tbuckley/cabot-search huggingface dataset:
Abstract 4141358: Body weight reduction-associated and -unassociated changes in lipid profile in people with obesity, with or without T2D, treated with tirzepatide: post-hoc analysis of SURMOUNT-1 and SURMOUNT-2
Authors: Bruno Linetzky, Sophia Kyoungah See, xiaotian zhang, Adam Stefanski, Jonathan Wilson, Giacomo Ruotolo
Journal: Circulation (2024)

Background: Tirzepatide 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 evaluated the contribution of body weight reduction-associated and -unassociated effects on the lipid profile of tirzepatide-treated participants living with obesity, without and with T2D, from the SURMOUNT-1 and SURMOUNT-2 clinical trials, respectively. Methods: Participants treated with tirzepatide (pooled doses of 5, 10, 15 mg in SURMOUNT-1 [N=1765] and 10 and 15 mg in SURMOUNT-2 [N=587]) were included in this analysis. The estimated treatment effects and the body weight reduction-associated and -unassociated attribution on changes from baseline in lipid profile (total cholesterol, HDL-C, LDL-C, non-HDL-C, VLDL-C, and triglycerides) at 24 and 72 weeks were assessed via the SAS CAUSALMED procedure. Results: In SURMOUNT-1, after 24 weeks of tirzepatide treatment in participants without T2D, 69-85% of the changes in total cholesterol, HDL-C, LDL-C, and non-HDL-C, and 41-43% of the changes in VLDL-C and triglycerides occurred unassociated with body weight reduction (Table). At 72 weeks, most of the effect on the lipid profile was associated with body weight reduction. In SURMOUNT-2, after 24 weeks of tirzepatide treatment in participants with T2D, most of the changes in the lipid profile occurred unassociated with body weight reduction. At 72 weeks, changes observed in the lipid profile were predominantly associated with body weight reduction, although 43-50% of those changes also occurred unassociated with body weight reduction, except for LDL-C which was almost completely (92%) associated with body weight reduction. Conclusions: In this post hoc analysis from SURMOUNT-1 and SURMOUNT-2, changes in lipid profile were mostly unassociated with body weight reduction after 24 weeks of tirzepatide treatment and associated with of body weight reduction at 72 weeks. Body weight reduction-unassociated mechanisms responsible for the initial changes in lipid profile in participants with obesity treated with tirzepatide warrants further research studies.
Abstract 4141692: Second-by-second monitoring of SpO <sub>2</sub> by wearable device during the six-minute walk test identifies patients at risk for worsening heart failure.
Authors: Isamu Sunayama, Kyung-Duk Min, Yoshiyuki Orihara, Masanori Asakura, Masaharu Ishihara
Journal: Circulation (2024)

Background: Assessment of exercise tolerance is crucial for risk stratification in patients with heart failure (HF), and the six-minute walk test (6MWT) is widely used. While the six-minute walk distance (6MWD) is an established metric, it shows significant variability among elderly patients due to numerous comorbidities and potential confounding factors, making relative risk assessment challenging. Therefore, a new comprehensive indicator for evaluating exercise tolerance in elderly patients with HF is required. Objective: This study aimed to evaluate the novel prognostic value of desaturation during the 6MWT, defined as the average decrease in peripheral oxygen saturation (ΔSpO 2 -Ex), in predicting rehospitalization in patients with HF. Methods: We retrospectively analyzed the data of 55 patients with acute HF aged ≥ 65 years who were prospectively registered at our hospital. The mean SpO 2 was calculated from data obtained at rest and during the 6MWT using a wearable pulse oximeter designed to record the SpO 2 value every second. ΔSpO 2 -Ex was defined as the difference between the highest SpO 2 at rest and average SpO 2 during the 6MWT. Patients were followed-up for 1 year for the composite outcome of rehospitalization due to HF exacerbation and cardiovascular death. Results: The mean age was 80.7 years, with 45 % being female. The mean 6MWD was 237.5 m, and the mean ΔSpO 2 -Ex was 5.8 %. Patients were categorized based on the cut-off values obtained from the ROC curve for both 6MWD and ΔSpO 2 -Ex. Kaplan-Meier analysis indicated a significantly higher risk of cardiovascular events when ΔSpO 2 -Ex exceeded 6.7 % compared to when the 6MWD was less than 220 m (HR 6.66, 95 % CI: 2.96-15.01, p&lt;0.001 and HR 2.40, 95 % CI: 1.08-5.32, p=0.031). Additionally, the combination of shorter 6MWD and higher ΔSpO 2 -Ex was associated with a significantly higher incidence of cardiovascular events. Conclusion: ΔSpO 2 -Ex is a powerful and independent prognostic marker for cardiovascular events in elderly patients with HF, surpassing the predictive power of 6MWD. These findings suggest that incorporating ΔSpO 2 -Ex into routine clinical assessments could enhance the risk stratification and management of patients with HF.
