tbuckley/cabot-search huggingface dataset:
Abstract 18685: Global Myocardial Blood Flow Measurements Correlate with Angiographic Severity of Coronary Artery Disease
Authors: Jun-Yang Lou, Balaji K Tamarappoo, Frank P Difilippo, Richard C Brunken, Manuel D Cerqueira, Rory Hachamovitch
Journal: Circulation (2012)

Background. The correct identification of multivessel coronary artery disease (CAD) is a potential limitation of routine stress-rest using positron emission tomography (PET) myocardial perfusion imaging .We examined whether PET-based myocardial blood flow (MBF) and flow reserve (MFR) can be used to enhance the identification of extensive CAD. Methods. We identified 115 consecutive patients (pts; 65±11 yrs, 75% men) who underwent Regadenoson stress 82 Rb PET and coronary angiography within 6 months. MBF during hyperemia and rest and their ratio (MFR) were quantified. PET metrics included summed rest, stress and difference scores (SRS, SSS and SDS, respectively), transient ischemic dilatation (TID) and changes in ejection fraction (ΔEF). PET results were stratified based on angiographic severity grade from 0 (no stenosis&gt;70% or left main&gt;50%) to 5 (significant 3 vessel and left main CAD) and were analyzed using one way analysis of variance. Results. In total, 26 pts had no significant CAD (severity score=0); 27, 30, 22 and 10 patients had severity scores of 1, 2, 3 and 4, respectively. Resting global MBF did not vary as a function of CAD severity (ANOVA F-statistic = 1.63, p = 0.17), where as there was a strong correlation between CAD severity and global MBF during stress (F=13.5, p&lt;0.0001, figure), SSS (F=12.8, P&lt;0.0001) and global MFR (F=10.8, p&lt;0.0001). Weaker correlations were observed between coronary severity and SDS, Delta EF, and TID, respectively (F=8.2, 3.1, and 0.6). In the 35 pts (30% of total) with left main stenosis or 3-vessel CAD, 31 (89%) pts had abnormal stress MBF and MFR (using cut-offs of 1.80 ml/min/g and ratio of 2.0, respectively); whereas 54% had negative [[Unable to Display Character: ▵]]EF and only 20% had abnormal TID. Conclusion. Absolute stress MBF and MFR enhance the diagnostic accuracy of cardiac PET over conventional parameters for the identification of high-risk, severe and extensive CAD. This approach may reduce the incidence of CAD underestimation by PET.
Abstract 18939: Impact of LDL Pattern on Risk for CHD in the Framingham Offspring Population
Authors: Peter P Toth, Krishnaji R Kulkarni, Joseph M Massaro, Ralph B D'Agostino
Journal: Circulation (2012)

Introduction : Low-density lipoprotein (LDL) particles that are small and dense are characteristic of pattern B. It has been assumed that such particles are more atherogenic than larger, more buoyant particles indicative of LDL pattern A. Additionally, there is evidence from observational studies to support LDL pattern B as an emerging risk factor for coronary heart disease (CHD) with the incidence of CHD increasing as the proportion of type B to type A LDL particles increases. Hypothesis: In participants in the Framingham Offspring Cohort Study (FOCS), LDL pattern B is a significant and independent risk factor for incident CHD (inclusive of coronary death, myocardial infarction, coronary insufficiency, and angina pectoris) and hard CHD (CHD endpoints exclusive of angina pectoris). Methods : Vertical auto profile measurements were performed on 819 men and women on no lipid-modifying therapy as part of an exploratory analysis of the FOCS. The relationship between increasing LDL pattern type (A, A/B, and B) and 12-year risk for CHD and hard CHD was quantified using multivariable Cox proportional hazard regression for two models adjusted for known Framingham risk factors (model 1 adjusts for age, sex, systolic blood pressure and use of antihypertensives, prevalent diabetes, and smoking; model 2 adjusts for model 1 risk factors, HDL-C, and total cholesterol). Results: LDL pattern B is a statistically significant ( p &lt; 0.05 ) independent risk factor for 12-year incident CHD with hazard ratios of approximately 1.4 in models 1 and 2. For incident hard CHD, LDL pattern B is a more significant risk factor with hazard ratios greater than two and p &lt; 0.005 across both models. There was no effect modification by sex ( p &gt; 0.7 ). Conclusions: In this exploratory analysis, LDL pattern B is an independent risk factor for CHD and hard CHD after controlling for known Framingham risk factors in men and women on no lipid-lowering therapy.
