tbuckley/cabot-search huggingface dataset:
Abstract 4138919: Evaluating Perioperative Colchicine's Influence On New-Onset Heart Block After Transcatheter Aortic Valve Implantation: A US Multicenter Retrospective Analysis
Authors: Kerollos Abdelsayed, Basma Amer, Michele Fouad, Khaled Elfert, Sittinun Thangjui, Sandi Banour, Basel Abdelazeem
Journal: Circulation (2024)

Background: New-onset heart block (NOHB) is a frequent early complication following transcatheter aortic valve intervention (TAVI), partially driven by mechanical edema. Colchicine, known for its anti-inflammatory properties and efficacy in reducing myocardial infarction in coronary artery disease, has never been studied for its effects on NOHB post-TAVI. Methods: This study used the TriNetX database (January 2013 to May 2024) to compare patients receiving colchicine (at least one dose within two days before and up to 12 days after their first TAVI) with those never exposed to colchicine up to one year after the procedure. A propensity score-matched (PSM) analysis controlled for baseline demographic and clinical characteristics (figure 1A). Outcomes included NOHB in addition to all-cause hospitalizations, all-cause mortality, new-onset atrial fibrillation (NOAF), acute coronary syndrome (ACS), and stroke at one and six months post-TAVI and were assessed through the risk ratio (RR) and 95% confidence interval (CI). Results: The control group included 49,384 patients, while the colchicine group included 725. After PSM, 712 patients were included in each group; 36.1% and 40.3% were females. The mean age was 77.8 (±8.9) and 78.1 (±8.8) years, respectively. Colchicine was associated with a significant reduction of NOHB at one month (RR= 0.64, 95% CI [0.49; 0.83], p=0.001 ) and six months (RR= 0.61, 95% CI [0.48; 0.78], p&lt;0.0001 ) post-TAVI. Similarly, all-cause hospitalizations and mortality were significantly lower in the colchicine group at one month (RR= 0.65, 95% CI [0.60; 0.71], p&lt;0.0001 ; RR= 0.41, 95% CI [0.21; 0.80], p=0.007 , respectively) and six months (RR= 0.96, 95% CI [0.64; 0.74], p&lt;0.0001 ; RR= 0.67, 95% CI [0.46; 0.97], p=0.03 , respectively). Other postprocedural complications were comparable between the groups at one and six months (figure 1B). Sensitivity analysis revealed an E-value of 2.26 at one month and 2.4 at six months for the RR of NOHB. Conclusion: Perioperative colchicine was associated with reduced risk of NOHB, all-cause hospitalization, and all-cause mortality at one and six months after TAVI. However, it was not associated with reduced postoperative risk of NOAF, ACS, or stroke at one or six months.
Abstract 4139022: Targeting Aurora Kinase B Improves Vascular Remodeling in Pulmonary Arterial Hypertension
Authors: Sarah-Eve Lemay, Manon Mougin, Melanie Sauvaget, EL-Kabbout Reem, Chanil Valasarajan, Keiko Yamamoto, Sandra Martineau, Andreanne Pelletier, Yann Grobs, Alice Bourgeois, Charlotte Romanet, Sandra Breuils Bonnet, Monica Montesinos, Min Lu, Huidong Chen, Charlie Theberge, Francois Potus, Soni Savai Pullamsetti, Steeve Provencher, Sebastien Bonnet, Olivier Boucherat
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by pulmonary artery (PA) remodeling. Extensive proliferation of PA smooth muscle cells (PASMCs) is perhaps the most important feature of PAH accounting for vascular remodeling for which current treatments have limited efficacy. Methods and Results: To discover novel actionable targets involved in vascular remodeling, we performed a comparative RNA-sequencing analysis between control and PAH-PASMCs, and next enriched our experiment with two publicly available datasets conducted on comparable cell lines. After merging the three datasets, 136 genes were found to overlap, of which 126 and 10 were up- and down-regulated in PAH-PASMCs, respectively. A connectivity map analysis using SigCom Library of Integrated Network-based Cellular Signatures was performed on the commonly upregulated genes and identified an aurora kinase B (AURKB) inhibitor as the top reverser drug of PAH-PASMCs gene signature. In this regard, aurora kinase B (AURKB), known