tbuckley/cabot-search huggingface dataset:
Abstract 4139317: Epidemiologic and genetic associations between proteomic markers and thoracic aortic diameter
Authors: Alexander Wells, James Brundage, Siavash Zamirpour, James Pirruccello
Journal: Circulation (2024)

Introduction: Enlargement of the thoracic aorta is clinically silent but predisposes to the highly morbid medical conditions of aortic dissection and rupture. Evidence suggests that clinical and genetic factors play a role in the pathogenesis of aneurysm. Here, we extend these efforts by identifying circulating proteomic markers linked to aortic diameter. Research Question: We investigate whether circulating protein levels correlate with aortic diameter Goals: 1. Identify proteins whose circulating levels correlated with aortic diameter 2. Investigate whether protein levels may causally influence aortic diameter using Mendelian randomization Methods: A total of 7,099 UK biobank participants had both ascending aortic diameter measured from MRI and 2,920 circulating proteomic markers measured with the Olink Explore 3072 panel. For each protein, a linear regression model was trained to estimate ascending aortic diameter, adjusted for age at time of MRI, time between Olink panel and MRI, and sex. A genome-wide association study (GWAS) of ascending aortic diameter was conducted after excluding participants related within 3 degrees of kinship to those with proteomic measurements, producing summary statistics for two-sample Mendelian randomization (2SMR). We used independent cis-protein quantitative trait loci (within 1 megabase of the gene) as the exposure and the ascending aortic diameter summary statistics as the outcome in a 2SMR framework. Results: Circulating levels of 185 proteins were associated with ascending aortic diameter. Using 2SMR, we observed evidence consistent with a causal role for 43 proteins. Three proteins were significant in both analyses: CCN3 (a suppressor of vascular smooth muscle proliferation); BMP6 (a member of the TGF-beta superfamily); and RGMA (depleted in aortic plaques). Both analyses found a direct relationship between CCN3 levels and aortic diameter and an inverse relationship between BMP6 levels and aortic diameter. The 2SMR found a direct relationship between RGMA levels and aortic diameter, whereas the regression model found an inverse relationship. The greatest 2SMR effect estimate was between greater levels of circulating methionine sulfoxide reductase A (involved in repair of oxidative damage in vascular smooth muscle cell mitochondria) and reduced ascending aortic diameter. Conclusions: Circulating protein levels were associated with ascending aortic diameter, some of which may play causal roles in aneurysm development.
Abstract 4139467: Application and Outcomes of Coronary Atherectomy in Patients with Acute Coronary Syndrome: A Report from the Nationwide J-PCI Registry
Authors: Tadao Aikawa, Yuichiro Mori, Shun Kohsaka, Yuya Matsue, Toshiki Kuno, Kyohei Yamaji, Dai Ozaki, Takashi Tokano, Ken Kozuma, Tohru Minamino
Journal: Circulation (2024)

Introduction: Acute coronary syndrome (ACS) has been generally considered a relative contraindication to coronary atherectomy. Aims: The objective of this study was to investigate the temporal trends and hospital variability in the use of coronary atherectomy and its outcomes among patients undergoing percutaneous coronary intervention (PCI) for ACS from a nationwide PCI registry in Japan. Methods: First, we analyzed the temporal trend in the use of rotational atherectomy (RA) and orbital atherectomy (OA) during PCI for ACS patients between 2014 and 2022 (822,237 PCIs from 1,269 hospitals). Next, we assessed the outcomes of the patients who underwent RA for ACS between 2019 and 2022 (7,421 patients across 662 hospitals). The primary outcome was in-hospital mortality after PCI. Patient outcomes associated with hospital PCI volumes and the device policy change on coronary atherectomy in Japan in 2020, which allowed operators to perform coronary atherectomy without on-site surgical backup, were also evaluated. Results: The rate of RA for ACS was low at 2.0% in the overall cohort (16,264/822,237 PCIs); the rate slightly increased from 1.9% in 2014-2019 to 2.1% in 2020-2022 (after the device policy change). The rate of PCI with OA for ACS was also low at 0.8% in 2021-2022 (1,404/185,141 PCIs). Increasing the complexity of baseline characteristics, including advanced age, diabetes, chronic kidney disease, dialysis, peripheral arterial disease, prior coronary artery bypass grafting, ST-segment elevation myocardial infarction, cardiac arrest within 24 h, cardiogenic shock within 24 h, three-vessel disease, and mechanical circulatory support during PCI was significantly associated with increased in-hospital mortality after PCI with RA in ACS patients (P&lt;0.05 for all). Annual hospital PCI volumes (odds ratio, 0.937; 95% CI, 0.653-1.361; P=0.729 for high- vs. low-volume hospitals) and newcomer facilities starting RA after the device policy change (odds ratio, 0.987; 95% CI, 0.651-1.361; P=0.951) were not significantly associated with in-hospital outcomes after RA for ACS. Conclusions: The present study using a nationwide multicenter PCI registry showed that the overall rate of PCI with coronary atherectomy for ACS was low but slightly increased after the device policy change in Japan. Hospital PCI volumes and newly accredited facilities on coronary atherectomy after the device policy change were not associated with in-hospital outcomes after RA for ACS.
