tbuckley/cabot-search huggingface dataset:
Abstract 15172: P21 Activated Kinase 2 Mediates Cardioprotection in Heart Failure With Preserved Ejection Fraction by Modulating Endoplasmic Reticulum Stress Response
Authors: Hongyuan Zhang, Tayyiba Azam, Min Zi, Xin Wang
Journal: Circulation (2023)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterised by diastolic dysfunction but normal systolic function. Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of HFpEF. Previous studies have reported that P21 activated kinase 2 (Pak2) confers cardioprotection against the endoplasmic reticulum stress response. Hypothesis: Pak2 protein can potentially alleviate the adverse effects of maladaptive ER stress in HFpEF. Methods: The HFpEF model was developed by feeding C57/BL6N male mice with a high-fat diet (HFD) and a constitutive nitric oxide inhibitor, L-NAME, in drinking water for 15 weeks. Cardiac function was assessed by echocardiography and hemodynamics. Heart and lung structure was detected by H&amp;E staining and Masson staining. Electron microscopy, immunoblotting, and RNA sequencing were used to investigate the ER structure and function. Cardiomyocyte-specific Pak2 knockout (Pak2 CKO ) mice and adeno-associated virus (AAV) 9 for Pak2 overexpression were used to investigate the role of Pak2 in the heart. Results: After 15 weeks of feeding, mice on the HFD+L-NAME diet developed an HFpEF phenotype, as indicated by cardiac hypertrophy, impaired diastolic function but preserved systolic function, and pulmonary remodelling. The ER structure and the IRE1/XBP1s pathway were impaired in the cardiomyocytes of HFD+L-NAME mice. Pak2CKO mice exhibited the HFpEF phenotype at 10 weeks. In addition, Pak2 overexpression prevented diastolic dysfunction after 15 weeks and preserved the activation of the IRE1/XBP1s pathway under stress conditions. Conclusions: HFD + L-NAME diet for 15 weeks recapitulated the features of HFpEF in mice. Pak2 plays a protective role in HFpEF progression by modulating the cardiomyocyte ER stress response through the IRE1/XBP1s signaling pathway.
Abstract 19026: Racial and Socioeconomic Disparities Among Inpatients With Pulmonary Hypertension: A Nationwide Study
Authors: Frempong Asafu-Adjaye, Francisco Somoza-Cano, Sedina Asafu-Adjaye, Joseph Amoah, Joseph A Akamah
Journal: Circulation (2023)

Introduction: Healthcare-associated racial disparities have become a significant public health concern. Due to the increase in morbidity and mortality associated with pulmonary hypertension (PH), we sought to explore whether race and socioeconomic status impact the disease’s burden. Methods: We identified adults 18 and above, with primary or secondary diagnoses of PH (all groups) using 2020 National Inpatient Sample (NIS) database. The ICD-10-CM codes were used. Data were analyzed using Stata 18. Results: Of 5,533,733 adults admitted, 4516 (8%) were diagnosed with PH. Mean age was 64.99 (SEM: ± 0.40), and 2784 (61.6%) were females. The mean length of stay was 5.09 ± 6.61 (SD). Data was missing for 92 patients regarding race. Of the sample of 4424, the majority (2743) were Caucasians (62.0%). The other races were Blacks 1066 (24.1%), Hispanic 398 (9.0%), Asia/Pacific Islanders 89 (2.0%), Native American 14 (0.3%), and others 114 (2.6%). Regarding socioeconomic status, 547 (20.0% of Caucasians), 518 (48.6% of Blacks), 162 (40.7% of Hispanics), 8 (9.0% of Asia/Pacific Islanders), and 35 (27.3% others) had low median household income defined as &lt; $50,000 (p &lt;0.001). The median cost of care was $73,337 ± 156,008. Among these patients with primary or secondary diagnoses of PH, the mortality rate was 2.8% (126/4516). Blacks had higher odds (cOR 1.62, 95% CI: 1.10-2.40, p&lt;0.05) of inpatient mortality compared to Caucasians. However, the multivariate logistic analysis revealed no significant association after adjusting for age, gender, length of stay, median household income, total charges, and Charlson index (comorbidities). Conclusions: Racial disparities exist regarding PH-related admissions, with a higher likelihood of mortality among Blacks and persons with low socioeconomic status. The cost of health care in this population was high. Additional research is needed to focus on reducing disparities in healthcare regarding PH.
Abstract 12491: Impact of Augmented Treatments on Physical Activity Outcomes in a Sequential Multiple Assignment Randomized Trial
Authors: Shannon Halloway, Manju Daniel, Joellen Wilbur, Michael Schoeny, Spyros Kitsiou, Tricia J Johnson, Sachin Vispute, Susan Buchholz
Journal: Circulation (2023)

