Right Ventricular Monophasic Action Potentials in Healthy Young Men

The right ventricular repolarization phase was studied in 48 healthy men between 20 and 40 years of age. The assessment of the repolarization time included the measurement of ventricular effective refractory periods and monophasic action potentials during constant ventricular stimulation. Computer-based analysis of the monophasic action potential allowed the duration at 90% and 50% repolarization, the amplitude, the maximal upstroke velocity and the total rise time of the depolarization to be determined. These results may serve as reference values in further studies on ventricular repolarization using the same monophasic action potential recording technique.     

Intraoperative Recordings of Monophasic Action Potentials with Chronically Implantable Pacemaker Leads

Since the development of fracially coaled Iridium electrodes recordings of monophasic action potentials are possible. Intraoperative recordings of MAP from 15 pacemaker implantations were done after positioning the chronically implantabie pacemaker leads (Biotronik, Berlin, Germany) in the right ventricle by using five screw-in electrodes and ten anchor electrodes. Intraoperative recordings of MAP are possible with all implanted pacemaker leads. The recordings of typical MAP signals were always accompanied with stable electrode positions and good sensing and pacing characteristics.     

An Automatic Microcomputer System for Analysis of Monophasic Action Potentials

A computer system for rapid measurement and analysis of monophasic action potentials (MAPs) recorded in vivo was developed. MAPs recorded from the epicardium of mongrel dogs using a contact electrode were digitized by analog-to-digital conversion at a sampling rate of 1 kHz per channel for computer data acquisition. Activation time was detected using a sliding 10-point window at the location where the average positive dV/dT exceeds an adjustable threshold value in order to eliminate spurious detection due to baseline variability or motion artifact. Action potential duration (APD) was determined at 50% and 90% (APD50, APD90) repolarization levels at the first sample point below these detection levels. In addition, a tangent algorithm (APDtan) that detects peak negative dV/dT during repolarization was developed. APDtan was determined from the location of onset of activation to the intersection of tangent and baseline. APDtan allowed estimation of APD in the presence of subsequent premature beats when APD90 was not measurable. To validate activation time measurements, 4,600 action potentials were analyzed during fixed rate pacing. Over a range of paced coupling intervals from 200 to 1000 msec, an R2 value of 0.99968 and a slope of 0.9959 were obtained by linear regression between paced and calculated intervals. To validate APD measurements, 5035 action potentials were analyzed in five animals during fixed rate pacing (longer than 3 minutes) when action potential duration should be constant. Average coefficient of variation of 1.25%, 1.65%, and 1.14% were obtained for APD50, APD90, and APDtan, respectively. This algorithm provides a rapid and accurate method to analyze MAP activation and duration for basic physiological studies such as the determination of initiation of arrhythmias.     

Early Afterdepolarizationlike Activity in Patients with Class IA Induced Long QT Syndrome and Torsades de Pointes

Early afterdepolarizations (EADs) have been linked to the mechanism of torsades de pointes in long QT syndrome. The purpose of this study was to investigate the role of EADs in Class IA induced torsades de pointes. We studied nine patients with Class IA induced torsades de pointes at the time this arrhythmia was present (acute period, n = 7) and after Class IA therapy was discontinued (chronic period, n = 6). ECCs and monophasic action potentials were recorded in both periods. In the chronic period, electrophysiological studies were performed before and after disopyramide infusion. In the acute period, QT_c interval was markedly prolonged (655 ± 32 ms^1/2), and EAD-like activity was recorded in all patients. QT_c interval returned to normal (428 ± 45 ms^1/2) and EAD-like activity disappeared after discontinuation of IA drug. Although, in the chronic period, disopyramide infusion prolonged QT_c interval from 428 ± 48 ms^1/2 to 479 ± 31 ms^1/2 and induced EAD in three of six patients, the degree was not as marked as observed in the acute period. EADs may play an important role in the genesis of long QT and torsades de pointes. Disopyramide infusion in the chronic period could not reproduce marked repolarization ahnormalities and torsades de pointes.     

