tbuckley/cabot-search huggingface dataset:
Abstract 9574: Enhanced Rho-kinase Activity in Circulating Neutrophils of Patients with Vasospastic Angina after the Great East Japan Earthquake
Authors: Taro Nihei, Jun Takahashi, Yoku Kikuchi, Kiyotaka Hao, Yusuke Takagi, Ryuji Tsuburaya, Takashi Shiroto, Yoshitaka Ito, Yasuharu Matsumoto, Masaharu Nakayama, Kenta Ito, Satoshi Yasuda, Hiroaki Shimokawa
Journal: Circulation (2012)

Purpose: We have recently demonstrated that Rho-kinase activity in circulating neutrophils is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). Coronary vasospastic activity is known to be enhanced under stressful conditions. On March 11, 2011, we experienced the Great East Japan Earthquake in our Tohoku area. In this study, we thus examined whether Rho-kinase activity was increased in VSA patients after the Earthquake. Methods: In 11 patients with proven VSA (M/F 8/3, 62±11 yrs), we were able to measure Rho-kinase activity in circulating neutrophils at 3 time points, before and 6 and 12 months after the Earthquake. Rho-kinase activity was defined by the ratio of phosphorylated form/total form of myosin-binding subunit (MBS), a substrate of Rho-kinase. We also quantitatively examined the extent of mental stress by the post-traumatic stress disorder (PTSD) questionnaire. Results: In the VSA patients, Rho-kinase activity was significantly increased at 6 months after the Earthquake despite the continued medical treatment with calcium channel blockers, which was returned to baseline level at 12 months (0.99±0.34 at baseline, 1.71±0.23 at 6 months, and 0.90±0.34 at 12 months) ( Figure ). Among the 11 patients, 3 patients were directly hit by the Tsunami, who complained increased frequency of angina attacks and the use of sublingual nitroglycerin after the Earthquake. Importantly, in those 3 patients, as compared with the remaining 8 patients without direct tsunami hit or changes in symptoms, both PTSD score (32±7 vs. 5±8, P=0.01) and the changes in Rho-kinase activity at 6 months from the baseline (268±232% vs. 55±40%, P&lt;0.05) were significantly higher. Furthermore, there was a significant correlation between the Rho-kinase activity changes and the PTSD score (r= 0.67, P&lt;0.05). Conclusions: These results indicate that Rho-kinase activity of VSA patients was transiently enhanced by the disaster-related mental stress.
Abstract 9689: Endothelial Function &amp; Sleep Quality
Authors: Muskaan Behl, Emir Veledar, Donald Bliwise, Lynn Cunningham, Jennifer Vazquez, Kenneth Brigham, Arshed Quyyumi
Journal: Circulation (2012)

Background: Sleep apnea is associated with cardiovascular disease (CVD). Although obstructive sleep apnea is also associated with abnormal endothelial function (EF), a precursor of CVD, it is unknown whether milder sleep disturbance affects EF. We investigated the relationship between sleep quality and EF, with the hypothesis that poor sleep quality, in the absence of sleep apnea, will be associated with endothelial dysfunction. Methods: 684 community participants free of CVD, 68% female, aged 37 to 60 years, were enrolled in the Emory-Georgia Tech Predictive Health Institute study. We measured CVD risk factors, sleep quality using the Epworth Sleepiness Scale (ESS) and selected questions from the Pittsburgh Sleep Quality Index (PSQI). EF was measured using brachial artery flow-mediated dilation (FMD). Multivariate analysis of covariance was used to adjust for age, race, gender, smoking, hypertension, diabetes, and body mass index. Results: Lower FMD measurements were correlated with higher ESS scores that reflect poor sleep quality (r = -0.0858, p = 0.03), a difference that remained significant after multivariate adjustment for the aforementioned risk factors (β = -0.0009, p = 0.03). Participants who reported cough or snoring during sleep in their PSQI questionnaire also tended to have lower FMD (6.2±3.4% compared to 6.9±4.3%, p = 0.056), a difference that remained significant after multivariate adjustment for risk factors above (p = 0.03). Conclusion: In a community-based population without clinically diagnosed sleep apnea, we demonstrate a significant association between sleep quality assessed by questionnaires and EF. Poor sleep quality reflected by symptoms of cough / snoring, or a high ESS score, may contribute to CVD and hypertension by adversely affecting EF.
Abstract 9693: The Least of Three Evils: Anemia, Transfusion, or Both?
Authors: Gabriel Loor, Jeevanantham Rajeswaran, Liang Li, Eugene H Blackstone, Joseph F Sabik, Colleen G Koch
Journal: Circulation (2012)

