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.

A prospective and randomized comparison of limited versus extensive atrial substrate modification after circumferential pulmonary vein isolation in nonparoxysmal atrial fibrillation.

INTRODUCTION: The optimal substrate ablation approach in patients with persistent atrial fibrillation (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE: <60 milliseconds) versus extensive (continuous CFAE plus variable CFAE: <120 milliseconds) atrial substrate modification in Per AF patients. METHODS AND RESULTS: We enrolled 120 Per AF patients in the study, and 30 patients with AF termination after pulmonary vein isolation (PVI) were excluded. In the remaining 90 patients, 45 were treated with limited approach (Group 1) and 45 with an extensive approach (Group 2). The end point of the study was the incidence of an atrial arrhythmia recurrence postblanking period. The patients were followed up for 15 months with 3-month clinical reviews, electrograms (ECGs), Holter recordings, and echocardiographic monitoring. Procedural AF termination and the single procedural efficacy were statistically comparable between the 2 groups (48.9% vs. 63.4% in Groups 1 and 2, respectively, P = 0.289). During the follow-up, patients who received limited ablation had a lower incidence of recurrent AFL (P = 0.04), and better reverse remodeling of the left atrium (LA, P = 0.04). After 2 procedures, the freedom from any atrial arrhythmia was better in Group 2 (62.2% vs. 87.8%, P = 0.009). Those with longstanding AF and a larger baseline LA size responded better to the extensive ablation. CONCLUSIONS: In the Per AF patients who failed to achieve AF termination after PVI alone, a specific atrial substrate modification approach targeting only continuous CFAEs could be considered as an initial ablation strategy.

Sinus node dysfunction in atrial fibrillation patients: the evidence of regional atrial substrate remodelling.

AIMS: It remains unclear as to whether regional atrial substrates of certain areas of the atrium in patients with atrial fibrillation (AF) can be related to sinoatrial node dysfunction. We investigated the relationship between the biatrial substrate characteristics and sinus node function in these patients. METHODS AND RESULTS: The study enrolled 34 patients (aged 57 ± 11 years old; 20 males) who underwent catheter ablation for symptomatic paroxysmal AF. Sinus node dysfunction was defined as having corrected sinus node recovery time longer than 550 ms. Atrial substrate analyses of both atria and atrial conductive properties were investigated in patients with (Group 1) and without sinus node dysfunction (Group 2). The mean global bipolar voltage of both atria and the atrial refractory period were similar between the two groups. Regional analysis showed that the mean bipolar voltage for patients in Group 1 was lower than in Group 2 (1.0 ± 0.3 vs. 2.1 ± 0.7 mV, P < 0.001) only in the sinus node region, while the electrophysiological properties were similar for both groups in other anatomic regions of both atria. The right atrial total activation time was significantly longer (97 ± 9 vs. 89 ± 10 ms, P = 0.023) and the conduction velocity along the crista terminalis was significantly slower (1.0 ± 0.2 vs. 1.2 ± 0.3 m/s, P = 0.019) in Group 1 patients than in Group 2 patients. CONCLUSION: In patients with AF, regional atrial remodelling near the sinus node area was associated with sinus node dysfunction.

Nonlinear analysis of fibrillatory electrogram similarity to optimize the detection of complex fractionated electrograms during persistent atrial fibrillation.

