tbuckley/cabot-search huggingface dataset:
Abstract 16473: Loss of the Apelin-Apelin Receptor Signaling Axis Worsens Hemodynamic Alterations and Right Ventricular (rv) Adaptation and Abrogates 17ß-Estradiol (E2)-Mediated Protection in Experimental Pulmonary Arterial Hypertension (PAH)
Authors: Andrea L Frump, Todd Cook, Amanda Fisher, Valerie Nadeau, Steeve Provencher, Sebastien Bonnet, Tim Lahm
Journal: Circulation (2020)

Introduction: Women are more likely to develop PAH but exhibit more favorable hemodynamics and better survival than men. These improved outcomes have been linked to protective effects of E2. We recently linked RV-protective effects of E2 to regulation of apelin signaling. However, the role of apelin and its receptor APJ in RV failure is unknown. Hypothesis: RV cardiomyocytes (RVCM)-derived apelin exerts beneficial effects on RV endothelial cells (RVECs). Apelin-APJ signaling is necessary for E2’s RV-protective effects. Methods: Apelin and APJ abundance were quantified (Western blot) and immunolocalized in RVs from PAH patients. In vivo , RV failure was induced in male Sprague-Dawley rats by pulmonary artery banding (PAB). A subset of PAB rats were treated with E2 ± APJ inhibitor ML221. Hemodynamics, RV function and molecular changes were assessed. To study the role of RVCM apelin, conditioned media was collected from RVCMs after apelin knockdown and then added to RVECs. In addition, conditioned media from untreated RVCMs was added to RVECs pretreated with ML221. Lastly, RVECs were treated with E2 ± siApelin or ML221. p&lt;0.05 was considered statistically significant. Results: In PAH RVs, apelin and APJ localized to RVCMs and RVECs and were decreased vs controls (p&lt;0.05). In PAB+E2+ML221 rats, inhibition of apelin signaling resulted in more RV hypertrophy and decreased RV function (p&lt;0.05 vs sham or PAB+E2). Conditioned media from RVCMs+siApelin reduced RVEC eNOS phosphorylation, transwell migration and ring formation (p&lt;0.05 vs scrambled control conditioned media). Concomitantly, treatment of RVECs with ML221 blocked transwell migration and ring formation induced by RVCM conditioned media (p&lt;0.05 vs RVEC+veh control). Lastly, treatment of RVECs with siApelin or ML221 abrogated stimulatory effects of E2 on angiogenic function (p&lt;0.05). Conclusions: Apelin and APJ are decreased in PAH-RVs and loss of apelin-APJ signaling results in more severe RV failure and abrogates E2-mediated RV protection. Apelin is secreted by RVCMs and exerts a beneficial paracrine effect on RVECs, where it is required for E2 to stimulate angiogenesis. Apelin-APJ signaling may represent a novel and therapeutically targetable, cell- and sex-specific signaling axis in the RV.
Abstract MP34: The Association Between Periodontal Disease And Incident Heart Failure: The Atherosclerosis Risk In Communities Study
Authors: Rebecca L Molinsky, Faye L Norby, Bing Yu, Amil M Shah, Pamela L Lutsey, Jim Pankow, Chiadi E Ndumele, Panos N Papapanou, Paolo C Colombo, Melana Yuzefpolskaya, James D Beck, Ryan Demmer
Journal: Circulation (2021)

