Increased wave break during ventricular fibrillation in the epicardial border zone of hearts with healed myocardial infarction.

BACKGROUND: The action potential duration (APD) restitution hypothesis of wave break during ventricular fibrillation (VF) in the epicardial border zone (EBZ) of hearts with chronic myocardial infarction is unknown. METHODS AND RESULTS: VF was induced by rapid pacing, and the EBZ with the two adjoining sites (right ventricle and lateral left ventricle) were sequentially mapped in random order in 7 open-chest anesthetized dogs 6 to 8 weeks after left anterior descending artery occlusion and in 4 control dogs. At each site, 3 seconds of VF was mapped with 477 bipolar electrodes 1.6 mm apart. The number of wave fronts and approximate entropy were significantly (P:<0.01) higher in the EBZ than all other sites in both groups independent of the rate of invasion of new wave fronts and epicardial breakthroughs. The higher wavelet density in the EBZ was caused by increased (P:<0.01) incidence of spontaneous wave breaks. There was no difference between the two groups in either reentry period (80 episodes) or VF cycle length. Reentry in the EBZ had a smaller core perimeter, slower rotational speed, and a small or no excitable gap (P:<0.01), often causing termination after one rotation. The dynamic monophasic action potential duration restitution curve in the EBZ had longer (P:<0.01) diastolic intervals, over which the slope was >1. Connexin43-positive staining was significantly (P:<0.01) and selectively reduced in the EBZ. CONCLUSIONS: A selective increase in wave break and alteration of reentry occur in the EBZ during VF in hearts with healed myocardial infarction. Increased wave break in the EBZ is compatible with the action potential duration restitution hypothesis.

Nicotine increases ventricular vulnerability to fibrillation in hearts with healed myocardial infarction.

The vulnerability of the infarcted hearts to ventricular fibrillation (VF) was tested in in situ canine hearts during nicotine infusion. The activation pattern was mapped with 477 bipolar electrodes in open-chest anesthetized dogs (n = 8) 5-6 wk after permanent occlusion of the left anterior descending coronary artery. Nicotine (129 +/- 76 ng/ml) lengthened (P < 0.01) the pacing cycle length at which VF was induced from 171 +/- 8.9 to 210 +/- 14. 7 ms. Nicotine selectively amplified the magnitude of conduction time and monophasic action potential (MAP) amplitude and duration (MAPA and MAPD, respectively) alternans in the epicardial border zone (EBZ) but not in the normal zone. With critical reduction of the MAPA and MAPD in the EBZ, conduction block occurred across the long axis of the EBZ cells. Block led immediately to reentry formation in the EBZ with a mean period of 105 +/- 10 ms, which, after one to two rotations, degenerated to VF. Nicotine widened the range of diastolic intervals over which the dynamic MAPD restitution curve had a slope >1. We conclude that nicotine facilitates conduction block, reentry, and VF in hearts with healed myocardial infarction by increasing the magnitude of depolarization and repolarization alternans consistent with the restitution hypothesis of vulnerability to VF.

Correlation of acute and chronic defibrillation threshold with upper limit of vulnerability determined in normal sinus rhythm.