Abstract 4141052: Rare Combo: An Unusual Case of a 54-year-old Filipino with Coronary Artery Fistula from Left Anterior Descending Artery to Main Pulmonary Artery and Acute Cerebellar Infarct: A Cardio – Cerebral Infarction Syndrome - Case Report
Authors: Michael Bonilla
Journal: Circulation (2024)

Introduction: Cardio-cerebral infarction, a rare clinical presentation involving simultaneous acute ischemic stroke and acute myocardial infarction, poses significant therapeutic challenges. The incidence of this dual infarction is currently unknown due to its rarity. Delaying intervention for one condition to address the other can lead to permanent morbidity, disability, or even death. Coronary artery fistulas are uncommon with estimated incidence of 0.3%. Among these, a fistula between the left anterior descending artery and the pulmonary artery is the rarest variant, comprising about 17% of all coronary artery fistula cases. Case: A 54-year-old male, with a known history of atrial fibrillation and hypertension, presented to our emergency department with non-rotatory dizziness. Physical examination was unremarkable, but neurological examination revealed medial rectus palsy and left facial asymmetry. A cranial MRI indicated a hyperacute infarction in the left cerebellum. Laboratory tests showed markedly elevated troponin I levels (&gt;50 ng/ml) and atrial fibrillation, along with inferior wall ST elevation on the electrocardiogram. Due to the high risk of hemorrhagic conversion, the loading of antiplatelets was deferred. Instead, the patient was treated with Aspirin 80 mg once daily, Clopidogrel 75 mg once daily, and Enoxaparin 0.4 ml subcutaneously once daily. A 2D echocardiogram revealed an ejection fraction of 43%, hypokinesia of the anterior and intraventricular septum from base to apex, and severe mitral stenosis. Cardiac catheterization identified a coronary artery fistula from the left anterior descending coronary artery to the main pulmonary artery. Treatment for acute coronary syndrome and acute cerebellar infarct continued. An open-heart surgery was considered. However, during his hospital stay, the patient experienced hemorrhagic conversion and altered sensorium. His condition further deteriorated, necessitating a tracheostomy and long-term care. Conclusion: Cardio-cerebral infarction is an extremely rare and poorly studied syndrome that presents significant treatment challenges and carries a grave prognosis if not addressed immediately. The medical conundrum of deciding which condition to treat first underscores the need for further research. Both interventional cardiologists and interventional neuroradiologists play crucial roles in the effective management of this emergency condition.
Abstract 4141378: Comparative Analysis of Hemodynamic Parameters in Heart Failure with Preserved Ejection Fraction Patients with and without Atrial Fibrillation Undergoing Exercise Right Heart Catheterization
Authors: Masih Tajdini, Radu Tanacli, Vivek Jani, Kavita Sharma
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with higher mortality. This study aims to compare hemodynamic parameters between HFpEF patients with and without AF to better understand the impact of AF on cardiac function in this population. Method: Patients from the Johns Hopkins HFpEF Clinic who underwent exercise right heart catheterization (July 2014 - May 2024) were included. They were categorized into two groups based on ECG findings of AF before catheterization: HFpEF-AF versus HFpEF-NonAF. Continuous variables were assessed for normal distribution using the Shapiro-Wilk test. Group differences were explored using one-way ANOVA or the Mann-Whitney U test. ANCOVA was performed to account for major confounders. Results: Sixty-six HFpEF patients were enrolled: 44 HFpEF-NonAF (66.7%) and 22 HFpEF-AF (33.3%). HFpEF-AF group was older (72.09 vs. 63.63 years, p &lt; .001) and had more males (54.5% vs. 27.3%, p = 0.03). No significant differences were observed in other baseline characteristics between the two groups. More patients in the HFpEF-NonAF group reached higher stages compared to the HFpEF-AF group, indicating poorer performance in the AF group (Figure A). There were no significant differences between the groups at early stages or peak exercise regarding mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, pulmonary vascular resistance, and heart rate. However, significant differences were observed in terms of cardiac output (CO) at baseline (5.81 vs. 4.77, p = 0.035) and during exercise (8.9 vs. 7, p = 0.019), and cardiac index (CI) during peak exercise (4.14 vs. 2.90, p &lt; 0.001) between the two groups (Figures B-F). A negative correlation between age, CO, and CI within the AF subgroup was observed. ANCOVA analysis showed HFpEF-AF patients have lower CI at peak exercise even after adjusting for age. Discussion: The study reveals that in HFpEF patients, those with AF exhibit significantly lower cardiac output and cardiac index during exercise compared to those without AF, despite similar pulmonary pressures. These findings underscore the importance of rhythm control strategy for AF in HFpEF patients.
