tbuckley/cabot-search huggingface dataset:
Abstract 18278: The Prognostic Value Of WFDC2, a New Biomarker for Heart Failure
Authors: Rudolf A de Boer, Qi Cao, Douwe Postmus, Kevin Damman, Adriaan A Voors, Tiny Jaarsma, Dirk J van Veldhuisen, Hans L Hillege, Herman H Silljé
Journal: Circulation (2012)

Aim s: Identification of plasma biomarkers that help to stratify heart failure (HF) patients may help to improve treatment. We investigated the prognostic value of WAP four-disulfide core domain protein 2 (WFDC2, also termed HE4), a biomarker not previously described in HF. Methods: Data of 567 patients participating in the Coordinating study evaluating outcomes of Advising and Counselling in Heart failure (COACH) study were analysed. Patients had been hospitalized for HF and were followed for 18 months. Several plasma biomarker levels were determined using an ELISA platform. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization. Results: Mean age was 71±11 years, 62% were males, mean LVEF was 33±14%, and mean eGFR was 54±20 mL/minute. WFDC2 was identified as a biomarker that showed strong correlation with HF severity, according to NYHA functional class and BNP levels ( P &lt; 0.001). WFDC2 also showed a strong positive correlation with GDF15 ( P &lt;0.001). In addition, WFDC2 levels correlated with kidney function (BUN, creatinine, and eGFR; all P &lt;0.001). Cox regression analysis revealed that a doubling of WFDC2 levels was associated with a hazard ratio (HR) of 1.73 (1.53-1.95) for the primary outcome ( P &lt;0.001). After correction for age, gender, BNP and eGFR the HR was 1.46 (1.23-1.72) ( P &lt;0.001) and after additional adjustment for GDF15 the HR lowered to 1.30 (1.07-1.59) ( P =0.009). The AUC in the ROC curve analysis increased from 0.7123 to 0.7375 when WFDC2 was included to the clinical model ( P =0.068). The IDI and NRI metrics for reclassification showed highly significant improvements when WFDC2 was added to the clinical model (NRI=0.12, P &lt;0.001) and this remained significant after inclusion of BNP to this model. Conclusion: WFDC2 plasma levels are correlated with markers of HF severity, show prognostic value, and improve risk assessment in HF.
Abstract 18267: Coronary Risk Factors and Prevalence and Severity of Coronary Atherosclerosis in the Young
Authors: Yuka Otaki, Heidi Gransar, Damini Dey, Fay Lin, Victor Cheng, Stephan Achenbach, Mouaz Al-Mallah, Budoff Matthew, Filippo Cademartiri, Tracy Q Callister, Hyuk-Jae Chang, Kavitha Chinnaiyan, Benjamin Chow, Augustin Delago, Martin Hadamitzky, Joerg Hauesleiter, Philippo Kaufmann, Erica Maeffei, LesLee Shaw, Daniel Berman, Gurdun Feuchtner, Allison Dunning, Todd Villines, James K Min
Journal: Circulation (2012)

Purpose. We examined the relationship between coronary risk factors (RF) and prevalence and severity of coronary atherosclerosis in young individuals undergoing coronary CT angiography (CCTA). Methods. Of 27125 patients undergoing CCTA, 1635 young (50%stenosis), and presences of calcified plaque (CP) and non-calcified plaque (NCP). Results. Among 1635 subjects (70% men, age 38±6 years), 6% had diabetes (DM), 31% had hypertension (HTN), 37% had dyslipidemia (CHOL), 21% had smoking (SM) and 33% had family history (FH) of CAD. Among all young individuals, any CAD, obs CAD, CP and NCP were observed in 19%, 4%, 5%, and 8%, respectively. Compared to women, men demonstrated higher rates of any CAD (21% vs 12% P&lt;0.001), CP (6% vs 3% P=0.01), and NCP (9% vs 5% P=0.008), although no difference was observed for rates of obs CAD (5% vs. 4% P=NS). Any CAD, obs CAD, and NCP were higher for young individuals with DM, HTN, CHOL, SM or FH of CAD; while only DM and CHOL were associated with CP (Table). In multivariable analysis adjusting for sex and RFs, male sex was the strongest predictor for any CAD (Odds Ratio [OR] 1.95, 95% Confidence Interval [CI] 1.43-2.66, P&lt;0.001), CP (OR 1.46, 95%CI 1.08-1.98, P=0.014) and NCP (OR 1.33, 95%CI 1.06-1.67, P=0.014); while FH of CAD was the strongest predictor for obs CAD (OR 2.71, 95% CI 1.65-4.45, P3 RFs manifesting a significant increase in any CAD (P&lt;0.001 for trend); obs CAD (P&lt;0.001 for trend); NCP (P&lt;0.001 for trend) and CP (P=0.008 for trend). Conclusions. CAD is present in 1 in 5 young individuals, with sex and coronary RFs associated with increasing presence and severity of CAD.
