tbuckley/cabot-search huggingface dataset:
Abstract 4136532: The Agonism of Macrophage Migration Inhibitory Factor Modulates Neutrophils Subsets and Rescues an Impaired Tolerance to Ischemic Insults in Aging
Authors: Hao Wang, Shriya Punati, Lily Slotabec, Blaise Seale, Nadiyeh Rouhi, Fernanda Filho, Michael Adenawoola, Ji Li
Journal: Circulation (2024)

Introduction: An impaired cardiac macrophage migration inhibitory factor (MIF) signaling in aging during ischemia and reperfusion (I/R) can be rescued by a MIF agonist, MIF20. Alterations in cardiac metabolic homeostasis cause inflammation under I/R. Thus, MIF agonism with MIF20 could modulate cardiac inflammatory response during I/R. Hypothesis: MIF20 modulates the polarization of neutrophil subset and rescues the impaired immune response under I/R in aging. Methods: Young (3-months)/aged (24 months) C57BL/6 wild type (WT) mice and MIF flox/flox (3 months)/cMIF -/- (cardiomyocyte MIF deletion, 3 months) were subjected to LAD ligation of for 45 min of ischemia, followed by 24 hr of reperfusion. MIF20 (0.15 µg/kg, i.v.) was injected at 5 minutes before reperfusion. The immune cells were determined with flow cytometry. mRNA and protein were measured by real-time qPCR, immunoblotting/cytokine array. Results: Administration of MIF20 reduced myocardial infarct by I/R in young/aged WT and MIF flox/flox but not in cMIF -/- mice. The flow cytometry showed that I/R stress dramatically triggered neutrophils infiltration, which occurred in both left ventricle and right ventricle. Intriguingly, MIF20 treatment reduced the I/R-induced neutrophil recruitment in hearts. Aged versus young WT myocardium recruited more N1 neutrophils (CD206 - ), while MIF20 treatment rescued the impaired N1 neutrophils response in aging. Moreover, MIF20 can increase infiltration of N2 neutrophils (CD206 + ) in both young and aged WT hearts. The recombinant MIF can directly trigger N2 neutrophil polarization and N1 neutrophil reduction in cMIF -/- hearts, indicating the critical role of MIF/CD74 axis in neutrophil polarization by I/R challenge. The cytokine array showed that MIF20 treatment can trigger cardiac TGF-β levels and upregulate IL-10 levels in serum under I/R, since TGF-β and IL-10 are critical factors involved in the N2 neutrophils’ polarization. Interestingly, MIF20 increased SiglecF marker on neutrophils in the aged versus young hearts, suggesting that MIF20 rescue the long-lived neutrophil population (SiglecF high ) which could enhance phagocytosis to repair damaged myocardium during I/R conditions. Conclusions: An impairment of metabolic homeostasis and inflammatory response occurred in cardiac aging. MIF agonism with small molecule MIF20 can rescue the capacity of MIF/CD74 signaling to maintain metabolic homeostasis and inflammatory response in aging under I/R pathological conditions.
Abstract 4136621: Efficacy of Empagliflozin in Heart Failure with Preserved Ejection Fraction is related to the presence of echocardiographic features of diastolic dysfunction in the EMPEROR-Preserved trial.
Authors: Andrew Coats, Javed Butler, Hendrik Zimmet, Stefan Anker
Journal: Circulation (2024)

