tbuckley/cabot-search huggingface dataset:
Abstract 4137726: A Deep Learning Digital Biomarker for Mitral Valve Prolapse using Echocardiogram Videos
Authors: Mostafa Al-Alusi, Emily Lau, Aeron Small, Christopher Reeder, Tal Shnitzer Dery, Carl Andrews, Shinwan Kany, Joel Ramo, Julian Haimovich, Shaan Khurshid, Danita Sanborn, Michael Picard, Jennifer Ho, Mahnaz Maddah, Patrick Ellinor
Journal: Circulation (2024)

Background: Mitral valve prolapse (MVP) has a prevalence of 2–3% and is a risk factor for heart failure and sudden death, but MVP diagnosis by transthoracic echocardiography (TTE) requires time and clinical expertise. We trained a deep learning model to classify MVP from TTE videos. Methods: DROID-MVP is a convolutional neural network trained to classify MVP using echocardiographer labels using 973,531 digital videos (parasternal long axis and apical views) from 45,657 studies performed in 15,728 cardiology patients at Massachusetts General Hospital. We validated DROID-MVP in 1,726 cardiology patients (4,869 studies) and 8,903 primary care patients (8,903 studies), and tested associations between predicted MVP score (range 0-1) and mitral regurgitation (MR) severity and left atrial (LA) anterior-posterior diameter in primary care patients with available measurements. Results: Of 15,728 patients (6,029 [38%] women; mean age at first TTE 61 ± 17 years) in the training set, 729 (4.6%) had at least 1 study with MVP. DROID-MVP identified MVP in both the cardiology (area under the receiver operating characteristic curve [AUC] 0.955 [95% confidence interval: 0.939-0.970]; average precision [AP] 0.716 [0.649-0.776]; prevalence 0.035) and primary care (AUC 0.966 [0.955-0.978]; AP 0.668 [0.601-0.730]; prevalence 0.022) test sets ( Figure 1 ). Discrimination persisted across strata of MR severity (AUC range 0.877-0.987). High (&gt;0.67) vs low (&lt;0.33) MVP score was associated with higher odds of moderate/severe MR (odds ratio 20.1 [12.2-33.4], p&lt;0.001) and higher LA diameter (2.7 [0.9-4.4] mm, p&lt;0.001; Figure 2 ), after adjusting for age, sex, height, and weight. Conclusions: A deep learning model identifies MVP from TTE videos with excellent discrimination and higher model predictions are associated with greater MR severity and LA size. Our work demonstrates how deep learning can automate MVP diagnosis and may serve as a digital biomarker of MVP-associated structural abnormalities.
Abstract 4134234: Association Between the Natriuretic Peptides-Cyclic Guanosine Monophosphate Cascade and Left Ventricular Reverse Remodeling After Acute Anterior Myocardial Infarction
Authors: Marina Arai, Yasuhide Asaumi, Satoshi Honda, Soshiro Ogata, Eri Kiyoshige, Hiroyuki Miura, Kazuhiro Nakao, Kota Murai, Takamasa Iwai, Kenichiro Sawada, Hideo Matama, Masashi Fujino, Shuichi Yoneda, Kensuke Takagi, Hiroyuki Takahama, Fumiyuki Otsuka, Yu Kataoka, Kunihiro Nishimura, Teruo Noguchi, Naoto Minamino, Satoshi Yasuda
Journal: Circulation (2024)

Background: Natriuretic peptides and their second messenger, cyclic guanosine monophosphate (cGMP), play a critical role in the pathogenesis of cardiovascular diseases by inhibiting the renin-aldosterone system, cardiac hypertrophy, and fibrosis. Recently developed chemiluminescent enzyme immunoassays for proBNP have enabled the estimation of mature BNP (emBNP) by calculating the difference between total BNP and proBNP. Research Questions: The role of cGMP in left ventricular remodeling after acute myocardial infarction (AMI) remains poorly understood. Aims: We aimed to investigate the relationship between the natriuretic peptide-cGMP cascade and left ventricular reverse remodeling (RR) in patients with anterior AMI. Methods: In a prospective 67 patients experiencing their first anterior AMI, plasma BNP fractions and cGMP levels were measured at immediate primary percutaneous coronary intervention (PPCI), 3 days, and 3 months