Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies.

BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To experimentally address the controversies concerning the correct way to record MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were recorded in isolated pig hearts with an exploring electrode grid, with a KCl reference electrode on the left ventricular myocardium, the aortic root, or the left atrium. Local activation was determined from calculated Laplacian electrograms. RESULTS: With the KCl electrode on the aortic root, local electrograms represented local activation. However, with the KCl electrode on the myocardium remote from the exploring electrode, a combined electrogram emerged consisting of local activation recorded from the grid and remote activation recorded from the reference electrode. The remote, inverted monophasic component did not show propagation and did not correlate with the Laplacian complex. When the KCl electrode was placed on the atrium during AV block, remote atrial monophasic components were completely dissociated from local, ventricular deflections. At left ventricular sites with a positive T wave, the Laplacian signal showed that the end of the T wave was caused by remote repolarization. During cooling-induced regional action potential prolongation, the T wave became negative, whereby the positive flank of the T wave remained correlated with repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are recorded from the depolarizing electrode. In both negative and positive T waves, the moment of maximum dV/dt corresponds to local repolarization.     

Monophasic action potential mapping in human subjects with normal electrocardiograms: direct evidence for the genesis of the T wave

T wave concordance in the normal human electrocardiogram (ECG) generally is explained by assuming opposite directions of ventricular depolarization and repolarization; however, direct experimental evidence for this hypothesis is lacking. We used a contact electrode catheter to record monophasic action potentials (MAPs) from 54 left ventricular endocardial sites during cardiac catheterization (seven patients) and a new contact electrode probe to record MAPs from 23 epicardial sites during cardiac surgery (three patients). All patients had normal left ventricular function and ECGs with concordant T waves. MAP recordings during constant sinus rhythm or right atrial pacing were analyzed for activation time (AT) = earliest QRS deflection to MAP upstroke, action potential duration (APD) = MAP upstroke to 90% repolarization, and repolarization time (RT) = AT plus APD. AT and APD varied by 32 and 64 msec, respectively, over the left ventricular endocardium and by 55 and 73 msec, respectively, over the left ventricular epicardium. On a regional basis, the diaphragmatic and apicoseptal endocardium had the shortest AT and the longest APD, and the anteroapical and posterolateral endocardium had the longest AT and the shortest APD (p less than .05 to less than .0001). RT was less heterogeneous than APD, and no significant transventricular gradients of RT were found. In percent of the simultaneously recorded QT interval, epicardial RT ranged from 70.8 to 87.4 (mean 80.7 +/- 3.9) and endocardial RT ranged from 80 to 97.8 (mean 87.1 +/- 4.4) (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient

OBJECTIVE: The contribution of regional electrophysiologic heterogeneity to the T-wave changes of long-term cardiac memory (CM) is not known. We mapped activation and repolarization in dogs after induction of CM and in sham animals. METHODS AND RESULTS: CM was induced by three weeks of AV-sequential pacing at the anterior free wall of the left ventricle (LV), midway between apex and base in 5 dogs. In 4 sham controls a pacemaker was implanted but ventricular pacing was not performed. At 3 weeks, unipolar electrograms were recorded (98 epicardial, 120 intramural and endocardial electrodes) during atrial stimulation (cycle length 450 ms). Activation times (AT) and repolarization times (RT) were measured and activation recovery intervals (ARIs) calculated. CM was associated with 1) deeper T waves on ECG, with no change in QT interval; 2) longer activation time at the site of stimulation in CM (29.7+/-1.0, X+/-SEM) than sham (23.9+/-1.3 ms p<0.01); 3) an LV transmural gradient in repolarization time such that repolarization at the epicardium terminated 12.4+/-2.4 ms later than at the endocardium p<0.01), in contrast to no gradient in shams (2.7+/-4.2 ms); in memory dogs, the repolarization time gradient was greatest at sites around the pacing electrode varying from 13.1+/-2.3 ms to 25.5+/-3.8 ms; 4) more negative left ventricular potentials at the peak of the body surface T wave (-4.9+/-0.8 vs -2.2+/-0.4 mV; p<0.05) but no altered right ventricular epicardial T-wave potentials. ARIs did not differ between groups. Right ventricular activation was delayed but was not associated with altered repolarization because of compensatory shortening of the right ventricular ARIs. CONCLUSION: CM-induced T-wave changes are caused by evolution of transmural repolarization gradients manifested during atrial stimulation that are maximal near the site of ventricular pacing.     

