tbuckley/cabot-search huggingface dataset:
Abstract 4124655: Multi-trait analysis identifies 307 genomic loci for thoracic aortic diameter and disease
Authors: Siavash Zamirpour, John Depaolo, James Brundage, Scott Damrauer, James Pirruccello
Journal: Circulation (2024)

Introduction: Thoracic aortic aneurysm and dissection (TAAD) is a morbid cardiovascular disease with 21 known common-variant genomic risk loci. Aneurysm represents an extreme of diameter, so we sought to jointly analyze TAAD and aortic diameter to enhance discovery power. Methods: Genome-wide association studies (GWAS) were performed for UK Biobank MRI-derived aortic diameter measured at the aortic root (N=62,919), ascending aorta (N=61,156), and descending aorta (N=62,412). Separately, TAAD GWAS summary statistics from UKB (1,076 cases, 416,263 controls), FinnGen (3,880 cases, 381,977 controls), and the Million Veteran Program (8,626 cases, 453,043 controls) were meta-analyzed. Genetic correlation was assessed with ldsc . Multi-trait analysis was then performed for the aortic measurements and TAAD with MTAG . A 1.1-million-variant polygenic risk score (PRS) was produced and tested in the All of Us biobank. Results: The genetic correlation between ascending aortic diameter and TAAD was 0.83 (P=6.6E-129). The TAAD meta-analysis had an effective sample size of 53,516, augmented to 147,377 after multi-trait analysis. We identified 59 risk loci for TAAD (189 in the multi-trait analysis). These loci included one on the X-chromosome near MIR222HG , previously reported to be regulated by angiopoietin-2; others were near TGF-β-superfamily members ( FBN1 , FBN2 , GDF6 , GDF7 , LTBP4 , TGFB2 , SMAD3 ); genes involved in vasoconstriction ( ADRA1D , ADRB1 , ANGPT1 , EDN1 , EDN2 , EDNRA , PDE3A ); and cell cycle regulators ( CCND2 , CCNE1 , CDC27 , CDK6 , CDKN1A , CDKN1B , CENPW , DSCC1 , MAD2L1 , TP53 ). 307 distinct loci were significantly associated with at least one of the four traits; all but 7 TAAD loci were genome-wide significant for one of the three aortic measurements, and all loci had at least sub-significant signal in those traits. Gene-set analyses highlighted contributions from fibroblasts, pericytes, and vascular smooth muscle cells. In All of Us , a one standard deviation (SD) greater PRS was associated with a hazard ratio (HR) of 1.88 for TAAD (P=1.2E-78) and 1.62 for thoracic aortic dissection (P=5.7E-05). Individuals in the top 5% for the PRS had HR 3.77 for TAAD (P=2.7E-48) and HR 2.87 for thoracic aortic dissection (P=3.3E-03). Discussion: The multi-trait analysis yielded an eight-fold expansion of loci for TAAD risk. The findings underscore that sporadic TAAD is a complex, common disease—intricately linked with the processes associated with normal variation in aortic diameter.
Abstract 4124585: Identification of Low-Value Carotid Ultrasound Tests: A Comparison of Administrative Claims Versus Chart Review
Authors: Robert Beale, Vinay Kini
Journal: Circulation (2024)

Introduction/Background: Low-value care is defined as care where harms or costs outweigh patient benefits. Prior studies have suggested that approximately 1 of every 10 carotid ultrasound tests are low-value because they were performed among patients without neurologic symptoms or a history of stroke. However, these studies have used administrative claims data that may not account for all patient symptoms or include all guideline-recommended indications. We assessed the validity of a claims-based measure of low-value carotid ultrasound testing compared to a reference standard of chart review. Hypothesis: Claims-based measures overestimate the proportion of carotid ultrasound tests classified as low-value care. Methods: We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries attributed to an accountable care organization with administrative claims data linked to electronic health record data. Using Current Procedural Technology codes, the first 150 patients that underwent carotid ultrasound in 2021 were identified. We applied a claims-based algorithm used by researchers and policymakers to identify if testing was low-value or appropriate. We used linked electronic health record data to assess appropriateness of testing using the 2012 American Heart Association clinical practice guidelines. We assessed agreement between claims and chart review using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen’s Kappa. Results: Among 150 patients (mean age 76, 55% male, 86% white) who underwent carotid ultrasound, 76 tests (51%) were considered low value by the claims measure and 63 (42%) by chart review. Claims based measures were 67% sensitive, 61% specific, with a PPV of 55% and NPV of 62%. Cohen’s Kappa coefficient was 0.27 (CI 0.11 - 0.42), indicating only fair agreement between claims and chart review. Conclusion: We found that an often-used claims-based measure to identify low-value carotid ultrasound testing misclassifies a substantial proportion of tests as low-value. Using claims-based measures alone for assessing provider quality and making payment decisions could harm provider reputations and erode trust in the quality reporting system.
