Effect of coronary angioplasty on precordial QT dispersion

Dispersion of the QT interval is a measure of inhomogeneity of ventricular repolarization. Because ischemia is associated with regional abnormalities of conduction and repolarization, we hypothesized that the surface electrocardiographic interval dispersion would increase in patients with symptomatic coronary artery disease in the absence of myocardial infarction and that successful revascularization would reduce QT interval dispersion. Thirty-seven consecutive patients with ischemia due to 1-vessel coronary artery disease without prior myocardial infarction who underwent percutaneous transluminal coronary angioplasty (PTCA) were evaluated. Standard 12-lead electrocardiograms were performed 24 hours before, 24 hours after, and late (>2 months) after PTCA. Precordial QT interval dispersions were determined from differences in the maximum and minimum corrected QT intervals. Mean QT interval dispersion before PTCA was 60 +/- 9 ms, immediately after PTCA 23 +/- 14 ms (p <0.001), and late after PTCA 29 +/- 18 ms (p <0.001 vs before PTCA). The shortest precordial QT interval increased immediately after PTCA (367 +/- 40 vs 391 +/- 39 ms; p <0.02) and then remained stable late after PTCA (376 +/- 36 ms, p = NS vs immediately after PTCA). Symptomatic recurrent ischemia in 8 patients with documented restenosis increased QT interval dispersion (56 +/- 15 ms [p <0.01] vs 25 +/- 14 ms immediately after PTCA), which decreased again after successful repeat PTCA (22 +/- 13 ms [p <0.01] vs before the second PTCA). QT interval dispersion decreases after successful coronary artery revascularization and increases with restenosis. Therefore, QT interval dispersion may be a marker of recurrent ischemia due to restenosis after PTCA.     

The practice of medical and surgical synovectomy: a UK survey

BACKGROUND: QT dispersion (QTd = QTmax-QTmin) measured as interlead variability of QT interval reflects the spatial inhomogeneity of ventricular repolarization times, and increased QTd may provide a substrate for malignant ventricular arrhythmias. Ischemia is associated with regional abnormalities of conduction and repolarization. HYPOTHESIS: This study aimed to investigate the effect of acute ischemia on QTd during successful percutaneous transluminal coronary angioplasty (PTCA). METHODS: Forty-three patients (10 women, 33 men, mean age 56 years) were enrolled in the study. Electrocardiogram (ECG) recordings were taken before PTCA and during balloon inflation period. QT maximum (QTmax), QT minimum (QTmin), and QTd (QTmax-QTmin) values were calculated from the surface ECG. RESULTS: There was no difference among QTmax values (p = 0.6). Mean QTmin during balloon inflation was lower than before PTCA (368 +/- 45 vs. 380 +/- 41 ms, p = 0.002). The difference between QTd values before and during balloon inflation was statistically important (65 +/- 9 vs. 76 +/- 10 ms, p = 0.001). This difference is caused by a decrease in QTmin during balloon inflation. CONCLUSION: Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd value, and this increment is the result of a decrease in QTmin interval. Therefore, QTd may be a marker of reversible myocardial ischemia.     

