tbuckley/cabot-search huggingface dataset:
Abstract 4140218: Trends and Determinants of Outcomes in STEMI Patients with COVID-19: A Nationwide Analysis, 2020-2021
Authors: Rahul Singh, Shalini Selvam, Dawid Ozga, Marc Sukhoo-Pertab, Aleksandre Toreli, Sudhanva Hegde
Journal: Circulation (2024)

Background: Prior data indicated a reduction in mortality among STEMI (ST-elevation myocardial infarction) patients with COVID-19 from 2020 to 2021 in the United States. Objective: To describe national trends and determinants of outcomes among STEMI patients with COVID-19 from 2020-2021. Methods: A retrospective cohort study was conducted using the 2020-2021 Nationwide Inpatient Sample of adults diagnosed with STEMI and COVID-19, assessing in-hospital mortality and the use of percutaneous coronary intervention (PCI), mechanical ventilation, and mechanical circulatory support (MCS). Results: The study included 6,195 STEMI patients with COVID-19 and revealed stable mortality (18% in 2020 to 21% in 2021, p =0.06). Demographic shifts occurred, with White patients increasing from 52% in 2020 to 66% in 2021 ( p &lt;0.01). Mechanical ventilation increased in 2021 (Adjusted Odds Ratio [aOR] 1.75; p &lt;0.01). Compared to White patients, 'Other' race patients had higher odds of mortality (aOR 2.46; p =0.01). Compared to Medicare beneficiaries, Medicaid recipients demonstrated a reduced risk of mortality (aOR 0.47; p =0.02), as did individuals residing in the highest income quartile zip codes compared to the lowest (aOR 0.54; p =0.03). Asian/Pacific Islander patients were less likely to receive PCI (aOR 0.43; p =0.03). Increased MCS was noted in Black (aOR 1.78; p =0.03), Hispanic (aOR 1.87; p =0.01), and 'Other' race patients (aOR 3.78; p &lt;0.01). Conclusion: This study found no statistically significant change in mortality among STEMI patients with COVID-19 from 2020 to 2021. The findings highlight persistent challenges and the need to improve the equity and effectiveness of cardiac care.
Abstract 4140636: Mapping Ventricular Arrhythmogenic Substrates: Insights from Electroanatomic and Cardiac Magnetic Resonance in Ischemic and Non-Ischemic Cardiomyopathies
Authors: Morgan Casper, Hannah Bernstein, Sasha Rosen, Soren Borgardt, Alexandra McCann, Ahmadreza Ghasemiesfe, Uma Srivatsa
Journal: Circulation (2024)

Background: Electroanatomic mapping (EAM) and cardiac magnetic resonance (CMR) identify substrates using parameters from ischemic cardiomyopathy (ICM). CMR's application to characterize scar in non-ischemic dilated cardiomyopathy (NIDCM) is limited. Objective: To assess scar burden and patterns in patients with VA and NIDCM or ICM and the concordance between CMR and EAM. Methods: We reviewed 27 patients with VA ablations (NIDCM and ICM) and prior CMR. ARVC, HCM and infiltrative diseases were excluded. Scar type and morphology were classified (table 2). Myocardial late gadolinium enhancement (LGE) (&gt; 2SD or 3SD) and T1 values were compared to remote myocardium. EAM defined bipolar scar &lt;1.5 mV and unipolar scar &lt;8.3 mV. Scar locations were assigned using the AHA 17-segment model. Cohen’s Kappa coefficient was used to assess categorical agreement of scar severity between CMR and EAM (table 4). Results: Scar distribution in NIDCM was predominant in the mid-myocardial septum and ICM in the sub-endocardium (p &lt;0.001). ICM patients had higher presence of posteromedial papillary muscle scar (p=0.001). The difference in myocardial T1 values at the mid-chamber and mid-septum was not significant, likely influenced by the mid-LV chamber short axis cut. The right ventricle was dilated with reduced function and non-compacted myocardium was thicker in NIDCM. Bipolar scar was predominant in AHA segments 1-3 and 9-10 for NIDCM patients and AHA segments 3-12 in ICM patients. AHA segments 4 and 8-12 had fair correlation between bipolar EAM and CMR. Unipolar mapping showed slight agreement in segments 1-6, 9, 11, 13, 15 and 16. Conclusions: Scar is predominant in the mid-myocardial septum in NIDCM compared to subendocardial location in ICM. Comparing CMR, EAM at best correlate fairly to midventricular segments in bipolar map slightly to most segments in unipolar map. Improved mapping tools will likely improve ablation success.
Abstract 4140066: In ACS patients within 4 hours of pain to balloon time, the impact of no-reflow after PCI and ultrasound attenuation as detected by intravascular ultrasound on the incidence of no-reflow.
Authors: Kazunobu Iidaka
Journal: Circulation (2024)

