tbuckley/cabot-search huggingface dataset:
Abstract 4146866: Associations Between Short-term Outdoor Heat Measures and Arterial Stiffness are Modifed by Neighborhood Greenness: The Green Heart Project
Authors: Daniel Riggs, Clara Sears, Sonia Cobbold, sanjay srivastava, Rachel Keith, Aruni Bhatnagar
Journal: Circulation (2024)

Introduction: Accumulating evidence suggests that cardiovascular disease (CVD) risk is associated with climatic variables and the impact of these factors is likely to be increasing with changes in the global climate. Nevertheless, the underlying physiological mechanisms remain unclear, and it remains unknown whether urban greenspaces could contribute to climatic resilience by mitigating these mechanisms. Moreover, to-date most studies assessing CVD risk consider only ambient temperature, which may not fully capture physiologically relevant thermal conditions. Accordingly, using varied measures of heat, our objective was to assess how short-term heat exposure is related to arterial stiffness, and whether these associations are modified by area greenness. Methods: Adult participants, aged 25-70 years, were recruited from a neighborhood in Louisville, KY during the summer months of 2018 and 2019. Arterial Stiffness was measured by augmentation index (AIX) via pulse wave analysis in 714 participants. We assessed 7 heat metrics, including ambient temperature, dew point temperature, net effective temperature, Heat Index, and Universal Thermal Climate Index (UTCI), calculated as the 24h mean on the day of participants’ visit. Greenness surrounding participants’ homes was assessed by tree canopy within a 500m buffer. Linear regression was used to estimate associations between heat metrics and arterial stiffness, adjusting for socio-demographic and behavioral factors. Subgroup analysis was performed by tertiles of greenness. Results: Participants were predominantly female (61%) and White (77%), with an average age of 49.5 years. The median daily temperature during study visits was 24.4°C (range=12.2 to 28.9°C) and the median daily UTCI was 26.1°C (IQR=5.4°C). The strongest association between heat metrics and AIX was observed for UTCI (2.0% per IQR; 95% CI:0.4, 3.6), followed by net effective temperature (1.8% per IQR; 95% CI: 0.1, 3.6), while dew point temperature had the weakest association (0.6% per IQR; 95% CI: -0.8, 2.0). Stratifying our analysis by tertiles of tree canopy, we observed significant associations between heat metrics and AIX in low canopy areas, with a dose response decrease in associations among medium and high canopy areas. Conclusion: Increased arterial stiffness could be an important contributor to excessive CVD risk associated with physiologically relevant measures of heat exposure, which could be mitigated by surrounding greenspaces.
Abstract 4147022: Aligned Mechanical Tension Improves Electrophysiology of iPSC-Derived Engineered Heart Tissue
Authors: Ghiska Ramahdita, Thao Chau, Riya Bhakta, Charlene Pobee, Huanzhu Jiang, Guy Genin, Nathaniel Huebsch
Journal: Circulation (2024)

Introduction: Cardiomyocyte alignment increases over time during normal heart development. This alignment is associated with aligned mechanical tension and plays a key role in electromechanical function of the tissue. Myocardial disarray, in which the alignment is disrupted, is a hallmark of cardiomyopathy. This structural disarray is often accompanied by electrophysiological disfunction. Prior work, including ours, suggests that sodium channel function in particular is enhanced in aligned 3D tissues engineered from human induced pluripotent stem cells (iPSC). We hypothesized that cardiomyocyte alignment in 3D tissue could lead to enhanced sodium channel function by improving sodium channel expression. Methods: To test our hypothesis, we developed a micro-engineered heart tissue (μEHT) platform in which total mechanical tension could be decoupled from cardiomyocyte alignment . The μEHTs were cultured for at least 7 days in either a 4-post configuration to induce high uniaxial tension (expected to cause cardiomyocyte alignment), or 8-post configuration to induce multiaxial tension (expected to cause cardiomyocyte disarray; Fig. 1a). Optocardiography was carried out to study calcium dynamics (GCaMP6f reporter) and action potential waveforms (voltage-sensitive dye, BeRST-1), in heart muscle engineered from induced pluripotent stem cells (iPSC) derived cardiomyocytes. A sodium channel blocker, Saxitoxin, was added for drug response study. Sodium channel expression was assessed with Western blot and immunofluorescence analysis. Results: 4-post mEHTs had a lower action potential excitation threshold and faster phase-0 in action potential duration, which suggests improved electrophysiology compared to 8-post EHT. Calcium dynamics data, however, did not show significant difference. Additionally, 4-post EHTs exhibited a more pronounced response to Saxitoxin. Immunofluorescence shows a trend of higher colocalization of NaV1.5 and N-cadherin in the area with high predicted uniaxial tension and cardiomyocyte alignment. Western analysis suggested that aligned mechanical tension led to higher overall expression of Na V 1.5, the cardiac sodium channel (paired t-test n=3, p=0.0315).
Abstract 4146832: Cardiac Fibroblast Atlas Reveals Myofibroblast Activation After Myocardial Infarction
Authors: John Lu, Michael Januszyk, Michael Longaker
Journal: Circulation (2024)

