tbuckley/cabot-search huggingface dataset:
Abstract 11007: Biochemical Urinalysis Predicts the Type of Decongestion and Worsening Renal Function due to Tolvaptan Administration in Patients With Acute Decompensated Heart Failure
Authors: Taiki Sakaguchi, Akio Hirata, Kazunori Kashiwase, Yoshiharu Higuchi, Yukihiro Koretsune, Hideo Kusuoka, Yoshio Yasumura
Journal: Circulation (2015)

Introduction: The diuretic response to tolvaptan (TLV) varies among patients with acute decompensated heart failure (ADHF). Although TLV is known to induce the excretion of free water, the accelerated excretion of sodium and urea has also been observed to varying degrees. Purpose: To classify the types of decongestion induced by TLV based on the initial induction of urinary sodium and urea excretion. Methods: We analyzed 90 ADHF patients who had been administered TLV. As markers of the initial TLV-induced excretion of sodium and urea, we measured changes in the fractional excretion of sodium (ΔFENa) and urea (ΔFEUN) prior to the first TLV administration and after eight hours. To evaluate the clinical course until normalization, 3-day and 7-day changes in body weight (ΔBW3, ΔBW7) and the inverse of hematocrit (Δ1/Ht3, Δ1/Ht7) after TLV administration were analyzed as markers of whole body and intravascular dehydration, respectively. Worsening renal function was assessed using 7-day changes in serum urea nitrogen (ΔUN7) and creatinine (ΔCr7) concentration. Results: Our analysis revealed negative correlations between ΔFEUN and ΔBW3 (r=-0.65, p&lt;0.001) and between ΔFENa and Δ1/Ht3 (r=-0.53, p&lt;0.001). Based on these findings, subjects were categorized into three groups. Firstly, subjects with positive and negative ΔFEUN were designated responders (n=60) and non-responders (n=30), respectively. Responders were further categorized based on the median value of ΔFENa (0.7%), where ΔFENa≥0.7 was the Natriuresis Group (n=30) and ΔFENa&lt;0.7 was the Aquaresis Group (n=30). During the 7 days after TLV administration, whole body dehydration was lowest in non-responders, intravascular dehydration was highest in the Natriuresis Group, and worsening renal function was lowest in the Aquaresis Group (Table). Conclusions: The initial induction of urinary sodium and urea excretion by TLV was able to predict the type of decongestion and worsening renal function in ADHF patients.
Abstract 17990: Ectopic Fat is Associated With Gender-specific Reductions in Left Ventricular Myocardial Perfusion Index During Dobutamine Stress
Authors: Michael E Hall, Tina E Brinkley, Timothy Morgan, Craig A Hamilton, Jennifer H Jordan, Richard B Stacey, Haroon Chugtai, Sandra Soots, William C Little, William G Hundley
Journal: Circulation (2013)

Background: Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing endothelial function. Accordingly, we evaluated the association of visceral fat and quantitative myocardial perfusion during peak dose dobutamine stress using MRI. Methods: We evaluated MRI myocardial perfusion index (MPI) in 59 individuals at risk for their first episode of symptomatic heart failure with a left ventricular (LV) ejection fraction &gt;45% and no MRI evidence of previous myocardial infarction or inducible ischemia. MPI was calculated after the first pass of gadolinium (by dividing the upslope of the signal intensity over time curve of the mid LV septum by the upslope of the LV cavity blood curve) after dobutamine and atropine were administered to achieve 80% of the maximum predicted heart rate response for age. Pericardial, subcutaneous (SQ), intraabdominal (IA) and retroperitoneal (RP) fat volumes were quantified using validated MRI techniques. All analyses were blinded to participant identifiers. Pearson’s coefficients were determined and a p-value of &lt; 0.05 was considered significant. Results: Participants averaged 66 ± 7 years in age; 34% were men, 27% African American, 43% diabetic, and 93% were hypertensive. Overall, pericardial, IA, and RP fat were negatively associated with MPI (Table). No fat depots were associated with reduced MPI in men. However pericardial (r=-0.57, p=0.02), IA (r=-0.34, p=0.04) and SQ fat (r=-0.42, p=0.01) were all negatively associated with MPI in women. Conclusions: Higher pericardial, IA and RP fat volumes are associated with reduced LV myocardial perfusion at peak dobutamine stress in women. These findings suggest visceral fat may contribute to abnormal microcirculatory coronary arterial perfusion syndromes, explaining why some women may exhibit more anginal symptoms despite typically lower grade coronary artery stenoses than men.
