An open-label randomized noninferior study of generic name and brand name of propafenone for rhythm control in patients with paroxysmal atrial fibrillation.

BACKGROUND: Propafenone is a class IC antiarrhythmic agent that is commonly used as the first-line therapy for patients with paroxysmal atrial fibrillation (AF) in Taiwan. This study compared the efficacy and safety of generic (Rhynorm) and brand name (Rytmonorm) propafenone for rhythm control of paroxysmal AF in Taiwan. METHODS: This was an open-label randomized multicenter noninferior study conducted in Taiwan. We enrolled 76 patients with AF. To investigate the efficacy of propafenone, we used a wearable electrocardiogram (ECG) event recorder to evaluate the daily burden of AF episodes in patients for 24 weeks. The primary efficacy endpoint was the frequency of AF with clinical significance, which was indicated by AF duration ≥30 seconds. The safety endpoints included proarrhythmic or hemodynamic adverse events. RESULT: To analyze the efficacy and safety of these agents, 71 patients (five patients with screen failure) were randomized to two groups, specifically a Rhynorm group (n = 37) and a Rytmonorm group (n = 34), for 24 weeks of the treatment period. The baseline patient characteristics were comparable between the groups. However, the Rhynorm group was older (65.4 ± 8.40 vs 59.8 ± 10.8 years; p = 0.02). The primary efficacy endpoint at week 24 decreased by 4.76% ± 18.5% (from 24.3% ± 33.9% to 19.0% ± 28.7%; p = 0.13) in the Rhynorm group and by 3.27% ± 15.2% (from 16.9% ± 26.4% to 13.6% ± 19.2%; p = 0.22) in the Rytmonorm group, with an intergroup difference of 1.5% ± 17.0%; p = 0.71. This finding indicates that Rhynorm is not inferior to Rytmonorm ( p = 0.023 for noninferiority). The safety profile of the agents was comparable between the two groups. CONCLUSION: Our results verified that Rhynorm was noninferior to Rytmonorm in terms of efficacy and safety for treating paroxysmal AF in Taiwan ( ClinicalTrials.gov Identifier: NCT03674658).

An observational study on the effect of premature ventricular complex burden on long-term outcome.

The long-term clinical impact of premature ventricular complexes (PVCs) on mortality and morbidity has not been fully studied. This study aimed to investigate the association between the burden of PVCs and adverse clinical outcome.A total of 5778 subjects, who were pacemaker-free and ventricular tachycardia-free at baseline, received 24-hour electrocardiography monitoring between January 1, 2002 and December 31, 2004. Clinical event data were retrieved from the Bureau of National Health Insurance of Taiwan. Multivariate Cox hazards regression models and propensity-score matching were applied to assess the association between PVCs and adverse clinical outcome.Average follow-up time was 10[REPLACEMENT CHARACTER]±â€Š1 year. In all, 1403 subjects expired, 1301 subjects were hospitalized in the cardiovascular (CV) ward, 3384 were hospitalized for any reason, and 631 subjects developed new-onset heart failure (HF). The optimal cut-off PVC frequency (12 beats per day) was obtained through receiver operator characteristic curves, with a sensitivity of 58.4% and specificity of 59.8%. Upon multivariate analysis, a PVC frequency >12 beats per day was an independent predictor for all mortality (hazard ratio [HR]: 1.429, 95% confidence interval [CI]: 1.284-1.590), CV hospitalization (HR: 1.127, 95% CI: 1.008-1.260), all-cause hospitalization (HR 1.094, 95% CI: 1.021-1.173), and new-onset HF (HR: 1.411, 95% CI: 1.203-1.655). Subjects with a PVC frequency >12 beats per day had an increased risk of cardiac death attributable to HF and sudden cardiac death. The incidence rates for mortality and HF were significantly increased in cases of raised PVC frequency. Propensity-score matching analysis also echoed the main findings.Increased PVC burden was associated with a higher incidence of all-cause mortality, CV hospitalization, all-cause hospitalization, and new-onset HF which was independent of other clinical risk factors.

