tbuckley/cabot-search huggingface dataset:
Abstract 17708: Hydrogel Loaded with Mesenchymal Stem Cells Preserves Cardiac Function and Ventricular Remodeling After Myocardial Infarction
Authors: Mathieu Eva, Lamirault Guillaume, Toquet Claire, Weiss Pierre, Guicheux Jérôme, Lemarchand Patricia
Journal: Circulation (2011)

Purpose: We hypothesized that the injection of mesenchymal stem cells (MSC) within an hydrogel would improve efficacy of cell therapy after myocardial infarction (MI). We have developed an hydrogel composed to Hydroxypropyl methylcellulose Silanyzed (Si-HPMC). Methods: The cytocompatibility was evaluated by the MSC viability cultivated in 3D within the hydrogel using cytotoxicity assays. Immediately after coronary ligation, hydrogel, 3.106 MSCs alone or with the hydrogel (MSC+hydrogel) were injected into the myocardium of rats (PBS used as control). Cardiac function was assessed using echocardiography over 56 days and left ventricular (LV) remodeling was assessed using histopathology. Results: The hydrogel maintained the MSC viability during the whole culture period. In the PBS group, MI induced a reduction in left ventricular ejection fraction (LVEF) (87.4±1.5% at baseline vs 47.4±2.4% at 56 days; p&lt;0.001) and an increase in LV diameters during the whole study. The injection of MSC+hydrogel in acute phase of MI induced an significant increased of LVEF at day 7 up to day 56 as compared to PBS group (at day 56: 47.4±2.4% in PBS group vs 68.5±2.0% in MSC+hydrogel group; p&lt;0.001) and an increase as compared to day 1 after MI (61.2±2.9% at day 1 vs 76.4±1.5 % at day 28; p&lt;0.001 as compared to day 1). The injection of hydrogel alone induced an increase in LVEF at 28 days as compared to PBS group but not at day 7 and 56 and the injection of MSC induced an increase at 28 and 56 days as compared to PBS group, but not at day 7. In the both groups the LV diameters and LVEF are not significantly altered during the whole study as compared to day 1. Interestingly when animals have been treated with MSC+hydrogel, their LVEF was higher at day 7 as compared to EF in MSC group and at day 56 in compared to hydrogel group. Conclusion: These results showed the major effects of Si-HPMC hydrogel are observed at the short-term. In acute phase of MI, the MSC delivery with hydrogel allowed a better preservation of cardiac function and LV remodeling as compared to injection of MSC alone.
Abstract 18379: Impact of Gender on Adverse Cardiovascular Events Following Percutaneous Coronary Intervention: Pooled Analysis from the SPIRIT II, III and IV trials
Authors: Usman Baber, Annapoorna S Kini, Nilusha Gukathasan, Roxana Mehran
Journal: Circulation (2012)

Background: Female gender is a consistent and strong correlate of increased cardiovascular risk following percutaneous coronary intervention (PCI). Emerging data suggest that 2 nd generation drug-eluting stents (DES) may improve event-free survival compared to 1 st generation DES. Whether or not this applies to both sexes is unknown. Methods: The SPIRIT II, III and IV randomized controlled trials compared the second-generation everolimus-eluting stent (EES) to the first-generation paclitaxel-eluting stent (PES). Summary-level data from the latest follow-up year of each study was pooled using meta-analytic techniques. We evaluated the overall and differential impact of gender on adverse events stratified by DES type. Relative risks and 95% confidence intervals were calculated for the following outcomes: definite or probable stent thrombosis (ST), target lesion revascularization (TLR), myocardial infarction (MI), major adverse cardiovascular events (MACE) and cardiac death. Results: Women (n=1583, 31.7%), were older, more often diabetic and less likely to have multivessel disease compared to men (n=3405, 68.3%). After a weighted mean follow-up of 2.3 years, among patients receiving PES, the incidence of MACE (13.3% vs. 10.1%, p=0.04) was significantly higher while rates of MI (5.3% vs. 4.0%, p=0.19) and TLR (8.4% vs. 6.6%, p=0.17) were modestly higher among women compared to men. In contrast, MACE rates were lower with EES than PES in both men and women, and outcomes were similar in men and women receiving EES (Table). Rates of ST (0.5% vs. 0.7%, p=0.65) and cardiac death (0.9% vs. 1.0%, p=0.95) in EES-treated patients did not differ in women vs. men, respectively. Conclusions: In this pooled analysis of RCT, adverse cardiovascular events were modestly higher among women compared to men treated with PES. In contrast, outcomes were improved with EES in both men and women such that female sex was no longer associated greater MACE.
