tbuckley/cabot-search huggingface dataset:
Abstract 12959: Association of Gender-Affirming Hormone Treatment With Metabolic Syndrome in Transgender Patients Compared With Cis-Gender Patients
Authors: Andriana Marijic Buljubasic, Michael Goodman, Matthew J Budoff, Jeffrey Gornbein, Leila Hashemi
Journal: Circulation (2023)

Background: The long-term effects of gender-affirming hormone therapy (GAHT) is an area of priority in transgender (TG) health research. Also, there is a great gap in our understanding of sex hormone and sex chromosomes and their role in Metabolic Syndrome (MetS) and therefore atherosclerosis risk. Hypothesis: sex hormones, (estradiol and Testosterone) affect the development of MetS and therefore heart disease. Methods: Using International Classification of Diseases ninth and tenth codes for gender dysphoria from the Veteran Health Affairs national data, we identified 284 transfeminine (TF) and 79 transmasculine (TM) patients with documented received GAHT initiation date (index date=ID) and MetS components data. GAHT consists of estradiol in TF and testosterone in TM individuals.TG individuals were matched to 252 cis-male (CM) and 111 cis-female (CF) referents. MetS z-scores were calculated as: where . In the longitudinal analyses, time (years) was computed from the ID (“Time 0”) with negative and positive values indicating pre- and post ID period, respectively. The mean MetS z-scores were compared among TG and cis-gender groups over time using a repeated measures analysis of variance model. Results: The mean age of cohort was 41, 84% non-Hispanic White and 9% non-Hispanic Black.Table 1 shows MetS z-score significantly changed overtime (p&lt;0.001) and differed across groups (p&lt;0.05). Fig 1 shows the changes in adjusted (year and group) MetS z-scores with locally estimated scatterplot smoothing curves. The data indicate that estrogen and testosterone may have different effects on metabolic status. hormones Conclusion: Sex hormones play an important role in the MetS development sex difference.
Abstract 12942: The D801N Variant in <i>ATP1A3</i> -Encoded Na/K-atpase Alpha 3 Shortens the Cardiac Myocyte Action Potential and Increases Risk for Calcium Mediated Arrhythmias
Authors: MINU BIDZIMOU, ZHUSHAN ZHANG, Jordan E Ezekian, Alex Clifford, Ninh Dao An Le, Mary E Moya-Mendez, Scott Zheng, Robin Perelli, Bo Sun, Arsen Hunanyan, Andrew Breglio, Abbigail Helfer, Donald M Bers, Nenad Bursac, Mohamad Mikati, Andrew P Landstrom
Journal: Circulation (2023)

Background: Alternating hemiplegia of childhood (AHC) is a rare de novo syndrome that manifests with episodic hemiplegia, seizures, dystonia, and, notably, sudden unexplained death. Gene positive patients carry a pathogenic variant in the ATP1A3 -encoded Na/K ATPase alpha 3 isoform (ATP1A3), and the variant D801N is the most common pathogenic variant. Our group recently found that AHC patients with ATP1A3-D801N missense have short QTc and are at risk of ventricular fibrillation. Hypothesis: We hypothesized that the D801N variant results in reduced ATPase function leading to Ca 2+ overload resulting in shortened repolarization time and increased arrhythmogenic risk. Methods: We differentiated iPSCs into cardiomyocytes from an AHC patient hosting the ATP1A3-D801N variant (iPSC-CM D801N ), and an ostensibly healthy individual (iPSC-CM WT ). Patch clamp was conducted to determine APD90, and the ratio of cells with delayed after depolarization events (DADs). iPSC-CM WT were perfused with 10 -7 M ouabain, an ATP1A3 inhibitor, and APD90 and DADs were measured. SR store ([Ca 2+ ] SR ) was measured with Cal-520 dye under 10 mM caffeine. Resting [Ca 2+ ] i was measured with Fura-2 dye, and Na/Ca exchanger (NCX) peak current was measured as Ni 2+ sensitive current in a stepwise voltage-clamp protocol. Results: iPSC-CM D801N APD90 was shorter 40% than iPSC-CM WT . IPSC-CM WT treated with ouabain had 17% shorter APD90 than vehicle. iPSC-CM D801N had DADs (3/11 cells) when iPSC-CM WT (0/24) did not, and 6/12 ouabain treated iPSC-CM WT had DADs vs vehicle treated (0/18). Post caffeine, iPSC-CM D801N had higher [Ca 2+ ] SR than iPSC-CM WT . Finally, iPSC-CM D801N had higher resting [Ca 2+ ] i than iPSC-CM WT and iPSC-CM D801N had higher peak NCX current density at +80mV but no difference at RMP. Conclusions: Our results show that both iPSC-CM D801N and ouabain-treated iPSC-CM WT , have a shorter APD compared to WT controls and exhibit DADs. This is associated with higher NCX-mediated influx of Ca 2+ and increased intracellular Ca 2+ . Our findings highlight the emerging role of ATP1A3-D801N in creating a myocardium vulnerable to arrhythmias.
