tbuckley/cabot-search huggingface dataset:
Abstract 9721: <i>Tmem100</i> , a Novel BMP9/10-dependent Endothelial Gene Essential for Arterial Development and Morphogenesis
Authors: Satoshi Somekawa, Hisaki Hayashi, Masahide Sakabe, Tomoko Ioka, Genki Sato, Ken Inada, Shiro Uemura, Osamu Nakagawa, Yoshihiko Saito
Journal: Circulation (2011)

Satoshi Somekawa, 2011 Finalist and Presenting Author
The Wise Use of Technology in the Care of Critically Ill Cardiac Patients
Authors: Marjorie Funk
Journal: Circulation (2011)

Technology permeates every dimension of critical care practice. Although it offers extraordinary benefits to patients and clinicians, technology may also create problems. The wise use of technology in the care of critically ill patients with heart disease is the focus of Marge Funk's research. During the 2011 Katharine A. Lembright Award Lecture she will describe the development of her program of research. She will give examples of studies that examined the safe and appropriate use of technology, its equitable distribution, and the human-machine interface. She will also discuss research related to the use of a particular type of technology – electrocardiographic monitoring – that has been a thread throughout her research career.
Abstract 9358: Accelerated Progression of Coronary Atherosclerosis in Patients With Ultrasonic Features of Plaque Vulnerability
Authors: Yu Kataoka, Kathy Wolski, Craig Balog, Kiyoko Uno, Rishi Puri, E.Murat Tuzcu, Steven E Nissen, Stephen J Nicholls
Journal: Circulation (2012)

Backgrounds: Vulnerable plaques typically contain large lipid cores accompanied by expansive vascular remodeling and spotty calcification. While non-occlusive plaque rupture has been proposed as a mechanism for sudden disease progression, the natural history of atheroma progression in patients with vulnerable plaques have not been well characterized. Methods: 3460 patients with angiographic coronary artery disease underwent serial intravascular ultrasound imaging to monitor atheroma progression in 7 clinical trials of anti-atherosclerotic therapies. Patients with (n=1063) and without (n=2397) focal vulnerable plaques, defined as the combination of percent atheroma volume (PAV) &gt;40%, expansive vascular remodeling and spotty calcification, were compared with regard to clinical characteristics and the rate of atheroma progression. Results: Patients with vulnerable plaques were less likely to be female (24 v. 31%, p&lt;0.001) and more likely to have hypertension (82 v. 78%, p=0.01) and diabetes (38 v. 30%, p&lt;0.001). Vulnerable plaque patients harbored more extensive atherosclerotic disease at baseline, with a greater PAV (42.5±7.4 v. 36.9±9.2%, p&lt;0.001) and total atheroma volume (TAV, 207.6±82.7 v. 184.6±82.7 mm3, p&lt;0.001). On serial evaluation, less progression of PAV (0.25±0.28 v. 0.46±0.27%, p=0.08) and TAV (-4.6±2.2 v. -3.0±2.2mm3, p=0.03) was observed in vulnerable plaque patients. Use of statins and optimal control of risk factors including LDL-C and HDL-C levels were associated with the slowest disease progression in patients with vulnerable plaques (Figure). Conclusions: While focal vulnerable plaques are associated with more extensive atherosclerotic burden, these patients demonstrate the greatest benefit of risk factor interventions. These findings suggest that while vulnerable lesions have the propensity to promote ischemic syndromes, they present a modifiable substrate that is sensitive to intensive use of medical therapies.
Abstract 9624: Concomitant Early Repolarization is the Independent Predictor for the Occurrence of Sustained Ventricular Tachyarrhythmias or Sudden Death in the Chronic Phase of Acute Myocardial Infarction
Authors: Yoshihisa Naruse, Hiroshi Tada, Yoshie Harimura, Mayu Hayashi, Akira Sato, Yukio Sekiguchi, Tomoya Hoshi, Kazutaka Aonuma
Journal: Circulation (2012)

