Antithrombotic Treatment May Reduce Mortality Among New-Onset Atrial Fibrillation Patients with Gray-Zone Risk of Stroke.

In clinical practice, some atrial fibrillation (AF) patients were classified as having low and moderate stroke risk by the CHADS2 score (≤ 1) in 2001 but in 2012 they were not truly classified as low risk of stroke according to the CHA2DS2-VASc score (≥ 2) (defined gray zone). Therefore, a treatment gap exists in gray zone AF patients. This study aimed to evaluate whether gray zone AF patients could benefit from reduced all-cause mortality under antithrombotic treatment. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance from January 2000 to December 2011. The new-onset AF patients consisted of a gray zone cohort with a total of 1237 patients being enrolled. The primary outcome was all-cause mortality between 2001 and 2011. Patients in the gray zone receiving antithrombotic treatment had a significant reduction in all-cause mortality [hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.16-0.28] compared with the no treatment group [warfarin only: HR, 0.28 (95% CI, 0.15-0.52); warfarin + Aspirin: HR, 0.21 (95% CI, 0.15-0.30); and Aspirin only: HR, 0.22 (95% CI, 0.16-0.29) ]. All-cause mortality was notably increased when any of the following risk factors were present: age 65-74 years, age ≥ 75 years, chronic kidney disease, and vascular disease. We concluded that AF patients in the gray zone must receive either anticoagulant and/or antiplatelet treatment and there is a lower mortality in these groups during long-term follow-up. Further investigation is needed to observe whether the antithrombotic drugs have benefits for patients with AF with a CHA2DS2-VASc score < 2.

Impact of cardiac reverse remodeling after cardiac resynchronization therapy assessed by myocardial perfusion imaging on ventricular arrhythmia.

BACKGROUND: Although cardiac resynchronization therapy (CRT) has been a useful treatment of heart failure, patients with CRT are still in risk of sudden cardiac death due to ventricular arrhythmia. The aim of this study was to investigate the impact of cardiac reverse remodeling after CRT on the prevalence of ventricular tachycardia or fibrillation (VT/VF). METHODS AND RESULTS: Forty-one heart failure patients (26 men, age 66 ± 10 years), who were implanted with CRT for at least 12 months, were enrolled. All patients received myocardial perfusion imaging (MPI) under CRT pacing to evaluate left ventricle (LV) function, dyssynchrony, and scar. VT/VF episodes during the follow-up period after MPI were recorded by the CRT devices. Sixteen patients (N = 16/41, 39%) were found to have VT/VF. Multivariate Cox regression analysis and receiver operating characteristic curve analysis showed that five risk factors were significant predictors of VT/VF, including increased left ventricle ejection fraction (LVEF) by ≤7% after CRT, low LVEF after CRT (≤30%), change of intrinsic QRS duration (iQRSd) by ≤7 ms, wide iQRSd after CRT (≥121 ms), and high systolic dyssynchrony after CRT (phase standard deviation ≥45.6°). For those patients with all of the 5 risk factors, 85.7% or more developed VT/VF. CONCLUSIONS: The characteristics of cardiac reverse remodeling after CRT as assessed by MPI are associated with the prevalence of ventricular arrhythmia.

Prediction of Both Electrical and Mechanical Reverse Remodeling on Acute Electrocardiogram Changes After Cardiac Resynchronization Therapy.

