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Objective The study objective was to determine whether mini-invasive transthoracoscopic atrial fibrillation ablation can delay the progression of atrial fibrillation from paroxysmal to persistent. Methods Patients aged 18 to 80 years with paroxysmal nonvalvular atrial fibrillation and a history of stroke or systemic thromboembolism were consecutively enrolled from September 2014 to June 2019. In the treatment group, patients underwent transthoracoscopic atrial fibrillation ablation plus left atrial appendage excision (atrial fibrillation ablation plus left atrial appendage excision group). Patients unwilling to receive surgical intervention were treated with antiarrhythmic drugs and oral anticoagulants and recruited as a control group (atrial fibrillation plus antiarrhythmic drugs group). The primary end point was the progression of atrial fibrillation from paroxysmal to persistent. Results This study included 49 patients in the atrial fibrillation plus antiarrhythmic drugs group (29 men) and 77 patients in the atrial fibrillation ablation plus left atrial appendage excision group (48 men). In the atrial fibrillation ablation plus left atrial appendage excision group, after a median follow-up of 951 days (interquartile range, 529-1366 days), 8 patients (10.4%) progressed to persistent atrial fibrillation. In the atrial fibrillation plus antiarrhythmic drugs group, after a median follow-up of 835 days (interquartile range, 548-1214 days), 14 patients (28.6%) progressed to persistent atrial fibrillation. The atrial fibrillation ablation plus left atrial appendage excision group had a significantly lower incidence of atrial fibrillation progression than the atrial fibrillation plus antiarrhythmic drugs group during follow-up (3.9 vs 12.3 per 100 person-years, log-rank 8.6, P = .003). Conclusions Patients with paroxysmal nonvalvular atrial fibrillation who chose to undergo transthoracoscopic atrial fibrillation ablation had a lower incidence of progression to persistent atrial fibrillation than patients who chose conservative therapy. This strategy might be especially suitable for patients with paroxysmal nonvalvular atrial fibrillation at high risk of stroke and high risk of bleeding.

Background A combination of endocardial and epicardial approaches has improved the overall success rate of ventricular tachycardia (VT) ablation in patients with cardiomyopathy. However, the origins of some VTs are truly intramural or close to coronary arteries, which makes this combined strategy either prone to failure or too risky. Objectives This observational study aimed to explore the feasibility and efficacy of direct epicardial ablation combined with intramural ethanol injection via surgical approach for inaccessible intramural VTs or VTs too close to coronary arteries. Methods In four canines ventricular lesions produced by direct epicardial injection of ethanol were assessed. Six consecutive patients with recurrent VT refractory to catheter endocardial and epicardial RF ablation and that remained inducible after surgical epicardial mapping and RF ablation were included. Ethanol was injected by needle at the epicardial RF ablation sites. The primary outcome was freedom of sustained VT determined by device interrogation and periodical 24h-holter recordings subsequently. Results In animal study, the lesions were homogenous and increased in size with the volume of ethanol injected. In all 6 patients ethanol injection at the target sites in the anterior or lateral left ventricle abolished inducible VT. Over a median follow-up of 22 months (range, 6~65), all patients remained free of sustained VT. One patient died of pulmonary infection one year after the procedure. Conclusions A hybrid strategy of surgical ablation combined with intramural ethanol injection is feasible and effective in patients with multiple failed percutaneous ablation attempts. This article is protected by copyright. All rights reserved.

Atrial fibrillation (AF) patients with a previous stroke are often at a high risk of recurrent stroke and bleeding. Anticoagulation therapy in such patients is a challenging dilemma. Thoracoscopic left atrial appendage excision (LAAE) plus AF ablation is an interventional approach offered to some AF patients. We hypothesized that this approach may be suitable as a secondary stroke prevention strategy for these high-risk patients. Between January 2013 and December 2016, a total of 44 patients (26 male; mean age 65.0 ± 9.1 years) with nonvalvular AF and a previous stroke or systemic thromboembolic event were enrolled. The patients underwent thoracoscopic LAAE plus AF ablation by experienced operators and were followed up for 2 years (at 1, 3, 6, 9, and 12 months postoperatively and every 6 months thereafter). Thromboembolic and major bleeding events were recorded. Cerebral computed tomography or magnetic resonance imaging and 7-day Holter monitoring were performed annually. Mean CHA2DS2-VASc and HAS-BLED scores were 4.2 ± 1.2 and 3.3 ± 0.7, respectively. All patients discontinued oral anticoagulation therapy after the surgical intervention. One patient suffered a periprocedural transient ischemic attack, and another was diagnosed with a new ischemic stroke at 491 days after surgery. The annual rate of total thromboembolism was 2.05%. No deaths or major bleeding events were observed postoperatively. The rate of successful AF ablation with no AF recurrence was 76.3%. Transthoracoscopic LAAE plus AF ablation may be a promising approach for this high-risk population. Thromboembolism event in this secondary prevention cohort was low, even without oral anticoagulation treatment.

Background: New-onset atrial fibrillation (AF) after ablation of typical atrial flutter (AFL) is not rare. This study aimed to investigate the predictive value of electrocardiographic parameters on new-onset AF post-typical AFL ablation.Methods: A total of 158 consecutive patients (79.1% males, mean age 57.8 ± 14.3 years) with typical AFL were enrolled between January 2012 and August 2017 in this single-center study. Patients with a history of AF before ablation were excluded. ECGs during sinus rhythm (SR) and AFL were collected. The duration of the negative component of flutter wave in lead II (DFNII), proportion of the DFNII of the total circle length of AFL (DFNII%), amplitude of the negative component of flutter wave in lead II (AFNII), duration (DPNV1), and amplitude (APNV1) of negative component of the P wave in lead V1, and P wave duration in lead II (DPII) during sinus rhythm were measured.Results: During a median follow-up of 26.9 ± 11.8 months, 22 cases (13.9%) developed new-onset AF. DFNII was significantly longer in patients with new-onset AF compared to patients without AF (114.7 ± 29.6 ms vs. 82.7 ± 12.8 ms, p < 0.0001). AFNII was significantly lower (0.118 ± 0.034 mV vs. 0.168 ± 0.051 mV, p < 0.0001), DPII (144.21 ± 23.77 ms vs. 111.46 ± 14.19 ms, p < 0.0001), and DPNV1 was significantly longer (81.07 ± 16.87 ms vs. 59.86 ± 14.42 ms, p < 0.0001) in patients with new-onset AF. In the multivariate analysis, DFNII [odds ratio (OR), 1.428; 95% CI, 1.039–1.962; p = 0.028] and DPII (OR, 1.429; 95% CI, 1.046–1.953; p = 0.025) were found to be independently associated with new-onset AF after typical AFL ablation.Conclusion: Parameters representing left atrial activation time under both the SR and AFL were independently associated with new-onset AF post-typical AFL ablation and may be useful in risk prediction, which needs to be confirmed by further prospective studies.

