tbuckley/cabot-search huggingface dataset:
Abstract 8832: Impact of Time Delay to Treatment on Ischemic Microvascular Damage and In-Hospital Complications in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Atsushi Yamamuro, Shuichiro Kaji, Makoto Kinoshita, Natsuhiko Ehara, Takeshi Kitai, Kitae Kim, Atsushi Kobori, Tomoko Tani, Shigefumi Morioka, Toru Kita, Yutaka Furukawa
Journal: Circulation (2011)

Background: Primary percutaneous coronary intervention (PCI) is more effective than thrombolytic therapy for the treatment of ST-segment elevation myocardial infarction (STEMI) when delivered by an experienced team soon after the onset of symptoms. However, data from experimental studies suggest that the extent of microvascular damage is worsened by longer durations of ischemia. The impact of ischemic time on microvascular damage and in-hospital complications has been insufficiently studied. The purpose of this study was to examine the effects of recanalization within 120 minutes on the coronary microvascular integrity and in-hospital event rate. Methods: Two hundred and eleven consecutive patients with first anterior STEMI who underwent successful PCI were subjected to coronary flow measurement with a Doppler guidewire. The coronary flow velocity spectrum provided the following parameters: systolic peak velocity (SPV) and diastolic deceleration time (DDT). We defined the presence of microvascular obstruction as DDT of ≤ 600 ms and the presence of systolic flow reversal. We classified the patients into two categories according to time from symptom onset to first balloon inflation: ≤ 120 minutes (group 1), 120 &lt; minutes (group 2). The in-hospital event rate was compared among the 2 groups. Results: As for the relationship between the ischemic time and the severity of microvascular damage, earlier reperfusion was associated with a significantly lower risk of microvascular obstruction: 0/12 (0%) for group 1 and 89/199 (45%) for group 2 (p&lt;0.05). The ischemic time was significantly correlated with the DDT (group 1 vs. group 2; 806±122 vs. 563±247 ms, p&lt;0.05) and the SPV (22±11 vs. -8±25 cm/s, p&lt;0.05). The in-hospital event rates for malignant arrhythmia and congestive heart failure were significantly higher in patients with late reperfusion group (0/12 patients, 0% vs. 87/199 patients, 44%; p&lt;0.05; 0/12 patients, 0% vs. 49/199 patients, 25%; p&lt;0.05, respectively). Conclusions: Early recanalization within 120 minutes critically determines coronary microvascular integrity, and recanalization delays in time to reperfusion with primary PCI adversely affect in-hospital complications in higher risk patients, such as those with anterior STEMI.
Abstract 19559: Risk of Atrial Fibrillation is Increased in Patients with Autoimmune Vasculitis: A Population-Based Cohort Study
Authors: Rowlens M Melduni, Mohammed N Nazmul, Shreyasee Amin, Bernard J Gersh, Kent R Bailey, Stephen S Cha, Leslie T Cooper, James B Seward, Hon-Chi Lee
Journal: Circulation (2012)

Introduction Current evidence suggests that abnormal ventriculo-vascular coupling may contribute to the development of atrial fibrillation (AF) by increasing ventricular filling pressures and consequently, left atrial pressure. Recent investigations have also suggested that inflammation might have a role in the pathophysiology of AF. We hypothesize that autoimmune vasculitis plays a significant role in the pathogenetic mechanism of AF. Methods In this longitudinal cohort study, residents of Olmsted County, MN with first- time diagnosed AF during 1980-2000 and a reference age- and sex-matched control group from the same underlying population and time period were identified and followed until death, or 2000. The relationship between autoimmune vasculitis and first documented AF was analyzed. Results Of a total of 8766 patients (mean age 61.1+14.9 years; 56% women), 691 (7.9%) were diagnosed with autoimmune vasculitis during the 20 year period. The prevalence of autoimmune vasculitis in the AF group was 9.9% and 5.9% in the control group; p &lt;0.001, respectively. After adjusting for CAD and LV dysfunction, the odds of autoimmune vasculitis in AF was 1.7 times higher than in controls (OR 1.69, 95%; CI 1.42 - 2.01, p &lt; 0.0001). AF patients with autoimmune vasculitis had a worse survival compared to controls; p=.0114 (log-rank test). Conclusion Autoimmune vasculitis strongly increases the risk of atrial fibrillation and portends shorter survival in the AF population. These observations may represent one mechanism linking increased arterial stiffness and inflammation in the pathogenesis and prognosis of AF as an age-related disorder.
Abstract 19519: Patient Health Questionnaire-9 Correlates with Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire in Measuring Heart Failure Patient Well-Being and Predicting Outcomes
Authors: Jesalyn A Tate, Mary E Davis, Tiffanie M Markus, Daniel J Lenihan
Journal: Circulation (2012)

