tbuckley/cabot-search huggingface dataset:
Abstract 4139239: Validation of ICD-10-CM diagnosis codes for heart failure classification within an integrated US administrative claims and electronic medical record (EMR) database
Authors: John Barron, Malvika Venkataraman, Chia-Chen Teng, Shiva Vojjala, Thomas Power, Vincent Willey
Journal: Circulation (2024)

Objective: Identification of individuals with reduced or preserved ejection fraction heart failure (HFrEF/HFpEF) within claims data is typically based on ICD-10-CM diagnosis codes that use systolic and diastolic HF (SHF/DHF) nomenclature. The objective of this study was to assess the performance characteristics of using ICD-10-CM diagnostic codes from claims data for HFrEF and HFpEF classification relative to a reference standard using EF results or clinician documentation within an integrated claims/EMR database. Methods: EMR data from the Healthcare Integrated Research Database (HIRD®) were searched to identify patients with EF assessment between 01/01/2016 and 01/31/2023. HFrEF was defined as EF ≤ 40% or documented reduced EF, while HFpEF was defined as EF ≥ 50% or documented preserved/normal EF. The most recent EF assessment date or EMR entry date (if EF assessment date not available) was set as the index date. Claims submitted from 7 days to 6 months post index date were then reviewed to identify SHF and DHF diagnoses as well as comorbid conditions. Analyses were performed to determine sensitivity, specificity, and positive/negative predictive values (PPV/NPV), accuracy and F1 scores of the claims-based algorithm, with a sensitivity analysis performed using the subset of patients with a known EF assessment date available. Results: A total of 45,272 patients had EF assessment in the EMR data with either a SHF or DHF diagnoses in the claims data. Mean (SD) age was 71.7 (12.7) years, 51.2% were male. The most common comorbidities of interest included hypertension (89.5%), dyslipidemia (71.9%), atrial fibrillation (45.9%), type 2 diabetes (43.7%), and chronic kidney disease (39.6%). Counts by heart failure classification and algorithm performance characteristics are in Table 1. Sensitivity analyses for those with known EF assessment dates showed similar results. Conclusions: Overall performance of the claims-based algorithm was good to very good, although EF data integrated with claims data can improve HF classification. Future claims-based algorithm development could also incorporate treatments and comorbidities to improve performance.
Abstract 4140236: Development and Accuracy of Natural Language Processing-based Expression Matching to Identify and Classify Cardiomyopathy from Cardiovascular Magnetic Resonance Reports
Authors: Ujwala Shenoy, Lu Zhang, Mawra Jha, Raymond Kwong, Warren Manning, Reza Nezafat, Connie Tsao
Journal: Circulation (2024)

Background: Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive assessment of cardiomyopathy (CM); however, interpretation and CM classification from reports by clinicians and researchers at scale can be unclear and time-consuming. Research Question: Can a large language model accurately classify CM from clinical CMR reports, to improve diagnostic accuracy? Aims: To establish a novel natural language processing (NLP) model employing expression matching for CM detection and differentiation, and to compare its effectiveness with established methods. Methods: In our study, an unsupervised rule-based NLP model was developed on 3561 consecutive text impressions from clinical CMR reports at Beth Israel Deaconess Medical Center and compared against physician adjudicated diagnosis (gold-standard labels) of 6 broad groups of CM ( Figure 1 ). A semi-supervised biomedical bidirectional encoder representation from transformers (BioBERT) model was fine-tuned (80% training/20% validation) using NLP labels to improve generalization. The models’ performance was compared with comprehensive keyword search and ChatGPT4. We performed external validation by testing 1202 clinical CMR text impressions from Brigham and Women’s Hospital. Results: The stepwise classification of our NLP model is shown in Figure 2 . NLP and NLP-based BioBERT outperformed other methods ( Table 1 ). In external validation, the mean AUC of NLP (0.92) and NLP-based BioBERT (0.93) had better performance compared to keyword search (0.71) and ChatGPT4 (0.73). Conclusion: Our rule-based NLP and NLP-based BioBERT models accurately identify CM from CMR reports, enabling applications in widespread CMR report comprehension and large dataset research of cardiomyopathies.
