tbuckley/cabot-search huggingface dataset:
Abstract 4139106: Prevalence and Prognostic Significance of Coronary Microvascular Dysfunction in Diabetic Heart Failure With Preserved Ejection Fraction Using Quantitative Perfusion Cardiac Magnetic Resonance
Authors: Yang Yang, Mu Zeng, Bilian Yu
Journal: Circulation (2024)

Background: The pathophysiological and clinical significance of coronary microvascular dysfunction in patients with diabetes mellitus and heart failure with preserved ejection fraction (HFpEF) remains uncertain. Research Questions: We aimed to use cardiac magnetic resonance to quantify coronary microvascular function, explore the relationship between perfusion and fibrosis, and assess the impact of coronary microvascular function on long-term clinical outcomes. Methods: In a prospective, observational study, patients with type 2 diabetes (T2DM) and heart failure were recruited alongside control subjects. All participants underwent clinical assessment and cardiac magnetic resonance, which included T1 mapping, extracellular volume mapping, as well as measurement of myocardial blood flow at rest and during maximal hyperaemia. The primary endpoint was defined as the composite outcome of death or hospitalization with a cardiovascular cause. Results: A total of 65 control individuals and 443 patients with T2DM were screened. Of 167 T2DM patients in the final analysis, 55 (32.9%) patients were categorized as HFpEF, 70 (41.9%) as heart failure with ejection fraction less than 50% (DM-non-HFpEF), and 42 (25.1%) as control subjects with no heart failure (DM-control). Patients with DM-HFpEF exhibited a comparatively diminished myocardial perfusion reserve (MPR) in comparison to the other three cohorts (all P&lt;0.05). Coronary microvascular function (defined as MPR &lt;2.0) was present in 81.82% of patients with DM-HFpEF. MPR was associated with cardiac troponin T levels (r =-0.3687; P&lt;0.0001) and diffuse fibrosis (extracellular volume: r =-0.5941; P&lt;0.0001). In all participants, during a mean follow-up of 284 days, there were 47 composite events. MPR demonstrated independent predictability of clinical outcomes even adjusting for clinical, blood, and imaging parameters. Patients with lower MPR (cutoff point, 1.95) exhibited a higher risk of adverse outcomes compared with patients with higher MPR (P=0.0001). Conclusions: In symptomatic patients with T2DM, a high prevalence of impaired MPR was observed specifically in individuals with HFpEF. MPR was associated with makers of myocardial injury and fibrosis and was predictive of adverse clinical outcomes. These findings could help identify high-risk patients, leading to more intensive treatment.
Abstract 4139038: Ibrutinib Increases Phosphorylation of the Src-Erk1/2 Signaling Pathway in Human Atrial-Specific Cardiomyocytes Derived from Induced Pluripotent Stem Cells
Authors: Matthew Fleming, Matthew O'Neill, Tao Yang, Joseph Solus, Brett Kroncke, Bjorn Knollmann, Javid Moslehi, Dan Roden
Journal: Circulation (2024)

Background: The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has revolutionized treatment for B-cell malignancies but increases the incidence of atrial fibrillation (AF) compared with conventional chemotherapy. Reports indicate that ibrutinib-mediated AF does not result from inhibition of BTK, but from off-target inhibition of a different kinase, C-terminal Src kinase (CSK). The signaling pathway by which CSK inhibition results in AF is unknown and may represent a novel molecular mechanism for AF. Objective: To identify kinase pathways that promote atrial fibrillation downstream from CSK. Methods: Studies were performed in human atrial-specific cardiomyocytes (hiPSC-aCMs) derived from population control induced pluripotent stem cells. Extracellular field potentials (EFPs) with the Nanion CardioExcyte 96 system demonstrated marked increased spontaneous beat-to-beat variability, an in vitro correlate of arrhythmogenic behavior, with exposure to ibrutinib but not to second-generation BTK inhibitors, which are less associated with AF (Figure 1A). Human phospho-kinase arrays determined the relative phosphorylation of 37 kinases in hiPSC-aCMs treated with ibrutinib or vehicle. Results: Treatment with ibrutinib increased phosphorylation of multiple kinases (Src, Erk1/2, CREB) in the Src-Erk1/2 pathway (Figure 2); the biggest increase was with Erk1/2 phosphorylation (3-fold). Pre-treatment of hiPSC-aCMs with the Erk1/2 inhibitors ulixertinib and SCH772984 inhibited the EFP arrhythmogenic signal seen with ibrutinib (Figure 1B). Conclusion: In hiPSC-aCMs, inhibition of CSK by ibrutinib results in increased arrhythmogenic behavior through Erk1/2-dependent phosphorylation. The downstream mechanisms by which this occurs remain unknown and represent novel potential target(s) for AF therapeutics.
Abstract 4139303: Temporal Trends in Cardiovascular Risk Factors and Cardiovascular Disease among Middle Eastern Immigrants in the National Health Interview Survey 2004-2018
Authors: Sunita Dodani, Yanal B. Kawaleet, Austin D. Le, Nehal P. Patel
Journal: Circulation (2024)