Introduction: Efficacy of SGLT2i empagliflozin in Heart Failure is seen across the LVEF spectrum and in multiple clinical subgroups, with diverse mechanisms of action. We hypothesized that objective echo evidence of diastolic dysfunction (DD) in HFpEF may predict the response to empagliflozin. Methods: We defined DD as the presence of LAVI ≥34 mL/m 2 , E/e ≥13 or LVMi &gt;115 (males) or &gt;95 (females) and created three categories with 0, 1 or ≥2 DD criteria. We report the impact of baseline DD on response to empagliflozin therapy and adverse effects. Analyses were performed using the intention-to-treat principle. For time-to-first-event analyses, differences in treatment effects across the three DD categories were assessed by a Cox proportional hazards model, with pre-specified covariates of age, gender, region, diabetes, LVEF, and eGFR. Total events were assessed using a joint frailty model, with CV death (CVD) as a competing risk. Results: Of 5988 patients in EMPEROR-Preserved 3766 (63%) had no baseline DD, 1619 (27%) one and 603 (10%) ≥2 measures. The percentage of males decreased as DD category increased, 57.2% for none, 54.2% for one and 46.6% for ≥2, p &lt;0.0001. Other demographic features significantly associated with DD categories were race, ethnicity and region and it was more common with age, with lower HR, DBP, body weight and eGFR. DD was more frequent with ischaemic aetiology and higher LVEF, but not with baseline NT−proBNP, DM or COPD. Time to HHF or CVD showed a progressive treatment effect across the three DD categories (interaction p-value 0.0014), with estimated HR’s of 0.91 (none present), 0.64 (1 present) and 0.49 (&gt;=2). A significant treatment-by-subgroup interaction was also observed for the total number of HHF, with estimated HR’s of 0.95 (none present), 0.52 (1 present) and 0.29 (≥2). In the responder analysis, ≥10 point improvement in KCCQ at week 52 showed a treatment induced change that was consistent across DD categories (interaction p-value 0.92). The safety profile was consistent across DD classes. Conclusions: Baseline echocardiographic DD predicted an improved clinical response to Empagliflozin in a graded fashion, suggesting the mode of action may target specific changes in diastolic performance.
Abstract 4136286: Safety Events with a Large-Bore Aspiration Thrombectomy Device for Pulmonary Embolism: An analysis of the U.S. Food and Drug Administration Manufacturer and User Facility Device Experiences from 2018 to 2024
Authors: Shannon Lee, Logan Schwarzman, Nichelle Megowan, JOSEPH THOMAS
Journal: Circulation (2024)

Introduction: Large bore thrombectomy is increasingly used to treat acute PE. Post-market surveillance using the U.S. FDA Manufacturer and User Facility Device Experience (MAUDE) database may capture serious device adverse events (AE) not described in small pre-market clinical trials. We aim to analyze serious AE associated with use of the Inari Medical (Irvine, California) large bore thrombectomy system to treat PE. Methods: All MAUDE events between January 1, 2018 and May 1, 2024 involving PE treatment with Triever and Flowtriever devices were reviewed and categorized based on device type, incident year, and clinical event. Based on narrative description, AE were placed into categories of cardiac, pulmonary, device malfunction, anemia, and other. Results: A total of 58 AE reports representing 50 unique clinical episodes were included. MAUDE event types were death (n=32), injury (n=23) and malfunction (n=3), and the majority (45/58) involved the larger aspiration catheters (Table 1). Death occurred in 27 of 50 unique episodes. Cardiac injury (n=19) and pulmonary injury (n=18) were most common and included 25 serious perforations. Serious AEs are listed in Table 2. Device malfunction/improper use was rare (n=7) and was not associated with death. Paradoxical embolism was described causing stroke and coronary occlusion. 3 of 4 blood loss AEs occurred prior to 2021. Conclusion: This report includes the largest description of reported AEs with large bore aspiration thrombectomy systems used to treat PE. This report describes serious events, often associated with death, that are likely infrequent and were not detected in pivotal studies or registries. Understanding these AEs may guide future technique and device refinement, and the current findings demonstrate the importance of large post-approval studies.
Abstract 4136346: A Comparative Analysis of Esophageal Cooling for Preventing Esophageal Injury Post Atrial Fibrillation Catheter Ablation: A Systematic Review and Meta-analysis
Authors: Momen Mohamed Ibrahim, Hussam Al Hennawi, Yousef Tanas, Youmna Abourady, Nourhan Sewedan, Ahmed Magdy Hashem, Karam R. Motawea
Journal: Circulation (2024)

Introduction: Thermal injury following atrial fibrillation catheter ablation is a rare but fatal complication. We aim to assess the safety profile of different forms of esophageal cooling methods versus standards of care. Methods: We searched PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials and cohort studies comparing esophageal cooling to Luminal esophageal temperature (LET) monitoring regarding esophageal thermal lesions (ETL) post atrial fibrillation ablation. Case reports, case series, reviews, conference abstracts and animal studies were excluded. Review manager software (version 5.4) was used to perform the meta-analysis. Results: We included 10 studies with 25662 patients in total: 14515 patients in the esophageal cooling group and 11147 patients in the LET group. Overall esophageal lesion analysis demonstrated no statistically significant difference between the esophageal cooling group and LET (RR = 0.72, 95% CI = 0.35 to 1.49, p-value = 0.38). Subgroup analysis showed no statistically significant difference for mild/moderate lesions (RR = 1.52, 95% CI = 0.80 to 2.90, p-value = 0.20). However, the subgroup analysis showed a statistically significant association between esophageal cooling and decreased severity of esophageal lesions compared with LET (RR = 0.29, 95% CI = 0.12 to 0.71, p-value = 0.007). Regarding AF recurrence, the pooled analysis showed no statistically significant difference between esophageal cooling group and LET (RR = 1.24, 95% CI = 0.95 to 1.61, p-value = 0.11). Conclusion: In patients undergoing AF catheter ablation, the implementation of esophageal cooling showed statistical significance in decreasing the severity of esophageal lesions compared to the LET group. Also, esophageal cooling demonstrated non-inferiority in AF recurrence compared to LET. Future research should focus on assessing the long-term effects of esophageal cooling during AF catheter ablation.
Abstract 4136412: Quantitative Cardiac Magnetic Resonance Standardized Signal Intensity Comparison in Dilated Cardiomyopathy versus Cardiac Sarcoidosis
Authors: Ting-Wei Ernie Liao, Lingyu Xu, MirMilad Khoshknab, Paul Mather, Paco Bravo, Benoit Desjardins, Saman Nazarian
Journal: Circulation (2024)

