tbuckley/cabot-search huggingface dataset:
Abstract 4144819: Efficacy and Safety of Coronary Sinus Reducer for Refractory Angina: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Ahmed Mazen Amin, Ubaid Khan, Basant Katamesh, Yehya Khlidj, Hossam Elbenawi, Abdelrahman Ewis, Arej Iltaf
Journal: Circulation (2024)

Background: Refractory angina severely affects patients' quality of life around the world. Among the new treatment methods, the coronary sinus reducer (CSR) is one of the most thoroughly researched. Purpose: We aim to investigate the efficacy and safety of CSR for refractory angina. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). Results: With the inclusion of three RCTs, our cohort comprised a total of 180 patients. Compared to the control group, after six months, CSR was significantly associated with decreased mean change of Canadian cardiovascular society (CCS) class (MD: -0.54 with 95% CI [-0.80, -0.27], P&lt; 0.01), an increased number of patients in the CCS class I (RR: 2.29 with 95% CI [1.14, 4.61], P= 0.02), a decreased number of patients in the CCS class III (RR: 0.53 with 95% CI [0.32, 0.87], P= 0.01), and increased exercise time (MD: 50.46 with 95% CI [9.47, 91.45], P= 0.02). However, there was no significant difference between CSR and the control group in CCS class II, class IV, across all Seattle Angina Questionnaire (SAQ) domains, the incidence of any serious adverse events (RR: 3.44 with 95% CI [0.82, 14.42], P= 0.09), stroke (RR: 2.13 with 95% CI [0.20, 22.88], P= 0.53), and all-cause mortality (RR: 1.06 with 95% CI [0.07, 16.59], P= 0.97). Conclusion: CSR has been shown to reduce angina severity by lowering CCS class scores and increasing exercise time. Large-scale RCTs are needed to confirm its effectiveness in patients with refractory angina.
Abstract 4144878: Comparison of Glycemic Profile, Cardiovascular Risk Factors, and Insulin Resistance in Type 2 Diabetic Patients with Metabolic Syndrome: A Retrospective Analysis
Authors: Pramod Tripathi, Lidiya Sul, Matthew Lee, aravinda Nanjundappa, Samir Kapadia, Dipitka Tiwari, Nidhi Kadam
Journal: Circulation (2024)

Background: Metabolic syndrome (MtS) is a cluster of risk factors, including hypertension, hyperglycemia, abdominal obesity, and dyslipidemia, which increase the risk of cardiovascular disease and poor glycemic control in type 2 diabetes (T2D) patients. Understanding the differences in glycemic profiles, cardiovascular risk factors, and insulin resistance between T2D patients with and without MtS is crucial for developing targeted interventions and identifying key predictors of MtS. Hypothesis: T2D patients with MtS show poor glycemic control and higher cardiovascular (CV) risk factors than those without MtS. Aims: This study aimed to compare the glycemic profile, cardiovascular risk factors, and insulin resistance, and identify predictors of metabolic syndrome in patients with T2D. Methods: Anthropometric and biochemical data of 2923 T2D patients (aged 18 years or older) who participated in a one-year online diabetes management program in India from 2020 to 2022 were examined retrospectively. The diagnosis of Metabolic Syndrome (MtS) was based on the NCEP-ATP III criteria (Triglyceride (TG) ≥150mg/dL, Blood Pressure≥130/85mmHg, and Fasting glucose ≥100mg/dL). Results: The mean age of the study population was 50±10 years. Among the 2923 patients, 7% had MtS. Patients with Mts displayed significantly higher BMI (27.2 vs. 25.6kg/m2), HbA1c (8.7 vs. 7.4%), fasting glucose (162 vs. 128 mg/dL), and postprandial blood glucose (195 vs.151 mg/dL) compared to those with MtS (p&lt;0.01) Additionally, individuals with T2D and MtS exhibited higher CV risk factors; HDL (39 vs. 41 mg/dL), LDL (119 vs. 99 mg/dL), TG (207 vs.121mg/dL), TG/HDL (5.3 vs.2.9), and blood pressure (140/90 vs.122/80 mmHg) (p&lt;0.01). Moreover, patients with MtS also demonstrated higher insulin resistance calculated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (3.9 vs.2.5), high sensitivity C-reactive protein (3.2 vs.1.7 mg/L), and urine microalbumin (11.2 vs.5.9 µg/ml), but lower vitamin D (19 vs. 23 ng/mL) (p&lt; 0.01) than those without MtS. Notably,TG/HDL emerged as a significant predictor of metabolic syndrome (p&lt;0.01). Conclusion: This study reveals significant differences in glycemic profiles, CV risk factors, and insulin resistance between T2D patients with and without metabolic syndrome, with the TG/HDL ratio identified as a key predictor of metabolic syndrome. This suggests the need for targeted strategies to reduce the risk factors associated with MtS in T2D patients.
Abstract 4145296: Aortic Valve Hemodynamics in Liver Cirrhosis
Authors: Radoslav Zinoviev, Olcay Aksoy
Journal: Circulation (2024)