Abstract 190: Cardiopulmonary Resuscitation with Rescue Breathing Is Superior to Hands-Only Cardiopulmonary Resuscitation for Children and Infants: Results of a Systematic Review
Authors: Richard N Bradley
Journal: Circulation (2012)

Introduction: Evidence supports teaching hands-only CPR for the initial treatment of cardiac arrest in adults. Unlike adults, however, children and infants with cardiac arrest are more likely to have non-cardiac causes. Hypothesis: The objective of this project was to conduct a structured literature review to answer the question, “In children and infants with cardiac arrest treated in an out-of-hospital setting, does compression-only CPR, alone or with supplemental oxygen, compared to CPR with rescue breathing lead to improved outcomes?” Methods: We performed a MEDLINE search (“compression only”[Title/Abstract]) AND cardiopulmonary resuscitation[MeSH Terms] with limits children (ages 0 -18). We also performed a search in the Cochrane database for systematic reviews, the Central Register of Controlled Trials, and EMBASE using similar search terms. We also searched applicable bibliographies and used the ‘Cited By’ function in Google Scholar. The study included papers if they evaluated the difference between compression only CPR and CPR with rescue breathing in infants or children. Papers that reported results from studies that used procedures that were beyond the basic life support level were excluded. Each paper was evaluated using specific criteria to determine the level of evidence. Results: Sixty-nine records were identified and screened. Fifty-four of these did not meet inclusion/exclusion criteria, leaving fifteen full-text articles that we assessed for eligibility. Eleven of these did not meet inclusion/exclusion criteria, leaving four that we included in the qualitative synthesis. Of these, one good quality study with level of evidence (LOE) 2a and 3 other studies (LOE 4) all opposed the hypothesis. There is a relative paucity of published data on this subject. The majority of the papers published describe evidence from animal models. Conclusions : In conclusion, rescuers should provide chest compressions with rescue breathing to children and infants in cardiac arrest; rescuers unwilling or unable to provide compressions with rescue breathing may provide chest compressions alone for these patients.
Abstract 17107: Induced Vascular Progenitor Cells Derived From Endothelial Cells Stimulate Coronary Collateral Growth
Authors: Liya Yin, Vahagn Ohanyan, Yuh Fen Pung, Angelo L Delucia, Erin Bailey, Molly Enrick, Kelly Stevanov, Christopher L Kolz, Giacinta Guarini, William Chilian
Journal: Circulation (2011)

Although regenerative medicine has great potential in stimulating vascular growth in the heart, there have been mixed results and the ideal cell type for therapy has not been resolved. Induced pluripotent cells (iPSCs) show promise, because they can be autologous, but they suffer from the problem of potential tumor formation. To circumvent this problem, we reasoned that reprogramming cells to a progenitor-type cell, rather than to pluripotency, but would reduce the chances for tumor formation; yet still enable their application in stimulating coronary collateral growth in a rat model of repetitive ischemia. Accordingly, we reprogrammed endothelial cells (EC(s)) to “induced vascular progenitor cell(s)” (iVPC(s)), which should remain committed to a vascular lineage. We hypothesized that these cells would better stimulate coronary collateral growth than fully reprogrammed iPSCs because the latter can differentiate into various cell types other than vascular lineage. Rat vascular ECs were transduced with Oct4, Klf4, Sox2 and c-Myc. A population of reprogrammed cells expressing pluripotent markers, Oct4, SSEA-1, Rex1 and AP and markers of hemangioblasts, CD133, Flk1, c-kit were generated. These cells were named iVPCs, because they remained committed to vascular lineage and could differentiate into vascular ECs or vascular smooth muscle cells in vitro. iVPCs demonstrated better in vitro angiogenic potential (tube network on 2D culture, tube formation in serum reduced matrigel) than native ECs. In contrast to iPSCs, iVPCs had far less risk of teratoma formation. When iVPCs were implanted into rat myocardium, they engrafted into the blood vessels, increased coronary collateral flow measured by microspheres and improved cardiac function during coronary occlusion measured by echocardiography better than iPSCs or sham treatment (all difference were significant at P&lt;0.05). Thus we successfully reprogrammed ECs into iVPCs. iVPCs had a better effect on coronary collateral growth and cardiac function during a coronary occlusion in vivo than iPS cells did. We conclude that “induced vascular progenitor cells,” generated by partial reprogramming of ECs, are an ideal cell type for regenerative therapy to stimulate coronary collateral growth.