Abstract 16932: Melatonin Inhibits Large Conductance, Calcium-Activated K Channel Activity in Porcine Coronary Artery Smooth Muscle Cells by Activating MT <sub>2</sub> -Receptors
Authors: Praveen Shukla, Fanrong Yao, P Borowicz, Chengwen Sun, Stephen ORourke
Journal: Circulation (2011)

Introduction: Increasing evidence indicates that melatonin plays a role in cardiovascular homeostasis by regulating blood vessel diameter, thereby impacting arterial blood pressure and local blood flow to organs and tissues. Alterations in circulating melatonin levels are associated with several cardiovascular disorders, including hypertension, ischemic heart disease, myocardial infarction, and heart failure. We have shown previously that melatonin impairs nitric oxide (NO)-induced relaxations in porcine coronary arteries by activating melatonin type-2 (MT 2 )-receptors (JPET 336: 127-33, 2011). Hypothesis: Melatonin impairs NO-induced relaxation of coronary arteries by inhibiting BK Ca channel activity in coronary artery smooth muscle cells (SMC). Methods and Results: Sodium nitroprusside (SNP), an exogenous NO-donor, caused relaxation of isolated porcine coronary arteries (-logEC 50 = 7.49 + 0.1; n=5). In the presence of either melatonin (10 -7 M) or iberiotoxin (IbTx; 10 -7 M), a selective BK Ca -channel blocker, the SNP dose-response was shifted to the right by approximately 6-fold (p&lt;0.05). The presence of BK Ca α- and β-subunits was identified by immunoblot analysis in intact porcine coronary arteries. Immunocytochemistry studies demonstrated that both subunits co-localized with α-actin in isolated single coronary SMC. Whole-cell K currents (10-mV steps from -70mV to +60mV, 200 ms duration) were obtained in freshly isolated coronary SMC in the absence or presence of IbTx (10 -7 M) or SNP (10 -5 M) (n=5-6). IbTx markedly inhibited (p&lt;0.05) both the voltage-dependent activation of whole-cell K currents and the SNP-induced increase in BK Ca currents in coronary SMC. Treatment of coronary SMC with melatonin (10 -7 M) inhibited the activation of BK Ca currents (56.8 ± 2.9% inhibition of peak current density at +60 mV; n=12; p&lt;0.05) and shifted the I-V curve to the right, as compared to control. The inhibitory effect of melatonin (10 -7 M) on BK Ca currents was abolished in the presence of the selective MT 2 -receptor antagonist, 4P-PDOT (10 -7 M). Conclusions: Melatonin acts via MT 2 -receptors to inhibit BK Ca activity in porcine coronary SMC, suggesting a mechanistic basis for the inhibitory effect of melatonin on NO-induced relaxation.
Abstract 8090: Identification Of <i>Rcn2</i> As A Novel Regulator Of Cytokine Expression
Authors: Weibin Shi, Qian Wang, Ani Manichaikul
Journal: Circulation (2011)

Background- Ath29 is an atherosclerosis susceptibility locus on chromosome 9 identified in an intercross between C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE −/− ) mice. This locus was subsequently replicated in two separate intercrosses that developed early or advanced atherosclerotic lesions. The objective of this study was to characterize Ath29 through construction and analysis of a congenic strain and identify underlying candidate genes. Methods and Results- Congenic strain was constructed by introgressing the chromosomal segment harboring Ath29 from C3H.apoE −/− into B6.apoE −/− mice. Congenic mice developed significantly smaller early and advance atherosclerotic lesions than B6.apoE −/− mice. Microarray analysis revealed 317 genes to be differentially expressed in the aorta of congenic mice compared with B6.apoE −/− mice. Pathway analysis of these genes suggested the calcium signaling pathway to be implicated in regulating atherosclerosis susceptibility. Rcn2 is located underneath the linkage peak of Ath29 and involved in calcium signaling. Multiple SNPs between B6 and C3H mice were detected within and surrounding Rcn2 with one SNP falling within an upstream cAMP response element. Immunostaining demonstrated its expression in atherosclerotic lesions. Knockdown of Rcn2 with siRNAs resulted in significant reductions in both baseline and oxidized phospholipid-induced VCAM-1 and MCP-1 expression by endothelial cells. Conclusions- Ath29 is confirmed to be a major atherosclerosis susceptibility locus affecting both early and advanced lesion formation in mice, and Rcn2 is identified as a novel regulator of cytokine expression.