Abstract 11829: Association of Adult Congenital Heart Disease and Serial Echocardiographic Parameters With Adverse Cardiac, Obstetric, and Neonatal Outcomes
Authors: Yamini Krishnamurthy, Matthew Lewis, Lilly Liu, Stephanie Purisch, Marlon S Rosenbaum
Journal: Circulation (2023)

Background: Risk factors for adverse cardiac, obstetric and neonatal outcomes in pregnant women with adult congenital heart disease (ACHD) are not well-defined. Objective: To assess the association of ACHD and serial echo parameters with adverse cardiac, obstetric and neonatal outcomes. Methods: ACHD patients with prenatal care and delivery at a tertiary care center from 2007-2022 were included. Serial echos during pregnancy and adverse cardiac outcomes (arrhythmia, heart failure, ICU admission) were reviewed. Adverse obstetric (pregnancy-induced hypertension, abruption, hemorrhage) and neonatal outcomes (small-for-gestational age, preterm delivery, NICU admission, fetal/neonatal demise) were compared between the ACHD cohort and an age- and gravidity-matched non-ACHD cohort. Logistic regression was used to calculate the odds ratio (OR) for adverse outcomes. Results: Of 188 ACHD patients (mean age 30.9 ± 5.9 years), 74.4% had moderate or greater anatomic complexity. 11.7% of ACHD patients had an adverse cardiac outcome. Adverse obstetric and neonatal outcomes were more common in ACHD patients (23.9% vs 10.4%, p &lt; 0.001; 35.3% vs 17.0%, p &lt; 0.001, respectively). Systemic ventricular dysfunction, systemic atrioventricular valve dysfunction, and decline in systemic ventricular function during pregnancy were associated with increased risk of adverse cardiac outcomes. ACHD was associated with increased risk of adverse obstetric and neonatal outcomes (OR 2.8, 95% Confidence Interval [CI] 1.7 - 4.8; OR 2.8, 95% CI 1.8 - 4.5, respectively). Echo predictors of adverse cardiac outcomes were not associated with increased risk of adverse obstetric or neonatal outcomes. Conclusion: ACHD is associated with adverse cardiac, obstetric and neonatal outcomes. Echo parameters are predictive of adverse cardiac, but not obstetric or neonatal outcomes. Large-scale studies are needed to identify drivers of adverse obstetric and neonatal outcomes in this population.