Background: The no-reflow has been reported to be associated with larger infarct size and mortality after acute myocardial infarction (AMI). A pathological classification of no-reflow was proposed: structural no-reflow—microvessels within the necrotic myocardium exhibit loss of capillary integrity (it is usually irreversible)—and functional no reflow—patency of microvasculature is compromised due to distal embolization, spasm, ischemic injury, reperfusion injury. It may be reversible. After about 6 hours of AMI, myocardial necrosis occurs, which leads to the coronary microcirculation to injury which contribute to no-reflow. The rate of no-reflow was lower in patients presented with AMI, who had reperfusion in less than 4 hours. In AMI within 4 hours of pain-to-balloon time, the proportion of reversible causes of no-reflow may be higher compared to irreversible causes. The incidence of no-reflow was higher in patients with attenuated plaque ≥5 mm in length as evaluated by intravascular ultrasound (IVUS). Objective: The aim of this study was to evaluate the effects of no-reflow after PCI and the association between attenuation plaque as detected by IVUS and no-reflow in ACS patients within 4 hours of pain-to-balloon time. Methods and Results: We retrospectively evaluated 77 ACS patients within 4 hours of pain-to-balloon time between December 2020 and March 2022. Patients were divided into the reflow group (final TIMI 3) (n = 58) and the no-reflow group (final TIMI &lt; 3) (n = 19). The median peak creatine kinase (CK) level was significantly higher in the no-reflow group compared to the reflow group (3754 IU/L [IQR: 4155] vs. 1712 IU/L [IQR: 2849]). Blood pressure decrease during PCI was significantly more pronounced in the no-reflow group (47.4% vs. 8.6%, p &lt; 0.001). The proportion of low attenuation plaque observed by IVUS with a length of ≥5 mm was significantly higher in the no-reflow group compared to the reflow group (52.6% vs. 25.5%, p = 0.032). The proportion of low attenuation plaque with an angle of ≥180 degrees was significantly higher in the no-reflow group compared to the reflow group (68.4% vs. 41.2%, p=0.043). Conclusion: In ACS patients within 4 hours of pain-to-balloon time, the peak CK and the decrease in blood pressure during PCI were significantly greater and the proportion of low attenuation plaque with a length of ≥5 mm and an angle of ≥180 degrees were significantly higher in the no-reflow group.
Abstract 4139912: Inflammatory biomarkers in people treated with tirzepatide living with overweight or obesity, without and with T2D: a post-hoc analysis from SURMOUNT-1 and SURMOUNT-2
Authors: Naveed Sattar, Subodh Verma, Harald Sourij, Jonathan Wilson, Adam Stefanski, xiaotian zhang, Ryan Griffin, Giacomo Ruotolo, Bruno Linetzky
Journal: Circulation (2024)

Background: Tirzepatide (TZP) is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D) and obesity. This post hoc analysis examined biomarkers of inflammation in people living with obesity, or overweight, without and with T2D, from SURMOUNT-1 and SURMOUNT-2. Furthermore, we evaluated the contribution of weight reduction- associated and - unassociated effects on biomarkers of inflammation. Methods: A total of 700 participants were randomly selected from SURMOUNT-1 and SURMOUNT-2 (100 participants from each treatment arm: placebo, 5, 10, and 15 mg in SURMOUNT-1 and placebo, 10 and 15 mg in SURMOUNT-2). The association of treatment with change from baseline in the inflammation biomarkers interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP) at 24 and 72 weeks was assessed along with the estimated percentages of the association attributable to weight loss through a mediation analysis. Results: In SURMOUNT-1, following 72 weeks of treatment with TZP without T2D, TZP was associated with significantly decreased IL-6 (-26% to -31%) and hsCRP (-51% to -65%), compared to placebo in all dose groups. In SURMOUNT-2, following 72 weeks of treatment with TZP in participants with T2D, changes of -16% to -23% in IL-6 and -55% to -56% in hsCRP were observed (significance seen for all groups except for TZP 15mg on IL-6). At 24 weeks, only 18% and 31% of hsCRP changes were associated with weight reduction in SURMOUNT-1 and -2, respectively. In SURMOUNT-1, 77% of IL-6 changes and 87% of hsCRP changes at 72 weeks were associated with weight reduction. In SURMOUNT-2, 78% of IL-6 changes and 57% of hsCRP changes at 72 weeks were associated with body weight reduction. Conclusions: In this post hoc analysis of SURMOUNT-1 and -2, early changes in hsCRP (week 24) were weight reduction-unassociated, while at week 72, changes in the inflammation biomarkers IL-6 and hsCRP observed in TZP-treated participants were mainly weight reduction-associated. The relative contribution of weight reduction-dependent effects was more prominent in participants without T2D, compared to those with T2D. Collectively, these data suggest TZP was associated with reduced inflammation in people with overweight/obesity and/or T2D.
Abstract 4139822: Adipocyte TRPM7 promotes aortic dissection by accelerating SMC phenotype switching
Authors: Mi Wang, Min Gao
Journal: Circulation (2024)

