tbuckley/cabot-search huggingface dataset:
Abstract 4146624: Computational Fluid Dynamics-Based Investigation and Development of an Axial-Flow Ventricular Assist Device Incorporating a Toroidal Blade Geometry for Improved Hemodynamics
Authors: Mohammed Usmaan Siddiqi, Pramod Bonde
Journal: Circulation (2024)

Introduction: Ventricular assist devices (VADs) present great promise as both bridge-to-transplant and destination therapies for patients with end-stage heart failure. However, complications – such as hemolysis, thrombosis, degradation of the von Willebrand factor, and gastrointestinal bleeding – stand in the way of their widespread application. High levels of wall shear stress resulting from poor hemodynamics within the bladed flow domain are primarily responsible. Computational fluid dynamics (CFD) software was used to model the hemodynamic performance of a novel VAD with a looped, toroidal blade design intended to reduce secondary flow effects at the blade tip – and provide detailed insight into the internal flow structures, leading to the shear stress levels within. Research Questions: Does the elimination of the open blade tip suppress tip recirculation and improve hemodynamics? What are the implications for wall shear stress in such a device, and how can we optimize the geometry as to improve pump performance, while minimizing shear stress? Methods: The toroidal impeller geometry file was imported into a computer aided design (CAD) software, and the generic scanned design file (STL) was converted to a 3D CAD surface model, from which the flow domain was subsequently extracted. The model was exported to a CFD software, and simulations were subsequently run to assess pump performance and impeller hemodynamics with respect to the wall shear stress parameter. Results: The VAD achieved an integrated pressure output equivalent to 108.84mmHg at the preliminary target flow rate of 0.5kg/s. The pressure is in the ideal range for supporting left ventricular pumping function. The efficiency of the VAD was calculated to be about 27%, which is reasonable for a VAD micromachine. There were regions of shear stress shown to be above the hemolytic threshold of 400 Pa, however. Conclusions: This toroidal impeller shows promise, which can be harnessed by applying heuristic, aerodynamic design methods to improve its hemodynamics. That is, further analysis, tuning, and optimization of the blade are necessary to enhance the operating efficiency of the VAD and minimize shear stress levels – specifically, optimization of the blade geometry for more balanced work distribution and reducing profile losses, as well as optimizing the size envelope of the device, currently 25mm in diameter.
Abstract 4146562: Diagnosis of Left Ventricular Diastolic Dysfunction using Deep Learning on electrocardiograms
Authors: Samantha Shetty, Joshua Lampert, Joy Jiang, Girish Nadkarni, Akhil Vaid
Journal: Circulation (2024)

Left Ventricular Diastolic Dysfunction (LVDD) is implicated in conditions with abnormal LV filling and reduced LV distension and relaxation. Classified into grades I to IV, LVDD can be progressive particularly when its underlying cause is not appropriately treated. The prevalence of LVDD varies greatly (10-35%) in the elderly population, likely in the setting of varying inclusion criteria, LVDD grading and definitions. Specifically, LVDD Grade II/III is associated with a higher mortality risk and has been shown to predict major adverse cardiac events including myocardial infarction, heart failure, and all-cause mortality. Echocardiography (echo) is used to quantify LVDD and its severity. Given its dynamic nature, identifying LVDD and its progression across other diagnostic modalities is vital. One such modality is the electrocardiogram (ECG). Although ECGs are widely accepted for the identification of abnormalities in cardiac conduction, pathology, and structure, some ECG findings may go undetected by human interpreters. Applying machine learning techniques to ECG for detection of LVDD may help address this need. In this study, we used rule-based Natural Language Processing (NLP) on echo reports to extract cardiologist-confirmed annotations for the presence and grading of LVDD. The NLP pipeline labelled reports as having no LVDD, indeterminate LVDD, or LVDD of grades I, II, or III. These labels were paired to ECG data collected within 7 days of the echo. ECGs paired with an echo of LVDD Grade II were considered cases and were paired to controls matched based on age, sex and race. Patients were excluded if their ECG diagnostic codes indicated conduction abnormalities, concurrent ischemia, and prior intervention. We trained a ConvNeXt Large model capable of processing images of up to 512x512 pixels over 25 epochs against a patient aware 80% training and 20% testing split. We collected 121,161 ECGs from 27,760 patients with an outcome prevalence of 31.4%. Our model detected patients with LVDD Grade II/III with AUROC of 0.87 (95% CI 0.86-0.87) and AUPRC of 0.82 (95% CI 0.81-0.83) (Figure 1). Saliency heatmaps showed regions around the QRS complex as more important for diagnosis of LVDD (Figure 2). Our study demonstrates how machine learning can augment clinical practice. Specifically, it may prove to be a useful screening tool for patients at risk of worsening cardiac disease, resource limited areas, and primary care settings in which ECG is readily available.
Abstract 4146621: Pulmonary Vascular Resistance Distribution in Pulmonary Hypertension Associated with Left Heart Disease
Authors: Zongye Cai, Kazunori Omote, Atsushi Tada, Ahmed Fayyaz, Yogesh Reddy, Katlyn Koepp, Andrew Rosenbaum, Atta Behfar, Robert Frantz, Margaret Redfield, Barry Borlaug
Journal: Circulation (2024)

