Pharmacological cardioversion of persistent atrial fibrillation with and without a history of drug-resistant paroxysmal atrial fibrillation.

BACKGROUND: Suppression by antiarrhythmic drugs of the maintenance mechanisms could convert persistent atrial fibrillation (AF) to sinus rhythm (SR). Whether a history of drug-resistant paroxysmal AF (PAF) would affect the outcome of pharmacological conversion of persistent AF by bepridil or in combination with aprindine was evaluated in the present study. METHODS AND RESULTS: The study group comprised 51 consecutive patients (24 men, 61+/-8 years) undergoing pharmacological conversion of persistent AF lasting >1 month. Drug-resistant PAF was defined as AF and at least 2 ineffective antiarrhythmic drugs for suppression of AF recurrence. Fast Fourier transform analysis of fibrillation waves was used to measure fibrillation cycle length (FCL) from the peak frequency. Fifteen patients had a history of drug-resistant PAF (Group I), and the remaining 36 did not (Group II) before diagnosis of persistent AF. Ten patients (67%) in Group I and 26 patients (72%) in Group II were restored to SR by bepridil alone or in combination with aprindine after 29+/-15 days of drug administration. Before conversion to SR, bepridil increased the FCL more in Group II than in Group I. During a 12-month follow-up period, 4 of 10 patients in Group I and 2 of 26 patients in Group II (p<0.01) had recurrence of persistent AF with bepridil alone or in combination with aprindine. CONCLUSIONS: A history of drug-resistant PAF does not affect the efficacy of pharmacological conversion by bepridil or in combination with aprindine. However, recurrence of AF was significantly higher in patients with such a history.

Bradycardia-dependent ECG changes in Brugada syndrome.

BACKGROUND: In patients with Brugada syndrome (BS), ventricular fibrillation (VF) occurs mainly during sleep; therefore, not only vagal activity but also bradycardia dependent changes in ECG may relate to the nighttime occurrence of VF. The present study aimed to examine the difference in bradycardia-dependent changes in the ECG of symptomatic and asymptomatic BS patients. METHODS AND RESULTS: Twenty-one patients with BS were categorized into symptomatic (n = 9) and asymptomatic (n = 12) groups. During the electrophysiologic study, the ECG changes were evaluated at RR intervals of 400, 600, 750, 1,000 and 1,100 ms during extrastimulation from the right atrium. The ST levels in V2, and the QT interval in both V2 and V5 were measured. Along with an increase in the RR interval from 400 to 1,100 ms, the ST levels in V2 increased in both groups; the increase did not differ between the 2 groups. In both leads V2 and V5, the prolongation of the QT interval along with an increase in the RR interval from 400 to 1,100 ms was significantly smaller and the QT intervals at an RR interval of 1,100 ms were significantly shorter in the symptomatic than in the asymptomatic group. CONCLUSIONS: In patients with BS, the ST elevation was augmented during bradycardia to a similar extent in both symptomatic and asymptomatic patients. However, a inhibited prolongation of the QT interval during bradycardia was characteristic of symptomatic patients. These unique repolarization dynamics could relate to the nighttime occurrence of VF during bradycardia in patients with BS.

Enalapril preserves sinus node function in a canine atrial fibrillation model induced by rapid atrial pacing.

METHODS AND RESULTS: Seventeen beagles were pretreated with either placebo (group I, n = 9) or enalapril 1 mg/kg/day (group II, n = 8) and paced at 500/min from the right atrial appendage for 4 weeks. Every week, corrected sinus node recovery time (CSNRT) and sinus cycle length (SCL) were measured. Quantitative analysis of interstitial fibrosis (IF) and adipose tissue (AT) in the SN was performed with Masson's trichrome stain, and apoptosis of the sinus nodal cells were detected with terminal deoxynucleotidyl transferase nick end-labeling. In group I, rapid atrial pacing prolonged both CSNRT and SCL. After 4 weeks of pacing, CSNRT and SCL were significantly shorter in group II (CSNRT, 410 +/- 37 msec; SCL, 426 +/- 34 msec) than in group I (CSNRT, 717 +/- 52 msec, P < 0.005; SCL, 568 +/- 73 msec, P < 0.05). Both IF and AT of the SN were greater in group I (IF, 9.7 +/- 1.9%; AT, 32.6 +/- 5.9%) than in seven sham dogs (IF, 2.4 +/- 0.9%, P < 0.05; AT, 4.0 +/- 1.7%, P < 0.05) and in group II dogs (IF, 4.0 +/- 2.0%, P < 0.05; AT, 4.0 +/- 1.7%, P < 0.05). End-labeling assay was positive in three of nine dogs in group I, but negative in group II and sham dogs. CONCLUSIONS: Rapid atrial pacing impaired SN function through IF and AT of the SN. Enalapril prevented these pacing-induced degenerative changes and improved SN function.