Abstract 18254: Provisional Side Branch Stenting for 1.1.1 Distal Left Main Percutaneous Coronary Intervention
Authors: Jérome van Rothem, Thierry Lefevre, Philippe Garot, Didier Carrié, Marie-Claude Morice, Yves Louvard
Journal: Circulation (2012)

Objective: To evaluate the impact of bifurcation characteristics on long-term clinical outcome after distal left main (LM) percutaneous coronary intervention (PCI) with a provisional side-branch (SB) stenting strategy. Background: Provisional SB stenting provides good results for patients with distal LM undergoing PCI. It is the preferred strategy in cases where a single ostium is involved (LAD or LCX). This strategy has never been specifically evaluated in more complex lesions involving the two side branches (medina 1.1.1). Methods: Individual data of patients with distal LM lesions included in the French Taxus, Friend, Lemax and large centers registries and treated with a provisional SB stenting strategy were analysed. Results: A total of 454 patients were included, 199 (43.8%) with a 1.1.1 bifurcation and 255 patients (56.2%) with any other type of bifurcation. Patients with a medina 1.1.1 had a higher Syntax score (28±10.2 vs. 21.9±8.7; p&lt;0.0001) and were treated with a higher rate of SB stenting (45.7% vs. 14.5%; p&lt;0.0001) compared to other lesion types. At multivariate logistic regression analysis, after adjustment for patient and procedure confounders, a medina class 1.1.1 emerged as a predictor of 36 months’ MACE (odd ratio: 2.332, 95% confidence interval 1.416 to 3.3841; p=0.001) and death (odd ratio: 3,689, 95% confidence interval 1.658 to 8.205). Conclusion: In this observational study, patients with Medina 1.1.1 LM lesions have worse baseline characteristics and clinical outcome compared to other lesion types. Even after adjustment for data confounders Medina 1.1.1 remained associated with a worse outcome suggesting that Medina 1.1.1 is by itself a risk factor.
