tbuckley/cabot-search huggingface dataset:
Abstract 15914: Cardiac Troponin I versus T for Revascularization and Survival in Non-ST Elevation Acute Coronary Syndrome in Patients With Chronic Kidney Disease
Authors: Bovey Wu, Dmitry Abramov, Janani Rangaswami, Mandeep S Sidhu, Sripal Bangalore, Roy O Mathew
Journal: Circulation (2023)

Introduction/Background Cardiac troponins (cTn) underlie the diagnosis of non-ST elevation (NSTE)- acute coronary syndrome (ACS). Utility of specific cTn types is less delineated for patients with chronic kidney disease (CKD). Goals/Aims Determine the predictive value of two cardiac enzymes-cTnI and cTnT- for revascularization procedures (percutaneous coronary intervention [PCI]/coronary artery bypass grafting [CABG]) and mortality. Methods/Approach Patients with CKD (estimated glomerular filtration rate &amp;lt 60mL/min/1.73m2) admitted with a diagnosis of NSTE-ACS within the Veterans Affair Healthcare System between 1999 and 2022 (n=56711). Proportional change of serial cTnI and cTnT was calculated. Outcomes included PCI and CABG, and inpatient and 12 months after hospitalization mortality. Classifier ability is quantified by comparison of area under receiver operating characteristic (AUROC) for proportional change in cTnI or cTnT; hypothesis testing is completed with empirical AUC, Mann-Whitney U testing. Results/Data Proportional change in serial cTnT was not found to be statistically different compared to cTnI in predicting revascularization (AUROC 0.524 vs 0.512; p = 0.423). Proportional cTnT change had statistically higher predictive ability compared to cTnI for inpatient mortality (AUROC 0.584 vs 0.500; p = 0.007) and 12-month mortality (AUROC 0.550 vs 0.515; p = 0.038) (Figure). Conclusion In CKD patients with NSTE-ACS, cTnT demonstrated higher predictive ability in the prognostication of short- and long-term outcomes. Prospective studies are needed to further characterize optimal cTn assay type in patients with kidney disease presenting with symptoms concerning for ACS.
Abstract 18418: Osteoprotegerin Mediates T-Cell Response in Myocardial Wound Healing Post-Ischemic Injury
Authors: Thomas W Knight, Marcus J Wagner, Emily Megill, Ngefor Asangwe, Lindsay Kraus, Hajime Kubo, Mohsin Khan, Sadia Mohsin
Journal: Circulation (2023)

Introduction: Myocardial Infarction (MI) triggers an inflammatory response associated with cardiac wound healing. T-regulatory cells (Tregs) play a crucial role in the MI heart during this inflammatory response via their regulation of cardiac repair and function. Stimulating and sustaining the pro-reparative T cell response after MI would aid in preserving cardiac structure and function. Cortical Bone derived Stem Cells (CBSCs) possess a diverse array of inflammatory signaling molecules that can influence the inflammatory microenvironment of the heart after MI. A paracrine factor, Osteoprotegerin (OPG), is abundantly present in CBSCs, but it is unknown if OPG can mediate Tregs in myocardial injury. Hypothesis: CBSCs-derived Osteoprotegerin can regulate cardiac wound healing post-MI by modulating T cell response. Methods and Results: T cells exposed to CBSC secretome underwent an upregulation of a Treg population (p≤0.0001) characterized by the expression of Tumor Necrosis Factor Receptor II (TNFRII). Further investigation into the CBSC secretome highlighted OPG as a potent signaling molecule responsible for inducing TNFRII+ Tregs (p≤0.0001) measured by FACS analysis. siRNA-mediated depletion of OPG studies showed compromised TNFRII+ Treg induction (p≤0.0001). In vivo studies, adult FoxP3-GFP (12-16 week) mice underwent left anterior descending artery ligation followed by intramyocardial injection of CBSCs, Mesenchymal Stem Cells (MSCs), or vehicle (saline) along the infarct border zone. Resident T-lymphocyte populations were assessed at 1- and 8-weeks post-MI via flow cytometry. CBSC-treated hearts yielded a greater prevalence of TNFRII+ Tregs at 1- and 8-weeks following MI compared to MSCs (p≤0.01; p≤0.0001) and vehicle (p≤0.0001; p≤0.05). CBSC induction following MI reduced infarct size compared to the vehicle (p≤0.05). Ablation of the Treg population in the ischemic zone following MI increased infarct size and solicited adverse cardiac remodeling (p≤0.05). Conclusion: Osteoprotegerin can promote cardiac wound healing by facilitating the expansion and preservation of pro-reparative TNFRII+ Tregs.
