tbuckley/cabot-search huggingface dataset:
Abstract 4141107: Genome-wide association study of aortic stiffness derived from deep learning in CMR images of 45,789 individuals identifies loci linked with cell-matrix structure
Authors: Nikhil Paliwal, Albert Henry, Chris Finan, Rhodri Davies, Alun Hughes, Bryan Williams, Anders Malarstig, Tom Lumbers, Aaron Hingorani
Journal: Circulation (2024)

Background: Aortic stiffness is associated with increased risk of cardiovascular events. Deep learning on large cardiac magnetic resonance (CMR) imaging samples has enabled detailed characterization of cardiac shape and function for use in genome-wide association studies (GWAS), leading to improved understanding of genetic aetiology of cardiovascular diseases (CVDs). Aim: We present a novel CMR-based pressure-independent measure of aortic stiffness, identify genetic factors and biological determinants using GWAS analysis of CMR imaging data from the UK Biobank. Methods: A pre-trained neural network was used to segment CMR images of participants in the UK Biobank to quantify ascending aorta diameter, which together with contemporaneous systolic and diastolic blood pressure measurements were used to calculate a pressure-independent measure of aortic stiffness ( β 0 ). The measurement assumes an exponential relationship between pressure and aortic diameter. We performed a GWAS on β 0 in 45,789 participants of European ancestry, excluding individuals with a prior history of CVDs. We performed stepwise conditional joint analysis to identify conditionally independent lead variants, and then defined a locus based on a 500kb flanking region centered on the variant. For each locus, we evaluated and combined scores from four complimentary approaches: variant-to-gene, polygenic priority score, gene-based association test and nearest gene. Candidate gene with the highest aggregate score was identified as the putative effector gene. We performed a pathway enrichment analysis for putative effector gene to identify potential biological pathways involving β 0 . Results: We identified 17 independent lead variants from the GWAS (Figure A). We were able to identify putative effector genes at 16 of 17 genomic loci (Figure B, one locus was not resolved). Among the putative effectors were ELN and LTBP4, genes implicated in elastin fiber formation pathway (p=1.9E-2); ELN, HAS2 and LTBP4 associated with extracellular matrix assembly pathway (p=7.5E-3), and ULK4, ARHGAP24, ELN, HAS2, SVIL, ARHGAP22, CDH13, SMG6 , and LTBP4 linked to regulation of cellular component organization (p=2.6E-2). Conclusion: A GWAS of CMR-derived aortic stiffness identified 17 independent loci, suggesting its links with genetic influences on extracellular matrix and cellular component organization. These findings provide insights into the determinants of aortic stiffness that may inform future mechanistic studies.
Abstract 4140690: Management of Ventricular Septal Defect after Bipolar Radiofrequency Ablation for Ventricular Tachycardia
Authors: Manasvi Gupta, Joshua Silverstein, Andrew Oehler, George Shaw
Journal: Circulation (2024)

Background: Ventricular septal defect (VSD) can develop as a rare complication in patients undergoing bipolar radiofrequency ablation for ventricular tachycardia (VT). Case: A 67-year-old male with nonischemic cardiomyopathy underwent three VT ablations over 2 years for recurrent LV summit VT. At the initial procedure, minimal bipolar voltage abnormality but significant unipolar voltage abnormality was found at the basal interventricular septum, periaortic tissue, and left ventricular (LV) summit, consistent with mid-myocardial fibrosis. Extensive endocardial unipolar radiofrequency ablation (RFA) was performed on the LV side. Despite lack of inducibility with triple extrastimuli, VT recurred that was treated with sotalol and mexiletine. One year ago, due to recurrent symptomatic VT, he underwent a redo ablation. The clinical VT mapped earliest to the right ventricular (RV) side of basal anteroseptum. Extensive RV and LV endocardial unipolar RFA was performed, but VT remained inducible. Therefore, ethanol ablation was performed through septal perforating branch of the distal coronary sinus, after which VT could not be induced. A month later, he returned in VT storm. Repeat study mapped clinical VT earliest to the basal anteroseptal RVOT, with a focal breakout pattern on both LV and RV consistent with a deep septal substrate (earliest activation signals ~40 ms preQRS). After attempting unipolar ablation from the LV aspect, bipolar ablation was performed across the basal anterior interventricular septum. VT could no longer be induced with triple extrastimuli, on isoproterenol. On recent routine outpatient visit 6 months later, a new murmur was noted. Multimodality imaging revealed a large (10 mm) outlet VSD in the anteroseptum with left to right shunt (Qp:Qs 1.5). LV function and cardiac index were mildly reduced (CI 2.0 ml/kg/m 2 ). No evidence of pulmonary hypertension or RV dysfunction. After multidisciplinary heart team discussion, decision was made to attempt surgical closure. Conclusion: Patients with refractory VT managed with multiple ablations at the same focus using different technologies should be closely monitored on an outpatient basis to evaluate for rare complications such as VSD.
Abstract 4141218: Prolonged Impella 5.5 Support – A Single-Center Experience
Authors: Ivan Kuznetsov, Jake Kieserman, Omar Toubat, Alison Ranum, Adrian Peterson, Alyson Brown, Mauer Biscotti, Jacob King, Marisa Cevasco, christian bermudez, Joyce Wald
Journal: Circulation (2024)

