tbuckley/cabot-search huggingface dataset:
Abstract 16396: A Tale of Two Maladies: An Interplay of Mendelian Principles
Authors: Reynaldo H Sanchez, Veena Rajaram, Nicholas Hendren
Journal: Circulation (2023)

A 22-year-old male with no medical history presented in acute decompensated heart failure and cardiogenic shock. Physical exam showed a thin body habitus, reduced muscle bulk, bilateral ptosis, limited extraocular motion, and upper extremity weakness. An echocardiogram revealed severe biventricular dilation and systolic dysfunction. Invasive hemodynamics revealed elevated cardiac filling pressures and low cardiac output. Coronary angiography excluded coronary artery disease and anatomical variants. He was initiated on dobutamine and eventually milrinone given persistently low index and elevated lactate. An evaluation for the etiology of his cardiomyopathy focused on nutritional deficiencies (e.g., Wet Beriberi), myocarditis, genetic mutations, infiltrative cardiomyopathy (e.g., Friedrich’s ataxia), and mitochondrial and myopathy-related cardiomyopathy. CMR had globally elevated T1 and normal T2 values ruling out acute myocarditis or infiltrative processes. Serum thiamine, TSH and B12 were within normal range. Muscle biopsy and mitochondrial genetic testing revealed a pathogenic deletion (m.7416_14556) and 70% heteroplasmy. Physical exam, biopsy and mitochondrial genetics were diagnostic of Kearns-Sayre Syndrome (KSS). Notably KSS does not typically cause severe cardiomyopathy suggesting an alternative cause. A genetic cardiomyopathy panel was sent revealing a pathologic mutation in the plakophilin 2 gene which was the suspected cause of his cardiomyopathy. A heart transplant evaluation was initiated as he developed refractory shock requiring mechanical support via an Impella 5.5, placed via the right innominate artery due to his small body and vessel size. He underwent an uncomplicated heart transplantation and is doing well. This case underscores the significance of a broad differential diagnosis, multidisciplinary collaboration, and a detailed physical examination in diagnosing and managing complex cardiac conditions.
Abstract 18628: Focal Pericoronary Adipose Tissue Evaluated by Electron Density Numbers on Contrast Spectral Computed Tomography Was Associated With Coronary Arterial Plaques: A Site-by-Site Analysis
Authors: Nobusada Funabashi, Atsushi Shukuya, Hiroki Asano, Akio Kawamura, Naoko Mizuno
Journal: Circulation (2023)

Introduction: Inflammation in pericoronary adipose tissue (PCAT) around the coronary arterial wall causes coronary arterial sclerosis. Many studies evaluated the relationship between total PCAT volume and coronary arterial sclerosis on a patient-by-patient basis. Hypothesis: Inflammation in PCAT may occur focally in coronary arterial system to which coronary arterial plaques localize. Using novel spectral CT, based on electron density number (EDN) as a new parameter, the focal characteristics of PCAT were evaluated. Methods: 17 patients (10 males, mean age 70 years) underwent cardiac spectral CT (7500, Philips, Tokyo, Japan). From contrast data, EDNs of PCAT were determined at a 1) right side site and 2) left anterior side site of a proximal portion of the right coronary arteries (RCA), 3) anterior side site of the left main coronary arteries, 4) left side site of a proximal portion of the left circumflex artery, and left side site of a distal portion of the RCA (five sites each patient). We also evaluated coronary arterial plaques on enhanced CT images at five corresponding sites for which EDNs were determined. Results: For a total of 85 sites among 17 patients using enhanced CT, 31 sites had no plaques (group 1), 14 sites had only non-calcified plaques (group 2), 20 sites had only calcified plaques (group 3), 16 sites had mixed plaques (group 4), and four sites had stent implantations (group 5). The mean of EDNS (%EDW) for 81 sites, excluding four sites with a stent implantation, were 93.7, 93.9, 94.0, and 94.3 in groups 1-4, respectively (P=NS). For a total of 81 sites, excluding four implantation sites, we evaluated the relationship between age and EDNs in groups 1-4. No correlations were observed in group 1 (R= 0.05), 3 (R= 0.09), and 4 (R= 0,15), however negative correlation was observed in group 2 (R= -0.42) between age and EDNs. No significant differences in EDNs were noted between males and females (P=NS). Conclusions: This is the first study in which focal PCAT was evaluated by EDNs and the relationship to coronary arterial plaques determined by site-by-site analysis. This new CT parameter may evaluate the status of PCAT and be a predictor of the future occurrence of coronary arterial plaques, which are related to PCAT inflammation.
Abstract 11425: Association Between Obstructive Coronary Disease and Diabetic Retinopathy: A Cross-Sectional Study of Coronary Angiotomography and Digital Retinal Images
Authors: Andre Campos, Eduardo Lima, Cesar Higa Nomura, Roberto dantas, Simao Lottenberg, Renata Maia, Sergio Pimentel, Livia Conci, Tomas Minelli, Pedro Rissoli, Andrea Morato, Carlos Serrano, Peter Karl Jacobsen
Journal: Circulation (2023)

