tbuckley/cabot-search huggingface dataset:
Abstract 99: Estimated Regional Oxy-hemoglobin Concentration is an Excellent and Simple Predictor of Neurological Outcome for Post Cardiac Arrest Syndrome: A Prospective Multicenter Observational Study
Authors: Kei Hayashida, Noritoshi Ito, Kei Nishiyama, Masaru Suzuki, Tomoyoshi Tamura, Masashi Kawakami, Hideki Arimoto, Takashi Unoki, Tomohiko Orita, Akira Murai, Tomoyuki Endo, Kazunobu Norimoto, Hideaki Anan, Masanori Masubuchi, Hideto Yasuda, Yutaro Nishi, Shingo Hori
Journal: Circulation (2013)

Background: We previously reported that an regional cerebral oxygen saturation (rSO2) at hospital arrival can predict neurological outcomes in patients who suffered out-of-hospital cardiac arrest. In this post-hoc analyses, we investigated whether estimated regional oxy-Hb (erHbO2), the product of Hb and rSO2 which might represent regional tissue oxy-Hb existence theoretically, plays pivotal role in the development of neurological impairment in patients with post cardiac arrest patients (PCAS). Methods &amp; Results: From May 2011 through July 2012, 363 consecutive comatose survivors admitted to hospitals were analyzed in this study. The primary outcome measure was a neurological outcome at 90 days. Forty-five patients (12.4%) presented good neurological outcome. The receiver operating characteristic curve analyses revealed rSO2 cutoff of 40% and erHbO2 cutoff of 3.6 had the maximum joint sensitivity and specificity to predict a good neurological outcome (rSO2: AUCs, 0.831; 95%CI, 0.770-0.892; sensitivity, 84.4%; specificity, 76.1%. erHbO2: AUCs, 0.872; 95%CI, 0.821-0.923; sensitivity, 91.1%; specificity, 71.4%). In a subgroup of patients with rSO2 &gt;40% of optimal cutoff (n=114, 38 [33.3%] patients with good outcome), multivariate analysis revealed that erHbO2 was a significant predictor of a good neurological outcome (Odds: 1.34, 95% CI; 1.04-1.71, p=0.02), such that a 1-point increase in erHbO2 is associated with approximately 35% increase in the odds for good neurological outcome. Conclusion: Our results demonstrate that rSO2 and erHbO2 can predict good neurological outcome. erHbO2 may be a useful index for neuro-protection in patients with PCAS.
Abstract 14227: A Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation
Authors: Jun Wang, Yan Bai, Na Li, Stephanie B. Greene, Min Zhang, Ye Tao, Xander H. T. Wehrens, James F. Martin
Journal: Circulation (2013)

Jun Wang, 2013 Finalist and Presenting Author
Abstract 9508: Neutrophil to Lymphocyte Ratio Predicts Short and Long Term Mortality After Revascularized ST Elevation Myocardial Infarction
Authors: Abhishek C Sawant, Prabhat Adhikari, Paul K Mills, Sanjay S Srivatsa
Journal: Circulation (2013)