Introduction: Periodontal disease, resulting from inflammatory host-response to dysbiotic subgingival microbiota, has been associated with incident hypertension, heart attack, stroke and diabetes. Limited data exist investigating the prospective relationship between periodontal disease and incident heart failure (HF) and HF subtypes. We hypothesize that periodontal disease is associated with increased risk for heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Methods: We studied 6,707 participants enrolled in the Atherosclerosis Risk in Communities Study who received a full-mouth clinical periodontal examination at visit 4 (1996-1998) and had longitudinal follow-up starting in 2005. Participants were classified as being periodontally healthy, having periodontal disease (based on the Periodontal Profile Classification (PPC)), or being edentulous. Hospitalization records were reviewed, and HF events were adjudicated and classified as HFpEF, HFrEF or HF of unknown ejection fraction (HFunknownEF) from 2005-2018. We used multivariable-adjusted Cox proportional hazards models to assess the association between periodontal disease or edentulism and incident HF. Results: Among participants 58% had periodontitis and 19% were edentulous. During a median follow-up time of 13 years, 1,178 cases of incident HF occurred (350 HFpEF, 319 HFrEF and 509 HFunknownEF). Periodontal disease and being edentulous were both associated with increased risk for both HFpEF and HFrEF (Table). Conclusion: Periodontal disease measured in mid-life was associated with both incident HFpEF and HFrEF. Adverse microbial exposures underlying periodontal disease might represent a modifiable risk factor for inflammation-induced heart failure pathophysiology.
Abstract P010: Cardiac Troponin T Based On The Latest Generation Assay And Cardiovascular Disease: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Yasuyuki Honda, Yejin Mok, Junichi Ishigami, Kellan E Ashley, Ron C Hoogeveen, Christie M Ballantyne, Amy Karger, Elizabeth Selvin, Kunihiro Matsushita
Journal: Circulation (2021)

Background: High-sensitivity cardiac troponin T (TnT) is a potent predictor of cardiovascular disease (CVD) in the general population. Recently, the US FDA has approved Roche fifth generation (Gen 5) TnT assay (more sensitive than the fourth generation [Gen 4] TnT assay). Since many previous epidemiological studies used Gen 4 TnT, it is important to characterize the association of Gen 5 TnT with major CVD events. Methods: We first assessed correlation of Gen 5 vs. Gen 4 TnT in a subsample of 91 participants. Then, as the main analysis, we examined the association of Gen 5 TnT at visit 3 (1993-1995) with major CVD events (coronary heart disease [CHD], stroke, heart failure [HF], and peripheral artery disease [PAD]). Gen 5 TnT was categorized as &lt;6 (limit of quantification), 6-&lt;8, 8-&lt;14, 14-&lt;19, and ≥19 ng/L. CHD and stroke events were adjudicated whereas HF and PAD were based on hospitalization codes. We also conducted a subgroup analysis by prevalent CVD at baseline. Results: Gen 5 TnT and Gen 4 TnT had a correlation coefficient of 0.98 (0.88 after excluding outliers &gt;3SD). Of 11,979 participants (mean age 60 [SD 6] years, 1,840 [15%] with prevalent CVD), 5,856 (49%) participants had quantifiable levels of TnT. During a median follow-up of 22.1 years, there were 1,850 CHD events, 1,075 stroke events, 2,908 HF cases, and 571 PAD cases. Gen 5 TnT showed a robust dose response association with each CVD type, with adjusted hazard ratio 2-4 for TnT ≥19 (vs.&lt;6) ng/L ( Table ). Even the category 6-&lt;8 ng/L showed significantly elevated risk for all outcomes except stroke. The associations were stronger for HF and PAD than CHD or stroke (all p-values using seemingly unrelated regression &lt;0.001). The associations were similar regardless of baseline CVD status. Conclusions: Gen 5 TnT was highly correlated with Gen 4 TnT and gave quantifiable values in half middle-aged adults. Gen 5 TnT was robustly associated with major CVD events (especially HF and PAD) in the general population, supporting its usefulness in epidemiological research and clinical practice.
Response to: ‘Correspondence on ‘Which factors are associated with bone marrow oedema suspicious of axial spondyloarthritis as detected by MRI in the sacroiliac joints and the spine in the general population?’ by Su<i>et al</i>
Authors: Xenofon Baraliakos, Adrian Richter, Carsten O Schmidt, Juergen Braun
Journal: Annals of the Rheumatic Diseases (2021)

We would like to thank our colleagues from Taiwan for their interest in our work and their comments.1 The Study of Health in Pomerania (SHIP) cohort is a population-based epidemiological study which was designed to investigate common risk factors, subclinical disorders and manifest diseases with no interest in one specific disease but rather in data relevant for the prevalence and incidence of common diseases and their risk factors. Importantly, this was the first population-based cohort study worldwide which included whole-body MRI, which raised our interest many years ago.

