Lidocaine Increases the Proarrhythmic Effects of Monophasic but not Biphasic Shocks

INTRODUCTION: Lidocaine increases monophasic shock defibrillation energy requirement (DER) values but does not alter biphasic shock DER values. However, the mechanism of this drug/shock waveform interaction is unknown. It may be that lidocaine increases the proarrhythmic actions of monophasic shocks but not biphasic shocks. Thus, lidocaine may increase monophasic shock DER values by increasing myocardial vulnerability to shock-induced ventricular fibrillation. METHODS AND RESULTS: Area of myocardial vulnerability (AOV), defined by a two-dimensional grid according to shock strength (y-axis) and shock coupling interval (x-axis), was assessed for biphasic shocks (n = 11) and monophasic shocks (n = 13) in intact swine hearts. Shocks were randomly delivered during right ventricular pacing at 10 shock strengths (50 to 500 V) and five coupling intervals (160 to 240 msec). AOV was defined as the number of points within the test grid that induced ventricular fibrillation. AOV, upper limit of vulnerability (ULV), and DER values were determined at baseline and during systemic infusion of lidocaine (10 mg/kg/hour). Lidocaine increased AOV, ULV, and DER values by 35%, 23%, and 36%, respectively, for monophasic shocks. However, lidocaine did not alter AOV, ULV, or DER values for biphasic shocks. CONCLUSION: Lidocaine increases the AOV to monophasic shocks, which is directly related to changes in ULV and DER values. This implies that lidocaine increases the proarrhythmic activity of monophasic shocks but not biphasic shocks. This may explain why lidocaine increases monophasic shock DER values.     

Effects of lidocaine on relation between defibrillation threshold and upper limit of vulnerability in open-chest dogs.

BACKGROUND. The purpose of the present study was to test the effects of lidocaine on the relation between the defibrillation threshold and the upper limit of vulnerability. METHODS AND RESULTS. The shock strength associated with a 50% probability of successful defibrillation (DFT50) and the shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 11 open-chest dogs by using the delayed up-down method before and during lidocaine (seven dogs) or normal saline (four dogs) infusion. The ventricles were paced at a cycle length of 300 msec. Shocks of various strengths were then given via a patch-patch electrode configuration on the anterior and posterior surfaces of the ventricle to determine the ULV50. Once ventricular fibrillation was induced, shocks were given 15-20 seconds later via the same electrode configuration to determine the DFT50. Lidocaine infusion resulted in a serum level of 15 +/- 4 micrograms/ml. This was associated with a lengthening of the QT interval but not with the widening of the QRS complex. In all dogs, both the ULV50 and the DFT50 increased significantly when tested during lidocaine infusion. Mean ULV50 during lidocaine infusion was 496 +/- 70 V or 13.1 +/- 4.3 J, which were significantly higher than the baseline values of 333 +/- 67 V or 5.3 +/- 2.2 J (p less than 0.001 for both voltage and energy). Mean DFT50 during lidocaine infusion was 407 +/- 41 V or 8.7 +/- 1.7 J, which were significantly higher than the baseline values of 300 +/- 38 V and 4.4 +/- 1.1 J (p = 0.004 for voltage and p = 0.013 for energy). The r values between the ULV50 and the DFT50 were 0.79 (p = 0.037) for voltage and 0.80 (p = 0.030) for energy at baseline and 0.85 (p = 0.016) for voltage and 0.88 (p = 0.009) for energy during the lidocaine infusion. However, the increments of the ULV50 (163 +/- 88 V or 7.8 +/- 4.6 J) were significantly greater than the increments of the DFT50 (107 +/- 51 V or 4.4 +/- 1.9 J, p = 0.035 for voltage and p = 0.023 for energy). Normal saline infusion did not alter DFT50 or ULV50. CONCLUSIONS. Lidocaine infusion significantly increases both ULV50 and DFT50. These results are compatible with the upper limit of vulnerability hypothesis of defibrillation. However, the greater increase of the upper limit of vulnerability than the defibrillation threshold with lidocaine infusion indicates that other factors may also need to be considered to explain the results.     