2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the management of atrial fibrillation.

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.

Association of Single Nucleotide Polymorphisms with Atrial Fibrillation and the Outcome after Catheter Ablation.

BACKGROUND: The association of gene variants with atrial fibrillation (AF) type and the recurrence of AF after catheter ablation in Taiwan is still unclear. In this study, we aimed to investigate the relationships between gene variants, AF type, and the recurrence of AF. METHODS: In our investigation, we examined 383 consecutive patients with AF (61.9 ± 14.0 years; 63% men); of these 383 patients, 189 underwent catheter ablation for drug-refractory AF. Thereafter, the single nucleotide polymorphisms rs2200733, and rs7193343 were genotyped using real-time polymerase chain reaction. RESULTS: The rs7193343 variant was independently associated with non-paroxysmal AF (non-PAF). In the PAF group, the rs7193343 variant was independently associated with AF recurrence after catheter ablation. However, the rs2200733 variant was not associated with AF recurrence in this group. The combination of the rs7193343 and rs2200733 risk alleles was associated with a better predictive power in the PAF patients. In contrast, in the non-PAF group, the SNPs were not associated with recurrence. The rs7193343 and rs2200733 variants were not associated with different atrial voltage and activation times. CONCLUSIONS: The rs7193343 variants were associated with AF recurrence after catheter ablation in PAF patients but not in non-PAF patients. The rs7193343 CC variant was independently associated with non-PAF.

Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.

INTRODUCTION: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS: Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

Periesophageal vagal plexus injury is a favorable outcome predictor after catheter ablation of atrial fibrillation.

BACKGROUND: Collateral damage to periesophageal vagal plexus associated with symptomatic gastric hypomotility and associated symptoms are not uncommon after catheter ablation of atrial fibrillation (AF). The injury may indicate transmural ablation lesions. OBJECTIVE: The purpose of this study was to evaluate the periesophageal vagal plexus injury (PNI) and long-term outcome after catheter ablation of AF. METHODS: A total of 441 consecutive patients with AF (mean age 54.71 ± 10.52 years; 134 women) who underwent catheter ablation (paroxysmal AF, n = 312; persistent AF, n = 129) were retrospectively enrolled from 2011 to 2013; group 1 was defined as patients with PNI and associated symptoms (n = 88), and group 2 was defined as patients without PNI or associated symptoms (n = 353). Baseline characteristics and electrophysiological properties were collected to analyze the relationship between PNI and clinical outcome. The association of AF recurrence after catheter ablation and PNI symptoms was also investigated. RESULTS: During a mean follow-up period of 37.3 ± 0.94 months, group 1 had longer AF-freedom days in sinus rhythm after AF ablation and had less recurrence after the blanking period compared with group 2 (mean recurrence days, 1254.22 ± 45.26 days vs 1065.21 ± 33.35 days; P < .01). Multivariate analysis also revealed that PNI was an independently protective predictor of AF recurrence (hazard ratio 0.527; 95% confidence interval 0.289-0.959; P = .036). There was no difference in baseline characteristics, CHA2DS2-VASc score, or echocardiography follow-up duration. CONCLUSION: PNI and associated symptoms are not uncommon after catheter ablation of AF. A better long-term outcome is thereby independently predicted, suggesting transmural ablation lesions during pulmonary vein isolation.

The assessment of anticoagulant activity to predict bleeding outcome in atrial fibrillation patients receiving dabigatran etexilate.