Abstract 19102: E-Cigarettes Induce Persistent Cardiac Autonomic Dysfunction and Molecular Signatures of Dilated and Arrhythmogenic Cardiomyopathy
Authors: Anand Ramalingam, Cory Kucera, Michael Merchant, Aruni Bhatnagar, Alex P Carll
Journal: Circulation (2023)

Introduction: Evidence is mounting that use of e-cigarettes (e-cigs) promotes cardiopulmonary injury and dysfunction, but the long-term consequences remain unclear. Consumption of menthol e-cigs has surged amid imminent bans on combustible menthol cigarettes and cigars. Recently, we found e-cig aerosols with menthol (but not tobacco) flavor acutely induced spontaneous ventricular arrhythmias in mice. Hypothesis: Menthol e-cigs induces persistent cardiac autonomic imbalance. Methods: Adult C57BL/6J male mice with electrocardiogram (ECG) and blood pressure (BP) telemeters were exposed for 4 weeks to menthol e-cig aerosols (JUUL, 180 puffs/day, 5 days/week; n=8) or filtered air (Air; n=7) and challenged with restraint stress to determine cardiovascular reactivity to stress. Hearts (n=5/group) were collected immediately after final exposure for phosphoproteomics. Results: Menthol e-cig exposures increased HR, decreased HR variability, and evoked ventricular premature beats only on exposure day 1, but consistently increased BP throughout the 20-day exposure (+16 mmHg systolic BP vs. Air). Additional exposures in females (n=4) recapitulated these acute effects. Pre-treatment with atenolol (n=4 males) abolished e-cig-induced arrhythmias, suggesting β 1 -adrenergic mediation of e-cig-induced arrhythmias. After 4-week JUUL Menthol exposure, mice had basal sinus bradycardia and impaired stress reactivity, characterized by reduced maximal HR and rapid recovery to baseline. All three effects persisted up to 3 weeks following cessation and were accompanied by prolonged ventricular repolarization (QT c ). Phosphoproteomic analysis revealed upregulation of protein kinase A signaling, and mitochondrial dysfunction in e-cig-exposed mice. Phosphoproteins associated with dilated &amp; arrhythmogenic cardiomyopathy (ATP2A2, FN1, CACNB2, PFKM, ADCY6, and PRKAR1A) were differentially regulated in e-cig-exposed mice. Conclusions: We demonstrate that menthol e-cigs induce persistent cardiac autonomic imbalance associated with molecular signatures of dilated &amp; arrhythmogenic cardiomyopathy. Autonomic imbalance and cardiac electrical dysfunction may contribute to the long-term health effects of repeated use of e-cigarettes.