心肌缺血对心室颤动的诱发和除颤效率的影响

近来埋藏式心律转复除颤器（ＩＣＤ）已成为抗心律失常药物治疗无效的高危病人的优先选择。由于大多数需要ＩＣＤ治疗的病人常伴有缺血性心脏病,因此急性心肌缺血对ＩＣＤ病人的除颤失败和心脏猝死可能起一定作用。本文在离体灌流兔心脏标本上测定了急性心肌缺血对单相动作电位（ＭＡＰ）各参数以及心室颤动（ＶＦ）诱发和除颤的影响。结果表明,心肌缺血１５ｍｉｎ缩短ＭＡＰ时程（复极达９０％,ＡＰＤ９０）（１５４±８ｍｓｖｓ１０２±１８ｍｓ,Ｐ＜０．００１）和复极时间（ＲＴ９０）（１８５±６ｍｓｖｓ１３８±１３ｍｓ,Ｐ＜０．００１）;使激活时间（ＡＴ）增加（３１±５ｍｓｖｓ３６±８ｍｓ,Ｐ＜０．０１）;同时使ＲＴ９０弥散明显增加（３７±１６ｍｓｖｓ６９±２９ｍｓ,Ｐ＜０．０１）。心肌缺血对易损性上限（ＵＬＶ）和除颤阈值（ＤＦＴ）稍有影响,但无统计学意义（ＵＬＶ：２７４±５３Ｖｖｓ２９４±４４Ｖ,Ｐ＝ＮＳ;ＤＦＴ２６８±４２Ｖｖｓ２７１±３３Ｖ,Ｐ＝ＮＳ）;却使易损窗（ＶＷ）的宽度增加三倍（对照２５±２２ｍｓ,缺血１５ｍｉｎ时７５±２６ｍｓ,Ｐ＜０．００１）。复极时间与ＶＷ边界的相关分析表明,ＶＷ左边界和１０个ＭＡＰ中最短的ＲＴ９０高度?     

Upper Limit of Vulnerability Predicts Chronic Defibrillation Threshold for Transvenous Implantable Defibrillators

ULV Predicts Chronic DFT. Introduction: The upper limit of vulnerability (ULV) is the shock strength at or above which ventricular fibrillation cannot be induced when delivered in the vulnerable period. It correlates acutely with the acute defibrillation threshold (DFT) and can be determined with a single episode of fibrillation. The goal of this prospective study was to determine the relationship between the ULV and the chronic DFT.
Methods and Results: We studied 40 patients at, and 3 months after, implantation of transvenous cardioverter defibrillators. The ULV was defined as the weakest biphasic shock that failed to induce fibrillation when delivered 0,20, and 40 msec before the peak of the T wave. Patients were classified as clinically stable or unstable based on prospectively defined criteria. There were no significant differences between the group means for the acute and chronic determinations of ULV (13.5 ± 5.3 J vs 12.4 ± 6.8 J, P = 0.25) and DFT (10.1 ± 5.0 J vs 9.9 ± 5.7 J, P = 0.74). Five patients (15%) were classified as unstable. The strength of the correlation between acute ULV and acute DFT (r = 0.74, P < 0.001) was similar to that between the chronic ULV and chronic DFT (r = 0.82, P < 0.001). There was a correlation between the change in ULV from acute to chronic and the corresponding change in DFT (r = 0.67, P < 0.001). The chronic DFT was less than the acute ULV + 3 J in all 35 stable patients, but it was greater in 2 of 5 unstable patients (P = 0.04).
Conclusions: The strength of the correlation between the chronic ULV and the chronic DFT is comparable to that between the acute ULV and the acute DFT. Temporal changes in the ULV predict temporal changes in the DFT. In clinically stable patients, a defibrillation safety margin of 3 J above the acute ULV proved an adequate chronic safety margin.     

