tbuckley/cabot-search huggingface dataset:
Abstract 18879: Procedural Success in the CONFIRM Trial is Independent of Use of Irrigated or Non-irrigated Ablation Catheters
Authors: David E Krummen, Amir A Schricker, Gautam Lalani, Tina Baykaner, Sanjiv M Narayan
Journal: Circulation (2012)

Introduction: Irrigated ablation catheters have become the preferred radiofrequency (RF) catheter for atrial fibrillation (AF) ablation due to greater energy delivery, particularly in areas of low blood flow. We hypothesized, however, for AF ablation not routinely incorporating mitral isthmus ablation (and therefore minimizing ablation within the coronary sinus), that non-irrigated ablation catheters would be non-inferior to irrigated catheters. Methods: We analyzed the results of the CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation, FIRM) trial with respect to type of ablation catheter used: irrigated (8.5 French, Thermocool, Biosense-Webster, Diamond Bar, CA) and non-irrigated (8 French, 8-mm tip, Blazer XP, Boston Scientific, Natick, MA). We analyzed the FIRM-guided and FIRM-blinded ablation limbs separately; analysis was performed on an intention-to-treat basis, and crossovers were not permitted. Statistics were calculated using SPSS Version 19 (IBM, Armonk, NY). Results: In 92 patients (age 62±9 y, EF 54±14%) undergoing 107 consecutive ablation procedures, overall freedom from AF and all atrial tachyarrhythmias (ATs) was 70.6% in the FIRM-guided and 39.1% in the FIRM-blinded limbs (p=0.003). Freedom from AF and ATs with the non-irrigated catheter was 87.5% in the FIRM-guided and 42.1% in the FIRM-blinded limbs, while with the irrigated catheter was 58.3% and 25.0% respectively, thus meeting the criteria for non-inferiority. The figure shows arrhythmia-free survival in the FIRM-guided limb of the CONFIRM trial for irrigated and non-irrigated catheters. Conclusions: The CONFIRM trial showed significantly improved ablation results with FIRM-guided ablation, independent of the use of irrigated or non-irrigated ablation catheters. Future studies should examine if similar outcomes are seen with other ablation energy sources such as cryoablation or high-frequency ultrasound.
Abstract 17600: Lipid Phosphate Phosphatase 3 Negatively Regulates Smooth Muscle Cell Phenotypic Modulation and Limits Neotimal Hyperplasia
Authors: Manikandan Panchatcharam, Sumitra Miriyala, Abdelghaffar Salous, Jessica Wheeler, Anping Dong, Manjula Sunkara, Diana Escalante-Alcalde, Andrew J Morris, Susan S Smyth
Journal: Circulation (2011)

Rationale: A common SNP in PPAP2b associates with risk of coronary artery disease (CAD). PPAP2b encodes the lipid phosphate phosphatases (LPP) 3 that degrades and thereby may attenuate lysophosphatidic acid (LPA) responsiveness of cells. However, a pathophysiologic role for LPP3 in vascular cells remains to be established. Objective: To determine the role and mechanisms by which LPP3 regulates vascular SMC responses. Methods and Results: Robust expression of LPP3 occurs in experimental atherosclerosis and following arterial injury, where SMC serve as the predominant source. Mice with selective inactivation of LPP3 in SMC display an exaggerated neointimal response to carotid ligation injury. Gain- and loss-of-function approaches establish that a major function of LPP3 in isolated SMC cells is to attenuate proliferation, ERK activity, Rho activation and migration in response to serum and LPA. These effects are, at least partially, a consequence of LPP3-catalyzed LPA hydrolysis. We did not observe systemic effects of SMC-deletion of LPP3 on either circulating LPA levels or hemodynamic parameters, suggesting that the predominate effects of LPP3 on SMCs are exerted in the local environment by regulating SMC responses. Conclusions: These findings implicate LPP3 as an important negative regulator of SMC phenotypic modulation and indicate that changes in LPP3 expression control the development of neointima by limiting SMC proliferation, migration, and vascular inflammation.
Abstract 18803: Myeloid Derived S100/calgranulins Promotes Visceral Obesity, Diabetes and Calcific Aortic Valve Disease in Transgenic Mice
Authors: Ling Yan, Judy Earley, Brandon Gardner, Honggang Ye, Marion Hofmann Bowman
Journal: Circulation (2012)

