tbuckley/cabot-search huggingface dataset:
Abstract 4142268: Calcium channel blocker-induced prescribing cascades: Signal detection using high-throughput sequence symmetry analysis
Authors: Priyanka Kulkarni, Asinamai Ndai, Kayla Smith, Shailina Keshwani, Jae Choi, Michael Luvera, Julia Hunter, Rebecca Galvan, Tanner Beachy, Matthew Molk, Shannon Wright, Marianna Calvet, Carl Pepine, Stephan Schmidt, Scott Vouri, Earl Morris, Steven Smith
Journal: Circulation (2024)

Background: Dihydropyridine calcium channel blockers (DHCCBs) are effective first-line therapy for hypertension but can cause adverse effects (AEs) leading to the prescription of a new drug, i.e., a ‘prescribing cascade.’ Aim: To identify potential DHCCB-induced prescribing cascades using high throughput sequence symmetry analysis (HTSSA). Methods: Using claims from 5% (2011-15) and 15% (2016-20) samples of Medicare fee-for-service beneficiaries, we identified new DHCCB users aged &gt; 66 y with continuous enrollment &gt; 360 days pre- and &gt; 180 days post-CCB initiation. We screened for the initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within + 90 days of DHCCB initiation. Adjusted sequence ratios (aSRs), representing proportions of DHCCB initiators starting the marker class after vs. those starting before DHCCB were calculated, with 95% CIs &gt;1 considered significant; for significant signals, the number needed to harm (NNTH) was also calculated. Independent clinical reviewers classified signals as potential prescribing cascades or not based on biological plausibility. Results: We identified 388,862 DHCCB initiators (mean + SD age 77 + 7.5 years; 62% female and 92% with hypertension). Of the 446 marker classes assessed, we identified 82 signals that warranted further exploration (aSR &gt; 1). After clinical review, 29 (35.36%) signals were classified as potential prescribing cascades (Figure 1). The top 3 potential prescribing cascades ranked by aSR were other systemic hemostatics (aSR 2.99 [1.10-8.16]), other nasal preparations (aSR 1.99 [1.47-2.70]), and drugs used in erectile dysfunction (aSR 1.85 [1.27-2.70]). Other clinically relevant signals included electrolyte solutions (NNTH 216, aSR 1.35), osmotically acting laxatives (NNTH 710, aSR 1.13), and sulfonamides (NNTH 104, aSR 1.50). Conclusion: HTSSA is a novel approach to identify DHCCB-induced potential prescribing cascades. Using this method, we identified known and underrecognized AEs of CCBs in this nationally-representative Medicare cohort. More research is needed to evaluate clinical outcomes attributed to these prescribing cascades.
Abstract 4142533: Ventricular rate of Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention and the Risk of Adverse Outcomes
Authors: Jingyang Wang, Jun Hao, YANMIN YANG
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) often coexists with acute coronary syndromes (ACS) or conditions requiring percutaneous coronary interventions (PCI), worsening the outcome. Although rate control is a cornerstone in AF management, the optimal rate-control target in patients with AF and ACS or undergoing PCI is not well-investigated. Methods: This study employed a post hoc analysis of a single-center prospective real-world cohort, including patients with AF and ACS or undergoing PCI who were receiving treatment with rate control drugs, from September 2016 to March 2020. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs) and all-cause death. We evaluated the impact of ventricular rate [(&lt;60, 60–79, 80–99, and 100–110, &gt; 110 beats per minute (bpm)] on subsequent adverse outcomes using multivariable Cox regression models. Results: The cohort consisted of 1004 patients with a median age of 68 years and predominantly male (72%). Patients with ventricular rates &gt;110 bpm showed the highest incidence of MACCEs (40.3%), all-cause death (30.6%) and cardiovascular death (24.2%) compared to other groups. Multivariable analysis confirmed that ventricular rates &gt;110 bpm were associated with greater risk of MACCEs (HR, 2.35; 95% CI, 1.38-4.00; P for trend = 0.0178) and all-cause death (HR, 2.64; 95% CI, 1.29-5.40; P for trend =0.0091). Additionally, clear evidence of a dose-response relationship existed between higher ventricular rates and the risks of MACCEs, all-cause death, and cardiovascular death. Conclusion: In patients with AF and ACS or receiving PCI who were managed with rate-control agents, ventricular rates &gt;110 bpm were associated with higher risks of MACCEs and all-cause death.
Abstract 4142436: The HeartPlus Clinic Project: Multidisciplinary Treatment for Patients with Stimulant-Associated Cardiomyopathy
Authors: Thu Tran, Soraya Azari, Elizabeth Johnson, Shirin Jimenez
Journal: Circulation (2024)