Aims Idiopathic epicardial ventricular arrhythmias (VAs) are clustered in the areas of the summit and crux. This study was to report a group of idiopathic epicardial VAs remote from the summit and crux areas. Methods In total, 9 patients (6 males, mean age 32±13 years) were enrolled. The locations were identified by epicardial mapping and ablation. The electrocardiographic and electrophysiological characteristics were compared to those of 9 patients who had VAs ablated at the opposite endocardial site. Results VAs were identified at the epicardium, with 4 patients had VAs located at the inferior wall, one at the anterior wall, one at the apex and 3 patients had VAs at the lateral wall. A “QS” type at the location-related leads was the only identified surface electrocardiogram indication suggesting epicardial origin (compared to that of the controls, 100% vs 0%, p

To determine the effectiveness of mobile health-based self-management interventions on medical/behavioral, role, and emotional management in breast cancer patients. The Embase, MEDLINE, SINOMED, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and Weipu (VIP) databases were extensively searched from inception to November 30, 2020, to identify eligible clinical trials. Outcomes included medical/behavioral management (self-management behavior, functional exercise compliance, self-efficacy, complications, and symptoms), role management (role functioning), and emotional management (anxiety and depression), social support, and health-related quality of life. Twenty-four studies were included in this meta-analysis. The results of the meta-analysis indicated that mobile health-based self-management interventions could potentially improve breast cancer patients’ self-management behavior, functional exercise compliance (WMD = 15.80, 95% CI = 10.53 to 21.08, P

Re-ablation has an important role in the control of recurrent atrial fibrillation (AF) post the first ablation. The present study was to report the outcome of AF re-ablation for patients who recurred after initial ablation, and to characterize the clinical and electrophysiological features predicting recurrence after redo ablation. From January 2012 to May 2017, patients undergoing re-ablation for AF in our hospital were consecutively enrolled. Clinical and electrophysiological data for the initial and second procedure were collected retrospectively and prospectively, respectively. All patients were followed up for one year and recurrences during the time were reported. Totally 259 patients entered into the analysis (age, 58.4 ± 10.5 years; 169 men). At the end of one-year follow-up, 85 patients recurred with atrial arrhythmias (32.8%). In the multivariate analysis, higher CHA2DS2-VASC score (p = 0.023, 95% CI 1.03–1.53) and shorter time to recurrence after the initial ablation (p = 0.001, 95% CI 0.93–0.98) were clinical factors predictive of one-year recurrence after the repeat ablation. The reconnection of the right pulmonary vein (PV) (p = 0.034, 95% CI 0.31–0.96) and the absence of not eliminated non-PV trigger at the second procedure (p = 0.032, 95% CI 1.25–142.80) independently predicted the better re-ablation outcome. About one-third of patients recurred after one year following re-ablation. CHA2DS2-VASC score and time to recurrence after the initial ablation were independent clinical factors predicting recurrence. Also, electrophysiological findings during the repeat ablation (the right PV reconnection and absence of not eliminated non-PV trigger) were associated with better outcome during one year of follow-up.

Background and Purpose: Complete P wave disappearance (CPWD) in patients without atrial fibrillation is an uncommon clinical phenomenon. We aimed to study the relationship between CPWD and thromboembolism. Methods: Between July 2007 and December 2018, consecutive patients with CPWD on surface ECG and 24-hour Holter recording were recruited into the study from 4 centers in China. All recruited patients underwent transesophageal echocardiography or cardiac computed tomography to screen for atrial thrombus. Atrial electrical activity and scar were assessed by electrophysiological study (EPS) and 3-dimensional electroanatomic mapping. Cardiac structure and function were assessed by multimodality cardiac imaging. Results: Twenty-three consecutive patients (8 male; mean age 48.5±14.7 years) with CPWD were included. Only 3 patients demonstrated complete atrial electrical silence with atrial noncapture. Thirteen patients who had invasive atrial endocardial mapping demonstrated extensive scar. Pulse-wave mitral inflow Doppler demonstrated absent and dampened A waves in 18 and 5 patients, respectively. Pulse-wave tricuspid inflow Doppler showed absent and dampened A waves in 19 and 4 patients, respectively. Upon recruitment, 8 patients had previous stroke and 3 patients had atrial thrombus. Warfarin was prescribed to all patients. During median follow-up of 42.0 months, 2 patients developed massive ischemic stroke due to warfarin discontinuation. Conclusions: Our study suggested that CPWD reflects extensive atrial electrical silence and significantly impaired atrial mechanical function. It was strongly associated with thromboembolism and the clinical triad of CPWD-atrial paralysis-stroke was proposed. Anticoagulation should be recommended in such patients.

Background: We aimed to evaluate the effect of Bachmann bundle (BB) impairment on electrical and mechanical function of the left atrium (LA), as well as the long-term clinical impact of such impairment. Design: We measured activation time in the five LA walls in 56 patients with atrial fibrillation. LA reservoir, conduit, and contractile function were also evaluated. Patients were divided into two groups based on ablation strategy: the circumferential pulmonary vein isolation (CPVI) group and CPVI with anterior wall linear ablation (LAWA) group. Patients in the CPVI+LAWA group were divided into two sub-groups based on ECG differences following ablation: the BB impairment group and intact BB group. LA activation time and function were then compared between the ablation strategy groups and the CPVI+LAWA subgroups. Results: Patients in the CPVI+LAWA group exhibited longer activation times in the anterior and lateral walls of the LA, poorer LA synchrony, and reduced LA contractile and reservoir function when compared with those in the CPVI group. In the BB impairment subgroup, we observed a discrepancy between electrical/mechanical remodeling. Among five walls, activation time was longest in this region. BB impairment was also associated with reduced LA function. Conclusion: Significant changes in LA function and conductibility were observed in patients with anterior wall ablation, especially those with iatrogenic BB impairment.

Background and aims Observational studies have suggested that plasma lipids contribute substantially to cardiovascular disease, but “cholesterol paradox” in atrial fibrillation (AF) remains. We sought to investigate the causal effects of lipid profiles on the risk of AF. Methods and results Two-sample Mendelian randomization (MR) framework was implemented to examine the causality of association. Summary estimations of genetic variants associated with low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, total cholesterol, triglycerides, lipoprotein-a [Lp(a)], apolipoprotein A1 (ApoA 1), and apolipoprotein B (ApoB) were 81, 99, 96, 61, 30, 10, and 23 single nucleotide polymorphisms, respectively. Genetic association with AF were retrieved from a genome-wide association study that included 1,030,836 individuals. The complications for AF were predefined as cardioembolic stroke (CES) and heart failure (HF). In the multivariable MR, the odds ratios for AF per standard deviation (SD) increase were 1.030 (95% confidence interval (CI) 0.979–1.083; P = 0.257) for LDL-cholesterol, 0.986 (95% CI 0.931–1.044; P = 0.622) for HDL-cholesterol, 0.965 (95% CI 0.896–1.041; P = 0.359) for triglycerides, 1.001 (95% CI 1.000–1.003; P = 0.023) for Lp(a), 1.017 (95% CI 0.966–1.070; P = 0.518) for ApoA1, and 1.002 (95% CI 0.963–1.043; P = 0.923) for ApoB. There was no evidence that other lipid components were causally associated with AF, CES, or HF, other than for a marginal association between triglycerides and HF. Conclusions This MR study provides robust evidence that high Lp(a) increases the risk of AF, suggesting that interventions targeting Lp(a) may contribute to the primary prevention of AF.