Abstract 18111: Engineered Cell Therapy With Embryonic Stem Cell-Derived Cardiomyocytes Encapsulated in Injectable Nanomatrix Gel Enhanced Engraftment and Promoted Cardiac Repair in Experimental Myocardial Infarction
Authors: Kiwon Ban, Hun-Jun Park, Sangsung Kim, Kyu-Won Cho, Jung Wook Hwang, Ho Jin Cha, Adinarayana Andukuri, Ho-Wook Jun, Young-sup Yoon
Journal: Circulation (2013)

Background: A significant barrier to the therapeutic use of stem cells is poor cell engraftment in vivo. To overcome this hurdle, studies have attempted to engineer stem cells using biomaterials. Particularly, injectable self-assembling nanomatrix gel has emerged as a highly promising biomaterial by providing a natural extracellular matrix-like microenvironment. Here, we evaluate the therapeutic potential of cardiomyocytes (CMs) derived from mouse embryonic stem cells (mESCs) encapsulated with injectable nanomatrix gel consisting of peptide amphiphiles incorporating cell adhesive ligand RGDS (PA-RGDS) on experimental myocardial infarction (MI). Methods and results: First, we examined the survival of CMs on RGDS. We cultured rat neonatal CMs on PA-RGDS for 7 days and found that higher than 90% of the CMs remained alive with well-defined CM structures as determined by live/dead and immuno stainings. Next, to test if PA-RGDS can increase the retention of CMs in the heart, we intramyocardially injected DiI (fluorescent probe)-labeled CMs into the uninjured hearts with or without PA-RGDS. Flow cytometry analysis with enzymatically digested heart tissues harvested at day 7 showed a ~3 fold higher rate of mESC-CM engraftment in the mice receiving CMs with PA-RGDS compared to those receiving only mESC-CMs (11.3% ± 0.4 vs 4.4% ± 0.2). Finally, we investigated the therapeutic effects of mESC-CMs with PA-RGDS on the MI in comparison with PBS control, CM alone, and PA-RGDS alone. Weekly echocardiography demonstrated that three groups (CM, PA-RGDS and CM+PA-RGDS) showed higher ejection fractions than the PBS group at week 2. However, in the CM or PA-RGDS alone groups, cardiac function was dramatically reduced between 3-4 weeks. In contrast, the CM+PA-RGDS group maintained cardiac function for up to 12 weeks. Confocal microscopic examination showed that injected CMs in PA-RGDS engrafted robustly in myocardium, formed clusters, integrated into host myocardium, and expressed representative CM proteins such as cTNT and MHC6/7. Conclusions: This study demonstrated that implantation of ESC-derived CMs encapsulated with PA-RGDS improves cell retention and cardiac function post-MI. This engineered cell therapy can develop into a novel option for treating MI.