Abstract 17195: Sex-Specific Differences in Outcomes Following Alcohol Septal Ablation or Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Ragavendar Saravanabavanandan, Aniket Jaimalani, Muhammad Ahsan Naseer Khan, Sania Riaz, Gabriel Mangas, Syed Muhammad Ahsan, Sarojini Posani, Tirath Patel, Moiz Fawad, Mohammed Al-Tawil
Journal: Circulation (2023)

Introduction: Clinical evidence and emerging studies suggest that the clinical heterogeneity observed in hypertrophic obstructive cardiomyopathy (HOCM) could be due to sex-based differences. However, definite evidence to guide sex-specific treatment is not yet available. We aim to explore the sex-related differences in treatment outcomes following alcohol septal ablation (ASA) and septal myectomy (SM). Methods: We searched PUBMED/MEDLINE, EMBASE, and SCOPUS to identify studies that report sex-stratified comparison of outcomes in adults undergoing ASA or SM. The primary outcomes were the short-term/ 30-day mortality, post-operative permanent pacemaker (PPM) requirement, and the length of in-hospital stay. Results: Fifteen studies totaling 31,907 patients (47% men and 53% women) met our eligibility criteria. Among patients undergoing ASA (n=13357) or SM (n=18550), females were found to be significantly older at the time of intervention (ASA - mean difference (MD): 7.55 years; 95% CI [4.83, 10.28]; p &lt; 0.00001; SM - MD: 4.41; 95% CI [2.79, 6.03]; p &lt; 0.00001).In both the ASA and SM treatment arms, females had a significantly higher risk of short-term all-cause mortality (ASA - RR: 0.48, 95% CI [0.32, 0.71]; p = 0.0003; SM - RR: 0.63; 95% CI [0.44, 0.90]; p = 0.01), greater PPM implantation rate (ASA - p = 0.002; SM - p = 0.05), and longer in-hospital stay (ASA - MD: 1.00 days; p &lt; 0.00001; SM - MD: 0.69; p &lt; 0.00001). Among those undergoing ASA, females had a significantly higher rate of atrioventricular (AV) block (p &lt; 0.00001). However, the 30-day re-admission rate following SM was similar in both sexes. Conclusions: This is the first meta-analysis to compare sex differences in HOCM treatment outcomes. Female patients were older, had higher short-term mortality, and required more PPM implants compared to males, regardless of whether they received ASA or SM. This emphasizes the critical need for a sex-specific treatment approach in managing HOCM.
Abstract 17066: Efficacy and Safety of the Pharmacoinvasive Strategy Compared With Primary Percutaneous Coronary Intervention in Patients Initially Presenting to Hospital Centers Without Capacity for Coronary Intervention
Authors: Mariana Robles-Ledesma, Nitzha Andrea Najera-Rojas, Alejandro Ezquerra Osorio, Alma Paola Alonso-Bringas, Giovanna Sánchez-Leony, Rodrigo Gopar-Nieto, Jorge Daniel Sierra Lara Martinez, Alexandra Arias-Mendoza, Diego Araiza
Journal: Circulation (2023)

Introduction: Primary PCI (pPCI) is the preferred treatment for reperfusion in STEMI patients. However, its feasibility in real-world scenarios raises questions about the effectiveness of the pharmacoinvasive strategy compared to pPCI for patients arriving at a healthcare facility without a catheterization laboratory. Hypothesis : A pharmacoinvasive strategy is more effective than transferring STEMI patients to a PCI-equipped hospital for those initially presenting to non-PCI centers. Aims: To compare the efficacy of the pharmacoinvasive strategy versus referral for primary PCI in STEMI patients initially presenting at non-PCI centers. Methods: This study is a pre-specified subanalysis of the PHASE-Mx registry (NCT NCT03974581), including consecutive STEMI patients from Mexico City treated within 12 hours of symptom onset. Patients received either the pharmacoinvasive strategy or were referred for pPCI. The primary composite endpoint was cardiovascular death, cardiogenic shock, recurrent myocardial infarction, or congestive heart failure at 30-day follow-up. Results: A total of 634 patients were included, with 61.3% treated with the pharmacoinvasive strategy and 38.6% referred for pPCI. Mean age was 58.3 (+/-10 years), and the majority were men (85.3%). Compared to those transferred for pPCI, pharmacoinvasive strategy showed a significant reduction in the risk of the primary endpoint beyond 30 days, with a hazard ratio (HR) of 0.60 (95% CI 0.39-0.94, p = 0.02). This risk reduction was primarily driven by a significant decrease in heart failure risk (HR 0.57, 95% CI 0.35-0.93, p = 0.025). Conclusions: Pharmacoinvasive strategy in STEMI patients initially attending hospitals without PCI capability resulted in a 40% risk reduction for cardiovascular death, heart failure, cardiogenic shock, and recurrent infarction at 30-day follow-up compared to referral for pPCI.