Abstract 18962: MrpL48 is Associated with Impaired Mitochondrial Function and Blood Pressure Regulation in Genetic Hypertension
Authors: Henrike Maatz, Jan Monti, Claudia Goesele, Tilmann Breiderhoff, Michal Pravenec, Thomas Willnow, Michael Sack, Norbert Hubner
Journal: Circulation (2012)

BACKGROUND: Aerobic metabolism has been implicated in the pathogenesis of cardiovascular diseases but the underlying genes that contribute to this process are incompletely understood. Here, we identified a novel gene within a previously mapped blood pressure QTL on rat chromosome 1 and demonstrate that the nuclear encoded mitochondrial ribosomal protein 48 (MrpL48) contributes to impaired aerobic metabolism and elevated blood pressure phenotypes in rats and mice. METHODES: We measured telemetric blood pressure and generated genome wide expression signatures in kidneys of 30 rat recombinant inbred strains that were established from the spontaneously hypertensive rat (SHR) and the BN normotensive reference strain as well as from chromosome 1 congenic rats spanning the chromosome 1 blood pressure QTL. This led to a positional candidate gene which was subsequently analyzed at the molecular level. We investigated mitochondrial bioenergetic processes and translation in vitro and ex vivo and subsequently monitored blood pressure in MrpL48 knockout mice by telemetry. RESULTS: Expression analysis in the congenic line as well as the HXB/BXH recombinant inbred panel showed that variation at the MrpL48 locus resulted in altered gene expression and significantly correlated with blood pressure levels. We demonstrated that MrpL48 plays an important role in mitochondrial translation and subsequently mitochondrial function in vitro and in vivo. MrpL48 knockout mice showed significantly increased pulse pressure levels. CONCLUSION: Our findings suggest that MrpL48 plays an important role in mitochondrial dysfunction and blood pressure regulation and identifies a so far unappreciated mechanism of blood pressure regulation.