Abstract 4124506: Short Physical Performance Battery as a Marker of Severity and Predictor of Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Authors: Lyle Dershowitz, Sergio Teruya, Dimitrios Bampatsias, Abdirahman Wardhere, Alfonsina Mirabal, Denisse Santana Del Rosario, Mathew Maurer
Journal: Circulation (2024)

Background: ATTR-CM has an age dependent prevalence and is a disorder that almost exclusively affects older adults. Objective evaluations of function are critical to assessing and managing ATTR-CM in older adults. The short physical performance battery (SPPB) is a valid measure of functional capacity that predicts morbidity and mortality in older adults but its utility in ATTR-CM remains unknown. Aims/hypothesis: To establish SPPB as a useful marker of disease severity and predictor of outcomes in ATTR-CM. We hypothesized that SPPB scores would correlate with validated markers of ATTR-CM severity and improve clinical prediction. Methods: This is a retrospective analysis of patients referred to the Columbia University Cardiac Amyloid Program. Patients were stratified into low (SPPB 0-6), moderate (7-9), and high (10-12) cohorts based on initial SPPB score and baseline characteristics were compared between groups. Cox proportional hazard models and Kaplan Meier (KM) curves were generated to assess associations with mortality as well as a composite of death and cardiovascular (CV) hospitalization in follow-up. Results: A total of 263 patients, age 78 years (IQR 73, 84), 86% male, 22% with ATTRv (variant) and 78% with ATTRwt (wild type) were studied. SPPB showed no limitation in 59%, mild limitation in 33%, and severe limitation in 8%. Lower SPPB was associated (p &lt;0.05) with older age, prior stroke/TIA, shorter 6-minute walk test, elevated NT-proBNP and HS-troponin, worse quality of life metrics on Kansas City Cardiomyopathy Questionnaire, more advanced NYHA and Mayo stages, and higher Columbia scores. On multivariate regression (adjusted for age, sex, genotype, NYHA), SPPB was independently associated with the composite of mortality and CV hospitalization, with each point increase corresponding to 13% lower incidence of the outcome (HR 0.87, p=0.01). Chair stands score, one of three SPPB subdomains, was independently associated with the composite and mortality. KM curves showed significant association with SPPB and both the composite and mortality (Fig. 1). Conclusions: SPPB score is a marker of ATTR-CM severity, associated with validated biomarkers and staging systems, and independently predicts clinical outcomes.
Abstract 4124293: Exercise Capacity in Patients with Fontan Physiology
Authors: Kalani Ruiz, Laurie Soine, Yonatan Buber, Andrew Pistner
Journal: Circulation (2024)

Introduction/Background: In the absence of a sub-pulmonary ventricle in the Fontan circulation, augmentation of pulmonary blood flow and filling of the systemic ventricle during exercise are limited. Cardiopulmonary exercise testing (CPET) is a reliable method for evaluation of aerobic capacity, gas exchange, and other physiologic parameters used for risk stratification in this population. Despite the ubiquitous use of CPET, reference ranges for patients with Fontan physiology are limited. The purpose of this study is to describe exercise characteristics and their relationship with different characteristics of Fontan physiology, imaging, and hemodynamics. Methods/Approach: In this retrospective cohort study, CPET results were reviewed for adult Fontan patients at the University of Washington between May 2021 and February 2024. Demographics, comorbidities, medications, type of Fontan conduit, imaging characteristics, hemodynamics, and exercise characteristics were included. Results were compared to a large previously published cohort of Fontan patients. Univariate linear regression was used to identify associations between demographics, cardiac anatomy, and exercise parameters. A p-value of less than 0.05 was considered statistically significant. Results/Data: Baseline demographics were notable for an older patient population (31±7 years) with lower indexed peak VO 2 (20.5±5.6 mL/kg/min) and greater V E /VCO 2 slope (37±7) compared to the historic cohort. Indexed peak VO2 was associated with age, BMI, type of Fontan conduit, FEV1, FVC, resting oxygen saturation, peak systolic blood pressure, and peak heart rate. Indexed peak VO 2 was notably not significantly associated with sex, systemic ventricular morphology, ventricular systolic function, Fontan pressure, or the presence of conventional heart failure medical therapy. Conclusions: In the growing population of older patients with Fontan physiology, development of age-specific population normative data may increase the clinical utility of CPET. Further investigation of the relationship between imaging characteristics, hemodynamics, and exercise parameters is needed in the Fontan population.