Background: Pulmonary vascular resistance (PVR) is commonly considered to reflect opposition to lung blood flow caused by the arteries (PVRa), but downstream venous resistance (PVRv) may also contribute to pulmonary hypertension (PH) associated with left heart diseases (PH-LHD). In patients referred for right heart catheterization, we investigated PVR distribution and its pathophysiologic implications in PH-LHD and other forms of PH. Methods: Patients with PH-LHD (n=292), pulmonary veno-occlusive disease (PVOD, n=10), chronic thromboembolic PH (CTEPH, n=36) and controls without PH (Ctrl, n=28) were included. Pulmonary capillary pressure (Pc) was calculated using the pulmonary artery occlusion technique. PVR was partitioned into PVRa ((mPAP-Pc)/CO) and PVRv ((Pc-PAWP)/CO) with each expressed as % of PVR. PH-LHD was divided into isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). Further, PH-LHD was categorized as heart failure with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF&lt;50%) ejection fraction or left valvular heart disease (L-VHD). In subsets, functional tests (n=71-81) and histological pulmonary venous (PV) remodeling (autopsy, n=15) were performed to investigate correlations with PVR distribution. Results: PVR distribution showed an arterial predominance in Ctrl and CTEPH, and increasing venous contribution in PH-LHD (both IpcPH and CpcPH) and PVOD (Figure A-F). In PH-LHD, patients with HFpEF had proportionately greater venous contribution to PVR than HFrEF and L-VHD (Figure G-I), though not to the extent observed in PVOD. In subsets, PVRv was more strongly correlated with E/e’, extravascular lung water estimated by sonographic B-lines, arterial PO 2 , pulmonary dead space fraction (VD/VT), DLCO, and, among the autopsy series, PV intimal thickness as compared to PVRa (Figure J-O). Conclusions: Pulmonary venous contributions to PVR are amplified in patients with PH-LHD, which is correlated with greater lung congestion, ventilatory and gas exchange abnormalities, and histological venous remodeling. Further study is required to determine the molecular mechanism and novel therapeutics of pulmonary venous disease in PH-LHD.
Abstract 4146613: Dual Trajectories of Allopurinol and Colchicine Use and Cardiovascular Outcomes among Older Adults
Authors: Earl Morris, Jenny Lo-CIganic, Mike Daniels, Richard Segal, Scott Vouri, Steven Smith
Journal: Circulation (2024)

Background: Several anti-inflammatory and urate-lowering drugs commonly used in gout have shown promise in reducing cardiovascular risk. However, there remains controversy regarding the benefits of concomitant allopurinol and colchicine in cardiovascular risk prevention, and many previous studies have failed to account for time-varying dose and duration of use for both medications. Thus, we aimed to 1) examine dual trajectories of allopurinol-colchicine use and 2) evaluate risk of major adverse cardiovascular events (MACE) according to trajectories. Methods: Using 2011-2020 Medicare claims, we identified new users of allopurinol. We defined the date of first allopurinol fill as the index date and required continuous enrollment in Medicare Parts A. B, and D for 12 months before and after index date Then, we used group-based multi-trajectory modeling to identify allopurinol and colchicine use patterns by calculating average daily dose for each medication separately during each 2-week period during the first 12 months of allopurinol use. We then constructed inverse probability of treatment weighted Cox survival models to compare time-to-incident MACE across trajectories. Results: We identified 59,429 beneficiaries (mean age: 73.9; 82.6% non-Hispanic white) and ten unique trajectories including: six trajectories with no colchicine use (Trajectory A-F) and four trajectories with colchicine use (Trajectory G-J). Compared to Trajectory A (rapidly decreasing allopurinol - no colchicine), we observed a lower risk for MACE among Trajectories E (~200 mg allopurinol - no colchicine; aHR: 0.89 [95% CI: 0.87-0.92), F (~300 mg allopurinol - no colchicine; aHR: 0.91 [95% CI: 0.89-0.94]), I (~100 mg allopurinol - ~1.2 mg colchine [stable]; aHR: 0.96 [95% CI: 0.93-0.99]), and J (~300 mg allopurinol - gradually decreasing colchicine; aHR: 0.88 [95% CI: 0.85-0.91]). Conclusions: These findings suggest that older adults may benefit from interventions aimed at optimizing dose and duration of allopurinol and colchcine when initiating allopurinol among older adults and further support the need for additional research on the role of concomitant allopurinol and colchicine in cardiovascular risk prevention.
Abstract 4146586: NT-proBNP: A Potential Diagnostic Tool for Left Ventricular Hypertrophy in Patients with Chronic Kidney Disease in a Tertiary Hospital In Sub-Saharan Africa
Authors: Sena Penda, Anastase DZUDIE, Hermine Fouda, Romain Ebene, Marie Patrice Halle
Journal: Circulation (2024)

