tbuckley/cabot-search huggingface dataset:
Abstract 4138824: Late Gadolinium Enhancement in the Basal Left Ventricle is Associated with Ventricular Arrhythmias in Patients with Pathogenic Titin Variants
Authors: James Laws, Bibin Varghese, Zain Virk, Daisuke Togashi, Majd El-Harasis, Mahsima Shabani, Cassady Pelphrey, Megan Lancaster, Dakota Grauherr, Hollie Williams, diane crawford, Lili Sun, Fei Ye, Prince Kannankeril, Arvindh Kanagasundram, Travis Richardson, Harikrishna Tandri, Zachary Yoneda, Lynne Stevenson, Dan Roden, William Stevenson, Jeffrey Dendy, BEN Shoemaker
Journal: Circulation (2024)

Introduction: Pathogenic titin ( TTN ) variants are associated with malignant ventricular tachycardia (VT) that often arises from fibrosis in the basal LV and may occur before severe LV systolic dysfunction. Late gadolinium enhancement (LGE) can identify the substrate for VT, but measurement of LGE in the basal LV is technically challenging. As genetic testing identifies more patients with earlier stages of TTN cardiomyopathy, methods are needed to stratify their risk for malignant VT. Hypothesis: LGE burden in the basal LV is greater in patients with pathogenic TTN variants compared to controls, and is associated with a higher risk of malignant VT. Methods: Patients with early-onset AF and/or ventricular arrhythmias (VAs) unrelated to ischemic heart disease underwent genetic sequencing. Cases had pathogenic or likely-pathogenic (P/LP) rare TTN variants. Controls had no P/LP variants in cardiomyopathy or arrhythmia genes and were matched by age, sex, and whether they had predominately AF or VAs. Cardiac MRIs were reanalyzed by two readers blinded to case/control status. Basal LV LGE was quantified using the 5-SD signal intensity method of 3 short axis segmented inversion recovery images 8mm apart beginning at the first segment below the LVOT. Risk of malignant VT was defined as: Low Risk (≤100 PVCs per day, no NSVT, no VT), Moderate Risk (NSVT or &gt;100 PVCs per day), or High Risk (prior sustained VT). Results: There were 16 TTN cases and 17 controls. Age ( TTN 53 years [Q1-Q3: 49-59]; controls 51 years [42-59]) and LVEF ( TTN 56% [49-62]; controls 60% [55-63]) were similar. Reanalysis identified basal LGE (defined as ≥5% burden) in 14 patients (42%) compared to only 7 (21%) in the original clinical reports. LVEF was &gt;50% in 10 of 14 patients with LGE. TTN cases had significantly higher basal LGE burden compared to controls ( TTN 9.0% [4.8-13.5] vs. controls 1.4% [0.0-2.3], p&lt;0.01). High and Moderate Risk groups for malignant VT had significantly more basal LV LGE compared to the Low Risk group (High Risk: N=2, median 16.1% [15.3-16.9]; Moderate Risk: N=9, 10.0% [5.9-13.4]; Low Risk: N=22, 2.1% [0.0-3.7] p=0.01). Conclusion: Among patients with relatively preserved LV systolic function, pathogenic TTN variants were associated with greater burden of LGE in the basal LV compared to controls, and basal LGE was associated with severity of ventricular arrhythmias. Measurement of LGE in the basal LV may be useful to assess arrhythmia risk in patients with pathogenic TTN variants.
