tbuckley/cabot-search huggingface dataset:
Abstract 4141370: Artificial Intelligence for Predicting Primary Antegrade Wiring Success of Chronic Total Occlusion Crossing
Authors: Michaella Alexandrou, Athanasios Rempakos, Deniz Mutlu, Dimitrios Strepkos, Pedro Carvalho, Ahmed Al-Ogaili, Ali Bahbah, Milkas Anastasios, Ioannis Tsiafoutis, Khaldoon Alaswad, Mir Basir, Rhian Davies, Farouc Jaffer, William Nicholson, Lorenzo Azzalini, sevket gorgulu, Jaikirshan Khatri, Sripal Bangalore, Bavana Rangan, Olga Mastrodemos, M Nicholas Burke, Yader Sandoval, Emmanouil Brilakis
Journal: Circulation (2024)

Background: Incorporating artificial intelligence (AI)-based clinical decision support in the cardiac catheterization laboratory could revolutionize percutaneous coronary intervention (PCI) and interventional cardiology. Research Questions: To compare predictions for successful primary antegrade wiring (AW) of chronic total occlusion (CTO) lesions made by interventional cardiologists (ICs) with those from a machine learning model. Methods: We conducted a survey to assess the estimates of ICs regarding primary AW crossing success, on a scale of 0-100%, for 15 CTO PCIs. For the AI based prediction we used a machine learning model with an area under the curve of 0.780. The primary endpoint was the difference between AI-generated and human estimates. Results: A total of 130 ICs participated in the survey. Mean participant age was 51.7±10.6 years. The median difference between the AI and the human prediction was &lt;20% for 7 cases; 20-30% for 6 cases; &gt;30% for 2 cases. Successful AW-based crossing by an experienced CTO operator was observed in 8/15 cases. The operator predictions aligned with the real-life outcomes in 9/15 cases (60.0%), while AI correctly predicted the success/failure of primary AW CTO crossing in 11/15 cases (73.3%). Operators with more experience (&gt;20 CTO PCIs annually) predicted higher success than less experienced operators for 5 cases. Operators who train dedicated advanced fellows predicted higher success for 6 cases and showed worse alignment with the AI prediction for 4 cases. Conclusions: Our study shows that, compared with physician’s estimations, a machine learning model could improve the accuracy of predictions for primary AW success and assist CTO PCI planning.
Abstract 4141596: Machine Learning Model Predicting In-Hospital Mortality for Cardiogenic Shock
Authors: Ajar Kochar, Henry Foote, William Ratliff, Suresh Balu
Journal: Circulation (2024)

Background: Cardiogenic shock *CS) confers a high mortality (30-50%). A key limitation of existing CS mortality models is the reliance on static parameters measured at admission which ignore the rapidly evolving natural history of CS. Hypothesis: A machine learning (ML) model that incorporates time series electronic health record (EHR) data including echocardiogram reports and invasive hemodynamics will accurately predict mortality in patients with cardiogenic shock Methods: Patients with an ICD-10 code of cardiogenic shock were identified using electronic health data (EHR) from 2015 - 2019. The primary outcome was a composite of in hospital mortality or discharge to hospice. We incorporated EHR data obtained within the first 24 hours of admission including demographics, comorbidities, vital signs, lab values, medication administration, use of mechanical circulatory support (MCS), echocardiogram data, electrocardiogram reports, and hemodynamics from pulmonary artery catheter or right heart catheterization. For dynamic values such as lab values we incorporated six hour, 12 hour, and 24 hours trends as well as maximum and minimum values. We used a LightGBM model with 70/10/20 split for training, hyperparameter fine-tuning, and testing. Results: We identified 5,048 total admissions. Median age was 65 years (IQR 52, 72) and 64% were male. Twenty five percent presented with acute myocardial infarction and 12% with cardiac arrest. The MCS distribution was: 17% intra-aortic balloon pump and 6% VA-ECMO. All-cause mortality was 32%. Our model demonstrated robust discrimination (AUROC 0.804), precision (0.699), and calibration (expected calibration error 3.2%). The five highest importance features were age at admission, mean serum albumin, mean glascow coma score, mean platelet value in the first six hours of admission, and total urine output. Our model performed favorably to a previously developed cardiogenic shock mortality risk scores (IABP SHOCK II: AUROC 0.71, AUPRC 0.55 in our cohort). Conclusion: This ML CS mortality model incorporating dynamic, time series EHR data capturing the trajectory of CS in the first 24 hours after amission has high precision and discrimination. This ML model could be readily embedded into EHR systems to allow for rapid risk statification at the bed-side.
Abstract 4141581: Surgical revascularization of ischemic heart failure: a comparison between patients with preserved (HFpEF) and reduced ejection fraction (HFrEF).
Authors: Andrea Garatti, Matteo Scarpanti, Elisa Gastino, Mariangela DOvidio, Alberto Canziani, Andrea Daprati, Stefano Buratti, Francesca Rusconi, Carlo de Vincentiis, Marco Guazzi, Alessandro Parolari, Lorenzo Menicanti
Journal: Circulation (2024)

