tbuckley/cabot-search huggingface dataset:
Abstract 4147562: Traditional modifiable cardiovascular risk factors and the risk of future CHD in the general population: an attempt towards better understanding residual risk.
Authors: Natalie Arnold, Alina Gossling, Benjamin Bay, Christopher Blaum, Fabian Brunner, Tanja Zeller, Allan Linneberg, Stefan Soderberg, Licia Iacoviello, Susana Sans, Giovanni Veronesi, Sameline Grimsgaard, Frank Kee, Veikko Salomaa, Kari Kuulasmaa, Barbara Thorand, Stefan Blankenberg, Christoph Waldeyer, Wolfgang Koenig
Journal: Circulation (2024)

Background: Up to 20% of patients presenting with an acute coronary heart disease (CHD) event do not report any traditional modifiable cardiovascular risk factors (CVRFs) on admission. However, major predictors of CHD events in the absence of CVRFs are still unknown. Aims: To establish whether increased concentrations of emerging circulating biomarkers at baseline (hsCRP, cystatin C, fibrinogen, NT-proBNP and troponin I), might be associated with future CHD events in subjects from the general population, who demonstrated no traditional CVRFs (hypertension, diabetes mellitus, dyslipidemia, smoking) at time of enrollment. Methods: Overall 213,310 subjects (median age 50.6 yrs.; 57.0% males) from 21 European prospective population-based cohorts were included. All participants were free of CHD at baseline and were followed-up prospectively for incident CHD events. Subjects were characterized in accordance to CVRF burden into2not present" or having 1 or ≥2 CVRFs at baseline. Fine and Gray competing risk-adjusted models were performed for the association between biomarkers and future CHD events in an interaction with the CVRF groups. Results: Overall, 18.6% of subjects revealed no traditional CVRF at baseline (n=39,722). During a median follow-up of 13.95 years, 17,544 subjects developed an incident CHD event (event rate 20.0%). Of those, 532 events were among subjects, who were free of four traditional CVRFs at baseline (event rate 6.7%). Among all studied biomarkers, only fibrinogen was not associated with incident CHD among those without CVRFs, whereas the association between all remaining biomarkers and future events was found to be even more prominent in subjects without than in those with CVRFs. The corresponding sub-distribution Hazard Ratios (sHRs) with 95% CI were for hsCRP (&lt;2 vs. ≥2 mg/L) 1.64 (1.22-2.19) in those without CVRFs vs. 1.37 (1.21-1.55)/1.24 (1.14-1.35) in those with 1 or ≥2 CVRFs, respectively; for cystatin C (&lt;median vs. ≥median) the sHRs were 1.79 (1.29-2.47) vs 1.30 (1.13-1.50)/1.10 (0.98-1.22), for NT-proBNP (&lt;90 th pctl vs ≥90 th pctl) 2.23 (1.40-3.56) vs. 1.42 (1.13-1.79)/1.50 (1.31-1.73) and for troponin I (&lt;6 vs. ≥6 ng/L) 2.03 (1.40-2.95) vs. 1.24 (1.07-1.45)/1.24 (1.12-1.36), respectively. Conclusion: In the general population low event rates for incident CHD were found among CVRF-free subjects at baseline. Moreover, circulating biomarkers might substantially improve the prediction of future CHD events in this low-risk population.
Abstract 4146692: Cardiovascular Health Declines During Young Adulthood – An Electronic Health Record Study of &gt;75,000,000 Individuals
Authors: Robin Ortiz, Sean Heffron
Journal: Circulation (2024)