Introduction/Background: Dilated cardiomyopathy (DCM) and cardiac sarcoidosis (CS) manifest unique late gadolinium enhancement (LGE) patterns on cardiac magnetic resonance (CMR), indicative of differing distributions of myocardial scar tissue. Nevertheless, these LGE patterns lack specificity, leading to significant overlap between the two conditions. Goals/Aims: This study seeks to introduce a novel quantitative method employing z-score analysis of LGE-CMR signal intensity to objectively evaluate and compare the spatial distribution of LGE intensity between DCM and CS. Methods/Approach: The retrospective cohort included 22 NICM patients (13 DCM, 9 CS) that underwent pre-procedural CMR prior to ventricular tachycardia (VT) ablation between November 2018 to May 2023. LGE images were delineated into sub-endocardial, mid-myocardial, and sub-epicardial layers, categorized into anterior, lateral, inferior, and septal walls based on the AHA 17 segment model for LV myocardial segmentation. CMR signal intensities were standardized as z-scores: z = (x−μ)/σ, where x is the MRI signal intensity for a specific myocardial segment and layer, and μ and σ are the mean and standard deviation across all myocardial segments and layers of the LV, to characterize regional intensity variations. Results/Data: Compared to patients with DCM, those with CS exhibited significantly higher CMR signal intensity z-scores in the septum (β=0.32, p=0.009), particularly in the endocardial third of the right ventricular side (β=0.56, p=0.001). A z-score greater than 0.40 in this area was associated with a CS diagnosis, with an area under the ROC curve of 0.692 in 5-fold cross-validation. Conclusions: Patients with CS exhibit higher affinity for contrast in the septum, particularly on the RV endocardium. Standardized analysis of CMR signal intensities provides a novel, quantitative method for distinguishing CS from DCM, with the former exhibiting higher CMR signal intensity z-scores in the septum.
Abstract 4136334: Treatment Satisfaction With an “Inclisiran First” Implementation Strategy Versus Usual Care in Patients With Atherosclerotic Cardiovascular Disease
Authors: Cara East, Michael Koren, Fatima Rodriguez, Yousuf Ali, Samiha Sarwat, Kelly Kleeman, Cheryl Abbas, Peter Toth
Journal: Circulation (2024)

Background: Despite the availability of effective lipid-lowering therapies (LLTs), most patients (pts) with ASCVD do not meet guideline-recommended LDL-C goals. In VICTORION-INITIATE (NCT04929249), an “inclisiran first” (IF) strategy of adding inclisiran immediately on failure to achieve LDL-C &lt;70 mg/dL, despite maximally tolerated statin therapy, in pts with ASCVD led to significantly higher LDL-C goal attainment vs usual care (UC) at Day 330. Objective: To evaluate change from baseline to Day 330 in pt-reported treatment satisfaction with an IF implementation strategy vs UC in pts with ASCVD enrolled in VICTORION-INITIATE. Methods: VICTORION-INITIATE, a Phase 3b, open-label, prospective trial, was conducted at 45 representative clinical sites across 20 US states. Pts randomized 1:1 (stratified by insurance status) received inclisiran 284 mg (300 mg inclisiran sodium) at Days 0, 90, and 270 plus UC or UC alone (lipid management directed by treating physicians). We evaluated change from baseline to Day 330 in pt-reported satisfaction with IF vs UC using the validated 11-question Treatment Satisfaction Questionnaire for Medication (TSQM)-II comprising 4 domains (effectiveness, side effects, convenience, and global satisfaction) scored from 0–100. As a post-hoc analysis of a pre-specified exploratory endpoint, we analyzed the difference in least-squares (LS) mean change in TSQM-II domain scores for IF vs UC using ANCOVA with baseline scores as a covariate. Results: We randomized 450 patients: median age 67 years, 30.9% female, 25.8% with a history of statin intolerance. From baseline to Day 330, difference in LS mean change (95% confidence interval) in TSQM-II scores for IF (n=139) vs UC (n=105) was significant (p&lt;0.001) for effectiveness (10.4 [5.4, 15.5]), convenience (10.5 [5.8, 15.2]), and global satisfaction (12.1 [7.2, 16.9]). Statistical comparison was not applicable for the side effects domain at Day 330 due to the small sample size (IF: n=6, UC: n=7). On Day 330, mean scores for IF exceeded UC for each TSQM-II question (Figure). Conclusions: An IF implementation strategy resulted in significantly greater change from baseline to Day 330 across multiple domains of pt-reported treatment satisfaction vs UC.
Abstract 4136025: Establishing normal values for central systolic blood pressure and augmentation index in healthy young people
Authors: Jeanne Hersant, Monique Breslin, Vimarsha Kodithuwakku, Pierre Boutouyrie, Elaine Urbina, Rosa Bruno, Rachel Climie
Journal: Circulation (2024)