Special circumstances may require the measurement of the anticoagulant effect of dabigatran etexilate. No data currently link any given coagulation test to bleeding outcomes in patients receiving dabigatran etexilate for atrial fibrillation. Nonvalvular atrial fibrillation patients receiving dabigatran etexilate of 110 mg (DE110) or 150 mg (DE150) were consecutively enrolled. The hemoclot thrombin inhibitor (HTI) assay, prothrombin time, and activated partial thromboplastin time (APTT) measurements were correlated with bleeding events during a prospective follow-up. There were 17 bleeding events (8.2%) in 208 patients (74.7 ±â€Š10.3 years old, 67.9% male, median follow-up: 364 days), whereas 15 patients with bleeding events used DE110. Compared with DE110, the patients receiving DE150 were younger and more often male and had lower HAS-BLED and CHA2DS2VASc scores and better renal function. Patients' HTI levels were very variable (DE110, 10-90th percentile: 20.5-223.9 ng/ml). A receiver-operator characteristic curve gave a median cutoff HTI level of 117.7 ng/ml to predict bleeding events (C-statistics: 0.65; P = 0.036), but no cutoff could be determined for prothrombin time or APTT. Based on the Kaplan-Meier analysis, a dabigatran etexilate level greater than 117.7 ng/ml was associated with a higher bleeding rate (15.4% vs. 4.9%, P = 0.01). After multivariate Cox regression analysis, HTI levels, history of stroke, and male sex were independent risk factors for bleeding events. Dabigatran etexilate-HTI levels were independently associated with bleeding in patients receiving routine clinical care. Blood sampling at multiple time points might be needed to increase reliability because of high variation of dabigatran etexilate-HTI levels.

Radiofrequency catheter ablation of ventricular arrhythmias originating from the continuum between the aortic sinus of Valsalva and the left ventricular summit: Electrocardiographic characteristics and correlative anatomy.

BACKGROUND: Radiofrequency ablation of ventricular arrhythmias (VAs) originating from the continuum between the aortic sinus of Valsalva (ASV) and the left ventricular (LV) summit is a challenge. OBJECTIVES: The objectives of this study were to investigate the electrocardiographic, electrophysiological, and anatomical characteristics of VAs and to develop an algorithm for predicting the successful ablation site. METHODS: We recruited 66 patients (mean age, 47 ± 15 years; 42 male patients) with symptomatic VAs originating from the continuum between the ASV and the LV summit who underwent radiofrequency ablation. Patients were classified into 4 groups (group 1: ASV, n = 20; group 2: subvalvular region, n = 15; group 3: great cardiac vein/anterior interventricular vein [GCV/AIV], n = 16; group 4: epicardium requiring pericardial access, n = 15). The QRS morphological characteristics of VAs were compared between the 4 groups. RESULTS: Electrocardiographic analysis revealed that the aVL/aVR Q-wave ratio is useful in the prediction of successful ablation sites in the ASV, subvalvular area, GCV/AIV, and epicardium requiring pericardial access at cutoff values of ≤1.415, 1.416-1.535, 1.536-1.740, and >1.740, respectively. The aVL/aVR Q-wave ratio was well correlated with the distance between the successful ablation site and the tip of the LV summit. A distance of >18.9 mm and an LV myocardial thickness of >9.1 mm predicted the need for the epicardial or GCV/AIV approaches. There were no major procedural complications. Eight patients (12.1%) developed VA recurrence during a mean follow-up of 15.9 months (interquartile range 9.2-24.2 months). CONCLUSION: The aVL/aVR Q-wave ratio is a useful parameter for predicting the successful ablation sites of VAs originating from the continuum between the ASV and the LV summit.

Additive Value of Heart Rate Variability in Predicting Obstructive Coronary Artery Disease Beyond Framingham Risk.

