Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF). This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria. METHODS: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes. RESULTS: Celecoxib (0.3, 1, and 3 µM) reduced PV spontaneous beating rates, and induced delayed afterdepolarizations and burst firings in four of eight PV preparations (50%, p<0.05). Celecoxib also reduced SAN beating rates and decreased AP durations (APDs) in RA and LA, but did not change the resting membrane potential. Indomethacin (0.3, 1, 3, and 10 µM) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 µM) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10 µM) suppressed celecoxib (3 µM)-induced PV burst firings in 6 (86%, p<0.05) of 7 PVs. KB-R7943 (10 µM) suppressed celecoxib (3 µM)-induced PV burst firings in 5 (71%, p<0.05) of 7 PVs. CONCLUSIONS: Selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis.

The uremic toxin indoxyl sulfate increases 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.

Electrophysiological characteristics of complex fractionated electrograms and high frequency activity in atrial fibrillation.

BACKGROUND: It is unclear whether atrial substrate with complex fractionated electrograms (CFAEs) is related to arrhythmogenesis. This study aimed to investigate the electrophysiology in CFAE and high dominant frequency (DF) areas. METHODS AND RESULTS: Atrial fibrillation (AF) was induced by rapid atrial pacing in heart failure (HF) rabbits (4 weeks after coronary artery ligation). Real-time substrate mapping, multielectrode array, and monophasic action potential recordings were used to study areas of CFAE and DF. Conventional microelectrode and western blot were used to record the action potentials (APs) and protein expression in isolated tissue preparations. CFAE site with high DF had the most depolarized resting membrane potential, highest incidence of early and delayed afterdepolarizations, and steepest maxima slope of 90% of AP duration (APD90) restitution curve (RC) compared to CFAE site with low DF or non-CFAE sites. CFAE site with high DF exhibited the slowest conduction velocity and shortest wavelength than the other areas. Upregulation of the Na(+)-Ca(2+) exchanger (NCX), apamin-sensitive small-conductance Ca(2+)-activated K(+) channel type 2 (SK2) and sarcoplasmic reticulum Ca(2+)-ATPase, and downregulation of the Kir2.1 were found at CFAE site with high DF compared to that observed in the 3 other areas. Inhibition of the NCX and SK channels prolonged the APD90, flattened the maximum slope of RC, and suppressed AF. CONCLUSIONS: CFAE site with high DF had an arrhythmogenic property differing significantly from the other areas of LA in an HF rabbit model, which may contribute to the genesis of AF.

Apelin regulates the electrophysiological characteristics of atrial myocytes.

BACKGROUND: Apelin, a potential agent for treating heart failure, has various ionic effects on ventricular myocytes. However, the effects of apelin on the atrium are not clear. The purpose of this study was to investigate the acute effects of apelin on the electrophysiological characteristics of atrial myocytes. METHOD: Whole-cell patch-clamp techniques were used to investigate the action potential (AP) and ionic currents in isolated rabbit left atrial (LA) myocytes before and after the administration of apelin. RESULT: Apelin reduced LA AP duration measured at 90%, 50% and 20% repolarization of the amplitude by 11 ± 3%, 24 ± 5%, 30 ± 7% at 1 nM (n = 11), and by 14 ± 4%, 36 ± 6% and 45 ± 5% at 10 nM (n = 11), but not at 0·1 nM. Apeline (0·1, 1, 10 nM) did not change the amplitude, or resting membrane potential in LA myocytes. Apelin (1 nM) increased sodium currents, ultra-rapid potassium currents and the reverse mode of sodium-calcium exchanger currents, but decreased late sodium currents and L-type calcium currents and did not change transient outward currents or inward rectifier potassium currents in LA myocytes. CONCLUSIONS: Apelin significantly changed the atrial electrophysiology with a shortening of AP duration, which may be caused by its effects on multiple ionic currents.

Heart failure enhances arrhythmogenesis in pulmonary veins.