We appreciate the comments of our colleagues from Taiwan on potentially better methods to assess MRI lesions suggestive of axial spondyloarthritis (axSpA). In general, we agree that the STIR sequence, in combination with a T1-weighted sequence, is currently the best method to identify axSpA-related lesions in sacroiliac joints (SIJs)2 and the spine. As a matter of fact, in our study, short tau inversion recovery (STIR) sequences for the evaluation of the SIJs were used. For the evaluation of spinal MRIs, T1 and T2 …
Abstract 13038: Utility of Left Atrial Strain Mechanics and Stiffness in Patients With Hypertrophic Cardiomyopathy
Authors: Yoshihito Saijo, Erik H Van Iterson, Maria Vega Brizneda, Milind Y Desai, Harry M Lever, Nicholas G Smedira, Per Wierup, Maran Thamilarasan, Zoran B Popovic, Richard A Grimm, Brian P Griffin, Bo Xu
Journal: Circulation (2020)

Introduction: Llittle is known about the relationship between LA strain mechanics and exercise intolerance in hypertrophic cardiomyopathy (HCM), or whether LA strain mechanics might serve as novel imaging markers in predicting the need for septal myectomy. Hypothesis: LA mechanical dysfunction would be associated with impaired exercise capacity and clinical deterioration necessitating septal myectomy in HCM. Methods: Consecutive patients with HCM who underwent exercise stress echocardiography and cardiopulmonary exercise testing between October 2015 and April 2019 were enrolled prospectively. LA structure parameters (maximum and minimum LA volume indices) and LA function parameters were measured. LA strain mechanics (reservoir, conduit and contractile strains) were analyzed by speckle tracking echocardiography. LA stiffness was calculated as the ratio of E/e’ to reservoir strain. Based on the quartile of percent-predicted peak VO 2 , the study cohort was divided into four groups. Exercise intolerance was defined as the lowest quartile of percent-predicted peak VO 2 (≤52%). Results: Of 536 HCM patients studied (mean age: 51 ± 15 years, 42% female), 212 (40%) demonstrated exercise intolerance. Receiver operating characteristics analysis demonstrated LA contractile strain, using a cut-off of 13.8%, to be optimal for predicting exercise intolerance (AUC: 0.68, p &lt;0.001). On multivariable logistic regression analysis, impaired LA contractile strain was an independent predictor for exercise intolerance (p &lt;0.001). Among 258 patients who were followed up at our center, patients with LA stiffness worse than the median value (≥0.41) had significantly higher probability of requiring myectomy, compared with those with LA stiffness below the median (p = 0.02, Figure ). Conclusions: Impaired LA contractile strain was an independent predictor of exercise intolerance in HCM. Patients with worse LA stiffness were more likely to require septal myectomy.
Progression vs Cyst Stability of Branch-Duct Intraductal Papillary Mucinous Neoplasms After Observation and Surgery
Authors: Giovanni Marchegiani, Tommaso Pollini, Stefano Andrianello, Giorgia Tomasoni, Marco Biancotto, Ammar A. Javed, Benedict Kinny-Köster, Neda Amini, Youngmin Han, Hongbeom Kim, Wooil Kwon, Michael Kim, Giampaolo Perri, Jin He, Claudio Bassi, Brian K. Goh, Matthew H. Katz, Jin-Young Jang, Christopher Wolfgang, Roberto Salvia
Journal: JAMA Surgery (2021)

The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information.To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations.The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months).Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination.A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001).These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.
Abstract 13379: Cause-specific Mortality by Diffuse Coronary Artery Calcium Phenotypes: Results From the Coronary Artery Calcium Consortium
Authors: Ramzi Dudum, Zeina A Dardari, David Feldman, Daniel Berman, Matthew J Budoff, Michael D Miedema, Khurram Nasir, Alan Rozanski, John A Rumberger, Leslee J Shaw, Miguel Cainzos Achirica, Jaideep Patel, Michael J Blaha
Journal: Circulation (2020)

