Maintenance Of Ventricular Tachycardia Research Articles

Optimisation of decrementing evoked potential mapping for functional substrate identification in ischaemic ventricular tachycardia ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Decrement evoked potential (DeEP) mapping has been shown to identify the functional substrate critical to the Ventricular Tachycardia (VT) circuit with a higher specificity than late potential mapping.[1] However, there is limited data on methodological optimisation of this technique which could identify more relevant regions of conduction delay and functional block that occurs during clinical VT by activating the substrate at coupling intervals closer to the VT cycle length (CL). Purpose The goal of this study was to investigate a range of short coupled extra-stimuli and decrement thresholds to improve DeEP mapping target identification in patients with ischaemic cardiomyopathy. Methods Thirteen patients (70±12 years) underwent VT ablation. Mapping was performed with the Advisor HD Grid multipolar catheter. Maps were generated using omnipolar electrograms (EGMs). DeEP mapping was performed using 3 different extra-stimuli (S2) sequentially in each case: (1) 400 ms (DeEP-400); (2) VT cycle length (VTCL); (3) ventricular effective refractory period (VERP) + 20 ms. For each of the DeEP-400, DeEP-VTCL and DeEP-VERP maps, the definition of a DeEP was altered from the standard 10 ms decrement to multiple thresholds of 10 ms to 50 ms in 10 ms increments (figure 1). DeEP maps were compared to the VT exit site identified with VT activation maps. All patients underwent DeEP-400 focused ablation. Results All patients had 1 clinical VT (VTCL = 353 ± 48 ms; VERP + 20 ms = 300 ± 20 ms). Mean left ventricular ejection fraction was 30 ± 12 %. Sensitivity and specificity analyses (figure 2) show the optimal threshold for defining a DeEP is with an EGM prolongation of ≥ 20 ms for the DeEP-400 (sens. 77%, spec. 79%, ROC AUC 0.84), DeEP-VTCL (sens. 77%, spec. 79%, ROC AUC 0.83) and DeEP-VERP (sens. 69%, spec. 74%, ROC AUC 0.76) maps. Proportional to total mapped area, the DeEP-400 map area was significantly smaller than DeEP-VERP map area (19.0 ± 7.6 % vs 26.4 ± 14.3%; p=0.02). Delivering the S2 at the conventional VERP + 20 ms using a 10 ms decrement definition yielded a sensitivity of 84.6% and a specificity of 62.0% with a target ablation area of 33.9 cm2. With the optimised protocol of delivering the S2 at 400 ms using a 20 ms decrement definition, the sensitivity remains high at 76.9% with an improved specificity of 79.0%, thus reducing the ablation target area by 50% to 16.8 cm2. 92% patients were free of any VT after DeEP-400 guided ablation at 6-month median follow-up. Conclusion In this prospective, mechanistic study utilising omnipolar technology to explore a range of S2 extra-stimuli and decrement thresholds, DeEPs were optimally defined by a conduction delay of ≥ 20 ms with an S2 extra-stimulus coupling interval of 400 ms or VTCL to more accurately localise the VT exit site. This optimised DeEP mapping protocol further refines identification of the critical myocardial sites involved in the initiation and maintenance of VT.

Role of Scar and Border Zone Geometry on the Genesis and Maintenance of Re-Entrant Ventricular Tachycardia in Patients With Previous Myocardial Infarction.

In patients with healed myocardial infarction, the left ventricular ejection fraction is characterized by low sensitivity and specificity in the prediction of future malignant arrhythmias. Thus, there is the need for new parameters in daily practice to perform arrhythmic risk stratification. The aim of this study is to identify some features of proarrhythmic geometric configurations of scars and border zones (BZ), by means of numerical simulations based on left ventricular models derived from post myocardial infarction patients. Two patients with similar clinical characteristics were included in this study. Both patients exhibited left ventricular scars characterized by subendo- and subepicardial BZ and a transmural BZ isthmus. The scar of patient #1 was significantly larger than that of patient #2, whereas the transmural BZ isthmus and the subdendo- and subepicardial BZs of patient #2 were thicker than those of patient #1. Patient #1 was positive at electrophysiologic testing, whereas patient #2 was negative. Based on the cardiac magnetic resonance (CMR) data, we developed a geometric model of the left ventricles of the two patients, taking into account the position, extent, and topological features of scars and BZ. The numerical simulations were based on the anisotropic monodomain model of electrocardiology. In the model of patient #1, sustained ventricular tachycardia (VT) was inducible by an S2 stimulus delivered at any of the six stimulation sites considered, while in the model of patient #2 we were not able to induce sustained VT. In the model of patient #1, making the subendo- and subepicardial BZs as thick as those of patient #2 did not affect the inducibility and maintenance of VT. On the other hand, in the model of patient #2, making the subendo- and subepicardial BZs as thin as those of patient #1 yielded sustained VT. In conclusion, the results show that the numerical simulations have an effective predictive capability in discriminating patients at high arrhythmic risk. The extent of the infarct scar and the presence of transmural BZ isthmuses and thin subendo- and subepicardial BZs promote sustained VT.

