A critical decrease in dominant frequency and clinical outcome after catheter ablation of persistent atrial fibrillation.

BACKGROUND: Termination of persistent atrial fibrillation (AF) by radiofrequency ablation (RFA) is associated with a high probability of freedom from AF but requires extensive ablation and long procedure times. OBJECTIVE: The purpose of this study was to determine whether a critical decrease in the dominant frequency (DF) of AF is a sufficient endpoint for RFA of persistent AF. METHODS: Antral pulmonary vein isolation (APVI) followed by RFA of complex fractionated atrial electrograms (CFAEs) in the atria and coronary sinus was performed in 100 consecutive patients with persistent AF. The DF of AF in lead V1 and in the coronary sinus was determined by fast Fourier transform (FFT) analysis at baseline and before termination of AF to identify a critical decrease in DF predictive of sinus rhythm after RFA. RESULTS: A > or =11% decrease in DF had the highest accuracy in predicting freedom from atrial arrhythmias, with a sensitivity of 0.71 and a specificity of 0.82 (P <.001). At a mean follow-up of 14 +/- 3 months after one ablation procedure, sinus rhythm was maintained off antiarrhythmic drugs in 8/35 (23%) and 20/26 (77%) of patients with a <11% and > or =11% decrease in DF, respectively (P <.001). Sinus rhythm was maintained in 24/39 patients (62%) in whom RFA terminated AF. The duration of RFA and total procedure time were longer in patients with AF termination (95 +/- 23 and 358 +/- 87 minutes) than in patients with a <11% decrease in the DF (77 +/- 16 and 293 +/- 70 minutes) or > or =11% decrease in DF (80 +/- 17 and 289 +/- 73 minutes), respectively (P <.01). Among the variables of age, gender, left atrial diameter, duration of AF, left ventricular ejection fraction, duration of RFA, a > or =11% decrease in DF, and termination of AF, a > or =11% decrease in DF (odds ratio = 9.89, 95% confidence interval [CI] 2.84-34.47) and termination during RFA (OR = 4.38, 95% CI 1.50-12.80) were the only independent predictors of freedom from recurrent atrial arrhythmias. CONCLUSION: In a retrospective analysis of consecutive patients with persistent AF, a decrease in the DF of AF by 11% in response to APVI and ablation of CFAEs was associated with a probability of maintaining sinus rhythm that was similar to that when RFA terminates AF.

Inadvertent electrical isolation of the left atrial appendage during catheter ablation of persistent atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) isolation is rare and may be associated with impaired transport function and thromboembolism. OBJECTIVE: The purpose of this study was to determine the mechanisms of inadvertent isolation of the LAA during atrial fibrillation (AF) ablation. METHODS: This study consisted of 11 patients (ejection fraction 0.43 +/- 0.18, left atrial diameter 51 +/- 8 mm) with persistent AF who had LAA conduction block during a procedure for AF (n = 8) or atrial tachycardia (AT) (n = 3). RESULTS: LAA conduction block occurred during ablation at the Bachmann bundle region in 6 patients, mitral isthmus in 3, LAA base in 2, and coronary sinus in 1. The mean distance from the ablation site to the LAA base was 5.0 +/- 1.9 cm. LAA isolation was transient in all 6 patients in whom LAA conduction was monitored and was permanent in the 4 patients in whom conduction was not monitored during energy delivery. The remaining patient was noted to have LAA isolation during a redo procedure before any ablation. Nine of (82%) the 11 patients have remained arrhythmia-free without antiarrhythmic drugs at mean follow-up of 6 +/- 7 months, and all have continued taking warfarin. CONCLUSION: Electrical isolation of the LAA may occur during ablation of persistent AF and AT even when the ablation site is remote from the LAA. This likely is due to disruption of the Bachmann bundle and its leftward extension, which courses along the anterior left atrium and bifurcates to surround the LAA. Monitoring of LAA conduction during ablation of persistent AF or AT is important in avoiding permanent LAA isolation.

A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation.