Abstract 17550: PPAR-δ Activation Induces Angiomyogenesis Through the Potentiation of Endothelial Progenitor Cell Paracrine Network
Authors: Hack-Lyoung Kim, Jung-Ku Han, Young-Eun Choi, Ki-Hyun Jeon, Hyun-Sook Lee, Yoo-Wook Kwon, Hyun-Jai Cho, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2011)

Background Endothelial progenitor cells (EPCs) paracrine network has been known to play a key role in neovascularization. We focused on skeletal muscle regeneration as well as new vessel formation by EPCs and their modulation by PPAR-δ. Methods and Results GW501516 , a PPAR-δ agonist enhanced MMP-9 mRNA expression, protein excretion and enzyme activity among several paracrine factors in EPCs. MMP-9 in conditioned media (CM) from GW501516 treated EPCs degraded IGFBP-3 in Western blot. The CM treatment phosphorylated IGF-1 receptor (R) in HUVECs, enhancing BrdU incorporation, Matrigel tube formation and migration. It also induced proliferation of C2C12 myoblast cells and protected them from hypoxia. Systemic treatment of GW501516 in mice increased MMP-9 expression in EPCs and degraded IGFBP-3 in serum Western. In mice which received bone marrow transplantation (BMT) from WT mice, continuous infusion of GW501516 phosphorylated IGF-1R in ECs and skeletal muscle. It increased capillary density and regenerating myotubes with central nuclei, and decreased muscle fibrosis in MT stain. IF for Ki67 and TUNEL stain demonstrated the in vivo proliferation and protection from apoptosis of ECs and skeletal muscle cells by GW501516. Limb perfusion recovery was also enhanced in LDPI. BMT from MMP-9 KO mice or IGFBP-3 systemic infusion abolished these effects. Intramuscular injection of ex vivo GW501516 treated EPCs to ischemic limbs showed the same effects. But EPCs from MMP-9 KO mice reversed the results. In skin punch wound model, GW501516 systemic administration enhanced wound healing with increased angiogenesis in WT mice, not in MMP-9 KO mice. Conclusion EPC paracrine network through MMP-9 mediated IGF-1 signaling pathway is important in angiomyogenesis, and is potentiated by PPAR-δ activation. Our results suggest PPAR-δ agonist as a good candidate drug for patients with peripheral vascular diseases who need angiomyogenesis for recovery.
Abstract 18941: Vasodilator Use Guided by Wireless Pulmonary Artery Hemodynamic Monitoring Reduces Heart Failure Hospitalizations in Both African American and Non-African American Heart Failure Patients: Results from the CHAMPION Trial
Authors: Maria Rosa Costanzo, Philip B Adamson, William T Abraham, Jeffries Bradley, Susan Neville, Pam Cowart, John Henderson, Jay S Yadav
Journal: Circulation (2012)

Introduction: It is unknown whether benefits produced by nitrates and hydralazine (HDZ) in African Americans (AA) also occur in non-African American (non-AA) patients. The CHAMPION Trial showed that, compared to usual care (UC) patients, those managed according to wirelessly measured pulmonary artery pressures (w-PAP) plus UC had a significant reduction in heart failure (HF) hospitalizations over 6 months. The current analysis evaluated pattern of use and effects of nitrates and HDZ in AA and non-AA CHAMPION trial subjects to determine if non-AA patients receiving these vasodilators according to w-PAP will have benefits similar to those occurring in non-AA. Methods: Retrospective comparison of changes in use of nitrates and HDZ in AA and non-AA subjects randomized in the CHAMPION trial and evaluation of the effects of these therapeutic changes on HF hospitalization rates. Results: Of 424 non-AA patients, 202 were assigned to w-PAP and 222 to UC. Of 126 AA, 68 were assigned to w-PAP and 58 to UC. Baseline nitrate and HDZ use was similar between w-PAP and UC for both non-AA and AA groups. At 6 months nitrate use increased more in the w-PAP than UC group in both non-AA [90 (44.6%) vs. 48 (21.6%); p&lt; 0.0001] and AA [23 (33.8%) vs. 17 (29.3%); p=ns due to small sample size]. At 6 months HDZ use increased more in the w-PAP than UC group in both non-AA [39 (19.3%) vs. 27 (12.2%); p&lt; 0.0452] and AA [22 (32.4%) vs. 15 (25.9%); p=ns due to small sample size] . Within the non-AA population nitrate dose increased at 6 months more in the w-PAP than in the UC group (20.43 mg vs. 4.21 mg; p= 0.05). HF hospitalization rates were significantly lower in w-PAP than UC subjects both within the non-AA (0.31 vs. 0.43 p = 0.0007) and the AA population (0.33 vs. 0.45 p=ns due to small sample size) and the magnitude of reduction in HF hospitalization was similar for non-AA and AA subjects. Conclusions: Greater utilization of nitrates and HDZ in HF patients managed with w-PAP produces significant and similar reductions in HF hospitalizations in non-AA and AA HF patients.