post-AMI. Change in left ventricular end-systolic index (delta-LVESVI) was calculated as the difference between median 10 months and day 10 using cardiac magnetic resonance imaging. Patients were divided into RR and non-RR groups based on regression analysis to compute residuals representing the differences between each individual’s observed delta-LVESVI and delta-LVESVI adjusted by plasma pro-BNP concentration at immediate PPCI because of an inverse correlation between delta-LVESVI and plasma pro-BNP concentration at immediate PPCI (r=0.243, p=0.047). RR group (n=33) demonstrated below-median residual delta-LVESVI, while non-RR group (n=34) had above-median residual. Results: RR group exhibited significantly higher freedom from major adverse cerebral and cardiovascular events (MACCE) during a median of 8.1-year (Interquartile range: 6.7–8.8) follow-up (P=0.024) (Figure A) . Multivariable analysis identified logarithmic plasma pro-BNP, and emBNP at day 3 post-AMI, and plasma cGMP levels at immediate PPCI and day 3 post-AMI, as independent predictors of RR (P&lt;0.05) even after adjusting age, male, hypertension, and infarct size. (Figure B-D) . Conclusion: Early-phase activation of the natriuretic peptides-cGMP cascade may play a protective role in left ventricular remodeling in patients with anterior AMI.
Abstract 4137716: Development and Content Validation of the Heart Failure Symptom Management Motivation Questionnaire
Authors: Natany da Costa Ferreira Oberfrank, Wen Liu, Karen Dunn-Lopez
Journal: Circulation (2024)

Introduction: Adequate heart failure (HF) self-management is crucial for alleviating distressing symptoms. While disease knowledge is important, it is insufficient for sustained self-care. Patient motivation plays a key role in successful self-management interventions. However, tools assessing motivation for HF symptom self-management are lacking. Aims: To develop the Heart Failure Symptom Management Motivation (HF-SMM) questionnaire and assess its content validity with nurse experts. Methods: A cross-sectional study occurred in three phases from November 2022 to April 2024. Initially, we conducted a systematic review to identify motivation assessment instruments for cardiovascular self-care and assess their psychometric properties. We then designed the HF-SMM items based on existing tools, guidelines, and clinical expertise, focusing on four HF symptoms: anxiety, depression, edema, and fatigue. The questionnaire comprised three subscales: autonomous motivation, controlled motivation, and amotivation. Nurse experts with doctoral degrees and HF experience assessed 96 items about questionnaire clarity and relevance via Delphi rounds, using a 4-point Likert scale. Items with a content validity index (I-CVI) between .80 to 1.00 were deemed acceptable. The average I-CVI of all items resulted in the scale content validity index average (S-CVI/Ave) with a cutoff point of .90. Results: We invited ten experts, with nine participating. They had an average of 17.1 ± 10.7 years of HF clinical experience and 11.6 ± 7.4 years of research experience. In the initial Delphi round, items scored I-CVI ranging from .44 to 1.00 for anxiety, depression, and fatigue, and .66 to 1.00 for edema, resulting in an S-CVI/Ave of .81. After the first round, 54 items with I-CVI &gt;.80 were retained (56.2%), and 42 items were revised (43.8%). A second Delphi round, with 77.7% of the original experts, showed most items with excellent I-CVI scores (&gt; .80; 84; 87.5%), with only ten items needing clarity revisions (10.4%). The overall CVI of the questionnaire was excellent with a S-CVI/ Ave of .90 after two rounds of validation. Conclusions: The HF-SMM questionnaire demonstrates excellent content validity for assessing motivation in HF self-management. Future studies should incorporate cognitive interviews to understand better patient perceptions about the items.
