tbuckley/cabot-search huggingface dataset:
Abstract 4139561: Exploring The Risks And Benefits of Upstream Loading of P2Y12 inhibitors In Acute Coronary Syndrome Patients
Authors: William Lim, Khaing Khaing Htwe, Muhammad Ahmad, Ali Akram Khan, Hameem Changezi
Journal: Circulation (2024)

Background: Acute coronary syndrome (ACS) is the leading cause of heart disease, resulting in over 300,000 deaths annually. The 2014 ACC/AHA guideline recommends a loading dose of a P2Y12 receptor inhibitor prior to PCI with stenting (Class IA). Objective: This study aims to evaluate the risks and benefits of upstream loading of P2Y12 inhibitors in ACS patients. Methodology: We retrospectively analyzed the charts of all ACS patients over 18 years old admitted to our community hospital in Michigan from August 2022 to July 2023. Exclusion criteria included patients with type II NSTEMI, hypersensitivity to P2Y12 inhibitors, active bleeding, hemoglobin levels less than 7 g/dl, those already on P2Y12 inhibitors, and pregnant patients. Results: Out of 518 patients reviewed, 399 were included in the study. Among 285 NSTEMI patients, 89.5% were not loaded with P2Y12 inhibitors in the ED, while 10.5% were. In the loaded group, 3% underwent CABG, 90% required PCI, and 6% received medical treatment. In the non-loaded group, 12.5% underwent CABG, one patient had an aortic dissection, and 53.8% and 33.7% required PCI and medical treatment, respectively. Among 114 STEMI patients, 74.5% were not loaded with P2Y12 inhibitors in the ED, while 25.5% were. In the loaded group, 100% required PCI. In the non-loaded group, 8.2% underwent CABG, and 92% required PCI. Conclusion: Our real-world data from a community hospital indicate that most ACS patients benefit from P2Y12 loading, with only a minority experiencing adverse effects. To address this, we plan to collaborate with our information technology department to implement reminders for ED physicians to consult with cardiologists about P2Y12 inhibitor loading in ACS patients.
Abstract 4139896: Prognosis of Pulmonary Arterial Hypertension after Treatment for Congenital Portosystemic Shunt in Children
Authors: Ryohei Matsuoka, Hazumu Nagata, Masaru Kobayashi, Kiyoshi Uike, Yusaku Nagatomo, Eiko Terashi, Yuichiro Hirata, Kenichiro Yamamura, Shouichi Ohga
Journal: Circulation (2024)

Introduction: Congenital portosystemic shunt (CPSS) is a rare vascular malformation which forms shunts between the portal and systemic veins. Pulmonary arterial hypertension (PAH) in CPSS patients heightens mortality risk. Research Questions: It remains unclear which patients’ characteristics are associated with the developing PAH in CPSS individuals. Additionally, it is not yet determined whether CPSS closure improves the prognosis of PAH in these patients. Methods: This single-center case-control study explored the data from 31 CPSS patients at Kyushu University Hospital, Japan between 2005 and 2023. Hemodynamics and portal pressure, crucial for treatment decisions, were assessed by cardiac catheterization in all treated patients. Based on these findings, patients were divided into two groups: PAH (n = 6) and non-PAH (n = 25). The primary outcome was the clinical characteristics of PAH, including patients` background, laboratory data, and cardiac catheterization findings. The secondary outcome was the effects of CPSS closure. Results: CPSS closure was performed in 28 of the 31 patients. There was no significant difference in age at diagnosis (median: PAH group 117 months vs. non-PAH group 18 months, p = 0.11) or prevalence of congenital heart disease (67% vs. 52%, p = 0.66) between the two groups. The prevalence of portal vein hypoplasia was 83% in the PAH group and 36% in the non-PH group. The PAH group exhibited significantly higher levels of total bilirubin (1.2 vs. 0.8 mg/dl, p = 0.02) and ALT (42 vs. 21 IU/l, p = 0.02). Before treatment, the PAH group had significantly higher median pulmonary artery pressure (39 vs. 12 mmHg, p &lt; 0.01) and pulmonary vascular resistance (7.3 vs. 0.95 unit/m 2 , p &lt; 0.01) compared to the non-PAH group. However, this study showed no significant difference in cardiac index between the two groups (5.3 vs. 4.9 l/min/m 2 , p = 0.31). In the PAH group, all cases initiated pulmonary vasodilator therapies before CPSS closure. Among them, 2 patients were able to reduce pulmonary vasodilator therapies and the other 2 patients were able to discontinue them after CPSS closure. Any patients were not deceased during this observational period. Conclusions: The clinical features of the PAH group include portal vein hypoplasia and hepatic dysfunction. Approximately one-third of PAH was reversible in the present study. Early diagnosis followed by CPSS closure and pulmonary vasodilators may improve the prognosis of CPSS-associated PAH.
