tbuckley/cabot-search huggingface dataset:
Abstract 18903: Stimulation of Angiotensin Type 2 Receptor as a Potential Therapy for Pulmonary Hypertension
Authors: Erin Bruce, Vinayak Shenoy, Joseph Francis, U. Muscha Steckelings, Thomas Unger, Colin Sumners, Mohan K Raizada, Michael J Katovich
Journal: Circulation (2012)

Pulmonary hypertension (PH) is characterized by an increased pressure in the lung vasculature, often leading to right heart failure, and for which current therapies are lacking. Activation of the ACE2/Ang-(1-7)/Mas axis of the renin angiotensin system attenuates much of the associated pathophysiology related to PH. Along with the ACE2/Ang-(1-7)/Mas axis, the AT2 receptor (AT2R) is considered vasoprotective, and activation of these components often mimic each other. In fact, both ACE2 and AT2R have a protective role in acute lung injury; however, the role of AT2R has yet to be investigated in PH. We hypothesize that activation of the AT2R, via selective agonist Compound 21 (C21), could be an effective treatment against PH. Sprague Dawely rats were injected sc with 50mg/kg of monocrotaline (MCT) at 8 weeks of age to induce PH. Control (Con) animals were given saline. After 2 weeks, when right ventricular systolic pressures (RVSP) were significantly elevated (PH 48.33±8.8; Con 32.0 ±2.4 mmHg), treatment began with animals receiving either 0.03mg/kg/day C21 ip (MCT+C21), 0.3mg/kg/day PD-123,319 (MCT+PD), C21 and PD (MCT+C21+PD), or vehicle (MCT, Con) for an additional 2 weeks, after which RV hemodynamic parameters were measured and tissues collected. Treatment with C21 significantly attenuated PH and associated cardiac pathophysiologies. The increase in RVSP and RV hypertrophy induced by MCT was significantly blunted by C21 treatment, and PD prevented this reduction. Furthermore, right heart dysfunction as measured by dP/dtmax, was significantly attenuated by C21 treatment, but was exacerbated in rats treated with PD. PD treatment also worsened the lung weight to tibia length ratio in comparison to MCT. To our knowledge these are the first results to indicate that activation of the AT2R halts the progression of PH and C21 should be considered for an additional drug arsenal in PH therapy.
Abstract 18630: Cost-effectiveness of Revascularization Strategies: A Preliminary Study from ASCERT
Authors: Zugui Zhang, Fred Edwards, Paul Kolm, Maria Grau-Sepulveda, Sean O'Brien, David Shahian, Angelo Ponirakis, Lloyd W Klein, Frederick L Grover, Kirk Garratt, Charles Mckay, William S Weintraub
Journal: Circulation (2012)

Background: Using data from the Society of Thoracic Surgeons (STS) Database and the American College of Cardiology Foundation (ACCF) National Cardiovascular Data Registry (NCDR) in ASCERT, we examined the cost-effectiveness of coronary-artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI). Methods: The STS Database and ACCF NCDR were linked to the Centers for Medicare and Medicaid Services (CMS) claims data from years 2004 to 2008. Costs were assessed at index, 1 year and 4 years by Diagnosis Related Group for hospitalizations. Effectiveness was measured via mortality rate and converted to life year gained (LYG) from Framingham survival data. Costs and effectiveness were adjusted using propensity scores and inverse probability weighting to reduce treatment selection bias. The incremental cost-effectiveness ratio (ICER) was expressed as cost per LYG. Results: Among patients (86,244 in CABG group and 103,549 in PCI group) at least 65 years old with two or three vessel coronary artery disease, costs were higher for CABG by $10,951 (95% CI: $10,899 to $11,003) during the index hospitalization and by $9,906 (95% CI: $9,824 to $9,988) at 1 year, compared to PCI. At 4 years, average total costs were $32,428 for CABG versus $24,623 for PCI, a difference of $7,825 (95% CI: $7,693 to $7,927). For life time, average total costs were $88,125 for CABG versus $82,020 for PCI, a difference of $6,105 (95% CI: $5,990 to $6,327); patients undergoing CABG gained an average of 0.1268 life-years relative to PCI; the ICER of CABG, compared to PCI, was $48,135 per LYG, with 15.3%, 40.5%, 78.2%, and 85.7% of bootstrap-derived estimates &lt;$25,000/LYG , &lt;$50,000/LYG , &lt;$75,000/LYG , and &lt;$100,000/LYG, respectively. Conclusions: In the period of less than 1 year, CABG was more costly and less effective than PCI. However, in the long run, CABG offers lower mortality at higher cost than PCI. Using a common threshold, CABG will often be a cost-effective strategy.
Abstract 16806: Assesment of Diastolic Ventricular Function in Fetuses of Gestational Diabetic Mothers
Authors: Feyza A Pac, Sevket Balli, Ibrahim Ece
Journal: Circulation (2011)