Abstract 4138113: C-X-C Motif Chemokine Receptor 4-directed Molecular Imaging of Mediastinal Lymph Nodes after Acute Myocardial Infarction in Patients
Authors: Theresa Reiter, Aleksander Kosmala, Anna Lena Doerrler, Natalie Hasenauer, Nils Kraus, Sebastian Serfling, Philipp E. Hartrampf, Wolfgang R. Bauer, Ulrich Hofmann, Andreas Buck, Takahiro Higuchi, Rudolf A. Werner
Journal: Circulation (2024)

Purpose: After acute myocardial infarction (MI), lymphocytes play a pivotal role in the scar formation and remodeling of the remote myocardium. Activation of lymphocytes takes places in mediastinal lymph nodes (MLN). Therefore, imaging of MLN as a read-out of the adaptive immune response to MI may identify subjects at increased risk for cardiac functional decline. Methods: The on-going prospective study (NCT05519735) enrolls patients with acute ST-elevation MI followed by complete reperfusion and multimodal imaging with C-X-C motif chemokine receptor 4 (CXCR4)-directed PET/CT and cardiac MRI (CMR) as baseline imaging. Follow-up (FU) CMR scans are repeated after 6 and 12 months. The CMR scans are analyzed regarding LV function, myocardial and LGE mass. Tracer uptake (SUVpeak) in the myocardium and MLN (defined as LN with most intense uptake) are determined. Infarct/remote myocardial (IRR), MLN/Remote LN (LNR) ratios and the overall LNR (including uptake from all LN) are calculated. Association of uptake with the function CMR parameters is tested. Results: Currently, 41 patients (29 males, median age 59 yo) were enrolled in the study (6 months FU 27/41, 12 months FU 17/41). At baseline, the median CMR EF was 49% and improved with the FUs (6mo: 52.8%, 12 mo 53.2%). LGE mass was 30.3 g and declined to 13.8 g after 12 months (LGE/Myocardial 15.8%). SUV peak from infarcted myocardium and mediastinal LN were consistently &gt;1, indicating increased uptake relative to background. Changes of LVEF correlated with LNR (6 mo FU: %LVEF, r= - 0.48; P = 0.01, 12 mo FU: %LVEF, r= - 0.55; P = 0.02) and overall LNR (6 mo FU: %LVEF, r= - 0.52; P&lt; 0.01; 12 mo FU: %LVEF; r= - 0.61; P = 0.01), but not with IRR (P= 0.498). LNR was increased in subjects with decreased LVEF. In logistic regression analysis, increasing LNR and overall LNR were significantly associated with decreased LVEF at the 12 months FU (LNR OR 1.32 (95% CL: 1.06-1.81, p = 0.03), Overall LNR OR 1.36 (95 % CL: 1.09-1.92, p = 0.03)). Conclusion: CXCR4-directed imaging of MLN provides information on the extent of local and systemic tissue inflammation in patients after acute MI. Especially MLN CXCR4 uptake holds predictive potential for cardiac adverse remodelling during follow up (LVEF decline) and may be used to identify patients who benefit from a selective immune modulation after acute MI. Funding: German Research Foundation (453989101).
Abstract 4138936: Outcomes of Over 1,000 Heart Transplants Using Donation After Circulatory Death Donors in the United States
Authors: Krishna Bhandari, Jennie Kwon, Atsuko Uehara, Sophia Sitsis, Zachary Sollie, Chakradhari Inampudi, Anthony Carnicelli, Vishal N. Rao, Brian Houston, Ryan Tedford, Arman Kilic
Journal: Circulation (2024)

Introduction: Heart transplantation (HT) with donation after circulatory death (DCD) donors has been increasing exponentially since its resurgence in the US. The aim of this study was to evaluate national outcomes of DCD HT. Methods: Adult HT recipients from 2019-2023 were identified from the United Network Organ Sharing registry. Patients were categorized based on donor-type (donation after brain death [DBD] or DCD). Kaplan-Meier and multivariable Cox regression analyses were used for survival. A propensity-matched analysis was also performed. A further sub-analysis was conducted comparing outcomes of DCD HT using normothermic regional perfusion (NRP) versus direct procurement and perfusion (DPP). Results: Among 19,684 HTs identified, 14,122 DBD and 1,139 DCD were included. The number of DCD HT increased from 7 in 2019 to 534 in 2023. In unadjusted analysis, 30-day (97.1% vs 96.7%, p=0.46) and 1-year (91.2% vs 90.5%, p=0.59) survival were comparable between DBD vs. DCD donors, although 3-year survival was worse in DCD recipients (DBD 83.7% vs DCD 76.8%, p=0.05; DCD multivariable HR 1.25, 95% CI 1.02-1.54; p=0.03). Similar findings were observed in the propensity-matched analysis, where DCD recipients had worse 1- and 3-year survival, findings that were confirmed after risk-adjustment (Figure). In sub-analysis comparing NRP versus DPP, unadjusted survival was comparable at all time intervals although there was a trend towards improved survival with NRP at 3-years (NRP 85.7% vs DPP 74.4%, p=0.08; NRP multivariable HR 0.63, 95% CI 0.39-1.02; p=0.06). Conclusions: This represents the largest real-world series to date of DCD HT and associated outcomes. DCD HT has increased substantially in the past several years and now comprises 15% of all HT performed in the United States. Although early outcomes are comparable with DBD donors, mid-term survival was worse by use of DCD, warranting further research. Although not statistically significant, use of NRP technique when using DCD for HT may confer a survival benefit.