Spurious associations in unreplicated selected lines

INTRODUCTION: Shocks during the vulnerable period of the cardiac cycle induce ventricular fibrillation (VF) if their strength is above the VF threshold (VFT) and less than the upper limit of vulnerability (ULV). However, the range of shock strengths that constitutes the vulnerable zone and the corresponding range of coupling intervals have not been defined in humans. The ULV has been proposed as a measure of defibrillation because it correlates with the defibrillation threshold (DFT), but the optimal coupling interval for identifying it is unknown. METHODS AND RESULTS: We studied 14 patients at implants of transvenous cardioverter defibrillators. The DFT was defined as the weakest shock that defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock that did not induce VF when given at 0, 20, and 40 msec before the peak of the T wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of 500 msec. The VFT was defined as the weakest shock that induced VF at any of the same four intervals. To identify the upper and lower boundaries of the vulnerable zone, we determined the shock strengths required to induce VF at all four intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT was 72 +/- 42 V, and the ULV was 411 +/- V. In all patients, a shock strength of 200 V exceeded the VFT and was less than the ULV. The coupling interval at the ULV was 19+/- 11 msec shorter than the coupling interval at the VFT (P < 0.001). The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at the VFT. A 20-msec error in the interval at which the ULV was measured could have resulted in underestimating it by a maximum of 95 +/- 31 V. The weakest shock that did not induce VF was greater for the shortest interval tested than for the longest interval at both the upper boundary (356 +/- 108 V vs 280 +/- 78 V; P < 0.01) and lower boundary (136 +/- 68 msec vs 100 +/- 65 msec; P < 0.05). CONCLUSIONS: The human vulnerable zone is not symmetric with respect to a single coupling interval, but slants from the upper left to lower right. Small differences in the coupling interval at which the ULV is determined or use of the coupling interval at the VFT to determine the ULV may result in significant variations in its measured value. An efficient strategy for inducing VF would begin by delivering a 200-V shock at a coupling interval 10 msec before the peak of the T wave.     

Modulated dispersion explains changes in arrhythmia vulnerability during premature stimulation of the heart

BACKGROUND: Previously, we have shown that a premature stimulus can significantly modulate spatial gradients of ventricular repolarization (ie, modulated dispersion), which result from heterogeneous electrophysiological properties between cells. The role modulated dispersion may play in determining electrical instability in the heart is unknown. METHODS AND RESULTS: To determine if premature stimulus-induced changes in repolarization are a mechanism that governs susceptibility to cardiac arrhythmias, optical action potentials were recorded simultaneously from 128 ventricular sites (1 cm2) in 8 Langendorff-perfused guinea pig hearts. After baseline pacing (S1), a single premature stimulus (S2) was introduced over a range of S1S2 coupling intervals. Arrhythmia vulnerability after each premature stimulus was determined by measurement of a modified ventricular fibrillation threshold (VFT) during the T wave of each S2 beat (ie, S2-VFT). As the S1S2 interval was shortened to an intermediate value, spatial gradients of repolarization and vulnerability to fibrillation decreased by 51+/-9% (mean+/-SEM) and 73+/-45%, respectively, compared with baseline levels. As the S1S2 interval was further shortened, repolarization gradients increased above baseline levels by 54+/-30%, which was paralleled by a corresponding increase (37+/-8%) in vulnerability. CONCLUSIONS: These data demonstrate that modulation of repolarization gradients by a single premature stimulus significantly influences vulnerability to ventricular fibrillation. This may represent a novel mechanism for the formation of arrhythmogenic substrates during premature stimulation of the heart.     

The effects of a left bundle-branch block on ventricular repolarization dispersion

Patients with left bundle-branch block (LBBB) often present electrocardiographic abnormalities and, therefore, are excluded from studies concerning electrocardiographic evaluation of ventricular repolarization. The aim of the study was to assess whether LBBB could influence dispersion of ventricular repolarization. Surface electrocardiograms of 16 patients (9 males and 7 females, mean age 58 +/- 14 years) with episodes of intermittent LBBB were analyzed. Six patients were affected by coronary artery disease, 6 by hypertensive cardiomyopathy and 4 by dilated cardiomyopathy. Maximal QT and JT corrected intervals, QT and JT dispersion, and QT and JT dispersion corrected for heart rate, were obtained before and after LBBB. We observed a significant prolongation of maximal QT (412 +/- 29 vs 433 +/- 25 ms; p < 0.05), and of maximal corrected QT (457 +/- 37 vs 497 +/- 56 ms; p < 0.05) after LBBB. Maximal JT interval, also corrected for heart rate, did not show any significant modification after LBBB. Moreover, we did not observe any significant difference in electrocardiographic parameters of dispersion of repolarization. Our results seem to indicate that LBBB did not alter significantly dispersion of ventricular repolarization. QT dispersion is considered an important marker of risk for incidence of ventricular arrhythmias. If our results will be confirmed in larger groups of patients, analysis of QT dispersion could be extended even to patients with LBBB.     