1. Heart failure (HF) predisposes to atrial fibrillation (AF) as a result of substrate remodelling. The present study aimed to investigate the impact of HF on the electrical remodelling of the pulmonary veins (PV) and left atrium (LA). 2. The electrical activity was recorded in LA and PV from control rabbits and rabbits with rapid ventricular pacing-induced HF, using a multi-electrode array system and conventional microelectrodes. 3. Compared with the control-PV (n = 21), the HF-PV (n = 13) had a higher incidence and frequency of rapid pacing-induced spontaneous activity (85 vs 29%, P = 0.005; 3.5 ± 0.2 vs 1.7 ± 0.1 Hz, P < 0.001) and high-frequency irregular electrical activity (92 vs 38%, P = 0.01; 23 ± 1 vs 19 ± 1 Hz, P = 0.003), greater depolarized resting membrane potential (-59 ± 1 vs -70 ± 2 mV, P < 0.001), higher incidence of early afterdepolarizations (EAD; 69 vs 6%, P = 0.001) and delayed afterdepolarizations (DAD; 92 vs 25%, P = 0.001), and slower conduction velocity (38 ± 2 vs 63 ± 2 cm/s, P < 0.05). In comparison to the HF-LA, the HF-PV had a higher incidence of spontaneous activity and high-frequency irregular electrical activity (85 vs 39%, P = 0.04; 92 vs 46%, P = 0.03), and higher incidence of EAD and DAD, and those differences were not found between the control-LA and control-PV. The control-PV with high-frequency irregular electrical activity had a higher incidence of DAD and spontaneous activity as compared with those without it. 4. HF contributed to an increased automaticity, triggered activity and conduction disturbance in the PV. The PV possessed more arrhythmogenic properties, which might play an important role in the genesis of AF in HF.

Sex differences in the electrophysiological characteristics of pulmonary veins and left atrium and their clinical implication in atrial fibrillation.

BACKGROUND: Sex and the autonomic nervous system play critical roles in the pathophysiology of atrial fibrillation (AF). Sex differences in electrophysiological characteristics of the pulmonary veins (PVs, AF initiator) and left atrium (LA, AF substrate) are not clear. METHODS AND RESULTS: Conventional microelectrodes were used to record the action potential in isolated PV and LA tissue preparations from male and female (age, 8≈10 months) rabbits before and after drug administration (adenosine, acetylcholine, and isoproterenol). Male PVs (n = 7) had a higher spontaneous beating rate (1.7 ± 0.2 versus 1.2 ± 0.1 Hz, P = 0.021) and incidence of burst firing (72% versus 11%, P = 0.038) than female PVs (n = 9). Male PVs without spontaneous activity (n = 10) and the LA (n = 11) had longer action potential durations than female PVs (n = 9) and LA (n = 9). Additionally, male PVs had a more-positive resting membrane potential (79 ± 3 versus 84±2 mV, P=0.022). Isoproterenol (3 µmol/L) increased the delayed afterdepolarizations to a greater extent in male than in female PVs. In PVs without spontaneous activity or LA, isoproterenol (0.1 and 3 µmol/L) consistently shortened the action potential durations in females but not in males. Acetylcholine (5.5 µmol/L) decreased the spontaneous activity of PVs and shortened the action potential durations in both groups. Adenosine (10 µmol/L) also similarly decreased the spontaneous activity of PVs and delayed afterdepolarizations in both groups. CONCLUSIONS: There are significant sex differences in PV and LA action potential characteristics in rabbits. The higher amplitude of delayed afterdepolarizations after isoproterenol superfusion in male PVs may contribute to sex-related arrhythmogenesis.

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.

Discrepant electrophysiological characteristics and calcium homeostasis of left atrial anterior and posterior myocytes.

The left atrial (LA) posterior wall has been demonstrated to have regional electrophysiological differences with a higher arrhythmogenic potential leading to atrial fibrillation (AF). However, the ionic characteristics and calcium regulation in the LA anterior and posterior myocytes have not been fully elucidated. The purpose of this study was to investigate the electrical characteristics of the LA anterior and posterior myocytes. Whole-cell patch-clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the ionic currents, action potentials, and intracellular calcium in single isolated rabbit myocytes in the LA anterior and posterior walls. The expression of the Na(+)-Ca(2+) exchanger (NCX) and ryanodine receptor (RyR) were evaluated by a Western blot. The LA posterior myocytes (n = 15) had a higher incidence (53 vs. 19%, P < 0.05) of delayed afterdepolarizations than the LA anterior myocytes (n = 16). The LA posterior myocytes had larger sodium currents and late sodium currents, but smaller inward rectifier potassium currents than the LA anterior myocytes. The LA posterior myocytes had larger intracellular Ca(2+) transient and sarcoplasmic reticulum Ca(2+) contents as compared with the LA anterior myocytes. However, the NCX currents in the LA posterior myocytes were smaller than those in the LA anterior myocytes. The LA posterior myocytes had a smaller protein expression of NCX, but a larger protein expression of RyR than the LA anterior myocytes. In conclusion, LA posterior myocytes contain a high arrhythmogenic potential and distinctive electrophysiological characteristics, which may contribute to the pathophysiology of AF.

Oxidative stress on pulmonary vein and left atrium arrhythmogenesis.