Abstract 4139469: Efficacy of Post-Procedure Voltage Mapping (PPVM) Guided Incremental Ablation Lesions in Improving 1-Year Success and Recurrence-Free Survival for Atrial Fibrillation Ablation
Authors: Hema Srikanth Vemulapalli, Juan Rodriguez-Riascos, Sumedh Iyengar, Shruti Iyengar, Padmapriya Muthu, Komandoor Srivathsan
Journal: Circulation (2024)

Introduction: Pulmonary Vein Isolation (PVI) has become the cornerstone during ablation of Atrial Fibrillation. The primary goal of the procedure is to prevent potential arrhythmogenic triggers from accessing the main left atrial substrate. However, incomplete fibrosis leading to PV reconnection has been identified as the primary reason for AF recurrence. It is unclear whether immediate voltage mapping and additional lesions delivered to areas of residual or recovered voltages will improve the outcome. This study evaluates the 1-year success and long-term recurrence-free survival in patients who underwent post-procedure voltage mapping (PPVM) to identify residual Low-Voltage Areas (LVAs) to guide the delivery of additional ablation lesions. Methods: We analyzed 588 patients who underwent PVI from 2015 to 2023. Of these, 243 had PPVM done to determine LVAs and guide additional ablation lesions. The control arm comprised 345 patients who underwent PVI by the same operators without PPVM. The primary endpoints were 1-year success and longer-term recurrence-free survival. Secondary endpoints were the incidence of complications and the prevalence of LVAs in patients who underwent PPVM. Results: Patients who underwent remapping were older than the control arm (68.3 vs 65.6 years, p = 0.005). There were no other significant differences in baseline characteristics between the two groups. At 1-year follow-up, the success rates were 79% in the treatment arm compared to 72% in the control arm (p = 0.038). Patients in the intervention arm had a recurrence-free survival rate of 65% and 54% at 2 and 4 years, respectively, compared to 62% and 43% in the control arm (p = 0.044). The prevalence of LVAs in the treatment arm was 56.8%. Additionally, complication rates were not increased in the remapping arm (3% vs 8%, p = 0.012). Conclusion: PPVM-guided incremental ablation lesions improve the 1-year success rate and recurrence-free survival at 2 and 4 years compared to traditional PVI without increasing complications due to additional lesion delivery.
Abstract 4139235: Colorectal Cancer Incidence in Heart Transplant Recipients: A Competing Risks Analysis
Authors: Amin Tajerian, Alan Abboud, Sharon Charles, Michael Clores, Marc Goldschmidt, Olga Aroniadis, Andreas Kalogeropoulos
Journal: Circulation (2024)

Background: Colorectal cancer (CRC) risk is elevated in solid organ transplant recipients. However, data on CRC risk in heart transplant (HT) patients are limited. Also, screening recommendations for CRC in the HT population, especially patients under age 45, are lacking. Previous studies have been constrained by single-center designs, outdated cohorts, and lack of competing mortality analysis. Objectives: We aimed to assess competing-risk incidence of post-HT CRC, with focus on the effect of age, to inform CRC screening recommendations. Methods: We identified patients ≥18 years old at the time of HT in the TriNetX Research Network, which encompasses healthcare records from over 80 systems in the US, using CPT codes for HT (33945) and combined lung-HT (33935). CRC was identified from ICD-10 CM codes (C18, C19&amp;C20). Because mortality is significantly higher than CRC risk in this population, we used the Fine and Gray competing-risks framework to estimate CRC incidence for the entire cohort and subgroups of interest. Results: We identified 4791 patients with HT or lung-HT between 1996 and 2024. After excluding 275 patients because of missing (N=266) or too short (N=9) follow-up, 4516 patients were included ( Table 1 ). After a median follow up of 3.6 years (25 th – 75 th percentile, 1.4 – 6.7), 48 patients developed CRC. The median time from HT to CRC was 4.5 years (0.7 – 8.0) and the median age at CRC was 65 (55 – 71). The cumulative incidence, adjusting for competing mortality, was 0.68% (95%CI: 0.45%, 1.0%) at 5 years and 1.7% (95%CI: 1.2%, 2.4%) at 10 years ( Figure 1 ), corresponding to an incidence rate of 170 cases per 100,000 patient-years, and did not differ between men and women (180 vs. 120; P=0.7). In comparison, all-cause mortality was 20% at 5 years and 38% at 10 years. Age at HT was not significantly associated with CRC risk (P=0.22); patients age &lt;45 at HT experienced similar risk as patients ≥45 ( Table 2 ). In comparison, the age-adjusted CRC rate in the US population for years 2016-2020 was 42 and 32 cases per 100,000 patient-years in men and women, respectively. Year of HT was not associated with CRC risk (P=0.69). Conclusion: In this cohort of HT recipients, the absolute CRC risk was lower compared to previous reports that did not account for the competing risk of death. However, rates of CRC were much higher compared to the general population and did not differ by age at HT, suggesting that all HT patients should be screened for CRC regardless of age.