BACKGROUND: The development of both electrical reverse remodeling and mechanical reverse remodeling (ERR+MRR) after cardiac resynchronization therapy (CRT) implantation could reduce the incidence of lethal arrhythmia, hence the prediction of ERR+MRR is clinically important.Methods and Results:Eighty-three patients (54 male; 67±12 years old) with CRT >6 months were enrolled. ERR was defined as baseline intrinsic QRS duration (iQRSd) shortening ≥10 ms in lead II on ECG after CRT, and MRR as improvement in LVEF ≥25% on echocardiography after CRT. Acute ECG changes were measured by comparing the pre-implant and immediate post-implant ECG. Ventricular arrhythmia episodes, including ventricular tachycardia and ventricular fibrillation, detected by the implanted device were recorded. Patients were classified as ERR only (n=12), MRR only (n=23), ERR+MRR (n=26), or non-responder (ERR- & MRR-, n=22). On multivariate regression analysis, difference between baseline intrinsic QRS and paced QRS duration (∆QRSd) >35 ms was a significant predictor of ERR+MRR (sensitivity, 68%; specificity, 64%; AUC, 0.7; P=0.003), and paced QTc >443 ms was a negative predictor of ERR+MRR (sensitivity, 78%; specificity, 60%; AUC, 0.7; P=0.002). On Cox proportional hazard modeling, ERR+MRR may reduce risk of ventricular arrhythma around 70% compared with non-responder (HR, 0.29; 95% CI: 0.13-0.65). CONCLUSIONS: Acute ECG changes after CRT were useful predictors of ERR+MRR. ERR+MRR was also a protective factor for ventricular arrhythmia.

Mesenchymal Stem Cell Derived Exosomes: A New Hope for the Treatment of Cardiovascular Disease?

UNLABELLED: Cardiovascular disease is a major target for numerous experimental stem (progenitor) cell-based therapies. Mesenchymal stem cells (MSCs) from different sources confer regenerative effects in animal models of cardiovascular disease. Some of these investigations have proceeded into phase I and II clinical trials for limb ischemia, heart failure, and acute myocardial infarction. The rationale for MSC therapy is increasingly recognized on a secretion (paracrine) rather than differentiation mechanism. Recently, several groups have demonstrated that the "exosome" is a secreted agent mediating MSC therapeutic efficacy. Unlike cell therapy, exosomes have no risk of aneuploidy, and a lower rate of immune rejection following allogeneic administration. In this short review, we will focus on the potential of using this novel therapeutic modality for the treatment of cardiovascular disease, particularly acute myocardial infarction. KEY WORDS: Cardiovascular disease; Exosome; Mesenchymal.

Academic Performance Antecedent Scale: validation with native and recent immigrant children.

This study aims to assess the measurement invariance of the three subscales of the newly developed Academic Performance Antecedent Scale (APAS)--School Factors, Mother's Parenting Style, and Individual Factors--across native and new immigrant children in Taiwan. The study sample comprised 527 Grade 4 students (M age = 10.4 yr., SD = 0.6), 263 boys and 264 girls. The three groups were urban and rural children of Taiwanese natives (n = 343, 65.1%), and 184 children with non-Taiwanese mothers (34.9%). The four-factor structure of the School Factors Subscale, the three-factor structure of the Mother's Parenting Style Subscale, and the five-factor structure of the Individual Factors Subscale all showed at least acceptable fit for the groups. In addition, metric invariance was confirmed for the School Factors and Individual Factors Subscales. Metric invariance was partially obtained for the Mother's Parenting Style Subscale. The findings provide validity evidences for cross-cultural generalizability of the APAS.

An Overview of Current Cardiac Resynchronization Therapy.

UNLABELLED: Cardiac resynchronization therapy (CRT) is currently an established device therapy for heart failure (HF) patients. Existing knowledge of implantation techniques, advances in device-based technologies and clinical trial experience have all significantly impacted this evolving therapy in recent years. This review article will address the updated CRT guidelines, and potentially new indications for CRT such as patients with mild HF symptoms and prolonged QRS duration; it also highlights new approaches for placement of the left ventricular (LV) lead, multi-site LV pacing, and the role of automatic device optimization in CRT. KEY WORDS: Cardiac resynchronization therapy; Guideline; Heart failure; Optimization.

Comparison of quick optimization of interventricular delay between simple methods: intracardiac electrogram and surface electrocardiogram after cardiac resynchronization therapy.

