tbuckley/cabot-search huggingface dataset:
Abstract 17162: Prediction of Functional Severity of Coronary Bifurcation Lesions by Means of Angiographically-Derived Score
Authors: Dobirn Vassilev, Niya Mileva, Pavel Nikolov, Georgi Dimitrov, Kiril Karamfiloff, Carlos Collet, Gianluca Rigatelli, Robert Gil, Patrick W Serruys
Journal: Circulation (2020)

Background: There is uncertainty about relation between clinical and angiographic characteristics and functional significance of bifurcation stenosis. Methods: We analysed patients from FIESTA registry (ClinicalTrials.gov:NCT01724957). Subjects (&gt;18 years) with stable angina, bifurcation lesions with diameter ≥2.5mm and ≤4.5 mm, SB diameter≥2.0 mm were included. We excluded patients with ST-segment elevation myocardial infarction, left main disease, hemodynamic instability. Provisional stenting was the default strategy in all patients. Fractional flow reserve(FFR) was performed using the PrimeWire or PrimeWire Prestige(Volcano Corp., USA). Bifurcation lesion with FFR above 0.80 were deferred from PCI. Results: A total of 171 patients, mean age 67±10 years, 66% males were included in the analysis. Of them 78(46%) had functionally significant bifurcation lesion (FSL) versus 93(54%) with non-significant lesion (nFSL). There were no differences (FSLvs.nFSL) in baseline characteristics: dyslipidemia(88%vs96%), diabetes(44%vs.32%), smoking (52%vs40%), past MI (24%vs15%), previous PCI(54%vs49%), atrial fibrillation (17%vs29%), peripheral artery disease (10%vs9%), renal failure(29%vs31%) –all p&gt;0.05. On logistic-regression analysis independent predictors of functional significance were: SYNTAX score≥11 (OR=5.523,CI:1.666-18.311,p=.005), lesion length≥25mm (OR=21.737,CI:4.963-95.202,p&lt;.001),MV%DS≥55%(OR=9.535,CI:2.508-34.883,p=.001) and MB%DS≥65% (OR=12.927,CI:3.015-55.418,p=.001). We created score for prediction of functional significance of bifurcation lesion with the following parameters: SYNTAX ≥11 gives 1 point, SB BARI≥12%- 1 point, MV%DS ≥55%- 1.5 point, MB%DS≥65%- 2 points, lesion length ≥25 mm – 3 points. The overall performance of the score was excellent with AUC=.960, p&lt;.001. With a cut-off value ≥4.5 points it has sensitivity of 90%, specificity 91%, accuracy 90%, p&lt;.001. Conclusion: Different degree of stenosis in proximal main vessel and distal side branch, lesion length, SB myocardium territory and SYNTAX score are significant predictors of functional severity of bifurcation lesion. A score based on those parameters was developed with excellent discriminatory ability.
Transcriptomic analysis of CFTR-impaired endothelial cells reveals a pro-inflammatory phenotype
Authors: Mathias Declercq, Pauline de Zeeuw, Nadine V. Conchinha, Vincent Geldhof, Anabela S. Ramalho, Melissa García-Caballero, Katleen Brepoels, Marjolein Ensinck, Marianne S. Carlon, Matthew J. Bird, Stefan Vinckier, Marijke Proesmans, François Vermeulen, Lieven Dupont, Bart Ghesquière, Mieke Dewerchin, Peter Carmeliet, David Cassiman, Lucas Treps, Guy Eelen, Peter Witters
Journal: European Respiratory Journal (2020)