Introduction: Several biomarkers of inflammation have been implicated in the pathogenesis of acute coronary syndromes. The role of inflammatory markers in predicting short and long term survival after revascularized STEMI remains poorly defined. Patient and methods: We retrospectively evaluated 250 consecutive STEMI patients admitted to a tertiary care center over one year. Exclusion criteria included:acute sepsis, trauma, recent surgery or underlying malignancy. Data analyzed included demographics, clinical presentation, leukocyte markers, electrocardiograms, therapy and major adverse cardiac events. Results: Mean age was 62±15 years, 70.4% subjects were males, almost equal number were Caucasians (49.4%) and non-Caucasians with mean follow up of 571±291 (Median=730) days. Considering available inflammatory markers, univariate predictors of mortality included only White Cell Count (14.52±8.09*10 3 /microliter;p&lt;0.001) and neutrophil to lymphocyte ratio [NLR] (9.12±8.75;p=0.011). Multivariate regression analysis of all univariate predictors revealed NLR (OR=2.64;p=0.026), female gender (OR=5.35;p&lt;0.001), cerebrovascular accident history (OR=3.36;p=0.023), low glomerular filtration rate (OR=0.98;p=0.012) and cardiac arrest on admission (OR=17.43;p&lt;0.001) as independent predictors of 2-year mortality. NLR was subdivided based on an optimal cut off value (OCV) of 7.4, when combined with Thrombolysis in Myocardial Infarction (TIMI) Score provided the highest predictive power for mortality with Area Under the Curve (AUC) of 0.799 (95 CI:0.734,0.865;p&lt;0.001). Short term (30 days) and long term (2-years) mortality stratified by NLR (Figure 1-A) and Kaplan Meier survival analysis (Figure 1-B) are illustrated. Conclusion: NLR based on OCV of 7.4 is an excellent predictor of short and long term survival with additive prognostic value to conventional clinical and angiographic scoring systems used for revascularized STEMI patients.
Abstract 9959: Chronic Administration of Pioglitazone and Pro-Oxidant Effects Within Chronic Hibernating Pig Hearts
Authors: Tammy A Butterick, Eric K Long, Cayla Duffy, Jesús A Cabrera, Christopher T Holley, Herbert B Ward, Rosemary F Kelly, Edward O McFalls
Journal: Circulation (2013)

Background: Glitazones have pleomorphic effects on myocardial metabolism. We hypothesized that the PPAR-gamma agent pioglitazone (PIO) would alter mitochondrial function and induce a pro-oxidant effect on chronically ischemic heart tissue. Methods: Eighteen pigs underwent a thoracotomy with placement of a fixed constrictor around the LAD artery. At 8-weeks post-instrumentation, they were given daily PIO (3 mg/kg) or placebo (P) in the chow for 4 weeks. Regional function by ECHO was measured at baseline and regional blood flows by μspheres were determined at baseline and during high-dose dobutamine (40 μg/kg/min). Using a high-speed drill, tissue was harvested and frozen for enzymatic analysis of high-energy nucleotides. Post-sacrifice, state 3 respiration was measured from isolated mitochondria and tissue levels of glutathionyl 4-oxo-2-nonenal (GS-ONE) were determined by liquid chromatography-tendem mass spectrometry measurement. Results: In all pigs, baseline regional wall thickening (%) was lower in the LAD versus Remote region (42±5% vs 58±5%; P&lt;0.05). LAD blood flow when normalized to the remote region was 83±5% at baseline and 64±7% during dobutamine, demonstrating the presence of chronic ischemic myocardium. The energetic state in the PIO group was more unfavorable than the placebo group, as manifested by lower transmural ATP levels (1.61±0.22 vs 2.35±0.25 μmol/g; P&lt;0.05) and depressed Phosphocreatine to ATP ratios (1.59±0.11 vs 2.11±0.16; P&lt;0.05). As shown by the figure, animals that received chronic PIO had higher levels of oxidant stress, as measured by GS-ONE levels and depressed rates of mitochondrial state 3 respiration. In summary, chronic administration of pioglitazone has a pro-oxidant effect on chronically ischemic hearts and an unfavorable effect on myocardial energetics, potentially by altering activity within the mitochondrial electron transport chain.
Abstract 9630: HMG-CoA Reductase Inhibitor Pitavastatin Enhances Renoprotective Effects of Angiotensin Receptor1 Blocker Olmesartan In Salt-Sensitive Hypertensive Rats
Authors: Aiko Inoue, Xian Wu Cheng, Takeshi Sasaki, Lina Hu, Haiying Jang, Li Xiang, Masafumi Kuzuya, Toyoaki Murohara, Kenji Okumura
Journal: Circulation (2013)