INTRODUCTION: Currently, the identification of complex fractionated atrial electrograms (CFEs) in the substrate modification is mostly based on cycle length-derived algorithms. The characteristics of the fibrillation electrogram morphology and their consistency over time are not clear. The aim of this study was to optimize the detection algorithm of crucial CFEs by using nonlinear measure electrogram similarity. METHODS AND RESULTS: One hundred persistent atrial fibrillation patients that underwent catheter ablation were included. In patients who required CFE ablation (79%), the time-domain fibrillation signals (6 seconds) were acquired for a linear analysis (mean fractionation interval and dominant frequency [DF]) and nonlinear-based waveform similarity analysis of the local electrograms, termed the similarity index (SI). Continuous CFEs were targeted with an endpoint of termination. Predictors of the various signal characteristics on the termination and clinical outcome were investigated. Procedural termination was observed in 39% and long-term sinus rhythm maintenance in 67% of the patients. The targeted CFEs didn't differ based on the linear analysis modalities between the patients who responded and did not respond to CFE ablation. In contrast, the average SI of the targeted CFEs was higher in termination patients, and they had a better outcome. Multivariate regression analysis showed that a higher SI independently predicted sites of termination (≥ 0.57; OR = 4.9; 95% CI = 1.33-18.0; P = 0.017). CONCLUSIONS: In persistent AF patients, a cycle length-based linear analysis could not differentiate culprit CFEs from bystanders. This study suggested that sites with a high level of fibrillation electrogram similarity at the CFE sites were important for AF maintenance.

Long-term outcome of catheter ablation in patients with atrial fibrillation originating from nonpulmonary vein ectopy.

INTRODUCTION: Data regarding the long-term outcome of catheter ablation in patients with nonpulmonary vein (NPV) ectopy initiating atrial fibrillation (AF) are limited. We aimed to evaluate the long-term result of patients with AF who had NPV triggers and underwent catheter ablation. METHODS AND RESULTS: The study included 660 consecutive patients (age 54 ± 11 years old, 477 males) who had undergone catheter ablation for AF. Group 1 consisted of 132 patients with AF initiating from the NPV, and group 2 consisted of 528 patients with AF initiating from pulmonary vein (PV) triggers only. Patients from Group 1 were younger than those from Group 2 (51 ± 12 years old vs 54 ± 11 years old, P = 0.001) and were more likely to be females (34.4% vs 25.8%, P = 0.049). The incidences of nonparoxysmal AF (36.4% vs 16.3%, P < 0.001) and right atrial (RA) enlargement (31.3% vs 19%, P = 0.004) were higher, and the biatrial substrates were worse in Group 1 than those in Group 2 (left atrial voltage 1.5 ± 0.7 mV vs 1.9 ± 0.7 mV, P < 0.001, RA voltage 1.6 ± 0.5 mV vs 1.8 ± 0.6 mV, P = 0.014). During a follow-up period of 46 ± 23 months, there was a higher AF recurrence rate in Group 1 than in Group 2 (57.6% vs 38.8%, P < 0.001). The independent predictors of AF recurrence were NPV trigger (P < 0.001, HR 2, 95% CI 1.4-2.85), nonparoxysmal AF (P = 0.021, HR 1.55, 95% CI 1.07-2.24), larger left atrial diameter (P = 0.002, HR 1.04, 95% CI 1.02-1.07) and worse left atrial substrate (P = 0.028, HR 1.3, 95% CI 1.03-1.64). CONCLUSION: Compared to AF originating from the PV alone, AF originating from the NPV ectopy showed a worse outcome.

A prospective, randomized comparison of modified pulmonary vein isolation versus conventional pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high-frequency AF nests may have a higher efficacy. METHODS AND RESULTS: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0-1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy-guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time-domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow-up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log-rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I. CONCLUSION: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy.

Relationship between the CHADS(2) score and risk of very late recurrences after catheter ablation of paroxysmal atrial fibrillation.

BACKGROUND: Catheter ablation of paroxysmal atrial fibrillation has been performed for more than 10 years. However, data about the long-term results were limited. OBJECTIVES: To evaluate the long-tem efficacy following paroxysmal atrial fibrillation ablation and to investigate whether there were different patterns of recurrences in patients with different CHADS(2) scores. METHODS: A total of 238 patients with paroxysmal atrial fibrillation who received a catheter ablation from 2004 to 2007 were enrolled. Free of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after ablation. RESULTS: There were 121 patients (50.8%) suffering from recurrences after the first ablation procedure during a median follow-up period of 5 years. The CHADS(2) score and left atrial diameter were significant predictors of recurrences in the multivariate analysis. Different patterns of recurrence were observed in different groups of patients categorized on the base of CHADS(2) score. Among patients with a CHADS(2) score of ≥3 without recurrences at 2 years postablation, 63.6% experienced episodes of arrhythmias during the subsequent follow-up period. In contrast, in patients with a CHADS(2) score of 0 without recurrences at 2 years postablation, the future recurrence rate was only 2.7%. CONCLUSIONS: After a successful ablation, recurrences may continue to occur without reaching a plateau during the long-term follow-up, especially in patients with a high CHADS(2) score. The optimal follow-up strategy may differ and should be individualized for patients with different scores.

