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Background: Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. Accurate detection of the timing and possibility of AF termination is vital for optimizing rhythm and rate control strategies. The present study evaluated whether the ventricular response (VR) in AF offers a distinctive electrocardiographic indicator for predicting AF termination. Methods: Patients experiencing sustained paroxysmal AF for more than 3 h were observed using 24‐h ambulatory Holter monitoring. VR within 5 min before AF termination (VR 0–5 min, BAFT) was compared with VR observed during the 60th to 65th min (VR 60–65 min, BAFT) and the 120th to 125th min (VR 120–125 min, BAFT) before AF termination. Maximum and minimum VRs were calculated on the basis of the average of the highest and lowest VRs across 10 consecutive heartbeats. Results: Data from 37 episodes of paroxysmal AF revealed that the minimum VR0–5 min, BAFT (64 ± 20 bpm) was significantly faster than both the minimum VR120–125 min, BAFT (56 ± 15 bpm) and the minimum VR60–65 min, BAFT (57 ± 16 bpm, p <.05). Similarly, the maximum VR0–5 min, BAFT (158 ± 49 bpm) was significantly faster than the maximum VR120–125 min, BAFT (148 ± 45 bpm, p <.05). In the daytime, the minimum VR0–5 min, BAFT (66 ± 20 bpm) was significantly faster than both the minimum VR60–65 min, BAFT (58 ± 17 bpm) and minimum VR120–125 min, BAFT (57 ± 15 bpm, p <.05). However, the mean and maximum VR0–5 min, BAFT in the daytime were similar to the mean and maximum VR120–125 min in the daytime, respectively. At night, the minimum, mean, and maximum VR0–5 min, BAFT were similar to the minimum, mean, and maximum VR120–125 min, respectively. Conclusions: Elevated VR rates during AF episodes may be predictors for the termination of AF, especially during the daytime and in patients with nondilated left atria. These findings may guide the development of clinical approaches to rhythm control in AF. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coexistence of idiopathic left fascicular ventricular tachycardia (ILFVT) and atrioventricular nodal reentrant tachycardia (AVNRT) has been rarely reported. Objectives: The study aimed at elucidating the prevalence of coexisted AVNRT in patients with ILFVT during longitudinal follow‐up. The electrophysiological properties and clinical predictors of coexisted ILFVT and AVNRT were investigated. Methods: From 1999 to 2017, a total of 108 patients (age: 33.7 ± 14.3, 84 male) with ILFVT from one tertiary center were consecutively enrolled. The prevalence of coexisted arrhythmias was explored during a longitudinal follow‐up and the electrophysiological parameters from the index procedure were compared. Results: During a mean follow‐up period of 106.8 ± 69.5 months, 21 of 108 patients (19.4%) had coexisted AVNRT. The electrophysiological study demonstrated patients with coexisted ILFVT and AVNRT were characterized by more antegrade dual AV node conduction (52.4% vs. 19.5%, P = 0.002; 9.5%), shorter antegrade slow pathway effective refractory period (285.1 ± 34.1 ms vs. 329.2 ± 69.2 ms, P = 0.034), longer retrograde fast pathway effective refractory period (368.9 ± 56.7 ms vs. 312.5 ± 95.2, P = 0.036), and less VA dissociation (19.0% vs. 60.9%, P = 0.001) than those without a coexisted AVNRT. Multivariate logistic analysis showed that presence of antegrade dual AV nodal physiology and retrograde VA conduction could predict a coexisted AVNRT in patients with ILFVT (P = 0.005, OR: 4.80, 95% CI: 1.65–14.37 and P = 0.002, OR: 0.14, 95% CI: 0.04–0.49, respectively). Conclusion: There was a high prevalence of coexisted AVNRT in patients with ILFVT during longitudinal follow‐up. The presence of antegrade dual AV nodal physiology and retrograde VA conduction can predict the coexisted AVNRT in patients with ILFVT. [ABSTRACT FROM AUTHOR]

Background Autonomic nervous activity plays a critical role in the genesis of paroxysmal atrial fibrillation (AF, PAF). However, the role of autonomic nervous activity on AF termination has not been elucidated. Heart rate variability (HRV) is widely used to evaluate autonomic nervous activity in humans. The purpose of this study was to assess whether autonomic nervous activity assessed by HRV contributes to AF termination. Methods Electrocardiograms (ECGs) and HRV were studied in patients with termination of sustained (>30 s) PAF by 24-hour ambulatory Holter monitoring. The 20-minute interval after termination of AF was divided into four segments of 5 minutes each, and a frequency analysis was applied to each 5-minute segment. Results In 52 AF episodes, the ultra-low-frequency power, very-low-frequency power, low-frequency power (LF), high-frequency power (HF), and total power significantly decreased with time after episodes of AF termination. The LF/HF (L/H) ratio, normalized LF (LFnu), and normalized HF (HFnu) significantly changed after AF termination. Eighteen (35%) episodes had decreased LFnu and increased HFnu (sympathetic withdrawal and vagal activation), which had slower average AF ventricular responses (92 ± 16 beats/min vs 105 ± 24 beats/min, P < 0.05) than the AF termination episodes (n = 34, 65%) with increased LFnu and decreased HFnu (sympathetic activation and vagal withdrawal). Moreover, older patients (aged >65 years) had a higher incidence (n = 27, 75%) of AF termination with increased LFnu and decreased HFnu than did younger patients (aged ≤65 years, n = 7, 44%, P < 0.05). Conclusion Autonomic changes critically regulate termination of PAF, which is modulated by aging. [ABSTRACT FROM AUTHOR]