Background: We recently demonstrated that the presence of early repolarization (ER) increased the risk of ventricular fibrillation (VF) ccurrences in the early phase of acute myocardial infarction (AMI). However, it is unknown whether there is an association between ER and VF occurrences in the chronic phase of AMI. Methods: This study included 1001 patients with AMI (67±12 years; 762 male; 239 female) who underwent successful percutaneous coronary intervention. The primary endpoint was occurrence of sustained ventricular tachyarrhythmias (VT/VF) or sudden death more than 14 days after AMI onset. We evaluated the presence of ER from the ECG recorded at pre-discharge. ER was defined as a QTS-ST junction elevation of &gt;0.1mV from baseline in at least 2 leads. We also analyzed the localization (inferior or lateral leads), amplitude, morphology (notching or slurring), and ST segment characteristics (upsloping or horizontal/descending) of ER to evaluate the significance of the ER pattern. Results: After a mean follow-up of 27.7±17.3 months, 16 (1.6%) patients had an episode of VT/VF or sudden death. The patients with VT/VF or sudden death had a greater prevalence of a left anterior descending culprit artery (75% vs. 45%; p&lt;0.05) and lower left ventricular ejection fraction (39±11% vs. 54±11%; p&lt;0.001) than those without. Furthermore, with the 12-lead ECG analysis recorded pre-discharge, ER was found in 7 (44%) of the patients with VT/VF or sudden death, which was more prevalent than in those without (11%; p&lt;0.01). A multivariate Cox regression analysis revealed that ER (hazard ratio [HR] 6.14; 95% confidence interval [CI] 2.24-16.83; p&lt;0.001) and a left ventricular ejection fraction lower than 35% (HR 15.77; 95% CI 5.69-43.73; p&lt;0.001) were independent predictors of the occurrence of VT/VF or sudden death. As features of the ER pattern, a J-point elevation in the inferior leads, notched morphology of the ER, and ER with a horizontal/descending ST-segment, all were significantly associated with VT/VF or sudden death occurrences. Conclusions: The presence of ER increases the risk for VT/VF or sudden death occurrences in the chronic phase of AMI, and may become a useful tool for deciding an indication for an implantable cardioverter defibrillator.
Abstract 9439: Inhaled Iloprost Improves Exercise Function in Subjects after Fontan Palliation
Authors: Jonathan Rhodes, Ana Ubeda-Tikkanen, Mathieu Clair, Susan M Fernandes, Dionne A Graham, Kevin Daly, Mary P Mullen, Michael J Landzberg
Journal: Circulation (2012)

Background: The exercise capacity of pts who have had Fontan surgery is often depressed. We hypothesized that an inability to reduce pulmonary vascular resistance appropriately during exercise contributes to this exercise intolerance, and that administration of an effective pulmonary vasodilator would improve exercise function after Fontan. Purpose: To determine whether treatment with iloprost, (ILO, a potent, selective, inhaled pulmonary vasodilator) improves exercise function in pts with Fontan. Methods: Double-blind, randomized, placebo controlled, crossover trial. All pts performed 2 symptom-limited cardiopulmonary exercise tests (CPX) on different days separated by &lt;1 month. Nebulizer treatment was administered before each test; one contained ILO (5 mcg), the other placebo. Results: We recruited 18 Fontan pts aged 12-49 (median 18) yrs. Mild throat/chest discomfort developed in 10/18 pts during ILO administration; all but 1 were able to complete treatment. No symptoms were reported during placebo treatments (p&lt;0.001). Two additional pts did not complete CPX: one was noted to be in recurrent atrial flutter, the other, with developmental issues, could not cooperate adequately for CPX. In the 15 subjects with analyzable CPX data, oxygen pulse (a surrogate for stroke volume) at peak exercise was significantly higher following ILO treatment (11.7±2.7 ml/beat vs. 10.4±2.1 ml/beat following placebo; p&lt;0.001). Peak oxygen consumption (VO 2 ) trended higher after ILO compared to placebo (28.7±6.7 vs. 27.5±5.9 ml/kg/min; p=0.18). Nine pts had a peak VO 2 &lt;30 ml/kg/min following placebo; each of these pts had a higher peak VO 2 following ILO (25.5±4.7 vs. 23.7±4.4 ml/kg/min; p&lt;0.002). In contrast, only 3/6 pts with peak VO 2 &gt;30 ml/kg/min on their placebo study had a higher peak VO 2 following ILO (p&lt;0.04). Conclusion: ILO therapy improves peak VO 2 in subjects with compromised exercise function after Fontan palliation. The improvement is related to an increase in the oxygen pulse at peak exercise. The therapy appears to be associated with minor side effects. These findings support the concept of pulmonary vasodilator therapy in Fontan pts with limited functional capacity.
Abstract 11784: Reduced BMPR2 Increases GM-CSF mRNA Translation by Inhibiting eIF2α Mediated Stress Granule Formation and Propensity to Pulmonary Vascular Disease
Authors: Hirofumi Sawada, Tero-Pekka Alastalo, Jason P Glotzbach, Roshelle Chan, Gabriele Fuchs, Michael Januszyk, Ying-Ju Lai, Vinicio de Jesus Perez, Toshie Saito, Edda Spiekerkoetter, Lingli Wang, Geoffrey C Gurtner, Peter Sarnow, Marlene Rabinovitch
Journal: Circulation (2011)

