tbuckley/cabot-search huggingface dataset:
Abstract 4124931: Usefulness of the AHEAD Score for Prediction of All-cause Death in Patients With Acute and Chronic Coronary Syndromes
Authors: Shunsuke Tamaki, Akinori Higaki, Hiroshi Kawakami, Kazuhisa Nishimura, Katsuji Inoue, Shuntaro Ikeda, Osamu Yamaguchi, Naoyuki Akashi, Tetsuya Matoba, Takahide Kohro, Tomoyuki Kabutoya, Kazuomi Kario, Arihiro Kiyosue, Masaharu Nakayama, Yoshihiro Miyamoto, Kenichi Tsujita, Hideo Fujita, Ryozo Nagai
Journal: Circulation (2024)

Background: The AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been introduced to predict all-cause death (ACD) in patients with heart failure. There is no information available on the utility of this score for the prediction of ACD in patients with coronary artery disease (CAD). Hypothesis: The AHEAD score may provide superior predictive value for ACD compared to the CHADS 2 score, which has been reported to be useful for predicting poor clinical outcomes in patients with acute (ACS) and chronic coronary syndromes (CCS). Methods: This retrospective multicenter cohort study analyzed data of the patients who underwent percutaneous coronary intervention for ACS or CCS between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The AHEAD score was calculated by assigning 1 point each for atrial fibrillation, hemoglobin &lt;13 mg/dL for men and &lt;12 mg/dL for women, age &gt;70 years, elevated creatinine levels (&gt;130 μmol/L), and diabetes mellitus. The CHADS 2 score was calculated as previously reported. The study endpoint was ACD. Results: In total, 9,033 patients were enrolled (median age, 72 years; 77% male; 3,920 with ACS and 5,113 with CCS). Higher AHEAD or CHADS 2 scores were significantly associated with a higher rate of left main disease or three-vessel disease in both patients with ACS and CCS. In addition, after accounting for multiple variables using Cox multivariate analysis, both the AHEAD (hazard ratio [HR], 1.83 [95% confidence interval, 1.63–2.06] for ACS and 1.66 [1.49–1.85] for CCS) and CHADS 2 scores (HR 1.27 [1.15–1.40] for ACS and 1.23 [1.12–1.35] for CCS) remained significantly associated with ACD. However, receiver operating characteristic curve analysis for predicting ACD revealed that the predictive value of the AHEAD score was significantly higher than that of the CHADS 2 score in both ACS and CCS (Figure). A significant difference was found in the rate of ACD among patients stratified by the AHEAD score in both groups (both P &lt;0.001). Conclusions: The AHEAD score had superior predictive value for ACD compared to the CHADS 2 score in patients with CAD, irrespective of ACS or CCS.
Abstract 4140126: Comparison of Clinical Risk Calculators for Atherosclerotic Cardiovascular Diseases: PREVENT, Pooled Cohort Equations, and QRISK3
Authors: Mohammadreza Naderian, Iftikhar Kullo
Journal: Circulation (2024)

Introduction: The cardio-kidney-metabolic pathway has a crucial role in ASCVD, motivating development of the PREVENT equation. There is a need for external validation of the PREVENT equation and assessment of its performance in independent cohorts to assess generalizability across diverse populations. Aim: To compare predictive performance of the PREVENT equation with previously developed risk calculators; pooled cohort equations (PCE), and QRISK3. Methods: We used data from 500k participants of the United Kingdom Biobank (UKB). ASCVD was defined as the composite outcome of fatal and non-fatal myocardial infarction, coronary revascularization, and stroke. We ascertained demographic and clinical covariates required to calculate ASCVD risk, using the base model of PREVENT, PCE, and QRISK3, at the time of recruitment. Those with a diagnosis of ASCVD at the time of recruitment or missing data on age, sex, or ethnicity were excluded. We used the area under the ROC curve (AUC) and calibration plots for analysis. Results: Of 459,681 participants (mean age 56.3±8.1 years, 44.4% male, and 94.7% White), 24,514 (5.4%) participants had a new diagnosis of ASCVD during a 10-year follow-up. The median [interquartile range] of estimated 10-y ASCVD risk was 3.7% [1.9% - 6.1%] for PREVENT, 5.6% [2.4% - 11.3%] for PCE, and 8.0% [3.9% - 13.8%] for QRISK3 (Figure 1A). The calibration slope (95% CI) was 1.71 (1.66 – 1.76) for PREVENT, 0.64 (0.63 – 0.66) for PCE, and 0.66 (0.64 – 0.67) for QRISK3 (Figure 1B). The AUC for ASCVD prediction was 0.741 (0.738 - 0.744) for PREVENT, 0.744 (0.741 – 0.747) for PCE, and 0.751 (0.749 – 0.755) for QRISK3 (Figure 1C). Conclusion: In the UKB cohort, the PREVENT equation underpredicted while the PCE and QRISK3 overpredicted ASCVD risk, with a similar discrimination. Consequently, fewer individuals would be eligible for primary prevention with statins, based on the actionable thresholds of 7.5% or 10% when considering ASCVD risk based on PREVENT. Therefore, the external application of the PREVENT equation requires recalibration and context-specific interpretation.
Abstract 4147638: Food Security, Depression, and the Association of Depression with Adherence to Cardiovascular Disease Risk Reduction Measures among Rural Caregivers of Patients with Chronic Diseases
Authors: Muna Hammash, Martha Biddle, Terry Lennie, Misook Chung, Debra Moser
Journal: Circulation (2024)