Objectives: To identify ventricular diastolic disfunction by tissue Doppler in fetuses of diabetic mothers and compare with control groups. Material and methods: Between November 2009, April 2011 36 mother with gestational diabetes mellitus and 55 control subjects were recruited prospectively. Fetal echocardiogram was performed at 24, 28, 32 and 36 weeks of gestation to assess cardiac diastolic function by using tissue Doppler and pulse wave Doppler echocardiography. Early(Ea) and late (Aa) diastolic peak tissue Doppler imaging at the base of right ventricular free wall, ventricular septum, left ventricular free wall and both atrioventricular valves early(E), late(A) inflow velocities were analyzed and compared between groups. Haemoglobin glycated(HbA1c) levels were obtained at 24 week of gestation. Values above 6,5 % were excluded. Blood glucose levels of gestational diabetic mothers were under control. Results: Fetal interventricular septal thickness increasing progressively with advanced gestation were significantly more than control group in the presence of gestational diabetes mellitus (p&lt; 0.001). Mean levels of HbA1c were 5,79±0.73 % in gestational diabetic mothers, 5.02±0.36 % in control group(p&lt;0.003). HbA1c was significantly higher in the gestational diabetic mothers. E, A, Ea, Aa, Ea/Aa and E/A ratios increased with gestational age at all sites in both group. Peak velocities of mitral E (p&lt;0.001), mitral A(p&lt;0,007), tricuspid E(p&lt;0.001) and tricuspid A (p&lt;0.002) were significantly higher in diabetic group. The ratio of E/A and Ea/Aa increase as a function of more rapid augmentation in early when compared with late diastolic velocities in both group. Increases of mitral E/A and tricuspid E/A ratios were lower in diabetic group with advancing gestation. Ea:Aa ratio of right ventricle was higher in fetuses of diabetic mothers with advancing gestation (p&lt;0,03). Conclusions: We conlude that maternal diabetes mellitus is associated with alterations ventricular diastolic function in the fetus. This is not closely related with interventricular septal hypertrophy. Impaired ventricular diastolic function develops as a result of decreased relaxation and compliance.
Abstract 18429: Is Metabolic syndrome post Liver Transplantation a Risk Factor for Cardiovascular Disease?
Authors: Surabhi Madhwal, Avirup Guha, Ashish Atreja, Puneet Gupta, Mazen Albeldawdi, Anthony Post, Marco Costa
Journal: Circulation (2012)

Introduction: Up to two-thirds of patients develop metabolic syndrome within five years post orthotopic liver transplant (OLT). Data on overall cardiovascular (CV) morbidity and mortality among OLT recipients, particularly those who develop metabolic syndrome, is limited and there are no specific guidelines on management of post OLT metabolic syndrome. Hypothesis: We assessed hypothesis that metabolic syndrome post OLT is associated with increased risk of CV events. Methods: Historical cohort study of all adult patients who underwent OLT at our institution for end-stage liver disease between from year 1987 to year 2011.Symptoms or confirmed diagnosis of coronary artery disease (with or without interventions) and stroke were categorized as CV events. CV deaths included deaths due to CV events as well as those from arrhythmias and heart failure. Results: From a total of 428 patients in our cohort (Male, 64%; Caucasian, 79.5%), more than half (55.8%) died in the follow-up period. Graft failure (17.9%), infection (21.4%) and CV disease (17.4%) were the top three causes of deaths. About one-third (30.3%) of patients had post transplant metabolic syndrome (DM, 46.9 %; mean HDL 40.6 +-16.7; mean triglycerides, 58.8 +_88.5; mean BMI, 29.04+_7.3). Patients with post transplant metabolic syndrome had higher incidence of myocardial infarction (14.3 % versus 3.7%, P 0.02) and overall CV events (73.4% versus 37.6%, P &lt; 0.001) as compared to patients without metabolic syndrome. There was no difference in all-cause mortality (41.9 % versus 50%, P =0.56) or CV deaths (18.2% versus 13.3 %, P=0.79) between the two groups. Conclusion: Metabolic syndrome after liver transplantation is associated with twice the risk of CV events and about four times the risk of myocardial infarction, as compared to patients without metabolic syndrome. This high risk group may potentially benefit from aggressive risk reduction strategies or modification of immunosuppressive regimen.
Abstract 19050: Does Type of Culprit Lesion Matter in Patients with Acute Coronary Syndrome and Prior Coronary Artery Bypass Graft Surgery Undergoing Percutaneous Coronary Intervention?
Authors: Ralf E Harskamp, Marcel A Beijk, Peter E Damman, Jan G Tijssen, Mitchell W Krucoff, Renato D Lopes, Robbert J de Winter
Journal: Circulation (2012)