Abstract 4124532: A Meta-Analysis on the Effect of Chronic Total Occlusion of Coronary Arteries on Cardiovascular Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Aman Goyal, Muhammad Daoud Tariq, Rubab Zahra, Hritvik Jain, Rozi Khan, GAURANGA MAHALWAR
Journal: Circulation (2024)

Background and Aims: Transcatheter aortic valve replacement (TAVR) has revolutionized the management of severe aortic stenosis, particularly prevalent in elderly patients. These patients often present with coexisting coronary artery disease (CAD) due to shared risk factors. There is evidence suggesting that underlying CAD may result in poorer outcomes for patients undergoing TAVR. Chronic total occlusion (CTO), representing a severe manifestation of CAD, could therefore be hypothesized to worsen prognosis in TAVR patients, although data supporting this hypothesis are limited. Our meta-analysis aims to consolidate all available data concerning patients undergoing TAVR with concurrent CTO. Methods: We conducted a thorough literature search across major bibliographic databases, including PubMed, Embase, Cochrane Library, and SCOPUS, from their inception until May 15, 2024, to identify studies comparing outcomes of TAVR in patients with and without CTO. Pooled odds ratios (OR) with 95% confidence intervals (CIs) were calculated using the random-effects model via Comprehensive Meta-Analysis Software. The primary outcome assessed was in-hospital mortality, with several secondary endpoints also evaluated. Statistical significance was determined at p&lt;0.05. Results: Eight studies, encompassing a total of 540,910 patients undergoing TAVR (11,679 with CTO; 529,231 without CTO), were included in this meta-analysis. TAVR in patients with CTO was associated with significantly increased odds of in-hospital mortality (OR: 1.25; 95% CI: 1.05, 1.49; p=0.011; I 2 =0%) and acute myocardial infarction (periprocedural) (OR: 1.68; 95% CI: 1.48, 1.91; p&lt;0.001; I 2 =0%). However, no significant difference was observed in all-cause mortality (OR: 1.18; 95% CI: 0.71, 1.96; p=0.525; I 2 =59.37%), acute kidney injury (OR: 1.32; 95% CI: 0.94, 1.85; p=0.11; I 2 =72.12%), and stroke (OR: 1.06; 95% CI: 0.89, 1.28; p=0.509; I 2 =0%) (see Figures 1 and 2). Conclusion: CTO emerges as a substantial risk factor for patients undergoing TAVR, elevating the risk of in-hospital mortality and acute myocardial infarction. Considering a heart team's multidisciplinary approach in patients with underlying CTO may be advisable during TAVR, allowing for a comprehensive assessment of the benefits versus risks of revascularization prior to TAVR.
Abstract 4124875: Association between Elevated Lipoprotein(a) and Cardiovascular Events and Mortality in a Nationally Representative Sample of US Medicare, Medicaid, and Commercial Enrollees with ASCVD
Authors: Xingdi Hu, Tony Lozama, Allison Petrilla, Barnabie Agatep, Donna McMorrow, Iman Mohammadi, Lonny Reisman, Nathan Wong
Journal: Circulation (2024)

Background: Elevated lipoprotein(a) [Lp(a)] is an independent and causal risk driver for atherosclerotic cardiovascular disease (ASCVD). Few patients with ASCVD receive Lp(a) screening and real-world data assessing the association between elevated Lp(a) and risk of cardiovascular (CV) events and mortality is limited. Objectives: To examine the association of elevated Lp(a) and risk of CV events and death in an ASCVD population using large US health claims databases. Methods: Patients with ASCVD were pooled from US Medicare, commercial, and Medicaid health plans from 2017 to 2022. Lp(a) levels were linked at the patient level from HealthVerity Lab Data and categorized as: &lt;30 mg/dL (&lt;75 nmol/L), ≥30-&lt;50 mg/dL ( &gt; 75-&lt;125 nmol/L), ≥50-&lt;70 mg/dL ( &gt; 125-&lt;175 nmol/L), ≥70-&lt;90 mg/dL (≥175-&lt;225 nmol/L) and ≥90 mg/dL (≥225 nmol/L). Patients were followed from the 1 st ASCVD diagnosis (index) to insurance plan disenrollment, death, or end of study. Cox regression, adjusted for age, sex, race, insurance, comorbidities, LDL-C, and other risk factors, measured the