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Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality., The outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) or atrial fibrillation (AF) are not known. A total of 3591 patients with active cancers were studied (907 on dabigatran; 2684 on rivaroxaban). In comparison with rivaroxaban, the use of dabigatran may be associated with lower risk of cancer‐related death and all‐cause mortality.

Aims The implications of ablation for atrial fibrillation in preventing stroke are controversial, and no studies have investigated whether ablation prevents ischaemic stroke (IS) in atrial flutter (AFL). Methods and results This study analysed data contained in the Taiwan National Health Insurance Research Database for 16 765 patients with a first diagnosis of solitary AFL during 2001–2013. Eligible patients were divided into two groups according to whether or not they had received ablation. Propensity score matching (PSM) was performed to mitigate the effects of potential confounding factors. The primary outcome was occurrence of IS during follow-up. After 1:2 PSM, the analysis included 1037 patients in the ablation group and 2074 patients in the non-ablation group. The incidence of IS was lower in the ablation group compared to the non-ablation group [subdistribution hazard ratio (SHR) 0.61, 95% confidence interval (CI) 0.41–0.90] during the 2-year follow-up period but not thereafter (SHR 1.03, 95% CI 0.72–1.48). When grouping by stroke history, it revealed that ablation affected the incidence of stroke in patients without history of stroke (SHR 0.59, 95% CI 0.38–0.91) but not in patients with history of stroke. When each group was stratified by CHA2DS2-VASc score, ablation lowered the incidence of stroke in patients with CHA2DS2-VASc ≤3 (SHR 0.31, 95% CI 0.16–0.60) but not in patients with CHA2DS2-VASc ≥4 in the initial 2-year follow-up. Conclusion The different incidence of IS in patients with/without ablation indicates that ablation reduces the risk of IS in AFL patients.

Out-of-hospital cardiac arrest (OHCA) remains a major threat to public health worldwide. OHCA patients presenting initial shockable ventricular tachycardia/ventricular fibrillation (VT/VF) rhythm have a better survival rate. We sought to develop a simple SACAF score to discriminate VT/VF from non-VT/VF OHCAs based on the Taiwan multicenter hospital-based registry database. We analyzed the in- and pre-hospital data, including demographics, baseline comorbidities, response times, automated external defibrillator information, and the 12-lead ECG recording closest to the OHCA event in bystander-witnessed OHCA patients. Among the 461 study patients, male sex (OR 2.54, 95% CI = 1.32–4.88, P = 0.005), age ≤ 65 years (OR 2.78, 95% CI = 1.64–4.70, P P P = 0.017) were independent risk factors for VT/VF OHCA (n = 81) compared with non-VT/VF OHCA (n = 380). A composite SACAF score was developed (male Sex, Age ≤ 65 years, Cardiovascular diseases, and AF) and compared with the performance of a modified CHA2DS2-VASc score (Cardiovascular diseases, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke, Vascular disease, Age 65–74 years, female Sex category). The area under the receiver operating characteristic curve (AUC) of the SACAF was 0.739 (95% CI = 0.681–0.797, P 2DS2-VASc was 0.474 (95% CI = 0.408–0.541, P = 0.464). A SACAF score of ≥ 2 was useful in discriminating VT/VF from non-VT/VF OHCAs with a sensitivity of 0.75 and a specificity of 0.60. In conclusion, the simple SACAF score appears to be useful in discriminating VT/VF from non-VT/VF bystander-witnessed OHCAs and the findings may also shed light on future mechanistic evaluation.

Objectives: Atrial fibrillation (AF) is linked to an increased risk of stroke and dementia. Atrial flutter (AFL) is also linked to an increased risk of stroke but at a different level of risk as compared to AF. Little is known about the difference in the risk of dementia between AF and AFL. This study aims to investigate whether the risk of dementia is different between AF and AFL.Methods: Patients with newly diagnosed AF and AFL during 2001–2013 were retrieved from Taiwan's National Health Insurance Research Database. Patients with incomplete demographic data, aged Results: A total of 232,425 and 7,569 patients with AF and AFL, respectively, were eligible for analysis. After 4:1 PSM, we included 30,276 and 7,569 patients with AF and AFL, respectively, for analysis. Additionally, patients with AF (n = 29,187) and AFL (n = 451) who received oral anticoagulants were enrolled for comparison. The risk of dementia was higher in patients with AF compared with patients with AFL (subdistribution hazard ratio (SHR) = 1.52, 95% CI 1.39–1.66; p < 0.0001) before PSM and remained higher in patients with AF (SHR = 1.14, 95% CI 1.04–1.25; p = 0.0064) after PSM. The risk of dementia was higher in patients with AF without previous history of stroke after PSM but the risk did not differ between patients with AF and AFL with previous history of stroke. Among patients who received oral anticoagulants, the cumulative incidences of dementia were significantly higher in patients with AF than in patients with AFL before and after PSM (all P < 0.05).Conclusions: This study found that, among patients without history of stroke, the risk of dementia was higher in patients with AF than in patients with AFL, and CHA2DS2-VASc score might be useful for risk stratification of dementia between patients with AF and AFL.

Background: Age affects the efficacy of pharmacological treatment for atrial fibrillation (AF). Catheter ablation, including radiofrequency (RF) or cryoballoon ablation, is an effective strategy for symptomatic AF. This meta-analysis aimed to analyze the efficacy and safety of AF ablation in elderly patients with AF compared to non-elderly patients with AF.Methods: We searched several databases for articles published between January 1, 2008 and March 31, 2020. Eighteen observational studies with 21,039 patients were analyzed. Data including recurrence of AF or atrial tachyarrhythmia (ATA), complications, procedural time, and fluoroscopic time were compared between the elderly and non-elderly groups.Results: The elderly patients had significantly higher incidences of recurrent AF or ATA after AF ablation compared to the non-elderly patients (Conclusions: The elderly patients had significantly higher incidences of recurrent AF or ATA and complications after ablation for non-paroxysmal AF compared to non-elderly patients with AF (

Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were 6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20–0.76) and IS/SE (HR = 0.12, 95% CI = 0.03–0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34–0.93) and IS/SE (HR = 0.26, 95% CI = 0.09–0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.

Background/Purpose: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. Methods: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. Results: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. Conclusion: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type. Keywords: Atrial fibrillation, Dronedarone, Observational, Safety, Quality of life

Summary Background Cardiac implantable electronic device (CIED) infection, a major complication of a CIED implant procedure, can prolong hospitalization and cause mortality. Aim To evaluate the efficacy of a bundled skin antiseptic preparation for preventing infection after implantation of a complex CIED. Methods This study analysed 1163 consecutive patients who had received a bundled skin antiseptic preparation before CIED implantation from July 2012 to December 2017. According to the complexity of the CIED implant procedure, the patients were divided into a complex CIED group (N = 370) and a non-complex CIED group (N = 793). A complex procedure was defined as a pacemaker replacement, implantation of implantable cardioverter defibrillator and cardiac resynchronization therapy, device upgrade, or lead revision. Findings During a mean follow-up of 2.9 ± 1.7 years, CIED infection developed in 15 patients (1.3%), and the incidence of minor and major infection was 1.1% and 0.2%, respectively. The incidence of CIED infection did not significantly differ between the complex CIED group and the non-complex CIED group (1.1% vs 1.4%, respectively; non-significant). Multivariate analysis indicated that procedural complexity was not an independent predictor of CIED infection. After 2:1 propensity score matching, the matched non-complex CIED group and the matched complex CIED group still showed no significant difference in the incidence of CIED infection. Conclusion Bundled skin antiseptic preparation is an effective and widely applicable strategy for decreasing infection risk after a complex CIED implantation.