Abstract 18243: Transplantation of Mesenchymal Cells Rejuvenated by Delivery of Telomerase and Myocardin Genes Promotes Revascularization and Tissue Repair in Ischemic Hindlimbs of Apolipoprotein-e-null Mice
Authors: Rosalinda Madonna, Shanshan Gao, Song Gao, Harnath S Shelat, Raffaele De Caterina, James T Willerson, Yong-Jian Geng
Journal: Circulation (2012)

Background and Objective: In adult bone marrow and other tissues the number and function of stem cells decline with aging. Myocardin (MyC) and telomerase (TeM), two nuclear proteins, may synergize to prevent senescence and to promote cardiovascular myogenesis. This study analyzed the impact of enhanced expression of MyC and TeM on survival, growth, and differentiation of mesenchymal stem cells (MSC) from old bone marrow and adipose tissues, as well as the therapeutic efficacy of transplantation of TeM + /McC + MSCs in murine hindlimbs with ischemic injury. Methods and Results: MSCs from adipose or bone marrow tissues of young (one month) and old (12 months old) male C57BL/6J and apolipoprotein E deficient (ApoE −/− ) mice were efficiently transduced or co-transduced with the 3 rd generation lentiviral vectors carrying the cDNAs coding for TeM-YFP (yellow fluorescence protein) or MyC-V5 epitope fusion proteins. Transduction with TeM, and to a less extent, MyC, but not empty vectors (mock), elevated MSC viability and BrdU uptake (p&lt;0.05 vs mock controls, at flow cytometry). Colony formation increased in the transduced cells, while apoptosis in response to Fas stimulation was inhibited (Table). Endogenous MyC, cardiac and smooth muscle α-actin occurred in the cells with MyC/TeM cDNA delivery (at immunoblotting). Doppler ultrasound imaging and immunohistochemistry showed marked improvement of blood flow (Figure A, B) and arteriogenesis (Figure C) in the ischemic hindlimbs of ApoE −/− mice transplanted with the TeM + /MyC + transduced MSCs. Conclusions: The simultaneous delivery of the TeM and MyC genes resuscitates MSCs from old adipose and bone marrow tissues by increasing their capacity of survival, proliferation, and differentiation. TeM + /MyC + MSCs possess the potential of repairing ischemic tissues and, when transplanted into the ischemic hindlimb, improve revascularization.
Abstract 18393: Survival after Post-Arrest Therapeutic Hypothermia: Secondary Analysis of The Strategies for Post-Arrest Care (SPARC) Stepped-Wedge Trial
Authors: Laurie J Morrison, Paul Dorian, Katie N Dainty, Steven C Brooks, Kevin Thorpe, Cathy Zhan, Damon C Scales
Journal: Circulation (2011)

Introduction: Current guidelines recommend early institution of therapeutic hypothermia (TH) in survivors of out of hospital cardiac arrest (OHCA) regardless of initial rhythm. This was based on trials employing concurrent or historical controls since the original randomized trials restricted the analysis to OHCA presenting with ventricular fibrillation (VF) or ventricular tachycardia (VT). We sought to measure the survival of patients after application of these recommended guidelines during a stepped-wedge randomized trial that compared KT strategies to improve TH in a network of 36 hospitals. Methods: After a baseline period of 12 months, 4 wedges of 8 to 10 hospitals were randomized to receive 12 months of passive KT followed by 4 months of active KT. We measured the secondary outcome of survival to hospital discharge in patients that had received therapeutic hypothermia. We used multilevel modeling to calculate odds ratios (OR) for survival after adjusting for time and the Utstein factors. Results: During the study, 4,742 OHCA patients were transported to hospital; 1,963 (39%) achieved ROSC and 1,104 (56%) of these were eligible for TH. 638 (58%) of the eligible patients had cooling initiated and 223 (35%) were cooled to 34 degrees within 6 hours. No survival advantage of cooling was observed for all eligible patients (cooling ever vs never, OR adjusted for time only 1.04, 95% CI 0.74-1.47; OR adjusted for prehospital variables (Utstein) 0.80, 95% CI 0.53-1.20). Similar findings were observed when the analyses were restricted to the 516 eligible patients that presented with VF/VT (OR adjusted for time only 0.74, 95% CI 0.44-1.24; OR adjusted for Utstein variables 0.84, 95% CI 0.52-1.37). Conclusions: During a stepped wedge knowledge translation randomized trial, we were unable to confirm the survival advantage associated with cooling after OHCA.
