tbuckley/cabot-search huggingface dataset:
Abstract 13627: Atrial Fibrillation is Associated With Worse Outcomes in Saddle Embolus of Pulmonary Artery Without Cor-Pulmonale
Authors: Amulya Reddy Dwaram, Yuliana Petryshyn, Ahmad Harb, Siri Chandana Swarna, Gowthami Koorapati, Amjad Harb, Paari Dominic
Journal: Circulation (2023)

Background: Pulmonary embolism (PE) is a common form of venous thromboembolism that could be potentially fatal. Atrial fibrillation (AF) is the most common arrhythmia, which may lead to thromboembolic complications. They are distinct medical conditions, but PE may lead to AF through right-sided pressure overload. AF, in turn, might lead to right atrial thrombus formation and, thereby, PE. AF can be seen as a presenting sign during early phase or later during recovery from PE. Methods: This is a retrospective cohort study in which we queried the National Inpatient Sample database between 2016 and 2019 to identify hospitalizations (age 18 and older) with a principal diagnosis of Saddle embolus of pulmonary artery without acute cor-pulmonale. The cohort was divided into patients with and without AF as a secondary diagnosis. The primary outcome was in-hospital mortality. The secondary outcomes were cardiogenic shock, acute respiratory failure, length of stay, and total hospital charges. All statistical analyses were performed using weighted values. Results: During the study period, there were 58,285 hospitalizations with a principal diagnosis of Saddle embolus of pulmonary artery without acute cor-pulmonale. Among them, 5800 (11%) had a diagnosis of AF. Baseline characteristics are shown in Table 1. After adjusting for all significant baseline characteristics, patients admitted with concomitant AF had higher in-hospital mortality (6.6% vs 3.7%; aOR 1.88, 95% CI:1.46 - 2.42, p &lt; 0.0001), cardiogenic shock (5.9% vs 2.0%; aOR 3.04, 95% CI: 2.3 - 4.0, p &lt; 0.0001), acute respiratory failure (4.2% vs 2.7%; aOR 1.65; 95% CI: 1.14 - 2.15), increased length of stay (7.59 vs 5.44 days p &lt; 0.0001), total hospital charges ($100,756 vs $ 69,396 p &lt; 0.0001) Conclusions: This study demonstrates that AF is associated with increased mortality, cardiogenic shock, acute respiratory failure, length of stay, and total hospital charges in saddle embolus of pulmonary artery without cor- pulmonale
Abstract 13514: Unfavorable Neurological Outcomes With Incremental Cardiopulmonary Resuscitation Duration in Cardiac Arrest Brain Injury: A Systematic Review and Meta-Analysis
Authors: Avilash Mondal, Bhaswanth Bollu, Nimra Shafi, Poojan Parmar, Abeera Kali, Qiming Dong, Maneeth Mylavarapu, SRIHARSHA DADANA, Muhammad Hassan Khan, Srija Shanker, Samia butt, Rupak Desai
Journal: Circulation (2023)

Introduction: Duration of Cardiopulmonary resuscitation (CPR) affects neurological outcomes. Data on its decremental effect on neurological outcomes haven’t been explored before Methods: PubMed, Scopus and Google Scholar were searched for relevant studies until May 2023 using relevant keywords. Odds of good neurological outcomes were studied. Binary random-effects models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Leave one out sensitivity analysis was performed. Heterogeneity was assessed using I2 statistics. For outcomes showing moderate or high heterogeneity, subgroup analyses were performed for follow-up duration or type of study. A p&lt;0.05 was considered statistically significant. Results: A total of 349,027 cardiac arrest patients (mean age: 70.2 years; males: 56.5%) from four studies were included in the meta-analysis. Of them the initial rhythm was shockable in 11% (38,465/349,027) and non-shockable in 88.97% (310,562/349,027) of the population. Odds of having favorable neurologic outcomes were OR 0.32 (95% CI 0.10-1.01, p=0.05) for 6-10-minute(n=14,118), OR 0.10 (95 %CI 0.02-0.64,p=0.02) for 11-15 min(n=43885), OR 0.05 (95% CI 0.01-0.36, p&lt;0.01) for 16-20 minutes(n=66,174), OR 0.04 (95% CI 0.01-0.21, p&lt; 0.01) for &gt; 20 min(n=181,262) and OR 0.03 (95% CI 0.00-1.55, p=0.08) for &gt; 30 minutes (n=66,461) when compared to patients receiving CPR for &lt; 5 mins (n=6420).(Fig.1) Conclusions: Steady decremental odds of favorable neurological outcomes were seen with every five minutes of increase in CPR duration with a statistically significant decline seen in CPR duration of 11-15 mins onwards
Abstract 15185: Plasma miR-132 Serves as a Blood Biomarker for Monitoring Treatment Efficacy of miR-132 Targeting Drugs Using a Novel CE-Marked Kit System
Authors: Janika Viereck, Steffen Rump, Sandra Rizk, Jana Hahm, Thomas Thum
Journal: Circulation (2023)