Abstract 4140394: Substantial cardiovascular risk reduction with icosapent ethyl in patients with prior cardiovascular events regardless of coronary artery disease history: REDUCE-IT CAD
Authors: Rahul Aggarwal, Deepak Bhatt, Christie Ballantyne, Michael Miller, Eliot Brinton, Terry Jacobson, Steven Ketchum, Armando Lira Pineda, Ralph Doyle, Jean-Claude Tardif, Philippe Steg
Journal: Circulation (2024)

BACKGROUND: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multinational, double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol, elevated triglycerides, and cardiovascular (CV) risk, to icosapent ethyl (IPE) 4 g daily or placebo. Randomization was stratified by established CV history (70.7%), or diabetes and other risk factors (29.3%). METHODS/RESULTS: We evaluated IPE in patients with CV history, further characterized as having a documented history of coronary artery disease (CAD), or not. Primary (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, hospitalization for unstable angina) and key secondary (CV death, nonfatal MI, nonfatal stroke) CV endpoints were evaluated. Of the 5,785 (70.7%) REDUCE-IT patients with established CV disease, 4,532 patients had a history of CAD (multi vessel CAD, prior MI, hospitalization for high-risk non-ST-segment elevation acute coronary syndrome) and 1,253 patients did not. IPE reduced primary and key secondary first and total (first plus recurrent) events in patients with and without a history of CAD. In patients with CAD, IPE demonstrated a 25% relative risk reduction in first (HR 0.75; 95% CI 0.66, 0.84; P &lt;0.0001; NNT 17) and 32% reduction in total primary endpoint events (RR 0.68; 95% CI 0.59, 0.78; P &lt;0.0001) compared with placebo ( Figure 1A ). In patients without CAD, IPE demonstrated a 34% relative risk reduction in first (HR 0.66; 95% CI 0.51, 0.85; P =0.0012; NNT 13) and 47% reduction in total primary endpoint events (RR 0.53; 95% CI 0.40, 0.70; P &lt;0.0001) ( Figure 1B ). In patients with and without CAD, similar robust reductions were observed for key secondary endpoint events. CV risk reductions were generally consistent across subgroup analyses by CAD history. Safety findings in patients with or without CAD were generally consistent with the overall study findings and did not differ substantially in patients with or without CAD. CONCLUSION: IPE demonstrated robust CV benefit in statin-treated patients with CV disease. Patients with and without CAD experienced large reductions in absolute and relative risk of CV events.
Abstract 4139262: Combined Dilation of Rheumatic Mitral and Tricuspid Stenosis in Youngest Patient With Quadrivalvular Disease
Authors: Prashant Bharadwaj, Amanpreet Wasir, ravi kalra, Hemali Passwala
Journal: Circulation (2024)

Background: Rheumatic heart disease with involvement of all the four valves is extremely rare with anecdotal case reports. Severe symptomatic multivalvular involvement is also rare. Case: A 12-year-old boy presented with gradually progressive dyspnea over two years to current New York Heart Association (NYHA) class IV status. He was hospitalized for a week with fever, sore throat and migratory polyarthralgia three years ago. Examination- pallor, facial and pedal edema, malnutrition (height= 127 cm, weight= 27 kg, body-mass index= 16.8 kg/m 2 ), Harrison’s sulcus, pulse= 90/minute, blood pressure= 104/64 mm of Hg, severe mitral and tricuspid stenosis, severe pulmonary arterial hypertension, and right ventricular failure. Electrocardiogram- sinus rhythm with right axis deviation and QRS morphology consistent with systemic pulmonary hypertension and severe mitral stenosis. X-Ray chest- bi-atrial enlargement with pulmonary arterial and venous hypertension. Echocardiography- severe mitral stenosis (mitral valve area= 0.3 cm 2 ), trivial mitral regurgitation, Wilkins Score= 8/16, mean gradient= 16 mm of Hg (maximum= 40 mm of Hg), doming of the thickened tricuspid valve with severe tricuspid stenosis, thickened aortic valve leaflets with mild aortic stenosis and trivial aortic regurgitation, and doming of thickened pulmonary valve with a c notch and trivial pulmonary regurgitation. There was associated severe pulmonary hypertension (suprasystemic) with right ventricular systolic pressure of 140 mm of Hg. Discussion: In view of young age, malnutrition and a fulminant presentation of severe mitral and tricuspid stenosis, the management hinged around the percutaneous versus the surgical options. Key factors included young age, financial constraints, and repeated reluctance of parents for open heart surgery. The patient underwent a percutaneous dilation of mitral and tricuspid stenosis with an Inoue balloon in a single intervention. Conclusion: We describe quadrivalvular rheumatic heart disease with severe symptomatic mitral and tricuspid stenosis in the youngest ever reported case. The combined balloon dilation of both valves at this age is also not reported.
