Shih A. Chen

Pulmonary vein morphology in patients with paroxysmal atrial fibrillation initiated by ectopic beats originating from the pulmonary veins: Implications for catheter ablation

BACKGROUND Successful ablation of ectopic beats originating from the pulmonary veins (PV) could eliminate paroxysmal atrial fibrillation (PAF). However, information about the structure of the PV in patients with PAF that is initiated by PV ectopic beats has not been reported. METHODS AND RESULTS We studied the morphology of the PVs and measured their diameters in 3 groups of patients. Group I included 52 patients (aged 66+/-14 years; 44 men) with focal atrial fibrillation (AF) from the PVs. Group II included 8 patients (aged 50+/-10 years; 3 men) with focal AF from the superior vena cava or cristal terminalis. Group III included 23 control patients (aged 55+/-16 years; 17 men). Of the control patients, 11 had AV node and 12 had AV reentrant tachycardia. After an atrial transseptal procedure, selective PV angiography using a biplane system with a right anterior oblique view of 30 degrees, a left anterior oblique view of 60 degrees, and a cranial angle of 20 degrees was performed. The ostial and proximal portions of the right and left superior PVs (RSPV and LSPV) were significantly dilated in group I patients compared with those in groups II and III. Furthermore, the ostia of the RSPV and LSPV were significantly dilated in group II compared with group III patients. However, the mean diameters of the inferior PVs were similar between the 3 groups. Comparisons of the individual PV diameters among the 3 subgroups of group I (which was divided according to where the ectopic focus was located) showed nonselective dilatation of the PV. CONCLUSIONS Nonspecific dilatation of the ostia and proximal portion of superior PVs were found in patients with PAF initiated by ectopic beats from the superior PVs.

Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes

OBJECTIVES This study was conducted to investigate the effects of thyroid hormone on the electrophysiological characteristics of pulmonary vein (PV) cardiomyocytes. BACKGROUND Hyperthyroidism is an important etiology of paroxysmal atrial fibrillation (AF). Pulmonary veins are known to initiate paroxysmal AF. METHODS The action potential and ionic currents were investigated in single rabbit PV and atrial cardiomyocytes with (hyperthyroid) and without (control) incubation of L-triiodothyronine using the whole-cell clamp technique. RESULTS Compared with the control cardiomyocytes, hyperthyroid PV and atrial cardiomyocytes had shorter action potential duration. Hyperthyroid PV cardiomyocytes had faster beating rates (1.82 +/- 0.13 Hz vs. 1.03 +/- 0.15 Hz, p < 0.005) and a higher incidence of delayed after depolarization (beating: 92% vs. 6%, p < 0.0001; non-beating: 45% vs. 3%, p < 0.005). However, only hyperthyroid PV beating cardiomyocytes had a higher incidence of early after depolarization (46% vs. 0%, p < 0.0001). The ionic current experiments showed that hyperthyroid PV beating cardiomyocytes had larger densities of overall slow inward (2.72 +/- 0.21 pA/pF vs. 2.07 +/- 0.19 pA/pF, p < 0.05), overall transient outward (1.39 +/- 0.21 pA/pF vs. 0.48 +/- 0.08 pA/pF, p < 0.001) and steady state outward currents (0.78 +/- 0.06 pA/pF vs. 0.58 +/- 0.04 pA/pF, p < 0.05) on depolarization and larger transient inward (0.021 +/- 0.004 pA/pF vs. 0.005 +/- 0.001 pA/pF, p < 0.001) on repolarization. By contrast, the hyperthyroid PV non-beating cardiomyocytes had larger densities of overall transient outward (1.01 +/- 0.14 pA/pF vs. 0.37 +/- 0.07 pA/pF, p < 0.001), steady state outward (0.61 +/- 0.06 pA/pF vs. 0.44 +/- 0.04 pA/pF, p < 0.05) and transient inward currents (0.011 +/- 0.002 pA/pF vs. 0.003 +/- 0.001 pA/pF, p < 0.05). CONCLUSIONS Thyroid hormone changes the electrophysiological activity of the PV cardiomyocytes. Increased automaticity and enhanced triggered activity may increase the arrhythmogenic activity of PVs in hyperthyroidism.