Hemodynamic collapse, geometry, and the rapidly paced upper limit of ventricular vulnerability to fibrillation by T-wave stimulation

There is an upper limit to the vulnerability (ULV) of the ventricles to fibrillation (VF) induced by T-wave stimuli. Across species, disease states, and pharmacological treatments, the ULV is correlated to the defibrillation threshold (DF50). However, one factor known to increase the ULV far above the DF50 is rapid pacing. In this article we test the hypothesis that this increase is owing to an accompanying hemodynamic collapse or geometric change. In 18 dogs, T-wave stimuli were delivered from transvenous defibrillating electrodes. The T-wave shock strength that induced VF 50% of the time (the ULV50) was measured using a 10-step Bayesian up-down protocol. T-wave stimuli were delivered after 15 paced beats at one of several rates: normal (80% of the R-R interval), rapid (the interval just fast enough to cause hemodynamic collapse), or 10 milliseconds greater than rapid (which did not cause hypotension). We measured the geometry of the left ventricle at the moment of T-wave stimulation using linear ultrasound. Rapid pacing significantly increased the ULV50 above the normal rate ULV (507 +/- 62.9 vs 379 +/- 70.6 V, P < .005, n = 18), even in the subset without hemodynamic collapse (505 +/- 84.4 vs 394 +/- 66.5 V, P < .005, n = 6). No significant geometric changes were noted between rapid (19.8 mm) and normal (20.6 mm, n = 6, P < NS) pacing, but QT interval reduction appears to correlate with the ULV50 (QT vs ULV50, r > 0, P < .01). Rapid pacing can dramatically increase the measured ULV50. The most likely cause is a concurrent change in the electrophysiology, eg, QT or APD, of the myocardium. As the only known factor to consistently alter the relationship between ULV and the DF50, rapid pacing offers a unique opportunity for the study of the link between defibrillation and ULV testing.     

Progressive Depolarization: A Unified Hypothesis for Defibrillation and Fibrillation Induction by Shocks

Progressive Depolarization Defibrillation Hypothesis Experimental studies of defibrillation have burgeoned since the introduction of the upper limit of vulnerability (ULV) hypothesis for defibrillation. Much of this progress is due to the valuable work carried out in pursuit of this hypothesis. Tbe ULV hypothesis presented a unified electrophysiologic scheme for linking the processes of defibrillation and shock-induced fibrillation. In addition to its scientific ramifications, this work also raised the possibility of simpler and safer means for clinical defibrillation threshold testing. Recent results from an optical mapping study of defibrillation suggest, however, tbat the experimental data supporting the ULV hypothesis could instead be interpreted in a manner consistent with traditional views of defibrillation such as the critical mass hypothesis. This review will describe the evidence calling for such a reinterpretation. In one regard the ULV hypothesis superseded the critical mass hypothesis by linking the defibrillation and shock-induced fibrillation processes. Therefore, this review also will discuss the rationale for developing a new defibrillation hypothesis. This new hypothesis, progressive depolarization, uses traditional defibrillation concepts to cover the same ground as the ULV hypothesis in mechanistically unifying defibrillation and shock-induced fibrillation. It does so in a manner consistent with experimental data supporting the ULV hypothesis but which also takes advantage of what has been learned from optical studies of defibrillation. This review will briefly deseribe how this new hypothesis relates to other contemporary viewpoints and related experimental results.     

The Effect of Cardiac Compression on Defibrillation Efficacy and the Upper Limit of Vulnerability