Objectives: Anemia and red blood cell (RBC) transfusion have been associated with increased perioperative morbidity. Patients with anemia undergoing cardiac surgery are the most likely to receive RBCs, which results in a double negative exposure. We sought to clarify the independent effects of anemia, RBC transfusion, and their combination on risk of organ dysfunction and mortality. Methods: From 11/1/2004 to 10/30/2009, 7,942 patients underwent cardiac surgery and did not receive RBCs, and 1,202 received only intraoperative transfusions. Patients were divided into 4 groups: intraoperative hematocrit (HCT) &gt;25% and &lt;25% without RBC transfusion and &gt;25% and &lt;25% with transfusion. The relationship between HCT, transfusion, and outcome was studied using propensity-score analysis. Outcomes included eGFR, troponin, ventilation time, hospital stay and mortality. Results: Following risk adjustment, comparison of all 4 groups showed that lower HCT and RBC transfusion were independently associated with increased risk of morbidity and mortality. However, patients with severe anemia (HCT &lt;25%) and transfusion had the worst renal function (lowest eGFR, P =.0008), most myocardial injury (highest troponin values, P =.01), longest postoperative ventilator requirement ( P &lt;.0001), longest stay ( P &lt;.0001) and highest mortality ( P =.007; Figure). Conclusions: The least of 3 evils is to tolerate mild to moderate anemia, followed by transfusion, if severe anemia can be avoided. Exposure to both anemia and transfusion is associated with the highest risk of adverse outcome.
Abstract 9612: The Left Atrial Emptying Velocity is Significantly Reduced in Patients With Persistent Atrial Fibrillation and A CHADS-Score ≥ 2 in Comparison o Patients With a CHADS-Score &lt; 2
Authors: Thomas Butz, Jill Deising, Marc van Bracht, Magnus Prull, Gunnar Plehn, Hans-Joachim Trappe
Journal: Circulation (2012)

Aim: A high CHADS2- as well as CHA2DS2-Vasc-Score on the one hand, and left atrial emptying velocity &lt; 20 cm/s (LAAEV) on the other hand have been separately proposed for risk assessment in patients (pts) with atrial fibrillation (AF). The aim of this study was the analysis of the relation between the CHADS2- and CHA2DS2-Vasc-Score as well as the left atrial emptying velocity (LAAEV), the severity of blood stasis (spontaneous echo contrast, SEC), and presence of LAA thrombi as assessed by transesophageal echocardiography (TOE) in pts with persistent AF. Methods: The clinical risk of thromboembolism was assessed with the CHADS2 and CHA2DS2-Vasc-Score in 150 patients (pts) with persistent AF, who had been headed for TOE-guided electrical cardioversion. LAAEV (averaged over 10 beats), SEC, and LAA thrombi were determined by TOE. Results: The 150 pts (age 69±13 years) had a mean LAAEV of 34±19 cm/s, 61 pts had no SEC (41%; SEC I: 37 pts; SEC II: 23 pts; SEC III 22 pts), and 29 LAA-thrombi were detected by TOE (LAAEV 50 cm/s: 25 pts, all without LAA-thrombi). The mean CHADS2-Score was 1.9±1.2 (CHADS2 ≥2: 63 %) and the CHA2DS2-Vasc-Score was 3.2±1.8 (CHADS2-Vasc ≥2: 39/46, 89%). There was a moderate inverse correlation between LAAEV and SEC (r: -0.55, p&lt;0.001), and a weak inverse correlation between LAAEV and the CHADS2- (r: -0.28) as well as CHA2DS2-Vasc-Score (r: -0.28). Moreover, Pts with a CHADS-Score ≥ 2 had a significant reduction of the LAAEV in comparison to pts with a CHADS-Score &lt; 2 (29±16 cm/s vs. 41±20 cm/s; p &lt; 0,001). Conclusion: This study demonstrated a significant reduction of the LAAEV in pts with a CHADS-Score ≥ 2, and a moderate inverse correlation between the CHADS2-Score and the LAAEV. Due to the fact that low LAAEV (&lt; 20 cm/s) on the one hand, and high CHADS2- as well as CHA2DS2-Vasc-Score on the other hand are predictive for the thromboembolic risk in AF, it might be a promising approach to combine clinical and echocardiographic risk assessments for individual decision making regarding the optimal therapy and risk stratification.
Abstract 9546: Oxidized Calcium Calmodulin Dependent Kinase II Causes Increased Mortality after Myocardial Infarction in Diabetic Mice
Authors: Min Luo, Xiaoqun Guan, Mark Anderson
Journal: Circulation (2012)