Introduction: Caregivers are at high risk of cardiovascular disease (CVD) and depression compared to non-caregivers. Food security has been suggested to be a risk factor for depression. Depression may be connected to poor self-care. Studies exploring food security, depression and its relationship to adherence to CVD risk reduction measures among rural caregivers are lacking. Aims: To determine: 1) the association between food security and depression in rural caregivers, and 2) the relationship between depression and caregiver burden, and reported adherence to recommended CVD risk reduction measures in rural caregivers of patients with chronic diseases. Method: In this cross-sectional study, 277 rural caregivers (mean age 54 ± 14 years; 76% were female; and 70% were married) provided self-reported data on their sociodemographic factors, food insecurity (US Household Food Security Survey Module), caregiver burden (Zarit Burden Interview), depression (Patient Health Questionnaire-9), and adherence to recommended CVD risk reduction measures (Medical Outcomes Study Specific Adherence Scale). Hierarchical regression analysis was performed. Results: In this study, food insecurity and high depressive symptoms were prevalent in 23% and 25% of rural caregivers, respectively. Food insecurity was associated with higher depressive symptoms ( β = 0.21; p &lt;.01), controlling for covariates. Caregivers who reported higher depressive symptoms had higher caregiver burden ( β = 0.49; p &lt;.01) and poor adherence to recommended CVD risk reduction measures ( β = 0.18; p &lt;.01) compared to those with low or no depressive symptoms, controlling for covariates. Conclusion: In rural caregivers, food insecurity was associated with higher depressive symptoms. Depressive symptoms were negatively associated with adherence to recommended CVD risk reduction behaviors. Greater attention should be given to food security and psychosocial factors to reduce CVD risk in this population.
Abstract 4141440: Pharmacokinetics and pharmacodynamics of SC furosemide in patients with HF and obesity
Authors: Tamas Alexy, Phani Kamineni, Mikako Harata, Katie Luepke, Matthew Goodwin, John Mohr
Journal: Circulation (2024)

Background: Obesity is increasingly prevalent in patients with heart failure (HF). Subcutaneous (SC) furosemide (Furoscix) is available as a 5-hour SC infusion via an on-body delivery device for the management of congestion, independent of ejection fraction. In a PK/PD study, the average bioavailability of Furoscix across the BMI spectrum was 99.6% with comparable diuresis and natriuresis to IV furosemide. However, the potential effects of obesity on the absorption and diuretic efficacy of Furoscix remain unknown. Goal: To evaluate PK/PD of SC furosemide compared to IV administration, stratified by BMI. Methods: Post-hoc analysis of SC furosemide pivotal PK/PD study was conducted to compare PK and urine output (UO) to IV furosemide, stratified by BMI. SC furosemide 80mg was administered over 5 hours per the typical biphasic administration schedule. IV furosemide was given as two 40mg injections, 2 hours apart. Plasma was collected to determine furosemide concentrations and UO was quantified over 8 hours. Descriptive statistics were reported. Results: Sixteen patients were included for UO and 15 for the PK analysis. Median BMI was 31.2kg/m 2 ; PK stratified by BMI is listed in Table 1. Peak plasma furosemide concentration (C max ) was lower in the BMI &gt;31.2kg/m 2 group with no difference in t 1/2 and greater UO at 8 hours in this cohort. There was no difference in any of the variables between the SC and IV agents across the BMI spectrum. Conclusion: Although Furosemide C max was lower in the cohort with BMI &gt;31.2kg/m 2 , total UO at 8 hours was higher. These findings were similar for the SC and IV formulations. Our data suggests that SC furosemide absorbs independent of BMI and provokes a reliable clinical response as measured by UO. Importantly, PK and UO results are consistently similar between the Furoscix and IV formulation across the BMI spectrum. Future research is warranted to investigate the reasons behind the increased UO in the population with higher BMI.
Abstract 4144577: Temporal Trends in Attainment of LDL-c Goals Post Coronary Artery Bypass Grafting (CABG): Data From a Large Integrated Healthcare System
Authors: Janine Yang, Douglas Stram, Ahmad Sheikh, Richard Ha, Seema Pursnani
Journal: Circulation (2024)