BACKGROUND: Heart rate variability (HRV) is usually reduced in patients with CAD. We therefore investigated whether reduced HRV is predictive of angiographic CAD beyond Framingham risk in patients with stable angina. METHODS AND RESULTS: A total of 514 patients (age, 66.1 ± 14.3 years, 358 men) were enrolled. Holter ECG was performed before catheterization, and 24-h HRV was analyzed in both the frequency domain (VLF, LF, HF and total power) and the time domain (SDNN, SDANN, RMSSD and pNN20). Angiographic CAD was defined as ≥ 50% diameter reduction of 1 or more coronary arteries. On coronary angiography 203 patients (39.6%) had angiographic CAD. Patients with CAD had significantly higher Framingham risk and lower HRV according to both frequency and time domain parameters. After controlling for age, gender, heart rate, SBP, renal function, lipids and Framingham risk, reduced HRV indices remained predictors of CAD (OR, 95% CI for LF, HF, SDNN, RMSSD and pNN20: 0.81, 0.66-0.99; 0.77, 0.63-0.94; 0.75, 0.59-0.96; 0.72, 0.58-0.88; and 0.76, 0.62-0.94, respectively). On subgroup analysis, HRV parameters appeared to be predictive of CAD only in subjects with high Framingham risk or diabetes. CONCLUSIONS: Reduced HRV is predictive of CAD in patients with stable angina, independent of traditional risk factors and Framingham risk. The predictive value of HRV may be relevant only in subjects with high Framingham risk or diabetes.

Prognostic Significance of Premature Atrial Complexes Burden in Prediction of Long-Term Outcome.

BACKGROUND: The prognostic significance of premature atrial complex (PAC) burden is not fully elucidated. We aimed to investigate the relationship between the burden of PACs and long-term outcome. METHODS AND RESULTS: We investigated the clinical characteristics of 5371 consecutive patients without atrial fibrillation (AF) or a permanent pacemaker (PPM) at baseline who underwent 24-hour electrocardiography monitoring between January 1, 2002, and December 31, 2004. Clinical event data were retrieved from the Bureau of National Health Insurance of Taiwan. During a mean follow-up duration of 10±1 years, there were 1209 deaths, 1166 cardiovascular-related hospitalizations, 3104 hospitalizations for any reason, 418 cases of new-onset AF, and 132 PPM implantations. The optimal cut-off of PAC burden for predicting mortality was 76 beats per day, with a sensitivity of 63.1% and a specificity of 63.5%. In multivariate analysis, a PAC burden >76 beats per day was an independent predictor of mortality (hazard ratio: 1.384, 95% CI: 1.230 to 1.558), cardiovascular hospitalization (hazard ratio: 1.284, 95% CI: 1.137 to 1.451), new-onset AF (hazard ratio: 1.757, 95% CI: 1.427 to 2.163), and PPM implantation (hazard ratio: 2.821, 95% CI: 1.898 to 4.192). Patients with frequent PAC had increased risk of mortality attributable to myocardial infarction, heart failure, and sudden cardiac death. Frequent PACs increased risk of PPM implantation owing to sick sinus syndrome, high-degree atrioventricular block, and/or AF. CONCLUSIONS: The burden of PACs is independently associated with mortality, cardiovascular hospitalization, new-onset AF, and PPM implantation in the long term.

Factors predisposing to ventricular proarrhythmia during antiarrhythmic drug therapy for atrial fibrillation in patients with structurally normal heart.

BACKGROUND: Ventricular arrhythmia (VA) can occur during propafenone therapy in atrial fibrillation (AF) patients with structurally normal heart. OBJECTIVE: The purpose of this study was to evaluate the incidence and characteristics of propafenone-associated VAs in AF patients with structurally normal heart. METHODS: We studied and compared the risk of new-onset VAs between AF patients with structurally normal heart taking and those not taking propafenone in a nationwide longitudinal cohort in Taiwan (n = 127,197 since 2000). We then investigated the association between propafenone and VA in AF patients with structurally normal heart in a single-center database (n = 396). RESULTS: In the nationwide cohort, 102 patients (0.008% per patient-year) developed ventricular tachycardia (VT)/ventricular fibrillation (VF) during a follow-up period of 9.8 ± 3.5 years. After multivariate Cox regression analysis, propafenone treatment was a significant risk factor for new-onset VT/VF with a hazard ratio (HR) of 3.59 (95% confidence interval [CI] 1.30-9.89, P = .0136). Propafenone treatment offered protection against ischemic stroke with HR 0.649 (95% CI 0.55-0.77, P<.001). In the single-center study using ECG and medical records, the presence of inferior J wave, wider QRS, and old age were independent risk factors for VA after adjustment for clinical, biochemical, and echocardiographic variables. CONCLUSION: Albeit with low incidence, propafenone therapy for AF was associated with new-onset VA in the nationwide longitudinal cohort study in Taiwan. Old age, presence of inferior lead J wave, and wider QRS on ECG were significant risk factors in our single-center study.