Aortic valve stenosis (AS) is often a contraindication to liver transplantation (LT). Despite the widely accepted impact of liver cirrhosis on aortic valve hemodynamics, the change in these parameters with LT or impact of AS on LT outcomes has not been described. Given the rising burden of both AS and liver disease, there is an urgent need to understand this interaction. We identified 674 patients with liver cirrhosis who received LT at UCLA from 1/1/2013 to 12/31/2023 and investigated the change in echocardiographic hemodynamics within a year of the procedure. Patients with severe AS were excluded due to sparsity of these patients in the LT cohort. Aortic valve peak velocity (AV Vmax ) increased steadily as patients neared transplant and dropped significantly immediately after transplantation (Figure 1A). There was a larger magnitude of change in pre- to post-LT AV Vmax in patients with moderate (2.0 vs 1.6 m/s, p &lt; 0.001) as compared to mild AS (1.5 vs 1.4 m/s, p &lt; 0.001) in analysis of variance models. When patients were sorted by ascending pre-operative AV Vmax , the magnitude of fall in AV Vmax steadily increased (Figure 1B). There was a similar change in mean gradients whereas aortic valve area and dimensionless index remained unchanged after LT. There was a significant decrease in all other echocardiographic parameters associated with volume after LT: biatrial volume and pressure, and biventricular size. There was a 5.5% drop in left ventricular ejection fraction (LVEF) after LT that was statistically significant in confounder-controlled regression models (p&lt;0.001) and negatively correlated with increasing preoperative AV Vmax (-6.2%/ms -1 , p = 0.02). The presence of mild or moderate aortic stenosis was not associated with a change in 30-day or 1-year mortality, need for intraoperative vasopressor or peri-operative blood products. Overall, our findings suggest that markers of volume and aortic transvalvular flow decrease after LT without significant change in aortic valve area. There is a significant post-operative fall in LVEF, the magnitude of which is proportional to pre-operative AV Vmax . Mild or moderate pre-operative AS are not associated with worse mortality or need for perioperative support.
Abstract 4144822: Association between serum anion gap and short-term mortality in sepsis patients complicated by pulmonary hypertension: A cohort study based on MIMIC-IV database
Authors: Zeying Zhang, Qiming Liu
Journal: Circulation (2024)

Background: The relationship between anion gap (AG) and short-term mortality in intensive care unit (ICU) sepsis patients complicated by pulmonary hypertension (PH) remains unclear. Methods: Retrospective analysis of incident sepsis patients complicated by PH first admitted to ICU in MIMIC database (2008 to 2019) were enrolled. Short-term outcomes include in-hospital mortality and 28-day mortality. According to the AG value (17.0 mmol/L), patients were divided into high and low AG groups. The Kaplan-Meier survival curve was used to compare the cumulative survival rates of the high and low groups using the log-rank test. Multivariable Cox regression analyses were constructed to assess the relationship between AG and short-term outcomes in sepsis patients complicated by PH. Results: 2012 sepsis patients with pulmonary hypertension were included. The in-hospital mortality rates (11.4%) and 28-day mortality rates (12.8%) in the high AG group were higher than those in the low AG group (5.0% or 7.2%, respectively; P &lt; 0.001). The Kaplan-Meier curve showed that the in-hospital and 28-day cumulative survival rates were lower in the high AG group than that in the low AG group ( P &lt; 0.001). Multivariable Cox regression analysis confirmed that elevated AG was an independent risk factor of in-hospital mortality, 28-day mortality, length of stay in ICU and hospital. The relationship between elevated AG and in-hospital mortality remain stable after subgroups analyses. Conclusions: Elevated serum AG is associated with increased risk-adjusted short-term mortality in sepsis patients complicated by PH, and it may remind clinicians to identify patients with poor prognosis as early as possible.
Abstract 4145097: IL-6 based designer cytokine IC7 ameliorates cardiac function by shaping immune response in the infarcted mouse heart
Authors: Zheheng Ding, Puyan Rafii, Simone Gorressen, Zhaoping Ding, Juergen Scheller
Journal: Circulation (2024)