Background: Acute coronary syndrome (ACS) in patients with prior coronary artery bypass graft (CABG) surgery may be due to graft failure or progression of native coronary artery disease. We studied whether the culprit lesion (graft vs. native) is associated with differences in hospital and long-term outcomes. Methods: We included ACS patients with prior CABG who underwent percutaneous coronary intervention (PCI) of &gt;=1 lesion at the Academic Medical Center - University of Amsterdam between 1998 and 2008. The primary outcome was 5-year mortality and the secondary outcome was a composite of in-hospital death, myocardial infarction, need-for-revascularization and stroke. Kaplan-Meier estimates were used to compare 5-year mortality between patients with graft vs. native culprit lesions. Predictors for 5-year mortality were identified using multivariable Cox proportional hazards modeling with backwards variable selection. Logistic regression was used to assess predictors for in-hospital outcomes. Results: Overall, 270 patients were included, of which 146 (54.1%) had a graft culprit lesion. Mean age was 70 (SD=9.5yrs), 21.9% were women. Multi-vessel PCI was performed in 50 (18.5%) patients. 5-year mortality was similar following graft versus native culprit lesion PCI (41.3% vs. 36.4%, HR:1.16, 95%-CI:0.73-1.84, p=0.52). In-hospital death, MI, need-for-revascularization and/or stroke was also comparable (16.4% vs. 13.7%, HR:1.24 (95%-CI:0.63-2.43), p=0.53). Similar results were seen after adjusting for important covariates. Older age, lack of prior aspirin use, and cardiogenic shock were independently associated with worse clinical outcomes. Conclusion: Type of culprit lesion (either native or graft) in patients presenting with ACS and prior CABG surgery was not associated with in-hospital or long-term clinical outcomes. Larger studies to validate our findings are warranted.
Abstract 19187: Sublingual Glycocalyx Measurement, a Novel Non-Invasive Technique to Predict Coronary Artery Disease
Authors: Judith Brands, Hans Vink, John J Pacella
Journal: Circulation (2012)

Background: A relatively thick endothelial lining, known as the glycocalyx (GC), forms the true interface between flowing blood and the vascular wall. The GC regulates several key endothelial functions including vascular permeability, coagulation and inflammation and contributes to the protection against atherogenic challenges. In healthy blood vessels, the GC provides limited access to flowing red blood cells (RBC). Recent observations have suggested that RBCs penetrate deeper into a damaged GC and therefore may serve as a marker for GC damage, which has been associated with microcirculatory dysfunction that accompanies, among others, coronary artery disease (CAD). Aim: In the present study we tested whether the presence of CAD could be predicted by measuring the dimension of the RBC perfused boundary region (PBR), which fills up the space between median RBC column width (MCW) and the outer edge of RBC permeable vascular lumen. In healthy blood vessels PBR is relatively small due to limited penetration of RBC into the GC and it is hypothesized that PBR will increase for a given MCW when GC is damaged. Method: We used sidestream dark field imaging, a novel stroboscopic LED ring-based clinical imaging modality, of the sublingual microvasculature in subjects with (N=10) and without (N=10, controls) angiographic CAD. From these images, MCW and PBR were determined in over 3000 vascular segments (vessel diameter between 10 and 20µm) per subject. Results: CAD patients displayed a significant increase in PBR compared to controls. The mean PBR increased from 2.31 ± 0.09µm to 2.64 ± 0.11µm (P&lt;0.05) comparing controls with CAD patients, respectively, consistent with a 0.3 µm deeper penetration of RBCs into the GC. Conclusion: These data demonstrate that CAD patients have a significant increase in the width of the RBC accessible component of the sublingual microvascular GC compared to control subjects. A wider permeable portion of the GC indicates a change in GC structure which may be associated with a reduced vascular protective function of the GC. Moreover, SDF imaging might provide a novel, noninvasive method to detect CAD.
Abstract 218: CPR Quality in an Urban Teaching Hospital Emergency Department: Are 2010 AHA Guidelines Being Implemented?
Authors: Jason R Roosa, Kyle McCarty, Brian Kitamura, Rianne Page, Paul B Dommer, Annemarie Silver, Ashish R Panchal, Frank LoVecchio, Daniel W Spaite, Bentley J Bobrow
Journal: Circulation (2011)