Correlation between refractory periods and activation-recovery intervals from electrograms: effects of rate and adrenergic interventions

Unipolar electrograms from ventricular epicardium in dogs were analyzed for the timing of local excitation and repolarization with computer assistance. The most rapid decrease in voltage in the QRS (dV/dt min) was used to determine local excitation time, and the maximum rate of voltage increase (dV/dt max) near the peak of the T wave was used to time local repolarization. The difference between dV/dt min and dV/dt max, the activation-recovery interval, is theoretically related to the net effect of the durations of the action potentials at that site. Paired data for refractory periods and activation-recovery intervals obtained from the same electrodes during fixed activation orders were obtained before and during repolarization changes induced by changes in cycle length, infusion of norepinephrine, and cardiac sympathetic nerve stimulation. Correlation coefficients were close to 1.00 and standard errors were 2.0 to 4.3 msec for changes at individual sites. Pooling of data from multiple sites increased standard errors and reduced correlation coefficients. Results provide quantification of errors in the use of unipolar electrograms to time local repolarization changes induced by variations in rate and adrenergic tone. They should increase the practical usefulness of the unipolar electrogram as a tool for assessing the time course and spatial distribution of repolarization changes.     

Dispersion of repolarization in canine ventricle and the electrocardiographic T wave: Tp-e interval does not reflect transmural dispersion

BACKGROUND: The concept that the interval between the peak (T(peak)) and the end (T(end)) of the T wave (T(p-e)) is a measure of transmural dispersion of repolarization time is widely accepted but has not been tested rigorously by transmural mapping of the intact heart. OBJECTIVES: The purpose of this study was to test the relationship of T(p-e) to transmural dispersion of repolarization by correlating local repolarization times at endocardial, midmural, and epicardial sites in the left and right ventricles with the T wave of the ECG. METHODS: Local activation times, activation-recovery intervals, and repolarization times were measured at 98 epicardial sites and up to 120 midmural and endocardial sites in eight open-chest dogs. In four of the dogs, long-term cardiac memory was induced by 3 weeks of ventricular pacing at 130 bpm because previous data suggest that, in this setting, delayed epicardial repolarization increases transmural dispersion. The other four dogs were sham operated. RESULTS: In sham dogs, T(p-e) was 41 +/- 2.2 ms (X +/- SEM), whereas the transmural dispersion of repolarization time was 2.7 +/- 4.2 ms (not significant between endocardium and epicardium). Cardiac memory was associated with evolution of a transmural gradient of 14.5 +/- 1.9 ms (P <.02), with epicardium repolarizing later than endocardium. The corresponding T(p-e) was 43 +/- 2.3 ms (not different from sham). In combined sham and memory dogs, T(p-e) intervals did not correlate with transmural dispersion of repolarization times. In contrast, dispersion of repolarization of the whole heart (measured as the difference between the earliest and the latest moment of repolarization from all left and right ventricular, endocardial, intramural, and epicardial recording sites) did correlate with T(p-e) (P <.0005, r = 0.98), although the latter underestimated total repolarization time by approximately 35%. The explanation for this finding is that parts of the heart fully repolarize before the moment of T(peak). CONCLUSION: T(p-e) does not correlate with transmural dispersion of repolarization but is an index of total dispersion of repolarization.     

Ventricular intramural and epicardial potential distributions during ventricular activation and repolarization in the intact dog.

Ventricular intramural and epicardial potential distributions were measured during normal excitation and repolarization in intact dogs. Potential distributions were chosen because they can be unambiguously measured, are useful in understanding the shapes of wave forms at many specific sites, and provide a direct measure of repolarization. Unipolar wave forms were recorded from intramural and epicardial electrodes and converted into potential distributions. Well-known shapes of wave forms recorded at the inner and outer layers of the ventricles as well as peak-to-peak voltages were shown by the potential distributions to be determined primarily by superposition effects of distant excitation waves. These effects were most prominent before epicardial breakthrough and then receded during the last half of the QRS complex. However, the potential distributions became more complex as excitation waves merged, collided, and terminated. During terminal depolarization, there were scattered positive repolarization potentials intramurally. Normal repolarization was characterized by positive potentials over the ventricular epicardium while there were changes intramurally and on the atrium. Throughout the T wave, there was a predominant transmural unidirectional gradient with the inner wall being more negative than the outer wall. This finding confirms that the sequence of repolarization is from the epicardium to the endocardium with the middle layers having an intermediate time.     

