tbuckley/cabot-search huggingface dataset:
Abstract 12055: Impaired Right Ventricular Function Affects Survival After Surgical Left Ventricular Reconstruction
Authors: Lotte E Couperus, Victoria Delgado, Meindert Palmen, Laurens F Tops, Marieke E Van Vessem, Hariette F Verwey, Robert J Klautz, Martin J Schalij, Saskia L Beeres
Journal: Circulation (2015)

Introduction: The determinants of survival after surgical left ventricular reconstruction (SVR) in ischemic heart failure remain not fully elucidated. Several left ventricular (LV) parameters have been associated with prognosis. The role of right ventricular (RV) function, however, remains to be determined. Hypothesis: Impaired preoperative RV function is associated with worse outcome in patients undergoing SVR. Methods: Consecutive patients (130 patients; age 62±10 years; 79% male; LV ejection fraction [LVEF] 27±7%; urgent surgery in 22%) underwent SVR between 2006 and 2012. Biventricular function was assessed by echocardiography before surgery. Parameters of impaired RV function were RV fractional area change (RVFAC) &lt;35%, tricuspid annular plane systolic excursion (TAPSE) &lt;16mm and RV longitudinal peak systolic strain (RV LPSS) ≥-19%. The independent association between these RV functional parameters and mortality was assessed in several non-nested multivariate analyses. Furthermore, the additive effect of multiple impaired RV parameters on mortality was assessed. Results: Survival 30 days after SVR was 89%. Impaired RVFAC (HR 3.59, 95%CI 1.21-10.68, p=0.02), TAPSE (HR 2.96, 95%CI 1.05-8.35, p=0.04) and RV LPPS (HR 3.78, 95%CI 1.11-12.85, p=0.03) were independently associated with 30 day mortality, after adjusting for LVEF, the need for urgent surgery and surgery time. Moreover, a higher number of impaired RV parameters per patient was independently associated with increased mortality (HR 5.57, 95%CI 0.94-32.85, p=0.06 for 1 impaired parameter; HR 6.90, 95%CI 1.20-39.76, p=0.03 for 2 impaired parameters; HR 21.27, 95%CI 3.11-145.56, p&lt;0.01 for 3 impaired parameters). Survival curves for impaired versus normal RVFAC, TAPSE and RV LPSS respectively and for multiple impaired parameters are presented in the figure. Conclusion: Impaired pre-operative RV function is associated with increased 30 day mortality in patients undergoing SVR.
Abstract 18355: Human S100/calgranulin Accelerates Calcific Valve Disease and Promotes Cardiac Hypertrophy in Chronic Kidney Disease in a RAGE-Dependent Manner
Authors: Ling Yan, Liby Mathew, Bijoy Chellan, Brandon Gardner, Judy Earley, Tipu S Puri, Marion A Hofmann Bowman
Journal: Circulation (2013)

Purpose: Serum S100A12 and FGF 23 are biomarker for cardiovascular mortality in patients with chronic kidney disease (CKD). We test the hypothesis that S100/calgranulin accelerates cardiovascular disease in CKD. Methods: Human S100/calgranulin is expressed using a bacterial artificial chromosome containing genes and regulatory elements for S1008/9 and S100A12 (60kb) in C57BL6/J mouse (hBAC-S100). CKD was induced in hBAC-S100 mice and in wild type (WT) littermate mice by surgical ligation of the ureters. The heart and aorta were analyzed after 10 weeks of CKD. Results: S100A12 protein is expressed in myeloid cells and in serum of hBAC-S100 mice (25ng/ml serum), and increased further in response to CKD. hBAC-S100 mice with CKD developed diastolic dysfunction, ectopic cardiac calcification, hypertrophy and fibrosis measured by in-vivo echocardiography, heart weight, histology and gene expression of ANP, β-MHC, TGF-β, CTGF, and Col 1a1. Serum FGF23 was equally increased in WT/CKD and hBAC-S100/CKD compared to sham operated animals. However, intra cardiac expression of FGF23 mRNA (6 fold) and protein (2 fold) was increased only in hBAC-S100, and co-localizes to osteoblast-like cells nearby calcified fibrous tissue of the aortic and mitral valve. However, cultured cardiac fibroblasts (and VSMC) in response to calcification- inducing medium containing 10mM glycerophosphate and 10nM dexamethasone up regulate ALP, BMP-2, and MGP, but reduced FGF23 mRNA by 90%. This suggests that FGF23-positive osteoblast like cells in the heart of hBAC-S100 might stem from cells other than fibroblasts. hBAC-S100 mice lacking RAGE, the endogenous receptor for S100A12, showed attenuation of ectopic cardiac calcification, LVH, diastolic dysfunction and cardiac FGF23 expression when subjected to CKD, and the cardiac phenotype was similar to WT mice with CKD. Furthermore, aortic valve calcification develops spontaneously in 10-12-month old hBAC/S100 mice, indicating that CKD accelerates this process in hBAC/S100 mice, but is not required. Conclusion: Myeloid-derived S100/calgranulin promotes calcific valve disease in a RAGE dependent manner, possibly by selective enrichment of FGF23-positive osteoblast like cells not stemming from cardiac fibroblasts.
Abstract 18479: New Heart Failure Diagnostic and Prognostic Biomarkers Discovered Using Capillary Electrophoresis Coupled to Mass Spectroscopy
Authors: Matthieu Berry, Michel Galinier, Clement Delmas, Pauline Fournier, Franck Desmoulin, Annie Turkieh, Manon Barutaut, celine Caubere, Harald Mischak, Andrea Kalogeropoulos, Vasiliki Georgiopoulou, Javed Butler, Fatima Smih, Philippe Rouet
Journal: Circulation (2013)