Signature signal strategy: Electrogram-based ventricular tachycardia mapping

Multiple decades of work have recognized complexities of substrates responsible for ventricular tachycardia (VT). There is sufficient evidence that 3 critical components of a re-entrant VT circuit, namely, region of slow conduction, zone of unidirectional block, and exit site, are located in spatial vicinity to each other in the ventricular scar. Each of these components expresses characteristic electrograms in sinus rhythm, at initiation of VT, and during VT, respectively. Despite this, abnormal electrograms are widely targeted without appreciation of these signature electrograms during contemporary VT ablation. Our aim is to stimulate physiology-based VT mapping and a targeted ablation of VT. In this article, we focus on these 3 underappreciated aspects of the physiology of ischemic scar-related VT circuits that have practical applications during a VT ablation procedure. We explore the anatomic and functional elements underlying these distinctive bipolar electrograms, specifically the contribution of tissue branching, conduction restitution, and wave curvature to the substrate, as they pertain to initiation and maintenance of VT. We propose a VT ablation approach based on these 3 electrogram features that can be a potential practical means to recognize critical elements of a VT circuit and target ablation.

Multicenter Study of Ischemic VentricularTachycardia Ablation WithDecrement-Evoked Potential (DEEP)Mapping With Extra Stimulus.

The authors conducted a multicenter study of decrement-evoked potential (DEEP)-based functional ventricular tachycardia (VT) substrate modification to evaluate if such a mechanistic and physiological strategy is feasible and efficient in clinical practice and provides reduction in the VT burden. Only a fraction of the myocardium targeted in current VT substrate modification procedures is involved in the initiation and perpetuation of VT. The physiological basis of the DEEP strategy for identification of areas of initiation and maintenance of VT was recently established. We included 20 consecutive patients with ischemic cardiomyopathy. During substrate mapping, fractionated and late potentials (LPs) were tagged, and an extra stimulus was performed to determine which LPs displayed decrement(DEEPs). All patients underwent DEEP-focused ablation: elimination of DEEP+ further radiofrequency (RF) if VT was still inducible. Patients were followed during 6 months. Patients were predominantly male (95%), and their mean age was 64.6 ± 17.1 years. Mean left ventricular ejection fraction was 33.4 ± 11.4%. Mean ablation time was 30.6 ± 20.4 min. Specificity of DEEPsto detect the isthmus of VT was better than that of LPs (0.97 [95% confidence interval [CI]: 0.95 to 0.98] vs. 0.82 [95% CI: 0.73 to 0.89]), without significant differences in terms of sensitivity (0.61 [95% CI: 0.52 to 0.69] vs. 0.60[95% CI: 0.44 to 0.74], respectively). Fifteen of 20 (75%) patients were free of any VT after DEEP-RF at 6 months of follow-up and there was a strong reduction in VT burden compared to 6 months pre-ablation. In a multicenter prospective study, DEEP substrate mapping identified the functional substrate critical to the VT circuit with high specificity. DEEP-guided VT ablation, by its physiological nature, may enable greater accesstofocused ablation therapy for patients requiring VT treatment.

Pro-arrhythmogenic effects of CACNA1C G1911R mutation in human ventricular tachycardia: insights from cardiac multi-scale models.