to play a critical role in the onset and progression of mitosis, was present among the overlapping upregulated genes in PAH-PASMCs. Further experiments revealed that FOXM1 positively regulates AURKB expression. Pharmacological (Barasertib) and molecular (siRNA) inhibition of AURKB reduced PAH-PASMC proliferation (EDU incorporation, Ki67 labeling&amp;WB PLK1), survival (TUNEL assay,&amp;WB Survivin) and was associated with mitotic defects. Acquisition of a senescence-like phenotype was observed in PAH-PASMCs that escaped apoptosis following AURKB inhibition (SA-βGal, p21, p53, SASP…). Barasertib treatment significantly improved pulmonary vascular remodeling and hemodynamics in MCT and Su/Hx rats with established PAH (RHC&amp;EVG) and resulted in a marked increase in p21 in small PAs. Similar effects were also observed in human precision-cut lung slices isolated from PAH patients. Finally, the combination of Barasertib with the p21 attenuator UC2288 was more effective in reducing vascular remodeling in Su/Hx rats than either drug alone (EVG, RHC, echocardiography). Conclusion: Our research identified AURKB as a novel therapeutic target and suggests that combining anti-remodeling drugs with senotherapeutics may be more effective in counteracting vascular remodeling in PAH.
Abstract 4139462: Admission and Discharge B-Natriuretic Peptide Profiles Are Predictive of 1-Year Mortality Above Intermountain Risk Score in Heart Failure Phenotypes
Authors: Pablo Sanchez, Christian ODonnell, shadi bagherzadeh, Bettia Celestin, Everton Santana, Tami Bair, Francois Haddad, Benjamin Horne
Journal: Circulation (2024)

Introduction: Pre-discharge and in-hospital trends of B-type natriuretic peptide (BNP) are predictive of mortality in patients recently discharged after acute decompensated heart failure (ADHF). The Intermountain risk score (IMRS) uses common serum laboratory data to predict outcomes in hospitalized patients. Considering that in-hospital BNP levels differ for HF with preserved (HFpEF) and HF with non-preserved EF (HFnpEF), the goal of this work was to assess whether BNP at admission and discharge provided prognostic information beyond the IMRS in either phenotype. Methods: In a hospitalized cohort with ADHF in Intermountain Health, adult patients were included if they had 1) a BNP value within 24 hours of admission, and 2) a separate BNP value within 3 days pre-discharge. HF phenotypes were determined using echocardiography within 1 year prior to admission (HFpEF &gt;= 50%, HFnpEF &lt; 50%). IMRS calculated on admission from CBC and CMP components. Within each HF phenotype, time-dependent ROC analyses were used to derive admission and discharge BNP thresholds for 1-year mortality (highest product of sensitivity and specificity). Patients were categorized as above or below their HF-specific admission and discharge thresholds (low-low, low-high, high-low, high-high). Nested multivariable Cox proportional hazard models for 1-year mortality evaluated admission BNP, discharge BNP, relative change in BNP, and admission-discharge BNP profile, in addition to IMRS and comorbidities. Results: A total of 2,933 patients were included, where 43.9% (1,287) had HFpEF and 56.1% (1,646) HFnpEF. Median BNP was lower in HFpEF compared to HFnpEF (admit: 703 vs 1300 pg/mL; discharge: 406 vs 796 pg/mL, both p&lt;0.001). In HFpEF, admission and discharge BNP thresholds were 763 pg/mL and 474 pg/mL, respectively, while in HFnpEF, the thresholds were 1520 pg/mL, and 1043 pg/mL. The best model above the baseline model used admission-discharge BNP profile (Table 1). In both HF phenotypes, the low-low profile had the lowest 1-year mortality, and the high-high profile had the highest mortality (Figure 1). After multivariable adjustment, each admission-discharge BNP profile was associated with higher 1-year mortality vs. low-low, meeting significance in high-high profile in HFpEF and high-high and low-high profiles in the HFnpEF (Table 2). Conclusions: The inclusion of admission-discharge BNP profiles was complementary and added significant and incremental value to the IMRS to predict mortality.