Dynamic changes in the QT-R-R relationship during head-up tilt test in patients with vasovagal syncope.

BACKGROUND: QT interval is influenced by preceding R-R intervals and autonomic nervous tone. Changes in QT intervals during vasovagal reflex might reflect autonomic modulation of ventricular repolarization; however, this issue has not been fully elucidated. This study aimed to evaluate dynamic response of QT interval to transient changes in R-R interval during vasovagal syncope (VVS) induced by head-up tilt test. METHODS: Eighteen patients with VVS and 18 age-and sex-matched controls were studied. All patients with VVS had a positive mixed-type response to head-up tilt and all controls had a negative response. CM5-lead digital electrocardiogram (ECG) was recorded and QT intervals were analyzed using Holter ECG analyzer. Using scatter plots of consecutive QT and the preceding R-R intervals, QT-R-R relations during tilt-up and tilt-back or during vasovagal reflex were independently fitted to an exponential curve: QT (second) = A + B x exp[k x R-R (second)]. RESULTS: During the tilt-up, A, B, and k did not differ between patients with VVS and controls. During the tilt back, k showed equivalent positive value compared to the tilt-up (4.1 +/- 1.3 vs -4.6 +/- 0.9) in controls. However, k remained negative (-1.3 +/- 1.5) during vasovagal reflex in patients with VVS. In six patients, in whom metoprolol was effective in eliminating VVS, QT-R-R relationship during the tilt-back became similar to that in controls. CONCLUSIONS: In patients with VVS, hysteresis of the QT-R-R relation is similarly shown during tilt-up as in controls, whereas this hysteresis is no longer evident and failure of QT prolongation is observed during VVS.

Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin43 in a canine model of atrial pacing-induced left ventricular dysfunction.

UNLABELLED: Effects of enalapril on a canine model of atrial pacing-induced atrial fibrillation (AF) with rapid ventricular responses were determined. METHODS: Four weeks of atrial rapid pacing was performed on twenty-four beagles pretreated with placebo (Group I, n = 14) or enalapril 1 mg/kg (Group II, n = 10). Atrial effective refractory period (ERP), P-wave width, duration of AF, and left ventricular ejection fraction (LVEF) were evaluated every week. AF cycle length was determined by spectral analyses of fibrillation waves. Quantitative analysis of histology was added. RESULTS: After 4 weeks of pacing, P-wave width was longer in Group I than in Group II, and the duration of induced AF was significantly longer in Group I (59.6 +/- 66.3 seconds) than in Group II (3.6 +/- 3.4 seconds, P < 0.05). AF cycle length was longer in Group I than in Group II despite similar shortening of atrial ERP. Mean ventricular rate during rapid atrial pacing was not different between the two groups. LVEF similarly decreased in both groups. Interstitial fibrosis and expression of connexin43 was greater in Group I than in Group II (interstitial fibrosis, 9.2 +/- 8.4 versus 1.9 +/- 2.1%, P < 0.05; connexin43, 5.3 +/- 2.2 versus 1.1 +/- 1.1%, P < 0.05). CONCLUSIONS: Enalapril suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by suppressing interstitial fibrosis, connexin43 over-expression and conduction delay.

Complex atrial reentrant circuits evaluated by entrainment mapping using a multielectrode basket catheter.