Hirofumi Sawada, 2011 Finalist and Presenting Author
Abstract 9991: Mesenchymal Stem Cells Overexpressing CXCR4 (MSC <sup>CR4</sup> ) Promote Neovascularization as Revealed by Suicide Gene Approach
Authors: Jialiang Liang, Wei Huang, Tiemin Zhao, Atif Ashraf, Meifeng Xu, Ronald W Millard, Kishore K Wary, Yigang Wang
Journal: Circulation (2011)

Background: Our previous studies indicated that MSC CR4 improved cardiac function after myocardial infarction (MI). This study was aimed to investigate the specific role of MSC CR4 in neovascularization of infarcted myocardium using a suicide gene approach. Methods: A regenerating recombinant lentivirus (Lentivector Expression System) was devised to deliver the CXCR4, herpes simplex virus-thymidine kinase (TK) driven by an endothelial-specific promoter of VE-cadherin (pCDH-TK), or without the promoter as negative control (pCDH-null) (Fig. 1A). Ganciclovir (GCV) induced suicide in cells expressing both TK and VE-cadherin. In vitro , pCDH-TK or pCDH-null was transduced into EC (EC TK or EC null ) and cells were treated with vehicle (VEH) or GCV (100µM) for 7 days. In vivo , female rats with myocardial infarction (MI) after permanent LAD ligation were transplanted with either male ordinary MSC (MSC Ord ), MSC (MSC Null ), MSC CR4 or MSC CR4 transduced with pCDH-TK (MSC CR4 -TK). Rats then received VEH or GCV (100mg/kg daily for 7 days) by IP injection before euthanasia. Results: GCV significantly decreased the number of EC TK but had no effect in EC null . Absent GCV, TK expression had no effect on EC growth (Fig. 1B &amp; C). In vivo: GCV reduced significantly neovascularization in post-MI hearts transplanted with MSC CR4 -TK. New vessel formation was not affected either after exposure to VEH or GCV in the absence of pCDH-TK. Y-chromosome positive nuclei were observed in newly formed vessels (Fig. 1D-H). Conclusion: MSC CR4 plays an important role in neovascularization during cardiac repair after infarction.
Abstract 9716: Who Needs a Statin? Impact of the New Expert Panel Guidelines for Screening and Management of Dyslipidemia in Children and Adolescents
Authors: Brian W McCrindle, Pascal Tyrrell, Rae-Ellen W Kavey
Journal: Circulation (2012)