A novel finding of the atrial substrate properties and long-term results of catheter ablation in chronic atrial fibrillation patients with left atrial spontaneous echo contrast.

BACKGROUND: The atrial substrate in chronic atrial fibrillation (AF) patients with a left atrial spontaneous echo contrast (LASEC) has not been previously reported. The aim of this study was to investigate the atrial substrate properties and long-term follow-up results in the patients who received catheter ablation of chronic AF. METHODS: Of 36 consecutive patients with chronic AF who received a stepwise ablation approach, 18 patients with an LASEC (group I) were compared with 18 age-gender-left atrial volume matched patients without an LASEC (group II). The atrial substrate properties including the weighted peak-to-peak voltage, total activation time during sinus rhythm (SR), dominant frequency (DF), and complex fractionated electrograms (CFEs) during AF in the bi-atria were evaluated. RESULT: The left atrial weighted bipolar peak-to-peak voltage (1.0 ± 0.6 vs 1.6 ± 0.7 mV, P = 0.04), total activation time (119 ± 20 vs 103 ± 13 ms, P < 0.001) and DF (7.3 ± 1.3 vs 6.6 ± 0.7 Hz, P < 0.001) differed between group I and group II, respectively. Those parameters did not differ in the right atrium. The bi-atrial CFEs (left atrium: 89 ± 24 vs 92 ± 25, P = 0.8; right atrium: 92 ± 25 vs 102 ± 3, P = 0.9) did not differ between group I and group II, respectively. After a mean follow-up of 30 ± 13 month, there were significant differences in the antiarrhythmic drugs (1.1 ± 0.3 vs 0.7 ± 0.5, P = 0.02) needed after ablation, and recurrence as persistent AF (92% vs 50%, P = 0.03) between group I and group II, respectively. After multiple procedures, there were more group II patients that remained in SR, when compared with group I (78% vs 44%, P = 0.04). CONCLUSION: There was a poorer atrial substrate, lesser SR maintenance after catheter ablation and need for more antiarrhythmic drugs in the chronic AF patients with an LASEC when compared with those without an LASEC.

Characteristics and significance of very early recurrence of atrial fibrillation after catheter ablation.

INTRODUCTION: Early restoration of sinus rhythm following ablation of atrial fibrillation (AF) facilitates reverse atrial remodeling and improves the long-term outcome. The purpose of this study was to determine the predictors and outcome in patients with very early AF recurrences (< 2 days). METHODS AND RESULTS: Ablation was performed in 339 consecutive AF patients (paroxysmal AF = 262). Biatrial voltage was mapped during sinus rhythm. If recurrent AF occurred within 2 days following the ablation, electrical cardioversion was performed to restore sinus rhythm. Very early recurrences of AF occurred in 39 (15%) patients with paroxysmal AF and 26 (34%) with nonparoxysmal AF. Patients with very early recurrence had a higher incidence of nonparoxysmal AF (40% vs 18.6%, P< 0.001), requirement of electrical cardioversion during procedure, larger left atrial (LA) diameter (43 ± 7 vs 39 ± 6 mm, P< 0.001), lower left ventricular ejection fraction (54 ± 10% vs 59 ± 7, P< 0.001), longer procedural time, and lower LA voltage (1.5 ± 0.7 vs 1.9 ± 0.8 mV, P< 0.001). A multivariate analysis revealed that the independent predictors of a very early recurrence were a longer procedural time and lower LA voltage. During a follow-up of 13 ± 5 months, a very early recurrence did not predict the long-term outcome of a single procedure recurrence in the patients with paroxysmal AF, but was associated with a late recurrence in the nonparoxysmal AF patients. CONCLUSION: Very early recurrence occurred in patients with paroxysmal AF is not associated with long-term recurrence. Nonparoxysmal AF is an independent predictor of late recurrence of AF in patients with very early recurrence.