Abstract 8517: Randomized Double-Blind Placebo-Controlled Pilot Study of Ranolazine Before Elective Percutaneous Coronary Intervention
Authors: Francesco Pelliccia, Giuseppe Marazzi, Vincenzo Pasceri, Alessio Arrivi, Gaetano Tanzilli, Enrico Mangieri, Carlo Gaudio, Giuseppe Mercuro
Journal: Circulation (2011)

Introduction. Ranolazine is a novel antianginal drug that reduces intracellular sodium and calcium accumulation during ischemia thus limiting ischemic injury. It remains unknown, however, if the drug can play a role in the pathophysiology of small myocardial infarctions after percutaneous coronary intervention (PCI). Hypothesis. Aim of this study was to verify in a randomized study if pre-treatment with ranolazine before PCI has any protective effect. Methods. Fifty patients with stable angina (32 men, age: 55+13 years) scheduled for elective coronary intervention entered a randomized, double-blind, placebo-controlled pilot trial. For 7 days prior to the procedure, 25 patients were assigned to receive ranolazine (500 mg twice daily) and 25 patients had placebo. Creatine kinase-MB, troponin-I and myoglobin levels were measured at baseline and at 8 and 24 hours post procedure. Results. Comparison between the two groups did not show any difference in age, sex, risk factors, cardiac function, and extension of coronary artery disease. Also, there was no difference in any technical aspect of PCI. Detection of markers of myocardial injury above the upper normal limit was significantly lower in the ranolazine vs placebo group: 12% vs 35% for creatine kinase-MB (p=0.001), 20% vs 48% for troponin-I (p=0.0004) and 22% vs 51% for myoglobin (p=0.0005). Myocardial infarction by creatine kinase-MB determination was less commonly seen after PCI in the ranolazine than in the placebo-group (5% vs 18%, p=0.025). Postprocedural peak levels of creatine kinase-MB (2.9+18 vs 7.5+18 ng/mL, p=0.0002) were also significantly lower in the ranolazine vs placebo group. No significant side effect was reported by the two groups of patients. Conclusions. Pretreatment with ranolazine 500 mg twice daily for 7 days significantly reduced procedural myocardial injury in elective PCI. These findings indicate that ranolazine may provide a friendly protection to ischemic cardiomyocytes. A multicentre randomized study is now ongoing and complete results will be available by 2012.