Background: Nearly half of women do not meet aerobic physical activity (PA) guidelines. Despite proven efficacy of PA interventions, response varies. Little is known about when treatment should be augmented. The Working Women Walking Program is a Sequential Multiple Assignment Randomized Trial testing two initial treatments (Fitbit vs. Fitbit+text messages) for eight weeks and two augmented treatments (personal calls vs. group meetings) added at eight weeks for non-responders to the initial treatments. Aims: We aim to compare the two augmented treatments among non-responders to the initial treatments on PA after 34 weeks of the program. Methods: Participants ( N = 301; women ages 18-70) were randomly assigned to an initial treatment of either Fitbit ( n = 149) or Fitbit+text messages ( n = 152). Both groups received a Fitbit and PA prescription (increase daily steps by ≥600 above baseline). Response to treatment was defined as (a) wearing the Fitbit 10 hours per day 3 of 7 days weekly in weeks 6-8 and (b) reaching a step goal ≥600 steps above baseline for 2-3 weeks in weeks 6-8. Non-responders were randomly assigned to an augmented treatment with personal calls ( n = 72; 50.7%) or group meetings ( n = 70; 49.3%). Objective PA was assessed with the waist-worn ActiGraph accelerometer (≥4 days with one weekend day and ≥10 hours daily wear time) at baseline and 34 weeks to assess daily steps and minutes of light and moderate-vigorous intensity PA (MVPA). Self-report PA was measured with the International PA Questionnaire to assess daily MVPA and walking. Results: Across all PA measures, there were no significant differences between augmented treatments (personal calls vs. group meetings). Overall, both treatments showed non-significant increases in objective PA, including steps ( d = .15; p = .30), light PA ( d = .11; p = .39), and MVPA ( d = .22; p = .15), but showed significant increases in self-report PA, including ( d = 1.02; p &lt; .001) and walking ( d = .73; p = .30). Conclusion: In this sample of working women who were non-responsive to an initial PA treatment (Fitbit or Fitbit+texts), augmenting with personal calls or group meetings did not yield a difference in PA outcomes. Next, we will explore participant characteristics that may differentiate response to augmented treatments.
Abstract 131: Sex-Based Differences in the Extracorporeal Cardiopulmonary Resuscitation Population for Out-of-Hospital Cardiac Arrest in the Minneapolis Metro Area
Authors: Garima Dahiya, Johnny Chahine, Christopher Gaisendrees, Deborah C Jaeger, Jason Bartos, Caleb Chiang, Alejandra Gutierrez, Lucinda Hodgson, Demetris Yannopoulos, Andrea M Elliott
Journal: Circulation (2023)

Background: Women constitute nearly 40% of out-of-hospital cardiac arrests (OHCA), receive less bystander CPR, and guideline-directed interventions such as post-arrest coronary angiography. Aims: To identify the presence of sex-based differences in utilization of extracorporeal cardiopulmonary resuscitation (ECPR) for refractory OHCA in the Minneapolis (MSP) metro area. Methods: Patients who met all eligibility criteria for the Minnesota Resuscitation Consortium (MRC) ECPR protocol between 2013-2021 were identified in the Cardiac Arrest Registry to Enhance Survival (CARES) registry. Patients who presented to the University of Minnesota (UMN) for the MRC ECPR protocol between 2014-2021 were identified. Arrest data, patient characteristics and mortality were compared between the sexes in both populations. Results: We identified 2790 OHCA patients through the CARES registry of whom 685 (24.6%) were women. There were 443 referrals to UMN for ECPR, of whom 87 (19.6%) were women. There were significantly more eligible women who arrested than those referred for ECPR (p =0.02). In the MSP metro area, women were more likely to suffer cardiac arrest at home (59% vs 66%, p&lt;0.01), less likely to receive bystander CPR (42% vs 35%, p&lt;0.01) and have greater time to professional CPR (6.3 vs 5.4 minutes, p&lt;0.01). Among referrals for MRC ECPR protocol, there were no differences in arrest characteristics or age between men and women. Multivariate analysis for neurologically favorable survival showed female sex was associated with decreased survival in the community (p=0.03), but trended towards increased survival in the UMN ECPR cohort (p=0.08) (Figure 1). Conclusion: Women suffering from cardiac arrest have higher mortality and are less likely to be referred for ECPR. However, after referral for ECPR, sex is not associated with survival. Pre-hospital factors result in fewer women referred for ECPR and warrant further investigation to identify potential interventions.
Abstract 17859: Real World Cardiovascular Events With Next Generation Bruton's Tyrosine Kinase Inhibitors - An Updated Analysis
Authors: Michael C Poliner, Benjamin Buck, Sanam Ghazi, Sunnia Chen, John A Gambril, Stephen Sansoterra, Tracy Wiczer, Seema Bhat, Leylah Azali, Lindsay Rosen, Sujay Kalathoor, Qiuhong Zhao, Kerry Rogers, Adam Kittai, Michael Grever, Farrukh Awan, Patrick Ruz, Marilly Palettas, Mussammat Ferdousi, Onaopepo Kola-Kehinde, Sneha Sharma, John Byrd, Jennifer Woyach, Daniel Addison
Journal: Circulation (2023)

