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.     

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.     

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.     

Broad Applicability of Ultrarapid Train Stimulation as an Efficient Alternative to Conventional Programmed Electrical Stimulation

FISHER, J.D., et al.: Broad Applicability of Ultrarapid Train Stimulation as an Efficient Alternative to Conventional Programmed Electrical Stimulation. Background and study objective:Conventional programmed electrical stimulation (PES) is useful for establishing inducibility or noninducibility of clinical ventricular arrhythmias (VA), but is complex and time-consuming. This study compared a standard PES protocol with ultrarapid train stimulation (UTS) in a broad range of patients with and without a history of ventricular arrhythmias or structural heart disease. Methods: Patients prospectively underwent electrophysiologic testing with both UTS and conventional PES protocols in a randomized, crossover design. Results: The results were concordant in 79% of 150 matched pairs of comparisons in 104 patients (NS). There were no differences related to underlying heart disease or arrhythmia, or antiarrhythmic treatment. Induction of nonclinical arrhythmias with the two methods was similar   (P = 0.524)   . Inhibition phenomena were minor except in some patients receiving amiodarone. Fewer drive-extrastimuli sequences and less time were needed to complete the trains protocol   (P < 0.0001)   . Conclusions: In cases where the main intent is to induce ventricular arrhythmias, UTS yields results that are similar to those of conventional PES protocols in a shorter length of time. (PACE 2003; 26[Pt. II]:518–523)     

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.     

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.     

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.     

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.     

Triggered Activity Induced By Pacing During Digitalis Intoxication: Observations During Programmed Electrical Stimulation in the Conscious Dog With Chronic Complete Atrioventricular Block

In isolated Purkinje fibers, digitalis intoxication induces triggered activity, which is based upon delayed afterdepolarizations. The characteristics of delayed afterdepolarizations have been studied systematically by programmed electrical stimulation. The present investigations were done to study the role of triggered activity during digitalis intoxication in the intact heart. For this purpose, a pacing protocol, similar to that used in experiments of isolated Purkinje fibers, was used. The experiments were done on conscious dogs with chronic complete atrioventricular block. Ventricular tachycardia was induced with digoxin IV 0.1 mg/kg/1-1 1/2 hr. The effect of programmed electrical stimulation on the first post-pacing interval was determined during sustained ventricular tachycardia and, following its spontaneous termination during an episode when ectopic activity could only be induced by pacing. During sustained ventricular tachycardia there was a direct linear relation between the interstimulus interval of regular pacing and the first post-pacing interval. During the episode when ectopic activity could only be induced by pacing, shortening of the post-pacing interval resulted in biphasic behavior of the first post-pacing interval. Pacing with interstimulus intervals of more than 400 ms induced a first post-pacing interval equal to the interstimulus interval, whereas shorter interstimulus intervals induced a first post-pacing interval twice the interstimulus interval. When during regular pacing only the last pacing interval was changed, a similar biphasic response resulted. When toxicity had almost subsided, ectopic activity could only be induced following short pacing intervals (200-320 ms). Again, a direct linear relation was found between the pacing interval and the first post-pacing interval. Our findings strongly suggest that at different levels of digitalis intoxication triggered activity is the underlying mechanism for the first post-pacing QRS complex.     

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.     

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.     

Detection of rapid changes in ventricular refractoriness in human studies

Conventional determination of the ventricular effective refractory period (VERP) is unsuitable for detection of rapid fluctuations in the effective refractory period (ERP). A programmed stimulation system was developed that adapts continuous atrioventricular sequential pacing, incremental extrastimulus interval (S1S2) scanning, and automatic detection of extrastimulus capture which is followed by shortening of S1S2 to execute repeated scanning. The accuracy of ERP determination was tested using variable incremental (2 and 4 ms) and decremental (4-16 ms) steps of the S1S2 interval. Based on a mean of 82 determinations in eight patients, the average VERP values stayed at 249.8-251.0 ms except during the highest capture frequency. Standard deviation of ERP values ranged from 1.1 to 2.5 ms on average at the tested incremental and decremental steps. One determination was accomplished within 7.8-15.6 seconds on average. The ability to track changes in ERP was tested by changing the drive cycle length. Time constants for the adaptation rate of VERP and ventricular monophasic action potential duration at a 90% level of repolarization were determined from each test, and were similar, 51 +/- 8 seconds (mean +/- SEM) for ERP and 51 +/- 6 seconds for the action potential duration. Thus, the developed method provides accurate ERP measurements during rapid variation in ventricular refractoriness. It allows studying the recovery of excitability and the action potential duration simultaneously, and would be valuable particularly in pathological conditions and pharmacologic interventions where these electrophysiological variables become dissociated.     