Blood heart failure (HF) biomarkers such as the natriuretic peptides (NP) are widely used but the NP biomarker family has limitations and HF diagnosis remains too often complicated because of atypical presentations and the need of specialized care access. More specific and accurate biomarkers with detection method allowing for facilitated large scale HF screenings are required. Indeed, 30 % of the patients admitted to emergency care for acute dyspnea have a BNP concentration in a « grey zone » that do not allow for diagnosis. Thus, diagnosis of these patients is costly and time-consuming while a rapid medical care of the patient has a positive impact on his health and reduces the treatment cost. Therefore, we have launched a prospective multicentric case-control study and investigated for urinary polypetides specific to acute (AHF) or chronic heart failure (CHF), using a capillary electrophoresis-mass spectroscopy strategy (CE-MS). Based on a screen of the urinary proteome of patients (CHF, AHF, and healthy controls matched for cardiovascular risk factors), we revealed a panel of polypeptides specific to HF. One polypeptide (X64, patent pending) seemed very relevant because it could discriminate AHF and CHF with a high specificity and specificity (AUC = 0,99; p&lt;0,0001). X64 plasma levels were assessed within Atlanta (n=340, follow-up 3 years) and Toulouse (n=187, follow-up 6 years) cohorts. The Atlanta cohort revealed that X64 level is associated with major clinical events: HR: 1.23 per 100 ng/mL (95% CI: 1.06 to 1.43); P=0.005 and with HF admissions: IRR: 1.20 per 100 ng/mL (95% CI: 1.00 to 1.44); P=0.05. Moreover, the Toulouse cohort revealed that high X64 levels were strong predictors of cardiac death (p&lt;0.0001). Our work provides with new biomarkers allowing for HF diagnosis in the BNP « grey zone » or prognosis and therefore allow for a better care of the HF patients at the hospital but also in general care.
Abstract 18397: Left Ventricular End Diastolic Pressure as a Tool to Detect Intracoronary Ergonovine-Induced Myocardial Ischemia During Provocation Test
Authors: Ho-Jun Jang, Won-Heum Shim
Journal: Circulation (2013)

A drug-induced coronary spasm provocation test is regarded as the gold standard for detection of variant angina. However, a suitable method to detect myocardial ischemia during provocation test is still lacking. We evaluated the feasibility of left ventricular end diastolic pressure (LVEDP) as a tool to detect myocardial ischemia caused by intracoronary (IC) bolus injection of ergonovine. Twenty-nine patients having chest pain without any significant (&gt; 80%) coronary stenosis underwent IC ergonovine provocation test. Epicardial artery spasm of more than 90% was considered as positive. LVEDP was monitored during the entire procedure using a pig-tail catheter. Of the overall 29 patients, ischemic symptom occurred in 16 (55%) and provocation positive was confirmed in 6 (21%). The amount of LVEDP change (ΔLVEDP) was significantly larger in symptomatic group (5.6±4.2 vs. 1.2±2.0 mmHg, p=0.002). The optimal cut-off value of ΔLVEDP for symptom was 4.4 (area under the curve 0.803, sensitivity 69%, specificity 92%) (Figure 1). Of the 6 patients of positive test, five occurred in RCA, one in LAD. Two patients with big patent LCX were not associated with LVEDP elevation more than 4.4 despite significant RCA spasm (Figure 2). Except for the 2, LVEDP elevated significantly in positive test group (7.9±2.9 mmHg, p &lt;0.001, n=4). Elevation of blood pressure and heart rate by IC ergonovine did not correlate with ΔLVEDP (p=0.142 and 0.154, respectively). In conclusion, ΔLVEDP is a specific marker for myocardial ischemia independent of hemodynamic parameters. LVEDP may aid detection of myocardial ischemia which is not associated with significant epicardial spasm during provocation test.
Abstract 18478: Depletion of Prolyl-4-Hydroxylase Domain 3 Protects Hearts From Injury Induced by Ischemia/Reperfusion and Inhibits Cardiomyocyte Apoptosis
Authors: Liang Xie, Zhongjing Wang, Julius Aitsebaomo, Xinchun Pi, Monte S Willis, Winston Patterson
Journal: Circulation (2013)