Current and state of the art on the electrophysiologic characteristics and catheter ablation of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited genetic disease caused by defective desmosomal proteins, and it has typical histopathological features characterized by predominantly progressive fibro-fatty infiltration of the right ventricle. Clinical presentations of ARVD/C vary from syncope, progressive heart failure (HF), ventricular tachyarrhythmias, and sudden cardiac death (SCD). The 2010 modified Task Force criteria were established to facilitate the recognition and diagnosis of ARVD/C. An implantable cardiac defibrillator (ICD) remains to be the cornerstone in prevention of SCD in patients fulfilling the diagnosis of definite ARVD/C, especially among ARVD/C patients with syncope, hemodynamically unstable ventricular tachycardia (VT), ventricular fibrillation, and aborted SCD. Further risk stratification is clinically valuable in the management of patients with borderline or possible ARVD/C and mutation carriers of family members. However, given the entity of heterogeneous penetrance and non-uniform phenotypes, the standardization of clinical practice guidelines for at-risk individuals will be the next frontier to breakthrough. Antiarrhythmic drugs are prescribed frequently to patients experiencing frequent ventricular tachyarrhythmias and/or appropriate ICD shocks. Amiodarone is the recommended drug of choice. Radiofrequency catheter ablation (RFCA) has been demonstrated to effectively eliminate the drug-refractory VT in patients with ARVD/C. However, the efficacy and clinical prognosis of RFCA via endocardial approach alone was disappointing prior to the era of epicardial approach. In recent years, it has been proven that the integration of endocardial and epicardial ablation by targeting the critical isthmus or eliminating abnormal electrograms within the diseased substrates could yield higher acute success and lower recurrence of ventricular tachyarrhythmias during long-term follow-up. Heart transplantation is the final option for patients with extensive disease, biventricular HF with uncontrollable hemodynamic compromise, and refractory ventricular tachyarrhythmias despite aggressive medical and ablation therapies.

Long-Term Follow-Up of Catheter Ablation of Ventricular Arrhythmias: Experiences from a Tertiary Referral Center in Taiwan.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an alternative therapeutic management for drug-refractory ventricular arrhythmias (VA). However, long-term follow-up of clinical outcome after RFCA for VAs in Taiwan remains unknown. METHODS: From 1999 to 2013, patients undergoing RFCA for VAs from a single referral center were consecutively enrolled. The annual distribution of cases, clinical characteristics, etiology, disease entity and electrophysiological studies were investigated. The clinical outcomes and recurrences between distinct entities were compared. RESULTS: A total of 502 patients receiving RFCA of VAs were eligible, including 388 patients for idiopathic VAs and 114 for substrate VAs. The annual distribution displayed a tendency towards a gradual increase in ablation cases within 2009-2013 compared with the prior decade (p < 0.001). Acute success was achieved in 453 patients (90.2%), partial success in 3 (0.6%), and failed ablation in 46 (9.2%). During a mean follow-up of 39.77 ± 48.75 months, 126 (25.1%) patients developed recurrences. Kaplan-Meier analysis demonstrated better prognosis after RFCA in patients with idiopathic fascicular VT and RVOT VAs (p < 0.001) and attenuation of the occurrences of sustained VT/VF, ICD therapies, and mortality in patients with BrS and ARVD/C (p = 0.036), as well as overall ICD interventions in substrate VAs (p < 0.001). CONCLUSIONS: RFCA could be an effective and alternative strategy in the elimination of idiopathic VAs and prevention of malignant events in substrate VAs at an experienced referral center in Taiwan. Distinct location of arrhythmogenic trigger and disease entities may result in non-uniform recurrences and prognosis. KEY WORDS: Idiopathic; Radiofrequency catheter ablation; Recurrence; Substrate; Ventricular arrhythmias.

