tbuckley/cabot-search huggingface dataset:
Abstract 4122120: Prospective Implementation of a Cardiovascular Implantable Electronic Device Algorithm-Based Management Pathway in Routine Heart Failure Care
Authors: Allison Kratka, Greg Rohrbach, CARRIE MARGARET PUCKETT, Thomas Rotering, Merritt Raitt, Mary Whooley, Sanket Dhruva
Journal: Circulation (2024)

Introduction: More than 1 million patients in the US are hospitalized annually with heart failure (HF), many of whom have cardiovascular implantable electronic devices (CIEDs). CIEDs monitor physiologic variables that could identify subacute HF decompensation and impending HF hospitalization (HFH). One such algorithm is Medtronic’s TriageHF TM , which integrates nine diagnostic inputs from remote monitoring data to stratify patients into categories of low-, medium-, or high-risk of HFH in the next 30 days. Goals/Aims: To implement and evaluate a program in which two Veterans Health Administration (VHA) cardiology clinics receive high-risk TriageHF TM scores for patients with CIEDs, followed by contacting and assessing patients and then taking appropriate clinical action. Methods: From 1/18/24 to 4/19/24, TriageHF TM risk scores were calculated from both HF-specific remote transmissions that were scheduled every 30 days and unscheduled remote transmissions. Clinicians then contacted patients with high-risk scores regarding possible symptoms and provided an empiric 3-day diuretic intervention (initiation or dose augmentation), adjusted guideline-directed medical therapy (GDMT), or performed another clinical action as appropriate. Results: Among 358 patients with 1140 transmissions, 72 (6%) patients had a high-risk transmission. Mean patient age was 72.8 years, 346 (97%) were male, and 221 (62%) had a pre-existing diagnosis of heart failure. Of the 72 patients with high-risk transmissions, 67 (93%) were successfully contacted; 34 (51%) had no HF symptoms, 24 (36%) had mild to moderate symptoms, 2 (3%) had severe symptoms, 4 (6%) had non-HF symptoms, and 3 (4%) could not report symptoms. Of the 67, 57 (85%) reported adherence to medications and 17 (25%) were identified as likely having a non-HF related high-risk score. Forty-six (69%) had a clinical action taken in response to the high-risk score, including 28 (42%) with a diuretic intervention, 12 (18%) with GDMT augmented, and 25 (37%) with other actions, such as being referred to HF clinic. Conclusions: In this implementation study, clinicians contacted and assessed nearly all patients at high-risk for HF decompensation based on CIED remote monitoring data. Approximately 70% of patients had an actionable high-risk score, with approximately half prescribed empiric diuretics or augmented GDMT. A randomized clinical trial is needed to determine whether this algorithm and subsequent intervention improves clinical outcomes.
Abstract 4118122: Effect of Beta Blockers on Exercise Capacity, Diastolic Function, and Quality of Life in Patients with Heart Failure with Preserved Ejection Fraction
Authors: Frank Weigel, Sakima Smith
Journal: Circulation (2024)

Introduction: In recent landmark HFpEF trials, 75-80% of patients are taking beta blockers (BB) without clear evidence of clinical or symptomatic benefit. Patients with HFpEF commonly have comorbidities that have been classically managed with BB (AF, CAD, HTN), though the utility of this medication class for these conditions is being reconsidered. It remains unclear what impact BB use, in patients with HFpEF, has on exercise capacity, diastolic function, and quality of life. Hypothesis: We hypothesized that BB use is associated with worse exercise capacity, diastolic function, and quality of life in HFpEF patients. Methods: This retrospective cohort study was completed using deidentified patient data from the INDIE-HFpEF and RELAX clinical trials (two trials of HFpEF patients). Patients were divided into two groups based on BB use at trial enrollment. The primary outcomes were exercise capacity, diastolic function, and quality of life at baseline evaluation. A multivariate logistic regression model was used to assess for statistically significant differences after