Cystic fibrosis (CF) is a life-threatening disorder characterised by decreased pulmonary mucociliary and pathogen clearance, and an exaggerated inflammatory response leading to progressive lung damage. CF is caused by bi-allelic pathogenic variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel. CFTR is expressed in endothelial cells (ECs) and EC dysfunction has been reported in CF patients, but a role for this ion channel in ECs regarding CF disease progression is poorly described.We used an unbiased RNA sequencing approach in complementary models of CFTR silencing and blockade (by the CFTR inhibitor CFTRinh-172) in human ECs to characterise the changes upon CFTR impairment. Key findings were further validated in vitro and in vivo in CFTR-knockout mice and ex vivo in CF patient-derived ECs.Both models of CFTR impairment revealed that EC proliferation, migration and autophagy were downregulated. Remarkably though, defective CFTR function led to EC activation and a persisting pro-inflammatory state of the endothelium with increased leukocyte adhesion. Further validation in CFTR-knockout mice revealed enhanced leukocyte extravasation in lung and liver parenchyma associated with increased levels of EC activation markers. In addition, CF patient-derived ECs displayed increased EC activation markers and leukocyte adhesion, which was partially rescued by the CFTR modulators VX-770 and VX-809.Our integrated analysis thus suggests that ECs are no innocent bystanders in CF pathology, but rather may contribute to the exaggerated inflammatory phenotype, raising the question of whether normalisation of vascular inflammation might be a novel therapeutic strategy to ameliorate the disease severity of CF.
Abstract 14945: Prognostic Value of Cardiac <sup>123</sup> I-MIBG Imaging for Predicting Cardiac Events After Transcatheter Aortic Valve Replacement
Authors: Yoshito Kadoya, Kan Zen, Nagara Tamaki, Masaki Yashige, Kazuaki Takamatsu, Nobuyasu Ito, Kensuke Kuwabara, Michiyo Yamano, Takeshi Nakamura, Hitoshi Yaku, Satoaki MATOBA
Journal: Circulation (2020)

Introduction: In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported; however, the prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123 I-metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR. Hypothesis: We hypothesized that the improvement in MIBG parameter with TAVR treatment can be an indicator of better prognosis. Methods: This single-center prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and after TAVR to evaluate the delayed heart-mediastinum ratio (d-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR d-H/M (≥2.0 or &lt;2.0) and on the presence of TAVR-related improvement in d-H/M (i.e. Δ d-H/M [post-TAVR – baseline] &gt;0 or ≤0). The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and hospitalization due to heart failure. Results: Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with d-H/M improvement and/or high post-TAVR d-H/M (≥2.0). Baseline d-H/M and frailty were associated with poor response of d-H/M to TAVR treatment. Moreover, post-TAVR d-H/M had significant effects on MACE, with an adjusted hazard ratio of 1.264 (95% confidence interval, 0.034-2.480; p=0.04). Conclusions: Both d-H/M improvement and high post-TAVR d-H/M were associated with better prognosis in patients who underwent TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR.
Abstract 14915: Incidence, Predictors and Clinical Impact of Left Ventricular Functional Recovery Following Coronary Artery Bypass Grafting in Patients With Ischemic Cardiomyopathy
Authors: Masaro Nakae, Satoshi Kainuma, Koichi Toda, Shigeru Miyagawa, Daisuke Yoshioka, Takuji Kawamura, Ai Kawamura, Noriyuki Kashiyama, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2020)

Introduction: CABG is considered the standard treatment for patients with ischemic cardiomyopathy (ICM). However, it remains unknown who would achieve postoperative LV function recovery after CABG. Furthermore, the relationship of postoperative LV function recovery with long-term outcomes remains unclear. Hypothesis: In patients with ICM who undergo CABG, postoperative LV function recovery, which would be influenced by degree of LV remodeling at baseline, is associated with improved outcomes. Methods: This multicenter retrospective study comprised 490 cases with LVEF of ≤40% who underwent CABG between 1993 and 2015. Clinical follow-up was completed in 467 cases (95%), with a mean follow-up of 65±46 months (range, 0-266). A total of postoperative echocardiographic assessments were carried with an average number of 3.7±2.4. LV function recovery was defined as LVEF ≥35% at more than one exam. Association of LV function recovery with mortality after adjustments for clinically relevant covariates was estimated using Cox proportional hazard model. Pre- and intraoperative associates of LV function recovery were identified using logistic regression model. Results: During follow-up, there were 203 mortalities (41%) and overall 10-year survival was 45%. LV function recovery was found in 368 cases (75%), while not in 122 (25%). Overall 10-year survival was significantly higher in patients who achieved LV function recovery as compared with those who did not achieve it (52% vs. 23%). Multivariate analysis identified LV function recovery was independently associated with decreased overall mortality (adjusted HR 0.40, p&lt;0.0001). Preoperative LVDs (adjusted OR 0.92, p&lt;0.0001), eGFR (adjusted OR 1.12, p=0.016) and revascularization using bilateral internal thoracic arteries (BITA) (adjusted OR 2.81, p=0.018) are the independent predictors of LV function recovery. Conclusions: Among patients with ICM who underwent CABG, 75% achieved substantial postoperative LV function recovery, in association with better long-term survival, as compared with the remaining 25% of patients who did not achieve it. Preoperative less LV remodeling and preserved renal function as well as revascularization with use of BITA might be associated with LV function recovery.
Abstract 13918: Prognostic Value of Plasma Ngal in the 12-month All-cause Mortality of Acute Heart Failure or Acute Decompensated Heart Failure
Authors: Hao T Phan
Journal: Circulation (2020)