Introduction: Historically, Middle-Eastern (ME) immigrants have been aggregated with Non-Hispanic White (NHW) individuals, masking disparities in cardiovascular diseases (CVD). This study analyzes yearly data from 2004-2018 to assess changes in the prevalence of CVD and the American Heart Association’s (AHA) Life’s Essential 8 (LE8) risk factors among ME immigrants. Hypothesis: Trends in CVD and LE8 risk factors from 2004-2018 will differ between ME immigrants and NHW adults. Methods: We used sample adult data limited to ME immigrant and US-born NHW adults ≥18 years of age in the National Health Interview Survey, a nationally representative household US survey for years 2004-2018. The study assessed the prevalence of CVD (heart attack, angina pectoris, coronary heart disease, other heart conditions, or stroke) and LE8 risk factors: insufficient physical activity (PA), nicotine exposure, sleep duration, obesity, physician-diagnosed high cholesterol, diabetes, and hypertension. Survey-weighted, multivariable logistic regression controlling for age, sex, family income-poverty-ratio, marital status, and years in the US was used to model the linear relationship between survey year and the prevalence of CVD and risk factors. Results: Our study sample included 534,278 adults (93.2% NHW&amp;6.8% ME immigrants), representing 179,176,566 adults living in the US (mean age= 45.9 years, [SD=18.9]) with 51% being female. Trends for NHW adults showed decreases in CVD, insufficient PA, and nicotine exposure, but increases in sleep duration, obesity, high cholesterol, diabetes, and hypertension (Table). For ME immigrants, no significant changes were observed over time for most risk factors (p&gt;0.05). However, each year was associated with lower odds of insufficient PA and higher odds of hypertension prevalence. Conclusion: Between 2004-2018, NHW adults had varying trends in CVD and LE8 risk factors whereas ME immigrant adults experienced a similar decrease only in insufficient physical activity prevalence and a greater increase in hypertension prevalence. Future research should focus on sustaining increases in physical activity and addressing hypertension in ME immigrant populations.
Abstract 4139045: Suicide and Self-Harm with GLP-1 Receptor Agonists: A Meta-Analysis of Randomized Controlled Trials
Authors: Kaveh Hosseini, Pouya Ebrahimi, Juan Batlle, Muhammad Haisum Maqsood, Aryan Ayati, Clarine Long, Natalie McGowan, Constantine Tarabanis, Gregory Laynor, Sean Heffron
Journal: Circulation (2024)