Abstract 4140083: Clinical Characteristics and the Response to IV Antihypertensive Therapy in Severe Hypertensive Disorders in Pregnancy: A Retrospective Cohort Study
Authors: Christopher Tanski, Krista Huybrechts, Katherine Singh, Justin Lappen
Journal: Circulation (2024)

Objective: Evidence-based recommendations guiding first-line antihypertensive agent selection for treatment of sustained severe hypertension in pregnancy (SSHP) are lacking. Our aim was to identify patient characteristics associated with response to initial IV antihypertensive therapy for SSHP. Study Design: We performed a single center retrospective cohort study using EHR data from Jan-Dec 2021. Patients with SSHP, defined as a blood pressure (BP) ≥ 160/110 mmHg for ≥ 15 minutes, were identified from institutional data generated for a state quality improvement project. Patients receiving initial treatment with IV labetalol or hydralazine were included. Patients were excluded if they received nifedipine, did not have a repeat BP measurement within 30 minutes of treatment, had resolution of SSHP without treatment, or did not receive at least two doses of the initial agent prior to changing therapy. Response was defined as a resolution of SSHP with ≤ 2 doses of IV therapy. Variables of interest were identified a priori. Baseline characteristics between groups were compared with standardized mean differences. Multivariable analysis was performed using LASSO regression with 10-fold cross-validation. Results: We identified 200 patients with SSHP, of which 114 (57%) received labetalol and 86 (43%) hydralazine. 173 (86.5%) patients were responders: 97 (85.1%) for labetalol vs 76 (88.4%) for hydralazine (p=0.50). Differences between responders and non-responders are listed in the Table. In regression analysis factors significantly associated with non-response included: pre-pregnancy BMI (OR 1.07; 1.02-1.12 per unit increase, kg/m 2 ) pre-treatment MAP &gt; 125 mmHg (2.90; 1.10-7.62), and preterm gestational age (&lt; 34 weeks OR 4.71; 1.10-20.20; 34-37 weeks, OR 3.18; 1.10-9.16) (Table). Conclusions: In patients with SSHP, multiple clinical factors are associated with response to initial therapy. Each unit increase in pre-pregnancy BMI) is associated with 7% higher odds of non-response. Clinical characteristics may guide risk stratification and antihypertensive dosing strategies for patients requiring acute treatment for SSHP.
