Yao-Ting Chang

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.

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.

History of hyperthyroidism and long-term outcome of catheter ablation of drug-refractory atrial fibrillation

BACKGROUND Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status. OBJECTIVE The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism. METHODS The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients. RESULTS Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P < .01), and higher prevalence of non-PV foci (42% vs 23%, P < .01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P < .01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history. CONCLUSION Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure.

A novel method to enhance phenotype, epicardial functional substrates, and ventricular tachyarrhythmias in Brugada syndrome

BACKGROUND Fever is associated with the manifestation of Brugada phenotype and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS). The thermal effect on the pathogenesis of functional substrates in BrS remains unknown. OBJECTIVE This study aimed to elucidate the thermal effect on BrS phenotype, VT/VF, and electrophysiological characteristics of epicardial functional substrates in BrS. METHODS We consecutively studied 15 patients with BrS receiving radiofrequency catheter ablation for drug-refractory ventricular tachyarrhythmias. Baseline characteristics, electrocardiographic features, and changes in epicardial functional substrates before and after epicardial warm water instillation (n = 6) were recorded and analyzed. RESULTS A total of 15 male patients (mean age 41.3 ± 10.3 years) with type 1 BrS presenting with ventricular tachyarrhythmias were consecutively enrolled. Epicardial mapping in 11 patients demonstrated a significantly larger epicardial scar/low-voltage zone (LVZ) area within the right ventricular outflow tract and anterior right ventricular free wall than within the endocardium (6.32 ± 12.74 cm2 vs 52.91 ± 45.25 cm2; P = .007). Epicardial warm water instillation in 6 patients led to a significant enlargement of the functional scar/LVZ area (123.83 ± 35.26 cm2 vs 63.53 ± 40.57 cm2; P = .03), accelerated conduction velocity of the endocardium and epicardium without scar/LVZ area, and increased VT/VF inducibility (16.7% vs 100%; P = .02). Ablation by targeting premature ventricular complexes and/or epicardial abnormal substrates rendered noninducibility of VT/VF and prevented the recurrences of VT/VF. CONCLUSION Epicardial warm water instillation enhanced functional epicardial substrates, which contributed to the increased inducibility of ventricular tachyarrhythmias in BrS. Ablation by targeting the triggers and abnormal epicardial substrates provided an effective strategy for preventing ventricular tachyarrhythmia recurrences in BrS.

Risk of Stroke in Patients With Short-Run Atrial Tachyarrhythmia

Background and Purpose— The risk of stroke in patients with short-run atrial tachyarrhythmia (AT) remains unclear. This study aimed to investigate the relationship between short-run AT and the stroke and the use of the CHA2DS2-VASc score for the risk stratification. Methods— From the registry of 24-hour Holter monitoring, 5342 subjects without known atrial fibrillation or stroke were enrolled. Short-run AT was defined as episodes of supraventricular ectopic beats <5 seconds. Results— There were 1595 subjects (29.8%) with short-run AT. During the median follow-up period of 9.0 years, 494 subjects developed new-onset stroke. Patients with short-run AT had significantly higher stroke rates compared with patients without short-run AT (11.4% versus 8.3%; P<0.001). In patients with short-run AT, the number of strokes per 100 person-years for patients with CHA2DS2-VASc score of 0 and 1 were 0.23 and 0.67, respectively. However, the number of them for patients with CHA2DS2-VASc score of 2, 3, 4, and ≥5 were 1.62, 1.89, 1.30, and 2.91, respectively. In patients with CHA2DS2-VASc score of 0 or 1, age (>61 years old) and burden of premature atrial contractions (>25 beats/d) independently predicted the risk of stroke. In subgroup analyses, short-run AT patients were divided into 3 groups based on their CHA2DS2-VASc scores: low score (score of 0 [men] or 1 [women]; n=324), intermediate score (score of 1 [men] or 2 [women]; n=275), and high score (score of ≥2 [men] or ≥3 [women]; n=996). When compared with low score, intermediate and high scores were independent predictors for stroke (hazard ratio, 6.165; P<0.001 and hazard ratio, 8.577; P<0.001, respectively). Conclusions— Short-run AT increases the risk of stroke. Therefore, the CHA2DS2-VASc score could be used for the risk stratification. Age and burden of premature atrial contractions were independent predictors for stroke in patients with CHA2DS2-VASc score of 0 or 1.

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.

