tbuckley/cabot-search huggingface dataset:
Abstract 15766: Patient Profile, Treatment and Outcomes in Patients With Acute Coronary Syndrome: Preliminary Results From the Get With the Guidelines Mexico Project Initiative at the National Institute of Cardiology
Authors: Diego Araiza, Nitzha Andrea Najera-Rojas, Mariana Robles-Ledesma, Alejandro Ezquerra Osorio, Luis Fernando De los ríos Arce, Manuel O De Los Rios, Leslie Marisol Lugo Gavidia, Jose Luis Leiva, Rodrigo Gopar-Nieto, Jorge Daniel Sierra Lara Martinez, Hector Gonzalez-Pacheco, Alexandra Arias-Mendoza
Journal: Circulation (2023)

Introduction: Acute coronary syndromes represent the first cause of cardiovascular mortality. However, important heterogeneity exists in patient profile, access to treatment and outcomes, especially in developing countries. Hypothesis: Barriers to improve outcomes in patients with ACS may differ in developing countries. Individualized strategies may be needed to improve adoption of guideline recommendations. Aims: To describe baseline characteristics, treatments and outcomes in patients with ACS in Mexico. Methods: Prospective study including patients with ACS who were either transferred from eight referring hospitals or arrived directly at a referral center in Mexico City between October 2022-April 2023. The data was collected as part of the GWTG-Coronary Artery Disease Mexico Project, powered by the American Heart Association. Continuous variables are reported as mean±standard deviation (SD), or median and interquartile range (IQR), according to their distribution. Results: A total of 206 patients were included, 73.5% with STEMI and 26.5% with NSTEMI &amp; UA. The mean age of the study population was 60 (54-69) years and 79.9% were male. The prevalence of diabetes was (56.8%), hypertension (41.6%) and smoking (62.5%). Median time from symptom onset to first medical contact was 8.4 (3.2-15.8) hours and 99.5% of patients arrived as walk-ins (mostly private vehicles). Among those transferred from a non-PCI center, 70% were transported by ambulance, 20% used private vehicles and 10% were transported by air. Amid STEMI patients, 86.6% received reperfusion during the first 12 hours since symptom onset: 36.4% primary PCI &amp; 52.0% pharmacoinvasive strategy; in patients with NSTEMI/UA, 62% underwent PCI. Prescription of guideline recommended medications at discharge was high: high intensity statins (97.3%), beta-blockers (84.2%), ASA (96.3%), ACEI/ARB (93.1%). The overall hospital survival was 95.1%. Conclusions: In these preliminary results from the GWTG Mexico Project Initiative, we observed high reperfusion rates and a high prescription of guideline recommended therapies at discharge; however, important deficiencies exist in the pre-hospital setting. These results may influence future healthcare policies to reinforce prehospital care.
Abstract 17721: Loss of p22 <sup>phox</sup> Exacerbates Heart Failure Through Increased Oxidation and Proteasomal Degradation of SERCA2a
Authors: Allen S Titus, Yasuki Nakada, Wataru Mizushima, Peiyong Zhai, Shinichi Oka, Junichi Sadoshima
Journal: Circulation (2023)