AIMS Pulmonary vein isolation (PVI) is an effective procedure for atrial fibrillation (AF). The role of additional cavotricuspid isthmus (CTI) block ablation remains controversial in AF patients without atrial flutter (AFL). Therefore, this study aimed to explore the clinical outcome of additional CTI block ablation in patients without AFL. METHODS Between January 2013 and December 2017, a total of 139 patients who did not have documented AFL and who underwent catheter ablation for AF were recruited. Fifty-seven patients were classified in additional CTI block ablation group and 82 patients were classified in without CTI group. The incidence of early-onset and late-onset atrial arrhythmia recurrence was compared between the two groups. RESULTS The additional CTI group had a higher prevalence of persistent or long-standing AF and larger left atrial volume. The additional CTI group had a higher incidence of late-onset atrial arrhythmia recurrence (38.6% vs 12.2%; P

Aims High demand right ventricular pacing may elicit left ventricular systolic dysfunction known as pacing‐induced cardiomyopathy, increasing the risks of heart failure (HF) hospitalization. Percentage of demand ventricular pacing is different between patients with sick sinus syndrome (SSS) and those with complete atrioventricular block (CAVB). This study aims to compare the incidence of HF admission and pacing‐induced cardiomyopathy between patients with SSS and CAVB. Methods and results A total of 824 patients who received single ventricular or dual‐chamber pacemaker implantation at our hospital between January 2003 and December 2012 were recruited for the study. Patients with HF, those without complete cardiac echocardiography, and those with significant coronary artery disease were excluded. Finally, 315 patients with SSS and 289 patients with CAVB were enrolled in this study. The CAVB group had a higher pacing percentage (39.37 ± 9.17% vs. 83.82 ± 33.06%; P

Background Endocardial late fractionated potentials during sinus rhythm mapping may reflect abnormal "subendocardial" substrates associated with right ventricular outflow tract (RVOT) ventricular arrhythmias (VAs). The aim of this study was to explore the clinical outcomes of catheter ablation guided by these late fractionated potentials for RVOT VAs in patients without structural heart disease. Methods From January 2016 to March 2018, 28 patients underwent catheter ablation for RVOT premature ventricular contractions (PVCs) or ventricular tachycardia (VT), guided by the EnSite NavX or Velocity V5.0 three-dimensional mapping system (Abbott, St. Paul, MN, USA). Among them, 10 patients (35.7%) were found to have endocardial late fractionated potentials during sinus rhythm mapping (Group 1). Group 2 was composed of 18 patients in whom no endocardial late fractionated potentials were seen. The burden of VAs, acute procedural success, and 3-month clinical outcomes were analyzed. Results The average duration of late fractionated potentials after the end of QRS during sinus rhythm mapping in group 1 was 45.00 ± 17.15 ms. Baseline demographics and morphology and burden of PVCs were similarly distributed between both groups. Group 1 had higher acute procedural success compared to group 2 (100% vs 66.7%; P = .039). Moreover, at 3-month follow-up, group 1 had lower total PVCs (49 (1-5986) versus 4316 (1-23231); P = .048), PVC burden (0% (0-5.9) vs 4.3% (0-18.9); P = .055), and higher clinical success (100% vs 55.6%; P = .025) compared to group 2. Conclusion The identification and elimination of endocardial late fractionated potentials during sinus rhythm mapping could improve the acute success and short-term outcomes of ablation for RVOT VAs.

BACKGROUND Atrial flutter (AFL)-related tachycardia-induced cardiomyopathy (TICM) is a treatable cause of heart failure (HF). This study aims to explore the effect of AFL ablation on left ventricular (LV) function in right AFL patients with or without advanced heart diseases. METHODS Between January 2013 and December 2019, 149 patients underwent ablation for persistent AFL. Among them, 60 patients with persistent right atrial (RA) flutter had symptomatic HF and elevated natriuretic peptide levels. Group 1 consisted of 35 patients without advanced heart diseases, and group 2 consisted of 25 patients with prior history of ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) or surgery for valvular heart disease (VHD). Follow-up echocardiography was performed 6 months later. Improvement of LV performance was defined as LV ejection fraction (EF) increase ≥50% of baseline EF without clinical HF symptoms or LVEF recovery to ≥60%. RESULTS Group 2 had larger LV end-diastolic volume (LVEDV) and LV end-systolic volume than group 1. At follow-up, group 2 had larger LV end-systolic volume than group 1. Group 1 had more increase in LVEF than group 2 (21.7 ± 15.2% vs 4.1 ± 13.2%; P

Background: Patients with hyperthyroidism have higher risk of atrial fibrillation (AF). However, the risk of thromboembolic event in patients with hyperthyroidism-related AF is controversial. Objectives: The aim of the study was to examine the risk of thromboembolic events in AF patients with/without hyperthyroidism. Methods: The national retrospective cohort study enrolled AF population was derived from the Taiwan National Health Insurance Research Database. The comparison between the AF patients with clinical hyperthyroidism (HT-AF group) and AF patients without hyperthyroidism (non-thyroid AF group) was made in a propensity score matched cohort and in a real-world setting, of which, the CHA2DS2-VASc level was treated as a stratum variable. The outcomes were ischemic stroke and systemic thromboembolism. Results: There were 3,880 patients in HT AF group and 178,711 in non-thyroid AF group. After propensity score analysis, the incidence of thromboembolism event and ischemic stroke were lower in HT AF patients than non-thyroid AF patients (1.6 versus 2.2 events per 100 person-years; HR, 0.73; 95% CI, 0.64–0.82 and 1.4 versus 1.8 events per 100 person-years; HR, 0.74; 95% CI, 0.64–0.84, respectively) in the 4.3 ± 3.2 year follow up period. The differences persistently existed in those receiving anticoagulants or not. In AF patients without anticoagulants, the incidence densities of ischemic stroke/systemic thromboembolism were significantly lower in HT AF group than those in non-thyroid AF group at CHA2DS2-VASc scores ≤ 4 (HR, 0.41; 95% CI, 0.35–0.48, p < 0.001), while the differences disappeared in case of score ≥ 5 (HR, 0.80; 95% CI, 0.63–1.02, p = 0.071). Conclusion: Patients with HT AF had lower incidence of thromboembolic events as compared to non-thyroid AF patients. The threshold of CHA2DS2-VASc score for anticoagulation in AF patients with clinical hyperthyroidism should be further evaluated. Highlights The incidence of thromboembolic event was different between hyperthyroidism-related atrial fibrillation (HT-AF) and non-thyroid AF patients. Hyperthyroidism did not confer additional risk of thromboembolic event at CHA2DS2-VASc of ≤ 4. The benefit of anticoagulation strategy in patients with hyperthyroidism-related AF should be further evaluated, especially at low CHA2DS2-VASc score.