Mutations in the CACNA1C gene are associated with ventricular tachycardia (VT). Although the CACNA1C mutations were well identified in patients with cardiac arrhythmias, mechanisms by which cardiac arrhythmias are generated in such genetic mutation conditions remain unclear. In this study, we identified a novel mechanism of VT resulted from enhanced repolarization dispersion which is a key factor for arrhythmias in the CACNA1C G1911R mutation using multi-scale computational models of the human ventricle. The increased calcium influx in the mutation prolonged action potential duration (APD), produced steepened action potential duration restitution (APDR) curves as well as augmented membrane potential differences among different cell types during repolarization, increasing transmural dispersion of repolarization (DOR) and the spatial and temporal heterogeneity of cardiac electrical activities. Consequentially, the vulnerability to unidirectional conduction block in response to a premature stimulus increased at tissue level in the G1911R mutation. The increased functional repolarization dispersion anchored reentrant excitation waves in tissue and organ models, facilitating the initiation and maintenance of VT due to less meandering rotor tip. Thus, the increased repolarization dispersion caused by the G1911R mutation is a primary factor that may primarily contribute to the genesis of cardiac arrhythmias in Timothy Syndrome.

End points for ablation of scar-related ventricular tachycardia.

The goal of catheter ablation strategies for the treatment of scar-related ventricular tachycardia (VT) is the interruption of critical areas of slow conduction within the VT circuits responsible for the development and maintenance of VTs.1,2 Clinical studies have consistently shown the superiority of radiofrequency catheter ablation compared with standard medical therapy in controlling recurrent VT.3,4 However, even after an acutely successful ablation, the long-term freedom from recurrent VT remains suboptimal, especially in patients with nonischemic substrates where the recurrence rates for long-term follow-up can be as high as 77%.5 Identification of the optimal end points for VT ablation is crucial to improve the success rate of this procedure. The response to programmed electric stimulation (PES) at the end of the procedure has been traditionally used to evaluate the acute success and predict long-term outcomes.1,2 Noninducibility by PES represents a classical end point for VT ablation and the only 1 endorsed by the current practice guidelines.1,2 Of note, a direct association between VT noninducibility at the end of the procedure and long-term arrhythmia-free survival has been suggested but not uniformly demonstrated.4,6–9 More recently, the increasing adoption of substrate-based ablation techniques, which target specific electrograms indexing slow conduction (ie, abnormal, split, and late electrograms) in sinus rhythm and reasonable surrogates for the VT isthmus,10,11 has been paralleled by an increasing need for new ablation end points. Although noninducibility at PES has been used as an end point also in studies evaluating substrate-based ablation approaches, other procedural end points have been described to validate the completeness of linear lesions and the elimination of abnormal potentials within the scar. This review will summarize the state of the art regarding procedural end points for …

Calcium alternans induced by enhanced dephosphorylation of phospholamban predisposes to inducibility of ventricular tachycardia in the type I diabetic Akita mouse (1078.9)

Introduction: Diabetes mellitus is associated with increased risk of sudden cardiac death. Little evidence exists to support specific mechanisms to account for this association. We studied the inducibility of ventricular tachycardia (VT) in the type I diabetic Akita mouse and ionic and molecular mechanisms of arrhythmogensis. Methods: Inducibility of VT was studied by programmed ventricular stimulation and optical mapping. Left ventricular myocytes were isolated for electrophysiology and calcium imaging studies. Sarcomere shortening and Ca2+ transients were measured using the Ionoptix system. Results: Programmed ventricular stimulation of Akita mice resulted in VT in 80% of mice compared to 20% of WT. Optical mapping of perfused hearts demonstrated multifocal breakthroughs which occasionally gave rise to short lived rotors consistent with focal initiation and maintenance of VT. Both contractile and Ca2+ transient alternans were observed in single ventricular myocytes of Akita mice at field stimulations above 4 Hz. 100nM Iso induced triggered activity in 90% of myocytes from Akita and 7% in WT mice. Ventricular myocytes from Akita mice demonstrated decreased SR Ca2+ reuptake (τ= 170±10 ms vs.138±7ms, n=20, p<0.01) compared to WT and increased cytosolic Ca2+[[Unsupported Character ‐ Codename ­]][[Unsupported Character ‐ Codename ­]]. Caffeine induced Ca2+ release was significantly decreased in Akita mice vs. WT. Western blot analysis showed that phosphorylated ser16 phospholamban (PLB) and the ratio of SERCA2a/total PLB were significantly decreased in Akita mice. Conclusions: Increased dephosphorylation of PLB caused abnormal SR Ca2+ loading resulting in cardiac alternans predisposing to the development of VT in type 1 diabetic Akita mice.Grant Funding Source: NIH

Increased inducibility of ventricular tachycardia and decreased heart rate variability in a mouse model for type 1 diabetes: effect of pravastatin