PHD3, a member of a family of Prolyl-4 Hydroxylase Domain (PHD) proteins, has long been considered as a pro-apoptotic protein. Although the pro-apoptotic effect of PHD3 requires its prolyl hydroxylase activity, it is independent of HIF-αs, the common substrates of PHDs. PHD3 is highly expressed in the heart, however, its role in cardiomyocyte apoptosis remains unclear. Whether depletion of PHD3 is cardioprotective need to be determined. To determine whether inhibition or depletion of PHD3 inhibits cardiomyocyte apoptosis and attenuates myocardial injury induced by ischemia-reperfusion, PHD3 knockout mice and their littermate control mice were subjected to left anterior descending (LAD) coronary artery ligation for 40 minutes and then released for reperfusion. By performing Evan’s Blue, triphenyl-tetrazolium chloride and TUNEL staining, we demonstrated that myocardial injury and cardiomyocyte apoptosis were significantly attenuated in PHD3 knockout mice. There were no changes of HIF-1α protein level, the expression of HIF target genes or myocardium capillary density in PHD3 null mice. In vitro, DNA damage response (DDR) and cardiomyocyte apoptosis induced by oxidative stress were significantly inhibited by prolyl hydroxylase inhibitor or depletion of PHD3. Interestingly, DDR activated by hypoxia-reoxygenation (H/R) was also inhibited by inhibition of PHD3. Therefore, we conclude that depletion or inhibition of PHD3 protected hearts from injury induced by ischemia-reperfusion and inhibited cardiomyocyte apoptosis induced by oxidative stress or hypoxia-reperfusion. DDR induced by oxidative stress was dramatically inhibited by depletion or inhibition of PHD3, which may partly contribute to the cardioprotective effect of depletion of PHD3.
Abstract 12202: Inhaled Nitric Oxide Improves Artificial Circulation and Clinical Outcomes After Prolonged Cardiac Arrest
Authors: Matthias Derwall, Andreas Ebeling, Anne Brücken, Christoph Nix, Kay W Nolte, Michael Fries
Journal: Circulation (2015)

Introduction: Primary survival after cardiac arrest can be improved by optimizing circulation during CPR when using a minimal invasive left ventricular assist device (iCPR). Hypothesis: Inhaled nitric oxide may facilitate transpulmonary bloodflow during iCPR and thereby improve the functional outcome following cardiac arrest. Methods: Ventricular fibrillation (VF) was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20ppm of inhaled nitric oxide (iNO, n = 10) or 0ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following return of spontaneous circulation (ROSC). Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains harvested for neurohistopathologic evaluation. Results: All animals in both groups achieved ROSC. iNO treated animals reached significantly higher iCPR flow during CPR (1.81 ± 0.30 L/min compared to 1.64 ± 0.51, p&lt;0.001), leading to significantly higher coronary perfusion pressure (CPP) values during the 6 minutes of CPR (25 ± 13 vs. 16 ± 6 mmHg, p = 0.002). iNO animals showed significantly lower S-100 serum levels thirty minutes post ROSC (0.26 ± 0.09 vs. 0.38 ± 0.15 ng/mL, p = 0.048), as well as lower blood glucose values 120-360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO treated animals as estimated with OPC (3 ± 2 vs. 5 ± 1, p = 0.036 on days 3 to 5). While n = 3 iNO treated animals were able to successfully participate in the spatial memory task, none of the controls were able to do so. Neurohistopathological examination of cerebral structures prone to ischemia-reperfusion injury revealed a trend towards less cerebral lesions in Neocortex, Archicortex, and Striatum when animals had been treated with iNO. Conclusions: In a model of prolonged cardiac arrest, the administration of 20ppm iNO during and following iCPR improved transpulmonary bloodflow and mitigated post-aggression metabolism, indicated by lower serum glucose levels. These effects translated into improved clinical outcomes in iNO treated animals.
Abstract 18599: Comparison of Outcomes for Eldelry Patients Treated With Pre-Hospital Reduced Dose Fibrinolytic Followed by Urgent Percutaneous Coronary Intervention versus Percutaneous Coronary Intervention Alone for Treatment of ST-Elevation Myocardial Infarction
Authors: Amirreza Solhpour, Kay-Won Chang, Ali E Denktas, Prakash Balan, Stefano M Sdringola, Chunyan Cai, H Vernon Anderson, Richard W Smalling
Journal: Circulation (2013)