Abstract 4139404: Post-Translational Regulation of Larp6 by IGF-1 Modulates Collagen Synthesis in Smooth Muscle Cells
Authors: Meng Zhang, Svitlana Danchuk, Sergiy Sukhanov, Patrice Delafontaine, Yusuke Higashi
Journal: Circulation (2024)

Introduction: Vascular smooth muscle cells (SMCs) play a crucial role in atherosclerosis, contributing to plaque stability by forming the main cellular component of the fibrous cap and synthesizing extracellular matrix. We previously showed that insulin-like growth factor-1 (IGF-1) increases expression of the collagen mRNA binding protein La ribonucleoprotein domain family member 6 (Larp6) and of collagen in atherosclerotic plaques. However, molecular mechanisms remain unclear. Hypothesis: We hypothesized that IGF-1 increases collagen synthesis via a post-translational regulation mechanism of Larp6. Methods: An SMC-specific Larp6 overexpression mouse model (SMC-Larp6) was generated using the Myh11 promoter. Entire aortas and aortic roots were isolated for plaque analysis. IGF-1 was injected in WT mice at a dosage of 1.5 mg/kg. For in vitro assays, human aortic SMCs were transduced with an adenoviral vector to overexpress Larp6 and treated with 50 ng/mL IGF-1 for 18 h. Results: SMC-Larp6 mice had no significant change in plaque collagen content. Additionally, IGF-1 increased Larp6 protein but not mRNA levels suggesting that IGF-1 likely regulated Larp6 via a post-transcriptional mechanism. Western blotting identified two major Larp6 bands at 67 kDa and 70 kDa. We observed a clear band shift from the lower to the upper band after IGF-1 treatment, with a concomitant increase in Procollagen I, suggesting that IGF-1 enhances Larp6's role in promoting collagen through post-translational modification. Mass spectrometry analysis revealed multiple phosphorylation sites on the LaM and LSA domains of Larp6, including S451, which is phosphorylated by the IGF-1/PI3K/AKT axis. We also observed this protein modification pattern in mouse aortic tissue lysates following IGF-1 injection. Conclusions: IGF-1 regulates Larp6 phosphorylation in SMC, thereby likely playing an important role in IGF-1 induced collagen synthesis. This study provides insight into molecular mechanisms underlying collagen production in SMCs and could inform therapeutic strategies for plaque stabilization.