BACKGROUND: The upper limit of vulnerability (ULV) is the stimulus strength above which ventricular fibrillation cannot be induced, even when the stimulus occurs during the vulnerable period of the cardiac cycle. Determination of ULV using T-wave shocks during ventricular pacing has been shown to closely correlate with the defibrillation threshold (DFT) at ICD implantation. However, there are no data correlating ULV determined in sinus rhythm at ICD implantation, with DFT determined at implantation or during long-term follow-up. This is of clinical importance since ULV may be used to estimate DFT during ICD implantation, both during ventricular pacing or sinus rhythm. METHODS AND RESULTS: Twenty-one patients receiving a transvenous ICD system were studied prospectively. There were 16 males and 5 females, mean age 68 +/- 15 years, with mean ejection fraction 37.4 +/- 17.4%. All had structural heart disease. The ULV was defined as the lowest energy that did not induce ventricular fibrillation with shocks at 0, 20 and 40ms before the peak of the T-wave, using a step-down protocol. The initial energy tested was 15J and the lowest energy 2J. DFT was determined following a similar step-down protocol. The DFT was defined as the lowest energy that successfully defibrillated the ventricles. The linear correlation coefficient between ULV and DFT was r = 0.73 (p < 0.001). At implant, mean ULV was 9.2 +/- 5J, not statistically different from mean DFT 9.4 +/- 4J. ULV plus 5J successfully defibrillated 19 of 21 patients. During long-term follow-up of 10.1 +/- 1.8 months in eight patients, DFT was 8.8 +/- 5.8J, not significantly different than the DFT of 7.5 +/- 4.1J or ULV of 8.0 +/- 5.3 at implant. CONCLUSION: 1) When determined during normal sinus rhythm the ULV significantly correlates with DFT. 2) ULV testing might be used in lieu of standard DFT testing to confirm adequate lead placement thus minimizing or eliminating VF inductions, particularly in hemodynamically unstable patients. 3) Since ULV + 5J has a high probability of successful defibrillation in most patients, programming ICD first shock energy for VF at ULV + 5J may result in lower first shock energies compared to the standard methods of programming first shock energy at twice DFT. CONDENSED ABSTRACT: The purpose of this study was to determine if the upper limit of vulnerability (ULV) determined during normal sinus rhythm correlates with the defibrillation threshold (DFT), as has been previously shown when determined during ventricular pacing. The linear correlation coefficient between the ULV and DFT was r = 0.73 (p < 0.001). Mean ULV at implant was 9.2 +/- 5J, not statistically different from mean DFT of 0.4 +/- 4J. During long-term follow-up of 10.1 +/- 1.8 months in 8 patients, DFT was 8.75 +/- 8J, not significantly different than the DFT of 7.5 +/- 4.1J or ULV of 8.0 +/- 5.3 at implant. Shocks energies of ULV + 5J successfully defibrillated 19 of 21 patients at implant and 8 of 8 at follow-up. This study indicates that the ULV determined in normal sinus rhythm closely correlates with the DFT, and that ULV + 5J defibrillated most patients. ULV testing could be used to predict DFT and reduce or eliminate the need for DFT testing and VF induction. Programming ICD first shock energy for VF to ULV + 5J will result in lower energy than that used with standard DFT testing.

Mechanism of acceleration of functional reentry in the ventricle: effects of ATP-sensitive potassium channel opener.

BACKGROUND: The effect of effective refractory period (ERP) shortening on the vulnerability and characteristics of induced functional reentry in the ventricle remain poorly defined. We hypothesized that ERP shortening increases ventricular vulnerability to reentry and accelerates its rate, as is the case in the atrium. METHODS AND RESULTS: The epicardial surfaces of 19 isolated and superfused canine right ventricular slices (4x4 cm and <2 mm thick) were mapped with 480 bipolar electrodes 1.6 mm apart. Vulnerability was tested during pacing at a cycle length (CL) of 600 ms and with a single premature stimulus of 5-ms duration at increasing current strength of 1 to 100 mA. Cromakalim (10 micromol/L), an ATP-sensitive potassium channel opener, caused a significant (P<0. 001) shortening of the ERP but had no effect on conduction velocity. Cromakalim increased (P<0.01) the vulnerability (product of current and the stimulus coupling interval) for reentry induction. Reentry had a significantly shorter CL and lasted for a longer duration (P<0. 001). The central core around which the wave front rotated became smaller, which caused shortening of the CL of reentry. A significant (P<0.001) linear correlation was found between core size and reentry CL. These effects of cromakalim were reversible. Two-dimensional simulation studies using the modified Luo-Rudy I model of cardiac action potential, in which the refractory period was variably shortened by a progressive increase of the time-independent potassium conductance, reproduced the experimental findings. CONCLUSIONS: ERP shortening by an ATP-sensitive potassium channel opener increases ventricular vulnerability to reentry and accelerates its rate by decreasing the core size around which the wave front rotates.