Effects of Indoxyl Sulfate on Pulmonary Vein and Atrial Arrhythmogenesis Background Chronic kidney disease (CKD) is associated with a higher incidence of atrial fibrillation (AF) with unclear mechanisms. Indoxyl sulfate (IS) accumulates in CKD patients. IS increases oxidative stress, which contributes to the genesis of AF. The arrhythmogenic effect of IS is unclear. Methods Conventional microelectrodes recorded the action potentials (AP) of isolated rabbit left atrium (LA), right atrium (RA), pulmonary vein (PV), and sinoatrial nodes (SANs) before and after treatment with IS with and without an antioxidant (ascorbic acid). Confocal microscopy with fluorescence and whole-cell patch clamp were used to evaluate intracellular calcium in isolated PV cardiomyocytes with and without IS. Results Compared to the control, IS induced more PV delayed afterdepolarizations at 0.1, 1, 10, and 100 μM, and induced more PV burst firings at 1, 10, and 100 μM. In contrast, IS (10 and 100 μM) reduced the SAN spontaneous beating rate. IS (100 μM) significantly shortened LA AP durations, but not RA. IS (100 μM)-treated PV cardiomyocytes had a similar calcium transient and sarcoplasmic reticulum calcium content, but a larger calcium leak than control PV cardiomyocytes. Burst pacing and isoproterenol induced a greater AF occurrence (50% vs. 100%; P = 0.009) and a longer AF duration (26 ± 9 vs. 5 ± 3 seconds; P < 0.05) in the LA (n = 8) with IS (100 μM) than without IS. Moreover, ascorbic acid (1 mM) attenuated the effects of IS on the LA, PV, and SANs. Conclusion IS increases PV and atrial arrhythmogenesis through oxidative stress. They may contribute to the occurrence of AF in CKD patients. [ABSTRACT FROM AUTHOR]

Cx40 Remodeling in Atrial Fibrillation Introduction Heart failure (HF) increases the susceptibility to atrial fibrillation (AF) and is associated with altered cardiomyocyte connexin. The regional remodeling of connexin(s) may contribute to the spatiotemporal organization of AF. This study sought to investigate the regional differences in connexin(s) and fibrosis in specific atrial regions and correlate that with the electrogram properties. Methods and Results Biatrial electroanatomic mapping during sinus rhythm (electrogram voltage and velocity) and AF (dominant frequency, DF) was performed in 6 ventricular pacing-induced HF dogs (at 252 beats/minute for 6 weeks) and 6 controls. Atrial tissues were sampled from 7 specific sites for analysis of the connexin and fibrosis. HF caused marked atrial dilatation, and increased the induced AF duration (P < 0.001). Remodeled connexins, including a lower expression and more lateralization of both connexin40 (Cx40) and Cx43 as well as increased regional dispersion of Cx40, in the presence of diffuse enhanced atrial fibrosis, characterized the atrial substrate of the HF dogs (P < 0.01). Regional analysis showed abnormal velocity and low electrogram voltage in the areas with downregulated Cx40 and Cx43 was enhanced in the presence of marked atrial fibrosis (>30% of area, P < 0.01). During AF, lower expression of the Cx40 was associated with higher DF in areas of less and more fibrosis, respectively (R = 0.67 and 0.58, P < 0.01). Conclusions An altered expression of connexins correlated with the electrogram properties in the existence of diffuse enhanced atrial fibrosis associated with HF. The regional remodeling of Cx40 is likely an important factor in the maintenance of AF in HF. [ABSTRACT FROM AUTHOR]

Long-Term Outcome of NPV AF Ablation. 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. (J Cardiovasc Electrophysiol, Vol. 24, pp. 250-258, March 2013) [ABSTRACT FROM AUTHOR]

Objectives and Background: The success rate of achieving electrical isolation by circumferential pulmonary vein ablation (CPVA) varies from 32% to 88%. We carried out ablation at the pulmonary vein carina to evaluate the elimination rates of the pulmonary vein potentials (PVPs) after one round of CPVA had failed to eliminate all the PVPs in the patients with atrial fibrillation (AF). Methods: Ninety-seven patients (75 males; mean age: 50 ± 12 years; 15 with persistent AF and 82 with paroxysmal AF) who underwent catheter ablation were analyzed. All patients underwent one round of CPVA with PVP elimination as the endpoint. The electrophysiology tracings were then analyzed to look for the presence of any gaps that were subsequently targeted by radiofrequency ablation. The patients in whom the PVPs still persisted underwent ablation at the pulmonary vein carina and the success rate of the PVP elimination was studied. The patients were followed up for a mean duration of 12.9 ± 8.2 months. Results: One hundred ninety-four ipsilateral pulmonary veins in 97 patients were subjected to CPVA with successful elimination of the PVPs in 110 ipsilateral pulmonary veins (success rate of 56.7%). A carina ablation was carried out in the remaining 84 ipsilateral pulmonary vein pairs harboring PVPs. Elimination of the PVPs was achieved in all the remaining ipsilateral pulmonary veins after the carina ablation. Conclusion: Considering the limited efficacy of CPVA in eliminating the PVPs, pulmonary vein carina ablation is advisable to substantially increase the PVP elimination rate. [ABSTRACT FROM AUTHOR]

Introduction: Paroxysmal supraventricular tachycardia (PSVT) is often associated with paroxysmal atrial fibrillation (AF). However, the relationship between PSVT and AF is still unclear. The aim of this study was to investigate the clinical and electrophysiological characteristics in patients with PSVT and AF, and to demonstrate the origin of the AF before the radiofrequency (RF) ablation of AF. Methods and Results: Four hundred and two consecutive patients with paroxysmal AF (338 had a pure PV foci and 64 had a non-PV foci) that underwent RF ablation were included. Twenty-one patients (10 females; mean age 47 ± 18 years) with both PSVT and AF were divided into two groups. Group 1 consisted of 14 patients with inducible atrioventricular nodal reentrant tachycardia (AVNRT) and AF. Group 2 consisted of seven patients with Wolff-Parkinson-White (WPW) syndrome and AF. Patients with non-PV foci of AF had a higher incidence of AVNRT than those with PV foci (11% vs. 2%, P = 0.003). Patients with AF and atypical AVNRT had a higher incidence of AF ectopy from the superior vena cava (SVC) than those with AF and typical AVNRT (86% vs. 14%, P = 0.03). Group 1 patients had smaller left atrial (LA) diameter (36 ± 3 vs. 41 ± 3 mm, P = 0.004) and higher incidence of an SVC origin of AF (50% vs. 0%, P = 0.047) than did those in Group 2. Conclusion: The SVC AF has a close relationship with AVNRT. The effect of atrial vulnerability and remodeling may differ between AVNRT and WPW syndrome. [ABSTRACT FROM AUTHOR]

