Reduction in atrial defibrillation threshold by a single linear ablation lesion.

INTRODUCTION: This study investigated a hybrid approach to reduce the atrial defibrillation threshold (ADFT) by determining the effect of a single linear radiofrequency ablation (RFA) lesion on both the ADFT and activation patterns during atrial fibrillation (AF). METHODS AND RESULTS: In 18 open chest sheep (45 to 57 kg), coil defibrillation electrodes were placed in a superior vena cava/right ventricular configuration. AF was induced by burst pacing and maintained with acetyl beta-methylcholine (2 to 42 microL/min). ADFTs were obtained before and after a linear RFA lesion was created in the left atrium (LAL; n = 6), right atrium (RAL; n = 6), or neither atrium as a control (n = 6). In animals receiving an LAL, a 504-unipolar-electrode plaque was sutured to the LA. For animals receiving an RAL, two 504-electrode plaques were placed, one each on the LA and RA. From each plaque, activations were recorded before and after ADFT shocks, and organizational characteristics of activations were analyzed using algorithms that track individual wavefronts. In sham-treated controls, the ADFT did not change. In contrast, LAL reduced ADFT energy 29%, from 4.5 +/- 2.3 J to 3.2 +/- 2.0 J (P < 0.05). RAL reduced ADFT energy 25%, from 2.0 +/- 0.9 J to 1.5 +/- 0.7 J (P < 0.05). AF activation was substantially more organized after RFA than before RFA for both the RAL- and LAL-treated animals. CONCLUSION: A single RFA lesion in either the RA or LA reduces the ADFT in this sheep model. This decrease is associated with an increase in fibrillatory organization.

Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold.

INTRODUCTION: Ventricular defibrillation is probabilistic and shock strength dependent. We investigated the relationship between defibrillation outcome and postshock activation patterns for shocks of the same strength (approximately 50% probability of success for defibrillation [ED50] to yield an equal number of successful and failed shocks). METHODS AND RESULTS: In five pigs, 10 shocks of approximately ED50 strength (right ventricle-superior vena cava, biphasic, 6/4 msec) were delivered after 10 seconds of ventricular fibrillation (VF). Epicardial activation sequences following shocks were mapped with a 504-electrode shock and analyzed by animating dV/dt of the electrograms. Intercycle interval (ICI, time between the onset of successive postshock cycles), wavefront conduction time (WCT, time between the earliest and latest activation of a cycle), and overlapping index (WCT of cycle[n]/ICI of cycle[n+1]) were determined for the first five postshock cycles. An overlapping index >1 indicates overlap between successive cycles. Of 50 defibrillation attempts, 25 were successes. There was no difference between successful and failed episodes for both ICI (68 +/- 9 msec vs 62 +/- 10 msec) and WCT (97 +/- 24 msec vs 100 +/- 14 msec) of cycle 1. However, starting at cycle 2, the ICI was longer, and the WCT was shorter for successful than failed episodes (P < 0.01). Overlapping cycles (index > 1) were found during the transition from cycles 2 through 5 in all failed (index >1) and in no successful episodes. CONCLUSIONS: (1) Defibrillation outcome cannot be determined during the first postshock cycle. (2) At least three rapid successive cycles with overlap of cycles 2 and 3 are present in all failed and in no successful episodes. (3) The overlapping index is a marker to predict defibrillation outcome.

Pacing following shocks stronger than the defibrillation threshold: impact on defibrillation outcome.

INTRODUCTION: A recent study of shocks near defibrillation threshold (DFT) strength demonstrated that at least three rapid cycles always occur after failed shocks but not after successful shocks, suggesting that the number and rapidity of postshock cycles are important in determining defibrillation success. To test this hypothesis, rapid pacing was performed following a shock stronger than the DFT that by itself did not induce rapid cycles and ventricular fibrillation (VF). METHODS AND RESULTS: Epicardial activation was mapped in six pigs using a 504-electrode sock. The DFT was determined by an up/down protocol with S1 shocks (right ventricle-superior vena cava, biphasic). Ten shocks that were 100 to 200 V above the DFT (aDFT) were delivered after 10 seconds of VF to confirm they always defibrillated. Then, S2, S3, etc., pacing at 5 to 10 times diastolic threshold was performed from the left ventricular apex after aDFT shocks during VF. First, the postshock interval after aDFT shocks was scanned with an S2 stimulus to find the shortest S1-S2 coupling interval (CI) that captured. This was repeated for S3, S4, etc., until VF was induced. To induce VF after aDFT shocks, three pacing stimuli (S2, S3, S4) with progressively shorter CIs were always required; S2 or S2,S3 never induced VF. For the S2-S4 cycles, the intercycle interval was shorter (P < 0.01), and the wavefront conduction time was longer (P < 0.01) for episodes in which VF was induced (n = 57) than for episodes in which it was not (n = 60). Following the S4 cycle that induced VF, two types of spontaneous activation patterns appeared: focal (88%) and reentrant (12%). CONCLUSION: VF induction after aDFT shocks always required at least three rapid successive paced-induced cycles. Thus, the number and rapidity of the first several postshock cycles rather than just the first postshock cycle may be determining factors for defibrillation outcome.