Introduction: Downregulation of sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ ATPase 2a (SERCA2a) accentuated by oxidative stress is a major driver of heart failure. NADPH oxidase (NOX) complexes are the key sources of reactive oxygen species (ROS) in cardiomyocytes. p22 phox , a transmembrane partner of NOX1-4, plays an essential role in mediating ROS production in multiple NOX complexes. We investigated the role of p22 phox in oxidative stress and SERCA2a levels during pressure overload (PO). Question: Does loss of p22 phox alleviate heart failure through reduction of oxidative stress and stabilization of SERCA2a levels during PO? Methods: Cardiac-specific p22 phox knockout ( p22 phox -cKO) mice were subjected to sham operation or transverse aortic constriction (TAC). The p22 phox interactome was analyzed by co-immunoprecipitation and mass spectrometry. Protein cysteine oxidation was probed by biotinylated iodoacetamide labelling. Results: The p22 phox -cKO mouse heart showed a 50% reduction in H 2 O 2 levels compared to WT after 1-week TAC (p&lt;0.01). Unexpectedly, p22 phox -cKO mice had 20% higher mortality (p&lt;0.05), lung congestion (2-fold, p&lt;0.05), and fibrosis (&gt;40%, p&lt;0.01) and a lower (40%, p&lt;0.01) left ventricle ejection fraction than WT after TAC. p22 phox directly interacted with SERCA2a. Lack of p22 phox led to oxidation of SERCA2a at cysteine 498 and promoted degradation of SERCA2a. SERCA2a C498S knock-in mice have better cardiac function and stable SERCA2a protein levels after TAC compared to WT mice. Further, p22 phox aided thioredoxin 1 (TRX-1) interaction with SERCA2a and prevented cysteine oxidation. SERCA2a was co-immunoprecipitated with Smad ubiquitination regulatory factor 1 (Smurf1) and HMG-CoA reductase degradation protein 1 (Hrd1) E3 ubiquitin ligases in the absence of p22 phox or TRX-1. Conclusion: p22 phox recruits TRX-1 to SERCA2a, prevents SERCA2a cysteine 498 oxidation, promotes its stability, and maintains cardiac function.
Abstract 15718: Valvulo-Arterial Impedance in ESKD Patients With Aortic Stenosis: Echocardiographic Correlates and Outcomes
Authors: Fredrick Ogugua, Lucas Zellmer, Roy O Mathew, Gautam R Shroff
Journal: Circulation (2023)

Introduction: Higher values of valvulo-arterial impedance (Zva), a marker of global hemodynamic load, are associated with worse outcomes in patients with aortic stenosis (AS). No studies have evaluated the impact of Zva on outcomes in end stage kidney disease (ESKD) patients with AS. Objectives We aim to evaluate clinical outcomes associated with Zva and echocardiographic correlates of Zva in patients with AS and ESKD. Methods: Consecutive ESKD patients on dialysis with AS on echocardiography from a single center between January 2000 and March 2021. AS severity was defined using AHA guideline recommendations. Zva [units: mmHg/ml/m 2 ] was calculated as (systolic arterial pressure + aortic valve mean gradient) divided by indexed stroke volume. The association of high Zva with the combined primary outcome of aortic valve replacement (AVR) or mortality was assessed using Cox proportional hazard analysis. Results: The cohort included 94 patients with co-prevalent ESKD and AS; mean age 66 years, 71% male; 43% Black, 24% severe AS. Patients with Zva&gt;4 mmHg/ml/m2 (median value; Table ) associated with lower indexed aortic valve area (0.52 vs. 0.71 cm 2 /m 2 , p&lt;0.001), lower stroke volume (66 vs. 84 ml; p&lt;0.001), lower cardiac output (5.3 vs. 6.1 L/min; p=0.005); Figure . Zva did not associate with the combined incidence of AVR or mortality (p=0.2). Conclusion: In ESKD patients with AS, high Zva was associated with smaller AVA and measures of low flow state; but not with the primary outcome of AVR or mortality. These findings should be validated in a larger cohort. Differences in prognostic information from Zva and flow states in the context of AS between ESKD vs non-ESKD patients deserve further study.