Background: The features of multiple catheter ablation procedures for paroxysmal atrial fibrillation (AF) are unknown. We aimed to investigate the electrophysiologic characteristics and the clinical outcomes in the patients with AF who received more than two ablation procedures. Methods: The study consisted of 15 consecutive patients (age 48 ± 14 years, 10 males) who had undergone three to five (3.3 ± 0.6) catheter ablation procedures for recurrent paroxysmal AF. Results: Ten patients had pulmonary vein (PV)-AF and one had AF originating from both PVs and the superior vena cava (SVC) in the first ablation procedure. All of them exhibited PV reconnection during the recurrent episodes. Four of the 15 patients had AF originating from non-PV foci (three from the SVC, one from the crista terminalis) in the first procedure, and two had AF recurrences due to recovered conduction from the SVC. In all patients with PV-AF recurrences, repeated PV isolation procedures could effectively eliminate the AF. The incidence of the need for additional LA linear ablation lesions was higher comparing between the first procedure and in the following ablation procedures (18% vs. 71%, P = 0.02). During a follow-up of 1.7 ± 1.1 years, 73% of the patients remained in sinus rhythm without any antiarrhythmic drugs after the final procedure. Conclusions: Recovered PV connection was the major cause of the AF recurrences despite undergoing multiple catheter ablation procedures. It is advisable to inspect all PVs during the AF recurrence. Repeated PV isolation plus left atrial linear ablations could effectively eliminate the AF with satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The atrial substrate plays an important role in the maintenance of atrial fibrillation (AF). Further investigation of the biatrial substrate may be helpful for understanding the mechanism of AF. The aim of this study was to investigate the properties of right and left atrial (RA and LA) substrate in AF patients and their impact on the catheter ablation. Methods: Biatrial electroanatomic mapping using a three-dimensional mapping system (NavX) was performed in 117 consecutive patients with paroxysmal (n = 99) and persistent (n = 18) AF. The biatrial voltage and total activation time (TAT) were obtained during sinus rhythm. Results: The LA had a lower voltage (1.6 ± 0.5 vs 2.0 ± 0.6 mV, P < 0.001) than the RA. The TAT correlated with the voltage (r =–0.65, P< 0.001). The patients with persistent AF had a lower atrial voltage, higher coefficient of variance for the LA voltage, longer LA TAT, and more extensive scar than those with paroxysmal. The patients with recurrent AF after catheter ablation had a lower LA voltage and higher incidence of LA scarring than those without recurrence. A scar located in the low anteroseptal or low posterior wall of LA was related to recurrence of AF. LA scarring was the independent predictor of AF recurrence after catheter ablation. Conclusion: The LA voltage was lower than the RA, and the atrial voltage correlated with the TAT. Electroanatomical remodeling of the atria could be crucial to the maintenance of AF. The LA substrate properties may play an important role in the recurrence of AF after catheter ablation of AF. [ABSTRACT FROM AUTHOR]

Background: Electrical isolation of pulmonary veins (PVs) is an effective therapy for atrial fibrillation (AF). Both segmental ostial PV ablation and circumferential ablation with PV–left atrial (LA) block have been implicated to eliminate AF. However, the mechanism of the recurrent AF after undergoing either strategy remains unclear. Methods and Results: Of the 73 consecutive patients with symptomatic AF that underwent PV isolation and had recurrences of AF, Group 1 consisted of 46 patients (age 56 ± 13 years old, 35 males) who underwent PV isolation by segmental ostial PV ablation and Group 2 consisted of 27 patients (age 51 ± 11 years old, 24 males) who underwent circumferential ablation with PV–LA block. In Group 1, the earliest ectopic beat or ostial PV potentials were targeted. In Group 2, circumferential ablation with PV–LA block was performed by encircling the extraostial regions around the left and right PVs. During the first procedure, all patients had PV–AF. There was no difference in the non-PV ectopy between Group 1 and Group 2. During the second procedure, the incidence of an LA posterior wall ectopy initiating AF was significantly lower (20% vs. 0%, P = 0.01) in Group 2. There was no difference in the PV ectopy initiating AF during the second procedure. Conclusion: Circumferential ablation of AF with PV–LA block may eliminate the LA posterior wall ectopy and decrease the incidence of LA posterior wall ectopy initiating AF during the second procedure. [ABSTRACT FROM AUTHOR]

Introduction: Some conflicting results of the efficacy of the inducibility test used in the catheter ablation of atrial fibrillation (AF) have been reported. The aim of this study was to investigate the inducibility and efficacy of circumferential ablation with pulmonary vein isolation (PVI) in patients with paroxysmal AF and its relationship to the atrial substrate. Methods and Results: This study consisted of 88 patients with paroxysmal AF who underwent catheter ablation. Electroanatomic mapping using a NavX system was performed and the biatrial voltage was obtained during sinus rhythm. After successful circumferential ablation with PVI, an inducibility test was performed to determine the requirement for creating left atrial (LA) ablation line. After procedure, patients with inducible AF had a higher recurrence rate than did those with noninducibility of AF (55% vs 18%, P = 0.02). The patients with inducible AF after the PVI had a lower biatrial voltage than did those with negative inducibility. The patients with inducible AF after the final procedure who had a recurrence had a lower LA voltage (1.3 ± 0.4 vs 1.8 ± 0.4 mV, P = 0.02) and longer LA total activation time (99 ± 18 vs 88 ± 13 msec, P = 0.02) than did those with noninducible AF and no recurrence. None of the patients had occurrence of LA flutter during the follow-up. Conclusion: After a single procedure of circumferential ablation with PVI and noninducibility, 82% patients did not have recurrence of AF. The inducibility of AF was related to the recurrence of AF. The atrial substrate affected the outcome of the inducibility. [ABSTRACT FROM AUTHOR]

