tbuckley/cabot-search huggingface dataset:
Abstract 18479: Lack of Catalytic and Non-Catalytic Function of PI3 Kinase Gamma in Mice Increases Hypoxia-Induced Pulmonary Hypertension
Authors: Leoni Gnatzy-Feik, Eva Berghausen, Marius Vantler, Müller Rebekka, Mario Zierden, Alessandra Ghigo, Emilio Hirsch, Stephan Baldus, Stephan Rosenkranz
Journal: Circulation (2023)

Rationale: Pulmonary hypertension (PH) is characterised by vasoconstriction and remodelling of pulmonary vessels, leading to elevated pulmonary arterial pressure and right ventricular (RV) hypertrophy. PI 3-kinase γ (PI3Kγ) is expressed in leukocytes, cardiomyocytes, and endothelial cells (EC) which are all involved in the pathogenesis of PH. The catalytic function of PI3Kγ is involved in leukocyte recruitment and EC proliferation which are important for vascular remodelling and maladaptive cardiac hypertrophy whereas its non-catalytic function affects cardiac contractility via cAMP signaling. Furthermore, inactivation of PI3Kγ impairs nitric oxide production by eNOS, which may lead to increased vascular resistance. Therefore, we investigated the role of both catalytic and non-catalytic functions of PI3Kγ in the pathogenesis of PH. Methods: PI3Kγ knockout mice (PI3Kγ -/- ), as well as mice with a catalytically inactive form of PI3Kγ (PI3Kγ KD/KD ) were exposed to hypoxia-induced PH (21 days at 10% O 2 hypoxia (HOX)). Systolic right ventricular pressure (RVSP) was measured using a Millar pressure catheter inserted via the jugular vein. RV hypertrophy was determined by Fulton's index. Results: PI3Kγ -/- mice showed significantly increased RVSP after hypoxia compared to WT controls (HOX WT 34.16±3.21 mmHg vs HOX PI3Kγ -/- 37.04±2.31 mmHg; p=0.0049). Already under normoxia (NOX), an increased RVSP was measured in PI3Kγ -/- mice (NOX WT 26.13±1.2mmHg vs. NOX PI3Kγ -/- 28.07±0.88 mmHg, p=0.0157). A significant increase in RVSP was also detected in PI3Kγ KD/KD (HOX WT 34.67±2.02 mmHg vs. HOX PI3Kγ KD/KD 37.95±1.39 mmHg; p=0.0228). Here, a significant increase in RV hypertrophy was evident for PI3Kγ KD/KD mice (HOX WT 0.38±0.06 vs. HOX PI3Kγ KD/KD 0.46±0.09; p=0.0037) which was not detected in PI3Kγ -/- compared to WT controls after hypoxia. Conclusion: The results show that both catalytic and non-catalytic inactivation of PI3Kγ in vivo do not counteract the pathogenesis of PH, but conversely enhance it. In this context, reduced phosphorylation of eNOS may play a crucial role, leading to increased vasoconstriction, whereas increased cAMP levels in PI3Kγ -/- may help the RV to adapt to the increased pressure. The exact mechanisms will be analysed in the future.
Abstract 16324: A Deep Learning Electrocardiogram Model Identifies Risk of Incident Heart Failure in Patients With Subclinical Hypothyroidism
Authors: Ryuichiro Yagi, Calum Macrae, Rahul C Deo, Shinichi Goto
Journal: Circulation (2023)