Transmembrane potential properties of atrial cells at different sites of a spiral wave reentry: cellular evidence for an excitable but nonexcited core.

Transmembrane action potentials (TAPs) were recorded during simultaneous mapping of a reentrant wavefront induced in canine isolated atria. The activation pattern was visualized dynamically using a high resolution electrode catheter mapping system. During functional reentry (spiral wave), cells in the core of the spiral wave remained quiescent near their resting membrane potential. Cells away from the core progressively gained TAP amplitude and duration, and at the periphery of the spiral wave the cells generated TAPs with full height and duration. During anatomical reentry, when the tip of the wavefront remained attached to the obstacle (a condition of high source-to-sink ratio), the TAP near the obstacle had normal amplitude and duration. However, when the tip of the wavefront detached from the obstacle (condition of lowered source-to-sink ratio) the TAP lost amplitude and duration. These results are consistent with the theory that the source-to-sink ratio determines the safety factor for wave propagation and wave block near the core. With decreasing source-to-sink ratio, TAP progressively decreases in amplitude and duration. In the center of the core, the cells, while excitable, remain quiescent near their resting potential. This decrease reflects a progressive decrease in the source-to-sink ratio. TAP vanishes in the core where cells remain quiescent near their resting potential. Functional and meandering reentrant wavefronts are compatible with the spiral mechanism of reentry where block at the rotating point is provided by the steep curvature of the wave tip.

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.

OBJECTIVES: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND: The role of increased fibrosis in reentry formation during human VF is unclear. METHODS: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS: Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS: In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.

Induction of meandering functional reentrant wave front in isolated human atrial tissues.

BACKGROUND: The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues. METHODS AND RESULTS: The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.4+/-0.3 mm thick, were excised and trimmed to 3.5x3.0 cm. The isolated atrium was placed endocardial surface down in a chamber with a 477 bipolar recording electrode array built into the bottom of the tissue bath. The interelectrode distance was 1.6 mm. The tissue was constantly superfused with 36.5 degrees C oxygenated Tyrode's solution at a rate of 10 mL/min. After eight baseline stimuli (S1) delivered at 400- or 600-ms cycle length from the edge of the tissue, a single premature stimulus (S2) was given at the center of the tissue to induce reentry. A total of nine episodes of reentry were induced with S1-S2 coupling intervals of 232+/-29 ms (range, 190 to 290 ms) and an S2 strength of 10+/-3 mA (range, 5 to 15 mA). In all samples, a single meandering reentrant wave front was induced, causing irregular and rapid bipolar electrogram activity. These wave fronts had a mean cycle length of 229+/-45 ms (160 to 290 ms) and persisted for 1.1+/-0.3 seconds (0.6 seconds to 2.5 seconds), or 5.2+/-1.4 (3 to 9) cycles, before spontaneous termination. CONCLUSIONS: A single meandering functional reentrant wave front can be induced in human atrial tissues and produce rapid and irregular electrical activity.

Attachment of meandering reentrant wave fronts to anatomic obstacles in the atrium. Role of the obstacle size.