Diabetes increases oxidant stress and doubles the risk of dying suddenly after myocardial infarction (MI) but the mechanisms for increased mortality are unknown. Mice with streptozotocin (STZ)-induced diabetes developed profound heart rate slowing and died at twice the rate of controls after MI surgery. Oxidized CaMKII (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic compared to non-diabetic patients after MI and from STZ-treated diabetic mice. STZ-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by MI. We developed a knock-in mouse model of oxidation-resistant CaMKIIδ (MM-VV). STZ-treated MM-VV mice and wild type mice infused with MitoTEMPOL, a mitochondrial-targeted antioxidant, showed significantly reduced ox-CaMKII, increased pacemaker cell survival, preserved heart rates and were resistant to diabetes attributable mortality after MI. Our findings suggest activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after MI.
Abstract 9311: Association of Traumatic Brain Injury with Subclinical Atherosclerosis Measured by Coronary Artery Calcium
Authors: Naser Ahmadi, Fereshteh Hajsadeghi, Hormoz Babaei, Ramin Ebrahimi
Journal: Circulation (2012)

Background: Traumatic brain injury (TBI) is a devastating condition resulted in cerebral edema and ischemia. Pre-clinical studies have documented production of cytokine, growth factor and inflammatory biomarkers following TBI. This study investigates the relation of TBI with subclinical atherosclerosis measured by coronary artery calcium (CAC). Method: This nested case-control study consists of 543 Veterans (age 59±10 years, 100% male) with and without TBI who underwent CAC scanning. VA electronic medical records from veterans were used to evaluate medical and psychological diagnoses, procedures, and risk factors. Logistic regression analysis was employed to assess the association of TBI with CAC. CAC was defined as 0, 1-100, 101-400 and 400+. Results: TBI was more prevalent with the presence and severity of CAC (p0 was significantly higher in individuals with TBI as compared to those without TBI (81.2% vs. 60.1%, p=0.0001). After adjustment for age and conventional risk factors, the relative risk of CAC&gt;0 was 176% higher in TBI as compared without TBI (RR: 2.76 (95%CI 1.5-4.9, p=0.001). Similarly, the median CAC was higher in TBI as compared to normal subjects (129A Agatston score vs. 52A Agatston score, p=0.001). After adjustment of risk factors, the relative risk of CAC 1-100, 101-400 and 400+ was 2.22(95%CI 1.03-4.78, p=0.04), 2.98(95%CI 1.49-5.97,p=0.002) and 3.26 (95%CI 1.74-6.14, p=0.001) in individuals with TBI as compared to their matched subjects without TBI, respectively. Conclusion: TBI is independently associated with the presence and severity of subclinical atherosclerosis measured by CAC. This highlights the importance of cardiovascular risk stratification in subjects with TBI.
Abstract 9643: Effect of Partial Fatty Acids Oxidation Inhibition With Trimetazidine on Survival in Heart Failure: Results From an International Multicentre Retrospective Cohort Study
Authors: Hamayak Sisakian, Giuseppe Rosano, Sang H Baek, Pericle Di Napoli, Luca Alberti, Seok-Min , Kang, Giliola Calori, Laura Sahakyan, Armen Sanosyan, Cristina Vitale, Giuseppe Marazzi, Alberto Margonato, Romualdo Belardinelli, Gabriele Fragasso
Journal: Circulation (2012)