Introduction: Subclinical hypothyroidism (SH) is associated with an increased risk of heart failure (HF). However, there are no established measures to predict HF development within the SH population. Hypothesis: Risk of incident heart failure in SH can be predicted from a 12-lead electrocardiogram using features extracted by a convolutional neural network-based model. Methods: To test the hypothesis, we developed a convolutional neural network (CNN)-based model to detect ECG features linked with low thyroid function by training to discriminate the presence of hypothyroidism from 10,745 ECGs (2,693 from patients with low free T4 (FT4) and 8,052 from age, sex-matched patients without evidence of low FT4). The model was applied to baseline ECGs from an external cohort of 2,293 patients with SH (defined TSH &gt;4.5mIU/L and FT4 within 0.9-1.9ng/dl) to estimate the cardiac phenotype induced by hypothyroidism (ECG-hypothyroidism score). Cumulative incidences of HF admission were compared between groups stratified by the tertile of the model output (low, intermediate, and high score groups). Adjusted hazard ratios (aHR) were calculated using Cox proportional hazard model. Results: HF admission was more frequent in the high score group (9.60/100 person-year), compared with the intermediate or low score groups (5.08 and 2.29 per 100 person-year in the, respectively; Fig ). Subgroup analyses by sex and age group yielded similar results. The association between the ECG-hypothyroidism score and HF admission remained significant after adjustment for patient characteristics, conventional ECG abnormalities, and baseline thyroid function (high vs low score group: aHR 3.56, [95%CI, 2.26-5.61]; high vs intermediate score group: aHR 1.78, [95%CI, 1.25-2.54]). Conclusions: The CNN-based model, trained to detect prevalent hypothyroidism, accurately identified patients at high risk for HF admission within the SH population using baseline ECG.
Abstract 16148: Calculating Indexed Aortic Root Diameters With Ideal Body Weight Leads to Significant Reclassification in Overweight and Obese Patients
Authors: Kevin John, Radhika Ghosalkar, Jing Li, Rachael Steinhauer, Benjamin Wessler, Ayan Patel, Brian Downey
Journal: Circulation (2023)

Introduction: Indexed Aortic root diameter (AoR diam) measured by transthoracic echocardiography (TTE) using body surface area (BSA) is important in children, adolescents, and small adults in whom non-indexed values may under detect dilation. However, indexed AoR diam may lead to misleading results in obese individuals as the AoR diam does not increase in proportion to body weight. Hypothesis: We hypothesize that using ideal body weight (IBW, using the Devine formula) in place of actual weight in BSA calculation reclassifies a significant proportion of indexed AoR diam in overweight and obese patients. Methods: We performed a retrospective review of all patients with a TTE at Tufts Medical Center in 2022 and Ao root diam &gt;4 cm for men and &gt;3.6 cm for women. We excluded patients &lt; 20 years old and those with inadequate TTE images or missing aortic measurements. TTE data and baseline characteristics were recorded. Indexed AoR diam was calculated using both actual and ideal body weights. The thresholds for for mildly, moderately, and severely dilated indexed AoR were ≥2.2, ≥2.4, and ≥2.6 in men, and ≥2.3, ≥2.4, and ≥2.6 in women, respectively. Results: 456 patients (400 males, 56 females) met our inclusion criteria, with a subset of 331 patients (72.6%) with BMI ≥25. When ideal body weight was used for indexing AoR diam, 58.7% of patients initially classified as having 'normal' indexed AoR diam were reclassified as at least 'mildly dilated' (p&lt;0.001). Patients with a BMI ≥25 were more often reclassified as at least ‘mildly dilated’ compared to those with lower BMI (64.6% vs. 13.3%, p&lt;0.001). In stratified analysis, upward reclassification occurred in 31.9% of patients with 'mildly dilated' AoR diam (45.8% in BMI ≥25) and 35.2% of patients with 'moderately dilated' AoR diam (80% in BMI ≥25). Conclusions: The use of ideal body weight instead of actual body weight for indexing AoR diam changes risk-stratification in over half of the patients with an abnormal AoR. This is more pronounced in patients with a BMI ≥25 and may have significant management implications. Further studies are needed to investigate if the use of actual weight in Ao root indexing systematically underestimates Ao root dilation in overweight and obese patients and if the use of IBW can improve risk assessment.
Abstract 18634: Quantification of Coronary Volume to Left Ventricular Mass Ratio Using CT Angiography
Authors: Negin Hadjiabdolhamid, Lynn Duong, Sabee Molloi
Journal: Circulation (2023)