Introduction: MicroRNAs are critical regulators of cardiovascular pathophysiology and detectable in most body fluids, proposing them as circulating biomarkers. The aim of this study was to investigate if plasma miR-132 can be used as a biomarker for monitoring treatment efficacy of miR-132 targeting drugs and to develop a CE-marked kit for relative quantification of plasma miR-132. Methods and Results: Correlation analysis of a porcine model of post myocardial infarction (MI) induced HF revealed a dose-dependent, highly significant linear correlation between plasma and cardiac miR-132 after treatment with CDR132L. Furthermore, significant correlations between reduced plasma miR-132 and functional improvement based on LVEF change as well as reduced plasma NT-proBNP were identified. Based on this data, we developed a qRT-PCR assay for detection of miR-132. RNA was extracted from cel-miR-39 spiked plasma samples and was transcribed into cDNA with specific primers for both miRs. The miRs were amplified in two singleplex qRT-PCRs based on hydrolysis probes. Delta Cq values were calculated between Cq values of miR-132 and the miR-39 spike-in control. No cross-reaction between both assays and no amplification on human DNA or RNA were observed confirming analytical specificity. Analytical sensitivity was verified by analysis of dilution series of cDNA templates. The clinical evaluation was carried out on a subset of 119 samples from the Phase 1b clinical trial, a safety and tolerability study for CDR132L including patients with chronic ischemic HF (NCT04045405), that also assessed target engagement. CDR132L administration was associated with a dose-dependent, statistically significant reduction in plasma miR-132 at study endpoint (day 112) whereas, the highest dosing groups showed sustained low miR levels. These results were in line with miR-132 levels assessed with commercially available research use only reagents. Conclusion: Plasma miR-132 was validated as a suitable target engagement and therapy monitoring biomarker and the newly developed CE-marked kit “CardiorHealth miR-132 Plasma PCR Kit (IVD)“ fulfilled its intended use to quantify plasma miR-132 and can be used for monitoring treatment with drugs targeting miR-132.
Abstract 14877: Spike Protein of SARS-CoV-2 Virus Induces Mitochondrial Dysfunction in Swine Heart via Redox Impairment of Heme Proteins and Increasing Superoxide Generation
Authors: Yeong-Renn Chen, Chwen-lih Chen, Chris Kolz, Patrick T Kang, William Lynch, Angelo L DeLucia, William M Chilian
Journal: Circulation (2023)

The cellular entry of the SARS-CoV-2 virus depends on the binding of spike (S) protein to its biological ligand, ACE2. Although the virus commonly causes respiratory distress, cardiac injury can occur in COVID-19 patients, which is consistent with the expression of ACE2 in myocytes. Previous reports indicate SARS-CoV-2 proteins can target cardiac mitochondria and suppress mitochondrial function via enhancing MPTP pore opening and perturbing cardiac bioenergetics. To explore the underlying mechanism of the effect of SARS-CoV-2 on cardiac mitochondria, we measured the interactions of SARS-CoV-2 proteins with swine heart mitochondria in vitro. Incubation of recombinant S protein with isolated mitochondria significantly decreased state-3 oxygen consumption rate (OCR, 95.10 vs 65.68 nmol/min/mg) and FCCP uncoupling OCR (82.94 vs 66.95 nmol/min/mg). We further detected that S protein impaired the enzymatic activities of electron transport chain (ETC) (by 15.62% to 34.44%). However, S protein had no effect on TCA cycle enzymes, indicating the involvement of mitochondrial membrane components in decreased OCR by S proteins. Recombinant nucleocapsid (N) protein of SAR-CoV-2 had no effect on the OCR and ETC activities of swine mitochondria. S proteins decreased the intensity of mitochondrial heme spectrum determined by dithionite reduction with UV/VIS spectroscopy (by 17.52% heme a , 15.82% heme c 1 ). The results were further assessed using isolated complex III (Cx3) and complex IV (Cx4). Treatment of isolated Cx3 and Cx4 with S protein decreased the spectral intensities of heme a and heme c 1 . The spectra of both Cx3 and Cx4 were not affected by N protein. The results suggested S protein downregulates redox potentials of ETC in swine mitochondria. Treatment of swine mitochondria with S proteins enhanced superoxide ( . O 2 – ) generation by Cx1 (by 43.7%) and by Cx3 (by 10.9-fold) assessed by EPR and cytochrome c reduction assays. However, we detected S proteins modestly decreased . O 2 – generation by swine mitochondria under state-2 condition (by 9.52%), indicating impairing pH gradient by S protein. In conclusion, the spike protein of SARS-CoV-2 virus mediates mitochondrial dysfunction of swine heart via impairing the redox function and increasing . O 2 – generation.
Abstract 18610: Focal Pericoronary Adipose Tissue Evaluated by Electron Density Numbers on Non-Contrast Spectral Computed Tomography Was Associated With Coronary Arterial Plaques: A Site-by-Site Analysis
Authors: Nobusada Funabashi, Atsushi Shukuya, Hiroki Asano, Akio Kawamura, Naoko Mizuno
Journal: Circulation (2023)