BACKGROUND: Stand-alone minimally invasive radiofrequency (RF) ablation with left atrial (LA) appendectomy has been an effective surgical intervention for non-paroxysmal atrial fibrillation (AF) (NPAF) in patients with a medical history of thromboembolism for secondary stroke prevention. This study sought to assess the impact of this surgery on LA function. METHODS: A total of 37 NPAF patients with a medical history of stroke or thromboembolism were enrolled in this prospective observational study, all of whom underwent stand-alone minimally RF ablation with LA appendectomy. Echocardiography was used to evaluate LA function preoperatively and 1 week and 3 months postoperatively. All patients were divided into two groups (Group AF and Group SR) according to whether sinus rhythm (SR) was restored after the surgery. RESULTS: The surgery had no impact on LA function in Group AF. Once NPAF patients were restored to SR, LA minimal volume (LAV(min)) decreased immediately compared with pre-operation (22.98±13.76 vs. 17.68±9.52 mL; P

BACKGROUND Renal impairment and atrial fibrillation (AF) often coexist. However, risk factors associated with renal impairment in AF patients have not been studied in a large population. Accordingly, this study investigated clinical factors associated with renal impairment in AF patients. METHODS From January 2012 to December 2016, 2,298 inpatients with non-valvular AF (NVAF) mainly for catheter ablation were enrolled in this cross-sectional study. Data collection included past medical history, echocardiography measurements, current medicine use and biochemical results. The estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal impairment was defined as a history of chronic kidney disease or an eGFR ≤90 ml/min/1.73 m2. Multivariate logistic regression was conducted to evaluate the relationship between the factors screened and eGFR. RESULTS The mean eGFR was 88.6 ± 17.1 ml/min/1.73 m2. The overall prevalence of renal impairment was 47.4%. Multivariate logistic regression showed that factors associated with renal impairment were age (OR: 1.12; 95% CI: 1.11-1.14), non-paroxysmal AF (OR: 1.28; 95% CI: 1.04-1.58), use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) (OR: 1.58; 95% CI: 1.28-1.95), congestive heart failure (OR: 1.80; 95% CI: 1.05-3.07), left ventricular ejection fraction (LVEF)

INTRODUCTION Atrial fibrosis is associated with atrial fibrillation (AF) recurrence after ablation. This study aims to determine the relationship between soluble ST2 (sST2), a profibrotic biomarker, and AF recurrence after radiofrequency catheter ablation (RFCA). METHODS AF patients referred for RFCA were consecutively included from October 2017 to May 2019. Baseline characteristics were collected, and sST2 levels were determined before ablation. Left atrial substrate mapping was performed after circumferential pulmonary vein isolation under sinus rhythm, and substrate was modified in low-voltage zones. A second procedure was recommended under recurrence. RESULTS Two hundred fifty-eight patients (146 males, average age 61.0 ± 8.8) were included. After a medium follow-up of 13.5 months, 52 patients (20.2%) had recurrence and received a second procedure. Preoperative sST2 level in patients with recurrence was significantly higher than that in patients without (31.3 ng/mL vs 20.3 ng/mL, P

Background: The increase of all-cause mortality in the areas with high COVID-19 transmission rate due to COVID-19 deaths and the collateral damage to other healthcare problems is well-known. However, the COVID-19 mortality is low in the regions with a low transmission rate and sufficient medical resources. In such regions, strict prevention measures altered people’s lifestyle and hygienic habits and had an impact on non-COVID-19 deaths. Yet, this aspect needs to be elucidated further. Methods: The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were estimated. Death rates were calculated and compared by weeks, months, seasons and years with a focus on the period of the COVID-19 pandemic from January 24 to March 27, 2020. The numerical values of all-cause death and the death rates of non-COVID diseases were compared in various time points. Findings: During the pandemic in Xuzhou region, a total of 79 COVID-19 infected patients were diagnosed and treated. Meanwhile, stringent public health measures were taken to contain the virus transmission. Surprisingly, mortalities of all-cause casualty, respiratory disorders, cerebrovascular disease, and cardiovascular disease are consistently lower than those in the same periods in 2018 and 2019. Moreover, the first two weeks in the lunar new year presented the highest death rates from 2018–2020 and lowest in 2020 due to COVID-19 control. The traffic death dropped significantly, while mortality of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time. Interpretation: Control strategies in the region of low SARS-CoV-2 transmission rate during the COVID-19 outbreak alter the lifestyles of people and further exert an impact on non-COVID deaths, which could have a practical value in guiding clinical work and future management of chronic diseases. Funding Statement: Xuzhou Talent Fellowship Program 2019 Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Institutional Review Board at the affiliated hospital of Xuzhou Medical University.

Aims Unexplained scar-related atrial tachycardia (AT) has been frequently encountered in clinical practice. We hypothesized that idiopathic, isolated fibrotic atrial cardiomyopathy (ACM) underlies this rhythm disorder. This study was aimed to characterize the underlying substrate and to explore the aetiology of this unexplained scar-related AT. Methods and results Twenty-six (11 men, aged 46 ± 13 years) of 52 non-surgical scar-related AT patients identified by three-dimensional voltage mapping were enrolled in this prospective observational study. Multimodality image examinations (echocardiography, cardiac magnetic resonance, 99Tc single-photon emission computed tomography), ventricular voltage mapping, and intracardiac pressure curve recording ruled out ventricular involvement. Catheter ablation was acutely successful for all the patients, and pacemaker implantation was performed in seven patients who presented sinus node dysfunction or atrial standstill after termination of the AT. In three patients with multiple AT recurrences, the diseased areas of the right atrium were resected and dechannelled via mini-invasive surgical interventions. Histological examinations revealed profound fibrosis without amyloidosis or adipose deposition. Viral and familial investigations yielded negative results. Fibrosis progression over a median of 45 (5-109) months of follow-up manifested as atrial arrhythmia recurrence in seven patients and atrial lead non-capture due to newly developed atrial standstill in two patients. Two patients suffered four ischaemic stroke events before receiving anticoagulation treatment. Conclusion Isolated, fibrotic ACM may underlie the idiopathic scar-related ATs. This novel cardiomyopathy has unique clinical characteristics with high morbidity including stroke and warrants specific therapeutic strategies. Further investigations are required to determine the aetiology and mechanism.

Introduction Ventricular tachycardia (VT) acceleration due to antitachycardia pacing (ATP) therapy could be often observed in patients with implantable cardioverter defibrillator (ICD), which usually results in additional shock. However, few studies focused on the risk factors for VT acceleration caused by ATP therapy. The purpose of this study was to investigate risk factors for VT acceleration due to ATP delivery. Methods We retrospectively reviewed 1056 ATP episodes in 33 patients with structural heart diseases, of whom clinical characteristics and episodes details were evaluated. Results At individual patient level, number of VT morphologies recorded in electrograms during follow‐up was a risk factor with cutoff point of 1 (AUC 0.79, sensitivity 72.7%, specificity 77.3%, P

Background: Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-β1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-β1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF). Methods: A total of 16 consecutive adult patients with CAF who underwent catheter ablation were enrolled. Blood samples for measurement of TGF-β1 were collected from periphery veins and coronary sinus before pulmonary vein isolation. The measurement was performed with a commercially available ELISA kit. Cardiac indices were measured using echocardiography. The left atrial electroanatomic mapping was performed after pulmonary vein isolation. Results: Serum level of TGF-β1 in peripheral blood was higher than that in coronary sinus (p