Compression Affects Defibrillation and ULV. Introduction: We determined the effects of decreasing the ventricular blood volume and altering cardiac geometry on defibrillation, the upper limit of vulnerability (ULV), and the relationship between them. Methods and Results: In six pigs, fibrillation/defibrillalion trials were performed with a left ventricular apex patch to a superior vena cava catheter electrode configuration and a biphasic waveform. Thirty trials each were performed on a compressed versus noncompressed (normal) heart. Compression was achieved using direct mechanical ventricular actuation. Dose-response curves were constructed, and the 50% probability points (KD50) were compared for leading edge voltage (LEV), leading edge current (LEI), and total energy (TE). In another 12 pigs, triplicate defibrillation thresholds (DFTs) and ULVs were determined for each heart state. The T wave was scanned with shocks in 10-msec steps for determining the ULV. Compression resulted in decreased ED50s for LEV (δ= 138 ± 77 V, P < 0.05, mean ± SD), LEI (A = 1.57 ± 0.7 A, P < 0.05), and TE (δ= 4.9 ± 3.6 J, P < 0.05) compared to normal. In the second study, compression significantly reduced DFT (P < 0.02) and ULV (P < 0.02) for LEV, LEI, and TE compared to normal. The ULV tended to be lower than the DFT for the normal heart state (δ= 23 ± 46 V LEV; P = NS). However, the ULV was significantly greater than the DFT for the compressed heart state (A = 19 ± 25 V LEV; P < 0.03). Conclusions: Shock delivery during cardiac compression improves defibrillation efficacy. Additionally, cardiac compression decreases both DFT and ULV, which supports the ULV hypothesis of defibrillation. Finally, maintaining the heart's geometric and volumetric state during ULV testing in paced rhythm and DFT testing in ventricular fibrillation moves the ULV higher than the DFT—the position predicted by the ULV hypothesis for defibrillation.     

Myocardial Vulnerability to T Wave Shocks: Relation to Shock Strength, Shock Coupling Interval, and Dispersion of Ventricular Repolarization

Myocardial Vulnerability to T Wave Shocks. Introduction: Induction of ventricular fibrillation (VF) by T wave shocks is of clinical interest due to the correlation between the upper limit of vulnerability (ULV) and the defibrillation threshold (DFT). However, the ULV bas not yet been defined precisely in reference to the entire “area of vulnerability” (AOV), which is defined bifunctionally by both shock strengths and shock coupling intervals, nor has it been related to the dispersion of ventricular repolarization, considered to be an important determinant of vulnerability. Methods and Results: In 11 isolated perfused rabbit hearts immersed in a tissue bath containing a 3-lead ECG recording system and two opposite plate electrodes for field shock administration, 7 monophasic action potentials (MAPs) were recorded simultaneously from different epicardial and endocardial regions of the right and left ventricles. An average of 90 ± 25 monophasic waveform shocks of varying shock strengths and coupling intervals were delivered to each heart to determine the horizontal and vertical boundaries of the AOV. The AOV approximated a rhomboid with homogenous VF inducibility. The ULV and lower limit of vulnerability (LLV) represented discrete corners of the AOV with significant changes in VF inducibility if either shock coupling intervals or shock strength were changed by only 10 msec or 10 V. respectively (P < 0.001). The ULV occurred at 7 ± 10 msec shorter coupling intervals than the LLV (P < 0.05), and VF-inducing shock strengths at the left corner of the AOV were 50 ± 67 V higher as compared to the right corner (P < 0.01). The maximal range of VF-inducing coupling intervals coincided (within < 2 msec) with the dispersion of MAPs at 70% repolarization, and the ULV coupling interval coincided (within < 4 msec) with the longest repolarization at 50%. Conclusions: (1) VF vulnerability to monophasic T wave shocks is defined by an AOV that bas the shape of a leftward tilted rhomboid. (2) Both the ULV and LLV are sharply defined upper and lower corners of the AOV rhomboid. (3) The width of the AOV corresponds to the dispersion of ventricular repolarization at the 70% level. (4) Considering the dispersion of ventricular repolarization may yield more precise ULV determinations and a better understanding of the correlation between the ULV and DFT.     

Shock-Induced Dispersion of Ventricular Repolarization:

Shock-induced Dispersion and VF Induction. Introduction: Shock-induced dispersion of ventricular repolarization (SIDR) caused by an electrical field stimulus has been suggested as a mechanism of ventricular fibrillation (VF) induction: however, this hypothesis has not been studied systematically in the intact heart. Likewise, the mechanism underlying the upper (ULV) and lower (LLV) limit of vulnerability remains unclear.
Methods and Results: In eight Langendorff-perfused rabbit hearts, monophasic action potentials were recorded simultaneously from ten different sites of both ventricles. Truncated biphasic T wave shocks were randomly delivered at various coupling intervals and strengths, exceeding the vulnerable window, ULV, and LLV. SIDR, defined as the difference between the longest and shortest postshock repolarization times, was 64 ± 15 msec for sbocks inducing VF. SIDR was 41 ± 17 msec for shocks delivered above the ULV, and 33 ± 14 and 27 ± 8 msec for shocks delivered 10 msec before and after the vulnerable window, respectively (all P < 0.01 vs VF-inducing shocks). Although SIDR was larger for shocks delivered below the LLV(93 ± 24 msec, P < 0.01 vs VF-inducing shocks), the repolarization extension was significantly smaller for shocks below the LLV (10.3%± 3.9% vs 16.3%± 4.9%, P < 0.01).
Conclusion: SIDR is influenced by the shock timing and intensity. Large SIDR within the vulnerable window and an SIDR decrease toward its borders suggest that SIDR is essential for VF induction. The decrease in SIDR toward greater shock strengths may explain the ULV. Small repolarization extension for shocks below the LLV may explain why these shocks, despite producing large SIDR, fail to induce VF.     

Defibrillation and the upper limit of vulnerability to fibrillation in a transthoracic guinea pig model.

Recent studies have shown sustained tachyarrhythmias in guinea pigs. We hypothesized that guinea pigs could be used as a model of ventricular fibrillation, focusing on defibrillation waveform efficacy and the upper limit of vulnerability to fibrillation. In 10 male guinea pigs, an esophageal/apical pacing electrode configuration was used. The electrocardiogram (ECG) and arterial blood pressure were continuously monitored. T-wave and defibrillation shocks were applied transthoracically. A modified up-down protocol was used. After up-down testing was completed, a tachyarrhythmia was induced without electrical termination. All animals died of a sustained tachyarrhythmia. The monophasic DFT50 (the 50% successful defibrillation voltage, 496 +/-176 V) was larger than the biphasic DFT50 (364+/-94 V, P < .005). The upper limit of vulnerability to fibrillation (ULV50) (the 50% successful induction voltage) was correlated with the DFT50 for both monophasic (r = .82, P < .005) and biphasic shocks (r = .88, P < .005). Its low cost and ease of handling may make the guinea pig a preferred model for some fibrillation and defibrillation studies.     

The Zone of Vulnerability to T Wave Shocks in Humans

Vulnerability to VF in Humans. 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 ± 88 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.     

Experimental cardiac tachyarrhythmias in guinea pigs

Despite years of intense research into the mechanisms of defibrillation, there remain many unanswered questions. In many fields, hypotheses are first tested in rodent models before confirming the results in larger animals. This work suggests the guinea pig as a rodent model for defibrillation. Twenty-eight guinea pigs were studied, all male retired breeders weighing over 900 g. T-wave stimuli (upper limit of vulnerability [ULVI]) were given after 15 rapid pacing beats, since the rapid pacing has been suggested to extend the tachyarrhythmia. Defibrillation (DF) was attempted after 5 seconds. The correlation between the ULV50 and DF50 in guinea pigs (0.82, n = 8) is very close to that seen in dogs (0.85). Also, the sensitivity of the DF50 to waveform is similar (476 ± 176 for monophasic vs 364 ± 94 V for biphasic P < 0.005, n = 10). The dose-response curve widths (2.3 ± 1.7 for ULV vs 1.9 ± 1.8 for defibrillation, n = 10) show the same trend of increasing curve widths for ULV, and similar magnitude to dogs (mean 1.8). We rarely (<1.5%) observed spontaneous conversion in less than 10 seconds. The guinea pig can be used as a model for defibrillation as it shows many of the same characteristics as dogs.     