Influence of polarity reversal on defibrillation success with biphasic shocks and a transvenous/subcutaneous defibrillator system in a porcine animal model

Clinical studies show that polarity reversal affects defibrillation success in transvenous monophasic defibrillators. Current devices use biphasic shocks for defibrillation. We investigated in a porcine animal model whether polarity reversal influences defibrillation success with biphasic shocks. In nine anesthetized, ventilated pigs, the defibrillation efficacy of biphasic shocks (14.3 ms and 10.8 ms pulse duration) with "initial polarity" (IP, distal electrode = cathode) and "reversed polarity" (RP, distal electrode = anode) delivered via a transvenous/subcutaneous lead system was compared. Voltage and current of each defibrillating pulse were recorded on an oscilloscope and impedance calculated as voltage divided by current. Cumulative defibrillation success was significantly higher for RP than for IP for both pulse durations (55% vs 44%, P = 0.019) for 14.3 ms (57% vs 45%, P < 0.05) and insignificantly higher for 10.8 ms (52% vs 42%, P = ns). Impedance was significantly lower with RP at the trailing edge of pulse 1 (IP: 44 +/- 8.4 vs RP: 37 +/- 9.3 with 14.3 ms, P < 0.001 and IP: 44 +/- 6.2 vs RP: 41 +/- 7.6 omega with 10.8 ms, P < 0.001) and the leading edge of pulse 2 (IP: 37 +/- 5 vs RP: 35 +/- 4.2 omega with 14.3 ms, P = 0.05 and IP: 37.5 +/- 3.7 vs RP: 36 +/- 5 omega with 10.8 ms, P = 0.02). In conclusion, in this animal model, internal defibrillation using the distal coil as anode results in higher defibrillation efficacy than using the distal coil as cathode. Calculated impedances show different courses throughout the shock pulses suggesting differences in current flow during the shock.     

Clinical shock tolerability and effect of different right atrial electrode locations on efficacy of low energy human transvenous atrial defibrillation using an implantable lead system

OBJECTIVES: The objectives of this study were 1) to evaluate the effect of different right atrial electrode locations on the efficacy of low energy transvenous defibrillation with an implantable lead system; and 2) to qualitate and quantify the discomfort from atrial defibrillation shocks delivered by a clinically relevant method. BACKGROUND: Biatrial shocks result in the lowest thresholds for transvenous atrial defibrillation, but the optimal right atrial and coronary sinus electrode locations for defibrillation efficacy in humans have not been defined. METHODS: Twenty-eight patients (17 men, 11 women) with chronic atrial fibrillation (AF) (lasting > or = 1 month) were studied. Transvenous atrial defibrillation was performed by delivering R wave-synchronized biphasic shocks with incremental shock levels (from 180 to 400 V in steps of 40 V). Different electrode location combinations were used and tested randomly: the anterolateral, inferomedial right atrium or high right atrial appendage to the distal coronary sinus. Defibrillation thresholds were defined in duplicate by using the step-up protocol. Pain perception of shock delivery was assessed by using a purpose-designed questionnaire; sedation was given when the shock level was unacceptable (tolerability threshold). RESULTS: Sinus rhythm was restored in 26 of 28 patients by using at least one of the right atrial electrode locations tested. The conversion rate with the anterolateral right atrial location (21 [81%] of 26) was higher than that with the inferomedial right atrial location (8 [50%] of 16, p < 0.05) but similar to that with the high right atrial appendage location (16 [89%] of 18, p > 0.05). The mean defibrillation thresholds for the high right atrial appendage, anterolateral right atrium and inferomedial right atrium were all significantly different with respect to energy (3.9 +/- 1.8 J vs. 4.6 +/- 1.8 J vs. 6.0 +/- 1.7 J, respectively, p < 0.05) and voltage (317 +/- 77 V vs. 348 +/- 70 V vs. 396 +/- 66 V, respectively, p < 0.05). Patients tolerated a mean of 3.4 +/- 2 shocks with a tolerability threshold of 255 +/- 60 V, 2.5 +/- 1.3 J. CONCLUSIONS: Low energy transvenous defibrillation with an implantable defibrillation lead system is an effective treatment for AF. Most patients can tolerate two to three shocks, and, when the starting shock level (180 V) is close to the defibrillation threshold, they can tolerate on average a shock level of 260 V without sedation. Electrodes should be positioned in the distal coronary sinus and in the high right atrial appendage to achieve the lowest defibrillation threshold, although other locations may be suitable for certain patients.     

Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443 +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74 vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24 +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs 40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.     

Effects of atrial defibrillation shocks on the ventricles in isolated sheep hearts

BACKGROUND: The effects of cardioversion of atrial fibrillation on the activation sequence of the ventricles have not been previously studied. In this study we examined the events in the ventricle that follow the application of atrial defibrillatory shocks. METHODS AND RESULTS: We used video imaging technology to study the sequence of activation on the surface of the ventricles in the Langendorff-perfused sheep heart. We recorded transmembrane potentials simultaneously from over 20000 sites on the epicardium before and after biphasic shocks applied by a programmable atrial defibrillator. The first epicardial activation after the shock depended on both the voltage and timing of the shock. During ventricular diastole shocks as low as 10 V produced ventricular excitation, although the time between the shock and the first epicardial activation (latency) was approximately 30 ms. As the shock voltage was increased to 120 V, latency decreased to zero and the entire epicardium was depolarized within 30 ms. For 120-V shocks delivered late in systole, the depolarization sequence produced by the shock was similar to the previous repolarization sequence. Shocks of 120 V applied 150 to 300 ms after the previous ventricular excitation induced ventricular fibrillation. Ventricular fibrillation was induced by multiple focal beats after the shock, which produced waves that propagated but broke down into reentry within regions of high repolarization gradients. CONCLUSIONS: These results demonstrate that atrial defibrillation shocks excite the ventricles even at low shock voltages. In addition, ventricular fibrillation can be induced by shocks given in the vulnerable period by producing focal patterns that break down into reentrant waves.     

Favorable effects of flecainide in transvenous internal cardioversion of atrial fibrillation

OBJECTIVES: The aim of the study was to evaluate the effects of intravenous (IV) flecainide on defibrillation energy requirements in patients treated with low-energy internal atrial cardioversion. BACKGROUND: Internal cardioversion of atrial fibrillation is becoming a more widely accepted therapy for acute episode termination and for implantable atrial defibrillators. METHODS: Twenty-four patients with atrial fibrillation (19 persistent, 5 paroxysmal) underwent elective transvenous cardioversion according to a step-up protocol. After successful conversion in a drug-free state, atrial fibrillation was induced by atrial pacing; IV flecainide (2 mg/kg) was administered and a second threshold was determined. In patients in whom cardioversion in a drug-free state failed notwithstanding a 400- to 550-V shock, a threshold determination was attempted after flecainide. RESULTS: Chronic persistent atrial fibrillation was converted in 13/19 (68%) patients at baseline and in 16/19 (84%) patients after flecainide. Paroxysmal atrial fibrillation was successfully cardioverted in all the patients. A favorable effect of flecainide was observed either in chronic persistent atrial fibrillation (13 patients) or in paroxysmal atrial fibrillation (5 patients) with significant reductions in energy requirements for effective defibrillation (persistent atrial fibrillation: 4.42+/-1.37 to 3.50+/-1.51 J, p < 0.005; paroxysmal atrial fibrillation: 1.68+/-0.29 to 0.84+/-0.26 J, p < 0.01). In 14 patients not requiring sedation, the favorable effects of flecainide on defibrillation threshold resulted in a significant reduction in the scores of shock-induced discomfort (3.71+/-0.83 vs. 4.29+/-0.61, p < 0.005). No ventricular proarrhythmia was observed for any shock. CONCLUSIONS: Intravenous flecainide reduces atrial defibrillation threshold in patients treated with low-energy internal atrial cardioversion. This reduction in threshold results in lower shock-induced discomfort. Additionally, flecainide may increase the procedure success rate in patients with chronic persistent atrial fibrillation.     

