tbuckley/cabot-search huggingface dataset:
Evolution of Embryo Implantation Was Enabled by the Origin of Decidual Stromal Cells in Eutherian Mammals
Authors: Arun R Chavan, Oliver W Griffith, Daniel J Stadtmauer, Jamie Maziarz, Mihaela Pavlicev, Ruth Fishman, Lee Koren, Roberto Romero, Günter P Wagner
Journal: Molecular Biology and Evolution (2020)

Abstract Mammalian pregnancy evolved in the therian stem lineage, that is, before the common ancestor of marsupials and eutherian (placental) mammals. Ancestral therian pregnancy likely involved a brief phase of attachment between the fetal and maternal tissues followed by parturition—similar to the situation in most marsupials including the opossum. In all eutherians, however, embryo attachment is followed by implantation, allowing for a stable fetal–maternal interface and an extended gestation. Embryo attachment induces an attachment reaction in the uterus that is homologous to an inflammatory response. Here, we elucidate the evolutionary mechanism by which the ancestral inflammatory response was transformed into embryo implantation in the eutherian lineage. We performed a comparative uterine transcriptomic and immunohistochemical study of three eutherians, armadillo (Dasypus novemcinctus), hyrax (Procavia capensis), and rabbit (Oryctolagus cuniculus); and one marsupial, opossum (Monodelphis domestica). Our results suggest that in the eutherian lineage, the ancestral inflammatory response was domesticated by suppressing one of its modules detrimental to pregnancy, namely, neutrophil recruitment by cytokine IL17A. Further, we propose that this suppression was mediated by decidual stromal cells, a novel cell type in eutherian mammals. We tested a prediction of this model in vitro and showed that decidual stromal cells can suppress the production of IL17A from helper T cells. Together, these results provide a mechanistic understanding of early stages in the evolution of eutherian pregnancy.
Abstract 16263: Association Between Visit-to-Visit Lipid Variability and Cardiovascular Events in Patients With Familial Hypercholesterolemia
Authors: Yexuan Cao, Ruixia Xu, Huiwen Zhang, Jinglu Jin, Huihui Liu, Yan Zhang, Ying Gao, Yuanlin Guo, Naqiong Wu, Chenggang Zhu, Chuanque Cui, Geng Liu, Qian Dong, Jing Sun, Jianjun Li
Journal: Circulation (2020)

Introduction: Visit-to-visit variability in lipid has been suggested as an predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). Hypothesis: This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy. Methods: A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM). Results: During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In multivariate Cox analysis, only Lp(a) variability parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival (Log-rank p &lt;0.05). The results were consistent in various subgroups. Conclusions: This is the first report to evaluate the prognostic value of lipid variability in real-world patients with FH and showed that Lp(a), but not LDL-C variability, was associated with MACEs, which emphasized the importance of regular lipid monitoring in patients with high risk.
Abstract 13461: Longitudinal Evolution of Epicardial Pacing Leads
Authors: Hugo Pierre Racine, Francois Philippon, Franck Molin, Jean-François Sarrazin, Isabelle Nault, Benoit Plourde, Karine Roy, Louis Blier, Gilles O'Hara, Frederic Jacques, Jean Champagne, Christian Steinberg
Journal: Circulation (2020)

Introduction: Implantation of epicardial pacing leads remains a well-known alternative to the standard transvenous approach in several situations. However, long-term data on the performance and safety of epicardial pacing leads remain scarce. Methods: We conducted a retrospective cohort study at a single tertiary center including all patients with right or left ventricular epicardial lead implantation between 1996 to 2018; n=255. Electrophysiological lead parameters at implantation and during follow-up were analyzed and compared with clinical data from the electronic medical records. Results: 230 patients were included in the analysis. Implanted lead models included the Medtronic 4968 (n=202) and Medtronic 5071 (n=28). Indications for epicardial lead implantation included upgrade to CRT in 153/230 (67%) individuals and standard right or left ventricular pacing only in 76/230 (33%). Of the 153 epicardial CRT patients, 50 had a history of failed transvenous CRT and 103 had concomitant cardiac surgery for other indications and were thought to have a likely indication for CRT in the nearby future. Mean follow-up time was 4,7years±4,2. Lead impedances were significantly higher in the 4968 model compared to the 5071. Pacing thresholds for both lead models were similar at implantation but were subsequently significant higher in the 5071 model. Higher pacing thresholds in the 5071 model did not result in premature battery depletion. Periprocedural complications related to the epicardial lead insertion occurred in 3/230 patients. Epicardial lead related complications at follow-up remained low (8/230; 3 dysfunctions, 2 dislodgments, 1 impending skin erosion). There were only 2 cases of epicardial lead infections at follow-up requiring surgical extraction. 4,3% of all implanted leads remained unconnected at follow-up. Conclusions: Epicardial lead implantation for either CRT or pacing indications is a durable and safe alternative to transvenous lead insertion.
Abstract 132: Cardiopulmonary Resuscitation with Chest Compressions During Sustained Inflations in a Pediatric Porcine Model - A Randomized Control Animal Trial
Authors: Georg Schmölzer, Siddhi Patel, Seung Yeon Kim, Gyuhong Shim, Sveva Monacelli, Tze-Fun Lee, Megan O'Reilly, Po-Yin Cheung
Journal: Circulation (2020)

