tbuckley/cabot-search huggingface dataset:
Abstract 18887: Trends and Outcomes of Use of Inotropes in Cardiac Arrest Survivors With Ventriculartachycardia/Fibrillation
Authors: Abhishek Dutta, Krunalkumar Patel, Vien T Truong, Avilash Mondal, Mansoor Ahmad, Durgesh Agrawal, Tilachan Parajuli, Chaudry N Majeed, Thomas Metkus, Waqas Qureshi, Sunil Dhar
Journal: Circulation (2023)

Introduction: Cardiac arrest remains a public health crisis with only 10% overall survival rate. Patients with arrest secondary toventricular tachycardia (VT)/ventricular fibrillation (VF) have relatively better survival rates. Post-arrest shock is usuallycardiogenic due to structural defects at baseline. The outcomes of inotrope use in this population is not well known. Hypothesis: We hypothesized that the use of inotropic support is not associated with better survival outcomes. Methods: This is a cohort study of 387 cardiac arrest patients in a tertiary care center enrolled from January 2012 to December2016 who were able to survive for 24 hours post-cardiopulmonary resuscitation after a VT/VF arrest. We compared thebaseline characteristics and 30-day outcomes of cardiac arrest patient who required inotropes and who did not requireinotropes. Results:Out of 338 cardiac arrest survivors with VT/VF arrest, 99 (29.3%) patients were treated with inotropes. 90 (90.9%) ofpatients in the inotrope group were simultaneously on vasopressors. 30-day mortality was higher (67.7%) in theinotrope group compared to patients with no inotrope use (46.2%). The neurological outcome was worse (cerebralperfusion category ≥3) in patients on inotropes (86.9 vs 63.6%). Conclusions: We observed that mortality was higher in VT/VF cardiac arrest survivors who were on inotropes. These patients hadhigher incidence of vasopressor use and were more likely hemodynamically unstable. Further studies are needed toinvestigate the use and outcomes of inotropes in these subsets of patients.
Abstract 13208: A Small Molecule Macrophage Migration Inhibitory Factor Agonist Ameliorates Age-Related Myocardial Intolerance to Ischemia-Reperfusion Insults <i>via</i> Metabolic Regulation
Authors: Hao Wang, Lily Slotabec, Steven Didik, Adewale James, Ji Li
Journal: Circulation (2023)

Introduction: The macrophage migration inhibitory factor (MIF) is emerged as a critical mediator during myocardia ischemia and reperfusion (I/R). An impaired MIF signaling is occurred in aging. MIF agonist, MIF20, can argument cardiac MIF signaling through increasing the binding affinity between MIF and its receptor, CD74/CD44. Hypothesis: Administration of MIF20 can increase the resistance of aged myocardium to ischemic insults caused by I/R via modulating the MIF signaling regulated energy metabolism. Methods: Young (3-5 months) and aged (24-26 months) wild-type C57BL/6J mice, cardiomyocyte specific MIF knock out C57BL/6J mice (cMIF-/-) and wild type littermates (MIF flox/flox ) were injected with MIF20 (0.15 μg/kg, I.V.) 5 minutes before reperfusion after 45 minutes of ischemia. The left ventricular myocardium was for immunoblotting, NAD/NADH assay, and metabolomics analysis. The working heart perfusion and the SeaHorse system were for metabolic measurements. Results: The small molecule MIF agonist, MIF20, which binds to MIF to increase signaling through its cognate receptor CD74/CD44 not only decreases infarct size but also preserves cardiac systolic function in the aged versus young hearts. MIF20 contributes to the maintenance of mitochondrial fitness and preserves the contractility of cardiomyocytes under hypoxia and reoxygenation stress. These beneficial effects of MIF20 are reduced in cardiomyocyte-specific MIF knock-out (cMIF -/- ) versus littermates (MIF flox/flox ) mice, supporting the autocrine role of MIF in mediating ischemic cardiac protection. The age-related disruption of metabolic homeostasis in aged versus young hearts was modulated by MIF20’s ability to upregulate glucose oxidation and downregulate the oxidation of fatty acid. These actions were associated with an upregulation of pyruvate dehydrogenase kinase 4 (PDK4) and downregulation of Long-chain acyl-CoA dehydrogenase (LCAD). MIF20 as MIF signaling agonism modulation of metabolic adaptation in aged hearts further led to reduced generation of reactive oxygen species (ROS) in the myocardium. Conclusions: MIF agonists such as MIF20 may have a therapeutic role by limiting cardiac damage and rescuing cardiac dysfunctions of senescent hearts to I/R stress.
Abstract 12902: Supraventricular Tachycardia During Pregnancy is Independently Associated With Adverse Obstetrical Outcomes
Authors: Alexandra Bekiaridou, Kristie M Coleman, Nikhil Sharma, Deepika George, Yan Liu, Eugenia Gianos, Stacey E Rosen, Jennifer H Mieres, Stavros Mountantonakis
Journal: Circulation (2023)