Abstract 18867: Multiple Biomarkers Predict Risk of Incident Heart Failure in Population Free of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis
Authors: Pelbreton C Balfour, Alain G Bertoni, Haiying Chen, Harjit Chahal, Joao A Lima, David M Herrington
Journal: Circulation (2012)

Background: Heart Failure is a complex syndrome with numerous patho-physiological mechanisms and altered biomarker profiles. Biomarkers that indicate risk for incident HF are less well established. Objective: To evaluate the predictive role of biomarkers reflecting different patho-physiological pathways for prediction of HF in the Multi-Ethnic Study of Atherosclerosis (MESA), a large multi-ethnic community based cohort. Methods: We evaluated 6,814 Caucasian, African-American, Hispanic, and Chinese participants with mean age 62.3 ± 10.3 (51.4% female). We examined individual and joint associations of CRP, fibrinogen, NT-proBNP, homocysteine, and urine albumin to creatinine ratio (UACR) with incident HF using Cox proportional-hazard models adjusting for age, sex, ethnicity, systolic BP, antihypertensive therapy, smoking, diabetes, total cholesterol, BMI, left ventricular hypertrophy by ECG, and estimated glomerular filtration rate. Hazard ratios (HR) were calculated per 1-SD change in log (biomarker). A multivariable-adjusted stepwise procedure (p for retention &lt; 0.05) was used to determine the independent contributions of the biomarkers for prediction of HF. We examined the increased model discriminative value with calculation of the C-statistic. Net reclassification index (NRI) was calculated with participants stratified in 3 risk categories; low (10%). Results: During median follow-up of 7.6 years, 176 participants developed HF. In multivariable-adjusted models, 3 of 5 biomarkers were individually associated with HF; NT-proBNP, CRP, and UACR [HRs: 2.46, (95% CI 2.11-2.87), 1.28 (1.09-1.50), and 1.29 (1.14-1.45), respectively]. After stepwise selection only NT-proBNP [HR: 2.56 (95% CI 2.17-3.03)] and CRP [HR: 1.20 (95% CI 1.03-1.41)] remained statistically significant. The C-statistic significantly increased when NT-proBNP and CRP were added to the model (0.864 vs. 0.808). The addition of biomarkers improved NRI (NRI 0.29, p &lt;0.0001). Conclusions: CRP and NT-proBNP are significant independent predictors and substantially improve risk classification for incident heart failure. More research is warranted to determine the clinical utility of measuring these biomarkers in subjects at risk for incident heart failure.
Abstract 19041: The Effectiveness of Intensive Medical Treatment of Patients Initially Referred as Refractory Angina: Preliminary Results
Authors: Luciana O Dourado, Nilson T Poppi, Alexandre C Pereira, Luiz Antonio M Cesar, Jose Eduardo Krieger, Luis Henrique W Gowdak
Journal: Circulation (2012)

Introduction: Refractory angina is a major clinical challenge. Many patients (pt) may be erroneously diagnosed as refractory angina (RA), if not on intensive medical therapy. Objectives: To evaluate the impact of intensive medical treatment on angina functional class, angina episodes and nitrate consumption per week in pt initially diagnosed as RA. Methods: 63 pt (68% male, 62±11 years) were included based on the following criteria: 1) disabling symptoms; 2) objectively documented myocardial ischemia; 3) coronary anatomy unsuitable for conventional myocardial revascularization procedures. Medical visits ocurred every 4 weeks during a 3-month period (V0 to V3). Pt were evaluated in each visit according to the functional class(CCS), and angina episodes and sublingual nitrate consumption per week were registered in pt's angina diary. Optimized medical therapy was strongly encouraged based on pt’s tolerance. Statistical analysis included the paired-sample T-test and logistic regression. Results: There was an overall improvement in CCS class between V0 to V3 of 0.89±1 (p&lt;0.001), from 2.9±0.8 to 2.1±1.0; a decrease in angina episodes of 3.2±6.2 (p=0.007), from 6.9±7.6 to 3.7±4.5, and in sublingual nitrates per week of 2.2±4.7 (p=0.04), from 4.7±5.0 to 2.4±2.6. In V0 and V3, anti-ischemic drugs were used as follows (%), respectively: beta-blockers (89 vs. 95), calcium channel blockers (78 vs. 89), long-acting nitrates (92 vs. 100), and trimetazidine (36 vs. 95), aspirin (81 vs. 81), statins (97 vs.98). There were non-significant changes in: mean HR (bpm) from 65±11 to 63±10 (p=0.09), in mean SBP from 125±22 to 122±22 (p=0.24), and DBP from 72±12 to 70±13mmHg (P=0.18), in mean waist circumference (cm) from 104±11 to 104±10(p=0.67) and in mean weight (kg) from 79±17 to 80±16 (p=0.39). The only predictive factor of clinical improvement found was CCS (p=0.04). Conclusion: Pt enrolled in this clinical program, although initially diagnosed as refractory angina, experienced a significant improvement in their clinical presentation, although little medical management changes were made. We believe that the regular visits at shorter intervals may have led to a better treatment adherence, emotional easiness and self-confidence.