Abstract 16884: CircNPHP1 Regulates Endothelial Function in Ischemic Heart Disease
Authors: Costanza Emanueli, Moumita Sarkar, Maryam Anwar, Aranzazu Chamorro-Jorganes, Kerrie Ford, Abas Laftah, gianni angelini, Prakash Punjabi
Journal: Circulation (2023)

Background: Ischemic heart disease (IHD), which is characterized by reduced myocardial blood flow, is aggravated by diabetes mellitus (DM). Non-coding RNAs, including microRNAs (miRs) and circular RNAs (circRNAs), regulate gene expression and impact angiogenesis. Canonically, miRs bind to the 3’UTR region of their target messenger RNAs (mRNA) to mediate post-transcriptional gene inhibition. CircRNAs can “sponge” and sequestrate miRs, thus preventing the repression of their mRNA targets. Hypothesis: The circRNAs/miR/mRNA interactions are deregulated in the diabetic heart, contributing to IHD. Aims: To identify and mechanistically investigate the circRNA-miRNA-mRNA networks deregulated in IHD and diabetes. Methods: We generated bulk RNA-seq data on whole transcriptome (for mRNAs and circRNAs) and small RNA (for miRs) using heart left ventricle biopsies of 3 groups of cardiac surgery patients (n=12/group) from the ARCADIA cohort (13/LO/ 1687): 1) and 2) suffering from IHD with/out type-2 DM and 3) non-ischemic non-diabetic controls. Customized bioinformatics approaches identified differentially expressed (DE) circRNAs, mRNAs and miR in IHD and IHD+T2DM patients (vs. Controls). Prediction tools and databases (CircInteractome, miRWalk) identified “sponging associations” between circRNAs and miRs and the targets of sponged miRs, producing the circRNA-miR-mRNA networks. The network’s individual components were filtered for endothelial cell (EC) expression using GEO datasets and for involvement in angiogenesis using KEGG, Wiki and Panther pathways and Gene Ontology. The endogenous role of the circRNAs in the top emerging network was tested in cultured ECs using siRNA-mediated silencing, while the circRNA-miRNA sponging interaction were confirmed determined after using circRNA pulldown with divergent primers. Results: A putative proangiogenic subnetwork commanded by circNPHP1 is DE in IHD+DM. circNPHP1 silencing in the ECs reduced angiogenesis and downregulated 2 validated target genes of miR-221-3p, namely VEGF and BCL2. The pull-down assay confirmed circNPHP1 binding to miR-221-3p. Conclusions: circNPHP1 supports vascular repair and holds potential as novel therapeutic target in IHD and DM.