Introduction: Diabetic retinopathy (DR) and obstructive coronary artery disease (OCAD) are the main microvascular and macrovascular complications of diabetes mellitus (DM), respectively. The assessment of DR by means of spectral domain optical coherence tomography (SD-OCT) and angiography (OCTA) conferred a remarkable progress. Objective: investigate if SD-OCT and OCTA can detect DR that is associated with OCAD, determined by coronary angiotomography (CCTA) Hypothesis: DR, assessed by OCTA and OCT-SD, is associated with OCAD, assessed by CCTA Methods: In this single-center, cross-sectional, single-blind study, patients with DM who had undergone CCTA in the previous 3 years (independent indication) were eligible. They were divided according to the presence of OCAD in two groups and underwent SD-OCT and OCTA. The association between OCAD and DR was evaluated through uni and multivariate analysis and another analysis was performed to identify variables independently associated with the presence of DR. Results: We included 171 patients, 87 OCAD and 84 without OCAD. Age (66 vs 64 y,p=0.28), DM duration (12 vs 13 y, p=0.5) and HbA1c (7.5% vs 6,9%,p=0.08) did not differ. Patients with OCAD were more frequently men (74% vs 38%, P&lt;0.01), had a higher prevalence of insulin use (52% vs 38%, p&lt;0.01) and 64% had already undergone some type of revascularization. SD-OCT and OCTA revealed a higher prevalence of DR (48% vs 22%,p=0.01). The main findings were: microaneurysms (25% vs 13%,p=0.04), intraretinal cysts (22% vs 8%, p=0.01) and areas of reduced capillary density in the superficial retinal plexus (46% vs 20%,p&lt;0.01).We also found lower mean vascular density (MVD) (15.7 vs 16.5, p=0.049) and lower circularity of the foveal avascular zone(FAZ) (0.64±0.1 vs 0.69±0.1, p= 0.04).There were significant and negative correlations between Duke coronary score and MVD (r=-0.189; p=0.03) and circularity of the FAZ (r=-0,206; p= 0.02). In an adjusted model, presence of OCAD increased the chance of DR (OR 4.05 [1.4 -11.6], p&lt;0.01). OCAD, DM duration and insulin use were independently associated to DR. Conclusions: OCAD was associated with a greater chance of presenting DR. OCAD, longer DM duration and insulin use were independently associated to the presence of DR.
Abstract 13339: Proteomic Associations of Cardiac Function Trajectories Through Mid- to Late Life
Authors: Anne Marie Reimer Jensen, James Ross, Victoria Lamberson, Michael E Hall, Kunihiro Matsushita, Brandon Lennep, Pamela L Lutsey, Tor Biering-Soerensen, Amil M Shah
Journal: Circulation (2023)