OBJECTIVES: This study sought to determine whether ablation of complex fractionated atrial electrograms (CFAEs) after antral pulmonary vein isolation (APVI) further improves the clinical outcome of APVI in patients with long-lasting persistent atrial fibrillation (AF). BACKGROUND: Ablation of CFAEs has been reported to eliminate persistent AF. However, residual pulmonary vein arrhythmogenicity is a common mechanism of recurrence. METHODS: In this randomized study, 119 consecutive patients (mean age 60 +/- 9 years) with long-lasting persistent AF underwent APVI with an irrigated-tip radiofrequency ablation catheter. Antral pulmonary vein isolation resulted in termination of AF in 19 of 119 patients (Group A, 16%). The remaining 100 patients who still were in AF were randomized to no further ablation and underwent cardioversion (Group B, n = 50) or to ablation of CFAEs in the left atrium or coronary sinus for up to 2 additional hours of procedure duration (Group C, n = 50). RESULTS: Atrial fibrillation terminated during ablation of CFAEs in 9 of 50 patients (18%) in Group C. At 10 +/- 3 months after a single ablation procedure, 18 of 50 (36%) in Group B and 17 of 50 (34%) in Group C were in sinus rhythm without antiarrhythmic drugs (p = 0.84). In Group A, 15 of 19 patients (79%) were in sinus rhythm. A repeat ablation procedure was performed in 34 of 100 randomized patients (for AF in 30 and atrial flutter in 4). At 9 +/- 4 months after the final procedure, 34 of 50 (68%) in Group B and 30 of 50 (60%) in Group C were in sinus rhythm without antiarrhythmic drugs (p = 0.40). CONCLUSIONS: Up to 2 h of additional ablation of CFAEs after APVI does not appear to improve clinical outcomes in patients with long-lasting persistent AF.

Relationship between the spectral characteristics of atrial fibrillation and atrial tachycardias that occur after catheter ablation of atrial fibrillation.

BACKGROUND: During catheter ablation of complex fractionated atrial electrograms, persistent atrial fibrillation (AF) may convert to an atrial tachycardia (AT). OBJECTIVE: The purpose of this study was to investigate the possible mechanisms of AT by examining the spectral and electrophysiologic characteristics of AF and ATs that occur after catheter ablation of AF. METHODS: The subjects of this study were 33 consecutive patients with persistent AF who had conversion of AF to AT during ablation of AF (group I) and 20 consecutive patients who underwent ablation of persistent AT that developed more than 1 month after AF ablation (group II). Spectral analysis of the coronary sinus (CS) electrograms and lead V(1) was performed during AF at baseline, before conversion, and during AT. The spatial relationship between the AT mechanism and ablation sites was examined. RESULTS: A spectral component with a frequency that matched the frequency of AT was present in the baseline periodogram of AF more often in group I (52%) than in group II (20%, P = .02). Ablation resulted in a decrease in the dominant frequency of AF but not in the frequency of the spectral component that matched the AT. There was a significant direct relationship between the baseline dominant frequency of AF and the frequency of AT in the CS in group I (r = 0.76, P <.0001) but not in group II (r = 0.38, P = .09). ATs were macroreentrant in 64% and 60% of patients in groups I and II, respectively (P = .8). The AT site was more likely to be distant (>1 cm) from AF ablation sites in group I (70%) than in group II (35%, P = .007). CONCLUSION: The findings of this study suggest that ATs observed during ablation of AF often may be drivers of AF that become manifest after elimination of higher-frequency sources and fibrillatory conduction.

Prevalence and characteristics of continuous electrical activity in patients with paroxysmal and persistent atrial fibrillation.

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) may play a role in the genesis of atrial fibrillation (AF). One type of CFAE is continuous electrical activity (CEA). The prevalence and characteristics of CEA in patients with paroxysmal and persistent AF are unclear. METHODS AND RESULTS: In 44 patients (age = 59 +/- 8 years) with paroxysmal (25) or persistent (19) AF, bipolar electrograms were systematically recorded for > or =5 seconds at 24 left atrial (LA) sites, including 8 antral sites, and 2 sites within the coronary sinus (CS). CEA was defined as continuous depolarization for >1 second with no isoelectric interval. CEA was recorded at the LA septum (79%), antrum (66%), posterior (68%) and anterior walls (67%), roof (66%), base of the LA appendage (61%), inferior wall (61%), posterior mitral annulus (48%), CS (41%), and in the LA appendage (14%). Antral CEA was equally prevalent in patients with paroxysmal (63%) and persistent AF (70%, P = 0.12). In patients with paroxysmal AF, the prevalence of CEA was similar among antral and nonantral LA sites, except for the LA appendage. However, in patients with persistent AF, CEA was more prevalent at the nonantral (80%) than antral sites (70%, P = 0.03). CEA at nonantral sites except the CS was more prevalent in persistent than in paroxysmal AF (80% vs 57%, P < 0.001). The mean duration of intermittent episodes of CEA was longer in persistent than in paroxysmal AF (P < 0.001). CONCLUSIONS: The higher prevalence and duration of CEA at nonantral sites in persistent than in paroxysmal AF is consistent with a greater contribution of LA reentrant mechanisms in persistent AF. However, the high prevalence of CEA at nonantral sites in paroxysmal atrial fibrillation (PAF) suggests that CEA alone is a nonspecific marker of appropriate target sites for ablation of AF. The characteristics of CEA that most accurately identify drivers of AF remain to be determined.