Introduction: Recent Expert Panel guidelines commissioned by the National Heart, Lung and Blood Institute recommended universal and targeted lipid screening for children and adolescents, together with specification of lipid cutpoints and additional risk factors used in decision-making regarding initiation of lipid-lowering drug therapy. Given the current epidemic of childhood obesity and associated dyslipidemia, we sought to determine the potential impact of these guidelines on the estimated proportion of adolescents would potentially screen positive and be recommended for medication. Methods: We examined serial cross-sectional assessments using National Health and Nutrition Examination Survey data (1999-2010) of US children ages 12 to 17 years. The weighted proportion of participants meeting guideline screening and management lipid and risk factor cutpoints was determined, and compared to that obtained by applying previous guidelines. Results: Based only on non-fasting lipid measurement, 24.7% of screened individuals would have dyslipidemia (non-HDL &gt;145 mg/dL + HDL &lt;40 mg/dL) and require further evaluation. Using fasting assessment, 20.3% would screen positive, with 6.6% having high LDL (&gt;130 mg/dL). Of those with fasting assessment, 17.2% were obese, 9.2% smoked, and 2.7% had hypertension. Assuming no improvement with lifestyle therapy and incorporating additional risk factors in decision-making, 0.85% (215,900 US children) might be recommended for statin therapy based on the new guidelines. For severely obese children with BMI &gt; 97 th %ile, 3.1% might be recommended for statin therapy. Applying previous guidelines, 0.50% would meet National Cholesterol Education Program 1992 criteria and 1.00% would meet American Academy of Pediatrics 2008 criteria for medication. Conclusions: Despite the recommendation for universal screening and greater specification regarding risk factors, only a small proportion of adolescents will be recommended for drug therapy with the new guidelines, appropriately targeting those with clustering of risk factors commonly associated with severe obesity, as well as those with familial dyslipidemias.
Abstract 9711: Cardioprotection by Endogenous Cardiac Myocyte P2x4; Receptors in Pressure Overload and Ischemic Heart Failure
Authors: Tiehong Yang, Jian-Bing Shen, John Redden, Ronghua Yang, Kimberly Dodge-Kafka, Bruce T Liang
Journal: Circulation (2012)

Despite progress in its therapy, heart failure is a leading cause of mortality and morbidity. In defining a biological role of the ligand-gated ion channel P2X4 receptor, we uncovered a protective role of this channel in heart failure. P2X4 gene was flanked by loxP sites bwteen exons 2 and 4. The second loxP site together with the Frt-PGKneo-Frt cassette was inserted in intron 1 in a direction opposite to P2X4 transcription. After targeting the ES cells, PGKneo was removed by breeding chimeric males with ROSA26-Flpe females to generate P2X4 flox/+ F1 pups. To create cardiac myocyte-specific knockout of P2X4 receptors, homozygous P2X4 floxed/floxed mice were bred with Tg mice (Myh6-cre/Esr1*, Jax stock no: 005650) containing a tamoxifen responsive Cre-estrogen receptor chimeric recombinase driven by the α-myosin heavy chain promoter. Knockout of P2X4 receptors (KO) was confirmed by lack of detectable P2X4 with immunoblotting and by lack of contractile response to the P2X agonist 2-methylthioATP. KO animals showed normal basal cardiac function but depressed contractile performance in both left coronary artery ligation and pressure overload models of heart failure by echocardiography and isolated working heart parameters. By contrast, cardiac myocyte-specific overexpression of the P2X4 receptor protected against pressure overload-induced and post-infarct heart failure. P2X4 receptors co-immunoprecipitated with nitric oxide synthase 3 (NOS3 or eNOS). Administration of eNOS inhibitor L-NIO blocked the salutary effect of cardiac P2X4 receptor overexpression in post-infarct heart failure as did eNOS knockout. The present study uncovered a protective role of endogenous cardiac myocyte P2X4 receptors in heart failure and demonstrated an important role of eNOS in mediating this protection.
Decoding the Cardiac Message
Authors: Gerald W. Dorn
Journal: Circulation (2011)