Background: Atrial substrate properties have been demonstrated to be related to atrial arrhythmias. This study investigated whether the atrial substrate exhibits progressive remodeling in patients with recurrence of atrial fibrillation (AF) after catheter ablation. Methods and Results: Fifteen consecutive AF patients (52 ± 12 years old, 12 males) underwent the same mapping technique (NavX, St. Jude Medical, Minnetonka, MN, USA) and same ablation technique for primary AF and recurrence of AF (170 ± 66 days after the first procedure). The bipolar mean peak-to-peak voltage (PPV) of the global left atrium during sinus rhythm significantly decreased in the second procedure (2.25 ± 0.62 vs. 1.79 ± 0.60 mV, P = 0.008). Also, the percentage of the surface area of the low voltage zone (LVZ; less than 0.5 mV) in the left atrium increased from 6 ± 4% to 13 ± 6% (P = 0.001) in the second procedure. There was no significant change in the right atrial bipolar mean PPV or surface area of the LVZ in the second procedure. Conclusion: Atrial substrate remodeling with a progressive decrease in the left atrial voltage was demonstrated in patients with recurrent AF. [ABSTRACT FROM AUTHOR]

Introduction: Radiofrequency ablation (RFA) of typical AFL is sometimes difficult because of the poor electroanatomic approach to the cavotricuspid isthmus (CTI). The aim of this study was to correlate the anatomy of the CTI between contact mapping (NavX) and right atrial angiography (RAG), and to investigate the impact of the electroanatomic characteristics of the CTI on the RFA of typical atrial flutter (AFL). Methods: One hundred patients with typical AFL undergoing RFA were studied. The image-guided group consisted of 50 consecutive patients with the guidance of NavX. NavX geometry and RAG were performed to investigate the morphology of the CTI. The bipolar voltages of the CTI were collected during sinus rhythm by a NavX. The control group consisted of 50 consecutive patients with the guidance of conventional fluoroscopy. Results: There was a good correlation between the angiography and NavX for the anatomy of the CTI. The pouch type had a longer length of CTI than the flat type (33.4 ± 5.0 vs 22.6 ± 8.4 mm, P < 0.0001) and deeper depth than the concave type (6.5 ± 2.2 vs 3.7 ± 0.8 mm, P < 0.0001) on the angiography. The pouch-type CTI had a longer ablation time and larger pulses of RFA than the other two types. The control group had a longer ablation time, fluoroscopy time, and larger pulses of RFA than image-guided group. Conclusions: The 3-D mapping system provided a good reconstruction of CTI, which may help in the RFA in patients with a complex anatomy of the CTI. [ABSTRACT FROM AUTHOR]

Introduction: The left atrial appendage (LAA) has been proven to be the most important site of thrombus formation in patients with atrial fibrillation (AF). However, the information regarding the morphometric alteration of the LAA related to the outcome of AF ablation is still lacking. Thus, we evaluated the long-term changes of the LAA morphology in patients undergoing catheter ablation of AF using magnetic resonance angiography (MRA). Methods and Results: Group 1 included 15 controls without any AF history. Group 2 included 40 patients with drug-refractory paroxysmal AF. They were divided into two subgroups: group 2a included 30 patients without AF recurrence after pulmonary vein (PV) ablation. Group 2b included 10 patients with late recurrence of AF. The LAA morphology before and after (20 ± 11 months) ablation was evaluated by three-dimensional MRA. The group 2 patients had a larger baseline LAA size (including the LAA orifice, neck, and length) and less eccentric LAA orifice and neck. After the AF ablation, there was a significant reduction in the LAA size in the group 2a patients, and the morphology of the LAA neck became more eccentric during the follow-up period. In group 2b, the LAA size increased and no significant change in the eccentricity of the orifice and neck could be noted. Conclusions: The morphometric remodeling of the LAA in the AF patients could be reversed after a successful ablation of the AF. Progressive dilation of the LAA was noted in the patients with AF recurrence. These structural changes in the LAA may play a role in reducing the potential risk of cerebrovascular accidents. [ABSTRACT FROM AUTHOR]

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) can usually be induced by atrial stimulation. However, it seldom may be induced with only ventricular stimulation, especially the fast-slow form of AVNRT. The purpose of this retrospective study was to investigate the specific electrophysiological characteristics in patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation. Methods: The total population consisted of 1,497 patients associated with AVNRT, and 106 (8.4%) of them had the fast-slow form of AVNRT and 1,373 (91.7%) the slow-fast form of AVNRT. In patients with the fast-slow form of AVNRT, the AVNRT could be induced with only ventricular stimulation in 16 patients, Group 1; with only atrial stimulation or both atrial and ventricular stimulation in 90 patients, Group 2; and with only atrial stimulation in 13 patients, Group 3. We also divided these patients with slow-fast form AVNRT (n = 1,373) into two groups: those that could be induced only by ventricular stimulation (Group 4; n = 45, 3%) and those that could be induced by atrial stimulation only or by both atrial and ventricular stimulation (n = 1.328, 97%). Results: Patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation had a lower incidence of an antegrade dual AVN physiology (0% vs 71.1% and 92%, P < 0.001), a lower incidence of multiple form AVNRT (31% vs 69% and 85%, P = 0.009), and a more significant retrograde functional refractory period (FRP) difference (99 ± 102 vs 30 ± 57 ms, P < 0.001) than those that could be induced with only atrial stimulation or both atrial and ventricular stimulation. The occurrence of tachycardia stimulated with only ventricular stimulation was more frequently demonstrated in patients with the fast-slow form of AVNRT than in those with the slow-fast form of AVNRT (15% vs 3%, P < 0.001). Patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation had a higher incidence of retrograde dual AVN physiology (75% vs 4%, P < 0.001), a longer pacing cycle length of retrograde 1:1 fast and slow pathway conduction (475 ± 63 ms vs 366 ± 64 ms, P < 0.001; 449 ± 138 ms vs 370 ± 85 ms, P = 0.009), a longer retrograde effective refractory period of the fast pathway (360 ± 124 ms vs 285 ± 62 ms, P = 0.003), and a longer retrograde FRP of the fast and slow pathway (428 ± 85 ms vs 362 ± 47 ms, P < 0.001 and 522 ± 106 vs 456 ± 97 ms, P = 0.026) than those with the slow-fast form of AVNRT that could be induced with only ventricular stimulation. Conclusion: This study demonstrated that patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation had a different incidence of the antegrade and retrograde dual AVN physiology and the specific electrophysiological characteristics. The mechanism of the AVNRT stimulated only with ventricular stimulation was supposed to be different in patients with the slow-fast and fast-slow forms of AVNRT. [ABSTRACT FROM AUTHOR]