Sildenafil promotes ischemia-induced angiogenesis through a PKG-dependent pathway.

BACKGROUND: Peripheral artery disease (PAD) is a prevalent cardiovascular disorder that results in tissue ischemia which can progress to critical limb ischemia. Restoration of tissue perfusion in the setting of chronic ischemia through stimulation of arteriogenesis and angiogenesis remains a key therapeutic target for PAD. However, experimental therapeutics, including growth factor and gene therapy, have had little clinical success indicating the need for a better understanding of molecular pathways required for therapeutic angiogenesis. METHODS AND RESULTS: Here we report that phosphodiesterase-5 inhibition by sildenafil significantly increases vascular perfusion, tissue blood flow, and vascular density during chronic ischemia of the mouse hind limb. Importantly, sildenafil therapy did not alter any of these parameters in nonischemic limbs. Sildenafil increased tissue cGMP levels independently of increases in nitric oxide production, and sildenafil therapy stimulated angiogenesis in ischemic limbs of eNOS-/- and iNOS-/- mice. Lastly, sildenafil-mediated angiogenic activity was blocked by inhibition of protein kinase G using the PKG antagonist DT-3. CONCLUSIONS: These data demonstrate that sildenafil therapy results in increased angiogenic activity through a PKG-dependent pathway that is independent of nitric oxide production or NOS activity and identify the angiogenic therapeutic potential of sildenafil for critical limb ischemia.

Gender differences in selection of pacemakers: a single-center study.

BACKGROUND: Previous studies have reported gender differences in pacemaker selection. OBJECTIVE: This study aimed to assess gender-related differences in pacemaker mode selection in patients undergoing their first implantation. METHODS: A retrospective analysis was undertaken from a single-center database of pacemaker implants during the years 2001 to 2003. Univariate and multivariate analyses were used to compare pacemaker mode selection adjusted for any significant difference between the sexes. RESULTS: A total of 274 pacemakers were implanted during the study period, 259 of which formed the basis of this study. Of the patients receiving pacemakers, 132 were male and 127 were female. The majority of patients (144 [55.6%]) had sick sinus syndrome as their indication for receiving a pacemaker, followed by complete heart block (75 [29.0%]), and second-degree or high-grade atrio-ventricular block (36 [13.9%]). Four (1.5%) patients had hypersensitive carotid sinus syndrome. The mean (SD) age of patients was 61.35 (15) years. Most (155 [59.8%]) patients were younger than age 65, and the women were significantly older than the men (P = 0.004). Atrial fibrillation (AF) was present in 53 (20.5%) patients. Dual-chamber (DDD) pacemakers were implanted in 196 (75.7%) patients, and single-chamber ventricular pacemakers in 63 (24.3%) patients. Significantly more DDD pacemakers were implanted in patients aged <65 years compared with those aged > or =65 years (P < 0.01). This difference was, however, primarily due to the higher rate of AF in the older patients versus patients aged <65 years. Although the rate of DDD implantations was observed to be higher among women (101/127 [79.5%]) compared with men (95/132 [72.0%]), the rate difference was nonsignificant, even when adjusted for the significant age difference between the sexes. Furthermore, DDD selection was independent of patients' health insurance status. CONCLUSIONS: We found no significant difference in pacemaker mode selection between male and female patients. However, we did find that patients aged <65 years were more likely to have DDD pacemakers implanted compared with older patients. This age-dependent difference was primarily due to the higher prevalence of AF in the older age group versus the younger patients. Key words: pacemaker implant gender difference gender and pacemaker selection.

Prevalence of asymptomatic recurrences of atrial fibrillation after successful radiofrequency catheter ablation.