Introduction: Despite surgical myocardial revascularization(CABG) in patients with ischemic HF and reduced EF(HFrEF) is strongly supported, there is only limited evidence to guide revascularization in patients with HF and preserved EF(HFpEF). Research Questions: Should CHF be considered an independent risk-factor in patients undergoing CABG, irrespectively of preoperative LVEF? Aims: To determine the prognostic role of preserved versus reduced EF on the outcomes of patients with ischemic HF undergoing CABG. Methods: Between 2005-2019, 4079 consecutive patients with multivessel CAD underwent isolated, on-pump CABG at a single institution. Preoperative CHF was ascertained according to clinical symptoms, laboratory values and medical therapy. Preserved LV function was defined as EF≥50%. Accordingly, the study population was divided into 4 groups: Group I [NoHFpEF,2663 pts(65%)], Group II [HFpEF,214 pts(5%)], Group III [NoHFrEF,970 pts(24%)], and Group IV [HFrEF,232 pts(6%)]. A deterministic record linkage with the National Health Institute Database allowed unique identification of long-term mortality and major adverse cardiovascular events[acute MI, repeated PCI and HF admission(MACE)]. Results: Patients with HFpEF presented with a similar preoperative clinical profile compared to NoHF patients, while the incidence of comorbidities significantly increased through reduced EF groups. Completeness of revascularization was consistent across the study groups. Perioperative morbidity was similar between HFpEF and NoHF patients, but progressively increased in reduced EF groups. Moreover, 30-day mortality was comparable between HFpEF and Group I(1.4%vs1.2%, P=NS), but significantly increased in Group III(3.1%) and IV(5.6%, p&lt;0.01 ). Finally, HFpEF showed a 10-years survival comparable to Group III(63%vs61%, p=NS) but significantly reduced to Group I(75%, p&lt;0.01 ). On the contrary, 10-year freedom from MACE was comparable between HFpEF and Group I(60%vs 67%, p=0.34), and significantly higher than Group III and IV(47% and 38% respectively, p&lt;0.01 – Figure1 ). Conclusions: HFpEF patients undergoing CABG showed comparable perioperative results to non-HF patients and significantly better long-term outcomes compared to HFrEF patients.
Abstract 4141547: Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart
Authors: Daniel Nguyen, Collin Wells, Madison Taylor, Kenneth Brittian, Robert Brainard, Bradford Hill
Journal: Circulation (2024)