Our understanding of the molecular underpinnings of cardiac development and stress-response has progressed non-linearly over the past 40 years. Preliminary observations that cardiac RNA content increases along with muscle mass in hypertrophy were followed in the 1980s by an explosion of information derived from the fruits of cDNA cloning: The use of individual gene-specific cDNA probes for spatio-temporal analysis of gene expression lead to the description of cardiac myosin and actin isoform mRNA regulation by thyroid hormone. Recombinant expression systems were developed as platforms for functional analyses of cDNA products. Assays of muscle-specific mRNAs after cellular manipulation revealed that intracellular proteins regulate gene transcription. The subsequent decades defined specific cis DNA elements and transactivating protein factors that reprogram individual cardiac genes in disease, and transcriptional profiling by microarray or RNA sequencing revealed genome-wide mRNA regulation under pathological conditions. However, the underlying mechanistic concepts about how mRNA expression is regulated did not change. Now, we are witnessing a second molecular revolution catalyzed by the recent observation that cytoplasmic microRNAs directly regulate mRNAs. Whereas transcriptional regulation is more “on” or “off” for a single gene, a single microRNA can fine-tune entire biological pathways according to physiological demand by partially suppressing or destabilizing multiple functionally related mRNAs. Concomitant transcriptional regulation of microRNAs and their mRNA targets in cardiac disease enhances diversity of response, but deconvoluting these interactions is a challenge to defining the role of microRNAs in heart disease. Understanding the determinants of microRNA-mRNA targeting will accelerate rational development of microRNA-based therapeutics.
Abstract 9355: Mitral Valve Disease in Marfan Syndrome Patients Undergoing Aortic Root Replacement
Authors: Meghana Kunkala, Hartzell Schaff, Zhou Li, Irina Volguina, Scott A LeMaire, Joseph Coselli, Heidi Connolly
Journal: Circulation (2012)

Background: The primary cardiac manifestations of the Marfan syndrome (MFS) include aortic root dilation and mitral valve prolapse (MVP). There are only scant data describing MV disease in MFS patients who undergo aortic root replacement. Methods: We retrospectively studied 239 patients (90 female; mean age 34 y) with MFS enrolled in a prospective multicenter registry. All patients were referred for repair of aortic root aneurysms with either composite graft aortic valve replacement (AVR, n=59) or an aortic valve-sparing procedure (AVS, n=180). MVP and mitral regurgitation (MR) severity was evaluated by echocardiography preoperatively and during follow-up (postoperatively, 6 months, and 1, 2, and 3 years after surgery). The severity of MR was graded as none, trivial (0), mild (1), moderate (2), moderate to severe (3), or severe (4). Preoperative echocardiography identified MVP in 166 (69%) patients without previous MV intervention. Results: Forty-one (25%) of 166 patients with MVP received AVR, and 125 (75%) received AVS, with similar proportions of patients with preoperative MR grade &gt;2 in the two groups ( p =0.7). Thirty-three patients (20%) underwent concomitant MV intervention: 29 repairs and 4 replacements (15 patients (45%) had MR &gt;2, 11 (33%) had MR=2, and 7 had MR ≤1). All patients with MR &gt;2 underwent a MV procedure. One patient following MV repair required MV replacement on postoperative day 16 after developing grade 4 MR. No other patient required MV reintervention during follow-up (mean clinical follow-up, 30±9 months). Echocardiography performed 21±13 (±1 SD) months postoperatively revealed MR &gt;2 in only 1 of 158 patients. There were 1 early death (bleeding) and 2 late deaths (multi-organ failure and unknown cause); all deaths occurred in patients with concomitant MV surgery. Conclusions: MVP is present in 69% of patients with MFS undergoing aortic root replacement; 20% of patients with MVP underwent a concomitant MV procedure. Short-term results suggest that a simultaneous MV procedure in patients with MR &gt;2 is reasonable because operative risk was not increased and subsequent MV procedures were rare. More follow-up is needed to learn if prophylactic MV intervention at the time of aortic surgery might benefit patients with MR ≤2.
Abstract 9410: Quantification and Characterization of Noncalcified Coronary Plaque by High Definition Computed Tomography : Comparison with Integrated Backscatter Intravascular Ultrasound
Authors: Tsuda Takuma
Journal: Circulation (2012)