Immediate Reproducibility of Upper Limit of Vulnerability Measurements in Patients Undergoing Transvenous Implantable Cardioverter Defibrillator Implantation

Reproducibility of ULV. Introduction : Measurement of the upper limit of vulnerability (ULV) with monophasic T wave shocks has been proposed as a patient-specific measurement of defibrillation efficacy that results in fewer episodes of ventricular fibrillation (VF) than measurement of a defibrillation efficacy curve.
Methods and Results : We sought to determine the magnitude of variance in ULV in 63 consecutive patients undergoing implantation of an implantable cardioverter defibrillator (ICD). We measured ULV as the strength at or above which VF is not induced when a stimulus is delivered at 310 msec after an 8-beat ventricular pacing drive at 400 msec. Defibrillation threshold (DFT) was measured in patients with an active can device using a biphasic waveform and the binary search method beginning at 12 J. Sixty-three patients were studied; they bad a mean age of 62 × 12 years and a mean ejection fraction of 35%± 15%. Three quarters of patients bad an ischemic cardiomyopathy. Each patient underwent 4.5 ± 0.8 measurements f ULV. Monophasic ULV correlated poorly with biphasic DFT (R between 0.19 and 0.28, P = 0.04 to 0.17). There was no change in ULV between second to third, third to fourth, and first to last measurement in 22% to 41% of patients. The reliability coefficient was 0.87. A ULV ≥ 20 J was found in eight patients. The only predictor of high ULV was a high DFT.
Conclusion : Monophasic ULVs do not closely predict biphasic active can DFTs using a standard protocol. High DFTs were predicted by high ULVs. There was little variation in the acute measurement of ULV between trials. These findings have important implications for using ULV measurements to determine changes in DFTs after interventions. The methodology of determining ULV is critical to its use for predicting DFTs and programming ICDs.     

Effects of Procainamide and Lidocaine on Defibrillation Energy Requirements in Patients Receiving Implantable Cardioverter Defibrillator Devices

Effects of Procainamide and Lidocaine on Defibrillation. intntduction: In acute canine studies, lidocaine. but not prucainamidc, increases defibrillation energy requirements. We evaluated the effects of lidocaine or procainamide on defihrillation energy requirements in 27 patients undergoing intraoperative testing fur implantable cardioverter dcfibrillator device placement.
Methods and Results: Patients were tested off antiarrhythmic drugs and again following either lidocaine (200 to 250 mg loading and 3 mg/min maintenance infusions) or procainamide (1 gm loading and 3 to 4 mg/min maintenance infusions). The defibrillation testing protocol consisted of initial testing at 15 J, followed by higher or lower energies to determine the lowest energy producing three consecutive successful defibrillations. Overall, the mean defibrillation energy increased from 14 ± 5 J to 18 ± 7 J during lidocaine (plasma concentration 5.1 ± 1.6 μ/mL; P < 0.02) but were similar at baseline (12 ± 5 J) and during procainamide infusion (13 ± 6 J) (plasma concentration: procainamide 10.7 ± 7.2 μ/rnl.; N-acetyl procainamide 1.0 ± 0.4 μ/niL). A positive linear correlation was found between lidocaine plasma concentration and percent change in defibrillation energy (lidocaine: r = 0.61; P = 0.01). Procainamide raised the defibrillation energy in three patients, two with supra therapeutic plasma concentrations. The increase in defibrillation energy equaled or exceeded 25 J in four patients after lidocaine and in one patient after procainamide.
Conclusion: The data suggest that at high plasma concentrations, lidocaine and procainamide adversely affect defibrillation energy requirements consistent with an adverse, concentration-dependent effect of sodium channel blockade on defibrillation energy requirements in patients.     