Objectives: We sought to assess characteristics of diffuse coronary artery calcium (CAC) phenotypes and their associations with cause-specific mortality. Background: CAC is a measure of subclinical atherosclerosis and improves risk stratification. CAC characteristics including vessel involvement, number of vessels, volume, and density have been shown to differentially impact risk. Less is known about clinical predictors of a diffuse CAC phenotype and its impact on cause-specific mortality. Methods: The CAC Consortium is a retrospective, multi-site cohort of 66,636 participants without CHD who underwent CAC scoring. Risk factor data were collected at enrollment or scan. Participants with CAC&gt;0 were included—CAC area, CAC density, and the CAC index of diffusion (the percentage of total CAC in the vessel with the highest CAC score) were calculated and the association between CAC characteristics and CVD- and CHD-specific mortality was assessed. Results: In 28,147 study participants (mean age 58.3 years, 25% female, and 89.6% white), ~66% had ≥2 calcified vessels. Diabetes, hypertension, and hyperlipidemia were predictors of multivessel involvement (p&lt;0.001). After controlling for CAC score, those with 4-vessel CAC had more CAC area involved with less dense calcification compared to those with 1-vessel involvement. After adjustment, those with CAC score 1-299 had a graded increase in CVD- and CHD-specific mortality with increasing vessel number compared with 1-vessel CAC. No difference was seen for individuals with CAC &gt;300. Among those with multivessel CAC involvement, all-cause survival was significantly worse in diffuse compared to other phenotypes. Conclusion: Diffuse CAC involvement was characterized by less dense calcification, more CAC area, multiple coronary vessel involvement, and presence of certain traditional risk factors. Multivessel CAC is associated with increased CVD- and CHD-specific mortality, particularly among CAC scores 1-299.
Covid-19: How will a waiver on vaccine patents affect global supply?
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Temporary dysphagia affects up to 50% of stroke patients in the acute stage of their illness and often necessitates tube feeding. In these patients, the placing of nasogastric tubes is often difficult or impossible. This study evaluated the efficiency and tolerability of a previously described new method for tube placing, which utilises the induction of the swallowing reflex and has therefore been called “reflex placement”. In 14 of 16 patients in whom the conventional approach failed, the new method was successful. A comparison of the cardiovascular responses to both methods in another 12 patients revealed significantly smaller increases in heart rate and systolic blood pressure during application of the new method. We therefore suggest the use of reflex placement in patients who have suffered a stroke and need tube feeding due to dysphagia.
Abstract 16054: Medical Management and Outcomes of Non-obstructive Coronary Artery Disease
Authors: Sarah Payne, Ethan Fry, Jeffrey Michel, Robert J Widmer
Journal: Circulation (2020)

Introduction: Non-obstructive coronary artery disease (NOCAD) is associated with increased morbidity and higher medical expenses compared to those without NOCAD. Currently there are no set guideline-directed interventions for this patient population. This study examined the management and subsequent cardiovascular (CV) events in those deemed to have NOCAD. Hypothesis: We hypothesized that maximal use of medical therapy would correlate with reduced events. Methods: We undertook a retrospective chart review of 1,752 patients who underwent cardiac catheterization from 10/23/2017 through 10/24/2018 at a tertiary care center. NOCAD was defined as patients underwent cardiac catheterization for ischemic symptoms/testing, but did not receive percutaneous coronary or surgical intervention, were not pre-operative, and had at least one year of follow-up post-catheterization. We obtained medications at the time of catheterization as well as subsequent CV testing and events including hospitalizations and emergency department (ED) visits. Results: Of the 168 patients diagnosed with NOCAD, 12 patients later suffered a CV event including NSTEMI, heart failure exacerbation, or stroke. Of these patients, 41.7% were not been placed on aspirin, statin, beta-blocker (BB), calcium channel blocker (CCB), aldactone, ACE inhibitor (ACEi), or angiotensin II receptor blocker (ARB). In NOCAD patients on statin therapy there was a reduced utilization of CV testing at one year (43.3% vs 58.7%, p=0.04). Furthermore we note a significant reduction in rehospitalizations and ED visits in those on statin (14.5% vs 29.4%, p=0.02) not seen in patients on aspirin (23.8% vs 20.6%, p=0.63), CCB (22.2% vs 25.0%, p=0.76), aldactone (36.7% vs 19.6%, p=0.05), ACEi/ARB (23.1% vs. 22.2%, p=0.90), and even note a significant increase in events in those on BB (30.3% vs 16.3%, p=0.03). Conclusions: While NOCAD is associated with increased morbidity and healthcare utilization, the initiation of statin appears to reduce future CV testing and rehospitalization/ED visits that is not noted with aspirin, BB, CCB, Aldactone, or ACEi/ARB use. Recognition of NOCAD, and initiation of statin therapy could be beneficial in this patient population.
Abstract P062: Trends And Disparities In Diabetes Among Adults In The United States, 1999-2018
Authors: Junxiu Liu, Stella S Yi, Rienna Russo, Victoria Mayer, Yan Li
Journal: Circulation (2021)