Abstract 18656: A Decade of Follow-up with Excellent Transmural Atrial Lead Performance in Complex Congenital Heart Patients
Authors: James C Perry, Suzanne M Shepard, Nicole K Boramanand, Matthew R Williams, John J Lamberti
Journal: Circulation (2012)

Background: Many patients (pts) with postoperative congenital heart disease require permanent pacing for rhythm management and cannot undergo transvenous atrial leads. Extensive epicardial scar can prohibit adequate acute and chronic pacing and sensing thresholds. We described transmural atrial lead (TMA, epicardial to endocardial) pacing previously and now report long-term lead performance. Methods: A bipolar, steroid eluting transvenous lead is placed from the epicardial surface via purse-string and affixed to position the lead against the atrial endocardium. 52 patients underwent TMA placement between 1998 and 2004. Records were reviewed for lead characteristics and acute and long term performance. Follow up data was available for 51 patients. TMAs were placed in the right atrial appendage, the lateral right atrial wall, left atrium, and dome of the left atrium. Medtronic 5072 (n=43), Guidant 4469 (n=6) or other (n=3) leads were used. Results: 52 pts underwent TMA at an avg age of 13.4 yrs; 19 to replace existing leads and 36 as part of a larger surgery. Pre-op, 25 pts had atrial tachycardia (AT). 22 pts had Fontan/revision. Acute TMA pace threshold was 0.87V @ 0.5msec. 43/52 leads remain active at an avg follow-up of 10.2 yrs. Chronic pace threshold avg is 0.96V @ 0.3-0.5msec; atrial electrogram is 2.97mV in 30/43 pts with intrinsic P waves. Atrial overdrive of AT using TMA was successful in 8/9 pts. No clots were oberved in any pt in follow-up. 3 pts died (one awaiting transplant, one sudden, one stroke (TMA on Fontan side, no fenestration). There were 2 TMA fractures, 3 removed for non-TMA reasons. Conclusions: TMAs show excellent late functional properties as an alternative to epicardial leads in complex pts, maintaining low atrial pacing thresholds, consistent sensing and the benefit of effective overdrive pacing of ATs. TMAs exhibit superior long term performance in complex Fontan and atrial switch patients.
Abstract 18372: Differences in Quantitative Assessment of Myocardial Scar and Gray Zone by Delayed Enhanced Cardiac Magnetic Resonance Imaging Using Established Gray Zone Protocols
Authors: Olurotimi Mesubi, Kelechi Ego-Osuala, Jean Jeudy, Martine Etienne-Mesubi, Dawn Ament, See Vincent, Anastasios Saliaris, Steve Shorofsky, Timm-Michael Dickfeld
Journal: Circulation (2012)

Background: Delayed enhanced cardiac magnetic resonance imaging (DE-CMRI) is the gold standard for scar evaluation. Heterogeneous areas in the scar, known as ‘gray zone’ (GZ), may serve as arrhythmogenic substrate. Various signal intensity (SI) thresholds have been described and validated for GZ and infarct core definition. Little is known about the effect of these protocols on the presence and amount of GZ and infarct core. We aimed to compare 3 previously described methods. Methods: Postprocessing analysis of good quality DE-CMRI images was performed in 14 patients with ischemic (12) or non-ischemic (2) cardiomyopathy and no implanted cardiac devices. Myocardial scar was defined as core and GZ using the following SI thresholds. The core was defined as &gt;50% of maximal SI (MSI) in the hyperenhanced area for the full width at half-maximum (FWHM) and ‘modified-FWHM’ (or ‘Roes’) methods and &gt;3SD of mean SI of remote myocardium for the n-standard deviation (NSD) method. GZ was defined as &gt; peak SI of remote myocardium to 50% of MSI (FWHM), between ≥ 35% -50% of MSI (Roes) and 2-3SD of mean SI of remote myocardium (NSD). Results: All patients had evidence of scar on DE-CMRI. The GZ mass was significantly different for the 3 methods with 46±38 g vs. 15±6 g vs. 17±7 g for FWHM, NSD and Roes respectively (p = 0.01). There was no difference in GZ mass between the NSD and Roes (p = 0.12). Infarct core mass was similar for FWHM and Roes (22±13 g) but significantly higher with NSD (63±36 g, p &lt; 0.01). There was a difference in total myocardial scar (core + GZ) with 68±40 g vs. 78±40 g vs. 39±19 g for FWHM, NSD and Roes respectively (p &lt; 0.01). The GZ extent (% of scar that was GZ) also varied significantly for the 3 methods, 62±22% vs. 22±10% vs. 45±11% for FWHM, NSD and Roes respectively (p &lt; 0.01). A strong correlation was shown between GZ mass and total myocardial scar (r = 0.94, p &lt; 0.01 for FWHM, r = 0.74, p &lt; 0.01 for NSD and r = 0.84, p &lt; 0.01 for Roes). Conclusion: Considerable variability exists among the current methods for MRI scar quantification of GZ and scar core. There is a 3-fold increase in GZ mass quantified by the FWHM method compared to the NSD and Roes methods. Infarct core and total myocardial scar mass also differ using these methods. Further evaluation of the most accurate quantification method is needed.