Introduction: Supraventricular tachycardias (SVT) are the most frequently encountered arrhythmias in pregnancy, however, their clinical significance is unclear. Hypothesis: We report the prevalence, describe the management and explore the association between SVT and adverse obstetric outcomes in women with structurally normal hearts. Methods: This is a case-control study of primiparous and multiparous women without history of cesarean section (CS), and no known cardiac diagnosis admitted in labor to one of 8 Northwell Health hospitals between January 2015 and August 2022. The study group consisted of women with at least one SVT episode during pregnancy and the control group was randomly selected in a 4:1 ratio. Multivariate analysis was used to examine the association between occurrence of SVT during pregnancy and incidence of cesarean section (CS), preterm labor (PTL), and length of stay (LOS). Results: Of 141,769 women meeting the inclusion criteria, SVT diagnosis was confirmed in 122. Of those, 76 (age 33.2±4.8 years) had at least 1 symptomatic episode during pregnancy. For the women with known SVT diagnosis prior to pregnancy, medical therapy with any antiarrhythmic agent was not associated with reduction of SVT recurrence during pregnancy (OR 1.07, 95% CI 0.41-2.80 p=0.89). On the contrary, catheter ablation prior to pregnancy was associated with significant reduction of SVT recurrence (OR 0.09, 95% CI 0.04-0.23, p&lt;0.0001). Women with SVT during pregnancy had a higher incidence of CS (39.5% vs 27.0%. p=0.03), and PLT (30.3% vs 8.6%, p&lt;0.001) compared to the control group. After adjusting for age and parity, SVT during pregnancy was independent predictor of CS, particularly elective CS (OR 2.89 95% CI 1.06-7.89) and PTL (OR 4.37 95%CI 2.30-8.31). Conclusions: SVT occurs in about 1 in every 1,000 women during pregnancy and is associated with higher rates of CS, particularly scheduled, and PLT. Any history of SVT should be sought and addressed during preconception counselling and SVT episodes during pregnancy should be approached in a multidisciplinary way to mitigate the risk of CS and associated complications.
Abstract 14123: Cardiovascular Disease Incidence Among Female Veterans by Sexual Orientation and Race
Authors: Meredith S Duncan, Carl G Streed, Kory R Heier, John R O'Leary, Melissa Skanderson, Joseph L Goulet
Journal: Circulation (2023)

Introduction: Studies of cardiovascular disease (CVD) in sexual minority (SM) women (i.e., lesbian, bisexual) vs. heterosexual women are limited by small sample sizes and lack of objective CVD ascertainment. Small samples also hinder study at the intersection of race and sexual orientation on CVD events. We used the Veterans Healthcare Administration Lesbian, Gay, Bisexual, Transgender Electronic Health Record cohort to fill these knowledge gaps. Methods: We studied 132,571 female cisgender veterans who were free of prevalent CVD and classified as SM or non-SM by a natural language processing tool. We defined incident CVD as first instance of AMI, ischemic stroke, cardiac revascularization, or CVD death between baseline and date of death or 8/31/22. We stratified sample statistics by SM status and race. We used Cox proportional hazards regression to assess the intersection of sexual orientation and race with incident CVD; we adjusted for Hispanic ethnicity and age. Based on the minority stress model, non-SM White women were the referent. Results: Within races, traditional CVD risk factors were similarly distributed by SM status but SM women had greater prevalence of stress-associated characteristics like substance use, depression, and anxiety. Regardless of sexual orientation, Asian women had lower CVD risk than non-SM White women, while Black/African American women had persistently increased CVD risk ( Table ). White lesbians had increased CVD risk vs. their non-SM counterparts. Unclassified SM women of American Native race or multiple races also had increased CVD incidence vs. non-SM White women. Conclusion: This is one of the first studies to examine the intersection of sexual orientation and race on CVD risk in female veterans. CVD risk appears increased or decreased in certain racial groups regardless of sexual orientation but this is not always true and invites further study into the mechanisms by which stress results in inequitable CVD events across groups.
Abstract 11812: Cardiopulmonary Exercise Test and Atrial Fibrillation in Obstructive Hypertrophic Cardiomyopathy: A Study From Septal Myectomy Patients
Authors: Tao Lu, Shuiyun Wang
Journal: Circulation (2023)