Abstract 204: Extracorporeal Membrane Oxygenation Supported Cardiopulmonary Resuscitation Is Not Associated with Increased Survival Compared to Conventional Cardiopulmonary Resuscitation for Pediatric In-Hospital Cardiac Arrest in the United States
Authors: Adam Lowry, Daniel E Graves, Pirouz Shamszad, Antonio G Cabrera, David L S Morales, Antonio Mott, Rossano W Joseph
Journal: Circulation (2011)

INTRODUCTION: Survival after cardiopulmonary resuscitation (CPR) in children remains poor. The use of extracorporeal membrane oxygenation (ECMO) during or shortly after CPR (E-CPR) has been advocated as a strategy to improve outcomes. However, previous studies have been limited by lack of a conventional CPR (C-CPR) control group. HYPOTHESIS: E-CPR is associated with improved survival to hospital discharge compared with C-CPR. METHODS: Retrospective review of the 2000, 2003, and 2006 Kids' Inpatient Database, a large nationally representative database of pediatric hospital admissions, was performed. All episodes of CPR were identified; E-CPR was defined as the use of ECMO on the same day as CPR. Propensity scores were constructed reflecting the likelihood of E-CPR with arrest. Univariate, multivariable, and propensity matched analyses were performed to assess the influence of E-CPR on survival. RESULTS: Out of 8.6 million pediatric hospitalizations, 9,000 CPR events were identified, of which 82 were E-CPR (0.9%). Factors associated with E-CPR use included age &gt; 1 year, congenital heart disease, myocarditis, and hospitalization in a children's hospital (p&lt;0.001 for all). E-CPR was associated with higher hospital charges (median $187,661, interquartile range (IQR) $107,865 - $311,196) compared to C-CPR (median $23,157, IQR $5,875 - $92,004) (p&lt;0.001). Overall, hospital mortality was significantly higher with E-CPR (65.9%) compared to C-CPR (50.9%) (OR 1.9, 95% CI 1.2 - 2.9). Other factors associated with increased mortality after CPR included age &gt; 1 year, sepsis, congenital heart disease, and acute renal failure (p&lt;0.001 for all). Multivariable analysis controlling for age, hospital type, and comorbid conditions revealed no survival difference between E-CPR and C-CPR (OR 0.94, 95% CI 0.6-1.5). Propensity matched analysis also demonstrated similar survival between E-CPR and C-CPR (OR 0.68, 95% CI 0.4-1.2). CONCLUSIONS: E-CPR is rarely utilized for pediatric in-hospital cardiac arrest in the US. E-CPR was not associated with improved survival compared to C-CPR. However, E-CPR was associated with an 8 fold increase in hospital charges. Further study is needed to identify patients most likely to benefit from this resource-intensive therapy.