Objective: The present studies was undertaken to investigate the potential effect of a statin to enhance the inhibitory effect of an ARB on renal injury and the cellular mechanism of theeffect of ARB on renal remodeling and proteinuria. Methods and Results: Dahl salt-sensitive (DS) rats on a high-salt diet were randomly assigned to four groups ( n = 10 for each group) that were treated with either vehicle (0.5% carboxymethyl cellulose), a low or high dosage of olmesartan (1 or 3 mg/kg/d), or pitavastatin (1 mg/kg/d) plus olmesartan (1 mg/kg/d) from 12 to 19 weeks of age. Rats fed a low-salt diet served as age-matched controls. Rats on the high-salt diet developed massive proteinuria and glomerulosclerosis, and these changes were attenuated by olmesartan in a dose-dependent manner. The amounts of mRNAs for AT1R, mineralocorticoid receptor (MR), osteopontin, monocyte chemoattractant protein-1 and collagen type I, and the activities for matrix metalloproteinase-9 and cathepsin S were significantly higher in the failing kidneys of vehicle-treated rats than in the age-matched control rats; olmesartan significantly attenuated these changes. Olmesartan attenuated both the decrease in the ratio of reduced glutathione to oxidized glutathione and the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity apparent in the kidney cortex of vehicle-treated rats. Furthermore, olmesartan inhibited kidney cortex vascular inflammation and renal fibrosis. The addition of pitavastatin significantly enhanced these beneficial effects by AT1R antagonism via anti-inflammation and anti-proteolysis. Conclusions: The beneficial renal effects of AT1R antagonism are likely attributable, at least in part, to the attenuation of renal oxidative stress and renal vascular inflammation induced by the AT1R-MR signaling interaction. The combination of statin with angiotensin receptor blocker (ARB) may be a potential therapeutic strategy for renal injury with proteinuria.
Abstract 19077: Correlation of Renal Insufficiency With Left Ventricular Diastolic Dysfunction: How Medications Impact This Association?
Authors: Roozbeh Sharif, Arnav Kumar, Sangeeta Mutnuri, Adnan Khan, Lamin Bangura, Mohammad Morsy, Yong-Fang Kuo, Wissam Khalife
Journal: Circulation (2013)

Background: Increasing evidence between the association of chronic kidney disease (CKD) and left ventricular diastolic dysfunction (LVDD) has been emerging, however the impact of medications on this association has not been well studied. Methods: In a cross-sectional study, we reviewed the medical records of patients who presented to the echocardiographic lab in a tertiary care academic center between 2008 and 2011. CKD staging was categorized based on the estimated glomerular filtration rate (eGFR). Diastolic function was evaluated based on echocardiographic characteristics. Using logistic regression analysis, the association between CKD severity and LVDD was examined after adjusting for potential demographic and clinical confounders. Then, we hypothesized that medications (i.e. angiotensin converting enzyme inhibitors [ACE-inh]/ Angiotensin II receptor blockers [ARB], statins, beta blockers, or any combination of these) might modify this association and examined the interaction term of medications in regards to the association between CKD severity (eGFR) and LVDD. Results: Among 2443 patients, 1018 (41.7%) had normal eGFR, 757 (31%) had stage II, 443 (18.1%) stage III, 106 (4.3%) stage IV, and 119 (4.9%) stage V. LVDD was found in 1697 patients. Our data suggested that patients with CKD stage V have higher likelihood of developing LVDD (OR: 2.63, 95%CI 1.48-4.67, p=0.0006). Besides, higher CKD stage was associated with more severe LVDD (6.5%, 12.3%, 13.8%, 17.0%, and 20.2% patients with CKD stage I, II, III, IV, and V had LVDD stages II or higher, respectively). The analysis of potential effect modifier indicated a significant interaction between CKD staging and treatment with statins, in regard to its association with LVDD (p=0.0008). Therefore, we categorized the patients based on the medications. The stratified analyses indicated that patients on Statins had weaker association between CKD stage V and LVDD (OR of 0.77 vs. 6.85). Conclusions: Higher CKD stage is associated with presence and severity of LVDD. Statins can play a protective role, particularly in the higher stages of CKD.
Abstract 19090: Assessing the Contribution of Dietary Factors to the Increased Prevalence of Insulin Resistance Amongst Uk Indian Asians Compared to Europeans
Authors: Sian-Tsung Tan, Baldeesh Rai, Louise Boustead, Farah Badii, Nazlin Howell, Gary Frost, James Scott, Paul Elliott, John C Chambers, Jaspal S Koner
Journal: Circulation (2013)