Introduction: Multisociety guidelines in secondary atherosclerotic cardiovascular disease (ASCVD) cholesterol goals have evolved over time. We aim to identify temporal trends in low density lipoprotein cholesterol (LDL-c) and statin use in a post coronary artery bypass grafting (CABG) population. Methods: This is a retrospective study of Kaiser Permanente Northern California members who underwent CABG from 2008 to 2019. Patients were stratified according to three time frames (2008-2013, 2014-2018, 2019) based on the release of multisociety guidelines in 1999, 2013 and 2018. LDL-c goal was defined as a last available value less than 70 mg/dL at 1 year follow up. Lipid lowering therapies were identified through pharmacy records. Cox proportional hazard modeling was used to identify major adverse cardiovascular event (MACE) free survival at up to 12 years follow up. Results: The cohort included 6422 patients, mean age 64.9 years, 83% male, with baseline LDL-c 95.9 mg/dL. Of the cohort, 47% of patients achieved an LDL-c &lt; 70 mg/dL at 1-year follow up. Of the stratified groups, the 2019 cohort demonstrated the highest attainment of LDL-c goal (65%, N=392) compared to 2008-2013 cohort (41%, N=1197) and 2014-2018 cohort (57%, N=1406) (Table 1). A relative increase in high dose statin monotherapy and a decrease in low/moderate dose statin monotherapy was temporally demonstrated in recent cohorts. There was a positive correlation between increasing year and attainment of LDL-c goal (R2=0.916) (Figure 1). Attainment of LDL-c &lt;70 at 1 year post CABG was associated with higher MACE free survival (log-rank p=0.057). Conclusions: Recent cholesterol guidelines post ASCVD have a stronger emphasis on specified LDL-c goals which is associated with increased attainment of LDL-c &lt;70 and improved MACE free survival in our post CABG patients.
Abstract 4144529: Cardiac Allograft Hypertrophy (CAH) at 6 Months Post Transplant Is a Prognostic Marker of Long-Term Outcomes: Are We Missing a Simple Biomarker?
Authors: Khush Patel, Varshni Nandakumar, Rajul Ranka, Guillermo Torre-Amione, Arvind Bhimaraj
Journal: Circulation (2024)