Circulating serum levels of human S100/calgranulins have been associated with diabetes, coronary artery disease and increased cardiovascular mortality in clinical studies. To test whether S100/calgranulins are biomarker of inflammation or directly mediate disease, we generated a novel humanized mouse with transgenic expression of human S100/calgranulin by expression of a bacterial artificial chromosome of the human S100/calgranulin gene cluster containing genes and regulatory elements for S100A8/9 and S100A12 (60kb) in C57BL6 mice. F3 animals of the hBAC-S100 mice their wild type (WT) control littermate mice on regular rodent chow diet or on high fat diet (HFD) were studied. Results: hBac-100 mice express human S100A12 in circulating myeloid cells and S100A12 was present in the serum of hBAC-S100 mice (25 ng/ml serum), but was not detected in WT mice. Moreover, serum IL-6 was elevated in hBAC-S100 mice at age 3 and 12 month. hBAC-S100 mice developed increased visceral adiposity after 12 months on regular chow diet (25% vs 12% body fat upon DEXA scanning, p&lt;0.05), or after 3 months on HFD. White adipose tissue (WAT) of lean hBAC-S100 age 4 weeks showed increased expression of T- and B cell marker and no macrophage marker compared to WT, followed by increase in gene expression for F4/80, CD68 and MCP-1 in obese hBAC-S100. Importantly, impaired oral glucose tolerance and hyperinsulinemia preceded the onset of adiposity in hBAC-S100 mice. Metabolic cage studies indicate reduced oxygen consumption and CO2 production as one mechanism leading to adiposity. This phenotype was attenuated in hBAC-S100 mice lacking RAGE. Moreover, 12-months old hBAC-S100 mice develop calcification of the aortic valve leafleat with presence of osteoblast-like cells in the ascending aortic media upon staining with Alizarin Red S. In vivo ECHO showed abnormal mitral valve doppler flow with reduced ratio of early (E) to atrial (A) filling (E/A ratio 0.85 and 1.22, p=0.03) indicative of diastolic dysfunction. Conclusion: Circulating myeloid derived human S100/calgranulin is sufficient to induce a sustained inflammatory state and is associated with the development of hyperinsulinemia, impaired glucose tolerance, adiposity and aortic valve calcification.
Abstract 19118: Motor and Cognitive Impairment Following Pediatric Heart Transplantation in the US <i>Analysis of Organ Procurement and Transplant Network Data</i>
Authors: Leslie B Smoot, Christina VanderPluym, Kimberlee Gauvreau, Melisa Oliva, TP Singh, Christopher Almond
Journal: Circulation (2012)

BACKGROUND: Studies suggest the cognitive and motor performance of pediatric heart transplant (HT) recipients falls below population norms; though the incidence and risk factors for these observations are not well characterized. We sought to identify independent predictors of cognitive and motor impairment after HT based on predictors recorded at the time of HT. METHODS: OPTN data were used to identify all children &lt;18 years of age with a post-HT neurodevelopmental screen available between 2007 and 2010, when the screen was mandatory for all children. Logistic regression was used to identify independent risk factors for definite or probable cognitive and motor impairment, respectively, as reported by transplant centers using a standardized screen. RESULTS: Of 1999 children with a cognitive screen available and 2048 children with a motor screen available, the median age at HT was 6 years, the median weight was 19.1 kg, 57% were white, 37% had congenital heart disease (CHD), 59% were listed UNOS status 1A at HT, 12% were ventilated, 11% were on VAD support, 43% had renal dysfunction, and 44% had Medicaid Insurance. Patients without screening data available were more likely to be younger at transplant but were otherwise similar. Overall, 15% of HT recipients were categorized as having definite (10%) or probable (5%) cognitive impairment; 7% had questionable impairment and 79% had no impairment. By contrast 10% were categorized as having definite (8%) or probable (2%) motor impairment; 5% had questionable impairment and 85% had no impairment. Multivariable risk factors for cognitive and motor impairment are summarized below. CONCLUSION: An important fraction of children demonstrate cognitive or motor impairment after HT. Younger age at HT, congenital diagnosis and invasive hemodynamic support were associated with impairments in both cognitive and motor performance. Hispanic race, renal dysfunction and Medicaid insurance were associated with cognitive impairment.
Abstract 18634: Middle School Wellness Program Shows Lasting Impact for Lower Income Community: A Report from Project Healthy Schools
Authors: Nicole L Corriveau, Roopa Gurm, Cydni A Smith, Allison Theurer, Elise Woznicki, Eva Kline-Rogers, Catherine Fitzgerald, Jean DuRussel-Weston, Caren Goldberg, Kim A Eagle, Elizabeth A Jackson
Journal: Circulation (2012)