Left ventricular apex ablation decreases the upper limit of vulnerability.

BACKGROUND: After shocks with an approximately 50% probability of success for the upper limit of vulnerability (ULV(50)) of strength, the first few activations appear focally on the epicardium at almost the same site at the left ventricular (LV) apex in both successful and failed induction of ventricular fibrillation (VF). We tested the hypothesis that subendocardial ablation at this early site would decrease the shock strength required for the ULV(50). METHODS AND RESULTS: Ten S1 stimuli were delivered from the right ventricular apex at a 300-ms coupling interval in 5 pigs. Biphasic shocks were delivered from right ventricular-superior vena cava electrodes after the last S1 stimulus. The ULV(50) was determined using an up/down protocol with T-wave scanning. Radiofrequency ablation was performed endocardially at the apical LV. The ULV(50) was determined again 30 minutes after ablation. To determine the importance of the ablation region, this protocol was repeated in another 5 pigs with ablation at the LV base. Delivered voltage (401+/-60 versus 323+/-50 V) and energy (11+/-3 versus 7+/-2 J) for the ULV(50) were significantly decreased after LV apex ablation by 19% and 34%, respectively. However, no difference existed in ULV(50) before and after LV base ablation. Lesions at both the LV apex and base were subendocardial and ranged from 0.8 to 1.1 cm in diameter. CONCLUSIONS: Subendocardial ablation at the apical LV markedly decreases ULV(50), which suggests that the activation originating from this postshock early site is responsible for VF initiation and that interventions to electrically silence this site can influence the outcome of VF induction by ULV shocks.

Pacing after shocks stronger than the upper limit of vulnerability: impact on fibrillation induction.

BACKGROUND: After upper-limit-of-vulnerability (ULV) shocks of the same strength and coupling interval (CI) during the T wave, (1) the epicardial activation pattern (EAP) for the first postshock cycle is indistinguishable between shocks that do (VF) and do not (NoVF) induce ventricular fibrillation (VF) and (2) >/=3 cycles in rapid succession always occur during VF but not during NoVF episodes. To study the role of these rapid cycles, rapid pacing was performed after a shock stronger than the ULV that by itself did not induce rapid cycles and VF. METHODS AND RESULTS: A 504-electrode sock was sutured to the heart in 6 pigs to map EAPs. The S2 shock strength and S1-S2 CI at the ULV were determined by T-wave scanning with an up/down protocol. Ten shocks 50 to 100 V above the ULV (aULV) were delivered at the same S1-S2 CI to confirm that VF was not induced. Then, the postshock interval after aULV shocks was scanned with an S3 pacing stimulus from the LV apex until the shortest S2-S3 CI that captured was reached. This was repeated for S4, S5, etc, until VF was induced. To induce VF, 3 pacing stimuli (S3-S5) with progressively shorter CIs were required; S3 or S3, S4 never induced VF. After cycle S5, which induced VF, 2 EAP types occurred: focal (74%) and reentrant (26%). CONCLUSIONS: At least 3 cycles with short CIs are necessary for VF induction after aULV shocks. Cycles S3-S4 may create the substrate for cycle S5 to initiate VF.

Effect of altering the left ventricular pressure on epicardial activation time in dogs with and without pacing-induced heart failure.