Abstract 4141154: The role and molecular mechanisms of cold-inducible RNA-binding protein in neural injury after acute ischemic stroke
Authors: Kangmei Shao
Journal: Circulation (2024)

Background: Acute ischemic stroke (AIS) is one of the leading causes of death and disability in adults worldwide, and effective treatments are still lacking. Cold-inducible RNA-binding protein (CIRP) is up-regulated in response to various stress conditions. Previous studies have indicated that CIBP could potentially influence the development of various diseases. Research questions: Nevertheless, the specific role and molecular mechanism of CIBP after AIS remain unclear. Methods: The levels of serum CIRP and other brain injury markers such as NSE, S100β, GSDMD, and NLRP3 were measured by ELISA to explore the relationship between CIRP and AIS. Additionally, middle cerebral artery occlusion models (MCAO) in rats were established to investigate its localization in brain tissue using immunofluorescence staining. Additionally, the CIRP knockout MCAO rat model was established, and evaluate the effect of CIRP deficiency on the neurological function of rats. while the role of CIRP was investigated through RNA sequencing and Western Blot analysis. Additionally, the potential protective effect of the CIRP inhibitor C23 on neural injury following AIS was examined. Results: (1) Compared to the healthy control group, the serum levels of CIRP and other brain injury markers (NSE, S100β) in AIS patients and MCAO rats were significantly elevated, and the elevated levels were positively correlated. (2) In the MCAO rat model, the CIRP was mainly located in neurons and microglia. (3) Compared with wild-type MCAO rats, CIRP knockout MCAO rats improved neurological function scores. (4) RNA-seq analysis revealed that genes differentially expressed between wild-type MCAO rats and CIRP knockout MCAO rats were enriched in inflammation-related pathways. (5) The expression of pyroptosis-related proteins (NLRP3, Caspase-1, GSDMD, and ASC) and inflammatory factors (IL-1β, TNF-α, etc.) decreased in CIRP knockout MCAO rats. (6) The CIRP inhibitor C23 significantly alleviated brain injury and improved neurological function. C23 treatment significantly decreased the expression levels of pyroptosis-related proteins and inflammatory factors. Conclusions: This study shows that CIRP plays an important role in AIS development. The levels of CIRP in AIS patients and MCAO rats are significantly increased and are positively correlated with nerve damage markers. Thus, supporting CIRP as a potential target for the treatment of AIS. This discovery provides new strategies for the treatment of AIS.
Abstract 4141412: Regulation of Vascular Smooth Muscle Cell Phenotype and Metabolic Profile by CD70
Authors: Arvind Pandey, Apabrita Das, Markus Waldeck-Weiermair, Shambhu Yadav, William Oldham, Thomas Michel, Joseph Loscalzo
Journal: Circulation (2024)

Introduction: We recently identified the tumor necrosis superfamily member CD70 as a novel regulator of redox homeostasis and mitochondrial function in endothelial cells. Whether CD70 exerts a regulatory role on metabolism and cellular function in vascular smooth muscle cells (VSMCs) is unknown. Methods: Human aortic VSMCs (AoVSMCs) were transfected with control or CD70-directed siRNA (n = 5-6). Metabolic function was assessed by Seahorse assay. Hydrogen peroxide, calcium, ATP, and NADH/NAD + ratio were assayed in live cells with fluorescent biosensors. Semi-quantitative proteomics were performed using liquid chromatography-tandem mass spectrometry. VSMC phenotype was evaluated by scratch assay and collagen gel contraction assay. VSMC function was assessed in control versus global CD70 knockout mice using wire myography. Results: CD70 knockdown significantly altered cellular metabolic profile, decreasing oxidative phosphorylation and glycolysis (Fig. 1A). This was accompanied by mitochondrial network dispersion, reduced mitochondrial membrane potential and impaired glucose-dependent ATP production (Fig. 1B-C). Markers for mitochondrial fusion and biogenesis, including the key regulator PGC1-alpha, were reduced (Fig. 1D-E). Cellular redox balance shifted towards an oxidized state with decreased NADH/NAD + ratio (Fig. 1F) and enhanced intracellular hydrogen peroxide generation. Proteomic analysis using intensity-based absolute quantification and a false discovery rate of 5% revealed that CD70 knockdown led to activation of pro-oxidative proteins, alteration in proteins involved in mitochondrial dynamics, and decreased expression of contractile proteins, all with significant p values. CD70 knockdown reduced VSMC contractile function (Fig. 1G) and intracellular calcium flux; migratory capacity increased. CD70 knockout mice had reduced aortic contractile reserve (Fig. 1H). Conclusions: CD70 has a previously unknown homeostatic role in maintaining VSMC metabolic and contractile function. Loss of CD70 disrupts mitochondrial networks and alters VSMC metabolism to promote phenotypic switching from a contractile to a migratory state. These results identify CD70 as a potential new target for regulating VSMC pathobiology.