Improved defibrillation efficacy with an ascending ramp waveform in humans

OBJECTIVES: The purpose of this study was to compare an ascending ramp waveform (RAMP) with a standard, clinically available biphasic truncated exponential waveform (BTE) for defibrillation in humans. BACKGROUND: In animal studies, RAMP had a lower defibrillation threshold (DFT) than BTE. METHODS: We studied 63 patients at implantable cardioverter-defibrillator placement using a dual-coil lead and left pectoral active can. The subjects were divided into two groups, one with a 12-ms ascending first phase and one with a 7-ms ascending first phase. Phase 2 of RAMP for both groups was a truncated exponential decay with 65% tilt and reversed polarity. The BTE had a 50% tilt in each phase. DFT and upper limit of vulnerability (ULV) were measured for both waveforms using a binary search protocol. RESULTS: The patient population was 77% male, with a mean age of 63 +/- 10 years and ejection fraction of 33 +/- 13%. Delivered energy at DFT was lower with the 7-ms RAMP vs BTE (5.4 +/- 2.6 J vs 6.5 +/- 3.4 J; P < .01) but unchanged with the 12-ms RAMP (7.4 +/- 4.5 J vs 7.1 +/- 4.9 J). Maximal voltage at DFT was significantly lower with either RAMP compared to BTE (P < .01). There was a strong correlation between ULV and DFT for both RAMP and BTE (P < .01). CONCLUSIONS: The 7-ms ascending ramp waveform significantly reduced delivered energy (18%) and voltage (24%) at DFT, whereas the 12-ms RAMP reduced only DFT voltage. This is the first report of a waveform that is superior to a BTE for defibrillation in humans. ULV correlates with DFT for RAMP, supporting the use of ULV testing for implantation of devices.     

Effects of pacing rate and timing of defibrillation shock on the relation between the defibrillation threshold and the upper limit of vulnerability in open chest dogs

To test the relation between the defibrillation threshold and the upper limit of vulnerability, the shock strength associated with 50% probability of successful defibrillation (DFT50) and that associated with 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 20 open chest dogs with use of the delayed up-down method, with pacing drive cycle lengths of 150 to 500 ms and either single 6-ms shocks (10 dogs) or 12-ms biphasic shocks (10 dogs) given at the mid-upslope, peak and mid-downslope of the T wave of electrocardiographic lead II. The shocks were given by means of a patch-patch configuration on the anterior and posterior surfaces of the heart, which was paced from a stimulating electrode attached to the left ventricular apex. Analysis of variance showed no statistically significant differences in ULV50 as determined with different pacing cycle lengths. For monophasic shocks, DFT50 (331 +/- 66 V or 5.8 +/- 2.7 J) was not significantly different from ULV50 determined at the mid-upslope of the T wave (318 +/- 64 V or 5 +/- 2 J). The correlation coefficients between the two values were 0.74 (p = 0.014) for voltage and 0.67 (p = 0.034) for energy. In contrast, DFT50 was significantly higher than ULV50 as determined at the peak of the T wave (219 +/- 43 V or 2.3 +/- 1 J) and mid-downslope of the T wave (200 +/- 38 V or 1.9 +/- 0.9 J). In three dogs, ventricular fibrillation could not be induced at the mid-downslope of the T wave with any baseline pacing (Si) cycle length.(ABSTRACT TRUNCATED AT 250 WORDS)     

Discrepancies between the upper limit of vulnerability and defibrillation threshold: prevalence and clinical predictors

INTRODUCTION: Upper limit of vulnerability (ULV) has a strong correlation with defibrillation threshold (DFT) in patients with implantable cardioverter defibrillators (ICDs). Significant discrepancies between ULV and DFT are infrequent. The aim of this study was to characterize patients with such discrepancies. METHODS AND RESULTS: The ULV and DFT were determined in 167 ICD patients. Univariate and multivariate analyses were used to evaluate clinical predictors of a significant difference (> or =10 J) between ULV and DFT. Only 8 patients (5%) had > or =10 J difference. ULV exceeded DFT in all of them. Absence of coronary artery disease (6/8 vs 48/159 patients; P = 0.05) and absence of documented ventricular arrhythmias (4/8 vs 12/159 patients; P = 0.01) were the only independent predictors of a significant ULV-DFT discrepancy. CONCLUSION: Significant discrepancies between ULV and DFT occur in 5% of patients with ICDs. Absence of coronary disease and documented ventricular arrhythmias predict such a discrepancy. At ICD implant, DFT testing is recommended in these patients and in patients with a high (>20 J) ULV before first-shock energy and the need for lead repositioning are determined.     