Introduction: The mechanisms of late (<1 year after the ablation) and very late (>1 year after the ablation) recurrences of paroxysmal atrial fibrillation (AF) after catheter ablation have not been reported. Methods and Results: Fifty consecutive patients undergoing a repeated electrophysiologic study to investigate the recurrence of paroxysmal AF after the first ablation were included. Group 1 consisted of 12 patients with very late (26 ± 13 months) and group 2 consisted of 38 patients with late (3 ± 3 months) recurrence of paroxysmal AF. In the baseline study, group 1 had a lower incidence of AF foci from the pulmonary veins (PVs) (67% vs 92%, P = 0.048) and a higher incidence of AF foci from the right atrium (50% vs 13%, P = 0.014) than group 2. In the repeated study, group 1 had a higher incidence of AF foci from the right atrium (67% vs 3%, P < 0.001) and a lower incidence of AF foci from the left atrium (50% vs 97%, P < 0.001), including a lower incidence of AF foci from the PVs (50% vs 79%, P = 0.07) and from the left atrial free wall (0% vs 29%, P = 0.046) than group 2. Furthermore, most of these AF foci (64% of group 1, 65% of group 2) were from the previously targeted foci. Conclusion: The right atrial foci played an important role in the very late recurrence of AF, whereas the left atrial foci (the majority were PVs) were the major origin of the late recurrence of AF after the catheter ablation of paroxysmal AF. [ABSTRACT FROM AUTHOR]

Ablation of AF. Background:Catheter ablation of atrial fibrillation (AF) has become another nonpharmacologic therapeutic option for medically refractory paroxysmal AF. Whether this method is better than atrioventricular (AV) junction ablation plus pacing therapy is unknown. The purpose of this study was to compare the very long-term (longer than 4 years) clinical outcomes of the 2 methods in elderly patients (>65 years old) with medically refractory paroxysmal AF.Methods:From January 1995 to December 2001, 71 elderly patients with medically refractory paroxysmal AF were included; group 1 included 32 patients with successful AV junction ablation plus pacing therapy and group 2, 37 patients with successful catheter ablation of AF.Results:After a mean follow-up of more than 52 months, the AF was better controlled in the group 1 patients than group 2 (100% vs 81%, P= 0.013), however, they had a significantly higher incidence of persistent AF (69% vs 8%, P<0.001) and heart failure (53% vs 24%, P= 0.001). Furthermore, the incidence of ischemic stroke and cardiac death was similar between the 2 groups. Compared with the preablation values, a significant increase in the NYHA functional class (1.7± 0.9 vs 1.4± 0.7, P= 0.01) and significant decrease in the left ventricular ejection fraction (44± 8% vs 51± 10%, P= 0.01) were noted in the group 1 patients, but not in the group 2 patients.Conclusions:Although AV junction ablation plus pacing therapy better controlled the AF in elderly patients with medically refractory paroxysmal AF, that method was associated with a higher incidence of persistent AF and heart failure than catheter ablation of AF in the very long-term follow-up.(J Cardiovasc Electrophysiol, Vol. 16, pp. 457-461, May 2005) [ABSTRACT FROM AUTHOR]

Atrial Fibrillation and Superior Caval Vein Ectopy. Introduction:The structural changes of the superior caval vein, pulmonary veins, and left atrium in atrial fibrillation initiated by superior caval vein ectopy have not been reported.Methods and Results:Nine patients with atrial fibrillation initiated by superior caval vein ectopic beats (male= 5, 54± 10 years) and 15 control (n= 15, male = 10, 52 ± 8 years) without any cardiac arrhythmias were included in this study. Using gadolinium-enhanced magnetic resonant angiography with three-dimensional reconstruction, the parameters of the superior caval vein morphology (length, various diameters, area, eccentricity, and volume) were measured. The morphological parameters of the four pulmonary veins (diameter, ostial area, and eccentricity) were also measured at the pulmonary vein–left atrial junction in an oblique sagittal section from the multiple-plane reconstruction images. The left atrial diameters and volume were measured. The different morphological parameters were compared between the two groups. The patients with atrial fibrillation initiated by superior caval vein ectopic beats exhibited a more eccentric structure of the second part of the superior caval vein as compared to the control group. All the ectopic beats initiating atrial fibrillation were located in the second part of the superior caval vein. Furthermore, the patients with atrial fibrillation initiated by superior caval vein ectopic beats had a larger superior caval vein volume, left atrial volume, and pulmonary vein size, and more eccentric pulmonary vein ostia than the controls.Conclusion:Structural changes of the superior caval vein were demonstrated in the patients with atrial fibrillation initiated by superior caval vein ectopic beats. These findings might explain the arrhythmogenic mechanism of atrial fibrillation initiated by superior caval vein ectopy.(J Cardiovasc Electrophysiol, Vol. 16, pp. 411-417, April 2005) [ABSTRACT FROM AUTHOR]