Abstract 4137682: Genome wide association study for residualized apolipoprotein B elucidates its role in coronary artery disease risk
Authors: Selena Zhang, Satoshi Koyama, Sara Haidermota, Whitney Hornsby, Michael Honigberg, Patrick Ellinor, Pradeep Natarajan
Journal: Circulation (2024)

Background: Recent studies have shown apolipoprotein B (ApoB), the principle atherogenic lipoproteins, to have greater predictive ability for coronary artery disease (CAD) risk over standard lipid parameters. Moreover, discordantly high ApoB relative to Low-density lipoprotein cholesterol (LDLC) has repeatedly been associated with increased CAD risk. Aim: Given the strong genetic effects of ApoB and LDLC, we sought to characterize the discordance between ApoB and LDLC by genetics to obtain mechanistic insights into this emerging risk factor. Method: We derived residualized-ApoB regressing ApoB on LDLC in European-like populations (N = 383,500) in the UK Biobank. Using residualized-ApoB as an outcome, we explored clinical associations and conducted genome wide association study (GWAS). Result: Residualized-ApoB only modestly correlated with ApoB and LDLC (Spearman’s rho = 0.248 and -0.0079 respectively). We observed increased residualized-ApoB in males and individuals with lipid lowering therapy. Increased residualized-ApoB was associated with increased risk for CAD [Odds Ratio; 1.25 (95% Confidence interval 1.23-1.27)] independent from LDLC, ApoB, and Triglycerides. By GWAS, we observed significant heritability for residualized-ApoB [h 2 = 12.3 (SE 0.012)] and 195 significantly associated genetic loci ( P &lt; 5 × 10 -8 ). Only 59 of these lead variants were associated with ApoB or LDLC. We also found different effects in ApoB-related loci. For example, ApoB-increasing alleles at APOB (rs533617) and APOE (rs7412) loci increased residualized-ApoB but ApoB-increasing alleles at ABCG8 (rs4245791) and HAPLN4-TM6SF2 (rs150641967) loci decreased residualized-ApoB. Conclusions: Exploiting genetics, we determined significant heritability of residualized-ApoB which was partially correlated with ApoB/LDLC. We identified distinct effects of genetic variants on residualized-ApoB. Our results provide the clues for further precise understanding of regulatory mechanisms between ApoB and LDLC.
Abstract 4137559: Assessing Veterans’ Risk of Cardiovascular Disease by Gender Identity
Authors: Carl Streed, Kory Heier, John Oleary, Guneet Jasuja, Joseph Goulet, Meredith Duncan
Journal: Circulation (2024)

Background: Extant literature suggests that transgender and gender diverse (TGD) individuals experience a higher burden of CVD risk factors and psychosocial stressors than their cisgender (cis) peers. However, prior studies have been limited by self-reported outcomes or small samples. Aim: To determine whether TGD veterans have greater CVD (MI, ischemic stroke, cardiac revascularization) incidence than cis veterans using large, nationwide data. Methods: We used EHR data from the Veterans Healthcare Administration to identify veterans with &gt;2 outpatient encounters in fiscal years 2010-2019. Veterans’ gender identity was classified using natural language processing in combination with gender-affirming hormone therapy (GAHT) and a previously validated algorithm for identifying TGD individuals using ICD codes and VHA data. Of 1,105,082 veterans without prior CVD, 42,149 were classified as TGD. We examined sample characteristics by gender identity and used Cox regression to assess the association of gender identity with incident CVD. Results: TGD veterans’ mean age (years) was 46 (cis females=40; cis males=53). Cis females had the fewest CVD risk factors, followed by TGD veterans and cis males. Adjusting for age, race, and Hispanic ethnicity, TGD veterans had 1.49 [1.42-1.56] and 0.93 [0.90-0.97] times the risk of CVD compared to cis females and cis males, respectively. Upon additional adjustment for other CVD risk factors, renal function, alcohol use disorder, depression, anxiety, and sexual minority status, results remained statistically significant. Significance also held in sensitivity analyses which matched each TGD veteran to cis female and male veterans on age within 2 years. In analyses stratified by gender identity, trans feminine (HR [95% CI]: 1.26 [1.14-1.40]) and uncategorized TGD veterans (HR [95% CI]: 1.29 [1.22-1.37]) were at higher CVD risk than cis female veterans; trans masculine (HR [95% CI]: 0.85 [0.77-0.93]) and trans feminine veterans (HR [95% CI]: 0.90 [0.82-0.99]) were at lower CVD risk than cis male veterans. Among TGD veterans, GAHT receipt was associated with an 11% decrease in CVD risk. Conclusion: TGD veterans’, particularly trans feminine and uncategorized TGD veterans’, CVD risk was greater than that of cis females. Contrary to prior findings, GAHT was associated with decreased CVD risk. These results invite further study into the mechanisms by which GAHT and other factors impact CV health across and within gender identities.
