tbuckley/cabot-search huggingface dataset:
Abstract 4142809: Artificial Intelligence Enabled Prediction of Future Structural Heart Disease and Cardiovascular Risk from Single-lead Electrocardiograms
Authors: Lovedeep Dhingra, Arya Aminorroaya, Aline Pedroso Camargos, Akshay Khunte, Veer Sangha, Luisa Brant, Sandhi Barreto, Antonio Luiz Ribeiro, Harlan Krumholz, Evangelos Oikonomou, Rohan Khera
Journal: Circulation (2024)

Background: Portable devices capable of recording single-lead electrocardiograms (ECGs) can enable large-scale community-based cardiovascular risk assessment. We developed a noise-adapted ensemble deep learning algorithm for lead I ECGs as the sole input and predicted the risk of major adverse cardiovascular events (MACE) and development of new-onset structural heart disorders (SHDs) across multinational cohorts, spanning a US health system and community-based cohorts in UK and Brazil. Methods: We included adults with outpatient ECGs in Yale New Haven Health System (YNHHS) and population-based cohorts of UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among individuals with ECGs without cardiomyopathy or heart failure at baseline, we isolated lead I ECGs and deployed a noise-adapted AI-ECG model trained to identify cross-sectional SHD (LV ejection fraction &lt; 40%, moderate/severe left-sided valve disease, severe LV hypertrophy [IVSd &gt; 15mm and LV diastolic dysfunction]). Across cohorts, we evaluated the association of the baseline AI-ECG probability with risk of MACE using adjusted Cox proportional hazard models and assessed discrimination using Harrel’s c-statistic. In YNHHS, among those with serial echocardiograms, we evaluated the risk of new-onset SHD. Results: There were 169,381 patients with outpatient ECGs at YNHHS (age 55 years [IQR, 40-68], 98023 women [58%]), 42,741 UKB participants (65 years [59-71], 21,795 women [52%]), and 13,454 ELSA-Brasil participants (56 years [41-69], 7,348 women [55%]) with baseline ECGs. A total of 12,483 patients had MACE and 8595 developed SHD in YNHHS over 4.5 years (2.6-6.6). In UKB and ELSA-Brasil, 768 and 388 participants had MACE over 3.1 years (2.1-4.5) and 4.2 years (3.7-4.5), respectively. Each 0.1 increment in the model output portended a 15-35% higher hazard of MACE across cohorts, independent of age, sex, and comorbidities (aHR: YNHHS 1.20 [1.19-1.21], UKB 1.15 [1.09-1.20], ELSA-Brasil 1.35 [1.28-1.44]). Among patients with serial echocardiograms in YNHHS, a positive AI-ECG screen portended a 2-fold higher risk of new-onset SHD (aHR: 2.09 [1.98-2.20]). Conclusions: In geographically and clinically distinct cohorts, a noise-adapted AI model with lead I ECGs as the only input defined the risk of MACE and new-onset SHD. This represents a scalable strategy that can use portable and wearable devices with ECG capabilities for cardiovascular risk stratification in the community.
Abstract 4142865: Determining the Physiologic Effect of the Cavopulmonary Connection on Caval Flows Using 4D Flow MRI
Authors: Vasupradha Suresh Kumar, Sarah Kollar, Yue-Hin Loke, Ravi Vegulla
Journal: Circulation (2024)

Background: The single ventricular (SV) palliative strategy involves routing the caval blood flow into the pulmonary arterial circulation. The superior cavopulmonary connection (SCPC) and Fontan connection generally raises caval pressures, although the changes to caval flows in SV patients has not been investigated. In this study, we determined the effect of SCPC and Fontan operation by comparing caval flows in SV pediatric patients against patients with biventricular (BiV) circulation as determined by 4D flow cardiac MRI (CMR). Methods: Clinically indicated CMR of two hundred and thirty-eight pediatric patients (≤18 years of age) were retrospectively analyzed. All included studies had ferumoxytol-enhanced 4D flow (Seimens 1.5T). Patients with systemic/pulmonary venous abnormalities were excluded. Flow in the superior vena cava (SVC) was measured by an independent observer using cloud-based platform Arterys ( Figure 1A ). The SVC flow was indexed against body surface area or expressed as a ratio of total venous return. Unpaired T-test and correlation analysis was used to compare differences between BiV and SV patients. Results: The cohort consisted of 149 BiV and 89 SV patients (8.5±5.7 years, body surface area 1.1±0.5 m 2 , 99 female). The indexed SVC flow negatively correlated with age (r=-0.313, p&lt;0.0001) and body surface area (r=-0.540, p &lt;0.0001). SVC flow as a ratio of total venous return was also negatively correlated with age (r=-0.332, p&lt;0.0001) and body surface area (r=-0.546, p&lt;0.0001- Figure 1B ). SV patients post-SCPC had associated lower SVC flow compared to BiV children (1.3±0.6 vs. 1.6±0.7 L/min/m 2 , p&lt;0.0001- Figure 1C ). Conclusion: The caval flow distribution in the pediatric population changes with age and body size. SV patients with an SCPC had associated lower SVC flow compared to BiV patients. Determining the general caval flow distribution provides insight into the evolving flow hemodynamics of the growing pediatric patient, which in turn could be used to optimize the cavopulmonary connection in SV patients.
Abstract 4142989: Myocardial Perfusion Reserve Index in Pediatric Heart Transplant Recipients
Authors: Andrew Lawson, Simon Lee, Andrada Popescu, Paul Tannous, Christina Laternser, Michael Markl, Cynthia Rigsby, Joshua Robinson, Defne Magnetta, Nazia Husain
Journal: Circulation (2024)

