tbuckley/cabot-search huggingface dataset:
Abstract 206: Effect of Airway Strategy Upon Chest Compression Quality in the Pragmatic Airway Resuscitation Trial
Authors: Henry E Wang, Xabier Jaureguibeitia, Ahamed H Idris, Unai Iruste, Erik Gonzalez, Tom P Aufderheide, Matthew L Hansen, Ryan Huebinger, Robert Schmicker, Jestin N Carlson, Riccardo Colella, Jeffrey Jarvis, Richard Gordon, Robert Suchting, Elisabete Aramendi
Journal: Circulation (2020)

Background: Chest compression (CC) quality is associated with improved out-of-hospital (OHCA) outcomes. Airway management efforts may adversely influence CC quality. We sought to compare the effects of initial laryngeal tube (LT) and initial endotracheal intubation (ETI) airway management strategies upon chest compression fraction (CCF), rate and interruptions in the Pragmatic Airway Resuscitation Trial (PART). Methods: We analyzed CPR process files collected from adult OHCA enrolled in PART. We used automated signal processing techniques (MATLAB) to identify and calculate CC quality measures. We defined a CC interruption as ≥3 second pause in chest compressions. We determined CC fraction, rate and interruptions (number and total duration) in 1-minute epochs for the entire resuscitation. We compared differences in CC quality between LT and ETI using t-tests. We repeated the analysis stratified by time before/after airway insertion as well as by successive 3-minute time segments. We also compared CC quality between single vs. multiple airway insertion attempts, as well as between BVM-only vs. ETI or LT. Results: Of 3,004 patients enrolled in PART, CPR process data were available for 1,996 (1,001 LT, 995 ETI). Mean resuscitation duration was: LT 22.6±10.8 min, ETI 25.3±11.3 min. Mean CC fraction (88% vs. 87%, p=0.045) and rate (114 vs. 114 bpm, p=0.59) were similar between LT and ETI. Median number of CC interruptions was similar between LT and ETI (11 vs. 12). Total CC interruption duration was lower for LT than ETI (160 vs. 181 sec, p=0.002); this difference was largest before airway insertion (56 vs. 78 sec, p=0.001). There were no differences in CC quality when stratified by 3-min time epochs. Total CC interruption duration was shorter for single than multiple airway insertion attempts (127 vs. 153 sec, p=0.005). Total CC interruption duration was shorter for BVM-only than LT or ETI (104 vs. 135 sec, p&lt;0.001). Conclusion: In PART, compared with ETI, LT was associated with shorter total CC interruption duration but not other CC quality measures. Single-attempt airway insertion and BVM-only were associated with shorter total CC interruption duration. OHCA airway management may influence CC quality.
Abstract 17235: Comparision of Outcomes in Patients Undergoing Catheter versus Surgical Ablation for Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction
Authors: Krunalkumar Patel, Kirtenkumar Patel, Jay Shah, Rajkumar Doshi, Amitkumar Patel, MUHAMMAD ZUBAIR KHAN
Journal: Circulation (2020)