Introduction: Coronary volume to left ventricular mass ratio (V/M) is a promising parameter that can detect physiological imbalances between coronary vasculature and the supplied myocardium. However, the existing method that assesses the V/M using epicardial vascular volume based on coronary CT angiography (CCTA) is labor intensive and prone to variability due to its dependence on coronary vasculature visualization. Hypothesis: A new technique based on CCTA and its associated bolus tracking data enables an efficient semi-automated approach that can reproducibly measure the V/M with less variability compared to the existing manual approach. Methods: The V/M was assessed by both existing manual and the new semi-automated techniques in 6 Yorkshire swine (49.1 ± 9.0 kg). Using a 320-slice CT scanner, 9 pairs of repeated CT measurements were made (100 kVp; 200 mA) with a 5-minute delay between each acquisition. Contrast (0.5 mL/kg; 370 mgI/mL) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70contrast/saline) were injected peripherally at 5mL/s. Bolus tracking and triggering were followed by a single scan acquired at the peak of the aortic enhancement. Using a first-pass analysis model, the bolus tracking and single volume scan data were used to derive the total vascular blood volume (mL). Standard myocardial segmentation was used for myocardial mass (g) measurement. The V/M was also calculated from CCTA using the manual technique, by segmenting coronary luminal volume and myocardial mass. The reproducibility of the V/M was assessed using regression analysis. The variability of the two techniques for determining normal V/M was quantified using the coefficient of variation. Results: The first ((V/M) 1 ) and second ((V/M) 2 ) measurements were related by (V/M) 2 = 1.039 (V/M) 1 + 0.002 (Pearson’s r = 0.90; RMSE = 0.01 mL/g). The coefficient of variation was 0.13 and 0.24 for the V/M calculated from the new semi-automated and existing manual techniques, respectively. Conclusion: A novel semi-automated technique can be used for quantification of V/M with low variability. This technique can potentially be used for early detection of physiological imbalances between coronary vasculature and the supplied myocardium following coronary artery disease.
Abstract 13078: Prognostic Significance of Reticulocyte Production Ability in Patients With Chronic Heart Failure
Authors: Motoki Nakao, Toshiyuki Nagai, Atsushi Tada, Taro Koya, Suguru Ishizaka, Yoshifumi Mizuguchi, Hiroyuki Aoyagi, Shogo Imagawa, Yusuke Tokuda, Yoshiya Kato, Masashige Takahashi, Hiroto Sakai, Masaharu Machida, Kenichi Matsutani, Takahiko Saito, Hiroshi Okamoto, Toshihisa Anzai
Journal: Circulation (2023)

Background: Anemia is frequently observed in patients with chronic heart failure (CHF), and many studies have evaluated the association between anemia and mortality in CHF. The quality of erythropoiesis is an intrinsic aspect of pathophysiology of anemia, and the ability of reticulocyte production would be one of the pivotal factors in the quality of erythropoiesis. However, it remains unclear whether reticulocyte production ability is associated with clinical outcomes in patients with CHF. Methods: We prospectively examined 1,274 symptomatic CHF patients (mean age 71.9±13.4 years, median LVEF 50 [IQR 36-63]%) in a multicenter registry (25 sites). The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum hematocrit. Patients were divided into four groups according to the presence of WHO defined anemia and the median value of RPI. The primary outcome was composite of all-cause death and hospitalization for worsening HF. Results: During a median follow-up period of 427 (IQR 273-642) days, the primary outcome occurred in 222 (17%) patients. The group with anemia and high RPI (≥0.982, the median) showed the highest incidence of the primary outcome among the groups ( P &lt; 0.001) (Figure A). In an anemic subgroup (n = 611), higher RPI was independently associated with increased adverse events (HR 1.67, 95% CI 1.31-2.13) adjusted for age, sex, estimated glomerular filtration rate, NT-pro BNP, hemoglobin, serum sodium and iron parameters. In this subgroup, erythrocyte counts were not significantly increased in patients with higher RPI compared to lower RPI (Figure B). Moreover, there were no significant differences on transferrin saturation and serum iron between the groups (Figure B). Conclusions: Higher reticulocyte production ability, which might reflect the impaired process of erythropoiesis, was associated with worse clinical outcomes in patients with CHF, especially with anemia.
Abstract 17120: ARO-ANG3, an Investigational RNAi Therapeutic, Silences the Expression of ANGPTL3 and Decreases Atherogenic Lipoproteins in Patients With Mixed Dyslipidemia: ARCHES-2 Study Results
Authors: Gerald F Watts, Daniel Gaudet, DARIO ALTAMIRANO, Robert Hegele, Christie M Ballantyne, Stephen Nicholls, Ting Chang, Sudar Alagarsamy, Ran Fu, Javier San Martin, Robert S Rosenson
Journal: Circulation (2023)