AIMS: It is time consuming to obtain optimal interventricular (VV) delay by conventional methods. This study is designed to compare quick optimization between intracardiac electrogram (IEGM) with surface electrocardiogram (ECG)-guided VV delay optimization for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Fifty-one heart failure patients (M/F = 34/17, age = 71 ± 10-year-old) scheduled for CRT implantation were included. After atrioventricular optimization, VV delay optimization was performed by either the IEGM or surface ECG method. Aortic velocity time integral (AVTI) was used  as a reference in comparing these two methods. Real-time three-dimensional echocardiography was studied under three varying parameters-CRT switched off or CRT switched on, and VV delay optimized by IEGM guided or surface ECG. The AVTI could be improved equally by either IEGM-guided or surface ECG-guided VV optimization. All the other parameters [QRS width, systolic dyssynchrony index (SDI), left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV)] could be improved by either the IEGM or ECG method in these patients. In the multivariate logistic regression analysis, the immediate improvement of acute LVEF was independently related to favourable outcomes (odds ratio 1.23, 95% CI = 1.03-1.47, P = 0.02). CONCLUSIONS: The AVTI, QRS width, SDI, LVEF, LVEDV, and LVESV could be improved equally by either IEGM-guided or surface ECG-guided method after CRT.

Novel tips for engaging the coronary sinus guided by right ventricular lead.

AIMS: This study investigated the relationship between the ostia of the coronary sinus (CS) and the tricuspid annulus (TA) for CS cannulation using a right ventricular (RV) lead, which could map out the TA by forming a curve when placed at the apex or low septum. METHODS AND RESULTS: Seventy patients (45 males, 67 ± 12 years) who were admitted for CRT device implant were included in the evaluation of the relationship between the CS ostia and TA. An electrophysiological (EP) mapping catheter was used to probe the CS. The ostium was shown by the CS venography at the left anterior oblique (LAO) 20° and caudal 20°. Local electrograms were collected with CS catheters in the CS or RV. Transthoracic echocardiography was evaluated before each procedure. All CS ostia were located within 3.75 cm around the tip of TA. Sixty-two subjects (Group I, 89%) had CS ostia located under the TA. Eight patients (Group II) with CS ostia over the TA revealed larger left ventricular (LV) size and a smaller ratio of left atrium (LA)/LV size. LV enlargement predicted the presence of CS ostia over the TA. Typical CS electrograms were used to further confirm if the EP catheter was in the CS in all the subjects. CONCLUSION: Use of the RV lead revealed that the CS ostia had a close relationship with the TA.

Relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging and cardiac reverse remodeling levels after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) can provide cardiac reverse remodeling (RR), which may include mechanical reverse remodeling (MRR) and/or electrical reverse remodeling (ERR). However, uncoupling of MRR and ERR is not uncommon, and the underlying mechanisms are not clear. This study aimed to evaluate the relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging (MPI) and cardiac RR post-CRT. MATERIALS AND METHODS: Forty-one patients (26 men, mean age 66 ± 10 years) with heart failure received CRT for at least 12 months were assigned to three groups according to their levels of RR: I, MRR + ERR (ESV reduced ≥15 % and intrinsic QRS duration reduced ≥10 ms); II, MRR only (ESV reduced ≥15 %); and III, non-responder (the others). All the patients also underwent MPI under transient CRT-off to evaluate the intrinsic myocardial substrates, including myocardial scar, LV volumes and function, systolic dyssynchrony, and activation sequences. In addition, ventricular tachycardia (VT) and ventricular fibrillation (VF) detected by the CRT devices during follow-up periods were also recorded. RESULTS: Quantitative analysis of MPI showed that there were significant differences for scar burden [15.9 ± 9.5, 26.8 ± 16.1, and 45.6 ± 15.1 % for group I (n = 15), II (n = 16), and III (n = 10), respectively, p < 0.001], EDV (136.6 ± 64.9, 221.6 ± 123.9, and 351.8 ± 216.3 ml, p = 0.002), ESV (82.6 ± 59.8, 172.3 ± 117.2, and 293.3 ± 209.6 ml, p = 0.001), LVEF (44.9 ± 15.0, 25.6 ± 10.9, and 21.5 ± 11.7 %, p < 0.001), systolic phase SD (23.4° ± 10.3°, 36.0° ± 16.2°, and 57.0° ± 22.2°, p < 0.001), and bandwidth (72.5° ± 31.1°, 113.4° ± 56.4°, and 199.1° ± 90.1°, p < 0.001). Myocardial scar interfered with the normal propagation of mechanical activation, resulting in heterogeneous activation sequences. Compared with group II (MRR only), group I (ERR + MRR) had significantly less initial activation segments (1.9 ± 1.0 vs. 2.6 ± 0.7, p < 0.05) and shorter maximal contraction delay (46.9° ± 12.9° vs. 58.8° ± 18.5°, p < 0.05). During the periods of follow-up, 21 patients developed VT/VF, including only 1 patient (1 VT) in group I (6.7 %), 8 patients (7 VT and 1 VF) in group II (50 %), and 9 patients (7 VT and 5 VF) in group III (90 %). CONCLUSION: The characteristics of myocardial substrates as assessed by MPI differed significantly between different levels of cardiac RR post-CRT. Myocardial scar played an important role in the development of ERR. Different cardiac RR levels contributed to different incidences of ventricular arrhythmia, and the combination of ERR and MRR provided highest anti-arrhythmic effects.

Combined use of brachial-ankle pulse wave velocity and ankle-brachial index for fast assessment of arteriosclerosis and atherosclerosis in a community.

BACKGROUND: Pulse volume recordings and blood pressures at arms and ankles can be obtained automatically and simultaneously to allow fast measurements of the brachial-ankle pulse wave velocity and the ankle-brachial index. We applied this novel technique to assess the extent of arteriosclerosis and atherosclerosis in a community. METHODS: A total of 1329 residents in Kinmen completed a health survey including interview, physical examination, blood test, and the measurements of brachial-ankle pulse wave velocity and ankle-brachial index in 10 working days. RESULTS: Brachial-ankle pulse wave velocity was significantly related to age, systolic blood pressure, body mass index, waist circumference, ankle-brachial index, and fasting blood levels of glucose, triglyceride, high-density lipoprotein cholesterol, uric acid, and creatinine, and was significantly related to the 10-year risk of developing coronary heart disease estimated from the Framingham risk function. The prevalence of arteriosclerosis as defined by brachial-ankle pulse wave velocity values higher than the age and sex stratified references from the low risk subjects was 27.1% for men and 25.4% for women. The prevalence of atherosclerosis defined by ankle-brachial index <0.9 was 2.8% in men and 1.7% in women. In men but not in women, subjects with low ankle-brachial index had significantly greater risk for developing coronary artery disease than those with normal values. CONCLUSIONS: Brachial-ankle pulse wave velocity and ankle-brachial index can be obtained simultaneously and quickly for the assessment of arteriosclerosis and atherosclerosis in a community.

Long-term efficacy and stability of atrial sensing in VDD pacing.

BACKGROUND: The efficacy and stability of atrial electrode sensing function is essential in maintaining atrioventricular (AV) synchrony and activity response in VDD pacing. Studies to evaluate the relationship between atrial sensing efficacy, stability, and implantation strategy are few. HYPOTHESIS: This study sought to determine the possible predictors, among the recipients' underlying clinical conditions and the implantation strategies used, of achieving the most stable and effective atrial sensing. METHODS: Eighty consecutive adults implanted with VDD pacemakers were studied retrospectively. Atrial electrodes were positioned where the optimal atrial potentials (APs) were measured during implantation. Interrogation parameters, including AV-synchrony ratio, were acquired immediately post implantation, at 1 year, and at 2 years after pacemaker implantation. Appropriate atrial sensing efficacy was defined as AV-synchrony ratio > or = 90%. The stability of atrial sensing was evaluated by the variation ranges of measured APs. RESULTS: The measured APs showed no statistical difference when age, gender, or comorbidity was considered. However, with pacing-lead bending angles < or = 90 degrees, patients may have presented with larger APs and narrower AP variation than patients with obtuse angles. There were no clinical parameters in our study that could have predicted the proper atrial sensing efficacy with an AV-synchrony ratio > or = 90%. CONCLUSIONS: The long-term sensing efficacy and stability of VDD pacing is reliable. More sophisticated implantation strategies may further improve the atrial sensing stability and efficacy in VDD pacing.