Background: Pediatric resuscitation guidelines recommend continuous chest compressions (CC) with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation (CPR) once an airway has been secured. However, the optimal CC technique remains unknown. Aim: To determine if CCs during sustained inflations (SI) improves return of spontaneous circulation (ROSC) of asphyxiated pediatric piglets compared to CCaV. Intervention and measurements: Piglets (age 20-23 days) were anesthetized, intubated, instrumented, and asphyxiated. Protocolized resuscitation was initiated when mean arterial blood pressure was &lt;25mmHg with bradycardia. Piglets (n=12/group) were randomized to receive CCaV resuscitation (CCaV group) according to the current resuscitation guidelines, or CC during SI (CC+SI group). The CC+SI group received a SI with a peak inflating pressure of 25 cmH 2 O for 30sec, CCs were provided at a rate of 100/min, and SI was interrupted after 30 sec for one second before a further 30sec SI was provided. CC and SI were continued until ROSC. Respiratory parameters, carotid blood flow, systemic artery pressures, and cerebral oxygenation were measured. Main results: Median (IQR) time to ROSC was significantly decreased in the CC+SI group compared to CCaV with 248 (41-346)sec vs. 720 (167-720)sec (p=0.049), respectively. CC+SI had a 100% higher rate of ROSC compared to CCaV with 10(83%) vs. 5(42%) (p=0.089), respectively. Piglets in the CC+SI group received a median (IQR) 3.5 (0-5.8) intravenous epinephrine boluses compared to 8.0 (1.8-11) in the CCaV group (p=0.123). Conclusions: Combining CC and SI significantly improved time to ROSC and survival in asphyxiated pediatric piglets when compared to the current standard of CCs with CCaV during pediatric CPR.
Abstract 17173: Association of Acute Gout Flares and Colchicine Use With Clinical Outcomes During Admission for Acute Decompensated Heart Failure
Authors: Melissa E Chinn, Mary E Roth, Steven P Dunn, Kenneth C Bilchick, Sula Mazimba
Journal: Circulation (2020)

Introduction: Gout is a common comorbidity in heart failure (HF) patients, and is often exacerbated by diuretic use. The impact of gout or the treatment of gout on HF outcomes is unknown. The purpose of this study was to assess clinical outcomes in patients being treated for an acute HF exacerbation and receiving colchicine for an acute gout flare. Methods: This was a single center, retrospective cohort study of patients treated for an acute HF exacerbation from March 2011 to February 2020. The gout group included patients receiving colchicine for an acute gout flare during admission. The control group included those who did not receive colchicine for an acute gout flare. The primary outcome was 30-day readmission rate. Secondary outcomes included in-hospital mortality and length of stay. Results: In the cohort of 1,047 patients (68.8 +/- 13.7 years, 38% female), 237 patients received colchicine for acute gout during admission. Length of stay was significantly greater (9.93 days vs. 7.96 days, p &lt; 0.0001) and in-hospital mortality was significantly lower (2.2% vs. 6.6%, p = 0.009) in patients with versus without gout. In a multivariate logistic regression model, in-hospital colchicine given for a gout flare was significantly associated with reduced in-hospital mortality (OR 0.322, 95% CI 0.105-0.779, p = 0.02) after adjustment for home beta blocker use, inotrope use, age, and diabetes mellitus (p &lt; 0.05 for all in the model). The association between colchicine and survival to hospital discharge was only observed in patients who received colchicine during the hospitalization, as opposed to home use only. There was no significant difference in 30-day readmission rate based on gout status for patients surviving to hospital discharge (21.5% vs. 19.5%, p = 0.495). Conclusions: Among patients with an acute HF exacerbation, patients treated for an acute gout flare with colchicine had a greater length of stay and lower in-hospital mortality compared with those not having gout. Future analyses are warranted to identify the relationship between colchicine use and HF outcomes.
Abstract 13342: Increasing Use of the Right Ventricle to Pulmonary Artery Shunt for Stage 1 Palliation: A Report From the National Pediatric Cardiology Quality Improvement Collaborative
Authors: Garick Hill, Haleh Heydarian, Elisa Marcuccio, Brooke Tepe, Laurel H Stein, Garick D Hill
Journal: Circulation (2020)