Background: Cardiovascular magnetic resonance (CMR) has an emerging role in graft surveillance for pediatric heart transplant recipients (PHTR). Transplanted grafts are susceptible to cardiac allograft vasculopathy, manifested as macrovascular narrowing on angiography, as well as micro-vessel disease. By CMR, myocardial perfusion abnormalities can be evaluated semi-quantitatively, by calculation of a myocardial perfusion reserve index (MPRI). However, normal MPRI values have not been well established in PHTR and prior investigation of associations between MPRI and graft pathology remain limited. Research Aims: The goals of this study were to describe the MPRI findings in a large cohort of PHTR and to evaluate clinical associations with low MPRI. Methods: We performed a retrospective chart review of consecutive, stress CMR studies at a single center from 2015-2024. Follow-up studies were excluded. Biventricular volume and function analyses were performed. A total dose of 0.15mg/kg gadobutrol was administered for rest and stress imaging. Regadenoson was the pharmacologic stressor at dose of 6-10mcg/kg, up to max 400mcg. Time signal intensity curves were obtained from perfusion datasets at stress and rest at the base, mid-ventricle, and apex. Segmental MPRI was calculated as a ratio of the maximal upslopes of the curves at stress versus rest. Global MPRI was computed as a mean of all segments. Results: 128 PHTR were included. Mean age was 12.5±5.3y, with 5.9±3.8y since transplant. A clinical concern prompted CMR in 18% of studies; in 82% the indication was routine surveillance. History of CAV was present in 6% and moderate or severe rejection in 22%. In 11 studies, images were inadequate for MPRI analysis. In the 117 studies included for analysis, global MPRI was normally distributed with mean 1.38±5.3. Mean MPRI observed at the mid-ventricle (1.49±0.46) was higher than at the base (1.32±0.32) and apex (1.33±0.39), (p&lt;0.001). PHTR with first tercile MPRI (&lt;1.25), when compared to third tercile (&gt;1.50), did not have significant differences in age, time since transplant, history of CAV, history of moderate or severe rejection, or LV or RV EF. Conclusions: Mean global MPRI values in this cohort of relatively healthy PHTR are significantly lower than reference values for healthy adults and similar to previously reported values in adult heart transplant patients. Future study should evaluate associations between MPRI and subsequent clinical outcomes.
Abstract 4142835: Remote Patient Monitoring and Excess Readmission Rates for Cardiovascular Conditions at Hospitals in the United States
Authors: Aline Pedroso Camargos, Zhenqiu Lin, Joseph Ross, Rohan Khera
Journal: Circulation (2024)

