tbuckley/cabot-search huggingface dataset:
Abstract 18201: Branch Pulmonary Artery Flow Reversal Can be Identified by Cardiac Magnetic Resonance and is Associated with Increased Collateral Flow Burden in Patients with Superior Cavopulmonary Connections
Authors: Kevin K Whitehead, Mark A Fogel, Marc S Keller, Yoav Dori, Andrew C Glatz, Jonathan J Rome, Matthew A Harris
Journal: Circulation (2012)

Background: We have described and validated a method of measuring systemic to pulmonary arterial collateral flow (CollF) in pts with superior cavopulmonary connections (SCPC) using magnetic resonan...
Abstract 5916: Delayed Mortality in Peripartum Cardiomyopathy Indicates Need for Long-Term Follow-Up
Authors: Kranti Gollapudi, Olaf Forster, Elena Libhaber, Kemi Tibazarwa, Winnie Tshani, Karen Sliwa
Journal: Circulation (2008)

Introduction: Peripartum cardiomyopathy (PPCM) is a rare form of cardiomyopathy occurring in women between one month antepartum and five months postpartum. It has been shown to carry a substantial risk of mortality within the first six months after diagnosis but few studies have outlined prospective long-term morbidity and mortality. The aim of this study is to assess long-term clinical outcome and mortality over a two-year period. Methods: Eighty consecutive women with PPCM were enrolled at diagnosis at a single center in a prospective study over a period of two years. Patients were started on standard heart failure therapy and detailed assessments, including echocardiography, were made at six-month intervals for twenty four months in surviving cases. Results: At baseline, the mean age of this cohort was 29.7 ± 6.4 years and 30 of 80 (38%) were in their first pregnancy. Overall, 71 (89%) patients presented in NYHA functional class III–IV at baseline and mean left ventricular ejection fraction (LVEF) was 29.7% ± 8.7%. During the two-year study period, 4 patients were lost to follow-up, 9 moved to remote areas, and 8 had a subsequent pregnancy, predisposing them to additional myocardial risk. In the remaining cases, mean LVEF was 45.1 ± 11.3, 46.3 ± 13.0 and 50.4 ± 13.5 at six, twelve, and twenty four months, respectively. Within two years, 22 women had died (28%), confirming the poor prognostic implications of PPCM. However, the majority of fatal events occurred between six and twenty four months (15 of 22; 68%). At six months, 7 of 80 (9%) patients had died. During extended follow-up, a further 15 of 69 (22%) died despite apparent recovery of left ventricular function. Conclusion: First, our findings emphasize the poor prognosis of PPCM. Furthermore, the fatality rate was higher than expected over a two-year period. The delayed mortality beyond six months observed in our study suggests the need for long-term clinical follow-up in women with PPCM.
Abstract 5790: Dual Molecular Imaging for Assessment of Matrix Metalloproteinase and Apoptosis in Atherosclerotic Lesions before and after Statin Therapy
Authors: Shinichiro Fujimoto, Dagmar Hartung, D. Scott Edwards, Michael Azure, Jun Zhou, Ai Fujimoto, Satoshi Isobe, Yuji Matsumoto, Navneet Narula, Junichi Yamazaki, Artiom Petrov, Jagat Narula
Journal: Circulation (2008)