Introduction: In the setting of myocardial infarction (MI), the IL-6 cytokine family members, including IL-6 and CNTF, entail the potential to protect the myocardium against ischemia / reperfusion injury. Activation of gp130, the common β receptor for the IL-6 family cytokines, has been implicated to play a pivotal role in cardiac regeneration in neonatal mice and its downstream STAT3 signaling is known to protect the heart via a pre-conditioning manner. Thus, we engineered the chimeric cytokine IC7, a hybrid between IL-6 and CNTF, in which one gp130 binding site of IL-6 was substituted by a CNTF binding site that is capable of binding to LIFR. In the present study, we aim to examine the impact of the novel chimeric cytokine IC7 on cardiac function after MI. Methods: Mice underwent LAD ligation surgery and received IC7 i.p. either before or after and 24 hours after surgery. Cardiac function and structural benefits were evaluated by echocardiography and histological analysis (TTC and trichrome staining). Cardiac bulk RNA-Seq was employed to delve into the mechanistical basis by which IC7 regulated cellular process at transcriptional level. Results: IC7 injection prior to ischemic episode ameliorated ejection fraction (41.44% vs. 26.78%; p&lt;0.01) and prevented pathological cardiac remodeling in the infarcted heart (end-diastolic volume 84.48 µl vs. 107.15 µl; p&lt;0.05), starting from 1 week after surgery, while injection after ischemia reverted the benefits. This is in line with the histological findings from trichrome staining, confirming the results with decreased collagen volume fraction (7.89% vs. 14.01% ; p&lt;0.05) and higher average wall thickness (0.81 mm vs. 0.57 mm ; p&lt;0.05). Interestingly, TTC staining 24 hours after ischemia already revealed significant cardiomyocyte survival within the infarct zone after IC7 treatment (26.92% vs. 13.98% ; p&lt;0.05). On a transcriptome level, RNA-Seq data unveils 24 up- and 14 downregulated genes in the IC7 treated heart, while IC7 in healthy hearts significantly upregulated 62 and downregulated 35 changed genes, primarily enriched with GO terms associated with immune response. Conclusions: Taken together, our results show, for the first time, how a synthetic cytokine (IC7) shapes the cardiac immune response to ischemic injury, leading to remarkably enhanced cardiomyocyte survival and alleviated cardiac remodeling. This finding points to a new promising category of therapeutics for ischemic heart disease.
Abstract 4144860: Sleep Duration as a Potential Modifiable Risk Factor in the Management of Clinical Depression among Patients with Cardiovascular Disease
Authors: Mohsen Abbasi-Kangevari, Sanobar Jaka, Tanmik Shah, Nicole Anzai, Omar El-Shahawy
Journal: Circulation (2024)

Background: Sleep duration has emerged as a potential modifiable risk factor influencing both cardiovascular disease (CVD) and mental health outcomes. This study aimed to assess the prevalence of clinical depression among participants with CVD, examine sleep duration, and assess the association between sleep duration and clinical depression. Methods: We used data from six waves of the Behavioral Risk Factor Surveillance System (BRFSS) with available sleep assessments (2013, 2014, 2016, 2018, 2020, 2022). We restricted the analyses for people reporting having CVD, with the final analytical sample including 319,470 adults. We used two sets of guidelines to categorize sleep based on its duration: A) normative (7-9 hours), short (&lt;7 hours), and long (≥9 hours); and B) Inadequate sleep (&lt;6 hours/day) versus adequate (≥6 hours/day). Weighted multivariate logistic regression was used to assess the association of clinical depression with sleep duration among people with CVD. Results: Participants were mostly male (55.3%) and white (69.4%). Among the whole sample (N=319,470), 85,547 (28.5%) were diagnosed with clinical depression. Regarding sleep duration, 179,407 (54.1%) participants reported normative duration, 110,921 (38.9%) participants reported short duration, and 21,932 (7%) reported long duration. When examining sleep adequacy, 208,549 (61.9%) were classified as having adequate sleep, while 110,921 (38.1%) had inadequate sleep. Compared to those with normative sleep duration, both, participants with short and long sleep duration were more likely to have clinical depression (Adjusted Odds Ratio (aOR) =1.5, p&lt;.001; aOR=1.7, p&lt;.001 respectively). Additionally, participants with inadequate sleep were more likely to have clinical depression (aOR=1.37, p&lt;.001) compared to those with adequate sleep. Conclusion: Regardless of the guidelines followed to categorize healthy sleep duration (whether 6 or 7 hours/day for adults) there was a significant association between insufficient sleep and clinical depression among people with CVD. Interventions aimed at improving sleep duration could play a vital role in the mental health wellbeing of individuals with CVD. This vulnerable population, having dual burden of clinical depression and CVD were more likely to experience inadequate sleep that may lead to poor treatment outcomes. Further research is needed to quantify the impact of sleep duration and outcomes on the co-morbidity of CVD and depression.
Abstract 4145171: The CCL22/CCR4 Axis Promotes Beige Adipocyte Formation
Authors: Ruoci Hu, Jooman Park, Shaolei Xiong, Pingwen Xu, Yuwei Jiang
Journal: Circulation (2024)