Background: Aortic dissection (AD) is a life-threatening condition with high mortality. It initiates from an acute intimal tear, which allows a large amount of blood to penetrate into media, leading to the formation of intramural hematoma or false lumen. Digging into and unravelling the pathogenesis of AD will aid in exploring novel therapeutics for AD. The major characteristics of AD is degeneration of aortic wall architecture. Particularly, the phenotypic switching of VSMCs and enhanced tissue inflammation are pivotal steps of AD progression. Studies have shown that upregulation of Trpm7 triggers the phenotypic switching of VSMCs. Perivascular adipose tissue (PVAT) harbors mature adipocytes that regulate vascular function physiologically and pathologically. Inflammatory cytokines secreted from PVAT promotes VSMC phenotypic switching. This study aims to explore whether the adipocyte TRPM7-mediated Ca2+ could uncouple Bip-IRE1a and perturb the inhibition of Bip on IRE1a, inducing PCG1a mRNA decay and inflammatory cytokines secretion, thus promoting VSMC phenotypic switching and the development of AD. Methods: Mouse breeding. Trpm7fl/fl mice were cross-bred with Ap2-Cre mice to generate adipocyte-specific Trpm7 KO mice. Mouse genotyping. Genomic DNA was extracted from the mouse tail for PCR to validate the genotype of mice. Establishment of BAPN-induced TAD mouse model. 3-week-old mice was administered with BAPN intragastrically (1g/kg/day) for 4 weeks. H&amp;E staining. Different segments of mouse aorta were subjected to H&amp;E staining to examine the lesions. EVG staining. Different segments of mouse aorta were subjected to EVG staining to examine the aortic wall architecture. Real-time quantitative PCR (qPCR). The expression level of inflammatory genes and VSMC contractile genes, including IL1b, TNF-a, Acta2, Cnn1, Tagln, S100A4, as well as Trpm7 were assessed by qPCR. Results: Adipocyte-specific Trpm7 KO mice (Trpm7fl/fl ; Ap2-Cre ) were successfully generated and each genotype was validated by PCR. BAPN-induced TAD mouse model was successfully established. The mortality rate reached to 50-80%. Adipocyte-specific deletion of Trpm7 hindered inflammation and the development of TAD effectively. Trpm7 inhibitors FTY720 hindered the progress of TAD significantly. Conclusion: Adipocyte-specific deletion of Trpm7, as well as Trpm7 blockers FTY720 markedly ameliorates TAD, suggesting that Trpm7 enhances TAD progression.
Abstract 4140020: Sex-Based Disparities in Cardiopulmonary Exercise Testing Response Among Patients with Postural Orthostatic Tachycardia Syndrome
Authors: Salaheddin Sharif, Thomas Olson
Journal: Circulation (2024)

