BioMed Research International: Cardiology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Evidential Value That Exercise Improves BMI -Score in Overweight and Obese Children and Adolescents Mon, 05 Oct 2015 11:54:12 +0000 Background. Given the cardiovascular disease (CVD) related importance of understanding the true effects of exercise on adiposity in overweight and obese children and adolescents, this study examined whether there is evidential value to rule out excessive and inappropriate reporting of statistically significant results, a major problem in the published literature, with respect to exercise-induced improvements in BMI -score among overweight and obese children and adolescents. Methods. Using data from a previous meta-analysis of 10 published studies that included 835 overweight and obese children and adolescents, a novel, recently developed approach (-curve) was used to test for evidential value and rule out selective reporting of findings. Chi-squared tests () were used to test for statistical significance with alpha () values <0.05 considered statistically significant. Results. Six of 10 findings (60%) were statistically significant. Statistically significant right-skew to rule out selective reporting was found ( = 38.8, = 0.0001). Conversely, studies neither lacked evidential value ( = 6.8, = 0.87) nor lacked evidential value and were intensely -hacked ( = 4.3, = 0.98). Conclusion. Evidential value results confirm that exercise reduces BMI -score in overweight and obese children and adolescents, an important therapeutic strategy for treating and preventing CVD. George A. Kelley and Kristi S. Kelley Copyright © 2015 George A. Kelley and Kristi S. Kelley. All rights reserved. Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives Mon, 05 Oct 2015 09:42:42 +0000 Advanced knowledge in the field of stem cell biology and their ability to provide a cue for counteracting several diseases are leading numerous researchers to focus their attention on “regenerative medicine” as possible solutions for cardiovascular diseases (CVDs). However, the lack of consistent evidence in this arena has hampered the clinical application. The same condition affects the research on endothelial progenitor cells (EPCs), creating more confusion than comprehension. In this review, this aspect is discussed with particular emphasis. In particular, we describe biology and physiology of EPCs, outline their clinical relevance as both new predictive, diagnostic, and prognostic CVD biomarkers and therapeutic agents, discuss advantages, disadvantages, and conflicting data about their use as possible solutions for vascular impairment and clinical applications, and finally underline a very crucial aspect of EPCs “characterization and definition,” which seems to be the real cause of large heterogeneity existing in literature data on this topic. Carmela R. Balistreri, Silvio Buffa, Calogera Pisano, Domenico Lio, Giovanni Ruvolo, and Giuseppe Mazzesi Copyright © 2015 Carmela R. Balistreri et al. All rights reserved. Biological Niches within Human Calcified Aortic Valves: Towards Understanding of the Pathological Biomineralization Process Mon, 05 Oct 2015 08:33:04 +0000 Despite recent advances, mineralization site, its microarchitecture, and composition in calcific heart valve remain poorly understood. A multiscale investigation, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectrometry (EDS), from micrometre up to nanometre, was conducted on human severely calcified aortic and mitral valves, to provide new insights into calcification process. Our aim was to evaluate the spatial relationship existing between bioapatite crystals, their local growing microenvironment, and the presence of a hierarchical architecture. Here we detected the presence of bioapatite crystals in two different mineralization sites that suggest the action of two different growth processes: a pathological crystallization process that occurs in biological niches and is ascribed to a purely physicochemical process and a matrix-mediated mineralized process in which the extracellular matrix acts as the template for a site-directed nanocrystals nucleation. Different shapes of bioapatite crystallization were observed at micrometer scale in each microenvironment but at the nanoscale level crystals appear to be made up by the same subunits. Valentina Cottignoli, Michela Relucenti, Giovanna Agrosì, Elena Cavarretta, Giuseppe Familiari, Loris Salvador, and Adriana Maras Copyright © 2015 Valentina Cottignoli et al. All rights reserved. Angiotensinase C mRNA and Protein Downregulations Are Involved in Ethanol-Deteriorated Left Ventricular Systolic Dysfunction in Spontaneously Hypertensive Rats Mon, 05 Oct 2015 08:04:20 +0000 The influences of angiotensinase C on ethanol-induced left ventricular (LV) systolic function were assessed in spontaneously hypertensive rats (SHRs). SHRs were fed by a liquid diet with or without ethanol for 49 days. The normotensive Wistar Kyoto rats (WKY) were fed by the liquid diet without ethanol and used as control. We evaluated LV systolic function, angiotensinase C mRNA and protein expressions, activation of the renin-angiotensin system (RAS), and the gene expressions of LV collagen (Col) III a1 and matrix metalloproteinases- (MMP-) 9. Compared to the WKY, LV systolic dysfunction (expressed by decreased fractional shortening and ejection fraction) was observed in the SHRs before ethanol treatment and further deteriorated by ethanol treatment. In the ethanol-treated SHRs, the following were observed: downregulations of angiotensinase C mRNA and protein, increased RAS activity with low collagen production as evidenced by angiotensin II and angiotensin type 1 receptor (AT1R) protein upregulation, R mRNA downregulation, and an MMP-9 mRNA expression upregulation trend with the downregulation of Col III a1 mRNA expression in LV. We conclude that chronic ethanol regimen is sufficient to promote the enhanced RAS activity-induced decrease in the production of cardiac collagen via downregulated angiotensinase C, leading to the further deterioration of LV systolic dysfunction in SHRs. Jinyao Liu, Ayako Hakucho, and Tatsuya Fujimiya Copyright © 2015 Jinyao Liu et al. All rights reserved. Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion Injury Mon, 05 Oct 2015 07:25:14 +0000 Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body’s antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury. Tingyang Zhou, Chia-Chen Chuang, and Li Zuo Copyright © 2015 Tingyang Zhou et al. All rights reserved. A Review of Computational Methods to Predict the Risk of Rupture of Abdominal Aortic Aneurysms Mon, 05 Oct 2015 07:15:51 +0000 Computational methods have played an important role in health care in recent years, as determining parameters that affect a certain medical condition is not possible in experimental conditions in many cases. Computational fluid dynamics (CFD) methods have been used to accurately determine the nature of blood flow in the cardiovascular and nervous systems and air flow in the respiratory system, thereby giving the surgeon a diagnostic tool to plan treatment accordingly. Machine learning or data mining (MLD) methods are currently used to develop models that learn from retrospective data to make a prediction regarding factors affecting the progression of a disease. These models have also been successful in incorporating factors such as patient history and occupation. MLD models can be used as a predictive tool to determine rupture potential in patients with abdominal aortic aneurysms (AAA) along with CFD-based prediction of parameters like wall shear stress and pressure distributions. A combination of these computer methods can be pivotal in bridging the gap between translational and outcomes research in medicine. This paper reviews the use of computational methods in the diagnosis and treatment of AAA. Tejas Canchi, S. D. Kumar, E. Y. K. Ng, and Sriram Narayanan Copyright © 2015 Tejas Canchi et al. All rights reserved. The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study Mon, 05 Oct 2015 07:01:34 +0000 Concentration-effect (CE) models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around are missed. Georg Ferber, Ulrike Lorch, and Jörg Täubel Copyright © 2015 Georg Ferber et al. All rights reserved. Two-Step Pseudomaximum Amplitude-Based Confidence Interval Estimation for Oscillometric Blood Pressure Measurements Sun, 04 Oct 2015 14:02:33 +0000 Blood pressure (BP) is an important vital sign to determine the health of an individual. Although the estimation of average arterial blood pressure using oscillometric methods is possible, there are no established methods for obtaining confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP). In this paper, we propose a two-step pseudomaximum amplitude (TSPMA) as a novel approach to obtain improved CIs of SBP and DBP using a double bootstrap approach. The weighted median (WM) filter is employed to reduce impulsive and Gaussian noises in the step of preprocessing. Application of the proposed method provides tighter CIs and smaller standard deviation of CIs than the pseudomaximum amplitude-envelope and maximum amplitude algorithms with Student’s -method. Soojeong Lee, Gwanggil Jeon, and Seokhoon Kang Copyright © 2015 Soojeong Lee et al. All rights reserved. MicroRNAs Based Therapy of Hypertrophic Cardiomyopathy: The Road Traveled So Far Sun, 04 Oct 2015 14:02:11 +0000 Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by variable expressivity, age penetrance, and a high heterogeneity. The transcriptional profile (miRNAs, mRNAs), epigenetic modifications, and posttranslational modifications seem to be highly relevant for the onset of the disease. miRNAs, small noncoding RNAs with 22 nucleotides, have been implicated in the regulation of cardiomyocyte function, being differentially expressed in several heart diseases, including HCM. Moreover, a different miRNA expression profile in the various stages of HCM development is also observed. This review summarizes the current knowledge of the profile of miRNAs characteristic of asymptomatic to overt HCM patients, discussing alongside their potential use for diagnosis and therapy. Indeed, the stability and specificity of miRNAs make them suitable targets for use as biomarkers for diagnosis and prognosis and as therapeutical targets. Catarina Roma-Rodrigues, Luís R. Raposo, and Alexandra R. Fernandes Copyright © 2015 Catarina Roma-Rodrigues et al. All rights reserved. Hypoglycaemia, Abnormal Lipids, and Cardiovascular Disease among Chinese with Type 2 Diabetes Sun, 04 Oct 2015 13:58:07 +0000 We recruited a group of 6713 consecutive Chinese patients with T2D but normal renal and liver function who were admitted to one of 81 top tertiary care hospitals in China. Mild hypoglycaemia was defined as having symptomatic hypoglycaemia in one month before hospitalization. Severe hypoglycaemia was defined as having hypoglycaemia that needed assistance from other people in three months before hospitalization. Prior cardiovascular disease (CVD) was defined as having coronary heart disease, stroke, or peripheral arterial disease. Of 6713 patients, 80 and 304 had severe and mild hypoglycaemia episodes, respectively, and 561 had CVD. Patients with severe and mild hypoglycaemia episodes were more likely to have prior CVD (32.5% versus 16.5% versus 7.7%, ). Both mild and severe hypoglycaemia were associated with increased risk of CVD (adjusted odds ratios (ORs): 2.64, 95% CI: 1.85–3.76 for mild hypoglycaemia; 6.59, 95% CI: 3.79–11.45 for sever hypoglycaemia) than those patients free of hypoglycaemia. Further adjustment for lipid profile did not change these two ORs. In the same way, the ORs of lipid profile for CVD were similar before and after adjustment for hypoglycaemia. We concluded that hypoglycaemia and lipid profile were independently associated with increased risk of CVD. Yijun Li, Yiming Mu, Qiuhe Ji, Qin Huang, Hongyu Kuang, Linong Ji, and Xilin Yang Copyright © 2015 Yijun Li et al. All rights reserved. Resting Heart Rate and Auditory Evoked Potential Sun, 04 Oct 2015 13:56:01 +0000 The objective of this study was to evaluate the association between rest heart rate (HR) and the components of the auditory evoked-related potentials (ERPs) at rest in women. We investigated 21 healthy female university students between 18 and 24 years old. We performed complete audiological evaluation and measurement of heart rate for 10 minutes at rest (heart rate monitor Polar RS800CX) and performed ERPs analysis (discrepancy in frequency and duration). There was a moderate negative correlation of the N1 and P3a with rest HR and a strong positive correlation of the P2 and N2 components with rest HR. Larger components of the ERP are associated with higher rest HR. Simone Fiuza Regaçone, Daiane Damaris Baptista de Lima, Vitor Engrácia Valenti, and Ana Cláudia Figueiredo Frizzo Copyright © 2015 Simone Fiuza Regaçone et al. All rights reserved. Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction Sun, 04 Oct 2015 13:47:38 +0000 Animal models have suggested a role of renin-angiotensin system (RAS) activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF). Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs), F2-isoprostanes (IsoPs), and ratios of oxidized to reduced glutathione ( GSH) and cysteine ( CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex , higher body mass index (BMI) , less oxidized CyS , lower DROMs , and lower IsoP . Higher BMI (OR: 1.3; 95% CI: 1.1–1.6) and less oxidized CyS (OR: 1.2; 95% CI: 1.1–1.4) maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01–1.05), ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF. Smita I. Negi, Euy-Myoung Jeong, Irfan Shukrullah, Emir Veleder, Dean P. Jones, Tai-Hwang M. Fan, Sudhahar Varadarajan, Sergei M. Danilov, Tohru Fukai, and Samuel C. Dudley Jr. Copyright © 2015 Smita I. Negi et al. All rights reserved. Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis? Sun, 04 Oct 2015 13:36:59 +0000 Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods. Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients ≤60 years () were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age- and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5. Results. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (). Conclusion. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity. Anna Södergren, Kjell Karp, Christine Bengtsson, Bozena Möller, Solbritt Rantapää-Dahlqvist, and Solveig Wållberg-Jonsson Copyright © 2015 Anna Södergren et al. All rights reserved. Neonatal Death and Heart Failure in Mouse with Transgenic HSP60 Expression Sun, 04 Oct 2015 13:02:07 +0000 Mitochondrial heat shock proteins, such as HSP60, are chaperones responsible for the folding, transport, and quality control of mitochondrial matrix proteins and are essential for maintaining life. Both prosurvival and proapoptotic roles have been proposed for HSP60, and HSP60 is reportedly involved in the initiation of autoimmune, metabolic, and cardiovascular diseases. The role of HSP60 in pathogenesis of these diseases remains unclear, partly because of the lack of mouse models expressing HSP60. In this study we generated HSP60 conditional transgenic mice suitable for investigating in vivo outcomes by expressing HSP60 at the targeted organ in disease models. Ubiquitous HSP60 induction in the embryonic stage caused neonatal death in mice at postnatal day 1. A high incidence of atrial septal defects was observed in HSP60-expressing mice, with increased apoptosis and myocyte degeneration that possibly contributed to massive hemorrhage and sponge-like cardiac muscles. Our results showed that neonatal heart failure through HSP60 induction likely involves developmental defects and excessive apoptosis. The conditional HSP60 mouse model is useful for studying crucial biological questions concerning HSP60. Tsung-Hsien Chen, Shan-Wen Liu, Mei-Ru Chen, Kuan-Hung Cho, Tzu-Yin Chen, Pao-Hsien Chu, Yu-Ying Kao, Ching-Han Hsu, and Kurt Ming-Chao Lin Copyright © 2015 Tsung-Hsien Chen et al. All rights reserved. Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity Sun, 04 Oct 2015 12:57:26 +0000 Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs). Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs. Blanca Humanes, Juan Carlos Jado, Sonia Camaño, Virginia López-Parra, Ana María Torres, Luís Antonio Álvarez-Sala, Emilia Cercenado, Alberto Tejedor, and Alberto Lázaro Copyright © 2015 Blanca Humanes et al. All rights reserved. Osteoprotegerin and TRAIL in Acute Onset of Atrial Fibrillation Sun, 04 Oct 2015 12:48:44 +0000 Background. There is a growing amount of evidence that inflammatory processes are involved in the development of atrial fibrillation (AF) and its complications. We decided to investigate the behavior of osteoprotegerin (OPG) and TNF-related apoptosis inducing ligand (TRAIL) in terms of acute onset of AF. Methods and Results. We included 60 patients with acute onset of AF, candidates for pharmacological cardioversion. The presence of cardiovascular comorbidities was connected with higher concentration of OPG and lower level of TRAIL right from the first hours of AF paroxysm. The initial TRAIL level correlated also positively with left ventricle ejection fraction and negatively with left atrium diameter. We found subsequent increase of OPG in subgroups selected on the basis of CHA2DS2-VASc scoring. Although basal concentrations of studied markers did not allow prediction of the restoration of sinus rhythm, we observed important increase of TRAIL concentration in subgroup with sinus rhythm maintenance (94.11 ± 29.46 versus 111.39 ± 30.23 pg/mL; ). Conclusions. OPG and TRAIL are associated with the underlying cardiovascular damage in AF, but their balance is modulated by the fact of sinus rhythm restoration. Determining the suitability of OPG and TRAIL as predictive markers in AF requires further prospective studies. Krzysztof Rewiuk and Tomasz Grodzicki Copyright © 2015 Krzysztof Rewiuk and Tomasz Grodzicki. All rights reserved. Short-Term Effects of Verapamil and Diltiazem in the Treatment of No Reflow Phenomenon: A Meta-Analysis of Randomized Controlled Trials Sun, 04 Oct 2015 12:27:41 +0000 Currently, there is still a lack of an optimal treatment for no reflow phenomenon (NRP). We analyzed the efficacy and safety of using nondihydropyridine calcium channel antagonists (NDHP, verapamil/diltiazem) in patients suffering from NRP. Eight RCTs with 494 participants were eligible for analysis. The pooling analysis showed that intracoronary verapamil/diltiazem injection significantly decreased the occurrence of the coronary NRP (RR: 0.3, 95% CI: 0.16–0.57; ) and reduced corrected thrombolysis in myocardial infarction (TIMI) frame Count (WMD = −9.24, 95% CI −13.91–4.57; ) in patients with NRP. Moreover, verapamil/diltiazem treatment showed superiority in reducing wall motion index (WMI) compared to the control at day 1 (WMD = 0.11, 95% CI: 0.02–0.20; ) (). There was also a significantly greater decline at occurrence of the major adverse cardiac events between verapamil/diltiazem and control groups (WMD: 0.4, 95% CI: 0.19–0.84; ). However, using verapamil/diltiazem did not provide additional improvement of left ventricular ejection fraction post procedure (at 7 days, WMD, 0.1; 95% CI, −2.43–2.63; ; at 30 days, WMD, 0.42; 95% CI, −2.09–2.92; ). NDHP use is beneficial in attenuating NRP and reducing 6-month MACEs in patients with NRP. Lan Wang, Zhong Cheng, Ye Gu, and Dingfeng Peng Copyright © 2015 Lan Wang et al. All rights reserved. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock Sun, 04 Oct 2015 11:48:51 +0000 Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated () and shock groups (). Hemorrhagic shock was induced by reducing mean arterial pressure (MAP) to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60–180 min). Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV) and capillary perfusion rate (CPR) were assessed by orthogonal polarization spectral (OPS) imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap ( gap), which significantly improved during the 120 min resuscitation phase. There was significant correlation between gap and sublingual RBCV (, ), CPR (, ), central venous oxygen saturation (, ), and central venous-to-arterial PCO2 difference (, ). This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock. Péter Palágyi, József Kaszaki, Andrea Rostás, Dániel Érces, Márton Németh, Mihály Boros, and Zsolt Molnár Copyright © 2015 Péter Palágyi et al. All rights reserved. The Impact of Thrombocytopenia on Outcome in Patients with Acute Coronary Syndromes: A Single Center Retrospective Study Sun, 04 Oct 2015 10:32:00 +0000 Background. In acute coronary syndromes (ACS), treated by combined antithrombotic therapy and percutaneous coronary interventions (PCI), thrombocytopenia may occur. Our aim was to evaluate predictors and the impact of thrombocytopenia on mortality in high-risk ACS patients. Methods. We retrospectively evaluated high-risk ACS patients. Thrombocytopenia was defined as platelet count <140.000/mL or a drop in platelet count of >50% during in-hospital stay. We compared demographic, laboratory, clinical, and mortality data between nonthrombocytopenic and thrombocytopenic ACS patients and evaluated independent predictors of thrombocytopenia. Results. In 371 ACS patients, thrombocytopenia was observed in 21.3%. Thrombocytopenic patients were significantly older and, less likely treated by PCIs (72.1% versus 89.7%, ) and combined antithrombotic therapy, with increased incidence of in-hospital complications and the use of additional treatments, but with increased mortality at 30 days (27.8% versus 10.2%, ) and 6 months (35.4% versus 13.6%, ) when compared to nonthrombocytopenic patients. The use of antibiotics, transfusions, insertion of intra-aortic balloon pump (IABP), and prior stroke independently predicted thrombocytopenia. Conclusions. Thrombocytopenia, observed in about 20% of high-risk ACS patients, was associated significantly with in-hospital complications and mortality. Predictors of thrombocytopenia were the use of antibiotics, transfusions, insertion of IABP, and prior stroke. Andreja Sinkovič and Maja Majal Copyright © 2015 Andreja Sinkovič and Maja Majal. All rights reserved. Space-Time Analysis to Identify Areas at Risk of Mortality from Cardiovascular Disease Sun, 04 Oct 2015 09:21:37 +0000 This study aimed at identifying areas that were at risk of mortality due to cardiovascular disease in residents aged 45 years or older of the cities of Cuiabá and Várzea Grande between 2009 and 2011. We conducted an ecological study of mortality rates related to cardiovascular disease. Mortality rates were calculated for each census tract by the Local Empirical Bayes estimator. High- and low-risk clusters were identified by retrospective space-time scans for each year using the Poisson probability model. We defined the year and month as the temporal analysis unit and the census tracts as the spatial analysis units adjusted by age and sex. The Mann-Whitney test was used to compare the socioeconomic and environmental variables by risk classification. High-risk clusters showed higher income ratios than low-risk clusters, as did temperature range and atmospheric particulate matter. Low-risk clusters showed higher humidity than high-risk clusters. The Eastern region of Várzea Grande and the central region of Cuiabá were identified as areas at risk of mortality due to cardiovascular disease in individuals aged 45 years or older. High mortality risk was associated with socioeconomic and environmental factors. More high-risk clusters were observed at the end of the dry season. Poliany C. O. Rodrigues, Emerson S. Santos, Eliane Ignotti, and Sandra S. Hacon Copyright © 2015 Poliany C. O. Rodrigues et al. All rights reserved. Phytochemical Compounds and Protection from Cardiovascular Diseases: A State of the Art Sun, 04 Oct 2015 09:11:43 +0000 Cardiovascular diseases represent a worldwide relevant socioeconomical problem. Cardiovascular disease prevention relies also on lifestyle changes, including dietary habits. The cardioprotective effects of several foods and dietary supplements in both animal models and in humans have been explored. It was found that beneficial effects are mainly dependent on antioxidant and anti-inflammatory properties, also involving modulation of mitochondrial function. Resveratrol is one of the most studied phytochemical compounds and it is provided with several benefits in cardiovascular diseases as well as in other pathological conditions (such as cancer). Other relevant compounds are Brassica oleracea, curcumin, and berberine, and they all exert beneficial effects in several diseases. In the attempt to provide a comprehensive reference tool for both researchers and clinicians, we summarized in the present paper the existing literature on both preclinical and clinical cardioprotective effects of each mentioned phytochemical. We structured the discussion of each compound by analyzing, first, its cellular molecular targets of action, subsequently focusing on results from applications in both ex vivo and in vivo models, finally discussing the relevance of the compound in the context of human diseases. Beniamino Pagliaro, Caterina Santolamazza, Francesca Simonelli, and Speranza Rubattu Copyright © 2015 Beniamino Pagliaro et al. All rights reserved. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model Sun, 04 Oct 2015 09:09:12 +0000 Mutations in the giant sarcomeric protein titin (TTN) are a major cause for inherited forms of dilated cardiomyopathy (DCM). We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC) in heterozygous (Het) Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction , while wild-type (WT) TAC mice did not. Het mice also trended toward increased ventricular end diastolic pressure and volume compared to WT littermates. We found an increase in histologically diffuse cardiac fibrosis in Het compared to WT in TAC mice. This study shows that a pattern of DCM can be induced by TAC-mediated pressure overload in a TTN-truncated mouse model. This model enlarges our arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure. Qifeng Zhou, Scott Kesteven, Jianxin Wu, Parwez Aidery, Meinrad Gawaz, Michael Gramlich, Michael P. Feneley, and Richard P. Harvey Copyright © 2015 Qifeng Zhou et al. All rights reserved. Comparative Analysis of Methods to Induce Myocardial Infarction in a Closed-Chest Rabbit Model Sun, 04 Oct 2015 09:08:53 +0000 Objective. To develop a rabbit model of closed-chest catheter-induced myocardial infarction. Background. Limitations of rodent and large animal models justify the search for clinically relevant alternatives. Methods. Microcatheterization of the heart was performed in 47 anesthetized 3-4 kg New Zealand rabbits to test five techniques of myocardial ischemia: free coils (), interlocking coils (), thrombogenic gelatin sponge (), balloon occlusion (), and alcohol injection (). In order to limit ventricular fibrillation, an antiarrhythmic protocol was implemented, with beta-blockers/amiodarone before and xylocaine infusion during the procedure. Clinical, angiographic, and echographic data were gathered. End points included demonstration of vessel occlusion (TIMI flow grades 0 and 1 on the angiogram), impairment of left ventricular function at 2 weeks after procedure (by echocardiography), and pathologically confirmed myocardial infarction. Results. The best arterial access was determined to be through the right carotid artery. The internal mammary guiding catheter 4-Fr was selected as the optimal device for selective intracoronary injection. Free coils deployed prematurely and tended to prolapse into the aorta. Interlocking coils did not deploy completely and failed to provide reliable results. Gelatin sponge was difficult to handle, adhered to the catheter, and could not be clearly visualized by fluoroscopy. Balloon occlusion yielded inconsistent results. Alcohol injection was the most efficient and reproducible method for inducing myocardial infarction (4 out of 6 animals), the extent of which could be fine-tuned by using a coaxial balloon catheter as a microcatheter (0.52 mm) to achieve a superselective injection of 0.2 mL of alcohol. This approach resulted in a 20% decrease in LVEF and infarcted myocardium was confirmed histologically. Conclusions. By following a stepwise approach, a minimally invasive, effective, and reproducible rabbit model of catheter-induced myocardial infarction has been developed which addresses the limitations of rodent experiments while avoiding the logistical and cost issues associated with large animal models. Marc-Antoine Isorni, Amaury Casanova, Julie Piquet, Valérie Bellamy, Charly Pignon, Etienne Puymirat, and Philippe Menasche Copyright © 2015 Marc-Antoine Isorni et al. All rights reserved. Vascular Damage in Resistant Hypertension: TNF-Alpha Inhibition Effects on Endothelial Cells Sun, 04 Oct 2015 09:08:30 +0000 Inflammatory cytokines have been associated with the pathophysiology of hypertension and target organ damage (TOD). Resistant hypertensive patients (RHTN) are characterized by poor blood pressure control and higher prevalence of TOD. This study evaluated the relationship between plasma levels of TNF-α and arterial stiffness (pulse wave velocity—PWV) in 32 RHTN and 19 normotensive subjects. Moreover, we investigated the effect of TNF-α inhibition on human endothelial cells (HUVECs) incubated with serum from RHTN and normotensive subjects. HUVECs containing serum obtained from normotensive and hypertensive individuals were treated with TNF-α inhibitor (infliximab). Cell suspensions were used for measurement of DNA fragmentation and reactive oxygen species (ROS) content. RHTN patients showed higher levels of TNF-α compared to normotensive subjects, as well as higher PWV. Positive correlation was found between TNF-α levels and PWV measures in the whole group. HUVECs incubated with serum from RHTN showed increased cell apoptosis and higher ROS