Background: Heart failure (HF) and acute myocardial infarction (AMI) have been a key focus of health policy initiatives targeting hospital readmission risk, but after initial improvements, progress has slowed. Digital remote patient monitoring (RPM) tools have been recognized as potential strategies for enabling better patient outcomes by tracking healthcare outside clinical settings. We evaluated patterns of RPM service use at US hospitals and their association with post-discharge outcomes for HF and AMI. Methods: We used the 2022 American Hospital Association (AHA) Annual Survey data to identify US hospitals offering RPM services and the nature of these services (post-discharge, chronic care, others), overall and across different hospital groups (based on bed size, location, ownership, teaching status, and region). We linked these with hospitals’ benchmarked risk-standardized relative performance on readmissions (excess readmission ratio [ERR]) from CMS Hospital Quality Report (2019-2022) to examine the association between RPM services at hospitals and lower than expected HF and AMI readmission rates (ERR&lt;1), accounting for hospital characteristics in multivariable logistic regression. Results: The study included 2,255 hospitals in the AHA Survey with paired readmission performance data. Of these, 55.7% offered RPM services: 41.7% for monitoring post-discharge care, 47.4% for chronic care management, and 40.2% for other RPM services. RPM service availability was highest at hospitals with bedsize ≥500 (81.1%) and those in the Northeast (73.6%). RPM services were also more frequently available at urban vs rural (57.5% vs 29.7%) and teaching vs non-teaching (86.4% vs 52.5%) hospitals (A) . Hospitals with RPM services compared with those without RPM services were more likely to have an ERR&lt;1 for HF (OR 1.24, 95% CI 1.03-1.49) but not for AMI (OR 1.20, 95% CI 0.95-1.51). However, availability of RPM services targeted explicitly at post-hospitalization monitoring was associated with greater likelihood of having an ERR&lt;1 for both HF (OR 1.33 95% CI 1.10-1.60) and AMI (OR 1.29, 95% CI 1.02-1.62) (B) . Conclusions: Large, urban, and teaching hospitals more frequently invested in RPM services, which was associated with lower-than-expected readmission rates for HF and AMI, especially when RPM specifically targeted post-discharge care. There is a need to rigorously evaluate the nature of services that enable the best post-discharge outcomes for each condition.
Abstract 4142910: Role of High-Sensitivity Troponin I and Troponin T in Prediction of Sudden Arrhythmic Death in Patients with Coronary Artery Disease
Authors: Jessica Mao, Natasha Cuk, Chi-Hong Tseng, Yunxian Liu, Alan Kadish, M. Vinayaga Moorthy, Nancy Cook, David Morrow, Christine Albert
Journal: Circulation (2024)

Introduction: While implantable cardiac defibrillators (ICDs) can prevent sudden arrhythmic death (SAD), less than 30% of SAD patients meet criteria for implantation. Improved risk stratification and prediction is necessary to identify individuals at risk. Objective: The purpose of this study was to evaluate the role of high-sensitivity troponin T (hs-TnT) and high sensitivity troponin I (hs-TnI) in predicting SAD. Methods: We prospectively evaluated the associations of hs-TnT and hs-TnI with the incidence of SAD in 5,764 participants enrolled in the PREDETERMINE study, which enrolled individuals with history of coronary artery disease (CAD) not meeting criteria for ICD implantation with left ventricular ejection fraction (LVEF) above 30%. Using multivariable Cox proportional hazards models, hs-TnT and hs-TnI were evaluated as continuous (log-transformed) variables, by quintile, and dichotomously by clinical thresholds. Spearman coefficients were calculated to assess biomarker correlations. Results: Over a median 8.1 years follow-up, 4.3% (n=249) of the study cohort experienced SAD. Within our cohort, hs-TnT and hs-TnI were highly correlated with a Spearman coefficient of 0.77. After multivariable adjustment, both hs-TnT and hs-TnI were associated with increased risk of SAD (HR 1.18, 95% CI 1.03-1.36 per 1-SD change for hs-TnT, and HR 1.19, 95% CI 1.04-1.37 per 1-SD change for hs-TnI). Risk for SAD was elevated in the highest quintile of hs-TnT (HR 2.53, 95% CI 1.47-4.37) and the highest quintile of hs-TnI (HR 3.23, 95% CI 1.86-5.60) compared to the lowest quintile. Elevated hs-TnT ≥19 ng/L (median) was associated with increased risk of SAD (1.69, 95% CI 1.27-2.25), as was hs-TnI ≥ 8.5 ng/L (HR 1.69, 95% CI 1.29-2.23). Conclusion: In our large, prospectively enrolled cohort of participants with CAD and LVEF above 30%, both increased hs-TnT and hs-TnI were each significantly associated with similarly increased risks of SAD. Among individuals who are at risk for SAD but do not qualify for prevention with ICD implantation, measurement of high-sensitivity troponin in conjunction with clinical data may help to identify those most likely to benefit from preventative therapy.
Abstract 4142887: Disentangling Abdominal Aortic Aneurysms and Coronary Artery Disease Through Circulating Proteomics
Authors: Alexander Vanmaele, Jose da Veiga Fernandes de Mira, Sanne Hoeks, Elke Bouwens, K. Martijn Akkerhuis, Jorg de Bruin, Sander ten Raa, Bram Fioole, Joost Daemen, Nicolas Van Mieghem, Robert-jan Van Geuns, Patrick Serruys, Hence Verhagen, Eric Boersma, Isabella Kardys
Journal: Circulation (2024)