Introduction: There is a lack of research comparing outcomes of Surgical Ablation (SA) and Catheter Ablation (CA) among Atrial Fibrillation(AF) patients with heart failure with Preserved Ejection Fraction (HFpEF) and . Hypothesis: The main objective is to compare short-term clinical outcomes of SA and CA in AF patients with HFpEF. Methods: We used the national inpatient sample to identify patients over 18 years with HFpEF hospitalization and AF, and undergoing SA and CA from 2016 - 2017. The clinical outcomes of SA versus CA in AF stratified as non-paroxysmal and paroxysmal were analyzed. Results: 1,530 HFpEF hospitalizations with AF who underwent SA and 1,045 HFpEF hospitalizations with AF who underwent CA were included in the analysis. Patients undergoing CA had higher baseline comorbidity. The in-hospital mortality between HFpEF with AF undergoing SA as compared to CA was similar (1.9% versus 1.4%, adjusted P-value 0.04). Patients undergoing SA had a significantly longer length of hospital stay, a higher percentage of post-procedural, and cardiac complications. In HFpEF patients with non-paroxysmal AF, SA as opposed to CA was associated with a higher percentage of in-hospital mortality (2.7% versus 0%, adjusted P-value=0.23), a longer length of stay, a higher cost of treatment, and a higher percentage of cardiac complications. Conclusions: In conclusion, CA is associated with lower in-hospital outcomes as compared to SA among AF with HFpEF patients. Further research with freedom from AF is needed between this group with long-term out c omes.
Abstract 14257: Endothelial SOX17 Deficiency Induces Pulmonary Arterial Hypertension
Authors: Zhiyu Dai, Dan Yi, BIN LIU, Shuai Li
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: Human genome-wide association studies identified that SOX17 locus variants are associated with PAH. SOX17 mutation is also found in patients with PAH. We hypothesis that endothelial SOX17 deficiency contributes to the pathogenesis of PAH. Methods: Mice with EndoSCL-CreERT mediated deletion of Sox17 ( Sox17 iCKO ) were generated. Sox17 iCKO and Sox17 f/f mice after tamoxifen injection were incubated with hypoxia (10% O 2 ) for 3 weeks to induced PAH. Hemodynamics and histological examination were measured to determine the PAH phenotypes and vascular remodeling. EC proliferation and apoptosis were assessed in SiRNA-mediated SOX17 knockdown in human lung microvascular endothelial cells (hLMVECs). The RNA-sequencing analysis was performed to understand the molecular mechanisms of SOX17 deficiency in ECs. Results: Sox17 iCKO mice exhibited exaggerative PAH evident by the increase of RVSP and RV hypertrophy after hypoxia treatment compared to Sox17 f/f WT mice. SOX17 knockdown in hLMVECs induced cell proliferation and reduced starvation-induced apoptosis. RNA-seq analysis and DAVID pathway analysis demonstrated that there was dysregulation of cell proliferation-related genes, which are enriched in the pathways related to cell cycle, cell division, and mitotic cell cycle. Transcriptional factor, target, and motif discovery analysis of the dysregulated gene set revealed the involvement of transcriptional factors FOXM1 and E2F1. siRNA mediated knockdown of E2F1 but not FOXM1 normalized SOX17 deficiency-induced hLMVECs proliferation and anti-apoptosis. Conclusions: Our study demonstrated that endothelial SOX17 deficiency exaggerates hypoxia-induced PAH. Loss of SOX17 promotes EC proliferation and anti-apoptosis via the upregulation of transcription factor E2F1.
Neutral Ceramidase Mediates Nonalcoholic Steatohepatitis by Regulating Monounsaturated Fatty Acids and Gut IgA+ B Cells
Authors: Xuemei Gu, Rui Sun, Liang Chen, Shenghui Chu, Mark A. Doll, Xiaohong Li, Wenke Feng, Leah Siskind, Craig J. McClain, Zhongbin Deng
Journal: Hepatology (2020)

Background and Aims Nonalcoholic steatohepatitis (NASH) is associated with obesity and an increased risk for liver cirrhosis and cancer. Neutral ceramidase (NcDase), which is highly expressed in the intestinal brush border of the small intestine, plays a critical role in digesting dietary sphingolipids (ceramide) to regulate the balance of sphingosine and free fatty acids. It remains unresolved whether obesity‐associated alteration of NcDase contributes to the manifestation of NASH. Here, we revealed that NcDase deficiency in murine models of NASH prevents hepatic inflammation and fibrosis but not steatosis. Approach and Results NcDase −/− mice display reduced stearoyl‐CoA desaturase (SCD) 1 expression with a compositional decrease of monounsaturated fatty acids (MUFAs) under the different dietary conditions. We further found that NcDase is a functional regulator of intestinal B cells and influences the abundance and quality of the secretory IgA response toward commensal bacteria. Analysis of composition of the gut microbiota found that Clostridiales colonization was increased in NcDase −/− mice. The colonization of germ‐free mice with gut microbiota from NcDase −/− mice resulted in a greater decrease in the expression of SCD1 and the level of MUFAs in the liver relative to gut microbiota from wild‐type littermates, which are associated with the alternation of IgA‐bound bacteria, including increase of Ruminococcaceae and reduction of Desulfovibrio . Mechanistically, NcDase is a crucial link that controls the expression of SCD1 and MUFA‐mediated activation of the Wnt/β‐catenin. Very importantly, our experiments further demonstrated that Wnt3a stimulation can enhance the activity of NcDase in hepatocytes. Conclusions Thus, the NcDase‐SCD1‐Wnt feedback loop promotes the diet‐induced steatohepatitis and fibrosis through the regulation of intestinal IgA + immune cells.
Abstract 16658: Patient Selection for Long-Term Secondary Prevention With Ticagrelor: Insights From PEGASUS-TIMI 54
Authors: Marc P Bonaca, Robert F Storey, Deepak L Bhatt, P. Gabriel Steg, Marc Cohen, KyungAh P Im, Per Johanson, Eugene P Braunwald, Marc S Sabatine
Journal: Circulation (2018)