Abstract 18756: Impact of Hospital Teaching Status on In-Patient Outcomes of Acute Myocardial Infarction
Authors: Smriti Khanal, Abhushan Poudyal, Ayusha Poudel, Bharosa Sharma, Nischit Baral
Journal: Circulation (2023)

Introduction: Prior studies have shown better outcomes for acute myocardial infarction (AMI) patients admitted to teaching compared to non-teaching hospitals. Similar trend was seen in studies limited to ST elevation myocardial infarction (STEMI) patients. We examined the impact of hospital teaching status on in-patient outcomes in AMI patients usingcurrent data and International Classification of Diseases 10 th Revision (ICD-10) system. Hypothesis: Acute myocardial infarction patients treated in teaching hospitals have better outcomes compared to patients treated in non teaching hospitals. Methods: We queried the 2016 and 2017 NIS databases to identify all patients over 18 years of age hospitalized for AMI. With hospital teaching status as an independent variable, multivariate logistic regression was used to compare mortality rates in AMI patients (primary outcome) and likelihood of revascularization within 24 hours for NSTEMI (secondary outcome); linear regression was used to compare length of stay(LOS) for NSTEMI patients (secondary outcome). Results: Of 1,308,314 patients with AMI (351,970 with STEMI and 955,314 with NSTEMI), 66.5% were admitted to teaching hospitals. In-patient mortality rate was higher in teaching (4.8%) compared to non-teaching (4.5%) hospitals [adjusted odds ratio (aOR) 1.16, 95% CI 1.12 to 1.21, p &lt; 0.001]. This was true for both STEMI [aOR 1.1, 95% CI 1.03 to 1.17, p = 0.004] and NSTEMI [aOR 1.16, 95% CI 1.10 to 1.22, p &lt; 0.001] patients. NSTEMI admitted to teaching hospitals were more likely to be revascularized within 24 hours of admission [aOR 1.27, 95% CI 1.22 to 1.33, p &lt; 0.001] compared to non-teaching hospitals. LOS for NSTEMI patients admitted to teaching hospitals was longer compared to non-teaching hospitals [4.9 vs 3.9 days, p &lt; 0.001]. Conclusions: Patients with AMI admitted to teaching hospitals had higher mortality rates compared to non-teaching hospitals. This contradicts the results of prior studies. Further research is warranted in this regard. NSTEMI patients admitted to teaching hospitals were more likely to be revascularized within 24 hours compared to non-teaching hospitals, but this did not translate to better mortality outcome. LOS was longer for NSTEMI patients admitted to teaching hospitals.
Abstract 17127: Rapid Progression of Conduction System Disease in Suspected Fulminant Nivolumab Myocarditis
Authors: Sanath Shetty, Tania Maheshwari, Geoffrey C Zarrella, Vasu Palli
Journal: Circulation (2023)

Background: Immune checkpoint inhibitors (ICI) have shown efficacy in treating a wide spectrum of malignancies, but have a known risk of cancer therapy related cardiac toxicity. We present a case that demonstrates how conduction system disease can rapidly progress in a patient with suspected nivolumab (PD1) induced fulminant myocarditis. Case: An 82-year-old male with a history of esophageal carcinoma presented with agonal breathing and altered mental status. He had received his second dose of PD1 therapy three days prior. He was intubated and admitted for hypoxic respiratory failure and elevated troponin. His initial EKG demonstrated new marked 1st degree AV block with right bundle branch block (RBBB) morphology. A stat echocardiogram noted an EF of 60-65% with no wall motion abnormalities. Decision-making: On Day 2, Mobitz Type I block was appreciated on telemetry. The patient met criteria for acute myocarditis with his clinical presentation, new conduction system disease, and high sensitivity troponin of 13,000. Given recent PD1 therapy, lack of infectious prodrome, and lack of prior heart disease, suspicion for ICI induced myocarditis was high. High dose steroid therapy was initiated. On Day 3, the patient was noted to have alternating left bundle branch block and RBBB. On Day 4, he progressed to complete heart block, prompting transvenous pacemaker (PM) placement with subsequent permanent PM placement. A repeat echo showed global hypokinesis with an EF of 40-45% and reduced RV function. He also required vasopressor support meeting criteria for fulminant myocarditis. Due to his hemodynamic instability and low clinical suspicion, he did not receive cardiac catheterization. Cardiac MRI and cardiac biopsy were not readily available in this institution. Conclusion: The clinical findings, lack of infectious prodrome, and worsening arrhythmia requiring pacing and vasopressor support, in patient with recent PD1 treatment suggests nivolumab induced fulminant myocarditis. In institutions without advanced testing infrastructure, rapid recognition of progressive conduction system disease may be used as an early marker for diagnosis, treatment initiation, and referral to tertiary care centers for advanced management of fulminant ICI myocarditis.