Atrial tachycardias after open heart surgery sometimes have complex reentrant circuits. A patient with a dual-loop atrial reentrant circuit occurring after mitral valve replacement was evaluated by entrainment mapping with a basket catheter. The position of the catheter was adjusted to obtain atrial electrograms of the anterior and posterior septal areas, the crista terminalis, the free wall, and the tricuspid annular region. Entrainment mapping identified a dual-loop reentry consisting of one circuit around the tricuspid annulus and another around the septal atriotomy scar. The reentrant circuit around the septal incision was eliminated by ablating the area between the septal incision and the inferior vena cava, and the circuit around the tricuspid annulus was terminated with an additional linear ablation between the tricuspid annulus and the inferior vena cava. Entrainment mapping using a multielectrode basket catheter is very useful for identifying complex atrial reentrant circuits.

Relation between transverse conduction capability and the anatomy of the crista terminalis in patients with atrial flutter and atrial fibrillation: analysis by intracardiac echocardiography.

Although crista terminalis (CT) has been identified as the barrier to transverse conduction during typical atrial flutter (AFL), the relation between transverse conduction capabilities and anatomy of the CT remains unclear. The aim of the study was to evaluate that relation using intracardiac echocardiography (ICE). Ten patients with typical AFL (group AFL), 7 patients with paroxysmal atrial fibrillation (PAF) (group AF) and 8 patients without PAF or AFL (group N) underwent electrophysiologic testing. Using ICE images, the maximum diameter of the short axis of the CT (dCT) was measured and mapping and pacing catheters were positioned precisely. From extrastimulation delivered 1-2 cm anteriorly (free wall) or posteriorly (posterior wall) to the CT, the effective refractory period (CT-ERP) was determined as the longest coupling interval that resulted in split potentials at the mapping catheter positioned along the CT, a finding consistent with a transverse conduction block at the CT. The dCT was greater in group AFL than in groups AF and N (5.0+/-0.8 vs 4.3 +/-0.7, p<0.05 and 4.2+/-0.4 mm, p<0.01, respectively). The CT-ERP was longer during pacing from the posterior wall than from the free wall (307+/-68 vs 266+/-29 ms, p<0.05) as a whole group. The CT-ERP for the posterior wall pacing was longer in group AFL than in group N (339+/-80 vs 255+/-13, p<0.05). CT-ERP did not correlate with dCT; however, dCT was greater in patients with split potentials at the CT than in patients without them (4.9 +/-0.8 vs 4.1+/-0.5 mm, p<0.05). Therefore, the transverse conduction block of CT was more likely to occur in a thick CT. A limited transverse conduction capability of the CT is related to its thickness and might contribute to the development of typical AFL.

Effects of a novel class III antiarrhythmic agent, NIP-142, on canine atrial fibrillation and flutter.

The effects of a new benzopyran derivative, NIP-142, on atrial fibrillation (AF) and flutter (AFL) and on electrophysiological variables were studied in the dog. NIP-142 (3mg/kg) was administered intravenously to pentobarbital-anesthetized beagles during vagally-induced AF and during AFL induced after placement of an intercaval crush. Isolated canine atrial tissues were studied using standard microelectrode technique. NIP-142 terminated AF in 5 of 6 dogs after an increase in fibrillation cycle length (CL) and prevented reinitiation of AF in all 6 dogs. NIP-142 terminated AFL in all 6 dogs without any appreciable change in flutter CL, and prevented reinitiation of AFL in all 6 dogs. NIP-142 prolonged atrial effective refractory periods (11+/-5%, 3+/-3%, 12+/-3%, and 10+/-5% from the baseline value at basic CLs of 150, 200, 300, and 350ms, respectively) without changes in intraatrial conduction time. The prolongation of the atrial effective refractory period was greater in the presence of vagal stimulation. NIP-142 decreased action potential phase-1 notch and increased phase-2 plateau height without making any changes in the action potential duration, although it did reverse carbachol-induced shortening of the action potential duration. In conclusion, NIP-142 is effective in treating AFL and vagally-induced AF by prolonging atrial refractoriness.