Introduction: Acalabrutinib and zanubrutinib are next generation Bruton’s tyrosine kinase inhibitors (BTKIs) associated with dramatic efficacy against B cell malignancies. In early trials, these BTKIs show less cardiac activity than ibrutinib. Yet, whether this is seen in longer term follow up is unknown. Methods: Leveraging the US Food and Drug Administration’s Adverse Events Reporting System (FAERS), we identified the relative incidence and predictive factors for atrial fibrillation (AF) after BTKI initiation from 2015-2022. Secondary outcomes were the reporting odds ratios (ROR) of major adverse cardiovascular adverse events (AEs), defined as AF, non-AF atrial arrhythmias, heart failure, conduction blocks, and ventricular arrythymias. In addition, using a registry cohort of 838 hematologic malignancy patients treated with ibrutinib or acalabrutinib from 2012-2020, we assessed the comparative incidence of new AF. Observed incident AF rates were compared with Framingham heart predicted rates, and absolute excess risks of AF were estimated. Multivariable logistic-regression models were used to identify factors associated with AF, other cardiac AEs, and mortality. Results: Among 21,435 events reported to FAERS during BTKI use, 3,453 were cardiovascular AEs. AF was the most reported AE (ROR 8.8, 95% CI, 8.3-9.4; Figure A ). The likelihood (ROR) of cardiac AE reporting in next generation BTKI treated patients was &gt;3.0 ( P &lt;0.05; Figure A ) for AF events. Furthermore, in acalabrutinib treated registry patients, 9.7% developed incident AF over a median follow up of 42 months. In those without prior ibrutinib use, the weighted average incidence was 281 per 10,000 person years compared to the Framingham predicted rate of 103 per 10,000 person years (RR 2.73, P &lt;0.001; AER 178; Figure B ). Conclusions: These data suggest residual AF risk with next generation BTKIs.
Abstract 12897: Automated Assessment of Left Ventricular Function in Tetralogy of Fallot - A Machine Learning Approach
Authors: Arnav Adhikari, Giles Vick, Minh B Nguyen, Tam Doan, Mounica Y Rao, David Ouyang, Anitha Parthiban, Lalita Wadhwa
Journal: Circulation (2023)