Computer Analysis of Monophasic Action Potentials: Manual Validation and Clinically Pertinent Applications

FRANZ, M.R., et al .: Computer Analysis of Monophasic Action Potentials: Manual Validation and Clinically Pertinent Applications . Monophasic action potential (MAP) recordings are increasingly being used in a variety of clinical and experimental situations but their manual measurement is cumbersome, especially when hundreds or thousands of beats must be analyzed to monitor the exact time course of action potential duration (APD) changes following heart rate alterations, during surveillance of APD alternans, or during the onset and stabilization of Class III drug effects. To facilitate this task we developed a computer program that automates programmed electrical stimulation, digitizes at 1-kHz sampling frequency MAP recordings up to 8 channels simultaneously, analyzes all APDs at repolarization levels from 10%–90% in 10% decrements (APD_10–90), and automatically outputs the analyzed numerical data into spreadsheets for graphical display or statistical analysis. To validate the computer algorithm, two independent observers manually analyzed 585 concurrent MAP recordings at a paper speed of 100 mm/s. Cycle length measurements by the computer were precise to 0.4 ± 0.5 ms as compared to the computer determined paced cycle length. Computer measurements of APD_{20, 50, and 90} differed from manual measurements by 2.0 ± 8.8 ms, 0.7 ± 7.9 ms, and 0.2 ± 8.5 ms, respectively, for observer 1; and by 12.2 ± 8.3 ms, 5.8 ± 7.5 ms, and 1.4 ± 10.1 ms, respectively, for observer 2. Inter-observer variability (IOV) was 10.3 ± 11.1 ms (APD₂₀), 5.1 ± 9.0 ms (APD₅₀), and 1.2 ± 7.8 ms (APD₉₀), which was similar to computer/observer-2 differences and significantly greater (0.001) than computer/observer-1 differences. This indicates that the computer analysis was at least as precise as manual measurements when compared to IOV, and more precise when comparing computer/observer-1 differences to IOV. While providing equal or greater precision, computer-aided analysis of 100 MAP signals took approximately 1 minute while manual analysis of the same data set took between 2.5 and 4 hours. The pacing and analysis software was subsequently applied to experiments that mimic clinically pertinent examples of MAP recordings: (1) automatic generation, analysis, and graphical display of electrical restitution curves at multiple ventricular sites simultaneously; (2) evaluation of myocardial pharmacokinetics by monitoring the progression of Class III antiarrhythmic drug effects by continuous MAP recordings, and displaying differences in drug action between multiple sites; (3) depiction of the adaptation time course of APD to abrupt changes in paced cycle length; and (4) quantitative analysis of APD alternans during myocardial ischemia. The results show that our computerized algorithm greatly facilitates the generation of cardiac electrophysiological, and clinically important, data.     

Clinical Application of a Microcomputer System for Analysis of Monophasic Action Potentials

Computerized analysis of monophasic action potentials (MAPs) has rarely been reported in clinical setting. We developed a computer system featuring on-line acquisition and user-monitored automatic measurement of multichannel MAPs with the capability of manual corrections. This system has been used in 34 patients in whom two-channel MAPs and 1-lead ECG were digitized during sinus rhythm, pacing, and programmed stimulation (PS). In total, 41,413 MAPs in 212 data files were measured. The correct determination rate was 100% for MAP onset and plateau, 99.78% (95.76% during PS) for MAP baseline, and 99.96% (54.29% during PS) for QRS onset. The comparison between the computerized and manual measurements in 292 MAPs showed that the former highly agreed with the latter, with the limits of agreement, defined as mean difference ± 2 SD, being from -4.8-4.9 ms for activation time and from – 4.1-6.0 ms for MAP duration measurements. Using this system, two-channel MAPs of more than 300 consecutive beats can be measured in a few minutes, which made it possible to determine the steady state of MAP duration individually, and evaluate the MAP changes during intervention in detail. The clinical routine procedure for testing the effective refractory period and several new MAP parameters were also evaluated using this system. Conclusion: The MAP measurement using this computer system is reliable, rapid and accurate; it can therefore replace the manual method and provide more useful information for clinical research.     