Introduction: Branched chain amino acids (BCAAs) are essential amino acids that are elevated in the failing heart and that have been linked with cardiovascular disease risk. Yet, it remains unclear how BCAAs influence the heart after injury. In this study, we examined in mice whether dietary alterations of BCAA levels influences cardiac structure and function after myocardial infarction (MI). Methods and Results: To assess whether altering dietary BCAA levels would impact circulating BCAA concentrations, mice were fed a low (1/3×), normal (1×), or high (2×) BCAA diet over a 7-day period. The low and high BCAA diets were matched for macronutrient content, nitrogen content, and caloric density. We found that mice fed the low BCAA diet had &gt;2-fold lower circulating BCAA concentrations when compared with normal and high BCAA diet feeding strategies (n=8/group; p&lt;0.05); notably, the high BCAA diet did not further increase BCAA levels over the normal chow diet. To investigate the impact of dietary BCAAs on cardiac remodeling and function after MI, male and female mice were fed either the low or high BCAA diet for 2 wk prior to MI and for 4 wk after MI. Although body weight (BW) or heart mass (HW/TL) were not different in female mice fed the custom diets, male mice fed the high BCAA diet had higher BW and HW/TL than those on the low BCAA diet (n = 7–10/group; p&lt;0.05). Echocardiography prior to MI (baseline) and at 2- and 4-wk post-MI revealed that the low BCAA diet preserved stroke volume (SV) and cardiac output (CO), whereas mice fed a high BCAA diet showed progressive decreases in SV and CO, which reached statistical significance by 4 wk post-MI (p&lt;0.05). Structural analysis further demonstrated higher LV mass in mice fed the high BCAA diet compared with the low BCAA diet (n = 7–10/group; p&lt;0.05). Although no differences in cardiac fibrosis or cardiomyocyte cross-sectional area were found between the dietary groups, male mice fed the high BCAA diet showed longer cardiomyocytes and higher capillary density compared with the low BCAA gorup (n = 6-10/group; p&lt;0.05). Conclusions: These preclinical results demonstrate that dietary BCAA levels influence cardiac structure and function after MI and suggest that a diet low in BCAAs minimizes deleterious remodeling, especially in male mice.
Abstract 4141687: Optimal Duration of Ambulatory Monitoring for Detecting Non-Sustained Ventricular Tachycardia (NSVT) in Pediatric and Adult Congenital Heart Disease Patients
Authors: Iqbal El Assaad, Lama Dakik, Abdel Rahman E'mar, Alison Heilbronner, Peter Aziz, Akash Patel
Journal: Circulation (2024)

Background: The frequency and clinical significance of non-sustained ventricular tachycardia (NSVT) detected on ambulatory monitors in pediatric and congenital heart disease (CHD) patients has not been thoroughly investigated. We sought to examine the prevalence of NSVT, analyze the presence of associated cardiovascular disease, and describe changes in management. Methods: We performed a retrospective cohort study of all patients evaluated in cardiology clinic at Cleveland Clinic who were found to have NSVT on ambulatory Zio monitors (2017 and 2023). Kaplan Meier curves and Cox proportional hazards model were performed to analyze time to NSVT detection and factors associated with detection. Results: Among 2805 patients, 172 (mean age 29 ± 14, 51% male) had NSVT yielding a prevalence of 6% and a mean monitoring duration of 7.5 ± 5.5 days. Cardiac diagnoses were as follows: 98 (57 %) CHD, 44 (26%) structurally normal hearts, 14 (8%) cardiomyopathy, 10 (6%) connective tissue disorder, and 6 (3%) channelopathy. Monitoring indications included symptoms (97, 56%), history of arrhythmias (34, 20%), screening (36, 21%) and others (5, 3%). Mean day of NSVT detection was 4.3 ± 3.7 years without significant difference amongst the various underlying cardiac diagnoses (p = 0.2). Of the patients who had a repeat ambulatory monitor, 39/113 (34%) were found to have NSVT. Management changes were made in 56 (32%) patients: medication change in 46, EP study in 1, implantable loop recorder placement in 4, and ICD placement in 5. Five patients died during the study period with only 1 suspected sudden cardiac death. The likelihood of NSVT detection increased with longer monitoring duration with only 55% of cases detected at 2 days (Figure 1). In a multivariable model, monitoring duration (HR 0.8, 95% CI: 0.77-0.84, p &lt; 0.001) but not underlying diagnosis, age, monitor indication, or single ventricle status, was associated with likelihood of NSVT detection. Conclusions: NSVT is not an uncommon arrhythmia in pediatric and CHD patients with increasing prevalence with longer monitoring duration regardless of underlying cardiac etiology. Although medical management changes based on monitor findings were frequent, sudden death was rare.
Abstract 4141564: Disparities in Healthcare Utilization following Endovascular Abdominal Aneurysm Repair
Authors: Emily St. John, Christina Marcaccio, Rebecca Ward, Robert Craig, Carmen Gacchina Johnson, Rebecca Torguson, Ronald Fairman, Marc Schermerhorn, Eric Secemsky
Journal: Circulation (2024)