Introduction: The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Renal dysfunction is common in patients with AHF or ADHF and is associated with significant early and late morbidity and mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in AHF or ADHF patients, its significance remains poorly understood. This study was aimed to evaluate the 12 month prognostic value of plasma NGAL in AHF or ADHF patients Hypothesis: plasma NGAL has value in prognosis of 12-month all-cause mortality of Acute Heart Failure or Acute Decompensated Heart Failure Methods: This was a prospective cohort study Results: there were 46 all-cause mortality cases (rate 33.1%) 12 months follow up after discharge. There were 11 cases (rate 7.9%) lost to follow-up; mean age 66.12 ± 15.77, men accounted for 50.4%. The optimal cut-off of NGAL for 12-month all-cause mortality prognosis was &gt; 383.74 ng/ml, AUC 0.632 (95% CI 0.53-0.74, p = 0.011), sensitivity 58.7 %, specificity 68.29 %, positive predictive value 50.9%, negative predictive value 74.7%. Kaplan-Meier analysis revealed that the high plasma NGAL (≥ 400 ng/ml) group exhibited a worse prognosis than the low plasma NGAL (&lt; 400 ng/ml) group in 12-month all-cause death (Hazard Ratio 2.56; 95%CI 1.35-4.84, P=0.0039. Independent predictors of 12-month all-cause-mortality were identified using multivarable Cox proportional-hazards regression models with backward-stepwise selection method consisted of two variables: level of NGAL, mechanical ventialtion at admission. Conclusions: Plasma NGAL and mechanical ventilation at admission were independent predictors of 12-month all-cause mortality in patients with AHF or ADHF. The survival probability 12-month follow-up of high level NGAL (≥ 400 ng/ml) groups were lower than that of low level NGAL (&lt;400 ng/ml,), difference was statistically significant χ2 = 8.31; p = 0.0047 by Kaplan-Meier curves.
Abstract 9889: Cardiomyocytes Differentiated From Ccnd2 Overexpressing Human Induced Pluripotent Stem Cells Remuscularize the Myocardial Scar in Mice a 6 Month Study
Authors: Chengming Fan, Vladimir G. Fast, Yawen Tang, Meng Zhao, James F. Turner, Wuqiang Zhu, Jianyi Zhang
Journal: Circulation (2019)

Introduction: Cardiomyocytes that have been differentiated from CCND2-overexpressing human induced-pluripotent stem cells (hiPSC-CCND2OE CMs) can proliferate when transplanted into mouse hearts aft...
Abstract 14268: Responses to Exercise During Right Heart Catheterisation in Pulmonary Hypertension
Authors: Stephanie Wiltshire, Katherine Kearney, Karen Brown, Carolyn Corrigan, Annette Pidoux, Erik Koppe, Edmund Lau, Kavitha Muthiah, Christopher S Hayward, Eugene Kotlyar, Anne Keogh
Journal: Circulation (2020)