Background: The ultimate treatment goal in ST-elevation myocardial infarction (STEMI) is rapid restoration of coronary blood flow. In general, fibrinolysis can be initiated earlier than primary percutaneous coronary intervention (PPCI) but it could be associated with bleeding risk, especially in elderly patients. For over 7 years we have used a strategy of field evaluation for STEMI using 12 lead EKGs obtained and transmitted by emergency services (EMS) personnel with over-read by emergency center physicians. Appropriate STEMI patients receive pre-hospital reduced dose fibrinolytic (10 units reteplase) along with aspirin, clopidogrel, and heparin, and are transported to our STEMI center for urgent PCI (termed FAST-PCI strategy). Methods: We examined the data for elderly patients (≥ 75 years) treated by either a FAST-PCI strategy or conventional PPCI. We compared demographic, clinical, angiographic data and outcomes. Ischemic time was defined as time from onset of pain to device activation. Bleeding was assessed using GUSTO criteria. Results: Between February 2006 and April 2013, we treated 1323 STEMI patients of which 214 (16.2%) were ≥75 years. FAST-PCI was employed in 120 (56%) and PPCI in 94 (44%) patients. The groups were well matched for age, cardiac risk factors and ischemic time. Data are shown in the table. Conclusions: In the elderly patients, compared with a PPCI strategy, the FAST-PCI strategy was associated with earlier infarct artery patency (Less TIMI 0 flow) and reduced 30 day mortality, as well as with lower incidence of cardiogenic shock at presentation without a bleeding penalty.
Abstract 18379: Echocardiography for Right Ventricular Failure Prediction After Implantation of Left Ventricular Assist Devices: Preliminary Results From a Prospective Cohort Study
Authors: Andreas P Kalogeropoulos, Vasiliki V Georgiopoulou, Sarawut Siwamogsatham, Daniel Sims, Anita Kelkar, Kris Wittersheim, Ann Pekarek, Maria A Pernetz, Duc Q Nguyen, Andrew L Smith, J David Vega, Javed Butler
Journal: Circulation (2013)

Background: Right ventricular failure (RVF) occurs in 20%-40% of left ventricular assist device (LVAD) recipients. Preoperative clinical scores inadequately predict RVF risk in these patients. Methods: Beginning 6/2012, all adults with INTERMACS ≥2 profile scheduled for LVAD implantation, without planned right ventricular (RV) support, were prospectively enrolled in an ongoing study evaluating standard and speckle-tracking echocardiographic parameters of RV function for RVF prediction. Preoperative echocardiograms were performed 5±5 days prior to LVAD implantation by study protocol. The primary endpoint was RVF, defined (by INTERMACS) as need for (1) inotropes or pulmonary vasodilators any time past 7 days post-LVAD implant with concomitant high central venous pressure and low cardiac index or (2) mechanical RV support. The secondary endpoint was RVF or death from any cause. Results: As of 5/2013, 26 patients have been enrolled. Table 1 summarizes the preoperative clinical and hemodynamic characteristics. At 30 days, 7 patients (26.9%) developed RVF and 3 (11.5%) died. Intensive care length of stay (LoS) was 8.0±3.6 days and total LoS was 16.3±9.5 days. Among echocardiographic parameters (Table 2), RV global longitudinal strain (GLS) was the strongest predictor of RVF with a C statistic of 0.86 (95% CI, 0.60-0.99). At a cut-off -6.0%, sensitivity and specificity were 86% and 79%, respectively. Similarly, RV GLS was the strongest predictor of death or RVF combined. Standard RV function parameters were weak outcome predictors. Conclusion: Among preoperative echocardiographic parameters, RV GLS by speckle tracking appears to be the strongest predictor of post-LVAD RVF.
Abstract 18424: Cardiovascular Death in Student-Athletes and in the General Population: Are Trained Athletes Really at Higher Risk?
Authors: Stephanie Rutten-Ramos, Ross F Garberich, Tammy S Haas, Barry J Maron
Journal: Circulation (2013)