Introduction: The prevalence of abdominal aortic aneurysms(AAA) is at least twice as high in patients with coronary artery disease(CAD), and about half of the AAA-patients have clinically relevant CAD. Detecting concomitant disease and intervening on pathophysiological mechanisms could potentially improve survival in these patients. Research Questions: Which circulating biomarkers and biological mechanisms can distinguish AAA and CAD? Aims: To differentiate the circulating proteomic profiles and biological pathways associated with AAA and CAD. Methods: Patients with AAA and/or stable CAD from two prospective cohort studies were age, sex, and comorbidity matched 1:1:1 (AAA only, AAA and CAD, CAD only). 369 plasma proteins were simultaneously measured in both cohorts using the Olink Explore Cardiometabolic I panel. We investigated differences in proteomic profiles using univariable linear regression and multivariable logistic elastic net regression. Differences in biomarker interactions(pathways) were studied through differential network analysis. Results: Each matched group consisted of 53 patients. Overall, the mean age was 70 years and 92% were men. In AAA-patients, the baseline median(25 th -75 th percentile) maximum diameter was 46(43,50) mm. The proteins IRAG2 and CORO1A were significantly downregulated in AAA-patients with CAD, compared to AAA only. After multivariable selection, only IRAG2 was independently associated with the presence of CAD in AAA-patients. Protein interactions in six pathways differed in AAA-patients with CAD, compared to AAA only(Figure 1A). Moreover, the IGFBP7, CD59, REG1A and CST3 proteins were univariably, significantly upregulated in CAD-patients with AAA, compared to CAD only. Multivariable selection in the proteomic profile proposed PLA2G2A, CD59 and REG1A as independently informative biomarkers for the presence of AAA in CAD-patients. In 14 biological pathways, proteins interacted differently in CAD-patients with AAA, compared to CAD only(Figure 1B). Conclusion(s): A small set of proteins differed between phenotypes. While the average level of most biomarkers was the same, many protein interactions, in pathways implied in AAA by basic research, differed between AAA- and CAD-patients.
Abstract 4142117: First Reported Case of Massive Gastrointestinal Bleeding Linked to Piperacillin-Tazobactam in a Patient on Rivaroxaban: A Comprehensive Case Review
Authors: Abbas Mohammadi, Sara Alleyasin, Nasim McDermott
Journal: Circulation (2024)

Introduction: The management of patients with Venous thromboembolism (VTE) receiving anticoagulant therapy is complicated by potential interactions with other medications, including antibiotics. Piperacillin-tazobactam (PTZ) has been implicated in unexpected disturbances in the coagulation cascade, which can be critical in patients concurrently using anticoagulants like rivaroxaban. This report explores the complexities of prescribing broad-spectrum antibiotics to patients with pre-existing cardiac conditions and the necessity of careful consideration of drug-drug interactions. Case Report: A 52-year-old white male with a history of deep vein thrombosis on rivaroxaban, presented with severe left leg cellulitis and subsequent gastrointestinal bleeding shortly after the initiation of piperacillin-tazobactam. His presentation was complicated by a rapid deterioration in his condition following a syncopal episode, characterized by hematochezia and hematemesis, necessitating urgent medical interventions including the cessation of all anticoagulation therapy, esophagogastroduodenoscopy and broad-spectrum antibiotics. Discussion: This case highlights the clinical challenges and potential risks of coagulopathies induced by PTZ or the interaction of PTZ with rivaroxaban, stressing the importance of multidisciplinary vigilance. The mechanisms by which PTZ may influence the coagulation pathways in patients already at risk due to their cardiac profiles underscore a significant area of concern for clinicians.
Abstract 4142807: DIFFERENTIAL CARDIAC PROTECTIVE RESIDENT MACROPHAGES IN FEMALE MICE WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Maria Paz Ocaranza, Ruth sepulveda, Jackeline Moya, Joaquin Rojas, Patricio Araos, Cristian Amador, Marcela Hermoso, Luigi Gabrielli, Jorge Jalil
Journal: Circulation (2024)