Long-term outcome of multiform premature ventricular complexes in structurally normal heart.

BACKGROUND: Multiform premature ventricular complexes (PVCs) are common electrocardiographic abnormalities in patients with structurally normal hearts. However, the prognostic value of these complexes remains unclear. This study aimed to clarify the role of PVC polymorphism in predicting adverse outcomes. METHODS AND RESULT: We examined the database for 24-hour electrocardiography monitoring between January 1, 2002 and December 31, 2004. We analyzed 3351 individuals with apparently normal hearts. Kaplan-Meier curves and multivariate Cox proportional hazards models were employed to estimate the effect of multiform PVC and uniform PVC on the number of incident adverse events. Average follow-up time was 10±1years. Patients with multiform PVC were older and had a higher prevalence of comorbidities. In multivariate analysis, patients with multiform PVC had an increased incidence of mortality (hazard ratio [HR]: 1.642, 95% confidence interval [CI]: 1.327-2.031), hospitalization (HR: 1.196, 95% CI: 1.059-1.350), cardiovascular hospitalization (HR: 1.289, 95% CI: 1.030-1.613), new-onset heart failure (HF; HR: 1.456, 95% CI: 1.062-1.997), transient ischemic accident (HR: 1.411, 95% CI 1.063-1.873), and new-onset atrial fibrillation (AF; HR: 1.546, 95% CI: 1.058-2.258) compared to the group without PVC. Patients with multiform PVC had a higher rate of mortality (HR: 1.231, 95% CI: 1.033-1.468) and all cause-hospitalization (HR: 1.147, 95% CI: 1.025-1.283) compared with patients with uniform PVC. CONCLUSION: The presence of multiform PVC was associated with a higher incidence of mortality, hospitalization, transient ischemic attack, new-onset AF, and new-onset HF independent of other clinical risk factors.

Colchicine suppresses atrial fibrillation in failing heart.

BACKGROUND: This study aimed to investigate the mechanism by which colchicine suppresses atrial fibrillation (AF) in a rabbit heart failure (HF) model. METHODS AND RESULTS: HF was induced by coronary ligation. Using the Langendorff perfusion system, monophasic action potentials were recorded in the left atrial appendage (LAA) of normal rabbits (n=6) and HF rabbits (n=6) treated with colchicine (100 µM) followed by colchicine (100 µM) plus paclitaxel (5 µM). Collagen content and mRNA and protein expression of ion channels through the PI3K/AKT/eNOS signaling pathway were evaluated in LAA of normal rabbits (n=6) and HF rabbits treated with vehicle (n=6) or colchicine (n=6) intraperitoneal injection for 2 days. Colchicine decreased action potential duration (74.1±2.6 vs 91.8±3.3 ms, P<0.001), effective refractory period, and maximum slope of the restitution curve in HF LAA. However, these effects were reversed by paclitaxel. The incidence of early afterdepolarizations, delayed afterdepolarizations, and AF inducibility was significantly lower after colchicine perfusion than at baseline or after colchicine plus paclitaxel perfusion. Cardiac function increased and LA fibrosis decreased after colchicine treatment. mRNA and protein expression of Kir2.1, Kv1.4, Kv1.5, Kv7.1, Cav1.2, and SERCA2a were upregulated after colchicine treatment, as was mRNA expression of PI3K, AKT, and eNOS. CONCLUSION: Colchicine regulates ion channel gene expression and activates the PI3K/AKT/eNOS signaling pathway in HF rabbits, which may reverse atrial remodeling and suppress AF.

Incidence and risk of atrial fibrillation in sleep-disordered breathing without coexistent systemic disease.