Introduction: Inflammation in pericoronary adipose tissue (PCAT) around the coronary arterial wall causes coronary arterial sclerosis. Many studies evaluated the relationship between total PCAT volume and coronary arterial sclerosis on a patient-by-patient basis. Hypothesis: Inflammation in PCAT may occur focally in coronary arterial system to which coronary arterial plaques localize. Using novel spectral CT, based on electron density number (EDN) as a new parameter, the focal characteristics of PCAT were evaluated. Methods: 17 patients (10 males, mean age 70 years) underwent cardiac spectral CT (7500, Philips, Tokyo, Japan). From non-contrast data, EDNs of PCAT were determined at a 1) right side site and 2) left anterior side site of a proximal portion of right coronary arteries (RCA), 3) anterior side site of the left main coronary arteries, 4) left side site of a proximal portion of the left circumflex artery, and left side site of a distal portion of the RCA (five sites each patient). We also evaluated coronary arterial plaques on enhanced CT images at five corresponding sites for which EDNs were determined. Results: For a total of 85 sites among 17 patients using enhanced CT, 31 sites had no plaques (group 1), 14 sites had only non-calcified plaques (group 2), 20 sites had only calcified plaques (group 3), 16 sites had mixed plaques (group 4), and four sites had stent implantations (group 5). The mean of EDNS (%EDW) for 81 sites, excluding four sites with a stent implantation, were 93.5, 93.3, 93.2, and 93.8 in groups 1-4, respectively (P=NS). For a total of 81 sites, excluding four implantation sites, we evaluated the relationship between age and EDNs in groups 1-4. Positive correlations were observed in group 1 (R= 0.40), and 3 (R= 0.40), however negative correlation was observed in group 2 (R= -0.22) and 3 (R= -0.22) between age and EDNs. No significant differences in EDNs were noted between males and females (P=NS). Conclusions: This is the first study in which focal PCAT was evaluated by EDNs and the relationship to coronary arterial plaques determined by site-by-site analysis. This new CT parameter may evaluate the status of PCAT and be a predictor of the future occurrence of coronary arterial plaques, which are related to PCAT inflammation even on non-contrast CT alone.
Abstract 15329: Echocardiographic Assessment of Cardiac Function in Preterm Miniature Pigs Supported With a Pumped Artificial Placenta
Authors: Henriette Kuehle, Jessica S Chow, Steven K Cho, Alex J Charest-Pekeski, Fu-Tsuen Lee, Tanroop Aujla, Alejandro Floh, Mark J McVey, Marvin Estrada, Lynn Crawford Lean, Dariusz Mroczek, Brahmdeep Saini, Jessie Mei Lim, Olivia J Moir, Jack R Darby, Janna L Morrison, Christoph Haller, Liqun Sun, Mike Seed
Journal: Circulation (2023)