Abstract 4137609: Lentiviral shRNA Library Screen Using Human Pluripotent Stem Cell-derived Cardiomyocytes Identified Mediators of Protection via MAP4K4 Inhibition against Doxorubicin-induced Cardiotoxicity
Authors: Yue Qin, Zuzanna Jablonska, Ursula Herbort-Brand, Momina Yazdani, Ranney Yi, Michael Schneider, Michela Noseda
Journal: Circulation (2024)

Background: Doxorubicin (Dox) is a common component in chemotherapy for a wide range of tumors, but the cardiotoxicity has restricted its use. There is an unmet need for novel therapeutics of Dox-induced cardiotoxicity (DIC). We previously identified the protein kinase MAP4K4 as a mediator of DIC. Notably, we showed that blocking MAP4K4 activity via DMX-5804 protected against Dox-induced cell death and dysfunction in human iPSCs derived cardiomyocytes (hiPSC-CMs). As a powerful tool to study the protective mechanism, pooled library screen performs high-throughput phenotypic examination, but its potential on hiPSC-CMs is poorly explored. Hypothesis: A pooled lentiviral shRNA library screen in hiPSC-CMs treated with Dox ± DMX-5804 could identify mediators of protection against DIC. Methods: To maximize the chances to uncover key factors mediating DMX-5804 protection, we performed a high-throughput loss-of-function screen. A pooled library of 1731 lentiviral shRNAs was generated. hiPSC-CMs were transduced, then treated with Dox ± DMX-5804. Cardiac troponin I ELISA was used to examine myocyte injury. Genomic DNA was isolated, followed by amplification and sequencing of the integrated shRNAs. Log2 fold change was calculated and transformed into Z score to identify significantly shifted shRNAs. Results: To build the shRNA library we included 1) genes identified via transcriptomic analysis of hiPSC-CMs treated with Dox ± DMX-5804; 2) genes in the MAP4K4 signaling cascade; 3) previously defined pro-death or pro-survival genes in DIC. To ensure single gene silenced per cell, we used a low MOI of 0.5. After transduction, cells were treated with Dox ± DMX-5804. Confirming the cardiotoxicity and protection, Dox induced a 2-fold increase of cardiac troponin I release and DMX-5804 significantly reversed it. Next, we recovered and sequenced the integrated shRNAs, and quantified the frequency of each. We identified 146 significantly enriched or depleted shRNAs (|Z score| &gt; 2). When comparing Dox treated group to vehicle or DMX-5804 protected group, shRNA enrichment indicates pro-death function of the targeted gene. Conversely, pro-survival genes can be inferred from shRNA depletion. Amongst the 5 most consistently targeted genes, we identified SIRT6 and GATA4 which are known pro-survival in DIC, suggesting the screen is potent to define key genes. Conclusion: We performed a proof-of-concept pooled library screen in human cardiomyocytes and identified mediators of protection against DIC.