In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine.

OBJECTIVES/BACKGROUND: Previous in vitro studies have suggested full repolarization of the epicardium coincides with the peak of the T wave (T(peak)) and that of the M cells coincides with the end of the T wave (T(end)). However, in vivo validation of the theory is lacking. METHODS: Monophasic action potentials (MAPs) were recorded using the CARTO mapping system from 51 +/- 10 epicardial sites and 64 +/- 9 endocardial sites of the left ventricle in 10 pigs and from 41 +/- 4 epicardial sites and 53 +/- 2 endocardial sites of the right ventricle in two of the 10 pigs. End of repolarization (EOR) times over the epicardium (EOR(epi)), endocardium (EOR(endo)), and over both (EOR(total)) were obtained. QT(peak) and QT(end) intervals were measured from simultaneously recorded 12-lead ECG. RESULTS: Minimal and maximal EOR(total) were observed in the left ventricle in all pigs. Minimal EOR(total) was on the epicardium in five pigs, and maximal EOR(total) was on the endocardium in nine pigs. Minimal, mean, and maximal QT(peak) intervals all were significantly smaller than maximal EOR(epi) (322 +/- 23 ms, P <.01). No significant difference was found between maximal QT(end) interval (338 +/- 30 ms) and maximal EOR(endo) (339 +/- 24 ms, difference = 1 +/- 19 ms, P =.92), between maximal QT(end) interval and maximal EOR(total) (341 +/- 24 ms, difference = 2 +/- 18 ms, P =.69), or between minimal QT(peak) interval (283 +/- 28 ms) and minimal EOR(total) (282 +/- 20 ms, difference = 0 +/- 15 ms, P =.95). CONCLUSIONS: In in vivo pig models, T(peak) does not coincide with full repolarization of the epicardium but coincides well with the earliest EOR, whereas the T(end) corresponds with the latest EOR. These findings suggest that not only the transmural gradients but also the apicobasal repolarization gradients contribute to genesis of the T wave.     

The effects of renovascular hypertension on repolarization of ventricular epicardium

BACKGROUND AND OBJECTIVE:

Alterations in the recovery sequence of hypertrophied myocardium favour the development of cardiac arrhythmias. The aim of the present study was to investigate apex-to-base and interventricular heterogeneities in the duration of epicardial ventricular repolarization in rats with renovascular hypertension.

METHOD:

Renovascular hypertension was induced in six Wistar rats by constricting the left renal artery for one month. Six sham-operated Wistar rats served as normotensive controls. Epicardial mapping was performed using 32 unipolar leads distributed over the apex and base of the heart ventricles under sinus rhythm. Activation-recovery intervals (ARIs) were calculated from electrograms.

RESULTS:

The ratio of left ventricular weight to body weight was increased in hypertensive rats compared with controls. In control rats, ARIs at the base of both ventricles were shorter than those at the apex. In hypertrophied hearts, ARIs were prolonged on both the left and right ventricular epicardium. Heterogeneous prolongation was observed via reduced apex-to-base differences in ARIs and increased interventricular differences, with a trend toward increasing dispersion of ARIs. In rats with renovascular hypertension, nonuniform prolongation of epicardial ARIs on both ventricles and the changes in the ARI distribution resulted in a reduction of the repolarization time gradient between the ventricles.

CONCLUSION:

Nonuniformly prolonged ARIs across the ventricular epicardium and the interventricular electrical inhomogeneity in rats with renovascular hypertension should be considered when interpreting the T wave alterations together with the reduction of the transmural and apex-to-base repolarization gradients.     