association between Lp(a) levels and risk of CV events and death. Results: Of 28.8 million ASCVD patients, 180,240 (0.6%) had Lp(a) levels: mean(±SD) age 68.6±1 years, 50.1% male, 5.9% Black, 2.8% Hispanic, 2.1% Asian, 72.8% Medicare, 21.8% commercial, and 5.4% Medicaid. Mean follow-up was 3.7 years; 23.3% and 15.7% had Lp(a) ≥50mg/dL [≥125 nmol/L] and ≥70 mg/dL (≥175 nmol/L), respectively. Black patients had highest median Lp(a) (50 mg/dL/111 nmol/L), followed by Asian (13.5 mg/dL/35.5 nmol/L), White (13 mg/dL/32 nmol/L), and Hispanic (11.5 mg/dL/29 nmol/L) patients. Lp(a) levels of ≥30-&lt;50 mg/dL, ≥50-&lt;70 mg/dL, ≥70-&lt;90 mg/dL, and ≥90 mg/dL were associated with 7%, 10%, 16%, and 26% greater risks of CV events vs. &lt;30 mg/dL (p-values &lt;0.0001; cumulative incidence reported in Figure 1). All-cause mortality risk was also greater for those with Lp(a) ≥90 mg/dL vs. &lt;30 mg/dL: hazard ratio (HR)=1.11, p=0.003. Similar trends persisted for patients with LDL-C ≤70 mg/dL. Conclusion: In this national-scale real-world cohort of patients with ASCVD, Lp(a) testing is infrequent and elevated Lp(a) levels were significantly associated with a greater risk of CV events and mortality.
Abstract 4124675: Deep Learning Screening of Cardiac MRIs Uncovers Undiagnosed Hypertrophic Cardiomyopathy in the UK BioBank
Authors: Dhamanpreet Kaur, Rohan Shad, Cyril Zakka, Robyn Fong, Brian Pogatchnik, Ross Filice, JOHN MONGAN, Kimberly Kallianos, Nishith Khandwala, David Eng, Victor Ferrari, Alejandro de Feria, Michael Acker, William Hiesinger
Journal: Circulation (2024)

Introduction: The prevalence of hypertrophic cardiomyopathy (HCM) in the UK Biobank based on ICD-10 codes (.07%) is lower than global estimates of disease prevalence (0.2 - 0.5%). Prior studies using this data have remarked on the limitations of findings given likely underdiagnosis. The availability of cardiac MRI scans on a fraction of the participants offers an opportunity to identify missed diagnoses. Aims: This study seeks to utilize a generalizable deep learning model to detect likely cases of undiagnosed hypertrophic cardiomyopathy from cardiac MRIs in the UK Biobank. Methods: The foundational model was trained on a multi-institutional dataset of 14,073 cardiac MRIs via a self-supervised contrastive learning approach that sought to minimize the divergence between scans and their associated radiology reports. The pre-trained model was fine-tuned to diagnose hypertrophic cardiomyopathy on a distinct cohort of 4,870 MRIs with 368 cases of HCM, achieving an AUC of 0.94. The fine-tuned model was applied to the UK Biobank cardiac MRI dataset to ascertain predicted probabilities of HCM. Cases exceeding a threshold of 95% – correlating to the top 0.5% of cases (expected specificity of 97% and sensitivity of 60%) – were screened in for manual reading. In a blinded fashion, a board-certified radiologist was tasked with diagnosing HCM on a sample of cases composed of high and low predicted probabilities. Results: Of the 43,017 patients with cardiac MRIs, only 9 (.02%) had an ICD diagnosis of HCM. 266 cardiac MRIs were manually reviewed: 216 had greater than 95% predicted probability of HCM; 50 negative controls were randomly selected amongst cases with predicted probability less than 10%. The radiologist concurred with an HCM diagnosis for 115 cases (sensitivity 53%, specificity 98%), 112 of which were previously undiagnosed. The prevalence of hypertension and aortic stenosis did not significantly differ between the cohort of true positives (69.2%) and false positives (76.6%). The corrected prevalence of HCM in the UK BioBank MRI cohort is estimated at 0.28%. Conclusions: The findings of this study illustrate the remarkable ability of a generalizable deep learning model to detect undiagnosed cases of a rare disease process from cardiac MRIs. This is an important milestone that may allow for widespread screening of hypertrophic cardiomyopathy while minimizing demand for radiologist labor, and thereby allow patients to reap the substantial benefits of earlier treatment.