BACKGROUND: The influence of an increased left ventricular end-diastolic pressure (LVEDP) on the development of lethal arrhythmias in chronic heart failure is unclear. We investigated the effect of chronic and acute LVEDP increase on the epicardial activation time of sinus (SB) and paced (PB) beats. METHODS: Six dogs underwent rapid ventricular pacing at 220-280[emsp4 ]beats/min for 6-14 weeks for induction of heart failure. On the study day, baseline (ba) LVEDP was determined for the surviving heart failure animals (HF-ba), and for seven control animals (C-ba). The epicardial activation time (EAT, time between the earliest and latest epicardial activation) for five consecutive SB and five ventricular PB during the baseline hemodynamic state were recorded using a 504 electrode mapping-sock. In the control animals a 2-litre volume (vl) was infused over 10[emsp4 ]min to acutely increase the LVEDP (C-vl) to a level comparable to the chronic increased LVEDP of the HF-ba. The same volume challenge was performed in two HF animals (HF-vl) and the EAT for SB and PB was redetermined. RESULTS: Three of six HF animals died during induction of heart failure. In the three remaining HF animals, chronic LVEDP increased from 6+/-1 to 17+/-10.8[emsp4 ]mmHg (P=0.07), EAT for SB increased by 68 % compared to control animals (HF-ba vs. C-ba, P<0.05). In contrast, in the control animals the acute rise in LVEDP from 6.8+/-4.5 to 14.7+/-6.2 mmHg P<0.05), shortened the EAT for SB (C-ba vs. C-vl, P<0.05). A similar decrease in EAT for SB caused by acute volume load was seen in the HF animals, but did not reach significance due to the small sample size (one of the three remaining HF animals died of spontaneous ventricular fibrillation before the volume load). Chronic LVEDP elevation significantly prolonged the EAT for PB from 72+/-11 to 120+/-31[emsp4 ]ms (C-ba vs. HF-ba) while acute LVEDP increase had no significant effect on EAT for PB. CONCLUSION: Chronic HF increases LVEDP and prolongs EAT, while an acute increase in LVEDP shortens the EAT for sinus beats. A prolongation of EAT in heart failure may make the heart more susceptible to ventricular arrhythmias and electromechanical dissociation.

Can early timed internal atrial defibrillation shocks reduce the atrial defibrillation threshold?

The defibrillation threshold is markedly reduced very early following the initiation of ventricular fibrillation. The purpose of this study was to determine if the same finding holds true for atrial defibrillation. Sustained, reproducible AF was induced with programmed atrial pacing using acetyl-beta-methylcholine chloride (40-640 microL/min) in six adult sheep (heart weight 245-300 g). Seven timing intervals (125 ms, 200 ms, 1 s, 3 s, 10 s, 30 s, and 5 min after AF induction) and two lead configurations: (1) RA as cathode and CS as anode; and (2) RA as cathode and RV apex as anode were tested. Single capacitor biphasic waveforms (3/1 ms) were delivered and atrial defibrillation thresholds (ADFTs) were determined in random order. No significant differences in leading edge voltage and total energy were detected for the RA-CS configuration for the seven timing intervals. For the RA-RV configuration, a significant difference was detected comparing the voltage for 125 ms to the 5-minute timing interval. For all times except 125 ms, the RA-RV threshold was significantly higher than the RA-CS level. In contrast to ventricular defibrillation, the ADFT does not change significantly within the first 5 minutes after the initiation of AF for the RA-CS configuration. However, if the shock is given very early (125 ms after AF induction) with the RA-RV configuration, the ADFT is lowered almost to the RA-CS level.

Energy levels for defibrillation: what is of real clinical importance?

Today, transthoracic and intracardiac defibrillation offer a well-accepted and widely used form of therapy for patients with life-threatening ventricular arrhythmias. Despite the wide clinical use of defibrillators, the mechanisms by which an electrical shock halts fibrillation are still not completely understood. During a shock, different amounts of current flow through the different parts of the heart and the current distribution is highly uneven. This current distribution is affected by changes in the shock potential gradient through the heart, changes in fiber orientation, and changes in myocardial conductivity caused by connective tissue barriers. It would be ideal if the potential gradient distribution throughout the ventricles could be measured directly for each individual patient during defibrillator implantation and follow-up and the shock strength could be programmed based on this measurement, but so far this is not possible. A more feasible approach is to determine, by trial and error, the magnitude of the shock strength delivered through the defibrillation electrodes for successful defibrillation. There is no distinct threshold value above which all shocks succeed and below which all shocks fail to defibrillate. Rather, increasing shock strength increases the likelihood the shock will succeed. Therefore, instead of a distinct defibrillation threshold, a probability of success curve exists. However, increasing the shock strength above an optimal range can actually decrease the success rate for defibrillation. One possible explanation is that the high voltage gradients caused by such large shocks damage cells and result in postshock arrhythmias that may reinitiate fibrillation. Another problem that can affect the probability of defibrillation success for a particular programmed energy setting is that the shock strength required for defibrillation may increase over time due to (1) the growth of fibrotic tissue around the defibrillation electrode; (2) migration of the lead; (3) acute ischemia; or (4) other changes in the underlying cardiac disease (e.g., worsening of heart failure). Such possible increases in the defibrillation shock strength requirement should be compensated for before they occur by adding a margin of safety to the shock strength needed for effective defibrillation. When programming an implantable defibrillator, it is important to keep in mind that the defibrillation shock should be (1) strong enough to defibrillate at least 98% of the time with the first shock; (2) weak enough not to cause severe post-shock arrhythmias or reinitiation of fibrillation; but (3) strong enough to compensate for changes of defibrillation energy requirements over time. This usually can be accomplished by setting the defibrillator 7-10 J higher than the defibrillation threshold determined by a standard step-down protocol.