Background: Young adulthood (YA, 19–39 years) is the life stage of greatest increase in cardiovascular (CV) risk and decline in CV health (CVH). Cosmos is a database of Electronic Health Record (EHR) data from all Epic EHR sites – including &gt;250 million patients. Previous observations of CVH in YA have been limited to small, epidemiological cohort studies. Purpose: The current study aimed to be the first to use Cosmos to describe CVH in a nationally representative, extremely large, cohort of YAs. Methods: The AHA Life’s Essential 8 framework for CVH includes target metrics for health behaviors (nicotine exposure, diet, physical activity (PA), and sleep) and clinical factors (BMI, non-HDL-C, glucose, and blood pressure (BP)). We aimed to trend the proportion meeting “ideal” (highest score) for available CVH metrics (smoking, systolic BP (SBP), non-HDL, BMI, hemoglobin A1c, PA) across the young adulthood (from 19 to 39 years), by extracting available Cosmos data spanning May, 2022 to April, 2024. Results: The total sample included 76,216,126 YA (54% White, 15% Black, 4% Asian, 14% Hispanic; 54% female) of age 19-39 years. CVH available data varied: 2, 3.5, and 4.3 million for non-HDL, PA, and A1c, respectively; 28.8, 47.8, and 66.6 million for BMI, SBP, and smoking, respectively. Overall, ideal CVH metrics were more common than poor (Table), except for BMI. However, prevalence of ideal CVH decreased with increasing age (Figure). A notable exception was the proportion reporting PA 6+ days/week, which was low and stable by age. Additional analysis showed a greater proportion reported PA 4+ (vs. 6+) days/week, potentially increasing by age (34.2% at 22-24y, ~42% at 31-39y, 44.6% at 19-21y). Conclusion: Among the largest group of YAs ever assessed, we found persistent declines in most CVH metrics with age. Within the context of analyses from much smaller cohorts, these findings support investigating interventions to effectively stem the decline in CVH in this at-risk group.
Abstract 4147113: Temporal Trends in Transcatheter Aortic Valve Implantation Outcomes: A Six-Year Analysis from the National Inpatient Sample (2016-2021)
Authors: Siddharth Agrawal, Yug Patel, Maharshi Raval, Labdhi Sanghvi, Sajid Siddiq
Journal: Circulation (2024)

Background: Transcatheter Aortic Valve Implantation (TAVI) is a rapidly evolving procedure with significant implications for patient outcomes. Understanding trends in TAVI outcomes over time can help identify areas for improvement and guide clinical practice. This study aims to analyze trends in mortality, procedural complications, length of stay (LOS), and total charges for TAVI patients from 2016 to 2021. Methods: We performed a trend analysis of TAVI procedures using data from the National Inpatient Sample (NIS) from 2016 to 2021. Outcomes assessed included in-hospital mortality, transfusion rates, permanent pacemaker (PPM) insertion, postprocedure shock, prosthetic valve dysfunction, intraprocedure stroke, LOS, and total hospital charges. The P-trend test was used to determine statistical significance over the six-year period. Results: A total of TAVI procedures were analyzed from 2016 to 2021. In-hospital mortality decreased significantly from 1.76% in 2016 to 1.06% in 2021 (P-trend &lt;0.001). Transfusion rates declined from 7.60% in 2016 to 3.90% in 2021 (P-trend &lt;0.001). The incidence of PPM insertion dropped from 8.59% in 2016 to 5.50% in 2021 (P-trend &lt;0.001). Postprocedure shock rates decreased from 2.71% in 2016 to 2.00% in 2021 (P-trend = 0.007). Prosthetic valve dysfunction rates declined from 1.81% in 2016 to 1.27% in 2021 (P-trend = 0.012). Intraprocedure stroke rates showed a non-significant downward trend, decreasing from 2.20% in 2016 to 1.82% in 2021 (P-trend = 0.168). Mean LOS for TAVI patients decreased significantly from 5.077 days in 2016 to 3.21 days in 2021 (P-trend &lt;0.001). Total hospital charges showed a significant downward trend from $261,883 in 2016 to $225,805 in 2021 (P-trend &lt;0.001). Conclusions: The analysis of TAVI outcomes from 2016 to 2021 demonstrates significant improvements in several key areas, including reductions in in-hospital mortality, transfusion rates, PPM insertion, postprocedure shock, prosthetic valve dysfunction, LOS, and total hospital charges. These findings highlight advancements in TAVI technology and procedural techniques over time. Continued monitoring of TAVI outcomes is essential to maintain and enhance the quality of care for patients undergoing this procedure.
Abstract 4147152: First Implantation of Atrial Leadless Pacemaker in Atriopulmonary Fontan
Authors: Jameson Wilbur, Mason Marcus, Patrick O'Hara, Emmanuella Egbonim, Akash Kataruka, Amit Khera, James Daniels
Journal: Circulation (2024)