Abstract 11520: Safety and Efficacy of Botulinum Toxin Type A for Prevention of Postoperative Atrial Fibrillation in Cardiac Surgery Patients: Pulmonary Function Test Results From the Phase 2 NOVA Study
Authors: Jason E Lang, Richard Leaback, Gorav Ailawadi, Alexander Iribarne, Kevin J Gleason, Alexandra OSullivan, Nuo-Yu Huang, William G Ferguson, Jeffrey Miller
Journal: Circulation (2023)

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Autonomic neuromodulation, including injection of botulinum toxin into epicardial fat pads, may suppress and/or attenuate atrial fibrillation. The respiratory safety of a potential preventative treatment for AF is critical. Aim: To assess efficacy and pulmonary safety of botulinum toxin type A (BoNT/A; AGN-151607) 125U and 250U vs placebo for prevention of POAF after coronary artery bypass graft and/or valve surgery. Methods: NeurOtoxin for the PreVention of post-operative Atrial fibrillation (NOVA; NCT03779841) was a phase 2, international, multicenter, randomized, placebo-controlled trial. The primary endpoint was proportion of patients with continuous AF ≥30 seconds within the first 30 days. Respiratory function was assessed via pulmonary function tests (PFTs) performed at baseline and day 30 after treatment. Adverse events (AEs), serious adverse events (SAEs), and time to extubation were recorded. Results: A total of 323 patients were randomized: BoNT/A 125U (n=106), 250U (n=109), placebo (n=108). The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125U group (relative risk [RR] vs placebo, 0.80 [95% CI: 0.58, 1.10]; P =0.16), and 47.2% of the 250U group (RR vs placebo, 1.04 [95% CI: 0.79, 1.37]; P =0.78). Baseline, day 30, and change from baseline PFT results were similar for active treatment vs placebo ( Table ). Median time to extubation was 9.7, 9.6, and 9.6 h in the placebo, 125U, and 250U groups, respectively. Respiratory AEs were reported in 42.9%, 38.1%, and 50.5% of patients, and respiratory SAEs in 11.4%, 6.7%, and 5.5% of patients in the placebo, 125U, and 250U groups, respectively. Conclusion: In this analysis of respiratory function, there appeared to be no detrimental effect of AGN-151607 compared with placebo, as evidenced by similar outcomes in PFT parameters and respiratory AE/SAE incidences among treatment arms.
Abstract 12665: Hospital Outcomes of Breast Cancer Patients With Concurrent Atrial Fibrillation
Authors: Yong Hao Yeo, Min Choon Tan, Qi Xuan Ang, Jia Yi Tan, Justin Lee, Nishaki M Mehta
Journal: Circulation (2023)

Background: It was estimated that 4% of newly diagnosed breast cancer patients had new onset of atrial fibrillation (AF). Data on the impact of AF on the in-hospital outcomes of breast cancer patients are scarce. Objective: This study aimed to determine and assess the in-hospital outcomes of breast cancer patients with concurrent AF. Methods: Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older with a diagnosis of breast cancer between 2017 and 2020. We categorized the cohort into two groups depending on the occurrence of AF during hospitalization. The primary endpoint of our study was the in-hospital outcomes and complications of breast cancer patients with and without concurrent AF. Results: 284,226 breast cancer patients were included in this study; 32,289 (11.4%, 76.5 ± 10.1 years of age) with concurrent AF and 251,937 (88.6%, 62.7 ± 14.0 years of age) without. Those with concurrent AF were associated with higher odds of early mortality (adjusted odds ratio [aOR]: 1.19; 95% confidence interval [CI]: 1.12- 1.27, p&lt;0.01), prolonged index hospital stay (aOR: 1.11; CI: 1.06- 1.16, p&lt;0.01), and non-home discharge (aOR: 1.42; CI: 1.35- 1.48, p&lt;0.01). The length of hospital stay was longer in the group with concurrent AF than those without concurrent AF (mean 6.3 days vs. 5.7 days, p&lt;0.01). During hospitalization, those with concurrent AF had higher odds of developing acute heart failure (aOR: 1.54; CI: 1.37- 1.74, p&lt;0.01), cardiogenic shock (aOR: 1.42; CI: 1.04- 1.93, p=0.03), pulmonary edema (aOR: 1.26; CI: 1.06- 1.49, p=0.01), and cerebral infarction (aOR: 1.51; CI: 1.21- 1.89, p&lt;0.01). Conclusion: Breast cancer patients with concurrent AF had worse in-hospital outcomes and complications than those without concurrent AF. Figure In-Hospital Outcomes and Complications of Breast Cancer Patients with Concurrent Atrial Fibrillation versus without Concurrent Atrial Fibrillation.