Background: The Impella 5.5 (Abiomed; I5.5) is a temporary mechanical circulatory support (tMCS) device currently approved for periods of ≤14 days. Although many centers have reported successful I5.5 utilization beyond this duration, the indications and clinical outcomes associated with this practice are unknown. Methods: We retrospectively analyzed patients at our institution receiving I5.5 from April 2021-September 2023. Inclusion criteria were patients which received I5.5 at our institution that reached first event– specified as death/hospice, durable VAD/heart transplant, or recovery – prior to discharge or transfer. The primary outcome was differences in first event between patients receiving I5.5 support for ≤14-days vs &gt;14-days. Secondary outcomes were complication rates, defined by occurrence of bleeding, stroke, significant hemolysis, or device migration/malfunction. Propensity-matching was utilized to help account for potential confounders. Statistical analysis involved Wilcoxon rank-sum testing and Chi-square/Fisher’s exact tests with Benjamini-Hochberg correction. Results: Among the 162 patients which met inclusion criteria, 76 (47%) required ≤14-days of support and 86 (53%) required &gt;14-days. Baseline demographics and baseline INTERMACS profile and SCAI class were similar. In the ≤14-days group vs &gt;14-day group, 54% vs 72% progressed to durable VAD/transplant (p = 0.02), 28% vs 21% died/pursued hospice (p = 0.48), and 18% vs 7% recovered (p = 0.04). Sub-group analysis on a propensity-matched cohort with similar INTERMACS profile and SCAI classification did not alter the above results, with similar probability of death/hospice (p = 0.52) and increased probability of durable VAD/transplant (54% ≤14-days, 71% &gt;14-days; p = 0.04). Time-adjusted complication rates between cohorts were similar (IRR = 1.1 ≤14 vs &gt;14-days; 95% CI 0.3 - 1.9), but overall complication frequency was higher in the &gt;14-day group (11% ≤14-days, 41% &gt;14 days, p &lt; 0.01). Conclusion: I5.5-based tMCS beyond 14 days was not associated with increased mortality or decreased probability of eventual durable VAD/transplant. We did not observe an increased incidence rate of complications for I5.5 usage beyond 14 days but did note an increased absolute probability of complications with prolonged support. Future randomized-control studies which better control for potential confounds are warranted to better identify appropriate indications for I5.5 tMCS utilization beyond 14 days.
Abstract 4141276: Valvular oxidized phospholipids correlate with severity of human aortic valvular stenosis
Authors: Craig Resch, Aleksandra Stamenkovic, Arun Surendran, Ashish Shah, Amir Ravandi
Journal: Circulation (2024)