BACKGROUND: Oxidative stress and pulmonary veins (PVs) play critical roles in the pathophysiology of atrial fibrillation. The purpose of the present study was to investigate whether oxidative stress and antioxidant agents can change the electrophysiological characteristics of the left atrium (LA) and PVs. METHODS AND RESULTS: Conventional microelectrodes were used to record the action potentials (APs) in isolated rabbit PV and LA specimens before and after H(2)O(2) administration with or without ascorbic acid or N-mercaptopropionyl-glycine (N-MPG, a free radical .OH scavenger). H(2)O(2) (0.02 and 0.2 mmol/L) decreased the PV spontaneous rates from 2.0+/-0.1 Hz to 1.6+/-0.1 Hz, and 1.7+/-0.1 Hz (n=10, P<0.05), but H(2)O(2) (2 mmol/L) increased PV spontaneous rates from 2.0+/-0.1 Hz to 2.8+/-0.2 Hz. H(2)O(2) easily induced PV burst firing and early afterdepolarizations, but not in the LA. H(2)O(2) shortened the AP duration and increased the contractile force to a greater extent in the LA than in PVs. In addition, the H(2)O(2)-induced PV burst firing and increasing spontaneous rates were suppressed or attenuated by pretreatment with ascorbic acid (1 mmol/L) or N-MPG (10 mmol/L). CONCLUSIONS: H(2)O(2) significantly changed the electrophysiological characteristics of PV and LA through activation of free radicals and may facilitate the occurrence of atrial fibrillation.

The different mechanisms between late and very late recurrences of atrial fibrillation in patients undergoing a repeated catheter ablation.

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.

Predictors of early and late recurrence of atrial fibrillation after catheter ablation of paroxysmal atrial fibrillation.

INTRODUCTION: The outcome of patients with early recurrence of atrial fibrillation (AF) (within one month) after ablation procedure is controversial. Furthermore, the predictors of early and late (up to mean follow-up 30 months) recurrence of AF are not investigated in depth. AIMS OF THE STUDY: The aim of the present study was to investigate the predictors of early and late recurrence of AF after catheter ablation of arrhythmogenic foci initiating AF in patients with paroxysmal AF. METHODS AND RESULTS: The study included 207 patients (155 men; mean age 62 +/- 13 years) who received catheter ablation of paroxysmal AF. Eighty-one (39%) patients had early recurrence of AF. Five clinical variables were related to the early recurrence of AF: (1) old age (>/=65 years) ( P = 0.004); (2) presence of associated cardiovascular disease ( P = 0.01); (3) presence of multiple AF foci ( P = 0.004); (4) presence of AF foci from left atrial free wall ( P = 0.039); (5) left atrial enlargement ( P = 0.038). Multivariate analysis demonstrated that presence of multiple AF foci could predict early recurrence of AF ( P = 0.013; ratio = 2.24; 95% CI 1.18 to 4.25). During the follow-up period (30 +/- 11 months), 70 (34%) patients had late recurrence of AF, and two clinical variables were related to the late recurrence of AF: (1) presence of early recurrence of AF ( P = 0.025); (2) presence of multiple AF foci ( P = 0.034). Multivariate analysis found that presence of early recurrence of AF could predict late recurrence of AF ( P = 0.046; hazard ratio = 1.62; 95% CI 1.01 to 2.59). Late recurrence of AF happened in 35 (43%) of the 81 patients with early recurrence of AF, and in 35 (28%) of the 126 patients without early recurrence of AF. CONCLUSIONS: Early AF recurrence could predict late AF recurrence.

Use of fluoroscopic views for detecting Marshall's vein in patients with cardiac arrhythmias.

INTRODUCTION: Recently, several studies showed that focal atrial fibrillation (AF) can be initiated by ectopic beats from the vein of Marshall (VOM). However, the incidence and best fluoroscopic views of VOM have never been reported. METHODS AND RESULTS: 106 patients (Non-AF = 52, AF = 54) underwent balloon-occluded coronary sinus angiography using seven fluoroscopic views (PA, Lateral, RAO 30 degrees, RA 30 degrees + Caudal 20 degrees, LAO 30 degrees, LAO 60 degrees, LAO 60 degrees + Cranial 20 degrees ). The total incidence of VOM was 74.5% (79/106), without significant difference in age (81.1 vs. 71.0%, >65 vs.

Clinical outcome of very late recurrence of atrial fibrillation after catheter ablation of paroxysmal atrial fibrillation.

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 (> or = 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.

Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy.