We evaluated the correlation between matrix metalloproteinase (MMP) and apoptotic activities in atherosclerosis lesions, and the impact of lipid lowering by dietary modification and statin therapy employing molecular imaging with Tc-99m broad MMP inhibitor (MPI) and indium-111 annexin A5 (AA5). Atherosclerosis was produced in 13 New Zealand White rabbits by balloon deendothelialization and hypercholesterolemic diet for 4 months; 6 unmanipulated rabbits on normal chow were used as controls. In the last month, 3 of the 13 atherosclerotic rabbits were changed to normal chow, and 4 received fluvastatin (1mg/kg) once a day. MPI and AA5 imaging were performed using micro-SPECT/micro-CT. After in vivo imaging, aortas were explanted to acquire ex vivo images and calculate percent injected dose per gram (%ID/g) uptake. Histological and immunohistochemical characterization and extent of MMP and apoptosis were evaluated in representative aortic samples. Both MPI and Annexin uptake were clearly visualized in the atherosclerotic lesions by noninvasive imaging; No uptake were observed after diet withdrawal, fluvastatin, and in normal control groups. %ID/g MPI and AA5 uptakes in the atherosclerotic lesions (0.09 ± 0.02%, 0.03 ± 0.01%) were significantly higher than the uptake in control abdominal aorta (0.014 ± 0.004%, 0.0007 ± 0.0002%; p&lt;0.0001). The quantitative uptake in fluvastatin (0.053 ± 0.013%, 0.02 ± 0.01%; p&lt;0.05) and diet withdrawal (0.047 ± 0.005%, 0.02 ± 0.004%; p&lt;0.05) groups were statistically significantly lower compared to diet uninterrupted group. There were significant direct relationship betweem MPI and AA5 uptake in all experimental group (r=0.62, p&lt;0.0001). The decrease in the tracer uptake maintained the relationship in the fluvastatin group (r=0.62, p&lt;0.0001) but became less apparent in the diet withdrawal (r=0.24, p&lt;0.05). Histopathological and immunohisto-chemical studies revealed a significant correlation of both MPI and Annexin uptake with macrophage infiltration, MMP-2, 9 expression and the extent of apoptosis. Dual imaging with MPI and AA5 showed good correlation between apoptosis and MMP expression except diet withdrawal group.
Evaluation of a gene signature to predict single agent dacetuzumab (SGN-40) activity in patients with DLBCL
Authors: R. Advani, B. Burington, X. Shi, S. de Vos, S. Ansell, A. Forero-Torres, A. Ebens, N. Whiting, D. Dornan
Journal: Journal of Clinical Oncology (2009)

11063 Background: Dacetuzumab (SGN-40) is a humanized IgG1 monoclonal antibody that binds to CD40, mediates effector cell functions, and activates downstream apoptosis signaling pathways. Dacetuzumab has shown single-agent activity in relapsed/refractory DLBCL in phase I and phase II trials, with multiple objective responses and 1/3 of patients demonstrating tumor shrinkage, defined as a decrease in tumor volume (SPD) of at least 10%. We previously reported a 14-gene signature (ASH 2008 #1593) that was strongly associated with dacetuzumab sensitivity in DLBCL cell lines. Here, we report an initial evaluation of the gene signature as a classifier of patients likely to demonstrate tumor shrinkage after dacetuzumab therapy. Methods: The original 14 microarray probes were chosen for high correlation with in vitro dacetuzumab sensitivity (IC 25 ) in 31 NHL cell line models. Matching qRT-PCR probes were developed and confirmed to correlate with the microarray probes in paired cell line samples. In this retrospective analysis, archived paraffin blocks from a 26 patient subset of the phase I and II trials, with a diagnosis of DLBCL and available tumor measurements, were assayed by qRT-PCR. Results: Overall, 42% of patients (11/26) exhibited decreased SPD of at least 10%. Of those who were marker +, 10 out of 13 (78%) had 10% or better decreases in SPD, whereas only 1 of 13 patients who were marker - demonstrated tumor shrinkage (8%). The overall accuracy for predicting tumor shrinkage was 85% (one-sided P=0.002, by permutation test). Among the 14 genes contributing to the multivariate signature, CD22 and VNN2 were the most strongly down-regulated in specimens from patients without at least a 10% decrease in SPD (P=0.14 and P=0.10, respectively), while IGF1R and CTSC were the most strongly up-regulated (P=0.05 and P=0.08, respectively). Conclusions: A 14-gene signature appears to predict tumor shrinkage in DLBCL patients receiving dacetuzumab in single-agent clinical trials (P=0.002). A larger clinical data set will be analyzed to further evaluate the correlation of this gene signature with objective clinical response rates.. [Table: see text]
Abstract 16892: Trends in the Presentation, Diagnosis and Outcomes of Acute Aortic Dissection Over 15 Years, From the International Registry of Acute Aortic Dissection (IRAD).
Authors: Linda Pape, Mazen Awais, Toru Suzuki, Santi Trimarchi, Arturo Evangelista, Truls Myrmel, Magnus Larsen, Kevin M Harris, Kevin Greason, Marco Di Eusanio, Daniel Montgomery, Kim A Eagle, Christoph A Nienaber, Eric M Isselbacher, Patrick O'Gara
Journal: Circulation (2011)