Introduction: Aortic valve stenosis (AVS) is a degenerative disease characterized by progressive calcification and stenosis, driven by a multifactorial inflammatory process. Oxidized phospholipids (OxPL) have been implicated in this process, yet their presence in aortic valve tissue remains unexplored. This study aims to fill this gap by developing a sensitive method to identify and quantify OxPL in the plasma and tissue of patients with severe AVS. Methods: We obtained aortic valve tissue from 70 patients undergoing aortic valve replacement surgery. The tissue samples were subjected to derivatization with DNPH, followed by LC/MS/MS analysis, enabling the identification and quantification of 60 individual OxPL across five different phospholipid classes. Results: Our analysis identified 34 OxPL species across five phospholipid classes in human valvular tissue, including oxidized phosphatidylcholine (OxPC), phosphatidylethanolamine (OxPE), phosphatidylinositol (OxPI), and phosphatidylserine (OxPS). OxPC was the most abundant class, with PONPC being the most prevalent molecule, constituting 35% of total OxPL. We observed a significant increase (p&lt;0.05) in 20 OxPL species in valvular tissue when comparing mild to moderate to severe valve stenosis based on pressure gradient. The most significant change occurred between mild and moderate AVS as PONPC increased by 90% (p=0.012) and total OxPC increased by 83% (p=0.004). Compared to plasma, valvular tissue had more OxPS species present and an increase in longer chain fatty acid aldehydes in the SN-2 position of OxPCs. Conclusion: Our findings indicate that OxPL infiltration of the valve tissue is an early event in the progression of AVS. This suggests that early intervention with OxPL-lowering therapies may prove beneficial in managing AVS.
Abstract 4141513: Effect of Dapagliflozin on Cardiovascular Outcome in Patients With Acute Myocardial Infarction; a Systematic Review and Meta-analysis
Authors: Abhigan Shrestha, Tanzina Afroze, Sajina Shrestha, Vikash Jaiswal, Suman Kadariya, Aman Goyal, Ravi Sankar Reddy Edara
Journal: Circulation (2024)

Background: The beneficial effect of SGLT-2 inhibitors in managing type 2 diabetes mellitus and heart failure with reduced ejection fraction has already been established. However, the outcomes of dapagliflozin on cardiovascular events in patients with acute myocardial infarction are not well studied. Hypothesis: Our study aims to investigate the effect of dapagliflozin in reducing cardiovascular events among patients with acute myocardial infarction. Methods: A systematic search was conducted using multiple electronic databases from inception until March 2024 using the appropriate Mesh terms, “ dapagliflozin,” “SGLT 2 inhibitors,” “acute myocardial infarction,” “heart failure,” “major cardiovascular events,” “all-cause mortality.” We used the random effect model to calculate the pooled relative risk and their corresponding confidence interval. A p-value of &lt;0.05 was considered statistically significant. Results: A meta-analysis was conducted using 5 studies that included 9321 patients (Dapagliflozin: 4404 and Placebo: 4917) with a mean age of 62.46 and 63.26 years respectively. Out of these, four studies included DM with heart failure patients and one study without DM and Heart failure patients. The average follow-up was 21.5 years. Pooled analysis showed that dapagliflozin is associated with a lower risk of acute kidney injury (RR 0.52, 95%CI: 0.12-0.92 p&lt;0.001). However, no statistically significant difference was noticed in reducing all-cause mortality rate (RR 0.73, 95% CI 0.32-1.14, p=0.09), major cardiovascular events (RR, 0.73, 95% CI 0.44-1.02, p=0.27), cardiovascular mortality rate (RR 0.95, 95% CI 0.70-1.20, p=0.54), stroke (RR 0.80, 95% CI 0.50-1.09, p=0.69), and serious adverse events (RR 1.00, 95%CI: 0.88-1.13, p=0.95). Conclusion: Dapagliflozin was associated with a lower risk of acute kidney injury. However, the risk of major cardiovascular events, and cardiovascular mortality rate were comparable between both groups of patients.
Abstract 4141366: Teamwork Makes the Dream Work: Self-care and Depressive Symptoms in Rural Heart Failure Dyads
Authors: Lucinda Graven, Laurie Abbott, Thomas Ledermann, M. Bryant Howren, Joan Grant
Journal: Circulation (2024)