Introduction: Healthcare utilization in postoperative management and surveillance following endovascular aneurysm repair (EVAR) is an important factor in achieving long-term treatment success. However, factors associated with poor healthcare utilization have yet to be elucidated. Hypothesis: Disadvantaged patients have lower rates of surveillance and higher rates of emergency health service use than their counterparts. Aims: Examine rates of healthcare utilization stratified by age, sex, race, dual-enrollment in Medicare and Medicaid, and residence in a distressed community. Methods: We performed an observational retrospective cohort study of Medicare beneficiaries who underwent infrarenal EVAR with a bifurcated endograft between 2011-2019. We examined annual rates of post-operative surveillance (EVAR-related outpatient visits, surveillance imaging), use of emergency department (ED) visits, and hospital readmission across several disparity measures using Modified Poisson Regression models. Results: In 111,381 Medicare beneficiaries undergoing EVAR, comorbidities associated with poor postoperative surveillance were chronic kidney disease (aRR:1.06[1.04-1.07]), heart failure (1.10[1.09-1.11]), hyperlipidemia (1.16[1.14-1.19]), hypertension (1.09[1.07-1.12]), and ischemic heart disease (1.15[1.14-1.17]). For EVAR-related office visits, patients with worse post-operative care included those &gt;85 years, female, Black, dual-enrolled, or living in distressed communities ( Table 1 ). Similarly, less surveillance imaging was performed in patients &gt;85 years, dual-enrolled, or living in distressed communities. There was a greater need for ER care or readmission among patients &gt;85 years, female, Black, dual-enrolled, or living in distressed communities. Conclusions: Our study revealed patterns of disparities in post-procedure EVAR-related office visits and EVAR imaging studies, and greater use of emergency health services associated with patient age, sex, race, and socioeconomic status. These findings may suggest barriers in access to appropriate surveillance and care which could be addressed by targeting the identified groups for intervention efforts to improve EVAR surveillance.
Abstract 4141327: Alternate Day Fasting Attenuates Arterial Thrombotic Risk via Increasing Indole-3-propionic acid
Authors: Ruijia Feng, Wenchao Yang, Guiyan Peng, Weiqi Feng, Ting Long, Zilun Li, Guangqi Chang, Kan Huang
Journal: Circulation (2024)

Background: Arterial thrombotic disease has long been a crucial worldwide health concern. Metabolic disorders have been validated to enhance platelet reactivity, thereby augmenting the thrombotic risk. Recent investigations have highlighted the metabolic improving effect of alternate day fasting (ADF). However, its impact on thrombosis remains unclear. Hypothesis: We hypothesize that ADF may reduce arterial thrombotic risk through its metabolic modulatory effect. Aims: To investigate the effects of ADF on thrombogenesis and unravel its underlying mechanisms. Methods: Thirty male C57BL/6J mice fed with high fat diet (HFD) for 6 weeks were randomly allocated into 3 groups: HFD, ADF, or pair feeding, for another 6 weeks dietary intervention, while mice fed standard laboratory diet were set as control. In vivo carotid artery ferric chloride injury model and multiple ex vivo platelet function assays were utilized to assess the impacts of ADF on thrombogenesis and platelet reactivity. Fecal microbiota transplantation was performed to further explore the causal relationship between gut microbiota and ADF-mediating effects on thrombosis. Moreover, fecal metagenomic and plasma untargeted metabolomics analyses were conducted to identify the alterations of gut microbiota composition and metabolite profiles under ADF intervention. Results: Our study demonstrated that ADF ameliorated HFD-induced heightened platelet reactivity and thrombotic tendency in mice on a gut microbiota dependent manner. Indole-3 propionic acid (IPA), a gut microbiota-derived metabolite, was enriched under ADF and further identified as a crucial factor mediating the anti-thrombotic effect of ADF. Supplementation of IPA impeded platelet activation via suppressing intraplatelet Rho-GTPase cycle and its downstream signals, thereby alleviating thrombotic formation without affecting hemostasis. Of note, we demonstrated that plasma IPA was remarkably decreased in patients with acute arterial thrombotic events, which also exhibited a significant negative association with platelet reactivity. Conclusions: Our study uncovers the protective effect of ADF on thrombogenesis, providing mechanistic insights and a potential therapeutic strategy for arterial thrombotic diseases.
Abstract 4141674: Inhibiting Detrimental Cardiac Functions Using Biased Allosteric Modulators Of β <sub>2</sub> -Adrenergic Receptor Modulating The Canonical Signaling
Authors: Sushrut Shah, Marilen Federico, Yuexing Yuan, Alexis Shatzman, Shey-Shing Sheu, Deepak Deshpande
Journal: Circulation (2024)