Background: Angiopoietin-like protein 3 (ANGPTL3) regulates lipoprotein metabolism by inhibiting lipoprotein and endothelial lipases. ANGPTL3 loss-of-function carriers have decreased circulating triglycerides (TGs), LDL-C, and HDL-C, and a lower risk of atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an investigational RNAi therapeutic designed to inhibit hepatic ANGPTL3 expression and reduce atherogenic lipoproteins. Aim: We report end-of-study results (data cutoff 09 December 2022) from ARCHES-2, a Phase 2b double-blind, placebo (pbo)-controlled study (NCT04832971) to evaluate the safety and efficacy of ARO-ANG3 in adults with mixed dyslipidemia (MD). Methods: Patients with fasting TGs 150-499 mg/dL and LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL were randomized to receive 50 mg, 100 mg or 200 mg ARO-ANG3 or pbo by subcutaneous injections on Day 1 and Week 12. Patients were on a stable diet and optimal lipid-lowering therapies. The primary endpoint was the percent change in TGs from baseline at Week 24. Liver fat was assessed at baseline and Week 24 in a subset of patients with hepatic steatosis. Mixed models repeated measures was used for statistical analyses. Results: At Week 24, ARO-ANG3 decreased ANGPTL3 (up to 77%), TGs (up to 56%), remnant cholesterol (up to 56%), and apolipoprotein B (apoB) (up to 20%). Other lipoproteins including LDL-C, non-HDL-C, lipoprotein(a) and HDL-C were also decreased. Liver fat decreased similarly in ARO-ANG3 and pbo groups. TEAEs were consistent with those expected in this patient population and with associated underlying comorbidities. Conclusions: ARCHES-2 data demonstrate ARO-ANG3 efficacy by significantly lowering ANGPTL3 and atherogenic triglyceride-rich lipoproteins (TRLs), LDL and total apoB in patients with MD. The favorable changes in serum lipids and lipoproteins and safety profile support the potential of ARO-ANG3 to treat residual ASCVD risk in patients with elevated TRLs not at LDL-C goal.
Abstract 13699: Comparing Patency Benefits of Pulmonary Stent Implantation and Balloon Angioplasty in Pulmonary Vein Stenosis: A Systematic Review and Meta-Analysis
Authors: Izza Batool, Muhammad Khuzzaim Khan, Muhammad Zohaib, Fatima Siddiqui, Muhammad Talal Ashraf, Ibrahim Ahmed Khan, Shreeja Shah, Hussam Al Hennawi, Bruce Klugherz
Journal: Circulation (2023)

Introduction: Pulmonary vein stenosis (PVS) may arise from various conditions and result in significant morbidity and mortality. Transcatheter approaches, including pulmonary stent implantation (PSI) and pulmonary balloon angioplasty (PBA) are associated with restenosis risks. We conducted a meta-analysis comparing PSI and PBA to understand restenosis risk and complications rate. Methods: We conducted a comprehensive search of PubMed, Google Scholar, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception until May 2023. A total of 1233 studies were screened, and 11 studies were included in our analysis. Our primary outcomes of interest were the risk of restenosis requiring reintervention, 5-year freedom from restenosis, and the risk of procedure-related complications. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a random-effects model and performed a meta-regression analysis. Results: We included a total of eleven observational studies in our meta-analysis, comprising 780 patients with PVS, 335 of whom underwent PBA and 445 underwent PSI. Our analysis showed that PSI was associated with a lower risk of restenosis requiring reintervention compared to PBA (OR 0.34, 95% CI 0.13, 0.87, P= 0.02). PSI was also associated with a significantly higher 5-year freedom from restenosis (OR 4.42, 95% CI 1.11, 17.62, P= 0.04) than PBA. There was no significant difference in the risk of procedure-related complications between PSI and PBA. Our meta-regression analysis revealed that age of patient and stent size did not significantly affect the risk of restenosis requiring intervention. Conclusions: PSI offers superior patency benefits compared to PBA for PVS. PSI was associated with a lower risk of restenosis requiring reintervention and a higher 5-year freedom from restenosis. Bases on these findings, PSI is the preferred strategy for the treatment of pulmonary vein stenosis.
Abstract 16802: Disparities in the Prevalence of Atrial Fibrillation and Associated Risk Characteristics Among Black and White Acute Ischemic Stroke Patients Treated With Alteplase
Authors: Udaya Tantry, Amit Rout, Joan Cutler, Kevin Bliden, Sanchit Duhan, Naval Walia, Sahib Singh, Swecha Goel, Paul Gurbel, William W Ashley
Journal: Circulation (2023)