Acetylcholine chloride (ACh) induces nonstationary meandering reentrant wave fronts in the atrium. We hypothesized that an anatomic obstacle of a suitable size prevents meandering by causing attachment of the reentrant wave front tip to the obstacle. Eight isolated canine right atrial tissues (area, 3.8 x 3.2 cm) were mounted in a tissue bath and superfused with Tyrode's solution containing 10 to 15 mumol/L ACh. Holes with 2- to 10-mm diameters were sequentially created in the center of the tissue with biopsy punches. Reentry was induced by a premature stimulus after eight regular stimuli at 400-ms cycle length. The endocardial activation maps and the motion of the induced reentry were visualized dynamically before and after each test lesion using 509 bipolar electrodes. In the absence of a lesion (n = 8), the induced single reentrant wave front, in the form of a spiral wave, meandered irregularly from one site to another before terminating at the tissue border. Holes with 2- to 4-mm diameters (n = 6) had no effect on meandering. However, when the hole diameters were increased to 6 mm (n = 8), 8 mm (n = 8), and 10 mm (n = 6), the tip of the spiral wave attached to the holes, and reentry became stationary. Transition from meandering to an attached state converted the irregular and polymorphic electrogram to a periodic and monomorphic activity with longer cycle lengths (101 +/- 11 versus 131 +/- 9 ms for no hole versus 10-mm hole, respectively; P < .001). Regression analysis showed a significant positive linear correlation between the cycle length of the reentry and the hole diameter (r = .89, P < .01) and between the cycle length of the reentry and the excitable gap (r = .89, P < .05). We conclude that a critically sized anatomic obstacle converts a nonstationary meandering reentrant wave front to a stationary one. This transition converts an irregular "fibrillation-like" activity into regular monomorphic activity.

Atypical atrioventricular node reciprocating tachycardia masquerading as tachycardia using a left-sided accessory pathway.

OBJECTIVES: The study was performed to document that atrioventricular node reciprocating tachycardia (AVNRT) can be associated with eccentric retrograde left-sided activation, masquerading as tachycardia using a left accessory pathway. BACKGROUND: The eccentric retrograde left-sided activation during tachycardia is thought to be diagnostic of the presence of a left free wall accessory pathway. However, it is not known whether AVNRT can occur with eccentric retrograde left-sided activation. METHODS: We studied 356 patients with AVNRT who underwent catheter ablation. Retrograde atrial activation during tachycardia and ventricular pacing were determined by intracardiac recordings, including the use of a decapolar coronary sinus catheter. RESULTS: The retrograde atrial activation was eccentric in 20 patients (6%). Eight of these patients had the earliest retrograde atrial activation recorded in the lateral coronary sinus leads, and 12 had the earliest retrograde atrial activation recorded in the posterior coronary sinus leads, with the most proximal coronary sinus electrode pair straddling the coronary sinus orifice. These tachycardias were either the fast-slow or the slow-slow form of AVNRT. The slow-fast form of AVNRT was also inducible in 17 of the 20 patients. Successful ablation of the slow pathway in the right atrial septum near the coronary sinus ostium prevented the induction and clinical recurrence of reciprocating tachycardia in all patients. CONCLUSIONS: Atypical AVNRT with eccentric retrograde left-sided activation was demonstrated in 6% of all patients with AVNRT masquerading as tachycardia using a left-sided accessory pathway. Ablation of the slow pathway at the posterior aspects of the right atrial septum resulted in a cure in these patients.

Meandering and unstable reentrant wave fronts induced by acetylcholine in isolated canine right atrium.