Electrophysiology and arrhythmogenic activity of single cardiomyocytes from canine superior vena cava

Background—The superior vena cava (SVC) has been proved to be a focal point in the initiation of paroxysmal atrial fibrillation. The autonomic nervous system plays an important role in the genesis of atrial fibrillation. However, the arrhythmogenic potentials of SVC and its responses to autonomic agents are not clear. The purpose of this study was to isolate single SVC cardiomyocytes and to investigate their electrophysiological characteristics, as well as the direct effects of autonomic agents. Methods and Results—Canine SVC cardiomyocytes were isolated by perfusion with digestive enzymes. The action potentials and ionic currents were investigated in single SVC cardiomyocytes using the whole-cell clamp technique. Dissociation of the SVC yielded rod-shaped single cardiomyocytes with (n=74, 51%) or without (n=71, 49%) pacemaker activities. There were similar densities of inward Ca2+, delayed rectifier K+, transient inward, inward rectifier K+, and pacemaker currents between SVC cardiomyocytes with and without pacemaker activity. SVC cardiomyocytes with pacemaker activity have, however, greater transient outward currents than those without pacemaker activity. In SVC cardiomyocytes, acetylcholine (5.5 &mgr;mol/L) abolished the spontaneous activities, but isoproterenol (10 nmol/L), atropine (10 &mgr;mol/L), and phenylephrine (10 &mgr;mol/L) accelerated the spontaneous activity and induced the occurrences of early or delayed afterdepolarizations. Conclusions—These findings suggest that SVC cardiomyocytes have distinct action potentials and ionic current profiles that may be responsible for the arrhythmogenic activity of the SVC.

Complex Electrophysiological Characteristics in Atrioventricular Nodal Reentrant Tachycardia With Continuous Atrioventricular Node Function Curves

BACKGROUND Although typical atrioventricular nodal reentrant tachycardia (AVNRT) with discontinuous AV node function curves has been well studied, there has been a lack of any significant information about AVNRT without evidence of dual AV nodal pathway physiology during atrial extrastimulus testing or atrial pacing. METHODS AND RESULTS Group 1 included 9 patients with continuous curves during atrial extrastimulus testing but without a jump (> or = 50 ms) of the atrial-His bundle (AH) interval during incremental atrial pacing. The maximal AH interval during atrial pacing (266 +/- 61 versus 168 +/- 27 ms, P = .007) or extrastimulus testing (290 +/- 60 versus 176 +/- 18 ms, P = .005) shortened significantly after ablation. Antegrade and retrograde AV node properties were similar before and after ablation. Group 2 included 14 patients with continuous curves and a jump of the AH interval during incremental atrial pacing. The atrial pacing cycle length with 1:1 AV conduction and effective refractory period (ERP) of the antegrade AV node increased significantly, whereas the maximal AH interval during atrial pacing (358 +/- 70 versus 203 +/- 28 ms, P = .001) or extrastimulus testing (338 +/- 75 versus 196 +/- 34 ms, P = .002) shortened significantly after ablation. Group 3 included 24 patients with discontinuous curves. The maximal AH interval during atrial pacing or extrastimulus testing and the ERP of the antegrade fast AV node shortened, whereas the ERP of the antegrade AV node increased significantly after ablation. The maximal AH interval before ablation, extent of decrease in maximal AH interval after ablation, ERP of the retrograde AV node before ablation, and tachycardia cycle length were significantly shorter in group 1 than groups 2 and 3. CONCLUSIONS In AVNRT with continuous AV node function curves, dual AV nodal pathway physiology may or may not be demonstrated during atrial pacing. Significant shortening of the maximal AH interval during atrial pacing after radiofrequency ablation suggests successful elimination of AVNRT.