Introduction: The assessment of patient well-being and correlation with outcomes is especially difficult, particularly with HF patients. Currently, the time-consuming Kansas City Cardiomyopathy Questionnaire (KCCQ) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) are typically used only in research protocols; conversely, the PHQ-9 is a much simpler questionnaire that can be completed and scored in a typical clinical setting. Hypothesis: We hypothesized that the scores of the PHQ-9 correlate with the scores of the KCCQ and MLHFQ, and that for clinical purposes, it may be beneficial to substitute the longer questionnaires with the PHQ-9. Methods: Using data obtained through the Vanderbilt Main Heart Registry, we compared patient scores on the KCCQ and MLHFQ in each depression category (none, mild, moderate, moderately-severe, and severe) in 294 patients with heart failure, as defined by patient PHQ-9 scores. We also assessed survival data for the patients that have been followed up to two years with annual PHQ-9 scores to evaluate the correlation between depression category and mortality. Results: The study group (N=294) was 55 years (range 18-90) and 60% male, most with symptomatic HF (93% ≥ NYHA II)( Table 1.). Twenty-five percent of patients with severe depression are deceased. Preliminary results indicate there is a direct correlation between PHQ-9 category and corresponding KCCQ (p &lt; 0.001) and MLHFQ (p &lt; 0.001) scores (Figure 1.). Conclusion: Our findings suggest that the PHQ-9 can be readily used as a screen for depression and quality of life in HF patient in the clinical setting. Additionally, PHQ-9 score appears highly correlated to major outcomes.
Abstract 19556: The Beneficial Effects of Statin Therapy on Total and Composition-Specific Plaque Volumes Measured by Computed Tomography Angiography
Authors: Naser Ahmadi, Vahid Nabavi, Jennifer Malpeso, Ramin Ebrahimi, Matthew Budoff
Journal: Circulation (2012)

Background: Coronary plaque volume and its progression is an independent predictor of cardiovascular mortality. This study evaluates the overall and composition-specific (noncalcified, mixed or calcified) change in plaque volume measured by computed tomography angiography (CTA) in response to statin therapy. Methods: One hundred and seven consecutive subjects (age 67±9 years, 80.7% men) who underwent serial clinically indicated CTAs with median interval of 1.2 year, were studied. clinical and demogrpahic findings of 31 with statin therapy and 75 without statin therapy were evaluated. Total and composition-specific plaque volume of target segment with luminal stenosis0.05). At follow-up, there were -38.2% decrease in plaque volume in individuals with statin therapy as compared to those without statin therapy (p=0.0001), and remained significant even after adjustment for age, gender and conventional risk factors. Similarly, significant decrease in noncalcified and mixed plaque as well as lack of progression of calcified plaque in statin therapy group was noted (p&lt;0.05). Risk factor adjusted median decrease in overall, mixed, calcified and noncalcified plaque volumes were 56%, 12%, 43% and 144% more in statin therapy group as compared to those without statin therapy, which was more robust in women(p&lt;0.05). Conclusion: Statin therapy was associated with significant decrease in plaque volume, especially noncalcified plaques, prominently in women. CTA accurately measures the overall and composition-specific change in plaque volume in response to statin therapy; highlighting its important role as a non-invasive modality, to monitor response to anti-atherosclerosis therapy and its management.
Abstract 19536: Primary and Secondary Prevention of Athletic Sudden Cardiac Death in Suffolk County Public High Schools, New York
Authors: Thanda W Htin, Nicole Moulinie, Kim JUng, Katherine Maccaro, Paul Maccaro, Kent Stephenson
Journal: Circulation (2012)