Background: Trimetazidine (TMZ) shifts myocardial energy production from free fatty acids to glucose oxidation, a more efficient metabolic pathway. Previous small studies in patients with chronic heart failure (CHF) have shown that TMZ can improve contractile left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. Methods: In this international multicentre retrospective cohort study 669 patients (521 post-ischaemic) from the CHF clinics of our institutions were recruited. 362 patients (288 post-ischaemic) were on TMZ (20 mg tid or 35 mg bid) due to symptoms persistence (dyspnoea on exertion, fatigue, orthopnoea, oedema, alone or in combination) despite up titration of optimal CHF medical therapy, while the remaining patients continued conventional CHF therapy alone. Effects of TMZ administration were evaluated by Kaplan-Meier survival analysis and Cox-Regression survival analysis. Obtained results were corrected with propensity score (PS) in order to minimize selection bias. The protocol has been registered in the Italian Pharmaceutical Agency (AIFA) - Italian Ministry of Health, on the observational studies registry, ID number 458. Results: Kaplan-Meier analysis for global mortality showed 11•3% improved global survival (p=0•015) and 8•5% improved survival for death from cardiovascular disease (CVD) causes (p=0•050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a PS-corrected hazard ratio (HR)= 0•189 (confidence interval - CI 95%: 0•079-0•454; p=0•0002). TMZ also showed a good risk reduction profile for CVD death causes (PS-adjusted HR=0•072, CI 95%: 0•019-0•268, p=0•0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p &lt; 0•0005) with increased hospitalization-free survival of •8 months. Conclusions: TMZ is effective in reducing both global and cardiovascular mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long-term survival in CHF patients.
Abstract 9193: Variation in Quality of Care Among Patients Hospitalized With Acute Heart Failure in an International Trial: Findings From ASCEND-HF
Authors: Jonathan G Howlett, Justin A Ezekowitz, Mohua Podder, Adrian F Hernandez, Rafael Diaz, Kenneth Dickstein, Paul W Armstrong, Gregg C Fonarow
Journal: Circulation (2012)

BACKGROUND: Translation of evidence-based heart failure (HF) therapies to clinical practice is incomplete and may be subject to international variation. We compared key HF quality indicators in acute HF (AHF) patients enrolled in the international Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. METHODS: Patients were admitted to hospital for AHF and comprised 5 regions (North America n=3149, Latin America n=658, Asia- Pacific n=1744, Central Europe n=966 and Western Europe n=490). Quality indicators assessed at hospital discharge from the US-based Get With The Guidelines program were used, including: medications (ACEI/ARB, beta blockers, aldosterone inhibitors, hydralazine-nitrates, statin therapy and warfarin) for eligible patients, use (or planned use) of implantable intracardiac devices (ICD, CRT) for eligible patients and blood pressure control (&lt;140/90 mmHg). RESULTS: 7007 intent-to-treat AHF patients in 398 centres were enrolled. There was significant variation in conformity between different quality indicators, ranging from 0% to 89% (See Table). Of all potential performance opportunities, 24,807 of 39874 (62%) were met, with Central Europe highest at 68%, followed by North America (65%), Western Europe (63%), Latin America (59%) and Asia-Pacific (56%), P&lt;0.0001. CONCLUSION: Quality of care for patients hospitalized with AHF remains suboptimal even within a randomized clinical trial. Moreover, significant unexplained inter-regional variability in quality of care exists. Further study is required to understand and overcome the global barriers to delivery of optimal evidence-based care.
Abstract 9709: CaMKII-mediated Aberrant Ca2+ Release May Play a Key Role in hte Arrhythmogenesis In Cardiac Troponin T-related Familial Hypertrophic Cardiomyopathy
Authors: Shinichi Okuda, Masakazu Fukuda, Takeshi Suetomi, Akihiro HIno, Takayoshi Kato, Masahiro Doi, Shigeki Kobayashi, Takeshi Yamamoto, Masunori Matsuzaki, Masafumi Yano
Journal: Circulation (2012)