Effect of Shock Waveform on Relationship Between Upper Limit of Vulnerability and Defibrillation Threshold

ULV-DFT Waveform. Introduction: The upper limit of vulnerability (ULV) correlates with the defibrillation threshold (DFT). The ULV can he determined with a single episode of ventricular fibrillation and is more reproducible than the single-point DFT. The critical-point hypothesis of defibrillation predicts that the relation between the ULV and the DFT is independent of shock waveform. The principal goal of this study was to test this prediction. Methods and Results: We studied 45 patients at implants of pectoral cardioverter defibrillators. In the monophasic-biphasic group (n = 15), DFT and ULV were determined for monophasic and biphasic pulses from a 120-μF capacitor. In the 60- to 110-μF group (n = 30), DFT and ULV were compared for a clinically used 110-μF waveform and a novel 60-μF waveform with 70% phase 1 tilt and 7-msec phase 2 duration. In the monophasic-biphasic group, all measures of ULV and DFT were greater for monophasic than biphasic waveforms (P < 0.0001). In the 60- to 110-/tF group, the current and voltage at the ULV and DFT were higher for the 60-μF waveform (P < 0.0001), hut stored energy was lower (ULV 17%, P < 0.0001; DFT 19%, P = 0.03). There was a close correlation between ULV and DFT for both the monophasic-biphasic group (monophasic r²= 0.75, P < 0.001; hiphasic r²= 0.82, P < 0.001) and the 60- to 110-μF group (60 μF r²= 0.81 P < 0.001; 110 μF r²= 0.75, P < 0.001). The ratio of ULV to DFT was not significantly different for monophasic versus biphasic pulses (1.17 ± 0.12 vs 1.14 ± 0.19, P = 0.19) or 60-μF versus 110-μF pulses (1.15 ± 0.16 vs 1.11 ± 0.14, P = 0.82). The slopes of the ULV versus DFT regression lines also were not significantly different (monophasic vs biphasic pulses, P = 0.46; 60-μF vs UO-μF pulses, P = 0.99). The sample sizes required to detect the observed differences between experimental conditions (P < 0.05) were 4 for ULV versus 6 for DFT in the monophasic-biphasic group (95% power) and 11 for ULV versus 31 for DFT in the 60- to 110-μF group (75% power). Conclusion: The relation between ULV and DFT is independent of shock waveform. Fewer patients are required to detect a moderate difference in efficacy of defibrillation waveforms by ULV than by DFT. A small-capacitor biphasic waveform with a long second phase defibrillates with lower stored energy than a clinically used waveform.     

胺碘酮对电击诱发心室颤动和除颤阈值的影响

目的研究胺碘酮对单、双相电击的易损窗、易损上、下限以及除颤阈值（ＤＦＴ）的影响。方法在离体Ｌａｎｇｅｎｄｏｒｆ灌流兔心脏上记录单相动作电位以测量激活时间、动作电位时程（ＡＰＤ９０）、９０％复极恢复时间及其离散度。结果与对照组相比，胺碘酮延长ＡＰＤ９０和９０％复极时间（Ｐ＜００５），但并不改变激活时间离散度和９０％复极时间离散度；使单、双相电击的易损窗都显著右移（Ｐ＜００１），但对易损窗的宽度无影响；对单相电击的易损下限无影响，但显著抬高双相电击的易损下限；对易损上限和ＤＦＴ无影响。结论胺碘酮将单、双相电击的易损窗都右移并提高双相电击的易损下限，但在该模型中对两种电击的易损上限、ＤＦＴ和易损窗宽度均无直接影响。     

Upper limit of vulnerability determination during implantable cardioverter-defibrillator placement to minimize ventricular fibrillation inductions

The defibrillation threshold (DFT) and upper limit of vulnerability (ULV) were determined using step-down protocols in 50 patients who underwent implantable cardioverter-defibrillator placement or testing. The sensitivity and specificity of each ULV energy level was assessed for detecting an increased DFT, correlation of the DFT and ULV, and optimal shock timing for ULV determination. A ULV <10 or 11 J (failure to induce ventricular fibrillation with 10- to 11-J shocks) was 100% predictive of an acceptable DFT and may be sufficient to exclude unacceptable DFTs in 60% of implantable cardioverter-defibrillator recipients. All 4 shocks used to scan the peak of the T wave during ULV testing were necessary for accurate ULV determination.