Abstract 4139408: Lipoprotein(a) levels in Polish population based on the STAR-Lp(a) cohort study. Prevalence, patient’s population, and risk factors.
Authors: Monika Burzynska, Piotr Jankowski, Mateusz Babicki, Maciej Banach, Michal Chudzik
Journal: Circulation (2024)

Background: Elevated Lipoprotein(a) [Lp(a)] is independently associated with increased cardiovascular disease (CVD) risk. Purpose: The study aimed to evaluate the Lp(a) levels in Polish population and determine the association between socio-demographic and health-related variables and elevated Lp(a). Methods: The analysis was conducted among 2475 outpatient primary prevention patients (69.7% - women). The median age was 66.0 years ±20 years. Lp(a) levels were assessed in groups: &lt;30 mg/dL (&lt;75 nmol/l) (normal level) and &gt;30 mg/dL (75-125 nmol/l) (elevated level). Statistical analysis was performed using STATISTICA 13.1. Qualitative variables were analyzed using descriptive statistics. The chi-square test was used to assess the relationship between quantitative variables. The Mann-Whitney test was used in the case of qualitative. Pearson's correlation coefficient was used to measure correlation. Multivariate logistic regression models were built to determine the effect of factors on the probability of elevated Lp(a) level. P&lt;0.05 was judged as significant. Results: Lp(a) &gt;30 mg/dL was recorded in 21.5% of patients (Fig. 1). The average age of patients with Lp(a)&gt;30 was significantly higher (67 years ±17 vs. 65 years ± 20; p=0.008). A significant relationship was observed between the level of Lp(a) and the presence of selected comorbidities, i.e., hypertension, hyperlipidemia and atrial fibrillation (AF). The share of people with these disorders was higher in patients with elevated Lp(a) by 5.8; 6.6 and 1.7 pp. respectively. People suffering from migraines less frequently had Lp(a)&gt;30 (5.6% vs 8.6%, p=0.025). Among patients with elevated Lp(a), there were significantly higher average levels of total cholesterol (TC), LDL cholesterol, non-HDL cholesterol, and hemoglobin A1C (HbA1C) (p=0.003; p=0.0004, p=0.003, p=0.021). A positive significant correlation was observed between the Lp(a) and the glucose level, both in patients with elevated Lp(a) level (r=0.19, p&lt;0.001) (Fig. 2A). An analogous relationship was noted for Lp(A) and HbA1C (r=0.24; p&lt;0.001) (Fig. 2B). In the regression model the factors determining the presence of elevated Lp(a)&gt;30 included: AF (OR 1.99; 95CI: 1.091-3.629), diagnosed hyperlipemia (OR =1.414; 95 CI – 1.084-1.843) HbA1C&gt;8 (OR=1.180; 95CI – 1.028-1.355), TC&gt;250 mg/dl (OR=1.005; 95CI: 1.003-1.008), migraine (OR=0.539; 95CI - 0.306-0.950). Conclusion: Assessment of Lp(a) may be useful in taking effective management to reduce CVD risk.
