tbuckley/cabot-search huggingface dataset:
Abstract 16962: A Polygenic Predictor of Baseline QT is Associated With Sotalol-Induced QT Prolongation
Authors: Megan C Lancaster, Giovanni E Davogustto, Edi Prifti, Claire Perret, Christian Funck-Brentano, Dan M Roden, Joe-Elie Salem
Journal: Circulation (2023)

Background: Drug-induced QT interval prolongation raises the risk of fatal arrhythmia and is a central issue in safety pharmacology. Yet individual QT drug response is highly variable, and risk stratification remains a challenge. We hypothesized that genetic factors underlying the baseline QT influence this variation in QT drug response. Methods: A cohort of 990 healthy subjects was prospectively challenged with a single 80 mg oral sotalol dose. Exclusion criteria included abnormal ECG, cardiac disease, and QT-prolonging drug use. ECGs were obtained at baseline and 3 hours post-dose. QT response was defined as absolute change in Fridericia heart-rate corrected QT (ΔQTc). Plasma sotalol was measured 3 hours post-dose. Subjects were genotyped on the MEGA array. Principal component analysis of genotypes was used to define genetic ancestry. A polygenic score (PGS) for the baseline QTc comprised of 465,399 common variants was calculated from assayed and imputed genotypes. The difference in PGS between subjects with high QT response (ΔQTc≥60 ms) and those with ΔQTc&lt;60ms was assessed by Mann Whitney test. A multivariable regression model was used to assess the association between PGS and ΔQTc after covariate adjustment. Results: Of the 990 subjects, 952 (96%) passed genomic quality control and were included in analysis. 62% were female (n=590), with median age 23 (interquartile range (IQR) 21-32). Self-reported ancestry was 89% European (n=850) and 11% North African (n=102). The median ΔQTc 3 hours post-sotalol was 21 ms (IQR 12-30). Ten subjects (1%) had ΔQTc≥60 ms, and their PGS was significantly higher compared to those with ΔQTc&lt;60 ms ( P =0.0097, Figure 1A). In the regression model, PGS was positively associated with ΔQTc ( P =0.0007, Figure 1B). Conclusion: Common genetic variants associated with the baseline QT also capture part of the repolarization response to sotalol. This adds to the emerging concept that the genetic architecture of a trait can predict drug response.
Abstract 17947: Mathematical Model of Cheyne-Stokes Respirations as an Educational Tool for Understanding Cardiorespiratory Interactions in Heart Failure
Authors: Aniruddh Balu, Ramani Balu
Journal: Circulation (2023)

Background: Patients with heart failure often develop Cheyne-Stokes Respirations (CSR): a breathing pattern characterized by alternating periods of hyperventilation and apnea. The cardio-respiratory interactions that result in CSR are complex and often difficult to understand for students learning cardiovascular physiology. Aims: We developed a mathematical model of CSR where cardiac output (CO), respiratory rate (RR) and arterial CO 2 (pCO 2 ) can be manipulated to evaluate how periodic fluctuations in different physiological variables develop, thus providing a deeper understanding of cardiorespiratory interactions in heart failure. Methods: Our model consisted of 3 coupled differential equations. (1) pCO 2 is directly proportional to metabolic CO 2 production and inversely proportional to alveolar ventilation (V A ). V A depends on RR, alveolar volume, and CO, with the interaction between CO and ventilation calculated by combining Fick’s principle and the Alveolar Gas Equation. (2) Changes in RR are modeled as a Hill function dependent on pCO 2 . (3) Finally, CO depends on pCO 2 , arterial O 2, and RR. The model was propagated forward in time using Euler’s method. A graphical user interface allows users to easily manipulate variables and observe heart lung interactions. Results: Initial values for RR, CO, and PCO 2 resulting in stable, aperiodic breathing were 10 breaths/min, 6 L/Min, and 40 mmHg, respectively. Perturbing any of these values resulted in periodic fluctuations in RR, CO, and pCO 2 (Figure 1). A key insight of the model is that progressive decreases in CO induce more prominent oscillations in RR and pCO 2 and that pCO 2 directly influences CO. Conclusions: Our mathematical model of cardio-respiratory interactions allows users to easily manipulate physiological variables to graphically visualize how changes in CO and respiratory function give rise to CSR. This may enable students to obtain a deeper understanding of cardiovascular physiology.
Abstract 263: Disparities in Antiarrhythmic Practices for Out-of-Hospital Cardiac Arrest
Authors: Anastasia Papin, Hei Kit Chan, Anna Maria Johnson, N. Clay Mann, Angela Child, Benjamin Fisher, Daniel Walter, Ryan Huebinger
Journal: Circulation (2023)