Introduction/Purpose: To examine trends in patient presentation, diagnosis and outcomes of acute aortic dissection over 15 years since the original report from the International Registry of Acute Aortic Dissection (IRAD). Methods: Patient data were collected at 28 international referral centers from 1996 up to the present. Trends were analyzed among 3275 patients divided according to date of enrollment into 6 equal groups and by Type: A (n=2110) or B (n=1165). Results: There was no change over time in the presenting complaints of severe or worst ever pain for Type A and Type B (90% and 96%, respectively), or in the incidence of chest pain ( 80% in Type A and 70% in Type B, respectively), with considerable overlap in chest vs. back pain between types. The report of pulse deficits did not change over time, present in 30% of Type A patients. Normal chest X-ray on presentation increased in Type A acute aortic dissection (AoD) from 13.7% to 31.3% over time (p-value for trend &lt;0.001). In Type B the report of normal chest X-ray increased from 19.9% to 40.9% (p-value for trend &lt;0.001). There were significant trends in initial imaging modalities for Type A: increased use of CT (from 49.4% to 71.6%, p-value for trend &lt;0.001) and decreased use of TEE (from 45.3% to 25.4%, p-value for trend &lt;0.001). For Type B, use of CT increased from 77.2% to 88.4% (p-value for trend .013). A decrease in overall mortality over time was significant for both Type A and Type B patients (see graph). Surgical mortality in Type A patients fell from 25.3% to 16.5% (p-value for trend 0 .003). Conclusions: No significant difference was seen over time in pain severity, chest pain, and presence of pulse deficits. The incidences of a normal chest X-ray, originally thought to be uncommon in dissection cases, increased over time to 30% in Type A and 40% in Type B AoD. Use of CT as the initial imaging modality increased for both Type A and Type B. Lastly, a significant decrease in overall mortality was seen for both Type A and Type B patients.
Abstract 17809: Advanced Computational Modeling for Therapeutic Decision-Making in Patients Undergoing Percutaneous Coronary Intervention: A Focus on Gastrointestinal Bleeding
Authors: Zeeshan Syed, Hitinder S Gurm
Journal: Circulation (2012)

Background: We explored the feasibility of a support vector machine (SVM) model to predict gastrointestinal (GI) bleeding in patients undergoing percutaneous coronary intervention (PCI) and to potentially guide therapeutic decision-making.  Methods: Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry data with 69 pre-procedural and angiographic variables from 68,022 PCI procedures in 2004-2007 were used to develop an SVM model to predict GI bleeding (n=786). The model was optimized for multivariate non-linear performance and tested on 42,310 PCI procedures performed in 2008-2009 (GI bleeding n=389). Model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). We further compared the observed outcomes of patients at variable predicted risks of GI bleeding, and assessed the complication rate in those treated with bivalirudin versus those treated with platelet glycoprotein IIbIIIa inhibtors.  Results: The SVM model provided high discrimination (AUROC 0.84) and improved reclassification relative to both L1-regularized (NRI 0.18, p  Conclusion: A computational model based on SVM classification can accurately help identify patients at risk for GI bleeding following PCI. Use of bivalirudin instead of platelet GP IIbIIIa inhibitors in the highest risk patients may help reduce the occurrence of this complication.
Abstract 14885: Delayed Umbilical Cord Clamping Among Infants With Congenital Heart Disease: A Randomized, Multi-Center, Controlled Trial
Authors: Carl Backes, Hong Huang, John A Bauer, Mark Galantowicz, Timothy M Hoffman
Journal: Circulation (2013)