The mechanism(s) by which acetylcholine (ACh) increases atrial vulnerability to reentry and maintains its activity for longer durations remains poorly defined. In the present study we used high-resolution activation maps to test the hypothesis that ACh promotes meandering of atrial reentrant wave fronts, resulting in breakup and the generation of new wave fronts that sustain the activity. Reentry was induced in 11 isolated canine right atrial tissues (3.8 x 3.2 cm) by a premature point stimulus (S2) before and after superfusion with ACh (15 x 10(-6) M). Endocardial isochronal activation maps were constructed with the use of 509 bipolar electrodes (1.6-mm spatial resolution), and the dynamics of the activation wave fronts were visualized with animation. A vulnerable period was found during which an S2 current strength > 4.4 +/- 2.5 mA [lower limit of vulnerability (LLV)] and < 26 +/- 13 mA [upper limit of vulnerability (ULV)] induced a single stationary reentrant wave front that lasted 3 +/- 2.5 s with a period of 159 +/- 17 ms (16 episodes). AC shortened the refractory period from 100 +/- 12 to 59 +/- 9 ms (P < 0.001) and increased vulnerability to reentry induction by simultaneous decrease in the LLV (0.7 +/- 0.2 mA, P < 0.001) and an increase in the ULV (82 +/- 24 mA, P < 0.01). ACh accelerated the rate (period of 110 +/- 16 ms, P < 0.001) and converted the stationary reentrant wave front to a nonstationary (meandering) reentrant wave front showing polymorphic electrograms, i.e., "fibrillation-like" activity (22 episodes). Rapid meandering of the reentry tip led to wave front breakup (18 episodes) and the generation of new wave fronts (19 episodes). These wave front dynamics also led to sustained (76 +/- 224 s, P < 0.001) fibrillation-like electrograms. We conclude that ACh increases the ULV and promotes meandering of a single reentrant wave front, leading to breakup and the generation of new wave fronts. Single meandering and complex wave front dynamics cause fibrillation-like activity and sustain the activity for longer duration.

Cellular graded responses and ventricular vulnerability to reentry by a premature stimulus in isolated canine ventricle.

BACKGROUND: The cellular mechanism by which a point strong premature stimulus (S2) induces reentry is unknown. We hypothesized that cellular graded responses induced by an S2 mediate and control tissue vulnerability to reentry. METHODS AND RESULTS: Reentry is induced in normal canine ventricular epicardial slices (30x38x2 mm, n=30) by an S2 at intervals shorter than the effective refractory period. The S1 is applied at the edge and the S2 at the center of the tissue. The line connecting the S1-S2 sites is parallel to the long axis of the fiber orientation. Isochronal activation maps were constructed with 56 to 480 bipolar electrodes, and the activation pattern was visualized dynamically. Reentry induced by an S2 is mediated by the graded responses as follows: The induced graded responses propagate with decrement toward recovered cells. When the amplitude of the propagated depolarizing graded responses reaches threshold relative to the recovering cells, an action potential is initiated along the fiber 2 to 3 mm away from the cathode of the S2. The distally initiated activation wave front blocks near the S2 site because the same S2-induced graded response prolongs the refractory period. The "broken" wave front then circulates around both sides of the block and reenters when the site of block recovers its excitability, completing the first figure-eight reentry cycle. Reentry cannot be induced when the S2 strength is >72+/-21 mA (upper limit of vulnerability) because these strong S2-induced graded responses convert the unidirectional block to bidirectional block by excess prolongation of the refractoriness. CONCLUSIONS: We conclude that the magnitude and the propagation of S2-induced cellular graded responses mediate and control vulnerability to reentry in the ventricular epicardium.

Upper limit of vulnerability predicts chronic defibrillation threshold for transvenous implantable defibrillators.

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.

Programming of implantable cardioverter-defibrillators on the basis of the upper limit of vulnerability.

BACKGROUND: A patient-specific measure of defibrillation efficacy that requires a minimum number of ventricular fibrillation (VF) episodes would be valuable for programming implantable cardioverter-defibrillators (ICDs). The upper limit of vulnerability (ULV) is the weakest shock strength at or above which VF is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It correlates with the defibrillation threshold (DFT) and can be determined with a single episode of VF. The objective of this study was to test the hypothesis that ICDs programmed on the basis of the ULV convert spontaneous ICD-detected VF reliably. METHODS AND RESULTS: We studied 100 consecutive patients at ICD implantation and during follow-up of 20 +/- 7 months. At implantation, the ULV and DFT were determined, and the ICD system was tested at a shock strength equal to the ULV + 3 J. During follow-up, the strength of the first shock was programmed to the ULV + 5 J for arrhythmias detected in the VF zone (cycle length < 292 +/- 17 ms). We reviewed stored detection intervals and electrograms from spontaneous episodes of ICD-detected VF to determine the success rate for appropriate first shocks. The programmed first-shock strength was 17.5 +/- 5.2 J. During follow-up, there were 120 appropriate first shocks in 37 patients. The arrhythmia was rapid monomorphic ventricular tachycardia (VT) in 70% of episodes (31 patients), VF in 11% (13 patients), polymorphic VT in 1%, and unclassified in 17% (15 patients). The first shock was successful in 119 of 120 episodes (99%; 95% CI, 93% to 100%). One unclassified episode required two shocks. No patient had syncope associated with an ICD shock or arrhythmic death. CONCLUSIONS: ICD shocks can be programmed on the basis of the ULV, a measurement made in regular rhythm, without a direct measure of defibrillation efficacy.