Relationship of quantitative parameters of myocardial perfusion SPECT and ventricular arrhythmia in patients receiving cardiac resynchronization therapy.

BACKGROUND: Ventricular arrhythmia is the major cause of sudden cardiac death for patients with heart failure, including those receiving implantation of cardiac resynchronization therapy (CRT). The purpose of this study was to assess the value of myocardial perfusion SPECT (MPS) in predicting ventricular arrhythmia for patients with CRT. METHODS AND METHODS: Fifty-one patients (35 males, mean age 64 ± 12 years) who had received CRT for at least 6 months were enrolled for resting gated MPS. Three main quantitative parameters of MPS, including extent of myocardial scar, left ventricular ejection fraction (LVEF) and LV dyssynchrony (phase SD), were generated by Emory Cardiac Toolbox. Using the recorded ventricular arrhythmia in the device, including ventricular tachycardia (VT) and ventricular fibrillation (VF), as the primary end point, the value of quantitative parameters of MPS in predicting the development of VT/VF was assessed. RESULTS: Twenty (39 %) of the 51 patients developed VT/VF during the follow-up (15.3 ± 12.7 months). The patients with VT/VF had significantly lower LVEF (24 ± 12 vs. 36 ± 17 %, p < 0.005), larger scar areas (36 ± 19 vs. 22 ± 12 %, p < 0.05) and larger phase SD (57° ± 20° vs. 43° ± 17°, p < 0.01). When categorizing the patients by the median values of LVEF, scar and phase SD, univariate regression analysis showed that lower LVEF (<29 %), larger scar (>23 %) and larger phase SD (>50°) were related to the development of VT/VF (p = 0.006, 0.011 and 0.064, respectively). However, only LVEF was marginally significant as an independent predictor of VT//VF on multivariate regression analysis (p = 0.0573). Survival analysis with Kaplan-Meier curves showed that the survival probability for VT/VF in those with LVEF >29 %, scar areas <23 % and phase SD < 50° was significantly better than in the others (HR 5.16, 95 % CI 1.20-22.16) by log-rank test (χ (2) = 5.9894, p = 0.014). CONCLUSION: Lower LVEF, larger scar and/or more dyssynchrony assessed by MPS were related to the development of ventricular arrhythmia for patients with CRT, and further defibrillator implantation may be considered for these patients.

Usefulness of attenuated heart rate recovery immediately after exercise to predict endothelial dysfunction in patients with suspected coronary artery disease.

Attenuated heart rate recovery after graded exercise, which is associated with decreased vagal activity, is a powerful predictor of overall mortality. Endothelial function plays a key role in determining the clinical manifestations of established atherosclerotic lesions and has shown to be suppressed by increased sympathetic tone. We designed this study to determine whether patients with an attenuated heart rate recovery after exercise could predict endothelium dysfunction. Sixty-six patients with suspected coronary artery disease were enrolled, and a noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation and endothelium-independent nitroglycerin-mediated vasodilation. The patients were divided equally into 3 groups according to heart rate recovery in 1 minute after peak exercise (n = 22 in each group): group 1 had heart rate recovery of /=29 beats. The endothelium-dependent flow-mediated vasodilation responses were significantly decreased in group 1 compared with groups 2 and 3 (2.5 +/- 3.0 vs 5.0 +/- 3.4 vs 5.4 +/- 2.7%, p = 0.006), but responses to sublingual nitroglycerin showed no difference among the 3 groups (p = 0.332). According to multivariate analysis, heart rate recovery after exercise was an independent predictor of endothelial function.