Abstract 4139036: Predictors of Flow Improvement Following Transcatheter Aortic Valve Replacement in Patients with Low-Flow Low-Gradient Aortic Stenosis
Authors: Besir Besir, Maryam Muhammad Ali Majeed-Saidan, Judah Rajendran, Tamari Lomaia, Shivabalan Kathavarayan Ramu, Odette Iskandar, James Yun, Serge Harb, Rhonda Miyasaka, Grant Reed, Rishi Puri, Amar Krishnaswamy, Samir Kapadia
Journal: Circulation (2024)

Background: Patients with low-flow low-gradient (LFLG) aortic stenosis (AS) are at risk of worse outcomes following transcatheter aortic valve replacement (TAVR). Flow is known to improve after TAVR, however the clinical and echocardiographic characteristics correlating with flow improvement in patients with LFLG AS are still unclear. Hypothesis: Some baseline and discharge clinical and echocardiographic characteristics correlate with flow improvement in patients with LFLG AS post-TAVR. Aims: The present study sought to explore the clinical and echocardiographic characteristics correlating with flow improvement in patients with LFLG AS post-TAVR. Methods: This is a retrospective cohort of patients &gt;18 years of age who underwent TAVR at Cleveland Clinic between 2016 and 2020. Only patients with aortic valve (AV) area &lt;1 cm 2 , AV mean gradient &lt;40 mmHg, and stroke volume index (SVI) &lt;35 mL/m 2 were included. Patients were classified into 2 groups according to whether SVI improved by 20% or more at the 30-day follow-up. Patients who underwent valve-in-valve TAVR were excluded. Binary logistic regression was used to evaluate the predictors of flow improvement. Results: A total of 2630 patients underwent TAVR between 2016 and 2020. The study included 633 patients. 228 patients (36%) had SVI improvement by 20% or more. Male sex (odds ratio (OR)=1.89, p=0.01), left ventricular ejection fraction (LVEF) improvement by 10% or more 1 month post-TAVR (OR=6.93, p&lt;0.001), and lower baseline SVI (OR=0.81, p&lt;0.001), were statistically significant predictors of flow improvement, whereas moderate to severe tricuspid regurgitation (TR) at discharge was a statistically significant predictor of no improvement in flow. Conclusions: The present study demonstrates that male sex, LVEF improvement post-TAVR, and lower baseline SVI are associated with flow improvement, whereas moderate to severe TR at discharge is associated with no flow improvement post-TAVR in patients with LFLG AS.