The zone of vulnerability to T wave shocks 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 +/- 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.

Mechanism of spontaneous termination of functional reentry in isolated canine right atrium. Evidence for the presence of an excitable but nonexcited core.

BACKGROUND: According to the spiral wave hypothesis of reentry, the core of functional reentry remains excitable but not excited. We sought to determine whether the core remains excitable and whether excitation of the core by an outside wave front leads to termination of the reentry in the atrium. METHODS AND RESULTS: In nine isolated canine right endocardial atrial tissues (3.8 by 3.2 cm wide), reentry was induced by a premature point stimulus (S2). The isochronal activation maps and dynamics of the activation patterns were visualized with the use of 509 bipolar electrodes (1.6-mm resolution). The S2 applied after 8 regular beats induced reentry with a mean cycle length of 162 +/- 20 ms (15 episodes). Reentry had a large excitable gap (93 +/- 26 ms) as determined by early capture with twice the level of threshold stimuli. The central area (core) around which the wave fronts rotated had a mean surface area of 12 +/- 3 mm2. The electrograms located in the core of the reentry registered no or very low amplitude potentials. In 13 of 15 episodes, reentry terminated when an outside new wave front merged with the original wave front and excited the core. Core excitation caused disruption of the original wave front, and the newly formed wave front(s) vanished at the tissue border within 77 +/- 18 ms. In 2 episodes, reentry terminated abruptly when an outside new wave front propagating in a direction opposite to the reentrant wave front collided with the leading edge of the reentrant wave front. CONCLUSIONS: Functional reentry in the atrium is compatible with a spiral wave of excitation with an excitable but nonexcited core and a large excitable gap. Reentry may be terminated either by direct excitation of the core that displaces the wave front to the tissue border or by collision with an outside new wave front.

Upper limit of vulnerability is a good estimator of shock strength associated with 90% probability of successful defibrillation in humans with transvenous implantable cardioverter-defibrillators.

OBJECTIVES: The goals of this study were to determine the probability of successful defibrillation at the upper limit of vulnerability and to evaluate a minimal safety margin for implantable cardioverter-defibrillator first shocks based solely on the upper limit of vulnerability. BACKGROUND: The upper limit of vulnerability is the strength at or above which ventricular fibrillation is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It has been proposed as an estimate of defibrillation efficacy because it correlates with the defibrillation threshold and can be determined with a single episode of fibrillation. METHODS: We studied 40 patients prospectively at implantation of transvenous cardioverter-defibrillators. Defibrillation threshold was defined as the weakest biphasic shock that defibrillated after 10 s of ventricular fibrillation. The upper limit of vulnerability was defined as the weakest biphasic shock that did not induce ventricular fibrillation when given at 0, 20 and 40 ms before the peak of the T wave in ventricular paced rhythm at cycle length 500 ms. After determination of the upper limit of vulnerability and defibrillation threshold, patients underwent six additional fibrillation-defibrillation episodes. The strength of five of the defibrillation shocks was equal to the upper limit of vulnerability; the strength of one of the six shocks was randomly selected to be equal to the upper limit of vulnerability plus 3 J. The implantable cardioverter-defibrillator was tested at the upper limit of vulnerability plus 3 J in 28 patients. RESULTS: The defibrillation threshold was 8.8 +/- 5.0 J (mean +/- SD), and upper limit of vulnerability was 11.3 +/- 4.6 J; the defibrillation threshold and upper limit of vulnerability were highly correlated (r = 0.89, p < 0.001). The success rate for the 200 defibrillation shocks with strength equal to the upper limit of vulnerability was 90% (95% confidence intervals based on proportion of successes in 40 patients: 86% to 94%). All five defibrillation test shocks at the upper limit of vulnerability were successful in 24 patients (60%); four of five were successful in 12 patients (30%); and three of five were successful in 4 patients (10%). All 40 test shocks and 28 implantable cardioverter-defibrillator shocks with a strength equal to the upper limit of vulnerability plus 3 J were successful. CONCLUSIONS: The upper limit of vulnerability is a good estimator of the shock strength associated with 90% probability of successful defibrillation (DFT90). A strength of 3 J above the upper limit of vulnerability is a good estimate of the minimal acute safety margin for implantable cardioverter-defibrillator first shocks.