Abstract 12099: The Racial Disparity Among the Clinical Outcomes Post Stroke and Its Intervention Outcomes: A Systematic Review and Meta-Analysis
Authors: Vikash Jaiswal, Muhammad Hanif, Vinay Suresh, Endurance O Evbayekha, FNU Ruchika, Navroop Momi, Jia Ee E Chia, Akash Jaiswal
Journal: Circulation (2023)

Background: The Racial disparity between the clinical outcomes post-stroke has not been well studied, with limited literature available.Objective: We conducted a meta-analysis to evaluate the post-stroke outcomes among White and Black patients. Methods: We systematically searched all electronic databases from inception until 1st March 2023. The primary endpoint was post-stroke in-hospital mortality and all-cause mortality. Secondary endpoints were post-stroke intervention in-hospital mortality, intracerebral hemorrhage, and all-cause mortality (ACM). Result: 1250397 patients were included in the analysis, with 1018892 (81.48%) patients of the White race and 231505 (18.51%) patients of the Black race. The mean age of the patients in each group was (73.55 vs 66.28). The most common comorbidity among White and Black patients was HTN (73.92% vs 81.00%) and DM (29.37% vs 43.36%). The odds of in-hospital mortality post-stroke (OR, 1.45(95%CI:1.35-1.55), P&lt;0.001), and all-cause mortality (OR, 1.40(95%CI:1.28-1.54), P&lt;0.001) were significantly higher among White patients compared with Black patients. Among patients with post-stroke intervention, the odds of in-hospital mortality (OR, 1.29 (95% CI: 1.05-1.59, P=0.02), and intracerebral hemorrhage(ICH) (OR, 1.15, (95%CI:1.06-1.26), P&lt;0.01) were significantly higher among White patients compared with Black patients post-intervention. However, all-cause mortality (OR,1.21(95%CI: 0.87-1.68, P=0.25) was comparable between both groups. Conclusion: Our study is the most comprehensive and first meta-analysis with the largest sample size thus far, highlighting that White patients are at increased risk of mortality and post-intervention intracerebral hemorrhage compared with Black patients.
Abstract 11546: Functional Co-Clustering of Physical Activity Patterns Among Sexual and Gender Minority Adults
Authors: David Lopez Veneros, Billy A Caceres, Kasey Jackman, Joseph Belloir, Yashika Sharma, Ipek Ensari
Journal: Circulation (2023)

Introduction: Physical activity (PA) is a important modifiable risk factor for cardiovascular disease (CVD) and CVD mortality. There is growing evidence that sexual and gender minority (SGM; lesbian/gay, bisexual, transgender) adults are at higher risk of insufficient PA and CVD. Accelerometers allow for collection of granular PA data that can identify individual- and temporal heterogeneity in daily patterns. To date, no studies have investigated accelerometry-based PA patterns among SGM adults. Goal: To characterize daily PA trajectories among SGM adults and identify distinct phenotypes using a time series-based clustering technique. Methods: We recruited an online sample of healthy SGM adults in the United States who completed continuous wrist-worn accelerometry for 30 days to collect step counts. For clustering, we used a functional latent block models (FLBMs), where each 24-hour period was a Fourier-smoothed data curve. FLBMs allow hierarchical time-series data clustering by simultaneously clustering person- and day-level data. The optimal number of clusters was selected using the integrated completed likelihood (ICL) criterion. Results: Forty-two SGM adults with a mean age of 27.0 years (+/- 7.7) provided 1207 person-level days of accelerometry (range=6-31 days/person). A final model with 4 blocks (2 x 2 clusters) provided the best fit (ICL= -70086.4). Two person-level clusters were identified, which were characterized by differences in the amount and distribution of steps throughout the day were identified. Cluster 1 (n=26) had higher overall steps counts with significant morning and evening increases in step counts. Cluster 2 (n=16) had fewer steps that were within a narrower time period. We further identified 2 day-level clusters. Cluster 2 (n=14) had a wider temporal distribution of step counts and a higher variance on weekend days vs. weekdays relative to Cluster 1 (n=17). Conclusions: This is the first study to elucidate daily PA trajectories in SGM people. Using FLBM, we accounted for individual heterogeneity and relations among days. Findings can help identify individuals at increased risk of physical inactivity and subsequent negative health outcomes, providing important knowledge to inform behavioral interventions.