Introduction: Beige adipocytes hold therapeutic promise for obese and diabetic patients. Beige adipocytes can be generated from tissue-residing beige progenitors (APCs) in response to cold temperatures preferably around lymph nodes (LN), suggesting that there are unique LN-derived signals controlling beige adipocyte generation. Methods: CCR4 KO mice (spCas9 mice were injected with AAV8-CCR4-sgRNA into biolateral inguinal adipose tissue) were generated on a C57BL/6 background. Stromal vascular cells were isolated and differentiated into beige adipocytes for in vitro studies. Flow cytometer analysis were conducted for sorting and identifying immune cells. Results: Here, we show that local LN removal greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived chemokine C-C motif ligand 22 (CCL22) into iWAT. Mechanistically, cold exposure increases the level of CCL22, which binds to its receptor C-C chemokine motif receptor 4 (CCR4), and then promotes beiging. Furthermore, CCL22 levels are inversely correlated with body weight and fat mass, and elevated CCL22 levels prevent diet-induced obesity along with increased energy expenditure in mice and humans. Conclusion: The results suggest that beige adipogenesis around the inguinal LNs of white adipose tissues depends on the CCL22-CCR4 signaling. Our findings underline the potential of targeting the CCL22-CCR4 axis to counter obesity and its associated health complications.
Abstract 4144880: GPR55 Promotes Mitochondrial Dysfunction and Atherosclerosis
Authors: Keman Xu, Fatma Saaoud, Yifan Lu, Ying Shao, Xiaohua Jiang, Wang Hong, Xiaofeng Yang
Journal: Circulation (2024)

Introduction: Atherosclerosis is the leading cause of death globally. Growing evidence suggests that mitochondrial dysfunction plays a significant role in atherosclerosis. However, the progression of mitochondrial energy generation disorders during atherosclerosis development remains unclear. In 2021, our lab indicated that activation of G-Protein Coupled Receptor 55 (GPR55) in human aortic endothelial cells (HAECs) could lead to EC activation, potentially increasing inflammation by altering mitochondrial transcription. EC activation is the central pathological event in atherosclerosis. However, whether and how mitochondrial dysfunction leads to EC activation in vivo and promotes atherosclerosis through the GPR55 pathway is still unknown. Methods: Lysophosphatidylinositol (lysoPI), an endogenous ligand for GPR55 activation, was used as a stimulus (20uM for 24hrs) to treat HAECs for Seahorse mitochondrial stress in vitro analysis. Wild-type mice, apolipoprotein E (ApoE-/-) deficiency mice, and GPR55/ApoE double knockout (DKO) mice were used for bulk RNA sequencing and En face analysis. Results: DKO mice showed a significant decrease in atherogenic lesions compared to ApoE-/- mice. In vitro Mito-stress indicated that GPR55 activation significantly increased basal respiration, spare capacity, maximal respiration, proton leak, and ATP production in HAECs, while inhibition of GPR55 reduced these parameters to basal levels. This suggests that GPR55 activation enhances mitochondrial function without affecting non-mitochondrial oxygen consumption, coupling efficiency, or mitochondrial membrane potential. We also generated a list of 289 genes associated with mitochondrial energy generation genetic disorders. Transcriptomic profiling of these genes in atherogenic mice fed with an HF diet for 3, 6, 12, 32, and 72 weeks showed a downward trend in significantly downregulated OXPHOS genes. This significant downregulation suggests increased OXPHOS biogenesis reprogramming as the disease progresses. Additionally, by comparing upregulated genes in ApoE-/- mice with those downregulated in DKO mice, we identified seven potential genes downstream of GPR55 signaling, including M2, MP, A1, F4, P8, H10, and S2, which are involved in the TCA cycle and metabolism, protein import, and lipid modification. Conclusion: Our study provides the first comprehensive examination of how impairments in mitochondrial OXPHOS biogenesis influence atherosclerosis progression via GPR55 signaling.
Abstract 4145275: Demonstrating Pulmonary Hypertension Reversibility Before Heart Transplantation: A Novel Bedside Technique Using Postural Change
Authors: Ravi Patel, Montana Goral, elizabeth hardin, Han Wool Kim, Paris Malensek, Hadi Beaini, Patrick O'Hara, Anas Jawaid, Fizza Hussain, Faris Araj
Journal: Circulation (2024)

