronary artery disease (CAD). A total of 38 healthy, adult subjects (23 men, mean age 31 ± 10 years) and 21 patients with CAD, diagnosed using x-ray angiography (11 men, mean age 57 ± 6 years) were studied using a commercial whole-body MRI system. In each subject, the proximal segment of a coronary artery was imaged for the cross-sectional area measurements using cine spiral MRI. The distensibility (mm Hg(-1) × 10(3)) was determined as (end-systolic lumen area - end-diastolic lumen area)/(pulse pressure × end-diastolic lumen area). The pulse pressure was calculated as the difference between the systolic and diastolic brachial blood pressure. A total of 34 healthy subjects and 19 patients had adequate image quality for coronary area measurements. Coronary artery distensibility was significantly greater in the healthy subjects than in those with CAD (mean ± SD 2.4 ± 1.7 mm Hg(-1) × 10(3) vs 1.1 ± 1.1 mm Hg(-1) × 10(3), respectively, p = 0.007; median 2.2 vs 0.9 mm Hg(-1) × 10(3)). In a subgroup of 10 patients with CAD, we found a significant correlation between the coronary artery distensibility measurements assessed using MRI and x-ray coronary angiography (R = 0.65, p = 0.003). In a group of 10 healthy subjects, the repeated distensibility measurements demonstrated a significant correlation (R = 0.80, p = 0.006). In conclusion, 3.0-Tesla MRI, a reproducible noninvasive method to assess human coronary artery vessel wall distensibility, is able to detect significant differences in distensibility between healthy subjects and those with CAD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: 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., Methods: 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., Results: 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)., Conclusion: 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.

Background: 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., Summary: 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., Conclusion: 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.

Coronary arterial fistulas are rare communications between vessels or chambers of the heart. Although cardiac symptoms associated with fistulas are well described, fistulas are seldom considered in the differential diagnosis of acute myocardial ischemia. We describe the case of a 64-year-old man who presented with left shoulder pain, signs of heart failure, and a new left bundle branch block (LBBB). Cardiac catheterization revealed a small left anterior descending (LAD)-to-pulmonary artery (PA) fistula. Diuresis led to subjective improvement of the patient's symptoms and within several days the LBBB resolved. We hypothesize that the coronary fistula in this patient contributed to transient ischemia of the LAD territory through a coronary steal mechanism. We elected to observe rather than repair the fistula, as his symptoms and ECG changes resolved with treatment of his heart failure.

Objectives: The goal was to test 2 hypotheses: first, that coronary endothelial function can be measured noninvasively and abnormal function detected using clinical 3.0-T magnetic resonance imaging (MRI); and second, that the extent of local coronary artery disease (CAD), in a given patient, is related to the degree of local abnormal coronary endothelial function., Background: Abnormal endothelial function mediates the initiation and progression of atherosclerosis and predicts cardiovascular events. However, direct measures of coronary endothelial function have required invasive assessment., Methods: The MRI was performed in 20 healthy adults and 17 patients with CAD. Cross-sectional coronary area and blood flow were quantified before and during isometric handgrip exercise, an endothelial-dependent stressor. In 10 severe, single-vessel CAD patients, paired endothelial function was measured in the artery with severe stenosis and the contralateral artery with minimal disease., Results: In healthy adults, coronary arteries dilated and flow increased with stress. In CAD patients, coronary artery area and blood flow decreased with stress (both p ≤ 0.02). In the paired study, coronary artery area and blood flow failed to increase during exercise in the mildly diseased vessel, but both area (p = 0.01) and blood flow (p = 0.02) decreased significantly in the severely diseased, contralateral artery., Conclusions: Endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified noninvasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) 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.

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 localized (31)P magnetic resonance spectroscopy decreased at 6 wk after first ADR injection (1.79 + or - 0.18 vs. 1.39 + or - 0.30, means + or - 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 + or - 3.9 vs. 55.9 + or - 4.2%, control vs. ADR, respectively, P < 0.002) and peak filling rate (0.56 + or - 0.12 vs. 0.30 + or - 0.13 microl/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.

Aortic stiffness increases with age and may contribute to adverse remodeling after myocardial infarction (MI). The authors examined whether vascular stiffness affects left ventricular (LV) size after MI using contrast-enhanced cardiac magnetic resonance imaging. Despite similar infarct sizes, patients aged 60 years or older (n=30) had a lower ejection fraction (42+/-15 vs 53+/-11%, P<.01) and greater end-systolic volume index (75+/-47 vs 44+/-18 mL/m(2), P<.01) than younger patients (n=19). As infarct size increased, LV end-systolic volumes (P<.0001) and ejection fraction (P<.0001) in the older participants were progressively greater. Participants with greater aortic stiffness had greater end-systolic volume indices (P<.0001) and lower ejection fraction (P<.0001) with increasing infarct size. Using multivariate analysis, MI size (P<.001) and aortic distensibility (P=.02) were significant predictors of end-systolic volume index. Older patients have increased LV size after MI compared with younger patients, possibly related to age-related decreases in aortic distensibility affecting LV remodeling.

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., ((c) 2006 Wiley-Liss, Inc.)

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. , Inc., (Copyright 2004 Wiley-Liss, Inc.)