Introduction: After a myocardial infarction (MI), cardiac fibroblasts are activated to deposit extracellular matrix that while prevents acute cardiac rupture in the short-term, causes long-term diastolic and systolic dysfunction. Despite the clinical burden of cardiac fibrosis, especially after MI, the molecular mechanisms driving cardiac fibroblasts to produce excessive scar tissue are unknown. To study MI scar formation, we sought to characterize the molecular drivers of cardiac fibroblast activation by creating a comprehensive single-cell transcriptomic atlas of cardiac fibroblasts after MI. Methods: We generated a comprehensive transcriptomic atlas of cardiac fibroblasts by integrating all single cell RNA sequencing (scRNA-seq) datasets of mouse post-MI samples that are publicly available on the NIH GEO and EBI ArrayExpress databases. We screened 104 total datasets, identifying 26 datasets that met inclusion criteria, which collectively include transcriptomic data from 125 mouse samples (85 MI / 19 sham MI / 1 IR / 1 sham IR / 19 healthy). Transcriptomic data were processed, integrated, and analyzed using Seurat and Harmony. Pseudotime analysis was performed using Monocle3. Results: To construct our comprehensive cardiac fibroblast atlas, we integrated scRNA-seq data from nearly 700,000 mouse cells from 125 mouse samples across 26 datasets (Fig. 1A). Using this integrated all-cells atlas, we computationally isolated over 171,000 cardiac fibroblasts. Sub-clustering of the cardiac fibroblasts revealed that there are nine subpopulations. Specifically, we identify that one of these subpopulations, which we term myofibroblasts, expands from ~1% to ~40% of all fibroblasts after MI (Fig. 1B). These myofibroblasts are characterized by increased production of extracellular matrix proteins (e.g., Col1a1, Cthrc1) relative to other fibroblast subpopulations (Fig. 1C). Pseudotime analysis reveals that increased pseudotime is correlated with increased expression of Cthrc1 (Fig. 1D). Conclusion: Our comprehensive single-cell atlas of cardiac fibroblasts after MI reveals a myofibroblast subpopulation that emerges after MI to deposit extracellular matrix to cause tissue fibrosis.
Abstract 4147474: Global and regional burden of alcohol-related atrial fibrillation from 1990 to 2021: An analysis of GBD study 2021
Authors: Muhammad Talha Shaukat, Wania Rehman, Malik Saad Hayat, Muhammad Shahzaib, Muhammad Khan Buhadur Ali, Muhammad Imaz Bhatti, Aleenah Mohsin, Aqeeb Ur Rehman
Journal: Circulation (2024)