Cellular mechanisms of ventricular bipolar electrograms showing double and fractionated potentials.

OBJECTIVES: This study sought to determine the types of trans-membrane action potentials associated with bipolar electrograms that show double and fractionated potentials. BACKGROUND: The cellular correlates of ventricular bipolar electrograms showing double potentials and fractionated low amplitude potentials remain poorly defined. METHODS: A bipolar electrogram (1-cm interelectrode distance [6F, USCI]) and two transmembrane action potentials (within 1 mm of each pole) were recorded simultaneously in 12 isolated canine right ventricular endocardial preparations (2 x 1 cm, 2 mm thick). The long axis of the bipolar electrode was parallel to the long axis of the superficial endocardial fibers, and the recordings were made at 40 to 500 Hz. RESULTS: The following phenomena were associated with double potentials: 1) an increase in conduction time between the two poles of the bipole during a) the propagation of premature action potentials (7 of 12 tissues in 4 mmol/liter extracellular potassium ion concentration [K+]o); b) rapid pacing and premature stimuli (3 of 6 in 9 mmol/liter [K+]o); and c) the propagation of slow responses induced by barium chloride (4 mmol/liter). There was a positive correlation between conduction time (CT) and interspike interval (IPI) of the double potential (IPI [ms] = 0.5 x CT [ms] + 35) during early afterdepolarizations induced by barium chloride (4 mmol/liter) superfusion (three of six tissues). The following events were associated with fractionated electrograms: 1) propagation of induced graded responses (six tissues) in 4 mmol/liter [K+]o; 2) induced reentry at cycle lengths of 140 to 170 ms in 9 mmol/liter [K+]o (four of six tissues); and 3) asynchronous afterdepolarizations induced by 4 mmol/liter barium chloride (four of six tissues). CONCLUSIONS: Endocardial double potentials and fractionated electrograms seen on clinically used bipolar electrodes occur under conditions of slowed or discontinuous conduction and induced reentry and during asynchronous automatic firing initiated by afterdepolarizations. Caution must be exercised in interpreting such bipolar electrograms because more than one type of cellular action potential may cause these abnormal electrographic results.

Optimal electrode configuration for pectoral transvenous implantable defibrillator without an active can.