Background: The process of cardiovascular disease (CVD), a leading cause of death worldwide, commences in childhood. Increasing evidence indicates that early exposure to CVD risk factors in childhood is associated with impaired arterial distensibility and other vascular alterations, suggesting that vascular ageing biomarkers, that capture the deterioration in vascular structure and function, can be used to identify children at risk. However, the identification of early vascular alterations in the young is hampered by the lack of a recognized, vascular biomarker that can be used in clinical practice. The Youth Vascular Consortium, an international collaborative open resource has been established to answer these gaps by analysing different biomarkers, including central systolic blood pressure (cSBP) and augmentation index (AIx). These two non-invasive measures are related to CVD and end-organ damage, however, their assessment in clinical practice is limited by the lack of established normal values. Aims: We aimed to establish cSBP and AIx normal values in a young, healthy, international population. Methods: The Consortium collected data on 36,973 participants from 24 countries. We included 14,476 and 5,047 subjects respectively for the cSBP and AIx populations. Subjects were free of any CVD or cardiovascular risk factors. Data were collected from participants aged from 1 to 40 years. Normal values of cSBP and AIx were calculated as percentiles stratified by age and sex. Percentiles curves were generated using generalised additive models. Results: The cSBP percentile curves increase with the same trend for both males and females until age 13 years. Over this age, males experience greater cSBP than females. This is in contrast to AIx, which decreases with the same trend in both sexes until 15 years of age, after which females experience increased AIx. Conclusion: Normal values of cSBP and AIx in healthy young are now available according to age and sex with a wide geographical representation. Incorporating these values into clinical practice for young could facilitate their utilization as targets for the introduction and monitoring of interventions.
Abstract 4135984: Comparison of Immediate and Staged Complete Revascularization in STEMI Patients with Multivessel Disease: Meta-Analysis of Randomized Controlled Trial
Authors: Abdulrahman Almizel, Jeremy Levett, Tetiana Zolotarova, Mark Eisenberg
Journal: Circulation (2024)

Background: Patients diagnosed with ST-segment elevation myocardial infarction (STEMI) frequently present with multivessel coronary artery disease (CAD) at the time of primary percutaneous coronary intervention (PCI). The optimal timing of complete revascularization (CR) in these cases remains a subject of ongoing debate. Objective: To assess major cardiovascular outcomes and procedural complications in STEMI patients with multivessel CAD undergoing immediate versus staged CR post index procedure. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing immediate to staged CR in STEMI and multivessel CAD. Trials were identified via a systematic search of MEDLINE, Embase, and Cochrane Libraries from database inception to March 6, 2024. The data were analyzed using RevMan software. Results: Among five RCTs (n=1,415) the majority of participants were male, the weighted mean follow-up duration across studies was 15.6 months. Immediate versus staged CR showed no significant differences in MACE (13.3% vs 9.8%; RR: 1.07, 95% CI [0.62, 1.83]), all-cause mortality (3% vs 4.55%; RR: 0.70, 95% CI [0.41, 1.21]), or MI (4.5% vs 2.6%; RR: 1.43, 95% CI [0.58, 3.55]). However, the staged group had higher unplanned revascularization incidence (8.6% vs 4.4%; RR: 1.92, 95% CI [1.21, 3.04]). Conclusion: Staged revascularization in STEMI patients with multivessel CAD demonstrates comparable effectiveness to immediate revascularization but leads to a greater number of unplanned revascularization procedures, likely due to delayed intervention. The early implementation of staged PCI during the initial hospitalization phase may provide equivalent efficacy to immediate complete revascularization. Nonetheless, further research is necessary to corroborate these findings.
Abstract 4136518: All-cause mortality for Patients with Preserved Ejection Fraction Heart Failure stratified by B-blocker Therapy and Presence of Permanent Pacemaker.
Authors: Jonas Leavitt, Gregory Cunn, Kristie Coleman, sana ahmad, Alexandra Bekiaridou, Christopher Gasparis, Joanna Fishbein, Stavros Mountantonakis
Journal: Circulation (2024)