Introduction: Using a novel Bayesian nonparametric modeling approach based jointly on LVEF and E/A ratio, we previously identified 3 trajectories of cardiac function through mid- to late life that associated with heighted risk of incident heart failure (HF): trajectory 1 demonstrated failure to increase LVEF with age; trajectory 2 had progressive LVEF decline; and trajectory 3 had steeper than expected rise in E/A ratio. Trajectories 1 and 2 associated with higher risk of HFrEF while trajectory 3 associated with HFpEF. Whether circulating proteins differ between trajectories is unknown. Methods: We assigned 4,419 HF-free participants with available proteomic data (SomaScan v4) at study Visit 5 of the Atherosclerosis Risk in Communities study to their most likely trajectory (2,201 trajectory 1, 162 trajectory 2, 348 to trajectory 3). Associations of plasma proteins with trajectory membership were assessed using multinominal logistic regression analyses adjusted for age and sex at a false discovery rate &lt;0.05. Two-sample Mendelian randomization (MR) was performed to assess potential causal effects between trajectory-associated proteins and LV volume and LVEF. Results: Mean age was 75±5 years and 58% were women. Several unique and shared proteins associated with each high-risk trajectory (Figure). MR identified potential causal effects of 13 trajectory-associated proteins on LV volume and LVEF. These included trajectory 3-associated proteins (B3GNT2, MFAP4) with genetically higher levels associated with smaller LV size and higher LVEF, consistent with the observed association with HFpEF. One trajectory 1-associated protein (HADH) had MR association with lower LVEF, consistent with the observed association with HFrEF. Conclusions: A Bayesian nonparametric model using multidimensional imaging data identifies trajectories of cardiac function with distinct proteomic associations, a subset of which have potential causal effects on cardiac function.
Abstract 15258: Associations Between HV Interval and Incident Pacemaker Implant in Over 3,000 Patients
Authors: Daniel Pipilas, Thomas Sommers, Patrick T Ellinor, Shaan Khurshid
Journal: Circulation (2023)

Introduction: The His Bundle-Ventricular (HV) interval is a measure of the conduction time between the bundle of His and the ventricular myocardium and has been shown to predict atrioventricular block (AV) in patients with conduction disease. Routine HV interval measurement during electrophysiology (EP) studies affords an opportunity to assess the utility of the HV interval as a marker for future conduction disease in a broader sample. Methods: We analyzed consecutive EP studies from over 600,000 primary care and cardiology patients in the Mass General Brigham network. We assessed associations between HV interval and incident pacemaker (PPM) implantation in Cox proportional hazard models adjusted for age, sex, hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, heart failure, atrial fibrillation, and stroke. Person-time began 30 days after index EP study to exclude PPM implant triggered by study findings. Cumulative risk was plotted using Kaplan-Meier curves and the functional form of the relationship between HV and PPM was fit using multivariable-adjusted splines. Results: Of 22,019 individuals with at least one EP report, we identified 3,283 patients (age 61.1±13.6, 63% male, 91.6% White) with an HV interval measurement. In multivariable-adjusted models, a longer HV interval was associated with increased risk of PPM implant (hazard ratio [HR] 1.24 per 10ms increase, 95% CI 1.08-1.43). When assessed at binary cutoffs, there were progressively larger increases in risk of incident PPM implantation (HV ≥55: HR 1.94 (1.28-2.93); HV ≥70: HR 2.18 (1.04-4.56); HV ≥100: HR 7.75 (2.18-27.5)). PPM implant risk increased linearly until 90ms, above which risk increased sharply (Figure). Conclusions: Among patients undergoing EP study, a prolonged HV interval was a strong risk marker for incident PPM implantation. Patients found to have a prolonged HV interval during EP study merit close observation for the development of overt conduction disease.
Abstract 350: Measuring the Return on Investment of an Artificial Intelligence (AI) Early Warning System
Authors: Dana P Edelson, Ashley Snyder, Stephen Knych, Thor Thordarson, Jeffrey Kuhlman, Stuart Marcus, David Bordo
Journal: Circulation (2023)

Background: The use of AI has been associated with decreased hospital mortality for at risk patients but the financial benefit is unknown. Aims: We sought to measure the change in mortality and cost in six priority clinical conditions following a multi-center phased implementation of eCART (AgileMD), an AI early warning system which utilizes electronic health record (EHR) data to predict clinical deterioration. Methods: eCARTv2 was integrated into the EHR (Oracle Cerner) at four Midwest hospitals in a rolling two-phase implementation. In Phase I, providers viewed scores on a stand-alone web dashboard. In Phase 2, the output was displayed in the EHR, linked to clinical pathways. Phase 0 consisted of a 12 month baseline. Mortality and inflation-adjusted direct variable cost data were compared across the phases in six predetermined diagnosis related group (DRG) conditions: sepsis, heart failure (HF), chronic obstructive pulmonary disease (COPD), stroke, acute myocardial infarction (AMI) and pneumonia. Results: Between 6/1/17 and 2/29/20, 15217 (20.3%) med-surg encounters met inclusion DRG criteria. eCART elevation was most common in sepsis (62.5%), followed by HF (47.4%), pneumonia (43.7%), AMI (39.0%), stroke (35.5%) and COPD (27.1%). Full eCART implementation was associated with significant cost reductions in sepsis, HF, pneumonia, COPD and AMI of $471-795 per encounter and mortality reductions in sepsis and HF (aOR 0.56 and 0.39, respectively). Conclusions: The mortality and cost benefits of eCART appear to be strongest for sepsis and heart failure, where eCART is most likely to be elevated. Savings for sepsis, HF, pneumonia and COPD are primarily driven by labor (ie LOS).
Abstract 14576: Circulating Bone Morphogenetic Protein 10 as a Prognostic Biomarker in Heart Failure: A BIOSTAT-CHF Study
Authors: Daan C Ceelen, Valentina Bracun, Bart J van Essen, Adriaan A Voors, Serge Masson, Rudolf A de Boer, Jozine M ter Maaten, Navin Suthahar
Journal: Circulation (2023)