Abstract 4140361: Evaluating Inflammatory Tone Following Consumption of Full-fat or Non-fat Yogurt: Peripheral Blood Mononuclear Cell Inflammatory Response
Authors: Victoria Taormina, Simonne Eisenhardt, Matthew Gilbert, C Kien, Matthew Poynter, Jana Kraft
Journal: Circulation (2024)

Inflammation is vital to maintaining homeostasis and immune defense, yet chronic, low-grade inflammation is a hallmark of many cardiometabolic diseases. Due to the high saturated fatty acid content in full-fat dairy foods, national dietary guidance recommends consuming low- or non-fat dairy foods to decrease cardiometabolic disease risk. However, many unique fatty acids found in dairy fat may elicit beneficial effects on chronic low-grade inflammation and the effect of dairy fat within its food matrix remains unclear. Thus, our research question centered on the effect of full-fat dairy foods on inflammatory tone. We hypothesized that short-term consumption of three daily servings of full-fat yogurt would beneficially affect inflammatory tone. The aim of the project was to compare the inflammatory response of individuals with prediabetes after a diet with and without dairy fat. An eight-week randomized controlled clinical trial was conducted comprising two, three-week experimental diet periods, differentiated by the daily consumption of either full-fat yogurt (3.25% fat) or non-fat yogurt. Each experimental diet was preceded by a one-week control diet. Following each diet period, peripheral blood mononuclear cells were isolated from whole blood and incubated in media with or without lipopolysaccharide stimulus. After a 24-hour incubation, cell supernatants were analyzed for interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α concentrations. Under unstimulated conditions, the concentration of IL-1β present in the cell supernatant was lower as a result of the full-fat yogurt diet, compared to the non-fat yogurt diet (0.1 pg/mL compared to 24 pg/mL, respectively; P &lt; 0.01), but there were no differences between diets in IL-1β concentrations at 1, 10, or 100 ng/mL lipopolysaccharide stimulation. Diet did not affect supernatant concentrations of IL-6, IL-8, IL-10, or tumor necrosis factor-α in the unstimulated and stimulated conditions. In conclusion, only minimal differences were observed between diets with three daily servings of full-fat or non-fat yogurt indicating that short-term consumption of dairy fat may not impact inflammation via peripheral blood mononuclear cell cytokine secretion. Funding for this project was provided by the National Dairy Council, Vermont Dairy Promotion Board, USDA National Institute of Food and Agriculture, and UVM Food Systems Research Center.
Abstract 4140326: Predictors of Developing Ischemia-Reperfusion Injury Immediately after Heart Transplantation
Authors: Yosef Manla, Jignesh Patel, Michelle Kittleson, Andriana Nikolova, David Chang, Evan Kransdorf, Lily Stern, Lawrence Czer, Jon Kobashigawa
Journal: Circulation (2024)

Introduction: Post-heart Transplant (HTx) ischemia-reperfusion injury (IRI) is not uncommon and has been associated with an increased risk of rejection and cardiac allograft vasculopathy. IRI may occur due to long ischemia time, high dose inotropes, and technical surgical reasons. Identifying other recipient and donor characteristics that might set patients at higher risk for developing IRI might help inform decision-making and improve patient outcomes. Therefore, we aim to investigate predictors of developing IRI immediately after HTx. Methods: Between 2010 and 2020, we assessed 893 patients undergoing HTx at our center. Recipient and donor characteristics were collected and compared between patients who were noted to have immediate post-HTx (within 30 days) IRI on their endomyocardial biopsy (n=241) vs. those who did not (n=652). Multivariable logistic regression was used to determine predictors of IRI development and included all univariate significant variables with (P&lt;0.1). Outcomes were represented as odds ratios with corresponding 95% confidence intervals. Results: Among 893 patients undergoing HTx, 241 (27%) had IRI within 30 days post-HTx (time to IRI was 14.4 ± 7.3 days). Compared to patients without IRI, those who developed IRI trended towards being older (57 ± 12 vs. 55 ±13 years, P=0.07), were less likely to receive induction therapy with anti-thymocyte globulin (ATG) (43.6 vs. 52.9%, P=0.01), and less likely to be listed with an urgent status at the time of HTx (62.7% vs. 71.9%, P=0.008). Patients listed with an urgent status were on optimal hemodynamic support. No other significant differences were recorded in other pre-transplant or peri-operative recipient characteristics among patients who developed IRI vs. those who did not. In regard to donor characteristics, those who developed IRI received hearts from older donors (37 ± 13.5 vs. 34.9 ± 12.2, P=0.03) and showed a trend toward a higher likelihood of donor-recipient sex mismatch (29.9% vs. 23.6%, P=0.059), regardless of recipient sex. On multivariable logistic regression, only ATG-induction [OR:0.69, 95%CI [0.51-0.93], P=0.015) therapy and urgent status at transplantation [OR:07, 95%CI [0.51-0.96], P=0.028) were significant predictors of IRI development Conclusion: Optimal prioritization of HTx candidates on the waitlist and use of ATG induction therapy seem to protect against immediate IRI post-HTx.