Introduction Detailed description of longstanding persistent accelerated idioatrial rhythm (AIAR) is lacking. This observational study investigated the clinical manifestations, electrophysiological characteristics, diagnosis, treatment and prognosis of this unusual arrhythmia. Methods and results Fifteen patients (11 males; average age 25.9±15.7 years) suspected with longstanding persistent AIAR were enrolled in our study. All patients had ECG, 24-hour Holter monitoring, isoproterenol provocation test, echocardiogram, and exercise treadmill test. Electrophysiological study (EPS) and catheter ablation were performed if necessary. The above noninvasive tests would be repeated during follow-up. Among the patients, 10 were asymptomatic; 5 had concomitant paroxysmal atrial tachycardia. Two asymptomatic patients had impaired left ventricular function. AIAR was observed throughout 24-hour Holter monitoring, showing chronotropic profile similar to sinus rhythm. Such AIAR exhibited competitive property with sinus rhythm (SR) when provoked by isoproterenol or during treadmill test. Twelve patients had EPS and 8 of them had successful ablation to eliminate AIAR. During a medium follow-up of 3.7 years, all patients were in well clinical course and preserved left ventricular dysfunction, and 3 patients spontaneously reverted to SR at 10-year follow-up. Conclusions Longstanding persistent AIAR is an unusual entity of atrial arrhythmias and in most situations a benign rhythm requiring no treatment. The clinical course will be worsened when AIAR develops rapid focal firing, is associated with focal atrial tachycardias or results in tachycardia-mediated cardiomyopathy, but can be resolved via catheter ablation. This article is protected by copyright. All rights reserved

Aims The aim of this study is to characterize the arrhythmogenic substrate for peri-mitral atrial flutter (PMAFL), thereby determining a personalized ablation strategy to treat PMAFL. Methods and results Thirty-six consecutive PMAFL patients (mean age: 63.8 ± 11.3, 23 males) underwent detailed three-dimensional electroanatomic mapping in left atrium (LA). The LA was divided into septal-anterior wall (SAW), posterior inferior wall (PIW), and mitral isthmus (MI) region, respectively. Ablation strategy was determined based on the endocardial bipolar voltage map. Based on electrophysiological substrates, 10, 17, and 9 cases were classified into iatrogenic, spontaneous, and no-substrate PMAFL, respectively. The mean voltage in SAW was significantly lower in spontaneous PMAFL (iatrogenic: 1.07 ± 0.66 mV; spontaneous: 0.65 ± 0.44 mV; no-substrate: 1.60 ± 0.53 mV, P

Background It remains unclear whether the curative result of paroxysmal atrial fibrillation (PAF) is a result of pulmonary vein (PV) isolation, PV antrum modification (PVAM), or both. We hypothesized that sufficient antrum modification (PVAM) is as important as PV isolation (PVI) for atrial fibrillation (AF) control and that PVAM can be evaluated by quantified lesion deployment using a force-sensing catheter. Methods and results Patients of symptomatic PAF were randomly assigned 2:1 into a PVAM group or a circumferential PV isolation (CPVI) group. In the PVAM group, circumferential quantitative ablation evaluated by automatical VisiTag module was performed. In the CPVI group, conventional circumferential ablation was performed to achieve the end point of all-PV isolation. In total, 180 patients with PAF were enrolled and randomly assigned to either the PVAM group (n = 120) or the CPVI group (n = 60). A total of 179 patients successfully underwent ablation. In the PVAM group, 68 patients achieved all PVI (PVAM-PVI), while 51 did not (PVAM-non-PVI). At 18 months, there was no significant difference in the maintenance of sinus rhythm between the PVAM and CPVI groups (84.9 vs 79.7%, P = .382). The PVAM-PVI subgroup demonstrated a higher arrhythmia-free survival compared with the PVAM-non-PVI subgroup (92.6 vs 74.5%, P = .006) and the CPVI group (92.6 vs 79.7%, P = .036). Conclusions The trial shows that sufficient force-sensing guided PVAM can result in satisfying outcomes in PAF patients. Notably, sufficient PVAM with all-PV isolated will further increase the success rate.

Aims The optimal procedural endpoint to achieve permanent pulmonary vein isolation (PVI) during ablation of atrial fibrillation (AF) remains unknown. We aimed to compare the impact of prolonged waiting periods and adenosine triphosphate (ATP) testing after PVI on long-term freedom from AF. Methods and results In total, 538 patients (median age 61 years, 62% male) undergoing first-time radiofrequency ablation for paroxysmal AF were randomized into four groups: Group 1 [PVI (no testing), n = 121], Group 2 (PVI + 30min waiting phase, n = 151), Group 3 (PVI+ATP, n = 131), and Group 4 (PVI + 30min+ATP, n = 135). The primary endpoint was freedom from AF. Repeat mapping to assess for late pulmonary vein (PV) reconnection was performed in patients who remained AF-free for >3 years (n = 46) and in those who had repeat ablation for AF recurrence (n = 82). During initial procedure, acute PV reconnection was observed in 33%, 26%, and 42% of patients in Groups 2, 3, and 4, respectively. At 36 months, no significant differences in freedom from AF recurrence were observed among all four groups (55%, 61%, 50%, and 62% for Groups 1, 2, 3, and 4, respectively; P = 0.258). Late PV reconnection was commonly observed, with a similar incidence between patients with and without AF recurrence (74% vs. 83%; P = 0.224). Conclusion Although PVI remains the cornerstone for AF ablation, intraprocedural techniques to assess for PV reconnection did not improve long-term success. Patients without AF recurrence after 3 years exhibited similarly high rates of PV reconnection as those that underwent repeat ablation for AF recurrence. The therapeutic mechanisms of AF ablation may not be solely predicated upon durable PVI.

Dabigatran is a widely used non-Vitamin K antagonist oral anticoagulant and has demonstrated a better efficacy and safety profile compared to Vitamin K antagonists. However, in some specific situations, the bleeding risk of dabigatran will be much increased. A 76-year-old female atrial fibrillation patient with concomitant nonrheumatic mitral valve regurgitation and chronic heart failure was described. She was on dabigatran 110 mg twice a day. On day 2 after admission, the patient presented with acute decompensated heart failure, the creatinine clearance level markedly decreased from 40.9 mL/min to 23.1 mL/min, and the trough-activated partial thromboplastin time exceeded the detection range. In this clinical context, renal and coagulation function should be monitored closely to avoid severe adverse events, especially major bleeding. Low-molecular-weight heparin might be considered to be applied temporarily, and rivaroxaban may be prescribed in this condition. The ethical approval was waived by the institutional review board of our hospital owing to the retrospective nature of the study.

Background: Several algorithms have been proposed to predict the origin of outflow tract (OT) ventricular arrhythmias (VAs) using standard 12-lead ECG. However, the additive value of right precordial and posterior leads is unknown. Methods: Standard 12-lead ECG, right precordial leads ECG (V 3 R, V 4 R, V 5 R) and posterior leads ECG (V 7 , V 8 , V 9 ) were recorded and analyzed in a development cohort of consecutive patients undergoing OT-VAs ablation at a single center. These findings informed the development of a novel algorithm incorporating right precordial and posterior leads to discriminate between left ventricular OT (LVOT) and right ventricular OT (RVOT) foci. The performance of this novel algorithm which includes the V 3 R/V 7 index was prospectively tested in a validation cohort of consecutive patients undergoing OT-VA ablation at 4 centers and compared with published algorithms. The location of the foci was determined by the successful ablation site. Results: One hundred ninety-one patients were recruited, of which 94 formed the validation cohort (mean age of 45.7±15.6, 39% male, 79% RVOT foci). During OT-VAs, a QS pattern in lead V 3 R and an S wave in lead V 7 were exclusively recorded in RVOT and LVOT foci, respectively. The V 3 R/V 7 index of LVOT origin was significantly greater than that of RVOT (1.05±0.83 versus 0.28±0.23, P 3 R/V 7 index ≥0.85 predicted an LVOT origin with 87% sensitivity and 96% specificity. In the prospective evaluation, when the V 3 R/V 7 index ≥0.85, an RVOT origin could be excluded with 98.6% accuracy. The area under the curve of V 3 R/V 7 index (0.954) was larger than that of previously reported ECG criteria, including V 2 S/V 3 R (0.896), V 2 transition ratio (0.792), and transition zone index (0.666). This novel index was also accurate in both patients without obvious LVOT or RVOT origins and subgroups with cardiac rotation or lead V 3 R/S transition. Conclusions: The V 3 R/V 7 index is a novel and accurate ECG criterion that predicts OT-VAs origin.