Introduction: Stage 1 palliation (S1P) of single ventricle heart defects with aortic hypoplasia consists of either the Norwood operation with a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS), or a hybrid procedure. Changes in national trends over time and factors influencing surgical approach remain unclear. Hypothesis: There has been an increase in national use of the RVPAS for S1P. Methods: Data from the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase 1 (6/2008-8/2016) and phase 2 (8/2016-9/2019) databases were used. S1P type was evaluated by year of operation. Factors influencing the choice of MBTS versus RVPAS, as well as length of stay after S1P and mortality prior to Stage 2 palliation (S2P) between shunt types, were evaluated. Sites were stratified by the number of patients in the database per year as small (&lt;5), medium (&lt;10) and large (≥10) centers. Results: The combined database included 3335 eligible patients; 1,028 (30.8%) with MBTS, 1,989 (59.7%) with RVPAS, and 318 (9.5%) with hybrid procedure. Overall, of 62 centers, 14.6% of S1P were at small centers (n=26), 40.6% at medium centers (n=24), and 44.7% at large centers (n=12). There was an increase in RVPAS use over time (p=0.02). In multivariable analysis, increasing hospital volume (OR 1.2 [95% CI 1.1-1.4], p=0.003) and absence of other organ system anomalies (OR 1.5 [95% CI 1.0-2.2], p=0.049) were associated with MBTS use over RVPAS. Median length of stay after S1P with MBTS was longer than with RVPAS (31 [95% CI 20-49] vs 29 [95% CI 19-47] days, p=0.054) and mortality was higher prior to S2P (12.3% vs 9.6%, p=0.03). Conclusions: Use of RVPAS with S1P has increased over time with a decrease in MBTS use and unchanged hybrid frequency. MBTS is used more commonly in centers with higher volume and in patients without other anomalies but is associated with longer post-op hospitalization and lower transplant-free survival to stage 2 palliation.
Covid-19 vaccine trials: we must preserve the ends when communicating the means
Authors: Henry D Marshall
Journal: BMJ (2020)

Inhaled corticosteroids (ICS) have a class effect of increasing pneumonia risk in patients with COPD. However, pneumonia incidence varies widely across clinical trials of ICS use in COPD. This review clarifies methodological differences in defining and recording pneumonia events in these trials and discusses factors that could contribute to the varying pneumonia incidence. Literature searches and screening yielded 40 relevant references for inclusion. Methods used to capture pneumonia events in these studies included investigator-reported pneumonia adverse events, standardised list of signs or symptoms, radiographic confirmation of suspected cases and/or confirmation by an independent clinical end-point committee. In general, more stringent pneumonia diagnosis criteria led to lower reported pneumonia incidence rates. In addition, studies varied in design and population characteristics, including exacerbation history and lung function, factors that probably contribute to the varying pneumonia incidence. As such, cross-trial comparisons are problematic. A minimal set of standardised criteria for diagnosis and reporting of pneumonia should be used in COPD studies, as well as reporting of patients’ pneumonia history at baseline, to allow comparison of pneumonia rates between trials. Currently, within-trial comparison of ICS-containing <i>versus</i> non-ICS-containing treatments is the appropriate method to assess the influence of ICS on pneumonia incidence.
Abstract 14563: Improved Outcomes in Patients With Anthracycline-Induced Cardiomyopathy Undergoing Left Ventricular Assist Devices: 10-Year Longitudinal INTERMACS Study
Authors: Avirup Guha, Cesar Caraballo, Elliott Miller, Jocelyn Owusu-Guha, Katherine Clark, Tariq Ahmad, Lauren A Baldassarre, Daniel Addison, Neal L Weintraub, Nihar R Desai
Journal: Circulation (2020)