Characteristics of Midseptal Accessory Pathways. Background:The purpose of the present study was to investigate the electrocardiographic and electrophysiologic characteristics of right midseptal (RMS) and left midseptal (LMS) accessory pathways (APs), and to develop a stepwise algorithm to differentiate RMS from LMS APs.Methods and Results:From May 1989 to February 2004, 1591 patients with AP-mediated tachyarrhythmia underwent RF catheter ablation in this institution, and 38 (2.4%) patients had MS APs. The delta wave and precordial QRS transition during sinus rhythm, retrograde P wave during orthodromic tachycardia, and electrophysiologic characteristic and catheter ablation in 30 patients with RMS APs and 8 patients with LMS APs were analyzed. There was no significant difference in electrophysiologic characteristics and catheter ablation between RMS and LMS APs. The polarity of retrograde P wave during orthodromic tachycardia also showed no statistical difference between patients with RMS and LMS APs. The delta wave polarity was positive in leads I, aVL, and V3 to V6 in patients with RMS and LMS APs. Patients with LMS APs had a higher incidence of biphasic delta wave in lead V1 than patients with RMS APs (80% vs. 15%, P= 0.012). The distributions of precordial QRS transition were different between RMS APs (leads V2; n= 10, V3; n= 7 and V4; n= 3) and LMS APs (leads V1; n= 1 and V2; n= 4) (P= 0.03). The combination of a delta negative wave in lead V1 or precordial QRS transition in lead V3 or V4 had a sensitivity of 90%, specificity of 80%, positive predictive value of 95%, and negative predictive value of 66% in predicting an RMS AP.Conclusions:Delta wave polarity in lead V1 and precordial QRS transition may differentiate RMS and LMS APs.(J Cardiovasc Electrophysiol, Vol. 16, pp. 1-7, March 2005) [ABSTRACT FROM AUTHOR]

Right Atrial Substrate of Supraventricular Tachyarrhythmias. Background:Voltage mapping has been used to detect diseased myocardium. However, accurate determination of the local atrial voltage at the same site, and simultaneous recordings from multiple mapping sites were limited. The purpose of this study was to investigate the right atrial (RA) substrate properties in patients with supraventricular tachyarrhythmias (SVT).Methods and Results:Forty patients (aged 55± 20 years) undergoing noncontact mapping and ablation of SVT constituted the study population. There were eight patients with atrioventricular node reentrant tachycardia (AVNRT), eight patients with focal atrial tachycardia (AT), 14 patients with atrial flutter (AFL), and 10 patients with atrial fibrillation (AF). The mean peak negative voltage (PNV) was analyzed in virtual unipolar electrograms, which were obtained from 256 equally distributed RA endocardial sites during sinus rhythm (SR), atrial pacing, and tachycardia. The mean PNV of global RA during SR (−1.34± 0.22 vs.−0.90± 0.40 vs.−1.00± 0.36 vs.−0.85± 0.35 mV, P= 0.04), atrial pacing at cycle lengths of 500 ms (−1.30± 0.29 vs.−0.70± 0.35 vs.−0.76± 0.25 vs.−0.64± 0.26 mV, P= 0.02), and 300 ms (−1.54± 0.47 vs.−0.94± 0.21 vs.−0.75± 0.27 vs.−0.57± 0.22 mV, P<0.01) were significantly greater in patients with AVNRT compared to AT, AFL, and AF. Furthermore, the mean PNV decreased during atrial pacing with shorter pacing cycle length was demonstrated only in patients with AFL and AF.Conclusion:Negative unipolar voltage analysis of global RA showed different RA substrate characteristics during various SVT. The substrate property of activation and cycle length-dependent voltage reduction may be related to the development of AFL and AF.(J Cardiovasc Electrophysiol, Vol. 16, pp. 1-8, March 2005) [ABSTRACT FROM AUTHOR]

LEE, S-H.,et al.: Electrophysiological Characteristics of Junctional Rhythm During Ablation of the Slow Pathway in Different Types of Atrioventricular Nodal Reentrant Tachycardia. Background:Junctional rhythm (JR) is commonly observed during radiofrequency (RF) ablation of the slow pathway for atrioventricular (AV) nodal reentrant tachycardia. However, the atrial activation pattern and conduction time from the His-bundle region to the atria recorded during JR in different types of AV nodal reentrant tachycardia have not been fully defined.Methods:Forty-five patients who underwent RF ablation of the slow pathway for AV nodal reentrant tachycardia were included; 27 patients with slow-fast, 11 patients with slow-intermediate, and 7 patients with fast-slow AV nodal reentrant tachycardia. The atrial activation pattern and HA interval (from the His-bundle potential to the atrial recording of the high right atrial catheter) during AV nodal reentrant tachycardia (HASVT) and JR (HAJR) were analyzed.Results:In all patients with slow-fast AV nodal reentrant tachycardia, the atrial activation sequence recorded during JR was similar to that of the retrograde fast pathway, and transient retrograde conduction block during JR was found in 1 (4%) patient. The HAJR was significantly shorter than the HASVT (57± 24 vs 68± 21 ms, P<0.01). In patients with slow-intermediate AV nodal reentrant tachycardia, the atrial activation sequence of the JR was similar to that of the retrograde fast pathway in 5 (45%), and to that of the retrograde intermediate pathway in 6 (55%) patients. Transient retrograde conduction block during JR was noted in 1 (9%) patient. The HAJR was also significantly shorter than the HASVT (145± 27 vs 168± 29 ms, P= 0.014). In patients with fast-slow AV nodal reentrant tachycardia, retrograde conduction with block during JR was noted in 7 (100%) patients. The incidence of retrograde conduction block during JR was higher in fast-slow AV nodal reentrant tachycardia than slow-fast (7/7 vs 1/11, P<0.01) and slow-intermediate AV nodal reentrant tachycardia (7/7 vs 1/27, P<0.01).Conclusions:In patients with slow-fast and slow-intermediate AV nodal reentrant tachycardia, the JR during ablation of the slow pathway conducted to the atria through the fast or intermediate pathway. In patients with fast-slow AV nodal reentrant tachycardia, there was no retrograde conduction during JR. These findings suggested there were different characteristics of the JR during slow-pathway ablation of different types of AV nodal reentrant tachycardia.(PACE 2005; 28:111–118) [ABSTRACT FROM AUTHOR]