Introduction: Congenital heart disease (CHD) is associated with significant cardiac anatomic and functional variability. This study tests the implementation and validation of a convolutional neural network algorithm (EchoNet-Dynamic) on a pediatric dataset via a transfer learning approach. We compare the echocardiographic systolic function measure, left ventricular ejection fraction (LVEF), with CMR as the gold standard. Methods: Patients ages 1-18 (44% female) who underwent a transthoracic echocardiographic evaluation and CMR for repaired Tetralogy of Fallot (TOF) were divided into 2 groups of EF &lt; and &gt;40%. 406 (2D-A4C views) videos with LVEF calculated using Bullet and Simpson method were identified. MRI EF as a ground truth label was compared with predicted EF data. Inference weights were derived from EchoNet-Dynamic and the weights from re-training the model on pediatric data. Correlation statistics were computed. The metrics included mean absolute error (MAE), root mean squared error (RMSE), and coefficient of determination (R2). Results: The R2 of actual vs predicted was 0.83 (0.71-0.89) with an MAE of 3.55. The predicted EF vs MRI EF resulted in an R2 of 0.48 and an MAE of 6.39 (Figure 1 a-c). Bland-Altman analysis between actual vs predicted EF estimates LVEF (bias = 1.64%) with 95% limits of agreement of -7.80% to 11.09%. MRI EF vs predicted values, the model estimates LVEF (bias = -3.12%) with 95% limits of agreement of -18.71% to 12.48%. The smaller body surface area and ages correlated with better model performance in both groups. Conclusions: EchoNet-Dynamic trained on a pediatric data set can accurately predict EF and this validates the model’s performance on a distinct CHD population. The predicted EF accurately compares with the MRI assessment. EchoNet Dynamic can be employed via a transfer learning method for automated real-time evaluations of cardiac function in CHD patients with compromised ventricular function and complex anatomical phenotypes.
Abstract 15377: Traditional Cardiovascular Risk Factors Do Not Fully Explain the Risk of CAD Population in Colombia
Authors: Victor Gil Aldana, Juan D Torres-Florez, Carol Paez-Canro
Journal: Circulation (2023)

Introduction: Major cardiovascular events occur even having reached LDL-C goals. Tolima department has the highest rate of cardiovascular mortality within Colombia. Hypothesis: in patients who underwent percutaneous coronary intervention (PCI) in a healthcare institution in Ibague Colombia, there is an increasing cardiovascular risk regardless of traditional risk factors. Methods: Descriptive, retrospective analysis of a cohort of patients with coronary artery disease (CAD) with PCI between 2020-2023. A multiple logistic regression model was developed, adjusted for predictors of CAD (Figure 1). Data was analyzed through R-4.3.0, JASP0.17.1 and Python3.11. Results: A sample size of 463 patients who underwent PCI was assessed (Table 1). Dyslipidemia was the most prevalent risk factor 43.2%(n=200). Mean LDL-C was 102, mean HDL was 38 and mean triglycerides was 186. The most incident coronary heart disease was NSTEMI 50.5%(n=234). Data was fitted into a logistic regression model accounting for comorbidities, risk factors and lipid profile values. Regression coefficients computed for CAD were around 0.07. Independent variables explain approximately 7 up to 16.1% of the variance observed in the dependent variable (Figure 1). Conclusions: In primary and secondary prevention for CAD, there is a high prevalence of risk factors. Although risk factors impact the outcome, they account for a relatively little variability within the model. Results imply that there are other key factors that contribute to the outcome and may not be measured currently. Further studies must be developed to evaluate markers in residual risk that may have an impact on the prognosis of patients with CAD.
Abstract 14328: Performance of Current Cardiovascular Risk Scores Among the Brazilian Population: Findings From the ELSA-Brasil Study
Authors: Aline Pedroso, Sandhi Maria Barreto, Luisa C Brant, Antonio Ribeiro, Marcio S Bittencourt, Roberta Figueiredo, Rohan Khera
Journal: Circulation (2023)

Background: Cardiovascular disease (CVD) poses a significant health burden in low- and middle-income countries (LMIC), yet existing risk stratification strategies are primarily designed and validated in high-income countries. Objectives: We evaluated the discrimination and calibration of four CVD risk scores - Framingham General Risk (FGR), Pooled Cohort Equations (PCE), World Health Organization CVD score (WHO), and European Society of Cardiology (Score-2) - within the largest Brazilian community-based cohort study (ELSA-Brasil). Methods: We included all individuals aged 40 to 75 years in the prospective ELSA-Brasil without prior CVD who were followed for incident adjudicated CVD events (fatal and non-fatal MI and stroke or CHD death). We compared the mean predicted CVD risk scaled to 4 years with the observed 4-year CVD events across baseline risk groups (&lt;5%, 5-10% and ≥10%.). For the total population and by race/sex group, we assessed discrimination by measuring the area under the ROC curve and calibration by predicted-to-observed risk (P/O) ratios using the Grønnesby-Borgan goodness-of-fit test. Results: 12,742 individuals (52.9±8.1 years, 55.5% female) had 134 events. The model discrimination was acceptable for all scores (AUC&gt;0.7), except for white women (AUC between 0.60 95% CI 0.44-0.76 and 0.64 95% CI 0.51-0.77). All risk scores overestimated the CVD risk in our study population (P/O ratio between 2.29 and 1.15). PCE and FGR scores displayed the highest overestimation (P/O ratio: 2.29 95% CI 2.07-2.51 and 2.19 95% CI 1.88-2.50, respectively), and the recalibrated WHO score for tropical Americas had the best calibration performance (P/O ratio: 1.15 95% CI 0.96-1.34). Conclusion: Current CVD risk scores have good discrimination but poor calibration in this admixed Brazilian population. The recalibrated WHO score showed the best calibration, highlighting the need for improved risk stratification and tailored risk-based prevention strategies in LMICs.
Abstract 14339: Guideline-Directed Intensive Management Improves Long-Term Survival and Compliance of Pulmonary Hypertension Patient
Authors: Jiajun Guo, Jiaqi Wang, Yuanwei Xu, yucheng chen
Journal: Circulation (2023)