Unipolar Waveforms and Monophasic Action Potentials in the Characterization of Slow Conduction in Human Atrial Flutter

Anisotropic propagation may be involved in the development of areas of slow conduction in atrial flutter. We evaluated monophasic action potentials (MAPs) and simultaneous unipolar (0.2–400 Hz) and bipolar electrograms from multiple atrial sites of patients undergoing RF ablation of idiopathic atrial flutter. Nine patients (mean age 46 ± 20 years) with typical atrial flutter (one with both types) were studied. Unipolar electrograms with triphasic complexes of small amplitude and with a slow, negative deviation of the baseline preceding the rS deflection indicated transversal conduction in relation to the orientation of cardiac fibers; smooth rS complexes longitudinal conduction; QS complexes onset of activation; and R complexes end of activation or collision. In all patients with typical atrial flutter, slow conduction occurred in the corridor between the inferior vena cava, the tricuspid annulus, and the coronary sinus. Transversal conduction was observed in this area, whereas the remaining sites showed longitudinal conduction. Anatomically guided RF ablation was successful in five patients. Transversal conduction was recorded in all successful sites. In the patient with atypical atrial flutter, slow conduction was noted in the high lateral right atrium, also exhibiting transversal conduction. Ablation at this area terminated the arrhythmia. All the areas of transversal conduction during flutter displayed longitudinal conduction after restoration of sinus rhythm. MAPs were normal in all patients during atrial flutter and sinus rhythm, even at the areas where transversal conduction was recorded. These findings suggest that anisotropic propagation is involved in the genesis of functionally determined areas of slow conduction during typical atrial flutter.     

Simultaneous Recording of Atrial and Ventricular Monophasic Action Potentials: Monophasic Action Potential Duration During Atrial Pacing, Ventricular Pacing, and Ventricular Fibrillation

A newly developed transvenous suction electrode was used in dogs to record monophasic action potentials (MAPs) from the right atrium and right ventricle simultaneously. Continuous MAP recordings could be made from the same endocardial site for test periods of 1.5 hours. Left ventricular pacing at increasing heart rates resulted in a statistically significant decrease of right ventricular MAP duration. A high degree of correlation was found between right ventricular MAP duration at 90% of repolarization and the QT interval during both right atrial and left ventricular pacing. At the onset of ventricular fibrillation (VF), right ventricular MAP duration shortened to 25% of the value obtained during left ventricular pacing at a cycle length of 250 ms. A cyclic alternation in amplitude of the right ventricular MAPs was observed during VF. Fast Fourier Transform Analysis of right ventricular MAPs during VF showed a significant dominant frequency at 12 Hz, with no levels of interest beyond this frequency. This observation might prove to be useful in elaborating a new algorithm for the automatic detection of ventricular fibrillation.     

Role of Early Afterdepolarization in Familial Long QTU Syndrome and Torsade de Pointes

Torsade de pointes (TdP) syncopal episodes were almost invariably precipitated by emotional stress or menstruation in a 17-year-old girl. V wave accentuation occurred during sinus rhythm without pauses in periods of heightened sympathetic tone. To examine the role of early afterdepolarization (EAD), monophasic action potentials were recorded during ventricular extrasystoles and TdP occurring spontaneously and induced by ventricular pacing. The effects of lidocaine, verapamil, propranolol, and epinephrine were assessed. Our data show that: (1) EAD plays a significant role in the genesis of familial long QTU syndrome and TdP; (2) rapid ventricular pacing causes postpause-dependent EADs, U waves, and TdP; and (3) EAD is enhanced by epinephrine infusion in the absence of pause, whereas EAD-triggered firing is inhibited by verapamil and propranolol but not by lidocaine.     