Abstract 188: Arterial Oxygen Saturation May Be the Limiting Factor for O <sub>2</sub> Delivery During Compression-Only CPR
Authors: Qian Li, Hovig Chitilian, Yanhong Liu, Robert M Kacmarek, Yandong Jiang
Journal: Circulation (2011)

Background Previous studies show that there is no difference in outcomes between bystander conventional and chest-compression-only (CCO) CPR. However, several points need to be addressed: 1) the equivalent, but low, survival rate indicates that there is much room for improvement. The question is whether effective ventilation can be achieved during CPR regardless of approach. 2) the subgroup of patients whose cardiac arrest was not of cardiac origin did not sustain any benefit from ventilation. This finding would imply that adequate ventilation was not achieved. Because cardiac output (CO) generated by chest-compression is low, O 2 delivery (DO 2 ) is mainly dependent on arterial O 2 content. We hypothesize that DO 2 is the rate limiting factor and improvement in DO 2 is mainly determined by O 2 content of arterial blood, since CO is at best only 1/3 of the normal value. Methods We modeled DO 2 in a range of 0 to critical DO 2 (8.2 ml/kg/min) at variable CO and O 2 contents of arterial blood. We assumed a 70kg patient with a hemoglobin level (Hb) of 15g/dl. Arterial O 2 Content (ml/L) = Hb × Arterial O 2 Saturation × 1.34 ×10. DO 2 (ml/min) = Arterial O 2 Content (ml/L) × CO (L/min). Result The half-critical DO 2 at arterial blood O 2 saturation of 80% can be achieved with CO of 1.8L/min. While to achieve the same level of DO 2 at O 2 saturation 40%, require CO of 3.6 L/min. Critical O 2 delivery and half-critical DO 2 are represented with horizontal yellow and red lines respectively. The vertical mahogany and blue lines represent the CO where half-critical delivery at O 2 saturations of 80% and 40%, respectively. Conclusion Since the CO obtained with chest compression is at best 1/3 of the normal value; to reach half-critical O 2 delivery requires an O 2 saturation of 80%. CCO seems unlikely to produce O 2 saturation greater than 80%. Therefore, effective ventilation during CPR is essential. Further study is needed to demonstrate whether confirmed adequate ventilation improves outcome during CPR.
Abstract 18255: MicroRNA Analysis in Experimental Models of Vein Graft Neointima Formation Indentifies a Critical Role For Mir-21 in Neointima Formation
Authors: Robert A McDonald, Junxi Wu, Katie M White, Keith E Robertson, Brain C Cooley, Ruifaug Lu, Jia Hu, Simon Kennedy, Roger M Wadsworth, Sarah J George, Song Wan, Andrew H Baker
Journal: Circulation (2012)

Background: Coronary artery bypass grafting (CABG) is an established treatment to relieve the symptoms of ischemic heart disease. However premature graft failure, in saphenous veins is a major limitation. One of the principal etiological factors responsible for vein graft failure is activation and phenotypic modulation of smooth muscle cells (SMC), resulting in accelerated rates of proliferation and migration. MicroRNAs (miRNAs) are short, single stranded, non-coding RNAs that play important roles in modulating cell phenotypes through regulation of gene expression. Methods and results: In order to assess the expression levels of miR-21 in the progression of vein graft neointimal formation we quantified miR-21 levels in three well-established models of vein graft disease. These were the in vivo porcine model of interposition graft, the isogenic mouse model, as well as the ex vivo human sapehnous vein model of neointimal formation. MiR-21 levels were up-regulated approximately 7-fold in both the porcine and murine models at 7 and 28 days following grafting (n=6). In surgically prepared HSV which were subjected to culture ex vivo we found that miR-21 levels were elevated approximately 3-fold following 7 and 14 days of culture (n=6). In situ localization in the HSV demonstrated that miR-21 was expressed most intensely in the neointimal layer of HSV which also stained positive for SMC actin. Co-localization studies in murine vein grafts revealed that miR-21 was localised to areas of the graft that stained positive for proliferating cell nuclear antigen with substantial co-staining with SMC actin. We assessed the potential functional role of miR-21 in vein graft failure using miR-21 knockout mice. Analysis of neointimal lesion size in miR-21 knockout mice revealed an 81% reduction in neointimal area compared to wild type controls (p&lt; 0.0001, n=7-10/group). Conclusion: These findings demonstrate that miR-21 is up-regulated in multiple models of vein graft disease and that genetic abolition of miR-21 levels can attenuate neointimal formation in response to grafting. Therein, modulation of miR-21 expression represents a novel therapeutic opportunity in the setting of vein graft neoinitma formation.