Remodeling of PV and LA after AF Ablation. Introduction:Understanding the structural remodeling and reverse remodeling of the left atrium (LA) and pulmonary vein (PV) after radiofrequency ablation of atrial fibrillation (AF) may provide important insights into the mechanism and management of AF. This study used magnetic resonance angiographic (MRA) images to investigate changes in PV and LA morphologies before and more than 1 year after ablation.Method and Results:Forty-five patients (36 men and 9 women, mean age 60± 13 years) who underwent MRA before and more than 12 months (mean 21± 11) after ablation of paroxysmal AF were included in the study. The patients were divided into two groups: group I included 35 patients without AF recurrence, and group II included 10 patients with late (>1 month postablation) recurrence of AF. The sizes of the LA and nonablated PV were compared before and after ablation. In group I, significant reduction of ostial area of both superior PVs was noted (left superior PV: from 2.85± 0.67 to 2.59± 0.73 cm2; right superior PV: from 2.89± 0.85 to 2.60± 0.73 cm2, both P<0.001). Geometric alteration toward a round shape was noted in the ostia of superior PVs during follow-up (eccentricity of right superior PV and left superior PV decreased from 0.31± 0.10 to 0.22± 0.13 and from 0.27± 0.11 to 0.19± 0.13, respectively, oth P<0.01). However, LA volume showed only borderline reduction (from 61.52± 19.06 to 56.64± 17.13 mL, P= 0.05). In group II, significant dilation of the LA (from 61.14± 17.54 to 78.73± 25.27 mL, P= 0.004) and right superior PV (from 3.41± 1.12 to 4.08± 1.31 cm2, P= 0.016) was noted during follow-up. Ostial area and eccentricity of the left superior, left inferior, and right inferior PVs and LA were similar before and after ablation.Conclusion:Structural remodeling of the superior PVs and LA can be reversible after successful ablation without AF recurrence; however, late recurrence of AF is associated with progressive LA dilation.(J Cardiovasc Electrophysiol, Vol. 16, pp. 7-12, January 2005) [ABSTRACT FROM AUTHOR]

Focal Atrial Tachycardia. Introduction:Adenosine can terminate most focal atrial tachycardias (ATs). However, information about the termination mechanism is limited. This study investigated the effects and mechanism of adenosine on terminating focal AT using a three-dimensional noncontact mapping system.Methods and Results:The study consisted of 7 patients (4 men and 3 women; age 44± 29 years) with focal AT. Cycle length variation and atrial activation pattern at baseline and just before AT termination by adenosine (3–12mg) were analyzed. Noncontact mapping demonstrated focal AT propagated from the origin (O) with preferential conduction and spread away from the breakout sites to the whole atrium. Compared to baseline AT, termination episodes revealed higher mean beat-to-beat variation of AT cycle length (11.7± 11.7 msec vs 4.7± 4.5 msec, P<0.001) and standard deviation of normalized AT cycle length (0.033± 0.014 vs 0.011± 0.005, P<0.001). In termination episodes, adenosine significantly decreased the peak negative voltage of AT-O (–27.2± 15.3%, P<0.01), preferential conduction (proximal:–32.1± 18.7, mid:–28.4± 22.8, distal portion:–29.6± 21.4%, P<0.01), and breakout (–31.4± 12.5%, P<0.01). However, adenosine did not affect voltage in nontermination episodes. Adenosine shifted the locations of AT-O in 5 of 10 AT episodes with termination. Mean number of shifting AT-O was 2.4± 1.5 (range 1–4), with maximum shifting distance of 15.0± 3.1 (range 10–19) mm. Focal activation at AT-O simply disappeared in all termination episodes and therefore was not due to conduction block within preferential conduction or breakout site. Catheter ablation lesions covered 50% of total shifting origins, without late recurrence.Conclusion:Adenosine-induced AT termination was associated with significantly decreased electrogram voltage, shifting AT-O locations, and disappearance of focal activation.(J Cardiovasc Electrophysiol, Vol. 15, pp. 1-7, December 2004) [ABSTRACT FROM AUTHOR]

The exact reentrant circuit of the verapamil-sensitive idiopathic left VT with a RBBB configuration remains unclear. Furthermore, if the fascicle of left bundle branch is involved in the reentrant circuit has not been well studied. Forty-nine patients with verapamil-sensitive idiopathic left VT underwent electrophysiological study and RF catheter ablation. Group I included 11 patients (10 men, 1 woman; mean age 25 ± 8 years) with left anterior fascicular block (4 patients), or left posterior fascicular block (7 patients) during sinus rhythm. Group II included 38 patients (29 men, 9 women; mean age 35 ± 16 years) without fascicular block during sinus rhythm. Duration of QRS complex during sinus rhythm before RF catheter ablation in group I patients was significant longer than that of group II patients (104 ± 12 vs 95 ± 11 ms, respectively, P = 0.02). Duration of QRS complex during VT was similar between group I and group II patients (141 ± 13 vs 140 ± 14 ms, respectively, P = 0.78). Transitional zones of QRS complexes in the precordial leads during VT were similar between group I and group II patients. After ablation, the QRS duration did not prolong in group I or group II patients (104 ± 11 vs 95 ± 10 ms, P = 0.02); fascicular block did not occur in group II patients. Duration and transitional zone of QRS complex during VT were similar between the two groups, and new fascicular block did not occur after ablation. These findings suggest the fascicle of left bundle branch may be not involved in the antegrade limb of reentry circuit in idiopathic left VT. (PACE 2003; 26:1986–1992) [ABSTRACT FROM AUTHOR]

Very Late Recurrence of AF. Introduction: High recurrence rate is still a major problem associated with ablation of paroxysmal atrial fibrillation (AF). Most of the recurrences occur within 6 months after ablation. The characteristics of very late recurrent AF (>12 months after ablation) have not been reported. Methods and Results: Two hundred seven patients with drug-refractory AF underwent successful focal ablation or isolation of AF foci. After the first ablation procedure, Holter monitoring and event recorders were used to evaluate symptomatic recurrent AF. A second ablation procedure was recommended if the antiarrhythmic drugs could not control recurrent AF. During long-term follow-up (mean 30 ± 11 months, up to 51 months), 70 patients had recurrent AF, including 13 patients (6%) with very late (>12 months) recurrent AF (group 1) and 57 patients (28%) with late (within 12 months after ablation) recurrent AF(group 2). Group 1 patients had a significantly lower incidence of multiple (≥2) AF foci (23% vs 63%, P = 0.02) than group 2 patients. In addition, the incidence of antiarrhythmic drugs use (38% vs 84%, P = 0.001) to maintain sinus rhythm after the first episode of recurrent AF was significantly lower in group 1 than group 2 patients, and the incidence of a second intervention procedure (8% vs 35%, P = 0.051) tended to be lower in group 1 than group 2 patients. Conclusion: The incidence of very late recurrent AF after ablation of paroxysmal AF is very low, and the clinical outcome of patients with very late recurrent AF is benign.(J Cardiovasc Electrophysiol, Vol. 14, pp. 598-601, June 2003). [ABSTRACT FROM AUTHOR]