Introduction: Anthracycline-induced cardiomyopathy (AC-CM) presenting as end-stage heart failure may require mechanical circulatory support. Hypothesis: We hypothesize that there is no difference in outcomes after LVAD placement in those with AC-CM compared to other forms of cardiomyopathy. Methods: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) dataset spanning from 2008 to 2017 was utilized to identify adult AC-CM patients undergoing continuous flow LVAD implantation excluding those who required concomitant cardiac procedures and right ventricular support (RVS). AC-CM patients were compared to those undergoing LVAD placement due to idiopathic dilated cardiomyopathy (IDM) and ischemic cardiomyopathy (ICM). Primary outcome of overall mortality was studied using Cox-proportional hazards model. Secondary outcomes of first infection, ischemic stroke, major bleeding and subsequent RVS were evaluated using Fine-Gray competing risk model accounting for appropriate competing risks. Subgroup analysis based on gender, race, ethnicity, and use of pre-transplant goal directed medical therapy (GDMT) for systolic heart failure was performed. Result: Overall, 248 AC-CM patients underwent continuous flow LVADs in the 10-year period. At 12-months, 85.1% of AC-CM, 86.0% of IDM and 80.2% of ICM patients were alive (log-rank P &lt; 0.001). There was no difference in mortality compared to ICM and IDM ( P &gt; 0.05). However, pre-LVAD GDMT improved mortality in only the AC-CM cohort when compared to those patients who were not on GDMT (adjusted hazards ratio (HR): 0.44; confidence interval (CI): 0.19 - 0.99). AC-CM patients had a higher risk of major bleeding compared to IDM patients (HR: 1.23; CI: 1.01 - 1.50). AC-CM patients had lower risk of stroke compared to ICM patients (HR: 0.31; CI: 0.15 - 0.62). There was no difference in the three subtypes of cardiomyopathy in hazards of first infection or subsequent RVS. Conclusion: Survival rates are similar in AC-CM, ICM and IDM patients who received continuous flow LVAD therapy in the contemporary era. There is improved mortality benefit in AC-CM patients who are on GDMT before LVAD. Further research into bleeding and stroke related disparities is warranted.
Abstract 14735: Volatile Organic Compounds Are Associated With Lower Ankle-Brachial Indexes in African Americans of the Jackson Heart Study
Authors: Rodney K Kipchumba, Solomon K Musani, Emelia J Benjamin, Adebamike A Oshunbade, Arsalan Hamid, Jessica L Fetterman, Ervin R Fox, Wendy B White, Rachel J Keith, Donald CLARK, Aruni Bhatnagar, Naomi M Hamburg, Michael E Hall
Journal: Circulation (2020)

Introduction: Cigarette smoking is associated with peripheral artery disease (PAD) in African Americans (AA), but the association between cigarette constituents and PAD remain inadequately studied. We evaluated the effect of volatile organic compounds (VOC) acrolein and crotonaldehyde on ankle-brachial index (ABI) as well as related biomarkers in AA participants of the Jackson Heart Study. Methods: Urinary VOC concentrations were measured in a subset of participants at baseline including 345 self-reported current smokers and 718 never smokers. Multivariable linear regression assessed the association between ABI and VOC concentrations after adjustment for acute (cotinine) and chronic (pack-years) smoking measures in models 1 and 2, respectively. The degree of association was assessed after adjusting for possible mediation (Baron &amp; Kenny procedure) by C-reactive protein (CRP), fibrinogen, and homocysteine (HCY) concentrations. VOC concentrations were natural log transformed for normal distribution and all models adjusted for relevant covariates. Results: The mean age of included participants was 52 years and 49% women. Individuals who smoked were more likely to be men, less educated, have prevalent cardiovascular disease, and lower mean ABI. In model 1, ABI was inversely associated with urinary acrolein and crotonaldehyde concentrations. Model 2 retained the inverse ABI association for both VOC. Crotonaldehyde was directly associated with CRP and HCY in models 1 and 2. In model 1, acrolein was associated with HCY (Table). Biomarker mediation of the VOC-ABI relationship was insignificant. Conclusions: Acrolein and crotonaldehyde concentrations are associated with lower ABI and higher measures of inflammation and thrombosis in a community-based sample of AA. These findings suggest reduction in VOC exposure may reduce the risk of PAD in AA who smoke cigarettes.
Abstract 15921: Correlation Between Repolarization Changes in Signal Averaged Electrocardiography and Myocardial Fibrosis in Adults With Hypertrophic Cardiomyopathy
Authors: Ramses Ramirez Damera, Hernan L Vera-Sarmiento, David Hurtado-de-Mendoza, Ketty Dolores-Cerna, Muhammad I Khan, Roselle Abraham
Journal: Circulation (2020)