Introduction: Cardiac hypertrophy is a known adverse prognostic marker in various non-transplant pathologies. In heart transplant patients, due to many confounders, it has been controversial on the relevance and timing of cardiac hypertrophy as an adverse remodeling vs acute injury pattern in an immunologically hostile environment. Previous studies have shown prognostication of hypertrophy on echocardiogram at 1-year post-heart transplant. Research Questions: Does cardiac hypertrophy within a year after transplant have long-term prognostic implications? Methods: We collected relevant clinical variables for all heart transplants using EPIC EHR’s Clarity database. Hypertrophy was defined based on LV Mass Indexed to body surface area where LV Mass = 0.8 x (1.04 x (((LVIDD + IVSd + PWd) 3 - LVIDD 3 ))) + 0.6. Relative Wall Thickness was defined as RWT = 2 x PWd / LVIDD. We used a rule-based natural language processing program validated by correlation with manual readings by trained cardiologists (r=0.96, p=0.007) to abstract echo variables. Results: Inclusion criteria were heart transplants performed from 2015 to 2023 at our center, with an echocardiogram closest to 6 months (+/- 1 month). Ten percent (n=33) showed hypertrophy on echocardiograms at 6 months (Table 1). Of these, 20 (61%) had mild, 3 (9%) severe, and 10 (30%) moderate hypertrophy. Of 33 patients, 28 (85%) had concentric, and 5 (15%) had eccentric hypertrophy. Patients with hypertrophy at 6 months had significantly worse survival at 5 years (p=0.01) and 10 years (p=0.05) compared to patients without hypertrophy (Fig 1). Survival at 5 and 10 years was not statistically different for patients with hypertrophy at 3 months (5 yrs p=0.17, 10 yrs p=0.06), 12 months (5 yrs p=0.38, 10 yrs p=0.30), and 18 months (5 yrs p=0.15, 10 yrs p=0.08) compared to those without hypertrophy. Conclusion: Cardiac hypertrophy on echocardiogram at 6 months predicts adverse long-term survival, while other time points did not.
Abstract 4143250: Individualized Interactomes from Pulmonary Arterial Hypertension Biopsies Predict Therapeutic Response: an <i>In Silico</i> Clinical Study
Authors: Ruisheng Wang, Navneet Singh, Henri Wathieu, grayson baird, Katherine Cox-Flaherty, James Klinger, Christopher Mullin, Mandy Pereira, Mary Whittenhall, Elizabeth Harrington, Brad Maron, Corey Ventetuolo
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a highly morbid cardiopulmonary disease characterized by substantial pathobiological and clinical heterogeneity, which is believed to underlie variable treatment-response observed in clinical trials and at point-of-care during real-world practice. Utilizing patient-specific pathogenetic information to inform drug selection for use in clinical practice is expected to improve clinical efficacy of PAH drugs, but such strategies are currently lacking. Methods: We conducted a retrospective analysis of 25 PAH patients (32 samples, receiving PAH therapies) undergoing right heart catheterization (RHC) for the routine clinical assessment of dyspnea at Rhode Island Hospital (Warren Alpert Medical School of Brown University) , along with 3 healthy controls. A minimally invasive "cell biopsy" approach was used to collect Pulmonary Arterial Endothelial Cells (PAECs) from the tips of pulmonary artery catheters. Transcriptomic RNA-seq was performed on mRNA isolated from cell passage 3 or 4 for all samples. We deployed an innovative network medicine method to construct sample-specific interactomes from the transcriptomic data and human protein-protein interactome. The individualized interactomes captured patient-specific molecular features, which could then be used to predict therapeutic response in PAH patients. Results: The individualized interactomes have a range of 5276 [4900, 7263] nodes and 7204 [6606, 12992] edges. We observed that an increase in 6MWD from baseline that was sustained at 12 months following treatment initiation was associated with higher fraction of drug targets in the individualized interactomes. By contrast, such a positive association was not observed in comparator drugs. Similarly, we observed a transition in BNP levels from elevated at baseline to within the normal range at 12 months that corresponded to an absolute decrease of ~250 pg/mL. Higher fraction of drug targets in the individualized interactomes was also associated with a significant improvement in REVEAL 2.0 Risk score at 6 months (p=0.004) and 12 months (p&lt; 0.001). Conclusions: "Cell biopsies" taken at point-of-care for clinically indicated RHCs may be leveraged to predict therapeutic response and inform precision-based initiatives in pulmonary vascular disease through transcriptome-derived sample-specific interactomes and systems pharmacology tools.
Abstract 4136901: Mechanosensitive channel protein Piezo1 synergizes with TLR4 to enhance osteogenic responses in human aortic valve interstitial cells
Authors: Xiangjie Lin, Shuwen Su, Xiaolin Duan, Wenyan Li, Dongtu Hu, Ying-wen Lin, Sijie Jiang, Liusheng Wang, Juncong Li, Dingli Xu, Zeng Qingchun
Journal: Circulation (2024)

Background: Calcific aortic valve disease (CAVD), a common heart valve disease in the elderly, has a complex pathogenesis. Abnormal blood flow shear can be regarded as an important factor in the development of CAVD, and a key molecule that responds to mechanical stress is the mechanosensitive ion channel protein Piezo1; however, the role of Piezo1 in CAVD has not been clarified. Methods and results: We collected CAVD patients and their age- and sex-matched controls, and compared the differences in the protein expression levels of Piezo1 and TLR4 between the two using Western blot and other techniques, and found that the expression of Piezo1 and TLR4 proteins was elevated in the CAVD group. We gave LPS or Piezo1 agonist Yoda1 to stimulate aortic valve mesenchymal stromal cells, respectively, and the Western blot results showed that ALP and Runx2 expression were elevated after LPS and Yoda1 stimulation, and immunofluorescence and alizarin red staining showed similar results. Inhibition of TLR4 or Piezo1 attenuated the osteogenic differentiation of AVICs. Cellular immunofluorescence results showed that TLR4 could be transported from the Golgi to the cell membrane under Yoda stimulation, and Golgi-cell membrane transport of TLR4 was attenuated after Rab3b knockdown by siRNA. After first pre-stimulation with Yoda1 and then stimulation with LPS, Western blot and immunofluorescence results showed that the protein levels of ALP and Runx2 as well as NF-κB phosphorylation were to be significantly increased. Conclusion: Stimulation of Piezo1 and TLR4 can enhance the osteogenic response of AVICs. Stimulation of Piezo1 enhances the transport of TLR4 from the Golgi to the cell membrane via Rab3b, and Piezo1 synergistically enhances the osteogenic response of AVICs with TLR4, thus promoting the development of CAVD.
Abstract 4144555: Atrial Fibrillation Catheter Ablation among Patients with Mediastinal Radiation; Insight from The National Inpatient Database (2015-2020)
Authors: Muhammad Osama, Nauman Naeem, asmaa ahmed, Hafsa Jawaid, Saif ur Rehman, Dmitry Chuprun, Mohan Rao
Journal: Circulation (2024)