Introduction: Patients with Fontan circulation are at an increased risk of sinus node dysfunction and atrial tachyarrhythmias. These are associated with significant morbidity and mortality, and management constitutes a significant clinical challenge. Case Description: A 44-year-old male with right ventricular hypoplasia, tricuspid and pulmonic valve atresia and a ventricular septal defect, corrected with a modified Blalock-Taussig Shunt, bidirectional Glenn Shunt and atrio-pulmonary Fontan, was admitted with a supraventricular tachycardia (SVT) and heart failure. His electrocardiogram showed a narrow complex mid-RP tachycardia consistent with atypical atrial flutter or atrial tachycardia. His echocardiogram showed an LVEF of 21%. He was started on a beta-blocker and loaded with dofetilide, resulting in bradycardia, QT interval prolongation and Torsades de Pointes. Amiodarone was substituted, but he had incessant SVTs. He was taken for an electrophysiology study and radiofrequency ablation of a right-sided re-entrant flutter around an area of block in the anterior septum. Four additional unstable atrial tachycardias were induced but not ablated. He was discharged, then readmitted within hours for SVT. Due to insurance status, the patient was not a candidate for transplant or Fontan revision. To enable treatment with a beta-blocker, an Abbott leadless atrial pacemaker (AVEIR AR) was implanted in the high lateral Fontan, in an area of normal voltage (Figure 1). Post-implant interrogation showed stable device parameters (capture 0.25 V @ 0.4 ms, sensing 7.6 mV, impedance: 380 Ω). Conclusions: This is the first case of an AVEIR AR implanted within an atrio-pulmonary Fontan circulation. Access to atriopulmonary Fontan circulation for endovascular device therapy is feasible, but requires careful pre-procedural planning to ensure vascular patency, and anatomic and physiologic feasibility. Leadless pacing mitigates complications from endocardial and epicardial pacing systems, but long-term safety and efficacy are unknown.
Abstract 4146813: Evaluating the Prevalence of Optimal Neurodevelopmental Outcome at 2 Years in Children Previously on VAD Support
Authors: Jennifer Conway, Holger Buchholz, Darren Freed, Mohammed Al Aklabi, Devilliers Jonker, Ari Joffe, Simon Urschel, Tara Pidborochynski, Joseph Atallah, Charlene Robertson
Journal: Circulation (2024)

Background: Ventricular assist devices (VADs) are becoming a standard part of advanced heart failure therapy in children. They are utilized mostly as a bridge to transplant (HTx) but also can be used for recovery. While information on complications during VAD therapy is available, there is limited information on long term outcomes in this patient population, specifically neurodevelopmental outcomes. Research Question: To determine the prevalence of ‘optimal neurodevelopmental outcomes’ in 2-year-old children previously treated with a VAD. Methods: Patients were followed through the Complex Pediatric Therapies Follow-Up Program. This study included patients born between January 2006 and December 2022, implanted with a VAD at &lt; 15 months of age and surviving to 2 years of age. A modified optimal neurodevelopmental outcome was defined as the Cognitive, Language and Motor Composite Scores on the Bayley Scales of Infant and Toddler Development and the Adaptive Behaviour Assessment System - General Adaptive Composite Score ≥ 80 each, with the absence of cerebral palsy, permanent hearing loss, visual impairment, or seizure disorder. Results: There were 56 patients who met inclusion criteria with 40 patients surviving to the age of 2 years. Of the survivors, the median (IQR) gestational age (GA) was 38 [37, 39] (4 [7.1%] &lt;37completed weeks GA), 70% were male and 7.5% had a chromosomal abnormality. The median age of implant was 0.39 [0.19, 0.64], years and weight 5.8Kg [4.1, 7.5]. The majority of patients did not have congenital heart disease (62.5%). The most common implant strategy was a left VAD (87.5%) with paracorporeal continuous support (42.5%). Most patients were supported with ECMO (55%) pre- or post-VAD implant. One-third of the cohort had a neurological insult either pre- or post-implant. Total duration of support was a median 32 days [8, 93] with 65% undergoing HTx and 35% decannulated for recovery. Thirty-nine patients underwent full neurodevelopmental testing at 2 years of age with only 25.6% (n=19) of the patients classified as having an optimal neurodevelopmental outcome with 43.6% (n=17) having a Bayley cognitive score &lt;80. Conclusion: Optimal neurodevelopmental outcome at 2 years of age was present in only one-quarter of children following a treatment pathway that included VAD therapy in infancy. Important next steps will be to identify associations, including modifiable risk factors, for optimal neurodevelopmental outcomes.
Abstract 4146849: Reassessing Thresholds for Pulmonary Hypertension in Healthy and Early Stage Heart Failure - Project Baseline Health Study
Authors: Fawaz Alenezi, Bettia Celestin, Everton Santana, shadi bagherzadeh, Hasan Alajmi, Michael Salerno, Svati Shah, Sudarshan Rajagopal, Pamela Douglas, Melissa Daubert, Francois Haddad
Journal: Circulation (2024)