Noncontact Mapping of SVC Tachycardia. Introduction: Information about the activation patterns inside the superior vena cava (SVC) and entry and exit sites at the SVC-right atrial (RA) junction during SVC tachyarrhythmia is limited. Methods and Results: A detailed characterization of electrophysiologic mechanisms and ablation strategies was performed using a noncontact three-dimensional mapping system in two cases of SVC tachycardia. The first case demonstrated SVC tachycardia originating from an ectopic focus inside the SVC, with sustained depolarization and conduction to the atrium. Entry and exit sites across the SVC-RA junction were located very close to each other. The second case demonstrated two different reentrant circuits, one inside the SVC and the other into and out of the SVC-RA junction. The entry and exit sites were located far away from each other. Conclusion: Noncontact mapping may help to reveal the mechanism of SVC tachyarrhythmias and to locate entry and exit sites at the SVC-RA junction as a guide for catheter ablation.(J Cardiovasc Electrophysiol, Vol. 14, pp. 533-539, May 2003). [ABSTRACT FROM AUTHOR]

P Wave Polarities of Paroxysmal AF. Introduction: The superior vena cava (SVC) and right superior pulmonary vein (RSPV) are anatomically close structures. Using 12-lead ECG may facilitate identification of ectopic foci from SVC or RSPV. The aim of this study was to assess whether P wave polarity on surface ECG is helpful in distinguishing an arrhythmogenic focus of paroxysmal atrial fibrillation (AF) from SVC or RSPV. Methods and Results: Thirty-four patients with paroxysmal AF from the SVC (group I: 17 patients, 10 men and 7 women; mean age 57 ± 12 years ) or RSPV (group II: 17 patients, 15 men and 2 women, mean age 62 ± 14 years ) underwent electrophysiologic study and radiofrequency (RF) catheter ablation. All of the AF foci were confirmed by successful ablation. P wave polarities on surface ECG inferior leads were positive during sinus rhythm and ectopic beats in both groups. Leads I, aVR, aVL, and V[sub 1] were further analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in predicting an arrhythmogenic focus of AF from SVC or RSPV were provided. P wave polarity in lead aVR was negative in all 34 patients. P wave polarity in lead V[sub 1] was positive in 47.1% of SVC ectopy but positive in all RSPV ectopy. The combination of a biphasic or isoelectric P wave polarity in lead V[sub 1] or a biphasic P wave polarity in lead aVL had a sensitivity of 71%, specificity of 82%, PPV of 80%, and NPV of 74% in predicting an arrhythmogenic focus of AF from SVC. Conclusion: P wave polarity in leads V[sub 1] and aVL may predict an arrhythmogenic focus of AF from SVC or RSPV. (J Cardiovasc Electrophysiol, Vol. 14, pp. 350-357, April 2003). [ABSTRACT FROM AUTHOR]

The authors reflect on the result of the study which assesses the effectiveness of patent foramen ovale (PFO) in performing catheter ablation of the left atrium. They contend that the utilization of PFO has been found to provide easy access of the left heart during catheter ablation of paroxysmal atrial fibrillation (AF), compared to transseptal puncture. The authors also assert that PFO prevents the development of complications observed with the use of transseptal puncture.

The article provides information concerning the routinely perform isolation of the superior vena cava in every atrial fibrillation patient in the U.S. The rapid evolution of atrial fibrillation (AF) ablation techniques has improved people's knowledge about the mechanisms of AF. The author infers that several studies have proven that right atrial triggers and the right atrial substrate are important for AF initiation and maintenance.

The article comments on the mechanism and ablation techniques of atrial fibrillation (AF). Researchers found that the persistent atrial fibrillation patients had a higher incidence of non-pulmonary veins triggers compared with the paroxysmal AF patients. AF is the most common sustained arrhythmia, and might also be the most complex arrhythmia.

Background: Chronic kidney disease (CKD) increases the occurrence of atrial fibrillation and pulmonary vein (PV) arrhythmogenesis. Calcium dysregulation and reactive oxygen species (ROS) enhance PV arrhythmogenic activity. The purposes of this study were to investigate whether CKD modulates PV electrical activity through dysregulation of calcium homeostasis and ROS., Methods and Results: Biochemical and electrocardiographic studies were conducted in rabbits with and without CKD (induced by 150 mg/kg per day neomycin sulfate and 500 mg/kg per day cefazolin). Confocal microscopy with fluorescence and a whole-cell patch clamp were applied to study calcium homeostasis and electrical activities in control and CKD isolated single PV cardiomyocytes with or without treatment with H89 (1 μmol/L, a protein kinase A inhibitor) and MPG (N-[2-mercaptopropionyl]glycine; 100 μmol/L, a ROS scavenger). The ROS in mitochondria and cytosol were evaluated via intracellular dye fluorescence and lipid peroxidation. CKD rabbits had excessive atrial premature captures over those of control rabbits. Compared with the control, CKD PV cardiomyocytes had a faster beating rate and larger calcium transient amplitudes, sarcoplasmic reticulum calcium contents, sodium/calcium exchanger currents, and late sodium currents but smaller L-type calcium current densities. CKD PV cardiomyocytes had a higher frequency and longer duration of calcium sparks and more ROS in the mitochondria and cytosol than did controls. Moreover, H89 suppressed all calcium sparks in CKD PV cardiomyocytes, and H89- and MPG-treated CKD PV cardiomyocytes had similar calcium transients compared with control PV cardiomyocytes., Conclusions: CKD increases PV arrhythmogenesis with enhanced calcium-handling abnormalities through activation of protein kinase A and ROS., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)