controlling for potentially confounding variables including age, sex, BMI, AF, prior MI, COPD, DM, HTN, serum creatinine, and NYHA functional class. Results: A total of 320 patients were included in this analysis, with 230 on BB (72%). Baseline demographics are shown in Table 1. Patients studied were older (68 years old), white (90%), obese (average BMI 34 kg/m 2 ) individuals with an average LVEF of 61%. Outcomes and multivariate linear regression results are shown in Table 2. After controlling for potential confounding variables, there were no differences in baseline exercise capacity [peak VO2 (mL/kg/min): 12.1 vs 13.2, P=0.233], diastolic function [average E/e’: 14 vs 12, P=0.125; LAVI (mL/m 2 ): 42 vs 37, P = 0.665; peak TR velocity (m/s): 2.8 vs 2.7, P = 0.165; PASP (mmHg): 41 vs 36, P = 0.357], quality of life [KCCQ: 54 vs 58, P = 0.206; MLHFQ 43 vs 46, P = 0.762], or NT-proBNP (633 vs 342; pg/mL, P = 0.208) in HFpEF patients on BB compared to those not on BB. Conclusion: There was no association with BB use and worse exercise capacity, diastolic function, or quality of life in HFpEF patients. This may be due to heterogenous treatment effects, with differing impact of BB based upon the underlying pathophysiology of unique HFpEF phenotypes. To definitively determine the impact of BB use in patients with HFpEF, both on clinical outcomes and symptoms, randomized controlled trials are necessary.
Abstract 4121589: Sex differences in Social Determinants of Health and Adverse Outcomes in Atrial Fibrillation: A UK Biobank Study
Authors: Yusheng Zhou, Jonathan Houle, Valeria Raparelli, hassan behlouli, Colleen Norris, Louise Pilote
Journal: Circulation (2024)

Background: Beyond the risk of thromboembolic stroke, people with atrial fibrillation (AF) are substantially burdened with a higher incidence of cardiovascular mortality, even among patients treated with anticoagulants. The reasons behind these outcomes are only partially understood. Social determinants of health (SDOH), strong independent predictors of major adverse cardiovascular events (MACE) in several cardiac diseases, may play a role; however, their impact on AF prognosis and the differences in SDOH by sex have been insufficiently explored. Objective: We investigated the sex differences in the association between SDOH and MACE in patients with AF. Methods: Data from the UK Biobank included participants enrolled from 2006 to 2010. An incident AF patient cohort, free of stroke and MI was created. Seventeen SDOH derived from three domains:: socio-economic status, psychosocial factors, and neighborhood/living environment were identified Cox proportional hazards models were used to evaluate the associations of individual SDOH components with the risk of MACE stratified by sex. Covariates including all variables of the CHA 2 DS 2 -VASc Score (Congestive heart failure, Hypertension, Age, Diabetes, prior stroke or transient ischemic attack, Vascular disease and Sex), current use of antiplatelet therapy or anticoagulation, smoking and body mass index. The primary outcome was a composite of MACE (including stroke, transient ischemic attack and arterial thromboembolic event, MI and cardiovascular mortality) and all-cause mortality. Results: A total of 23,113 participants with AF (mean age, 62.44 ± 5.88 years; female sex 39.7%) were included. The composite outcome occurred in 5,151 (22%) of participants over 10-year follow up. In the multivariate adjusted model, several SDOH were independently associated with an increased risk of adverse outcomes. Males showed a broader range of SDOH that were significantly associated with outcomes, including unfavourable economic factors and low social support. Despite females had fewer significant SDOH, education-related factors and local crime rates were significant predictors of adverse outcomes (Figure 1). Conclusions: Adverse SDOHs are associated with a higher risk of MACE and all-cause mortality in AF, with sex-specific variations. These findings underscore the need of incorporating routinely SDOH assessment into clinical practice to more accurately stratify risk and tailor preventive strategies based on sex-specific data.