content compared to normotensive subjects. Infliximab attenuated the apoptosis of HUVECs incubated with serum from RHTN, but no effect in ROS production was observed. Our findings suggest that TNF-α might mediate, at least in part, vascular damage in resistant hypertension. Natália Ruggeri Barbaro, Thiago Matos de Araújo, José Eduardo Tanus-Santos, Gabriel Forato Anhê, Vanessa Fontana, and Heitor Moreno Copyright © 2015 Natália Ruggeri Barbaro et al. All rights reserved. Presence of Periodontopathic Bacteria DNA in Atheromatous Plaques from Coronary and Carotid Arteries Sun, 04 Oct 2015 09:07:23 +0000 Objectives. Interest in periodontitis as a potential risk factor for atherosclerosis and its complications resulted from the fact that the global prevalence of periodontal diseases is significant and periodontitis may induce a chronic inflammatory response. Many studies have analyzed the potential impact of the Porphyromonas gingivalis, major pathogen of periodontitis, on general health. The purpose of this study was to find the presence of the Porphyromonas gingivalis DNA in the atherosclerotic plaques of coronary and carotid arteries and in the periodontal pockets in patients with chronic periodontitis, who underwent surgery because of vascular diseases. Methods and Results. The study population consisted of 91 patients with coronary artery disease or scheduled for carotid endarterectomy. The presence of Porphyromonas gingivalis DNA in atheromatous plaques and in subgingival samples was determined by PCR. Bacterial DNA was found in 21 of 91 (23%) samples taken from vessels and in 47 of 63 (74.6%) samples from periodontal pockets. Conclusions. Porphyromonas gingivalis DNA is frequently found in atheromatous plaques of patients with periodontitis. That is why more research should be conducted to prove if this periopathogen may have an impact on endothelium of patients at risk of atherosclerosis. Malgorzata Szulc, Wojciech Kustrzycki, Dariusz Janczak, Dagmara Michalowska, Dagmara Baczynska, and Malgorzata Radwan-Oczko Copyright © 2015 Malgorzata Szulc et al. All rights reserved. Beyond the Limits: Clinical Utility of Novel Cardiac Biomarkers Sun, 04 Oct 2015 09:05:14 +0000 Preoperative assessment of cardiovascular risk is essential when it comes to extensive noncardiac surgery procedures. Therefore, accurate and timely diagnosis of myocyte damage is vital. In modern medical practice it is believed that the so-called “multimarker” approach is the most appropriate and most accurate, but new research points out that there are novel biomarkers which could be used independently. Studies that evaluate miRNA, H-FABP, and MR-PAMP give encouraging results. When it comes to miRNA clinical studies show high statistical significance, especially in the case of acute myocardial infarction (). Statistical significance of was found in acute coronary syndrome, when H-FABP was measured. Biochemical marker MR-PAMP showed statistical significance of in most clinical studies. Radmilo Janković, Danica Marković, Nenad Savić, and Vesna Dinić Copyright © 2015 Radmilo Janković et al. All rights reserved. Novel Model of Pulmonary Artery Banding Leading to Right Heart Failure in Rats Sun, 04 Oct 2015 08:59:23 +0000 Background. Congenital heart diseases often involve chronic pressure overload of the right ventricle (RV) which is a major cause of RV dysfunction. Pulmonary artery (PA) banding has been used to produce animal models of RV dysfunction. We have devised a new and easier method of constricting the PA and compared it directly with the partial ligation method. Methods. Eight-week-old male Sprague-Dawley rats (240–260 g) were divided into three groups: sham operation, partial pulmonary artery ligation (PAL) procedure, and pulmonary artery half-closed clip (PAC) procedure. RV function and remodeling were determined by echocardiography and histomorphometry. Results. Surgical mortality was significantly lower in the PAC group while echocardiography revealed significantly more signs of RV dysfunction. At the 8th week after surgery RV fibrosis rate was significantly higher in the PAC group. Conclusions. This procedure of pulmonary artery banding in rats is easier and more efficient than partial ligation. Masataka Hirata, Daiki Ousaka, Sadahiko Arai, Michihiro Okuyama, Suguru Tarui, Junko Kobayashi, Shingo Kasahara, and Shunji Sano Copyright © 2015 Masataka Hirata et al. All rights reserved. Prevalence, Risk Factors, and Genetic Traits in Metabolically Healthy and Unhealthy Obese Individuals Sun, 04 Oct 2015 06:49:17 +0000 Objective. To assess prevalence of metabolically healthy individuals among patients with abdominal obesity (AO) and to determine phenotype and potential genetic traits associated with a benign metabolic status. Methods. 503 AO patients without cardiovascular diseases were examined. Waist circumference (WC), BMI, blood pressure, plasma glucose and serum insulin levels, HOMA-IR, lipid profile, and adiponectin (AN) and leptin (LEP) concentrations in serum were measured. Polymorphisms A19G and Q223R of the LEP and LEP receptor gene, and G276T and T45G of the AN gene were investigated. Results. 91.3% of patients were metabolically unhealthy obese (MUO), and 8.7% metabolically healthy obese (MHO). MHO patients were younger, and had lesser BMI and WC, while duration of obesity, frequency, and duration of physical training were greater than MUO patients . In MHO and MUO patients distribution of the G19G, G19A, and A19A genotypes of the LEP gene and G276G, G276T, and T276T genotypes of AN gene did not differ. The Т45Т genotype was associated with increase of metabolic disorders’ risk for patients with АО (OR = 2.331; 95%  ). Conclusions. Prevalence of MHO individuals among patients with AO is low. Benign metabolic status was associated with younger age, lower waist circumference, and higher physical activity, shorter duration of obesity, and G45G adiponectin genotype carriage. A. Berezina, O. Belyaeva, O. Berkovich, E. Baranova, T. Karonova, E. Bazhenova, D. Brovin, E. Grineva, and E. Shlyakhto Copyright © 2015 A. Berezina et al. All rights reserved. Characteristics and Outcomes of Patients with Acute Myocardial Infarction at Non-PCI Capable Hospitals in 2007 and in 2014 Sun, 04 Oct 2015 06:47:48 +0000 Background. There is little known about whether characteristics and outcomes of patients with acute myocardial infarction (AMI) have changed over the years in non-PCI capable hospitals in real-life. Our aim was to assess them between 2007 and 2014. Methods. It was a retrospective cohort study. Characteristics and in-hospital mortality (standardized in cases of different characteristics between the groups by original simple method) were assessed for all patients with non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI) at two non-PCI capable hospitals: one in 2007 () and another in 2014 (). Results. In 2014, females were older than in 2007 (80.18 ± 7.54 versus 76.15 ± 8.77, ), males were younger (71.61 ± 11.22 versus 79.20 ± 7.63, ), less had renal failure (RF) (19% versus 34.6%, ) and reinfarction (13.8% versus 35.6%, ), and the proportion of males (31% versus 43.3%, ) and the proportion of NSTEMI (60.3 versus 69.2, ) decreased. In cases of STEMI there were no differences in patient characteristics. STEMI (18.8% versus 21.7%) and standardized mortalities by gender, RF, and reinfarction NSTEMI (19.47%, 15.34%, and 17.5%, resp., versus 17.1%) showed no differences between 2007 and 2014. Conclusions. There were some differences in patient characteristics but not in mortality for AMI at non-PCI capable hospitals between 2007 and 2014. Egle Kalinauskiene, Dalia Gerviene, Inga Sabeckyte, and Albinas Naudziunas Copyright © 2015 Egle Kalinauskiene et al. All rights reserved. True Unipolar ECG Machine for Wilson Central Terminal Measurements Thu, 01 Oct 2015 13:07:20 +0000 Since its invention (more than 80 years ago), modern electrocardiography has employed a supposedly stable voltage reference (with little variation during the cardiac cycle) for half of the signals. This reference, known by the name of “Wilson Central Terminal” in honor of its inventor, is obtained by averaging the three active limb electrode voltages measured with respect to the return ground electrode. However, concerns have been raised by researchers about problems (biasing and misdiagnosis) associated with the ambiguous value and behavior of this reference voltage, which requires perfect and balanced contact of at least four electrodes to work properly. The Wilson Central Terminal has received scant research attention in the last few decades even though consideration of recent widespread medical practice (limb electrodes are repositioned closer to the torso for resting electrocardiography) has also sparkled concerns about the validity and diagnostic fitness of leads not referred to the Wilson Central Terminal. Using a true unipolar electrocardiography device capable of precisely measuring the Wilson Central Terminal, we show its unpredictable variability during the cardiac cycle and confirm that the integrity of cardinal leads is compromised as well as the Wilson Central Terminal when limb electrodes are placed close to the torso. Gaetano D. Gargiulo Copyright © 2015 Gaetano D. Gargiulo. All rights reserved. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease Thu, 01 Oct 2015 10:04:21 +0000 Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials. Aditya Bhat, Ye Min Kuang, Gary C. H. Gan, David Burgess, and Alan Robert Denniss Copyright © 2015 Aditya Bhat et al. All rights reserved. Dissemination of Health-Related Research among Scientists in Three Countries: Access to Resources and Current Practices Thu, 01 Oct 2015 08:56:23 +0000 Objectives. In public health and clinical settings insufficient dissemination of evidence-based practices limits the reach of new discoveries to broad populations. This study aimed to describe characteristics of the dissemination process by researchers across three countries (Brazil, United Kingdom, and United States), explore how designing for dissemination practices has been used, and analyze factors associated with dissemination. Methods. A similar online survey was used to query researchers across the three countries; data were pooled to draw cross-country conclusions. Findings. This study identified similarities and differences between countries. Importance of dissemination to nonresearcher audiences was widely recognized as important; however, traditional academic venues were the main dissemination method. Several factors were associated with self-rated dissemination effort in the pooled sample, but these predictive factors (e.g., support and resources for dissemination) had low prevalence. Less than one-third of researchers rated their level of effort for dissemination as excellent. Respondents reported limited support and resources to make it easier for researchers who might want to disseminate their findings. Conclusion. Though intentions show the importance of dissemination, researchers across countries lack supports to increase dissemination efforts. Additional resources and training in designing for dissemination along with improved partnerships could help bridge the research-practice gap. Rachel G. Tabak, Rodrigo S. Reis, Paul Wilson, and Ross C. Brownson Copyright © 2015 Rachel G. Tabak et al. All rights reserved. Hemodynamic and Biologic Determinates of Arteriovenous Fistula Outcomes in Renal Failure Patients Thu, 01 Oct 2015 08:39:41 +0000 The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vascular access. Although a variety of access options are available, the arteriovenous fistula remains the best vascular access. Unfortunately the success rate of mature fistula use remains poor. The creation of an arteriovenous fistula is followed by altered hemodynamic and biological changes that may result in neointimal hyperplasia and eventual venous stenosis. This review provides an overview of these changes and the needed research to provide a long lasting vascular access and hence improve outcomes for patients with end-stage renal disease. Mary Hammes Copyright © 2015 Mary Hammes. All rights reserved. Guided Tissue Regeneration in Heart Valve Replacement: From Preclinical Research to First-in-Human Trials Thu, 01 Oct 2015 08:34:02 +0000 Heart valve tissue-guided regeneration aims to offer a functional and viable alternative to current prosthetic replacements. Not requiring previous cell seeding and conditioning in bioreactors, such exceptional tissue engineering approach is a very fascinating translational regenerative strategy. After in vivo implantation, decellularized heart valve scaffolds drive their same repopulation by recipient’s cells for a prospective autologous-like tissue reconstruction, remodeling, and adaptation to the somatic growth of the patient. With such a viability, tissue-guided regenerated conduits can be delivered as off-the-shelf biodevices and possess all the potentialities for a long-lasting resolution of the dramatic inconvenience of heart valve diseases, both in children and in the elderly. A review on preclinical and clinical investigations of this therapeutic concept is provided with evaluation of the issues still to be well deliberated for an effective and safe in-human application. L. Iop and G. Gerosa Copyright © 2015 L. Iop and G. Gerosa. All rights reserved. Does Defensive Medicine Change the Behaviors of Vascular Surgeons? A Qualitative Review Thu, 01 Oct 2015 07:29:16 +0000 Although in literature few successful claims have been shown in comparison with other medical specialties such as gynaecology and orthopaedics, vascular surgery is included among high-risk specialties. The high-risk of receiving medical claims may lead vascular surgeons to practice defensive medicine, as is normal in several other areas of clinical practice. No studies are available to our knowledge of the incidence of defensive medicine in the field of vascular surgery. Taking into consideration the scarce amount of information, the authors provide a critical discussion regarding the application of defensive medicine behaviour among vascular surgeons. Paola Frati, Francesco Paolo Busardò, Pasqualino Sirignano, Matteo Gulino, Simona Zaami, and Vittorio Fineschi Copyright © 2015 Paola Frati et al. All rights reserved. Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+ Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy Thu, 01 Oct 2015 07:07:03 +0000 According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+ cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106 of CD133+ cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+ cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106 cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial). Daniela Belotti, Giuseppe Gaipa, Beatrice Bassetti, Benedetta Cabiati, Gabriella Spaltro, Ettore Biagi, Matteo Parma, Andrea Biondi, Laura Cavallotti, Elisa Gambini, and Giulio Pompilio Copyright © 2015 Daniela Belotti et al. All rights reserved. Heart Rate Variability in Shift Workers: Responses to Orthostatism and Relationships with Anthropometry, Body Composition, and Blood Pressure Thu, 01 Oct 2015 07:01:51 +0000 In order to investigate the response of heart rate variability (HRV) components to postural change and their association with cardiovascular risk factors in shift workers, a cross-sectional study with 438 Brazilian males rotating shift workers was done. Anthropometric, body composition, and clinical measures were collected. Electrocardiogram was recorded for 3 minutes, in the supine and orthostatic position, and HRV components were extracted. Descriptive analyses showed that mean values of body mass index, waist circumference (WC), waist-to-height ratio, visceral fat area (VFA), and blood pressure (BP) were higher than the reference values. In the regression model, age, WC, VFA, and systolic BP showed negative association with HRV components. These findings suggest the need for determining effective strategies for the evaluation and promotion of health among shift workers focused on the altered variables. Nayara Mussi Monteze, Breno Bernardes Souza, Henrique José de Paula Alves, Fernando Luiz Pereira de Oliveira, José Magalhães de Oliveira, Silvia Nascimento de Freitas, Raimundo Marques do Nascimento Neto, Maria Lilian Sales, and Gabriela Guerra Leal Souza Copyright © 2015 Nayara Mussi Monteze et al. All rights reserved. The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells Thu, 01 Oct 2015 06:53:56 +0000 Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs. Camilla Siciliano, Isotta Chimenti, Antonella Bordin, Donatella Ponti, Paola Iudicone, Mariangela Peruzzi, Erino Angelo Rendina, Antonella Calogero, Luca Pierelli, Mohsen Ibrahim, and Elena De Falco Copyright © 2015 Camilla Siciliano et al. All rights reserved. Using Multicriteria Decision Analysis to Support Research Priority Setting in Biomedical Translational Research Projects Thu, 01 Oct 2015 06:24:48 +0000 Translational research is conducted to achieve a predefined set of economic or societal goals. As a result, investment decisions on where available resources have the highest potential in achieving these goals have to be made. In this paper, we first describe how multicriteria decision analysis can assist in defining the decision context and in ensuring that all relevant aspects of the decision problem are incorporated in the decision making process. We then present the results of a case study to support priority setting in a translational research consortium aimed at reducing the burden of disease of type 2 diabetes. During problem structuring, we identified four research alternatives (primary, secondary, tertiary microvascular, and tertiary macrovascular prevention) and a set of six decision criteria. Scoring of these alternatives against the criteria was done using a combination of expert judgement and previously published data. Lastly, decision analysis was performed using stochastic multicriteria acceptability analysis, which allows for the combined use of numerical and ordinal data. We found that the development of novel techniques applied in secondary prevention would be a poor investment of research funds. The ranking of the remaining alternatives was however strongly dependent on the decision maker’s preferences for certain criteria. Gimon de Graaf, Douwe Postmus, and Erik Buskens Copyright © 2015 Gimon de Graaf et al. All rights reserved. Comparison between Procalcitonin, Brain Natriuretic Peptide, and Uric Acid in Children with Cardiomyopathy and Controls Thu, 01 Oct 2015 05:55:33 +0000 Objective. This study was performed to determine the level of procalcitonin, Brain Natriuretic Peptide (BNP), and uric acid in children with cardiomyopathy in comparison with controls and the association with echocardiographic findings. Methods. The levels of BNP, procalcitonin, and serum uric acid were measured and the amounts of biomarkers compared with echocardiographic findings. Results. In this study mean age of participants was the same (). The majority of echocardiographic indices in left and right heart have different means in case and controls (). Means of BNP, procalcitonin, and uric acid were 213.814 ± 309.601, 9.326 ± 3.881, and 6.846 ± 1.814 for case group and 2.76 ± 1.013, 1.851 ± 1.466, and 3.317 ± 0.924 for control (), respectively. In the patients group there was relationship of Ross classification with BNP (χ2 = 15.845, ) and with age (χ2 = 8.946, ). For uric acid and procalcitonin no significant relationships were observed. Conclusions. procalcitonin, uric acid, and BNP had significant relationship with many echocardiographic findings in participants. For patients, procalcitonin did not show correlation. The severity of illness based on the Ross classification showed significant correlation with BNP level and age in patients. Noor Mohammad Noori, Maziar Mahjoubifard, Iraj Shahramian, Alireza Teimouri, and Alireza Jahangirifard Copyright © 2015 Noor Mohammad Noori et al. All rights reserved. Malnutrition and Gut Flora Dysbiosis: Specific Therapies for Emerging Comorbidities in Heart Failure Wed, 30 Sep 2015 11:58:40 +0000 Chronic heart failure is a complicated multifactorial disease with wide-spread social-economic consequences. In spite of the recent development of new drugs and therapeutic strategies, CHF-related mortality and morbidity remain high. Recent evidence suggests that changes in organs such as skeletal muscle and gut flora may play an important and independent role in CHF prognosis. This paper illustrates these phenomena, proposing how to identify them and presenting current therapies which treat organs all too often underestimated but which have a fundamental role in worsening CHF. Evasio Pasini, Roberto Aquilani, Giovanni Corsetti, and Francesco S. Dioguardi Copyright © 2015 Evasio Pasini et al. All rights reserved. Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome Wed, 30 Sep 2015 09:41:43 +0000 The receptor of advanced glycation end products (RAGE) and its ligands are linked to the pathogenesis of coronary artery disease (CAD), and circulating soluble receptor of advanced glycation end products (sRAGE), reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS). The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently. Louise J. N. Jensen, Allan Flyvbjerg, and Mette Bjerre Copyright © 2015 Louise J. N. Jensen et al. All rights reserved. Associations of C1q/TNF-Related Protein-9 Levels in Serum and Epicardial Adipose Tissue with Coronary Atherosclerosis in Humans Thu, 17 Sep 2015 06:20:36 +0000 Objective. To investigate the correlation of CTRP9 with coronary atherosclerosis. Methods. Coronary angiography confirmed CAD in 241 patients (62 received CABG) and non-CAD in 121 (55 received valve replacement). Results. Serum levels of LDL-C, CRP, TNF-α, IL-6, and leptin in CAD patients were significantly higher than those in non-CAD patients (), but APN and CTRP9 were lower (). Serum levels of CTRP9 and APN were negatively related to BMI, HOMA-IR, TNF-α, IL-6, and leptin but positively to HDL-C () in CAD patients. After adjustment of APN, CTRP9 was still related to the above parameters. Serum CTRP9 was a protective factor of CAD (). When compared with non-CAD patients, leptin mRNA expression increased dramatically, while CTRP9 mRNA expression reduced markedly in epicardial adipose tissue of CAD patients (). The leptin expression and macrophage count in CAD group were significantly higher than in non-CAD group, but CAD patients had a markedly lower CTRP9 expression (). Conclusions. Circulating and coronary CTRP9 plays an important role in the inflammation and coronary atherosclerosis of CAD patients. Serum CTRP9 is an independent protective factor of CAD. Jing Wang, Tao Hang, Xun-min Cheng, De-min Li, Qi-gao Zhang, Li-jun Wang, Yong-ping Peng, and Jian-bin Gong Copyright © 2015 Jing Wang et al. All rights reserved. Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone Thu, 10 Sep 2015 12:52:17 +0000 The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models. N. Muñoz-Durango, A. Vecchiola, L. M. Gonzalez-Gomez, F. Simon, C. A. Riedel, C. E. Fardella, and A. M. Kalergis Copyright © 2015 N. Muñoz-Durango et al. All rights reserved. Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade Tue, 01 Sep 2015 07:09:37 +0000 Background. The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients. Julien Guihaire, Tobias Deuse, Dong Wang, Elie Fadel, Hermann Reichenspurner, and Sonja Schrepfer Copyright © 2015 Julien Guihaire et al. All rights reserved. The Role of Cardiolipin in Cardiovascular Health Sun, 02 Aug 2015 13:50:37 +0000 Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs), including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK) pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health. Zheni Shen, Cunqi Ye, Keanna McCain, and Miriam L. Greenberg Copyright © 2015 Zheni Shen et al. All rights reserved. Application and Progress of Combined Mesenchymal Stem Cell Transplantation in the Treatment of Ischemic Cardiomyopathy Wed, 29 Jul 2015 08:20:18 +0000 Treatment of ischemic cardiomyopathy caused by myocardial infarction (MI) using mesenchymal stem cell (MSC) transplantation is a widely researched field, with promising clinical application. However, the low survival rate of transplanted cells has a severe impact on treatment outcome. Currently, research is focused on investigating the strategy of combining genetic engineering, tissue engineering materials, and drug/hypoxia preconditioning to improve ischemic cardiomyopathy treatment outcome using MSC transplantation treatment (MSCTT). This review discusses the application and progress of these techniques. Ping Hua, Jian-Yang Liu, Jun Tao, and Song-Ran Yang Copyright © 2015 Ping Hua et al. All rights reserved. Incidence and Predictors of New-Onset Silent Atrial Fibrillation after Coronary Artery Bypass Graft Surgery Tue, 28 Jul 2015 08:58:57 +0000 Aims. We investigated the incidence, risk factors, and prognostic impact of silent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. Methods. This observational study prospectively included 100 patients referred for CABG surgery. Holter ECG monitoring was used to record every arrhythmic event for 7 days. AF was defined as at least one episode >30 s. Episodes recorded on Holter ECG monitoring but not clinically identified were classified as silent AF. Results. Among 34 patients who developed new-onset AF, 13 had silent AF. Compared with patients with maintained sinus rhythm (SR), silent AF patients had a significantly higher logistic EuroSCORE (2.9 (1.5–5.2) versus 2.3 (1.4–3.7), ) and were more likely to have previous sleep apnea (31% versus 8%, ) and left atrial diameter >45 mm (36% versus 5%, ). At one-year follow-up, 30% of silent AF patients had developed symptomatic AF versus 7% in the SR group () and 11% in the clinical AF group (). Conclusion. After CABG surgery, silent AF is common and may be associated with a higher incidence of recurrences at one-year follow-up than clinical AF. Improved screening for silent AF may help to reduce thromboembolic events in this high-risk population. Charles Guenancia, Charline Pujos, Frederique Debomy, Ghislain Malapert, Gabriel Laurent, and Olivier Bouchot Copyright © 2015 Charles Guenancia et al. All rights reserved. MicroRNA and Cardiovascular Disease Tue, 21 Jul 2015 08:03:35 +0000 Xiao-Bo Liao, Vinicio A. de Jesus Perez, Magdalena Król, Chi-Hsiao Yeh, and Ling-Qing Yuan Copyright © 2015 Xiao-Bo Liao et al. All rights reserved. The Different Effects of BMI and WC on Organ Damage in Patients from a Cardiac Rehabilitation Program after Acute Coronary Syndrome Mon, 13 Jul 2015 06:28:18 +0000 One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson’s test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future. Lin Xu, Hui Zhao, Jian Qiu, Wei Zhu, Hongqiang Lei, Zekun Cai, Wan-Hua Lin, Wenhua Huang, Heye Zhang, and Yuan-Ting Zhang Copyright © 2015 Lin Xu et al. All rights reserved. Rank-One and Transformed Sparse Decomposition for Dynamic Cardiac MRI Sun, 12 Jul 2015 12:33:13 +0000 It is challenging and inspiring for us to achieve high spatiotemporal resolutions in dynamic cardiac magnetic resonance imaging (MRI). In this paper, we introduce two novel models and algorithms to reconstruct dynamic cardiac MRI data from under-sampled space data. In contrast to classical low-rank and sparse model, we use rank-one and transformed sparse model to exploit the correlations in the dataset. In addition, we propose projected alternative direction method (PADM) and alternative hard thresholding method (AHTM) to solve our proposed models. Numerical experiments of cardiac perfusion and cardiac cine MRI data demonstrate improvement in performance. Xianchao Xiu and Lingchen Kong Copyright © 2015 Xianchao Xiu and Lingchen Kong. All rights reserved. Atrial Fibrillation: Biophysics, Molecular Mechanisms, and Novel Therapies Thu, 09 Jul 2015 07:40:41 +0000 Alexey V. Glukhov, Leonid V. Rosenshtraukh, Anamika Bhargava, Michele Miragoli, and Bas J. D. Boukens Copyright © 2015 Alexey V. Glukhov et al. All rights reserved. The Utility of 3D Left Atrial Volume and Mitral Flow Velocities as Guides for Acute Volume Resuscitation Tue, 07 Jul 2015 12:41:58 +0000 Left ventricular end-diastolic pressure (LVEDP) is the foundation of cardiac function assessment. Because of difficulties and risks associated with its direct measurement, correlates of LVEDP derived by pulmonary artery (PA) catheterization or transesophageal echocardiography (TEE) are commonly adopted. TEE has the advantage of being less invasive; however TEE-based estimation of LVEDP using correlates such as left ventricular end-diastolic volume (LVEDV) has technical difficulties that limit its clinical usefulness. Using intraoperative acute normovolemic hemodilution (ANH) as a controlled hemorrhagic model, we examined various mitral flow parameters and three-dimensional reconstructions of left atrial volume as surrogates of LVEDP. Our results demonstrate that peak E wave velocity and left atrial end-diastolic volume (LAEDV) correlated with known changes in intravascular volume associated with ANH. Although left atrial volumetric analysis was done offline in our study, recent advances in echocardiographic software may allow for continuous display and real-time calculation of LAEDV. Along with the ease and reproducibility of acquiring Doppler images of flow across the mitral valve, these two correlates of LVEDP may justify a more widespread use of TEE to optimize intraoperative fluid management. The clinical applicability of peak E wave velocity and LAEDV still needs to be validated during uncontrolled resuscitation. Claudia M. Santosa, David D. Rose, and Neal W. Fleming Copyright © 2015 Claudia M. Santosa et al. All rights reserved. The Role of Magnetic Resonance Imaging and Cardiac Computed Tomography in the Assessment of Left Atrial Anatomy, Size, and Function Tue, 07 Jul 2015 12:34:54 +0000 In the last decade, there has been increasing evidence that comprehensive evaluation of the left atrium is