Background: The distinct electrophysiological features of bundle branch reentry ventricular tachycardia (VT) in patients without structural heart disease have not been systemically characterized. Methods: Nine patients (mean age, 29.6 years) with normal left ventricular function were enrolled. Bundle branch reentry VT with right and left bundle branch block (BBB) patterns was induced in 1 and 9 patients, respectively. The right bundle was attempted to record by a 6F decapolar or quadripolar catheter. Electroanatomic mapping of the left ventricle was performed in 6 patients. In all left BBB pattern VT, the mean VT cycle length was 329.3±89.1 ms, and the median HV interval during tachycardia was longer than that of baseline (78 [73–100] versus 71 [64.5–88] ms; P =0.11). Results: The H-RB interval during VT was slightly shorter ( P =0.14); however, the median RB-V interval was markedly longer than that during sinus rhythm (50 [29.5–83] versus 30 [8–51] ms; P =0.043]. In 6 patients with 3-dimensional mapping of the left ventricle, a slow anterograde or retrograde conduction over left HIS-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje-related VTs (1.0±1.3 types) were also induced in 5 patients. Ablation was applied in distal left BB in patients with baseline left BBB and in one narrow QRS patient with sustained Purkinje-related VT, whereas right BB was targeted in other patients. During a mean follow-up of 31.4 months, frequent premature ventricular contractions occurred in one patient, and new VT developed in the other patient. Conclusions: Bundle branch reentry VT can occur in young patients with extensive conduction disturbances within HIS-Purkinje system. Ablation targeting at the distal left BB which bifurcates into left posterior and anterior fascicle can preserve the residual atrioventricular conduction, but intensive follow-up is needed.

Recent studies have shown that premature ventricular contractions (PVCs) could enlarge the heart, but its risk factors are incompletely understood as a single 24-hour recording cannot reflect the true PVC burden due to day-to-day variability. Our purpose was to investigate the effect of burden and origin sites on left ventricular (LV) function in patients with PVCs by 7-day Holter electrocardiography (ECG). From May 2012 to August 2013, 112 consecutive patients with PVCs were recruited from the authors' affiliated hospital. All patients received 2-dimensional transthoracic echocardiography, 12-lead routing ECG and 7-days Holter ECG. Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured. A total of 102 participants with PVCs were included in the final analysis. Origin of PVCs from the tricuspid annulus had the highest burden and NT-proBNP level. LV papillary muscle had a higher LV ejection fraction (EF) level and a lower LV end-systolic dimension (ESD) than other PVC foci (P

Aims To identify unique electrophysiological characteristics of pulmonary artery (PA) ventricular arrhythmias (VA) and determine long-term clinical outcomes following non-contact mapping (NCM)-guided ablation. Methods and results The NCM array was deployed in consecutive patients undergoing clinically indicated ablation of outflow tract (OT) VA with left bundle branch block morphology, inferior axis and the precordial lead transition zone ≥V3. Activation, pace and NCM mapping parameters, and electrocardiogram analysis of PA VA patients were compared with 50 patients with right ventricular OT (RVOT) or aortic coronary cusps (ACC) foci. Of 170 consecutive patients, 20 (12%) patients (8 male, 39.7 ± 12.8 years old) with PA VA were identified. Electrocardiogram morphologies of PA ventricular tachycardia (VT) (located 10.8 ± 15.1 mm above the PV) were indistinguishable from RVOT VT, particularly those arising from the septal RVOT. Pulmonary artery VT can be mapped and ablated by targeting the site of earliest activation on NCM maps, with success rates of 90% after a single procedure, without anti-arrhythmics and mean follow-up of >5 years. Pace-mapping in the PA is complicated by frequent inability to capture ( P < 0.01). Small far-field atrial potentials and smaller ventricular electrograms were more frequently recorded at successful sites of ablation in the PA ( P < 0.05). Conclusion Non-contact mapping is a useful technique to map PA VT and ablation at sites of earliest activation above the pulmonary valve is associated with excellent long-term clinical success.

Background— Accelerated idioventricular rhythm (AIVR) or ventricular tachycardia (VT) originating from the right bundle branch (RBB) is rare and published clinical data on such arrhythmia are scarce. In this study, we will describe the clinical manifestations, diagnosis, and management of a cohort of patients with this novel arrhythmia. Methods and Results— Eight patients (5 men; median age, 25 years) with RBB-AIVR/VT were consecutively enrolled in the study. Pharmacological testing, exercise treadmill testing, electrophysiological study, and catheter ablation were performed in the study patients, and ECG features were characterized. All RBB-AIVR/VTs were of typical left bundle-branch block morphology with atrioventricular dissociation. The arrhythmias, which demonstrated chronotropic variability, were often isorhythmic with sinus rhythm and were accelerated by physical exercise, stress, and intravenous isoprenaline infusion. The rate of RBB-AIVR/VT varied from 45 to 200 beats per minute. Two patients experienced syncope, and 3 had impaired left ventricular function. Metoprolol was proven to be the most effective drug to decelerate the arrhythmia rate and relieve symptoms. Electrophysiology study was performed in 5 patients and the earliest activation with a sharp RBB potential was localized in the mid or distal RBB area. Catheter ablation terminated the arrhythmia with subsequent RBB block morphology during sinus rhythm. During follow-up, patients’ symptoms were controlled with normalization of left ventricular function either on metoprolol or by catheter ablation. Conclusions— RBB-AIVR/VT is an unusual type of ventricular arrhythmia. It can result in significant symptoms and depressed ventricular function and can be successfully treated with catheter ablation.

Late cure after a previously failed ablation of ventricular arrhythmias (VAs) is a relatively common phenomenon. The present study sought to delineate the incidence and electrophysiological characteristics of late cure in idiopathic VA patients.Totally, 45 idiopathic VA cases (mean age 44 ± 18 years, 27 males) either failed acutely or recurred within 12 h were enrolled in this study. Based on intensive clinical observations in the acute period, 19 (42%) patients demonstrated late cure in the first week after the procedure.The late cure patients had significantly better acute and cumulative ablation effects during the procedure than did those without a late cure. Additionally, they had a prediction that originated from the right ventricular outflow tract, aortic-mitral continuum, and left summit area relative to other sites (13/18 vs 6/27, p 0.01). In a median follow-up of 24 [14, 46] months, 7/19 (37%) patients had their VAs recurred. The late cure group had significantly more patients cured at long-term follow-up than those without (12/19 vs 0/26, p 0.01). A cutoff value of the "time to eliminate VAs" 7.0 s was able to predict a long-term recurrence of the VAs with 62.5% sensitivity and 85.7% specificity.The late cure of VAs occurs in more than one third of patients who have a seemingly unsuccessful ablation session, which is clustered in the first week after the procedure. However, long-term recurrence of VAs occurred in 37% of the late cure patients, emphasizing the importance of long-term follow-up.