INTRODUCTION: The long-term efficacy of radiofrequency catheter ablation of atrial fibrillation (AF) has been based on patient-reported symptoms suggestive of AF. However, asymptomatic recurrences of AF may remain undetected. The aim of this study was to determine the prevalence of asymptomatic recurrences of AF after an apparently successful catheter ablation procedure for AF. METHODS AND RESULTS: Among 244 consecutive patients (mean age 53 +/- 11 years) who underwent a pulmonary vein isolation procedure for symptomatic paroxysmal AF and who reported no symptoms of recurrent AF at > or =6 months after the procedure, 60 patients with a history of > or =1 episode of AF per week were asked to participate in this study. Preablation, these patients had experienced 19 +/- 13 episodes of AF per month. The patients were provided with a patient-activated transtelephonic event recorder for 30 days, a mean of 642 +/- 195 days after the ablation procedure, and were asked to record and transmit recordings on a daily basis and whenever they felt palpitations. Seven patients (12%) felt palpitations during the study, although they had not experienced symptoms previously. Each of these 7 patients had an episode of AF documented with the event monitor during symptoms. In these 7 patients, the mean number of episodes per month decreased from 19 +/- 14 preablation to 3 +/- 1 postablation (P < 0.001). Among the 53 asymptomatic patients, an episode of AF was captured in 1 (2%) patient during the study period. CONCLUSION: Asymptomatic recurrences of AF after an apparently successful catheter ablation procedure for symptomatic paroxysmal AF are infrequent.

Clinical significance of inducible atrial flutter during pulmonary vein isolation in patients with atrial fibrillation.

OBJECTIVES: This study was designed to determine the prevalence and clinical significance of atrial flutter (AFL) that occurs during catheter ablation for atrial fibrillation (AF). BACKGROUND: Atrial flutter frequently occurs in patients with AF. METHODS: Pulmonary vein isolation was performed in 133 consecutive patients (age 52 +/- 11 years) for paroxysmal (n = 112) or persistent (n = 21) AF. A clinical episode of AFL was documented in 40 of the 133 patients (30%). During the ablation procedure, AFL occurred in 86 patients (65%), either spontaneously (n = 36) or by rapid atrial pacing (n = 50), with AFL being typical in the majority (80%). Cavo-tricuspid isthmus ablation was performed in 28 of the 133 patients. RESULTS: Among the 105 patients who did not undergo isthmus ablation, 25 patients (24%) were documented to have symptomatic AFL during a mean follow-up of 609 +/- 252 days. Among the clinical variables of age, gender, history of clinical AFL, ejection fraction, left atrial diameter, duration of AF, and occurrence of AFL during ablation, only a history of clinical AFL (p = 0.05) and occurrence of typical AFL during the ablation (p = 0.01) were independent predictors of symptomatic AFL during follow-up. The incidence of symptomatic AFL during follow-up was similar among patients who did and did not have long-term freedom from recurrent AF. CONCLUSIONS: In patients with AF who have either a history of AFL or an episode of typical AFL during an electrophysiologic study, symptomatic AFL is common after pulmonary vein isolation. Therefore, cavo-tricuspid isthmus ablation is appropriate during pulmonary vein isolation if AFL has been observed clinically or in the electrophysiology laboratory.

Incremental value of isolating the right inferior pulmonary vein during pulmonary vein isolation procedures in patients with paroxysmal atrial fibrillation.

Electrical isolation of the left superior, left inferior, and right superior pulmonary veins (PVs) is often, but not always, effective in eliminating paroxysmal atrial fibrillation (PAF). The incremental clinical value of also isolating the right inferior PV has not been well defined. PV isolation by ostial applications of radiofrequency energy guided by PV potentials was performed in 176 consecutive patients (mean age 52 +/- 11 years) with PAF. The left superior, left inferior, and right superior PVs were targeted in 106 patients, and all four PVs were targeted 70 patients. Successful isolation was achieved in 96% of targeted PVs. The mean duration of follow-up was 15 +/- 7 months. At 1-year follow-up, 58% of patients in whom three PVs were isolated were free of recurrent PAF in the absence of antiarrhythmic drug therapy, compared to 73% of patients in whom all four PVs were isolated (P = 0.07). There is a trend towards a better outcome when all four PVs are isolated than when only the three major PVs are isolated. Whenever feasible, the right inferior PV should be isolated along with the other three PVs during the first ablation procedure in patients with PAF.

Pulmonary vein isolation for vagotonic, adrenergic, and random episodes of paroxysmal atrial fibrillation.