Introduction: Hypertrophic Cardiomyopathy (HCM) is known as one of the most common causes of sudden cardiac death. Its propensity to lethal arrhythmias is a result of myocardial remodeling leading to aberrant conduction and increased reentrant electrical activity. Previous studies suggest an association between the amount of myocardial fibrosis found on Cardiac Magnetic Resonance (CMR) and the risk of these ventricular arrhythmias. Signal Average Electrocardiography ( SAECG) is a noninvasive technique used to detect subtle conduction abnormalities that can be missed on standard Electrocardiography ( ECG ). Hypothesis: Non-uniform conduction through fibrotic tissue seen in CMR leads to unsynchronized myocardial depolarization which correlates with further repolarization abnormalities that can be detected by SAECG. Method: In this retrospective study, results of SAECG were used to classify 73 HCM patients into Normal or Abnormal groups based on the presence of two or more of three predetermined criteria (fQRS, RMS40, LAS40). Replacement fibrosis was assessed by measuring late gadolinium enhancement (LGE) . Interstitial fibrosis was assessed by measuring T1 relaxation times, using the Look-Locker sequence. Results: A statistically significant association between the presence of myocardial fibrosis on CMR and abnormal SAECG was found with a difference of proportions of 41.3% between the subgroups. Left ventricular mass index was found to be significantly higher in the abnormal subgroup (Normal: 61.2 ± 19.6; Abnormal: 82.4 ± 37.1; p = &lt;0.003, CI 95% [2.93; 39.47]). The presence of T wave inversions on standard ECG was only seen in those who had an abnormal SAECG exam. Conclusion: Abnormal SAECG in patients with HCM is associated with the presence of LGE on CMR. This study showed a subset of patients with absence of LGE despite having abnormal SAECG, which implies that there are other complex mechanisms besides replacement fibrosis, that predisposes this population to ventricular arrhythmias. This can also be highlighted by the fact that there was no difference between the two groups in the T1 mapping time. We believe that SAECG could be an objective assessment of the arrhythmogenic substrate present in patients with HCM.
Abstract 15552: Learning and Innovation Among Interventional Cardiologists, Insights From an International Survey
Authors: Evangelia Vemmou, Ilias Nikolakopoulos, Bavana V Rangan, Iosif Xenogiannis, Judit Karacsonyi, M Nicholas Burke, Kevin J Croce, Brian A Bergmark, Emmanouil S Brilakis
Journal: Circulation (2020)

Introduction: The willingness of interventional cardiologists to adopt innovation and implement changes in day-to-day practice has received limited study. Methods: Online-based survey on learning and innovation involving 38 questions distributed via email list to interventional cardiologists. Results: The survey was distributed to 8,110 e-mails and completed by 621 (7.6% , 92% men, 60% in the 35 to 54-year-old age group). Of the respondents who perform coronary interventions, 45% perform &gt;100 cases of non-complex percutaneous coronary interventions per year and of the respondents who perform structural interventions, 15% perform more than &gt;100 transcatheter aortic valve replacements per year. Most respondents (86%) are highly likely/likely to introduce recently approved equipment in everyday practice and 48% have tried a new coronary guidewire in the past six months ( Figure ). Regarding specific techniques, most (69%) use the double kissing crush technique when treating coronary bifurcations with a 2-stent strategy, followed by T -stenting (60%). Radial access in STEMI cases is always used by 43% of the respondents and 54% always use radial access for coronary angiography. Of those who use femoral access, 32% always use ultrasound guidance and 91% have used a closure device in the last six months. The majority read journals to keep up with current practice and believe that the most effective way to learn is through attendance of workshops/short courses (79%), followed by proctorship (61%). Most of the respondents (69%) are involved in research. Conclusions: Interventional cardiologists who participated in the survey are highly likely to adopt innovation in daily clinical practice.