Introduction: Pre-transplant pulmonary hypertension (PH) increases the risk of post-heart transplant right ventricular failure and as a result, morbidity, and mortality. Irreversible pulmonary hypertension is a contraindication to heart-only transplantation. Invasive and non-invasive methods to show PH reversibility include temporary and durable mechanical circulatory support (MCS), pulmonary vasodilators, diuretics, and inotropes. We herein describe a novel bedside technique to show PH reversibility and discuss its potential implications. Case: A 58-year-old female with advanced nonischemic cardiomyopathy was evaluated for heart transplant. There was no history of diabetes or dysautonomia. Supine right heart catheterization showed significant PH with the following data: PA 70/37 mmHg (48 mmHg); PCWP 25 mmHg; CO 4.03 L/min; PVR 5.7 WU. Diuretic therapy and sodium nitroprusside (SNP) were started, however due to hypotension SNP was stopped, and milrinone was initiated. Incidentally, we noticed that while seated in a chair her pulmonary hemodynamics dramatically improved without additional intervention: BP 111/73 (85) mmHg; PA 36/20 (25 mmHg); CO 3.91L/min. Once back in the supine position, the PA pressures returned to baseline. The findings were reproducible (Figure). Management: The patient continued IV diuretic and milrinone. SNP was not reintroduced, and IABP unloading was avoided as we felt reassured that the postural change in PA pressure was equivalent to vasodilator associated PH reversibility and identified a favorable phenotype for transplant. The patient underwent heart transplant and did not require an RVAD, or prolonged inotrope wean. Conclusion: To our knowledge this is the first case to describe the utility and predictive value of postural reversibility in PH in heart transplant. This is a simple bedside technique that can be performed at no extra cost using gravity to change cardiac loading conditions and may be as effective as more expensive and invasive treatments. Implications include the use of lower body negative pressure (LBNP) to prevent PH while supine during sleep or in bed. LBNP decreases venous return, leading to reduced preload and afterload, and thus reduces PH and in theory may avoid the need for durable MCS to treat PH in those needing heart transplant. We encourage further studies to determine the cost-effectiveness, clinical utility, and predictability of this novel technique for both RV failure post heart transplant and post-LVAD.
Abstract 4145166: Early Report of Heart Failure Readmissions and Guideline-Directed Medical Therapy Use in A Virtual Hospital at Home Model of Care
Authors: Harsh Patolia, Nicholas Platek, Ryan Tang, Jessica Hohman, Nancy Albert, Samir Kapadia, Jerry Estep, Conor Delaney, Richard Rothman, Trejeeve Martyn
Journal: Circulation (2024)

Background: Interest in hospital at home (HaH) has grown, driven by recognition of potential to ameliorate capacity constraints and lower total costs of care associated with traditional “brick-and-mortar” (BaM) hospitalizations. Heart failure (HF) patients often require decongestion with intravenous diuretics and titration of multiple guideline-directed medical therapies (GDMT). We aimed to demonstrate that a virtual HaH model represents a safe and feasible option for patients with acute heart failure (AHF). Methods: This was a retrospective cohort analysis of patients admitted to the Cleveland Clinic HaH after clinical and social screening and enrollment in HaH from 4/2023 to 1/2024 (Fig 1). Patients with AHF were identified through pre-specified ICD-10 codes. We performed chart abstraction to evaluate demographic characteristics, admissions, vitals, lab values, 30-day readmissions/death, use of individual HF medications, and tabulated GDMT scores among this cohort of HaH patients. Statistical analysis involved parametric and non-parametric paired analysis at admission and discharge. Results: 81% of patients (78/96) with AHF that were offered HaH as an alternative to BaM hospitalization opted to enroll in HaH. Patient were of median age 81 years [IQR 16], median LVEF 51.0% [IQR 20], and median admission NTproBNP 3518 [IQR 4619]; 66% of patients were male. Among the cohort, 7 (8.9%) patients were readmitted 30 days from discharge, and there were no deaths in the cohort at 30 month follow-up. By paired analysis, there was a net increase in GDMT score. Systolic blood pressure, diastolic blood pressure, and weight significantly trended down after admission to the HaH (Fig 2). Conclusions: In an early cohort of patients, HaH was selected by most eligible patients over BaM hospital care. There were low rates of readmission and net improvement in GDMT use. HaH can be safe and effective for selected HF patients, though further prospective research is needed.