Background: Noninvasive assessment of coronary plaque is important for coronary risk stratification. The utility of 64-slice CT remains unclear for evaluation of coronary plaque component. Recently high definition computed tomography (HDCT) with new gemstone detector has been developed, which has high spatial resolution. We evaluated the accuracy of HDCT for quantification and characterization of noncalcified coronary plaque compared with integrated backscatter intravascular ultrasound (IB-IVUS). Methods: We enrolled consecutive 33 patients with unstable or stable angina. Noncalcified plaque of target lesion was evaluated by HDCT and the findings were compared with those of IB-IVUS at the same sites. Plaque was classified as lipid (-42 to 60 HU: Hounsfield unit), fibrous (61 to 112 HU) or calcified (&gt;500 HU) by HDCT and we evaluated minimum lumen area (MLA), percentage of stenosis (%stenosis), total plaque volume, lipid volume, percentage of lipid volume (%lipid), fibrous volume and percentage of fibrous volume (%fibrous). Results: A total 38 noncalcified coronary plaques were evaluated. HDCT was well correlated with IB-IVUS for assessing MLA (2.53 ± 0.89mm vs. 2.62 ± 0.71mm, r=0.658, P&lt;0.001), %stenosis (65.6 ± 12.4% vs. 63.5 ± 12.9%, r=0.870, P&lt;0.001), plaque volume (156.2 ± 87.8mm 3 vs. 144.0 ± 100.6mm 3 , r=0.886, P&lt;0.001), lipid volume (86.1 ± 52.7mm 3 vs. 76.5 ± 65.0mm 3 , r=0.901, P&lt;0.001), %lipid (53.7 ± 10.6% vs. 49.8 ± 12.2%, r=0.570, P&lt;0.001), fibrous volume (56.2 ± 25.6mm 3 vs. 57.5 ± 35.8mm 3 , r=0.761, P&lt;0.001) and %fibrous (38.7 ± 11.0% vs. 42.4 ± 10.0%, r=0.747, P&lt;0.001). Conclusion: HDCT with new gemstone detector can accurately quantify and characterize noncalcified coronary plaque compared with IB-IVUS. HDCT can be a useful tool for noninvasive assessment of vulnerable plaque.
Abstract 95: Does Real-Time Audiovisual Feedback for Public Access Defibrillation Enhance Device Usability and Outcomes? A Simulated Pilot Study on a Disposable Home-Use Defibrillator
Authors: Rebecca Di Maio, David Brody, James McAnlis, Lauren Crawford, Paul McCanny, Allister McIntyre, Andrew Howe
Journal: Circulation (2012)

Introduction: A public access defibrillator (PAD) must be simple to operate, because in many cases the operator is a first-time user with minimal or no training. Effective treatment should be delivered to the patient in a manner which emphasises safe use of the device and minimises the risk of injury to patient and rescuer. We assessed the hypothesis that the addition of audio-visual feedback delivered to PAD users ensures they correctly place the electrodes, quickly and safely deliver a defibrillation shock, and effectively administer CPR. Methods: Informed consent was received from 24 participants (58% male) who took part in this prospective randomised study. The participants were split into two groups - BLS trained and untrained, and randomly assigned a training defibrillator (HeartSine PDU 400 or Philips FRx). The participants were videoed so that CPR and resuscitation quality parameters could be retrospectively analysed. Between the trained and untrained group we measured differences in time to first shock, adequacy of pad placement and time to place pads as main outcome parameters, and, compression depth and rate, correct hand positions and adherence to hands- off prompts as secondary outcome parameters. Results: All 24 participants delivered a rescue shock. The minimally trained group had the fastest time to first shock (94±23 sec versus 139±53 sec, p=0.017) and the fastest time to place pads (69±19 sec versus 115±52 sec, p=0.012). There was no statistical difference between the two groups in terms of electrode placement, CPR quality, and adherence to hands-off prompts or the device used. Conclusions: It can be concluded that audio-visual feedback systems in PADs allow minimally trained and untrained users administer effective defibrillation therapy and CPR to SCA victims. The main difference seen between the two groups is the time to first shock, which may represent the untrained users’ hesitancy to initiate the resuscitation by turning on the PAD.