Associations among the CHADS(2) score, atrial substrate properties, and outcome of catheter ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The CHADS2 score (congestive heart failure, hypertension, age >75 years, diabetes, and previous stroke/transient ischemic attack) is used for the risk stratification of strokes in patients with atrial fibrillation (AF). OBJECTIVE: This study aimed to investigate the associations between the CHADS2 score, atrial substrate, and outcome of catheter ablation in patients with paroxysmal AF. METHODS: A total of 247 paroxysmal AF patients who received catheter ablation were enrolled. The patients were divided into 3 groups according to their CHADS2 score (group 1: score 0, group 2: score 1 to 2, and group 3: score 3 to 6). The bi-atrial substrate properties and outcome of catheter ablation were analyzed. RESULTS: The CHADS2 scores in these 3 groups were 0 (group 1), 1.24 ± 0.48 (group 2), and 3.60 ± 0.83 (group 3), respectively. The left atrial voltage became lower (group 1 vs. 2 vs. 3 = 2.08 ± 0.73 mV vs. 1.80 ± 0.81 mV vs. 1.06 ± 0.69 mV) and the activation time longer (group 1 vs. 2 vs. 3 = 93.4 ± 17.7 ms vs. 101.9 ± 21.2 ms vs. 112.2 ± 21.7 ms), whereas the CHADS2 score increased. During a follow-up of 17.3 ± 7.0 months, 23.1% of the study population suffered from recurrences. The recurrence rates of these 3 groups were 13.0% (group 1), 27.6% (group 2), and 45.9% (group 3), respectively. The groups of different CHADS2 scores remained as the independent predictor of recurrence in the multivariate analysis. CONCLUSION: A high CHADS2 score was associated with different left atrial substrate properties and a poor outcome after catheter ablation of paroxysmal AF.

The impact of age on the electrophysiological characteristics and different arrhythmia patterns in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Information about the impact of age on the electrophysiological characteristics of accessory pathways (APs) in patients with Wolff-Parkinson-White (WPW) syndrome remains limited. METHODS AND RESULTS: A total of 1,885 consecutive patients (mean age 43 ± 17 years, male 61.5%) with WPW syndrome who were referred to the tertiary center for an electrophysiological study and radiofrequency catheter ablation were investigated. The patients were divided into 4 groups based on their age (Group 1: <20; Group 2: 20-39; Group 3: 40-59; Group 4: ≧60 years old). With age, more left-sided APs (53.2%, 67.7%, 71.7%, 75.7%, P < 0.001) and a longer duration of the arrhythmia (4.3 ± 2.8 years, 10.1 ± 7.0 years, 12.4 ± 10.9 years, 14.0 ± 12.4 years, P < 0.001) were noted. The incidence of concealed APs (53.5%, 53.0%, 57.8%, 60.9%, P = 0.01), and orthodromic atrioventricular (AV) reentrant tachycardia (92.4%, 94.2%, 96.5%, 96.3%, P = 0.023) increased with age. The tachycardia cycle length, antegrade (275.5 ± 42.2 ms, 286.7 ± 62.7 ms, 302.5 ± 66.5 ms, 315.2 ± 80.2 ms, P < 0.001) and retrograde AP effective refractory periods (APERPs) (254.0 ± 42.5 ms, 263.3 ± 51.8 ms, 274.5 ± 100.5 ms, 292.7 ± 57.0 ms, P < 0.001), atrial ERP, antegrade AV node effective refractory period (AVNERP), and ventricular effective refractory period (VERP) lengthened as the age increased. The incidence of decremental APs, multiple APs, and a catecholamine response were similar. The duration of the catheter ablation, total fluoroscopy time, acute success rate, complication rate, and incidence of a secondary procedure were similar between the different age groups. CONCLUSION: The electrophysiological characteristics and pattern of the arrhythmic attack associated with the AP changed with age.