Abstract 4121970: Early to Mid-Gestational Testosterone Excess Sex-specifically Reprograms Cardiac Transcriptome and Metabolome Profiles of Sheep Fetuses
Authors: Bashar Alkhatib, Venkateswaran Ramamoorthi Elangovan, Kevin Cho, Leah Shriver, Gary Patti, Vasantha Padmanabhan, Arpita Vyas
Journal: Circulation (2024)

Exposure of sheep to excess testosterone (T) from days 30-90 of gestation (term 147 days) perturbs maternal systemic lipidome in late gestation, induces fetal growth restriction and sexually dimorphic perturbation in the cardiac left ventricular (LV) transcriptome in gestational (GD) day 90 fetuses culminating in cardiometabolic dysfunction in adult female offspring. We hypothesized that the detrimental impact of prenatal T excess on fetal cardiac transcriptome is a programmed event that will persist even after cessation of excess T exposure and will be accompanied by changes in fetal metabolome. Pregnant ewes were injected with 100 mg intramuscular T propionate or vehicle (C), twice weekly from GD 30-90. On GD120±5, 30 days after cessation of T treatment fetal weights were recorded, left ventricle (LV) tissue and fetal plasma processed for transcriptomics by RNA sequencing and metabolomics analysis (Female C (FC) n=6, T (FT) n=7; Male C (MC) n=6, T (MT) n=7). LV transcriptome-based pathways enrichment analysis revealed 1) downregulation of pathways associated with oxidative phosphorylation, citric acid cycle, pyruvate metabolism; 2) upregulation of TGF-β signaling pathway in T fetuses compared to C (p&lt;0.05, FDR&lt;0.1); 3) selective downregulation of the glycolytic pathway in MT relative to MC as opposed to downregulation of mitochondria-related pathways in FT vs FC (p&lt;0.05, FDR&lt;0.1). LV lipidomics analyses found glycerophospholipids and sphingolipids as main class lipid metabolites to be enriched in FT relative to FC fetuses (p&lt;0.05, ER&gt;1). Fetal systemic lipidome main class metabolites enriched (p&lt;0.05, ER&gt;2) in T vs C fetuses included 1) sphingomyelins in both sexes 2) fatty acyls metabolites only in MT vs MC as opposed to glycerophospholipids only in FT vs FC. LV polar metabolites enriched (p&lt;0.05, ER&gt;2) included 1) arginine&amp;proline metabolism pathways in T vs C in both sexes 2) nicotinate and nicotinamide metabolism only in MT vs MC (p&lt;0.05, ER&gt;3), and porphyrin, riboflavin metabolism and N-glycan biosynthesis pathways only in FT vs FC. Systemic polar metabolites enriched (p&lt;0.05, ER&gt;2) included 1) D-amino acid metabolism pathways in T vs. C, 2) valine, leucine, and isoleucine pathways only in FT vs FC and glycerophospholipid and sphingolipid metabolism only in MT vs MC. These results suggest persistence of sex-specific perturbation in fetal transcriptome and systemic and cardiac metabolome in late gestational fetuses exposed to prenatal T excess.