Background: GLP-1 receptor agonists (RA) improve diabetes, reduce cardiovascular events, and cause substantial weight loss. However, concerns have been raised about increased adverse psychiatric effects – namely suicide. Given the explosive increase in use of these agents, detection of even rare side effects is of great clinical importance. We aimed to perform the first meta-analysis of adverse psychiatric outcomes (suicidal ideation/attempt/completion or self-harm) in randomized, placebo-controlled, clinical trials (RCTs) of GLP-1 RA. Methods: A comprehensive literature search through 8/29/23 was conducted to identify RCTs involving adults with diabetes and/or overweight/obesity treated with GLP-1 RA or placebo for ≥6 months. 7,229 non-duplicate articles were screened for inclusion and 144 had data extracted. After querying all available data sources, including direct contact with principal investigators or corresponding authors, 21 of the 144 studies were found to have recorded incidence of adverse psychiatric outcomes. A random-effects meta-analysis was performed to estimate risk ratios and 95% confidence intervals (CI) for the primary outcome. Results: In total, 36,168 subjects received GLP-1 RA and 30,445 placebo. The event rate was very low (63 – GLP-1 RA; 45 – placebo). The pooled odds ratio for incidence of the primary outcome was 0.88 [95% CI, 0.60-1.29] Figure . Notably, 6 studies, including a total of 11,828 subjects, had a history of suicide attempt/depression as exclusion criteria for enrollment. Removal of these studies did not change the overall findings (OR 0.77 [95% CI, 0.38, 1.57]). Conclusion: Our comprehensive meta-analysis of placebo-controlled RCTs does not support an association of GLP-1 RA use with increased adverse psychiatric events among adults with diabetes or overweight/obesity. However, these outcomes were recorded in &lt;15% of all trials, and &gt;1/5 excluded subjects predisposed to these outcomes. More research is necessary, and continued surveillance remains warranted, to establish the safety of GLP-1 RA, particularly in patients at risk for self-harm/suicide.
Abstract 4139274: Implications of Electrocardiographic-Based Artificial Intelligence on Patients with Exercise-Induced Cardiomyopathy
Authors: Marta Figueiral, Luca Fazzini, Jenny Jia Ling Cao, Scott Hubers, Christopher Scott, Robert McCully, Matteo Castrichini, Akanksha Mohananey, Rachad Ghazal, Min Wang, Li Wang, Rajiv Gulati, Roberta Montisci, Patricia Pellikka, Naveen Pereira
Journal: Circulation (2024)

Background: Electrocardiography-based artificial intelligence (AI-ECG) validated models that detect cardiac disease are increasingly being applied in clinical practice. The utility of such tools to detect insidious cardiac disease in patients with normal baseline left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise stress echocardiography (ESE), and do not have coronary artery disease (CAD) or hypertension, is unknown. Hypothesis: AI-ECG is useful to diagnose insidious cardiac disease and predict clinical outcomes in patients with exercise-induced cardiomyopathy. Aims: To assess the utility of AI ECG in patients with exercise-induced cardiomyopathy. Methods: Among all ESE performed between January 2003 and December 2022, patients without a hypertensive response to exercise and without CAD (confirmed by coronary angiography within 90 days after ESE), with resting LVEF ≥50% and a paradoxical ≥5% LVEF decrease during ESE were identified. A previously validated AI-ECG algorithm that predicts atrial fibrillation (AF), reduced LVEF, and cardiac amyloidosis (CA) was applied to the baseline ECG closest to the time of ESE. The predicted probability of AF, reduced LVEF, and CA if above the published thresholds, was determined. Results: There were 134 patients with exercise-induced cardiomyopathy who were identified. The mean age of this cohort was 66±10 years, 76% were women and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. The median follow-up period was 6.8 years (IQR 3.0-12.2). Among patients without a baseline history of AF (n=112), AI-ECG identified 29% with a significant probability of AF, which was associated with a subsequent AF diagnosis at univariable analysis (HR 2.505, 95%CI 1.016-6.177, p=0.046). There were 10 patients with an AI-ECG prediction of reduced LVEF among whom 3 were subsequently hospitalized with HF. AI-ECG was positive for CA in 8 and 3 amongst these had subsequent HF hospitalizations (Table). Conclusions: Baseline AI-ECG may help predict subsequent AF and diagnose preclinical amyloid cardiomyopathy in patients who by resting echocardiography do not seem to have cardiac disease but with exercise develop reduced LVEF.
Abstract 4139209: Racial/Ethnic Disparities in Outcomes of Post-Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Shubhadarshini Pawar, Rohit Ganduboina, Palak Dutta, Shipra Gulati, Sagar Ranka
Journal: Circulation (2024)