Effect of a passive endocardial electrode on defibrillation efficacy of a nonthoracotomy lead system.

OBJECTIVES: We investigated the impact of an inactive endocardial lead on the 50% effective dose (ED50%) for successful ventricular defibrillation. BACKGROUND: The presence of abandoned epicardial mesh patch electrodes detrimentally affects the defibrillation efficacy of an endocardial lead system. It is not known whether abandoned endocardial electrodes produce a similar effect. METHODS: An endocardial lead system (ENDOTAK, model 0062, Cardiac Pacemakers, Inc.) was implanted in eight dogs (mean +/- SD weight 23.7 +/- 1.0 kg). The ED50% for each of seven lead configurations was determined by a three-reversal point protocol in a balanced-randomized order with and without a second electrically passive endocardial lead system in the right ventricle (power 0.97 to detect a 50-V difference). Biphasic shocks with 80% tilt were delivered 10 s after the induction of ventricular fibrillation. In one configuration the active electrode made contact with the passive electrode in the right ventricular (RV) apex. In another configuration the active electrode was placed in a more proximal position to avoid contact. Additionally, the ED50% was determined for the endocardial lead system with a passive pacing lead positioned in the RV apex. RESULTS: ED50% values for peak voltage, peak current and delivered energy were not significantly different with or without a passive RV electrode, and this was true whether or not the active electrode touched the passive electrode. However, ED50% values were significantly higher when the active electrode was slightly proximal than when it was positioned at the apex. CONCLUSIONS: Physical contact between active and passive endocardial electrodes does not significantly alter defibrillation efficacy in this dog model. An increase in ED50% energy was caused by a slightly proximal position. Therefore, a good electrode position within the right ventricle is a more important determinant of defibrillation efficacy than is avoidance of the electrode touching a passive electrode.

Influence of epicardial patches on defibrillation threshold with nonthoracotomy lead configurations.

BACKGROUND: In previous studies, epicardial patch electrodes decreased transthoracic defibrillation efficacy. We studied the effects of two inactive epicardial 14-cm2 titanium mesh patches on defibrillation energy requirements with nonthoracotomy internal lead configurations. METHODS AND RESULTS: A 6/6-millisecond biphasic shock wave-form was delivered via several electrode configurations 10 seconds after ventricular fibrillation was initiated with a 60-Hz generator. In two series, a total of 16 dogs (weight, 23.3 +/- 2.4 kg) underwent an up-down defibrillation protocol. In the first series, the defibrillation threshold (DFT) was determined for each electrode configuration in the presence of two inactive epicardial patches. In the second series, DFTs were determined in the presence of an inactive right ventricular (RV) or left ventricular (LV) patch alone. For several nonthoracotomy lead configurations tested in the first 8 dogs, the mean +/- SD DFT energy increased 49% to 97% with two inactive patches on the heart compared with no patches on the heart as follows: RV to superior vena caval (SVC) electrode, from 8.9 +/- 2.6 to 18.0 +/- 14.3 J; RV to SVC plus subcutaneous array electrode, from 7.0 +/- 2.4 to 10.7 +/- 5.3 J; RV to subcutaneous pectoral plate electrode, from 6.2 +/- 1.3 to 11.4 +/- 4.0 J (P < or = .05). The lowest DFT was achieved by defibrillating between the epicardial patches (3.8 +/- 3.3 J). The second series showed that DFT voltage requirements increased significantly for all three nonthoracotomy lead configurations with the inactive LV patch alone (P < or = .05) but not with the inactive RV patch alone. CONCLUSIONS: Inactive epicardial patches can significantly increase the defibrillation energy requirements for nonthoracotomy lead configurations. This negative impact may be due to an insulating effect of the patches and to a disturbance of the potential gradient field under the patches. If the same holds true in patients, these results have clinical implications. Functioning epicardial patch leads should be incorporated in the defibrillation lead system if already present. If the LV patch is nonfunctioning, such as because of a lead fracture, the marked increase in DFT due to an inactive LV patch calls for thorough DFT testing during surgery and, in selected patients, may necessitate patch removal to produce an effective transvenous-based system.