Background: CPR quality is closely linked to outcome in cardiac arrest. AHA 2010 Guidelines recommend monitoring CPR quality performed by healthcare providers both inside and outside the hospital. We recently reported that CPR quality varies significantly during the transition from the prehospital to emergency department (ED) setting in cases of out-of-hospital cardiac arrest (OHCA). While many EMS systems are now monitoring CPR quality, most EDs do not. We began an ongoing ED CPR quality improvement program based upon the 2010 AHA Guidelines. This two-phase study will measure the baseline quality of ED CPR, followed by measurement of CPR quality with the initiation of real-time CPR feedback technology. Here we report preliminary data showing the baseline CPR quality from Phase I. Methods: Prospective, IRB-approved study at an urban, teaching hospital ED. Chest compression (CC) quality was measured using accelerometer-equipped monitor/defibrillators (ZOLL R-Series, Chelmsford, MA). These baseline data were collected with the real-time audiovisual CPR feedback feature disabled. Results: CC data were captured over 7 months from 31 adult patients in cardiac arrest resulting in 6.5 hours of CPR and 37,348 individual CCs. CC fraction was 76.2%. Mean CC depth was 1.89 ± 0.61 inches and average rate was 122.4 ± 16.5 compressions/min. Using the 2010 AHA Guideline-recommended CC depth &gt;2 inches, 61.0% of compressions were too shallow. The rate of compressions was below 100/min in 6.3%. The mean pre-shock and post-shock pauses in CC were 7.8 and 7.4 sec, respectively (n=24 defibrillations/cardioversions). Conclusions: We describe the quality of CPR in a large urban teaching hospital ED. At the beginning of our ED CPR QI program, a large proportion of chest compression depth was less than the 2010 AHA Guideline of 2 inches. These data will be used for resuscitation training during the next phase of the program which will include real-time audiovisual CPR feedback and debriefing sessions for the ED providers.
Abstract 18437: B-type Natriuretic Peptide and Subclinical Atherosclerosis in Healthy Population
Authors: Yoshiko Mizuno, Toru Suzuki, Takahide Kohro, Satoshi Iimuro, Tsutomu Yamazaki
Journal: Circulation (2012)

Background: B-type natriuretic peptide (BNP) is associated with both coronary artery calcium, a marker of subclinical atherosclerosis, as well as myocardial ischemia and cardiac events. We examined the correlation of BNP with carotid intima-media thickness (IMT) in healthy asymptomatic population. Methods: The population of this study included 425 asymptomatic subjects (mean age 61 years, 53% male) free of cardiovascular disease who underwent IMT measurements by high-resolution carotid duplex Doppler studies. BNP levels were measured using the immune enzymometric assay (E test TOSOH II assay kit TOSHO, Japan). To reduce skewness, BNP levels were log transformed before regression analyses. Multivariate regression analyses adjusted for age, sex, smoking, blood pressure, eGFR, and other cardiovascular risk factors were performed. IMT was also categorized into two groups, increased and normal IMT, according to the age-modified IMT criteria. After the categorization, Student's t test was applied to evaluate the correlation between BNP and IMT. Results: In our study population, there were no significant differences in BNP levels between the two IMT categories. However, higher levels of BNP was observed amongst female subjects with increased IMT (BNP=27.25±1.36mm vs. 19.31±3.02mm for increased IMT vs. normal IMT, p=0.0171). Although there was no statistical difference in the levels of IMT between the sex (male 1.71±0.03pg/ml vs. female 1.61±0.03pg/ml, p=0.0595), higher IMT remained independently associated with higher BNP in female subjects. In multivariate models, log BNP (p=0.0302) was the second greatest estimator of IMT in females, while age (p=0.0002) and blood pressure (p=0.0314) were also statistically significant estimators. BNP, however, did not show any significant impact on IMT in males. Conclusions: Elevated BNP identifies a substantially increased likelihood of IMT progression. Therefore, BNP may serve as a marker of subclinical atherosclerosis. However its utility may be limited to female subjects.
Abstract 203: Insulin Alleviates Cardiac Dysfunction After Mechanical Trauma by Inhibiting TNF-α--Mediated ROS Generation via the PI3K/Akt Pathway
Authors: Jia Li, Yi Liu, Ya F Feng, De X Wang, Wen C Liu, Xiao Q Cai, Feng Gao
Journal: Circulation (2011)