Doxorubicin-induced Changes of Ventricular Repolarization Heterogeneity: Results of a Chronic Rat Study

Anthracycline chemotherapy produces cardiac repolarization abnormalities and arrhythmias because of cardiac toxicity of drugs. Ventricular arrhythmogenesis is attributable to increase in repolarization heterogeneity that is characterized by spatial dispersion of repolarization. The purpose of this work was to study the delayed effects of doxorubicin, the most frequently used anthracycline, on repolarization heterogeneity of the ventricular epicardium. Doxorubicin was administered to rats in a cumulative dose of 15?mg/kg (six equal intraperitoneal injections over a period of 2?weeks). Six weeks after the last injection, electrophysiological mapping of the ventricular epicardium was performed by sequential superimposition of a 64-electrode array on the left ventricular base, left ventricular apex, right ventricular base, and right ventricular apex. Activation?Crecovery intervals (ARIs) were measured. In doxorubicin-treated rats, ARIs were inhomogeneously prolonged, the overall ARI dispersion and local ARI dispersions were increased, and the interregional differences in ARI dispersion were decreased. These data demonstrate that doxorubicin-induced inhomogeneous prolongation of repolarization of the ventricular epicardium results in increasing heterogeneity of ventricular repolarization because of increasing intraregional heterogeneity while interregional differences are lost. Repolarization of the right ventricle is more sensitive to doxorubicin than that of the left one.     

Alteration of Ventricular Fibrillation by Propranolol and Isoproterenol Detected by Epicardial Mapping with 506 Electrodes

Adrenergic Effects on VF. Introduction: We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation. Methods and Results: We used a 528-channel mapping system to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fibrillation. A plaque of 506 (22 × 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the anterior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg/kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 μg/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activation front excited 40%± 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation alter propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control. Conclusions: Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.     

Epicardial and endocardial activation in patients with endocardial cushion defect

Epicardial and left ventricular endocardial activation were assessed in 5 patients (aged 4 months to 9.5 years) with endocardial cushion defect (ECD) during surgical repair. Epicardial activation was recorded from 40 to 47 sites over the epicardium; left ventricular endocardial activation was measured at 3 sites immediately after institution of cardiopulmonary bypass. Compared with the reported activation sequence in normal hearts, the pattern of excitation in hearts of patients with ECD was abnormal; epicardial excitation began at the left ventricular diaphragmatic surface and spread laterally and anteriorly over the anterobasal left ventricle. It then merged with right ventricular wavefronts ending along the right ventricular anterior atrioventricular groove and outflow tract. Left ventricular endocardial activation also occurred earliest in the diaphragmatic segment of the left ventricle with later wavefronts recorded laterally and anteriorly. This study demonstrates, for the first time in human subjects, correlation between left ventricular epicardial and endocardial activation in patients with ECD. The data indicate that earliest endocardial and epicardial activation occurs at the left ventricular diaphragmatic segments of the heart, and are consistent with the known posterior and inferior displacement of the specialized atrioventricular conduction system in patients with ECD.     

Epicardial activation in human left anterior fascicular block.

Four patients with coronary artery disease and chronic marked left axis deviation, defined as a frontal QRS axis more negative than -45 degrees, were studied with epicardial mapping during coronary bypass surgery. All patients had normal right ventricular and inferior left ventricular epicardial breakthrough sites and activation sequence. Normal breakthrough in the basal anterolateral left ventricular epicardium was absent in all four patients. Two patients had breakthrough in the apical region of the anterolateral left ventricle. In the other two this region was activated from wave fronts emerging in the right ventricle and inferior left ventricle. The latest site of left ventricular activation was the basal segment of the anterolateral wall, a site never found to be the latest activated in our previously studied patients without conduction defects. This site was activated during or slightly after the terminal portion of the QRS complex. It is concluded that marked left axis deviation in patients with coronary artery disease reflects delayed activation of the basal anterolateral left ventricle, and is consistent with the presence of block or delay in the anterior "fascicle" of the left bundle branch.     

Ventricular activation process in minipigs.