Background: Antiarrhythmics are an important treatment for out-of-hospital cardiac arrest (OHCA) with a shockable rhythm, but little is known about racial and ethnic disparities in antiarrhythmic administration practices. Objective: This study aims to investigate the association between community race/ethnicity and antiarrhythmic administration for OHCA. Hypothesis: OHCAs in minority communities receive antiarrhythmics less often and with a longer delay. Methods: We conducted a retrospective study of a national prehospital database, NEMSIS, linked to Census data. We included all cardiac arrests from 2018-2021 with a shockable rhythm. We stratified patients based on majority (&gt;50%) zip code race/ethnicity (non-Hispanic White (White), non-Hispanic Black (Black), and Hispanic). For patients with a shockable rhythm at any point, we performed a mixed logistic regression model evaluating the association ZIP code race/ethnicity to administration of antiarrhythmic medication. We modeled EMS agency as a random intercept and adjusted for possible confounders. For patients with an initial shockable rhythm, we compared the time from EMS dispatch to first antiarrhythmic administration between strata. Results: Of 763,944 cardiac arrests, 203,816 had an initial shockable rhythm at any point during the encounter and 111,778 had an initial shockable rhythm. For patients with a shockable rhythm at any point, the median age was 65 (IQR 54-75), 68.5% were male, 65.9% occurred in a private residence, and 67.1% were bystander witnessed. Majority White (33.9%) received antiarrhythmics at a higher rate than majority Black (31.8%; aOR 0.89, 95% CI 0.85-0.94) and majority Hispanic (28.1%; aOR 0.89, 95% CI 0.84-0.94). For patients with an initial shockable rhythm, the time to antiarrhythmic for White (mean 22.2, SD 10.8, median 19.8 minutes, IQR 15-26.6 minute), was lower than Black (mean 22.6, SD 10.7, median 20.3 minutes, IQR 16.1-26.5 minutes, p=0.02) but higher than Hispanic (mean 20.3, SD 9.7, median 18.1 minutes, IQR 14.3-23.6 minutes, p&lt;0.01). Conclusion: While antiarrhythmic administration rate was lower for minority communities and time to antiarrhythmic was higher for Black OHCAs, time to antiarrhythmic administration was lower for Hispanic OHCAs.
Abstract 156: Incidence and Long-Term Outcomes of Acute Myocardial Infarction Among Survivors of Out-of-Hospital Cardiac Arrest
Authors: Jun Wei Yeo, Zheng Huili, Celeste Ng, Pin Pin Pek, Benny Ng, Yip Han Chin, Timothy Jia Rong Lam, Truls Ostbye, Jasper Tromp, Marcus E Ong, Andrew Fu Wah Ho
Journal: Circulation (2023)

Introduction: Despite the increasing long-term survival after out-of-hospital cardiac arrest (OHCA), the risk of subsequent acute myocardial infarction (AMI) remains poorly understood. We aimed to determine the incidence, predictors, and long-term outcomes of AMI among OHCA survivors. Methods: We assembled a retrospective cohort of patients with OHCA who survived to 30 days or discharge from hospital regardless of time from index event between 2010-2019 by linking the Pan-Asian Resuscitation Outcomes Study (Singapore participants), Singapore Myocardial Infarction Registry, and the Singapore Registry of Births and Deaths. We calculated the risk of subsequent AMI defined as AMI occurring 30 days after index OHCA or following discharge from hospital post-OHCA, among OHCA survivors compared to the general population using age- and sex-specific standardised incidence ratios (SIR) and the cumulative incidence of subsequent AMI among OHCA survivors. We investigated predictors of subsequent AMI among OHCA survivors and whether AMI predicted mortality using Cox regression hazard ratios for time-to-event analyses. Results: In total, 882 OHCA survivors were analysed. OHCA survivors had an increased risk of subsequent AMI compared to the general population when matched for age and sex (SIR 4.64, 95% CI: 3.52-6.01). Age-specific risks of subsequent AMI for males (SIR 3.29, 95%CI: 2.39-4.42) and females (SIR 6.15, 95%CI: 3.27-10.52) were significantly increased. 7.2%, 8.3%, and 14.3% of OHCA survivors had subsequent AMI at 3 years, 5 years, and end of follow-up respectively. Age at OHCA (HR 1.04, 95%CI: 1.02-1.06) and past medical history of prior AMI, defined as any AMI preceding or during the index OHCA event (HR 1.84, 95%CI: 1.05-3.22), were associated with subsequent AMI. OHCA survivors with subsequent AMI had a higher risk of mortality (HR 1.58, 95%CI: 1.12-2.22) than those without. Conclusion: Long-term OHCA survivors have an increased risk of subsequent AMI, compared to the general population. Prior AMI significantly increases this risk and subsequent AMI predicts mortality. Intensive cardiovascular risk factor control and revascularisation may improve outcomes in selected patients with a cardiac etiology.
Abstract 13590: Comparative Efficacy and Safety of Bare-Metal versus Drug-Eluting Stents in Managing Saphenous Venous Graft Disease: A Meta-Analysis and Systematic Review
Authors: Mansoor Rahman, Muhammad Hanif, Mahrukh Mumtaz, Abhinav Nair, Junaid Ali, Babar Khan, Waqas Ullah, Michael P Savage
Journal: Circulation (2023)