Abstract 4124709: Accelerometer-Measured Sedentary Behavior and Future Cardiovascular Disease
Authors: Ezimamaka Ajufo, Shinwan Kany, Joel Ramo, Timothy Churchill, James Guseh, Krishna Aragam, Patrick Ellinor, Shaan Khurshid
Journal: Circulation (2024)

Background: Current consensus guidelines emphasize the importance of achieving 150 minutes or more of moderate to vigorous physical activity (MVPA) per week to promote cardiovascular health but give little guidance about sedentary behavior. Research Question: Is sedentary behavior associated with cardiovascular (CV) disease in a manner distinct from insufficient physical activity? Aims: Examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential interactions with MVPA. Methods: Using 89,530 individuals providing one week of accelerometer-based physical activity data from the UK Biobank, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between sedentary time (as a spline term) and incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on these associations by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold. Results: Among 89,530 individuals (age 62±8 years, 56.4% women) undergoing accelerometry, median sedentary time was 9.4 hours/day (quartile-1: 8.2, quartile-3: 10.6). In multivariable models, using the second quartile (8.2-9.4 hours/day) as a referent, sedentary time in the top quartile (&gt;10.6 hours/day) was associated with greater risk of HF (hazard ratio [HR] 1.45, 95% CI 1.28-1.65), and CV mortality (HR 1.62, 95% CI 1.34-1.96), with evidence of a threshold effect at 10.6 hours/day. Higher sedentary time was also associated with greater risk of incident AF (HR 1.11, 95% CI 1.01-1.21) and MI (HR 1.15, 95% CI 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted after adjustment for MVPA, as well as among individuals both above and below the guideline-based activity threshold of ≥150 minutes MVPA/week. Conclusions and Relevance: Sedentary behavior is broadly associated with future adverse CV outcomes. For HF and CV mortality, associations appear distinct from insufficient MVPA, and sedentary time in excess of 10.6 hours/day conferred an increased risk.
Abstract 4124323: Extensive atrial cardiomyopathy indicated by left atrial low-voltage areas predicts subsequent stroke after atrial fibrillation ablation
Authors: Satoshi Kudo, Yasuhiro Matsuda, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takuya Tsujimura, Yosuke Hata, Hiroyuki Uematsu, SHO NAKAO, Masaya Kusuda, Wataru Ariyasu, Subaru Fujii, Hirotaka Ooka, Toshiaki Mano
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is a leading cause of stroke. However, predictors of stroke after AF ablation have not been well clarified, therefore, evidences of anticoagulation therapy after the procedure have been limited. Although left atrial low-voltage areas (LVAs) reflects atrial cardiomyopathy, which is a potential cause of thromboembolism, there are few reports of an association between LVAs and stroke. The purpose of this study was to investigate the association between atrial cardiomyopathy assessed by LVAs and stroke in patients undergoing AF ablation. Methods: The study design was a single center, retrospective observational study. This study included 1,486 (age, 68 ± 10 years; female, 501 [34%]; persistent AF, 905 [61%]) consecutive patients who underwent initial AF ablation from December 2014 to March 2022. The definition of LVAs were areas with a bipolar voltage of &lt;0.5 mV in the left atrium. The area of LVAs in the whole left atrium was divided into 3 groups, namely &lt;5cm 2 , 5-20 cm 2 and ≥20 cm 2 . Stroke after AF ablation was followed for 60 months. Results: Of 1,486 patients, LVAs were found in 352 (24%) patients, and 25 (1.7%) patients developed stroke (hemorrhagic stroke, 4 [16%] patients; ischemic stroke 21 [84%] patients). Freedom from stroke was significantly lower in patients with LVAs than in those without (&lt;5cm 2 : 98.3%, 5-20 cm 2 : 95.4%, ≥20 cm 2 : 88.8%, p&lt;0.001). Additionally, LVAs ≥20 cm 2 was an independent predictor of the development of stroke after AF ablation (hazard ratio 4.9, 95% confidence interval: 2.0-12; p=0.001, adjusted by estimated glomerular filtration rate and AF recurrence after ablation). Conclusion: In patients with initial AF ablation, freedom from stroke after AF ablation was significantly lower in patients with LVAs ≥20 cm 2 than in patients with LVAs 5-20 cm 2 and in patients with LVAs &lt;5cm 2 . Particularly, LVAs ≥20 cm 2 was an independent predictor of the development of stroke after AF ablation.