Background The association of postimplant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. Hypothesis This study aimed to explore the clinical outcomes of progressive postimplant TR after permanent pacemaker (PPM) implantation. Methods A total of 1670 patients who underwent a single ventricular or dual‐chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, history of HF, and baseline abnormal TR and TRPG were excluded. Finally, a total of 1075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and TRPG of >30 mmHg after implant. Results In 198 (18.4%) patients (group 1) experienced progressive postimplant TR and elevated TRPG, whereas 877 patients (group 2) did not have progressive postimplant TR. Group 1 had larger change in postimplant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p

OBJECTIVES In observational studies, patients with chronic kidney disease (CKD) exhibited a controversial risk of atrial fibrillation (AF) recurrence following radiofrequency (RF) or cryoballoon ablation compared with non-CKD patients. This meta-analysis analysed the impact of CKD on AF recurrence following ablation. METHODS We searched the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases for articles published between January 1, 2010, and May 31, 2020. In total, seven observational studies with 23 468 patients were analysed. Data included demographics, AF classification, left atrial size, incidence of AF recurrence, and ablation method. RESULTS The prevalence of CKD was 8.0% (7.6%-24.4%) in the AF ablation population. The CKD population was older and had a higher prevalence of diabetes mellitus, hypertension, and heart failure, a higher CHA2DS2-VASc score, larger left atrial dimension, and lower left ventricular ejection fraction compared with the non-CKD population. The CKD patients had a higher AF recurrence rate following ablation than non-CKD patients (odds ratio [OR], 3.71; 95% confidence interval (CI), 1.35-10.19). CKD was associated with higher AF recurrent risk after ablation in patients with only paroxysmal AF (OR = 4.81, 95% CI 2.48-9.35). CKD was associated with higher AF recurrent risk in patients receiving radiofrequency ablation (OR = 3.28, 95% CI 2.17-4.94) or cryoballoon ablation (OR = 6.50, 95% CI 2.24-18.89) and in Asian region (OR = 4.86, 95% CI, 2.69-8.78). CONCLUSIONS CKD population had worse outcomes in terms of AF recurrence following RF or cryoballoon ablation.

Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) share several risk factors related to arterial thromboembolism. No study has reported the differential contribution to arterial thromboembolic events and mortality between these two conditions in the same population. We therefore assessed the differential arterial thromboembolic events between AF and VTE.Methods: We included AF and VTE national cohorts derived from Taiwan National Health Insurance Research Database between 2001 and 2013. The eligible population was 314,861 patients in the AF cohort and 41,102 patients in the VTE cohort. The primary outcome was arterial thromboembolic events, including ischemic stroke, extracranial arterial thromboembolism (ECATE) and myocardial infarction (MI). Secondary outcomes were all-cause mortality and cardiovascular death.Results: After a 1:1 propensity matching, 32,688 patients in either group were analyzed. The risk of arterial thromboembolic events was lower in the VTE cohort than that in the AF cohort (subdistribution hazard ratio [SHR], 0.60; 95% confidence interval [CI], 0.57–0.62). The risk of ischemic stroke (SHR, 0.44; 95% CI, 0.42–0.46) and MI (SHR, 0.80; 95% CI, 0.72–0.89) were lower in the VTE cohort, while the risk of ECATE (SHR, 1.23; 95% CI, 1.14–1.33; particularly lower extremities) was higher in the VTE cohort. All-cause mortality rate was higher in the VTE cohort (HR, 1.18; 95% CI, 1.15–1.21) while the risk of cardiovascular death was lower in the VTE cohort (HR, 0.96; 95% CI, 0.93–0.995).Conclusions: Patients with AF had higher risks of arterial thromboembolic events compared to patients with VTE, despite having risk factors in common. The VTE cohort had higher risks of all-cause mortality and ECATE, particularly lower extremity events, compared to AF patients. The differential manifestations of thromboembolism sequelae and mortality between AF and VTE patients merit further investigation.

Background: Ivabradine is indicated for heart failure (HF) patients with reduced left ventricular ejection fraction who are in sinus rhythm. However, limited data are available with regards to the use of ivabradine in symptomatic HF patients with reduced EF (HFrEF) and a history of paroxysmal atrial fibrillation (AF). Methods: We conducted a multi-center observational matched cohort study enrolled patient who was diagnosed with symptomatic HFrEF from 2015/01/01 to 2018/12/31 with had a history of paroxysmal AF in Chang Gung Memorial Hospital medical database in Taiwan. After inverse probability of treatment weighting (IPTW), the outcomes of interest during a 12-month observation period were analyzed. The primary outcome was HF hospitalization and cardiovascular death. Results: A total of 2,042 patients were eligible for the study, of whom 887 were prescribed with ivabradine and 1,115 were not. After IPTW, the ivabradine group had a significant lower mean heart rate after 12 months than the non-ivabradine group (P < 0.05). The primary outcome was also significantly higher in the ivabradine group than the non-ivabradine group after 12 months (hazard ratio [HR] = 1.58; 95% confidence interval [CI], 1.26-2.00, P < 0.001). Moreover, the ivabradine group had a significantly higher event rate of HF hospitalization (HR = 1.56; 95% CI, 1.40-1.75, P < 0.001) and HF death (HR = 1.67; 95% CI, 1.14-2.44, P = 0.009) than the non-ivabradine group. Conclusions: Ivabradine treatment was associated with an increased risk of HF hospitalization in symptomatic HFrEF patients with a history of paroxysmal AF, and further prospective studies are warranted. Funding Information: This work was supported by a grant from Chang Gung Memorial Hospital, Taiwan (grant CGRPG6J0041, CMRPG6H0481 and CMRPG6H0482). Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: The Institutional Review Board of Chang Gung Memorial Hospital: (201900915B1).

Aims Anticoagulation therapy is indicated to prevent stroke in atrial flutter (AFL) and atrial fibrillation (AF) patients. However, the outcomes of solitary AFL patients may differ from those with AFL who develop AF during follow-up. This study aimed to investigate the differences in clinical outcomes: (i) among patients with solitary AFL, AF, and AFL developing AF thereafter and (ii) between solitary AFL patients with vs. without anticoagulation therapy. Methods and results This nationwide cohort study enrolled patients with solitary AFL, solitary AF, and AFL developing AF from a 12 years National Health Insurance Research Database in Taiwan. There were 230 367 patients without anticoagulation therapy in the solitary AF cohort, 8064 in the solitary AFL cohort, and 4495 in the AFL with AF cohort. The AFL with AF and solitary AF cohorts had higher incidences of ischaemic stroke and major bleeding than the solitary AFL cohort. Solitary AFL patients with anticoagulation therapy had a lower ischaemic stroke rate than those without (P

Background Currently, several geographies around the world remain underrepresented in medical device trials. The PANORAMA 2 study was designed to assess contemporary region-specific differences in clinical practice patterns of patients with cardiac implantable electronic devices (CIEDs). Methods In this prospective, multicenter, observational, multinational study, baseline and implant data of 4,706 patients receiving Medtronic CIEDs (Medtronic plc, Minneapolis, MN, USA; either de novo device implants, replacements, or upgrades) were analyzed, consisting of: 54% implantable pulse generators (IPGs), 20.3% implantable cardiac defibrillators (ICDs), 15% cardiac resynchronization therapy -defibrillators, and 5.1% cardiac resynchronization therapy -pacemakers, from 117 hospitals in 23 countries across four geographical regions between 2012 and 2016. Results For all device types, in all regions, there were fewer females than males enrolled, and women were less likely to have ischemic cardiomyopathy. Implant procedure duration differed significantly across the geographies for all device types. Subjects from emerging countries, women, and older patients were less likely to receive a magnetic resonance imaging-compatible device. Defibrillation testing differed significantly between the regions. European patients had the highest rates of atrial fibrillation (AF), and the lowest number of implanted single-chamber IPGs. Evaluation of stroke history suggested that the general embolic risk is more strongly associated with stroke than AF. Conclusions We provide comprehensive descriptive data on patients receiving Medtronic CIEDs from several geographies, some of which are understudied in randomized controlled trials. We found significant variations in patient characteristics. Several medical decisions appear to be affected by socioeconomic factors. Long-term follow-up data will help evaluate if these variations require adjustments to outcome expectations.