Introduction: Immediate umbilical cord clamping (ICC) at birth is routine practice but recent studies suggest that a delay in cord clamping (DCC) may improve neonatal health status including exposu...
Abstract 9543: Targeted Deep Resequencing Identifies Coding Variants in The PEAR1 Gene That Play a Role in Platelet Aggregation in Individuals at High Risk for Coronary Artery Disease
Authors: Rasika A Mathias, Yoonhee Kim, Lisa Yanek, Nauder Faraday, Alexander F Wilson, Diane Becker, Lewis Becker
Journal: Circulation (2011)

Background: The Genetic Study of Aspirin Responsiveness (GeneSTAR) is a family-based study, designed to examine genetic determinants of platelet aggregation in African American (AA) and European American (EA) healthy subjects with a family history of CAD. Platelet aggregation is heritable, and a previous genomewide association study (GWAS) detected strong association with a common genetic variant in intron 1 of the platelet endothelial aggregation receptor1 (PEAR1) gene in AA and EA GeneSTAR subjects. To build upon these results, we exploited a sequencing approach to identify additional functional genetic variants in PEAR1 that may also play a role in platelet aggregation. Methods: 104 subjects (45% male, age = 52.34±13.27) were selected based on the hyper and hypo aggregation across three different platelet agonists (Collagen, Epinephrine, and ADP). A 0.3Mb target including PEAR1 was Sanger sequenced at deCODE Genetics. Variants were annotated for function and novelty. Single-variant tests for association (variant presence/absence vs. hyper/hypo aggregation) were performed using Fisher's Exact Test. Collapsed multi-variant tests for association were performed using the Combined Multivariate Collapsing and the Weighted Sum methods. For these tests, variants were collapsed based on: 1) minor allele frequency (MAF) and 2) predicted function. Results: 235 variants were identified, and 104 were novel. Sixteen missense variants were observed, ten of which were novel. More rare variants (MAF &lt; 5%) were noted in AAs compared to EAs (108 vs. 45). The common intronic GWAS-identified variant (rs12041331) demonstrated the most significant association signal in the AA sample (p=7.9E-5); no association was seen for additional exonic variants. However, collapsed multi-variant tests suggest that exonic variants play a more significant role in the EA sample (p = 0.01 for the collapsed coding variants compared to p = 0.05 for rs12041331). Conclusions: Genetic variants in the PEAR1 are determinants of an individual's platelet aggregation response. We confirm that a common intronic variant has the strongest association in African Americans, and show that additional exonic variants play a role in platelet aggregation, particularly in European Americans.
Abstract 15303: Role of BNP and CT Aortic Valve Calcium Score in the Assessment of Severity of Aortic Stenosis
Authors: Jhansi Ganji, Mohammad Najib, Suresh Challa, Amol Raizada, Hari Chaliki
Journal: Circulation (2011)

Introduction- Although B-type naturetic peptide (BNP) levels and aortic valve calcium scores (AVC) have been shown to determine prognosis in patients with preserved EF and aortic stenosis (AS), the...
Age-Related Differences in Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis
Authors: Susan Cheng
Journal: Circulation (2007)

Abstract 1752 Susan Cheng, Brigham and Women’s Hospital, Boston, MA; Veronica R Fernandes, David A Bluemke, Joao A Lima, Johns Hopkins University, Baltimore, MD Susan Cheng, 2007 Finalist and Presenting Author
Abstract P169: Has Implementation of the Guidelines 2005 Improved Outcome From Out-of-hospital Cardiac Arrest?
Authors: Hiroshi Kaneko, Tetsuo Hatanaka, Aki Nagase, Hiroko Noguchi, Atsuko Nagatani, Tetsuya Sakamoto, Seishiro Marukawa
Journal: Circulation (2009)