Abstract 4138210: In-hospital Mortality and Cardiovascular Complications in Acute Pericarditis among patients with Heart Failure with Preserved Ejection Fraction
Authors: Jamal Perry, Oluwasegun Akinti, Charles poluyi, Emmanuel Ukenenye, Henry Aiwuyo, Esther Duodu
Journal: Circulation (2024)

Background: Heart failure with preserved ejection fraction (HFpEF), often referred to as diastolic heart failure, presents significant treatment challenges. Acute pericarditis (AP) is a life-threatening illness, yet the literature on its epidemiology and outcomes in HFpEF patients is scarce. Hypothesis: Acute pericarditis in HFpEF patients is associated with increased risks of myocardial infarction, various types of heart block, cardiac tamponade, ventricular arrhythmia, cardiogenic shock, and in-hospital mortality. Aim: This study aims to outline the association of major cardiovascular outcomes with acute pericarditis in hospitalized HFpEF patients. Methods: A retrospective observational cohort study was conducted using the National Inpatient Sample from 2016 to 2020. We included patients with documented AP among those with HFpEF, identified using validated ICD-10 codes. Univariate and multivariate logistic regression analyses identified outcomes and adjusted for potential confounders using the Elixhauser comorbidity index. Results: Among 471,145 hospitalized HFpEF patients, approximately 424 (0.09%) had AP between 2016 and 2020. The mean age was 67, predominantly female (58%), with a mean length of stay (LOS) of 8 days. Among patients with HFpEF, increased cardiovascular complications were associated with AP, including heart block in 5% of patients (OR = 1.3, 95% CI 1.1 to 1.6, p = 0.002), cardiac arrest in 2.3% (OR = 1.6, 95% CI 1.2 to 2.1, p &lt; 0.001), and myocardial infarction in 4.5% of patients (OR = 1.3, 95% CI 1.1 to 1.6, p = 0.015). Ventricular arrhythmias occurred in 2.4% (OR = 1.5, 95% CI 1.2 to 1.9, p &lt; 0.001), cardiogenic shock in 0.39% (OR = 5.4, 95% CI 4.3 to 6.8, p &lt; 0.001), cardiac tamponade in 16.5% (OR = 144, 95% CI 127.2 to 164, p &lt; 0.001), and mortality was 4.25%. However, the association between AP and mortality was not statistically significant (OR = 2.4, p = 0.152) (see Figure 1). Conclusion: Acute pericarditis, while rare in HFpEF patients, is associated with increased major cardiovascular complications, including ventricular arrhythmias, tamponade, cardiogenic shock, and cardiac arrest, particularly with a significant odds ratio for cardiac tamponade.
Abstract 4139440: A 3-Year, Pre-Trial, Real-world Data Analysis of Patients Enrolled in VICTORION-INITIATE: Insights Using Tokenization
Authors: Fatima Rodriguez, R Wright, Elsie Ross, Yousuf Ali, Biswajit Kumar, Guangyang Han, Beilei Cai, Cheryl Abbas, Amy Ryan, irene cosmatos, Nihar Desai
Journal: Circulation (2024)

Background: VICTORION-INITIATE (NCT04929249) showed significantly greater LDL-C lowering in patients (pts) with ASCVD with an inclisiran first (IF) strategy (adding inclisiran immediately on failure to achieve LDL-C &lt;70 mg/dL on maximally tolerated statin therapy) vs usual care (UC). Tokenization can be leveraged to link clinical trial data to pt-level real-world data (RWD) to provide a comprehensive overview of the pt journey pre- and post-trial and enhance understanding of clinical trial and long-term pt outcomes. Aim: To utilize tokenization and linked RWD to characterize the pt journey pre-VICTORION-INITIATE enrollment. Methods: Eligible pts from VICTORION-INITIATE were deidentified and tokenized with unique IDs, allowing linking to RWD (EMR, claims, hospital, and lab records) to follow the pt journey in the 3-year pre-trial and 2-year post-trial periods. Here we present demographics, clinical characteristics, and lipid-lowering therapy (LLT) use of pts with linked pre-trial RWD. Results: Of 450 pts randomized, 383 (85.1%) were linked with pre-trial RWD (IF arm, n=193; UC arm, n=190); 26.9% were female, first available recorded mean (SD) age was 64 (9.36) years. Among the 74.2% (n=284) of pts with linked, pre-trial, lipid test RWD, mean (SD) earliest and latest LDL-C values were 100.1 mg/dL (35.70) and 99.3 mg/dL (30.06), respectively, for pts in the IF arm vs 97.3 mg/dL (40.43) and 97.8 mg/dL (27.60) for pts in the UC arm ( Table ). Overall, in the pre-trial period, LLT was dispensed/prescribed to 66.1% of pts, statins to 64.5%, ezetimibe to 4.4%, and PCSK9i to 4.4%. Of pts with ≥1 recorded ASCVD events in the pre-trial period (n=141), 53.2% and 68.8% had available LLT dispensing/prescription records pre- and post-event, respectively. Conclusions: In the 3 years pre-VICTORION-INITIATE, mean LDL-C levels were above recommended goals, non-statin LLT prescription was infrequent, and ~31% of pts with ≥1 recorded ASCVD event had no evidence of post-event LLT use, highlighting a need for more aggressive LDL-C management. Full data visibility for each pt is a limitation of this approach. Tokenization post-trial will allow for long-term evaluation of LLT practices.