ObjectivesFemale sex is an inconsistent ischaemic stroke risk factor in patients with atrial fibrillation (AF). We hypothesised that the ischaemic stroke risk varies with age among women compared with men.MethodsWe retrieved the patients with newly diagnosed AF during 2001–2013 from Taiwan’s National Health Insurance Research Database. Patients with missing information, age ResultsAfter exclusion criteria, 87 369 men and 71 853 women remained for analysis (aged 73.1±14.4 years). After 1:1 PSM, we included 59 583 men (aged 73.5±13.7 years) and 59 583 women (aged 73.4±13.8 years) for analysis. We also stratified patients by age. The ischaemic stroke risk varied with age in women compared with men: lower in the ≤55 years (subdistribution HR (SHR)=0.75, 95% CI 0.62 to 0.90) and 56–65 years (SHR=0.87, 95% CI 0.78 to 0.98) groups, neutral in the 66–75 years group (SHR=1.01, 95% CI 0.94 to 1.08) and adverse in the >75 years group (SHR=1.14, 95% CI 1.09 to 1.19).ConclusionsThe female/male ischaemic stroke risk ratio varied with age. Only women aged >75 years had a higher risk, whereas women aged 2DS2-VASc score, used to make decision regarding anticoagulation treatment in AF patients.

AIMS Catheter ablation has become an effective treatment modality for atrial fibrillation (AF). However, the relationship between common pulmonary vein (PV) and recurrent atrial tachyarrhythmia (ATA) after PV isolation (PVI) remains controversial. This study aimed to explore the function of common PV on the risk of recurrent ATA after PVI. METHODS We identified a total of 191 patients who received radiofrequency catheter ablation for paroxysmal AF at our hospital between July 2010 and December 2017 for retrospective chart review. We collected the following data for analysis: results of preprocedural computed tomography, including the anatomy of PV and left atrial (LA) volume; the incidence of early- and late-onset recurrence of ATA. We compared these characteristics between the two groups defined by the presence or absence of the late-onset recurrence of ATA. RESULTS Compared to the no ATA recurrence group, the ATA recurrence group had larger LA size, larger LA end-diastolic and systolic volumes, larger maximal diameter of PV, higher prevalence of common PV, and higher incidence of early-onset recurrence of ATA. In multivariate logistic regression analyses, presence of common PV and early-onset recurrence were independently associated with late-onset recurrence of ATA. Compared to patients without common PV, patients with common PV had larger diameter of PV and higher incidence of late-onset recurrent ATA. CONCLUSION In patients with paroxysmal AF, early-onset recurrence of ATA and the presence of common PV were independently associated with late-onset recurrent ATA after radiofrequency catheter ablation.

Background MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored. Methods This case–control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria. Results Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls. Conclusions Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients.

Background: There are few reports about non-vitamin K antagonist oral anticoagulant (NOAC) treatment for resolution of left atrium (LA) or left atrial appendage (LAA) thrombus. LAA thrombus is an important cause of cardiogenic cerebral thromboembolism, and the detection rate increases due to more and more patients receiving catheter ablation. However, the results from NOAC use for LA or LAA thrombus are still unknown in real-world practice. The aim of this study was to discover the resolution of LA or LAA thrombus after anticoagulant treatment in real-world practice. Method: From January 2013 to December 2016, a total 864 patients underwent transesophageal echocardiography (TEE), and 41 cases of LA or LAA thrombus were detected in our hospital. Among them, a total of 22 patients underwent follow-up TEE to detect the resolution of LA or LAA thrombus. Result: The average age of the study patients was 72.0 ± 11 years old, and 61% were male. The average CHA2DS2-VASc scores were 3.76 ± 2.01 points. A total of 22 patients underwent follow-up TEE, and 19 (86.4%) patients presented LA or LAA thrombus resolution. The average resolution duration was 258.47 ± 218.17 days. One-year all-cause mortality was 4.9%, and the incidence of ischemic stroke was 4.9%. Most physicians favored titration of the dosage of NOAC or warfarin in real-world practice. Conclusion: In real-world practice, most physicians favored titration of the dosage of NOAC or warfarin for LA or LAA thrombus. LA or LAA thrombus could exist if the patient received a reduced dose of NOAC. High frequency of LAA or LA thrombi could resolve, and a low incidence of ischemic stroke occurred after adjustment of oral anticoagulant treatment.

Apoptosis occurs in atrial cardiomyocytes in mitral and tricuspid valve disease. The purpose of this study was to examine the respective roles of the mitochondrial and tumor necrosis factor-α receptor associated death domain (TRADD)-mediated death receptor pathways for apoptosis in the atrial cardiomyocytes of heart failure patients due to severe mitral and moderate-to-severe tricuspid regurgitation. This study comprised eighteen patients (7 patients with persistent atrial fibrillation and 11 in sinus rhythm). Atrial appendage tissues were obtained during surgery. Three purchased normal human left atrial tissues served as normal controls. Moderately-to-severely myolytic cardiomyocytes comprised 59.7±22.1% of the cardiomyocytes in the right atria and 52.4±12.9% of the cardiomyocytes in the left atria of mitral and tricuspid regurgitation patients with atrial fibrillation group and comprised 58.4±24.8% of the cardiomyocytes in the right atria of mitral and tricuspid regurgitation patients with sinus rhythm. In contrast, no myolysis was observed in the normal human adult left atrial tissue samples. Immunohistochemical analysis showed expression of cleaved caspase-9, an effector of the mitochondrial pathways, in the majority of right atrial cardiomyocytes (87.3±10.0%) of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial cardiomyocytes (90.6±31.4%) and left atrial cardiomyocytes (70.7±22.0%) of mitral and tricuspid regurgitation patients with atrial fibrillation. In contrast, only 5.7% of cardiomyocytes of the normal left atrial tissues showed strongly positive expression of cleaved caspase-9. Of note, none of the atrial cardiomyocytes in right atrial tissue in sinus rhythm and in the fibrillating right and left atria of mitral and tricuspid regurgitation patients, and in the normal human adult left atrial tissue samples showed cleaved caspase-8 expression, which is a downstream effector of TRADD of the death receptor pathway. Immunoblotting of atrial extracts showed that there was enhanced expression of cytosolic cytochrome c, an effector of the mitochondrial pathways, but no expression of membrane TRADD and cytosolic caspase-8 in the right atrial tissue of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial and left atrial tissues of mitral and tricuspid regurgitation patients with atrial fibrillation. Taken together, this study showed that mitochondrial pathway for apoptosis was activated in the right atria in sinus rhythm and in the left and right atria in atrial fibrillation of heart failure patients due to mitral and tricuspid regurgitation, and this mitochondrial pathway activation may contribute to atrial contractile dysfunction and enlargement in this clinical setting.

Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients.

Aims To evaluate the efficacy of bundled skin antiseptic preparation to prevent cardiac implantable electronic device (CIED) infections. Methods and results From January 2010 to November 2013, 665 consecutive patients were divided into two groups according to the strategy of skin preparation. In Period 1 (January 2010 to June 2012), 395 patients received the standard skin antiseptic preparation. In Period 2 (July 2012 to November 2013), 270 patients received a triple-step skin antiseptic preparation, ‘bundled skin antiseptic preparation’, consisting of applying 75% alcohol over anterior chest on the night before the index day, povidone-iodine 10 min before operation, and the standard skin antiseptic preparation before incision. During follow-up, the occurrence of CIED infection was recorded. Multiple logistic regression analysis was used to determinate the risk factors of CIED infection. During a mean follow-up of 26.9 ± 16.2 months, 20 episodes of CIED infection developed in 19 patients (2.9%), and the incidence of minor and major infection episodes was 2.2% and 0.8%, respectively. Patients with the bundled skin antiseptic preparation had a significantly lower incidence of CIED infection, compared with patients with the standard preparation (0.7 vs. 4.3%, P = 0.007). In multivariate analysis, pocket haematoma ( P = 0.020), atrial fibrillation ( P = 0.033), and complex procedures ( P = 0.047) were independent predictors for CIED infection. In contrast, the bundled skin antiseptic preparation was a significant predictor against CIED infection ( P = 0.014). Conclusion Pocket haematoma was the most important risk factor for CIED infection. The bundled skin antiseptic preparation strategy significantly reduced the risk of minor CIED infection.

Background: The radiofrequency (RF) maze procedure can effectively restore sinus rhythm in most patients with persistent atrial fibrillation (AF) and mitral disease. However, long-term results and predictors for late AF recurrence are still under investigation. Methods: From December 1995 to November 2011, 207 consecutive patients with persistent AF and mitral disease underwent RF maze procedure and concomitant mitral surgery. The mean age was 54±12.4 year-old. Mitral surgery was performed in all patients and concomitant procedures including tricuspid surgery, aortic valve surgery, and atrial septal defect closure were carried on 164 patients. Results: The in-hospital mortality was 3.9% (n=8) and late mortality was 8.2% (n=17). After a mean follow-up period of 101±50.9 months, 154 patients (74.4%) had long-term sinus conversion. A permanent pacer was implanted in 8 patients (3.9%). By Cox multivariate survival regression analysis, predictors for long-term sinus conversion were identified to be the duration of persistent AF, preoperative left atrial (LA) diameter, preoperative right atrial (RA) area, and preoperative beta-blocker use. The receiver operating characteristic (ROC) curve analysis showed that the best cutoff value for persistent AF duration, preoperative LA diameter, and preoperative RA area were 59.5 months, 59.85 mm, and 25.65 cm 2 . Conclusions: Longer persistent AF duration, larger preoperative LA diameter, larger preoperative RA area and preoperative beta-blocker use were the predictors for negative long-term outcome of RF maze procedure for the patients with persistent AF underwent concomitant mitral surgery. Timely referral of patients for surgery is mandatory.

Background. Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. Methods. Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. Results. Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P=0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. Conclusions. Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.

Background Atrial flutter ( AFL ) has been identified to be equivalent to atrial fibrillation ( AF ) in terms of preventing ischemic stroke, although differences exist in atrial rate, substrate, and electrophysiological mechanisms. This study aimed to investigate differences in clinical outcomes between nonvalvular AF and AFL . Methods and Results AF and AFL patients without any prescribed anticoagulation were enrolled from a 13‐year national cohort database. Under series exclusion criteria, ischemic stroke, heart failure hospitalization, and all‐cause mortality were compared between the groups in real‐world conditions and after propensity score matching. We identified 175 420 patients in the AF cohort and 6239 patients in the AFL cohort, and the prevalence of most comorbidities and frequency of medications were significantly higher in the AF group than the AFL group. In the real‐world setting the AF patients had higher incidence rates of ischemic stroke, heart failure hospitalization, and all‐cause mortality than the AFL patients (all P AF cohort was 1.63‐fold higher than in the AFL cohort ( P AF cohort was 1.70‐fold higher than in the AFL cohort ( P AF cohort was 1.08‐fold higher than in the AFL cohort ( P =0.002). Conclusions There were differences between AF and AFL in comorbidities and prognosis with regard to ischemic stroke, heart failure hospitalization, and all‐cause mortality.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the incidence and prevalence of AF are increasing, and the burden of AF is becoming huge. Many innovative advances have emerged in the past decade for the diagnosis and management of AF, including a new scoring system for the prediction of stroke and bleeding events, the introduction of non-vitamin K antagonist oral anticoagulants and their special benefits in Asians, new rhythm- and rate-control concepts, optimal endpoints of rate control, upstream therapy, life-style modification to prevent AF recurrence, and new ablation techniques. The Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the information and have appointed a jointed writing committee for new AF guidelines. The writing committee members comprehensively reviewed and summarized the literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation. This guideline presents the details of the updated recommendations, along with their background and rationale, focusing on data unique for Asians. The guidelines are not mandatory, and members of the writing committee fully realize that treatment of AF should be individualized. The physician's decision remains most important in AF management.

Background Differentially expressed genes in the left atria of mitral regurgitation (MR) pigs have been linked to peroxisome proliferator-activated receptor (PPAR) signaling pathway in the KEGG pathway. However, specific genes of the PPAR signaling pathway in the left atria of MR patients have never been explored. Methods This study enrolled 15 MR patients with heart failure, 7 patients with aortic valve disease and heart failure, and 6 normal controls. We used PCR assay (84 genes) for PPAR pathway and quantitative RT-PCR to study specific genes of the PPAR pathway in the left atria. Results Gene expression profiling analysis through PCR assay identified 23 genes to be differentially expressed in the left atria of MR patients compared to normal controls. The expressions of APOA1, ACADM, FABP3, ETFDH, ECH1, CPT1B, CPT2, SLC27A6, ACAA2, SMARCD3, SORBS1, EHHADH, SLC27A1, PPARGC1B, PPARA and CPT1A were significantly up-regulated, whereas the expression of PLTP was significantly down-regulated in the MR patients compared to normal controls. The expressions of HMGCS2, ACADM, FABP3, MLYCD, ECH1, ACAA2, EHHADH, CPT1A and PLTP were significantly up-regulated in the MR patients compared to patients with aortic valve disease. Notably, only ACADM, FABP3, ECH1, ACAA2, EHHADH, CPT1A and PLTP of the PPAR pathway were significantly differentially expressed in the MR patients compared to patients with aortic valve disease and normal controls. Conclusions Differentially expressed genes of the PPAR pathway have been identified in the left atria of MR patients compared with patients with aortic valve disease and normal controls.