Background and Aims: Atrial fibrillation constitutes a major global public health issue, with its epidemiological patterns having changed significantly over the past decades. In this study, we aimed to analyze trends of mortality due to alcoholic atrial fibrillation from 1990-2021, including identifying the patterns in age-standardized death rates (ASDR), years of life lost (YLL), and disability-adjusted life years (DALY) over time, and raising awareness about the global health burden of alcoholic atrial fibrillation. Methods: Data on alcohol-related atrial fibrillation was extracted from the Global Burden of Diseases 2021 study, including ASDR, YLL, and DALY from 1990 to 2021. The dataset was globally divided and categorized by continents and World Bank income levels. Joinpoint regression analysis was performed to determine average annual percentage changes (AAPC) from 1990 to 2021. Results: Globally, the Age standardized death rates (ASDR) for alcohol-related atrial fibrillation had a constant trend from 1990-2021. The ASDR was determined to be 0.15 (95% UI 0.1-0.2) both in 1990 and 2021 (AAPC=-0.014; 95% CI -0.014 to -0.036). Although the overall trend is constant, a considerable spike in mortality rates was observed from 2000-2010 (APC=0.38). Globally, the disability-adjusted life-years (DALYs) and the age standardized years of life lost (YLL) have remained fairly constant with AAPCs of -0.052 (95% CI -0.063 to -0.036) and -0.07 (95% CI -0.098 to -0.047), respectively. In continent wise analysis, North America and Asia had intermittent spikes in ASDRs while Europe and Africa showed a constant trend throughout the analysis. From 1990 to 2021, North America had an AAPC of 1.26 (95% CI 1.23-1.29), showing a deviation from global trend with an incline. Similarly, Asia had an increasing trend with AAPC of 0.58 (95% CI 0.55-0.6). Africa also had a minutely increasing trend from 1990 to 2021 with an AAPC of 0.36 (95% CI 0.33 to 0.38). According to World Bank income levels, high-income countries had the highest death rates, followed by upper-middle income, lower-middle income and low-income countries in descending order. Conclusions: Although trends in the burden of alcohol-related atrial fibrillation have varied globally, the net change in years of life lost (YLL) and age-standardized death rates (ASDR) from 1990 to 2021 have been minimal. The data highlights the need for further research, to develop specific strategies that are targeted at specific populations.
Abstract 4147551: Comparison of HFpEF Cardiac Output Augmenters versus Non-Augmenters during Exercise Right Heart Catheterization
Authors: Radu Tanacli, Masih Tajdini, Vivek Jani, Virginia Hahn, Kavita Sharma
Journal: Circulation (2024)

Introduction: Exercise intolerance is a hallmark feature of heart failure with preserved ejection fraction (HFpEF), resulting in reduced quality of life. We report here several characteristics associated with a incomplete cardiac index (CI) augmentation during supine bicycle exercise RHC in patients with HFpEF. Methods: We evaluated 67 patients with HFpEF and RHC exercise stress testing from the Johns Hopkins Heart Failure with Preserved Ejection Fraction Clinic. Histopathologic examination for cardiomyocyte hypertrophy, interstitial fibrosis, and inflammatory infiltrate was available 56 patients with RHC endomyocardial biopsy (EMB). Demographic, clinical, echocardiography, blood tests and pulmonary function tests (PFTs) were included in the analysis. Results: We found that 60 of 67 (90%) of HFpEF patients improved their baseline CI during exercise, with a mean percent increase between baseline and maximal exercise stage of 53.5±41.6 %. The mean stage of exercise attained was 3.1±1.7 with mean energy of 26.0±17.8 watts. We further divided the patients in 2 groups: patients with ≥50% CI increase at maximal effort (HFpEF-augmenters) and, those with &lt; 50% CI increase (HFpEF-non augmenters). HFpEF-augmenters achieved higher exercise stage, higher maximal HR and maximal SV. Of the HFpEF-augmenters, 23 (74%) saw an increase in both SV and HR; 6 (19%) increase in SV only, 2 (6%) increase in HR only. Of the HFpEF-non-augmenters, only 15 (42%) had an increase in both SV and HR, 14 (39%) had an increase in HR but decline in SV and 8 (22%) had an increase in SV but a decline in HR ( Figure ). Presence of comorbidities and NYHA class distribution were similar between the 2 subgroups. HFpEF-non augmenters had higher log NT-proBNP, hepatic enzymes, uric acid and cystatin C, lower cholesterol, higher pulmonary vascular resistance and lower PFTs (total lung capacity, forced vital capacity and FEV1) than HFpEF-augmenters ( Table ). Degrees of hypertrophy, fibrosis and inflammation on EMB did not differ between groups. Conclusion: In an obese HFpEF cohort with exercise hemodynamic testing those unable to augment cardiac index had a variable degree of chronotropic and inotropic/lusitropic incompetence, higher log NT-proBNP, elevated markers of hepatic and renal impairment, lower cholesterol and lower PFTs.
Abstract 4146994: Electronic Health Record Based Clinical Decision Support Increases Guideline-Directed Medical Therapy Initiation or Dosage Intensification in Patients with Heart Failure with Reduced Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Mehras Motamed, Jairo Nunes, Chandak Upagupta, Daniel Shi, Jacob Udell
Journal: Circulation (2024)