Abstract 14710: The Landscape of Pharmacological Interventional Trials for the Treatment or Prevention of Coronary Artery Disease: Analysis of clinicaltrials.gov Listings From 2008 to 2022
Authors: Gerald Chi, Cecilia Bahit, Serge Korjian, Laith Allaham, Syed Hassan A. Kazmi, Paul Nara, Alka Shaunik, Charles Gibson
Journal: Circulation (2023)

Background: Coronary artery disease (CAD) has been the leading cause of death and disability over the past two decades. Aims: To systematically assess the characteristics and trends of clinical trials pertaining to the treatment or prevention of CAD. Methods: The analysis included studies that (1) were registered in the ClinicalTrials.gov database from 2008 to 2022; (2) involved ≥1 pharmacological intervention; and (3) were designed to treat or prevent CAD or its complications. Study records were downloaded on December 27, 2022 for screening and analysis. Pharmacological interventions were classified according to the World Health Organization Anatomical Therapeutic Chemical Classification System. Annual trends by the year of study registration were assessed with a two-sided Cochran-Armitage test. Results: A total of 1,619 trials were identified from a pool of 437,319 studies. There was a declining trend in the number of CAD trials (Figure A). The majority of trials (47.5%) were targeted to enroll ≤100 participants, while 39.4% targeted 101-1000 participants, 10.5% targeted 1001-5000 participants, and 2.6% were mega-trials (&gt;5000 participants). The distribution of study duration was as follows: ≤12 months (25.3%), 13-60 months (67.3%), and &gt;60 months (7.5%). Of note, the open-label design was more commonly employed in treatment trials (41.8% vs. 31.6%; p=0.02), while the parallel assignment was more frequently utilized in prevention trials (88.8% vs. 82.0%; p=0.03). In addition, declining trends in the proportions of phase 3 trials (p=0.0008; Figure B) and trials of lipid-modifying (p=0.0043) or anti-thrombotic agents (p=0.03; Figure C) were observed. Conclusion: Between 2008 and 2022, the clinical trial landscape of CAD diminished and was mainly shaped by studies with small to moderate sample sizes and short to intermediate follow-up duration. Research focus trended toward study interventions other than anti-thrombotic or lipid-modifying agents.
Abstract 14946: Sex Differences in Growth Differentiation Factor-15 and Association With Acute Myocardial Infarction and Death at 90 Days in Emergency Department Patients Presenting With Acute Chest Pain and Normal Troponin Levels
Authors: Nipun Bhandari, Nam K Tran, Brandon R Allen, Robert H Christenson, Richard M Nowak, Richard G Wilkerson, Troy E Madsen, Michael T Weaver, Fan Yi, Simon A Mahler, Bryn Mumma
Journal: Circulation (2023)

Introduction: Growth differentiation factor (GDF)-15, a novel biomarker of cardiac stress, has been recently studied as a tool in predicting cardiovascular outcomes in patients with acute chest pain, when compared against high-sensitivity troponin T (hs-TnT). However, GDF-15 is not approved for cardiac indications in the United States, with limited nationwide data evaluating subpopulations by key demographic and clinical characteristics. Hypothesis: GDF-15 levels demonstrate sex-specific differences and serve as an independent predictor of 90-day acute myocardial infarction (MI) and all-cause death in patients presenting to the emergency department (ED) with acute chest pain and normal hs-TnT levels. Methods: This study was a secondary analysis of the STOP-CP (High Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification) trial, which prospectively enrolled adults ≥ 21 years presenting to eight EDs in the US with suspected acute MI over a twenty-month period. Blood sampling was performed at presentation, with hs-TnT and GDF-15 assays performed at a central laboratory. The outcomes of interest were the composite of acute MI and all-cause death at 90 days. Multiple logistic regression models were fitted for timepoint with multiple independent variables including the following: age, sex, ischemic electrocardiogram, hs-TnT, GDF-15, and creatinine. Results: We studied 1,428 patients; median age was 58 years and 54% (765) were male. The composite outcome of acute MI or death occurred in 3% (37) at 90 days. In multivariable regression models in patients with baseline normal hs-TnT levels, GDF-15 was associated with acute MI or all-cause death at 90 days (Odds Ratio 1.03, 95% Confidence Interval 1.01-1.05). Median GDF-15 levels were 1266 pg/mL in males (25th percentile-75th percentile, 914-2038 pg/mL), and 1504 pg/mL in females (25th percentile-75th percentile, 987-2197 pg/mL). Conclusions: Among adult ED patients presenting with acute chest pain with normal troponin levels, the novel biomarker GDF-15 was independently associated with 90-day acute MI or death, with higher median GDF-15 levels in females compared to males. These data suggest a role for GDF-15 in short-term cardiac risk stratification.