Supplemental Digital Content is available in the text, Chronic kidney disease (CKD) increased the incident cardiac implantable electronic device (CIED) infection, but risk factors of CIED infection in CKD patients remain unclear. Patients who received new CIED implantation between January 1, 1997 and December 31, 2011 were selected from the Taiwan National Health Insurance Database and were divided into 3 groups: patients with normal renal function, CKD patients without dialysis, and CKD patient with dialysis. Two outcomes, CIED infection during index hospitalization and within 1 year after discharge, were evaluated. This study included 38,354 patients, 35,060 patients in normal renal function group, 1927 patients in CKD without dialysis group, and 1367 patients in CKD with dialysis group. CKD patients without dialysis (adjusted odds ratio [aOR], 2.14, 95% confidence interval [CI], 1.32-3.46) and CKD patients with dialysis (aOR, 3.78, 95% CI, 2.37-6.02) increased incident CIED infection during index hospitalization compared to patients with normal renal function. Use of steroid (aOR: 2.74, 95% CI, 1.08-6.98) increased the risk of CIED infection in CKD patients without dialysis while chronic obstructive pulmonary disease (COPD) (aOR: 2.76, 95% CI, 1.06-7.16) increased the risk of CIED infection in CKD patient with dialysis during index hospitalization. CKD is a risk of CIED infection during index hospitalization. Use of steroid and COPD are important risks factors for CIED infection in CKD patients.

Background Oxidative stress is linked with several cardiovascular diseases. However, the NADPH oxidase activity in severe mitral regurgitation patients with and without atrial fibrillation has not yet been explored. Methods This study involved 16 adult patients (eight patients with persistent atrial fibrillation and eight with sinus rhythm) with severe mitral and moderate-to-severe tricuspid regurgitation and five control patients without mitral and tricuspid disease. Atrial tissues of the right and left atrial appendages were obtained during surgery. Superoxide anion production was measured by lucigenin-enhanced chemiluminescence, and the expression of nox2 containing NADPH oxidase mRNA was measured by quantitative real-time RT-PCR. Additionally, immunohistochemical study was performed. Results NADPH-stimulated superoxide release was significantly higher than basal superoxide production from right [5671.9±3498.7 vs. 232.7±70.0 relative light units per second per milligram of protein (RLU s −1 mg protein −1 ), P =.008) and left atrial homogenates (6475.1±1890.8 vs. 229.0±79.6 RLU s −1 mg protein −1 , P =.008) in atrial fibrillation patients. The NADPH-stimulated superoxide release from right atrial homogenates was also significantly higher than basal superoxide production in sinus patients (6809.1±1327.1 vs. 244.2±65.5 RLU s −1 mg protein −1 , P =.008). Additionally, there was a borderline significant correlation between NADPH-stimulated superoxide production from left atrial homogenates and left atrial sizes ( r =0.683, P =.062) in atrial fibrillation patients. Membrane-bound nox2 containing NADPH oxidase mRNA expression was increased and was similar in both the atrial fibrillation patients and sinus patients. The NADPH-stimulated superoxide production in right atrial homogenates in control atrial samples was 1863.7±137.2 RLU s −1 mg protein −1 . Immunohistochemical study demonstrated increased expression of nox2 in myocytes with moderate-to-severe myolysis and hypertrophy. Conclusions Results of this study demonstrate that membrane-bound nox2 containing NADPH oxidase activity and expression in the atrial myocardium is increased in patients with severe mitral regurgitation, possibly contributing to atrial remodeling in this clinical setting.

Background The reported presence of DNA breaks, based on a positive reaction to the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) assay, in fibrillating human right atria of cardiac valve disease may suggest apoptotic myocyte death. However, TUNEL positivity may reflect conditions other than cell death. Methods This study comprised 27 adult patients (14 patients with persistent atrial fibrillation and 13 in sinus rhythm) with significant mitral and tricuspid valve diseases. Atrial tissues were obtained during surgery. Results Immunohistochemical study demonstrated that 31.1±12.2% of the myocytes had TUNEL-positive nuclei in the fibrillating right atria whereas 37.4±23.2% of the myocytes had TUNEL-positive nuclei in the right atrial myocardium in sinus rhythm ( p =0.505). However, most nuclei of TUNEL-positive myocytes in the right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair but never Ki-67, a replication-associated antigen (TUNEL + /PCNA + vs. TUNEL + /PCNA − , 30.5±10.8% vs. 1.2±1.5%, p =0.005, in the atrial fibrillation group and 32.8±18.6% vs. 4.6±8.1%, p =0.003, in the sinus group), suggesting that most TUNEL-positive myocytes were undergoing DNA repair. In addition, the incidence of TUNEL-positive myocytes significantly and positively correlated with the incidence of PCNA-positive myocytes ( r =0.5, p r =0.661, p Conclusions Cell death by apoptosis occurs in a small percentage of atrial cardiomyocytes in mitral and tricuspid valve diseases and DNA repair is more important and preserves the cardiomyocytes.

Background: Percutaneous coronary intervention (PCI) with stent implantation is now considered a safe and feasible treatment for stenosis of the unprotected left main coronary artery (ULMCA). Because few studies have focused on de novo distal ULMCA lesions, a propensity score-matched cohort study was conducted to compare bare metal stents (BMS) with drug-eluting stents (DES) for long-term outcomes following PCI. Methods and Results: This study reviewed the outcomes of patients undergoing PCI with DES (n=127) or BMS (n=51) for distal de novo ULMCA stenosis. The baseline demographic, angiographic and procedural characteristics differed between the 2 groups, indicating potential selection bias. The propensity score-matched cohort showed that the DES group had significantly less target lesion revascularization (TLR) and major adverse cardiovascular events (MACE) following PCI than the BMS group. Furthermore, heart failure (HF) of New York heart Association functional class III/IV was associated with an increased risk of TLR and MACE, whereas implantation of DES in patients with significant HF led to more favorable outcomes. Conclusions: Lower rates of TLR and MACE occurred in patients following PCI with DES implantation than with BMS implantation for distal ULMCA stenosis. Implantation of DES in patients with significant HF may improve the unfavorable outcome. When PCI is chosen to manage distal ULMCA stenosis, DES is the preferred stent type. (Circ J 2011; 75: 290-298)

This study analyzed the corrected QT dispersion (cQTd) before and at 24 hours after successful primary percutaneous coronary intervention (PCI) in 81 patients with single coronary artery disease and acute ST elevation myocardial in-farction. Major cardiovascular events (MACE) at 1 year were defined as death, nonfatal myocardial infarction, life-threatening arrhythmias, and heart failure hospitalization. The cQTd before primary PCI was significantly longer in patients without MACE than in patients with MACE (73.1 ± 29.3 versus 56.3 ± 25.2 msec, P = 0.026). The cQTd at 24 hours after primary PCI was significantly shorter in patients without MACE than in patients with MACE (38.4 ± 20.8 versus 50.8 ± 28.7 msec, P = 0.045). Thus, the absolute cQTd change was significantly higher in patients without MACE compared to patients with MACE (P = 0.001). By multivariate analysis, absolute cQTd change was an independent predictor for the development of MACE, with an odds ratio of 1.498 for each 10-msec decrement in absolute cQTd change (95 percent confidence interval, 1.157 to 1.939, P = 0.002). In conclusion, the absolute cQTd change after primary PCI was an independent predictor of the development of MACE in patients with single vessel disease and acute ST elevation myocardial infarction.