Abstract 12098: Evaluation of Inflammatory Biomarkers and Causal Association With Abdominal Aortic Aneurysm Development
Authors: Pranav Sharma, James Yarmolinsky, Ville Karhunen, Dipender Gill, Tanmoy Roychowdhury, Michael Levin, Scott M Damrauer
Journal: Circulation (2023)

Introduction: Observational analyses have linked circulating inflammatory biomarkers with an increased risk of abdominal aortic aneurysms (AAA). Although observational studies implicate inflammatory biomarkers in AAA, whether these are a cause or consequence of the disease is unknown. A limited number of trials have explored agents that reduce inflammation in slowing the progression of AAA. Observational study quality may be limited by residual confounding and reverse causality. We sought to leverage genetic instruments and Mendelian Randomization (MR) to evaluate the human genetic evidence supporting inflammatory biomarkers in the pathogenesis of AAA. Methods: We leveraged a meta-analysis of 6 genome-wide association studies (GWAS) of 66 circulating inflammatory markers including up to 59,969 participants of European ancestry. We tested the association for each biomarker with AAA using summary statistics from a meta-analysis of 17 individual GWAS from 14 discovery cohorts in the AAAgen consortium comprising 39,221 individuals with AAA. We employed Wald ratio or inverse-variance weighted MR; weighted median and weighted mode methods were applied as sensitivity analyses. Results: After accounting for multiple testing by controlling the false discovery rate (q &lt; 0.05), we identified a total of 6/66 (9.1%) inflammatory biomarkers that had a significant association with AAA: sIL6R, CCL8, CCL7, ILRN, F2, and PIGF. These results were consistent across a range of linkage-disequilibrium thresholds to identify independent genetic instruments. Some of these biomarkers have been previously implicated in the development of AAA but have not been validated in human RCTs of aneurysm development, growth, or rupture. Conclusions: This analysis highlights the role of several circulating inflammatory markers in the development of AAA. These findings represent potential therapeutic targets for further investigation in mechanistic trials.