Introduction: Managing heart failure (HF) in the home is stressful and complex for rural dyads who experience unique challenges and barriers to optimal HF self-care (SC). Innovative, tailored, dyadic problem-solving interventions are needed which support teamwork in managing HF SC problems in the home to enhance dyadic HF SC and reduce depressive symptoms. Research Question: Will participation in a 3-month dyadic, telephone-based problem-solving intervention focused on dyadic HF SC problems experienced in the home improve patient and care partner-contributed HF SC and reduce depressive symptoms in rural dyads living with HF? Methods: Using a dyadic single-group repeated-measures design, 41 rural dyads (patient-informal care partner) living with HF participated in 8 telephone sessions with a registered nurse to identify and develop management strategies for dyadic HF SC problems experienced in the home. Data were collected at baseline and 5-, 9-, and 13-weeks post baseline using the Self-care of HF Index (SCHFI), Caregiver Contribution to the SCHFI, and the Center for Epidemiological Studies – Depression Scale. HF patients were mostly female (59%), married (66.7%) Caucasians (69.2%), with 2-3 comorbidities (53.8%) and Class 2 NYHA HF (69.2%). Care partners were primarily female (58.5%), married (75.6%) Caucasians (70.7%), and spouses of the HF patient (68.3%), with 0-1 comorbidities (58.6%), and had been providing care for ≥ 5 years (46.3%). Descriptive statistics were used to examine dyad characteristics and outcome variables at each time point. Changes in patients' and care partners’ outcomes were analyzed using dyadic Growth Curve Modeling within the Multilevel Modeling framework. Results: Across time, patient scores improved for depressive symptoms ( b = -1.81, p = .002) and SC maintenance ( b = 2.29, p &lt; .001). SC confidence increased in both patients ( b = 2.51, p &lt; .001) and care partners ( b = 2.26, p = .01). Increases in patient SC management across time was noted but non-significant ( b = 1.46, p = .133 for patients; b = 0.60, p = .561 for care partners). Conclusions: Problem-solving interventions in rural dyads living with HF may be helpful in addressing HF SC issues and depressive symptoms in the home, especially in HF patients. However, more research is needed to examine this promising intervention in a larger clinical trial.
Abstract 4140688: Bioactive Oxylipins Predict Aortic Vascular Calcification Severity in Heart Failure with Preserved Ejection Fraction
Authors: Vaishnavi Aradhyula, Anas Fares, John Vergis, Prabhatchandra Dube, Alborz Sherafati, Alex Kloster, XBellaX XKhatib-ShahidiX, Ahmed Elzanaty, Omar Sajdeya, Sareeta Manandhar, Krishna Rao Maddipati, Pamela Brewster, Robert Smith, Steven Haller, David Kennedy, Samer Khouri, Rajesh Gupta
Journal: Circulation (2024)

Background: Aortic calcification has been significantly linked to the development of heart failure with preserved ejection fraction (HFpEF). Both HFpEF and aortic calcification are associated with inflammation, vascular dysfunction, and remodeling. Circulating polyunsaturated fatty acid oxidized lipids, or oxylipins, have been well described to initiate and resolve inflammation in cardiovascular disease. We questioned the role of these bioactive oxylipins in predicting aortic vascular calcification severity in HFpEF. Hypothesis: We hypothesize that oxylipins can predict and distinguish aortic vascular calcification severity in HFpEF patients. Methods: We collected venous blood samples during right heart catheterization from 57 HFpEF patients. We categorized patients by CT-based aortic vascular calcification severity: none (control; n=8), mild (&lt;25%, n=14), moderate (26-50%, n=9), and severe (&gt;50%, n=26). We measured 143 oxylipins in all study participants using mass spectrometry. Along with unpaired T-tests, machine learning analysis was used to determine oxylipin permutation importance and evaluate predictive accuracy for aortic vascular calcification severity. Results: Demographic variables showed no significant differences between groups. Pro-inflammatory TXB2 levels were elevated in severe aortic calcification vs control (p=0.036). This is further substantiated by increased 12(S)-HHTrE (a degradation product of TXA2) levels in severe aortic calcification vs control (p=0.0266). Anti-inflammatory 7(8)-EpDPE was also elevated in severe aortic calcification compared to control (p=0.0067). Finally, the inactivated anti-inflammatory 5,6 DiHETrE levels were higher in severe aortic calcification vs control (p=0.019). Out of 143 oxylipins, the 12-lipid panel of 5(S),15(S)-DiHETE, 5,6-DiHETrE, PGE2, 4-HDoHE, 15-keto PGE2, 11dh-2,3-dinor TXB2, iPF-VI, 19,20-DiHDoPE, 9(S)-HOTrE, 13,14dh-15k-PGE2, 5-oxoETE, and PD1 were the most significant predictors of severe (n=26) vs non-severe (none, mild, moderate; n=31) aortic vascular calcification, with 100% predictive accuracy. Conclusion: In HFpEF patients, aortic vascular calcification severity can be predicted with remarkable accuracy by a novel panel of circulating, bioactive venous oxylipins.
Abstract 4140997: Exercise Right Ventricular to Pulmonary Circulation Uncoupling and NT-pro-BNP Levels Correlations In Heart Failure
Authors: GIULIA CRISCI, Violetta Serrantoni, Maurizio Losito, Tania Zagarra, Daniele Ginelli, Francesca Bursi, Marco Guazzi
Journal: Circulation (2024)