Background: Project Healthy Schools (PHS) is a school based intervention that provides middle-schoolers with in-class learning activities and environmental changes to reduce cardiovascular (CV) and diabetes risks. PHS has 5 main goals: (1) decrease mindless screen time, (2) exercise 150 minutes/week, (3) make better beverage choices, (4) eat more fruits and vegetables and (5) eat less fast and fatty foods. Prior studies have shown positive change among PHS students, and a persistent positive effect through ninth grade in an affluent community; the long-term impact in a lower income community is unknown. Methods: Follow up data was collected from 238 sixth grade students in Ypsilanti, a lower income community in Southeast Michigan (median household income $34,685). Data collected included height, weight, lipid levels, blood pressure, heart rate, and a modified SPAN self-evaluation, of healthy eating and other lifestyle behaviors. Data was collect prior to the study, after the study in the sixth grade and annually in the seventh, eighth and ninth grades. Results from each consecutive year were evaluated using chi-squared analyses and paired t-tests. Results: After the intervention, students reported an increase in participation in sports teams, a decrease in TV time and playing video games. The students’ physiological measurements total cholesterol, LDL cholesterol (see figure) also improved. Conclusions: The follow-up data reflects positive changes in physiological measurements and sedentary behaviors , in the four years following the initial intervention. This suggests that wellness programs such as PHS can be successful in influencing healthy behaviors and reducing long term CV risk, in both affluent and lower income communities.
Abstract 18696: Feasibility of Transcatheter Closure of Secundum Atrial Septal Defect with Deficient Rims Other than the Antero Superior
Authors: Alain Fraisse, Issam Kammache, Anass Assaidi, Philippe Aldebert, Julien Mancini, Gilbert Habib
Journal: Circulation (2012)

Introduction. Transcatheter closure of secundum atrial septal defect (ASD) with deficient rims is usually contraindicated except in cases with a deficient antero-superior rim in whom percutaneous closure is well demonstrated. Our goal was to assess the feasibility of transcatheter closure for secundum ASD with deficient rims (&lt;5 mm) other than the antero-superior. Method. Between January 1st, 2008 and december 31, 2011, 192 patients underwent percutaneous closure of ASD in our institution under transesophageal echocardiography guidance in children and intracardiac echocardiography guidance in adults. Amplatzer devices (Amplatzer Septal Occluder or Cribriform) were used in 191 whereas one case without deficient rim was closed with intrasept ASD occluder. We retrospectively analyzed the outcomes of the 43 patients (22.4%, 26 children) with one or more deficient rim. Results.The median age and weight was 16(1.1 to 85) years and 56(8.8 to 99)Kg, respectively. Deficiency of the inferior (toward the AV valves, n= 11), inferior- posterior (toward the inferior vena cava, n=15), and the superior -posterior rim (toward the superior vena cava, n= 17) was confirmed by transesophageal echocardiography in all the cases. Transcatheter closure was successfully accomplished in 37 (86%) of the cases with a median device size of 28(10 to 40) mm. A modified method of implantation (sizing balloon technique) was used in 30 patients (70%).In 6 patients (5 children) the ASD could not be closed. Four children experienced device embolization few hours after successful transcatheter closure and underwent surgical ASD closure without further complication. By Fisher’s exact test, deficiency of the inferior-posterior rim was associated with failure or embolization(p = 0.05)and there was a trend for adult age to be associated with a low risk of embolization or failure (p= 0,06). Conclusion. Transcatheter closure of secundum ASD is feasible in patients with deficient rims. However, this cannot be recommended because of an intolerable rate of embolization. Possibly, transcatheter closure of such secundum ASDs with deficient rims may be more successful in the adult population.
Abstract 16918: Autologous Tissue Engineering Scaffolds for Cellular Cardiomyoplasty
Authors: Angel Chan, Takahiro Higuichi, Dongdong Sun, Iossif Strehin, Xiaoping Lin, Qiaozhi Lu, Patrick Armstrong, Brian O'Rourke, Jennifer Elisseeff, Maria Roselle Abraham
Journal: Circulation (2011)