INTRODUCTION: Based on the clinical history, paroxysmal atrial fibrillation (PAF) may be classified as vagotonic, adrenergic, or random. It is unclear whether pulmonary vein (PV) isolation is equally effective for these types of PAF. METHODS AND RESULTS: Segmental ostial ablation to isolate the PVs was performed in 188 consecutive patients (mean age 53 +/- 12 years) with PAF. Based on the clinical history, PAF was classified as random in 136 patients (72%), adrenergic in 30 (16%), and vagotonic in 22 (12%). Three or four PVs were targeted for isolation in all patients, and successful isolation was achieved in 96% of targeted PVs. At 1-year follow-up, 69% of patients with random AF, 83% of patients with adrenergic AF, and 50% of patients with vagotonic AF were free from recurrent episodes of AF in the absence of any antiarrhythmic drug therapy. Vagotonic AF was an independent clinical predictor of recurrent AF (P = 0.03). CONCLUSION: PV isolation has a lower efficacy in patients with vagotonic PAF than in patients with adrenergic or random episodes of PAF, suggesting that the PVs less often play an important role in vagotonic PAF.

Randomized comparison of anatomical versus voltage guided ablation of the cavotricuspid isthmus for atrial flutter.

OBJECTIVES: The purpose of this prospective study was to compare radiofrequency catheter ablation of the cavotricuspid isthmus using a strictly anatomic approach to an approach guided by a bipolar voltage map to avoid high voltage zones in the cavotricuspid isthmus. BACKGROUND: It is not clear whether local atrial electrogram amplitude influences the achievement of complete cavotricuspid isthmus block during radiofrequency catheter ablation for atrial flutter. METHODS: Thirty-two patients with atrial flutter were randomized to cavotricuspid isthmus ablation using an anatomical approach (group I, 16 patients) or guided by a bipolar voltage map (group II, 16 patients). A 3-dimensional electroanatomic mapping system and an 8-mm-tip ablation catheter were used in all patients. With the anatomical approach, an ablation line was created in the cavotricuspid isthmus at a 6 o'clock position in the 45 degree left anterior oblique projection. During voltage-guided ablation, a high-density bipolar voltage map of the cavotricuspid isthmus was created, and then contiguous applications of radiofrequency energy were delivered to create an ablation line through the cavotricuspid isthmus sites with the lowest bipolar voltage. RESULTS: Complete cavotricuspid isthmus conduction block was achieved in 100% of patients in each group. The mean maximum voltages along the line were 3.6 +/- 1.5 mV in group I, and 1.2 +/- 0.9 mV in group II (P < .01). Creating a high-density voltage map was associated with approximately 15-minute increase in the total procedure time (P = .2). During a mean follow-up of 177 +/- 40 days, there were no recurrences of atrial flutter in either group. There were no complications in either group. CONCLUSIONS: When cavotricuspid isthmus ablation for atrial flutter is performed with an 8-mm-tip catheter, complete block can be achieved in all patients regardless of local voltage. Ablation of high voltage zones is not associated with a higher recurrence rate. Therefore, anatomic ablation without voltage mapping is the preferred initial approach for cavotricuspid isthmus ablation.

Catheter ablation for paroxysmal atrial fibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation.

BACKGROUND: Segmental ostial catheter ablation (SOCA) to isolate the pulmonary veins (PVs) and left atrial catheter ablation (LACA) to encircle the PVs both may eliminate paroxysmal atrial fibrillation (PAF). The relative efficacy of these 2 techniques has not been directly compared. METHODS AND RESULTS: Of 80 consecutive patients with symptomatic PAF (age, 52+/-10 years), 40 patients underwent PV isolation by SOCA and 40 patients underwent LACA to encircle the PVs. During SOCA, ostial PV potentials recorded with a ring catheter were targeted. LACA was performed by encircling the left- and right-sided PVs 1 to 2 cm from the ostia and was guided by an electroanatomic mapping system; ablation lines also were created in the mitral isthmus and posterior left atrium. The mean procedure and fluoroscopy times were 156+/-45 and 50+/-17 minutes for SOCA and 149+/-33 and 39+/-12 minutes for LACA, respectively. At 6 months, 67% of patients who underwent SOCA and 88% of patients who underwent LACA were free of symptomatic PAF when not taking antiarrhythmic drug therapy (P=0.02). Among the variables of age, sex, duration and frequency of PAF, ejection fraction, left atrial size, structural heart disease, and the ablation technique, only an increased left atrial size and the SOCA technique were independent predictors of recurrent PAF. The only complication was left atrial flutter in a patient who underwent LACA. CONCLUSIONS: In patients undergoing catheter ablation for PAF, LACA to encircle the PVs is more effective than SOCA.