Introduction: Left ventricular hypertrophy (LVH) is a prognostic marker for cardiovascular events in patients with chronic kidney disease (CKD). Detecting LVH is a desirable goal in the management of CKD patients, but ECG has a limited performance and echocardiography is not always available nor is it cost-effective. NT-proBNP is a biomarker released in the setting of LVH, easily measurable but has been shown to also increase with declining kidney function. We aimed to assess the diagnostic value of NT-proBNP for LVH in CKD patients. Research Question: What is the diagnostic utility of NT-proBNP for left ventricular hypertrophy in CKD patients without kidney replacement therapy at the Douala General Hospital, Cameroon, Africa? Material and Methods: We conducted a cross-sectional analytical study at the Douala General Hospital, Cameroon between January and May 2022; 57 patients with CKD stage 2-5 without kidney replacement therapy were matched to 52 healthy control patients by age and gender. Both groups underwent NT-proBNP measurement using enzyme-linked fluorescence with Vidas, Biomerieux® equipment and a transthoracic echocardiography. Left ventricular mass index (LVMI) was assessed in accordance with American Society of Echocardiography guidelines. The correlation between LVMI and NT-proBNP was assessed, the specificity, sensitivity, negative and positive predictive values were calculated. Results: Overall we included 109 patients in our study. Median (IQR) age of CKD patients was 64 (51-70) years and 41 (72%) of CKD patients were male. In CKD patients, median NT-proBNP of 222 pg/ml (118 – 737) was significantly higher than in non-CKD patients, 29 pg/ml (19.5 – 53), p&lt;0.001. Median NT-proBNP increased with CKD stage (p=0.006). In CKD patients left ventricular mass index (LVMI) and LVH frequency increased across NT-proBNP quartiles, p=0.015 and 0.031 respectively. LVMI correlated positively with NT-proBNP (r=0.36, p=0.006) in CKD patients. At a cut-off of 483.5 pg/ml, NT-proBNP area under the curve was 0.75 (0.59 – 0.91) 95 CI, with a specificity of 83%, sensitivity of 75%, positive predictive value of 63% and negative predictive value of 90% for LVH. Conclusion: NT-proBNP is moderately sensitive and highly specific for diagnosing LVH in patients with CKD. NT-proBNP may be used for LVH diagnosis, further studies are warranted to confirm its contribution for cardiovascular risk stratification of patients with CKD.
Abstract 4146618: Differential Impact of Left Atrial Volume on Post-Ablation Recurrence Rates in Patients with Normal and Reduced Left Atrial Ejection Fraction: A DECAAF II Subanalysis
Authors: Mayana Bsoul, Yingshuo Liu, Ala' Assaf, ghassan bidaoui, Yishi Jia, Hadi Younes, Han Feng, Mario Mekhael, Francisco Tirado Polo, Chanho Lim, Yanpei Hui, Abboud Hassan, Swati Rao, Amitabh Pandey, Omar Kreidieh, eoin donnellan, Nassir Marrouche
Journal: Circulation (2024)