Abstract 4140222: Oxytocin treatment for spinal neuraxial modulation of ventricular excitability
Authors: Abigail Hellman, Sydney Callenberger, Yuki Kuwabara, Siamak Salavatian, aman mahajan, Kimberly Howard-Quijano
Journal: Circulation (2024)

Introduction: Cardiac sympathoexcitation is a major contributor to the pathogenesis of ventricular tachyarrhymias (VTs) during ischemia reperfusion (I/R) and chronic myocardial infarction (MI). Afferent network connections in the spinal cord control sympathetic output to the heart. Our team reported spinal cord stimulation (SCS) decreased cardiac sympathoexcitation and reduced VTs during ischemia. RNAsequencing data revealed that oxytocin (OXT) receptor is significantly upregulated with SCS; however, whether OXT alone can modulate the cardiospinal neural network to reduce sympathoexcitation and VTs is unknown. Hypothesis: Both intranasal (IN) and intrathecal (IT) administration of oxytocin agonist reduce sympathoexcitation, VTs, and cellular activation. Methods: Two models of cardiac ischemia were used in Yorkshire domestic swine. In acute I/R, a suture was placed around the left anterior descending (LAD) coronary artery, after sternotomy. Chronic infarction (MI) was created by polystyrene microspheres (1ml) injected via a 3mm angioplasty balloon catheter to the left circumflex under fluoroscopy guidance. Animals recovered post-MI for 6-8wk. Intrathecally, OXT agonist (TGOTFisher Scientific, 90ug) was delivered via catheter placed at T1-T4 level. Intranasally, OXT Pitocin (20U) was administered. The therapeutic doses were chosen based on dose response curve experiments, determining lowest effective dose based on activation recovery interval (ARI) change. We compared ventricular excitability, and arrhythmic substrate between experimental groups by measuring ARI, a validated marker for action potential duration. ARI changes signify the functional density and regional myocardial responses to interventions. After, T2-T4 spinal cord was collected postmortem for molecular analysis. Fluorescence in situ hybridization protocol for RNAscope Fluorescent v2 Assay (ACD) was followed. Cell counts represented as 3 puncta or more centered around DAPI. Results: We report that both ARI and VTs significantly increased as a result of I/R and MI and returned to baseline with administration of both IN and IT OXT (p&lt;0.05, two-way ANOVA n=6-8 animals) Additionally, FOS, a marker of cellular activation, increased with I/R and MI and decreased as a result of both IT and IN OXT in the spinal cord. Conclusions: By evaluating the role of OXT in reducing cardiac sympathoexcitation at the level of the spinal cord, we provide insights into developing new pharmacologic therapies.
Abstract 4139913: Obstructive sleep apnoea predicts a worse survival in patients with obstructive hypertrophic cardiomyopathy following septal myoectomy
Authors: yanhai meng, Changrong Nie, Zhengyang Lu, Changsheng Zhu, Shuiyun Wang
Journal: Circulation (2024)

Background: Obstructive sleep apnoea (OSA) is highly prevalent in patients with obstructive hypertrophic cardiomyopathy (oHCM), and the severity of OSA appears to worsen following septal myoectomy. The effect of OSA on the survival of oHCM following myoectomy remains uncertain. In this study, we aimed to investigate the clinical outcomes in oHCM patients with different severities of OSA. Method: We prospectively enrolled 330 oHCM who underwent septal myoectomy at our institution from January 2015 to December 2019. All patient underwent a standard polysomnography was performed on . The total apnea-hypopnea index (AHI), representing the number of respiratory events per hour of sleep, was calculated using the total recording time as the denominator. Mild, moderate, and severe OSA were respectively defined as an AHI &gt;5 events/h, ≥15 events/h, and ≥30 events/h. Result: Of 330 patients, 152 patients had OSA including 87 patients with mild OSA and 65 patients with moderate or severe OSA. Compared to patients without OSA, patients with OSA were much older ( 44.00 ± 12.18 vs. 52.22 ± 10.33 vs. 51.38 ± 10.31, p &lt;0.001), less likely to be female [75 (42.1%) vs. 27 (31.0%) vs. 10 (15.4%), p&lt;0.001], had a higher body mass index (24.81 ± 3.35 vs. 26.32 ± 3.00 vs. 27.77 ± 3.26, p&lt;0.001), a higher proportion of atrial fibrillation, hypertension, and history of smoking. The proportion of coronary artery bypass graft and valvular intervention were comparable between patients with and without OSA. The Cox maze procedure seems higher in patients with OSA than that in patients without OSA [ 10(5.6%) vs. 12 (13.8%) vs. 4 (6.2%) , p= 0.057]. During a median follow-up of 23.1 (16.8-44.6) months, 2 death, 35composite endpoint (2 death, 10 patients readmitted for atrial fibrillation ablation, 21 patients for heart failure, and 2 patients for other arrhythmias, 1 patient experienced a stroke) were observed. The Kaplan-Meier survival curve showed no difference in all cause mortality but higher composite endpoints in patients with moderate or severe OSA(Image 1). Cox hazard regression model revealed that compared to patients without OSA, patients with moderate or severe OSA was independently associated with a worse survival [HR: 2.54, 95%CI (1.08 - 6.00), p=0.033)(Image 2). Conclusion: OSA is common in patients with oHCM, and patients with moderate or severe OSA may indicate a worse survival.