Background: There is increasing evidence that current thresholds for diagnosing pulmonary hypertension (PH) may underestimate its prevalence and importance in clinical practice. Objective: To determine reference values and correlates of right ventricle systolic pressure tricuspid regurgitation (TR) velocity and (RVSP) in the Project Baseline Health Study (PBHS), with a particular focus on diastolic function and preclinical lung and heart diseases. Methods: In the PBHS, 2,082 participants underwent transthoracic echocardiography. Of these, 1,132 have tricuspid regurgitation (TR) velocity with reliable estimations of peak TR velocity and RVSP. The association between TR velocity and RVSP and common clinical and TTE parameters were assessed using multidimensional network and multivariable-adjusted regression analyses. Analysis included extensive cardiometabolic risk factors, and diastolic and pulmonary function test parameters. We used the Cox proportional hazard model to analyze the relationship between TR velocity and event-free cardiovascular survival. Results: The mean age of the participants was 51 years, with 56.6% female and 62.6% White. Overall, 33.7% had hypertension; 10.8% had diabetes; and 78% had CAC &lt;100. The 97 th quantile TR velocity was 2.6 m/s and the RVSP was 30mmHg ( fig 1 ). While there was a significant increase in TR velocity with age with significant median and upper quantile relationships, the overall nominal change was small. In our study, RVSP was most strongly associated with diastolic parameters (e’ and E/e’) and forced expiratory volume in 1 second (FEV1). In the multivariable-adjusted analysis, age, history of CVD, and e' were independently associated with RVSP after adjustment for traditional risk factors. While TR velocity and RVSP were related to event-free survival on univariable assessment, survival was more closely associated with e’ velocity on multivariable analysis. Conclusion: In the multiracial deeply phenotyped PBHS study, TR velocity thresholds were consistent with ASE guidelines and recent The World Alliance Societies of Echocardiography (WASE) studies. The RVSP was mainly related to diastolic parameters and FEV1.
Abstract 4147265: Title: Immortalization of human cardiac fibroblasts using a combination of SV40 large T antigen and hTERT.
Authors: Josiane Semaan, Matthew Stratton
Journal: Circulation (2024)

Background: Fibroblasts are critical regulators of health and disease. Unfortunately, primary isolated fibroblasts retain limited proliferation potential. To enable robust biochemical experimentation in cardiac fibroblasts we immortalized human cardiac fibroblasts using lentiviral delivered SV40 large T antigen (SV40), human telomerase reverse transcriptase (hTERT), or both tools in combination. Methods: Following virus treatment with immortalization genes and hygromycin selection, we characterized subsequent immortalized cell lines for proliferative capacity and ability to become activated in response to TGF-β1 treatment. Expression of Periostin (POSTN), alpha smooth muscle actin (αSMA) and Sertad4 was measured via qPCR after 48hrs of vehicle or TGF-β1 (10ng/ml) treatment. Western Blot analysis was performed to detect the phosphorylation of SMAD2, AKT and P38 in response to TGF-β1 and cell doubling time was calculated at each passage through passage 20. Results: Fibroblasts immortalized with SV40 did not proliferate past passage 18 while those immortalized with hTERT quiesced at passage 19. Only the combination treatment resulted in fibroblasts that proliferated through passage 20 (last measured doubling time of 3.25 days – shortest doubling time of 1.23 days at passage 11). Early passage fibroblasts (passage 7) from each immortalization strategy showed increased mRNA expression of Sertad4, POSTN and αSMA following TFG-β1 treatment. However, only the combination strategy resulted increased Sertad4 and POSTN expression in higher passage cells upon stimulation. All immortalization strategies resulted in decreased αSMA expression upon TGF-β1 treatment in fibroblasts beyond passage 10. All cell lines tested retained the ability to increase AKT and SMAD2 phosphorylation in response TGF-β1 treatment. Conclusions: These results indicate that fibroblast immortalization through a combined SV40 large T antigen and hTERT expression approach is superior to individual manipulation. The combination strategy resulted in increased proliferative capacity and more robust TGF-β responsiveness. These cells may be a useful tool for investigating molecular mechanisms of fibroblast activation when the inability to expand primary cultures would be limiting
Abstract 4146687: Hemodynamic Impacts of Central Arterial Stiffness and Coronary Flow Reserve on LV filling Impairment in Patients With Normal Left Ventricular Systolic Function
Authors: YOUNING CHANG, Shih-Hsien Sung
Journal: Circulation (2024)