Optimal strategies to prevent and treat SCD (Sudden Cardiac Death) in student athletes remain debatable. To identify students at risk of SCD, American Heart Association (AHA) has recommended a 12-point pre-participation evaluation (PPE) tool. NY State laws require the presence of Automated External Defibrillators (AEDs) during high school sports activities. Aim: To examine (1) adherence to AHA’s 12 element PPE (2) presence, training and implementation of AEDs in Suffolk County public schools. Methods: In 2010, voluntary surveys were sent out to 53 public school districts in Suffolk County. Each district’s PPE forms were requested to evaluate adherence to AHA recommendations. AED survey included its presence, training and use. Results: A total of 52 districts responded to PPE request (response rate 98.1%). No districts used all 12 elements in their forms; 11 districts (21.5%) used no elements; majority (35 districts, 67.31%) used ≤ 4 elements. Maximum number of elements used was 8 in 19 districts (15.38%). Most frequently used element was syncope (57.9%). Each elements frequency is tabulated. 27 districts completed AED survey (response rate 50.9%). Each school had at least 2 AEDs (range 2-34, mean 19.2); students per AED was 70.9. Coaches (92.6%) were mostly to be trained in AED formally followed by 85.2% of school nurses, 51.9% of security staff, 32.14% of teachers, and 17.85% of students. A total 25 districts (89.29%) had emergency response plan, 26 (92.85%) had access to early defibrillation, 21 (75%) had practiced emergency response plan. There was no significant correlation between number of AEDs in a school and number of AHA elements used in PPE forms (ρ = -0.3251, P &lt; 0.2567). CONCLUSION: In the absence of legislation mandating implementation of the AHA PPE tool, suboptimal adherence persists. In contrast, implementation of AEDs appears more promising. Future management guidelines should focus on broader AED training of students and teachers.
Abstract 208: Innovative Web-Based e-Registry Enhances Survival After Out-of-Hospital Cardiac Arrest
Authors: Patrick Chow-In Ko, Wen-Chu Chiang, Allen Wen-Hsiang Chiu, Chi-Hung Lin, Hsien-Tang Lin, Qing-Mei Chen, Guang-Hua Xiong, Ying-Wen Hsiao, Matthew Heui-Ming Ma
Journal: Circulation (2012)

Introduction: Patient and prehospital predictors of survival after OHCA include ventricular fibrillation, witnessed arrest, and receiving bystander cardiopulmonary resuscitation. Whether systems-based approaches on Emergency Medical Service (EMS) such as new registry or reform could improve survival have not been well studied. Hypothesis: An innovative web-based e-registry may enhance survival after OHCA. Methods: An urban EMS with 2.62 million residents in 272 squared km was studied. Traditionally the EMS operated an OHCA Registry by manual-traced paper archives that coordinated data collections across dispatch center, ambulance teams and receiving hospitals. After a 2-year redesign, a computerized Web e-Registry in 2010 was established. The ambulance team initiated an individual patient data block right after an OHCA event, and that data block was immediately pushed to the customized webpage of receiving hospital so that they could easily upload patient outcomes anytime online, and periodically update patient status to the Web system. Health Bureau tracked the compliance with data uploading among receiving hospitals. Fire Department staff reviewed and uploaded prehospital and defibrillator data to the Web. The outcomes of 2-hour sustained return of spontaneous circulation (2hr ROSC), survival to discharge, and favorable Cerebral Performance Category 1 and 2 at discharge (fCPC), and data-missing rate for 4 years before the e-Registry (n=7,499) were compared to those 1 year after (n=1,777). Results: After e-Registry, for arrest of shockable rhythm, fCPC increased by 9.5% (95% CI: 4.2-16.1%); for non-shockable arrest, 2hr ROSC (4.2%, 95% CI: 1.4-7.1%) and fCPC (0.7%, 95% CI: 0.2-1.4%) increased significantly. After adjusting for patient and EMS variables, e-Registry was associated with fCPC (adjusted odds ratio: 1.9, 95% CI: 1.1-3.6) for shockable arrest, 2hr ROSC (adjusted OR: 1.2, 95% CI: 1.1-1.4) and fCPC (adjusted OR: 2.3, 95% CI: 1.1-5.1) for non-shockable arrest. Outcomes data-missing rate was significantly reduced by 5.3% (95% CI: 2.8-7.9%). Conclusions: Compared to paper archives, systems-based intervention by launching web-based e-registry may enhance favorable CPC after OHCA and reduce outcomes data-missing rate.
Abstract 9197: <i>In Situ</i> Stem Cell Therapy Using Human Adipose Tissue-Derived Multi-lineage Progenitor Cells Combined with HMG-CoA Reductase Inhibitor Synergistically Reduce Serum Cholesterol Level in Hyperlipidemic Watanabe Rabbits
Authors: Hanayuki Okura, Ayami Saga, Mayumi Soeda, Jyunko Tani, Mariko Moriyama, Hiroyuki Moriyama, Shizuya Yamashita, Akihiro Ichinose, Shinya Tahara, Takao Hayakawa, Akifumi Matsuyama
Journal: Circulation (2011)