Effects of initial polarity on defibrillation threshold with biphasic pulses

BACKGROUND: Previous studies have shown that the polarity of epicardial patches significantly affects the defibrillation efficacy of monophasic shocks. However, whether this improvement can be extended to different pulsing methods and lead systems, such as biphasic shocks using endocardial defibrillating electrodes, is unknown. METHODS: Twenty consecutive patients undergoing testing and permanent implant using an Endotak lead system with a biphasic device were included in the study. In each patient the defibrillation threshold was determined delivering biphasic pulses with the distal coil as the cathode and the proximal coil as the anode during the positive phase and with the polarity reversed. The initial electrode polarity tested was chosen randomly. The defibrillation threshold was defined as the lowest pulse amplitude that effectively terminated ventricular fibrillation induced with 60-Hz alternating current. For each biphasic pulse peak voltage, pulse duration, resistance, and stored energy were recorded. RESULTS: Of the 20 patients, 12 (60%) had lower defibrillation threshold when the proximal coil was negative, whereas only 2 patients had a lower defibrillation threshold when the distal coil was negative. In four patients a subcutaneous patch would have been required if only the biphasic pulse with the distal coil as negative had been tested. The mean stored defibrillation threshold energy was lower with the configuration using the proximal coil as cathode (16.3 +/- 8.8 J vs 21.5 +/- 11 J; P < 0.01). CONCLUSION: Change in the initial polarity of biphasic shocks may influence defibrillation efficacy and should, therefore, be assessed in each patient to achieve a more satisfactory safety margin and minimize the use of more invasive lead configurations.     

Anti-verotoxin-neutralizing antibody in intravenous gammaglobulin preparations

BACKGROUND: A previous retrospective study by our group suggested that shocks timed to the upslope of the shocking lead electrogram improved defibrillation efficacy. The goal of this study was to prospectively determine whether defibrillation threshold could be reduced by use of an algorithm that timed shocks to the upslope of coarse ventricular fibrillation (test treatment) compared with shocks delivered asynchronously after 10 seconds of fibrillation (control treatment). METHODS AND RESULTS: Ten pigs were instrumented with a 3-lead system for internal defibrillation. Initial estimates of the energy required to achieve defibrillation E50 for both treatments were made by an up/down method. Subsequently, additional shocks at V50+/-10% and V50-20% were given for each treatment to obtain data points at higher and lower intensities. Probability-of-success curves were estimated for both treatments by the best-fit method. Energies required were significantly lower for the timed shocks than for the asynchronous shocks (P<0.00 1). E80 was reduced 15.5%, from 27.1+/-2.5 to 22.9+/-1.8 J (P<0.002). The width of the probability-of-success curve (E80-E20) for the test treatment was also significantly narrower than that for the control treatment (7.1+/-0.9 versus 10.8+/-1.7, P<0.01). Normalized curve width (E80-E20)/E50 was decreased from 51+/-5% of E50 for control shocks to 37+/-4% of E50 for synchronous shocks (P<0.02). CONCLUSIONS: In this model, defibrillation threshold is lower and more deterministic when shocks are timed to the upslope of the shocking lead electrogram. If a similar reduction is observed in humans, shock timing may lower defibrillation threshold and simplify programming of shock intensity.     

Ventricular fibrillation-induced intracellular Ca2+ overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]i overload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i overload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]i overload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.     