Abstract 4139982: Ventricular Pre-excitation Related Cardiac Dysfunction Secondary to Accessory Pathway in the Absence of Tachyarrhythmia: A Systematic Review
Authors: Mansoor Rahman, Ahmad Alayyat, Sundal Aziz, Muhammad Haseeb ul Rasool, Waqas Ullah, Behzad Pavri
Journal: Circulation (2024)

INTRODUCTION: Asynchronous ventricular pre-excitation over an accessory pathway (AP) in the absence of tachyarrhythmia is sometimes reported to cause left ventricular dysfunction (LVD). AIMS: To analyze the pathophysiological mechanism, role of AP location, evaluation modalities, and management of pre-excitation-related LVD. Methods: PubMed and Google Scholar databases were searched for reports on pre-excitation-induced LVD regardless of patient's age, and publication date. Results: Out of 11,775 citations retrieved, 53 met inclusion criteria, including 41 case reports and 12 observational studies with 611 total participants, age range of 1.14-60.8 years, and M: F of 325:265 (Table). At initial presentation, acute HF was common in pediatric patients, with poor response to medical therapy; while adults were more often asymptomatic. Right septal and right free wall were the commonest APs location associated with LVD. Amiodarone and propafenone achieved improvement in HF status by causing AP block and restoring ventricular synchrony in pediatric patients deemed unfit for catheter ablation (CA). Septal dyskinesia (SD) and intra-LV dyssynchrony (ILVD) were the key pathophysiological mechanisms causing LVD, leading to regional myocardial wall thinning and hypotrophy. Two-dimensional strain echocardiography (2D-STE) was used in quantifying regional myocardial strain, noninvasive localization of APs, and assessing therapeutic response to CA. Systolic intervals ratio [(pre-ejection period (PEP)/LV ejection time (LVET)] assessed via continuous Doppler detected derangement in LVEF with high accuracy. Preexcitation-induced myocardial changes were usually reversible after CA of APs with recovery of LV function. However, irreversible myocardial tissue damage even after CA was reported, especially in adults. Resolution of ILVD and SD in the immediate post-CA period was predictive of response to CA. Conclusions: We report the largest aggregation of data regarding preexcitation-induced LV dysfunction. Long-term asynchronous activation of the LV via an AP, even without tachyarrhythmias, can causes adverse myocardial changes leading to cardiac dysfunction, especially in children with right-sided APs. 2D-STE and systolic intervals (PEP/LVET) are efficient tools for evaluation. Ablation of APs usually restores cardiac function largely; however, irreversible myocardial fibrosis can ensue. Based on these data, early CA of the APs associated with LV dysfunction is, therefore, recommended.