Abstract 18441: Adenosine-Free Functional Assessment of Coronary Stenosis Severity by Contrast-Induced Submaximal Hyperemia
Authors: Froukje Nolte, Tim P van de Hoef, Wouter de Klerk, Jan Baan Jr., Tim P Lockie, Jos A Spaan, Jan J Piek, Maria Siebes
Journal: Circulation (2012)

Background Detection of clinically significant stenoses by fractional flow reserve (FFR) or hyperemic stenosis resistance (HSR) requires maximal vasodilation, which varies with the amount of adenosine (ADO) given. However, the hemodynamic effect of a coronary artery stenosis is uniquely determined by its quadratic pressure gradient-velocity (ΔP- v ) relationship over a range of physiological flow velocities. Hypothesis Functional stenosis severity can be defined from the ΔP- v relationship in terms of the mean pressure gradient at a fixed submaximal velocity (dP v ). Since contrast medium (CM) induces reactive hyperemia, it provides a convenient means to increase flow for this purpose. Methods In 64 patients, aortic pressure (P a ) and intracoronary pressure (P d ) and v distal to an intermediate stenosis were recorded throughout the response to an i.c. ADO injection (30-60 µg). The curve fit (ΔP=A v +B v 2 ) of each ΔP-v relationship was used to obtain the mean dP v at 20, 25, 30, and 40 cm/s. Ischemic cut-off values for each dP v were defined with respect to FFR (=P d /P a ) &lt;0.75 and HSR (=ΔP/ v ) &gt;0.80 mmHg/cm/s. The dP v with the least discordance was used to assess diagnostic performance. Measurements were repeated after i.c. CM injection (3 ml) in 20 patients. Similarity between ADO and CM-derived ΔP- v relationships was evaluated by comparing the dP v at all fixed velocities. Results ADO-based FFR ranged from 0.27 to 0.97 and HSR from 0.08 to 9.12 mmHg/cm/s. Maximal v after CM was 17 ± 16% lower (p&lt;0.01) and P d was 9 ± 11% higher (p&lt;0.001) compared to ADO. Corresponding ADO and CM ΔP-v relationships showed good agreement; no significant differences were found for dP v at any of the tested velocities. Diagnostic performance was highest for dP v at a velocity of 25 cm/s (dP v25 ), with a cut-off &gt;15.8 mmHg. Sensitivity, specificity, and accuracy compared to FFR were 84%, 92% and 87% for ADO and 88%, 92% and 90% for CM-based dP v25 , respectively. Sensitivity, specificity and accuracy were 100% compared to HSR for both ADO and CM-based dP v25 . Conclusion dP v25 is a promising new index of functional stenosis severity that is based on stenosis hemodynamics and yields a high diagnostic accuracy. This index can be obtained from CM injections and obviates problems associated with the use of adenosine.