Low-energy endocardial defibrillation using dual, triple, and quadruple electrode systems

The feasibility of achieving both universal application of nonthoracotomy leads and low (< or = 15 J) defibrillation energy requirements by optimizing lead system configuration for use with low-output (<30 J) biphasic shock pulse generators was examined. Sixteen patients (mean age 62 +/- 8 years and mean left ventricular ejection fraction of 38 +/- 15%) were included in the study. All patients had either experienced syncope with induced ventricular tachycardia (n = 4) or had documented sustained ventricular tachycardia (n = 7) or ventricular fibrillation (n = 5). Defibrillation threshold testing was performed in 2 stages on different days in these patients. In the first stage, 2 defibrillation catheter electrodes were positioned in the right ventricle and superior vena cava with an axillary cutaneous patch. Fifteen-joule, 10- and 5-J biphasic shocks were delivered across 3 different electrode configurations-right ventricle to superior vena cava, right ventricle to axillary patch, right ventricle to a combination of superior vena cava and axillary patch. In the second stage, an 80-ml can electrode was added subcutaneously in a pectoral location to the previous leads. Configurations compared were the right ventricle to pectoral can, and right ventricle to an "array"-combining superior vena cava, can, and axillary patch leads. The defibrillation threshold was determined using a step-down method. In stage 1, mean defibrillation threshold for the right ventricle to axillary patch (12.7 +/- 5.9 J) and right ventricle to superior vena cava plus axillary patch (9.8 +/- 5.2 J) configurations was lower than the right ventricle to superior vena cava configuration (14.2 +/- 6.4 J, p <0.05). In stage 2, the defibrillation was higher for the right ventricle to pectoral can (9.2 +/- 5.1 J) configuration compared with the right ventricle to the array (5.6 +/- 3.6 J, p < or =0.05). The right ventricle to array had the lowest defibrillation threshold, whereas the right ventricle to pectoral can was the best dual electrode system. Low-energy endocardial defibrillation (< or =10 J) was feasible in 72% of tested patients with > 1 electrode configuration at 10 J, whereas only 53% of successful patients could be reverted at >1 electrode configuration at 5 J (p <0.05). Reduction in maximum pulse generator output to < or =25 J using these electrode configurations with bidirectional shocks is feasible and maintains an adequate safety margin.     

The effects of lidocaine on the vulnerable period during ventricular fibrillation

INTRODUCTION: It was postulated that a subthreshold defibrillation shock failed to halt ventricular fibrillation because the shock itself reinitiated ventricular fibrillation by falling into the vulnerable period of the wavefronts. Whether or not the timing of the vulnerable period is determined by the ventricular fibrillation cycle length is unknown. METHODS AND RESULTS: We determined the patterns of epicardial activation in ten dogs by computerized mapping techniques during unsuccessful defibrillation. Lidocaine was then given to prolong the ventricular fibrillation cycle length, and the computerized mapping studies were repeated. The results showed that lidocaine increased the ventricular fibrillation cycle length from 110 +/- 13 msec to 156 +/- 5 msec (P < 0.001). Among 55 episodes of unsuccessful defibrillation, the site of the earliest postshock activation occurred in the center of the mapped tissue 12 times at baseline and 14 times during lidocaine infusion. At electrodes that registered as postshock early sites, the preshock intervals clustered within a narrow range both before (58 +/- 14 msec) and during (101 +/- 18 msec, P < 0.001) lidocaine infusion. The correlation between the preshock intervals and the ventricular fibrillation cycle length was significant for these 26 sites (r = 0.87, P < 0.001). CONCLUSION: We conclude that a vulnerable period is present during ventricular fibrillation, and the timing of the vulnerable period is determined by the ventricular fibrillation cycle length.     