Abstract 18571: Stroke and Outcomes in Patients with Acute Type A Aortic Dissection
Authors: Eduardo Bossone, Kevin M Harris, Toru Suzuki, Rossella Fattori, Stuart Hutchison, Marek P Ehrlich, Reed E Pyeritz, P. Gabriel Steg, Kevin Greason, Arturo Evangelista, Matthias Voehringer, Daniel G Montgomery, Eric M Isselbacher, Christoph A Nienaber, Kim A Eagle
Journal: Circulation (2012)

Background: Stroke is one of the most dreaded complications of type A acute aortic dissection (TA-AAD). However, few data exist on its incidence and association with prognosis. Methods: We evaluated 2202 TA-AAD patients [pts, mean age 61.9 ± 14.4, 1487 (67.5%) male] from the International Registry of Acute Aortic Dissection (IRAD) to determine the incidence and prognostic influence of stroke in TA-AAD. Results: Stroke was present at arrival in 132 (6.0%) TA-AAD pts. Stroke pts were older (65±12 vs. 62±15 yrs; p=.002) and more likely to have hypertension (86% vs. 71%; p=.001) or atherosclerosis (29% vs. 22%; p=.042). While chest pain at arrival was less common (70% vs. 82%; p&lt;.001), stroke pts presented more often with syncope (44% vs. 15%; p&lt;.001), shock (14% vs. 7%; p=.005) or pulse deficit (51% vs. 29%; p=&lt;.001). Arch vessels involvement was more frequent among the stroke pts (68% vs. 37%; p&lt;.001). Stroke pts were treated less frequently by surgery (74% vs. 85%; p&lt;.001). Hospital stay was significantly longer in patients presenting with stroke (median 17.9 versus 13.3 days, p&lt;0.001). Stroke patients demonstrated more frequent in-hospital complications (Table) and higher mortality (adjusted OR 1.62, 95% CI .99-2.65, p=.055) Among hospital survivors, mortality at follow-up was similar in pts with and without stroke (adjusted HR 1.15, 95% CI 0.46-2.89, p=.761). Conclusions: Stroke occurred in greater than 1 of 20 pts with TA-AAD and was associated with increased morbidity and in-hospital, but not long-term mortality. Whether aggressive early intervention will reduce morbidity and improve mortality remains to be evaluated in future studies.
Abstract 18573: Unmasking Phenotypic Micro-heterogeneities in Adult Cardiac Progenitor Cells: Clonal Analysis, Single Cell QRT-PCR, and Fate Mapping
Authors: Michela Noseda, Mutsuo Harada, Sara J McSweeney, Elisa Belian, Thomas Leja, Iain Macaulay, Farah Al-Beidh, Marta S Abreu Pavia, Richard T Lumbers, Stephanie Koenemann, Robert Sampson, Sten E Jacobsen, Michael D Schneider
Journal: Circulation (2012)

Characterization of adult cardiac progenitor cells (CPC) is incompletely resolved and their potential heterogeneity needs further investigation. Here, we assess the molecular signature, heterogeneity, and origin of adult heart-derived Lin-/Sca-1+ mouse CPCs by clonal analysis, single cell QRT-PCR and fate-mapping. Clonal growth was predicted by the side population (SP) phenotype. Cloned cardiac Lin-/Sca-1+/SP+ CPCs (cSPC) were propagated for &gt;10 months without senescence or loss of the Sca-1/SP phenotype. QRT-PCR of 43 genes in &gt;30 clones showed a consensus signature defined by stem cell-associated markers and key cardiac transcription factors, but lacking markers of pluripotency, primitive or pre-cardiac mesoderm, hematopoiesis, and cardiomyocytes. Clonal analysis revealed mutually exclusive patterns of three core factors (Gata4, Mef2c, Tbx5), masked in the mixed population. Cloned cSPCs showed cardiac (cTnI, MLC2v, sarc MyHC, sarc α-actin), endothelial (vWF) and smooth muscle (SM-MyHC) differentiation after