Background: Stimulant-associated cardiomyopathy is an increasingly common cause of non-ischemic cardiomyopathy. Unfortunately, the last decade has seen dramatically higher rates of hospitalization for heart failure related to stimulant use. There are currently no Food and Drug Administration-approved medications for stimulant use disorder treatment (SUD). However, contingency management is a behavioral treatment that has been shown to be effective for SUD. In partnership with UC San Francisco, we developed a heart failure-addiction medicine co-management clinic (HeartPlus) to offer guideline-directed medical therapy in conjunction with contingency management to treat stimulant-associated cardiomyopathy over twelve weeks. The most common stimulant of abuse was methamphetamine. Methods: Our retrospective chart review assessed the feasibility of an Addiction Medicine and Heart Failure Cardiology co-management clinic at UC Davis. The clinic combined contingency management including point of care urine drug testing, as well as guideline-directed medical therapy for heart failure. We evaluated how many patients attended HeartPlus clinic at least once, how many completed the twelve-week program, and of those patients who completed the program, how many had improvement in self-reported symptoms as assessed by Kansas City Cardiomyopathy Questionaire (KCCQ-12) and left ventricular systolic function as assessed by echocardiogram. Results: A total of 39 patients were referred to HeartPlus Clinic. Of those referred, 25 patients attended the initial visit, and 7 patients successfully completed the 12-week program. Of the 7 patients who completed the program, 4 patients had improvement in left ventricular ejection fraction by at least ten percentage points. All 7 patients demonstrated improvement in KCCQ-12 scores by at least ten points (generally accepted as moderate improvement). Conclusions: The HeartPlus Clinic is a feasible treatment intervention for patients with stimulant-associated cardiomyopathy. For those patients who completed the program, they reported encouraging improvement in heart failure symptoms and four of seven demonstrated significant improvement in left ventricular systolic function. At an average cost of $74 per participant, this twelve-week multidisciplinary program is a promising area for future efforts to treat this growing population of disproportionately young patients.
Abstract 4142242: Phenylacetylglutamine accelerated endothelial senescence and early-stage atherosclerosis formation by modulating cholesterol synthesis
Authors: Rong Huang, Xueying Jiang, Siyu Hou, Jie Li
Journal: Circulation (2024)

Background: Early-onset acute coronary syndrome (EO-ACS) poses a significant health burden, necessitating a deeper understanding of its underlying mechanisms. Dysfunction or loss of endothelial cells is an early detectable change and contributes to the onset of atherosclerosis. This study aimed to investigate the role of PAGln, in early-onset ACS, endothelial dysfunction, and atherosclerosis progression. Results: Plasma metabolic signatures were measured with untargeted metabolomics in patients with EO-ACS and control subjects. The potential role of PAGln and PAGly, a homologous metabolite of PAGln, in atherosclerosis was evaluated in ApoE −/− mice through PAGln or PAGly supplementation via i.p. injection. Various functional experiments involving PAGln treatment were performed on HUVECs or HAECs to unravel the underlying mechanism. Methods: Elevated levels of circulating PAGln were found to be increased in patients with EO-ACS and positively associated with endothelial chemokine levels. PAGln and PAGly treatment were observed to promote the initiation of atherosclerotic lesion formation in the early-stage and accelerate endothelial senescence. In vitro experiments demonstrated that increased cholesterol synthesis in endothelial cells mediated PAGln-induced endothelial senescence. Conversely, inhibition of cholesterol synthesis alleviated PAGln-induced acceleration of endothelial senescence and delayed the natural aging process of endothelial cells. Conclusion: This study further provide evidence to the detrimental impact of elevated PAGln levels on cardiovascular dysfunction, thus offering valuable insights into the mechanisms underlying early-onset ACS and endothelial senescence.
Abstract 4142243: Efficacy of Radiation Protective Shields on Operator Radiation Exposure During Cardiac Interventions: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Authors: Ahmed Saad Elsaeidy, Yazan Almohtasib, Mohamed Abuelazm, Ahmed Mazen Amin, Ahmed Almahdy Mohamed, Obieda Altobaishat, Ahmed Abdelhalem, Muhammad Imran, Basel Abdelazeem
Journal: Circulation (2024)