Abstract 4139501: Transthoracic Transmitral Atrial Flow is Independently Associated with Ischemic Stroke Risk in Patients with Paroxysmal Atrial Fibrillation
Authors: Su-kiat Chua, Pang-Shuo Huang, Jien-jiun Chen, Fu-chun Chiu, Juey Jen Hwang, Chih-hsien Wang, Chia-Ti Tsai
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Prior studies have shown that reduced blood flow velocity in the left atrial appendage, measured by the invasive transesophageal echocardiography (TEE) procedure, is associated with higher stroke risk. However, TEE is an invasive procedure with inherent risks. In this study, we aimed to investigate whether transmitral atrial flow velocity (MVA) obtained through the non-invasive transthoracic echocardiography (TTE) technique could also predict the risk of stroke in patients with AF. Methods: We conducted a longitudinal cohort study of 10,150 patients with paroxysmal AF who underwent TTE to assess MVA. The patients were followed up from January 2010 to December 2021, with the primary outcome being hospitalization for ischemic stroke. Results: Over a mean follow-up of 4.26±3.52years, 2419 (23.8%) patients developed ischemic strokes (5.59% per 100 person-years). Patients with MVA &lt; 50 cm/s had a higher stroke incidence rate than those with MVA ≥ 50 cm/s (6.57% vs 5.47%, P&lt;0.001). On multivariable analysis adjusting for CHA 2 DS 2 -VASc score, MVA was independently associated with stroke incidence. Every 10 cm/s reduction in MVA velocity conferred 4% higher stroke risk (adjusted hazard ratio [HR] 0.96 [0.94-0.97], P&lt;0.001). AF patients with MVA &lt; 50 cm/s had a 39% increase in stroke risk compared to those with MVA ≥ 50 cm/s (adjusted HR 1.39 [1.22-1.58], P&lt;0.001). In patients with CHA 2 DS 2 -VASc score 0 or 1, the stroke incidence increased from 1.33 % to 2.28% when they had MVA &lt; 50 cm/s, which was similar to those with CHA 2 DS 2 -VASc score 2 points (2.51 %). Conclusions: Reduced transthoracic MVA independently predicts higher ischemic stroke rates in paroxysmal AF patients. MVA assessment easily enhances risk stratification and could help guide targeted stroke prevention therapies, especially in low-risk patients with CHA 2 DS 2 -VASc scores of 0 or 1.
Abstract 4140212: Cardiac Electrophysiologic Response to Single-dose AUX-001, a Once-Daily Extended-Release Nicorandil in Development for Chronic-stable Angina in Adult Healthy Volunteers under Fasting and Fed Conditions
Authors: Uwe Tigoer, Dawid Chabowski, Marlene Fonseca
Journal: Circulation (2024)

INTRODUCTION: Nicorandil, a dual mechanism anti-anginal used in Europe, Asia, and Australia for &gt;20 years acts as NO donor and K + ATP channel opener, providing balanced pre- and afterload vasodilation. Antianginal efficacy matches beta and calcium channel blockers, and long-acting nitrates but without tolerance build-up. Immediate release nicorandil (IR NIC) taken 2-3 times daily with 80% dose release in 45 min, requires high patient adherence. While EU labeling and trials highlight no proarrhythmogenicity lack of recent data remains along with prior reports of potential impact of IR NIC on EKG patterns. Once-daily extended-release nicorandil (ER-NIC) AUX-001 is being developed to improve compliance, symptom control, and QoL for chronic stable angina patients. ONJECTIVE: Examine ER NIC impact on EKG patterns before and after 2 sequential 24h single-dose exposures during fed and fasting status. METHODS: 12-lead EKG was recorded in 16 adult healthy volunteers at baseline. Peak systemic exposure of ER NIC was predicted at 6h post dose. Consequently, postdose EKG was scheduled at 6h after AUX-001 administration, with 24h monitoring. Variables included PR, ST, QT, and TP interval and P, QRS and T wave duration. QT interval was corrected using Bazett’s and Fridericia’s formula. Results: 12-lead EKGs were available on 16 fasting and 15 fed patients. None discontinued due to safety or tolerability. 13 EKGs at baseline on day 1, and 14 on day 8 showed non-clinically relevant abnormalities. No clinically relevant abnormalities were found at baseline or 6h postdose. Mean HR was 58±5.8 and 59±6.2 at baseline and 68±8.2 and 67±6.7 at 6h for fasting and fed. Mean QTc (Bazett) was 395±19 ms pre- and 400±18 ms 6h postdose under fasting and 395±14 and 399±16 ms under fed status. Mean PR interval was 170±22 ms pre- and 160±21 ms 6h post-dose fasting and 169±17 and 158±18 under fed status. CONCLUSION: Single dose AUX-001 caused near no QTc changes in healthy volunteers compared to baseline. 6h postdose PR intervals physiologically adjusted to changing HR, and stayed within normal range. Similar to IR NIC, AUX-001 had no discernable effect on EKG patterns during fasting or fed conditions. Findings highlight no relevant AUX-001 effect on electrophysiological safety providing additional safety information supporting development of ER NIC. Findings also confirm previous healthy volunteer trials with IR NIC highlighting no tendency promoting arrhythmia in normal, non-ischemic myocardium.