Background: Heart failure with preserved left ventricular ejection fraction (LVEF) prevails in subjects who complained of exercise intolerance, which is characterized by elevated left ventricular filling pressure (LVFP). While arterial stiffness has been related to left ventricular diastolic dysfunction, little is known whether the coronary flow reserve mediates the association. The invasive study then investigated the correlations between arterial stiffness, coronary flow reserve and LVFP. Methods: Subjects, referred for coronary angiography were eligible for this study and patients with stenotic lesions coronary artery disease (CAD) over 70% in any of which coronary vessels were excluded. Pressure waveforms of right radial artery (RRA), ascending aorta, and left ventricle were obtained, and left ventricular end-diastolic pressure (LVEDP) were measured. Aortic augmentation index (AI), aorto-radial pulse wave velocity (arPWV), and left ventricular diastolic time constant (Tau) were calculated. Three-dimensional quantitative coronary angiography (3D-QCA)-based vessel FFR (vFFR) of each coronary artery were measured. Increased LVFP was defined as LVEDP ≥ 20mmHg. Results: Among a total of 244 participants, 152 subjects had increased LVFP. While the demographic data, morbidities, hemogram, biochemistries, blood pressure, FFR, and LVEF were almost similar between groups, subjects with increased LVFP had higher RRA AI, aortic AI, subendocardial viability ratio, and Tau. Stepwise regression showed subendocardial viability ratio and Tau played the crucial role while increased LVFP. Correlation matrix analysis showed aortic AI, Tau, and RRA AI and all three vessels vFFR correlated with LVEDP. The multiple logistic regression analysis demonstrated positive correlation between radial AI, and Tau but inversely correlation between subendocardial viability ratio and no correlation between three vessels vFFR with increased LVFP. Conclusions: Among subjects with CAD but no stenotic lesions over 70% among three vessels, aortic stiffness was associated with elevated LVFP, suggesting some hemodynamic impacts of central arterial stiffness on LV filling impairment patients with normal left ventricular systolic function. About coronary flow reserve and other diastolic indices, represented with vFFR and subendocardial viability ratio and Tau, respectively, the discordance results among correlation matrix and logistic regression analysis needs further studies to investigate.
Abstract 4146727: Intensive lifestyle intervention, cardiac biomarkers and atherosclerotic cardiovascular disease in type 2 diabetes and overweight or obesity – a post-hoc analysis of the Look Action for Health in Diabetes (AHEAD) trial
Authors: Kershaw Patel, Zainali Chunawala, Matthew Segar, Katelyn Garcia, Chiadi Ndumele, Thomas Wang, James Januzzi, Javed Butler, Carolyn Lam, Alain Bertoni, Mark Espeland, Ambarish Pandey
Journal: Circulation (2024)

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with atherosclerotic cardiovascular disease (ASCVD) risk in type 2 diabetes (T2D). However, the association of longitudinal changes in these cardiac biomarkers with ASCVD risk in T2D is not well-established. Furthermore, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers is not well-characterized. Methods: Participants of the Look AHEAD (Action for Health in Diabetes) trial with T2D and overweight or obesity were included. Hs-cTnT and NT-proBNP were measured at baseline, 1- and 4-year follow-up (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1-, and 4-year change in cardiac biomarkers with ASCVD risk (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina). The effects of the ILI targeting weight loss versus diabetes support and education (DSE) on cardiac biomarker changes were summarized as the geometric mean ratio (GMR) and 95% confidence interval (CI). Results: Among 3,984 participants with available cardiac biomarker data, there were 771 ASCVD events (median follow-up: 12 years). Higher hs-cTnT and NT-proBNP at baseline were each significantly associated with higher ASCVD risk ( Figure 1A ). Changes in hs-cTnT and NT-proBNP over 1-year follow-up were not significantly associated with ASCVD risk. However, sustained increases in hs-cTnT and NT-proBNP over 4-year follow-up were each significantly associated with higher ASCVD risk. The ILI versus DSE was significantly associated with lower hs-cTnT at 1- and 4-year follow-up (GMR [95% CI]: 0.96 [0.93-0.99] and 0.94 [0.92-0.97]), respectively) ( Figure 1B ). In contrast, NT-proBNP increased with the ILI (vs. DSE) at 1-year (GMR [95% CI]: 1.11 [1.05-1.17]), but this difference was attenuated and no longer significant at 4-years. Conclusions: Among adults with T2D, sustained increases in hs-cTnT and NT-proBNP over 4-year follow-up were associated with higher ASCVD risk. An ILI targeting weight loss led to a significant reduction in hs-cTnT and transient rise in NT-proBNP that attenuated over time.