Early Recurrence of Atrial Fibrillation After External Cardioversion

Early recurrence of atrial fibrillation (AF) has been reported to occur in a significant number of patients after internal cardioversion. However, information about early recurrence of AF after external cardioversion has never been reported. The present study was conducted to investigate the clinical and electrophysiological characteristics of early recurrence of AF and its role in failure of cardioversion in patients with chronic AF. Methods and Results: The study included 50 consecutive patients, age 69 ± 9, with a history of chronic AF for more than 3 months duration and electrical cardioversion. They were divided into two groups according to the presence (group 1) or absence (group 2) of early recurrence of AF. There were 13 (26%) patients in group 1 and 37 (74%) patients in group 2. The age, gender, duration of AF, left ventricular function, left atrial dimension, and underlying heart disease were similar between group 1 and 2. Forty‐five patients were successfully converted to sinus rhythm with a mean energy of 158 ± 57 J. Among those who failed to be converted to sinus rhythm, 4 (80%) belonged to group 1 and 1 (20%) belonged to group 2. The early recurrences of AF were initiated with consecutive APDs; but the numbers of APD in the first 30 seconds after cardioversion were similar between group 1 and 2. However, the coupling interval of the second APD was shorter in group 1 than group 2 (188 ± 22 vs 324 ± 59 ms, P = 0.003). Nine of the 13 early recurrences were prevented by an increase of shock energy (n = 3) or intravenous amiodarone infusion (n = 6). There were no differences in duration of follow‐up, recurrence rate, and time interval to recurrence between group 1 and group 2. Early recurrence of AF occurred in 26% of chronic AF patients who underwent external electrical cardioversion and was a major cause of failure in cardioversion. Early recurrence of AF was initiated by APDs with decreasing coupling intervals and could be prevented with an increase of shock energy or amiodarone.

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 &mgr;mol/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 &mgr;mol/L) consistently shortened the action potential durations in females but not in males. Acetylcholine (5.5 &mgr;mol/L) decreased the spontaneous activity of PVs and shortened the action potential durations in both groups. Adenosine (10 &mgr;mol/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.

Testosterone replacement increases aged pulmonary vein and left atrium arrhythmogenesis with enhanced adrenergic activity

BACKGROUND Aging and testosterone deficiency contribute to the pathogenesis of atrial fibrillation (AF). We determine the effects of testosterone replacement on the electrophysiology and arrhythmogenesis of pulmonary vein (PV) and left atrium (LA) in aged rabbits. METHODS Electrocardiography, heart rate variability, echocardiography, Western blot and conventional microelectrodes were used in aged rabbits (age, >2 years) with and without (control) testosterone treatment (10mg/kg, 12 weeks). RESULTS Testosterone-treated aged rabbits had longer corrected QT interval, higher low frequency/high frequency, greater left ventricle (LV) mass but lower LA total emptying fraction and LV ejection fraction than control rabbits. In tissue preparations, the spontaneous rate was faster for testosterone-treated PVs than for control PVs. Angiotensin II concentration-dependently increased the amplitude of delayed afterdepolarizations (DADs) in testosterone-treated PVs but only did so at the highest angiotensin II concentration (100 nM) in control PVs. Isoproterenol increased the incidence of early afterdepolarizations (EADs) and DADs in testosterone-treated PVs but not in control PVs. Testosterone-treated PVs had more H2O2-induced burst firing and EADs than control PVs. Testosterone-treated LAs had more isoproterenol-induced DADs and spontaneous activity than did control LAs. However, acetylcholine infusion and rapid atrial pacing (10-20 Hz) induced AF in control LAs but not in testosterone-treated LAs. In addition, as compared with control LAs, testosterone-treated LAs expressed more androgen receptor, β1-adrenergic receptor, and Cav 1.2 and less G protein-coupled receptor kinase-2 and Kv 4.2. CONCLUSIONS Testosterone replacement increased arrhythmogenesis in PV and LA by enhancing adrenergic activity in aged rabbits.

Radiofrequency Ablation-Induced Asystole During Transaortic Approach for a Left Anterolateral Accessory Pathway.: A Bezold-Jarisch-Like Phenomenon

RF Ablation‐Induced Cardiac Asystole. We present a case of cardiac asystole induced by radiofrequency catheter ablation of a left anterolateral accessory pathway in a 28‐year‐old woman with Wolff‐Parkinson‐White syndrome who was experiencing recurrent palpitation. Radiofrequency current applied on the ventricular aspect of the mitral annulus corresponding to the aforementioned site provoked profound slowing of the sinus rate preceded by disappearance of the preexcitation, and then asystole ensued. The proposed causal mechanism was a reflexogenically mediated hypotension‐bradycardia syndrome (Bezold‐Jarisch‐like phenomenon) through stimulation of either nearby vagal afferent pathways or sensory terminal receptors at the ablation site.