Introduction: Preterm birth is the leading cause of infant mortality and morbidity. Artificial placenta (AP) technology aims to support premature fetal piglets in an environment simulating intrauterine physiology to maintain fetal circulation and improve outcomes and survival. Hypothesis: We sought to understand the fetal cardiovascular physiology and mode of cardiac failure associated with a pumped extracorporeal membrane oxygenation circuit connected to the fetal circulation. Methods: Following umbilical cannulation, connection to a centrifugal pump and neonatal oxygenator and transition of preterm Yucatan miniature piglets to a fluid-filled biobag, echocardiographic studies measured ventricular function and fluid status including Dopplers, and strain analysis both prenatally and while maintained on the AP circuit. Results: AP fetuses (n=13; GA 102±4d; 616±139g; survival 46.4±46.8h) were tachycardic and hypertensive with supraphysiologic circuit flows initially. Strain analysis revealed significantly reduced RV strain rate within the first five hours of AP support compared to paired prenatal measurements (p=0.005) . Fetuses supported for &lt;24h had significantly lower overall RV global longitudinal strain (p=0.001) than those surviving &gt;24h. M-mode imaging revealed progressive cardiac hypertrophy with an increase in interventricular septum (p=0.03) and LV free (p=0.04) wall thickness from first to last measurements. Doppler measurements showed elevated peak flow velocity patterns in the MCA and reductions in MCA-PI from start to end of support (p=0.04) as well as compared to unpaired prenatal controls (p=0.03, p=0.001) . Imaging findings included ascites, skin edema, and dilated hepatic veins. Conclusions: AP fetuses exhibited signs of excessive volume and pressure loading resulting in impaired contractility, including supraphysiologic umbilical flows, reduced RV strain and strain rate, and evidence of elevated filling pressures. Myocardial hypertrophy and changes in cerebral perfusion indicated adaptation to increased afterload, potentially affecting cardiovascular and cerebrovascular development and leading to fetal deterioration. Further advancements in AP technology are necessary before clinical translation.
Abstract 15540: Comparative Outcomes of Femoropopliteal Intravascular Ultrasound Interventions: A Report From the XLPAD Registry
Authors: David Fernandez Vazquez, Sarah Weideman, Blake Bruneman, Aravinda NANJUNDAPPA, Christopher Metzger, sameh sayfo, Zachary Rosol, Shirling Tsai, Mehdi H Shishehbor, Subhash Banerjee
Journal: Circulation (2023)

Background: Intravascular ultrasound (IVUS) during peripheral artery intervention is being increasingly used, however there is limited real-world procedural and outcomes data. Methods: We examined 4847 patients from the XLPAD Registry (NCT01904851) from 2006-2021 that underwent femoropopliteal (FP) endovascular intervention. The primary outcome was the incidence of major adverse limb events (MALE), which includes death, clinically driven revascularization, amputation, myocardial infarction (MI), and stroke. Comparative analyses were done between patients with IVUS and no IVUS interventions. Results: 322 (6.6%) patients underwent an IVUS guided FP intervention and 4525 without. Mean age 67, predominantly men (83% IVUS-group vs. 71% non-IVUS, p&lt;0.0001) and Caucasian (71% vs. 69%, p=NS). IVUS patients had worse risk profiles, with more smokers (59% vs. 47 %, p&lt;0.0001), heart failure (20% vs. 14%, p=0.006) and prior-MI (31% vs. 22%, p&lt;0.0001), and similar proportion of hypertensives, diabetics, dyslipidemics, or those with chronic kidney disease. IVUS patients had more multivessel intervention (2.4 vs. 1.9 lesions, p&lt;0.0001), SFA being the most common artery, followed by the popliteal artery in both groups. Balloon angioplasty was more common in the non-IVUS group (68% vs. 75%, p=0.005), whereas drug coated balloons (19% vs. 12%, p=0.005), drug-eluting stents (15 vs. 9%, p=0.001) and vascular mimetic stents (13 vs. 4%, p&lt;0.0001) were more frequent in the IVUS patients. Fluoroscopy time was longer in IVUS patients (35 min vs 30 min., p=0.005) with similar rates of procedural (90% vs. 93, p=NS) and technical success (94% vs. 95%, p=NS). There were no differences in peri-procedural complications, or 12-month MALE (21% vs. 20%, p=NS). Only death from any cause was significantly higher in the non-IVUS group (0.7 vs 3.0%, p=0.017). Conclusion: IVUS use is under 7% of all FP interventions in the XLPAD registry with IVUS guidance is used in patients with more adverse clinical risk profile, however with no difference in technical, procedural success and 12-month MALE events.
Abstract 150: Non-Linear Association Between the Time of Reaching the Targeted Temperature and the Neurological Outcome in Patients Undergoing Targeted Temperature Management After Out-of-Hospital Cardiac Arrest Observational Multicenter Cohort Study
Authors: Tetsuro Nishimura, Toshihiro Hatakeyama, Hisako Yoshida, Takeyuki Kiguchi, Yohei Okada, Yasumitsu Mizobata, Tetsuhisa Kitamura, Taku Iwami
Journal: Circulation (2023)