Abstract 4139418: Self-monitoring of Home Blood Pressures Identifies a High Prevalence of White Coat and Masked Hypertension in Cardiac Rehabilitation Patients
Authors: Jady Yang, Humberto Andrade, Alexandra Diaz, Anthony Ramirez, Taliyah Borromeo, John Grubbs, Javier Lopez
Journal: Circulation (2024)

Introduction: Hypertension (HTN) is a highly prevalent risk factor that is targeted for the risk reduction and recovery of patients attending cardiac rehabilitation (CR) after a CV event. Self-measured home blood pressure monitoring (SM-BPs) is becoming a main approach for BP management, but how SM-BPs relate to BPs measured during in-center CR participation (CR-BPs) has not been previously reported. Objective: To compare concordance between SM-BPs and CR-BPs during the rehabilitation of high-risk CV patients. Methods: We studied 143 CR patients with SM-BPs in addition to CR-BPs. Patients were classified as having HTN if their starting BP in CR ≥130/80 (average of first 3 sessions). The prevalence of white coat (WC) and masked HTN were determined based on concomitant home BP readings. Concordance of SM-BP and CR-BP trajectories over time was determined using a linear mixed-effects model in 90 patients (63%) who had at least 2 weeks of concomitant measurements. Results: Of the 90 included patients (65±12 (SD) years, 33% female, 34% non-White), 77%, 41%, 24%, 23%, 37% and 22% had a history of HTN, any tobacco use, DMT2, HF, CAD, and PVD, respectively. Of the 30% of patients with high CR-BP initially, 17 (63%) were found to have WC HTN and 8% of normotensive patients had masked HTN (Figure 1, panel A). Twenty-nine patients (32%) had statistically significant discordance between SM-BPs and CR-BPs throughout CR participation (p &lt; 0.05; Figure 1, panel B). Conclusion: To the best of our knowledge, this case series represents the 1st report of concomitant SM-BP and CR-BP trajectories over time. We identified white coat HTN (63%) among hypertensive patients and masked uncontrolled HTN (8%) among normotensive patients. Masked HTN may contribute to missing a prevention target whereas WC HTN may contribute to medical overtreatment of BP while adopting healthy lifestyle modifications. Not surprisingly, BP readings changed over time and 32% of patients had significant discordance between home and center, which could inform rational therapies in CR if recognized in a timely manner. We propose that SM-BPs should be rigorously and systematically measured during CR to further guide BP management in high-risk CV patients.
Abstract 4139399: Targeting Hepatic Complement C3 Attenuates Pulmonary Arterial Hypertension Phenotype in Rodents
Authors: Merve Keles, Nadine Arnold, Laura West, Helena Turton, Sung-Kwon Kim, Melissa Lasaro, Meera Rammanujam, C-Hong Chang, M Wilkins, Allan Lawrie
Journal: Circulation (2024)

Background: Pulmonary arterial hypertension (PAH) is a severe condition characterized by pulmonary vascular remodelling leading to right ventricle failure. Emerging evidence highlights inflammation as crucial pathogenic factor of PAH. Members of the complement pathway have been identified as dysregulated in multiple studies. We aimed to investigate the relative contribution of different complement pathway components in PAH pathogenesis using pre-clinical rodent models. Methods and Results: The Sugen 5416 (20 mg/kg, i.p.) plus hypoxia (SuHx) model in both male C57Bl/6 mice (weekly Sugen + 3 weeks hypoxia) and Wistar rats (single Sugen, 3 weeks hypoxia, 6 weeks in room air) were used to assess the effect of complement inhibition on PAH. Targeting the terminal complement pathway with TPP-903, an anti-C5 antibody administered at 3- or 6 weeks, failed to demonstrate any beneficial effects on the PAH phenotype in SuHx rats. To investigate the alternative pathway, we first utilised the mouse SuHx model, targeting hepatic C3 knockdown using anti-C3 siRNA administered 1 week