Abstract 15569: The Effect of Cardiac Pulmonary Nerve Stimulation on Cardiac Inotropy and Quality of Life in Patients With Acute Decompensated Heart Failure
Authors: Sitaramesh Emani, Andrew Civitello, Naeem K Tahirkheli, Istvan F Edes, Imad Libbus, Julio C Spinelli
Journal: Circulation (2023)

Background: Acute decompensated heart failure (ADHF) results in over 1 million hospitalizations annually and involves neurohormonal disruption as well as autonomic dysfunction. Neuromodulation of the cardiac plexus using cardiopulmonary nerve stimulation (CPNS), currently being evaluated in clinical trials, is a novel strategy to treat ADHF. Methods: An interim analysis of 12 patients from ongoing trials was conducted. Patients were admitted with a principal diagnosis of ADHF (elevated NT-proBNP and LVEF≤50%) and underwent implant of a 16-electrode catheter (Figure 1A) in the right pulmonary artery, allowing cardiac plexus stimulation for 48 hrs. Stimulation was performed at 20 Hz frequency, 2.0 ms pulse width, and stimulation amplitude/vector (2.5-10 mA) to optimize cardiac function. LV pressure, arterial pressure, and ECG were concurrently recorded. An additional 12 patients not implanted were followed as a parallel standard of care (SOC) cohort. Results: There were no device-related serious adverse events (SAEs) during the index hospitalization or at 30 days post-discharge. Two SAEs unrelated to device occurred in 2 patients (clonic seizure and post-discharge pneumonia resulting in death). In response to stimulation, there was a statistical increase in maximum LV dP/dt (from 799 to 824 mmHg/sec, p&lt;0.01) and a statistical decrease in pressure time index (from 27.9 to 27.5 mmHg*sec, p&lt;0.05). Patients that received CPNS reported a significantly greater improvement in symptoms, function, and quality of life at 30 days (KCCQ-12; from 14.1 to 74.7, p&lt;0.0001) compared to patients in the SOC cohort (Figure 1B; 60.6 vs. 8.4, p&lt;0.05). Conclusion: In-hospital CPNS therapy is feasible and well-tolerated in ADHF patients. Stimulation increased cardiac inotropy, decreased energy consumption, and improved symptoms, function, and quality of life. Further investigation is required to determine if CPNS therapy leads to sustained improvement in clinical outcomes.
Abstract 14280: Real-World Study of Fondaparinux in Chinese Non-ST-Segment Elevation Acute Coronary Syndrome Patients: REFOCAS
Authors: Yundai Chen, dandan li, Xiaodan Tuo, Yani Yu
Journal: Circulation (2023)

Introduction: In NSTE-ACS patients, fondaparinux appears to have superior benefits than LWMH, however its application in patients with different risk stratification is still not obvious. Hypothesis: The use of fondaparinux or LMWH has an impact on prognosis in NSTE-ACS patients with different ischemic and bleeding risks. Methods: A multicenter, prospective, open-label, real-world study was conducted in 8066 adult patients with non-emergency PCI at 89 hospitals from July 2019 to July 2021. Patients received fondaparinux (2.5 mg/d) or LMWH (1 mg/kg, twice/day) , they were followed-up within 6-month. The GRACE and CRUSADE scores were used to stratify the included patients. The primary outcome was the incidence of NACCE (all-cause death, reinfarction, nonfatal stroke, or BARC≥type 2 bleeding) at 30 days, and secondary endpoints included BARC≥type 2 bleeding or MACE during hospitalization, 30 days, and six months. Results: In total, 5430 patients received fondaparinux treatment and 2636 received LMWH treatment, with 4976 and 2477 completed the trial respectively. The primary outcome occurred in 136 patients (2.7%) receiving fondaparinux and in 110 patients (4.4%) in LMWH [HR=0.608(0.471,0.785), p&lt;0.001]. The rate of BARC≥2 bleeding at 30-day was significantly lower in the fondaparinux group compared with the LMWH group[68(1.4%) vs. 66(2.6%), HR=0.509(0.361,0.716), P&lt;0.001]. Reduction in rate of NACCE and BARC ≥ type 2 bleeding were still observed during hospitalization and at six-month follow-up in fondaparinux group. In low bleeding risk individuals (CRUSADE score≤40), fondaparinux reduced the rate of BARC≥2 bleeding at 30-day by 0.9% compared with LMWH, which decreased by 3.1% in high bleeding risk individuals(CRUSADE score&gt;40). Among patients with low ischemic risk (GRACE score≤140 ), fondaparinux significantly reduced the incidence of NACCE, MACE, and BARC ≥ 2 bleeding at each follow-up visits. Conclusions: In Chinese patients with NSTE-ACS, fondaparinux reduced the incidence of the composite endpoint event of bleeding and ischemia of 30 days compared with LMWH. Meanwhile, fondaparinux exhibited better safety in patients with high bleeding risk, and in the low ischemic risk group, the overall efficacy and safety were also better than LMWH.