BACKGROUND: Cellular cardiomyoplasty for treatment of cardiomyopathy is limited by low levels of acute retention (∼20%) of transplanted stem cells in the myocardium which results in low long term engraftment (&lt;5%), causing marginal functional benefit. OBJECTIVES: To design a biocompatible and biodegradable autologous hydrogel scaffold for improving acute retention, preventing anoikis/apoptosis, and increasing engraftment. METHODS: Hydrogel scaffolds were prepared by cross-linking modified hyaluronic acid (HA) with polyethylene glycol (PEG), autologous blood (Bl) or serum (Ser). Cardiosphere-derived cells (CDCs) were isolated from syngeneic, male Wistar Kyoto rats. Cell viability and integrin activation in scaffolds were examined by 2-photon microscopy. Glucose ( 18 FDG) uptake of CDC in scaffolds was measured to assess cellular metabolic status, and compared with 18 FDG uptake of suspended and adherent cells. Acute retention rate in the myocardium was determined by ex-vivo counting with a gamma-counter and PET/CT imaging after intra-myocardial injection of 1x10 6 18 FDG labeled CDC. RESULTS: Hydrogel scaffolds with similar mechanical strength as myocardium (2-4 kPa) were found to be optimal for animal survival. CDC viability in the autologous scaffolds was superior to HA-PEG in the absence of external nutrients with &gt;80 ± 10% vs. 0% viability when cultured in Tyrode for 10 days. 18 FDG uptake of cells encapsulated within various scaffolds was similar to adherent cells, but found to be 9 fold for HA-Bl, 11 fold for HA-Bl:Ser, and 15 fold for HA-Ser ( p &lt; 0.05) compared with suspended cells. Integrin activation in the cells was observed within 95 ± 2.6% in scaffolds compared to 15.7 ± 8.2% in PBS. CONCLUSIONS: Autologous biodegradable tissue engineering scaffolds composed of HA and blood components greatly increased acute CDC retention in the myocardium after intramyocardial delivery. These scaffolds also served as a temporary matrix for cellular attachment and a source of nutrients/growth factors for stem cells survival.
Abstract 18904: High-denisty Lipoprotein Distribution in Obesity Favors Apolipoprotein E and C-III-containing Subfractions Associated with Risk for Future Coronary Heart Disease
Authors: Beatriz Talayero, Jeremy Furtado, Frank Sacks
Journal: Circulation (2012)

Human high-density lipoprotein (HDL) particles are highly heterogeneous in composition. Both the plasma concentration of HDL with apoC-III and the concentration of apoE in HDL predict higher incidence of coronary heart disease (CHD). Little is known about the concentration of HDL apoA-I associated with apoE or apoC-III, whether apoE and apoC-III are present in smaller or larger cholesterol ester-rich HDL, and whether the distribution is affected in obesity. We studied 20 normal weight subjects (BMI 23-25) and 20 obese subjects (BMI 30-35) matched by age (mean age, 51 years). Sixteen distinct HDL subpopulations were separated from plasma samples by first using anti-apoAI, anti-apoE and anti-apoC-III immunoaffinity chromatography in sequence followed by size separation using nondenaturing electrophoresis. The mean HDL-cholesterol and plasma apoA-I concentrations in the normal weight group were 65 and 179mg/dL respectively, compared to 50 and 170mg/dL in the obese group. Mean apoA-I concentrations of HDL fractions without apoE or apoC-III was 160mg/dL in the normal weight group, compared to 136mg/dL in the obese; with apoE only 9 and 12mg/dL respectively; with apoC-III only 7.4 and 14.7 mg/dL; and with both apoE and apoC-III 2.6 and 7.5mg/dL (p&lt;0.01 for a difference in apoA-I concentration and distribution across HDL types). All told, about 10% of HDL apoA-I in normal weight subjects contained apoE, apoC-III or both, compared to 20% in obese subjects. The concentrations of apoE and apoC-III in HDL in the obese were about double that of the normal weight group (p&lt;0.01). In the obese group, the high concentration of HDL with apoE was distributed to small HDL. More so, obese had a higher percent of large HDL containing apoC-III and no apoE. In conclusion, despite similar plasma total apoA-I levels in obese and normal weight groups, the obese had higher concentrations of HDL containing apoE or apoC-III, subfractions which are associated with CHD, whereas the normal weight group had higher concentration of HDL without apoE or apoC-III, a subtraction with protective association against CHD. Mechanistically, the increased presence of apoC-III in large size HDL and apoE in small size HDL in obese may indicate a reduced capacity of HDL for RCT.
Abstract 8158: Prior Incidence of Ventricular Tachyarrhythmias Predict Subsequent Episodes of Ventricular Tachyarrhythmias and Increased Mortality in Subjects with Mildly Reduced Ejection Fraction on Cardiac Resynchronization Therapy -A MADIT study analysis
Authors: Saurav Chatterjee, Alon Barsheshet, Debabrata Mukherjee, Edgar Lichstein, Ilan Goldenberg
Journal: Circulation (2011)