Abstract 4118415: Device Dislodgement and Embolization associated with a New Leadless Pacemaker
Authors: Ali Bahbah, Jay Sengupta, Dawn Witt, Edwin Zishiri, John Zakaib, Raed Abdelhadi, Robert Hauser
Journal: Circulation (2024)

Background: Leadless pacemakers (LP) avoid the pocket and lead-related complications of transvenous pacing. A potential complication of LPs is dislodgement and/or embolization (D/E) during or after implant. No D/E occurred in the original 725-patient Micra™ VR clinical trial. However, in the 526-patient LEADLESS II-phase 2 trial, the rate of dislodgement for 200 Aveir™ VR LPs was 1.5%. Thus, there appears to be a significant difference in D/E rates between these LPs that have different fixation mechanisms and insertion tools. Aims: We aimed to determine if the Aveir VR LP has continued to exhibit D/E since it was approved by the Food and Drug Administration (FDA) in April 2022. Methods: We queried the FDA's Manufacturers and User Facility Device Experience (MAUDE) database for Aveir D/E that occurred in the U.S. and were reported by the manufacturer from April 2022-December 2023. The number of Aveir VR implants in the U. S. was obtained from the manufacturer's publicly available product performance report. D/E outside the U.S. were excluded. Results: During the 21 months, 55 of 3,139 (1.75%) Aveir VR implants exhibited D/E. More D/E (34;61.8%) occurred during implant, with 18 (52.9%) of these happening after release of the device from the tether mode. Fourteen (41.2%) of the intra-procedural D/E occurred when the device prematurely released from the delivery catheter, and two dislodged during cardiopulmonary resuscitation (CPR). D/E occurred in 21 patients (38.2%) after implant and were signified by loss of pacing or inability to interrogate the device. Four (19%) out of those 21 patients presented with symptomatic bradycardia. The dislodged devices commonly embolized to the pulmonary artery and right atrium/vena cava. LP retrieval was successful in 49 (89%) cases. Thirty-two patients (58.1%) received a new LP, 5 patients were transitioned to a transvenous system, and a replacement device was not specified for 17 (31%) patients. One patient died during implantation due to ventricular fibrillation (VF) not related to D/E. Conclusions: Fixation issues and premature separation of the device from the delivery catheter appear to be responsible for most of these D/E. Studies are needed to determine if impedance or another metric is associated with adequate Aveir fixation. The manufacturer should address the premature separation problem with Aveir. Success of D/E retrieval may be related to tools specific for Aveir. Further studies are needed to compare between the two LPs.
Abstract 4116949: Specialized Pericyte Subtypes in the Pulmonary Capillary
Authors: Tim Klouda, Yunhye Kim, Han-Seong Baek, Mantu Bhaumik, Yu Liu, Tiffany Liu, Jianwen Que, Joseph Wu, Benjamin Raby, Vinicio Dejesus, Ke Yuan
Journal: Circulation (2024)

Introduction: Lung pericytes (PCs) are mural cells in close contact with endothelial cells (ECs) in the microvasculature. A significant challenge in investigating PC biology is largely due to the absence of a unique cell marker, making it difficult to distinguish them from other mural cell populations. The identification of such a marker would allow investigators to describe the role of PCs in various diseases including pulmonary arterial hypertension. Hypothesis: We hypothesize that HIG1 hypoxia-inducible domain family member 1B ( Higd1b ) is exclusively expressed in lung PCs, which contributes to hypoxia (Hx)-induced vascular remodeling. Methods: We utilized single-cell RNA sequence (scRNA-seq) databases, spatial transcriptomics, and RNAscope from human and murine lungs to identify a PC-specific cell marker and compare the gene expression between PC subtypes. We utilized Cre-LoxP and CRISPR technology to construct a novel tamoxifen-inducible Higd1b-CreERT2 knock-in mouse model and performed lineage-tracing studies to describe the role of PC subtypes in Hx-induced pulmonary hypertension (PH). Results: ScRNA-seq analysis from the lungs of humans and mice identified Higd1b as a specific gene marker for PCs whose expression is absent in other mural cell populations. Validation with a reporter mouse line Higd1b-CreERT2::R26-tdT confirmed Higd1b-Cre+ cells specifically label PCs and no other mural cells ( Fig 1A ). Lineage tracing in the Hx-induced murine model of PH demonstrated the accumulation of PCs in the muscularized distal arterioles ( Fig 1B ). Through scRNA-seq and immunofluorescence validation, we identified two HIGD1B + PC subtypes that exist in the pulmonary capillary: Type 1 PCs, which are quiescent in the capillaries, and Type 2 PCs exhibit multipotent cell-like properties and accumulate in the arterioles after exposure to Hx. Furthermore, we found Type 2 PCs transited into SMC-like cells via the upregulation of Vimentin, contributing to vascular remodeling in Hx-induced PH. Conclusion: We identified Higd1b as a unique marker for PCs and generated a novel Higd1b-CreERT2 mouse that specifically labels PCs in the lungs. The discovery of PC-subtype specialization advances our understanding of lung pericyte biology and PC’s contribution to capillary remodeling under pathological conditions.