of utmost importance. Numerous studies have clearly demonstrated the prognostic value of left atrial volume for long-term outcome. Furthermore, advances in catheter ablation procedures used for the treatment of drug-refractory atrial fibrillation require the need for detailed knowledge of left atrial and pulmonary venous morphology as well of atrial wall characteristics. This review article discusses the role of cardiac magnetic resonance and computed tomography in assessment of left atrial size, its normal and abnormal morphology, and function. Special interest is paid to the utility of these rapidly involving noninvasive imaging methods before and after atrial fibrillation ablation. Petr Kuchynka, Jana Podzimkova, Martin Masek, Lukas Lambert, Vladimir Cerny, Barbara Danek, and Tomas Palecek Copyright © 2015 Petr Kuchynka et al. All rights reserved. Echocardiographic Evaluation of Left Atrial Mechanics: Function, History, Novel Techniques, Advantages, and Pitfalls Tue, 07 Jul 2015 12:05:09 +0000 Left atrial (LA) functional analysis has an established role in assessing left ventricular diastolic function. The current standard echocardiographic parameters used to study left ventricular diastolic function include pulsed-wave Doppler mitral inflow analysis, tissue Doppler imaging measurements, and LA dimension estimation. However, the above-mentioned parameters do not directly quantify LA performance. Deformation studies using strain and strain-rate imaging to assess LA function were validated in previous research, but this technique is not currently used in routine clinical practice. This review discusses the history, importance, and pitfalls of strain technology for the analysis of LA mechanics. Roman Leischik, Henning Littwitz, Birgit Dworrak, Pankaj Garg, Meihua Zhu, David J. Sahn, and Marc Horlitz Copyright © 2015 Roman Leischik et al. All rights reserved. Left Atrial Appendage: Physiology, Pathology, and Role as a Therapeutic Target Tue, 07 Jul 2015 09:03:11 +0000 Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. AF poses patients at increased risk of thromboembolism, in particular ischemic stroke. The CHADS2 and CHA2DS2-VASc scores are useful in the assessment of thromboembolic risk in nonvalvular AF and are utilized in decision-making about treatment with oral anticoagulation (OAC). However, OAC is underutilized due to poor patient compliance and contraindications, especially major bleedings. The Virchow triad synthesizes the pathogenesis of thrombogenesis in AF: endocardial dysfunction, abnormal blood stasis, and altered hemostasis. This is especially prominent in the left atrial appendage (LAA), where the low flow reaches its minimum. The LAA is the remnant of the embryonic left atrium, with a complex and variable morphology predisposing to stasis, especially during AF. In patients with nonvalvular AF, 90% of thrombi are located in the LAA. So, left atrial appendage occlusion could be an interesting and effective procedure in thromboembolism prevention in AF. After exclusion of LAA as an embolic source, the remaining risk of thromboembolism does not longer justify the use of oral anticoagulants. Various surgical and catheter-based methods have been developed to exclude the LAA. This paper reviews the physiological and pathophysiological role of the LAA and catheter-based methods of LAA exclusion. Damiano Regazzoli, Francesco Ancona, Nicola Trevisi, Fabrizio Guarracini, Andrea Radinovic, Michele Oppizzi, Eustachio Agricola, Alessandra Marzi, Nicoleta Carmen Sora, Paolo Della Bella, and Patrizio Mazzone Copyright © 2015 Damiano Regazzoli et al. All rights reserved. Surgical Left Atrial Appendage Exclusion Does Not Impair Left Atrial Contraction Function: A Pilot Study Tue, 07 Jul 2015 08:40:31 +0000 Background. In order to reduce stroke risk, left atrial appendage amputation (LAAA) is widely adopted in recent years. The effect of LAAA on left atrial (LA) function remains unknown. The objective of present study was to assess the effect of LAAA on LA function. Methods. Sixteen patients with paroxysmal AF underwent thoracoscopic, surgical PVI with LAAA (LAAA group), and were retrospectively matched with 16 patients who underwent the same procedure without LAA amputation (non-LAAA group). To objectify LA function, transthoracic echocardiography with 2D Speckle Tracking was performed before surgery and at 12 months follow-up. Results. Mean age was 57 ± 9 years, 84% were male. Baseline characteristics did not differ significantly except for systolic blood pressure (). In both groups, the contractile LA function and LA ejection fraction were not significantly reduced. However, the conduit and reservoir function were significantly decreased at follow-up, compared to baseline. The reduction of strain and strain rate was not significantly different between groups. Conclusions. In this retrospective, observational matched group comparison with a convenience sample size of 16 patients, findings suggest that LAAA does not impair the contractile LA function when compared to patients in which the appendage was unaddressed. However, the LA conduit and reservoir function are reduced in both the LAAA and non-LAAA group. Our data suggest that the LAA can be removed without late LA functional consequences. Gijs E. De Maat, Stefano Benussi, Yoran M. Hummel, Sebastien Krul, Alberto Pozzoli, Antoine H. G. Driessen, Massimo A. Mariani, Isabelle C. Van Gelder, Wim-Jan Van Boven, and Joris R. de Groot Copyright © 2015 Gijs E. De Maat et al. All rights reserved. Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and Perioperative Management Thu, 02 Jul 2015 09:09:22 +0000 Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring. Both United States and European Guidelines recommend NOACs for stroke prevention in patients with atrial fibrillation. This review discusses each of the NOACs, along with their efficacy and safety data. It explores the most recent guidelines regarding their perioperative use in atrial fibrillation patients. It also discusses bleeding complications, perioperative management, and reversal agents. Fadi Shamoun, Hiba Obeid, and Harish Ramakrishna Copyright © 2015 Fadi Shamoun et al. All rights reserved. Heartbeat Cycle Length Detection by a Ballistocardiographic Sensor in Atrial Fibrillation and Sinus Rhythm Wed, 01 Jul 2015 09:44:16 +0000 Background. Heart rate monitoring is especially interesting in patients with atrial fibrillation (AF) and is routinely performed by ECG. A ballistocardiography (BCG) foil is an unobtrusive sensor for mechanical vibrations. We tested the correlation of heartbeat cycle length detection by a novel algorithm for a BCG foil to an ECG in AF and sinus rhythm (SR). Methods. In 22 patients we obtained BCG and synchronized ECG recordings before and after cardioversion and examined the correlation between heartbeat characteristics. Results. We analyzed a total of 4317 heartbeats during AF and 2445 during SR with a correlation between ECG and BCG during AF of (95% CI 0.68–0.71, ) and (95% CI 0.73–0.77, ) during SR. By adding a quality index, artifacts could be reduced and the correlation increased for AF to 0.76 (95% CI 0.74–0.77, , ) and for SR to 0.85 (95% CI 0.83–0.86, , ). Conclusion. Heartbeat cycle length measurement by our novel algorithm for BCG foil is feasible during SR and AF, offering new possibilities of unobtrusive heart rate monitoring. This trial is registered with IRB registration number EK205/11. This trial is registered with clinical trials registration number NCT01779674. Matthias Daniel Zink, Christoph Brüser, Patrick Winnersbach, Andreas Napp, Steffen Leonhardt, Nikolaus Marx, Patrick Schauerte, and Karl Mischke Copyright © 2015 Matthias Daniel Zink et al. All rights reserved. Diagnosing Paroxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia? Wed, 01 Jul 2015 08:46:50 +0000 Atrial fibrillation (AF) is the commonest sustained arrhythmia globally and results in significantly increased morbidity and mortality including a fivefold risk of stroke. Paroxysmal atrial fibrillation (PAF) constitutes approximately half of all AF cases and is thought to represent an early stage of the disease. This intermittent form of atrial arrhythmia can be a challenge to identify and as a result many affected individuals are not prescribed appropriate antithrombotic therapy and hence are at risk of stroke and thromboembolism. Despite these adverse outcomes there have been relatively few diagnostic advances in the field since the introduction of the Holter monitor in 1949. This review aims to establish the available evidence for electrophysiological, molecular, and morphological biomarkers to improve the detection of PAF with reference to the underlying mechanisms for the condition. P. J. Howlett, F. S. Hatch, V. Alexeenko, R. I. Jabr, E. W. Leatham, and C. H. Fry Copyright © 2015 P. J. Howlett et al. All rights reserved. Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study Wed, 01 Jul 2015 07:34:00 +0000 Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation , which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in . Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies. Francesca Cacciani and Massimiliano Zaniboni Copyright © 2015 Francesca Cacciani and Massimiliano Zaniboni. All rights reserved. Atrial Fibrillation and Fibrosis: Beyond the Cardiomyocyte Centric View Wed, 01 Jul 2015 07:27:49 +0000 Atrial fibrillation (AF) associated with fibrosis is characterized by the appearance of interstitial myofibroblasts. These cells are responsible for the uncontrolled deposition of the extracellular matrix, which pathologically separate cardiomyocyte bundles. The enhanced fibrosis is thought to contribute to arrhythmias “indirectly” because a collagenous septum is a passive substrate for propagation, resulting in impulse conduction block and/or zigzag conduction. However, the emerging results demonstrate that myofibroblasts in vitro also promote arrhythmogenesis due to direct implications upon cardiomyocyte electrophysiology. This electrical interference may be considered beneficial as it resolves any conduction blocks; however, the passive properties of myofibroblasts might cause a delay in impulse propagation, thus promoting AF due to discontinuous slow conduction. Moreover, low-polarized myofibroblasts reduce, via cell-density dependence, the fast driving inward current for cardiac impulse conduction, therefore resulting in arrhythmogenic uniformly slow propagation. Critically, the subsequent reduction in cardiomyocytes resting membrane potential in vitro significantly increases the likelihood of ectopic activity. Myofibroblast densities and the degree of coupling at cellular border zones also impact upon this likelihood. By considering future in vivo studies, which identify myofibroblasts “per se” as a novel targets for cardiac arrhythmias, this review aims to describe the implications of noncardiomyocyte view in the context of AF. Michele Miragoli and Alexey V. Glukhov Copyright © 2015 Michele Miragoli and Alexey V. Glukhov. All rights reserved. Results from the Registry of Atrial Fibrillation (AFABE): Gap between Undiagnosed and Registered Atrial Fibrillation in Adults—Ineffectiveness of Oral Anticoagulation Treatment with VKA Wed, 01 Jul 2015 07:25:14 +0000 Objective. This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC) medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk. Method. A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were , HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores. Results. The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a score; a risk of bleeding in important subgroups using OAC without indication (37.50% score); the use of OAC with TTR < 60% (33.1%), of whom 47.6% had a HAS-BLED score ≥3. Thus, 35.4% of the expected AF prevalence achieved an optimal time in the therapeutic range. Conclusions. The expected AF prevalence was 10.9% ( 5267), but the registered prevalence was 7.5% ( 3638). Only 35.04% (CI = 95%, 33.7–36.3) of AF patients treated with vitamin K antagonists (VKAs) achieve the goal of TTR > 60%. Anna Panisello-Tafalla, Josep Lluís Clua-Espuny, Vicente F. Gil-Guillen, Antonia González-Henares, María Lluisa Queralt-Tomas, Carlos López-Pablo, Jorgina Lucas-Noll, Iñigo Lechuga-Duran, Rosa Ripolles-Vicente, Jesús Carot-Domenech, and Miquel Gallofré López Copyright © 2015 Anna Panisello-Tafalla et al. All rights reserved. Atorvastatin Treatment for Atrial Fibrillation Reduces Serum High-Sensitivity C-Reactive Protein Levels Wed, 01 Jul 2015 06:32:08 +0000 We investigated whether serum hs-CRP levels predict the efficacy of atrial fibrillation (AF) treated with atorvastatin. Bibliographic databases were exhaustively searched for studies relevant to the research topic. Newcastle-Ottawa Scale (NOS) criteria, combined with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), were applied for study quality assessment. Our meta-analysis identified seven cohort studies (2006~2013), providing information on the change in serum hs-CRP levels in AF patients receiving atorvastatin therapy. After atorvastatin treatment, hs-CRP level in AF patients decreased significantly (SMD = 1.02, 95% CI: 0.58–1.47, ). Subgroup analysis by country and hs-CRP detection methods suggested a negative relationship between atorvastatin treatment and hs-CRP levels among Chinese AF patients (SMD = 1.34, 95% CI: 1.00–1.69, ) and by using ELISA method (SMD = 1.11, 95% CI: 0.51–1.71, ), but not among Turkish population and using INA method (all ). Egger’s test showed no publication bias (). hs-CRP was clearly lowered in AF patients treated with atorvastatin, which may be helpful in the choice of statin agents for AF treatment. However, longer follow-ups are necessary to assess the clinical value of lowering hs-CRP in the clinical setting of AF treatment outcomes. Fang-Cheng Su, Xi-Dong Li, Shao-Xia Sun, Ming-Yu Shi, Feng-Hua Xue, Shi-Chao Teng, Li Jiang, Jing Zhu, Feng Yin, and Hong-Yue Gu Copyright © 2015 Fang-Cheng Su et al. All rights reserved. Impact of Dabigatran versus Phenprocoumon on ADP Induced Platelet Aggregation in Patients with Atrial Fibrillation with or without Concomitant Clopidogrel Therapy (the Dabi-ADP-1 and Dabi-ADP-2 Trials) Wed, 01 Jul 2015 06:28:43 +0000 Background. A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel’s efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals. Methods. The “Dabi-ADP-1” and “Dabi-ADP-2” trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 () patients with clopidogrel therapy were excluded and in Dabi-ADP-2 () patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Results. There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650–983] AU × min versus phenprocoumon: 839 [666–1039] AU × min, and Dabi-ADP-2: 326 [268–462] versus 350 [214–535], ) or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Conclusion. Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy. Amadea M. Martischnig, Julinda Mehilli, Janina Pollak, Tobias Petzold, Anette K. Fiedler, Katharina Mayer, Stefanie Schulz-Schüpke, Dirk Sibbing, Steffen Massberg, Adnan Kastrati, and Nikolaus Sarafoff Copyright © 2015 Amadea M. Martischnig et al. All rights reserved. Surgical Treatment of Concomitant Atrial Fibrillation: Focus onto Atrial Contractility Wed, 01 Jul 2015 06:25:18 +0000 Background. Maze procedure aims at restoring sinus rhythm (SR) and atrial contractility (AC). This study evaluated multiple aspects of AC recovery and their relationship with SR regain after ablation. Methods. 122 mitral and fibrillating patients underwent radiofrequency Maze. Rhythm check and echocardiographic control of biatrial contractility were performed at 3, 6, 12, and 24 months postoperatively. A multivariate Cox analysis of risk factors for absence of AC recuperation was applied. Results. At 2-years follow-up, SR was achieved in 79% of patients. SR-AC coexistence increased from 76% until 98%, while biatrial contraction detection augmented from 84 to 98% at late stage. Shorter preoperative arrhythmia duration was the only common predictor of SR-AC restoring, while pulmonary artery pressure (PAP) negatively influenced AC recuperation. Early AC restoration favored future freedom from arrhythmia recurrence. Minor LA dimensions correlated with improved future A/E value and vice versa. Right atrial (RA) contractility restoring favored better left ventricular (LV) performance and volumes. Conclusions. SR and left AC are two interrelated Maze objectives. Factors associated with arrhythmia “chronic state” (PAP and arrhythmia duration) are negative predictors of procedural success. Our results suggest an association between postoperative LA dimensions and “kick” restoring and an influence of RA contraction onto LV function. Claudia Loardi, Francesco Alamanni, Claudia Galli, Moreno Naliato, Fabrizio Veglia, Marco Zanobini, and Mauro Pepi Copyright © 2015 Claudia Loardi et al. All rights reserved. Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies? Mon, 29 Jun 2015 12:42:11 +0000 Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets. Brian R. Weil and Cevher Ozcan Copyright © 2015 Brian R. Weil and Cevher Ozcan. All rights reserved. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling Mon, 29 Jun 2015 07:31:44 +0000 A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles. Dmitry A. Chistiakov, Igor A. Sobenin, Alexander N. Orekhov, and Yuri V. Bobryshev Copyright © 2015 Dmitry A. Chistiakov et al. All rights reserved. The Role of Epigenetics in Arterial Calcification Mon, 29 Jun 2015 07:28:05 +0000 Arterial calcification is highly prevalent and correlated with cardiovascular mortality, especially in patients with ESRD or diabetes. The pathogenesis of arterial calcification is multifactorial, with both genetic and environmental factors being implicated. In recent years, several mechanisms contributing to arterial calcification have been proposed. However, these can only explain a small proportion of the variability in arterial calcification, which is a major obstacle for its prevention and management. Epigenetics has emerged as one of the most promising areas that may fill in some of the gaps in our current knowledge of the interaction between the environmental insults with gene regulation in the development of diseases. Epigenetics refers to heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Well-known components of epigenetic regulation include DNA methylation, histone modifications, and microRNAs. Epigenetics research in the regulation of arterial calcification has only recently been elucidated. In this review, we will summarise recent progress in epigenetic pathways involved in arterial calcification and discuss potential therapeutic interventions based on epigenetic mechanisms. Shan-Shan Wu, Xiao Lin, Ling-Qing Yuan, and Er-Yuan Liao Copyright © 2015 Shan-Shan Wu et al. All rights reserved. MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes Sun, 28 Jun 2015 12:36:44 +0000 The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process. Xiaomin Zhang, Gohar Azhar, Emmanuel D. Williams, Steven C. Rogers, and Jeanne Y. Wei Copyright © 2015 Xiaomin Zhang et al. All rights reserved. miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress Sun, 28 Jun 2015 12:15:09 +0000 Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression. Ana Mondadori dos Santos, Laurent Metzinger, Oualid Haddad, Eléonore M’baya-Moutoula, Fatiha Taïbi, Nathalie Charnaux, Ziad A. Massy, Hanna Hlawaty, and Valérie Metzinger-Le Meuth Copyright © 2015 Ana Mondadori dos Santos et al. All rights reserved. MicroRNAs: Novel Players in Aortic Aneurysm Sun, 28 Jun 2015 11:03:09 +0000 An aortic aneurysm (AA) is a common disease with potentially life-threatening complications. Despite significant improvements in the diagnosis and treatment of AA, the associated morbidity and mortality remain high. MicroRNAs (miRNAs, miR) are small noncoding ribonucleic acids that negatively regulate gene expression at the posttranscriptional level by inhibiting mRNA translation or promoting mRNA degradation. miRNAs are recently reported to be critical modulators for vascular cell functions such as cell migration, contraction, differentiation, proliferation, and apoptosis. Increasing evidences suggest crucial roles of miRNAs in the pathogenesis and progression of cardiovascular diseases such as coronary artery disease, heart failure, arterial hypertension, and cardiac arrhythmias. Recently, some miRNAs, such as miR-24, miR-155, miR-205, miR-712, miR-21, miR-26a, miR-143/145, miR-29, and miR-195, have been demonstrated to be differentially expressed in the diseased aortic tissues and strongly associated with the development of AA. In the present paper, we reviewed the recent available literature regarding the role of miRNAs in the pathogenesis of AA. Moreover, we discuss the potential use of miRNAs as diagnostic and prognostic biomarkers and novel targets for development of effective therapeutic strategies for AA. Xian-ming Fu, Yang-zhao Zhou, Zhao Cheng, Xiao-bo Liao, and Xin-min Zhou Copyright © 2015 Xian-ming Fu et al. All rights reserved. The Emerging Role of miR-223 in Platelet Reactivity: Implications in Antiplatelet Therapy Sun, 28 Jun 2015 08:50:47 +0000 Platelets are anuclear cells and are devoid of genomic DNA, but they are capable of de novo protein synthesis from mRNA derived from their progenitor cells, megakaryocytes. There is mounting evidence that microRNA (miRNA) plays an important role in regulating gene expression in platelets. miR-223 is the most abundant miRNAs in megakaryocytes and platelets. One of the miR-223-regulated genes is ADP P2Y12, a key target for current antiplatelet drug therapy. Recent studies showed that a blunted response to P2Y12 antagonist, that is, high on-treatment platelet reactivity (HTPR), is a strong predictor of major cardiovascular events (MACEs) in coronary heart disease (CHD) patients receiving antiplatelet treatment. Recent clinical cohort study showed that the level of circulating miR-223 is inversely associated with MACE in CHD patients. In addition, our recent data demonstrated that the level of both intraplatelet and circulating miR-223 is an independent predictor for HTPR, thus providing a link between miR-223 and MACE. These lines of evidence indicate that miR-223 may serve as a potential regulatory target for HTPR, as well as a diagnostic tool for identification of HTPR in clinical settings. Rui Shi, Xin Zhou, Wen-Jie Ji, Ying-Ying Zhang, Yong-Qiang Ma, Jian-Qi Zhang, and Yu-Ming Li Copyright © 2015 Rui Shi et al. All rights reserved. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease Sun, 28 Jun 2015 08:19:20 +0000 miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options. Mario Notari, Julián Pulecio, and Ángel Raya Copyright © 2015 Mario Notari et al. All rights reserved. miR-27 and miR-125 Distinctly Regulate Muscle-Enriched Transcription Factors in Cardiac and Skeletal Myocytes Sun, 28 Jun 2015 07:25:49 +0000 MicroRNAs are noncoding RNAs of approximately 22–24 nucleotides which are capable of interacting with the 3′ untranslated region of coding RNAs (mRNAs), leading to mRNA degradation and/or protein translation blockage. In recent years, differential microRNA expression in distinct cardiac development and disease contexts has been widely reported, yet the role of individual microRNAs in these settings remains largely unknown. We provide herein evidence of the role of miR-27 and miR-125 regulating distinct muscle-enriched transcription factors. Overexpression of miR-27 leads to impair expression of Mstn and Myocd in HL1 atrial cardiomyocytes but not in Sol8 skeletal muscle myoblasts, while overexpression of miR-125 resulted in selective upregulation of Mef2d in HL1 atrial cardiomyocytes and downregulation in Sol8 cells. Taken together our data demonstrate that a single microRNA, that is, miR-27 or miR-125, can selectively upregulate and downregulate discrete number of target mRNAs in a cell-type specific manner. Estefania Lozano-Velasco, Jennifer Galiano-Torres, Alvaro Jodar-Garcia, Amelia E. Aranega, and Diego Franco Copyright © 2015 Estefania Lozano-Velasco et al. All rights reserved. A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic Remodeling Sun, 28 Jun 2015 06:52:43 +0000 Spontaneous self-terminating atrial fibrillation (AF) is one of the most common heart rhythm disorders, yet the regulatory molecular mechanisms underlying this syndrome are rather unclear. MicroRNA (miRNA) transcriptome and expression of candidate transcription factors (TFs) with potential roles in arrhythmogenesis, such as Pitx2, Tbx5, and myocardin (Myocd), were analyzed by microarray, qRT-PCR, and Western blotting in left atrial (LA) samples from pigs with transitory AF established by right atrial tachypacing. Induced ectopic tachyarrhythmia caused rapid and substantial miRNA remodeling associated with a marked downregulation of Pitx2, Tbx5, and Myocd expression in atrial myocardium. The downregulation of Pitx2, Tbx5, and Myocd was inversely correlated with upregulation of the corresponding targeting miRNAs (miR-21, miR-10a/10b, and miR-1, resp.) in the LA of paced animals. Through in vitro transient transfections of HL-1 atrial myocytes, we further showed that upregulation of miR-21 did result in downregulation of Pitx2 in cardiomyocyte background. The results suggest that immediate-early miRNA remodeling coupled with deregulation of TF expression underlies the onset of AF. Mario Torrado, Diego Franco, Estefanía Lozano-Velasco, Francisco Hernández-Torres, Ramón Calviño, Guillermo Aldama, Alberto Centeno, Alfonso Castro-Beiras, and Alexander Mikhailov Copyright © 2015 Mario Torrado et al. All rights reserved. Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells Sun, 28 Jun 2015 06:48:56 +0000 We previously reported that Runx2/miR-3960/miR-2861 regulatory feedback loop stimulates osteoblast differentiation. However, the effect of this feedback loop on the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) remains unclear. Our recent study showed that miR-2861 and miR-3960 expression increases significantly during β-glycerophosphate-induced osteogenic transdifferentiation of VSMCs. Overexpression of miR-2861 or miR-3960 in VSMCs enhances β-glycerophosphate-induced osteoblastogenesis, whereas inhibition of miR-2861 or miR-3960 expression attenuates it. MiR-2861 or miR-3960 promotes osteogenic transdifferentiation of VSMCs by targeting histone deacetylase 5 or Homeobox A2, respectively, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Furthermore, overexpression of Runx2 induces miR-2861 and miR-3960 transcription, and knockdown of Runx2 attenuates β-glycerophosphate-induced miR-2861 and miR-3960 transcription in VSMCs. Thus, our data show that Runx2/miR-3960/miR-2861 positive feedback loop plays an important role in osteogenic transdifferentiation of VSMCs and contributes to vascular calcification. Zhu-Ying Xia, Yin Hu, Ping-Li Xie, Si-Yuan Tang, Xiang-Hang Luo, Er-Yuan Liao, Fei Chen, and Hui Xie Copyright © 2015 Zhu-Ying Xia et al. All rights reserved. MicroRNA-143/-145 in Cardiovascular Diseases Sun, 28 Jun 2015 06:29:54 +0000 MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145. Wang Zhao, Shui-Ping Zhao, and Yu-Hong Zhao Copyright © 2015 Wang Zhao et al. All rights reserved. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration Mon, 15 Jun 2015 09:12:23 +0000 Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming. Olivia Chen and Li Qian Copyright © 2015 Olivia Chen and Li Qian. All rights reserved. State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews Mon, 15 Jun 2015 09:09:02 +0000 Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11), effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%]), and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]). No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores () and showed more pronounced effect estimates (). Higher citations were associated with journal impact factor (), corresponding author from North America/Europe (), and inclusion of nonrandomized trials (). Conclusions. Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates. Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chimenti, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, and Giacomo Frati Copyright © 2015 Mariangela Peruzzi et al. All rights reserved. Stem Cell-Based Therapies in Chagasic Cardiomyopathy Mon, 15 Jun 2015 09:03:01 +0000 Chagas disease is caused by Trypanosoma cruzi and can lead to a dilated cardiomyopathy decades after the prime infection by the parasite. As with other dilated cardiomyopathies, conventional pharmacologic therapies are not always effective and as heart failure progresses patients need heart transplantation. Therefore alternative therapies are highly desirable and cell-based therapies have been investigated in preclinical and clinical studies. In this paper we review the main findings of such studies and discuss future directions for stem cell-based therapies in chronic chagasic cardiomyopathy. Antonio Carlos Campos de Carvalho and Adriana Bastos Carvalho Copyright © 2015 Antonio Carlos Campos de Carvalho and Adriana Bastos Carvalho. All rights reserved. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Cardiovascular and Cerebrovascular Diseases Thu, 28 May 2015 06:03:33 +0000 MicroRNAs (miRNAs) are composed of a group of endogenous and noncoding small RNAs which control expression of complementary target mRNAs. The extended functions of miRNAs enhance the complexity of gene-regulatory processes in cardiovascular and cerebrovascular diseases. Indeed, recent studies have shown that miRNAs are closely related to myocardial infarction, heart failure, atrial fibrillation, cardiomyopathy, hypertension, angiogenesis, coronary artery disease, dyslipidaemia, stroke, and so forth. These findings suggest a new therapeutic pointcut for cardiovascular and cerebrovascular diseases and show the extensive therapeutic potential of miRNA regulation. Moreover, it has been shown that circulating extracellular miRNAs are stable in bodily fluids, which indicates circulating miRNAs as potential and emerging biomarkers for noninvasive diagnosis. This review highlights the most recent findings indicative of circulating miRNAs as potential clinical biomarkers for diagnosis of cardiovascular and cerebrovascular diseases. Meng Li and Junping Zhang Copyright © 2015 Meng Li and Junping Zhang. All rights reserved. Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels Sun, 03 May 2015 15:24:21 +0000 The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation. Md. Ibrahim Khalil, E. M. Tanvir, Rizwana Afroz, Siti Amrah Sulaiman, and Siew Hua Gan Copyright © 2015 Md. Ibrahim Khalil et al. All rights reserved. Changes of the eSheath Outer Dimensions Used for Transfemoral Transcatheter Aortic Valve Replacement Thu, 23 Apr 2015 11:01:35 +0000 Innovative catheter systems with lower-profile sheaths and a dynamic expansion mechanism (DEM) were recently introduced for transcatheter aortic valve replacement (TAVR). However, the labeling of 14 F and 16 F eSheaths denote the inner nominal diameter. Exact changes of the clinically relevant outer diameters during usage are not available. eSheaths were measured every 30 mm using a digital caliper. Unused 14 F and 16 F eSheaths served as controls. Maximum eSheath diameters were measured after insertion of the Edwards Commander Delivery System (ECDS) into 14 F and 16 F eSheaths.Finally, eSheaths were retrieved and measured after TAVR. Outer diameters of control 14 F eSheaths were 5.8 mm and 6.50 mm for the 16 F eSheath. Introduction of the 23 mm and 26 mm ECDS into 14 F eSheaths showed a maximum diameter of 7.65 mm and 7.64 mm (). Introduction of the 29 mm ECDS into the 16 F eSheath showed the greatest diameter of 8.18 mm (). After TAVR, diameters of the 14 F eSheaths were 7.14 mm (23 mm valve) and 7.26 mm (26 mm valve) (), while 16 F eSheaths were 8.10 mm (29 mm valve) (). Nominal 14 F and 16 F eSheaths showed a significant increase of the outer diameter during advancement of the ECDS and after TAVR implantation. Till Koehler, Michael Buege, Heinrich Schleiting, Melchior Seyfarth, Klaus Tiroch, and Marc Vorpahl Copyright © 2015 Till Koehler et al. All rights reserved. Cardioprotective Activity of Pongamia pinnata in Streptozotocin-Nicotinamide Induced Diabetic Rats Tue, 14 Apr 2015 14:21:31 +0000 Pongamia pinnata (L.) Pierre has been used in traditional medicine for the treatment for diabetes and metabolic disorder. The aim of this study was to investigate the effect of petroleum ether extract of the stem bark of P. pinnata (known as PPSB-PEE) on cardiomyopathy in diabetic rats. Diabetes was induced in overnight fasted Sprague-Dawley rats by using injection of streptozotocin (55 mg/kg, i.p.). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Rats were divided into group I: nondiabetic, group II: diabetic control (tween 80, 2%; 10 mL/kg, p.o.) as vehicle, and group III: PPSB-PEE (100 mg/kg, p.o.). The blood glucose level, ECG, hemodynamic parameters, cardiotoxic and antioxidant biomarkers, and histology of heart were carried out after 4 months after STZ with nicotinamide injection. PPSB-PEE treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters; and histological changes in STZ induced diabetic rats. PPSB-PEE (100 mg/kg, p.o.) decreased blood glucose level, improved electrocardiographic parameters (QRS, QT, and QTc intervals) and hemodynamic parameters (SBP, DBP, EDP, max , contractility index, and heart rate), controlled levels of cardiac biomarkers (CK-MB, LDH, and AST), and improved oxidative stress (SOD, MDA, and GSH) in diabetic rats. PPSB-PEE is a promising remedy against cardiomyopathy in diabetic rats. Sachin L. Badole, Swapnil M. Chaudhari, Ganesh B. Jangam, Amit D. Kandhare, and Subhash L. Bodhankar Copyright © 2015 Sachin L. Badole et al. All rights reserved. A Preliminary Real-Time and Realistic Simulation Environment for Percutaneous Coronary Intervention Mon, 23 Mar 2015 13:49:54 +0000 Percutaneous coronary intervention (PCI) is a minimally invasive surgery procedure that is widely used in the treatment of coronary artery disease. This procedure requires interventional cardiologists to have high proficiency and therefore demands an extensive training period in order to ensure successful surgical outcome. In this paper, a realistic and real-time interactive simulator for training PCI procedure is presented. A set of new approaches for core simulation components is devised and integrated into the simulator. Trainees can interact with the virtual simulation environment with real instruments and essential maneuvers encountered in real PCI procedure. Although presently targeted at PCI, our simulator could be easily extended to mimic the necessities of any vascular interventional radiology procedures by updating vascular anatomy. Preliminary validation of the proposed physical model of instruments is conducted on vascular phantom to demonstrate its performance and effectiveness. Jianhuang Wu, Haoyu Wang, Peng Zhang, Xin Ma, and Qingmao Hu Copyright © 2015 Jianhuang Wu et al. All rights reserved. Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance Sun, 15 Mar 2015 13:29:18 +0000 Around 5 million annual births in EU and 131 million worldwide give a unique opportunity to collect lifesaving Wharton’s jelly derived mesenchymal stem cells (WJ-MSC). Evidences that these cells possess therapeutic properties are constantly accumulating. Collection of WJ-MSC is done at the time of delivery and it is easy and devoid of side effects associated with collection of adult stem cells from bone marrow or adipose tissue. Likewise, their rate of proliferation, immune privileged status, lack of ethical concerns, nontumorigenic properties make them ideal for both autologous and allogeneic use in regenerative medicine applications. This review provides an outline of the recent findings related to WJ-MSC therapeutic effects and possible advantage they possess over MSC from other sources. Results of first clinical trials conducted to treat immune disorders are highlighted. Ilona Kalaszczynska and Katarzyna Ferdyn Copyright © 2015 Ilona Kalaszczynska and Katarzyna Ferdyn. All rights reserved. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study Tue, 10 Mar 2015 11:34:34 +0000 Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs) with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs). Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ) was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells. Isaac Perea-Gil, Marta Monguió-Tortajada, Carolina Gálvez-Montón, Antoni Bayes-Genis, Francesc E. Borràs, and Santiago Roura Copyright © 2015 Isaac Perea-Gil et al. All rights reserved. Impact of Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Cardiovascular Research Tue, 10 Mar 2015 11:25:15 +0000 Over the years, cell therapy has become an exciting opportunity to treat human diseases. Early enthusiasm using adult stem cell sources has been tempered in light of preliminary benefits in patients. Considerable efforts have been dedicated, therefore, to explore alternative cells such as those extracted from umbilical cord blood (UCB). In line, UCB banking has become a popular possibility to preserve potentially life-saving cells that are usually discarded after birth, and the number of UCB banks has grown worldwide. Thus, a brief overview on the categories of UCB banks as well as the properties, challenges, and impact of UCB-derived mesenchymal stem cells (MSCs) on the area of cardiovascular research is presented. Taken together, the experience recounted here shows that UCBMSCs are envisioned as attractive therapeutic candidates against human disorders arising and/or progressing with vascular deficit. Santiago Roura, Josep Maria Pujal, Carolina Gálvez-Montón, and Antoni Bayes-Genis Copyright © 2015 Santiago Roura et al. All rights reserved. Shengmai Injection Improved Doxorubicin-Induced Cardiomyopathy by Alleviating Myocardial Endoplasmic Reticulum Stress and Caspase-12 Dependent Apoptosis Mon, 09 Mar 2015 09:20:10 +0000 Background. Apoptosis plays vital roles in the progression of doxorubicin-induced cardiomyopathy (DOX-CM). Endoplasmic reticulum stress (ER stress) could induce specific apoptosis by caspase-12 dependent pathway. Shengmai Injection (SMI), a famous Traditional Chinese Medicine, could alleviate the heart damage via inhibiting myocardial apoptosis. However, it is unknown whether SMI can alleviate ER stress and its specific apoptosis in the setting of DOX-CM. Objective. To explore the effects of SMI on heart function, myocardial ER stress, and apoptosis of DOX-CM rats. Methods. Rats with DOX-CM were treated by SMI. Heart function was assessed by echocardiography and brain natriuretic peptide. Myocardial apoptosis was detected by TUNEL assay. ER stress was assessed by detecting the expressions of GRP78 and caspase-12. Results. At the end of eight-week, compared to control, significant heart dysfunction happened in DOX group. The ratio of apoptotic cardiomyocytes and the expressions of GRP78 and caspase-12 increased significantly (). Compared to DOX group, the apoptotic ratio and the expressions of GRP78 and caspase-12 significantly decreased in DOX + SMI group (), accompanied with improved heart function. Conclusion. SMI could alleviate myocardial ER stress and caspase-12 dependent apoptosis, which subsequently helped to improve the heart function of rats with DOX-CM. Yu Chen, Yong Tang, Yin Xiang, Yu-Quan Xie, Xiao-Hong Huang, and Ya-Chen Zhang Copyright © 2015 Yu Chen et al. All rights reserved. The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients Sun, 08 Mar 2015 07:55:49 +0000 Background. Several polymorphisms of a locus on chromosome 1p13.3 have a significant effect on low-density lipoprotein cholesterol (LDL-C), atherosclerosis, and acute coronary syndrome (ACS). Methods. We aimed to investigate the association between rs599839, rs646776, and rs4970834 of locus 1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients. Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed on Arab patients undergoing coronary angiography for ACS. Patients were divided into group A (ACS with insignificant stenosis (<50%)) and group B (with significant stenosis (≥50%)). Results. Patients carrying the minor G allele in rs599839 had significantly lower mean of LDL-C (2.58 versus 3.44 mM, ) than homozygous A allele carriers (GG versus AA). Carriers of minor C allele in rs64776 had significantly higher mean of HDL-C (2.16 versus 1.36 mM, ) than carriers of the T alleles (AA versus GG). The odd ratio and 95% confidence interval for dominant model for G allele carriers of rs599839 were 0.51 (0.30–0.92), , among patients with significant stenosis. Conclusions. Polymorphisms rs646776 and rs599839 of locus 1p13.3 were significantly associated with LDL-C and other lipid parameters. In addition, the G-allele carriers of variant rs599839 had a significant protective effect against the atherosclerosis. Nasser M. Rizk, Ayman El-Menyar, Huda Egue, Idil Souleman Wais, Hissa Mohamed Baluli, Khalid Alali, Fathi Farag, Noura Younes, and Jassim Al Suwaidi Copyright © 2015 Nasser M. Rizk et al. All rights reserved. Validation of New and Existing Decision Rules for the Estimation of Beat-to-Beat Pulse Transit Time Mon, 02 Mar 2015 07:05:54 +0000 Pulse transit time (PTT) is a pivotal marker of vascular stiffness. Because the actual PTT duration in vivo is unknown and the complicated variation in waveform may occur, the robust determination of characteristic point is still a very difficult task in the PTT estimation. Our objective is to devise a method for real-time estimation of PTT duration in pulse wave. It has an ability to reduce the interference caused by both high- and low-frequency noise. The reproducibility and performance of these methods are assessed on both artificial and clinical pulse data. Artificial data are generated to investigate the reproducibility with various signal-to-noise ratios. For all artificial data, the mean biases obtained from all methods are less than 1 ms; collectively, this newly proposed method has minimum standard deviation (SD, <1 ms). A set of data from 33 participants together with the synchronously recorded continuous blood pressure data are used to investigate the correlation coefficient (CC). The statistical analysis shows that our method has maximum values of mean CC (0.5231), sum of CCs (17.26), and median CC (0.5695) and has the minimum SD of CCs (0.1943). Overall, the test results in this study indicate that the newly developed method has advantages over traditional decision rules for the PTT measurement. Xiaolin Zhou, Rongchao Peng, Hongxia Ding, Ningling Zhang, and Pan Li Copyright © 2015 Xiaolin Zhou et al. All rights reserved. Comparative Myocardial Deformation in 3 Myocardial Layers in Mice by Speckle Tracking Echocardiography Mon, 02 Mar 2015 07:04:43 +0000 Background. Speckle tracking echocardiography (STE) using dedicated high-resolution ultrasound is a relatively new technique that is useful in assessing myocardial deformation in 3 myocardial layers in small animals. However, comparative studies of STE parameters acquired from murine are limited. Methods. A high-resolution rodent ultrasound machine (VSI Vevo 2100) and a clinically validated ultrasound machine (GE Vivid 7) were used to consecutively acquire echocardiography images from standardized parasternal long axis and short axis at midpapillary muscle level from 13 BALB/c mice. Speckle tracking strain (longitudinal, circumferential, and radial) from endocardial, myocardial, and epicardial layers was analyzed using vendor-specific offline analysis software. Results. Intersystem differences were not statistically significant in the global peak longitudinal strain (−16.8 ± 1.7% versus −18.7 ± 3.1%) and radial strain (46.8 ± 14.2% versus 41.0 ± 9.5%), except in the global peak circumferential strain (−16.9 ± 3.1% versus 27.0 ± 5.2%, ). This was corroborated by Bland Altman analysis that revealed a weak agreement in circumferential strain (mean bias ± 1.96 SD of −10.12 ± 6.06%) between endocardium and midmyocardium. However, a good agreement was observed in longitudinal strain between midmyocardium/endocardium (mean bias ± 1.96 SD of −1.88 ± 3.93%) and between midmyocardium/epicardium (mean bias ± 1.96 SD of 3.63 ± 3.91%). Radial strain (mean bias ± 1.96 SD of −5.84 ± 17.70%) had wide limits of agreement between the two systems that indicated an increased variability. Conclusions. Our study shows that there is good reproducibility and agreement in longitudinal deformation of the 3 myocardial layers between the two ultrasound systems. Directional deformation gradients at endocardium, myocardium, and epicardium observed in mice were consistent to those reported in human subjects, thus attesting the clinical relevance of STE findings in murine cardiovascular disease models. Nicole Tee, Yacui Gu, Murni, and Winston Shim Copyright © 2015 Nicole Tee et al. All rights reserved. Acute Myocardial Infarction: A Comparison of the Risk between Physicians and the General Population Mon, 23 Feb 2015 11:57:30 +0000 Physicians in Taiwan have a heavy workload and a stressful workplace, both of which may contribute to cardiovascular disease. However, the risk of acute myocardial infarction (AMI) in physicians is not clear. This population-based cohort study used Taiwan’s National Health Insurance Research Database. We identified 28,062 physicians as the case group and randomly selected 84,186 nonmedical staff patients as the control group. We used a conditional logistic regression to compare the AMI risk between physicians and controls. Subgroup analyses of physician specialty, age, gender, comorbidities, area, and hospital level were also done. Physicians have a higher prevalence of HTN (23.59% versus 19.06%, ) and hyperlipidemia (21.36% versus 12.93%, ) but a lower risk of AMI than did the controls (adjusted odds ratio (AOR): 0.57; 95% confidence interval (CI): 0.46–0.72) after adjusting for DM, HTN, hyperlipidemia, and area. Between medical specialty, age, and area subgroups, differences in the risk for having an AMI were nonsignificant. Medical center physicians had a lower risk (AOR: 0.42; 95% CI: 0.20–0.85) than did local clinic physicians. Taiwan’s physicians had higher prevalences of HTN and hyperlipidemia, but a lower risk of AMI than did the general population. Medical center physicians had a lower risk than did local clinic physicians. Physicians are not necessary healthier than the general public, but physicians, especially in medical centers, have a greater awareness of disease and greater access to medical care, which permits timely treatment and may prevent critical conditions such as AMI induced by delayed treatment. Yen-ting Chen, Chien-Cheng Huang, Shih-Feng Weng, Chien-Chin Hsu, Jhi-Joung Wang, Hung-Jung Lin, Shih-Bin Su, How-Ran Guo, and Chi-Wen Juan Copyright © 2015 Yen-ting Chen et al. All rights reserved. Cardiac Function in a Long-Term Follow-Up Study of Moderate and Severe Porcine Model of Chronic Myocardial Infarction Mon, 23 Feb 2015 08:52:31 +0000 Background. Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed. Methods. Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) or mid-left anterior descending artery (LAD) for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations. Results. Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group compared to only a moderate reduction in the LCx group and this effect remained unchanged during 12 weeks of follow-up. Conclusion. Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx. Renate de Jong, Gerardus P. J. van Hout, Jaco H. Houtgraaf, S. Takashima, Gerard Pasterkamp, Imo Hoefer, and Henricus J. Duckers Copyright © 2015 Renate de Jong et al. All rights reserved. Effects of Dantrolene on Arrhythmogenicity in Isolated Regional Ischemia-Reperfusion Rabbit Hearts with or without Pacing-Induced Heart Failure Thu, 19 Feb 2015 13:20:59 +0000 Dantrolene was reported to suppress ventricular fibrillation (VF) in failing hearts with acute myocardial infarction, but its antiarrhythmic efficacy in regional ischemia-reperfusion (IR) hearts remains debatable. Heart failure (HF) was induced by right ventricular pacing. The IR rabbit model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo in both HF and non-HF groups (n = 9 in each group). Simultaneous voltage and intracellular Ca2+ (Cai) optical mapping was then performed in isolated Langendorff-perfused hearts. Electrophysiological studies were conducted and VF inducibility was evaluated by dynamic pacing. Dantrolene (10 μM) was administered after baseline studies. The HF group had a higher VF inducibility than the control group. Dantrolene had both antiarrhythmic (prolonged action potential duration (APD) and effective refractory period) and proarrhythmic effects (slowed conduction velocity, steepened APD restitution slope, and enhanced arrhythmogenic alternans induction) but had no significant effects on ventricular premature beat (VPB) suppression and VF inducibility in both groups. A higher VF conversion rate in the non-HF group was likely due to greater APD prolonging effects in smaller hearts compared to the HF group. The lack of significant effects on VPB suppression by dantrolene suggests that triggered activity might not be the dominant mechanism responsible for VPB induction in the IR model. Chung-Chuan Chou, Hui-Ling Lee, Po-Cheng Chang, Hung-Ta Wo, Ming-Shien Wen, and San-Jou Yeh Copyright © 2015 Chung-Chuan Chou et al. All rights reserved. Left Ventricle: Fully Automated Segmentation Based on Spatiotemporal Continuity and Myocardium Information in Cine Cardiac Magnetic Resonance Imaging (LV-FAST) Sun, 08 Feb 2015 09:30:18 +0000 CMR quantification of LV chamber volumes typically and manually defines the basal-most LV, which adds processing time and user-dependence. This study developed an LV segmentation method that is fully automated based on the spatiotemporal continuity of the LV (LV-FAST). An iteratively decreasing threshold region growing approach was used first from the midventricle to the apex, until the LV area and shape discontinued, and then from midventricle to the base, until less than 50% of the myocardium circumference was observable. Region growth was constrained by LV spatiotemporal continuity to improve robustness of apical and basal segmentations. The LV-FAST method was compared with manual tracing on cardiac cine MRI data of 45 consecutive patients. Of the 45 patients, LV-FAST and manual selection identified the same apical slices at both ED and ES and the same basal slices at both ED and ES in 38, 38, 38, and 41 cases, respectively, and their measurements agreed within  mL,  mL, and for EDV, ESV, and EF, respectively. LV-FAST allowed LV volume-time course quantitatively measured within 3 seconds on a standard desktop computer, which is fast and accurate for processing the cine volumetric cardiac MRI data, and enables LV filling course quantification over the cardiac cycle. Lijia Wang, Mengchao Pei, Noel C. F. Codella, Minisha Kochar, Jonathan W. Weinsaft, Jianqi Li, Martin R. Prince, and Yi Wang Copyright © 2015 Lijia Wang et al. All rights reserved. Using Coronary Artery Calcification Combined with Pretest Clinical Risk Assessment as a Means of Determining Investigation and Treatment in Patients Presenting with Chest Pain in a Rural Setting Thu, 05 Feb 2015 08:27:14 +0000 462 patients presenting with chest pain to a rural district general hospital underwent calcium scoring and pretest clinical risk assessment in order to stratify subsequent investigations and treatment was retrospectively reviewed. The patients were followed up for two years and further investigations and outcomes recorded. Of the 206 patients with zero calcium score, 132 patients were immediately discharged from cardiac follow-up with no further investigation on the basis of their calcium score, low pretest risk of coronary artery disease, and no significant incidental findings. After further tests, 267 patients were discharged with no further cardiac therapy, 88 patients were discharged with additional medical therapy, and 19 patients underwent coronary artery by-pass grafting or percutaneous intervention. 164 patients with incidental findings on the chest CT (computed tomography) accompanying calcium scoring were reviewed, of which 88 patients underwent further tests and follow-up for noncardiac causes of chest pain. The correlations between all major risk factors and calcium scores were weak except for a combination of diabetes and hypertension in the male gender (), The use of calcium scoring and pretest risk appeared to reduce the number of unnecessary cardiac investigations in our patients: however, the calcium scoring test produced a high number of incidental findings on the associated CT scans. Baskar Sekar, Mark Payne, Azad Hanna, Abdul Azzu, Martin Pike, and Michael Rees Copyright © 2015 Baskar Sekar et al. All rights reserved. Advanced Glycation End Products Induce Endothelial-to-Mesenchymal Transition via Downregulating Sirt 1 and Upregulating TGF-β in Human Endothelial Cells Sun, 01 Feb 2015 14:21:30 +0000 In the present study, we examined the advanced glycation end products- (AGEs-) induced endothelial-to-mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Results demonstrated that AGE-BSAs significantly reduced the cluster of differentiation 31 (CD 31) expression, whereas they promoted the expression of fibroblast-specific protein-1 (FSP-1), α-smooth muscle antibody (α-SMA), and collagen I at both mRNA and protein levels in HUVECs. And the AGE-BSAs also promoted the receptors for AGEs (RAGEs) and receptor I for TGF-β (TGFR I) markedly with a dose dependence, whereas the Sirt 1 was significantly downregulated by the AGE-BSA at both mRNA and protein levels. Moreover, the Sirt 1 activity manipulation with its activator, resveratrol (RSV), or its inhibitor, EX527, markedly inhibited or ameliorated the AGE-mediated TGF-β upregulation. And the manipulated Sirt 1 activity positively regulated the AGE-induced CD31, whereas it negatively regulated the AGE-induced FSP-1. Thus, Sirt 1 was confirmed to regulate the AGE-induced EndMT via TGF-β. In summary, we found that AGE-BSA induced EndMT in HUVECs via upregulating TGF-β and downregulating Sirt 1, which also negatively regulated TGF-β in the cell. This study implied the EndMT probably as an important mechanism of AGE-induced cardiovascular injury. Wei He, Jian Zhang, Tian-yi Gan, Guo-jun Xu, and Bao-peng Tang Copyright © 2015 Wei He et al. All rights reserved. Irrigated Tip Catheters for Radiofrequency Ablation in Ventricular Tachycardia Thu, 29 Jan 2015 09:04:45 +0000 Radiofrequency (RF) ablation with irrigated tip catheters decreases the likelihood of thrombus and char formation and enables the creation of larger lesions. Due to the potential dramatic consequences, the prevention of thromboembolic events is of particular importance for left-sided procedures. Although acute success rates of ventricular tachycardia (VT) ablation are satisfactory, recurrence rate is high. Apart from the progress of the underlying disease, reconduction and the lack of effective transmural lesions play a major role for VT recurrences. This paper reviews principles of lesion formation with radiofrequency and the effect of tip irrigation as well as recent advances in new technology. Potential areas of further development of catheter technology might be the improvement of mapping by better substrate definition and resolution, the introduction of bipolar and multipolar ablation techniques into clinical routine, and the use of alternative sources of energy. Andreas Müssigbrodt, Matthias Grothoff, Borislav Dinov, Jedrzej Kosiuk, Sergio Richter, Philipp Sommer, Ole A. Breithardt, Sascha Rolf, Andreas Bollmann, Arash Arya, and Gerhard Hindricks Copyright © 2015 Andreas Müssigbrodt et al. All rights reserved. Body Composition Indices and Predicted Cardiovascular Disease Risk Profile among Urban Dwellers in Malaysia Thu, 29 Jan 2015 07:15:35 +0000 Objectives. This study aims to compare various body composition indices and their association with a predicted cardiovascular disease (CVD) risk profile in an urban population in Kuala Lumpur, Malaysia. Methods. A cross-sectional survey was conducted in metropolitan Kuala Lumpur, Malaysia, in 2012. Households were selected using a simple random-sampling method, and adult members were invited for medical screening. The Framingham Risk Scoring algorithm was used to predict CVD risk, which was then analyzed in association with body composition measurements, including waist circumference, waist-hip ratio, waist-height ratio, body fat percentage, and body mass index. Results. Altogether, 882 individuals were included in our analyses. Indices that included waist-related measurements had the strongest association with CVD risk in both genders. After adjusting for demographic and socioeconomic variables, waist-related measurements retained the strongest correlations with predicted CVD risk in males. However, body mass index, waist-height ratio, and waist circumference had the strongest correlation with CVD risk in females. Conclusions. The waist-related indicators of abdominal obesity are important components of CVD risk profiles. As waist-related parameters can quickly and easily be measured, they should be routinely obtained in primary care settings and population health screens in order to assess future CVD risk profiles and design appropriate interventions. Tin Tin Su, Mohammadreza Amiri, Farizah Mohd Hairi, Nithiah Thangiah, Maznah Dahlui, and Hazreen Abdul Majid Copyright © 2015 Tin Tin Su et al. All rights reserved. Relationship between Sum of the Four Limbs’ Pulse Pressure and Brachial-Ankle Pulse Wave Velocity and Atherosclerosis Risk Factors in Chinese Adults Wed, 28 Jan 2015 08:18:32 +0000 The aim of the present study was to analyze the relationship between the sum of the four limbs’ pulse pressure (Sum-PP) and brachial-ankle pulse wave velocity (baPWV) and atherosclerosis risk factors and evaluate the feasibility of Sum-PP in diagnosing atherosclerosis systemically. For the purpose, a cross-sectional study was conducted on the basis of medical information of 20748 adults who had a health examination in our hospital. Both Sum-PP and baPWV exhibited significant variations among different human populations grouped by gender, smoking, drinking, and age. Interestingly, Sum-PP had similar varying tendency with baPWV in different populations. And further study in different populations showed that Sum-PP was significantly positively related to baPWV. We also investigated the relationship between Sum-PP, baPWV, and cardiovascular risk factors, respectively. We found that both Sum-PP and baPWV had significant positive correlation with atherosclerosis risk factors while both of them were negatively related to HDL-c. In addition, there was a significant close correlation between Sum-PP and baPWV in the whole population (, ). Thus, Sum-PP is closely related to baPWV and is of important value for clinical diagnosis of atherosclerosis. Yansong Zheng, Zongbin Li, Hua Shu, Minyan Liu, Zhilai Chen, and Jianhua Huang Copyright © 2015 Yansong Zheng et al. All rights reserved. Epicardial Adipose Tissue Reflects the Presence of Coronary Artery Disease: Comparison with Abdominal Visceral Adipose Tissue Tue, 27 Jan 2015 11:31:39 +0000 Accumulation of visceral adipose tissue is associated with a risk of coronary artery disease (CAD). The aim of this study was to examine whether different types of adipose tissue depot may play differential roles in the progression of CAD. Consecutive 174 patients who underwent both computed tomography (CT) and echocardiography were analyzed. Cardiac and abdominal CT scans were performed to measure epicardial and abdominal visceral adipose tissue (EAT and abdominal VAT, resp.). Out of 174 patients, 109 and 113 patients, respectively, presented coronary calcification (CC) and coronary atheromatous plaque (CP). The EAT and abdominal VAT areas were larger in patients with CP compared to those without it. Interestingly, the EAT area was larger in patients with CC compared to those without CC, whereas no difference was observed in the abdominal VAT area between patients with CC and those without. Multivariable logistic regression analysis revealed that the presence of echocardiographic EAT was an independent predictor of CP and CC, but the abdominal VAT area was not. These results suggest that EAT and abdominal VAT may play differential pathological roles in CAD. Given the importance of CC and CP, we should consider the precise assessment of CAD when echocardiographic EAT is detected. Masayoshi Oikawa, Takashi Owada, Hiroyuki Yamauchi, Tomofumi Misaka, Hirofumi Machii, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, and Yasuchika Takeishi Copyright © 2015 Masayoshi Oikawa et al. All rights reserved. Noninvasive Physiologic Assessment of Coronary Stenoses Using Cardiac CT Tue, 20 Jan 2015 12:27:27 +0000 Coronary CT angiography (CCTA) has become an important noninvasive imaging modality in the diagnosis of coronary artery disease (CAD). CCTA enables accurate evaluation of coronary artery stenosis. However, CCTA provides limited information on the physiological significance of stenotic lesions. A noninvasive “one-stop-shop” diagnostic test that can provide both anatomical significance and functional significance of stenotic lesions would be beneficial in the diagnosis and management of CAD. Recently, with the introduction of novel techniques, such as myocardial CT perfusion, CT-derived fractional flow reserve (), and transluminal attenuation gradient (TAG), CCTA has emerged as a noninvasive method for the assessment of both anatomy of coronary lesions and its physiological consequences during a single study. This review provides an overview of the current status of new CT techniques for the physiologic assessments of CAD. Lei Xu, Zhonghua Sun, and Zhanming Fan Copyright © 2015 Lei Xu et al. All rights reserved. Circulating miR-765 and miR-149: Potential Noninvasive Diagnostic Biomarkers for Geriatric Coronary Artery Disease Patients Thu, 15 Jan 2015 13:32:23 +0000 The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD) patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years) and 32 unstable CAD (72.03 ± 4.3 years) and 20 healthy subjects (71.7 ± 5.2 years), matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC) of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people. Md Sayed Ali Sheikh, Ke Xia, Fei Li, Xu Deng, Umme Salma, Hai Deng, Liu Wei Wei, Tian-Lun Yang, and Jun Peng Copyright © 2015 Md Sayed Ali Sheikh et al. All rights reserved. Influence of Two Common Polymorphisms in the EPHX1 Gene on Warfarin Maintenance Dosage: A Meta-Analysis Tue, 06 Jan 2015 06:32:02 +0000 We conducted a meta-analysis to investigate the influence of two common single nucleotide polymorphisms (SNPs) (rs2292566 G>A and rs4653436 A>G) in the EPHX1 gene on warfarin maintenance dosages. Relevant literatures were searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, TX, USA) was used for this meta-analysis. Standard mean difference and its corresponding 95% confidence interval (95% CI) were calculated. Seven studies met the inclusion criteria, including 2,063 warfarin-treated patients. Meta-analysis results illustrated that EPHX1 rs2292566 G>A polymorphism might be strongly correlated with a higher maintenance dose of warfarin. However, no interaction of EPHX1 rs4653436 A>G polymorphism with warfarin maintenance dosage was detected. A further subgroup analysis based on stratification by ethnicity indicated that EPHX1 rs2292566 G>A polymorphism was positively correlated with warfarin maintenance dosage among Caucasians, but not Asians. No associations were observed between EPHX1 rs4653436 A>G polymorphism warfarin maintenance dosage among both Caucasians and Asians. Our meta-analysis provides robust and unambiguous evidence that EPHX1 rs2292566 polymorphism may affect the maintenance dose of warfarin in Caucasians. Hong-Qiang Liu, Chang-Po Zhang, Chang-Zhen Zhang, Xiang-Chen Liu, and Zun-Jing Liu Copyright © 2015 Hong-Qiang Liu et al. All rights reserved. Long-Term Effects and Prognosis in Acute Heart Failure Treated with Tolvaptan: The AVCMA Trial Mon, 10 Nov 2014 10:48:22 +0000 Background. Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. We previously reported the efficacy and safety of tolvaptan compared to carperitide in hospitalized patients with ADHF. There were some reports of cardio- and renal-protective effects in carperitide; therefore, the purpose of this study was to compare the long-term effects of tolvaptan and carperitide on cardiorenal function and prognosis. Methods and Results. One hundred and five ADHF patients treated with either tolvaptan or carperitide were followed after hospital discharge. Levels of plasma B-type natriuretic peptide, serum sodium, potassium, creatinine, and estimated glomerular filtration rate were measured before administration of tolvaptan or carperitide at baseline, the time of discharge, and one year after discharge. These data between tolvaptan and carperitide groups were not different one year after discharge. Kaplan-Meier survival curves demonstrated that the event-free rate regarding all events, cardiac events, all cause deaths, and rehospitalization due to worsening heart failure was not significantly different between tolvaptan and carperitide groups. Conclusions. We demonstrated that tolvaptan had similar effects on cardiac and renal function and led to a similar prognosis in the long term, compared to carperitide. Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi Suzuki, Shu-ichi Saitoh, Isao Kubota, and Yasuchika Takeishi Copyright © 2014 Satoshi Suzuki et al. All rights reserved. Genetic Identification and Risk Factor Analysis of Asymptomatic Bacterial Colonization on Cardiovascular Implantable Electronic Devices Sun, 02 Nov 2014 11:40:39 +0000 Asymptomatic bacterial colonization of cardiovascular implantable electronic devices (CIEDs) is widespread and increases the risk of clinical CIED infection. The aim of the study was to evaluate the incidence of bacterial colonization of generator pockets in patients without signs of infection and to analyze the relationship with clinical infection and risk factors. From June 2011 to December 2012, 78 patients underwent CIED replacement or upgrade. Exclusion criteria included a clinical diagnosis of CIED infection, bacteremia, or infective endocarditis. All patients were examined for evidence of bacterial 16S rDNA on the device and in the surrounding tissues. Infection cases were recorded during follow-up. The bacterial-positive rate was 38.5% (30 cases); the coagulase-negative Staphylococcus detection rate was the highest (9 cases, 11.5%). Positive bacterial DNA results were obtained from pocket tissue in 23.1% of patients (18 cases), and bacterial DNA was detected on the device in 29.5% of patients (23 cases). During follow-up (median 24.6 months), two patients (6.7%, 2/30) became symptomatic with the same species of microorganism, S. aureus and S. epidermidis. Multivariable logistic regression analysis found that the history of bacterial infection, use of antibiotics, application of antiplatelet drugs, replacement frequency, and renal insufficiency were independent risk factors for asymptomatic bacterial colonization. Xian-Ming Chu, Bing Li, Yi An, Xue-Bin Li, and Ji-Hong Guo Copyright © 2014 Xian-Ming Chu et al. All rights reserved. Genetic Diversity of SCN5A Gene and Its Possible Association with the Concealed Form of Brugada Syndrome Development in Polish Group of Patients Mon, 20 Oct 2014 09:14:39 +0000 Brugada Syndrome (BS) is an inherited channelopathy associated with a high incidence of sudden cardiac death. The paper presents the discovery of new genetic variants of SCN5A gene which might be associated with the development of a concealed form of Brugada Syndrome. The study involved a group of 59 patients (37 men) with suspected concealed form of Brugada Syndrome. Pharmacological provocation with intravenous ajmaline administration was performed. Six patients with positive test results were subjected to molecular analysis of SCN5A gene with MSSCP method. Additionally, MSSCP genotyping was performed for samples obtained from the family members with Brugada Syndrome, despite the fact that they had negative ajmaline challenge test results. Genetic examinations of the SCN5A gene at 6 positive patients showed 6 known polymorphisms, 8 new single nucleotide point (SNP) variants located at exons, and 12 new single nucleotide point variants located at introns. Among new SNPs localized in SCN5A gene exons three SNPs affected the protein sequence. Beata Uziębło-Życzkowska, Grzegorz Gielerak, Paweł Siedlecki, and Beata Pająk Copyright © 2014 Beata Uziębło-Życzkowska et al. All rights reserved. Serum Fetuin-A Levels in Patients with Cardiovascular Disease: A Meta-Analysis Thu, 16 Oct 2014 13:01:01 +0000 Background. Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. Method. Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. Results. Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD = 1.36, 95%CI: 0.37–2.36, ). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD = 1.73, 95%CI: 0.20–3.26, ), but not in Asians (SMD = 1.04, 95%CI: −0.33–2.40, ). Conclusion. The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs. Ze-Lin Sun, Qi-Ying Xie, Gong-Liang Guo, Ke Ma, and Yuan-Yuan Huang Copyright © 2014 Ze-Lin Sun et al. All rights reserved. Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension: A Sensitive Tool for Detection of Subclinical LV Impairment Wed, 15 Oct 2014 07:32:52 +0000 Early diagnosis of cardiac alterations in hypertensive heart disease is still challenging. Since such patients might have depressed global LV systolic strain or strain rate when EF is still normal, speckle-tracking echocardiography (STE) and tissue-Doppler imaging (TDI) combined with stress echocardiography might improve early diagnosis of cardiac alterations. In this prospective study standard 2D Doppler echocardiography, STE, and TDI were performed at rest and during bicycle exercise in 92 consecutive patients—46 hypertensive subjects with normal ejection fraction and 46 healthy controls. STE and TDI were used to measure global peak systolic LV circumferential strain (CS), longitudinal strain (LS), and longitudinal strain rate (SR). Mean arterial blood pressure was significantly higher in hypertensive patients at rest (100.8 mmHg SD 13.5 mmHg; ) and during physical exercise testing (124.2 mmHg SD 13.4 mmHg; ). Hypertensive patients had significantly reduced values of systolic CS (), LS (), and SR () at rest as well as during physical exercise—CS (), LS (), and SR (). Using STE and TDI, reduced LV systolic strain and strain rate consistent with early cardiac alterations can be detected in patients with arterial hypertension. These findings were evident at rest and markedly pronounced during exercise echocardiography. Kai O. Hensel, Andreas Jenke, and Roman Leischik Copyright © 2014 Kai O. Hensel et al. All rights reserved. The Prognostic Impact of High On-Treatment Platelet Reactivity with Aspirin or ADP Receptor Antagonists: Systematic Review and Meta-Analysis Mon, 13 Oct 2014 07:55:07 +0000 Objective. Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64–68) and 22.7% (22.4–27.8), of female gender. After a median follow-up of 1 year (0.1–1), cardiac adverse events occurred in 8.3% (3–11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], ). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89–1.22, 0%). Conclusions. After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed. Fabrizio D’Ascenzo, Umberto Barbero, Marta Bisi, Claudio Moretti, Pierluigi Omedè, Enrico Cerrato, Giorgio Quadri, Federico Conrotto, Giuseppe Biondi Zoccai, James J. DiNicolantonio, Mauro Gasparini, Sripal Bangalore, and Fiorenzo Gaita Copyright © 2014 Fabrizio D’Ascenzo et al. All rights reserved. Novel Study on N-Nitrosamines as Risk Factors of Cardiovascular Diseases Wed, 27 Aug 2014 00:00:00 +0000 Millions of people are exposed daily to N-nitrosamines from different environmental sources. The present study aims at investigating the role of N-nitrosamines in the alteration of homocysteine, lipid profile, oxidative stress, paraoxonase activity, antioxidant enzymes, and free radicals which are important risk factors for CVD. In addition, biomarkers of cardiovascular diseases such as creatine kinase MB activity (CK-MB) and lactate dehydrogenase (LDH) as well as protein expression of both glutathione peroxidase and glutathione S-transferase π isozyme were assayed after treatment of rats with 0.2 mg/kg body weight of N-nitrosodibutylamine (NDBA), N-nitrosoethylbutylamine (NEBA), N-nitrosobutylpropylamine (NBPA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosodiphenylamine (NDPA) as a daily dose for two weeks. LDL levels, paraoxonase activity, reduced glutathione levels, and glutathione reductase activities were increased, whereas HDL levels decreased after treatment of rats with most of N-nitrosamines compared to control group. Moreover, levels of free radicals and catalase activity increased, whereas protein expression of both glutathione peroxidase and glutathione S-transferase decreased after treatment of rats with some N-nitrosamines. The data showed that most N-nitrosamines increased CK-MB and LDH activities. It is concluded that N-nitrosamines increased levels of free radicals, and decreased the activity of antioxidant enzymes which may consequently increase the incidence of CVDs. Salah A. Sheweita, Heba A. El-Bendery, and Mostafa H. Mostafa Copyright © 2014 Salah A. Sheweita et al. All rights reserved. Evaluation of the Effect of Andrographolide on Atherosclerotic Rabbits Induced by Porphyromonas gingivalis Mon, 18 Aug 2014 07:00:58 +0000 Epidemiologic evidence has demonstrated significant associations between atherosclerosis and Porphyromonas gingivalis (Pg). We had investigated the effect of andrographolide (AND) on atherosclerosis induced by Pg in rabbits. For experimental purpose, we separated thirty male white New Zealand rabbits into 5 groups. Group 1 received standard food pellets; Groups 2–5 were orally challenged with Pg; Group 3 received atorvastatin (AV, 5 mg/kg), and Groups 4-5 received 10 and 20 mg/kg of AND, respectively, over 12 weeks. Groups treated with AND showed significant decrease in TC, TG, and LDL levels () and significant increase in HDL level in the serum of rabbits. Furthermore, the treated groups (G3–G5) exhibited reductions in interleukins (IL-1β and IL-6) and C-reactive protein (CRP) as compared to atherogenicgroup (G2). The histological results showed that the thickening of atherosclerotic plaques were less significant in treated groups (G3–G5) compared with atherogenicgroup (G2). Also, alpha-smooth muscle actin (α-SMA) staining decreased within the plaques of atherogenicgroup (G2), while it was increased in treated groups (G3–G5). Lastly, groups treated with AV and AND (G3–G5) showed significant reduction of CD36 expression () compared to atherogenicgroup (G2). These results substantially proved that AND contain antiatherogenic activity. Rami Al Batran, Fouad Al-Bayaty, Mazen M. Jamil Al-Obaidi, Saba F. Hussain, and Tengku Z. Mulok Copyright © 2014 Rami Al Batran et al. All rights reserved. Effects of β-Adrenoceptor Subtypes on Cardiac Function in Myocardial Infarction Rats Exposed to Fine Particulate Matter (PM2.5) Tue, 12 Aug 2014 08:39:53 +0000 The pathophysiological mechanisms of heart failure (HF) stems were mainly from longstanding overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Recent studies highlighted the potential benefits of β1-adrenoceptor (β1-AR) blocker combined with β2-adrenergic receptor (β2-AR) agonist in patients with HF. Long-term exposure to fine particulate air pollution, such as particulate matter ≤ 2.5 μm in diameter (PM2.5), has been found associated with acute myocardial infarction (AMI) which is the most common cause of congestive HF. In this study, we have investigated the effect of combined metoprolol and terbutaline on cardiac function in a rat model of AMI exposed to PM2.5. Our results demonstrated that short-term exposure to PM2.5 contributes to aggravate cardiac function in rats with myocardial infarction. The combined use of β1-AR blocker and β2-AR agonist is superior to β1-AR blocker alone for the treatment of AMI rats exposed to PM2.5. The combination of β1-AR blocker and β2-AR agonist may decrease the mortality of patients with myocardial infarction who have been exposed to PM2.5. Yuping Gao, Jiyuan Lv, Yuanyuan Lin, Xuewen Li, Lixia Wang, Yanping Yin, and Yan Liu Copyright © 2014 Yuping Gao et al. All rights reserved. Adiponectin Ameliorates Endotoxin-Induced Acute Cardiac Injury Sun, 10 Aug 2014 08:25:35 +0000 Background. Obesity is a risk factor for cardiovascular disease. Increasing evidence suggests that reduced levels of the adipocyte-derived plasma protein adiponectin are associated with an increased cardiovascular risk. Here, we examined the effects of adiponectin on lipopolysaccharide- (LPS-) induced acute cardiac injury in vivo. Methods and Results. A single dose of LPS (10 mg/kg) was intraperitoneally injected into wild-type (WT) and adiponectin-knockout (APN-KO) mice. Following LPS administration, APN-KO mice had exacerbation of left ventricular (LV) systolic dysfunction compared with WT mice. Administration of LPS to WT and APN-KO mice led to an increased expression of inflammatory cytokines including TNF- and IL-6 in the heart, but the magnitude of this induction was greater in APN-KO mice compared to WT mice. Systemic delivery of an adenoviral vector expressing adiponectin (Ad-APN) improved LPS-induced LV dysfunction in APN-KO mice, and this effect was accompanied by the reduced expression of TNF- and IL-6 in the heart. Administration of etanercept, a soluble TNF receptor abolished the reduced LV contractile function in response to LPS in APN-KO mice. Conclusion. These results suggest that adiponectin protects against LPS-induced acute cardiac injury by suppressing cardiac inflammatory responses, and could represent a potential therapeutic target in sepsis-associated myocardial dysfunction. Yoshio Watanabe, Rei Shibata, Noriyuki Ouchi, Takahiro Kambara, Koji Ohashi, Li Jie, Yoko Inoue, Toyoaki Murohara, and Kimihiro Komori Copyright © 2014 Yoshio Watanabe et al. All rights reserved. Coronary CT Angiography in the Quantitative Assessment of Coronary Plaques Tue, 05 Aug 2014 05:16:27 +0000 Coronary computed tomography angiography (CCTA) has been recently evaluated for its ability to assess coronary plaque characteristics, including plaque composition. Identification of the relationship between plaque composition by CCTA and patient clinical presentations may provide insight into the pathophysiology of coronary artery plaque, thus assisting identification of vulnerable plaques which are associated with the development of acute coronary syndrome. CCTA-generated 3D visualizations allow evaluation of both coronary lesions and lumen changes, which are considered to enhance the diagnostic performance of CCTA. The purpose of this review is to discuss the recent developments that have occurred in the field of CCTA with regard to its diagnostic accuracy in the quantitative assessment of coronary plaques, with a focus on the characterization of plaque components and identification of vulnerable plaques. Zhonghua Sun and Lei Xu Copyright © 2014 Zhonghua Sun and Lei Xu. All rights reserved. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart Thu, 24 Jul 2014 06:41:21 +0000 The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. Sarai Limon-Miranda, Diana G. Salazar-Enriquez, Jesus Muñiz, Mario V. Ramirez-Archila, Enrique A. Sanchez-Pastor, Felipa Andrade, Jose G. Soñanez-Organis, Edgar F. Moran-Palacio, and Adolfo Virgen-Ortiz Copyright © 2014 Sarai Limon-Miranda et al. All rights reserved. The Study of Fetal Rat Model of Intra-Amniotic Isoproterenol Injection Induced Heart Dysfunction and Phenotypic Switch of Contractile Proteins Sun, 20 Jul 2014 08:53:12 +0000 To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure. Yifei Li, Jie Fang, Yimin Hua, Chuan Wang, Dezhi Mu, and Kaiyu Zhou Copyright © 2014 Yifei Li et al. All rights reserved. Intra-QT Spectral Coherence as a Possible Noninvasive Marker of Sustained Ventricular Tachycardia Tue, 15 Jul 2014 12:55:40 +0000 Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the wave to the T wave peak () and the one from T wave peak to the T wave end (Te) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the -Te spectral coherence. The latter was significantly lower in patients with sustained VT than in those without ( versus , ). Although the responsible mechanism remains conjectural, the -Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias. Gianfranco Piccirillo, Federica Moscucci, Alessandro Persi, Daniele Di Barba, Maria Antonella Pappadà, Pietro Rossi, Raffaele Quaglione, Bich Lien Nguyen, Francesco Barillà, Matteo Casenghi, and Damiano Magrì Copyright © 2014 Gianfranco Piccirillo et al. All rights reserved. Cardiac Troponin T (TNNT2) Mutations in Chinese Dilated Cardiomyopathy Patients Mon, 07 Jul 2014 09:46:49 +0000 Background. Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. Although more than 40 genes have been reported to cause DCM, the role of genetic testing in clinical practice is not well defined. Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM. Therefore, the aim of the present study was to determine the genetic variations in TNNT2 and the associations of those variations with DCM in Chinese patients. Methods. An approximately 4 kb fragment of the TNNT2 gene was isolated from 103 DCM patients and 192 healthy controls and was analyzed by DNA sequence analysis for genetic variations. Results. A total of 6 TNNT2 mutations were identified in 99 patients, including a G321T missense mutation (Leu84Phe) and 5 novel intronic mutations. Alleles of two novel SNPs (c. CA, OR , 95% CI: , ; c. GA, OR , 95% CI: , ) and SNP rs3729843 (OR , 95% CI: ; ) were significantly correlated with DCM. Conclusions. These results suggest that the missense mutation (Leu84Phe) and two novel SNPs (c. CA, c. GA) in TNNT2 gene might be associated with DCM in the Chinese population. Xiaoping Li, Rong Luo, Haiyong Gu, Yun Deng, Xiaolei Xu, Xiushan Wu, and Wei Hua Copyright © 2014 Xiaoping Li et al. All rights reserved. Beneficial Effects of Testosterone Therapy on Functional Capacity, Cardiovascular Parameters, and Quality of Life in Patients with Congestive Heart Failure Sun, 06 Jul 2014 11:29:56 +0000 Background. According to the present evidences suggesting association between low testosterone level and prediction of reduced exercise capacity as well as poor clinical outcome in patients with heart failure, we sought to determine if testosterone therapy improves clinical and cardiovascular conditions as well as quality of life status in patients with stable chronic heart failure. Methods. A total of 50 male patients who suffered from congestive heart failure were recruited in a double-blind, placebo-controlled trial and randomized to receive an intramuscular (gluteal) long-acting androgen injection (1 mL of testosterone enanthate 250 mg/mL) once every four weeks for 12 weeks or receive intramuscular injections of saline (1 mL of 0.9% wt/vol NaCl) with the same protocol. Results. The changes in body weight, hemodynamic parameters, and left ventricular dimensional echocardiographic indices were all comparable between the two groups. Regarding changes in diastolic functional state and using Tei index, this parameter was significantly improved. Unlike the group received placebo, those who received testosterone had a significant increasing trend in 6-walk mean distance (6MWD) parameter within the study period (). The discrepancy in the trends of changes in 6MWD between study groups remained significant after adjusting baseline variables (mean square = 243.262, index = 4.402, and ). Conclusion. Our study strengthens insights into the beneficial role of testosterone in improvement of functional capacity and quality of life in heart failure patients. Ahmad Mirdamadi, Mohammad Garakyaraghi, Ali Pourmoghaddas, Alireza Bahmani, Hamideh Mahmoudi, and Mojgan Gharipour Copyright © 2014 Ahmad Mirdamadi et al. All rights reserved. Adenylyl Cyclase Signaling in the Developing Chick Heart: The Deranging Effect of Antiarrhythmic Drugs Mon, 23 Jun 2014 00:00:00 +0000 The adenylyl cyclase (AC) signaling system plays a crucial role in the regulation of cardiac contractility. Here we analyzed the key components of myocardial AC signaling in the developing chick embryo and assessed the impact of selected β-blocking agents on this system. Application of metoprolol and carvedilol, two commonly used β-blockers, at embryonic day (ED) 8 significantly downregulated (by about 40%) expression levels of AC5, the dominant cardiac AC isoform, and the amount of Gsα protein at ED9. Activity of AC stimulated by forskolin was also significantly reduced under these conditions. Interestingly, when administered at ED4, these drugs did not produce such profound changes in the myocardial AC signaling system, except for markedly increased expression of Giα protein. These data indicate that β-blocking agents can strongly derange AC signaling during the first half of embryonic heart development. Lucie Hejnova, Klara Hahnova, Radka Kockova, Jarmila Svatunkova, David Sedmera, and Jiri Novotny Copyright © 2014 Lucie Hejnova et al. All rights reserved. Cardiac Proteomics Sun, 15 Jun 2014 07:08:35 +0000 Jatin G. Burniston, Anthony O. Gramolini, and R. John Solaro Copyright © 2014 Jatin G. Burniston et al. All rights reserved. The Effects of Beta-Glucan Rich Oat Bread on Serum Nitric Oxide and Vascular Endothelial Function in Patients with Hypercholesterolemia Thu, 12 Jun 2014 06:53:56 +0000 Introduction. Oats are high in soluble fibers and effective in reducing the risk of cardiovascular diseases (CVD). We assessed the effects of beta-glucan from oat bran on serum nitric oxide (NO) endothelial function in patients with hypercholesterolemia. Method. Sixty hypercholesterolemic patients were randomly divided to receive an experimental bread rich in beta-glucan from oat bran (intervention) or bread rich in wheat fiber (control) for four weeks. All subjects had the same diet for two-week baseline period and hypocaloric diet for four weeks of intervention. Serum NO concentration and flow-mediated dilation (FMD) were determined before and after the experiment. Results. Mean age of the participants was 51.1 ± 9.3 years and 65% () were female. After intervention, serum NO concentration increased by 50.2 ± 19.8 μmol/lit in the intervention group (), but no change was observed in the control group (17.5 ± 27.5 μmol/lit; ). No change of FMD was observed in the intervention (0.48 ± 0.78%; ) or in the control group (0.59 ± 0.92%; ). Conclusion. Consumption of oat bread for four weeks increases serum NO concentration but has no effect on FMD. Further studies are warranted in this regard. Faezeh Tabesh, Hamid Sanei, Mansour Jahangiri, Amir Momenizadeh, Elham Tabesh, Kiana Pourmohammadi, and Masoumeh Sadeghi Copyright © 2014 Faezeh Tabesh et al. All rights reserved. Biomechanical Evaluation of Ascending Aortic Aneurysms Wed, 04 Jun 2014 09:00:19 +0000 The biomechanical properties of ascending aortic aneurysms were investigated only in the last decade in a limited number of studies. Indeed, in recent years, there has been a growing interest in this field in order to identify new predictive parameters of risk of dissection, which may have clinical relevance. The researches performed so far have been conducted according to the methods used in the study of abdominal aortic aneurysms. In most cases, uniaxial or biaxial tensile tests were used, while in a smaller number of studies other methods, such as opening angle, bulge inflation, and inflation-extension tests, were used. However, parameters and protocols of these tests are at present very heterogeneous in the studies reported in the literature, and, therefore, the results are not comparable and are sometimes conflicting. The purpose of this review then thence to provide a comprehensive analysis of the experimental methodology for determination of biomechanical properties in the specific field of aneurysms of the ascending aorta to allow for better comparison and understanding of the results. Andrea Avanzini, Davide Battini, Lorenzo Bagozzi, and Gianluigi Bisleri Copyright © 2014 Andrea Avanzini et al. All rights reserved. Electrophysiological Studies in Patients with Pulmonary Hypertension: A Retrospective Investigation Mon, 26 May 2014 11:26:37 +0000 Few studies have investigated patients with pulmonary hypertension and arrhythmias. Data on electrophysiological studies in these patients are rare. In a retrospective dual-centre design, we analysed data from patients with indications for electrophysiological study. Fifty-five patients with pulmonary hypertension were included (Dana Point Classification: group 1: 14, group 2: 23, group 3: 4, group 4: 8, group 5: 2, and 4 patients with exercised-induced pulmonary hypertension). Clinical data, 6-minute walk distance, laboratory values, and echocardiography were collected/performed. Nonsustained ventricular tachycardia was the most frequent indication () for an electrophysiological study, followed by atrial flutter (). In summary 36 ablations were performed and 25 of them were successful (atrial flutter 12 of 14 and atrioventricular nodal reentrant tachycardia 4 of 4). Fluoroscopy time was 16 14.4 minutes. Electrophysiological studies in patients with pulmonary hypertension are feasible and safe. Ablation procedures are as effective in these patients as in non-PAH patients with atrial flutter and atrioventricular nodal reentrant tachycardia and should be performed likewise. The prognostic relevance of ventricular stimulations and inducible ventricular tachycardias in these patients is still unclear and requires further investigation. Dirk Bandorski, Jörn Schmitt, Claudia Kurzlechner, Damir Erkapic, Christian W. Hamm, Werner Seeger, Ardeschir Ghofrani, Reinhard Höltgen, and Henning Gall Copyright © 2014 Dirk Bandorski et al. All rights reserved. Percutaneous Extraction of Transvenous Permanent Pacemaker/Defibrillator Leads Mon, 26 May 2014 05:58:50 +0000 Background. Widespread use of cardiovascular implantable electronic devices has inevitably increased the need for lead revision/replacement. We report our experience in percutaneous extraction of transvenous permanent pacemaker/defibrillator leads. Methods. Thirty-six patients admitted to our centre from September 2005 through October 2012 for percutaneous lead extraction were included. Lead removal was attempted using Spectranetics traction-type system (Spectranetics Corp., Colorado, CO, USA) and VascoExtor countertraction-type system (Vascomed GmbH, Weil am Rhein, Germany). Results. Lead extraction was attempted in 59 leads from 36 patients (27 men), mean ± SD age years, with permanent pacemaker , defibrillator , or cardiac resynchronisation therapy with a mean ± SD implant duration of months. The indications for lead removal included pocket infection , endocarditis , and ventricular and atrial lead dysfunction . Traction device was used for 33 leads and countertraction device for 26 leads. Mean ± SD fluoroscopy time was minutes/lead for leads implanted <48 months and minutes/lead for leads implanted >48 months , . Complete procedural success rate was 91.7% and clinical procedural success rate was 100%, while lead procedural success rate was 95%. Conclusions. In conclusion, percutaneous extraction of transvenous permanent pacemaker/defibrillator leads using dedicated removal tools is both feasible and safe. Stylianos Paraskevaidis, Dimitrios Konstantinou, Vassilios Vassilikos, Efstratios Theofilogiannakos, Lilian Mantziari, Athanasia Megarisiotou, Ioannis Galitsianos, and Charalambos Karvounis Copyright © 2014 Stylianos Paraskevaidis et al. All rights reserved. Evaluation of Alexithymia, Somatosensory Sensitivity, and Health Anxiety Levels in Patients with Noncardiac Chest Pain Sun, 25 May 2014 11:21:37 +0000 Objective. Noncardiac chest pain (NCCP) is seen more frequently in young population and in these patients loss of function is evolving in social and professional areas. The aim of the study is to evaluate the levels of anxiety and somatic perception in patients with chest pain presenting to cardiology clinic. Methods. Fifty-one patients with noncardiac chest pain and 51 healthy controls were included in the study. All participants performed self-report based health anxiety inventory (HAI), somatosensory amplification scale (SAS), and Toronto alexithymia scale (TAS). Results. The patient group had significantly higher scores on the SAS, HAI-1, and HAI-T scales compared to controls (, , and , resp.). SAS, HAI-1, and HAI-T scores were significantly higher in female patients than male (, 0.036, and 0.039, resp.). There were significant differences in all TAS subscale scores between two groups. Patients, who had total TAS score more than 50, also presented higher levels of health anxiety (). Conclusions. Anxiety, somatic symptoms, and the exaggerated sense of bodily sensations are common in patients with NCCP. These patients unnecessarily occupy the cardiology outpatient clinics. These negative results can be eliminated when consultation-liaison psychiatry evaluates these patients in collaboration with cardiology departments. Selma Bozkurt Zincir, Murat Sunbul, Esra Aydin Sunbul, Bahar Dalkilic, Fatma Cengiz, Tarik Kivrak, and Erdal Durmus Copyright © 2014 Selma Bozkurt Zincir et al. All rights reserved. Forces Applied during Transvenous Implantable Cardioverter Defibrillator Lead Removal Wed, 21 May 2014 11:09:23 +0000 Methods. 