Abstract 4137782: Fibrinogen-to-Albumin Ratio Does Not Correlate with Comprehensively Assessed Coronary Artery Disease Severity or High-Risk Plaque Features on Coronary Computed Tomographic Angiography
Authors: Joseph Nguyen, Nisha Hosadurg, Christine Flora, Toral Patel, Coleen McNamara, Todd Villines
Journal: Circulation (2024)

Background: Fibrinogen-to-albumin ratio (FAR) has been proposed as a readily available inflammatory biomarker associated with coronary artery disease (CAD). However, its association with CAD severity and prognosis has predominantly been assessed in patients with acute coronary syndromes (ACS). The Leiden score is a validated comprehensive measure of CAD incorporating stenosis proximity, severity, and plaque type that independently predicts cardiovascular events. Whether FAR is associated with Leiden score or high-risk plaque features on coronary computed tomographic angiography (CCTA) in stable outpatients is unknown. Methods: Adult outpatients undergoing clinically indicated CCTA were enrolled (5/2021-9/2023) in a prospective study assessing the relationship of plaque to immune markers and provided same-day pre-scan peripheral venous blood samples. CCTAs were post-processed and analyzed by the consensus of two expert readers blinded to clinical data using a 17-segment model to determine coronary artery calcium (CAC), Leiden score, and high-risk plaque features. Patients were grouped by FAR (quartiles), Leiden score (&lt;5, 5-20, &gt;20), and CAC score (0, &gt;0-100, &gt;100-300, &gt;300-1000, &gt;1000). Numerical variables were compared via Wilcoxon and Kruskal-Willis tests. Spearman correlation was calculated between FAR and Leiden score. Results: Of 284 patients, 53.8% were male, 86.7% were white, and 58.8% were on a statin (Table 1). Median FAR was 70.3 mg/g, 64.0% had a non-zero CAC score, and 25.0% had at least one segment with one high-risk plaque feature. Across quartiles of FAR, there was no difference in Leiden score (5.8 (IQR: 0.0-18.5), 12.4 (3.1-20.7), 8.0 (0.0-19.9), 6.8 (0.0-21.1), p=0.50) or probability of having at least one segment with at least one (29.6%, 23.9%, 23.9%, 22.5%, p=0.69) or two (18.3%, 14.1%, 12.7%, 15.5%, p=0.66) high-risk plaque features. There was no correlation between FAR and Leiden score (R=0.03, p=0.66). There was no difference in FAR when stratified by Leiden score (Table 1, p=0.53), CAC score (Table 2, p=0.50), or number of segments with at least one high-risk plaque feature (Table 3, p=0.18). Conclusion: In a prospective cohort of adult outpatients across a wide spectrum of CAD burden with high rates of baseline statin use, FAR was not associated with CAD or presence of high-risk plaque features on CCTA. Further evaluation of its role as an inflammatory biomarker in larger populations, particularly patients without ACS, is required.
Abstract 4134539: Hybrid Cardiomyocyte Targeting Peptide Down-regulates NF-κB Pathway in Human Cardiomyocytes
Authors: Jingyu Wang, Jack Lopuszynski, Daniella Sahagun, Maliha Zahid
Journal: Circulation (2024)

Introduction: Role of NF-κB driven inflammation leading to heart failure with preserved ejection fraction has received little attention. Our previous in vivo work with cardiac targeting peptide (CTP) in guinea pigs identified suppression of NF- κB pathway by CTP. In the current work we sought to further study the effects of a hybrid version of CTP (hCTP: amino acids at positions 3 and 11 substituted with D-amino acids) on TNF-α mediated NF-κB activation, as well as expression of its downstream inflammatory markers IL-1β and IL-8. Methods: Human cardiomyocytes (CMCs) were transfected using Lipofectamine 3000 with a reporter luciferase plasmid carrying an NF-κB promoter site upstream of the luciferase gene. Cells were treated with various concentrations of hCTP for 24 hours, followed by a TNF-α challenge (20ng/mL), addition of luciferin as substrate, and measurement of luminescence. Cell viability in response to above manipulations was assessed by FACS using live-dead stain. CMCs were treated as above, and cell culture supernatants analyzed for IL-8 levels using human ELISA kit. In another set of