Backgrounds: Cardiac troponin T (cTnT) mutations causes Familial Hypertrophic Cardiomyopathy (FHC), which leads to sudden cardiac death. In many of the non-dilated forms of FHC-linked cTnT mutations, Ca2+ sensitivity in myofilament is increased. However, the underlying mechanism by which the cTnT mutations leads to lethal arrhythmia remains elusive. Here, we hypothesized that aberrant Ca2+ release via the cardiac ryanodine receptor (RyR2) would occur in FHC. To verify this hypothesis, we investigated local Ca2+ release property in transgenic (TG) mouse model with FHC-related cTnT mutation (delta160E). Methods and results: In the TG mouse model, there was no appreciable difference in the structural or functional features of the hearts between wild-type (WT) and TG mice in 6th month of age. In response to isoproterenol (ISO; 10 nmol/L), the Ca2+ spark frequency (SpF: s-1•100µm-1; by fluo4) was much higher in TG cardiomyocytes than in WT cardiomyocytes TG (n=10): 7.8±0.9; WT (n=5): 3.6±0.4; p&lt;0.01. It was largely reversed by CaMKII inhibitor (KN-93 ;1 µM), TG with KN-93(n=5: 5.0±0.3; p&lt;0.05), but not by PKA inhibitor (H-89; 1 µM), TG with H-89(n=5: 7.6±0.3; n.s). In ISO-treated TG cardiomyocytes, time from peak to 70% decline of Ca2+ transient was attenuated by KN-93 (1 µM, n=5: 6.44±0.35 x10-2sec; p&lt;0.05 vs ISO-treated TG (n=5: 7.61±0.18 x10-2sec;), but not by H-89 (1 µM, n=5: 6.88±1.15 x10-2sec; n.s.). ISO-treated TG cardiomyocytes (but not ISO-treated WT: 0/14; n=14) showed spontaneous Ca2+ transient (sCaT) after 5 Hz pacing (12/18; n=13). The spontaneous Ca2+ transient was again attenuated by KN-93 (0/5; n=5), but not by H-89 (3/5; n=5). Moreover, all of these abnormal events in ISO-treated TG cardiomyocytes (i.e. increase in SpF and appearance of sCaT) were reproduced by adding EGTA-AM into ISO-treated WT cardiomyocytes, suggesting that increased Ca2+ buffering capacity, causing an increase in diastolic [Ca2+], predisposes to aberrant Ca2+ release events. Conclusions: In FHC-linked cTnT mutated hearts aberrant local Ca2+ release is induced by beta-adrenergic stimulation, presumably due to mutation-linked, increased Ca2+ buffering capacity, and subsequent CaMKII activation.
Abstract 9532: Anaemic Patients With Chronic Heart Failure are Common in Clinical Practice, Insufficiently Treated and With an Impaired Prognosis Independent of Confounding Factors
Authors: Harm Wienbergen, Rico Osteresch, Matthias Hochadel, Michael Boehm, Matthias Pauschinger, Ruth H Strasser, Wolfgang von Scheidt, Jochen Senges, Rainer Hambrecht
Journal: Circulation (2012)