Objective: Discussing whether occurs reperfusion malignant ventricular arrhythmia by intravenous injecting metoprolol before the intervention treatment of Left Anterior Descending (LAD) of Acute Myocardial Infarction (AMI) and observing the change of heart rate.

Background— Atrial tachycardias (ATs) after extensive ablation are increasingly common and challenging arrhythmias. The prolonged intra-atrial conduction time (IACT) during ATs in the milieu may complicate the mapping of focal ATs. In this present study, we aim to characterize the electrophysiological features of ATs in this unique setting and to delineate an effective mapping strategy further. Methods and Results— In total, 13 patients (average age, 59±7 years) in a cohort of 80 patients referred for AT ablation were selected for the study. The patients all demonstrated an undistinguishable map not ready to be interpreted the 3-dimensional mapping. A total of 13 ATs were mapped with mean tachycardia cycle length of 296±70 ms. Two activation patterns were identified, which were referred to as pseudo-macroreentry and chaotic activation. The former was a focal AT originating from the vicinity of an area of conduction block with the IACT less than the window of interest duration (4 cases; IACT/window of interest ratio range, 0.93–0.98). The latter refers to a focal AT exhibiting a disorderly color mapping display with IACT exceeding the window of interest duration (9 cases; IACT/window of interest ratio range, 1.02–1.29). The IACT was determined after resetting the annotation. All ATs were successfully eliminated at the originating site. Conclusions— We delineated a series of focal ATs in the setting of a significantly prolonged IACT encountered in patients after previous extensive ablation. Two activation patterns were identified, which may help facilitate the mapping of focal ATs in this setting.

AT-Induced Cardiomyopathy Objective Focal atrial tachycardias (ATs) are known to have the potential to develop tachycardiomyopathy (TCM). The aim of the study was to investigate the incidence, risk factors, and long-term outcome of TCM patients complicated by focal ATs. Methods and Results A total of 237 patients undergoing electrophysiological studies were enrolled, among which 216 patients were diagnosed as focal ATs. In total, 18 patients (8.3%, 13 males) were identified to have TCM. The TCM patients were younger (29.8 ± 20.1 vs. 45.9 ± 17.3; P < 0.000) and were more frequently males (13/18 vs. 80/198; P = 0.014). The ATs were more likely to be persistent (11/18 vs. 32/198; P < 0.001). There was no difference between the 2 groups in terms of the tachycardia cycle length (392 milliseconds vs. 380 milliseconds; P = 0.56) and heart rate (144 bpm vs. 156 bpm; P = 0.15). The persistence and incidence of symptoms and prevalence of structural heart disease were comparable between the groups. In a multivariable analysis, the younger age and persistent nature were independently associated with TCM. In a 56 ± 21-month follow-up, all TCM patients had improved left ventricle ejection fraction after successful catheter ablation or medical therapy (43.9 ± 5.8% vs. 61.1 ± 3.5%; P ＜ 0.05). However, 1 patient suffered sudden cardiac death due to unauthorized withdrawal of the drug and progressive heart failure. Conclusions The incidence of TCM in focal ATs patients was 8.3%. Younger age and persistent nature were the independent risk factors of TCM. Most TCM patients had a benign outcome; however, long-term risk of sudden death does exist.

A 58-year-old man presented with incessant atrial flutter (AFL) ([Figure 1A][1]); he had twice undergone unsuccessful attempts at ablation of the cavotricuspid isthmus (CTI) and was referred for ablation. Counterclockwise CTI-dependent AFL was verified by activation mapping ([Figures 1B and 1C][1

The purpose of this study is to explore the left atrium (LA) electrophysiologic abnormalities in atrial fibrillation (AF) patients detected during sinus rhythm and to determine the relationship between the type of AF and the electrophysiologic substrate in the LA. Eighty patients with AF (30 paroxysmal AF, 22 persistent AF, and 28 long-standing AF) and 20 age- and sex-matched patients with left-sided accessory pathway were prospectively studied. High-density three-dimensional electroanatomic mapping was performed during sinus rhythm in LA, which was divided into six segments for regional analysis. Mean bipolar voltage, low voltage zone (LVZ) distribution, LA activation time, and electrogram complexity were assessed. The LA mean voltage was 3.67 ± 0.68 mV in no AF group, 2.16 ± 0.63 mV in the paroxysmal, 1.81 ± 0.36 mV in the persistent, and 1.48 ± 0.34 mV in the long-standing AF patients (P

Background Catheter ablation of persistent atrial fibrillation (AF) has been performed with varying results using a combination of different techniques. We sought to evaluate the efficacy of additional linear lesion and defragmentation of left atrium (LA). Methods A cohort of 169 patients with persistent AF was studied. Ablation was performed following a sequential strategy consisted of circumferential pulmonary vein isolation (CPVI), LA roof linear ablation, posterior mitral area, coronary sinus and cavotricuspid isthmus, and complex fractionated electrograms ablation. Results During a mean follow-up of 15±8months after a single procedure, 84 (50%) patients were in sinus rhythm, 34 (20%) had an AF recurrence and 51(30%) developed atrial tachycardias (ATs). Repeat procedures were performed in 24 recurrent AF and 46 AT patients. A total of 81 different ATs were mapped and ablated in 46 AT patients, characterized as focal for 45 and macroreentry for 36 ATs. Most of the ATs were likely to be attributed to the previous lesions by an analysis of substrate and activation mapping in the redo procedure and a review of the lesions placed in the initial procedure. Overall, 75 (93%) ATs were ablated successfully. Procedural complications occurred in 11 of the 239 procedures. After a mean follow-up of 20±9months, 128 (76%) patients were free of arrhythmias after the final procedure. Conclusions CPVI supplemented by linear ablation and defragmentation does not seem to improve the overall success rate of persistent AF. The efficacy of linear ablation and defragmentation might be diluted by their proarrhythmic effects.

Background Atrial tachycardia (AT) is a frequent late sequel of surgical valve replacement procedures in patients with rheumatic heart disease (RHD). The aim of this study was to evaluate the acute and long-term outcome of catheter ablation in such patients. Methods and Results A total of 21 consecutive RHD patients with AT after a valve replacement were enrolled in this study. The mean interval between the occurrence of symptomatic AT and the surgical intervention was 38.2 ± 48.7 months. The initial procedure was performed 8.4 ± 8.9 months after first onset of AT. During the first procedure, an electroanatomic mapping was completed for 25 ATs, 18 of which were cavotricuspid isthmus-dependent atrial flutter, five that were right atrial free wall AT, and two that were left AT. Acute success was obtained in 95% (20/21) patients. Nine patients with recurrent AT had repeat radiofrequency catheter ablation, and newly developed left AT was identified in five patients after the first right AT ablation. After a mean follow-up of 42.7 ± 17.3 months, only 33% of the patients remained free of ATs, while 14% and 53% of the patients had AT recurrence and the development of atrial fibrillation (AF), respectively. Conclusion Right but not left macroreentry is the most common AT postmitral valve replacement in patients with RHD. The incidence of AF is very high after AT ablation in such patients during the long-term follow-up.