Abstract 4116639: Efficacy of Transcatheter Aortic Valve Replacement for Severe Pure Native Aortic Valve Regurgitation: A Meta-Analysis
Authors: Mayank Jha, Arya Harikrishna, Madho Mal, Hritvik Jain, Pawan Daga, Muhammad Hanif, Muhammad Aamir, Yasotha Rajeswaran, Jerome Zacks
Journal: Circulation (2024)

Background: Surgical aortic valve replacement (SAVR) is the preferred treatment option for patients with severe aortic regurgitation (AR). Recently, several patients with mixed aortic valve disease, comprising severe aortic stenosis (AS) and at least moderate AR, have been successfully treated with TAVR. However, the treatment of severe native aortic valve regurgitation (NAVR) without AS remains a matter of contention, and the efficacy of TAVR remains uncertain. Aims: The primary outcomes were 30-day mortality and the incidence of device success. The secondary outcomes included incidence of myocardial infarction (MI), stroke, major bleeding, acute kidney injury (AKI) ≥ stage 2, moderate-to-severe paravalvular leak (PVL), permanent pacemaker implantation (PPM), and post-procedural moderate-to-severe AR. Methods: We systematically searched PubMed, Cochrane Library, Scopus and ClinicalTrials.gov for published articles from inception until 2nd April 2024 to evaluate clinical outcomes of TAVR in patients with NAVR. The statistical analysis was conducted using R-Studio 5.3.3. The rates of events with 95% confidence intervals (CI) and the heterogeneity was assessed using p-value and I 2 statistics. Results: A total of 23 published articles with 4,397 patients were included. All-cause mortality at 30 days was 12% (95% CI: 6% to 23%), while device success was 86% (95% CI: 81% to 92%). The incidence of complications such as MI (3%, 95% CI: 2% to 4%), stroke (3%, 95% CI: 2% to 3%), major bleeding (8%, 95% CI: 5% to 11%), AKI ≥ stage 2 (8%, 95% CI: 5% to 12%), and major vascular complications were relatively low (6%, 95% CI: 4% to 7%). PPM was required for 15% of patients (95% CI: 11% to 18%). PVL was observed in 10% of patients (95% CI: 2% to 41%) and post-procedural moderate-to-severe AR occurred in 9% of patients (95% CI: 4% to 20%). Conclusion: TAVR is a viable and reasonable option for a specific population with NAVR. Nevertheless, it is imperative to conduct larger studies with a longer duration of follow-up to obtain more robust evidence of the feasibility of TAVR in patients with NAVR. &lt;/div&gt;
Abstract 4118178: Echocardiographic Measure of Right Ventricular-Pulmonary Arterial Coupling Predicts Survival in Lung Cancer
Authors: Zvonimir Rako, Michael Cekay, Athiththan Yogeswaran, Selin Yildiz, Philipp Friedrich Arndt, Nils Kremer, Simon Schaefer, Patrick Janetzko, Bruno Brito da Rocha, Chris Mummert, Johanna Franken, Henrik Soethe, Hannah Werner, Rio Dumitrascu, Friedrich Grimminger, Ardeschir Ghofrani, Soni Savai Pullamsetti, Werner Seeger, Robert Naeije, Rajkumar Savai, Bastian Eul, Khodr Tello
Journal: Circulation (2024)

Background: Echocardiographic indicators of pulmonary hypertension have been reported to predict decreased survival in lung cancer. We sought to test the hypothesis that this may be associated with impaired right ventricular (RV)-systolic pulmonary arterial pressure (sPAP) coupling, further enhancing the prognostic strength of echocardiography in lung cancer. Methods: This prospective observational study included 220 patients with non-small cell lung cancer (NSCLC) examined by Doppler, strain and 3D echocardiography before starting therapy. Prediction of overall survival was assessed by univariable analysis followed by multivariate Cox regression, receiver operating characteristic (ROC) curves and Kaplan-Meier analyses. Results: Echocardiographic examination was on average within normal limits, even though 30% of the patients had sPAP ≥35 mm Hg. In univariable analysis, overall survival was associated with measures of RV systolic function and probability of pulmonary hypertension. In multivariate Cox regression, only RV global longitudinal strain (GLS)/sPAP (HR: 5.766 [95% CI: 1.025–32.443]) and Eastern Cooperative Oncology Group performance status &lt;2 (HR: 0.332 [95% CI: 0.171–0.644]) independently predicted survival. The optimal ROC curve-derived RV GLS/sPAP cut-off to predict survival was −0.54%/mm Hg. Among patients in Union for International Cancer Control (UICC) stage 4, those with impaired RV-arterial coupling (RV GLS/sPAP &gt;−0.54%/mm Hg) had worse survival than those with maintained RV-arterial coupling (HR: 2.8 [95% CI: 1.5–5.3]); the latter subgroup had similar survival compared with patients in UICC stage 3 (HR: 0.57 [95% CI: 0.28–1.14]). Conclusion: RV GLS/sPAP as an echocardiographic measure of RV-arterial coupling adds to prognostication by the UICC status in NSCLC.