BACKGROUND: Cardiac diseases such as heart failure (HF) are characterized by irregular cardiac contraction and relaxation due to repeated damage to the myocardium. β-adrenergic receptors (βAR) on cardiomyocytes (CMs) are predominant regulators of cardiac contractility and hence β-blockers are utilized in the treatment of HF. Biasing βAR-mediated signaling in CMs presents an opportunity for developing alternative therapies. We have recently discovered a new allosteric modulators (AMs) that preferentially diminish βAR-Gαs signaling, not affecting β-arrestin mediated signaling. Considering the functional significance of βAR-mediated Gαs- and β-arrestin signaling in CMs, our objective is to investigate the impact of our recently identified β 2 AR AMs on CM contractility and heart function. We hypothesize that Negative AMs (NAMs) of β 2 AR will inhibit the βAR-Gαs signaling induced by β-agonists thereby decreasing cardiac contractility in vitro and in vivo. METHODS: In isolated adult ventricular murine CMs (AVCM), we assessed the effect of NAM on isoproterenol-induced contractility and calcium transients using the IonOptix System. A subset of cells were pre-treated with β 1 AR-antagonist. To examine the effect in the whole heart, we treated perfused hearts in Langendorff Apparatus with ISO (100nM) and vehicle/NAM. Finally, to assess effects of AMs on heart functions in vivo , we performed electrocardiogram (ECG) and echocardiogram in mice treated with ISO. RESULTS: In AVCMs, ISO augmented CM contractility and calcium. Concomitant NAM treatment significantly attenuated ISO-induced cell contractility, elevation of calcium peak and decreased time-to-relaxation. Interestingly, pretreatment of CMs with β 1 AR-antagonist reversed the inhibitory effect of NAM on ISO-mediated contractility. Our ex vivo perfused heart experiments demonstrated an inhibition of ISO-induced cardiac contractility by the β 2 AR NAM. ECG studies demonstrated an attenuation of ISO-induced increase in parameters including heart rate and PVCs. Echocardiogram recording confirmed the decrease in heart rate and revealed alleviation of ISO-induced reduction in ejection fraction and fractional shortening and inhibition of ISO-induced isovolumic contraction time and myocardial performance index. CONCLUSIONS: These data collectively demonstrate that our recently discovered biased NAM could preferentially ameliorate cardiotoxic Gαs signaling and function in CMs.
Abstract 4141562: Functional evidence of regulation of the Na <sub>V</sub> 1.5 channel through homomeric interaction of its α-subunits in the cellular membrane
Authors: Mikhail Tarasov, Przemyslaw Radwanski
Journal: Circulation (2024)

Recent structural findings reveled potential interaction between Na V 1.5 in the plasma membrane. However, functional effects of this interaction on Na + current (I Na ) remain elusive. Cell-attached patch-clamp in Chinese hamster ovary (CHO) cells stably expressing Na V 1.5 revealed a significant increase in the ratio of persistent-to-peak I Na (R persist ) in single- vs. multi-channel patches. These data suggest that reduced Na V 1.5 surface density impacts R persist . Indeed, reduction of Na V 1.5 membrane density by paclitaxel (TXL, 100 µM, 2 hours) significantly increased R persist of multi- but not single-channel patches relative to untreated Na V 1.5 expressing cells ( Fig. 1 ). This was further supported by a divergence in peak I Na predicted by a single-channel Markov model based on single-channel activity relative to experimental multi-channel recordings. To overcome the limitation of this classical model, we implemented a novel Markov model which accounts for channel interaction. Importantly, this approach not only replicated our experimental findings but also predicted a reduction of a fraction of channels in the fast inactivated state and consequently an acceleration of recovery from fast inactivation in multi-channel recordings ( Fig. 2 ). Consistent with this prediction, experimental application of lidocaine (50 µM), an agent which blocks Na V 1.5 during fast inactivation, exhibited reduced inhibitory effect in multi- vs. single-channel patches. Confirming the dependence of R persist on Na V 1.5 membrane density, whole-cell patch clamp recordings in CHO cells transiently transfected with the inactivation-deficient ΔKPQ-Na V 1.5 mutant reveled a significant negative correlation between the magnitude of whole-cell peak I Na density and R persist . Notably, increasing Na V 1.5 cluster density with SB216763 (5 µM) in cardiomyocytes isolated from mice harboring this mutation (ΔKPQ +/- ) significantly reduced whole-cell R persist relative to untreated myocytes ( Fig. 3 ). Our study suggests that Na V 1.5 homomeric interaction may impact Na V 1.5 kinetics and can serve as a therapeutic target for arrhythmia prevention.