Controversy remains as to whether the 2005 CPR guidelines have improved outcome from out-of-hospital cardiac arrest. We retrospectively reviewed the cardiac arrest database of Nagoya, Japan to evaluate the effect of the new guidelines.   [Methods]  In the city of Nagoya with a population of 2.2 million, data were collected by the EMS personnel in accordance with the Utstein-style reporting guidelines. We reviewed the data from Jan. 2005 through Dec. 2008, and compared the rate of return of spontaneous circulation (ROSC) and favorable neurological outcome (CPC category 1–2) at 1 month post-arrest before and after the G2005 implementation. The whole cohort of witnessed, non-traumatic cardiac arrests was divided into two cohorts according to the initial ECG (VF/VT or PEA/asystole) and was analyzed separately.   [Results]  Of the 379 patients with VF/VT, 168 received CPR with the G2000 and 211 with the G2005. The rate of ROSC changed from 44.6 % to 68.7% with the G2005 implementation, and the rate of the favorable neurological outcome changed from 13.8 % to 22.4%. Of the 1955 patients with PEA/asystole, 879 received CPR with the G2000 and 1076 with the G2005. The rate of ROSC changed from 36.8 % to 46.3 % with the G2005 implementation, and the rate of the favorable neurological outcome changed from 2.4 % to 1.6 %. The adjusted odds ratios are shown in the table.   [Discussion]  The major changes of the CPR protocol in the G2005 include immediate resumption of chest compressions after non-stacked shocks and increasing the compression:ventilation ratio to 30:2, with the former factor concerning only with patients with VF/VT. Although we expected a greater improvement in the VF/VT cohort than in the PEA/asystole cohort, the improvement was comparable across the 2 cohorts, and was limited to the rate of ROSC. Although the failure to demonstrate improved neurological outcome may be merely due to lack of statistical power, our data may support the similar findings reported recently by the Norwegian group.
Abstract 2071: Can Increased Myocardial Contractility During Dobutamine Infusion Be Reliably Measured By Speckle Tracking?
Authors: Amit Bhan, Stamatis Kapetanakis, Bushra S Rana, Francesco Casella, Mark J Monaghan
Journal: Circulation (2007)

Introduction: Speckle tracking is emerging as a useful adjunct in the evaluation of myocardial function, both at rest and during stress. We assessed the hypothesis that a novel software package inc...
Abstract 9687: Vagal Reflexes as a Simple Clinical Tool to Stratify Risk Among LQT1 Patients
Authors: Lia Crotti, Carla Spazzolini, Alessandra Porretta, Emilio Vanoli, Althea Goosen, Marshall Heradien, Paul A Brink, Alfred L George, Peter J Schwartz
Journal: Circulation (2011)

Background We demonstrated that lower baroreflex sensitivity (BRS) values can identify Long QT Syndrome 1(LQT1) patients at lower risk for life-threatening arrhythmias, suggesting a protective role of “blunted” autonomic responses. However, the complexities of the phenylephrine method to assess BRS have limited its use for risk stratification in clinical practice. Objectives To identify an easily quantifiable marker of reflex vagal activation that might perform as well as BRS in predicting a differential risk for life-threatening arrhythmias in LQT1 patients. Specifically, to test the predictive value of heart rate (HR) recovery during the first minute after cessation of an exercise stress test. Methods In a South African LQT1 founder population segregating KCNQ1-A341V, 44 mutation carriers (MCs) underwent an exercise stress test and a phenylephrine test off-β-blockers. The HR decrease during the first minute of recovery from the peak of exercise (Δ 1min-rec ) was measured and subsequently correlated with BRS values among symptomatic (syncope, cardiac arrest, sudden death) and asymptomatic patients. Results Asymptomatic MCs had a smaller decrease in HR during the first minute of recovery from peak exercise (Δ 1min-rec ) than symptomatic MCs (13±5 vs 19±7 bpm, p&lt; 0.05). A Δ 1min-rec &lt;15 bpm, which corresponds to the first tertile of its distribution, predicted a much lower probability of being symptomatic (OR 0.13, 95%CI 0.028-0.63, p&lt;0.05). The Δ 1min-rec values were significantly correlated with BRS values (r=0.64, p=0.001). Both tests performed similarly and quite accurately in discriminating between MCs with or without cardiac events (AUC 0.77 and 0.80). Conclusions LQT1 patients are at risk for life-threatening arrhythmias especially in association with rapid HR changes in either direction. Blunted autonomic responses, identified by lower values of BRS and - as vagal reflexes are concerned - by smaller HR reductions at the end of exercise, can usefully contribute to their risk stratification in a novel, simple, and inexpensive way.
Abstract 968: Cross-Sectional Relationships of Urinary Albumin Excretion with Asymmetric Dimethylarginine and Low-Grade Inflammation in Essential Hypertension
Authors: Costas Tsioufis, Kyriakos Dimitriadis, Karmen Vasiliadou, Dimitris Tsiachris, Maria Selima, Dimitris Tousoulis, Christodoulos Stefanadis, Ioannis Kallikazaros
Journal: Circulation (2007)