Background: The cumulative exposure to X-ray radiation during cardiac intervention can indeed pose various health risks. This meta-analysis aims to compare radiation protective shields (drapes and X-ray shields) versus conventional safety measures (lead apron) on the operator’s procedural radiation exposure during cardiac interventions. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. We used the random-effects model to report continuous outcomes using mean difference (MD) with a 95% confidence interval (CI). Results: We included 16 RCTs with 3370 patients. Radiation shields were significantly associated with low total operator radiation dose (MD: -7.3, 95%CI [-11.9, -2.7], P&lt; 0.01) with no significant difference between both arms regarding chest radiation dose (MD: -20.7, 95%CI [-48.9, 7.6], P= 0.15) and thyroid radiation dose (MD: -15.4, 95%CI [-32.4, 1.7], P= 0.08). Also, shields were significantly associated with low air kerma (MD: -46.4, 95%CI [-87.3, -5.5], P= 0.03) and low fluoroscopy duration (MD: -0.3, 95%CI [-0.6, -0.04], P= 0.02). However, there was no difference between both arms regarding the total procedure time (MD: -0.7, 95%CI [-3.1, 1.6], P= 0.54), contrast volume (MD: -3.2, 95%CI [-10.2, 3.7], P= 0.36), and dose area product (MD: 628.4, 95% CI [-3466.9, 4723.8], P= 0.76). Also, we found no differences between drape and shields subgroups in all outcomes. Conclusion: Radiation protection shields significantly reduced the total radiation dose exposure and air kerma. Also, shields are associated with lower fluoroscopy duration, insignificant lower procedure time, and contrast volume.
Abstract 4142421: The Impacts of Blood Pressure Variability on Clinical Outcomes in Patients with Out-of-hospital Cardiac Arrest
Authors: Shih-Neng Lin, Chen-Hsi Chang, Chin-Chou Huang
Journal: Circulation (2024)

Background: Out-of-hospital cardiac arrest (OHCA) is associated with unfavourable survival rates and neurological outcomes. Blood pressure control is crucial in intensive care management, yet there are limited studies highlighting the influence of blood pressure variability (BPV). This study aims to investigate the impact of BPV within the first 48 hours on the outcomes in patients experiencing OHCA. Methods: A retrospective analysis was conducted on data from OHCA patients. Blood pressure measurements were collected and categorised into four intervals: 0-12 hours, 13-24 hours, 25-36 hours, and 37-48 hours after ROSC. BPV was assessed using the standard deviation (SD) and coefficient of variation (CoV) of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). Mortality and cerebral performance category (CPC) were utilized in the study to assess the clinical outcomes at 30 days post-OHCA event. Results: A total of 185 patients who survived more than 48 hours after ROSC were enrolled. Survivors (n = 98) exhibited significant differences in BPV measures compared to non-survivors (n = 86). Higher BPV of SBP and MAP were associated with increased mortality for all four time intervals. Higher BPV of MAP in the initial 12 hours after ROSC were identified as predictors of 30-day mortality (hazard ratio [HR] 1.052, 95% confidence interval [CI] 1.029-1.075, P &lt; 0.001 for SD of MAP). Furthermore, higher BPV of MAP in the initial 12 hours after ROSC were also identified as predictors of poor neurological outcomes (odds ratio [OR] 1.163, 95% CI 1.081-1.252, P &lt; 0.001 for SD of MAP). Overall, BPV within the first 48 hours after ROSC were correlated with higher 30-day mortality, and BPV within the first 36 hours after ROSC were correlated with poor neurological outcomes. Conclusion: Increased BPV within the first 48 hours after ROSC is a significant predictor of mortality and poor neurological outcomes in OHCA patients. These findings underscore the importance of monitoring and managing BPV in the early post-arrest period to improve patient outcomes.
Abstract 4142387: Sodium-Glucose Cotransporter-2 Inhibitors In Children With Left Ventricular Systolic Dysfunction
Authors: David Newland, Yuk Law, Erin Albers, Reda Ali, Joshua Friedland-Little, Christina Hartje-Dunn, Mariska Kemna, Lisa Knorr, Thomas Nemeth, Kathryn Spencer, Bethany Wisotzkey, Borah Hong
Journal: Circulation (2024)