Amiodarone reduces transmural heterogeneity of repolarization in the human heart

OBJECTIVES: The present work was designed to test the effects of amiodarone therapy on action potential characteristics of the three cell types observed in human left ventricular preparations. BACKGROUND: The electrophysiologic basis for amiodarone's exceptional antiarrhythmic efficacy and low proarrhythmic profile remains unclear. METHODS: We used standard microelectrode techniques to investigate the effects of chronic amiodarone therapy on transmembrane activity of the three predominant cellular subtypes (epicardial, midmyocardial [M] and endocardial cells) spanning the human left ventricle in hearts explanted from normal, heart failure and amiodarone-treated heart failure patients. RESULTS: Tissues isolated from the ventricles of heart failure patients receiving chronic amiodarone therapy displayed M cell action potential duration (404+/-12 ms) significantly briefer (p < 0.05) than that recorded in tissues isolated from normal hearts (439+/-22 ms) or from heart failure patients not treated with amiodarone (449+/-18 ms). Endocardial cells from amiodarone-treated heart failure patients displayed longer (p < 0.05) action potential duration (363+/-10 ms) than endocardial cells isolated from normal hearts (330+/-6 ms). As a consequence, the heterogeneity of ventricular repolarization in tissues from patients treated with amiodarone was considerably smaller than in the two other groups, especially at long pacing cycle lengths. CONCLUSIONS: These findings may explain, at least in part, the reduction of ventricular repolarization dispersion and the lower incidence of torsade de pointes observed with chronic amiodarone therapy as compared with other class III agents.     

Dispersion of ventricular repolarization in left ventricular hypertrophy: influence of afterload and dofetilide

INTRODUCTION: Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts. METHODS AND RESULTS: Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49+/-4 days postsurgery in the working heart mode using a blood-buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50+/-7 mmHg) afterload and high afterload (97+/-12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42+/-8 msec) compared with control hearts (26+/-8 msec, P < 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P < 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31+/-9 msec) compared with control hearts (30+/-9 msec, P = NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60+/-39 msec) compared with control hearts (30+/-13 msec, P < 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was -18+/-21 msec in control hearts and 7+/-21 ms in hypertrophied hearts (P < 0.05). CONCLUSION: Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload-induced shortening of the APD. This effect may be due in part to altered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.     

Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure

Delivery of a strong electric shock to the heart remains the only effective therapy against ventricular fibrillation. Despite significant improvements in implantable cardioverter defibrillator (ICD) therapy, the fundamental mechanisms of defibrillation remain poorly understood. We have recently demonstrated that a monophasic defibrillation shock produces a highly nonuniform epicardial polarization pattern, referred to as a virtual electrode pattern (VEP). The VEP consists of large adjacent areas of strong positive and negative polarization. We sought to determine whether the VEP may be responsible for defibrillation failure by creating dispersion of postshock repolarization and reentry. Truncated exponential biphasic and monophasic shocks were delivered from a bipolar ICD lead in Langendorff-perfused rabbit hearts. Epicardial electrical activity was mapped during and after defibrillation shocks and shocks applied at the plateau phase of a normal action potential produced by ventricular pacing. A high-resolution fluorescence mapping system with 256 recording sites and a voltage-sensitive dye were used. Biphasic shocks with a weak second phase (<20% leading-edge voltage of the second phase with respect to the leading-edge voltage of the first phase) produced VEPs similar to monophasic shocks. Biphasic shocks with a strong second phase (>70%) produced VEPs of reversed polarity. Both of these waveforms resulted in extra beats and arrhythmias. However, biphasic waveforms with intermediate second-phase voltages (20% to 70% of first-phase voltage) produced no VEP, because of an asymmetric reversal of the first-phase polarization. Therefore, there was no substrate for postshock dispersion of repolarization. Shocks producing strong VEPs resulted in postshock reentrant arrhythmias via a mechanism of phase singularity. Points of phase singularity were created by the shock in the intersection of areas of positive, negative, and no polarization, which were set by the shock to excited, excitable, and refractory states, respectively. Shock-induced VEPs may reinduce arrhythmias via a phase-singularity mechanism. Strong shocks may overcome the preshock electrical activity and create phase singularities, regardless of the preshock phase distribution. Optimal defibrillation waveforms did not produce VEPs because of an asymmetric effect of phase reversal on membrane polarization.     