Background: Hemodynamic changes during exercise at right heart catheterisation (RHC) may be a diagnostic and prognostic tool in pulmonary arterial hypertension (PAH). Method and Results: We retrospectively assessed the hemodynamic response to exercise during RHC of 138 patients with PAH secondary to idiopathic PAH (IPAH), connective tissue disease (CTD) or congenital heart disease (CHD). RHCs were performed at a single centre between 2007 and 2018. A submaximal comfort-based protocol on a reclined bicycle or straight leg raise test (SLRT) was employed. IPAH demonstrated the highest mean pulmonary artery pressure (mPAP) at rest, rising 47% with exercise, but a 66% rise in CO allowed pulmonary vascular resistance (PVR) to fall. Those with CTD demonstrated a 56% rise in mPAP, 70% rise in CO and PVR remained unchanged. In CHD, there was a 46% rise in mPAP, 49% rise in CO and a rise in PVR. Notably, there was a rise in pulmonary artery wedge pressure (PAWP) in all groups, most marked in those with IPAH. Total peripheral resistance (TPR), pulmonary artery compliance (PAC) and pulmonary artery elastance (Ea) changes were variable. TPR marginally decreased in IPAH patients, remained unchanged in those with CTD and increased in CHD. PAC decreased in all groups, with the lowest values observed in those with IPAH. Ea increased in all groups but was most notably higher in those with IPAH. Right ventricular stroke work index (RVSWI) increased in all patients, the lowest values before and after exercise were observed in the CTD cohort. Mean pulmonary artery pulsatility index (PaPi) increased in all groups, although was subtle and didn’t meet statistical significance for those with CTD and CHD. Conclusions: The hemodynamic response to exercise in patients with PAH differs between aetiologies. A rise in PAWP occurred in all groups, with ventricular interdependence a possible explanation. Whether there is a relationship between exercise hemodynamic changes and prognosis remains undetermined.
Development and Validation of Machine Learning–Based Race-Specific Models to Predict 10-Year Risk of Heart Failure: A Multicohort Analysis
Authors: Matthew W. Segar, Byron C. Jaeger, Kershaw V. Patel, Vijay Nambi, Chiadi E. Ndumele, Adolfo Correa, Javed Butler, Alvin Chandra, Colby Ayers, Shreya Rao, Alana A. Lewis, Laura M. Raffield, Carlos J. Rodriguez, Erin D. Michos, Christie M. Ballantyne, Michael E. Hall, Robert J. Mentz, James A. de Lemos, Ambarish Pandey
Journal: Circulation (2021)

Heart failure (HF) risk and the underlying risk factors vary by race. Traditional models for HF risk prediction treat race as a covariate in risk prediction and do not account for significant parameters such as cardiac biomarkers. Machine learning (ML) may offer advantages over traditional modeling techniques to develop race-specific HF risk prediction models and to elucidate important contributors of HF development across races.
Abstract 15057: Electromechanical Discoordination is Present in Patients With Duchenne Muscular Dystrophy Independent of Tissue Fibrosis
Authors: Alex Hoffner Heinike, Michal Schafer, Benjamin Frank, Dunbar D IVY, Alex Barker, Lorna Browne, Michael Di Maria, Brian Fonseca, Shelley D Miyamoto, Scott R Auerbach
Journal: Circulation (2020)

Introduction: Progressive ventricular dysfunction is a cardinal symptom in Duchenne Muscular Dystrophy (DMD). Some of the earliest signs of cardiomyopathy in DMD are myocardial fibrotic deposition and LV strain defects. Electromechanical discoordination, as measured by Systolic Stretch Fraction (SSF) and Diastolic Relaxation Fraction (DRF), has been shown to be a sensitive marker of ventricular dysfunction. The presence of this discoordination in relation to fibrotic deposition in DMD has yet to be elucidated. Hypothesis: Patients with DMD will have abnormal SSF and DRF on cardiac MRI (CMR) tissue tracking analysis and associated with fibrotic deposition. Methods: Patients with DMD (n=31)(mean age: 14 ± 4 yrs) and controls (n=20) (mean age: 15 ± 3 yrs) underwent CMR for volumetric and functional analysis as well as Gadolinium (Gd) enhancement to evaluate the presence of fibrosis. Circumferential strain and strain rate indices from each segment were used to calculate electromechanical discoordination. Strain rate data was used to calculate SSF and DRF. Results: Patients with DMD showed increased median LV SSF compared to controls [0.027 (IQR: 0.015-0.041) vs 0.007 (IQR:0.005-0.013), P = 0.002] as well as increased median LV DRF [0.371 (IQR: 0.310-0.473) vs 0.300 (IQR: 0.264-0.325), P &lt; 0.001] (Figure). When comparing Gd(+) (n=14) vs Gd(-) (n=17) DMD patients, there was no difference between groups in either SSF [0.027 (IQR: 0.016-0.042) vs 0.026 (IQR: 0.008-0.040), P= 0.929] or DRF [0.371 (IQR: 0.309-0.537) vs 0.379 (IQR: 0.322-0.464), P= 0.931]. The SSF was associated with ESVi (R=0.71, P&lt;0.001), EDVi (R=0.65, P&lt; 0.001) and inversely associated with EF (R=-0.63, P&lt;0.001). Conclusion: Patients with DMD showed increased levels of LV electromechanical discoordination independent of qualitative presence of fibrosis noted by Gd enhancement. This allows speculation that changes in electromechanical discoordination may precede visible fibrotic change in DMD.
Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions
Authors: Michael L. Cheng, Eirini Pectasides, Glenn J. Hanna, Heather A. Parsons, Atish D. Choudhury, Geoffrey R. Oxnard
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract The application of genomic profiling assays using plasma circulating tumor DNA (ctDNA) is rapidly evolving in the management of patients with advanced solid tumors. Diverse plasma ctDNA technologies in both commercial and academic laboratories are in routine or emerging use. The increasing integration of such testing to inform treatment decision making by oncology clinicians has complexities and challenges but holds significant potential to substantially improve patient outcomes. In this review, the authors discuss the current role of plasma ctDNA assays in oncology care and provide an overview of ongoing research that may inform real‐world clinical applications in the near future.
Virological surveillance of influenza viruses in the WHO European Region in 2019/20 – impact of the COVID-19 pandemic
Authors: Angeliki Melidou, Dmitriy Pereyaslov, Olav Hungnes, Katarina Prosenc, Erik Alm, Cornelia Adlhoch, James Fielding, Miriam Sneiderman, Oksana Martinuka, Lucia Pastore Celentano, Richard Pebody
Journal: Eurosurveillance (2020)