Background: Beta blockers (BB) and particularly high dose beta blockers might be beneficial for patients with heart failure with preserved ejection fraction (HFpEF), however their use is often limited by commonly coexisting sinus node dysfunction. It is unclear whether the presence of permanent pacemakers (PPM) allows for adequate therapy with BB which in turn confers a mortality benefit. Objective: We sought to evaluate differences in BB treatment between HFpEF patents with and without PPM and evaluate their effect on outpatient mortality. Methods: We identified patients admitted to 1 of 13 Northwell hospitals receiving intravenous diuretics in response to elevated BNP and included in our analysis only those with left ventricular ejection fraction &gt;45%. Status on BB therapy and presence of PPM was assessed at discharge. The vital status of our cohort was identified for the length of the observation period. Results: Of 17,682 patients (42.8% female, 73.5 ± 15.7 years) admitted for HFpEF, 7,910 (44.7%) were discharged on BB, while PPM was present in 397 (2.3%). Treatment with BB was more common among patients with PPM (51.4% vs 48.6%, p=X￼). There were 1,316 deaths during a follow-up period of 2.4 ± 0.9 years post index admission. Mortality was highest among patients discharged on a BB without PPM and lowest among patients on both BB and PPM (log rank p=0.003) Conclusion: Additional studies are required to assess the complimentary role of pacing and BB therapy in patients with HFpEF.
Abstract 4136202: Incident Hypertension and Survival Outcomes After Immune Checkpoint Inhibitor Initiation
Authors: Alexander Balinski, Rachel Royfman, Prem Patel, Sarah Khan, Keaton Wieschhaus, Onaopepo Kola-Kehinde, Sanam Ghazi, Mussammat Ferdousi, Patrick Ruz, Margaret Gatti-Mays, T.M. Ayodele Adesanya, Daniel Addison
Journal: Circulation (2024)

Introduction: Immune checkpoint inhibitors (ICIs) are commonly used as anticancer agents linked with dramatic antitumor response but are associated with cardiotoxicity. Recent isolated reports have suggested ICIs may link with hypertension (HTN) after years of treatment. Yet, the timing and long-term ramifications of this HTN are unknown. Methods: From a large cohort of well-phenotyped cancer patients treated with ICIs from 2011-2022, we assessed the incidence of new or worsened HTN [systolic blood pressure (SBP) ≥130 mmHg (or in a higher HTN stage) on two occasions within a three-month period or addition of an antihypertensive medication] after ICI initiation. Secondary endpoints included major cardiovascular events (MACE), defined as symptomatic arrhythmia, myocardial infarction, stroke, heart failure, or cardiac death. Observed incident HTN rates were compared to Framingham-predicted rates, using JNC 8 cutoffs of 140/90 mmHg. Landmark analysis, excluding patients who were observed to have new HTN but had SBPs ≥130 mmHg on two occasions within six-months prior to ICI initiation, identified patients with possible undiagnosed HTN. Multivariable regression and survival analysis were used to define factors associated with new worsened HTN and MACE and the relationship between SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of ICI-related HTN will be assessed. Results: Overall, from 312 patients treated with ICIs (mean age 63.5 years, 67.4% baseline HTN, 11.0% on dual ICI-therapy), 50.0% (156/312) developed new or worsened HTN over a mean of 27 months follow-up. Cumulative incidence of new HTN by 1-year was 50.0% wherein the mean peak increase in SBP was 12 mmHg. In landmark analysis, excluding those with undiagnosed HTN and applying the JNC 8 cutoff of ≥140/90 mmHg, the observed new HTN rate was 21.4% at 1 year, &gt;2-fold higher than the Framingham-predicted rate of 9.3% (RR 2.3, P &lt;0.0001). In those with preexisting HTN, 49% developed worsened HTN. In multivariate analysis, only time on ICI treatment, ECOG status, and autoimmune disease history were associated with new or worsened HTN after ICI-initiation ( P &lt;0.05 for all). Further, only prior autoimmune disease and ECOG status associated with MACE; while beyond traditional cancer factors, only new or worsening HTN associated with lower mortality. Conclusions: Collectively, these data suggest that HTN may be common with ICIs, and prognosticates survival.