Abstract 4139504: Associations Between Changes in Maximum Daily Atrial Fibrillation Duration, Ischemic Stroke and Mortality among Patients with Cardiac Implantable Electronic Devices
Authors: Graham Peigh, Jodi Koehler, Shubha Majumder, Yong Cho, Sean Landman, Shantanu Sarkar, Paul Ziegler, Rod Passman
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) outcomes are strongly associated with continuous measures of AF burden. Objectives: To assess the association between changes in maximum daily AF duration (MDAFD) and the combined endpoint of ischemic stroke and mortality among patients with cardiac implantable electronic devices (CIEDs) capable of continuous AF detection. Methods: The Optum ® de-identified electronic health record (EHR) (2007-2021) was linked with the Medtronic CareLink ® heart rhythm database for this study. CIED patients with healthcare activity recorded in the EHR &gt; 12 months pre- and &gt; 6 months post-CIED implant were included, excluding those with oral anticoagulation (OAC) prescription. MDAFD was assessed during the first 30 days post-implant (baseline period) and the 30 days prior to censoring or an event. Associations between change in MDAFD and the combined endpoint were evaluated, adjusting for the individual components of CHA 2 DS 2 -VASc, baseline MDAFD category and chronic kidney disease (CKD). Results: Of 26,400 patients (68±13 years; 60% male; follow-up 2.6±1.6 years) analyzed, 2,544 (9.6%) had AF during baseline. In all patients, increased (vs. stable or decreased) MDAFD in follow-up was associated with a higher adjusted rate of stroke and mortality (HR 1.80 [1.61-2.01]). There was no association between decreased MDAFD in follow-up and the combined endpoint. Subgroup analysis by baseline MDAFD category demonstrated that increased MDAFD in follow up was associated with a greater risk of stroke or mortality among patients with no AF at baseline, and decreased MDAFD in follow-up was associated with a lower adjusted risk of stroke or mortality among patients with baseline MDAFD 1hour-&lt;5.5hours and 5.5hours-&lt;23.5hours (Figure). Conclusions: Results from the present study suggest that progression from low burden AF is associated with negative outcomes, and that there may be threshold effects of baseline AF duration that benefit from enhanced rhythm control. These data encourage continued monitoring of AF duration over time to enhance risk stratification and further inform treatment efforts.
Abstract 4139378: Paclitaxel-Coated Balloon Angioplasty vs. Uncoated Balloon Angioplasty in Patients with Coronary In-Stent Restenosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: David Curi, Bárbara Mariz Ferreira Passos, Victor Machado Viana Gomes, Giovanna Moraes, Ana Beatriz Nepomuceno Cunha, Edielle de Sant Anna Melo
Journal: Circulation (2024)

Introduction: The potential benefits and risks of paclitaxel-coated balloon (PCB) angioplasty over uncoated balloon (UB) angioplasty in the management of coronary in-stent restenosis (ISR) is not well established. Hypothesis/Aims: This study aims to determine whether PCB angioplasty is superior to UB angioplasty in patients with coronary ISR in terms of target lesion revascularization (TLR), myocardial infarction (MI), and all-cause mortality rates. Methods: PubMed, Embase and Cochrane Central databases were systematically searched for randomized clinical trials (RCT) comparing PCB with UB angioplasty in patients with coronary ISR. Statistical analyses were performed using Review Manager version 5.4.1. Risk Ratios (RR) with 95% confidence intervals (CI) for dichotomous endpoints were computed with the use of a Mantel-Haenszel random effects model. Results: A total of 1,407 patients from 7 randomized clinical trials were included. Follow-up periods in the included studies ranged from 6 months to 1 year. PCB angioplasty significantly reduced TLR (RR 0.28; 95% CI 0.16-0.48; p&lt;0.001) and MI (RR 0.57; 95% CI 0.36-0.92; p=0.02). However, there were no significant differences in all-cause mortality (RR 0.75; 95% CI 0.38-1.50; p=0.42). Conclusion: In the management of coronary ISR, PCB angioplasty reduced TLR and MI compared with UB angioplasty. Nevertheless, PCB did not have a significant impact on all-cause mortality in comparison with UB. Further studies with extended follow-up are necessary to determine long-term mortality effects.
Abstract 4139284: Most Important Predictors of 30-Day Death in Patients with Heart Failure Presenting with Acute Dyspnea
Authors: Karina Kraevsky-Phillips, Paul Scott, Sarumathi Thangavel, Salah Al-Zaiti
Journal: Circulation (2024)

Background: Heart failure (HF) manifests with burdensome symptoms leading to frequent emergency department (ED) visits and high rates of poor outcomes and mortality. Dyspnea is a nonspecific chief complaint, making risk stratification in this group very challenging. The purpose of this study was to determine patient characteristics related to poor outcomes in patients with HF seen in the ED for dyspnea. Methods: This was a secondary analysis of a retrospective observational cohort study of patients with known HF seen in the ED for a chief complaint of dyspnea between January 2018 and December 2022 at any one of 40 UPMC-affiliated hospitals in Pennsylvania. Trained independent chart reviewers collected study variables using a structured data collection form. Variables with &lt;10% prevalence or &gt;50% missingness were omitted. Multiple imputation was used to handle sparsely missing data. Primary outcome was all-cause death within 30-days of ED admission calculated from date of ED admission using death dates available in charts and manual obituary search. We used LASSO regression with 10-fold cross-validation to obtain the most significant predictors from 150 data points available early in the ED course (i.e., past medical history, initial vitals, demographics, ED treatments). Nine important variables were selected to build a logistic regression model to derive unbiased coefficients. Analysis was performed using Stata version 18. Results: The sample included 296 patients (mean age 73±14 years, 53% female, 13% Black, mean EF 50±13%) of whom 22 (7.4%) died within 30 days of ED admission. LASSO regression selected nine variables: age, systolic blood pressure, history of Afib/flutter, CAD, MI, stents, sleep apnea (OSA), fluid bolus in ED, and home aspirin. In the subsequent logistic regression using those variables, fluid bolus (OR=3.4, 95% CI 1.08-10.67, p=0.036) and history of sleep apnea (OR=0.09, 95% CI 0.011-0.76, p=0.027) remained significant. Conclusions: Our analysis suggest that patients who received a fluid bolus experienced higher odds of 30-day mortality and patients with a history of OSA experienced lower odds of mortality. The complex relationship of these variables with 30-day death should be investigated further.