A new 83 cm3 implantable cardioverter-defibrillator (ICD) designed for pectoral implantation has been implanted most frequently using right ventricular and superior vena cava (RV-->SVC) electrodes; a patch electrode (RV-->patch + SVC) has been added when necessary to decrease the defibrillation threshold (DFT). The goal of this prospective study was to compare biphasic waveform DFTs for 3 electrode configurations: RV-->patch, RV-->SVC, and RV-->patch + SVC in 25 consecutive patients. The patch was positioned in a left retro-pectoral pocket, and the SVC electrode was positioned with the tip at the junction of the SVC and innominate vein. In the first 15 patients, all 3 electrode configurations were tested in random order; in the last 10 patients, only the RV-->patch and RV-->patch + SVC configurations were tested. In the first 15 patients, the stored-energy DFT for the RV-->SVC configuration (15.2 +/- 7.7 J) was higher (p < 0.001) than the DFT for the RV-->patch configuration (11.3 +/- 6.2 J) and the RV-->patch + SVC configuration (10.0 +/- 5.8 J). For all 25 patients, the DFT was lower for the RV-->patch + SVC configuration (9.7 +/- 5.1 J) than for the RV-->patch configuration (12.4 +/- 6.6 J, p = 0.005). The pathway resistance was highest for the RV-->patch configuration (72 +/- 9 omega), lower for the RV-->SVC configuration (63 +/- 6 omega, p < 0.01), and lowest for the RV-->patch + SVC configuration (46 +/- 3 omega, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Wolff-Parkinson-White syndrome in a cardiac allograft.

A 61-year-old man underwent orthotopic heart transplantation for end-stage ischemic cardiomyopathy. The donor presented with Wolff-Parkinson-White syndrome and the allograft was successfully transplanted. The accessory pathway was interrupted postoperatively by radiofrequency current catheter ablation, and the patient is clinically well and free of preexcitation 24 months later.

Upper limit of vulnerability reliably predicts the defibrillation threshold in humans.

BACKGROUND: The upper limit of vulnerability is the stimulus strength above which electrical stimulation cannot induce ventricular fibrillation even when the stimulus occurs during the vulnerable period of the cardiac cycle. The purpose of this study was to test the hypothesis that the upper limit of vulnerability can accurately predict the defibrillation threshold in patients undergoing implantable cardioverter-defibrillator (ICD) implantation using nonthoracotomy lead systems. METHODS AND RESULTS: We studied 77 patients at the time of ICD implantation. Multiple endocardial-endocardial and endocardial-subcutaneous shock pathways were used. Two different protocols were used to test the upper limit of vulnerability. In protocol 1 (n = 17), the upper limit of vulnerability was tested with two shocks on the peak or the up-slope of the T wave of paced rhythm. The shocks were given randomly either at the peak and 20 milliseconds before the peak of T wave (n = 7) or at 20 and 40 milliseconds before the peak of T wave (n = 10). In protocol 2 (n = 60), the upper limit of vulnerability was tested with three shocks delivered at 0, 20, and 40 milliseconds before the peak of the T wave. The weakest shock that failed to induce ventricular fibrillation by a 5-J step-down or step-up method was defined as the upper limit of vulnerability. The defibrillation threshold was also determined by a 5-J step-down or step-up method. In protocol 1, the upper limit of vulnerability (9 +/- 6 J) was significantly lower than the defibrillation threshold (13 +/- 7 J) with a correlation coefficient of .87 and P < .001. In protocol 2, the upper limit of vulnerability (13 +/- 6 J) was not significantly different from the defibrillation threshold (13 +/- 6 J) with a correlation coefficient of .85 and P < .001. In 45 of the 60 patients, the upper limit of vulnerability was < or = 15 J; all had a defibrillation threshold of < or = 20 J. In 51 of the 60 patients, the upper limit of vulnerability was within 5 J of the defibrillation threshold. The upper limit of vulnerability overestimated the defibrillation threshold by > 10 J in 8 patients and underestimated the defibrillation threshold by > 10 J in only 1 patient. The overestimation and underestimation occurred only in patients with the upper limit of vulnerability > 15 J. CONCLUSIONS: When tested with three shocks on and before the peak of the T wave, the upper limit of vulnerability accurately predicted the defibrillation threshold in patients undergoing ICD implantation using nonthoracotomy lead systems. This method required either one or no episodes of ventricular fibrillation in most patients.