Effect of the addition of an abdominal hot can cardioverter/defibrillator pulse generator on the defibrillation energy requirements in a single-lead endocardial defibrillation system

AIMS: The effects of a cardioverter/defibrillator system with an electrically active generator can, applied without recourse to thoracotomy, have not been investigated in the abdominal position in humans. The purpose of this acute clinical study was to evaluate the defibrillation efficacy of an abdominally positioned hot can electrode in connection with a single lead endocardial defibrillation system. PATIENTS AND METHODS: Thirty consecutive patients undergoing implantation of a cardioverter/defibrillator or pulse generator replacement were enrolled in this study Each patient received an integrated, tripolar single-lead system. This was tested using an asymmetrical biphasic defibrillation waveform with constant energy delivery. Defibrillation energy, peak voltage, peak current and impedance were compared between two electrode configurations: (A) in this configuration the distal right ventricular coil was negative and the proximal coil positive; (B) in this configuration the distal right ventricular coil was negative and the proximal coil and the abdominal hot can (65 ccm), as common anode, were positive. Defibrillation threshold testing started at 15 J with stepwise energy reduction (10 J, 8 J, 5 J and 3 J) until defibrillation was ineffective. RESULTS: Compared to the single-lead configuration, the abdominal hot can configuration revealed at 17.5% reduction in defibrillation energy requirements (8.6 J +/- 4.3 J vs 10.43 J +/- 3.9 J; P = 0.041), a 15.7% reduction in peak voltage (308.6 V +/- 63 V vs 365.3 V +/- 68 V; P = 0.003), and a 21.6% reduction in impedance (41.1 omega +/- 6.3 omega vs 52.4 omega +/- 6.6 omega; P < 0.001). Peak current showed a significant increase during hot can testing of 8.2% (7.2 A +/- 1.8 A vs 7.8 A +/- 2.2 A; P = 0.16). CONCLUSION: An abdominally placed hot can pulse generator lowered defibrillation energy requirements in patients with an endocardial defibrillation lead system.     

Encircling overlapping multipulse shock waveforms for transthoracic defibrillation

OBJECTIVES: This study was performed to determine the efficacy of new encircling overlapping multipulse, multipathway waveforms for transthoracic defibrillation. BACKGROUND: Alternative waveforms for transthoracic defibrillation may improve shock success. METHODS: First, we determined the shock success achieved by three different waveforms at varying energies (18-150 J) in 21 mongrel dogs after short-duration ventricular fibrillation. The waveforms tested included the traditional damped sinusoidal waveform, a single pathway biphasic waveform, and a new encircling overlapping multipulse waveform delivered from six electrode pads oriented circumferentially. Second, in 11 swine we compared the efficacy of encircling overlapping multipulse shocks given from six electrode pads and three capacitors versus encircling overlapping shocks given from a device utilizing three electrodes and one capacitor. RESULTS: In the first experiment, the encircling overlapping waveform performed significantly better than biphasic and damped sinusoidal waveforms at lower energies. The shock success rate of the overlapping waveform (six pads) ranged from 67+/-4% (at 18-49 J energy) to 99+/-3% at > or = 150 J; at comparable energies biphasic waveform shock success ranged from 26+/-5% (p < 0.01 vs. encircling overlapping waveforms) to 99+/-5% (p = NS). Damped sinusoidal waveform shock success ranged from 4+/-1% (p < 0.01 vs. encircling overlapping waveform) to 73+/-9% (p = NS). In the second experiment the three electrode pads, one capacitor encircling waveform achieved shock success rates comparable with the six-pad, three-capacitor waveform; at 18-49 J, success rates were 45+/-15% versus 57+/-12%, respectively (p = NS). At 100 J, success rates for both were 100%. CONCLUSIONS: We conclude that encircling overlapping multipulse multipathway waveforms facilitate transthoracic defibrillation at low energies. These waveforms can be generated from a device that requires only three electrodes and one capacitor.