Eur J Clin Invest 2011; 41 (3): 299–307 Abstract Background Myolysis of atrial cardiomyocytes occurs in patients with severe mitral and tricuspid regurgitation. This morphological remodelling may involve autophagy. Methods This study comprised 20 patients (10 with long-standing persistent atrial fibrillation and 10 with sinus rhythm) with severe mitral and tricuspid regurgitation. Atrial appendageal tissues were obtained during surgery. The appearance of autophagosomes (LC3B) in myocytes can reflect autophagy induction. Complement 9 is used as a reliable marker of oncosis. Results In the fibrillating right atria, 68·4 ± 18·9% of total myocytes showed moderate-to-severe myolysis, while 64·2 ± 15·8% of total myocytes comprised these cells in right atrial myocardium with sinus rhythm. Immunohistochemical study revealed LC3B-positive myocytes in 8·0% of myocytes without myolysis, 11·9% of myocytes with mild myolysis and 49·4% of myocytes with moderate-to-severe myolysis in right atrial myocardium with sinus rhythm (P

This cohort study uses Taiwan National Health Insurance database data to evaluate the incidence of ischemic stroke, hospitalization for heart failure, and all-cause mortality among patients with atrial fibrillation and atrial flutter stratified by CHA2DS2-VASc score., Key Points Question Do clinical outcomes differ between atrial fibrillation and atrial flutter by CHA2DS2-VASc scores? Findings This nationwide cohort study of 219 416 age- and sex-matched individuals in Taiwan found that the incidence of ischemic stroke among patients with atrial flutter was significantly lower than that among patients with atrial fibrillation at a CHA2DS2-VASc score less than 5, whereas the incidences of heart failure hospitalization and all-cause mortality were different across different CHA2DS2-VASc scores. Meaning The current recommended level of CHA2DS2-VASc score (≥2) used to prevent ischemic stroke in patients with atrial flutter should be reevaluated and prospectively studied., Importance Current guidelines support treating atrial fibrillation (AF) and atrial flutter (AFL) as equivalent risk factors for ischemic stroke stratified by CHA2DS2-VASc scores, recommending anticoagulation therapy for patients with a CHA2DS2-VASc score of 2 or higher, but some studies found differences in clinical outcomes. Objective To investigate differences in clinical outcomes among AF, AFL, and matched control cohorts. Design, Setting, and Participants This nationwide cohort study analyzed data from the Taiwan National Health Insurance Research Database from January 1, 2001, through December 31, 2012. Follow-up and data analysis ended December 31, 2012. A total of 219 416 age- and sex-matched individuals participated in the study. Clinical outcomes were compared after stratification by CHA2DS2-VASc score (possible score range, 0-9; higher scores indicate greater risk of ischemic stroke). Main Outcomes and Measures Ischemic stroke, heart failure hospitalization, and all-cause mortality among the AF, AFL, and matched control cohorts were analyzed using Cox proportional hazards regression. Results This study comprised 188 811 patients in the AF cohort (mean [SD] age, 73.8 [13.4] years; 104 703 [55.5%] male), 6121 patients in the AFL cohort (mean [SD] age, 67.7 [15.8] years; 3735 [61.0%] male), and 24 484 patients in the matched control cohort (mean [SD] age, 67.3 [15.6] years; 14 940 [61.0%] male). The patients with AF were older, were more predominantly female, and had higher CHA2DS2-VASc scores than the patients with AFL and the control participants. After stratification by CHA2DS2-VASc score, the incidence densities (IDs; events per 100 person-years) of ischemic stroke (AF cohort: ID, 3.08; 95% CI, 3.03-3.13; AFL cohort: ID, 1.45; 95% CI, 1.28-1.62; controls: ID, 0.97; 95% CI, 0.92-1.03), heart failure hospitalization (AF cohort: ID, 3.39; 95% CI, 3.34-3.44; AFL cohort: ID, 1.57; 95% CI, 1.39-1.74; controls: ID, 0.32; 95% CI, 0.29-0.35), and all-cause mortality (AF cohort: ID, 17.8; 95% CI, 17.7-17.9; AFL cohort: ID, 13.9; 95% CI, 13.4-14.4; controls: ID, 4.2; 95% CI, 4.1-4.4) were significantly higher in the AF cohort than in the matched control cohort. For the AFL cohort vs the matched control cohort, the incidences of heart failure hospitalization and all-cause mortality were significantly higher across all levels, but the incidence of ischemic stroke was only significantly higher at CHA2DS2-VASc scores of 5 to 9. For the AF cohort vs the AFL cohort, the incidences of ischemic stroke and heart failure hospitalization were significantly higher at a CHA2DS2-VASc score of 1 or higher, but the incidence of all-cause mortality was significantly higher only at CHA2DS2-VASc scores of 1 to 3. Conclusions and Relevance This study found different clinical outcomes between patients with AFL and AF and those without AF and AFL. The current recommended level of the CHA2DS2-VASc score in preventing ischemic stroke in patients with AFL should be reevaluated.

The optimal right ventricular pacing site remains controversial. The aim of this study was to assess how acute right ventricular outflow tract (RVOT) pacing affects global left ventricular function and intraventricular dyssynchrony of the left ventricle.Thirty-six patients with sick sinus syndrome and intact intrinsic atrioventricular conduction were enrolled. All patients underwent dual-chamber permanent pacemaker implantation, with the atrial lead placed in the right atrial appendage and the right ventricle lead positioned at the septal site of the RVOT. Chamber size, dyssynchrony index, myocardial performance index, and global left ventricular ejection fraction were determined using transthoracic two-dimensional echocardiography, tissue Doppler echocardiography, and real-time three-dimensional echocardiography.RVOT pacing increased the myocardial performance index (0.42 +/- 0.21 with RVOT pacing vs 0.35 +/- 0.21 without RVOT pacing, P = .002) and decreased the global left ventricular ejection fraction on real-time 3-dimensional echocardiography (51.4 +/- 6.2% with RVOT pacing vs 55.9 +/- 7.1% without RVOT pacing, P = .001). Intraventricular dyssynchrony of the left ventricle induced by RVOT pacing was determined by increased septal-to-posterior wall motion delay (69.7 +/- 54.0 ms with RVOT pacing vs 22.8 +/- 22.3 ms without RVOT pacing, P.0001), increased systolic and diastolic dyssynchrony by tissue Doppler echocardiography, and increased systolic dyssynchrony index when assessed using real-time three-dimensional echocardiography (5.56 +/- 1.74% with RVOT pacing vs 4.05 +/- 1.61% without RVOT pacing, P.0001).Acute RVOT pacing adversely affects left ventricular function and increases intraventricular dyssynchrony in patients with sick sinus syndrome.