Introduction: Long-term treatment with ticagrelor 60 mg added to ASA reduces ischemic risk but increases bleeding in patients with prior MI. Hypothesis: Clinical characteristics predicting bleeding and ischemic risk respectively applied in PEGASUS-TIMI 54 (NCT01225562) will identify subgroups who derive greater benefit with lower risk Methods: Predictors of bleeding (anemia at baseline, prior hospitalization for bleeding) and subgroups associated with greater ischemic risk reduction were merged into a selection algorithm. Efficacy (PEP - CV death, MI or stroke), safety (TIMI major bleeding) and net outcomes (CV death, MI, stroke, ICH or fatal bleeding) of ticagrelor 60 mg were evaluated by risk group. Results: Patients (N=13938) were divided into 4 groups first by the presence of a bleeding predictor (High Bleeding Risk - HBR, N=2703, 19%) and then the remainder (Low Bleeding Risk - LBR, N=11235, 81%) divided by the number of ischemic risk factors. In those with HBR, ticagrelor did not reduce the PEP (ARD 0.0%) but did increase bleeding by 2.2%. Of those with LBR, 22% had only 0 or 1 ischemic risk indicators, and in this subgroup ticagrelor reduced PEP by 0.5%, but increased bleeding by 1.0%. The remaining 59% of patients had no bleeding risk indicators and at least 2 ischemic risk indicators, and in this subgroup ticagrelor significantly reduced the risk of the PEP by 1.9% (P=0.0024, NNT 52) and only increased bleeding by 1.0% (P&lt;0.0001, NNH 102). In this latter subgroup, ticagrelor significantly reduced CV death (HR 0.66, 95% CI 0.50 - 87, p=0.0034, ARR 1.2%) and all-cause mortality (HR 0.75, 95% CI 0.61 - 0.95, p=0.018, ARR 1.1%) and the net outcomes (HR 0.80, 95% CI 0.68 - 0.93, p=0.0031, ARR 1.9%). Conclusions: A patient selection strategy first identifying those at low bleeding risk and then stratifying according to number of ischemic high-risk features identifies a population that derives significant ischemic benefit with reductions in all-cause mortality and net outcomes.
Abstract 13903: Accurate Assessment of Hypertension and Belief in Clinical Readings by Cardiologists
Authors: Martha Gulati, Lori-Ann Peterson, Anathasia Mihailidou
Journal: Circulation (2020)

Background: The accurate measurement of blood pressure (BP) is essential for the diagnosis &amp; management of hypertension. In clinical practice, BP is estimated using noninvasive methods but there is significant variability in practice, despite guidelines and recommendations for accurate BP assessment. Individual clinical practices implementation of guidelines for BP assessment influence accuracy and clinical certainty of BP measurements. Hypothesis: We sought to assess how BP is assessed in clinical practice of cardiologists and to assess the clinical certainty of the BP obtained in their clinics. Methods: A survey was administered through professional societies that include predominately cardiologists &amp; via Twitter. Assessment of adherence to guideline recommendations for BP assessment was measured and compared to belief and reliability of BP assessment in clinic. Results: 612 surveys were completed in 30 days, 364 completed by cardiologists; 49 (13%) preventive cardiologists. Majority of cardiologists based in United States. 53% routinely check BP in both arms at initial visit, 48% check BP only 1X/per visit; 64% wait 5 minutes before initial BP assessment. Automated BP assessment is used in 58% of respondents’ clinics. 83% trust their BP readings in clinic. Only 23% (85) of all cardiologist accurately measure BP as recommended by guidelines &amp; it is more likely to be done by a preventive cardiologist (P=0.017). For those who do measure BP correctly, 80% repeat BP manually compared with 54% who do not measure BP accurately (P&lt;0.001). For those who perform BP accurately, 86% report trusting their BP readings in clinic, similar to those who assess BP inaccurately (P=0.45). Conclusions: Accurate BP assessment by cardiologists remains suboptimal. Reliability of BP assessment in clinic requires education, implementation of recommendations and empowerment of the entire team to improve BP assessment &amp; results in improved cardiovascular outcomes for our patients.
Abstract 12852: Cardioembolic Myocardial Infarction in the Setting of Complex Immunologic Disease
Authors: Lowell A Safren, Ravi Masson, Sean Whelton, Allen Taylor, Martin McNamara
Journal: Circulation (2020)