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are proven to reduce risk of cardiovascular death and hospitalization for heart failure (HF) in adults with reduced or preserved ejection fraction (EF). There are limited data on SGLT2i use in pediatric HF. Hypothesis: Addition of SGLT2i to standard HF medical therapy in children with left ventricular (LV) systolic dysfunction is associated with improved clinical outcomes. Methods: Single-center observational analysis of 65 pediatric patients (≤ 21 years old) with LV systolic dysfunction (n=44 dilated cardiomyopathy; n=21 repaired biventricular congenital heart disease) who had SGLT2i added to standard HF medical therapy since January 2020. Patients must have received SGLT2i for minimum of 3 months to be included. Patients with single ventricular physiology or already supported by a ventricular assist device (VAD) were excluded. Results: Median age at SGLT2i initiation was 11.2 years (range 2 months to 21 years), 54% were female, and 46% were started on SGLT2i (89% dapagliflozin; 11% empagliflozin) during an inpatient hospitalization. Median daily SGLT2i dose received was 5 mg or 0.14 (IQR 0.11-0.17) mg/kg/day. Sixty percent had a HF hospitalization within the prior year preceding SGLT2i start. Chronic HF medications at latest follow-up included sacubitril/valsartan (82%) or ACE inhibitor (6%), beta-blocker (83%), and mineralocorticoid receptor antagonist (77%). Median follow-up was 16.2 months (IQR 8.1-27.1). Median LVEF increased significantly from 35% (IQR 27-41) to 41% (IQR 32-52) and B-type natriuretic peptide (BNP) decreased from 300 pg/mL (IQR 84-728) to 86 pg/mL (IQR 18-308) (both p&lt;0.01). There was a significant difference in NYHA/Ross Class from baseline (I: 12%; II: 62%; III: 20%; IV: 6%) to latest follow-up (I: 35%; II: 49%; III: 6%; IV: 9%) (p&lt;0.01) with 32% improved, 62% unchanged, and 6% worsened. HF hospitalization occurred for 20% of the patients at median time of 7.9 months (IQR 3.2-16.5) after SGLT2i initiation. Eleven percent of the cohort were listed for transplant, died, or underwent VAD implant at latest follow up. Conclusion: Long-term use of SGLT2i in addition to standard HF medications in children with LV systolic dysfunction is associated with significant improvement in LVEF, BNP, and NYHA/Ross class. Use of SGLT2i in pediatric HF is evolving and further larger scale studies should be supported to determine efficacy.
Abstract 4142565: Dysfunction of left atrial physiology in patients with pAF despite return to sinus rhythm
Authors: Simon Feseha, Dwight Bibby, Qizhi Fang, Armeen Namjou, Sachiyo Hang, Jeffrey Olgin, Nelson Schiller
Journal: Circulation (2024)

Background: Knowledge of physiologic and anatomic abnormalities that attend the spectrum of atrial fibrillation (AF) is incomplete. Left atrial physiology in patients who have developed atrial fibrillation and have converted to sinus rhythm may be a productive focus for exploration. Hypothesis: We hypothesize that left atrial function is altered in patients with a history of paroxysmal AF despite conversion to sinus rhythm and may precede development of AF. Methods: 33 patients with paroxysmal atrial fibrillation (pAF group) and 40 healthy age matched patients (control group) underwent echocardiography while in sinus rhythm. 28 patients with risk factors for AF (risk group) were compared to control. Results: Table 1 shows baseline characteristics of age matched control and pAF groups, with mean age of 60 and 62. Of the pAF group, 58% had a history of hypertension and trended towards obesity (Table 1, p&lt;0.001). Left atrial end systolic volume index (LAESVI) and left atrial end diastolic volume index (LAEDVI) was increased in pAF (36 and 19) compared to controls (28 and 11) (Table 2, p&lt;0.001). Emptying fraction was diminished in pAF group when compared to controls with 46% and 59% (Figure 3, p&lt;0.001). LA global longitudinal strain is diminished in pAF at -29% compared to controls at -33% (Table 2, p=0.014). Emptying fraction was diminished in risk group at 53% compared to control group 59% (Figure 1, p=0.007). Conclusion: The left atrium remains significantly altered in both its physiology and anatomy in atrial fibrillation despite conversion to sinus rhythm, LA volumes are increased throughout the cardiac cycle and LA contractile performance (strain) is reduced. Left atrial abnormalities precede development of AF in risk group.
Abstract 4142450: In Hospital Outcomes of Mitral Valve Transcatheter Edge to Edge Repair (M-TEER) in Patients with Coronary Chronic Total Occlusion (C-CTO). Insight From The National Inpatient Database
Authors: asmaa Ahmed, Mahmoud Eisa, Mohamed Mohamed, Andrew Takla, Muhammad Osama, Sahej Arora, Scott Feitell
Journal: Circulation (2024)