Introduction: Although the overall survival of PH patients improved in the current era, better management of PH patients still needs further exploration. Hypothesis: We hypothesized that guideline-directed, nurse-led, and multidisciplinary intensive management of PH patients would improve the overall survival of PH patients. Methods: We prospectively enrolled patients with PH from October 2013 to December 2020. Patients were divided into intensive management group and usual care group voluntarily. Intensive management was nurse-led and delivered by multidisciplinary teams, including patient education, symptoms monitoring, and patient adherence improvement with careful outpatient assessment every 3 months and medicine prescription whenever needed. Patients with usual care were treated by primary cardiologists’ consultants and telephone follow-ups every year. Results: Overall, 413 PH patients were finally included with a median follow-up period of 25.2 months(interquartile range: 12.4-44.3 months). Both overall survival (p&lt;0.001) and event-free survival (p=0.008) of the intensive management group were significantly higher than the usual care group. After adjustment of age and sex, intensive management was also an independent protective predictor for both primary [all-cause mortality, HR 0.378, 95% CI (0.214-0.668), p&lt;0.001] and composite endpoints [all-cause mortality and re-hospitalization, HR 0.648, 95% CI (0.454-0.927), p=0.017]. Conclusions: Guideline-directed, nurse-led, multidisciplinary intensive disease management strategy could be an ideal method to further improve the overall survival and event-free survival of PH patients.
Abstract 17067: Long-Term Transplant-Free Survival is Improved in Hypoplastic Left Heart Syndrome With Cell-Based Therapy
Authors: Sunjay Kaushal, Eric Naioti, Kevin N Ramdas, Danial Mehranfard, Lisa McClain-Moss, Michael E Davis, Linda M Lambert, Shaji C Menon, Narutoshi Hibino, David Morales, Adil Husain, Kaitlyn Masih, Kristopher B Deatrick, Sarah Speed, Anthony Oliva, Joshua M Hare
Journal: Circulation (2023)

Hypoplastic left heart syndrome (HLHS) is a univentricular congenital heart defect that has high morbidity and mortality and requires three-stage surgical reconstruction so that the right ventricle (RV) delivers systemic circulation. Poor outcomes result from RV failure in the systemic position. Accordingly, we conducted a phase I clinical trial (called ELPIS) of Lomecel-B™, an allogeneic bone-marrow derived cell-based therapy designed to improve cardiovascular performance, delivered as a one-time treatment during the Stage II (Glenn) surgery at approximately 4 months after birth. This trial met its primary endpoint (safety through 1-year post-treatment). To assess whether Lomecel-B™ has survival benefits, all ELPIS patients ( n=10, 7 males, and 3 females) were enrolled in a multi-year follow-on study and compared to a retrospective control group which was identified by a relevant clinical HLHS database. Patients in both studies were assessed for up to 5 years (range 3.5 - 5.0 years post-treatment for ELPIS) for mortality, heart transplants, and stage III (Fontan) surgery. Outcomes were compared with long-term historical data from patients in the Single Ventricle Reconstruction (SVR) Trial receiving the same shunt type at Stage I (Norwood) operation. 5-year Kaplan-Meier survival was 100% in ELPIS patients with none requiring heart transplant. This compared to 81.6% (95% CI= [76.5, 87.0]) transplant-free survival in the SVR trial through 5 years post-Glenn surgery, and a 5.2% (95% CI= [2.0, 8.3]) heart transplantation rate (Figure 1). No stem cell related safety issues were reported. These findings support Lomecel-B™ as a potential adjunct to HLHS reconstruction surgery to improve clinical benefits and reduce the need for subsequent heart transplantation. Further long-term follow-up and controlled trials are both warranted and underway.