Abstract 18068: Basis for a Major Genetic Alteration in Essential Hypertension: Inherited Defect in RBC-K Function and Oxygen Transport
Authors: Antonio R Delgado-Almeida, Maria C Delgado-Lelievre
Journal: Circulation (2013)

For decades, the pathogenesis and management of hypertension have been focused on dietary salt consumption, low potassium (K) intake, or hormonal factors triggering elevation of BP. In this context, our description of an inherited defect in RBC-K transport serially recorded in hypertensive subjects and in 52% of their normotensive adolescents offspring implies a genetic defect from erythropoietic cells and a biochemistry abnormalities in the circulating RBC as K-dependent pyruvate kinase activity for ATP synthesis, or allosteric K-O2 binding by hemoglobin, recently described by our Laboratory. Methods: A pedigree analysis was performed in randomized hypertensive patients (HT, aged ≥30-years) with essential hypertension (BP&gt;140/90 mmHg), confirmed in the last 3-years, and having low RBC K content (&lt;92 mmol/l of cell). Normotensive (NT) group were healthy subjects matched for sex-age-race and having normal BP and higher RBC-K. Family data includes sex-age-race of parents, siblings, spouses, children and presence of hypertension, diabetes (D), coronary heart diseases (CHD) and Stroke. For each family the number of deceased, age and cause of death were accurately obtained. Results: Fifty two hypertensive subjects disclosed family data (104 parents, 219 siblings, 24 spouses and 64 children= 411 cases) with large number of HT and CV disease: a) Parents: 63 hypertensive and 15 diabetic HT (75% incidence) with 3 AMI, 3 Stroke, 1 CRF and 21 CV deaths at age 58±7; b) Siblings: 142 out of 219 were HT (64.8 %; range 33-90%), 7 of them Stroke, 4 DM, CAD 15, 25 CV deaths at age 58±10 year; c) spouse 8 HT 33 %, children: &lt;30 years (9, 14% HT), ≥30 years, 15 HT, 23%), the remaining being NT. From 104 HT parents were born 142 HT (17 CV deaths, 125 alive, aged 52±6). In contrast, from 24 NT subjects there were: 48 parents, 153 siblings, 16 spouses and 48 children (total 265): a) Parents: 12 HT (25%), 2 AMI, 5 CAD, 3 DM, 13 no CV deaths at age 73±7 years; Siblings: 14 HT (9.2%) 7 DM, CV, no deaths, all alive aged 52±7; c) spouses HT 29%, children 7 HT, 14.5%. From 48 NT parents were born only 14 HT subjects. In Conclusion: This study strongly suggests the presence of a major hereditary defect in essential hypertension, involving defective RBC-K transport and function.
Abstract 18128: Prediction of Elastin Degradation in Aorta Using a Novel Infrared Spectroscopic Methodology
Authors: Rabee Cheheltani, Jayashree Rao, David A Vorp, Nancy Pleshko, Mohammad F Kiani
Journal: Circulation (2013)

Introduction: In vivo quantification of elastin degradation has significant implication in advancing diagnosis of abdominal aortic aneurysm (AAA) expansion. We hypothesize that Fourier transform infrared spectroscopy (FTIR) can be used to predict elastin content using a methodology that has the potential for assessing elastin degradation in a clinical setting. Here, a model of AAA was created by varying levels of enzymatic degradation in pig aorta and a multivariate model was developed based on acquired FTIR spectra of the specimens. This model was further validated in human AAA sections. Methods: Porcine aorta specimens (n=54) were cut into strips of 100 mg and divided into groups of elastase treated, collagenase treated or untreated by submerging them in enzyme or buffer solutions for different durations. After treatment, samples were cut into half for biochemical assay (Fastin elastin assay) and FTIR. For latter, 9 μm cross sections of frozen tissue were mounted on low-e slides and were scanned with an FTIR spectrometer. Average spectra of specimens were combined with values of elastin content from assay, to develop a partial least squares (PLS) regression model. To further validate, factor-1 matrix of model, was used as reference spectrum in a correlation map to visualize elastin in a section of human AAA wall. This specimen was excised from an aneurysm patient during their elective surgical repair, paraffin embedded, and sectioned on low-e and glass slides, for FTIR analysis and histology. Results and Conclusion: The multivariate model predicted elastin content of the specimens (varying between 0% and 80% d/w) with a strong correlation (R 2 =0.81) and could be used to map elastin in human AAA wall sections (Figure). In conclusion, our developed methodology predicts elastin degradation in the imaging modality of FTIR. Expanding this method to fiber optic modality has a potential for clinical assessment of elastin degradation in a minimally invasive fashion.