Introduction: M-TEER is a minimally invasive procedure for selected patients with symptomatic mitral regurgitation. It remains unknown whether the concomitant C-CTO would affect the outcomes of M-TEER procedure. Methodology: We used the Nationwide Inpatient Sample Data between January 2016 and December 2020 to identify M-TEER hospitalizations with concomitant C-CTO. Baseline characteristics including demographic data and comorbidities were identified. Primary outcomes were in-hospital all-cause mortality and net all cardiac periprocedural complications defined as a composite of acute myocardial infarction, pacemaker placement, cardiac tamponade, pericardiocentesis, pericardiotomy, pericarditis, and hemopericardium. Results: 48,835 cases of M-TEER were identified during the study period, of whom 700 patients (1.5%) had the diagnosis of C-CTO. The mean age of M-TEER patients was not significantly different between the two groups (76 vs. 75 years, p=0.11), however the CTO cohort had more males (66.72% vs. 53.41%, p=0.002), and more comorbisities as; previous myocardial infarction (32.14% vs.15.66%, p= 0.0003), peripheral artery disease (32.1% vs. 22.67%, p=0.03), complicated hypertension (80% vs. 68.6%, p= 0.001) and renal failure (52.8% vs. 37.3%, p= 0.0007). A higher percentage of M-TEER procedures in patients with CTO were performed in elective setting (62.8% vs. 46.5%, p=0.0008). M-TEER among patients with CTO was associated with a higher incidence of net all periprocedural cardiac complications (21.4% vs. 13.4%, p=0.04) with however similar in-hospital mortality between both groups (3.57% vs. 2.35%, p=0.46). The results remained consistent on adjusted analysis; M-TEER-CTO cohort had higher odds of net all cardiac periprocedural complications (aOR 1.83 ,95% CI (1.17-2.84), p=0.007) with no difference in in-hospital mortality (aOR 1.54, 95 %CI (0.52-4.56), p =0.43). M-TEER utilization in CTO patients was associated with higher costs ($270,385 vs. $237,190 p=0.05), however, no significant difference in mean length of stay (5.8 vs. 4.8 days, p 0.17) Conclusions: In patient undergoing M-TEER, concomitant C-CTO increases the risk of net all cardiac periprocedural complications with no significant increase in mortality
Abstract 4142627: Cardiac Resident Macrophage Produces Collagen I and Contribute to Vascular Maturation After Myocardial Infarction
Authors: Daile Jia, Jinghong Zhang, AIJUN SUN, Junbo Ge
Journal: Circulation (2024)

Background: Cardiac resident macrophages engage in a wide array of functions such as endocytosis, angiogenesis, and regeneration and are essential to the maintenance of homeostasis in the steady heart. After myocardial infarction, cardiac resident macrophages are highly heterogenous with diverse functions and therapeutic potentials and primarily within the infarct border zone. Cardiac resident macrophages drive postinfarction remodeling by secreting proteins that impart signals to nearby cells expressing their cognate receptors. The full complexity of this intercellular cross-talk that shapes wound healing and functional adaptation after MI remains incompletely understood. Methods: Single-cell transcriptomes from human and mouse acute myocardial infarction documented CCR2 − collagen I + macrophage expansion. Multiple transgenic mice such us Col1a1 F/F ; LysM Cre , and Col1a1 F/F ; Cx3cr1 CreER were used to determine the functional significance of collagen I derived from macrophage in MI. Moreover, collagen I expression from macrophages was analyzed by immunohistochemistry and qPCR in the cardiac tissues of patients with ischemic cardiomyopathy and healthy controls.We generated a genetic lineage-tracing system that uses dual recombinases (Cre and Dre) to specifically track collagen I + macrophages in vivo. Results: Dual recombinases-mediated genetic system targeted CCR2 − MHC-II low Col1a1 + macrophages specifically and efficiently. Lineage tracing study revealed accumulation of CCR2 − MHC-II low Col1a1 + macrophages in the border zone after MI. Macrophage-specific deletion of Col1a1 significantly reduced collagen I production in the border area and resulted in a considerable exacerbation in cardiac function, accompanied with impaired epicardial cell migration and new vessel formation. Collagen I derived from cardiac resident macrophage controls epicardial cell migration through the DDR1–NF-κB–MMP9/Efna1/Adgra2 axis. Conclusions: In this study, we deciphered how cardiac resident macrophage and epicardial cells cross-talk that shapes wound healing and functional adaptation after myocardial infarction.