Introduction: Earlier studies addressing racial disparity in patients with acute ischemic stroke (AIS) and atrial fibrillation included significantly lower percentage of blacks. Demographics and post-intervention risk among white vs. black patients with AIS and AF have not been reported in a community hospital setup. Methods: In this retrospective analysis, baseline demographics, procedural characteristics and one-year clinical outcomes were collected from hospital database and compared between blacks and whites who are admitted with AIS and treated with alteplase. Results: 228 and 274 black patients with AIS admitted to our hospital during 2016 to 2021 were included in the analysis. Blacks compared to whites were younger (67 ±13 vs. 74 ± 14 years) and had lower prevalence of cardioembolism (49% vs. 61%), atrial fibrillation (10% vs. 34%), coronary artery disease (17% vs. 26%), prior coronary artery disease or myocardial infarction (17% vs. 26%), depression (16% vs. 25%), dyslipidemia (53% vs. 65%), ischemic risk at admission (6.1 ± 3.6 vs. 8.2 ± 3.8), and NIHSS-obtained (11±11 vs. 14±13), but higher prevalence of small vessel disease (15% vs. 7.9%), cryptogenic stroke (20% vs. 13%), diabetes (39% vs. 25%), smokers (26% vs. 14%), drug/alcohol abuse (21% vs. 9%), prior stroke (24% vs.15%) and one year recurrent ischemic stroke (4.7 % vs. 1.3%) (p&lt;0.05 for all comparisons). Among patients with AF, blacks were of similar age compared to whites (75±13 vs. 79±14 years) and similar prevalence of cardioembolism (99% and 96%), prior myocardial infarction/coronary artery disease (26% vs. 30%) and obesity (59% vs. 48%, p=ns for all), but higher prevalence of prior stroke (48% vs. 20%), diabetes (41% vs. 22%), renal insufficiency 30% vs. 18%) and recurrent ischemic stroke (7.4% vs. 1.3%, p&lt;0.05 for all). Conclusions: Blacks patients with AIS exhibit distinct demographics and higher prevalence of recurrent ischemic events compared to whites. Despite lower prevalence, blacks with AIS have higher prevalence of comorbidities and recurrent stroke events in the presence of AF. These data provide springboard for ongoing biomarker studies at our hospital to understand the racial disparity in the underlying pathophysiology of stroke and associated outcomes in blacks.
Abstract 11918: Simultaneous Presentation of Pyogenic Pericarditis, Coronavirus Infection, and Endocarditis: A Challenging Triad in a Single Patient
Authors: Bradley Casey, Amol A Bahekar, Divyang Patel, Manoj Bhandari, Amudhan Jyothidasan, Raviteja Guddeti, Usman Younus, Alejandro Chapa-Rodriguez
Journal: Circulation (2023)

Background: Pyogenic pericarditis is a rapidly progressive infection with high mortality near 100%. In the present antibiotic age, bacterial pericarditis is an uncommon cause of acute pericarditis. The reported incidence of pyogenic pericarditis is less than 1% of all pericarditis cases. Case: 54 year-old male patient that presented with complaints of generalized weakness, fatigue, and fever. He was diagnosed with Coronavirus 229E by PCR. He was in respiratory distress, and CT chest showed concern for large pericardial effusion. Transthoracic echocardiogram showed large pericardial effusion (Image) without tamponade effect. Patient decompensated overnight and bedside point of care ultrasound overnight showed concern for tamponade effect. Pericardial window was performed and 800 ml thick purulent drainage evacuated. While in the ICU patient underwent transesophageal echocardiogram that showed Small hyper-mobile echo-density on the aortic valve concerning for endocarditis (image). Patient also had Type 1 Bicuspid aortic valve with heavily calcified raphe. Cultures on the pericardial effusion grew methicillin sensitive Staphylococcus Aureus. Patient will need 6 weeks of IV antibiotics and aortic valve replacement. Infectious disease recommended lifelong suppression therapy for MSSA. Decision-making: It is not uncommon for bacterial endocarditis and viruses to cause pericardial effusions. It is uncommon for a patient to have bacterial endocarditis, Coronavirus, and be diagnosed with pyogenic pericardial effusion. Cardiac tamponade is a clinical emergency, and evacuation of pericardial fluid to assist reduce the pressure surrounding the heart is used to treat cardiac tamponade. Conclusion: Here we present a case to our knowledge that has never been described before. This is a case of a patient that had infective endocarditis with confirmed Coronavirus that resulted in a pyogenic pericardial effusion.