BACKGROUND: Although the link between sleep-disordered breathing (SDB) and atrial fibrillation (AF) has been reported, a population-based longitudinal cohort study was lacking. The goal of the present study was to investigate the AF risk carried by SDB, using the National Health Insurance Research Database in Taiwan. METHODS AND RESULTS: From 2000 to 2001, a total of 579,521 patients who had no history of cardiac arrhythmias or significant comorbidities were identified. Among them, 4,082 subjects with the diagnosis of SDB were selected as the study group, and the remaining 575,439 subjects constituted the control group. The study endpoint was the occurrence of new-onset AF. During a follow-up of 9.2±2.0 years, there were 4,023 patients (0.7%) experiencing new-onset AF. The occurrence rate of AF was higher in patients with SDB compared to those without it (1.3% vs. 0.7%, P<0.001). The AF incidences were 1.38 and 0.76 per 1,000 person-years for patients with and without SDB, respectively. After anadjustment for age and sex, SDB was a significant risk factor of AF with a hazard ratio of 1.536. The AF risk increased with increasing clinical severity of SDB, represented by the requirement of continuous positive airway pressure use. CONCLUSIONS: SDB itself, without the coexistence of other systemic diseases, was a risk factor of AF.

Relationship between intrinsic cardiac autonomic ganglionated plexi and the atrial fibrillation nest.

BACKGROUND: Spectral analysis of the left atrium can identify high dominant frequency (DF) sites, which might play a role in the perpetuation of atrial fibrillation (AF). Furthermore, the role of the cardiac autonomic nervous system (CANS) in the genesis of AF has been demonstrated. The relationship between CANS and the high-DF sites (AF nest) was the aim of the investigation. METHODS AND RESULTS: In 12 dogs, high frequency stimulation was applied to locate 4 major left atrial (LA) ganglionated plexi (GPs). An Ensite Array and a mapping catheter were delivered into the left atrium for electroanatomical mapping. During sinus rhythm, spectral analysis was performed on the bipolar electrograms in the left atrium before and after epicardial GP ablation. The majority of AF nests were close to the GPs (52±18% of total AF nests). After GP ablation, the mean LA DF values decreased from 54±7Hz to 49±4Hz (P=0.023), and DF values of the AF nest decreased from 93±2Hz to 87±4Hz (P=0.001). Most of the previous AF nest sites close to the GPs disappeared (85±23%). The surface area of the AF nest decreased from 9±5cm(2) to 3±2cm(2) (P=0.001). CONCLUSIONS: Catheter ablation of the GP decreased the DF values, AF nest areas and diminished the number of AF nests; particularly those close to the GPs, indicating that the CANS might play an important role in the mechanism of the AF nest.

Long-Term Prognosis in Recipients of Implantable Cardioverter-Defibrillators for Secondary Preventions in Taiwan - A Multicenter Registry Study.

BACKGROUND: The use of an implantable cardioverter-defibrillator (ICD) has a proven capacity to prevent sudden cardiac death (SCD), and can also improve survival duration in well-selected patients. The goal of the present study was to investigate the long-term prognosis and predictors of mortalities among ICD recipients in Taiwan. METHODS: From 1998 to 2009, 238 consecutive patients who experienced SCDs or life-threatening ventricular tachyarrhythmias without correctable causes and received ICD implantations in 3 medical centers (Taipei, Taichung and Kaohsiung Veterans General Hospital) were enrolled in this study. The clinical endpoint was defined as the occurrence of all-cause mortality during the follow-up. RESULTS: The mean age of the patients was 63.0 ± 15.3 years, and 76.5% of them were male. Ischemic cardiomyopathy was the leading cause for the ICD implantations (39.1%). During the mean follow-up duration of 36.8 ± 29.8 months, there were 48 patients (20.2%) who died. Patients with structural heart diseases had a higher mortality rate than those without such diseases. Additionally, old age, low left ventricular ejection fraction (LVEF) and a history of diabetes mellitus (DM) were significant predictors of mortality. The optimal cutoff values for age (70 years) and LVEF (40%) in predicting mortality were further identified using the receiver operating characteristic curves. CONCLUSIONS: Based on the ICD registry from 3 medical centers in Taiwan, the annual mortality rate was around 6.6% and was higher in those patients with structural heart diseases. We observed that old age, low LVEF and a history of DM were significant predictors of mortality. KEY WORDS: Implantable cardioverter-defibrillator; Mortality; Predictor; Taiwan.