Background: Sudden death due to cardiovascular (CV) disease in competitive athletes has become a highly visible concern in the physician and lay communities. Previous studies have reported mortality rates from CV disease in young athletes as 2 to &gt;4/100,000 person-years. However, while CV death rates are believed to be increased for competitive athletes, they have not been placed in the context of normal CV mortality within the general U.S. population. Methods: Using 2002 to 2006 cause of death (COD) data from CDC Division of Vital Statistics and population data from U.S. Census Bureau, CV-associated death rates were calculated by gender for populations ages 15-19 and 20-24 years. Comparisons were made to mortality rates obtained for high school athletes in Minnesota and U.S. college athletes. Results: Within the general population, CV death rates were 1.9 and 3.5/100,000 person-years for ages 15-19 and 20-24, respectively. When compared to death rates of 0.7/100,000 athlete-years in competitive high school athletes, the rate of CV death in the general population is 2.7 fold higher. Similarly, when compared to the reported death rate of 2.3/100,000 athlete-years, in NCAA athletes the rate of CV death in the general population is 1.5-fold higher. General population CV death rates were 1.9-fold higher for males compared to females in both age groups, and similar to competitive athletes for which male deaths predominate 9:1 (Table). Within the general population, African-American males and females, ages 15-19, had CV death rates 2-fold higher than their white counterparts, and for ages 20-24, African-American men/women had rates 2.3 and 2.7-fold higher than white counterparts, respectively. Conclusion: Although high school and college student-athletes are believed to be at increased risk for CV death, comparisons to the general population of similar age suggest otherwise with competitive athletes actually less likely to experience fatal CV events.
Abstract 12483: Perceived CVD and Type 2 Diabetes Risk and Knowledge is Low Among Well-Educated Chinese Mothers
Authors: Jill Howie Esquivel, Jia Guo, Jyu-Lin Chen
Journal: Circulation (2016)

Introduction: Non-communicable diseases (NCDs) such as CVD and type 2 diabetes (T2D) account for up to 80% of deaths in China. An intervention that reduces CVD and T2D risk in early motherhood could have great impact on the health of Chinese. However, little is known about mothers’ perception of risk for both CVD and T2D. Therefore, we aimed to identify knowledge level and perceived CVD and T2D risk among Chinese women with young children. Methods: A cross-sectional study design was used to recruit mothers with children aged 3-5 years in 2 preschools in Hunan Province. Validated questionnaires and measures for Chinese populations were completed to assess: Child feeding practice, family eating and physical activity habits, body weight, waist circumference, parental risk perception for diabetes, and CVD risk survey. Multivariate regression was used to determine variables that independently predicted higher perceived risk. Results: Mothers’ (N=196) were mean age 31.0 ±4.3, mean BMI 19.9 ± 3.9, and highly educated as 54% (n=106) had completed college/graduate education. Just 7.3% were overweight/obese (n=14), but 37% (n=73) had waist circumference &gt;80cm. Using the CVD risk survey, 37% (n=73) and 45% (n=88) of mothers reported no perceived risk for coronary heart disease or hypertension, respectively. The parental risk perception for diabetes survey demonstrated low T2D knowledge scores (4.1, range 0-11), 55% (n=107) perceived no risk for developing T2D, and 14% (n=27) reported moderate/high risk for T2D. Predictors associated with increased perceived risk for CVD or T2DM included: Worry about developing T2D (p = .0001) and having blood-related relatives diagnosed with CVD or T2D (p = .003, p = .024 respectively). Conclusions: This is the first known study of perceived CVD and T2D risk in early motherhood in China. Despite highly educated participants, more than one-third perceived no risk for heart disease, almost half no risk for hypertension and more than one-half no risk for T2D, although the vast majority of Chinese will die from NCDs such as CVD and T2D. Having blood relatives increases perceived risk of NCDs but it is speculated that education for young mothers regarding their risk and preventive behaviors would improve CVD outcomes.