Optimizing the Geometry of Implantable Leads for Recording the Monophasic Action Potential with Fractally Coated Electrodes

This study investigates the influence of various lead geometry on intracardial signals like the monophasic action potential (MAP) to optimize the geometry of implantable MAP leads. The experimental results were compared with a field theoretical approach to the origin of MAP from the transmembrane potential (TAP). During the experiments several lead geometries (tip surface: 1.3 to 12 mm²; tip-ring distance: 0.8 mm to 25 cm; ring surface: 1.8mm² to 40 mm²) were investigated in endo- and epicardial positions in 12 dogs (17±9 kg). The electrodes were fixed passively (tines) or actively (screws). MAP was recorded during several interventions and correlated with MAP measured using an Ag-AgCl MAP catheter. The experimental results showed that small tips provided high MAP amplitudes with less pressure. No difference was observed using active and passive fixations. A tip-ring distance smaller than 5 mm with a ring surface smaller than the tip (<5 mm²) avoided artifacts in the repolarization course. For the theoretical approach the quasistatic, anisotropic bidomain model was calculated in smalt unity volumes V_i where the TAP φ_m was constant and represented by the current density J. Two solutions for electrode positions at and outside the heart were achieved. By superposition of each solution φ_ei the summed potential at the electrode position was calculated. The theoretical findings show in good correlation with the experimental results that a larger distance than 10 mm leads to distortions in repolarization course by signals proportional to φ_out.     

Simultaneous Recordings of the Monophasic Action Potential with Silver Chloride- and Ir-Coated Electrodes

Ag AgCI and Ir-coated electrodes allow the recording of the monophasic action potential (MAP) due to their electrical properties like non-polarisability. This study investigates the correlation of MAP recorded with both types of electrodes. In 20 mongrel dogs (18 ± 6 kg) an Ag/AgCI and an Ir-coated catheter (Ir) were placed endo-cardially in the apex of the right ventricle. The effects of isoproterenol and verapamil were investigated during spontaneous rhythm and stimulation simultaneously recorded with both types of electrodes in 10 dogs without AV-node ablation. The correlation at different heart rates were investigated in 10 other dogs with complete AV-block. The morphology and amplitudes of MAP were comparable (AgCl: 15±7 mV; Ir: 13±8 mV). Following an i.v. bolus of 2μg/kg isoproterenol the spontaneous rate increased (175±18 to 245±25 bpm). During stimulation with 250 ms cycle length the duration shortened (MAPd90: AgCl: 160 ± 11 to 130 ± 12 ms; Ir: 154 ± 18 to 128±15 ms). The alterations reversed after 20 mm. An i.v. bolus of 0.2 mg/kg verapamil decreased the spontaneous rate (167±11 to 104 ± 23 bpm) and lengthened the MAPd90 (AgCl: 182 ± 14 to 220±13 ms; Ir: 174 ± 16 to 216, 21 ms) at 300 ms stimulation. The correlation between the MAPd90 of both lead types was r=0.98 during all measurements. Under the effect of beta-agonist and Ca²⁺ -antagonist medication MAP showed a strong correlation recorded with both types of electrodes. Thus, both leads allow the recording of MAP but only the Ir-electrodes with their long-term stability are implantable and allows us to control the effects of drugs with implantable devices.     

Arrhythmia Risk: Eiectrophysiological Studies and Monophasic Action Potentials

Shortly after in the introduction of progrommed electrical stimulotion (PES) of the heart to study and localize cardiac arrhythmias in the intact human heart, the technique was used for risk stratification of the arrhythmia patient. Two decades later we have to conclude that especially in ventricular arrhythmias the technique of PES did not live up to our expectations and the left ventricular function is a better long-term predictor than the induction of ventricular arrhythmias or the ability to find an antiarrhythmic drug able to prevent the initiation of the classically documented ventricular arrhythmia. Another sobering finding come from the analysis of the characteristics of the patient dying suddenly out-of-hospital, which showed that most of those patients could not be classified before the event as being at high risk using noninvasive or invasive testing, not even in those with o previous cardiac history. Monomorphic action potential (MAP) recordings have been of importance in our understanding of torsade de pointe arrhythmias in congenital and acquired QT prolongation. A major problem in case of a less generalized electrophysiological abnormality is the identification of the appropriate place where to put the MAP-electrode.     