Background: Cardiopulmonary exercise test (CPET )is currently used to quantify functional limitation and to evaluate the indications for surgery among patients with hypertrophic cardiomyopathy (HCM). Patients with HCM often have atrial fibrillation (AF) and their relationship is not clear. Objective: To investigate the function limitation among HCM patients who meet indications for septal myectomy and the association between it and AF. Method: We reviewed 565 consecutive patients who underwent myectomy from February 2019 to October 2021, of which 212 did CPET and 24h Holter before surgery. Results: In this cohort (median age: 50.55(37.6-58) years; male: 126(59.4%); left ventricular outflow tract gradient (LVOTG)≥ 50 mmHg: 190(89.6%)), there was a severely impaired function (Peak Oxygen consumption (Peak VO2): 16.44 ± 4.02 ml/min/kg, adjusted Peak VO2%: 58.27%). Comparing different groups divided by Peak VO2, the lowest group was characterized by older age (58 vs 50 vs 43.9 years, p &lt; 0.001), more female patients (57.7% vs 38% vs 25.7%, p &lt; 0.001), higher NT-proBNP level (1299 pg/ml vs 1049 pg/ml vs 742.5 pg/ml, p = 0.004), and larger left atrial diameter (46.8mm vs 43.77 mm vs 42.71 mm, p &lt; 0.001). The incidence of AF also significantly increased (30.98% vs 14.08% vs 7.14%, p &lt; 0.001). Among various indicators of CPET, Peak VO2 showed the strongest correlation with AF (point-biserial correlation coefficient: -0.347, p &lt; 0.001; 0.2279, p = 0.011; -0.2502, p &lt; 0.001; for Peak VO2, ventilatory efficiency, and anaerobic threshold, respectively). Additionally, the incidence of AF decreased with increasing severity of obstruction (60% vs 33.3% vs 16.2% vs 7.1% among non-obstructive, 30≥maximum LVOTG &lt; 50 mmHg, 50≥LVOTG &lt; 100 mmHg, &gt;100 mmHg patients, respectively, p = 0.001). In multivariate regression analysis adjusting for age, sex, BMI, and left atrial diameter, Peak VO2 and LVOTG remained independently associated with the development of AF (OR 0.854, 95% CI 0.743-0.973, p = 0.021 and OR 0.969, 95% CI 0.949-0.987, p = 0.002, respectively). Conclusions: CPET indicator, particularly PeakVO2, was independently associated with the occurrence of AF in eligible surgical patients with HCM. We also found that the higher extent of obstruction, the lower the incidence of AF.
Abstract 13959: A Role for Striated Muscle Nuclear Receptor Co-Regulator RIP140 ( <i>Nrip1</i> ) in the Control of Endurance Fitness
Authors: Elizabeth K Pruzinsky, Tsunehisa Yamamoto, Kirill Batmanov, Tejvir Khurana, Daniel P Kelly
Journal: Circulation (2023)