Background: Women with heart failure with preserved ejection fraction (HFpEF) exhibit better clinical outcomes than men. In the recent murine model of HFpEF elicited by a high-fat diet (HFD) coupled with N [w]-nitro-l-arginine methyl ester (L-NAME), female mice showed less cardiac remodeling than males, independently from sex hormones. Also, male cardiac macrophages (Mo) from mice are more susceptible to inflammatory stimuli. It is unknown whether cardiac pro-inflammatory Mo derived from monocytes (CCR2 + MHCII + ) and resident repair Mo (CCR2 - MHCII + and CCR2 - MHCII - ) differ between males and females. Purpose: To characterize in mice of both genders with HFpEF the cardiac pro-inflammatory and the protective resident repair Mo. Methods: 12-week-old male and female C57BL/6N mice received HFD (60% kcal from fat) and L-NAME (0.65 g/L in drinking water) or control diet during 15 weeks and then sacrified. Cardiac function and cardiac pro-inflammatory and repair Mo were determined. Results: (mean±SEM, n=11-13 mice/group). Compared with males, female mice with HFpEF gained less BW (30% vs 47%, p&lt;0.001) and walked a greater distance on the treadmill (550±52 vs 365±28 mts, p&lt;0.01). Blood pressure was similar and significantly increased in both genders (p&lt; 0.001). Glucose intolerance was observed only in males with HFpEF. The left ventricle septum and posterior wall were thicker in HFpEF males vs controls and HFpEF females (p≤0.001, F=67.1). Left atrium size was increased only in males with HFpEF by 24% (p&lt;0.0001). In the female myocardium, the CCR2 - MHCII - Mo were significantly increased both in controls and in HFpEF mice vs male (p&lt;0.001, F=11.4). Only in males with HFpEF, the CR2 + MHCII + Mo increased by 59% (p&lt;0.001, F=12.9) and the CCR2 - MHCII + Mo decreased by 29% (p&lt;0.05, F=3.7). Conclusions: The protective resident Mo (CCR2 - MHCII - ) are significantly increased in the heart of females versus males. In females, the HFpEF did not modify the levels of protective residents Mo which was associated to less CRM and better exercise performance in females versus males. Only in males with HFpEF, the cardiac monocyte-derived macrophages (CCR2 + MHCII + ) increased and resident macrophages (CCR2 - MHCII + ) that are partially replaced by monocytes decreased. The activation of resident cardiac Mo may be an important mechanism for prevention and treatment of cardiac remodeling in HFpEF. FONDECYT 1221585 (MPO), 1231604 (JJ), 1231909 (CAA), 11241074 (PA) and FONDAP 15130011(MPO, LG).
Abstract 4142869: Heritable heart failure traits in mice undergoing early life stress
Authors: sarah costantino, Era Gorica, Shafeeq Mohammed, Francesca Manuella, Samuele Ambrosini, Chiara Boscardin, Frank Ruschitzka, Isabelle M Mansuy, Francesco Paneni
Journal: Circulation (2024)

Introduction: Adverse childhood experiences, also known as early life stress (ELS), are associated with increased risk of cardiovascular disease in later life, yet the underlying mechanisms remain elusive. Recent evidence indicates that parental life experiences can be transmitted to the offspring. Aim: To investigate the effects of ELS on cardiac structure and function in exposed parents and in their offspring, across 3 generations. Methods: We used ELS mouse model based on unpredictable separation of mouse pups (F1) from their mother (F0) each day for 3 hours from postnatal day 1 (PND1) to PND14 combined with dams exposure to an additional unpredictable stressor (forced swim in 18°C water for 5 minutes or 20-minute physical restraint in a tube) during separation. Control litters were raised normally. Echocardiography was performed at 6, 12 and 18 months in exposed animals (F0), their unexposed offspring (F1) and grand-offspring (F2). Both male and female mice were studied. Heart weight/tibia length was used to assess cardiac mass while Masson's Trichrome was employed to detect fibrosis. Lung congestion was assessed as lung wet/dry weight ratio. Single-cell RNA sequencing (scRNAseq) was performed in MSUS and control hearts. A 6-week environmental enrichment (EE) program (cages containing running wheels, maze) was employed to test the possible rescue of ELS effects in adult males and their offspring. Results: F1 MSUS mice displayed increased LV mass, impaired diastolic function (assessed by conventional and tissue Doppler analysis) myocardial fibrosis and lung congestion. Time-dependent worsening of cardiac performance was observed from 6 to 18 months, both in males and females. ScRNAseq unveiled dysregulation of transcriptional programs underlying inflammation and lipotoxicity in the cardiomyocyte and endothelial cell clusters. MSUS offsprings did not show changes of cardiac function at 6 months, however diastolic dysfunction and lung congestion were observed at 12 and 18 months. A similar impairment of cardiac function was observed in the MSUS grandoffspring (F3). Of interest, 6-week exposure to an environmental enrichment protocol was able to improve LV mass, diastolic function and lung congestion in 12 months-old MSUS mice. Conclusions: ELS induces a transgenerational transmission of cardiac phenotypic alterations which can be rescued by EE. Our results shed light on the potential role of ELS on heart failure development and potential mitigation strategies.