Background: The left atrial volume (LAV) has been known to be positively correlated with the atrial fibrillation (AF) recurrence rates after catheter ablation (CA) but negatively correlated with the left ventricular ejection fraction (LVEF). We hypothesized that LAV plays different roles for patients with normal LVEF (LVEF ≥ 50%) and those with lower LVEF (LVEF &lt; 50%). Method: Out of 843 patients from the DECAAF II trial, 674 patients with baseline LAV and LVEF data were included. Among these, 506 patients were characterized as having normal LVEF, while 168 patients had lower LVEF. For each group, the effect of LAV was studied against the AF recurrence through the Cox model, adjusting for age, sex, baseline LA fibrosis, and comorbidities, including coronary artery disease (CAD), hypertension (HTN), congestive heart failure (CHF), diabetes (DM), and hyperlipidemia (HLD). Patients were further divided into high and low LAV groups and compared performance after CA through the Kaplan-Meier curves and log-rank tests. Result: From Cox models, in the high LVEF group, LAV was identified as a significant predictor of the AF recurrence, with a hazard ratio (HR) of 1.009 (95% CI: 1.006-1.013, p &lt; 0.001) for each unit of increase (Table 1a). In the low LVEF group, LAV was not associated with AF recurrence (Table 1b). As in Figure 1, among lower LVEF patients, high LAV and low LAV provide similar AF recurrence rates. However, low LAV patients with normal LVEF have the lowest AF recurrence rate, while high LAV and normal LVEF patients have the highest AF recurrence rates after CA (p &lt; 0.001). Conclusion: The study found that baseline left atrial volume (LAV) is a strong predictor of AF recurrence after CA for patients with normal LVEF but not for patients with lower LVEF. Patients with large LAV and normal LVEF have even worse outcomes compared to those with large LAV and lower LVEF.
Abstract 4146553: Efficacy and Safety of Catheter Ablation in Patients with Hematologic Malignancies
Authors: Ishan Paranjpe, Ekanath Rangan, Sanjiv Narayan, Tina Baykaner, Muhammad Fazal
Journal: Circulation (2024)

Introduction: Patients with cancer have an increased risk for arrhythmias. Patients with hematologic malignancies face unique challenges in medical management of arrhythmias including increased bleeding risk limiting the use of anticoagulation therapies, increased clotting risk due to malignancy leading to a higher risk of stroke in the setting of atrial arrhythmias and lastly drug-drug interactions with chemotherapy agents limiting medical treatment options of arrhythmias. Safety and efficacy of catheter ablation in patients with hematologic malignancies have not previously been assessed. Hypothesis: We hypothesized that catheter ablation in patients with hematologic malignancies is safe, with reasonable acute and long term outcomes. Methods: We performed a retrospective analysis of consecutive patients with hematologic malignancies who underwent catheter ablation of AF, documenting procedural safety, acute and long term outcomes. Results: We identified 33 patients (n=21 with chronic lymphocytic leukemia, n=3 with chronic myeloid leukemia, n=4 with Waldenstrom's Macroglobulinemia, n=5 other) who underwent catheter ablation for arrhythmias after oncologic diagnosis between 2013-2024. Mean left-ventricular systolic ejection fraction was 57 ± 10%. Mean indexed left-atrial volume was 43±17 ml/m2. 11 (33%) patients underwent AF ablation alone, and 12 (36%) patients underwent AF and AFL ablation. 7 (21%) patients underwent typical AFL ablation with a cavotricuspid isthmus ablation alone. 5 (15%) patients underwent other SVT ablations (AVNRT, AT). 1 (3%) patient had pericardial effusion requiring pericardiocentesis. Over a mean follow up of 26 ± 22 months from catheter ablation, 12 (36%) patients had their oncologic therapy held due to arrhythmias. Out of the 23 patients that underwent AF ablation, 10 (43%) had AF recurrence at 2-year follow up. Of the patients who had AFL ablation, 2 (11%) had recurrent AFL at 2 year follow up. No recurrences were noted in the SVT ablation group. 17 (51%) patients were treated with tyrosine kinase inhibitors (TKI) which have been associated with incident AF, and 13 (39%) were maintained on TKIs at the time of ablation. Conclusion: Catheter ablation can be a safe and effective strategy for management of arrhythmias in patients with hematologic malignancies, with outcomes similar to the general population.
Abstract 4146605: A Non-odorant Olfactory Receptor Ligand Depolymerizes the Platelet Actin Cytoskeleton to Prevent Thrombosis
Authors: Anu Aggarwal, Nancy Wang, Vara Prasad Josyula, Moua Yang, Shim Young, Quinn Kennedy, Reina Samuel, Naseer Sangwan, Suman Guntupalli, Matthew Godwin, MAriya Ali, Courtney Jennings, Bhairavi Rajasekar, Alliefair Scalise, Shaun Stauffer, Keith McCrae, Thomas McIntyre, Scott Cameron
Journal: Circulation (2024)