Because the form of QRS from the body surface of pigs is different from that of carnivores or ungulates, and because that form is dependent upon pathways of ventricular activation, this study was designed to study pathways of ven tricular activation in pigs. Twelve pigs were anesthetized and right or left hemithoracotomies were performed to expose the heart. Contiguous bipolar electrograms were recorded from button electrodes on the epicardium and from both faces of the interventicular septum, and from multipolar plunge electrodes introduced into the intramural regions of both ventricles. Electrograms were recorded simultaneous with the Z-axis ECG at 625 mm/sec paper speed on a photographic oscillograph. Times of arrival of waves of activation at numerous points in the ventricle were referenced to the peak of the R-wave in the Z-axis ECG. During the initial 10 msec of QRS, the apical-third of the interventricular septum is activated from left to right. During the next 40 msec of QRS, waves of activation originating at the cranial portion of the right ventricle and the caudal portion of the left ventricle engulf the epicardium toward the interventricular septum and slightly in an apico-basilar direction. Activity begins slightly earlier at the caudal aspect of the left ventricular free-wall and terminates on the pulmonary conus region. During the terminal 30 msec of QRS, the basilar third of the interventricular septum is activated in a general apico-basilar direction. Through regions of either right or left ventricular free-walls was a general endocardial to epicardial activation observed. These pathways of ventricular activation may be explained by the rather complete penetration of Purkinje fibers through both ventricular free-walls in a manner similar to that of ungulates but different from carnivores and primates.     

Two years old

In an attempt to elucidate the genesis of bifid T waves, we recorded transmembrane potentials of subepicardial ventricular muscle fibers simultaneously with a bipolar ventricular electrogram in isolated, perfused rabbit hearts, and the timing of the two apices of the T wave (aT₁, aT₂) was correlated with ventricular repolarization. The following results were obtained. (1) In seven of the nine hearts in which the repolarization process was mapped on the anterior and posterior surfaces of both ventricles, the 80% repolarization times of the left and the right ventricles were scattered around aT₁ and aT₂, respectively, and their average values closely corresponded to Q-aT₁ and Q-aT₂ intervals. This suggested that aT₁ and aT₂ depended on repolarization of the left and the right ventricles, respectively. (2) In one heart, aT₁ appeared to reflect repolarization of the posterior ventricular wall, and aT₂ that of the anterior wall. (3) In the remaining heart, aT₂ coincided with repolarization of the anterobasal portion of the right ventricle, and aT₁ that of the remaining portions of the ventricles. Even when ventricular repolarization was modified by low K⁺, low Ca²⁺ or procainamide perfusion, or by premature atrial stimulation, the close temporal correlation of the left and right ventricular repolarization with the two apices of the T wave was maintained. Selective cooling of the perfusate in either the left or the right coronary artery resulted in the production of bifid T waves in which aT₂ coincided with the delayed repolarization of the cooled ventricle. We conclude that either physiologically or pathologically delayed repolarization in certain portions of the ventricles is most likely the cause of bifid T waves.     

Induction of Ventricular Fibrillation by T Wave Shocks: Observations from Monophasic Action Potential Recordings

Introduction: Shocks given during the vulnerable period of cardiac repolarization may induce ventricular fibrillation (VF). However, the relationship of the vulnerable period and the monophasic action potential (MAP) has not yet been reported in humans. The purpose of this study was, therefore, to determine how the monophasic action potential recorded from the right ventricle correlates with inducibility of VF using T wave shocks during ventricular pacing.Methods: Eleven patients undergoing implantable cardioverter defibrillator (ICD) implantation had a MAP catheter positioned in the right ventricle (RV). The local monophasic action potential duration at 90% repolarization (MAP90) duration was measured during pacing at 400 ms. VF induction was attempted by pacing at 400 ms for 10 cycles and then giving a 1.0 joule monophasic T wave shock at varying coupling intervals (CI) to the last paced stimulus. The maximum and minimum CI that induced VF were determined and mapped in relation to the MAP90 recording.Results: The average paced MAP duration was 275 ± 20ms. The minimum and maximum CI to induce VF were 255 ± 24ms and 325 ± 36ms respectively. This ranged from 93% to 118% of the MAP90 duration but because of delay in conduction time to the MAP catheter, shocks that induced ventricular fibrillation occurred between 74% and 99% of local repolarization time.Conclusion: VF is inducible with low energy T wave shocks falling during the last 25% of the right ventricular MAP90 recording. This corresponds with VF initiation during phase III repolarization.     