Introduction: Diabetes (DM) increases cardiovascular disease morbidity and mortality and the risk of severe complications/death among patients with COVID-19. We aimed to estimate the trends of DM over time among adults in the US. Hypothesis: We anticipated an increase in DM and persistent disparities by racial/ethnic and socioecnomic subgroups from 1999 to 2018. Methods: Data were from a nationally representative sample of US adults (≥20 years; NHANES 1999-2018). Diagnosed DM was defined as a self-reported previous diagnosis of DM by a physician or any other health professionals (other than during pregnancy). Undiagnosed DM was defined as elevated levels of fasting plasma glucose (FPG≥126 mg/dL) or HbA1c (≥6.5%). Total DM included those who had either diagnosed or undiagnosed diabetes. Prediabetes was defined as no DM but a HbA1c level of 5.7% - 6.4% or an FPG level of 100 mg/dL-125 mg/dL. All estimates were age-standardized to the 2010 US census population for age groups 20-44, 45-64, and 65+ years. All analyses accounted for the complex survey design. Logistic regressions were conducted to calculate a P-value for trend. Results: Our sample included 53,533 US adults. From 1999 to 2018, the age-adjusted prevalence of total DM increased significantly from 9.05% (95% CI, 7.80%-10.2%) to 13.9% (95% CI, 12.5%-15.4%) and the prevalence of prediabetes increased from 22.5% (20%-25.2%) to 40.2% (37.4%-43.1%) (P-trends&lt;0.001). The rate of increase in prevalence was higher among Mexican Americans but lower among non-Hispanic black individuals compared to non-Hispanic white individuals (all P-trends&lt;0.01, P-interaction=0.003). Trends in total DM by education and income levels were similar to the overall trend but disparities persisted between low- and high-socioeconomic groups (all P-trends&lt;0.001, P-interaction&gt;0.05) ( Figure 1 ). Conclusions: The prevalence of DM increased significantly from 1999 to 2018 among US adults. There are substantial and persistent disparities between racial/ethnic and socioeconomic subgroups.
Abstract 14288: Substantial Hospital-level Variation in Troponin Testing After Non-cardiac Surgery
Authors: Paymon M Azizi, Lu Han, Maria Koh, Angela Jerath, Harindra C Wijeysundera, Duminda N Wijeysundera, Peter Austin, Dennis T Ko
Journal: Circulation (2020)

Introduction: There is an increasing emphasis in detecting postoperative myocardial infarction (PMI) using routine troponin testing after non-cardiac surgery. However, clinical practice guidelines vary considerably in their recommendations. We conducted a population-based cohort study in Ontario, Canada to assess the degree of hospital-level variation associated with troponin testing after three commonly performed surgeries. Methods: We conducted a retrospective cohort study of adults (40-105 y) undergoing major orthopedic, colorectal, or vascular surgery in Ontario, Canada from January 1, 2010 to December 31, 2017. Hierarchical logistic regression modeling was used to model the association of patient, surgery, and hospital factors with postoperative troponin testing, while accounting for clustering at the hospital level. Results: We identified 176,454 eligible patients. Canadian Cardiovascular Society guidelines recommended troponin testing for 73.5%, 90.8% and 95.6% of orthopedic, colorectal, and vascular surgery patients respectively, but only 6.7%, 16.6%, and 50.2% were actually tested. Inter hospital variation in testing rates was considerable for the three surgeries (Figure; 0-33%, 0-38% and 18-84%). Even after risk-adjustment, the median odds ratio for testing across hospitals was still 1.74, 1.63, and 2.65 for orthopedic, colorectal, and vascular surgery, respectively. This corresponded to intraclass correlation coefficients of 9.3%, 7.4%, and 24.2% respectively. Conclusion: Despite strong recommendations by Canadian guidelines for troponin testing after non-cardiac surgery, testing rates were low overall and varied significantly across hospitals.