Background: The occurrence of left atrial appendage (LAA) thrombus formation and embolic myocardial infarction (MI) is rarely reported in the absence of atrial fibrillation (AF). In patients with a history of immunologic disease, a multidisciplinary approach is critical for prompt evaluation and treatment. Presentation: A 46-year-old woman with chest pain and lower extremity paresthesias was found to have NSTEMI. Past medical history was notable for vasculitis and multiple organ infarcts. Coronary angiogram and cardiac MRI showed no obstructive or structural disease. One month later she had recurrent chest pain with inferior ST-elevations on ECG and troponin of 24ng/mL. Investigations and Outcome: Coronary catheterization showed multiple embolic occlusions (Figure 1A and 1B). Subsequent TEE showed LAA thrombus (Figure 1C). Continuous telemetry and serial ECGs from initial presentation were negative for AF. Hypercoagulable and antiphospholipid testing was negative. Brain MRI for paresthesias showed dural enhancement and subsequent biopsy found an IgG4 inflammatory process. Treatment with warfarin, corticosteroids, and rituximab was initiated. No atrial fibrillation was detected on serial EKGs and an event monitor during one year of follow-up. There was no embolic recurrence. Conclusion: Autoimmune diseases can have complex organ involvement through lesser known mechanisms which often present as diagnostic challenges. This case identifies the potential for cardioembolic events, including myocardial infarction, in IgG4 vasculitis even in the absence of atrial fibrillation or hypercoagulability.
Abstract 17148: Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Aortic Stenosis: Two-Year Results From the LRT Trial
Authors: Ron Waksman, Christian Shults, Rebecca Torguson, Paul Gordon, Afshin Ehsan, Sean R Wilson, John Goncalves, Robert Levitt, Chiwon Hahn, Puja Parikh, Thomas Bilfinger, David Butzel, Scott Buchanan, Nicholas N Hanna, Robert Garrett, Maurice Buchbinder, Federico M ASCH, Gaby WEISSMAN, itsik ben-dor, Corey Shea, Syed Ali, Hector M Garcia-Garcia, Lowell F Satler, Toby Rogers
Journal: Circulation (2020)

Objective: To evaluate clinical outcomes and transcatheter heart valve hemodynamics at 2 years after transcatheter aortic valve replacement (TAVR) in low-risk patients. Background: Early results from the Low Risk TAVR (LRT) trial demonstrated that TAVR is safe in patients with symptomatic severe aortic stenosis (AS) who are low surgical risk. Methods: The LRT trial was an investigator-initiated, prospective, multicenter study and was the first Food and Drug Administration-approved Investigational Device Exemption trial to evaluate feasibility of TAVR in low-risk patients. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints included clinical outcomes and valve hemodynamics at 2 years. Results: The LRT trial enrolled 200 low-risk patients with symptomatic severe AS to undergo TAVR at 11 centers. Mean age was 73.6 years and 61.5% were men. At 30 days, there was zero mortality, zero disabling stroke, and a low permanent pacemaker implantation rate. At 2-year follow-up, mortality was 4.4%, stroke rate was 4.6%, and permanent pacemaker implantation rate was 9.0%. Four patients (2.3%) presented with endocarditis; two of these underwent surgical reintervention. Of the 14% of TAVR subjects who had evidence of subclinical leaflet thrombosis at 30 days, there was no impact on valve hemodynamics at 2 years or stroke rate (4.8%) versus 4.2% in patients who did not have leaflet thickening. Conclusions: TAVR in low-risk patients with symptomatic severe AS remains safe at 2 years. Subclinical leaflet thrombosis, observed in a minority of TAVR patients at 30 days, did not impact valve hemodynamics in the longer term.
Abstract 17142: Long Term Results of Non-Invasive Ultrasound Therapy (NIUT) in Severe Symptomatic Aortic Valve Stenosis - First-in-Man
Authors: Emmanuel Messas, Alexander Ijsselmuiden, Selina Vlieger, Peter den Heijer, Guillaume Goudot, Etienne Puymirat, Samuel ZARKA, Bernard CHOLLEY, Christian Spaulding, Albert A Hagege, Eloi Marijon, Mickael Tanter, Benjamin BERTRAND, Mathieu C Remond, Mathieu Pernot, Rene Spaargaren
Journal: Circulation (2020)