Objective The aim of this study was to examine the serum oxidative stress in patients with severe mitral regurgitation. Design and methods This study analyzed serum oxidative stress index in patients with severe mitral regurgitation [persistent atrial fibrillation (AF) or sinus rhythm], paroxysmal lone AF patients and healthy subjects. Results The serum oxidative stress index was significantly higher in the mitral regurgitation AF group and sinus group than in the lone AF group and healthy subjects (p

Background: Although recent studies suggest that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) achieves clinical outcomes comparable to coronary artery bypass graft surgery (CABG) for unprotected left main coronary artery (ULMCA) disease, long-term studies are rarely performed. Methods and Results: This study reviewed outcomes in 363 patients undergoing CABG (n=216), PCI with DES (n=94) or PCI with bare-metal stent (BMS) (n=53) for ULMCA stenosis between January 2000 and March 2007. The CABG group had more patients with diabetes (50.5%) and 3- or 4-vessel disease (77.3%) than the PCI group. Kaplan-Meier survival estimates showed higher TLR-free survival and revascularization-free survival in CABG group. Although cardiac-death-free survival did not significantly differ between the 3 groups, the DES group had the highest overall survival. Age (hazard ratio (HR): 1.060; 95% confidence interval (CI): 1.017-1.104) and diffuseness score (HR: 1.157; 95%CI: 1.019-1.313) were significant independent risk factors for cardiac death. Conclusions: There was higher TLR in the PCI group with either DES or BMS, but cardiac death did not significantly differ between the 3 groups. Advanced age and diffuse coronary atherosclerosis may increase the risk of cardiac death following revascularization. (Circ J 2009; 73: 705 - 712)

Background Acute ST-segment elevation myocardial infarction (STEMI) caused by left main coronary artery (LMCA) obstruction is uncommon. Although the link between this catastrophic disease and very high mortality is well recognized, even after undergoing emergent revascularization, the systemic risk stratification and long-term outcome are currently unclear. The clinical presentation, parameter-related in-hospital death and long-term outcomes of these patients with acute LMCA obstruction undergoing emergency revascularization were carefully reviewed. Methods and Results From January 2000 through December 2007, 1,588 patients were diagnosed to have STEMI and received emergent cardiac catheterization. The 38 (2.4%) of these 1,588 patients were enrolled into the present study due to LMCA obstruction. The analytical results identified the 30-day mortality rate as 42.1% (16/38). Multivariate analysis demonstrated that renal insufficiency was independently predictive of in-hospital mortality (odds ratio (OR): 5.642; p=0.029), whereas successful revascularization was independently predictive of freedom from in-hospital mortality (OR: 0.174; p=0.044). The cut-off value of a Parsonnet score >20 was strongly associated with 30-day mortality (p=0.002). Conclusions Even undergoing emergency revascularization for patients with acute LMCA obstruction, the in-hospital mortality remains very high. Additionally, the worse clinical outcome was observed in those with renal insufficiency and Parsonnet score of >20. (Circ J 2008; 72: 1598 - 1604)

Previous study demonstrated that the percentage of circulating endothelial progenitor cells was reduced in patients with coronary artery disease. However, the relationship of the percentage of circulating endothelial progenitor cells to the severity of coronary artery disease has not been investigated. The percentages of circulating endothelial progenitor cells were measured in 78 consecutive patients with unstable angina, as well as in 32 healthy volunteers. Dual-stained cells expressing CD34 and vascular endothelial growth factor receptor-2 were judged to be endothelial progenitor cells and were analyzed using flow cytometry. On stepwise multiple linear regression analysis, the percentages of circulating endothelial progenitor cells were independently decreased in patients with unstable coronary artery disease compared with those in the healthy volunteers (P < 0.05). Among patients with unstable coronary artery disease, the percentage of patients with at least one occluded vessel was significantly higher in patients with multi-vessel disease than in patients with single-vessel disease (P < 0.04). On stepwise multiple linear regression analysis, the percentages of circulating endothelial progenitor cells were independently decreased in patients with multi-vessel coronary artery disease compared with those in patients with single-vessel coronary artery disease (P < 0.03). Among patients with unstable coronary artery disease, the percentage of circulating endothelial progenitor cells was significantly related to the severity of coronary artery disease.

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 +/- 1.47; Gensini score: 31.3 +/- 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score > or =2 than in the risk control group (242.3 +/- 110.6 vs 209.8 +/- 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (beta = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than in the middle (176-246 pg/ml) and the lowest (

Background Percutaneous coronary intervention (PCI) is considered an excellent alternative treatment for unprotected left main coronary artery (ULMCA) stenoses. Most PCIs for ULMCA stenoses are performed via the transfemoral approach. The feasibility and safety of the transradial approach for this particular entity are unknown. The present study assessed the feasibility, safety and 1-year outcomes of the transradial approach for stenting of ULMCA stenoses. Methods and Results Of 131 consecutive patients who underwent coronary stenting for ULMCA stenoses, 113 patients (86.3%) received stenting using the transradial approach. All 113 procedures were performed with 6 or 7 French (Fr) catheters except 1 procedure requiring an 8 Fr guiding catheter for directional atherectomy. The technical success rate was 100%, and angiographic success was achieved in 96 patients (85.9%). Two patients had local hematoma (1.8%), and no procedure-related deaths, Q-wave myocardial infarction, repetitive PCI, stroke or emergent coronary artery bypass graft surgery during hospitalization were noted. One (0.9%) in-hospital cardiac death occurred due to ventricular tachyarrhythmia. More than half of our patients stayed in hospital by ≤3 days. The 1-year target lesion revascularization and cardiac death rate were 14.2% and 3.5%, respectively. Conclusions This investigation demonstrated the feasibility, safety and accepted short-term clinical outcomes of transradial stenting for ULMCA stenosis. This procedure may offer a feasible alternative to the transfemoral approach. (Circ J 2007; 71: 855 - 861)

Background Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. Methods and Results Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07–0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08–0.83; P = 0.023). Conclusions There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

We assessed whether the simultaneous sequential strategy could (1) achieve additional sinus restoration for those patients who were not in sinus rhythm while coming off bypass after modified left maze procedure and (2) attain the same long-term success rates as the bi-atrial maze procedure in patients with persistent atrial fibrillation (AF) and mitral valve disease.Twenty-seven consecutive patients - ten men and 17 women with a mean age of 52 +/- 13 years, all with persistent AF and mitral valve disease - underwent the modified maze procedure with the simultaneous sequential strategy. In the first phase, the modified left atrial maze operation was carried out with concomitant valvular surgery; the right side maze operation was subsequently carried out as a second phase of the sequential strategy only if AF re-appeared following the spontaneous restoration of heart beats during the operation.Twenty patients (74.1%) underwent the left atrial maze procedure only, and seven patients (25.9%) required the subsequent right atrial maze procedure as part of the sequential strategy. At a mean follow-up of 15.1 +/- 7.7 months, six of the 27 patients (22.2%) who underwent additional right atrial maze procedure had restored sinus rhythm. At a mean follow-up of 17.8 +/- 7.3 months, 24 of the 27 patients (88.9%) had restored sinus rhythm and 22 patients (81.5%) had restored bi-atrial transport function (right atrial filling fraction: 40.8 +/- 11.7%; left atrial filling fraction: 22.9 +/- 8.1%) after application of the sequential strategy.Compared with modified left atrial maze procedure, the application of the simultaneous sequential strategy successfully restored sinus rhythm in an additional 22.2% of patients with persistent AF. The overall sinus conversion rate of 88.9% was comparable with that of the standard bi-atrial maze procedure.

Background The association between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognostic outcomes in patients after ischemic stroke remains unknown. The present study tested the hypothesis that NT-proBNP level is noticeably increased after ischemic stroke and that elevated NT-proBNP is associated with unfavorable clinical outcomes (UFCO). Methods and Results Blood samples for NT-proBNP levels were collected serially and examined with sandwich immunoassay after acute ischemic stroke in 86 consecutive patients. The NT-proBNP levels were also measured in 30 healthy control volunteers and 30 at-risk control subjects. The NT-proBNP levels were significantly higher at 4 intervals after ischemic stroke than in healthy and at-risk control subjects (all p