Abstract 4139450: Prevalence of Cardiovascular-Kidney-Metabolic Conditions Across the Spectrum of Body Mass Index Among US Adults, 2017-March 2020
Authors: John Ostrominski, Jamie Hirsch, Benjamin Miao, Effie Kuti, Bonnie MK Donato, Marjorie Crowell, Christina Parrinello, Jonathan Woolley, Thomas O'Connell, Muthiah Vaduganathan
Journal: Circulation (2024)

Background: Obesity is a major risk factor for the onset and progression of cardiovascular-kidney-metabolic (CKM) conditions. However, there is substantial epidemiological and phenotypic heterogeneity across the spectrum of body mass index (BMI), and whether the contemporary prevalence of CKM conditions varies according to BMI in the US population has not been rigorously evaluated. Methods: In this serial cross-sectional analysis of nonpregnant US adults aged ≥20 years participating in the nationally representative pre-pandemic National Health and Nutrition Examination Survey (2017-March 2020), we evaluated the prevalence of CKM conditions (cardiovascular disease [atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF)], at least moderate-risk chronic kidney disease [CKD], and metabolic disease [type 2 diabetes (T2D) or metabolic dysfunction-associated steatotic liver disease (MASLD)] by BMI category (18.5-&lt;25, 25-&lt;30, 30-&lt;35, 35-&lt;40, and ≥40 kg/m 2 ). Associations between each BMI category with prevalent CKM conditions were expressed as prevalence ratios (PR) with 95% CI, estimated using Poisson regression. Results: Among 6,337 US adults (mean age, 48 years; 51% women), 26% had BMI 18.5-&lt;25, 32% had BMI 25-&lt;30, and 42% had BMI ≥30 kg/m 2 . Nearly half (48%) of US adults with BMI ≥40 kg/m 2 were aged &lt;45 years. CKM multimorbidity (≥2 CKM conditions) generally increased with increasing BMI category; 4.2% among those with BMI 18.5-&lt;25 vs. 21.3% among those with BMI ≥30 kg/m 2 ( Figure, A ). Overall, increasing BMI was associated with a higher prevalence of all CKM conditions ( P ≤0.001 for all), with strongest associations observed for MASLD (BMI ≥40 vs. 18.5-&lt;25 kg/m 2 ; PR, 20.8, 95% CI 12.8-33.8; P &lt;0.001), T2D (BMI ≥40 vs. 18.5-&lt;25 kg/m 2 ; PR, 5.8, 95% CI 4.3-7.8; P &lt;0.001), and HF (BMI ≥40 vs. 18.5-&lt;25 kg/m 2 ; PR, 5.2, 95% CI 2.7-10.1; P &lt;0.001) ( Figure, B ). Conclusions: This analysis highlights the robust association between higher BMI and the prevalence of CKM conditions among US adults, supporting weight management as a core component of comprehensive CKM-oriented care strategies. These findings also support efforts to enhance screening and management for the full spectrum of CKM conditions in overweight/obesity.