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.     

Frequency Dependent Effects of d-Sotalol and Amiodarone on the Action Potential Duration of the Human Right Ventricle

Frequency dependent effects of d-Sotalol (2.0 mg/kg IV, n = 6) and amiodarone (400 mg/day for 3 months, n = 9) were studied on the action potential duration (APD) in 14 patients who underwent electrophysiological testing. Monophasic action potentials were recorded from the right ventricle at five different steady-state paced cycle lengths (700 msec, 600 msec, 500 msec, 400 msec, and 350 msec), and during ventricular extra stimuli with coupling intervals between 300 msec and 1000 msec, before and after d-sotalol and amiodarone, respectively. D-sotalol caused a prolongation of the APD at slow steady-state stimulation rates (11 ± 5% at cycle length of 700 msec), which became attenuated at faster cycle lengths (5 ± 3% at cycle length of 350 msec). Prolongation of APD after amiodarone was independent of pacing rate, e.g., 12 ± 9% at cycle length of 700 msec, and 11 ± 6% at cycle length of 350 msec. Similar frequency dependent prolongation of the APD was observed during abrupt changes of cycle lengths after d-sotalol, whereas amiodarone caused uniform prolongation of the APD at different extrasfimulus intervals. Thus, d-sotalol, a nonselective potassium channel blacker, has reverse use-dependent effects on the human ventricular APD, while amiodarone with greater potassium channel selectivity, has equal ability to prolong the ventricular APD at fast and slow heart rates.     

Increased Temporo-Spatial Dispersion of Repolarization During Double Premature Stimulation in the Intact Ventricle

The degree of temporo-spatial variation of repolarization during single (S₂) and double (S₃) premature stimulation was evaluated in five closed-chest anesthetized dogs. Monophasic action potentials (MAP) were simultaneously recorded with contact electrode and MAP duration (MAPD) restitution curves constructed from right ventricular (RV) and left ventricular (LV) endocardial sites. At a given coupling interval, S₃ was associated with significantly greater dispersion of MAPD then S₂ spatial dispersion, i.e., between RV and LV). Similarly, at a given diastolic interval, S₃ at RV and LV sites, was associated with significantly greater dispersion of MAPD then S₂ (temporal dispersion). It is concluded that S₃ is associated with greater temporo-spatial dispersion of repolarization then S₂.     

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。     

Amiodarone: Value of Programmed Electrical Stimulation and Holter Monitoring

The value of programmed electrical stimulation (PES) and Holter monitoring in the assessment of amiodarone efficacy was reviewed. Many physicians have been disturbed by the persistent inducibility of arrhythmias in patients treated with amiodarone, who nevertheless do very well during the follow-up period. Noninducibility was associated with a favorable prognosis among 366 VT patients. Eighty-eight (24%) were noninducible on amiodarone, and 10% of these had recurrences, vs 39% in patients who remained inducible. Further, increased difficulty of induction with PES or induction of a slower or better tolerated VT may indicate a favorable outlook, and add to the value of PES. Few papers rigorously employed Holter monitoring in the assessment of amiodarone. In general, suppression of previously frequent arrhythmias implies excellent protection for patients with benign arrhythmias and moderate protection with malignant arrhythmias. By Holter assessment in 186 VT patients, arrhythmias were suppressed in 114 (61%), and 18% of these had recurrences vs 50% in patients whose arrhythmias were not suppressed. Studies attempting to correlate the results of PES and Holter monitoring in the same patients are lacking and may prove useful.     