Introduction: Postural orthostatic tachycardia syndrome (POTS) is a chronic syndrome with symptoms of orthostatic intolerance, tachycardia, and exercise intolerance. POTS predominately affects young females, with notable variations in incidence and manifestations between females and males. Limited data exist on sex differences in the response to cardiopulmonary exercise test (CPET) in patients diagnosed with POTS. Methods: Retrospective analysis of 307 POTS patients who underwent CPET between 2000 and 2023 at Mayo Clinic. Diagnosis of POTS was confirmed by tilt-table testing with a sustained increase in heart rate (HR)≥ 30 bpm or HR&gt;120 bpm 10-min post-tilt and without orthostatic hypotension. Patients were grouped by sex (male: n=48 and female: n=259). Predicted peak values were calculated and independent t-tests were used to compare between-group differences. Results: There were no significant differences between males and females for age (28±8 vs 27±7, years) or body mass index (24±5 vs 24±5, kg/m 2 ) (both p&gt;0.05). The time between diagnosis and CPET was not significantly different between males and females (21±113 vs 44±280 days, p&gt;0.05). Resting HR was lower in male patients (76±17 vs 85±18 bpm, p&lt;0.05). At peak exercise, there was no difference in respiratory exchange ratio (1.18±.2 vs 1.17±0.1, p&gt;0.05). Males had significantly lower peak HR (171±22 vs 176±19 bpm) and lower percent (%) predicted peak HR (88±12 vs 93±13 %) (both p&lt;0.05) compared to females. Peak oxygen consumption (VO 2 peak) was significantly higher in males (29.2±8 vs 24.9±7 mL/kg/min), however; % predicted VO 2 peak was lower in males (65±17 vs 71±18 %) (both p&lt;0.05). Peak oxygen (O 2 ) pulse was higher in males (14±4 vs 9±2 mL/beat, p&lt;0.05) with no difference in % predicted peak O 2 pulse (73±17 vs 78±17 %, p&gt;0.05). Conclusion: These data suggest male patients achieved a lower peak HR, % predicted peak HR, and % predicted VO 2 peak than female patients. Both male and female patients utilized a similar % predicted peak O 2 pulse. These findings suggest male POTS patients demonstrate more impaired exercise tolerance compared to female patients. Additional research is needed to fully elucidate the underpinning physiologic mechanisms responsible for impaired exercise tolerance in POTS and the apparent sex differences in exercise capacity.
Abstract 4140204: Relationship of Oxidized Phospholipids and Lp(a) to Outcomes after Acute Coronary Syndrome: A Post Hoc Analysis of the ODYSSEY OUTCOMES Trial
Authors: Sotirios Tsimikas, Michael Szarek, Christa Cobbaert, Esther Reijnders, J Jukema, Deepak Bhatt, Vera Bittner, Rafael Diaz, Sergio Fazio, Genevieve Garon, Yuan Chong, Xiaomin Gong, Shaun Goodman, Robert Harrington, Harvey White, Andreas Zeiher, Philippe Steg, Gregory Schwartz
Journal: Circulation (2024)

Background: Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles. Objectives: To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment. Methods: OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log 2 -transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable. Results: Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p&lt;0.001). At 4-months, ALI reduced median (IQR) PBO-corrected OxPL-apoB by 15%, P&lt;0.001. In the placebo group, when analyzed in separate models with multivariable adjustment, pre-randomization OxPL-apoB (HR (95% CI) 1.081 (1.026-1.139), p=0.003) and Lp(a) (HR (95% CI) 1.080 (1.041-1.120), p&lt;0.001) each predicted MACE. However, when OxPL-apoB and Lp(a) were placed in the same model only Lp(a) remained significant (HR (95% CI) 1.069 (1.023, 1.118), p=0.003). In the alirocumab group, neither baseline OxPL-apoB nor Lp(a) predicted MACE in individual or joint models. Baseline high sensitivity C-reactive protein predicted all-cause death, but OxPL-apoB and Lp(a) did not. Conclusions: In statin-treated patients with recent ACS assigned to placebo, the increased risk of MACE due to elevated OxPL-apoB appears to be mainly driven by their presence on Lp(a). In patients assigned to alirocumab, these variables were not predictive of MACE, suggesting mitigation of OxPL-apoB and Lp(a)-mediated risk by alirocumab.
Abstract 4139933: Hypercholesterolemia and proprotein convertase subtilisin/kexin type 9 potentiate inflammatory response against aortic valve bioprosthetic tissue post-implantation.
Authors: Marine Salle, Guillaume Guimbretière, Pascal Aumond, Benjamin Le Vely, Cedric Le May, Bertrand Cariou, Thierry Le Tourneau, claire toquet, Jean Merot, Jean Christian Roussel, Romain Capoulade
Journal: Circulation (2024)