Background: There has been growing awareness and recognition of discrepant health outcomes based on ethnic and racial background in patients undergoing cardiovascular procedures. Transcatheter aortic valve procedures has become the primary treatment for aortic stenosis and is currently the standard of care. Despite widespread adoption of TAVR, African Americans (AA) have continued to remain underrepresented and typically suffer poorer outcomes. Thus, we conducted a systematic review and meta-analysis to compare TAVR outcomes between AA and non-AA populations. Methodology: We systematically searched all electronic databases (PubMed, EMBASE, Scopus, Web of science) from inception until May 25 th , 2024. A pooled analysis of data from observational studies and randomized controlled trials reporting post-TAVR outcomes based on racial background were included. The key endpoints evaluated were in-hospital mortality, post-procedure myocardial infarction (MI), pacemaker placement, in-hospital stroke, vascular complications, major bleeding, acute kidney injury (AKI). We used the I2 statistic to assess heterogeneity among studies using the Random-Effects model, with significance set at I2 &gt; 50%. All analysis was carried out using R version 4.3.2. Results: The meta-analysis of eleven observational studies, involving 953,892 TAVR patients [912,301 (95.64%) Caucasians and 41,591 (4.36%) AAs], showed a statistically significant higher risk of post-procedure pacemaker placement (OR 1.08, 95% CI: 0.77-1.51, p=&lt;0.001, I2=99%) for Caucasians compared to AAs. In secondary outcomes, AAs had significant higher risk of in-hospital stroke (OR 0.83, 95% CI: 0.67-1.02, p &lt;0.01, I2=90%), major bleeding (OR:0.89, 95% CI: 0.77-1.02, p &lt;0.01, I2=74%), AKI (OR: 0.77, 95%CI:0.67-0.88, P=0.04, I2=59%) compared to Caucasians. However, no significant differences were found for in-hospital mortality, MI, vascular complications as mentioned in Figure 1-3. Conclusion: The current study suggests a worse clinical outcome for AA undergoing TAVR. Further studies are needed to evaluate the factors responsible for the discrepancy and implementing mitigation strategies.
Abstract 4138955: Artificial intelligence-guided screening of rheumatic heart disease from single-view two-dimensional echocardiography
Authors: Evangelos Oikonomou, Bruno Nascimento, Aline Pedroso Camargos, Bernardo Lombo, Robert McNamara, Ruchika Karnik, Craig Sable, Antonio Ribeiro, Rohan Khera
Journal: Circulation (2024)

Introduction: Rheumatic heart disease (RHD) is the most common acquired heart disorder in children and adolescents worldwide. We developed and validated an automated artificial intelligence (AI)-guided RHD screening algorithm adapted for point-of-care ultrasonography (POCUS) in school-aged children. Methods: We employed a cross-domain transfer learning approach, in which a 3D convolutional neural network (CNN) was first trained to detect structural RHD deformation of the mitral or aortic valves in 244,523 videos, representing all views from 5,614 adult transthoracic echocardiograms (1:5 age and sex-matched cases and controls; median age 69 [58-80] years, 76.4% female) in a large US health system. The model was fine-tuned for stage ≥B (“definite”) RHD in 21,472 POCUS videos (2D parasternal and apical acquisitions) from 5,525 studies (75% training, 25% validation) in a pediatric screening program (median age 11 [IQR 10-13] years, 54.6% female) in Brazilian low-income schools. Testing was performed in a held-out set of 1,966 parasternal long-axis (PLAX) videos from 1,138 studies in Brazil (14 [1.2%] with stage ≥B RHD) as well as in an external pediatric screening set in Uganda consisting of 249 videos from 96 studies (34 [35.4%] with stage ≥B RHD) ( Fig. 1 ). Results: Our model ( Fig. 2 ) achieved a study-level AUROC (area under the receiver operating characteristic curve) of 0.88 across the held-out/external testing sets for identifying stage ≥B RHD from cardiac POCUS ( Fig. 3A ). On a video-level the model learned a continuous spectrum of phenotypes on PLAX acquisitions spanning stage ≥B (“definite”) and stage A (“borderline”) cases, ranging from a median video-level AI probability of 0.13 [0.01-0.73] for stage ≥B to 0.00 [0.00-0.01] for non-RHD POCUS ( Fig. 3B ). At the threshold that maximized Youden’s J in the held-out Brazil set, our algorithm’s performance in the set from Uganda showed 97% recall (sensitivity), a positive predictive value (precision) of 46%, and a negative predictive value of 95%. Conclusions: A transfer learning approach that employs multi-view learning achieves excellent performance for RHD on single-view two-dimensional cardiac POCUS without Doppler. Our study suggests a scalable approach to AI-enabled RHD detection with images that can be acquired by individuals with modest training.
Abstract 4138112: A Case of Caseous Mitral Annular Calcification and the Utility of Multimodality Cardiac Imaging
Authors: Amanda Nguyen, Carter English, Ahmadreza Ghasemiesfe, Sandhya Venugopal
Journal: Circulation (2024)