Introduction: Guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) remains underprescribed despite overwhelming evidence of clinical benefit. Electronic health record (EHR)-based clinical decision support (CDS) tools provide healthcare providers with evidence-based recommendations and reminders within the electronic health record system. EHR-based CDS tools offer an innovative and economical strategy to enhance GDMT prescription rates. Hypothesis: We hypothesized that EHR-based CDS is associated with increased GDMT initiation or dosage intensification in patients with HFrEF. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) published from inception to May 2024 on four databases: PubMed, Embase, CENTRAL, and MEDLINE. We included RCTs that assessed the impact of EHR-based CDS on GDMT initiation or dosage increase in patients with HFrEF. The primary outcome was a composite of GDMT initiation or dosage increase. Random effects meta-analysis was performed by Review Manager version 5.4 software. I 2 statistics was used to assess heterogeneity. Results: Out of 6716 retrieved studies, 5 RCTs involving 4881 patients met inclusion criteria. The inter-rater agreement was excellent (κ = 0.911). The primary outcome showed an overall effect size of 1.38 (95% CI: 1.00-1.91, P = 0.05; I 2 = 86%). Adjusted relative risk was not reported for most studies, and hence this data could not be provided. Visual inspection of the funnel plot was balanced. Conclusions: This meta-analysis indicates that EHR-based CDS tools show a potential to increase initiation of GDMT or increase GDMT dosage in HFrEF patients. Further investigation is required to validate these findings due to significant heterogeneity and limited included studies.
Abstract 4147450: Pulsed-field ablation versus thermal ablation for paroxysmal atrial fibrillation: A systematic review and meta-analysis
Authors: Douglas Cavalcante, Maria Antonia Cruz Akabane, Roberto Mazetto, Iury RIBEIRO, Caroline De Oliveira Fischer Bacca, Imara Barbosa
Journal: Circulation (2024)

Introduction: Conventional thermal ablation (TA) has been used to treat paroxysmal atrial fibrillation (AF) refractory to medical therapy. Despite this, the energy used to isolate the pulmonary veins can extend through the myocardium and adjacent tissues, causing complications. Pulsed-field ablation (PFA), which delivers high-voltage electric fields in microseconds, may limit this tissue damage outside the myocardium. However, the efficacy of pulsed-field ablation compared with conventional thermal ablation in this population remains uncertain. Research Question: What are the benefits of using PFA in patients with paroxysmal atrial fibrillation compared to AT Objective: The purpose of this study was to evaluate the efficacies and safety of PFA compared with TA in patients with paroxysmal atrial fibrillation Methods: PubMed, Embase, and Cochrane Central databases were systematically searched in May 2024 for studies that directly compared PFA and TA for the treatment of paroxysmal AF and reported safety or efficacy outcomes. We evaluated the following outcomes at ≥12 months of follow-up: (1) stroke, (2) arrhythmia recurrence and (3) redo procedures. Heterogeneity was assessed with I 2 statistics. Rstudio was used for statistical analysis. Results: We included 1,677 patients (734 male – 43.76%) from three studies. PFA was used to treat AF in 519 (30.94%) patients and thermal energy was used in 1.158 (69.05%) patients. There was no significant incidence of stroke after performing PFA compared to TA in the pooled population (OR 1.31; 95%CI 0.11-15.59; P = 0.832). As compared to thermal ablation, PFA demonstrated similar freedom from recurrent atrial fibrillation (OR 0.77; 95%CI 0.51- 1.18; P = 0.237). There were no statistically significant differences in redo procedures (OR 0.61; 95%CI 0.36- 1.03; P = 0.066). Conclusion: Compared to TA, PFA did not show significant differences in the occurrence of stroke after the procedure or in the recurrence of paroxysmal atrial fibrillation. Additionally, it was not associated with a lower rate of redo procedures.
Abstract Sa302: Protective effects of hemodilution in emergency cardiopulmonary bypass resuscitation after cardiac arrest
Authors: Xin Sui, Wenjia Xu, Chengke Yin, Baobin Cui, Tong Wu, Chang Liu, Fei Han
Journal: Circulation (2024)