Abstract 18796: Evaluation of Vasomera™, A Novel VPAC2-selective Vasoactive Intestinal Peptide Agonist, in Rats with Doxorubicin-Induced Cardiomyopathy: Evidence for Chronic Cardio-Protection
Authors: Carlos L del Rio, Bradley Youngblood, Steve T Yeh, Lynne Georgopoulos, Sue Arnold, Jeff Wallery, Robert L Hamlin
Journal: Circulation (2012)

The natural vasoactive intestinal peptide (VIP) has been proposed as a therapeutic agent for heart failure via the activation of the G-protein-coupled VPAC1 and VPAC2 receptors; however, VIP's clinical utility is limited due to its short half-life and VPAC1-mediated side-effects. Vasomera™ is a novel long-acting biopolymer-based selective VPAC2-receptor agonist. Here, the chronic functional/geometrical effects of Vasomera when given daily to rats with doxorubicin-induced cardiomyopathy were evaluated. Sprague-Dawley rats were assigned to receive daily therapy with either Vasomera (9 mg/kg/day SQ; n = 15) or placebo (n = 10), and had heart failure induced via doxorubicin (DOXO, 3 mg/kg IP on M-W-F for 2 weeks; 18 mg/kg total); treatments started prior to HF induction (5 days) and continued until the end of the study. LV function/geometry were evaluated (via echo) prior to the start of dosing, as well as weekly during/after (for up to 3 weeks) HF induction. Animals were terminally studied to evaluate LV mechano-energetics. DOXO lead to marked LV dysfunction/remodeling, characterized by depressed systolic function (e.g., FS: -18 ± 4 %, P &lt; 0.05), myocardial dilatation (e.g., LVIDd: +12 ± 2, P &lt; 0.05), and wall-thinning (WT: -15 ± 5 %, P &lt; 0.05). Vasomera therapy prevented DOXO-induced myocardial wasting/wall-thinning (WTs: +1 ± 4%, N.S.), ameliorating ventricular dysfunction (e.g., FS, -8 ± 2%, P &lt; 0.05) and dilatation (LVIDd: +3 ± 3, N.S.). Vasomera treatment also tended to preserve the LV to body-weight ratio (-2.4 ± 2.0% vs. CTRL, N.S.), when compared to un-treated animals (-7.5 ± 3.0% vs. CTRL, P &lt; 0.1). Terminally, Vasometra-treated animals tended (P &lt; 0.1) to have lower LV filling pressures (EDP: 13 ± 1 vs. 9 ± 2 mmHg) and more-compliant ventricles (EDPVR: 2.9 ± 0.4 vs. 2.0 ± 0.3 mmHg/RVU). Daily treatment with Vasomera, a novel VPAC2 agonist, attenuated doxorubicin-induced myocardial remodeling/dysfunction in rats. In particular, Vasomera treatment prevented myocardial wall-thinning/muscular wasting. Moreover, acute Vasomera administration (IV) to rats with doxorubicin-induced cardiomyopathy, dose-dependently decreased myocardial loading and energetic demand, while improving LV systolic/diastolic function in a load-independent manner.
Abstract 8160: Risk Factors For Hospital Mortality And Morbidity Following The Norwood Procedure: Results From The Multicenter Single Ventricle Reconstruction Trial
Authors: Sarah Tabbutt, Nancy Ghanayem, David S Cooper, Deborah U Frank, Minmin Lu, Peter Frommelt, Wyman W Lai, Caren S Goldberg, Eric M Graham, Catherine Dent Krawczeski, Lynn Mahony, Chitra Ravishankar, Lynn A Sleeper, Joel A Kirsh, Alan Lewis, Andrew Lodge, Rick Ohye, Christian Pizarro, Janet Simsic, Ellen Spurrier, Mario Stylianou, Peter Laussen
Journal: Circulation (2011)

BACKGROUND We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in a large prospective cohort of newborns with hypoplastic left heart syndrome and variants enrolled in the Single Ventricle Reconstruction trial. METHODS Potential predictors for outcome included patient and procedure related variables and center/surgeon volumes. Outcome variables occurring during the Norwood procedure and prior to hospital discharge or stage 2 surgery included: mortality, end-organ complications, length of ventilation and hospital length of stay (LOS). Variables with univariate p ≤ .2 were used as candidate predictors for multivariable regression modeling (p &lt; .05, significant). A reliability estimate of greater than 50% obtained by bootstrapping was required for terms to remain in the mortality model. RESULTS Analysis included 549 patients from 15 centers. Hospital mortality was 16% at a median of 16 (1 - 149) days after the Norwood procedure. Shunt type at the end of the Norwood procedure was not a significant risk factor for mortality during the Norwood hospitalization. Independent risk factors for mortality (n=88), renal failure (n=46), sepsis (n=93), length of ventilation among survivors (7 days, range 1 - 270) and hospital LOS among survivors (24 days, range 6 - 270) are shown in the Table. CONCLUSION Innate patient factors, pre-operative condition and lower center volume impact post-operative mortality and morbidity during the Norwood hospitalization.