Background Right atrial tachycardia (AT) is a common arrhythmia postsurgical valve replacement in patients with rheumatic heart disease (RHD). However, the substrate and the mechanism of left AT in such patients and the ablation efficacy is less known. Methods and results Twenty-seven RHD patients with AT were enrolled in this study; nine of them (33%) had left AT. Five and four patients had left AT during the first and second procedure, respectively. A spontaneous scar in the left posterior wall was identified in all patients, and obvious anterior scar in three patients. Dual-roof-dependent AT was found in three patients and macroreentry AT surrounding right pulmonary vein was identified in one patient, two of whom had left anterior scar. Three patients had AT circuit going around the mitral annulus, one of whom had left anterior scar. Entrainment pacing at different sites confirmed the mechanism of these macroreentries. Two patients had a focal origin, one was localized in posterior wall at the edge of the scar and the other one was originated from the left septum with normal voltage. After a mean follow-up of 27.4 ± 7.9 months, the left AT group had a similar recurrence rate compared with the right AT group alone (67% vs 56%, P = 0.58). In the left AT group, 11% of patients had AT recurrence and 56% of patients developed atrial fibrillation. Conclusion Left atrial AT can occur in RHD patients postmitral valve replacement. Catheter ablation is feasible with high acute success rate. The incidence of late development atrial fibrillation is considerable after successful ablation.

Background— The high incidence of postprocedural atrial tachycardia reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat nonparoxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low-voltage zones and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation in patients with NPAF is superior. Methods and Results— A total of 86 consecutive patients with NPAF were enrolled in study group. After circumferential pulmonary vein isolation, cavotricuspid isthmus ablation and cardioversion to SR, high-density mapping of left atrium was performed. Areas with low-voltage zone and SR-AE were targeted for further homogenization and elimination, respectively; 78 consecutive sex- and age-matched patients with NPAF who were treated with the stepwise approach served as the historical control group. In the study group, 92% (79/86) were successfully cardioverted after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation. Among the patients converted to SR, 70% (55/79) had low-voltage zone and SR-AE and received additional ablation, whereas in 30% (24/79) without SR-AE or low-voltage zone, no further ablation was performed. During a follow-up period of >30 months, the Kaplan–Meier estimated probability to maintain SR at 24 months was 69.8% versus 51.3%. And after a single procedure, 3.5% (3/86) developed postprocedural atrial tachycardia in study group, compared with 30% (24/78) in control group ( P =0.0003). Conclusions— A strategy of selective electrophysiologically guided atrial substrate modification in SR after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation is clinically more effective than the stepwise approach for NPAF ablation. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT01716143.

Depression is one of the major side effects of interferon alpha (IFN-α) treatment, but the molecular mechanism underlying IFN-α-induced depression remains unclear. Several studies have shown that the serotonin receptors 5-HTR1b and 5-HTR4 play key roles in the anti-depression effects associated with p11 (S100A10). We investigated the effects of IFN-α on the regulation of p11, 5-HTR1b and 5-HTR4 in mice and human neuroblastoma cells (SH-sy5y). We found that intraperitoneal injection with IFN-α in Balb/c mice resulted in an increased immobility in FST and TST and potently lowered the protein levels of p11, 5-HTR1b and 5-HTR4 in the hippocampus or cingulate gyrus. IFN-α significantly down-regulated the protein levels of p11, 5-HTR1b and 5-HTR4 in SH-sy5y cells, in a time- and dose-dependent manner. Our study revealed that over-expression of p11 could prevent the IFN-α-induced down-regulation of 5-HTR1b and 5-HTR4. The results indicated that IFN-α treatment resulted in p11 down-regulation, which subsequently decreased 5-HTR1b and 5-HTR4 in vitro or in vivo. Our findings suggested that p11 might be a potential regulator on 5-HTR1b and 5-HTR4 as well as a predictor of or a therapeutic target for IFN-α-induced depression.

Background The potential clinical application of bone marrow or peripheral blood-derived progenitor cells for cardiovascular regeneration in patients with diabetes mellitus (DM) is limited by their functional impairment. We sought to determine the mechanisms of impaired therapeutic efficacy of peripheral blood-derived progenitor cells in type 2 DM patients and evaluated the use of cell-free conditioned medium obtained from human embryonic stem cell-derived endothelial-like cells (ESC-ECs) to reverse their functional impairment. Methods The angiogenic potential of late outgrowth endothelial cells (OECs) and cytokine profile of the conditional medium of proangiogenic cells (PACs) derived from peripheral blood-mononuclear cells of healthy control and DM patients and ESC-ECs was compared by in vitro tube formation assay and a multiplex bead-based immunoassay kit, respectively. The in vivo angiogenic potential of ESC-ECs derived conditioned medium in rescuing the functional impairment of PB-PACs in DM patients was investigated using a hindlimb ischemia model. Results Human ESC-ECs had similar functional and phenotypic characteristics as OECs in healthy controls. Cytokine profiling showed that vascular endothelial growth factor, stromal cell-derived factor 1 and placental growth factor were down-regulated in PACs from DM patients. Tube formation assay that revealed functional impairment of OECs from DM patients could be rescued by ESC-ECs conditioned medium. Administration of ESC-ECs conditioned medium restored the therapeutic efficacy of PB-PACs from DM patients in a mouse model of hindlimb ischemia. Conclusions Our results showed that peripheral blood-derived progenitor cells from DM patients have impaired function because of defective secretion of angiogenic cytokines, which could be restored by supplementation of ESC-ECs conditioned medium. Copyright © 2012 John Wiley & Sons, Ltd.

We examined the use of lipid lowering medications and control of dyslipidemia among US adults in 1999-2006.Data were extracted from the National Health and Nutrition Examination Survey 1999-2006.The mean low-density lipoprotein-cholesterol (LDL-C) level significantly decreased from 3.25+/-0.03 mmol/L in 1999-2002 to 3.02+/-0.02 mmol/L in 2003-2006 in men, and from 3.11+/-0.03 to 2.98+/-0.03 mmol/L in women (p0.001). Statins and fibrates were the most commonly used medications. Among those diagnosed with hypercholesterolemia, the proportion on treatment increased from 32.4% to 38.9% (p=0.001) in the 8-year period. The proportion of participants with a history of diabetes treated with a statin increased from 20.9+/-2.2% in 1999-2002 to 37.6+/-2.5% in 2003-2006 (p0.001). However, only 39.9% of people with diabetes and 45.4% of people with ischemic heart disease (IHD) achieved LDL-C target levels.Between 1999 and 2006, LDL-C level decreased in US adults and use of lipid lowering medications increased. More effort is still needed to detect and treat dyslipidemia in the community, particularly in people at high cardiovascular risk.

Obesity is associated with increased risk of conditions such as hypertension, dyslipidaemia, diabetes mellitus, and obstructive sleep apnoea. Pharmacotherapy for obesity should be considered in combination with lifestyle changes in obese patients, or overweight patients with other conditions that put them at risk of developing heart disease. Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use. Sibutramine is a serotonergic and adrenergic drug that reduces food intake. Orlistat is a gastrointestinal lipase inhibitor that interferes with fat absorption. However, it commonly causes flatulence and diarrhoea. Rimonabant is the first of a series of endocannabinoid receptor antagonists. It was approved by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMEA) as an adjunct to diet and exercise in treating obesity in 2006. However, despite the extensive clinical trial data, EMEA announced in 2008 that it has recommended suspension of rimonabant because of its psychiatric side effects. Studies evaluating the long-term safety and efficacy of anti-obesity agents are needed. © 2009 The British Pharmacological Society., link_to_OA_fulltext