Abstract 4140279: Myeloid/Macrophage Annexin A2 Promotes Kidney Fibrosis
Authors: Ling Lin, Elyse Richardson, Kebin Hu
Journal: Circulation (2024)

Background: Annexin A2 is a Ca 2+ - and phospholipid-binding protein widely expressed in various cells and tissues. It acts as a cell surface receptor for tissue plasminogen activator (tPA) and plasminogen, regulating the homeostasis of blood coagulation, fibrinolysis and matrix degradation. However, its role in kidney fibrosis remains largely unknown. Our previous in vitro work has shown that annexin A2 mediates NF-κB activation and promotes macrophage M2 to M1 phenotypic change, suggesting a critical role of macrophage annexin A2 in kidney fibrogenesis. Methods: We generated a novel myeloid/macrophage-specific annexin A2 knockout mouse by crossbreeding LysMCre mice and annexin A2 flox mice. Unilateral ureteral obstruction (UUO) was induced in the myeloid/macrophage-specific annexin A2 knockout mice and their wildtype counterparts, as well as C57BL/6 mice. Renal histology was evaluated. Kidney fibrosis and renal annexin A2 level were examined in these mice. Results: After UUO injury, annexin A2 was dramatically induced in the fibrotic kidneys from C57BL/6 mice in a time-dependent manner, and its induction correlated with the extent of fibrotic injury as indicated by fibronectin deposition. Intriguingly, double immune staining analysis found that annexin A2 was dramatically induced in the interstitial F4/80-positive macrophages. It was further found that, after obstructive injury, myeloid/macrophage-specific annexin A2 knockout mice displayed significantly reduced tubular epithelial damage and dramatically decreased deposition of matrix components such as collagen and fibronectin than that of their control littermates. Additionally, obstruction-induced epithelial transdifferentiation was significantly reduced in the myeloid/macrophage specific-annexin A2 knockout mice as indicated by increase of Ecadherin and decrease of de novo induction of αSMA. Conclusion: Thus, it is clear that myeloid/macrophage annexin A2 promotes epithelial transdifferentiation and kidney fibrosis after obstructive injury.