Background : Familial hypercholesterolemia (FH) is an autosomal co-dominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis. We examined the response to the combination of in situ stem cell therapy using human adipose tissue-derived multi-lineage progenitor stem cells (hADMPC) and HMG-CoA reductase inhibitor in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of homozygous FH. Methods : WHHL rabbits received hADMPC via the portal vein, followed by a course of immunosuppressive therapy to avoid xenogenic rejection. In situ reprogramming of the hADMPC into hepatocytes was examined by immunohistochemistry and QT-PCR analysis. Lipid profiles were examined before-transplantation, after-transplantation and/or after transplantation followed by 4 weeks of treatment with HMG-CoA reductase inhibitor, pravastatin. LDL clearance was examined at the end of the study by125I-LDL turnover studies. Results : The hADMPC were integrated into the hepatic parenchyma after transplantation, and expressed human hepatocyte markers such as albumin, indicating that these cells were reprogrammed into hepatocytes-like cells in situ . hADMPC-transplantation reduced serum cholesterol levels and improved LDL turnover. Transplantation followed by 4-week treatment with pravastatin further reduced serum cholesterol levels compared with untreated rabbits. LDL clearance was significantly augmented in the pravastatin-treated rabbits. Conclusion : Transplantation of hADMPC corrected the metabolic defects and the effects were augmented by statins in WHHL rabbits, in which no significant effects were observed by statins. In situ stem cell therapy combined with other drugs is a potentially useful strategy for FH.
Abstract 9254: Downregulation of SR Ca <sup>2+</sup> -ATPase as a Contributing Cause of Impaired Cardiomyocyte Basal and Beta-Adrenergic Regulation of [Ca <sup>2+</sup> ]i with Myocyte Dysfunction in Monkeys with Chronic Heavy Alcohol Consumption
Authors: Nadeen Wajih, Heng-Jie Cheng, Peng Zhou, James B Daunais, David P Friedman, William C Little, Kathleen A Grant, Che Ping Cheng
Journal: Circulation (2011)

Background . Recent evidence indicates that the main effect of chronic alcohol ingestion is the loss of left ventricle (LV) contractility that progressively induces the development of alcoholic cardiomyopathy (ACM) and heart failure. However, the mechanisms underlying this sequela of events remain unclear. We tested the hypothesis that chronic alcohol-intake-caused progressive LV dysfunction is intrinsic to cardiomyocytes, and that impaired SR Ca 2+ -ATPase (SERCA 2a) function may play a key role. Methods . We compared the expression and activity of cardiac SERCA 2a and assessed myocyte contractile, [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to isoproterenol (ISO, 10 -8 M), a β-adrenergic receptor (AR) agonist, in isolated myocytes obtained from biopsied LV tissues of cynomolgus monkeys: 6 normal controls (N) and 6 monkeys who chronically self-administered high levels of alcohol (HA) (4% alcohol, 3.3±0.7 g/kg) for 12 months. Results. Compared with controls, in alcoholic myocytes, SERCA 2a protein expression was decreased 56% (0.50 vs 0.89) and Ca 2+ -dependent activity of SERCA 2a was decreased 69% (32.7 vs 107.2 nmol/mg protein/min) (p&lt;0.05). This change of SERCA 2a was associated with significant decreases in basal cell systolic amplitude (SA) (79%, HA: 6.4±1.3% vs N: 11.5±1.6%), velocity of shortening (dL/dt max ) (38%, 64.8±5.0 vs 104.8±6.0 μm/s), velocity of relengthening (dR/dt max ) (39%, 54.2±4.7 vs 88.4±5.3 μm/s), and a 34% prolonged time to peak of shortening. In the alcoholic myocytes, the peak [Ca 2+ ] iT (33%, HA: 0.21±0.05 vs N: 0.31±0.05) was significantly reduced, but the diastolic [Ca 2+ ] iT was increased and the decline of [Ca 2+ ] i was slower. These alterations were accompanied by diminished ISO-stimulated positive inotropic effect. Compared with normal controls, in alcoholic cardiomyocytes, ISO (10 -8 M) significantly blunted the increases in SA (HA: 27% vs N: 60 %), dL/dt max (49% vs 79%), dR/dt max (24% vs 38%) and [Ca 2+ ] iT (16% vs 32%). Conclusions. Chronic heavy alcohol intake causes downregulation of cardiac SERCA 2a with depressed myocyte contractile performance and abnormal myocyte basal and β-adrenergic regulation of [Ca 2+ ] i . These findings support a mechanistic role of chronic alcohol-induced cardiac SERCA 2a dysfunction in ACM.
Abstract 19610: Role of Hypoglycemic Agents on Ischemic Preconditioning in Diabetic Patients with Stable Multivessel Coronary Artery Disease
Authors: Rosa M Garcia, Whady Hueb, Augusto H Uchida, Paulo C Rezende, Eduardo G Lima, Cibele L Garzillo, Carlos A Segre, Desiderio Favarato, Jose A Ramires, Roberto Kalil Filho
Journal: Circulation (2012)