Background: Mitral annular calcification (MAC) is a common incidental finding associated with advanced renal dysfunction, hyperlipidemia, hypertension, or abnormal calcium metabolism. Caseous mitral annular calcification (CMAC) is a less common MAC variant involving central liquefaction necrosis, which results in a paste-like substance consisting of calcium, fatty acids, and cholesterol. Case description: A 64-year-old female presented to clinic with chronic shortness of breath and fatigue that started after COVID-19 pneumonia in 2021. As part of the initial evaluation, a transthoracic echocardiogram (TTE) was done, which revealed moderate annular calcification, 3+ mitral valve regurgitation, and a 1.8x1.5 cm echogenic mass on the posterior mitral annulus, concerning for possible fungal vegetation. Further multimodality imaging was pursued. Transesophageal echocardiogram confirmed the presence of a 2.0x1.7 cm cystic mass but demonstrated normal mitral valve function. Cardiac MR further identified a 1.2x0.8x1.5 cm hypointense mass, with surrounding late gadolinium enhancement, suggesting an associated inflammatory/degenerative process. Gated cardiac CT scan showed a mass with ring-like dense peripheral calcification and low central attenuation. Overall, findings from multimodality imaging were most consistent with CMAC. In the present case, the patient was monitored conservatively, as her symptoms of shortness of breath improved, and she did not experience any associated complications. Discussion: The present case demonstrates an incidental finding of an echogenic mass on the posterior mitral annulus, later identified as CMAC. Initial imaging with TTE helps evaluate for CMAC. However, on TTE alone, CMAC is often misdiagnosed with other conditions, including intracardiac tumors, abscesses, vegetations, or thrombi, and more advanced imaging is often recommended. On cardiac MR, CMAC is usually hypointense due to the elevated calcium content and may have surrounding late gadolinium enhancement due to associated inflammation. On gated cardiac CT, CMAC presents with a hyperintense rim due to calcification and a hypointense center consistent with central necrosis. As in this patient, CMAC is usually a benign condition that can be monitored conservatively. Indications for invasive intervention include significant valvular dysfunction, embolization, or conduction abnormalities. Multimodal imaging can aid in appropriate diagnosis to mitigate unnecessary interventions.
Abstract 4138964: Longer AF Diagnosis-to-Ablation Time is Associated with AF Inducibility Post-Pulmonary Vein Isolation
Authors: Grace Bailey, Caitlin Phalunas, Minesh Lathia, Elizabeth Belden, William Belden, Amit Thosani, Joshua Silverstein, George Shaw, Tharian Cherian, Mati Friehling, Chaojing Duan, Emerson Liu
Journal: Circulation (2024)

Background: Post-ablation atrial fibrillation (AF) inducibility has been associated with AF recurrence and is often used as an endpoint for Pulmonary Vein Isolation (PVI). Little is known regarding factors affecting inducibility after PVI, as AF inducibility is common even after PV isolation. Prolonged episodes of untreated AF can result in remodeling of the atrium and the formation of new arrhythmogenic substrate, which may make treatment of AF more challenging. We hypothesized that longer diagnosis-to-ablation time (DAT) is associated with higher rates of post-PVI AF inducibility. Objective: To evaluate DATs in cases of inducible vs. non-inducible AF post ablation. Methods: A single-center, retrospective analysis of 168 consecutive patients who underwent 1 st time PVI between 1/1/2022 and 12/01/2023 was performed. Following PVI, inducibility of AF was tested by programmed stimulation using decremental pacing in 50ms windows for 10 seconds each (from 400 ms down to 200 ms or until loss of 1:1 atrial capture). Results were categorized by type of rhythm induced (non-inducible, AF) and duration (sustained, non-sustained). DAT was obtained from review of the medical records. Descriptive statistics were used to compare demographics and AF type, and parametric and non-parametric tests were used for analysis of the diagnosis-to-ablation window and its relationship to inducibility. Results: There was no difference in demographic data or AF type between the two groups. 85 patients (50.6%), had no inducible AF. 83 out of 168 cases (49.4%) had inducible sustained AF. Overall DATs ranged from 0 to 40 years. DAT was significantly higher in the inducible vs. non-inducible groups (3.810 vs. 2.906 years, p=0.023). Conclusion: Longer DAT is associated with AF inducibility post-PVI despite successful ablation. This association may reflect the increased persistence of AF as it progresses over time. Future studies are needed to evaluate the clinical implications of DAT times.