Muscarinic Effects on Action Potential Duration and its Rate Dependence in Canine Purkinje Fibers

Studies of the autonomic influence on action potential duration (APD) in the ventricles show direct effects of muscarinic stimulation on epicardial, but not endocardial, APD and conflicting results regarding direct vagal effects on the conduction system. In canine Purkinje fibers, we analyzed the action of the M₂ agonist oxotremorine (OXO, 0.1μM) on APD and on its cycle length (CL) dependence. Fibers were impaled with glass microalectrodes and superfused with Tyrode s solution. APD₉₀ was measured after 3 minutes of drive at CL between 0.3 and 5 seconds. The best fit for the APD/CL relationship at steady state was a hyperbole: APD = APD_max*CL/(CL+CL₅₀), where APD_max (APD at infinite CL) is a rate independent measure of APD, and CL₅₀ (CL at which 50% APD_max is reached) is an index of the rate dependence of APD. In five fibers, OXO reduced APD at all CL (P < 0.05), APD_max was also reduced to 377 ± 41 ms from 447 ± 34 ms (P < 0.05), while CL₅₀ was unchanged (405 ± 46 ms from 437 ± 28 ms). No effects of OXO on APD and APD_max were seen in two fibers obtained from dogs pretreated with pertussis toxin (PTX). In conclusion, stimulation of M₂ receptors in intact, and not PTX treated, Purkinje fibers affects APD but not its CL dependence. This may reflect the activation of a rate independent, background current through a GTP binding protein-linked pathway, such as, I_K.ACH These data differ from those obtained in endocardial and epicardial muscle, stressing the regional differences in vagal modulation of ventricular electrophysiological properties.     

Programmed Ventricular Stimulation Using Tandem Versus Simple Sequential Protocols

The objective was to determine whether two commonly used ventricular stimulation protocols, one more complex than the other, produced concordant results. If such were the case, the simpler protocol would streamline activities in clinical electrophysiology laboratories. Background: Two programmed ventricular stimulation protocols were compared. (1) With the tandem method, the first extrastimulus (S₂) is moved stepwise to the effective refractory period and then moved out 50 msec; the second extrastimulus (S₃) is then decremented until it fails to capture; S₂ and S₃ are then decremented in a semialternating (tandem) fashion so that both continue to capture. When S₂ reaches the refractory period + 10 msec and S₃ fails to capture, S₃ is then moved out 50 msec, and S₄ is decremented as described for S₃. (2) With the simple sequential method, the first extrastimulus (S₂) is decremented stepwise to the refractory period, and then moved out 10 msec to assure capture; S₃ is then similarly decremented to the refractory period and then moved out 10 msec; and S₄ is then similarly decremented. Methods: This was a prospective, randomized, crossover, consecutive series study. Both protocols were tested in each patient on the same day in randomized order. Results: There were 84 matched studies. Fifty-six patients provided data from baseline electrophysiological studies, and 28 of these provided additional data during drug trials. There was a 93% concordance between the two methods, including tbe primary outcomes of inducibility of clinical arrhythmias, inducibility of nonclinical arrhythmias, and noninducibility (P < 0.001). Discordances were few and evenly distributed between the two protocols (P = NS). Results were similar for baseline studies and drug trials. The simple sequential method required less time to perform (P ≤ 0.01). Conclusions: Tandem and simple sequential protocols provide concordant results. No advantage could be demonstrated for the more complex tandem method.     

Programmed Ventricular Stimulation During Variant Angina: Report of a Case

Programmed ventricular stimulation was performed in a 74-year-old patient who had a history of syncope following chest pain. In the baseline state, ventricular tachycardia was not inducible. Immediately following the study protocol, the patient complained of her usual chest pain and ST elevation was documented in lead II with reciprocal ST depression in leads AVF and V1. Programmed ventricular stimulation was repeated (presumably during the occlusive phase of coronary spasm) and a polymorphic ventricular tachycardia with a cycle length of 200 msec was repeatedly induced. Following intravenous nitroglycerin and resolution of chest pain, ventricular tachycardia was not inducible. Coronary angiography with ergonovine testing confirmed coronary spasm of the right coronary artery. We speculate that syncope was caused by ventricular tachycardia following coronary artery spasm. During a 12-month follow-up with calcium blockers and nitrates, there has been no recurrence of chest pain or syncope.