Introduction: The no-reflow phenomenon is considered to be one of the important mechanisms of ischemia-reperfusion injury. Low hematocrit (Hct) after hemodilution can increase microcirculation flow by reducing blood viscosity and improve the non-reflow phenomenon after cardiac arrest. However, the effect of hemodilution remains controversial. Hypothesis: To investigate the protective effect of hemodilution and the optimal Hct in emergency cardiopulmonary bypass (ECPB) resuscitation after cardiac arrest. Methods: Male SD rats, 400-450 g were subjected to 8 min asphyxial CA and followed by ECPB resuscitation. Sham, Hct 30%-35%, Hct 25%-30% and Hct 20%-25% groups were included. Survival and Neurologic Deficit Score (NDS) were assessed at 24 h, 48 h and 72 h after return of spontaneous circulation (ROSC). Immunohistochemical staining for NeuN, IBA1, GFAP and Tunel staining were performed to assess neurological outcomes. HE staining and Tunel staining were performed to assess the outcomes of heart and kidney. Results: There was no significant difference in survival among all groups. NDS in Hct 20%-25% group was significantly better than that in the Hct 30%-35% and Hct 25%-30% groups at 24 h after ROSC ( P &lt;0.05). Hippocampus was less injured in the Hct 20%-25% than in the Hct 30%-35% and Hct 25%-30% groups (Figure). Hct 20%-25% significantly attenuated damage to heart and kidney. Conclusions: Hemodilution to Hct 20%-25% has a protective effect on the hippocampus, heart and kidney in ECPB resuscitation after cardiac arrest.
Abstract 4147489: POLA-R-CHP: Promising Results in DLBCL with Cardiac Involvement
Authors: Sneha Sharma, Akash Goyal, Daniel Addison, Adam Potter
Journal: Circulation (2024)

Polatuzumab Vedotin is a novel antibody-drug conjugate that targets CD79b, a B-cell antigen receptor expressed in mature B-cell lymphomas such as Diffuse Large B-Cell Lymphoma (DLBCL) 1 . Yet, its effect on cardiac disease is unknown. We present a case illustrating clinical outcome of a patient treated with Polatuzumab plus standard Rituximab, Vincristine and Prednisone (Pola-R-CHP) for metastatic DLBCL with profound cardiac involvement. She is a 56-year-old female who presented with pre-syncope associated with night sweats, myalgia and weight loss. On examination, a grade II/VI tricuspid regurgitation murmur was auscultated. CT showed chronic right lower lobe pulmonary embolism along with axillary and mediastinal lymphadenopathy. New findings of a mass protruding into the right atrium with thickening of right atrial and ventricular walls, a right atrial thrombus and small pericardial effusion were reported. Cardiac MRI characterized the mass to be partially vascularized with extension from right to left chambers encasing RCA and coronary sinus with diffuse interstitial expansion and inflammation (Image 1). Axillary lymph node biopsy was consistent with aggressive B cell lymphoma with positive CD19, CD20 and BCL2 markers. Hospital course was significant for polymorphic VT with degeneration into VFib arrest. ROSC was achieved after one round of ACLS. Multiple factors may have contributed to VT including myocardial inflammation, possible tumor induced RCA compression and prolonged QT. Amiodarone and anticoagulation were initiated and patient was discharged with a wearable cardiac defibrillator along with oncology and cardio-oncology referrals. Traditionally, DLBCL is treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone), however up to 40% of patients develop refractory disease or have a relapse 1 . As in the recent POLARIX trial 1 , our patient underwent three cycles of novel regimen of Pola-R-CHP. Follow up PET showed dramatic response with metabolic remission (Image 3). Cardiac MRI showed reduction in RV tumor, RA thrombus and inflammatory burden with preserved LV and RV function (Image 2). No further arrhythmias were noted and the patient completed chemotherapy. This case highlights a positive outcome in a patient with aggressive DLBCL with cardiac metastasis treated with Polatuzumab based therapy. References 1. Tilly H et al. Polatuzumab vedotin in previously untreated diffuse large B-Cell lymphoma. NEJM 2022;386:351–363