Introduction: Calcific aortic valve stenosis is the more frequent valvular disease, affecting more than 10% of patients &gt;75 years old. Surgical or transcatheter aortic valve replacement is the only treatment available. There is an increase use of bioprosthetic valves, even if they present a limited durability with the progressive development of structural bioprosthetic deterioration (SVD). Recent clinical studies highlighted an association between circulating lipid factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), Lipoprotein (a) and LDL-cholesterol, and SVD. However, the underlying mechanisms remain unknown. Objective: We aim at deciphering the role of hypercholesterolemia and/or PCSK9 on the early processes leading to SVD. Methods: Subcutaneous implantation of bioprosthetic tissue was performed on 10-week old wild type (WT), PCSK9 knock-out (KO) and PCSK9 overexpressing C57BL/6J mice for 28 days. A qualitative anatomopathological score evaluating cell density, infiltration, and tissue degradation was developed. Infiltrated immune cells were characterized by IHC, with a focus on anti- (CD163+) and pro-inflammatory (F4/80+) macrophages, lymphocytes (CD3+) and polynuclear eosinophils (CCR3+). Results: An important infiltration of mononuclear cells into the explanted punches was observed among the 3 groups (n=10 mice/group). Cell recruitment was more pronounced in mice overexpressing PCSK9 compared to WT and KO. The anatomopathological score of PCSK9 overexpressing mice was significantly higher as compared to WT and KO (7.0 [4.1-8.4] vs 4.0 [3.0-4.5] and 2.8 [2.0-3.9], respectively; p=0.008). The infiltrate was mainly composed of macrophages (CD163+ F4/80+) and polynuclear eosinophils, even if few lymphocytes were observed. Polynuclear eosinophils were more abundant in mice overexpressing PCSK9 compared to WT and KO (p=0.01 and p=0.002). Conclusion: Hypercholesterolemia and/or high PCSK9 level promote the cellular response against the bioprosthetic tissue. It potentiates the infiltration of polynuclear eosinophils and macrophages, pointing out for an exacerbated inflammatory response, post implantation. Deeper cellular/molecular analyses are ongoing to provide mechanistic clues to better understand the link between hypercholesterolemia/PCSK9 and the early inflammatory processes leading to SVD.
Abstract 4140508: Adaptive Cardiac Arrest Training Curriculum for Capacity Building in Northern Ghana: Addressing Contextual Challenges for Sustainability
Authors: Dzifa Ahadzi, Claudia Leung, Rahma Al-Hassan, Yabasin Iddrisu Baba, Abdul-Subulr Yakubu, Annette Cournooh, SCOTT IKEDA, Samuel Alomatu, Patience Sakeah, Laud Boateng, Odalys Rivera Hernandez, Prosper Akanbong
Journal: Circulation (2024)

Background: Structured institutional cardiac resuscitation response training is critical to prepare healthcare workers to respond in emergencies. Best practices require context-adapted training while maintaining quality and fidelity. Resource-limited settings face unique challenges, including deficiencies in basic life support training, limited resources, and a lack of certified trainers. An approach to contextualize training, build capacity, and ensure long-term sustainability is needed. Objective: To describe the adaptive approaches used to implement and scale up in-hospital cardiac arrest response training at a teaching hospital in northern Ghana, addressing specific challenges and focusing on long-term sustainability. Methods: Leveraging an international academic partnership known as AMPATH Ghana, a multidisciplinary team designed an adapted cardiovascular life support training program inspired by the American Heart Association ACLS training. The program was tailored to local challenges, such as resource limitations, knowledge gaps, and institutional capacity (Table 1). Trainers used a combination of didactic learning, hands-on practice, simulations, and structured feedback. Participant surveys assessed the program’s impact and guided subsequent training iterations. Results: 198 healthcare workers were trained over four iterations (74% nurses, 35% medical officers, 1% pharmacists). Before the training, 23.4% of trainees felt very confident in their ability to work effectively in a code situation. This increased to 75.3% post-training (p&lt;0.001). With each iteration, adaptations enhanced training quality and fidelity. Medical officers (general practitioner level) were trained as co-facilitators after the first iteration, and additional resources were developed with institutional support to enhance fidelity and sustainability. Conclusion: Through a bilateral academic partnership, an adaptive approach to contextually appropriate cardiac arrest response training has improved knowledge and healthcare worker confidence in a teaching hospital in northern Ghana. This adaptive approach may be replicated in similar resource-limited settings to effectively and sustainably scale up training and enhance healthcare capacity.