Background: We aimed to identify the most favourable time from the introduction of targeted temperature management (TTM) to achieving the targeted temperature in patients experiencing out-of-hospital cardiac arrest. Methods: This multicenter cohort study was performed using the Comprehensive Registry of Intensive Care for OHCA Survival study, we collected patients’ information, including that on in-hospital care. We enrolled all consecutive patients transported to participating institutions in Osaka, Japan from 1 July 2012 through 31 December 2017. Eligible were persons aged ≥18 years whose cardiac arrest was of cardiac etiology and who received in-hospital TTM. Primary outcome was favourable neurological survival with a Cerebral Performance Category scale of 1 or 2 one-month after cardiac arrest, which was designated as “one-month favourable neurological survival”. After adjusting for several factors, a non-linear multivariable logistic regression analysis assessed the time from the introduction of TTM to reaching the targeted temperature and the probability of the primary outcome. Also, we subdivided patients according to five quintiles based on the time from the introduction of TTM to achieving the targeted temperature. To compare the probability of the primary outcome among quintiles, a multivariable logistic regression analysis calculated adjusted odds ratios and 95% confidence intervals. Results: We analyzed 483 patients. p for non-linearity was &lt;0.01 in the non-linear multivariable logistic regression analysis. In the first quintile (&lt;26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥352.2 minutes), one-month favourable neurological survival was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% CI for the primary outcome in the first, second, third, and fifth quintiles, compared with the fourth quintile as the reference, were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusions: Time to reaching the targeted temperature was associated with favourable outcome in patients with cardiac arrest.
Abstract 13994: PKM2 Ablation Increases Pro-Inflammatory Signaling in Mice
Authors: Katie Lee, Allison L Williams, Ralph V Shohet
Journal: Circulation (2023)

Introduction: The predominant isoform of pyruvate kinase (PKM1) promotes oxidative metabolism in the healthy heart. We previously described a hypoxia and ischemia-mediated switch to the alternatively spliced isoform PKM2, known to promote glycolysis. Pkm2 has also been shown to reduce oxidative damage and promote cardiomyocyte cell proliferation after myocardial infarction (MI). PKM2 is also a metabolic regulator of immune cell differentiation. Hypothesis: We hypothesize that PKM2 has a role in limiting inflammatory stress by regulating the migration and activity of immune cells. Methods: PKM2 control and global KO mice were subjected to permanent ligation of the left anterior descending coronary artery to mimic an MI (n=3). Hearts were excised after 3 days and the transcriptomes and gene ontologies (GO) were then assessed by RNA-sequencing and pathway analysis. Circulating C-reactive protein (CRP) was assessed using an ELISA (n=12) and cytokines in plasma and heart tissue were assessed using a multiplex assay (n=3-5). Neutrophil myeloperoxidase secretion and differentiated cardiac macrophages were analyzed by immunofluorescent staining (n=3). Results: GO term enrichment analysis of RNA-seq results showed increased abundance of genes for neutrophil chemotaxis and apoptosis, regulation of cytokine production, and the inflammatory response in PKM2 KO hearts after MI compared to controls. PKM2 KO hearts showed increased neutrophil myeloperoxidase secretion and Ly6G/C staining for neutrophils and monocytes compared to controls. Similarly, M1 macrophages appeared to be more abundant in PKM2 KO hearts compared to controls. IL-6 levels were elevated in PKM2 KO plasma at baseline compared to controls, while CRP was elevated in PKM2 KO plasma across all conditions. IL-6 was also substantially elevated in PKM2 KO hearts after MI compared to controls. Conclusions: Loss of PKM2 increased pro-inflammatory signaling in the heart of KO mice. We saw increased cardiac and plasma IL-6 and CRP, likely related to the polarization of macrophages towards the M1 phenotype, and increased neutrophil activity in PKM2 KO hearts. We suggest that PKM2, induced by a hypoxia-related splicing event, protects the heart against the inflammation that accompanies infarction.