高胆固醇血症家兔心脏单相动作电位及钙电流的特征

目的观察高胆固醇血症对家兔心脏单相动作电位及钙电流的影响。方法24只家兔分为高胆固醇饮食组和对照组各12只,分别给予高胆固醇饲料和标准饲料饲养10周后,检测血脂、心电图和室颤阈值,记录离体灌流心脏单相动作电位,并记录心室肌细胞的L型钙通道电流。结果高胆固醇饮食组兔的血脂水平明显高于对照组(P<0.01);室颤阈值(10.2±1.7)V,低于对照组的(13.9±1.3)V(P<0.05);单相动作电位复极90%的时程(MAPD90)较对照组延长并呈更明显的逆频率依赖性,在1500ms起搏时MAPD90为(348±21)ms,而对照组为(271±16)ms;心室肌细胞的L型钙通道电流密度为(14.7±0.8)pA/pF,明显高于对照组的(10.9±1.1)pA/pF(P<0.01)。结论高胆固醇血症家兔的心脏单相动作电位及心肌细胞L型钙通道电流明显改变,复极时程延长,室颤阈值降低。     

Global Repolarization Sequence of the Ventricular Endocardium: Monophasic Action Potential Mapping in Swine and Humans

The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.     

T Wave Alternans in Idiopathic Long-QT Syndrome: Insight from Body Surface Mapping

Body surface mapping was recorded during T wove alternans in two patients with idiopathic long QT syndrome. Eighty-seven had ECGs of two consecutive beats during T wave alternans demonstrated that alternating changes in the morphology and polarity of the T wave existed mainly in the left frontal chest. The QRST isointegral maps of the same two consecutive beats showed alternation of a large negative area appearing mainly in the left frontal chest. These results indicate that T wave alternans in the two patients were related to alternate heterogeneous prolongation of the action potential duration in this region.     

Electrical Atrial Remodeling Assessed by Monophasic Action Potential and Atrial Refractoriness in Patients with Structural Heart Disease

The present study was performed to assess the effect of induced atrial fibrillation (AF) on atrial monophasic action potentials (MAPs) and atrial refractory period (ERP) in patients with structural heart disease. An electrode MAP catheter was placed in the right atrium to continuously measure atrial potential duration (APD₉₀) in 13 patients (coronary artery disease, 10 patients; dilated cardiomyopathy, 2 patients; hypertrophic cardiomyopathy, 1 patient) without spontaneous AF episodes. AF was induced by rapid atrial stimulation (300–1500/min). If sinus rhythm returned within 10 minutes, AF was reinduced. The atrial ERP was measured during atrial pacing at a basic cycle length of 550 ms before AF induction and after its conversion. Results: The mean atrial ERP and the atrial APD₉₀ before AF was 242 ± 34 ms and 256 ± 23 ms, respectively. ERP and APD_go shortening was observed after 3 minutes of AF. After 11 ± 0.5 min (10 min 20 s-13 min 10 s) of AF, ERP and APD₉₀ reached their minimal values of 72%± 13% and 71%± 10% of baseline, respectively. ERP and APD₉₀ returned to their initial values within 10 minutes after conversion of AF. A tendency toward longer duration of consecutive AF episodes and facilitation of their induction was observed. Conclusion: The present study confirms that short episodes of AF modify the electrophysiological properties of the atria in humans. In patients with structural heart disease, induced atrial fibrillation shortens the atrial ERP as well as the atrial APD₉₀. The changes were reversible within 10 minutes after arrhythmia termination.     

Relationship of the Effective Refractory Period and Monophasic Action Potential Duration after a Step Increase in Pacing Frequency

Adaptation of effective refractory period (ERP) and monophasic action potential (MAP) shortening after a step increase in drive frequency was determined at adjacent endocardial sites in the right ventricle of six patients without myocardial disease. ERP and MAP shortening occurred simultaneously. ERP shortening and MAP shortening were similar in time course in individuals, although the degree of shortening varied between individuals as the size of the step increase in pacing frequency varied. Shortening of both ERP and MAP was complete after a mean of 67 +/- 7.5 seconds. To allow group analysis, the percent change from baseline of action potential duration and ERP was calculated for each patient at intervals during adaptation and mean percent change for the group plotted against time from the beginning of the step rate increase. A mean step increase in pacing frequency of 49.3% of baseline for the group caused the ERP to shorten by a mean of 18.12%, and MAP90 by 17.43% of baseline. There was no significant difference (P = 0.05) between the action potential and ERP adaptation curves of the group. We conclude that in normal myocardium, there is a close relationship between shortening of ventricular ERP and action potential duration after a change in rate.     