before PAH induction. There was a significant decrease in both the percentage of remodelled vessels and the degree of remodelling but no significant effect on right ventricular systolic pressure (RVSP). To further assess hemodynamic outcomes alongside vascular remodelling, we repeated the use of anti-C3 siRNA (from week 5) in the more severe rat SuHx model. Treatment with anti-C3 siRNA was associated with more than 90% reduction in C3 RNA expression in the liver, as well as around 91% reduction in circulating C3 levels. Considerable improvement in the PAH phenotype, as evidenced by reduction in RVSP (94.63 vs. 69.71 mmHg, p&lt;0.001, n=8), improvement RV cardiac function (RV-fractional area change (RV-FAC%): 33.54 vs. 43.86%, p&lt;0.05, n=8) were associated with reduced pulmonary vascular remodelling (75 vs. 57%, n=4) compared to vehicle treated rats. Furthermore, there was a reduction in cardiac fibrosis in anti-C3 siRNA treated rats, as assessed by Sirius red staining. Conclusion: The therapeutic benefits observed in both right ventricular function and pulmonary vasculature emphasize the potential of complement pathway modulation, particularly through hepatic targeting of C3 as an approach for the treatment of PAH. Ongoing investigations aim to uncover the localized mechanisms driving this therapeutic effect, providing valuable insights for future clinical applications.
Abstract 4139384: Retrospective Review of the Safety and Effectiveness of a Low Carbohydrate Ketogenic Diet in Overweight or Obese Patients with Heart Failure
Authors: Garrett Moseley, Josephine Harrington, Eric Westman, William Yancy
Journal: Circulation (2024)

Background: Recent evidence suggests a therapeutic role for ketosis in patients with heart failure (HF). However, little is known regarding the safety and effectiveness of a low carbohydrate ketogenic diet (LCKD) in patients with overweight or obesity and HF. Purpose: To examine the safety and effectiveness of a LCKD in patients with overweight or obesity and HF. Methods: A retrospective review from 2006-2024 was conducted of all patients with overweight or obesity and HF who followed a LCKD with clinical oversight for at least one year in a university health system. Changes in metabolic outcomes, echocardiographic measures, and medication use were assessed. Heart failure hospitalization (HFH) rates and rate ratios (RR) and all-cause mortality rates were calculated and stratified by HF classification. Results: A total of 125 patients met inclusion criteria, including 59 patients with HF with reduced ejection fraction (HFrEF) and 66 patients with HF with preserved ejection fraction (HFpEF). Patients lost a median (interquartile range) of 11.2 kg (-19.5, 4.4; p &lt;0.0001) of body weight, and patients who adhered more strictly to the diet lost a larger percentage of body weight ( p =0.0011). Aspartate amino-transferase and alanine amino-transferase levels decreased by a median (interquartile range) of 2.0 IU/L (-6.0, 2.5; p &lt;0.05) and 3.0 IU/L (-8.8, 2.0; p &lt;0.01), respectively, in patients with HFpEF. There were no significant changes in total cholesterol or LDL-C levels. Patients with type 2 diabetes significantly decreased their insulin dose while following a ketogenic diet ( p &lt;0.006). There were no significant changes in left ventricular ejection fraction, but the rate of HFH decreased significantly among all patients combined and patients with HFpEF while following the diet (RR=0.5; 95% CI: 0.4, 0.9 and RR=0.5; 95% CI: 0.3, 0.9; respectively) and decreased nonsignificantly among patients with HFrEF (RR=0.6; 95% CI: 0.3, 1.1). The overall all-cause mortality rate was 3.2 per 100 person-years of follow-up (95% CI: 1.0, 5.3). Conclusion: A LCKD among patients with overweight or obesity and HF appears safe and effective for weight loss, with a potential additional benefit for improving metabolic markers and the rate of HFH.