Background: Not all patients with severe aortic valve stenosis are eligible for open-heart surgery or TAVR. CARDIAWAVE (Paris, France) has developed Valvosoft, a unique non-invasive ultrasound therapy device to treat aortic stenosis. The therapy aims to improve the opening of severely calcified aortic valves by cracking the calcium and reducing the stiffness in the aortic valve tissue by delivering transthoracically local shock waves on the valve leaflets. This study assesses the safety, feasibility and performance of this novel technique. Methods: This is a multi-center, prospective, first-in-man study designed to evaluate the safety and feasibility of the Valvosoft device. Ten patients with severe symptomatic calcific aortic stenosis and not eligible for SAVR/TAVR underwent a Valvosoft ultrasound therapy. Echocardiographic evaluation was performed by an independent core lab at baseline, discharge, and at 1, 3, 6 and 12 months along with clinical follow up. Results: Enrolled patients were advanced in age (84.1±6.5 yrs) with severe comorbidities (8 with heart failure, 5 with coronary heart disease and 5 with kidney failure). All had extensive aortic valve calcification with mean AVA of 0.61±0.17 cm2 and mean pressure gradient of 37.5±10.5 mmHg. At one-month follow-up, six patients had significantly improved their AVA with increase of 27.5% (p=0.03) and mean pressure gradient decrease of 23.2 % (p=0.025). These patients also received the highest dose and longest treatment duration. During one year follow up, 4 patients died due to progression of end stage heart failure not linked to the procedure and one patient had undergone a TAVR procedure. At 12 months, the five remaining patients has no device or procedure related major adverse events nor deterioration of neurological status. Echo, brain-MRI and clinical follow up will be presented. Conclusions: Non-invasive ultrasound therapy is feasible and safe in patients with severe aortic valve stenosis and can improve AVA and hemodynamic parameters. NIUT can be an important tool complementary to TAVI in treating patients with aortic valve stenosis.
Abstract 14088: Pro-neurotensin/neuromedin N is Associated With Incident Metabolic Syndrome
Authors: Charles D Nicoli, April P Carson, Timothy B Plante, Leann Long, Leslie A McClure, Janin Schulte, Mary Cushman
Journal: Circulation (2020)

Introduction: The tridecapeptide neurotensin increases dietary fatty acid uptake and is implicated in insulin resistance in animal models and—through plasma levels of its stable precursor pro-neurotensin/neuromedin N (pro-NT/NMN)—with human diabetes mellitus, obesity, and cardiovascular disease. We evaluated the association of pro-NT/NMN with incident metabolic syndrome (MetS). Methods: This analysis included a subcohort of 2,770 Black and White participants without prevalent MetS at baseline (2003-2007) from the REasons for Geographic And Racial Differences in Stroke study who had fasting plasma pro-NT/NMN measured by immunoassay and completed a second assessment from 2013-2016. Incident MetS was defined as ≥3 harmonized criteria at follow-up: impaired glycemic control, high systolic blood pressure, high triglycerides, low high-density lipoprotein (HDL), and increased waist circumference. Four sequential weighted logistic regression models were fitted to incident MetS overall and for each criterion separately, incorporating demographic factors, metabolic risk factors, HOMA-IR, and diet scores. Results: Over mean 9.4 (standard deviation [SD] 1.0) years follow up, 564 participants developed MetS. Median [IQR] plasma pro-NT/NMN was 160 [118-218] pmol/L. In the overall group, higher log pro-NT/NMN was associated with incidence of lower HDL (odds ratio [OR] per SD pro-NT/NMN 1.16, 95% confidence interval [CI] 1.00-1.35) and impaired glycemic control (1.25, 95% CI 1.11-1.40), but not other MetS components. Each SD higher log pro-NT/NMN was associated with a 22% increased odds of incident MetS, adjusted for demographics (Table); this was not significant when controlling for HOMA-IR in all but the White subgroup (race p -interaction 0.05). No differences by sex were observed. Conclusions: Higher neurotensin likely augments insulin resistance to increase odds of incident metabolic syndrome through impaired glycemic control and lower HDL.