17 physicians, experienced in transvenous lead removal, performed a lead extraction manoeuvre of an ICD lead on a torso phantom. They were advised to stop traction only when further traction would be considered as harmful to the patient or when—based on their experience—a change in the extraction strategy was indicated. Traction forces were recorded with a digital precision gauge. Results. Median traction forces on the endocardium were 10.9 N (range from 3.0 N to 24.7 N and interquartile range from 7.9 to 15.3). Forces applied to the proximal end were estimated to be 10% higher than those measured at the tip of the lead due to a friction loss. Conclusion. A traction force of around 11 N is typically exerted during standard transvenous extraction of ICD leads. A traction threshold for a safe procedure derived from a pool of experienced extractionists may be helpful for the development of required adequate simulator trainings. Carsten Lennerz, Herribert Pavaci, Christian Grebmer, Gesa von Olshausen, Verena Semmler, Alessandra Buiatti, Tilko Reents, Sonia Ammar, Isabel Deisenhofer, and Christof Kolb Copyright © 2014 Carsten Lennerz et al. All rights reserved. Glycoprotein IIb/IIIa Inhibitors Use and Outcome after Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction Thu, 08 May 2014 08:13:33 +0000 Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival () or MACE (). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (). Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding. J. P. Howard, D. A. Jones, S. Gallagher, K. Rathod, S. Antoniou, P. Wright, C. Knight, A. Mathur, R. Weerackody, and A. Wragg Copyright © 2014 J. P. Howard et al. All rights reserved. Significance of Soluble Lectin-Like Oxidized LDL Receptor-1 Levels in Systemic and Coronary Circulation in Acute Coronary Syndrome Wed, 07 May 2014 13:12:43 +0000 Background. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) level is a novel biomarker for diagnosis of acute coronary syndrome (ACS); however, this level in the coronary circulation has yet to be examined. Methods. Twenty-seven consecutive patients with ACS and 40 patients with effort angina pectoris (EAP) undergoing percutaneous coronary intervention (PCI) had levels of soluble LOX-1 and LOX-1 index measured in paired blood samples from aorta (Ao) and coronary sinus (CS) just prior to the PCI. Results. We found positive correlations between soluble LOX-1 levels in the Ao and CS in both ACS and EAP patients (, for both). The soluble LOX-1 levels in the Ao and CS were higher in ACS than in EAP patients (, for both). The levels of soluble LOX-1 and LOX-1 index of the CS were significantly greater than those of the Ao in both ACS and EAP patients (, for both). Receiver operating characteristic curves for ACS detection demonstrated high sensitivity and specificity for the soluble LOX-1 and LOX-1 index with no differences between the Ao and CS. Conclusions. The present study showed that circulating soluble LOX-1 originates from coronary circulation and soluble LOX-1 and LOX-1 index are useful biomarkers for ACS. Tomofumi Misaka, Satoshi Suzuki, Nobuo Sakamoto, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Tatsuya Sawamura, Toshiyuki Ishibashi, and Yasuchika Takeishi Copyright © 2014 Tomofumi Misaka et al. All rights reserved. Long-Term Anabolic Androgenic Steroid Use Is Associated with Increased Atrial Electromechanical Delay in Male Bodybuilders Sun, 04 May 2014 15:12:02 +0000 We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids (AAS) on atrial electromechanical delay (AEMD) in male bodybuilders. We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders. Mustafa Akçakoyun, Elnur Alizade, Recep Gündoğdu, Mustafa Bulut, Mehmet Mustafa Tabakcı, Göksel Açar, Anıl Avcı, Zeki Şimşek, Serdar Fidan, Serdar Demir, Ramazan Kargın, and Mehmet Yunus Emiroğlu Copyright © 2014 Mustafa Akçakoyun et al. All rights reserved. A Novel Stent Coated with Antibodies to Endoglin Inhibits Neointimal Formation of Porcine Coronary Arteries Sun, 04 May 2014 13:51:26 +0000 Endoglin/CD105 is an accessory protein of the transforming growth factor- receptor system that plays a critical role in proliferation of endothelial cells and neovasculature. Here, we aimed to assess the effect of novel stents coated with antibodies to endoglin (ENDs) on coronary neointima formation. Thirty ENDs, thirty sirolimus-eluting stents (SESs), and thirty bare metal stents (BMSs) were randomly assigned and placed in the coronary arteries in 30 juvenile pigs. Histomorphometric analysis and scanning electron microscopy were performed after stent implantation. Our results showed that after 7 days, there was no difference in the neointimal area and percent area stenosis in ENDs compared with SMSs or BMSs. After 14 days, the neointima area and percent area stenosis in ENDs were markedly decreased than those in BMSs or SESs . Moreover, the percentage of reendothelialization was significantly higher in ENDs than that in SESs or BMSs at 7 and 14 days. The artery injury and the inflammation scores were similar in all groups at 7 and 14 days. In conclusion, our results demonstrated for the first time to our knowledge that endoglin antibody-coated stents can markedly reduce restenosis by enhancing reendothelialization in the porcine model and potentially offer a new approach to prevent restenosis. Song Cui, Jing-Hua Liu, Xian-Tao Song, Guo-Lin Ma, Ben-Jun Du, Shu-Zheng Lv, Li-Jun Meng, Quan-Sheng Gao, and Kefeng Li Copyright © 2014 Song Cui et al. All rights reserved. Endothelium in Diseased States Wed, 30 Apr 2014 12:22:27 +0000 Iveta Bernatova, Ramaroson Andriantsitohaina, Silvia M. Arribas, and Vladimir V. Matchkov Copyright © 2014 Iveta Bernatova et al. All rights reserved. Mas-Mediated Antioxidant Effects Restore the Functionality of Angiotensin Converting Enzyme 2-Angiotensin-(1–7)-Mas Axis in Diabetic Rat Carotid Tue, 29 Apr 2014 13:44:46 +0000 We hypothesized that endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species during type I-diabetes impairs carotid ACE2-angiotensin-(1–7)-Mas axis functionality, which accounts for the impaired carotid flow in diabetic rats. We also hypothesized that angiotensin-(1–7) chronic treatment of diabetic rats restores carotid ACE2-angiotensin-(1–7)-Mas axis functionality and carotid flow. Relaxant curves for angiotensin II or angiotensin-(1–7) were obtained in carotid from streptozotocin-induced diabetic rats. Superoxide or hydrogen peroxide levels were measured by flow cytometry in carotid endothelial cells. Carotid flow was also determined. We found that endothelial AT1-activated NAD(P)H oxidase-driven generation of superoxide and hydrogen peroxide in diabetic rat carotid impairs ACE2-angiotensin-(1–7)-Mas axis functionality, which reduces carotid flow. In this mechanism, hydrogen peroxide derived from superoxide dismutation inhibits ACE2 activity in generating angiotensin-(1–7) seemingly by activating , while superoxide inhibits the nitrergic Mas-mediated vasorelaxation evoked by angiotensin-(1–7). Angiotensin-(1–7) treatment of diabetic rats restored carotid ACE2-angiotensin-(1–7)-Mas axis functionality by triggering a positive feedback played by endothelial Mas receptors, that blunts endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species. Mas-mediated antioxidant effects also restored diabetic rat carotid flow, pointing to the contribution of ACE2-angiotensin-(1–7)-Mas axis in maintaining carotid flow. Larissa Pernomian, Mayara Santos Gomes, Carolina Baraldi Araujo Restini, and Ana Maria de Oliveira Copyright © 2014 Larissa Pernomian et al. All rights reserved. Effects of Hypertension and Exercise on Cardiac Proteome Remodelling Sun, 27 Apr 2014 11:25:44 +0000 Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined. Bernardo A. Petriz and Octavio L. Franco Copyright © 2014 Bernardo A. Petriz and Octavio L. Franco. All rights reserved. Building and Repairing the Heart: What Can We Learn from Embryonic Development? Thu, 17 Apr 2014 11:03:39 +0000 Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed. Ana G. Freire, Tatiana P. Resende, and Perpétua Pinto-do-Ó Copyright © 2014 Ana G. Freire et al. All rights reserved. Factors Influencing Adaptation and Performance at Physical Exercise in Complex Congenital Heart Diseases after Surgical Repair Tue, 15 Apr 2014 13:19:22 +0000 In the last thirty years, steady progress in the diagnostic tools and care of subjects affected by congenital heart diseases (CHD) has resulted in a significant increase in their survival to adulthood, even for those affected by complex CHD. Based on these premises, a number of teenagers and adults affected by corrected (surgically or through interventional techniques) CHD ask to be allowed to undertake sporting activities, both at a recreational and competitive level. The purpose of this review is to examine the mechanisms influencing the adaption at physical exercise of patients suffering from complex CHD. The conclusion is that even if there are some modest risks with exercise, they should be seen in perspective, and the life-long benefits of regular exercise on general health, mood, and well-being should be emphasized. P. P. Bassareo, L. Saba, P. Solla, C. Barbanti, A. R. Marras, and G. Mercuro Copyright © 2014 P. P. Bassareo et al. All rights reserved. Neural Regulation of Cardiovascular Response to Exercise: Role of Central Command and Peripheral Afferents Wed, 09 Apr 2014 07:19:37 +0000 During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed. Antonio C. L. Nobrega, Donal O'Leary, Bruno Moreira Silva, Elisabetta Marongiu, Massimo F. Piepoli, and Antonio Crisafulli Copyright © 2014 Antonio C. L. Nobrega et al. All rights reserved. Improvement in Hemodynamic Responses to Metaboreflex Activation after One Year of Training in Spinal Cord Injured Humans Mon, 07 Apr 2014 14:02:57 +0000 Spinal cord injured (SCI) individuals show an altered hemodynamic response to metaboreflex activation due to a reduced capacity to vasoconstrict the venous and arterial vessels below the level of the lesion. Exercise training was found to enhance circulating catecholamines and to improve cardiac preload and venous tone in response to exercise in SCI subjects. Therefore, training would result in enhanced diastolic function and capacity to vasoconstrict circulation. The aim of this study was to test the hypothesis that one year of training improves hemodynamic response to metaboreflex activation in these subjects. Nine SCI individuals were enrolled and underwent a metaboreflex activation test at the beginning of the study (T0) and after one year of training (T1). Hemodynamics were assessed by impedance cardiography and echocardiography at both T0 and T1. Results show that there was an increment in cardiac output response due to metaboreflex activity at T1 as compared to T0 ( mL·min−1 versus  mL·min−1, ). Moreover, ventricular filling rate response was higher at T1 than at T0. Similarly, end-diastolic volume response was increased after training. We concluded that a period of training can successfully improve hemodynamic response to muscle metaboreflex activation in SCI subjects. Raffaele Milia, Silvana Roberto, Elisabetta Marongiu, Sergio Olla, Irene Sanna, Luca Angius, Pierpaolo Bassareo, Marco Pinna, Filippo Tocco, Alberto Concu, and Antonio Crisafulli Copyright © 2014 Raffaele Milia et al. All rights reserved. Human Pluripotent Stem Cell-Derived Cardiomyocytes as Research and Therapeutic Tools Wed, 02 Apr 2014 14:12:08 +0000 Human pluripotent stem cells (hPSCs), namely, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with their ability of indefinite self-renewal and capability to differentiate into cell types derivatives of all three germ layers, represent a powerful research tool in developmental biology, for drug screening, disease modelling, and potentially cell replacement therapy. Efficient differentiation protocols that would result in the cell type of our interest are needed for maximal exploitation of these cells. In the present work, we aim at focusing on the protocols for differentiation of hPSCs into functional cardiomyocytes in vitro as well as achievements in the heart disease modelling and drug testing on the patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). Ivana Acimovic, Aleksandra Vilotic, Martin Pesl, Alain Lacampagne, Petr Dvorak, Vladimir Rotrekl, and Albano C. Meli Copyright © 2014 Ivana Acimovic et al. All rights reserved. The Chromosome 9p21 Variant Not Predicting Long-Term Cardiovascular Mortality in Chinese with Established Coronary Artery Disease: An Eleven-Year Follow-Up Study Wed, 02 Apr 2014 07:44:57 +0000 Introduction. We examined whether the variant at chromosome 9p21, rs4977574, was associated with long-term cardiovascular mortality in Han Chinese patients with coronary artery disease (CAD). Methodology. Subjects who underwent coronary angiography for chest pain were consecutively enrolled. Fasting blood samples were collected for laboratory and genotype assessments. The information was correlated with data collected from the national death database. Results. There were 925 cases with CAD and 634 without CAD enrolled in the present study. The G allele conferred a significant increase in risk of CAD (odds ratio = 1.47, in the dominant model; odds ratio = 1.36, in the recessive model). During a median of 11 years (inter-quartile range between 5.2 and 12.5 years) of follow-up, neither the total nor the cardiovascular mortality was different among CAD subjects with different genotypes. Using Cox regression analysis, genotypes of rs4977574 still failed to predict cardiovascular mortality (hazard ratio = 1.25, in the dominant model; hazard ratio = 1.05, in the recessive model). Conclusions. The rs4977574 at chromosome 9p21 is associated with presence of CAD in Han Chinese. However, rs4977574 could not predict cardiovascular mortality in these CAD subjects during the eleven-year period of the study. I-Te Lee, Mark O. Goodarzi, Wen-Jane Lee, Jerome I. Rotter, Yii-der Ida Chen, Kae-Woei Liang, Wen-Lieng Lee, and Wayne H.-H. Sheu Copyright © 2014 I-Te Lee et al. All rights reserved. Analysis of Pericardial Effusion from Idiopathic Pericarditis Patients by Two-Dimensional Gel Electrophoresis Wed, 02 Apr 2014 07:00:30 +0000 Pericardial fluid (PF) is often considered to be reflection of the serum by which information regarding the physiological status of the heart can be obtained. Some local and systemic disorders may perturb the balance between synthesis and discharge of PF and may cause its aberrant accumulation in the pericardial cavity as pericardial effusion (PE). PE may then lead to an increased intrapericardial pressure from which the heart function is undesirably affected. For some cases, the causes for the perturbance of fluid balance are well understood, but in some other cases, they are not apparent. It may, thus, be helpful to understand the molecular mechanisms behind this troublesome condition to elucidate a clinical approach for therapeutic uses. In this study, protein profiles of PEs from idiopathic pericarditis patients were analyzed. Control samples from patients undergoing elective cardiac surgery (ECS) were included for comparison. In addition to high abundant serum-originated proteins that may not hold significance for understanding the molecular mechanisms behind this disease, omentin-1 was identified and its level was higher for more than two-fold in PE of IP patients. Increased levels of omentin-1 in PE may open a way for understanding the molecular mechanisms behind idiopathic pericarditis (IP). Sadan Yavuz, Murat Kasap, Gurler Akpinar, Ersan Ozbudak, Dilek Ural, and Turan Berki Copyright © 2014 Sadan Yavuz et al. All rights reserved. The Endothelium, A Protagonist in the Pathophysiology of Critical Illness: Focus on Cellular Markers Tue, 01 Apr 2014 11:41:19 +0000 The endotheliumis key in the pathophysiology of numerous diseases as a result of its precarious function in the regulation of tissue homeostasis. Therefore, its clinical evaluation providing diagnostic and prognostic markers, as well as its role as a therapeutic target, is the focus of intense research in patientswith severe illnesses. In the critically ill with sepsis and acute brain injury, the endothelium has a cardinal function in the development of organ failure and secondary ischemia, respectively. Cellular markers of endothelial function such as endothelial progenitor cells (EPC) and endothelialmicroparticles (EMP) are gaining interest as biomarkers due to their accessibility, although the lack of standardization of EPC and EMP detection remains a drawback for their routine clinical use. In this paper we will review data available on EPC, as a general marker of endothelial repair, and EMP as an equivalent of damage in critical illnesses, in particular sepsis and acute brain injury. Their determination has resulted in new insights into endothelial dysfunction in the critically ill. It remains speculative whether their determination might guide therapy in these devastating acute disorders in the near future. Sabrina H. van Ierssel, Philippe G. Jorens, Emeline M. Van Craenenbroeck, and Viviane M. Conraads Copyright © 2014 Sabrina H. van Ierssel et al. All rights reserved. Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins Sun, 30 Mar 2014 07:15:23 +0000 Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb) is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT) and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ) Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200 mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5 min of limb ischemia followed by 5 min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC. Safa Abdul-Ghani, Kate J. Heesom, Gianni D. Angelini, and M-Saadeh Suleiman Copyright © 2014 Safa Abdul-Ghani et al. All rights reserved. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity Wed, 26 Mar 2014 06:54:43 +0000 The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW), wall-to-lumen ratio (W/L), and media cross-sectional area (MCSA). Dose-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA), nitrites, and total antioxidant capacity (TAC). We observed a significant reduction in WW (), W/L (), and MCSA () and improved endothelium-dependent relaxation ( = versus = , ) in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6 to 10−4 mol/l) for SHR-E with respect to WKY. SOSA () and nitrite () values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR. Ana Arnalich-Montiel, María Carmen González, Emilio Delgado-Baeza, María Jesús Delgado-Martos, Luis Condezo-Hoyos, Antonia Martos-Rodríguez, Pilar Rodríguez-Rodríguez, and Begoña Quintana-Villamandos Copyright © 2014 Ana Arnalich-Montiel et al. All rights reserved. The Association between the LPA Gene Polymorphism and Coronary Artery Disease in Chinese Han Population Tue, 25 Mar 2014 11:16:41 +0000 Lp(a) has been well known as an independent risk factor for coronary artery disease (CAD). The LPA gene, as it encodes apo(a) of the Lp(a) lipoprotein particle, was associated with increased risk of CAD. The purpose of this study was to analyze the relationship between the polymorphisms of LPA gene and CAD in Chinese Han population. Five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in the LPA gene were genotyped using Sequenom MassARRAY time-of-flight mass spectrometer (TOF) in 560 CAD patients as case group and 531 non-CAD subjects as control group. The numbers of these two groups were from Chinese Han ancestry. The results showed that allele () and genotype () of rs9364559 in the LPA gene was associated with CAD. The frequency of rs9364559 minor allele (G) in case group was obviously higher than that in control group. Results of haplotype analysis showed that 4 haplotypes which contained rs9364559-G were associated with increased risk of CAD in this population. This study explored rs9364559 in the LPA gene may be associated with the pathogenesis of CAD; and the risk of CAD might be higher in the population carrying 4 haplotypes of different blocks in the LPA gene. Zi-Kai Song, Hai-Di Wu, Hong-Yan Cao, and Ling Qin Copyright © 2014 Zi-Kai Song et al. All rights reserved. Age and SPARC Change the Extracellular Matrix Composition of the Left Ventricle Mon, 24 Mar 2014 08:09:14 +0000 Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (/group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18–29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, ). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction. Lisandra E. de Castro Brás, Hiroe Toba, Catalin F. Baicu, Michael R. Zile, Susan T. Weintraub, Merry L. Lindsey, and Amy D. Bradshaw Copyright © 2014 Lisandra E. de Castro Brás et al. All rights reserved. Proteomic Profiling of the Dystrophin-Deficient mdx Phenocopy of Dystrophinopathy-Associated Cardiomyopathy Thu, 20 Mar 2014 09:46:46 +0000 Cardiorespiratory complications are frequent symptoms of Duchenne muscular dystrophy, a neuromuscular disorder caused by primary abnormalities in the dystrophin gene. Loss of cardiac dystrophin initially leads to changes in dystrophin-associated glycoproteins and subsequently triggers secondarily sarcolemmal disintegration, fibre necrosis, fibrosis, fatty tissue replacement, and interstitial inflammation. This results in progressive cardiac disease, which is the cause of death in a considerable number of patients afflicted with X-linked muscular dystrophy. In order to better define the molecular pathogenesis of this type of cardiomyopathy, several studies have applied mass spectrometry-based proteomics to determine proteome-wide alterations in dystrophinopathy-associated cardiomyopathy. Proteomic studies included both gel-based and label-free mass spectrometric surveys of dystrophin-deficient heart muscle from the established mdx animal model of dystrophinopathy. Comparative cardiac proteomics revealed novel changes in proteins associated with mitochondrial energy metabolism, glycolysis, signaling, iron binding, antibody response, fibre contraction, basal lamina stabilisation, and cytoskeletal organisation. This review summarizes the importance of studying cardiomyopathy within the field of muscular dystrophy research, outlines key features of the mdx heart and its suitability as a model system for studying cardiac pathogenesis, and discusses the impact of recent proteomic findings for exploring molecular and cellular aspects of cardiac abnormalities in inherited muscular dystrophies. Ashling Holland and Kay Ohlendieck Copyright © 2014 Ashling Holland and Kay Ohlendieck. All rights reserved. Endothelial Function Increases after a 16-Week Diet and Exercise Intervention in Overweight and Obese Young Women Thu, 20 Mar 2014 08:11:17 +0000 Weight loss improves endothelial function in overweight individuals. The effects of weight loss through combined aerobic and resistance training and caloric restriction on in vivo vascular measures and blood markers associated with the regulation of endothelial function have not been comprehensively examined. Therefore, we investigated brachial artery endothelial function and potential regulatory blood markers in twenty overweight women (30.3 ± 2.0 years) who participated in 16 weeks of aerobic (5 d/wk) and resistance training (2 d/wk) (combined: ≥250 kcal/d) and caloric restriction (−500 kcal/d versus requirement). Resting brachial artery flow mediated dilation (FMD) and circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) were assessed at baseline and following the intervention. Relative and absolute FMD increased (before: 4.0 ± 0.5% versus after: 6.9 ± 0.6%, and before: 0.14 ± 0.02 mm versus after: 0.23 ± 0.02 mm, , resp.), while body mass decreased (before: 86.9 ± 2.4 kg versus after: 81.1 ± 2.4 kg, following the intervention. There were no changes in either blood marker (IL-6: before: 1.5 ± 0.2 pg/mL versus after: 1.5 ± 0.1 pg/mL, and ET-1: before: 0.55 ± 0.05 pg/mL versus after: 0.59 ± 0.09 pg/mL, ). 16 weeks of combined aerobic/resistance training and diet-induced weight loss improved endothelial function in overweight and obese young women, but this increase was not associated with changes in blood markers of vasoconstriction or inflammation. Lisa M. Cotie, Andrea R. Josse, Stuart M. Phillips, and Maureen J. MacDonald Copyright © 2014 Lisa M. Cotie et al. All rights reserved. Age-Related Alterations in Endothelial Function of Femoral Artery in Young SHR and WKY Rats Thu, 20 Mar 2014 07:49:43 +0000 The present study was designed to evaluate the effects of vascular aging in juvenescence on endothelial function in femoral arteries and to assess differences between normotensive and hypertensive rats. The aim of the study was to determine if age affected nitric oxide- (NO-) mediated relaxations in normotensive and hypertensive rats. Juvenile (7-week-old) and young adult (22-week-old) male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were used in this study. Femoral artery (FA) reactivity was determined by wire myograph and NO synthase activity by conversion of [3H]-L-arginine. During juvenescence systolic blood pressure (tail-cuff) increased significantly only in SHR, while NO synthesis decreased significantly in both strains. Endothelium-dependent relaxations to acetylcholine were reduced in the FA of SHR compared to age-matched WKY at both ages, yet these parameters were unchanged in adult rats compared with juvenile animals. The NO-dependent component of vasorelaxation was markedly reduced, whereas the NO-independent component was increased in adult compared to juvenile rats in both strains. The endothelial dysfunction in SHR at both ages was associated with reduction of NO-independent mechanisms. In conclusion, aging in early periods of life was associated with reduction of vascular NO production and bioavailability in both strains investigated. This reduction was however fully compensated by accentuation of NO-independent mechanisms. Angelika Puzserova, Veronika Ilovska, Peter Balis, Peter Slezak, and Iveta Bernatova Copyright © 2014 Angelika Puzserova et al. All rights reserved. Association of P2Y12 Gene Promoter DNA Methylation with the Risk of Clopidogrel Resistance in Coronary Artery Disease Patients Tue, 18 Mar 2014 11:32:12 +0000 Background. Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR). Methods. The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR. Result. Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, ; CpG2, ) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients () and in subgroup of Albumin < 35 (). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR. Conclusions. The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR. Jia Su, Xiaojing Li, Qinglin Yu, Yahui Liu, Yaqing Wang, Haojun Song, Hanbin Cui, Weiping Du, Xiaohong Fei, Junsong Liu, Shaoyi Lin, Jian Wang, Wenyuan Zheng, Jinyan Zhong, Lulu Zhang, Maoqing Tong, Jin Xu, and Xiaomin Chen Copyright © 2014 Jia Su et al. All rights reserved. Recent Insights in the Paracrine Modulation of Cardiomyocyte Contractility by Cardiac Endothelial Cells Thu, 13 Mar 2014 16:17:58 +0000 The cardiac endothelium is formed by a continuous monolayer of cells that line the cavity of the heart (endocardial endothelial cells (EECs)) and the luminal surface of the myocardial blood vessels (intramyocardial capillary endothelial cells (IMCEs)). EECs and IMCEs can exercise substantial control over the contractility of cardiomyocytes by releasing various factors such as nitric oxide (NO) via a constitutive endothelial NO-synthase (eNOS), endothelin-1, prostaglandins, angiotensin II, peptide growth factors, and neuregulin-1. The purpose of the present paper is actually to shortly review recent new information concerning cardiomyocytes as effectors of endothelium paracrine signaling, focusing particularly on contractile function. The modes of action and the regulatory paracrine role of the main mediators delivered by cardiac endothelial cells upon cardiac contractility identified in cardiomyocytes are complex and not fully described. Thus, careful evaluation of new therapeutic approaches is required targeting important physiological signaling pathways, some of which have been until recently considered as deleterious, like reactive oxygen species. Future works in the field of cardiac endothelial cells and cardiac function will help to better understand the implication of these mediators in cardiac physiopathology. Jacques Noireaud and Ramaroson Andriantsitohaina Copyright © 2014 Jacques Noireaud and Ramaroson Andriantsitohaina. All rights reserved. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence? Thu, 13 Mar 2014 10:02:58 +0000 Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models. Iveta Bernatova Copyright © 2014 Iveta Bernatova. All rights reserved. Comparison of the Ventricle Muscle Proteome between Patients with Rheumatic Heart Disease and Controls with Mitral Valve Prolapse: HSP 60 May Be a Specific Protein in RHD Wed, 12 Mar 2014 08:05:44 +0000 Objective. Rheumatic heart disease (RHD) is a serious autoimmune heart disease. The present study was aimed at identifying the differentially expressed proteins between patients with RHD and controls with mitral valve prolapse. Methods. Nine patients with RHD and nine controls with mitral valve prolapsed were enrolled for this study. Two-dimensional difference in-gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were performed. Results. A total of 39 protein spots with differential expressions were identified between the two groups (, Average Ratio > 1.2 or Average Ratio < −1.2) and four upregulated proteins (including heat shock protein 60 (HSP 60), desmin, PDZ and LIM domain protein 1, and proteasome subunit alpha type-1) and three downregulated proteins (including tropomyosin alpha-1 chain, malate dehydrogenase, and chaperone activity of bc1 complex homolog) were determined. Conclusion. These seven proteins, especially HSP 60, may serve as potential biomarkers for the diagnosis of RHD and provide evidence to explain the mechanisms of this complex disease in the future. Dawei Zheng, Limin Xu, Lebo Sun, Qiang Feng, Zishan Wang, Guofeng Shao, and Yiming Ni Copyright © 2014 Dawei Zheng et al. All rights reserved. Genotype-Related Effect of Crowding Stress on Blood Pressure and Vascular Function in Young Female Rats Wed, 05 Mar 2014 13:14:10 +0000 This study investigated the influence of chronic crowding stress on nitric oxide (NO) production, vascular function and oxidative status in young Wistar-Kyoto (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone and accelerated BP ( versus basal) only in BHR. NO production and superoxide concentration were significantly higher in the aortas of control BHR and SHR versus WKY. Total acetylcholine (ACh)-induced relaxation in the femoral artery was reduced in control SHR versus WKY and BHR, and stress did not affect it significantly in any genotype. The attenuation of ACh-induced relaxation in SHR versus WKY was associated with reduction of its NO-independent component. Crowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function. Peter Slezak, Angelika Puzserova, Peter Balis, Natalia Sestakova, Miroslava Majzunova, Ima Dovinova, Michal Kluknavsky, and Iveta Bernatova Copyright © 2014 Peter Slezak et al. All rights reserved. Nitric Oxide, Oxidative Stress, and Interplay in Diabetic Endothelial Dysfunction Wed, 05 Mar 2014 07:06:30 +0000 Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production, protein. Alessandra Magenta, Simona Greco, Maurizio C. Capogrossi, Carlo Gaetano, and Fabio Martelli Copyright © 2014 Alessandra Magenta et al. All rights reserved. Brachial Artery Endothelial Responses during Early Recovery from an Exercise Bout in Patients with Coronary Artery Disease Mon, 03 Mar 2014 16:48:19 +0000 This study examined the acute endothelial responses to an exercise bout in coronary artery disease (CAD) patients. Nineteen males with CAD ( years) were assessed at rest and 15 minutes following a submaximal exercise bout (recovery). Brachial artery endothelial-dependent function was assessed using flow-mediated dilation (FMD). Brachial artery diameters and velocities were measured using Duplex ultrasound at baseline, and for 3 minutes following a 5-minute ischemic period. Endothelial-independent function was assessed using a 0.4 mg dose of nitroglycerin (NTG). FMD responses were unchanged from rest to recovery; however, there were 2 types of responses: negative and positive FMD responders. Post-hoc analysis revealed that positive responders had lower resting FMD compared to negative responders ( versus , ). NTG-mediated dilation was reduced in recovery ( versus , for rest versus recovery). In conclusion, acute endothelial-dependent responses to submaximal exercise are affected by the degree of resting endothelial dysfunction. The observation of attenuated NTG-mediated dilation during recovery is novel and warrants the investigation of possible mechanisms and clinical significance. Furthermore, it highlights the necessity of both endothelial-dependent and endothelial-independent assessments when evaluating endothelial function changes with an intervention. Katharine D. Currie, Robert S. McKelvie, and Maureen J. MacDonald Copyright © 2014 Katharine D. Currie et al. All rights reserved. The Prognostic Values of Leukocyte Rho Kinase Activity in Acute Ischemic Stroke Thu, 27 Feb 2014 07:05:20 +0000 Objective. It has been reported that leukocyte ROCK activity is elevated in patients after ischemic stroke, but it is unclear whether leukocyte ROCK activity is associated with clinical outcomes following acute stroke events. The objective of this study is to investigate if leukocyte ROCK activity can predict the outcomes in patients with acute ischemic stroke. Materials and Methods. We enrolled 110 patients of acute ischemic stroke and measured the leukocyte ROCK activity and plasma level of inflammatory cytokines to correlate the clinical outcomes of these patients. Results. The leukocyte ROCK activity at 48 hours after admission in acute ischemic stroke patients was higher as compared to a risk-matched population. The leukocyte ROCK activity significantly correlated with National Institute of Health Stroke Scale (NIHSS) difference between admission and 90 days after stroke event. Kaplan-Meier survival estimates showed lower stroke-free survival during follow-up period in patients with high leukocyte ROCK activity or plasma hsCRP level. Leukocyte ROCK activity independently predicted the recurrent stroke in patients with atherosclerotic stroke. Conclusions. This study shows elevated leukocyte ROCK activity in patients with ischemic stroke as compared to risk-matched subjects and is an independent predictor for recurrent stroke. Cheng-I. Cheng, Yu-Chun Lin, Tzu-Hsien Tsai, Hung-Sheng Lin, Chia-Wei Liou, Wen-Neng Chang, Cheng-Hsien Lu, Chun-Man Yuen, and Hon-Kan Yip Copyright © 2014 Cheng-I. Cheng et al. All rights reserved. Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention Wed, 26 Feb 2014 15:39:03 +0000 The endothelium, which forms the inner cellular lining of blood vessels and lymphatics, is a highly metabolically active organ that is involved in many physiopathological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion, and trafficking and inflammation. In this review, we summarized and described the following: (i) endothelial cell function in physiological conditions and (ii) endothelial cell activation and dysfunction in the main cardiovascular diseases (such as atherosclerosis, and hypertension) and to diabetes, cigarette smoking, and aging physiological process. Finally, we presented the currently available evidence that supports the beneficial effects of physical activity and various dietary compounds on endothelial functions. Gaia Favero, Corrado Paganelli, Barbara Buffoli, Luigi Fabrizio Rodella, and Rita Rezzani Copyright © 2014 Gaia Favero et al. All rights reserved. Nitric Oxide and Superoxide Anion Balance in Rats Exposed to Chronic and Long Term Intermittent Hypoxia Wed, 26 Feb 2014 06:45:01 +0000 Work at high altitude in shifts exposes humans to a new form of chronic intermittent hypoxia, with still unknown health consequences. We have established a rat model resembling this situation, which develops a milder form of right ventricular hypertrophy and pulmonary artery remodelling compared to continuous chronic exposure. We aimed to compare the alterations in pulmonary artery nitric oxide (NO) availability induced by these forms of hypoxia and the mechanisms implicated. Rats were exposed for 46 days to normoxia or hypobaric hypoxia, either continuous (CH) or intermittent (2 day shifts, CIH2x2), and assessed: NO and superoxide anion availability (fluorescent indicators and confocal microscopy); expression of phosphorylated endothelial NO synthase (eNOS), NADPH-oxidase (p22phox), and 3-nitrotyrosine (western blotting); and NADPH-oxidase location (immunohistochemistry). Compared to normoxia, (1) NO availability was reduced and superoxide anion was increased in both hypoxic groups, with a larger effect in CH, (2) eNOS expression was only reduced in CH, (3) NADPH-oxidase was similarly increased in both hypoxic groups, and (4) 3-nitrotyrosine was increased to a larger extent in CH. In conclusion, intermittent hypoxia reduces NO availability through superoxide anion destruction, without reducing its synthesis, while continuous hypoxia affects both, producing larger nitrosative damage which could be related to the more severe cardiovascular alterations. Patricia Siques, Ángel Luis López de Pablo, Julio Brito, Silvia M. Arribas, Karen Flores, Karem Arriaza, Nelson Naveas, M. Carmen González, Alexander Hoorntje, Fabiola León-Velarde, and M. Rosario López Copyright © 2014 Patricia Siques et al. All rights reserved. The Endothelial ADMA/NO Pathway in Hypoxia-Related Chronic Respiratory Diseases Tue, 25 Feb 2014 07:34:03 +0000 Since its discovery, many adhere to the view that asymmetric dimethylarginine (ADMA), as an inhibitor of the synthesis of nitric oxide (NO), contributes to the pathogenesis of various diseases. Particularly, this is evident in disease of the cardiovascular system, in which endothelial dysfunction results in an imbalance between vasoconstriction and vasodilatation. Even if increased ADMA concentrations are closely related to an endothelial dysfunction, several studies pointed to a potential beneficial effect of ADMA, mainly in the context of angioproliferative disease such as cancer and fibrosis. Antiproliferative properties of ADMA independent of NO have been identified in this context. In particular, the regulation of ADMA by its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) is the object of many studies. DDAH is discussed as a promising therapeutic target for the indirect regulation of NO. In hypoxia-related chronic respiratory diseases, this controversy discussion of ADMA and DDAH is particularly evident and is therefore subject of this review. Nicole Lüneburg, Lars Harbaum, and Jan K. Hennigs Copyright © 2014 Nicole Lüneburg et al. All rights reserved. Contribution of Ca2+-Dependent Cl− Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing Sun, 23 Feb 2014 13:38:02 +0000 The activation of Ca2+-dependent Cl− channels during norepinephrine-induced contraction of vascular smooth muscle was suggested to depolarize cell membrane and to increase Ca2+ entry. Hypertension and ageing are associated with altered Ca2+ handling including possible activation of Ca2+-dependent Cl− channels. Our study was aimed to determine Ca2+-dependent Cl− channels contribution to norepinephrine-induced contraction during hypertension and ageing. Norepinephrine-induced concentration-response curves of femoral arteries from 6- and 12-month-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were recorded using wire myograph. Pretreatment with Ca2+-dependent Cl- channel inhibitor indanyloxyacetic acid 94 [R(+)-IAA-94](IAA) attenuated norepinephrine-induced contraction in all groups, but relatively more in WKY than SHR arteries. The attenuation of norepinephrine-induced contraction after Ca2+-dependent Cl− channels blockade was partially reduced in 12-month-old WKY rats, but substantially diminished in 12-month-old SHR. IAA effect was enhanced after NO synthase inhibition but decreased by ageing. In 20-month-old WKY rats norepinephrine-induced contraction was not affected by IAA but was almost abolished after cyclooxygenase inhibition by indomethacin or niflumic acid. In conclusion, contribution of Ca2+-dependent Cl− channels to norepinephrine-induced contraction diminished with age, hypertension development, and/or NO synthesis inhibition. Ca2+-dependent Cl− channels are important for maintenance of normal vascular tone while their inactivation/closing might be a pathological mechanism. Silvia Liskova, Miriam Petrova, Petr Karen, Michal Behuliak, and Josef Zicha Copyright © 2014 Silvia Liskova et al. All rights reserved. Endothelial Function in a Mouse Model of Myeloperoxidase Deficiency Sun, 23 Feb 2014 00:00:00 +0000 Myeloperoxidase (MPO) activity is suggested to reduce the function of vascular nitric oxide, thereby contributing to endothelial dysfunction, although data in rodents are inconclusive. We examined vascular contractile and relaxant responses in MPO-deficient () and wild-type mice to investigate the role for myeloperoxidase in the development of endothelial dysfunction. Carotid and saphenous arteries were taken from 8-month-old mice and studied in a myograph. Responses of carotid arteries to phenylephrine, high potassium, or acetylcholine (Ach) were statistically not different from controls. Treatment with lipopolysaccharide (LPS; to enhance endothelial dysfunction) reduced responses to Ach in but did not affect responses in wild-type. In response to high concentrations of Ach, carotid arteries responded with transient contractions, which were not different between the groups and not affected by LPS treatment. Saphenous arteries from had smaller normalized diameters and developed less contractile force. Vessels from were less sensitive to Ach than controls. These data suggest that mature MPO-deficient mice do not show enhanced endothelial function compared to wild-type mice, even when provoked with LPS treatment. The EDHF response appears to be reduced in MPO deficiency. Veronika Golubinskaya, Ulla Brandt-Eliasson, Li-Ming Gan, Martin Kjerrulf, and Holger Nilsson Copyright © 2014 Veronika Golubinskaya et al. All rights reserved. GCK Gene-Body Hypomethylation Is Associated with the Risk of Coronary Heart Disease Mon, 17 Feb 2014 09:15:24 +0000 Objectives. Glucokinase encoded by GCK is a key enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Variants of GCK gene were shown to be associated with type 2 diabetes (T2D) and coronary heart disease (CHD). The goal of this study was to investigate the contribution of GCK gene-body methylation to the risk of CHD. Design and Methods. 36 patients (18 males and 18 females) and 36 age- and sex-matched controls were collected for the current methylation research. DNA methylation level of the CpG island (CGI) region on the GCK gene-body was measured through the sodium bisulfite DNA conversion and pyrosequencing technology. Results. Our results indicated that CHD cases have a much lower methylation level (49.77 ± 6.43%) compared with controls (54.47 ± 7.65%, ). In addition, GCK gene-body methylation was found to be positively associated with aging in controls (, ). Conclusions. Our study indicated that the hypomethylation of GCK gene-body was significantly associated with the risk of CHD. Aging correlates with an elevation of GCK methylation in healthy controls. Limin Xu, Dawei Zheng, Lingyan Wang, Danjie Jiang, Haibo Liu, Leiting Xu, Qi Liao, Lina Zhang, Panpan Liu, Xinbao Shi, Zhaoyang Wang, Lebo Sun, Qingyun Zhou, Ni Li, Yi Huang, Yanping Le, Meng Ye, Guofeng Shao, and Shiwei Duan Copyright © 2014 Limin Xu et al. All rights reserved. Shear Stress, Energy Losses, and Costs: A Resolved Dilemma of Pulsatile Cardiac Assist Devices Wed, 08 Jan 2014 09:09:52 +0000 Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopathology and law of physics. It concerns a double lumen disposable tube device that could be adapted to conventional cardiopulmonary bypass (CPB) and/or CAD, for inducing a homogenous, downstream pulsatile perfusion mode with lower energy losses. In this study, the device’s prototypes were tested in a simulated conventional pediatric CPB circuit for energy losses and as a left ventricular assist device (LVAD) in ischemic piglets model for endothelial shear stress (ESS) evaluations. In conclusion and according to the study results the pulsatile tube was successfully capable of transforming a conventional CPB and/or CAD steady flow into a pulsatile perfusion mode, with nearly physiologic pulse pressure and lower energy losses. This represents a cost-effective promising method with low mortality and morbidity, especially in fragile cardiac patients. Sayed Nour, Jia Liu, Gang Dai, Daniel Carbognani, Daya Yang, Guifu Wu, Qinmei Wang, and Juan Carlos Chachques Copyright © 2014 Sayed Nour et al. All rights reserved. The Role of Bioactive Lipids in Stem Cell Mobilization and Homing: Novel Therapeutics for Myocardial Ischemia Mon, 06 Jan 2014 12:29:49 +0000 Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI) and ischemic heart disease (IHD) remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD. Yuri M. Klyachkin, Anush V. Karapetyan, Mariusz Z. Ratajczak, and Ahmed Abdel-Latif Copyright © 2014 Yuri M. Klyachkin et al. All rights reserved. Peripheral Arterial Stiffness Is Independently Associated with a Rapid Decline in Estimated Glomerular Filtration Rate in Patients with Type 2 Diabetes Sun, 29 Dec 2013 13:15:08 +0000 Introduction. Diabetes and its vascular complications are main noncommunicable chronic diseases and major global health issues. Peripheral arterial disease (PAD) is highly prevalent in diabetes with nephropathy. We evaluated the associations of variables of arterial stiffness and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. Materials and Methods. A total of 577 type 2 diabetic patients (mea: age, years) were enrolled. A rapid decline in eGFR was defined as progressively lower eGFR detected at both the 6- and 12-month follow-up visits, plus a reduction in eGFR more than 3 mLmin−1per 1.73 m2 per year. Results. Higher glycated hemoglobin (HbA1c), systolic blood pressure (SBP), pulse pressure (PP), and brachial-ankle pulse wave velocity (ba-PWV) at baseline were independently associated with a rapid decline in eGFR. The adjusted odds ratios (95% confidence intervals) for a rapid decline in eGFR for ba-PWV, SBP, and PP were 1.072 (1.011–1.136), 1.014 (1.004–1.025), and 1.025 (1.008–1.041), respectively, after adjustment for gender, age, body mass index, smoking, HbA1c, and baseline eGFR in separated models. Conclusions. Ba-PWV may serve as a simple and noninvasive predictor of rapid renal function progression in type 2 diabetic patients. Yi-Jing Sheen, Jiann-Liang Lin, Tsai-Chung Li, Cho-Tsan Bau, and Wayne Huey-Herng Sheu Copyright © 2013 Yi-Jing Sheen et al. All rights reserved. Interval and Continuous Exercise Training Produce Similar Increases in Skeletal Muscle and Left Ventricle Microvascular Density in Rats Tue, 26 Nov 2013 15:37:49 +0000 Interval training (IT), consisting of alternated periods of high and low intensity exercise, has been proposed as a strategy to induce more marked biological adaptations than continuous exercise training (CT). The purpose of this study was to assess the effects of IT and CT with equivalent total energy expenditure on capillary skeletal and cardiac muscles in rats. Wistar rats ran on a treadmill for 30 min per day with no slope (0%), 4 times/week for 13 weeks. CT has constant load of 70% max; IT has cycles of 90% max for 1 min followed by 1 min at 50% max. CT and IT increased endurance and muscle oxidative capacity and attenuated body weight gain to a similar extent (). In addition, CT and IT similarly increased functional capillary density of skeletal muscle (CT: %; IT: %) and the capillary-to-fiber ratio in skeletal muscle (CT: %; IT: %) and in the left ventricle (CT: %; IT: %). In conclusion, at equivalent total work volumes, interval exercise training induced similar functional and structural alterations in the microcirculation of skeletal muscle and myocardium in healthy rats compared to continuous exercise training. Flávio Pereira, Roger de Moraes, Eduardo Tibiriçá, and Antonio C. L. Nóbrega Copyright © 2013 Flávio Pereira et al. All rights reserved. Is the Blood Pressure Paradox Observed in All Heart Failure Patients? Mon, 25 Nov 2013 11:11:48 +0000 Background. Heart failure (HF) patients with higher systolic blood pressure (SBP) survive longer. Diabetes mellitus (DM) is a frequent comorbidity in HF. We evaluated the prognostic significance of low SBP according to DM in acute HF. Methods. We prospectively recruited 589 patients admitted with acute HF. DM was defined according to the 2011 American Diabetes Association recommendations. Patients were followed for 6 months and HF-death was the endpoint. A multivariate Cox-regression model was used to assess the prognostic impact of SBP. A stratified analysis according to DM was performed. Results. Median patients’ age was 79 years and DM was present in 50.8%. Ischemic aetiology HF and hypertension history were more common in diabetics. Diabetic patients had worse renal function and lower total cholesterol and were more often discharged with antiplatelet therapy and statin. During followup, 89 patients died due to HF. The multivariate-adjusted HR for the 6-month HF death in non-diabetic patients with an admission SBP < 115 mmHg (1st quartile) was 2.94 (95% CI: 1.49–5.79), while lower admission SBP was not associated with HF mortality in diabetics. Conclusions. The blood pressure paradox in HF is only observed in non-diabetic HF patients. Diabetic patients seem to be a particular subgroup of HF patients. F. M. Cunha, P. Lourenço, M. Couto, P. Tavares, S. Silva, J. T. Guimarães, and P. Bettencourt Copyright © 2013 F. M. Cunha et al. All rights reserved. Effects of DL-Homocysteine Thiolactone on Cardiac Contractility, Coronary Flow, and Oxidative Stress Markers in the Isolated Rat Heart: The Role of Different Gasotransmitters Sun, 24 Nov 2013 10:11:02 +0000 Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μM DL-Hcy TLHC alone or in combination with 30 μM L-NAME, 10 μM DL-PAG, or 10 μM PPR IX. The following parameters were measured: dp/dt max, dp/dt min, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2, , and H2O2 concentrations. The administration of DL-Hcy TLHC alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF, , H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increased dp/dt max but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease in dp/dt max, SLVP, HR, CF, and TBARS. Vladimir Zivkovic, Vladimir Jakovljevic, Olga Pechanova, Ivan Srejovic, Jovana Joksimovic, Dragica Selakovic, Nevena Barudzic, and Dragan M. Djuric Copyright © 2013 Vladimir Zivkovic et al. All rights reserved. Association of CILP2 and ACE Gene Polymorphisms with Cardiovascular Risk Factors in Slovak Midlife Women Wed, 20 Nov 2013 14:45:38 +0000 The aim of this study is to assess the association of two polymorphisms, the cartilage intermediate layer protein 2 (CILP2) G/T and angiotensin converting enzyme (ACE) I/D, with blood pressure and anthropometrical and biochemical parameters related to the development of cardiovascular disease. The entire study sample comprised 341 women ranging in age from 39 to 65 years. The CILP2 genotypes were determined by PCR-RFLP and the ACE genotypes by PCR. The Bonferroni pairwise comparisons showed the effect of the CILP2 genotype on high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), apoB-to-apoA1 ratio, the total cholesterol (TC)-to-HDL-C ratio, non-HDL-C, and the LDL-C-to-HDL-C ratio (). Here, higher mean levels of HDL-C and lower mean levels of the remaining above mentioned lipid parameters were registered in the GT/TT genotype carriers than in GG carriers. Statistically significant association was identified between the ACE genotype and the following parameters: TC, LDL-C, and non-HDL-C (). The II genotype can lower serum level of TC (), LDL-C (), and non-HDL-C levels. The results of this study suggest that the minor T allele of CILP2 gene and I allele of ACE gene have a protective effect against elevated serum lipid and lipoprotein levels. Lenka Luptáková, Dominika Benčová, Daniela Siváková, and Marta Cvíčelová Copyright © 2013 Lenka Luptáková et al. All rights reserved. Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells Sun, 10 Nov 2013 09:56:30 +0000 IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology. Piera D’Elia, Vittoria Ionta, Isotta Chimenti, Francesco Angelini, Fabio Miraldi, Alessandro Pala, Elisa Messina, and Alessandro Giacomello Copyright © 2013 Piera D’Elia et al. All rights reserved. Gsk-3β Inhibitors Mimic the Cardioprotection Mediated by Ischemic Pre- and Postconditioning in Hypertensive Rats Wed, 30 Oct 2013 14:07:15 +0000 The aim of this study was to examine the effects of GSK-3β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR). Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1-hour reperfusion (R); PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl) or indirubin-3′-monoxime,5-iodo-(IMI) as GSK-3β inhibitors. All interventions reduced the infarct size observed in IC group. The expressions of P-GSK-3β and P-Akt decreased in IC and were restored after PRE, POS, and GSK-3β inhibitors treatments. An increase of cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An increase of P-GSK-3β/VDAC physical association and a partial recovery of mitochondrial permeability were also detected after interventions. These data show that, in SHR hearts, GSK-3β inhibitors mimic the cardioprotection afforded by PRE and POS and suggest that a decrease in mitochondrial permeability mediated by P-GSK-3β/VDAC interaction is a crucial event. Luisa F. González Arbeláez, Ignacio A. Pérez Núñez, and Susana M. Mosca Copyright © 2013 Luisa F. González Arbeláez et al. All rights reserved. Rapid Induction of Aldosterone Synthesis in Cultured Neonatal Rat Cardiomyocytes under High Glucose Conditions Mon, 28 Oct 2013 18:12:43 +0000 In addition to classical adrenal cortical biosynthetic pathway, there is increasing evidence that aldosterone is produced in extra-adrenal tissues. Although we previously reported aldosterone production in the heart, the concept of cardiac aldosterone synthesis remains controversial. This is partly due to lack of established experimental models representing aldosterone synthase (CYP11B2) expression in robustly reproducible fashion. We herein investigated suitable conditions in neonatal rat cardiomyocytes (NRCMs) culture system producing CYP11B2 with considerable efficacy. NRCMs were cultured with various glucose doses for 2–24 hours. CYP11B2 mRNA expression and aldosterone concentrations secreted from NRCMs were determined using real-time PCR and enzyme immunoassay, respectively. We found that suitable conditions for CYP11B2 induction included four-hour incubation with high glucose conditions. Under these particular conditions, CYP11B2 expression, in accordance with aldosterone secretion, was significantly increased compared to those observed in the cells cultured under standard-glucose condition. Angiotensin II receptor blocker partially inhibited this CYP11B2 induction, suggesting that there is local renin-angiotensin-aldosterone system activation under high glucose conditions. The suitable conditions for CYP11B2 induction in NRCMs culture system are now clarified: high-glucose conditions with relatively brief period of culture promote CYP11B2 expression in cardiomyocytes. The current system will help to accelerate further progress in research on cardiac tissue aldosterone synthesis. Masami Fujisaki, Tomohisa Nagoshi, Tetsuo Nishikawa, Taro Date, and Michihiro Yoshimura Copyright © 2013 Masami Fujisaki et al. All rights reserved. Pulmonary Hypertension in Portugal: First Data from a Nationwide Registry Mon, 21 Oct 2013 08:11:07 +0000 Introduction. Pulmonary arterial hypertension (PAH) is a rare disease that must be managed in specialized centers; therefore, the availability of epidemiological national data is critical. Methods. We conducted a prospective, observational, and multicenter registry with a joint collaboration from five centers from Portugal and included adult incident patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH). Results. Of the 79 patients enrolled in this study, 46 (58.2%) were classified as PAH and 33 patients (41.8%) as CTEPH. PAH patients had a mean age of 43.4 ± 16.4 years. Idiopathic PAH was the most common etiology (37%). At presentation, PAH patients had elevated right atrial pressure (RAP) (7.7 ± 5.9 mmHg) and mean pulmonary vascular resistance (11.4 ± 6.5 Wood units), with a low cardiac index (2.7 ± 1.1 L·min−1·m−2); no patient was under selective pulmonary vasodilators; however, at follow-up, most patients were on single (50%), double (28%), or triple (9%) combination vasodilator therapy. One-year survival was 93.5%, similar to CTEPH patients (93.9%), that were older (60.0 ± 12.5 years) and had higher RAP (11.0 ± 5.2 mmHg, ). Conclusions. We describe for the first time nationwide data on the diagnosis, management, and prognosis of PAH and CTEPH patients in Portugal. Clinical presentation and outcomes are comparable with those reported on other national registries. Rui Baptista, José Meireles, Ana Agapito, Graça Castro, António Marinho da Silva, Teresa Shiang, Fabienne Gonçalves, Susana Robalo-Martins, António Nunes-Diogo, and Abílio Reis Copyright © 2013 Rui Baptista et al. All rights reserved. Cardiometabolic Diseases and Related Complications: Current Status and Future Perspective Wed, 09 Oct 2013 11:21:46 +0000 Joseph Fomusi Ndisang and Sharad Rastogi Copyright © 2013 Joseph Fomusi Ndisang and Sharad Rastogi. All rights reserved. Association of the KLF14 rs4731702 SNP and Serum Lipid Levels in the Guangxi Mulao and Han Populations Mon, 30 Sep 2013 08:14:31 +0000 The objective of the present study was to detect the association of the rs4731702 single nucleotide polymorphism (SNP) and serum lipid levels in the Guangxi Mulao and Han populations. A total of 727 subjects of Mulao and 740 subjects of Han Chinese were included. Serum low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels were higher in Mulao than in Han (). The T allele carriers had higher serum LDL-C and ApoAI levels in Mulao, whereas they had lower high-density lipoprotein cholesterol (HDL-C) levels and ratio of ApoAI to ApoB in Han () than the T allele noncarriers. Subgroup analyses showed that the T allele carriers had higher HDL-C, LDL-C, and ApoAI levels in Mulao males and lower ApoAI levels and ratio of ApoAI to ApoB in Han males than the T allele noncarriers. The subjects with TT genotype in Han females also had higher total cholesterol, LDL-C, ApoAI, and ApoB levels than the subjects with CT or CC genotype. Serum lipid parameters were also correlated with several environmental factors in both ethnic groups. The differences in the association of KLF14 rs4731702 SNP and serum lipid levels between the two ethnic groups might partly result from different gene-environmental interactions. Ping Huang, Rui-Xing Yin, Ke-Ke Huang, Xiao-Na Zeng, Tao Guo, Quan-Zhen Lin, Jian Wu, Dong-Feng Wu, Hui Li, and Shang-Ling Pan Copyright © 2013 Ping Huang et al. All rights reserved. First Evidence of Increased Plasma Serotonin Levels in Tako-Tsubo Cardiomyopathy Mon, 23 Sep 2013 08:57:12 +0000 Background. There is no data about the serotonergic activity during the acute phase of Tako-Tsubo Cardiomyopathy (TTC). The objective of our study was to investigate evidence of serotonin release from patients with TTC in comparison with patients with ST elevation myocardial infarction (STEMI) and healthy control subjects (HCS). Methods and Results. Plasma serotonin levels in 14 consecutive patients with TTC were compared with those in 14 patients with STEMI and 14 HCS. Plasma serotonin levels at admission were markedly higher in patients with TTC and STEMI as compared to HCS (, versus control; , versus control; and  ng/mL, resp.). There was no difference in serotonin levels between patients with TTC and those with STEMI (). Conclusion. This finding suggests that serotonin could participate to the pathophysiology of TTC. C. Rouzaud Laborde, C. Delmas, J. Mialet-Perez, N. Pizzinat, C. Biendel-Picquet, N. Boudou, N. Dumonteil, O. Spreux-Varoquaux, D. Carrié, M. Galinier, A. Parini, and O. Lairez Copyright © 2013 C. Rouzaud Laborde et al. All rights reserved. Feasibility, Reproducibility, and Agreement between Different Speckle Tracking Echocardiographic Techniques for the Assessment of Longitudinal Deformation Sun, 22 Sep 2013 11:28:22 +0000 Background. Left ventricular (LV) longitudinal deformation can be assessed with new echocardiographic techniques like triplane echocardiography (3PE) and four-dimensional echocardiography (4DE). We aimed to assess the feasibility, reproducibility, and agreement between these different speckle-tracking techniques for the assessment of longitudinal deformation. Methods. 101 consecutive subjects underwent echocardiographic examination. 2D cine loops from the apical views, a triplane view, and an LV 4D full volume were acquired in all subjects. LV longitudinal strain was obtained for each imaging modality. Results. 2DE analysis of LV strain was feasible in 90/101 subjects, 3PE strain in 89/101, and 4DE strain in 90/101. The mean value of 2DE and 3PE longitudinal strains was significantly higher with respect to 4DE. The relationship between 2DE and 3PE derived strains () was significantly higher (, ) than that between 2DE and 4DE () and that between 3PE and 4DE (; , ). The mean bias between 2DE and 4DE strains was while between 3PE and 4DE strains; the bias between 2DE and 3PE strain was of . Intraobserver and interobserver variabilities were acceptable among the techniques. Conclusions. Echocardiographic techniques for the assessment of longitudinal deformation are not interchangeable, and further studies are needed to assess specific reference values. Sergio Buccheri, Ines Monte, Sarah Mangiafico, Vera Bottari, Stefano Leggio, and Corrado Tamburino Copyright © 2013 Sergio Buccheri et al. All rights reserved. Does Off-Pump Coronary Artery Bypass Grafting Negatively Impact Long-Term Survival and Freedom from Reintervention? Wed, 11 Sep 2013 10:31:14 +0000 Recently published evidence has raised concerns about worse late mortality and increasing need for reintervention after off-pump coronary artery bypass grafting. We undertook this study to assess the impact of off-pump coronary artery bypass grafting on survival and freedom from reintervention at 10 years. From January 2002 to December 2002, 307 consecutive patients who had isolated multivessel off-pump coronary artery bypass grafting at our institution were compared to a control group of 397 patients that underwent multivessel on-pump coronary artery bypass grafting during the same period. In addition, univariate and risk-adjusted comparisons between the two groups were performed at 10 years. Kaplan-Meier survival was similar for the two cohorts. After adjusting for clinical covariates, off-pump coronary artery bypass grafting did not emerge as a significant independent predictor of long-term mortality (Hazard Ratio 0.91; 95% Confidence Interval 0.70–1.12), readmission to hospital for cardiac cause (Hazard Ratio 0.96; 95% Confidence Interval 0.78–1.10), or the need for reintervention (Hazard Ratio 0.93; 95% Confidence Interval 0.87–1.05). Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting does not adversely impact survival or freedom from reintervention at a 10-year follow-up. Shahzad G. Raja, Mubassher Husain, Florentina L. Popescu, Dimple Chudasama, Siobhan Daley, and Mohamed Amrani Copyright © 2013 Shahzad G. Raja et al. All rights reserved. Periodontal Disease Is an Independent Predictor of Intracardiac Calcification Wed, 11 Sep 2013 10:11:07 +0000 Background. Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. Hypothesis. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Methods. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Results. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, ) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (). There was no significant interaction by study site, race, or gender. Conclusions. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification. Gregg S. Pressman, Atif Qasim, Nitin Verma, Masami Miyamae, Kumiko Arishiro, Yasuhiro Notohara, Vitalie Crudu, and Vincent M. Figueredo Copyright © 2013 Gregg S. Pressman et al. All rights reserved. Determinants of Thyrotoxic Cardiomyopathy Recovery Sun, 08 Sep 2013 15:13:45 +0000 The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment. Lucia Oliveros-Ruiz, Maite Vallejo, L. Fernando Diez Canseco, Manuel Cárdenas, and J. Antonio G. Hermosillo Copyright © 2013 Lucia Oliveros-Ruiz et al. All rights reserved. Materials and Manufacturing Technologies Available for Production of a Pediatric Bioabsorbable Stent Sun, 08 Sep 2013 14:49:37 +0000 Transcatheter treatment of children with congenital heart disease such as coarctation of the aorta and pulmonary artery stenosis currently involves the use of metal stents. While these provide good short term results, there are long term complications with their use. Children outgrow metal stents, obligating them to future transcatheter dilations and eventual surgical removal. A bioabsorbable stent, or a stent that goes away with time, would solve this problem. Bioabsorbable stents are being developed for use in coronary arteries, however these are too small for use in pediatric congenital heart disease. A bioabsorbable stent for use in pediatric congenital heart disease needs to be low profile, expandable to a diameter 8 mm, provide sufficient radial strength, and absorb quickly enough to allow vessel growth. Development of absorbable coronary stents has led to a great understanding of the available production techniques and materials such as bioabsorbable polymers and biocorrodable metals. Children with congenital heart disease will hopefully soon benefit from the current generation of bioabsorbable and biocorrodable materials and devices. Ryan D. Alexy and Daniel S. Levi Copyright © 2013 Ryan D. Alexy and Daniel S. Levi. All rights reserved. Influence of Positive End-Expiratory Pressure on Myocardial Strain Assessed by Speckle Tracking Echocardiography in Mechanically Ventilated Patients Wed, 28 Aug 2013 16:06:23 +0000 Purpose. The effects of mechanical ventilation (MV) on speckle tracking echocardiography- (STE-)derived variables are not elucidated. The aim of the study was to evaluate the effects of positive end-expiratory pressure (PEEP) ventilation on 4-chamber longitudinal strain (LS) analysis by STE. Methods. We studied 20 patients admitted to a mixed intensive care unit who required intubation for MV and PEEP titration due to hypoxia. STE was performed at three times: (T1) PEEP = 5 cmH2O; (T2) PEEP = 10 cmH2O; and (T3) PEEP = 15 cmH2O. STE analysis was performed offline using a dedicated software (XStrain MyLab 70 Xvision, Esaote). Results. Left peak atrial-longitudinal strain (LS) was significantly reduced from T1 to T2 and from T2 to T3 (). Right peak atrial-LS and right ventricular-LS showed a significant reduction only at T3 (). Left ventricular-LS did not change significantly during titration of PEEP. Cardiac chambers’ volumes showed a significant reduction at higher levels of PEEP (). Conclusions. We demonstrated for the first time that incremental PEEP affects myocardial strain values obtained with STE in intubated critically ill patients. Whenever performing STE in mechanically ventilated patients, care must be taken when PEEP is higher than 10 cmH2O to avoid misinterpreting data and making erroneous decisions. Federico Franchi, Agnese Faltoni, Matteo Cameli, Luigi Muzzi, Matteo Lisi, Lucia Cubattoli, Sofia Cecchini, Sergio Mondillo, Bonizella Biagioli, Fabio Silvio Taccone, and Sabino Scolletta Copyright © 2013 Federico Franchi et al. All rights reserved. A New Coated Nitinol Occluder for Transcatheter Closure of Ventricular Septal Defects in a Canine Model Tue, 27 Aug 2013 13:52:25 +0000 Aims. This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. Methods and Results. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs () as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, , Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. Conclusion. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization. Yong Zhou, Feng Chen, Xinmiao Huang, Xianxian Zhao, Hong Wu, Yuan Bai, and Yongwen Qin Copyright © 2013 Yong Zhou et al. All rights reserved. End-Systolic Elastance and Ventricular-Arterial Coupling Reserve Predict Cardiac Events in Patients with Negative Stress Echocardiography Mon, 19 Aug 2013 09:09:28 +0000 Background. A maximal negative stress echo identifies a low-risk subset for coronary events. However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of this study was to assess the prognostic value of stress-induced variation in cardiovascular hemodynamics in patients with negative stress echocardiography. Methods. We enrolled 891 patients (593 males mean age , ejection fraction ), with negative (exercise 172, dipyridamole 482, and dobutamine 237) stress echocardiography result. During stress we assessed left ventricular end-systolic elastance index (), ventricular arterial coupling (VAC) indexed by the ratio of the to arterial elastance index (), systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from rest to peak stress (reserve) were tested as predictors of main outcome measures: combined death and heart failure hospitalization. Results. During a median followup of 19 months (interquartile range 8–36), 50 deaths and 84 hospitalization occurred. Receiver-operating-characteristic curves identified as best predictors reserve for exercise (AUC = 0.871) and dobutamine (AUC = 0.848) and VAC reserve (AUC = 0.696) for dipyridamole. Conclusions. Patients with negative stress echocardiography may experience an adverse outcome, which can be identified by assessment of reserve and VAC reserve during stress echo. Tonino Bombardini, Marco Fabio Costantino, Rosa Sicari, Quirino Ciampi, Lorenza Pratali, and Eugenio Picano Copyright © 2013 Tonino Bombardini et al. All rights reserved. Sleep-Disordered Breathing in Patients with Heart Failure: New Trends in Therapy Sun, 28 Jul 2013 15:46:45 +0000 Heart failure (HF) is a growing health problem which paradoxically results from the advances in the treatment of etiologically related diseases (especially coronary artery disease). HF is commonly accompanied by sleep-disordered breathing (SDB), which may directly exacerbate the clinical manifestations of cardiovascular disease and confers a poorer prognosis. Obstructive sleep apnoea predominates in mild forms while central sleep apnoea in more severe forms of heart failure. Identification of SDB in patients with HF is important, as its effective treatment may result in notable clinical benefits to the patients. Continuous positive airway pressure (CPAP) is the gold standard in the management of SDB. The treatments for central breathing disorders include CPAP, bilevel positive airway pressure (BPAP), and adaptive servoventilation (ASV), with the latter being the most modern method of treatment for the Cheyne-Stokes respiration and involving ventilation support with a variable synchronisation dependent on changes in airflow through the respiratory tract and on the patient’s respiratory rate. ASV exerts the most favourable effect on long-term prognosis. In this paper, we review the current state of knowledge on the diagnosis and treatment of SDB with a particular emphasis on the latest methods of treatment. Anna Kazimierczak, Paweł Krzesiński, Krystian Krzyżanowski, and Grzegorz Gielerak Copyright © 2013 Anna Kazimierczak et al. All rights reserved. Pharmacodynamic Effect of Clopidogrel in Patients Undergoing Transcatheter Aortic Valve Implantation Mon, 15 Jul 2013 11:23:59 +0000 The aim of this study was to analyze periprocedural and mid-term effect of clopidogrel on platelet function using the VerifyNow P2Y12 point-of-care assay in patients undergoing TAVI. Platelet reactivity was measured at the beginning of the procedure after 300 mg clopidogrel bolus administration and during the follow-up (at 1 month after the procedure) in 52 patients undergoing TAVI using the Medtronic CoreValve prosthesis (Medtronic CoreValve). A cutoff value of 240 PRU was used to identify nonresponders to clopidogrel treatment with high residual platelet reactivity (HRPR). Baseline HRPR was identified in 80% of patients and in 72% of patients during 6-month follow-up. There was no significant difference in the pharmacodynamic effects of clopidogrel on platelet reactivity from baseline to 6-months follow-up ( vs. ; ). Ischemic event occurred only in 3 patients (5.8%) from the study group. In conclusion, majority of patients undergoing TAVI had high residual platelet reactivity after pretreatment with 300 mg of clopidogrel and during the 6-month follow-up at dual antiplatelet treatment. The noneffectiveness of clopidogrel in the TAVI population raises the question of the routine use of dual antiplatelet treatment in this setting. Petr Tousek, Viktor Kocka, Jakub Sulzenko, Frantisek Bednar, Hana Linkova, and Petr Widimsky Copyright © 2013 Petr Tousek et al. All rights reserved. Transcriptomic Profiling of the Four Adenosine Receptors in Human Leukocytes of Heart Failure Patients Mon, 08 Jul 2013 13:40:06 +0000 In this study the transcriptomic profiling of adenosine receptors (ARs) in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (), was evaluated. Total RNA was extracted from leukocytes of () and of HF patients (NYHA I-II ; NYHA III-IV ) with a PAXgene Blood RNA Kit. An increase as a function of clinical severity was observed in each AR (A1R: , NYHA , NYHA ,    versus NYHA III-IV, NYHA I-II versus NYHA III-IV; A2aR: , NYHA , NYHA ,    versus NYHA III-IV, NYHA I-II versus NYHA III-IV; A2bR: , NYHA , NYHA , : NYHA I-II versus NYHA III-IV; A3R: , NYHA , NYHA ,    versus NYHA III-IV and NYHA I-II versus NYHA III-IV, resp.). The mRNA expression of the ectonucleoside triphosphate diphosphohydrolase (CD39) and the ecto-5′-nucleotidase (CD73) were also evaluated. They resulted up-regulated. These findings show that components of adenosine metabolism and signalling are altered to promote adenosine production and signalling in HF patients. Thus, HF may benefit from adenosine-based drug therapy after confirmation by clinical trials. Manuela Cabiati, Raffaele Caruso, Alessandro Verde, Laura Sabatino, Maria-Aurora Morales, and Silvia Del Ry Copyright © 2013 Manuela Cabiati et al. All rights reserved. Mechanostimulation Protocols for Cardiac Tissue Engineering Mon, 08 Jul 2013 09:51:57 +0000 Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field. Marco Govoni, Claudio Muscari, Carlo Guarnieri, and Emanuele Giordano Copyright © 2013 Marco Govoni et al. All rights reserved. Detection of Gender Differences in Incomplete Revascularization after Coronary Artery Bypass Surgery Varies with Classification Technique Mon, 08 Jul 2013 08:47:55 +0000 Background. Incomplete revascularization negatively affects survival after coronary artery bypass surgery (CABG). Since gender and classification technique might impact outcome and reporting, we investigated their effect on revascularization patterns and mortality. Methods. A cohort of bypass patients (, 23% women) was enrolled prospectively. The degree of revascularization was determined as mathematical difference between affected vessels upon diagnosis and number of grafts or the surgeon’s rating on the case file. Results. Although men displayed more triple-vessel disease, they obtained complete revascularization more frequently than women (85% versus 77%, ). The two calculation methods identified analogous percentages of incompletely revascularized patients, yet there was only a 50% overlap between the two groups. Mathematically, more women, older patients, and patients with NYHA class III/IV appeared incompletely revascularized, while the surgeons identified more patients undergoing technically challenging procedures. Regardless of the definition, incompleteness was a significant risk factor for mortality in both genders (mathematical calculation: HR 2.62, 95% CI 1.76–3.89, ; surgeon: HR 2.04, 95% CI 1.35–3.89, ). Conclusions. Given the differences in identification patterns, we advise that the mathematical calculation be performed after-procedure in all patients regardless of the surgeons’ rating to uncover additional subjects at increased risk. Sabine Oertelt-Prigione, Friederike Kendel, Martin Kaltenbach, Roland Hetzer, Vera Regitz-Zagrosek, and Rufus Baretti Copyright © 2013 Sabine Oertelt-Prigione et al. All rights reserved. Quantitative PCR as an Alternative in the Diagnosis of Long-QT Syndrome Tue, 02 Jul 2013 11:17:11 +0000 Congenital long-QT syndrome is a genetic disorder associated with abnormalities in the function and/or structure of cardiac ion channels. Up to the present, 13 types of the disease have been described (LQTS1-13) which result from the fact that 13 genes of which mutations can have an influence on the occurrence of the disease have been identified. Characteristic symptoms of the disease include the changes in the ECG (QT interval prolonged above 450 ms), “torsade de pointes,” fainting, and even sudden cardiac death. The present study has been focused on two types of the disease, namely, LQTS1 and LQTS2. The examination of two appropriate genes expression (KCNQ1; KCNH2) at the transcription level by QRT-PCR in a group of LQTS patients and a healthy control group showed different transcriptional activities of KCNH2 gene in LQTS2 patients compared to the control individuals. KCNQ1 gene expression study did not reveal such differences between both groups. The results indicate that QRT-PCR may serve as a complimentary method to the identification of molecular alterations in genetic determinants of LQTS2 only, but it cannot be used as a sole diagnostic criterion. Ewa Moric-Janiszewska, Ludmiła Węglarz, and Magdalena Szczurko Copyright © 2013 Ewa Moric-Janiszewska et al. All rights reserved. Echocardiography in the Era of Multimodality Cardiovascular Imaging Wed, 26 Jun 2013 11:34:05 +0000 Echocardiography remains the most frequently performed cardiac imaging investigation and is an invaluable tool for detailed and accurate evaluation of cardiac structure and function. Echocardiography, nuclear cardiology, cardiac magnetic resonance imaging, and cardiovascular-computed tomography comprise the subspeciality of cardiovascular imaging, and these techniques are often used together for a multimodality, comprehensive assessment of a number of cardiac diseases. This paper provides the general cardiologist and physician with an overview of state-of-the-art modern echocardiography, summarising established indications as well as highlighting advances in stress echocardiography, three-dimensional echocardiography, deformation imaging, and contrast echocardiography. Strengths and limitations of echocardiography are discussed as well as the growing role of real-time three-dimensional echocardiography in the guidance of structural heart interventions in the cardiac catheter laboratory. Benoy Nalin Shah Copyright © 2013 Benoy Nalin Shah. All rights reserved. Therapeutic Application of Cardiac Stem Cells and Other Cell Types Wed, 26 Jun 2013 11:29:45 +0000 Various researches on regenerative medicine were carried out experimentally, and selected modalities have been introduced to the clinical arena. Meanwhile, the presence of resident stem cells in the heart and their role in physiological cell turnover were demonstrated. So far skeletal myoblasts, bone marrow-derived cells, mesenchymal stromal cells, and resident cardiac cells have been applied for therapeutic myocardial regeneration. Among them, autologous transplantation of c-kit-positive cardiac stem cells in congestive heart failure patients resulted in an outstanding outcome, with long-lasting beneficial effects without major adverse events. By reviewing these clinical trials, an endeavor was made to seek for an ideal cellular therapy for cardiovascular diseases. Emiko Hayashi and Toru Hosoda Copyright © 2013 Emiko Hayashi and Toru Hosoda. All rights reserved. Effects of Community-Based Cardiac Rehabilitation on Body Composition and Physical Function in Individuals with Stable Coronary Artery Disease: 1.6-Year Followup Tue, 25 Jun 2013 17:05:21 +0000 Objective. To examine long-term changes in physical function and body composition in coronary artery disease (CAD) patients participating in ongoing community-based cardiac rehabilitation (CR). Design. Thirty-four individuals ( years; 79% men) participated in this longitudinal observational study. Baseline and follow-up assessments included incremental shuttle walk, short physical performance battery, handgrip strength, chair stands, body composition, last year physical activity, and CR attendance. Results. Participants attended sessions during year followup. A significant increase in 30-second chair stands ( to , ), body weight ( to  kg, ), and body fat ( to %, ) and a decline in handgrip strength ( to kg·f, ) and muscle mass ( to %, ) were observed during followup. There was no significant change in shuttle walk duration. CR attendance was not correlated to observed changes. Conclusions. Elderly CAD patients participating in a maintenance CR program improve lower-body muscle strength but experience a decline in handgrip strength and unfavourable changes in body composition, irrespective of CR attendance. Sandra Mandic, Claire Hodge, Emily Stevens, Robert Walker, Edwin R. Nye, Dianne Body, Leanne Barclay, and Michael J. A. Williams Copyright © 2013 Sandra Mandic et al. All rights reserved. Cardiovascular Profile of Xanthelasma Palpebrarum Thu, 20 Jun 2013 18:03:12 +0000 Xanthelasma palpebrarum (XP) are yellow plaques that occur most commonly near the inner canthus of the eyelid and are often associated with atherosclerosis, dyslipidemia, and coronary artery disease. This study was planned to address the issue of associated cardiovascular morbidity in xanthelasma patients attending our cardiac clinic. Materials and Methods. A total of 61 patients were detected to be having xanthelasma and constituted the study group. The control group constituted of 130 apparently normal individuals. Each patient underwent detailed history, examination, and investigations. Results and Discussion. The most prevalent age group was 40 to 60 years. Males outnumbered females. A percentage of 39.3% of cases had concomitant nicotine addiction. Dyslipidemia was present in 60% of cases, hypertension in 37.7%, prehypertension in 8.77%, diabetes mellitus in 18.03%, and prediabetes in 26.3%. Smokers and obese patients with xanthelasma had a higher prevalence of hypertension. Coronary artery disease (CAD) was found in 6.56% of XP cases. The waist circumference and diastolic blood pressures were significantly higher in XP patients. Conclusion. A significant number of cases of xanthelasma palpebrarum are combined with smoking, central obesity, hypertension, diabetes mellitus, and dyslipidemia which are the major risk factors for CAD. Efforts should be made to rule out the same in high-risk xanthelasma subjects. Anupam Dey, Ramesh Aggarwal, and Shridhar Dwivedi Copyright © 2013 Anupam Dey et al. All rights reserved. Carotid Artery Segmentation in Ultrasound Images and Measurement of Intima-Media Thickness Thu, 20 Jun 2013 08:54:18 +0000 Background. The segmentation of the common carotid artery (CCA) wall is imperative for the determination of the intima-media thickness (IMT) on B-mode ultrasound (US) images. The IMT is considered an important indicator in the evaluation of the risk for the development of atherosclerosis. In this paper, authors have discussed the relevance of measurements in clinical practices and the challenges that one has to face while approaching the segmentation of carotid artery on ultrasound images. The paper presents an overall review of commonly used methods for the CCA segmentation and IMT measurement along with the different performance metrics that have been proposed and used for performance validation. Summary and future directions are given in the conclusion. Vaishali Naik, R. S. Gamad, and P. P. Bansod Copyright © 2013 Vaishali Naik et al. All rights reserved. Ventricular Dyssynchrony and Function Improve following Catheter Ablation of Nonseptal Accessory Pathways in Children Tue, 18 Jun 2013 16:15:45 +0000 Introduction. Paradoxical or hypokinetic interventricular septal motion has been described in patients with septal or paraseptal accessory pathways. Data regarding nonseptal pathways is limited. Methods and Results. We quantified left ventricular dyssynchrony and function in 16 consecutive children, years, weighing  kg, prior to and following catheter ablation of bidirectional septal () and nonseptal () accessory pathways. Following ablation, the left ventricular ejection fraction increased by % () from a baseline value of . By tissue Doppler imaging, the interval between QRS onset and peak systolic velocity (Ts) decreased from a median of 33.0 ms to 18.0 ms (). The left ventricular ejection fraction increased to a greater extent following catheter ablation of nonseptal (, ) versus septal (, ) pathways. The four patients with an ejection fraction <50%, two of whom had left lateral pathways, improved to >50% after ablation. Similarly, the improvement in dyssynchrony was more marked in patients with nonseptal versus septal pathways (difference between septal and lateral wall motion delay before and after ablation  ms () versus  ms ()). Conclusion. Left ventricular systolic function and dyssynchrony improve after ablation of antegrade-conducting accessory pathways in children, with more pronounced changes noted for nonseptal pathways. Sylvia Abadir, Anne Fournier, Marc Dubuc, Georgia Sarquella-Brugada, Patrick Garceau, and Paul Khairy Copyright © 2013 Sylvia Abadir et al. All rights reserved.