Introduction: Bone morphogenetic protein 10 (BMP10) plays a central role in cardiac embryogenesis and is known to facilitate cardiac repair after myocardial injury in adults. The prognostic value of BMP10 in heart failure (HF) remains largely unknown. Objectives: To identify biological processes related to elevated BMP10 concentrations and to investigate the prognostic utility of circulating BMP10 in HF patients. Methods: Serum BMP10 concentrations were measured in 2085 chronic HF patients from the European BIOSTAT cohort using a prototype electrochemiluminescence immunoassay developed by Roche Diagnostics. First, we performed gene set enrichment analysis to identify biological pathways related to elevated BMP10. Next, we examined the predictive value of BMP10 for all-cause mortality, HF hospitalization and a combined endpoint of mortality and/or HF hospitalization on top of an established risk score, atrial fibrillation (AF) and stroke using Cox-regression analysis after log-transformation and standardization. Results were validated in an independent cohort of HF patients (n=1487). Results: High BMP10 was related to pathways of growth and growth factor activity, regulation of bone, extracellular region, and response to hormones/glucocorticoids. After adjusting for the BIOSTAT risk scores, AF and stroke, log-BMP10 remained a strong predictor of 2-year all-cause mortality (Hazard Ratio [HR] =1.17, Confidence Interval [CI]= 1.06-1.28), HF hospitalization (HR [CI]=1.13 [1.03-1.25]) and the combined endpoint (HR [CI]=1.10 [1.02-1.19]). Similar trends were seen in the validation cohort (Figure 1). Conclusions: BMP10 is an independent predictor of HF-rehospitalization and all-cause mortality in patients with HF.
Abstract 14285: Sodium Glucose Co-Transporter 2 Inhibition Eliminates Senescent Cells Through Downregulation of PD-L1 and Improves Pathological Aging
Authors: Goro Katsuumi, Masayoshi Suda, Ippei Shimizu, Yohko Yoshida, Takaaki Furihata, Yusuke Joki, Chieh Lun L Hsiao, Tohru Minamino
Journal: Circulation (2023)

Introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been developed as a new class of anti-diabetic drug, and shown cardio- and renal-protective effects in patients with diabetes, heart failure, and chronic kidney diseases. SGLT2 inhibitor also has effect to expand lifespan in aged mice, suggesting anti-aging effect. But the detailed machinery of these protective effects is still to be clarified. Here we demonstrate that canagliflozin has a effect to eliminate senescent cells from pathological tissues, so-called "senolysis" in murine aging or age-related disease models. Methods: Canagliflozin mixed in food at 0.03% (w/w) was administered for up to 4 weeks to high-fat-fed diabetic mice, for 2 weeks to ApoE-knockout atherosclerotic mice model, for 20 weeks for chronological aged mice, and for lifetime to Zmpste-knockout progeroid mice. Burden of senescent cell accumilation as well as pathological or aged phenotype were measured in each mice model. Results: Canagliflozin reduced senescent cells in visceral adipose tissue within 1 week. Also, we found that senolytic effect of canagliflozin was provided through enhancing endogenous senolytic function by immune cells such as CD8+T cells. This machinery was mediated by enhanced AMPK signaling through incrase of endogenous AICAR production, which leads to the downregulation of PD-L1 expression on senescent cells. Oppositely, inhibition of AMPK signaling with Compound C administration (10mg/kg ip daily) resulted in abolishing senolytic effect of canagliflozin. Furthermore, canagliflozin reduced their senescent cell burden and alleviated atherosclerosis in ApoE-knockout mice, extended lifespan in progeroid mice, and altered physical function in aged mice. Conclusions: Our results showed new aspect of protective efficacy of SGLT2 inhibitors and would be promising evidence that SGLT2 inhibitors can be used as not only cardio- or renal-protective drugs but also anti-aging drugs.
Abstract 14865: A Paradigm Shift in the Incidence of Early-Onset Atrial Fibrillation and Flutter
Authors: Pojsakorn Danpanichkul, Sorawit Ongsupankul, Thanaboon Yinadsawaphan, Phakkamon Pingwang, Nonlawan Songmueang, Chalida Nonthasoot, Yatawee Kanjanakot, Juthipong Benjanuwattra, Teerapat Nantsupawat
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) and atrial flutter (AFL) are the most prevalent cardiac arrhythmias. Although the incidence and disease burden have been increasing, once adjusted for age, the standardized incidence has been decreasing, reaching 57.10 per 100,000 as of 2019. This study aims to explore this epidemiological trend pertaining to the younger population which are often underrepresented in AF/AFL studies. Methods: Utilizing the Global Burden of Disease (GBD) database, we calculated the incidence and disability-adjusted life years (DALYs) of AF/AFL patients aged 15-49 years along with the age standardized rates (ASR) and annual percentage changes (APC) for the incidence and DALYs from 2010 to 2019. We also calculated these values for populations according to socio-demographic index (SDI) group, region, and gender. Result: From 2010 to 2019, the standardized incidence and DALYs of early onset AF/AFL (EOAF/AFL) had increased globally. The APC of ASR of incidence had been +0.15% (95% confidence interval (CI) 0.21%-0.08%) and the APC of ASR of DALYs had been 0.28% (95% CI 0.36%-0.21%), respectively. Women demonstrated higher APC of both ASRs of incidence (+0.45% (95% CI 0.40%-0.50%) and DALYs (+0.50% (95% CI 0.45%-0.55%) while men experienced a stable trend of ASR of incidence and declining trend of ASR of DALYs. Geographic analysis showed that Eastern Mediterranean population had the highest APCs of both ASRs of incidence (+1.53% (95% CI 0.40%-0.50%)) and DALYs (+1.61%95% CI 0.40%-0.50%)), while both ASR and DALYs declined in the United States Conclusion: The incidence and DALYs of EOAF/AFL had been increasing globally, especially among women. However, rates differed by geographic region. For example, Eastern Mediterranean regions showed the largest increases across all age groups. In contrast, the incidence of EOAF/AFL had continued to decline in the United States. Future study is warranted to explore the geographical impact on the risk factors of AF/AFL.
Abstract 15158: Prognostic Impact of Right Ventricular-Pulmonary Arterial Coupling Ratio in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Hideaki Kanzaki, Yuki Irie, Makoto Amaki, Kensuke Takagi, Naonori Kawamoto, Satsuki Fukushima, Takeshi Kitai, Chisato Izumi
Journal: Circulation (2023)

Introduction: Right ventricular (RV) dysfunction is known as an important prognostic factor in heart failure. As reduced RV systolic reserve, RV contractility no longer increases against afterload, resulting in lower ratios of RV function to pulmonary artery (PA) pressure, known as RV-PA coupling ratios. Hypothesis: The assessment of RV-PA coupling ratios provides prognostic information for patients undergoing transcatheter aortic valve replacement (TAVR). Methods and Results: A total of 540 patients with TAVR (age, 84 ± 6 years; 186 men, 354 women) were included in this study. The RV-PA coupling ratio was calculated by dividing the tricuspid annular plane systolic excursion (TAPSE) by the PA systolic pressure (PASP) using transthoracic echocardiography before TAVR. Based on the median TAPSE/PASP (0.584 mm/mmHg), the patients were divided into two groups. Kaplan-Meier analysis demonstrated a higher incidence of adverse cardiac events (cardiac death and heart failure hospitalization) in the group with a low TAPSE/PASP ratio (log-rank test, P &lt;0.001). In multivariate Cox regression analysis, TAPSE/PASP was identified as an independent prognostic parameter (adjusted hazard ratio, 0.259; P = 0.028), whereas neither TAPSE alone nor PASP alone demonstrated any significant prognostic value. Conclusion: The RV-PA coupling ratio serves as a prognostic predictor for adverse cardiac events in patients undergoing TAVR.