experiments, CMCs were transfected with NF-κB reporter plasmid, and after treatment for 24 hours with various concentrations of hCTP, incubated with 10nM angiotensin 2 (Ang2) and 100nM phenylephrine (PE) for 24hrs to assess levels of IL-1β in the cell culture media using an ELISA assay. Results: hCTP inhibited TNF-α mediated NF-κB activation with a dose-response curve, with maximum inhibition with hCTP seen at 10µM concentrations (p&lt;0.001). Treatment with hCTP inhibited the TNF-α induced IL-8 secretion with significant decreases seen even at the 1µM dose. Similarly, secretion of IL-1β production by CMCs in response to Ang2/PE stimulation was suppressed by hCTP even at the lowest tested dose (1µM; p&lt;0.5). Conclusions: Our data suggests that hCTP inhibited NF-κB pathway transcriptional activity in response to TNF-α stimulation in a dose-dependent fashion in human CMCs. Furthermore, treatment with hCTP inhibited TNF-α induced IL-8 and IL-1β secretion even at doses as low as 1µM. The ability of hCTP to efficiently targeting this inflammatory pathway suggests that it has therapeutic potential in the treatment of heart failure. Further in vivo studies are ongoing to test this hypothesis.
Abstract 4135178: Short Term Outcomes Of Transcatheter Tricuspid Valve Interventions On Post-Procedural Length Of Hospital Stay, Readmissions For Heart Failure And Procedure Success If An Intracardiac Device Is Present: A Systematic Review And Meta-Analysis In A New Era Of Tricuspid Interventions
Authors: Dilesha Kumanayaka, Laura Hernandez Perez, Wajeeha Aiman, Yazeed Abu ruman, Aishwarya Chandra, Palak Patel, Aharnish Patel, Addi Suleiman
Journal: Circulation (2024)

Background: Tricuspid regurgitation (TR) is no longer considered forgotten. Transcatheter tricuspid valve repair/replacement (TVRR) has become widely accepted as gauged by clinical outcomes. FDA approved two tricuspid valve devices for the purpose of improving quality of life and not necessarily to improve TR severity. We aim to support evidence-based use of TVRR, by summarizing the latest evidence on the clinical effectiveness in terms of post-procedural length of hospital stay, readmissions for heart failure and procedure success if an Intracardiac device is present. Methods: We searched Pubmed, Embase and Cochrane databases and performed a meta-analysis of the included cohort studies using a fixed-effects model. Studies were excluded if they did not present an outcome in each intervention group or did not have enough information required for continuous data comparison. We performed a meta-analysis of hazard ratio (HR) for two outcomes and odds ratio (OR) for one outcome using the random effects model to remove inconsistency and compared the results with fixed effects model. The compared findings of both methods were similar. The variables used for analysis were number of events in exposure group and total amount of events. All data analyses were performed using MedCalc® Statistical Software version 22.023. Results: Of 161 potentially relevant studies, 8 retrospective studies with a total of 1,717 patients were included in the meta-analysis. Procedure (TVRR) success was associated with fewer readmissions for heart failure in all three studies included in the analysis of pooled HR (HR = 0.46, 95% confidence interval [CI]: 0.33 - 0.63, p&lt;0.001). Procedure success was also associated with shorter length of hospitalization post-procedure in all three studies included in the analysis of pooled HR (HR = 0.48, 95% CI: 0.33 - 0.72, p&lt;0.001). There was no significant association between procedure success and having an intra-cardiac device in all three studies included in the analysis of pooled OR (OR = 0.79, 95% CI: 0.56 - 1.12, p=0.18). Conclusion: Our meta-analysis showed that successful TVRR for high risk patients with severe TR is associated with significant positive outcomes on post-procedural length of hospital stay and readmissions for heart failure, regardless of presence of an intracardiac device. With emerging improvements in device technology and procedural performance, TVRR should be considered in severe and functional TR, to improve clinical prognosis.