Abstract 4140802: Detection of subclinical carotid and femoral arterial disease in patients with prior percutaneous coronary intervention: Insights from the LAI-ACP study
Authors: Kunal Mahajan, Raman Puri, Jai Bharat Sharma, Surender Himral, Savio Dsouza, Prashant Patel, Pankaj Chandel, Anuradha Kapoor, Komal Mohite, Shivali Sandal
Journal: Circulation (2024)

Background: Poly-vascular disease, characterized by atherosclerosis in multiple vascular beds, significantly increases the risk of cardiovascular death, myocardial infarction, and stroke. The severity correlates with the number of affected regions. The Lipid Association of India classifies patients with poly-vascular disease in the extreme risk category and recommends a lower LDL cholesterol target ( &lt; 30 mg/dl) compared to those with atherosclerosis in a single territory (&lt;50 mg/dl). Research Hypothesis: Indian patients likely show a higher prevalence of poly-vascular disease, possibly explaining the aggressive atherosclerosis observed in Indian and South Asian populations. Aim: This study aimed to assess the prevalence of subclinical carotid and femoral artery disease in Indian patients with post-percutaneous coronary intervention (PCI). Methods: Post-PCI patients attending a cardiology outpatient clinic over eight months were enrolled. Exclusions were patients with prior ischemic stroke, vascular limb event and carotid or peripheral intervention. Femoral and carotid artery Doppler ultrasounds were performed for plaques. Plaque was defined as either intima-media thickness exceeding 1.5 mm or protruding into the lumen by at least 50% of the surrounding thickness. Results: A total of 357 patients (mean age 63.1±10.7 years; 80.9% male) were enrolled. Diabetes mellitus and hypertension were present in 33.3% and 53.8% of patients, respectively. A history of ACS was noted in 88.8% of participants. Double or triple vessel disease was observed in 75.6% of patients. Carotid and femoral plaques were detected in 78.4% and 65.2%, respectively, with both present in 56.3%, and either of them in 87.7%. Mean LDL-cholesterol was higher in patients with both carotid and femoral plaques than those without (57.23 ± 27.12 versus 54.49 ± 28.15 mg/dl, p&lt;0.001). The majority (80.7%) were on combination LDL-cholesterol lowering treatment with high intensity statins plus ezetimibe or bempedoic acid. Conclusion: Indian patients with CAD and a history of PCI exhibit a high prevalence of diabetes, hypertension, and triple vessel disease. Poly-vascular disease was prevalent, with majority having either subclinical carotid or femoral artery disease. Given the high incidence of recurrent events in poly-vascular disease patients, cardiometabolic risk targets, especially the LDL-C targets for Indian patients, may need to be lower than Western guidelines suggest.