Background: Intensive insulin treatment protects injured myocardium and reduces mortality in surgical critically ill patients but the mechanisms involved remain unclear. This study was designed to investigate whether insulin may alleviate cardiac dysfunction after mechanical trauma (MT) and the underlying mechanisms. Methods and Results: Male adult rats were subjected to non-lethal MT (Noble-Collip drum trauma, 35 r/m, 200 r) and randomly received different treatments. Non-lethal MT increased cardiac TNF-α (13.8±2.4 vs . 5.7±2.7 pg/mg protein, P &lt;0.01) and reactive oxygen species (ROS) production 0.5 h after trauma, resulted in immediate cardiac dysfunction 0.5 h post-trauma with subsequent myocardial injury as evidenced by increased serum troponin I (cTnI) and significant cardiomyocyte apoptosis 2 h post-trauma (n=6, all P &lt;0.01). Administration of GIK (250 g/L glucose, 60 U/L insulin, 80 mmol/L potassium) markedly inhibited TNF-α and ROS overproduction together with reduced myocardial injury and alleviated cardiac dysfunction at 1 h, 2 h, 3 h and 4 h after trauma. However, MT had no effect on blood glucose level compared with the sham-operated group and there was no difference in blood glucose between the GIK-treated and vehicle-treated rats during the 4-h experiment (n=6, P &gt;0.05). Blockade of TNF-α with etanercept (a fusion protein blocker of TNF-α, 16 mg/kg, i.p .) attenuated ROS generation and preserved cardiac function after MT (n=6, both P &lt;0.01). Furthermore, combining GIK and etanercept treatment did not exert any additive effects on these two parameters. In addition, pretreatment with Tempol (30 mg/kg, i.v .), a ROS scavenger, enhanced cardiac functional recovery after MT. Interestingly, cotreatment with the PI3K inhibitor wortmannin completely abolished the anti-TNF-α, anti-oxidative and cardioprotective effects afforded by GIK. Conclusions: These results demonstrated for the first time that insulin alleviates myocardial dysfunction after trauma by inhibiting TNF-α-mediated ROS generation via the PI3K/Akt pathway. The anti-inflammatory and anti-oxidative properties elicited by insulin may prevent cardiac dysfunction and improve outcomes in surgical critically ill patients.
Abstract 19136: Incidence of Diabetes Mellitus in Patients with Congenital Heart Disease
Authors: Mikael Dellborg, Anna Bjork, Nabi Pirouzi, Anneli Ambring, Peter Eriksson, Ann-Marie Svensson, Soffia Gudbjornsdottir
Journal: Circulation (2012)

Introduction: Today 0.8-1 % of all children are born with congenital heart defects (CHD) and most live into adulthood, with estimations and registry data indicating that 90-95% of all CHD now reach adulthood. CHD may increase the risk of infections and subsequently higher risk of diabetes type 1. Diabetes type 2 (T2D) increases and CHD could lead to a more sedentary lifestyle with a higher risk of developing T2D. Rhe relation between CHD and diabetes has previously not been investigated. Hypotheses: We estimated the risk of developing diabetes in a large cohort of patients with CHD as found in the nationwide diabetes registry in Sweden, NDR Methods: the National Diabetes Registry, NDR has an estimated coverage above 70% for Sweden. We identified patients with CHD in the NDR and compared to two controls groups, control group 1 never hospitalized paired patients with T1D or T2D and a second control group randomly selected paired patients with diabetes T1D or T2D and previous hospitalization for any reason. Both control groups were adjusted by age and gender. The analyzed characteristics were age, gender, type of diabetes, diabetes duration, systolic blood pressure, BMI, waist measurement, HbA1c, smoking, microalbuminuria, antihypertensive, lipid lowering drug use and type of hypoglycaemic treatment. Results: We found 1860 patients in the NDR with CHD as additional diagnosis. With a presumed prevalence of between 0.3 and 0.4% of the adult population, diabetes was found in 6.2 to 8.2% of all adults with CHD, for an odds-ratio of 1.35 (1.3-1.4, p&lt;0.001) for diabetes of any kind to occur in patients with CHD as compared to adults without CHD. CHD and diabetes with the Swedish population at age 18-100 years CHD Total pop OR P Total no 25.000 (est) 7.562.648 With diabetes 1860 425.375 with diabetes 7.4% 5.6% 1.35 (1.3-1.4) &lt;0.0001 Conclusion. Based on estimated prevalence of adults with congenital heart disease in Sweden, the prevalence of diabetes seems to be higher in the CHD population than in the population without CHD, given an OR of 1.35.