Aim: Right ventricle to pulmonary circulation (RV-Pc) uncoupling represents a mainstay in staging progression of heart failure (HF), being an independent predictor of mortality. In addition, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a well-established diagnostic and prognostic serum biomarker. In lack of clear clinical evidences on the relationship between exercise levels of NT-proBNP and RV-Pc uncoupling, this represents the aim of our investigation. Methods and Results: A cohort of 13 HF stable patients (mean age 71.6 ± 8.1; 48% female, mean left ventricular ejection fraction 57±13%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing (iCPET) with RV 3D-imaging analysis and were compared with a control population. Natriuretic peptides levels were obtained at rest and peak exercise. RV-Pc coupling was addressed by using the length-force relationship TAPSE/PASP ratio (tricuspid annular plane systolic/excursion pulmonary arterial systolic pressure). As expected, HF patients exhibited a higher level of NT-pro-BNP compared to controls (mean 831 ng/ml vs 131 ng/ml, at rest; mean 793.3 vs 138 ng/ml at peak). In HF, TAPSE/PAPS at peak exercise decreased compared to rest (0.73 ± 0.19 vs 0.47 ± 0.15 respectively) with an inverse correlation between NT-pro-BNP and TAPSE/PAPS exercise (r=0.60, p&lt;0.01). See figure. Conclusion: Our investigation demonstrates a parallel trend between peak TAPSE/PASP and peak NT-pro-BNP. These findings suggest that natriuretic peptide may serve as a surrogate of underlying RV to Pc uncoupling and the right heart plays a crucial role in the biomarker activity during maximal exercise in advanced HF.
Abstract 4141117: Semaglutide and cardiovascular outcomes by blood pressure in the SELECT trial
Authors: Subodh Verma, John Deanfield, Yaron Arbel, Bertrand Cariou, Ana Laura S.A. Matos, G. Kees Hovingh, Ole Kleist Jeppesen, Steven Kahn, Gustavs Latkovskis, Ildiko Lingvay, Michael Maeng, Vincent Maher, Oleksandr Parkhomenko, Neil Poulter, Philippe van de Borne, Peter Kure, Abraham Lincoff
Journal: Circulation (2024)

Introduction: Although glucagon-like peptide-1 receptor agonists have been shown to reduce BP and major cardiovascular adverse events (MACE), little is known about whether the benefits of these therapies vary in individuals with hypertension (HT) or across the spectrum of BP categories. Research Question and Aim: To evaluate the effect of once-weekly semaglutide 2.4 mg vs placebo on cardiovascular (CV) outcomes by baseline BP categories in SELECT. Methods: SELECT was a double-blind, randomized, placebo-controlled trial that included patients aged ≥45 years with preexisting CV disease and BMI ≥27 kg/m 2 without diabetes. Patients received once-weekly semaglutide 2.4 mg or placebo; the primary endpoint was time to first MACE analyzed with a Cox proportional hazards model with semaglutide and placebo as fixed factors according to baseline BP categories. Results: Among 17,604 randomized patients, 14,392 (82%) had a history of HT. Patients with history of HT were older and more likely female, with a higher BMI, lower eGFR, and higher UACR. A higher proportion presented with atrial fibrillation, obstructive sleep apnea, and heart failure NYHA class II/III, but fewer underwent coronary revascularization (Table). Patients with HT who received placebo had a higher incidence rate of MACE vs semaglutide (2.6 vs 2.1 per 100 patient-years, respectively). Semaglutide generally exhibited consistent benefits for CV outcomes regardless of history of HT or baseline BP categories (Figure). Compared with placebo, semaglutide significantly and consistently reduced systolic BP (SBP) across BP categories (normal, −2.9 [95% CI−4.0; −1.9]; elevated BP, −2.8 [−4.0; −1.6]; stage 1, −3.4: [−4.1; −2.6]; stage 2, −3.7 [− 4.4; −2.9]). Conclusions: HT is highly prevalent in people with overweight or obesity and atherosclerotic CV disease without diabetes and is associated with increased MACE. Semaglutide led to consistent reductions in MACE and lowered SBP irrespective of baseline BP category.