Background: An incidence of ventricular tachyarrhythmia (VA)(including ventricular tachycardia and ventricular fibrillation) in a patient with reduced ejection fraction is a marker of increased all-cause mortality. We aimed to assess the impact of prior VAs on clinical outcomes in patients with mild heart failure symptoms who received cardiac resynchronization therapy with a defibrillator (CRT-D). Methods: We evaluated benefit of CRT-D vs. ICD-only therapy in the reduction of ventricular tachyarrhythmias or death by the presence of a history of VA among 1820 patients enrolled in the MADIT-CRT trial. Results: A history of VA was a significant risk factor for the occurrence of VT/VF or death during the trial (HR 2.06, 95% CI 1.55-2.74, p&lt;0.001). Multivariate analysis showed that CRT-D therapy was associated with a significant reduction in the risk of ventricular tachyarrhytmias among patients without a history of VA, whereas risk-reduction associated with CRT-D therapy was not statistically significant among patients with a history of prior VA (Table). Conclusions: Our findings suggest that a history of prior VA is a powerful risk factor for the development of subsequent ventricular tachyarrhythmias and mortality among patients with mild CHF symptoms who receive device therapy. The benefit of CRT-D therapy appears to be attenuated among patients with prior VA.
Abstract 18398: Long-term Surgical Outcome of Mitral Valve Repair for Degenerative Mitral Regurgitation with Chronic Atrial Fibrillation: The Impact of Maze Procedure on Long-term Survival and Cardiac Function
Authors: Takashi Murashita, Yukikatsu Okada, Naoto Fukunaga, Yasunobu Konishi, Tadaaki Koyama
Journal: Circulation (2012)

Introduction: It is unclear whether maze procedure for atrial fibrillation (AF) would positively affect long-term survival, stroke and cardiac function. The aim of this study is to investigate the long-term surgical outcomes of mitral valve repair for degenerative mitral regurgitation with chronic AF and to determine the impact of concomitant maze procedures on long-term survival, cardiac events, stroke and cardiac function, comparing the outcomes of patients who underwent maze procedure and patients who did not undergo maze procedure. Methods: We retrospectively investigated 159 patients who underwent mitral valve repair for degenerative mitral regurgitation with chronic AF between 1991 and 2010. The mean age was 63.1±10.5 years old. We started Cox-maze IV procedure in 2002. As a result, 65 patients underwent concomitant maze procedure (maze(+) group) and 94 patients did not undergo maze procedure (maze(-) group). Follow-up was completed in 156 patients (98.1%). The median follow-up duration was 7.6 years (max 21 years). Results: There was one operative death (0.63%). The survival rate was significantly better in the maze(+) group than maze(-) group (5-year survival; 100% vs 85.2±4.0%, p&lt;0.001). The actual freedom from atrial fibrillation in the maze(+) group was 86.4±4.5% at 1 year and 81.1±5.6% at 5 years. The actual freedom from cardiac events (cardiac death, cardiac-related re-admission and re-operation) was not different between the maze(+) group and maze(-) group (5-year freedom rate; 81.6±5.9% vs 88.9±3.5%, p=0.113). The rate of freedom from stroke was better in the maze(+) group than maze (-) group (5-year freedom rate; 92.1±3.9% vs 82.6±4.2%), though the difference of them was not statistically significant (Log-rank p=0.081). The latest NYHA functional class was worse in the patients who did not covert to sinus rhythm (AF group) than who did (SR group)(1.4±0.5 vs 1.1±0.3, p&lt;0.001). The systolic and diastolic diameter of left ventricle gradually enlarged in AF group, which became significant difference during the long-term period. Conclusions: Maze procedure can improve long-term survival, rate of freedom from stroke and cardiac function in the patients with degenerative mitral regurgitation with chronic atrial fibrillation.