Cellular Basis for Complex T Waves and Arrhythmic Activity Following Combined IKr and IKs Block

INTRODUCTION: A growing number of cardiomyopathies have been shown to result in a reduction in both I(Kr) and I(Ks) yet little is known about the electrophysiologic and ECG characteristics of combined I(Kr) and I(Ks) block. METHODS AND RESULTS: To address this gap in our knowledge, transmembrane action potentials (APs) from epicardial, M, and endocardial cells were recorded simultaneously, together with a transmural ECG from arterially perfused canine left ventricular wedge preparations exposed to combined I(Kr) (d-sotalol; 100 micromol/L) and I(Ks) (chromanol 293B; 30 to 60 micromol/L) block. Under baseline conditions, the T wave was typically upright; epicardium repolarized first, coinciding with the peak of the T wave, and the M cells repolarized last, coinciding with the end of the T wave (T(end)). Complex (inverted, biphasic, and triphasic) T waves developed following combined I(Kr) and I(Ks) block. M and epicardial APs prolonged dramatically, so that the endocardial AP was now the earliest to repolarize, coinciding with the first nadir of the complex T wave. In the case of biphasic/triphasic or inverted T waves, Tend coincided with repolarization of either M or epicardial cells, whichever was the last to repolarize. QT intervals prolonged from 286+/-13 msec up to 744+/-148 msec and transmural dispersion of repolarization (TDR) increased from 33+/-10 msec up to 244+/-71 msec. Early afterdepolarizations (EADs) developed in M and epicardial cells, evoking extrasystoles that precipitated polymorphic ventricular tachycardia. Acceleration-induced EADs and T wave alternans also were observed. CONCLUSION: Combined I(Kr) and I(Ks) block gives rise to inverted, biphasic, and triphasic T wave morphologies, a dramatic increase in TDR, and a high incidence of EADs. The diversity of T wave morphologies derives from a preferential AP prolongation of different transmural layers leading to variation in the predominance of voltage gradients on either side of the M cell region. Our study provides direct evidence linking EADs that arise in ventricular epicardial and M cells to the triggered beats that precipitate polymorphic ventricular tachycardia. Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG.     

Nonuniform epicardial activation and repolarization properties of in vivo canine pulmonary conus

The relation between nonuniform epicardial activation and ventricular repolarization properties was studied in 14 pentobarbital anesthetized dogs and with a computer model. In 11 dogs, isochrone maps of epicardial activation sequence were constructed from electrograms recorded from the pulmonary conus with 64 electrodes on an 8 X 8 grid with 2-mm electrode separation. The heart was paced from multiple sites on the periphery of the array. Uniformity of epicardial activation was estimated from activation times at test sites and their eight neighboring sites. Acceleration shortened and deceleration prolonged refractory periods. The locations of acceleration and deceleration sites of activation differed during drives from various sites, and differences in uniformity of activation during pairs of drives were correlated to differences in refractory periods (r = 0.76, range 0.59-0.93). In three additional experiments, transmural activation sequence maps were constructed from electrograms recorded from needle-mounted electrodes placed upstream and downstream to epicardial activation delays. Activation proceeded from epicardium to endocardium upstream to the delays and from endocardium to epicardium downstream to the delays. A computer simulation of two-dimensional action potential propagation based on the Beeler-Reuter myocardial membrane model provided insights to the mechanism for the results of the animal experiments. The two-dimensional sheet modeled the transmural anisotropic histology of the canine pulmonary conus and corresponded to previous reports and histology of specimens from five experiments. Simulated activation patterns were similar to those found in the experimental animals. In addition, action potentials were electronically prolonged at sites of deceleration and shortened at sites of acceleration, results comparable to the animal experiments. Our findings demonstrate that the location of areas of nonuniform epicardial activation is dependent on drive site and that nonuniform activation electronically modulates repolarization properties. Therefore it seems likely that the site of origin of ectopic ventricular complexes, especially in ischemic myocardium where activation is nonuniform, could be an important determinant of whether ectopic activity initiates sustained tachyarrhythmias.     

Impact of left ventricular epicardial and biventricular pacing on ventricular repolarization in normal-heart individuals and patients with congestive heart failure.