Background: Indian Asians comprise a quarter of the world’s population. Insulin resistance (IR) is highly prevalent amongst Indian Asians, contributing to their 4-fold higher risk of type-2 diabetes (T2D) compared to Europeans. Unfavourable diet (high intake of total and saturated fat, and high glycaemic index foods) is an important determinant of IR. We carried out chemical analysis of duplicate diet samples to investigate whether unfavourable diet contributes to higher risk of IR and T2D in Indian Asians compared to Europeans. Methods: We recruited 92 Indian Asian and 94 European men from the lists of primary care physicians in West London (UK). Clinical characterisation included clinical questionnaire, anthropometric measurements and fasting blood samples (including lipid profile, glucose and insulin). Two 24-hour duplicate diets (comprising duplicate portions of all food and drink consumed) were collected, weighed, and homogenised. 30 ml aliquots were sent for chemical analysis (lipids - gas chromatography; carbohydrate - spectrophotometer quantification; protein - Kjeldahl method). Results: UK Indian Asians had higher body mass index, waist hip ratio, fasting insulin and were more insulin resistant [homeostatic model assessment-IR (HOMA[[Unable to Display Character: –]]IR)] than Europeans. Intakes of total protein, total fat and monounsaturated fat were lower, carbohydrate higher, and saturated, polyunsaturated and trans fat similar among Indian Asians compared to Europeans. HOMA[[Unable to Display Character: –]]IR was 32% (95% CI, 17[[Unable to Display Character: –]]46%) higher in Indian Asians (p&lt;0.001). In multivariate regression, differences in macronutrients (including fatty acids, p&lt;0.001) did not account for higher HOMA[[Unable to Display Character: –]]IR in Indian Asians. Conclusion: Unfavourable diet does not account for the differences in prevalence of IR amongst Indian Asians compared to Europeans. Metabolic profiling of diet samples and plasma may help identify the role of fatty acids and micronutrients with increasing susceptibility to IR in Indian Asians.
Abstract 9906: Aldosterone Targets Raptor to Promote Pulmonary Smooth Muscle Cell Proliferation and Modulate Pulmonary Arterial Hypertension
Authors: Reza Aghamohammadzadeh, Joseph Loscalzo, Jane A Leopold, Bradley A Maron
Journal: Circulation (2013)

In pulmonary arterial hypertension (PAH), elevated levels of aldosterone (ALDO) induce pulmonary smooth muscle cell (PSMC) proliferation and hypertrophy of distal arterioles. Raptor, part of the mammalian target of rapamycin (mTOR) complex 1, modulates PSMC growth; however, the role of ALDO-raptor signaling in PAH is not known. We hypothesized that stimulation of raptor by ALDO increases PSMC proliferation to promote vascular dysfunction in PAH. To test our hypothesis, human PSMCs were treated with vehicle control (V) or ALDO (10 -7 mol/l) for 15, 30, or 60 min. Compared to V-treated cells, ALDO for 60 min increased protein levels of P-mTOR(Ser2448) (26.1 ± 12.8 vs. 61.4 ± 17.8 units, p&lt;0.05) and P-raptor(Ser792) (19.4 ± 7.1 vs. 32.1 ± 2.2 units, p&lt;0.05) without affecting total mTOR/raptor levels. We next explored the effect of ALDO on Akt, which is an upstream mediator of raptor activation. ALDO increased the P-Akt(Ser473)/Akt ratio at 15 and 30 min by 56% (P&lt;0.02) and 80% (P&lt;0.02), respectively. ALDO also induced a time-dependent (0, 15, 30, 60 min) increase in levels of the raptor target P-p70S6k (Thr389) (56.8 ± 3.1 vs. 75.6 ± 3.6 vs. 79.0 ± 2.8 vs. 84.6 ± 4.8 units, P&lt;0.01), and increased cell proliferation by 29% (P&lt;0.02) as assessed by the tetrazolium assay. Next, we investigated the effect of ALDO-raptor signaling on vascular remodeling in PAH in vivo . Compared to controls, immunohistochemistry of pulmonary arterioles from rats with monocrotaline (MCT)-PAH demonstrated increased P-p70S6k(Thr389) (114 ± 16 vs. 188 ± 25 units, P&lt;0.02). In turn, inhibition of ALDO with eplerenone (10 μM) decreased P-p70S6k levels in ALDO-treated cells in vitro (33.6 ± 1.9 vs. 27.5 ± 2.2 units, P&lt;0.03), and spironolactone (25 mg/kg/d) decreased P-p70S6k levels in pulmonary arterioles of MCT-PAH rats in vivo (188 ± 25 vs. 96 ± 27 units, P&lt;0.02). Attenuation of P-p70S6k expression in MCT-PAH by spironolactone was associated with a decrease in indexed pulmonary vascular resistance (35.9 ± 3.2 vs. 21.5 ± 3.2 mmHg*min*g/ml, P&lt;0.05) and the number of muscularized arterioles by 54% (P&lt;0.05). These data demonstrate that Akt/raptor/p70S6k activation by ALDO promotes PSMC proliferation, and may represent a novel mechanism by which to account for pulmonary vascular remodeling in PAH.
Abstract 9873: Inhibition of IL-1β Signaling Prevents Aneurysm Formation in a Novel Model of Thoracic Aortic Aneurysm
Authors: William F Johnston, Morgan Salmon, Gang Su, Matthew L Stone, Nicolas H Pope, Guanyi Lu, Gilbert R Upchurch, Gorav Ailawadi
Journal: Circulation (2013)