Background: Despite antiplatelet therapy use, some patients have residual thrombotic risks due to High residual platelet reactivity (HRPR). We identified ectopic expression of Olfactory Receptor (OR) 2L13, a G protein-coupled receptor, in human platelets that suppresses platelet reactivity when activated. Our goal was to identify agonists in a high throughput screen for OR2L13 as an alternative strategy to suppress HRPR. Methods: Using an OR2L13 reporter cell line, 8K bioactive compounds were screened. Lead compounds were validated, and orthogonally tested for antiplatelet effects by Light Transmission Aggregometry (LTA) and Flow cytometry. Using murine models, the impact of OR2L13 agonists was determined by evaluating thrombosis and hemostasis. Lastly, the impact of a lead OR2L13 agonist on HRPR in patients with coronary artery disease (CAD) and peripheral artery disease (PAD) was determined. Biased and unbiased platelet phospho-proteomic profiling examined the OR2L13 signaling pathway. Results: 169 molecular hits were identified exceeding the 25% threshold, of which 6 ligands (CCF0054500, CCF0054432, CCF0053070, CCF0052249, CCF0051970 and CCF0058399) were persistently specific for OR2L13. Only CCF0054500 suppressed platelet aggregation and α-granule exocytosis through P2Y 12, PAR1, TP and GPVI receptors suggesting a downstream common mediator. In a murine cremaster arterial injury model, platelet accumulation at the injury site was reduced by 88.9% by CCF0054500 than vehicle (P&lt;0.0003) without altering fibrin generation. CCF0054500 had no impact on hemostasis in mice (tail bleeding assay). CCF0054500 inhibited HRPR through P2Y 12, PAR1, TP and GPVI in patients with CAD and PAD, even when taking other anti-platelet agents. Phospho-proteomics revealed CCF0054500 phosphorylates heat shock protein 27 (HSP27) which depolymerizes platelet actin cytoskeleton that we further validated by clot retraction assay (CCF0054500 70.6 area vs. 5.2 area vehicle. P&lt;0.0001), and this protective effect is reversed by an HSP27 inhibitor, area 3.56, P&lt;0.0001) Conclusion: We identified the first non-olfactory ligand therapeutic that is bioavailable to engage a platelet OR and inhibit platelet activation and thrombosis via HSP27-mediated cytoskeleton rearrangement. Furthermore, CCF0054500 suppresses platelet reactivity irrespective of the receptor-stimulated and circumvents the issue of HRPR in patients with established vascular disease.
Abstract 4146568: Hemodynamics of Acute Type B Aortic Dissections with 4D Flow MRI
Authors: Hannah Cebull, MUHAMMAD NAEEM, Minliang Liu, Hai Dong, Rudolph Gleason, John Elefteriades, Marina Piccinelli, John Oshinski, Bradley Leshnower
Journal: Circulation (2024)

Background: Type B aortic dissections (TBAD) develop from a tear in the intimal layer of the aorta, distal to the left subclavian artery. This tear separates the aorta into true (TL) and false lumens (FL), increasing the risk of dilation and rupture. In cases of surgical intervention, treatment for type B aortic dissections (TBAD) after the acute phase (&gt; 14 days) is associated with worse outcomes. Identification of those patients who will experience aortic growth could identify patients who would benefit from early intervention. This study aims to characterize blood flow for risk stratification using 4D flow MRI. We identified possible markers of interest: entry tear velocity, pulse wave velocity (PWV), and wall shear stress (WSS). Methods: TBAD patients (n = 7; 3 F) from Emory University Hospital were enrolled. We acquired 4D flow MRI during the acute phase (3T Prisma Fit; Siemens Healthcare). We created image-derived 3D models of lumens and measured velocity at entry tears. We estimated PWV using cross correlation of waveforms at perpendicular, evenly-spaced planes throughout the true lumens. We estimated WSS throughout the false lumen using a previously developed method (Matlab, Ansys EnSight). Growth rates were measured from at follow up computed tomography exams. Results: Three of the patients (P2, P3, P7) did not grow, while P1, P4-P6 grew 2.1, 1.2, 5.3, and 2 mm/month, respectively. Peak entry tear velocities were higher in growth (143 cm/s) than non-growth (90 cm/s) cases, with P5 having the highest (180 cm/s). Forward flow was greatest in the distal end of FL near visceral branches (growth = 17.1, non-growth = 11.0 ml/cycle). Pulse wave velocity measurements between growth and non-growth were similar (4.5 and 3.5 m/s). Both averages were lower than PWV for non-dissected aortas. Regions of high vorticity and WSS can be observed in the true and FL near tears, but no trends were found between growth and non-growth cases. Conclusion: We anticipate stronger trends as enrollment continues, but our preliminary findings demonstrate the first MRI study to enroll acute TBAD subjects and identify markers of interest. Sources of Funding: This study is supported by NIH R01HL155537 and the National Center for Advancing Translational Sciences under Award Numbers UL1TR002378 and TL1R002382.