AIMS: Malignant ventricular arrhythmias can arise in a subset of congestive heart failure (CHF) patients after they undergo cardiac resynchronization therapy (CRT), thus counteracting the haemodynamic benefits typically associated with biventricular pacing. This study seeks to assess whether alteration of the ventricular transmural repolarization and conduction due to reversal of the depolarization sequence during epicardial or biventricular pacing facilitate the development of ventricular arrhythmias. METHODS AND RESULTS: ECGs and monophasic action potential (MAP) were recorded during programmed stimulation from right ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or both (biventricular, Bi-V) in 15 individuals without structural heart diseases. In patients with severe CHF and CRT (n=21), ECGs were collected during RV-Endo, LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT, and T(peak)-T(end) intervals on ECGs at different pacing sites were measured and compared. In subjects with or without structural heart disease, compared with RV-Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+/-61.97 ms with LV-Epi, 325.86+/-59.69 ms with Bi-V vs. 286.14+/-38.68 ms with RV-Endo in CHF individuals, P<0.0001) or T(peak)-T(end) interval (121.55+/-19.88 ms with LV-Epi, 117.71+/-42.63 ms with Bi-V vs. 102.28+/-12.62 ms with RV-Endo in normal-heart subjects, P<0.0001; 199.70+/-62.44 ms with LV-Epi, 184.89+/-74.08 ms with Bi-V vs. 146.41+/-31.06 ms with RV-Endo in CHF patients, P<0.0001), in addition to prolonged myocardial repolarization time and delayed endocardial activation. During follow-up, sudden death and arrhythmia storm occurred in two CHF patients after CRT. CONCLUSION: Epicardial and biventricular pacing prolong the time and increase the dispersion of myocardial repolarization and delay the transmural conduction. All of these should be considered as potential arrhythmogenic factors in CHF patients who receive CRT.     

Ventricular repolarization sequences on the epicardium and endocardium. Monophasic action potential mapping in healthy pigs

To investigate repolarization sequence, monophasic action potentials were recorded from a mean of 153 ± 54 left and right ventricular epicardial and endocardial sites in 10 pigs using the CARTO mapping system (Biosense Webster, Waterloo, Belgium). The activation time and end-of-repolarization (EOR) time were measured and 3-dimensional maps of activation and repolarization sequences constructed. RESULTS: In 8 of 9 pigs, both the activation and EOR times appeared first in the septum and last in the latero-basal areas on the endocardium, not on the epicardium. The EOR followed the activation sequence, both on the epicardium (in 8/9 pigs) and endocardium (in 8/8 pigs). The maximal EOR differences were 84 ± 20 ms, whereas the local EOR differences between paired sites against each other on the left ventricular epicardium and endocardium were 11 ± 9 ms in the apex and 12 ± 12 ms in the anterior wall. CONCLUSION: The EOR follows the activation sequence both on the epicardium and endocardium. The apico-basal gradients are predominant repolarization gradients, as compared with the epicardial-endocardial gradients.     

Quantitative analysis of systolic function of the right ventricule by Doppler echocardiography

The recording of the velocity of tricuspid valve regurgitation by continuous wave Doppler enables the calculation of the instantaneous systolic pressure gradient between the right ventricle and right atrium. As right atrial pressure is relatively constant, the rate of acceleration of the regurgitant jet reflects the quality of the rise in pressure in the right ventricle in early diastole, and therefore right ventricular contractility. The authors studied 3 Doppler parameters of the rate of velocity increase of the tricuspid regurgitation; the maximum rate of acceleration (dV/dt max), the maximum derivative of the pressure (dP/dt max) and the mean rate of increase in pressure (T). The interobserver variability of these indices is low (r greater than 0.96); reproducibility is good in patients with sinus rhythm but mediocre in atrial fibrillation. The comparison of the Doppler indices with the right ventricular isotopic fraction in 26 patients with tricuspid regurgitation showed a good correlation (dV/dt max, r = 0.79, p less than 0.0001; dP/dt max, r = 0.69, p less than 0.0001; T, r = 0.60, p = 0.0012). These results show that right ventricular systolic function can be evaluated by continuous wave cardiac Doppler by recording the spectral envelope of tricuspid regurgitation.