Preventing phrenic nerve stimulation by a patch insulation in an intact swine heart model.

INTRODUCTION: Phrenic nerve stimulation (PNS) could be prevented by a silastic patch over the epicardial lead. We studied the effects in preventing PNS by placing a silastic patch directly over an epicardial lead or placing a graft around the phrenic nerve (PN). METHODS AND RESULTS: Fourteen Lanyu swine were enrolled. A bipolar lead was placed epicardially on the left ventricle (LV) inferior to the PN. An implantable cardioverter-defibrillator (ICD) lead was placed into the right ventricle (RV). The maximal influential distance (MID) was measured under 3 pacing configurations to express the influential electrical field on the PN. The threshold of the LV and PN were evaluated epicardially. Then, PTFE patches of different sizes (10×10 mm, 20×20 mm and 30×30 mm) were placed between the LV lead and PN to study the rise in PN threshold in 7 swine. On the other hand, the PN were surrounded by a PTFE graft of different lengths (10 mm, 20 mm, and 30 mm) in the remaining 7 swine. LV-bipolar pacing showed the shortest MID when compared to the other 2 unipolar pacing configurations at pacing voltage of 10 V. The patch was most effective in preventing PNS during LV-bipolar pacing. PNS was prevented under all circumstances with a larger PTFE patch (30×30 mm) or long graft (30 mm). CONCLUSIONS: PNS was avoided by placing a PTFE patch over the LV lead or a graft around the PN despite pacing configurations. Hence if PNS persisted during CRT implantation, a PTFE patch on the LV lead or a graft around the PN could be considered.

Flow-injection enzymatic analysis for glycerol and triacylglycerol.

A flow-injection enzymatic analytical system was developed for determination of glycerol and triacylglycerol based on enzymatic reactions in capillary followed by electrochemical detection. The hydrogen peroxide produced from the enzyme reaction was monitored by a platinum-based electrochemical probe. Different immobilization strategies on silica support were studied. The best and most effective configuration found for the measurement of glycerol and triacylglycerols in this system was the tandem connection of a lipase column and a silica-fused capillary column coimmobilized with glycerokinase (GK) and glycerol-3-phosphate oxidase (GPO). Lipase helps the breakdown of triacylglycerol to yield free fatty acids and glycerol, while glycerokinase catalyzes the adenosine-5-triphosphate-dependent phosphorylation of glycerol to yield alpha-glycerol phosphate, which can subsequently be oxidized by 3-glycerol phosphate oxidase to produce hydrogen peroxide. Response-surface methodology (RSM) was applied to optimize the proposed system for glycerol. Experiment settings were designed by central composite design to investigate the combined effects of pH, flow rate, reaction temperature, and ATP concentration on collected signals. The fitted model, per RSM, showed that the optimum conditions of the system are 2 mM ATP in 0.1 M carbonate buffer (pH 11.0), flow rate of 0.18 mL/min, temperature of 35 degrees C, 20 microL of sample injection, and applied voltage of 0.650 V. The proposed biosensing system using lipase, GK, and GPO exhibited a flow-injection analysis peak response of 2.5 min and a detection limit of 5 x 10(-5) M glycerol (S/N = 3) with acceptable reproducibility (CV < 4.30%). It also had linear working ranges from 10(-4) to 10(-2) M for glycerol and from 10(-3) to 10(-2) M for triacylglycerol. The capillary enzyme reactor was stable up to 2 months in continuous operation, and it was possible to analyze up to 15 samples per hour. The present biosensing system holds promise for on-line detection of triacylglycerol in serum and glycerol content in fermented products.