Abstract 10035: Oesophageal Heat Exchangers With a Diameter of 11mm or 14,7mm are Equally Effective for Conduction of Mild Therapeutic Hypothermia
Authors: Daniel C Schroeder, Maria Guschlbauer, Alexandra Maul, Simon R Finke, Peter Paal, Stephan A Padosch, Wolfgang A Wetsch, Bernd W Böttiger, Anja Sterner-Kock, Holger Herff
Journal: Circulation (2015)

Introduction: Induction of mild therapeutic hypothermia (MTH) is recommended for adult patients after out-of-hospital-cardiac-arrest (OHCA) [1]. Conventional surface cooling methods are simple to apply, but reveal inaccuracy during maintenance of MTH and are accompanied by more adverse events [2]. Internal cooling with an endovascular cooling device (ECD) is effective and reliable during maintenance of MTH, but is difficult to apply. Since the esophagus is located adjacent to the heart, aorta and inferior cava vein fast temperature conduction from and to the blood-stream could be achieved by use of a semi-invasive esophageal heat exchanger (EHE) that can be inserted easily and safely. Hypothesis: MTH can be conducted accurately, effectively, safely and without esophageal tissue damage with a newly developed EHE in pigs. Methods: Sixteen pigs (28.8±0.6kg) were randomly assigned to an EHE of 11mm (n=8) or 14.7mm (n=8) diameter. After induction of anesthesia, EHE were blindly inserted and connected to a chiller (HICO Variotherm 555, Hirtz &amp; Co.KG, Cologne, Germany). Via the EHE, pigs were cooled to a target temperature of 33°C, maintained at 33°C for 1 hour, then covered with a silver-blanket and rewarmed with a rate of 0,25°C/h. After 10h of rewarming esophagi including larynx and cardia were resected in their entire lengths and analyzed by means of histopathology. Pulmonary artery temperature was recorded continuously. Results: Mean cooling rates were 2.8±0.1°C/h (11mm) and 2.9±0.1°C/h (14.7mm) (p=0.41). Average deviations from target temperature during maintenance were 0.1±0°C in both groups (p=0.44). Rewarming rates were 0.17±0.03°C/h (11mm) and 0.19±0.02°C/h (14.7mm) (p=0.65). Occasional mild diffuse mononuclear acute inflammatory transepithelial infiltrates were found in the laryngeal region, but not in the esophagus. Conclusions: Use of the EHE for MTH in pigs seemed to be efficient, safe and reliable. References: [1] Bernard,S.A., et al., Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med, 2002. 346 (8) [2] Oh, S.H.et al., An observational study of surface versus endovascular cooling techniques in cardiac arrest patients: a propensity-matched analysis. Crit Care, 2015.