Abstract 18673: Lack of Influence of Comorbidities on NT Pro-BNP/BNP Ratio in ATTR-CA: A Prospective, Single Sample, Paired Data Analysis
Authors: Bharadwaj Satyavolu, Marcio Bittencourt, Georgia M Vasilakis, Majd F Al Ahmad, Brent Medoff, Prem Soman
Journal: Circulation (2023)

Introduction: Scores to stage amyloidosis include laboratory values of NT pro-BNP and BNP. However, no prior data on the correlation between the two markers is available for the same sample in ATTR patients with a spectrum of co-morbidities. While established staging systems for cardiac amyloidosis use NT-pro BNP, many centers routinely measure BNP. To facilitate universal staging, we explored the relationship between NT-pro BNP and BNP measured from a single blood sample in ATTR patients with a spectrum of co-morbidities. Hypothesis: The ratio of NT pro-BNP to BNP is influenced by atrial fibrillation, BMI, left ventricular and renal function. Methods: ATTR-CA patients had serial NT pro-BNP and BNP measured from a SINGLE blood sample. Ratios were compared in patients stratified by co-morbidities. A regression equation to derive BNP from NT pro- BNP was created. Results: Among 101 patients, (85% men, 84% Caucasian), co-morbidities were prevalent (atrial fibrillation: 56%, LVEF &lt; 50%: 46%, GFR &lt;60 mL/min/1.73 m 2 : 51%, BMI ≥ 27: 51%); 4% were on ARNI. A strong correlation (r = 0.83) and a ratio of the log transformed data of 1.32 (95% CI: 1.29 - 1.34) was found between NT-pro BNP and BNP levels, which was not different among patients stratified according to co-morbidities. The relationship between NT pro-BNP and BNP was defined by ln(BNP) = 0.59 + 0.69 ln(NT pro-BNP). Conclusions: Our study suggests a robust correlation between NT-pro BNP and BNP in ATTR-CA patients and a constant ratio among patients with different co-morbidities. A regression equation may facilitate deriving BNP levels from NT- pro BNP and must be validated independently.
Abstract 16235: Older Patients Presenting With Cardiogenic Shock Have Worse Outcomes: Insights From a Quaternary Referral Center Registry
Authors: Darshan H Brahmbhatt, Fernando Scolari, Julie K Vishram-Nielsen, Vicki N Wang, Kristine A Keon, Emily Shin, Ava Isabella De Pellegrin Overgaard, Mahrukh Nisar, Filio Billia, Chris Overgaard, Adriana Luk
Journal: Circulation (2023)

Background Cardiogenic shock (CS) is a life-threatening clinical syndrome of reduced cardiac output that leads to multi-organ failure. Despite improvements in the possible therapies available, it remains a significant cause of morbidity and mortality among patients admitted to the Cardiac Intensive Care Unit (CICU). It remains unclear how age of the admitted patient may affect outcomes. Aim We investigated survival of CS patients admitted to a single quaternary North American center stratified by age. Methods: All CS patients aged 18 years and older admitted between January 2014 and December 2021 were identified from a prospective CICU admissions registry. Patients with durable left ventricular assist device (LVAD) and heart transplant (HT) were excluded, as were CICU readmissions during the index hospitalization. Patient characteristics, co-morbidities and outcome data were collected. Survival between age groups (&lt;30, 30-40, 40-50, 50-60, 60-70 and &gt;70 years old) was compared using Kaplan-Meier methods. A Cox proportional hazards model evaluating survival differences by age as a continuous variable was created and quantified the association between age and mortality with other covariates: sex, etiology, admission creatinine, sodium, lactate, white blood count (WBC) and mean arterial pressure (MAP). All analyses were right-censored for LVAD or HT. Results: 1284 CS patients were identified, with mean age 60 years, 71% male, 21% due to acute MI. In-hospital survival stratified by age was significantly different (figure), p(Log Rank&lt;0.001). In the unadjusted model, increasing age led to an increased mortality, hazard ratio (HR) 1.029, p&lt;0.001. In the adjusted model for mortality, age remained significant, HR 1.023, 95% confidence interval 1.015-1.030, p&lt;0.001. Conclusion In a contemporary CICU registry, patients admitted with CS had higher mortality with advancing age. This should be a consideration in planning the use of potentially limited CICU resources.