Abstract 4141501: 9p21.3 variants drive coronary calcification by suppressing statherin expression
Authors: Fariborz Soheili, Naif Almontashiri, Niloufar Heydarikhorneh, Ragnar Vilmundarson, Hsiao-huei Chen, Alexandre Stewart
Journal: Circulation (2024)

Background: Genetic variants on chromosome 9 at p21.3 confer a heightened risk of atherosclerosis and coronary artery calcification. The 9p21.3 variants cause the selective expression of non-coding RNA transcripts (ANRIL) that regulate many genes through ALU element mediated silencing. However, to date, none of these regulated genes account for the effect of 9p21.3 variants on coronary calcification. Methods and Results: To identify genes differentially regulated by the 9p21.3 risk variants, primary human aortic smooth muscle cells (HAoSMCs) from 11 different donors genotyped for 9p21.3 risk variants (n=3-4/genotype) were analyzed for whole-genome expression using microarrays. We identified the mRNA for the hydroxyapatite-binding protein statherin as the most impacted by 9p21.3 genotypes—its mRNA was silenced in carriers homozygous for risk variants. Transfection of ANRIL with an expression plasmid bearing the ALU element from the first intron of the Statherin gene silenced statherin expression. HAoSMCs also express another hydroxyapatite binding protein called matrix GLA protein (MGP). Mice lack a native statherin gene, and if they lose the Mgp gene, they develop severe arterial calcification and die of aortic rupture. In contrast, humans with MGP deficiency (aka Keutel syndrome) rarely develop calcified arteries, suggesting that statherin might compensate for MGP loss. As has been reported for MGP, statherin was found to inhibit bone morphogenic protein 4 (BMP4)-dependent activation of a BMP-responsive luciferase reporter, suggesting functional redundancy of statherin and MGP to inhibit arterial calcification. Lentiviral vectors expressing human statherin blocked calcification of primary aortic smooth muscle cells from Mgp KO mice. Furthermore, expression of human statherin from a transgene conditionally recombined only in smooth muscle cells prevented arterial calcification in Mgp KO mice. Conclusion: The 9p21.3 risk variants expedite arterial calcification by suppressing statherin expression. Since microcalcifications hasten atherosclerosis, targeting this statherin-dependent mechanism could reduce atherosclerotic burden and benefit up to 75% of individuals of European and Asian ancestry that carry the 9p21.3 risk variants.
Abstract 4140865: Clinical Outcomes Of P2Y12 Inhibitor Monotherapy Versus Dual Antiplatelet Therapy After Percutaneous Coronary Intervention In Patients With Acute Coronary Syndrome: A Meta-Analysis Of Randomized Controlled Trials
Authors: Soumya Gupta, Aditya Thakkar, Devika Aggarwal, Kirtipal Bhatia, James Choi, Kristen Carter, Arpanjeet kaur, Abel Casso
Journal: Circulation (2024)

Introduction: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is recommended after percutaneous coronary intervention (PCI) to lower the risk of cardiovascular events. However, prolonged DAPT has been shown to increase bleeding risk, while some studies have shown that shorter-duration of DAPT followed by aspirin alone increases ischemic risk. Research question: This study aimed to compare the risks and benefits of monotherapy with P2Y12 inhibitors and DAPT after PCI. Methods: We searched the Medline, Embase, and Cochrane databases for randomized controlled trials (RCTs) involving adult patients hospitalized with ACS who underwent PCI. Our primary outcome was the composite of death, myocardial infarction (MI), and stroke. The secondary outcomes were net adverse clinical events (NACEs which is the primary outcome and risk of major bleeding), all-cause mortality, cardiac death, MI, stroke, stent thrombosis, target vessel revascularization, clinically relevant bleeding, and major bleeding. We used Review Manager 5.4 for the statistical analysis, employing risk ratios (RRs) with 95% confidence intervals (CIs). Results: Nine RCTs were included, involving a total of 34,322 patients, with 48.9% receiving P2Y12 inhibitor monotherapy after 1–3 months of DAPT. Regarding the primary outcomes, the risk of the composite of all-cause mortality, MI and stroke was significantly lower in patients receiving P2Y12 monotherapy as compared to patients on DAPT (RR 0.91[95% CI 0.84–0.98], I2=0%, p=0.01). With respect to the secondary outcomes, there was a significantly lower risk of NACEs (RR 0.86 [95% CI 0.76–0.97], I2=58%, p=0.01), clinically relevant bleeding (RR 0.59 [95% CI 0.38–0.93], I2=92%, p&lt;0.00001), major bleeding (RR 0.57 [95% CI 0.40–0.82], I2=79%, p=0.002) as well as cardiac death (RR 0.80 [95% CI 0.64–0.99], I2=0%, p=0.04) in patients receiving P2Y12 inhibitor monotherapy. There was no significant difference in the risk of all-cause mortality, MI, stroke, target vessel revascularization, and stent thrombosis between the 2 groups. Conclusion: This meta-analysis found a significant decrease in the risk of the composite of death, MI, and stroke in patients receiving P2Y12 inhibitor monotherapy. It also showed that the risk of net adverse clinical events and major bleeding is lower in patients receiving P2Y12 inhibitor monotherapy.