BACKGROUND: Most of the ectopic beats initiating paroxysmal atrial fibrillation (PAF) originate from the pulmonary vein (PV). However, only limited data are available on PAF originating from the non-PV areas. METHODS AND RESULTS: Two hundred forty patients with a total of 358 ectopic foci initiating PAF were included. Sixty-eight (28%) patients had AF initiated by ectopic beats (73 foci, 20%) from the non-PV areas, including the left atrial posterior free wall (28, 38.3%), superior vena cava (27, 37.0%), crista terminalis (10, 3.7%), ligament of Marshall (6, 8.2%), coronary sinus ostium (1, 1.4%), and interatrial septum (1, 1.4%). Catheter ablation eliminated AF with acute success rates of 63%, 96%, 100%, 50%, 100%, and 0% in left atrial posterior free wall, superior vena cava, crista terminalis, ligament of Marshall, coronary sinus ostium, and interatrial septum, respectively. During a follow-up period of 22+/-11 months, 43 patients (63.2%) were free of antiarrhythmic drugs without AF recurrence. CONCLUSIONS: Ectopic beats initiating PAF can originate from the non-PV areas, and catheter ablation of the non-PV ectopy has a moderate efficacy in treatment of PAF.

Double potential interval and transisthmus conduction time for prediction of cavotricuspid isthmus block after ablation of typical atrial flutter.

BACKGROUND: Complete bi-directional isthmus block is the endpoint of typical atrial flutter ablation. The purpose of this study was to investigate the feasibility of the local double potential (DP) interval and the change in transisthmus conduction time for predicting complete isthmus block after ablation of the cavotricuspid isthmus. METHODS: The study population consisted of 32 patients with typical atrial flutter after a procedure of radiofrequency (RF) ablation of the cavotricuspid isthmus (16 had incomplete block and 16 had complete block). The transisthmus conduction time was determined during pacing from the proximal coronary sinus and low lateral right atrium before and after RF ablation. The DP interval close to the ablation line was evaluated after final RF energy application. RESULTS: In the counterclockwise direction, transisthmus conduction time had an increase of 37 +/- 25.4% and 127.3 +/- 35.5% (P < 0.001), and the DP interval was 63.3 +/- 8.7 ms and 120 +/- 17.4 ms (P < 0.001) after achievement of incomplete and complete block, respectively. The sensitivity, specificity, positive and negative predictive values of an increase in the transisthmus conduction time > or =50% were 100%, 81%, 84% and 100%, respectively; those of DP interval > or =100 ms were 100%. In the clockwise direction, transisthmus conduction time had an increase of 38.8 +/- 28.6% and 135.7 +/- 63.6% (P < 0.001), and the DP interval was 63.6 +/- 13.8 ms and 127.7 +/- 27.1 ms (P < 0.001) after achievement of incomplete and complete block, respectively. The sensitivity, specificity, positive and negative predictive values of an increase in the transisthmus conduction time > or =50% were 100%, 67%, 83% and 100%, respectively; those of the DP interval > or =100 ms were 100%. CONCLUSIONS: The transisthmus conduction time > or =50% increase or DP interval > or =100 ms was feasible to predict complete bi-directional isthmus block.

Noncontact three-dimensional mapping and ablation of upper loop re-entry originating in the right atrium.

OBJECTIVES: This study was aimed at delineating the reentrant circuit of right atrial (RA) upper loop re-entry using noncontact three-dimensional mapping. BACKGROUND: Various forms of atypical atrial flutter including lower loop re-entry and left atrial flutter have been demonstrated. However, little is known about upper loop re-entry in the RA. METHODS: The study population consisted of eight patients (65 +/- 12 years, seven men) with atypical atrial flutter. Right atrial activation during atrial flutter was visualized using a noncontact mapping system (EnSite-3000 with Clarity Software, St. Paul, Minnesota) for a three-dimensional reconstruction of the endocardial depolarization. The narrowest part of the re-entrant circuit was targeted using radiofrequency catheter ablation. RESULTS: Noncontact mapping showed macro-re-entry confined to the RA free wall with RA activation time accounting for 100% of the cycle length (214 +/- 21 ms) in all eight patients. Two patients had counterclockwise activation, and six patients had clockwise activation around the central obstacle, which was composed of the crista terminalis, the area of functional block, and superior vena cava. The lower turn-around points were located at the conduction gap in the crista terminalis. Radiofrequency linear ablation of the conduction gap in the crista terminalis was performed and eliminated atrial flutter in six patients without recurrence during a follow-up of 3.2 +/- 1.1 months. CONCLUSIONS: Atypical atrial flutter could arise from upper loop re-entry in the RA with conduction through the gap in the crista terminalis. Radiofrequency linear ablation of the conduction gap was effective in eliminating this atrial arrhythmia.