Introduction: Current understanding of the relative safety and efficacy of bare metal stents (BMS) vs. drug eluting stents (DES) in patients with saphenous venous graft disease (SVGD) relies on analysis of small datasets. Methods: Literature search was performed using PubMed, Embase and Web of Science to identify relevant articles on outcomes of BMS vs. DES in patients with SVGD. A random effects model was used to calculate odds ratios (ORs) for several safety and efficacy outcomes including major adverse cardiovascular events (MACE), target lesion revascularization (TLR), total vessel revascularization (TVR), in-stent restenosis, and stent thrombosis. Results: Of 3644 total citations on the initial search, 40 studies comprising 83,151 (33,306 BMS, 49,845 DES) patients qualified for quantitative analysis. The mean age was 72 years, and the mean ejection fraction was 47%. The inter group proportion of hypertension was 78% vs. 83%, diabetes mellitus was 37% vs. 14%, and hyperlipidemia was 69% vs. 78% in patients with BMS vs. DES, respectively (Table). Patients receiving DES had significantly lower odds of MACE (OR 0.63, 95% CI 0.52-0.77), and its components; TLR (OR 0.67, 95% CI 0.49-0.92), TVR (OR 0.61, 95% CI 0.46-0.81); and stent restenosis (OR 0.61, 95% CI 0.45-0.84) compared with BMS (Figure). The risk of stent thrombosis (OR 0.84, 95% CI 0.61-1.15) was similar between the two groups. Conclusions: Compared with BMS, patients receiving DES for SVGD demonstrated a lower risk of adverse events, stent stenosis, and need for revascularization.
Abstract 14928: Coronary Artery Disease Impacts Cardiac Remodeling in Patients Treated for Severe Aortic Stenosis in the PARTNER Trials
Authors: Melissa A Daubert, Ke Xu, Rebecca T Hahn, Philippe Pibarot, Jonathon Leipsic, Marie-Annick A Clavel, Sammy Elmariah, Neil J Weissman, Federico M Asch, Omar Khalique, Martin B Leon, Paul C Cremer, Brian R Lindman, Maria Alu, Pamela S Douglas
Journal: Circulation (2023)

Introduction: Coronary artery disease (CAD) is common in patients with severe aortic stenosis (AS), but the impact on cardiac remodeling and outcomes after AS treatment is unknown. Hypothesis: We hypothesize that greater CAD burden will be associated with less beneficial remodeling and increased adverse events. Methods: Patients with severe AS in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2 or 3 trials, with baseline and 1 year echoes, were categorized as: 1. Obstructive CAD (coronary stenosis ≥50% on invasive angiography, prior myocardial infarction (MI) or previous revascularization); or 2. Non-obstructive or no CAD (all stenosis &lt;50% and no prior MI or revasc). Clinical and imaging characteristics were compared and changes in cardiac structure and function were assessed at 1 year. Associations between CAD, cardiac remodeling and cardiovascular (CV) events at 2 years were examined. Results: Among 5552 patients with severe AS, 1598 (28.8%) had non-obstructive or no CAD and were more likely to be female (67.1%), have fewer CAD risk factors, and receive SAVR (28% vs. 19%) compared to those with obstructive CAD (all p&lt;0.0001). Despite lower LV mass index (LVMi), patients with non-obstructive or no CAD had higher aortic valve velocities, gradients, ejection fraction (EF) and stroke volume index compared to those with obstructive CAD. After 1 year, the decrease in LVMi was similar between groups (p=0.91), but patients with obstructive CAD were more likely to increase EF by ≥5% (p=0.006), reduce LV dimensions (p=0.04), or decrease mitral regurgitation (p=0.01). After adjustment for baseline factors and AS treatment, CV death or heart failure (HF) hospitalization was higher among patients with obstructive CAD (HR 1.16, 95% CI: 1.03-1.30, p=0.01). When LV remodeling at 1 year was also adjusted for, the point estimate was similar but there was no significant difference in the landmarked rate of CV death or HF hospitalization between year 1 and 2 (HR 1.22, 95% CI: 0.95-1.56, p=0.12). Conclusions: Nearly a third of patients with severe AS did not have obstructive CAD and had a better prognosis after treatment for AS. However, patients with obstructive CAD and LV remodeling were not at greater risk for CV events compared to those with non-obstructive or no CAD.
Abstract 15267: Differential Effect of Calcium Score on Major Adverse Cardiac Events in Men and Women
Authors: Usman Naseer, EMMANUEL FOHLE, Catherine Hajek, Marian S Petrasko, Adam Stys, Naveen Rajpurohit, Eric Larson, Max Weaver, Shubhi Bartaria, SHAOPENG GU, Tom Stys
Journal: Circulation (2023)