Abstract 15576: The Association of Structural Racism With Cardiovascular Disease Death Rates
Authors: Amaris Williams, T.M. Ayodele M Adesanya, Guy Brock, Joshua J Joseph
Journal: Circulation (2023)

Background Structural racism is an upstream influencer of social determinants of health, which impact cardiovascular disease (CVD) death rates. The association between structural racism and CVD death rates has not been conclusively quantified, and this association may vary by race/ethnicity. Method Year 2020 census data on disparities in income, wealth, education, employment, and digital access and segregation were available at the census block group level and were used to quantify structural racism’s effects. Data from each block group and its 9 nearest neighbors were used to compute the structural racism sub-scores for that block group, which were transformed to a scale of 1-100 based on 100 quantiles. The composite score was then calculated as the weighted sum of the sub-scores (weights in Table 1). Mean structural racism score (SRS), weighted by population of each block group, was computed for each county in the United States. Then SRS was fit as the exposure in linear models controlling for state and predicting 2020 county-level CVD death rates per 100,000 adults for all residents, non-Hispanic Black (NHB) residents, non-Hispanic White (NHW) residents, and Hispanic residents, as reported by the Centers for Disease Control. Results: Data from 50 states and the District of Columbia were used (3137 counties). A 1-point higher SRS score (range 1-100) was associated with 1.0 (95% CI: 0.8, 1.3) more CVD deaths per 100,000 adults. Among NHB residents, there were 1.5 (95% CI: 1.0, 2.0) more CVD deaths per 1-point higher SRS score. Among Hispanic and NHW residents, CVD deaths were 0.8 (95% CI: 0.4, 1.2) and 0.6 (95% CI: 0.3, 0.8) higher per 1-point higher SRS. Conclusion: Structural racism is associated with greater CVD mortality among all United States residents, but the magnitude of association is greatest among NHB residents. Eliminating structural racism is likely to reduce CVD mortality of all residents while reducing race-based disparities in CVD mortality.