Abstract 4115645: NLRP3 Inflammasome Inhibition With Dapansutrile in Type 2 Diabetes and Elevated Systemic Inflammation: Rationale and Design of the DAPAN-DIA study
Authors: Matthias Hepprich, Nathalie Esser, Jean-Baptiste Julla, Sabine Kahl, Christian Herder, Etienne Larger, Roberto Mallone, Nicolas Venteclef, Michael Roden, Louis Potier, Nicolas Paquot, Antonio Abbate, Mustafa Noor, charles dinarello, J-F Gautier, Marc Donath
Journal: Circulation (2024)

Background: Monoclonal antibodies against IL-1β decrease inflammation, improve insulin secretion and glycaemia, and reduce residual CV risk, but must be injected and are associated with higher incidence of fatal infection. There remains an unmet need for an oral treatment for T2D patients at risk for cardiometabolic complications to safely reduce IL-1β-mediated inflammation chronically&amp;with low risk of immunosuppression. In an initial dose-range finding study in heart failure patients with T2D, we reported evidence of anti-hyperglycaemic efficacy and improvement in LVEF with dapansutrile an oral specific inhibitor of the NLRP3 inflammasome. Objectives: To investigate the potential of preventing the transition to organ complications, The EU funded consortium INTERCEPT-T2D in collaboration with US based biotech Olatec Therapeutics has launched a clinical trial of anti-inflammatory therapy with dapansutrile targeting T2D patients with low-grade inflammation. Methods: Dapansutrile in Diabetes and Complications (DAPAN-DIA, NCT06047262) aims to determine whether NLRP3 inhibition with dapansutrile has the potential to not only improve glycaemia but also reduce micro- and macro-vascular risk and complications from diabetes. DAPAN-DIA is a multicenter, pbo-controlled, prospective, randomized, double-blind trial conducted in Switzerland, France, Belgium and Germany. A total of 300 patients with T2D, HbA1c &gt;7.5% and hsCRP&gt;1.5 mg/L are being randomized to either dapansutrile 1000 mg BID or matching PBO tablets for 6 months (2:1 ratio dapansutrile: pbo). The primary endpoint is change from baseline HbA1c. Secondary endpoints include biomarkers associated with diabetic complications, progression of MASLD as well as chronic inflammation (IL-1 β, IL-6 and hsCRP). A subject-assessed QoL questionnaire is also collected. To detect an absolute difference of 0.5% in HbA1c between groups, approximately 300 subjects will be randomized 2:1 ratio to achieve 80% power, assuming a standard deviation of 1.2% in change from baseline in HbA1c at week 26. Results: The trial has launched and currently is enrolling subjects. Conclusions: DAPAN-DIA is the first placebo-controlled, adequately powered, large, multi-center study with an oral NLRP3-specific Inhibitor, dapansutrile. The trial will generate important data on a new clinically relevant dimension in T2D care where consideration at diagnosis of inflammatory parameters are of importance for the transition to T2D-related complications.