Abstract 4139457: The Efficacy of Sacubitril-Valsartan in Congestive Heart Failure Patients Who Also Have End Stage Renal Disease
Authors: Usman Kazi, Abraheim AL-Nasseri, Steven Mirabella, Nishant Nerella, Suman Pasupuleti
Journal: Circulation (2024)

Introduction: The PARADIGM-HF trial demonstrated that angiotensin receptor-neprilysin inhibitor was superior to enalapril in reducing risks of death and hospitalization for heart failure; however, the trial excluded patients with a GFR &lt;30mL/min/1.73m2. This poses limited data when treating patients with concomitant congestive heart failure (CHF) and end-stage renal disease (ESRD). We observe the effects of sacubitril-valsartan on all-cause mortality, acute kidney injury (AKI), ventilation requirements, hyperkalemia, and intensive care unit (ICU) admissions in patients with both CHF and ESRD. Methods: We conducted a multicenter retrospective cohort on patients diagnosed with CHF and ESRD (defined as a GFR below &lt;15mL/min/1.73m2) from 01/01/2017 to 06/01/2023 across 16 West Florida hospitals. Patients receiving sacubitril-valsartan were compared to those not taking sacubitril-valsartan. Chi-square and binary logistic regression were used to predict the clinical outcomes of all-cause mortality, AKI, ventilation requirements, hyperkalemia, and ICU admissions between the two groups. Results: Among 18,116 patients with CHF and ESRD, 712 (3.9%) were taking sacubitril-valsartan and 17,406 (96.1%) were not taking sacubitril-valsartan. Among those taking sacubitril-valsartan compared to those who were not, similar likelihood was seen in terms of all-cause mortality (OR 1.04, 95% CI 0.74-1.47; p=0.8325), hyperkalemia (OR 0.88, 95% CI 0.73-1.05; p=0.1464), and ICU admissions (OR 0.86, 95% CI 0.73-1.02; p=0.0825). The likelihood of AKI was higher in patients taking sacubitril-valsartan compared to those who were not (OR 1.20, 95% CI 1.02-1.43; p=0.0330). There was a significantly less likelihood of ventilation requirement among those taking sacubitril-valsartan compared to those who were not (OR 0.79, 95% CI 0.67-0.92; p=0.003). Conclusion: In patients with concomitant CHF and ESRD, the odds of all-cause mortality, hyperkalemia, and ICU admissions were similar among patients taking sacubitril-valsartan compared to those who were not. Patients taking sacubitril-valsartan were less likely to require ventilation but more likely to develop AKI. Although these patients are more likely to develop AKI, this does not significantly impact mortality rate. This study highlights outcomes excluded in the PARADIGM-HF trial.
Abstract 4139456: Integrin α5β1 contributes to pathological remodeling of the right ventricle in pulmonary arterial hypertension
Authors: Sarah-Eve Lemay, Monica Montesinos, Yann Grobs, Alice Bourgeois, Charlotte Romanet, Melanie Sauvaget, Sandra Breuils Bonnet, Charlie Theberge, Sandra Martineau, Blaise Lippa, Bryan Goodwin, Albert Lin, Hua Wang, James Dowling, Min Lu, Qi Qiao, T. Andrew McTeague, Terence I. Moy, Francois Potus, Steeve Provencher, Olivier Boucherat, Sebastien Bonnet
Journal: Circulation (2024)

Introduction: Right ventricular (RV) function is an important prognosis factor in pulmonary arterial hypertension (PAH). In response to pressure overload, the RV undergoes morphological changes driven by the accumulation of extracellular matrix (ECM) elements and cardiomyocyte hypertrophy. Integrins (Itg) are members of the cell adhesion receptor superfamily. Through ECM-binding, Itg are known to transduce extracellular cues to cardiac cells resulting in the activation of pro-hypertrophic and pro-fibrotic signaling pathways. Among them, integrin α5β1 is one of the most abundant heterodimers in cardiac tissue. We thus hypothesized that α5β1 signaling promotes pathological RV remodeling. Methods&amp;Results: Using Western blot (WB), we found elevated levels of Itgα5 and Itgβ1 protein in RV isolated from PAH patients compared to controls. Similar findings were observed in monocrotaline (MCT) and pulmonary artery banding (PAB) rats. In adult rat cardiomyocytes, pharmacological inhibition of α5β1 decreased phenylephrine-induced hypertrophy and reversed established hypertrophy induced by MCT treatment (assessment of cell surface area by F-actin labeling). In human RV fibroblasts (RVFB) inhibition of α5β1 prevented TGFβ1-induced activation of control RVFB and decreased proliferation and activation of RVFB derived from PAH patients (WB PCNA, αSMA, COL1; immunofluorescence Ki67). In vivo , inhibition of α5β1 using a small molecule inhibitor or a blocking-antibody improved RV dysfunction (CO, TAPSE, RVFAC, RV strain, as assessed by echocardiography, right heart catheterization and cardiac magnetic resonance imaging) and diminished RV hypertrophy and fibrosis (Fulton index, H&amp;E and Masson’s trichrome staining) in MCT-injected rats with established PAH and PAB rats. Ex vivo , inhibition of α5β1 attenuated cardiomyocyte hypertrophy and RV fibrosis in human precision-cut RV slices exposed to phenylephrine and TGFβ1. Conclusion: Our results suggest that integrin α5β1 plays a key role in pathological RV remodeling in PAH.