Rate and Time Dependent Effects of D-Sotalol on the Monophasic Action Potential After Sudden Increase of the Heart Rate

Experimental and clinical data suggests that almost all Class III antiarrhythmic agents diminish their ability to prolong cardiac repolarization at fast heart rates. However, only limited data exists about the time course of efficacy decay of Class III agents after sudden increase of the heart rate. In the present study, we assessed both rate and time dependent changes of the efficacy of d-sotalol in higher stimulation frequencies following an abrupt increase in heart rate. This might imitate the situation seen in the development of paroxysmal tachycardias. Monophasic action potentials were recorded from the right ventricular apex during sinus rhythm and constant stimulation with the paced cycle length (PCL) of 550 ms, 400 ms, and 330 ms in the baseline and 20 minutes after intravenous administration of d-sotalol (2.5 mg/kg) in seven patients with documented life-threatening ventricular tachyarrhythmias. D-sotalol significantly prolonged monophasic action potential duration at different steady-state heart rates (sinus rhythm: 21.1%± 3.6%; PCL 550 ms: 16.6%± 4.3%, 400 ms: 11.2%± 2.7%, 330 ms: 5.8%± 2.1%). The prolongation is significantly shorter in higher steady-state pacing, confirming a pronounced reverse-use dependent decrease of the efficacy of d-sotalol at faster stimulation frequencies. After the abrupt increase in heart rate, the beat-to-beat adaptation of the postdrug action potential prolongation exhibits only slight reverse-use dependent shortening. The decrease of the efficacy of d-sotalol is insignificant for the first 20 consecutive beats at the stimulation frequency of the PCL of 400 msec (from 16.6% at PCL of 550 ms to 14.6% at the 20th beat of the PCL of 400 ms), and for the first ten consecutive beats at the stimulation frequency of the PCL of 330 ms (from 16.8% at PCL of 550 ms to 12.3% at the 10th beat of the PCL of 330 ms). This slow decay of action potential prolongation after an abrupt increase in heart rate might contribute to the antiarrhythmic action of d-sotalol in cardiac tachyarrhythmias.     

Electrophysiological Observations During QRS Alternans in a Patient with Incessant Tachycardia

Electrophysiological observations during preoperative and intraoperative study of a 46-year-old patient with incessant ventricular tachycardia and QRS alternans demonstrated a potential mechanism for this electrocardiographic finding. During QRS alternans, conduction delay (or block) was recorded from the site of origin of the tachycardia, high on the anterior septum to the His bundle: After procainamide infusion, the tachycardias slowed and, concurrent with the disappearance of QRS alternans, conduction from the site of tachycardia origin to the His bundle could no longer be demonstrated.     

Brady Cardie-Dependent Early Afterdepolarizations in a Patient with QTU Prolongation and Torsade de Pointes in Association with Marked Bradycardia and Hypokalemia

Endocardial monophasic action potentials (MAPs) were recorded at the right ventricular apex in a patient with QTU prolongation and torsade de pointes (TdP) in association with marked bradycardia and hypokalemia. There was a distinct hump on phase 3 repolarization of the MAPs characteristic of early afterdepolarizations (EADs), which was associated with marked prolongation of the QTU interval on the surface electrocardiogram. EAD amplitude was bradycardia dependent, and there was a strong correlation (r = 0.91) between the preceding RR interval and the amplitude of the EAD (percent of MAP amplitude). Intravenous administration of lidocaine or right ventricular pacing suppressed the ventricular premature complexes and TdP in association with the suppression of the EADs on the MAPs. Furthermore, these EADs were not recorded on the MAPs 1 month later when the QTU prolongation and TdP had disappeared. These findings suggest that the TU abnormality and QTU prolongation responsible for TdP were due to bradycardia-dependent EADs.