Background: Ischemic preconditioning (IPC) protects the heart from irreversible injury and some hypoglycemic drugs can abolish IPC, affecting infarct size and contractile function and contributing to a worse prognosis. We aimed to evaluate the effect of 2 hypoglycemic agents on myocardial IPC in patients with type 2 diabetes and symptomatic coronary artery disease. Methods: We evaluated 81 patients, consecutively included, with type 2 diabetes, previous positive exercise test and multivessel coronary disease confirmed by coronary angiography. In phase I, without drug, all patients underwent 2 consecutive treadmill exercise tests (T1 and T2). After that, we started the phase II: 42 patients received repaglinide 6 mg per day (group R) and 38 pacients received Vildagliptin 100 mg per day ( group V), during one week and underwent 2 sequential tests (T3 and T4). The time interval between the exercise tests was 30 minutes. Results: In phase 1, IPC was demonstrated, in all patients, by improvement in the time to 1.0 mm of ST segment depression (T-1.0mm) in second of two sequential tests. All patients developed ischemia in T3; however, 83.3% of patients in group R experienced ischemia earlier in T4, indicating the cessation of IPC ( P &lt;0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still preserving the protective effect ( P &lt;0.0069). Conclusions: Repaglinide eliminated myocardial IPC, probably by its effect on the ATP-K channel. Vildagliptin did not affect this protective mechanism in a relevant way in patients with type 2 diabetes and coronary artery disease, suggesting a good alternative treatment in this population.
Abstract 19674: Late Endothelial Progenitor Cells (EPCs) and Platelets Interact through Endothelial Differentiation Gene (Edg)-2-Lysophosphatidic Acid (LPA) Axis under the Regulation of Peroxisome Proliferator-Activated Receptor (PPAR)-δ, Leading to Vasculogenesis
Authors: Jung-Kyu Han, Hyo-Sook Ahn, Joo-Yun Won, Jee-Hoon Kang, Han-Mo Yang, Hyun-Jai Cho, Kyung-Woo Park, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2012)

Background PPAR-δ has been implicated in various cellular metabolism, but the roles in vascular biology are largely unexplored. Here, we investigated the effects of PPAR-δ activation on late EPC-platelet network. Methods &amp; Results GW501516 (500nM), a highly selective PPAR-δ agonist treatment enhanced BrdU incorporation to human late EPCs, and augmented their pro-vasculogenic effects such as Matrigel tube formation and scratch-wound healing dose-dependently. To reveal the mechanism, the expression level of Edg family members was screened in late EPCs after PPAR-δ activation. We found that only Edg-2 mRNA and protein expression, which is a major receptor for LPA, were specifically upregulated by GW501516. ChIP and promoter assays demonstrated the direct transcriptional regulation of Edg-2. Edg-2 is a membrane receptor for LPA which is the major lysophospholipid growth factor generated on platelet activation. GW501516 (500nM), the supernatant of activated platelets, or LPA (100nM) induced the proliferation (BrdU incorporation) of late EPCs, and enhanced their provasculogenic functions such as chemotaxis (Transwell), planar migration (scratch wound healing), and capillary tube formation (in vitro Matrigel). Co-treatment of GW501516 and the supernatant synergistically enhanced the above results, suggesting the interaction between late EPCs and platelets augmented by PPAR-δ activation. But GSK0660 (1μM, PPAR-δ antagonist) or Ki16425 (3μM, EDG-2 blocker) treatment reversed the results. In vivo Matrigel plug assay (n=4, each group), the combination of late EPCs (106/plug) and platelets robustly induced capillary formation, compared with late EPCs or platelets alone. GW501516 potentiated the interaction, leading to more capillaries. In vivo mouse skin wound model (n=4, each group), late EPCs in platelet gel enhanced the wound healing with new vessel formation, which was augmented by GW501516 , confirming the interaction in vivo. PPAR-δ or EDG-2 siRNA transfection blocked all the in vivo effects of GW501516. Conclusions Platelets and late EPCs play a key role in vascular regeneration via Edg-2 - LPA axis. PPAR-δ augments the interaction through Edg-2 upregulation, suggesting its agonist as a good therapeutic tool for vascular regeneration.