Introduction: There is an increasing interest in the role of anaemia in patients with heart failure (HF). We analyzed data of the EVITA-HF registry with respect to prevalence, therapy and prognosis of patients with chronic HF and hemoglobin &lt; 12 g/dl in the actual clinical practice. Methods: The EVITA-HF registry is a multicenter registry of consecutive patients with chronic HF and left ventricular ejection fraction &lt; 40%. Data are collected in 17 centers in Germany, Austria and Switzerland. Results: 3082 HF-patients were included in the EVITA-HF registry in the time period 01/2009 to 03/2012. In 734 patients (23.8%) hemoglobin levels were &lt; 12 g/dl. Anaemic patients were older (71 + 12 years vs. 65 + 13 years, p &lt; 0.01) and more often female (33.2% vs. 20.6%, p &lt; 0.01) than patients without anaemia and had a higher rate of comorbidities as renal failure and malignant comorbidities. Patients with anaemia received less often adequate medical HF-therapy (especially ACE inhibitors, aldosterone antagonists), had a lower rate of oral anticoagulatives in spite of a high rate of atrial fibrillation and had less often ICD/CRT implanted (32.1% vs. 40.3%, p &lt;0.01) compared to patients without anaemia. Patients with anaemia had a worse clinical outcome compared to their non-anaemic counterparts with a significantly increased hospital (3.8% vs. 1.4%, p &lt; 0.01) and 1-year mortality (23.3% vs. 10.6%, p &lt;0.01). In a multivariate analysis adjusting for 14 prognostic factors hemoglobin &lt; 12 g/dl was independently associated with a significantly elevated 1-year mortality (HR 1.45, 95% CI 1.04-2.02, p 0.031). Conclusions: Nearly ¼ of the HF-patients of the EVITA-HF registry had hemoglobin levels &lt; 12 g/dl. These patients received less often adequate guideline-recommended HF-therapy compared to non-anaemic patients. HF-patients with hemoglobin &lt; 12 g/dl had a more than doubled 1-year mortality, nearly every fourth of these patients died within 1 year. Anaemia in HF-patients was not only a marker of a high-risk patient group, but also an independent prognostic risk factor in a multivariate analysis.
Abstract 9692: Lower Achieved Systolic Pressure (≤130 mm Hg) is Associated With a Decreased Risk of New Diabetes Mellitus in Hypertensive Patients With Electrocardiographic Left Ventricular Hypertrophy: The LIFE Study
Authors: Peter M Okin, Darcy A Hille, Lars H Lindholm, Sverre E Kjeldsen, Björn Dahlöf, Richard B Devereux
Journal: Circulation (2012)

Background: There is a well-established association between higher blood pressure (BP) and insulin resistance and hypertensive patients are at increased risk of developing diabetes mellitus (DM). Although lower achieved systolic BP (SBP) was not associated with reduced mortality or cardiovascular outcomes in diabetic hypertensives or in hypertensive patients with ECG left ventricular hypertrophy (LVH) in the LIFE study, whether more aggressive reduction of SBP is associated with a lower incidence of DM has not been examined. Methods: Risk of new-onset DM was examined in relation to last in-treatment SBP prior to DM diagnosis or last in-study measurement in the absence of new DM in 7485 hypertensive patients with ECG LVH with no history of DM randomly assigned to losartan- or atenolol-based treatment. Patients with in-treatment SBP ≤130 mm Hg (lowest quintile at last measurement) and SBP between 131 and 141, were compared with patients with in-treatment SBP ≥142 (median SBP at last measurement). Results: During 4.6±1.2 years follow-up, new-onset DM was diagnosed in 520 patients (6.9%). In univariate analyses, compared with in-treatment SBP ≥142, in-treatment SBP ≤130 entered as a time-varying covariate was associated with a 57% lower risk (95% CI 39-69%) of new DM and in-treatment SBP between 131 and 141 with a 30% lower risk (95% CI 14-42%) of developing DM. After adjusting for randomized treatment, age, sex, race, prior antihypertensive therapy, baseline body mass index (BMI), uric acid, serum glucose and baseline HDL cholesterol entered as standard covariates, and for in-treatment Cornell product LVH, diastolic BP, BMI, HDL, hydrochlorothiazide and statin use treated as time-varying covariates, achievement of a SBP ≤130 remained associated with a 38% lower incidence (95% CI 12-57%) of new DM whereas an in-treatment SBP between 131 and 141 was no longer predictive of a reduced risk of new DM. Conclusions: Achieved SBP ≤130 is associated with a significantly lower risk of developing new-onset DM in hypertensive patients with ECG LVH, independent of other known and possible risk factors for DM. Further study will be needed to determine whether targeting hypertensive patients without DM to lower SBP goals can reduce the burden of new DM in this high-risk population.