grafting to the heart. Fresh (non-propagated) cSPCs were profiled with microarrays, compared to 3 clones at passage 40, heart, and ESCs: clones largely resembled fresh cSPCs, excepting an increase in proliferation-associated GO categories. Single cell QRT-PCR (Fluidigm) on &gt;40 single fresh cSPCs confirmed both the transcriptional signature of the clones and heterogeneous expression of core cardiac factors. Thus, cSPCs resemble an incomplete but stable form of heart-forming mesoderm. By Cre/lox fate-mapping, we traced cSPCs’ embryological origin. Cardiac SP cells are derived from pre-cardiac mesoderm (98% labelled in Mesp1-Cre/R26R-tdTomato mice) and are not “lapsed” myocytes, neural crest, or hematopoietic in origin (0.2%, 1.2%, 0.2% with Myh6-, Wnt1-, or Vav-Cre). Half are derived from cells formerly expressing Nkx2.5 or Isl1 (52%, 57%), though these are rarely detected in fresh adult single cells (&lt;2%). Thus, our analyses unmask micro-heterogeneities in adult cSPCs, which may represent different states of differentiation or lineage. Expression of key cardiogenic transcription factors in mutually exclusive patterns may represent a mechanism to maintain the stem cell pool and prevent precocious differentiation.
Abstract 18238: Transition from Vitamin-K-antagonists to New Oral Anticoagulants in Daily Care - First Results of the Prospective <i>NOAC Registry</i> (NCT 01588119)
Authors: Christina Koehler, Sebastian Werth, Vera Gelbricht, Ulrike Hänsel, Luise Tittl, Ines Beyer-Westendorf, Thomas Schreier, Jan Beyer-Westendorf
Journal: Circulation (2012)

Background: New oral anticoagulants (NOAC) have been approved in a number of countries for long-term anticoagulation in atrial fibrillation (AF) and venous thromboembolism (VTE). Currently, many patients are switched from Vitamin-K antagonists (VKA) to NOAC. We evaluated the transition process (time gap between last intake of VKA, last INR sampling and first intake of NOAC) in unselected patients from daily care. Patients and methods: A network of 115 physicians from private practice and hospitals enrol patients in the NOAC registry. Inclusion criteria are: 1) indication for NOAC anticoagulation &gt;3 month; 2) age &gt; 18 years; 3) written informed consent; 4) availability for follow-up. No Exclusion criteria apply. Patients are prospectively followed by phone visits at day 30 day and quarterly thereafter to collect efficacy and safety data. Results: Until June 6 th 2012, 683 patients were registered. Of the 266 patients switched from VKA, data on the transition process were available in 213 patients (70.0% AF, 30.0% VTE). Of these, only 104 patients (48.8%) had a recorded INR measurement at the end or within 7 days before the end of VKA treatment (mean INR 2.4 for all, 2.6 in AF and 2.1 in VTE patients; table 1). In patients with INR tests, time between last INR and start of NOAC was around 3 days (5 days in AF and 2 days in VTE patients). For all patients, time between last VKA and start NOAC was around 7 days (8 days in AF; 4 days in VTE patients). Conclusion: In unselected patients in daily care, only 50% of patients have a documented INR test before NOAC is started. Despite documented INR values in the lower therapeutic range, physicians are reluctant to start NOAC therapy immediately and allow for another 2 to 5 days before NOAC is started. However, no major vascular events or major bleedings were observed in VKA transition patients at day 30, indicating that this procedure is safe.