Introduction: Asymmetric dimethylarginine (ADMA) levels are elevated in endothelial dysfunction states, whereas microalbuminuria and subclinical inflammation are associated with atherosclerosis progression.

Hypothesis: Urinary albumin excretion, expressed as the albumin to creatinine ratio (ACR), may be correlated with high-sensitivity C-reactive protein (hs-CRP) and ADMA in essential hypertensive subjects.

Methods: Our population consisted of 158 newly diagnosed untreated non-diabetics with stage I to II essential hypertension [106 men, mean age=49 years, office blood pressure (BP)= 151/97 mmHg]. According to the ACR values determined as the mean of two non-consecutive morning spot urine samples, the study population was divided into microalbuminurics (n=32) (mean ACR=30 –300mg/g) and normoalbuminurics (n=126) (mean ACR=30 mg/g). In all patients venous blood sampling was performed for estimation of hs-CRP and ADMA concentrations.

Results: Microalbuminurics compared to normoalbuminurics were older (53±7 vs 49±6 years, p<0.05), had higher 24-h systolic BP (144±11 vs 133±12 mmHg, p<0.001), while did not differ regarding sex, smoking status and metabolic profile (p=NS for all). Moreover, microalbuminurics compared to normoalbuminurics exhibited higher ADMA (0.61±0.04 vs 0.55±0.03 μmol/l, p=0.001) and hs-CRP values (4.5±1.7 vs 2±1.1 mg/l, p<0.0001). In the total population, ACR was associated with 24-h systolic BP (r=0.263, p<0.0001), ADMA (r=0.366, p<0.0001) and hs-CRP (r=0.318, p<0.0001), while ADMA was related to waist to hip ratio (r=0.208, p<0.05), and 24-h pulse pressure (r=0.604, p<0.0001). Multiple regression analysis revealed that hs-CRP (b=0.582, p<0.0001) and ADMA (b=0.238, p<0.0001) were independent predictors of ACR. Moreover, analysis of covariance showed that ADMA and hs-CRP values were significantly different between groups after adjustment for confounders (p<0.05).

Conclusion: Microalbuminuria in hypertension is associated with pronounced inflammatory activation and endothelial dysregulation, as reflected by increased hs-CRP and ADMA levels. Moreover, ACR estimation could identify hypertensive patients with vascular dysfunction associated with ADMA and hs-CRP proatherosclerotic pathways.
Abstract 16886: First Quantification of Intestinal-apoB48 and Hepatic-apoB100 Particles in Human Atherosclerotic Plaque by Dual Immunofluorescence Staining
Authors: Jesus G Vazquez-Figueroa, Sarah Rinehart, Alexander McCree, Tamio Teramoto, Teruhiko Matsushima, Makoto Kinoshita, Andy Pryor, Brett Alman, Hong Yi, Parag Joshi, Szilard Voros
Journal: Circulation (2010)

Introduction: ApoB particles are atherogenic. We have previously demonstrated the presence and different localization of intestinal apoB48 and hepatic apoB100 particles in human atherosclerotic pla...