The COVID-19 pandemic negatively impacted the 2019/20 WHO European Region influenza surveillance. Compared with previous 4-year averages, antigenic and genetic characterisations decreased by 17% (3,140 vs 2,601) and 24% (4,474 vs 3,403). Of subtyped influenza A viruses, 56% (26,477/47,357) were A(H1)pdm09, 44% (20,880/47,357) A(H3). Of characterised B viruses, 98% (4,585/4,679) were B/Victoria. Considerable numbers of viruses antigenically differed from northern hemisphere vaccine components. In 2020/21, maintaining influenza virological surveillance, while supporting SARS-CoV-2 surveillance is crucial.
Abstract 14993: Dysfunctional Extracellular Microvesicles in Andean Highlanders With Excessive Erythrocytosis
Authors: Madden Brewster, Anthony R Bain, Vinicius P Garcia, Hannah K Fandl, Rachel Stone, Noah M DeSouza, Jared J Greiner, Michael M Tymko, Francisco C Villafuerte, Philip N Ainslie
Journal: Circulation (2020)

Background: Chronic mountain sickness, a maladaptation to high altitude (&gt;2,500 m) characterized by excessive erythrocytosis (EE) and often severe hypoxemia, is prevalent in Andean highlanders. EE increases the risk of cardiovascular events and contributes to vascular dysfunction. Circulating extracellular microvesicles (MVs) are key mediators of cardiovascular health and disease through their interaction with the vascular endothelium. The experimental aim of this study was to determine the effects of MVs isolated from adults with EE on endothelial cell inflammation, oxidative stress, apoptosis and nitric oxide (NO) production. Methods: Twenty-six male residents of Cerro de Pasco, Peru (4,340 m) were studied: 12 highlanders without EE (healthy; age: 40±4 yr; BMI: 26.4±1.7; Hb: 17.4±0.5 g/dL, SpO 2 : 86.9±1.0%) and 14 highlanders with EE (EE: 43±4 yr; 26.2±0.9; 24.4±0.4 g/dL; 79.7±1.6%). MVs were isolated from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with MVs from either healthy or EE men. Results: MVs from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8±2.7 vs 77.1±1.9 pg/mL) and IL-8 (62.0±2.7 vs 53.3±2.2 pg/mL) compared with MVs from healthy highlanders. Although intracellular expression of total NF-κB p65 (65.3±6.0 vs 74.9±7.8.9 AU) was not significantly affected, MVs from EE men resulted in ~25% higher (P&lt;0.05) expression of p-NF-κB p65 (Ser536; active NF-κB) (173.6±14.3 vs 132.8±12.2 AU). Additionally, cell expression of the anti-inflammatory miR-146a and miR-181b were significantly suppressed by EE MVs. Cell oxidative stress and apoptotic susceptibility were not significantly affected by MVs from EE men. However, eNOS activation (231.3±15.5 vs 286.6±23.0 AU) and NO production (8.3±0.6 vs 10.7±0.7 μM/L) were significantly lower in cells treated with MVs from EE vs healthy men. Conclusion: Increased inflammation and decreased eNOS activity and NO production renders the vascular endothelium highly susceptible to atherosclerosis and thrombosis. Andean highlanders with EE exhibit dysfunctional circulating extracellular MVs that induce a proatherogenic endothelial phenotype contributing to their increased cardiovascular risk.