Abstract 4139506: Comparative Analysis of 30-Day Surgical Outcomes: Univalvular vs. Multivalvular Procedures in Contemporary Practice
Authors: Fernanda Tessari, Vitor Rosa, Daniella Nazzetta, Mariana Lopes, Layara Fernanda Vicente Pereira Lipari, CARLOS CAMPOS, Camila Andrade, Giovanna de Souza, Laura Beatriz Ferola, Roney SAMPAIO, Flavio Tarasoutchi
Journal: Circulation (2024)

Introduction: Data on multivalvular surgery are heterogeneous, not contemporary, and are underrepresented from low-income countries where rheumatic disease is prevalent Objectives: To compare clinical, epidemiological data, and surgical outcomes between patients undergoing surgery for one vs. 2 or more concomitant valve diseases. Methods: Patients in the INCORVALV Registry were divided into groups based on the number of valves treated in the same procedure: univalvular vs. multivalvular (2 or more). Outcomes were evaluated at 30 days. Results: Of 459 patients, 400 had single-valve and 59 had multivalve surgery, with only 1 having 3-valve surgery. Groups were similar in age (55±16 vs. 55±15 years, p=0.98), male sex (49.3% vs. 52.5%, p=0.74), NYHA class III or IV (66.7% vs. 76%, p=0.08) and comorbidities such as hypertension (59.6% vs 54.2%, p=0.57) and diabetes (18% vs 22%, p=0.57). Multivalvular patients had higher pulmonary arterial pressure (47.7±19.4 vs. 59.2±19.6 mmHg, p&lt;0.01) and lower creatinine clearance (72.7±33.4 vs. 62.4±25.4 mL/min, p=0.03). In the univalvular group, aortic valve replacement (45.4%) and mitral valve replacement (34.9%) predominated, while in the multivalvular group, aortic valve replacement occurred in 69.5%, mitral valve replacement in 50.8%, mitral valve repair in 42.4%, and tricuspid valve repair in 16.9% of patients. Cardiopulmonary bypass time (101.9±38.1 vs. 139.6±55.3 min, p&lt;0.01) and cross-clamp time (79.3±31.3 vs. 115.2±51.7 min, p&lt;0.01) were higher in the multivalvular group. However, there was no difference in 30-day mortality (12.8% vs. 22.0%, p=0.08), cardiovascular mortality (10.5% vs. 18.6%, p=1.00), stroke (1.3% vs. 3.4%, p=0.23), major bleeding (9.2% vs. 15.5%, p=0.21), surgical site infection (9.2% vs. 8.6%, p=1.00), need for reoperation (8.1% vs. 10.2%, p=0.61) or 30-day hospitalization (5.0% vs 1.7%, p=0.50). Multivalvular surgery was not a predictor of 30-day mortality (HR:1.50, 95% CI 0.611-3.68, p=0.38). Predictors were: diabetes (HR:2.56, 95% CI 1.21-5.43, p=0.01), mitral valve replacement (HR:3.01, 95% CI 1.46-6.19, p&lt;0.01), left ventricular ejection fraction (HR:0.96, 95% CI 0.93-0.99, p&lt;0.01) and creatinine clearance (HR:0.96, 95% CI 0.95-0.98, p&lt;0.01). Conclusion: Multivalvular surgery presents a comparable risk to univalvular surgery, despite older studies. This is likely due to advancements in surgical techniques and a predominance of younger patients, many with rheumatic etiology.
Abstract 4139502: Projected Impact of GLP-1 adoption on 5-year coronary stent rates among Medicare beneficiaries with cardiovascular disease
Authors: Saif Rathore, Andrew Epstein, Eric Zuk, Jeptha Curtis
Journal: Circulation (2024)

Background: Semaglutide reduced 5-year rates of coronary revascularization by 23% in SELECT. The impact of broader adoption of glucagon-like peptide 1 (GLP-1) agonists on coronary stent use among elderly patients with cardiovascular (CV) disease is unclear. Methods: To project the impact of GLP-1 adoption on 5-year rates of coronary stent use, we analyzed claims data for the 5% random sample of fee-for-service Medicare and Medicare Advantage beneficiaries identified in 2016 (n=1,847,213). Patient risk for CV events was derived using the REGARDS study administrative CV risk algorithm. Five-year observed coronary stent use was based on treatment in 2017–21. The unadjusted association between derived CV event risk and observed stent use was modeled as a flexible linear spline. Projected impact of increased GLP-1 use on patients’ 5-year risk of stent use was calculated by applying SELECT estimates of coronary revascularization