Objective: To determine the role of IL-1β signaling in a novel model of thoracic aortic aneurysms (TAAs). Methods: To develop a TAA model, 8-10 week old male C57Bl/6 wild type mice (WT) underwent thoracotomy with topical placement of an elastase soaked sponge (WT elastase) or saline soaked sponge (WT saline) for 5.5 minutes. Mice recovered and aortic dilation was measured in vivo at 3, 7, 14, 21 and 28 days (n=5 each). Next, to determine the contribution of IL-1β signaling in TAA formation, TAAs were induced in mice deficient of IL-1β (IL-1β KO) or IL-1 receptor (IL-1R KO) (n=10 each). Maximal aortic dilation was measured and thoracic aortas were harvested for histology and protein analysis. Last, WT mice pre-treated with either IL-1R antagonist anakinra (100mg/kg/day) or vehicle alone (n=8 per group) underwent the elastase TAA model to determine effects of pharmacologic IL-1R antagonism. Results: Application of an elastase soaked sponge to the thoracic aorta resulted in a progressive dilation over time with maximal aortic dilation of 99.6±24.7% at day 14 compared to 14.4±8.2% for WT saline control (p&lt;0.0001). WT elastase aortas had increased elastin fragmentation, smooth muscle cell degradation, and infiltration by macrophages and neutrophils compared to saline aortas. Compared to positive WT controls, genetic deletion of IL-1β and IL-1R significantly decreased thoracic aortic dilation (WT control = 104.7±23.8% vs. IL-1β KO = 54.2±16.8% and IL-1R KO = 62.6±17.2%, p&lt;0.05 for both). Both IL-1β KO and IL-1R KO aortas demonstrated preserved elastin and smooth muscle cell staining and decreased macrophage and neutrophil staining. Correspondingly, IL-1β and IL-1R KO aortas had significantly decreased inflammatory cytokines and MMP-9. Pretreatment of WT mice with anakinra inhibited TAA formation with reduction in maximal aortic dilation from 99.2±15.5% in the vehicle-treated mice to 73.3±24.9% in mice treated with anakinra (p&lt;0.05). Conclusions: Topical application of elastase to the thoracic aorta reproducibly produces aortic dilation with molecular and histologic features that are consistent with TAA disease. Both genetic and pharmacologic inhibition of IL-1β signaling prevent TAA formation and may be a potential therapeutic target in human disease.
Abstract 9542: Do ICDs Prevent Hip Fractures or Are Physicians Selecting Appropriate Candidates for ICDs?
Authors: Soko Setoguchi, Lynne Warner Stevenson, Garrick G Stewart, Deepak L Bhatt, Andrew E Epstein, Manisha Desai, Lauren Williams, Chih-Ying Chen
Journal: Circulation (2013)