During the development of heart failure (HF), the capacity for myocardial fatty acid oxidation (FAO) and oxidative phosphorylation is reduced, leading to an energy-starved state. Similar metabolic derangements occur in skeletal muscle during HF and with physical inactivity associated with chronic disease states. Receptor Interacting Protein 140 (RIP140) is a nuclear receptor co-regulator that has been shown to repress the transcription of genes involved in mitochondrial energy transduction in highly metabolic tissues. We recently demonstrated that striated muscle-specific RIP140 KO mice (str-RIP140 -/- ) were protected against the development of HF and had an adaptive form of cardiac hypertrophy (PMID: 36927960). To assess the impact of RIP140 deficiency on skeletal muscle function, we conducted physiological and genomic interrogation of str-RIP140 -/- mice. We found that the str-RIP140 -/- mice display an endurance performance phenotype. Specifically, str-RIP140 -/- mice run significantly longer on an endurance treadmill regimen (str-RIP140 -/- = 118.0 min, WT= 73.38 min; p= &lt;0.0001) with increased VO 2max compared to controls (str-RIP140 -/- = 9779 ml/kg/hr, WT= 7748 ml/kg/hr; p= &lt;0.0001). Respiratory Exchange Ratio (RER) was maintained at a decreased level during exercise in str-RIP140 -/- mice vs controls, indicative of increased utilization and capacity for FAO. The response of str-RIP140 -/- mice to endurance exercise training was also assessed. str-RIP140 -/- mice achieved a greater VO 2max following 8 weeks of training compared to control trained mice (str-RIP140 -/- = 9589 ml/kg/hr, WT= 8366 ml/kg/hr; p= 0.002). RNA-sequence analysis comparing RIP140 -/- and control fast-twitch muscle (EDL) prior to and following exercise training identified differentially upregulated genes involved in an array of pathways activated with endurance training including mitochondrial FAO, triglyceride turnover, the slow-twitch fiber program, angiogenesis, and components of the neuromuscular junction. We conclude that RIP140 serves as a co-repressor of a network of genes involved in skeletal muscle endurance. These results suggest that RIP140 could prove to be a target for novel metabolic therapies aimed at cardiac and skeletal muscle diseases.
Abstract 17536: Real World Analysis from the "Fast STEMI" Registry on Adherence and Discontinuation of Statin Therapy Within 6 Months After ST-Elevation Myocardial Infarction on First Year Follow-Up: Prognostic Impact and Predictors of Adherence
Authors: arianna morena, Federico Giacobbe, Umberto Annone, Emanuele Ravetti, umberto di vita, Giuseppe Giannino, Mattia Troncone, Ludovica Carmagnola, Veronica Dusi, Marco Nebiolo, Ovidio De Filippo, Francesco Bruno, Fabrizio D'Ascenzo, Massimo Giammaria, Gaetano Maria De Ferrari
Journal: Circulation (2023)

Background: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world patients is understudied. Objectives: to identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. Methods: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7±1,6 years; 299 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. Results: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI. After univariate and multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Statin discontinuation within 6 months showed an increase of both cardiovascular (5% vs 1.7%; HR 2.23; 95%CI 1.37-3.65; p=0,001) and all-cause mortality (14.8% vs 5.1%, HR 2.32; 95%CI 1.73-3.11; p&lt;0,001) at 1 year follow-up. Regarding cardiovascular outcomes, statin optimal adherence (&gt;80%) reduced ischemic stroke incidence (1% vs 2.5%, p=0.001) and both cardiovascular and all-cause death (0.1% vs 4.6%; 0.3% vs 13.4%; p&lt;0.001) at 1 year follow-up. Age over 75 years old, chronic renal failure, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. Conclusions: In our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke. This analysis confirmed the predictive factors of adherence and discontinuation therapy already described in literature.
Abstract 18179: Metabolic Biomarker Signatures for Incident Heart Failure Hospitalisation Compared to Different Types of Cardiovascular Events: Evidence From NMR Metabolomics in 250,000 Individuals
Authors: Peter Wurtz, Heli Julkunen, Sara Lundgren, Kirsten Schut, Sini Kerminen, Jeffrey Barrett
Journal: Circulation (2023)

Introduction: Metabolomic biomarker profiling by Nuclear Magnetic Resonance (NMR) is a powerful technique to examine molecular signatures for heart failure risk and clarify pathological differences to cardiovascular outcomes. Hypothesis: Blood lipids and metabolite biomarkers may differ in how they relate to prediction of heart failure vs coronary and stroke outcomes. Methods: We measured detailed plasma lipids and metabolites by NMR metabolomics in ~250,000 individuals from UK Biobank. We assessed shared and discordant biomarkers for heart failure hospitalisation in relation to myocardial infarction, ischemic stroke, peripheral artery disease, cardiac arrest and cardiovascular death. During 10 years of follow-up, 7.800 incident heart failure hospitalisation events occurred and 5-10.000 incident events for cardiovascular outcomes. Results: The overall pattern of biomarker associations differed for heart failure compared to for example, myocardial infarction, with biomarkers of LDL metabolism and apolipoprotein being especially discordant (Figure). In contrast, biomarkers of chronic inflammation and circulating fatty acids were concordant for the risk of heart failure and myocardial infarction. There were also prominent differences in the metabolic biomarker signatures for the risk of different types of cardiovascular diseases, such as between chronic ischemic heart disease, and different types of stroke. The biomarker association magnitudes were strongest for cardiovascular mortality and especially strong for short time to event onset. Conclusions: Heart failure and different cardiovascular endpoints have partly different metabolic biomarkers signatures. These may represent pathophysiological differences and have relevance for cardiovascular risk prediction, especially if using the five-point major adverse cardiovascular event definition.
Abstract 15644: A Systematic Review and Meta-Analysis Exploring Impact of Beta-Blocker Therapy on Long Term Mortality in Takotsubo Cardiomyopathy
Authors: Muhammad Junaid Ahsan, Soban Ahmad, Amman Yousaf, Mariam Dvalishvili, Behram A Khan, Muhammad Z Ahsan, Ammad Naeem, Ahmed H Qavi, Gardar Sigurdsson, Andrew M Goldsweig
Journal: Circulation (2023)