Abstract 4139570: A Hard Start: Early, Intensive Healthcare Utilization for Children with Critical Congenital Heart Disease
Authors: Danielle Ellis, Matthew Hall, Elizabeth Blume, Joanne Wolfe, Jennifer Snaman, Jay Berry
Journal: Circulation (2024)

Introduction/Background: Critical congenital heart disease (CCHD), requiring surgical intervention in the neonatal period, confers significant morbidity including high healthcare utilization, symptom burden, and psychosocial difficulties. Families also face the challenge of numerous decisions surrounding early, high-risk operative and procedural interventions. Pediatric palliative care (PPC) can facilitate goals of care/decision-making conversations and as such has great potential to improve the experiences of and outcomes for children with CCHD and their families. Goals/Aims: We examined the healthcare utilization of children with CCHD and how this differed by sociodemographic and clinical factors, as well as PPC consultation. Methods: We performed a retrospective review of infants with one of five CCHD (anomalous pulmonary venous return [APVC], single ventricle disease [SVD], tetralogy of Fallot [TOF], transposition of the great arteries [TGA], and truncus arteriosus [TA]) enrolled from birth to 2 years old between 2016 and 2020 in Medicaid in 12 U.S states participating in the Merative Marketscan Medicaid. Healthcare utilization included inpatient stays, outpatient and emergency visits, pharmacy encounters, and surgical interventions (SI), and were summed to determine total healthcare days (HD). PPC consultation was also assessed. Multivariable log-normal models assessed patient factors [including complex chronic conditions (CCC)] associated with total HD. Results: The cohort included 615 children (28% non-White, 46% female, and 67% with at least two other CCC) who underwent a median of 8 SI and had 69 HD during the two-year follow up period. SVD patients had the highest utilization and intervention burden (median 117.5 HD, 11.5 SI), followed by TOF (82 HD, 10 SI), TGA (58 HD, 8 SI), APVC (51 HD, 7 SI), and TA (47.5 HD, 3.5 SI) (p&lt;0.001). Having three or more CCC was associated with greater HD for all conditions (p&lt;.001). PPC consultation was uncommon (4.5%), but greatest in SVD (13%) (p&lt;0.001). Conclusions: Children with CCHD, especially those with SVD and greater medical complexity, had significant healthcare utilization including numerous SI. PPC consultation occurs for few patients. Given the clinical and psychosocial implications of frequent decision making and medicalization for children with CCHD, greater PPC engagement should be investigated.
Abstract 4139928: Ketone Body Metabolism Exerts an Anti-hypertrophic Effect on Cardiomyocytes by Alleviating Fatty Acid Overload and Increasing Glucose Utilization.
Authors: Toshihiro Yamada, kei morikawa, Akira Fujiyama, Takumi Nagakura, Xu Yuquing, Miho Kataoka, Kenta Kikuchi, Daisuke Kurotaki, Terumasa Umemoto, Shinji Hino, Miki Bundo, Kazuya Iwamoto, Zeeshan Ahmed, Suvi Linna-Kuosmanen, Shinsuke Hanatani, Hiroki Usuku, Yasushi Matsuzawa, Yasuhiro Izumiya, Eiichiro Yamamoto, Kenichi Tsujita, Yuichiro Arima
Journal: Circulation (2024)

Background: Ketone body metabolism, known for its multifaceted effects, is gaining attention as a potential therapeutic target for cardiovascular diseases. However, the impact of ketone bodies on cardiac hypertrophy and Heart Failure with Preserved Ejection Fraction (HFpEF) remains unclear. Research Questions: To elucidate the effects of ketone bodies on cardiac hypertrophy. The aim of the present research is to investigate the impact of ketone bodies on cardiac hypertrophy induced by metabolic abnormalities using organ-specific ketone body synthesis-deficient mice. Methods: Obesity and hypertension were induced by a high-fat diet combined with NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME) (Combined Stress), and the resultant cardiac hypertrophy and ketone body synthesis were evaluated. Subsequently, organ-specific knockout mice of HMG-CoA synthase 2 ( Hmgcs2 ), a rate-limiting enzyme in ketone body synthesis, were subjected to Combined Stress to assess the impact on cardiac hypertrophy. To conduct a metabolism-focused analysis, cell type-specific nuclei were isolated and subjected to RNA sequencing (RNA-seq) and comprehensive metabolomics analysis. To evaluate the direct effects of ketone bodies, H9C2 cells, rat cardiac cells ,were treated with β-hydroxybutyrate, followed by analysis of oxygen consumption and metabolomics. Results: Combined Stress resulted in increased myocardial cross-sectional area and enhanced ketone body synthesis in the liver and heart. Hepatocyte-specific Hmgcs2 knockout mice ( Hmgcs2 ΔHep ) subjected to Combined Stress exhibited exacerbated myocardial hypertrophy (cardiomyocyte cell size; Hmgcs2 flox : 322.8 ± 88.3 μm 2 : Hmgcs2 ΔHep : 444.0 ± 118.5 μm 2 ; p &lt; 0.0001). RNA-seq analysis revealed that the upregulation of glycolytic genes induced by Combined Stress did not occur in Hmgcs2 ΔHep mice, and a metabolic phenotype favoring fatty acid oxidation persisted. In the liver, hepatocyte destruction and increased serum fatty acid levels were observed. Additionally, H9C2 cells treated with β-hydroxybutyrate showed decreased fatty acid utilization and increased glucose utilization. Conclusion: In cardiac hypertrophy induced by obesity and hypertension, ketone body synthesis mitigates fatty acid overload and promotes glucose utilization, thereby exerting an anti-hypertrophic effect.