Abstract 17985: Deletion of Tissue Factor Pathway Inhibitor in Zebrafish Leads to Enhanced Thrombosis, Atherosclerosis, and Myocardial Infarction Injury
Authors: Scott J Hoffman, Karl J Clark, Tanya L Poshusta, Stephen C Ekker, Robert D Simari
Journal: Circulation (2013)

Background: The extent to which tissue factor pathway inhibitor (TFPI) may regulate the extrinsic clotting cascade, atherogenesis, and MI is uncertain. Reverse genetic studies in the mouse, including deletion of the TFPI Kunitz-1 (K1) domain, have been hindered by intrauterine lethality. We sought to determine the role of TFPI in an alternative animal model, by knocking out the zebrafish ortholog tfpia . Methods and results: High-efficiency transcription activator-like effector nucleases (TALENs), targeting the 5’ region of tfpia, were microinjected into 1-cell zebrafish embryos. Sequence analysis of genomic DNA derived from adult caudal fin tissue revealed indels causing a frameshift mutation and premature stop codon prior to K1. Somatic mutants were outcrossed to WT fish, and the embryos were screened for germline mutations. Founders (F 1 ) were raised and incrossed to produce embryos (F 2 ), including approximately 25% with the desired biallelic null mutation ( tfpia -/- ) that were physically and developmentally indistinguishable, but functionally disparate from heterozygous ( tfpia +/- ) or WT ( tfpia +/+ ) siblings. At 6 days post-fertilization (dpf), F 2 tfpia -/- larvae exhibited a reduction in time to occlusion of the dorsal aorta after exposure to ferric chloride, which was more significant in 6-dpf F 3 tfpia -/- larvae (generated by incrossing F 2 tfpia -/- adults) lacking a possible maternal effect. Furthermore, F 2 tfpia -/- fish had in vivo evidence of increased fatty streaking as late larvae, after receiving a high cholesterol diet, and enhanced cardiac injury as adults, 4 days after cryoinjury-induced MI. Conclusions: Deletion of tfpia does not significantly effect zebrafish development, but leads to hypercoagulability in early larvae, enhanced atherogenesis in late larvae, and increased injury related to MI in adults, indicating a fundamental role for TFPI in the pathogenesis of cardiovascular disease.
Abstract 18011: The Impact of Institutional Stage I Surgical Volume on Mortality, Length of Stay, and Hospital Charges in Infants With Hypoplastic Left Heart Syndrome, a Review of the Texas Inpatient Public Use Data File From 1999-2012
Authors: Hari P Tunuguntla, Wendy Nembhard, Mary K Ethen, Mark A Canfield, David E Fixler, Shaine A Morris
Journal: Circulation (2013)

OBJECTIVE: Studies to date have suggested an association between center surgical volume and lower mortality in children undergoing heart surgery. While this has been investigated in national sampled data and registries, contemporary statewide data specifically relevant to public health insurance have not been investigated in detail. METHODS: The Texas Inpatient Public Use Data File, a database of hospital discharges in the state of Texas, was queried from 1999-2012. Infants with the diagnosis of HLHS undergoing a Stage I Palliation (S1P) as defined by an aortopulmonary shunt (ICD-9 39.0) or right ventricle to pulmonary artery conduit (35.92) were included. Univariable and multivariable analyses were used to investigate the relationship between center S1P surgical volume and hospital mortality, length of stay, and total charges. The association between insurance status and race/ethnicity and mortality were also investigated. RESULTS: Of &gt;37 million discharges, 780 infants with HLHS underwent S1P at 14 hospitals. The mean number of annual S1Ps at each hospital varied from &lt;1 to 16.1 with 53% of infants undergoing surgery at a center with &gt;15 S1Ps/year. Fifty-four percent of the infants were covered by public insurance. In univariable analysis, lower surgical volume was associated with increased mortality, with mortality in hospitals performing &lt;5 surgeries per year 30.6%, 5-15 surgeries per year 27.1%, and &gt;15 surgeries per year 15.6% (p for trend&lt;0.001). Higher surgical volume was not associated with length of stay (Rho=0.004) or total charges (Rho=0.057). In multivariable analysis, adjusting for discharge year and preterm birth, lower surgical volume remained associated with increased mortality (compared to &gt;15 surgeries/year, &lt;5/year 2.62, 95%CI 1.78-3.85, 5-15/year 2.44, 95%CI 1.40-4.28). No categories of race/ethnicity or insurance status were associated with increased mortality. CONCLUSION: Institutions with higher Stage I surgical volume had lower HLHS hospital mortality, without increased charges or length of stay. Given the large population of infants covered by public insurance, governmental health care plan support of regionalization of care in neonatal HLHS has the potential to improve mortality rates in this population.