Introduction: Conflicting data exist regarding the effects of beta-blocker (BB) therapy on long-term survival in Takotsubo cardiomyopathy (TC). This study aims to address this gap by examining the potential impact of BB therapy on long-term mortality in patients with TC. Methods: We searched Pubmed (MEDLINE), Google Scholar, and EMBASE for relevant studies from inception to May 18 th , 2023. We included observational studies reporting the impact of BB use on all-cause mortality during long-term follow-up in patients with TC. Hazard ratios (HRs) of all-cause mortality with their 95% confidence interval (CI) for beta-blocker use were extracted. Study-specific estimates were pooled using an inverse-variance, random-effects model. Results: We identified seven eligible studies enrolling 3,446 patients with TC with a mean follow-up duration of up to 5.8 years. The primary meta-analysis for long-term all-cause mortality combining all HRs showed significant long-term mortality reduction with BB use (HR=0.62; 95%CI [0.50-0.79], P&lt;0.0001, I 2 =10%). Similarly, pooled analysis of adjusted HRs for long-term all-cause mortality demonstrated improved survival with BB therapy (HR=0.61; 95%CI [0.43-0.88], P=0.008, I 2 =33%) (Figure 1). Conclusions: Observational data suggest that the use of BB therapy is associated with a significant improvement in long-term survival in patients with TC. Randomized control trials should be performed to evaluate this effect further.
Abstract 13979: Titin-Truncating Variants Predispose to Dilated Cardiomyopathy in Patients Genetically Similar to African Reference Populations
Authors: John Depaolo, Marc Bornstein, Renae Judy, Michael Levin, Zoltan Arany, Scott M Damrauer
Journal: Circulation (2023)

Introduction: Heterozygous mutations within the TTN gene can cause the translation of shortened forms of the titin protein known as titin-truncating variants (TTNtvs) leading to dilated cardiomyopathy (DCM) among certain individuals. We previously reported an odds ratio (OR) of 18.7 for DCM among individuals genetically similar to the European reference population (EUR) with high percentage spliced in (hiPSI) TTNtvs, however we were unable to show a similar relationship among individuals genetically similar to the African reference population (AFR). Methods: Penn Medicine Biobank volunteers with whole exome sequencing were screened for TTNtvs with minor allele frequency &lt;0.001 and percent spliced in &gt;0.9. Participants were also screened for a DCM diagnosis defined using International Classification of Diseases, ninth and tenth revision diagnoses codes. Left ventricular ejection fraction (LVEF) values were extracted from structured transthoracic echocardiography reports. Logistic and linear regression were employed to evaluate the association between hiPSI TTNtvs and DCM or LVEF adjusting for age, sex, and first five genetic principal components. Results: Of the 43,731 participants with sequencing data, 11,136 (27.1%) were genetically similar to the AFR reference population, 50.3% were male, and the median age was 57.8 years (IQR: 44.9-69.5 years). One percent (418 individuals) had a hiPSI TTNtv. The age- and sex-adjusted OR of having DCM was similar among AFR and EUR participants carrying hiPSI TTNtvs (AFR OR: 4.37, 95% CI 2.68 to 7.13, P &lt; 0.001; EUR OR: 5.86, 95% CI 4.58 to 7.49, P &lt; 0.001; meta OR: 5.48, 95% CI 4.31 to 6.97, P &lt; 0.001). Among those individuals with echocardiography data available, hiPSI TTNtvs were associated with significantly decreased minimum LVEF independent of genetic reference population similarity (EUR β: -10.08, 95% CI -12.71 to -7.44, P &lt; 0.001; AFR β: -12.83, 95% CI -18.39 to -7.27, P &lt; 0.001; Meta β: -10.58, 95% CI -12.96 to -8.20, P &lt; 0.001). Conclusions: Our analysis demonstrates a strong association between hiPSI TTNtv and both DCM and minimum LVEF in diverse populations suggesting that genetic testing and counseling recommendations should not differ between these populations.