Abstract 4139976: Efficacy of High-Power Short-Duration Ablation on Epicardial Conduction Gap Following Pulmonary Vein Isolation and Carina Ablation, and Utility of High Unipolar-voltage-areas at the Carina as Indicators of Epicardial Connection Sites.
Authors: Masashi Kamioka, Tomonori Watanabe, Hisaki Makimoto, Hiroaki Watanabe, Takafumi Okuyama, Ayako Yokota, Takahiro Komori, Tomoyuki Kabutoya, Yasushi Imai, Kazuomi Kario
Journal: Circulation (2024)

Introduction: In pulmonary vein isolation (PVI), the carina is often refractory to ablation and require linear ablation, and some patients have epicardial connections. Hypothesis: High-power Shor-duration (HP-SD) ablation can prevent gap formation, and high unipolar-voltage-area (HUV), defined &gt;2.7 mV, will identify the epicardial connection site. Aims: To investigate the impact of HP-SD ablation on durable PVI and the efficacy of HUV for the prediction of epicardial connection site. Methods: Ninety-three atrial fibrillation (AF) patients who underwent successful PVI were enrolled. Forty-one patients underwent HP-SD ablation, while fifty-two patients underwent conventional ablation. First pass isolation was achieved in 66 patients, while the remaining 27 patients needed carina ablation. The epicardial conduction gap (EG) of the PVI line was defined as the continuous propagation pattern across the PVI line under the high right atrial pacing. The epicardial connection (EC) was defined that the propagation pattern was defined as a centrifugal pattern with the earliest site located around the mid-carina, more than 5 mm far from PVI line. Results: Carina ablation following PVI was needed more frequently in conventional ablation group than in HP-SD group (38% vs. 17%, P = 0.020). However, there was no statistical difference in EC between HP-SD and conventional ablation groups ［2 of 41 (4.8%) in HP-SD vs. 3 of 52 (5.7%) in conventional, P = 0.852］. This suggests that HP-SD ablation could suppress EG formation more effectively. Among the 5 patients with EC, 4 patients (80%) had HUV adjacent to the earliest activation site at the mid-carina (3 in right and 1 in left). Notably, the EC was eliminated by ablation at the HUV but not at the earliest activation site. During a one-year follow-up, 7 patients experienced AF recurrence. Patients who underwent HP-SD ablation showed lower tendency for recurrence compared to those with conventional ablation (4.8% vs 13.4%, P = 0.126). Notably, no patients who underwent EC ablation in the HP-SD ablation group experienced recurrence, whereas all patients in the conventional ablation group experienced recurrence (0% vs 100%). Among patients requiring carina ablation, 1 of 2 in the HP-SD group and 6 of 7 in the conventional group experienced recurrence (50% vs. 85.7%). Conclusion: HP-SD ablation was effective to prevent EG and EC, and HUV was useful indicator of epicardial breakthrough site to endocardium.