Introduction: Coronary artery calcium (CAC) is well-validated for cardiovascular risk stratification. There are well-known gender differences in the presentation, diagnosis, and management of cardiac diseases that have been extensively studied in the past. To date, there have not been extensive studies to look at the differential effect of CAC score on major adverse cardiac events (MACE; defined as death, MI, stroke, or coronary revascularization) amongst men and women. The objective of our study is to look at this aspect. Methods/Results: Data were analyzed on a group of 1,380 patients who had participated in both the Sanford Health Heart Screen Program and the Sanford Health Preemptive Genomic Screening Program. These patients had their heart screen between 2011 and 2021 and their genetic testing between 2018-2022. Patients consented to both forms of screening independently, and the results were analyzed by means of a retrospective review. While other genetic factors were excluded from this study, we separated patients by sex. This sample had 64% female and 36% male. 10% of males had a MACE event and 4.9% of females had a MACE event. Males had higher levels of CAC (M=249.55, SD=550.41) compared to that of females (M=57.97, SD=190.5). The correlation between CAC and MACE was higher for males (r=0.33, p&lt;0.01) than it was for females (r=0.17, p&lt;0.05), Zou’s CI [.06, .26]. Conclusion: Males, overall had a higher level of CAC score compared to females. The correlation between the CAC score and MACE was also higher for males, as compared to females.
Abstract 14961: Revitalizing Graft Patency: Intravascular Lithotripsy in Calcified Saphenous Vein Graft to Left Anterior Descending Artery Stenosis
Authors: Chetan Singh, Dishita Pandya, Mohammad Raza, Neeraj Shah
Journal: Circulation (2023)

A 73-year-old man with coronary artery disease (CAD), coronary artery bypass graft, heart failure [EF 25%] &amp; hypertension presented with Non-ST Segment Myocardial Infarction. Angiography revealed multivessel CAD with chronic total occlusion (CTO) of mid-left anterior descending (LAD) after a large first diagonal branch, CTO of mid-left circumflex &amp; distal right coronary artery. Saphenous vein graft (SVG) to obtuse marginal was patent. SVG-diagonal &amp; SVG-ramus intermedius were occluded. Mid SVG-LAD showed severe calcified stenosis (Fig. 1A). Native LAD beyond the SVG provided left to right collaterals to right posterior descending artery. Complex high-risk coronary intervention was performed on the SVG-LAD with mechanical circulatory support (MCS; Impella CP). SVG-LAD had a balloon undilatable lesion despite high pressure inflation with 4.0 mm cutting balloon (Fig. 1B). Intravascular ultrasound (IVUS) revealed severe stenosis with extensive circumferential calcification (Fig. 1C). Subsequently, intravascular lithotripsy (IVL) with 4.0 mm Shockwave balloon followed by high pressure balloon angioplasty with 4.5 mm noncompliant (NC) balloon was performed with significant luminal gain and fractures in calcium (Fig. 1D). The lesion was treated with 5.0 mm drug eluting stents that were post dilated with 5.0 mm NC balloon with excellent angiographic and IVUS result (Figs. 1E &amp; F). MCS was successfully removed at the end of the case.SVG grafts are associated with poor long-term patency compared to arterial grafts. PCI to SVG has a high failure rate and PCI of native vessel is often preferable. High risk SVG interventions with atherectomy have been recently reported, though data is limited. IVL has been safely used in heavily calcified native coronary arteries, however, its use in SVG disease is rare. We report the first off-label use IVL of SVG-LAD with MCS for treatment of a last-remaining conduit. Additional studies to assess IVL efficacy in vein grafts are warranted.
Abstract 14988: Clinical Impact of Biventricular vs. Isolated Left Ventricular Involvement Among Patients With Takotsubo Cardiomyopathy- An Updated Meta-Analysis
Authors: Saliha Erdem, Mohammad Hamza, Dhruvil Patel, Amrit kanwar, Amro Taha, John Dayco, Luis Afonso
Journal: Circulation (2023)