Introduction/Background: Radiation therapy (RT) is one of the most common treatment modalities for mediastinal cancers. RT has multiple adverse cardiovascular effects and it has been identified as an independent risk factor for atrial fibrillation (AF). The efficacy of catheter ablation in AF is well established, however there is limited data on procedural safety and outcomes in patients with mediastinal cancers and history of radiation Methods: The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify admissions for AF catheter ablation among patients with previous history of mediastinal radiation exposure using the 10-PCS (International Classification of Diseases, procedure coding system) codes. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes. Results: We identified 257,240 admissions for AF catheter ablation of which 1720 patients (0.67%) had a history of mediastinal radiation exposure. In the adjusted analysis, the odds of in-hospital mortality (aOR 0.639, 95% CI 0.34-1.20, p 0.1637), major complications (aOR 0.876, 95% CI 0.73-1.05, p 0.1443), any gastrointestinal or hematological complication (aOR 0.853, 95% CI 0.63-1.15, p 0.3017), renal complications (aOR 1.017, 95% CI 0.88-1.18, p 0.0509) were similar in both cohorts. The odds of any cardiovascular complication (aOR 0.825, 95% CI 0.70-0.97, p 0.0208) was lower and odds of any pulmonary complication (aOR 1.433, 95% CI 1.27-1.62, p&lt;.001) was higher in the mediastinal radiation cohort. Conclusion: AF catheter ablation in patients with history of mediastinal radiation is a safe treatment modality. It is not associated with higher in-hospital mortality or cardiac complications in a nationwide registry.
Abstract 4143281: The Influence of Personal and Family Support on Maternal Cardiovascular Health: Insights from a TriNetX Study
Authors: Toluwalase Awoyemi, Anderson Anuforo, Oluwaremilekun Tolu-Akinnawo, Ikeoluwapo Bolakale-Rufai, Ugochukwu Ebubechukwu, Chinenye Odo, Kayode Ogunniyi
Journal: Circulation (2024)

Background: Maternal cardiovascular health during and after pregnancy is influenced by various factors, including personal and family support. However, the specific impact of abnormal personal and family support on maternal outcomes remains understudied. Methods: Utilizing the TriNetX global health research network within the US Collaborative Network, we investigated the influence of abnormal personal and family support (ICD10CM:Z63) on maternal cardiovascular outcomes within one year post-pregnancy. Cohort 1 comprised women aged 15 to 60 with documented problems relating to primary and family support during or after childbirth between 2008 and 2023. Cohort 2 included a similar demographic with good primary and family support. Data were extracted from electronic health records, and the cohorts were matched based on diverse sociodemographic traits and medical comorbidities. Results: Our analysis revealed significant associations between problems relating to primary and family support during and after pregnancy and adverse maternal cardiovascular outcomes. Specifically, the presence of such challenges significantly increased the risk of major adverse cardiac and cerebrovascular events (MACCE) (OR: 4.823, 95% CI: 3.361 to 6.919, p&lt;0.001) and all-cause mortality (OR: 8.461, 95% CI: 5.184 to 13.812, p&lt;0.001). Interestingly, it was associated with a reduced risk of peripartum or postpartum preeclampsia (OR: 0.603, 95% CI: 0.403 to 0.903, p&lt;0.001). However, no significant association was observed between these personal and family support challenges and acute MI (OR: 1.092, 95% CI: 0.482 to 2.747, p=NS), ischemic stroke (OR: 1.403, 95% CI: 0.623 to 3.160, p=NS), hemorrhagic stroke (OR: 1.000, 95% CI: 0.416 to 2.404, p=NS), heart failure (OR: 1.075, 95% CI: 0.636 to 1.817, p=NS), or peripartum cardiomyopathy (OR: 0.586, 95% CI: 0.322 to 1.068, p=NS). Conclusion: Our findings highlight the significant impact of abnormal personal and family support on maternal cardiovascular health outcomes during and one year after pregnancy. Addressing challenges related to primary and family support during and after pregnancy may be crucial for reducing adverse outcomes and enhancing overall maternal well-being.