Abigail Louise D. Te

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.

Long-term outcome of non-sustained ventricular tachycardia in structurally normal hearts

Background The impact of non-sustained ventricular tachycardia (NSVT) on the risk of thromboembolic event and clinical outcomes in patients without structural heart disease remains undetermined. This study aimed to evaluate the association between NSVT and clinical outcomes. Methods The study population of 5903 patients was culled from the “Registry of 24-hour ECG monitoring at Taipei Veterans General Hospital” (REMOTE database) between January 1, 2002 and December 31, 2004. Of that total, we enrolled 3767 patients without sustained ventricular tachycardia, structural heart disease, and permanent pacemaker. For purposes of this study, NSVT was defined as 3 or more consecutive beats arising below the atrioventricular node with an RR interval of <600 ms (>100 beats/min) and lasting < 30 seconds. Result There were 776 deaths, 2042 hospitalizations for any reason, 638 cardiovascular (CV)-related hospitalizations, 350 ischemic strokes, 409 transient ischemic accident (TIA), 368 new-onset heart failure (HF), and 260 new-onset atrial fibrillation (AF) with a mean follow-up duration of 10 ± 1 years. In multivariate analysis, the presence of NSVT was independently associated with death (hazard ratio [HR]: 1.362, 95% confidence interval [CI]: 1.071–1.731), CV hospitalization (HR: 1.527, 95% CI: 1.171–1.992), ischemic stroke (HR: 1.436, 95% CI: 1.014–2.032), TIA (HR 1.483, 95% CI: 1.069–2.057), and new-onset HF (HR: 1.716, 95% CI: 1.243–2.368). There was no significant association between the presence of NSVT and all-cause hospitalization or new-onset AF. Conclusion In patients without structural heart disease, presence of NSVT on 24-hour monitoring was independently associated with death, CV hospitalization, ischemic stroke, TIA, and new onset heart failure.

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.

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.

Characteristics and long-term catheter ablation outcome in long-standing persistent atrial fibrillation patients with non-pulmonary vein triggers

BACKGROUND There are limited literatures regarding the non-pulmonary vein (NPV) triggers in long-standing persistent atrial fibrillation (LSPAF). The goal of the present study was to investigate the characteristics and long-term outcome of catheter ablation among these patients. METHODS The study included 776 patients (age 53.59±11.38years-old, 556 males) who received catheter ablation for drug-refractory atrial fibrillation (AF). We divided these patients into 3 groups. Group 1 consisted of 579 patients with paroxysmal AF (PAF), group 2 consisted of 103 patients with persistent AF (PerAF) and group 3 consisted of 94 patients with long-standing persistent AF (LSPAF). The average follow-up duration was 28.53±23.21months. RESULTS The clinical endpoint was the recurrence of atrial tachyarrhythmia. Among these 3 groups, higher percentages of male (93.6%, P<0.001), NPV triggers (44.7%, P<0.001), longer AF duration (6.65±6.72years, P=0.029), larger left atrium diameter (44.44±6.79mm, P<0.001), and longer procedure time (181.94±70.02min, P<0.001) were noted in LSPAF. After the first catheter ablation, the recurrence rate of AF was highest in LSPAF (Log Rank, P<0.001). Larger left atrium diameters (LAD) (P=0.006; HR: 1.063; CI: 1.018-1.111) and NPV triggers (P=0.035; HR: 1.707; 1.037-2.809) independently predicted AF recurrence in LSPAF. CONCLUSIONS Compared with PAF and PerAF, LSPAF had a higher incidence of NPV triggers and worse long-term outcome after catheter ablation. NPV triggers and LAD independently predicted AF recurrence after catheter ablation in LSPAF.

Gender differences in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy: Clinical manifestations, electrophysiological properties, substrate characteristics, and prognosis of radiofrequency catheter ablation

BACKGROUND Gender differences in the penetrance and clinical expression of genetic mutations have been reported in patients with arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C). Our study aimed at clarifying the impact of gender on ventricular substrates and clinical outcomes after radiofrequency catheter ablation (RFCA). METHODS Patients with ARVD/C underwent RFCA for drug-refractory ventricular arrhythmias (VAs) were consecutively enrolled. Baseline characteristics, electrocardiograms, ventricular substrates, and VA recurrences after RFCA were extracted for comparison between genders. RESULTS A total of 70 consecutive unselected patients with definite ARVD/C (36 men [51%], age 45±14years) were studied. Male patients had a higher incidence of sustained ventricular tachycardia and ventricular fibrillation or sudden cardiac arrest as initial manifestations. Electroanatomical mapping demonstrated that men with ARVD/C had a larger epicardial RV unipolar low-voltage zone, a larger endocardial and epicardial area with late potentials, and longer local abnormal ventricular activity. Cox regression analysis demonstrated that gender and late potential area predicted the recurrences of VAs. CONCLUSION Patients with ARVD/C displayed different characteristics of VAs and substrate properties between men and women. Male gender and the presence of larger area of abnormal electrograms independently predicted VA recurrences after RFCA.

Ablation of ventricular arrhythmia originating at the papillary muscle using an automatic pacemapping module

BACKGROUND Ventricular arrhythmia originating from the papillary muscle (VA-PM) is characterized by multiple exits and morphologic alternations. The conventional ablation strategy relies on activation mapping, but the results might be suboptimal. OBJECTIVE The purpose of this study was to propose a novel pacemapping strategy aimed at multiple exits using high-output software as a complementary approach to the conventional strategy. METHODS A consecutive 13 patients with VA-PM were enrolled in this study. Novel pacemapping based on an automatic matching algorithm and integrated electroanatomic mapping was used to quantify the morphology variation in these patients and to identify the potential exits of VA-PM. Complementary ablation targeting at the best matching site of each morphology was performed. RESULTS Twelve of 13 patients (92%) experienced morphologic alternation, and a total of 34 morphologies were detected (2.6 ± 1.0 per patient). A total of 23 (68%) morphologies were detected as spontaneous pleomorphic ventricular premature complexes (VPCs) before procedure, and 4 morphologies (12%) were induced under isoproterenol infusion. Another 7 of 34 morphologies (21%) could be found only after radiofrequency ablation attempts. Exits with a high pacemapping correlation index for corresponding morphology would be mapped, so preferential exits could be identified. Mean interexit distance was 15.1 ± 5.9 mm. Acute success rate was 100%. During mean follow-up of 12.2 ± 6.9 months, only 1 case recurred with ventricular tachycardia. Although 3 cases recurred with different VPC morphologies, the VPC burden decreased from 16.3% ± 8.8% to 2.6% ± 1.7%. CONCLUSION This novel pacemapping strategy could effectively eliminate multiple exits as a complementary approach to the conventional strategy.