Endocardial carbon-braid electrodes. A new concept for lower defibrillation thresholds.

BACKGROUND: In the treatment of patients with life-threatening ventricular arrhythmia, transvenous implantable cardioverter/defibrillators provide significant advantages over devices requiring a thoracotomy. This study tested the hypothesis that a new carbon-fiber electrode, designed at the Technische Universität in Munich, Germany, has a lower defibrillation threshold (DFT) than standard transvenous defibrillation electrodes. METHODS AND RESULTS: In 8 mongrel dogs (weight, 25.2 +/- 0.8 kg; heart weight, 192 +/- 19 g), we examined the efficacy and electrical characteristics of a right ventricular endocardial carbon prototype defibrillation electrode (9.5F, 4.4-cm2 surface) compared with a standard CPI 0062 Endotak electrode and a Medtronic 6966 Transvene endocardial right ventricular defibrillation electrode. The new electrode consists of 24 braided, tubular carbon filaments, each containing 1000 highly isotropic carbon fibers of 7-microns diameter, yielding a theoretical electrical surface of 480 cm2. The DFTs were determined in random order between each of the three right ventricular electrodes and a subcutaneous wire array anode placed on the left thorax. A standard step-down/up DFT protocol of 20-V shock steps was applied. Two different biphasic waveforms with a 1-ms delay between phases were tested: 3.2-ms first phase/2.0-ms second phase, and 6.0-ms first phase/6.0-ms second phase. For the 3.2/2.0-ms waveform, we found a significantly lower DFT for the carbon lead (4.96 +/- 1.58 J) compared with the CPI 0062 (6.93 +/- 1.67 J) and the Medtronic 6966 (7.49 +/- 0.99 J) leads. For the 6.0/6.0-ms waveform, the DFT for the carbon electrode (5.97 +/- 2.09 J) was significantly lower than for the Medtronic 6966 lead (8.55 +/- 1.93 J) but not for the CPI 0062 lead (6.30 +/- 1.41 J). The impedance with carbon was lower than with the other two leads for the 6.0/6.0-ms waveform but not for the 3.2/2.0-ms waveform. For the carbon electrode, the 3.2/2.0-ms waveform had a lower DFT than the 6.0/6.0-ms waveform. CONCLUSIONS: The present canine study found a lower DFT for a new carbon electrode compared with DFTs for endocardial defibrillation electrodes made of standard metal. Further long-term animal studies and clinical studies are needed to determine whether carbon materials and braided-lead technology are practical and beneficial in patients.

Improved defibrillation threshold with a new epicardial carbon electrode compared with a standard epicardial titanium patch.

BACKGROUND: Recent studies show that depending on the type of shock morphology used, 5% to 15% of patients requiring implantable defibrillators cannot be treated with a nonthoracotomy system. In these cases, an epicardial patch-based system becomes necessary. In this study, we investigated a newly developed epicardial carbon electrode as an alternative to a standard epicardial titanium patch. METHODS AND RESULTS: A tubular epicardial braided carbon electrode of 7F diameter and 14-cm length applied in a U-shape to the epicardium was compared with a standard left ventricular epicardial 15-cm2 titanium mesh patch (CPI Inc). As cathode, a CPI endocardial lead, a Medtronic lead, or a carbon-platinum-iridium prototype electrode was used. Ventricular fibrillation was induced with a 60-Hz generator and allowed to continue for 10 seconds before a shock was given. Two different biphasic shock waveforms (3.2/2- and 6/6-millisecond) were delivered by the six electrode configurations. Eight dogs (weight, 24.5 +/- 1.3 kg) underwent an up-down defibrillation protocol. The order of testing the epicardial electrodes, the endocardial cathodes, and the waveform was randomized. With the epicardial carbon electrode, the mean defibrillation threshold (DFT) energy decreased 39% to 56% and the voltage decreased 24% to 35% compared with the titanium patch: from 8.3 +/- 2.5 to 4.9 +/- 3.6 J with the CPI lead and the 3.2/2-millisecond waveform, from 6.2 +/- 2.5 to 2.9 +/- 2.1 J with the carbon-platinum-iridium prototype, and from 6.4 +/- 3.4 J to 3.5 +/- 2.6 J with the Medtronic lead (P < or = .05). The DFT determinations with the 6/6-millisecond biphasic waveform showed a similar trend with slightly higher values. CONCLUSIONS: Compared with a titanium patch, the new braided epicardial electrode significantly decreases the defibrillation energy requirements. This effect can be maximized by using an endocardial carbon-platinum-iridium prototype as cathode and a short duration biphasic waveform.