Abstract 13681: Association of Serum Trimethylamine N-oxide Levels With Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Teenie Siu, Sandhya sahye-pudaruth, Fahmida Mannan, raphael blanc, Andreea Zurbau, Melanie Paquette, Darshna Patel, Laura Chiavaroli, Sonia Blanco Mejia, Tauseef Khan, Cyril Kendall, John L Sievenpiper, David Jenkins
Journal: Circulation (2023)

Background: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite of red meat, has emerged as a potential biomarker for CVD and all-cause mortality. It is also found in preformed amounts in fish. However, the association between serum TMAO levels and CVD outcomes remain unclear. Aim: To conduct a systematic review and dose-response meta-analysis evaluating the association between serum TMAO and CVD and all-cause mortality in prospective cohort studies. Methods: A comprehensive literature search was conducted in MEDLINE, EMBASE, and Cochrane Library up to and including March 6, 2023. A manual search through references found in reviews and meta-analyses was also conducted. Studies reporting hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs) for the association between serum TMAO levels and CVD or all-cause mortality in adults ≥ 18 years with follow-up of ≥ 1 year were included. Random-effects models were utilized for pooled risk estimates and assess the dose-response. GRADE was used to evaluate certainty of evidence. Results: 2459 papers, 44 prospective cohort studies were included involving 84771 participants included in final analysis (fig.1). Pooled analyses revealed a significant positive association between elevated serum TMAO levels and the risk of total CVD (RR 1.29 [1.16-1.44]), CVD mortality (RR 1.51 [1.23-1.87]) and all-cause mortality (RR 1.30 [1.21,1.39]). Non-significant associations were found for MI, stroke, total CHD, MI mortality and CHD mortality. All outcomes were of low to very low certainty.Dose response analysis revealed a significant linear association with all-cause mortality (RR 1.01 [95% CI 1.01, 1.02] per 2μM/L) up to a threshold of 6μM/L and total CVD (RR 1.04 [1.02-1.06]). Conclusion: This study provides evidence supporting the positive association of serum TMAO levels with increased risk of total CVD, CVD mortality and all-cause mortality. A recent review found 13/15 studies demonstrated a strong positive correlation between TMAO and fish intake, complicating the hypotheses relating TMAO in red meat and CVD risk. Thus, further assessments of diet components are needed to explore the clinical implications of the associations found in our study.
Abstract 12441: Ambient Fine Particulate Matter Air Pollution but Not Ozone is Associated With Elevated Risk of All-Cause Hospitalization in Patients With a Prior Diagnosis of Atrial Fibrillation
Authors: Benjamin D Horne, Francois Haddad, Elizabeth A Joy, Mary Prunicki, Jeffrey L Anderson, Juyong B Kim, Daniel Bride, Tami L Bair, Kari Nadeau, Kirk U Knowlton
Journal: Circulation (2023)

Introduction: Short-term increases (days to weeks) in fine particulate matter (PM 2.5 ) air pollution are associated with atrial fibrillation (AF) episodes. We previously reported that PM 2.5 was not associated with severe AF measured as emergency or inpatient hospitalization for the primary diagnosis of AF. Mild AF, though, may influence all-cause hospitalizations. This study evaluated if short-term increases in PM 2.5 and ozone were associated with all-cause hospitalization at 11 Intermountain Health hospitals in patients with AF, and if this differed between wildfire (June-Oct.) and winter inversion (Nov.-March) seasons. Methods: Patients carrying an AF diagnosis (N=347,157) were evaluated for all-cause hospitalization and, secondarily, AF hospitalization (N=25,601) and first AF diagnosis (N=77,893). PM 2.5 levels were measured from January 1, 1999 to March 31, 2022 (ozone: 2006-2022) in subjects residing on Utah’s Wasatch Front. Using the case-crossover design that matched individual-level characteristics, Poisson regression also adjusted for weather variables. Results: Mean age was 72±15 years and 51.0% were female. Overall, PM 2.5 increases at a lag of 0 days, 1 day, 3-day moving average (mAvg) (days 0-2), and 7-day mAvg (days 0-6) were associated with all-cause hospitalization [respectively: odds ratio (OR)=1.010, 1.008, 1.011, 1.009 per +10 μg/m 3 ; p=0.0004, 0.006, 0.0004, 0.028]. Associations differed by seasons (Figure). Regressions entering both ozone and PM 2.5 mildly increased PM 2.5 ORs for all-cause hospitalization. PM 2.5 was not associated with first AF diagnosis. Increases in ozone were not associated with higher risk of any outcome. Conclusions: Short-term increases in PM 2.5 air pollution were associated with all-cause hospitalization in patients with a prior AF diagnosis. Lag structure varied for wildfire and inversion seasons, with greater effect sizes in wildfire season. Increases in ozone did not associate with elevated risk.