Heterogeneous distribution of substrates between the endocardium and epicardium promotes ventricular fibrillation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Aims Whether the distribution of scar in arrhythmogenic right ventricular cardiomyopathy (ARVC) plays a role in predicting different types of ventricular arrhythmias is unknown. This study aimed to investigate the prognostic value of scar distribution in patients with ARVC. Methods and results We studied 80 consecutive ARVC patients (46 men, mean age 47 ± 15 years) who underwent an electrophysiological study with ablation. Thirty-four patients receive both endocardial and epicardial mapping. Abnormal endocardial substrates and epicardial substrates were characterized. Three groups were defined according to the epicardial and endocardial scar gradient (<10%: transmural, 10-20%: intermediate, >20%: horizontal, as groups 1, 2, and 3, respectively). Sinus rhythm electrograms underwent a Hilbert-Huang spectral analysis and were displayed as 3D Simultaneous Amplitude Frequency Electrogram Transformation (SAFE-T) maps, which represented the arrhythmogenic potentials. The baseline characteristics were similar between the three groups. Group 3 patients had a higher incidence of fatal ventricular arrhythmias requiring defibrillation and cardiac arrest during the initial presentation despite having fewer premature ventricular complexes. A larger area of arrhythmogenic potentials in the epicardium was observed in patients with horizontal scar. The epicardial-endocardial scar gradient was independently associated with the occurrence of fatal ventricular arrhythmias after a multivariate adjustment. The total, ventricular tachycardia, and VF recurrent rates were higher in Group 3 during 38 ± 21 months of follow-up. Conclusion For ARVC, the epicardial substrate that extended in the horizontal plane rather than transmurally provided the arrhythmogenic substrate for a fatal ventricular arrhythmia circuit.

Circulating microRNAs in arrhythmogenic right ventricular cardiomyopathy with ventricular arrhythmia.

Aims MicroRNAs (miRNAs) have been implicated in cardiac diseases. This study aimed to characterize the circulating miRNAs in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and correlate the miRNAs with the clinical outcomes of ARVC. Methods and results This study included 62 patients with ventricular arrhythmia (VA): 28 patients (45%) had definite ARVC, 11 (18%) had borderline or possible ARVC, and 23 (37%) had idiopathic ventricular tachycardia (VT). In addition, 33 age- and sex-matched healthy subjects were enrolled as normal control subjects. The expression of selected miRNAs was analysed in all study subjects. The clinical outcomes of patients with definite ARVC after catheter ablation were further investigated. On the basis of the miRNA polymerase chain reaction array, we selected 11 miRNAs for analysis of their expression in the plasma of all subjects. Definite ARVC patients had significantly higher expression of circulating miR-144-3p, 145-5p, 185-5p, and 494 than the three other groups. Out of 25 definite ARVC patients who underwent radiofrequency catheter ablation, recurrent VA occurred in 8 patients (32%) during the follow-up period (45 ± 20 months). Definite ARVC patients with recurrent VA had a higher level of circulating miR-494 than did those without recurrence. Receiver operating characteristic analysis showed miR-494 to be a predictive factor of recurrent VA (area under the curve: 0.832). Conclusion Plasma levels of miR-144-3p, 145-5p, 185-5p, and 494 were significantly elevated in definite ARVC patients with VA. An increased plasma level of miR-494 was associated with the recurrence of VA after ablation in definite ARVC patients.

The use of a novel signal analysis to identify the origin of idiopathic right ventricular outflow tract ventricular tachycardia during sinus rhythm: Simultaneous amplitude frequency electrogram transformation mapping

Introduction The signal characteristics of intracardiac bipolar electrograms at the origin of idiopathic RVOT-VT during sinus rhythm remain unclear. Objective The study sought to develop a novel real-time/online technique, simultaneous amplitude frequency electrogram transformation (SAFE-T), to quantify and localize the diseased ventricular substrate in idiopathic RVOT-VT. Methods We retrospectively investigated the intracardiac bipolar recordings in 70 consecutive patients (26% male, mean age 42±12 years) who underwent successful radiofrequency catheter ablation of idiopathic RVOT-VT. We quantified the extent of the frequency fraction of ventricular potentials during sinus rhythm or ventricular pacing using a novel formula, the product of instantaneous amplitude and frequency, and showed that in a 3D geometry as an online SAFE-T map. Results The characteristics of the HHT spectra of electrograms derived from VT origins demonstrated high frequency components (>70 Hz), which were independent of the rhythm. The density of the abnormal potentials at the VT origins were higher (VT origins, 7.5±2.3 sites/cm2 vs. surrounding myocardium, 1.5±1.3 sites/cm2, p<0.001), and were significantly decreased after ablation (0.7±0.6 sites/cm2, p<0.001). A small region of abnormal potentials were observed in the VT origins (mean area of 1.5±0.8 cm2). The SAFE-T maps predicted the VT origins with 92% sensitivity, 78% specificity with optimal cut-off value of >3.0 Hz·mV. Conclusion The online SAFE-T map was feasible for quantifying the diseased ventricular substrate, irrespective of the rhythm of activation, and can be used to identify the optimal ablation targets for idiopathic RVOT-VT. We found a limited region of abnormal potentials where the RVOT-VT origins were successfully ablated.

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

Abstract 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]± 1 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.