Abstract 15044: The Relationship of Pericardial Fat With Metabolic Change and Myocardial Remodelling Following Bariatric Surgery
Authors: Alessandra Maria Ardissino, George Joy, James D Crane, Kristopher D Knott, Joao B Augusto, Clement Lau, Anish N Bhuva, Andreas Seraphim, Amrit Chowdhary, Marianna Fontana, Sven Plein, Sasindran Ramar, Francesco Rubino, Peter Kellman, Hui Xue, Iain Pierce, Rhodri H Davies, James C Moon, Kennedy Cruickshank, Barbara M McGowan, Charlotte Manisty
Journal: Circulation (2023)

Introduction: Pericardial fat is a cardiometabolic risk factor that can be quantified from routine cardiovascular magnetic resonance (CMR) studies. However the extent to which this is modifiable, and its relationship with cardiometabolic markers remains unclear. Aims: Determine the effect of bariatric surgery on pericardial fat and associate with cardiometabolic improvements post-surgery. Methods: Thirty-eight people referred for bariatric surgery were assessed pre-operatively using CMR, blood biomarkers and anthropometry. Six months post-operatively, twenty-seven participants underwent paired follow-up assessments. Pericardial fat was quantified manually from routine short axis cine stacks by a single blinded clinical observer. Linear regression was used to assess the association of pericardial fat volume and cardiometabolic parameters, at baseline and changes pre- vs post-surgery. Results: At baseline, pericardial fat volume was associated with multiple cardiometabolic parameters including weight (r=0.46 p=0.004), fasting insulin (r=-0.46, p=0.007) hepatic fat concentration (Hepafat) (r=0.37 p=0.029) and LV mass (r=0.38, p=0.019). Pericardial fat remained independently associated with waist circumference after adjusting for the above (β=0.68, 95% CI: 1.24,9.23, p=0.012). At 6 months post-bariatric surgery pericardial adipose tissue reduced by an average of 29% (95% CI: -21-36%, p&lt;0.001). This change was associated with improvements in fasting insulin levels even after adjusting for changes in weight, Hepafat and LV mass (β=0.72, 95% CI: 0.15, 0.70, p=0.005). Conclusion: Pericardial fat in obesity associates with multiple adverse cardiometabolic parameters, including waist circumference. Bariatric surgery causes a significant reduction in pericardial fat which associates with reduced insulin resistance, providing a potential modifiable mechanism to reduce cardiovascular risk in patients living with obesity.
Abstract 12980: Left Ventricular Alterations in Neonatal Encephalopathy - A Case-Control Study Using 3D Echocardiography
Authors: Pierre Elias, Sariya Sahussarungsi, Ouma Thibert, Gabriela Simoes Lopes-Letendre, Punnanee Wutthigate, Amanda Ohayon, Shiran S Moore, Daniela Villegas Martinez, Jessica Simoneau, Catherine Henin, Wadi Mawad, Tiscar Cavalle, PIa Wintermark, Anie Lapointe, Gabriel Altit
Journal: Circulation (2023)

Introduction: Despite therapeutic hypothermia (TH), neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction, including cardiac alterations in the first days of life. Objectives: Describe the cardiac performance of neonates with moderate to severe NE treated with TH using three-dimensional echocardiography (3D-ECHO) relative to a control population without NE. Methods: Single-centre prospective case-control study of neonates with moderate to severe NE treated with TH between 2019 and 2021, compared to healthy neonates. The control group were newborns recruited in the nursery without need for resuscitation. 3D-ECHO was performed on day of life (DOL) 2. Left ventricular (LV) metrics were measured using 3D-Speckle Tracking Echocardiography. Descriptive statistics were used to compare the two groups. Results: We included 16 neonates with NE and 50 controls. Birthweight and gestational age at birth were similar (Table 1). Neonates with NE had lower systolic blood pressure (BP) but similar diastolic BP at ECHO, while 11/16 were exposed to cardiovascular medications at ECHO. These neonates had lower LV end-diastolic volume (4.2 [1.2] vs 5.0 [1.4] mL; p=0.04), lower stroke volume (2.2 [0.7] vs 2.9 [0.8] mL; p=0.002) and lower ejection fraction (52 [6] vs 56 [8] %; p=0.0008). These infants also had lower peak global circumferential strain (-25 [5] vs -28 [5] %; p=0.03). The association between NE and LV-ejection fraction remained significant after adjusting for weight (b=-5.7%, 95% Confidence Interval [-9.2; -2.2], p=0.002). Conclusions: Neonates with moderate to severe NE had reduced LV functional markers on DOL 2 as comparted to healthy controls. They had decreased systolic BP and LV end diastolic volume. These findings may be secondary to the asphyxia, catecholamines and medications exposure, or to TH. Future studies should consider 3D-ECHO as a modality to investigate these patients and the impact of therapeutic interventions.