Introduction: Takotsubo Cardiomyopathy (TC) is a form of acute nonischemic cardiomyopathy manifesting as a transient state of cardiac dysfunction. Isolated left ventricular TC (ILVTC) is most commonly observed, less frequently, superimposed right ventricular involvement is apparent - referred to as biventricular TC (BVTC). Few analyses have been done to characterize the implications of biventricular TC on hospital courses and outcomes. Methods: A literature search was conducted on PubMed and Google Scholar to identify qualifying studies. Inclusion criteria were adult patients with TC, and studies reporting comparison of outcomes (cardiogenic shock, use of inotropes, all causes of mortality, and length of hospital stay) between patients with BVTC and ILVTC. Exclusion criteria were any studies that reported on patients younger than 18 years or did not report all the outcomes for BVTC vs ILVTC. Results: A total of 1,156 patients with TC were analyzed from 6 included studies, of which 15% had BVTC (n=175), and 85% had ILVTC (n=981). Patients with BVTC were found to have a higher incidence of cardiogenic shock patients (OR:3.3; 95% CI=1.40-7.77) and use of inotropes (OR:3.66; 95% CI =1.60-8.35). All-cause mortality did not reach statistical significance between the two groups (OR:2.05; 95% CI=0.81 - 5.22; p &lt;0.13). There was also no significant difference in length of hospital stay (Hedges’ g = 0.22; 95% CI = -0.01 to +0.45; p = 0.0593). Conclusions: In comparison to ILVTC, BVTC increasingly predisposes to cardiogenic shock development. Yet, the presence of biventricular involvement does not impact the risk of mortality or hospital length of stay when compared to ILVTC.
Abstract 13615: Diagnostic Accuracy of Cardiac MRI for Detecting Wall Motion Abnormalities and Coronary Artery Stenosis - A Systematic Review and Umbrella Meta-Analysis
Authors: Viraj Panchal, Johnnie Saifa-Bonsu, Tenzin Tamdin, Nagaraj Sanchitha Honganur, Farahnaz Noei, Srujana Konka, Vikramaditya R Samala Venkata, Barath Prashanth Sivasubramanian, lokesh manjani, Mihir Dave, Priya Savani, Richa Jaiswal, Umabalan Thirupathy, Urvish K Patel, Pratikkumar Vekaria
Journal: Circulation (2023)

Introduction: Conventional coronary angiography (CCA) is the gold standard for the diagnosis of coronary artery disease (CAD). It is an invasive test and carries risks. Increased mortality is linked with reduced coronary flow, thus aggressively measuring coronary flow is important. Cardiac MRI (cMRI) is an emerging non-invasive test that can also help in assessing ventricular function, myocardial perfusion, and detecting anomalies. Aim: We aimed to analyze the diagnostic accuracy of cMRI compared to CCA through an umbrella meta-analysis. Methods: We searched PubMed articles comparing the diagnostic accuracy of cMRI with CCA in patients having CAD published from 2000 to 2022 according to PRISMA guidelines. We used the generic inverse variance method to pool sensitivity (SN), specificity (SP), negative likelihood ratio, positive likelihood ratio, and diagnostic odds ratio (DOR) with 95% confidence interval keeping alpha criteria of 0.05 as significant. RevMan 5.4 was used to calculate random effects models. Results: In this umbrella meta-analysis, 9 studies with 14615 patients met inclusion criteria. Overall pooled SN was 0.88 (95% CI: 0.87-0.90), SP was 0.85 (0.81-0.89), PLR was 6.07 (5.02-7.33), NLR was -1.99 (-2.10 to -1.87), and DOR 38.94 (31.96-47.46). (p&lt;0.00001) Conclusion: The diagnostic accuracy of a non-invasive, cMRI is comparable, if not superior to an invasive test like CCA.