Differences in the atrial electrophysiological properties between vagal and sympathetic types of atrial fibrillation.

INTRODUCTION: Autonomic modulation of the cardiac activity plays an important role in the pathogenesis of atrial fibrillation (AF). The aim of this study was to assess the differences in the atrial electrical and structural properties between patients with vagal and sympathetic AF. METHODS: The study included 30 patients (53 ± 12 years old, male 26) with frequent attacks of symptomatic paroxysmal AF. All cases underwent 24-hour ambulatory Holter monitoring before the catheter ablation. The onset of AF accompanied with an increased HF component and decreased L/H ratio was designated as a vagal type (group 1, n = 12), whereas a decreased HF component and increased L/H ratio was classified as a sympathetic type (group 2, n = 18). Electrical and structural properties were evaluated during the ablation procedure. RESULTS: All patients had AF originating from PVs. There was a higher incidence of non-PV triggers in group 2 patients than that in group 1 (44% vs 8%, P = 0.04). Group 1 had a higher bipolar peak-to-peak voltage and mean DF of the global left atrium (LA), shorter total activation time, and smaller LA volume than group 2, whereas the electrical and structural properties in the right atrium were similar. After a follow-up of 15 ± 7 months, there was a lower incidence of AF recurrence in group 1 than that in group 2 (0% vs 28%, P = 0.02). CONCLUSION: There are better electrical properties and a smaller LA volume in patients with vagal-type AF. In contrast, the LA substrate is worse, and coexisting non-PV triggers and recurrence following ablation are more prevalent in patients with the sympathetic-type AF.

Five-Year Outcomes after Acute Myocardial Infarction in Patients with and without Diabetes Mellitus in Taiwan, 1996-2005.

BACKGROUND: Diabetes mellitus (DM) is a strong risk factor of cardiovascular disease. To date, the impact of DM on outcomes after acute myocardial infarction (AMI) in Taiwan is undetermined. The aim of this study was to compare five-year outcomes after AMI in patients with and without diabetes in Taiwan. METHODS: A nationwide cohort of 25,028 diabetic and 56,028 non-diabetic patients who were first hospitalized with AMI between 1996 and 2005 was enrolled through linkage with the Taiwan National Health Insurance research database. Patient mortality rates within 30 days after AMI, and 1, 3, and 5 years thereafter were compared. RESULTS: Length of hospital stay (8.9 ± 8.7 vs. 8.2 ± 8.0 days, p < 0.01) and medical cost during admission (in Taiwan dollars: $129,123 ± $158,073 vs. $121,631 ± $157,018, p < 0.01) were significantly higher in diabetic patients. The difference in mortality rate within 30 days was insignificant between diabetic and non-diabetic patients (18.1% vs. 17.6%, p = 0.06). Mortalities within 1 year (31.0% vs. 26.8%, p < 0.01), 3 years (42.4% vs. 34.7%, p < 0.01), and 5 years (50.6% vs. 41.1%, p < 0.01) were significantly higher in diabetic patients. In patients with AMI who underwent percutaneous coronary intervention (PCI) during index admission, the mortality rate within 30 days was insignificant (6.3% vs. 6.4%, p = 0.70) but mortalities within 1 year (15.2% vs. 11.6%, p < 0.01), 3 years (24.1% vs. 17.2%, p < 0.01), and 5 years (32.2% vs. 22.6%, p < 0.01) were significantly higher in diabetic patients. CONCLUSIONS: The average patient length of hospital stay and medical cost during admission were significantly higher in diabetic patients. Additionally, the difference in mortality rate within 30 days after AMI was insignificant between diabetic and non-diabetic patients. Also, long-term mortality after AMI was significantly higher in diabetic patients. KEY WORDS: Acute myocardial infarction; Diabetes mellitus; Length of hospital stay; Medical cost; Mortality; National health insurance.