Background: In real world practice, treatments are not randomly allocated but selected based on indications and other considerations. If not taken into account, these selection factors can impact comparative effectiveness estimates in observational studies. Objective: To assess the potential contribution of unmeasured general health status to patient selection in assessing clinical effectiveness of ICDs for primary prevention. Methods: Linking CMS ICD registry, National Cardiovascular Data Registry (NCDR®) ICD Registry™, a heart failure (HF) registry, and Medicare files (2005-2009), we identified HF patients ≥66 years who were eligible for primary prevention ICDs. We compared the risk of nontraumatic hip fracture, skilled nursing facility (SNF) admissions, and 30-day mortality between hospitalized HF patients with and without ICDs. Crude and adjusted hazard ratios were estimated by Cox proportional hazards regression. Results: Compared with 17,853 patients without ICDs, 11,573 patients with ICDs were younger and had lower ejection fractions and more cardiac hospitalizations, but fewer noncardiac hospitalizations and comorbid conditions. Patients with ICDs had greater freedom from unrelated events: hip fracture (HR 0.39; 95% CI, 0.37-0.41, Figure), SNF admission (HR 0.53 95% CI, 0.50-0.55), and 30-day mortality (HR 0.10; 95% CI, 0.09-0.12%). After adjustment for multiple measured patient characteristics, risks in the two groups were less disparate but still substantially lower in ICD patients (HRs ranged from 0.20 to 0.84). Conclusion: The lower risks of these outcomes likely reflect unmeasured differences in comorbidity burden and frailty. These findings highlight potential pitfalls of observational comparative effectiveness research. The findings also support that physicians in clinical practice consider general health status in selecting patients for ICD implantation, avoiding implantation in patients who are less likely to benefit.
Abstract 19050: Accelerated Neointimal Hyperplasia in a Diabetic Mouse Model via Elevated microRNA-221/222
Authors: Daniel J Lightell, Jr., Thomas C Woods
Journal: Circulation (2013)

Introduction: Neointimal hyperplasia is increased in the diabetic population, promoting accelerated plaque development and an increased risk of stroke and myocardial infarction. Two microRNA, miR-221/222, that are known to promote neointimal hyperplasia in response to vascular injury through down regulation of the cyclin dependent kinase inhibitor, p27Kip1, are elevated in the internal mammary arteries of diabetic subjects. We hypothesized that miR-221/222 would be elevated in the arteries of a mouse model of diabetes and that this increase in miR-221/222 would promote a decrease in p27Kip1 and an increase in neointimal hyperplasia following vascular injury. Methods: Femoral artery wire injury coupled with perivascular local delivery of a low dose of either non-targeting (NT) or miR-221/222 targeting antisense oligonucleotides (AS) was performed in NONcNZO10 mice fed a diabetes inducing diet (DM) or normal chow (ND). We compared neointimal hyperplasia and the expression of miR-221/222 and p27Kip1 in DM and ND mice in the presence and absence of AS treatment. Results: DM mice exhibited a ~2 fold elevation in expression of miR-221/222 both pre- and post-injury compared to ND mice. This was coupled with significant decreases in p27Kip1 mRNA and protein as well as the decreases in the mRNA for two additional targets of miR-221/222, c-Kit and p53 up-regulated modulator of apoptosis. In DM mice AS treatment reduced miR-221/222 expression (Figure 1A) and restored normal p27Kip1 mRNA and protein levels, with no effect in the ND mice. Similarly, neointimal hyperplasia was significantly elevated in the NT treated arteries of the DM mice, but AS treatment reduced neointimal hyperplasia to levels comparable to the ND mice (Figure 1B). Conclusions: We conclude that diabetes is accompanied by an increased arterial expression of miR-221/222 that in turn accelerates neointimal hyperplasia in response to arterial injury.