Abstract 18003: 9p21 is Associated With Risk of First but Not Recurrent Major Adverse Cardiovascular Events
Authors: Riyaz S Patel, Folkert W Asselbergs, Arshed A Quyyumi, Harry Hemingway, Aroon Hingorani, Michael V Holmes
Journal: Circulation (2013)

Background: The chromosome 9p21 locus is a recognized risk factor for coronary heart disease (CHD). Emerging data suggest that it may not confer additional risk in patients with established CHD. We sought to examine the association of 9p21 with first and recurrent major adverse cardiovascular events (MACE) through systematic review and meta-analysis. Methods: We searched PubMed and EMBASE from inception to May 2013. All prospective studies reporting association for 9p21 and MACE (comprising any combination of death, fatal/nonfatal MI, revascularisation) were included. We supplemented identified studies with two unpublished cohorts. Data on clinical setting (healthy/established CHD), outcomes assessed and per-allele effect size and confidence limits were extracted. In 6 studies reporting data separately by 9p21 genotype, we estimated the per-allele effect using meta-regression. We performed a meta-analysis, stratified by clinical setting, and compared estimates using the Altman &amp; Bland test for interaction. Results: We identified 32 cohorts of which 3 were excluded as reported estimates could not be incorporated into meta-analysis. In 15 studies, of 161,043 individuals predominantly free of CHD and with 14,827 events, 9p21 associated with a pooled HR for a first event of 1.19 (95% CI: 1.17, 1.22). In contrast, in 14 studies of 25,059 patients with established CHD, reporting 4,628 events, the pooled HR of 9p21 for recurrent MACE was 1.02 (95% CI: 0.98, 1.06). There was strong evidence of heterogeneity between the estimates for first and recurrent MACE (P=1.1x10-11 for heterogeneity). Conclusions: In contrast to association with first MACE, 9p21 may not associate with recurrent MACE in patients with established CHD. This may reflect mechanistic differences in disease onset versus progression or attenuation of effect by CHD therapies. With implications for genetic risk prediction, further studies are needed to precisely define the role of 9p21 in those with CHD.
Abstract 18124: Skeletal Muscle Proteomic Signature in Pulmonary Arterial Hypertension
Authors: Aude Pflieger, François Potus, Simon Malenfant, Sandra Breuils-Bonnet, Sebastien Bonnet, Steeve Provencher
Journal: Circulation (2013)

Introduction: Most pulmonary arterial hypertension (PAH) patients exhibit severe dyspnea and fatigue resulting in restricted exercise capabilities and poor quality of life. Numerous observations suggest that exercise limitation in PAH is not solely due to cardio-pulmonary impairment, but that other determinants such as skeletal muscle abnormalities are involved. In order to better understand the origins of exercise limitation in PAH, we studied the proteomic signature of skeletal muscle impairment in PAH. Methods and results: Muscle proteins from 4 idiopathic PAH patients and 4 matched controls were extracted following quadriceps muscle biopsy. Fractioned peptides were then tagged using an isobaric Tags for Relative and Absolute Quantitation (iTRAQ, ABsciex) specific for each patient. Tagged peptides were then mixed, fractioned, identified and quantified using mass spectrometry quantitative method. Over 900 proteins were identified using iTRAQ analysis, among them, 9 were under-expressed and 7 were over-expressed in all iPAH patient quadriceps. More than 75% of the under-expressed proteins are involved in oxidative metabolism and most other highlighted proteins play a role in myogenesis. In addition, structural differences between control and PAH skeletal muscles were explored by electronic microscopy. PAH skeletal muscles had decreased mitochondrial density and impaired mitochondrial structure resulting in abnormal metabolism. Finally, PAH skeletal muscles had impaired micro-vessels structure and decreased in their density. Conclusions: Proteomic data allowed us to highlight proteins that could be responsible for exercise limitation in PAH. Taken together with electronic microscopy experiments, these data suggest that as shown in both the lungs and the right ventricle (RV), impairment of oxidative metabolism is also present in skeletal muscles of PAH patients. Similarly to the RV, metabolism unbalanced is associated with abnormal mitochondria and micro-vessels. In addition to shedding light on exercise limitation in PAH, this study might lead to the discovery of an early and less invasive diagnostic method for PAH.