Introduction Myocardium fibrosis is a hallmark of cardiomyopathy and a proposed substrate for cardiac arrhythmias. Nevertheless, fibrosis of atrial myocardium and fibrotic atrial cardiomyopathy has not been systemically addressed. Hypothesis We hypothesized that idiopathic, isolated, fibrotic atrial cardiomyopathy (IIF-ACM) is a specific cardiomyopathy, which is characterized by atrial fibrosis and related arrhythmias. Methods In the past 8 years, 34 patients (male 13, mean age 46.5±13.3 yrs) were diagnosed with IIF-ACM based on: 1) clinical evaluation; 2) cardiac image examination; and 3) electro-anatomic mapping detected atrial scarring. Serum biomarkers of collagen metabolism and cardiomyopathy-related genetic screening were performed. Tissue pathology and virus detections were done for two patients. Results During clinical evaluation, electric silent areas were detected in all patients by intra-cardiac electro-anatomical mapping. Among 34 patients, 26 presented with atrial tachycardia (AT), 5 with sick sinus syndrome (SSS) and 3 with atrial standstill. 5 AT patients further developed SSS during the correction of AT by radiofrequency ablation. Late gadolinium-enhancement cardiovascular magnet resonance showed mild to severely dilated atria, without bilateral ventricular scarring or functional impairment. Serum biomarkers of collagen screening demonstrated significant increased collagen synthesis than collagen degradation in IIF-ACM patients. Cardiomyopathy-related genetic screening depicted no clinically relevant mutation. Histological studies showed global fibrosis of atria (Fig. 1). Conclusions We systemically reported 34 patients with IIF-ACM, which is characterized by atrial scarring and relevant arrhythmias. Ventricular functions of note were preserved in all patients. However, the underlying etiology of IIF-ACM remains to be investigated.

Background Most postsurgical macroreentry atrial tachycardias (PS-MATs) are atriotomy related; however, underlying mechanisms and prevention remain undefined. Objective The purpose of the present study was to investigate the electrophysiological and histologic bases of right atriotomy incision arrhythmogenicity and whether a modified atriotomy that extends the incisional line to the tricuspid annulus (TA) and inferior vena cava (IVC) prevents PS-MAT. Methods Atrial arrhythmia induction and electrophysiological and histologic characteristics were studied 8 weeks after right atriotomy in 30 adult swine according to incision distance to TA or IVC (groups A, B, and C: broad, narrow, and closed corridors, respectively; group D, no-incision sham; n=6 per group, except n=12 for group B). Results Sustained PS-MATs were induced and mapped in the broad- and narrow-corridor groups (A, 1 of 6 [16.7%] vs B, 5 of 12 [41.7%]) but not in the closed-corridor (C) or sham (D) groups ( P = .087). With 20-ms pacing cycle–length decrements (from 350 to 270 ms), mean conduction time over 20 mm at the atriotomy-to-TA corridor was 29.2 ± 2.2, 31.0 ± 4.2, 26.0 ± 1.9, and 17.0 ± 1.4 ms for 5 and 10 mm (both group B), 15 mm (group A), and sham incision ( P = .017), respectively. Conduction properties correlated with histologic findings: the wider the corridor, the healthier its tissue. In group C (modified atriotomy), both corridors were replaced by dense scar with complete conduction block. Conclusion Atriotomy corridor width determines conduction properties and contributes to arrhythmogenicity. A modified right atriotomy that extends to the TA and IVC prevents PS-MAT.

Atrial hypertrophy and fibrosis are essential pathological features of atrial fibrillation. Recently, adiponectin has become a protein of interest due to its beneficial effects on cardiovascular diseases. However, the molecular mechanism of atrial structural remodeling and signaling pathways evoked by adiponectin remain unclear. In the present study, we investigated the cardioprotective effect of globular adiponectin (gAcrp) on angiotensin II-induced atrial hypertrophy and fibrosis in neonatal Sprague-Dawley rat. To further investigate the molecular mechanisms underlying the preventive effect of gAcrp, transfection of cells with siRNA was used to suppress the mRNA expression of adiponectin receptor 1 (AdipoR1) and its downstream adaptor protein APPL1. Non-silencing-Cy-3 labelled siRNA was used to determine transfection efficiency using fluorescence microscopy. The expression of atrial natriuretic peptide and procollagen type1 α-1, hypertrophy marker and fibrosis one, respectively, was detected by real-time PCR. Furthermore, the expression of adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) and Akt was detected by western blotting. In addition, nuclear p65 translocation activity was analyzed by EMSA supershift assay. Our results showed that AdipoR1 and the adaptor protein APPL1 mediated the protective effects of gAcrp. In addition, the function of adiponectin and phosphorylation of AMPK were prominently diminished by inhibition of PI3K. Furthermore, nuclear factor-κB (NF-κB) transcription was diminished by the specific inhibition of AMPK. Taken together, AMPK pivotally interacts with NF-κB and PI3K, mediating the cardioprotective effect of adiponectin, and may serve as a therapeutic target for preventing atrial hypertrophy and fibrosis. Our present study suggests that gAcrp could ameliorate AngII-induced cardiac hypertrophy and fibrosis in rat atrial cells, which is mediated by the activation of AMPK signaling pathways. APPL1 and AdipoR1 are the key factors involved in the downstream of gAcrp approach.

In many countries, combination therapy with amlodipine and atorvastatin is indicated for the treatment of patients with hypertension and hypercholesterolemia. The aim of this study was to investigate the impact of this combination therapy on plasma adiponectin levels.Combination therapy with amlodipine and atorvastatin would increase plasma adiponectin levels.A total of 25 patients with coronary artery disease and concomitant hypertension and hypercholesterolemia were evaluated. The combination of amlodipine and atorvastatin in 8 different dosage strengths were flexibly titrated over a period of 14 weeks. Lipid profile and plasma adiponectin were measured. Brachial flow-mediated dilation (FMD) was determined by vascular ultrasound.As compared with baseline, combination therapy with amlodipine and atorvastatin significantly reduced systolic and diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol (all P0.05). Furthermore, there were significant increases in adiponectin levels (mean [95% confidence interval (CI)], 12.1 [10.7-13.7] vs 8.1 [6.5-10.0] μg/mL; P0.001) and brachial FMD (4.4 ± 0.6% vs 5.6 ± 0.5%; P = 0.046) over 14 weeks of treatment. The change in adiponectin levels correlated significantly with the changes in diastolic blood pressure (r = -0.49; P = 0.014) and FMD (r = 0.55; P = 0.007).The results of this study indicate that along with its antihypertensive and cholesterol-lowering effects, combination therapy with amlodipine and atorvastatin appears to increase plasma adiponectin levels and improve endothelial function.

ObjectiveLow plasma adiponectin level can predict the development of hypertension after 5 years in our population. We therefore investigated whether single-nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with hypertension.Design and methodsWe genotyped 14 tagging SNPs in 1616 subjects with persistent normotensive or hypertensive status during a 6.4-year follow-up period in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2). Plasma adiponectin level was measured in 1385 subjects using in-house sandwich ELISA.ResultsThe minor G allele of the SNP rs266729 was significantly associated with higher odds of hypertension (odds ratio (95% confidence interval)=1.49 (1.13–1.95), P=0.0044) after adjusting for covariates. In stepwise multiple logistic regression, this SNP (P=0.006) was a significant independent factor of hypertension, together with age (PPP=0.021), and insulin resistance index (Pβ=−0.067, P=0.0037), −10677C>T (β=0.069, P=0.0027), rs182052 (β=−0.097, Pβ=0.103, PConclusionIn our population, genetic variants in the adiponectin gene influenced plasma adiponectin levels, and one of them was associated with hypertension. This study has provided further evidence for a role of adiponectin in the development of hypertension.