reduction (HR 0.77 95% CI 0.68–0.87) to patients’ REGARDS-derived CV event risk and estimating stent use at the GLP-1-driven reduced derived CV event risk level. We projected impact on 5-year stent use as GLP-1 use increased from 0% to 100% of beneficiaries under 4 CV risk-based adoption scenarios: highest CV risk first; lowest CV risk first; median CV risk patients first (base case); and random adoption. Results: Sixty percent adoption of GLP-1 (current statin use) by median CV risk patients first would reduce coronary stent use overall by 6.9% (95% CI 3.6%–9.8%). Impact varied by role of CV risk in GLP-1 adoption, with 60% use in highest CV risk patients first resulting in 21.5% (95% CI 14.3%–25.8%) reduction as opposed to 5.9% (95% CI 3.3%–8.3%) if driven by population with 60% lowest CV risk (Figure). Adoption by 25% highest CV risk would achieve 70% benefit of complete population use. Reductions varied more than two-fold across hospital referral regions (HRRs) in the base case, ranging from 4.5% (95% CI 2.4%–6.1%) to 9.2% (95% CI 4.7%–13.3%); the highest CV-risk-first approach impact ranged from 13.6% (95% CI 9.0%–16.8%) to 30.7% (95% CI 20.7%–35.6%). Conclusion: GLP-1 adoption by Medicare beneficiaries comparable to current statin use could reduce coronary stent use nationally by 6.9% if focused on median CV risk, but up to 21.5% if focused on highest CV risk patients first. Impact varies by HRR, with high GLP-1 use among highest CV risk patients reducing stent use as much as &gt;30%.
Abstract 4140348: Characterization of Isolated Right Ventricular Congestion in Cardiogenic Shock
Authors: Gurleen Kaur, David Berg, Sean Van Diepen, Jason Katz, Jianping Guo, David Morrow, Erin Bohula
Journal: Circulation (2024)

Introduction: Right ventricular (RV) congestion has been associated with poor outcomes in cardiogenic shock (CS); however, the clinical profile of pts with CS&amp;isolated RV congestion has been less well characterized. We aimed to describe the severity of illness, resource utilization&amp;mortality in pts with isolated RV congestion compared to other congestive profiles. Methods: The Critical Care Cardiology Trials Network is a multicenter registry of CICUs coordinated by the TIMI Study Group (Boston, MA). Pts with CS with invasive hemodynamic assessment within 24h of CICU admission (2018-2023)&amp;not on mechanical circulatory support (MCS) at the time were included. Congestive profiles were defined by right atrial pressure (RAP)&amp;pulmonary capillary wedge pressure (PCWP): isolated RV (RAP≥12&amp;PCWP&lt;18); isolated left ventricular (LV: RAP&lt;12&amp;PCWP≥18); biventricular (BiV: RAP≥12&amp;PCWP≥18), and non-congested (NC: RAP&lt;12&amp;PCWP&lt;18). Results: Of 2121 pts with CS, 1186 (56%) met the inclusion criteria with 7.1% classified as RV congestion, 61.6% as BiV, 18.5% as LV&amp;12.7% as NC. The RV group was more likely to be female&amp;have pulmonary disease than others&amp;less likely to have prior HF or severe valve disease than LV&amp;BiV. The RV congestion group had lower pulmonary artery pulsatility index&amp;higher pulmonary vascular resistance than LV&amp;NC (p&lt;0.05 for all); MAP&amp;CI were similar across groups. PE was a contributor to CS in 1.2% and pHTN in 13.1% of RV cases. The RV group more often presented with de novo HF-CS, where BiV&amp;LV more often had acute on chronic HF-CS. The RV group tended to have worse shock severity by SOFA score, lactate, vasoactive-inotropic score (global p&lt;0.05 for all)&amp;SCAI stage (panel A) and was more likely to have a cardiac arrest (p=0.010). The RV group had greater use of mechanical ventilation&amp;renal replacement, but lower use of MCS (panel B). CICU mortality was significantly higher in the RV group compared to other profiles (panel C), including after adjustment for cardiac arrest&amp;CS etiology. Conclusion: In pts with CS, isolated RV congestion was associated with the highest presenting illness severity, resource utilization&amp;mortality when compared to other congestive profiles.