Effect of high intensity drive train stimulation on dispersion of atrial refractoriness: Role of autonomic nervous system

OBJECTIVES This study evaluated the effect of high intensity drive train (S1) stimulation on the atrial effective refractory period (ERP) and its relation to the autonomic nervous system. BACKGROUND High intensity S1 stimulation was demonstrated to shorten the ventricular ERP and to increase dispersion of refractoriness. These effects may be due to local release of neurotransmitters. The response of the atrium and ventricle to neurotransmitters was different. The effects of high intensity S1 stimulation at the atrial tissue were evaluated. METHODS Forty patients without structural heart disease were studied. In group 1, 20 patients, the atrial ERP was measured at 0, 7, 14, 21 and 28 mm away from the S1 site under both twice diastolic threshold and high intensity (10 mA) S1 stimulation. The same protocol was repeated after sequential administration of propranolol (0.2 mg/kg body weight) and atropine (0.04 mg/kg). In group 2, the other 20 patients, the atrial ERP was studied at three atrial sites (high lateral right atrium [HLRA], right posterior interatrial septum [RPS] and distal coronary sinus [DCS] with twice diastolic threshold and high intensity S1 stimulation at baseline and after sequential autonomic blockade. The three atrial sites were randomly assigned as the S1 location. RESULTS In group 1, high intensity S1 stimulation shortened the atrial effective refractory period most prominently at the site of S1: (mean +/- SD) 13.3 +/- 6.4% (p < 0.001), 8.1 +/- 3.8% (p < 0.001), 4.8 +/- 4.3% (p < 0.001), 3.7 +/- 4.7% (p < 0.001) and 0.5 +/- 2.6% at 0, 7, 14, 21 and 28 mm from the S1 site, respectively. The effect of high intensity S1 stimulation was blunted with propranolol and autonomic blockade but persisted after atropine alone. High intensity S1 stimulation also increased dispersion of refractoriness (from 23 +/- 11 ms to 31 +/- 12 ms, p = 0.01), which was eliminated with autonomic blockade. In group 2, high intensity S1 stimulation had similar effects at different locations (ERP shortening of 10.8 +/- 2.7%, 10.8 +/- 2.2% and 12.2 +/- 4.6% at the HLRA, RPS and DCS, respectively). The responses to sequential autonomic blockade were similar to those in group 1. However, high intensity S1 stimulation at HLRA increased dispersion of refractoriness, but at DCS it reduced dispersion of refractoriness. CONCLUSIONS High intensity S1 stimulation led to local shortening of the atrial ERP and increased dispersion of refractoriness. These effects were blunted with propranolol and autonomic blockade. High intensity S1 stimulation at the HLRA increased dispersion of atrial refractoriness, whereas the same stimulation at the DCS decreased dispersion of atrial refractoriness.

Different effects of dronedarone and amiodarone on pulmonary vein electrophysiology, mechanical properties and H2O2-induced arrhythmogenicity

Dronedarone and amiodarone are anti-atrial fibrillation agents with different potency. Pulmonary veins play a critical role in the genesis of atrial fibrillation. Oxidative stress can enhance pulmonary vein arrhythmogenesis. This study was done to compare the effects of dronedarone and amiodarone on pulmonary vein electrophysiological and mechanical properties, and oxidative stress-induced arrhythmogenecity. Conventional microelectrodes were used to record action potentials in isolated rabbit pulmonary vein specimens before and after dronedarone and amiodarone with or without the presence of H2O2 (2mM). Dronedarone (0.1, 1 and 10 μM) concentration-dependently decreased pulmonary vein beating rates (from 2.2±0.1 to 1.9±0.1, 1.8±0.1 and 1.7±0.1Hz, n=8, P<0.01). Amiodarone (0.1, 1 and 10 μM) also concentration-dependent decreased pulmonary vein beating rates (from 2.5±0.2 to 2.3±0.2, 2.2±0.2 and 2.0±0.2Hz, n=7, P<0.01). However, dronedarone decreased pulmonary vein beating rates to a greater extent at 0.1 μM (12% versus 4%, P<0.005) and 1μM (17% versus 9%, P<0.005). Dronedarone or amiodarone (0.1, 1 and 10 μM) did not change the pulmonary vein contractility. However, dronedarone (1 and 10 μM) concentration-dependent reduced pulmonary vein diastolic tension by 13±2 mg (P<0.005) and 18±3 mg (P<0.005). In contrast, amiodarone did not change pulmonary vein diastolic tension. Dronedarone (10 μM) and amiodarone (10 μM) attenuated H2O2-induced pulmonary vein burst firings from 100% to 33.3% (P<0.01), and to 0% (P<0.005), respectively. In conclusion, amiodarone and dronedarone both significantly reduced pulmonary vein spontaneous beating rates and H2O2-induced pulmonary vein arrhythmogenesis. However, only dronedarone produced pulmonary vein vasodilation.