Although a reduction in the high-frequency (HF) component of heart rate variability (HRV) is a major complication of diabetes and a risk factor for sudden death, its relationship to ventricular tachycardia (VT) is unknown. We developed a mouse model for the study of VT and its relationship to changes in HRV in the Akita type 1 diabetic mouse. Programmed ventricular stimulation of anesthetized mice demonstrated that Akita mice were more inducible for VT compared with wild-type mice: 78.6% versus 28.6% (P = 0.007). Optical mapping of perfused hearts demonstrated multifocal breakthroughs that occasionally gave rise to short-lived rotors consistent with focal initiation and maintenance of VT. Treatment of Akita mice with pravastatin, which had been previously shown clinically to decrease ventricular ectopy and to increase HRV, decreased the inducibility of VT: 36.8% compared with 75.0% with placebo treatment (P = 0.022). The HF fraction of HRV was reduced in Akita mice (48.6 ± 5.2% vs. 70.9 ± 4.8% in wild-type mice, P = 0.005) and was increased compared with placebo treatment in pravastatin-treated mice. Pretreatment of Akita mice with the muscarinic agonist carbamylcholine or the β-adrenergic receptor blocker propranolol decreased the inducibility of VT (P = 0.001). In conclusion, the increased inducibility of focally initiated VT and reduced HF fraction in Akita mice were partially reversed by both pravastatin treatment and pharmacologic reversal of parasympathetic dysfunction. In this new animal model for the study of the pathogenesis of VT in type 1 diabetes, pravastatin may play a role in the prevention of VT by attenuating parasympathetic dysfunction.

The main trunk of the left bundle branch is not part of the re-entry circuit of verapamil-sensitive idiopathic left ventricular tachycardia

We report the case of a 19-year-old man with verapamil-sensitive idiopathic left ventricular tachycardia (ILVT), who had paroxysmal palpitations for 3 years. Programmed right atrial and ventricular stimulation easily induced ventricular tachycardia (VT) with QRS duration of 125ms, right bundle branch block pattern, and right inferior axis, which are characteristics of ILVT. Left ventricular endocardial mapping accidentally produced a complete left bundle branch block and provoked prolongation of the QRS duration of VT, which was 143ms. However, no changes occurred in the cycle length, inducibility, or maintenance of VT. The VT was eliminated successfully by catheter ablation at the pre-Purkinje potential (PP) recording site. These findings suggest that the main trunk of the left bundle branch is not a critical component of the re-entry circuit of ILVT.

High-Density Substrate Mapping in Brugada Syndrome

Two principal mechanisms are thought to be responsible for Brugada syndrome (BS): (1) right ventricular (RV) conduction delay and (2) RV subepicardial action potential shortening. This in vivo high-density mapping study evaluated the conduction and repolarization properties of the RV in BS subjects. A noncontact mapping array was positioned in the RV of 18 BS patients and 20 controls. Using a standard S(1)-S(2) protocol, restitution curves of local activation time and activation recovery interval were constructed to determine local maximal restitution slopes. Significant regional conduction delays in the anterolateral free wall of the RV outflow tract of BS patients were identified. The mean increase in delay was 3-fold greater in this region than in control (P=0<0.001). Local activation gradient was also maximally reduced in this area: 0.33+/-0.1 (mean+/-SD) mm/ms in BS patients versus 0.51+/-0.15 mm/ms in controls (P<0.0005). The uniformity of wavefront propagation as measured by the square of the correlation coefficient, r(2), was greater in BS patients versus controls (0.94+/-0.04 versus 0.89+/-0.09 [mean+/-SD]; P<0.05). The odds ratio of BS hearts having any RV segment with maximal restitution slope >1 was 3.86 versus controls. Five episodes of provoked ventricular tachycardia arose from wave breaks originating from RV outflow tract slow-conduction zones in 5 BS patients. Marked regional endocardial conduction delay and heterogeneities in repolarization exist in BS. Wave break in areas of maximal conduction delay appears to be critical in the initiation and maintenance of ventricular tachycardia. These data indicate that further studies of mapping BS to identify slow-conduction zones should be considered to determine their role in spontaneous ventricular arrhythmias.

ECG Clues for Diagnosing Ventricular Tachycardia Mechanism

Three mechanisms underlie the initiation and maintenance of ventricular tachycardia: automaticity, triggered activity, and reentry. As straightforward as these mechanisms are, assessing which mechanism is operative in a particular patient's ventricular tachycardia can be difficult. The optimal treatment strategy for ventricular tachycardia in a given patient can be influenced by the mechanism underlying the ventricular tachycardia. Appropriately counseling patients, choosing the optimal pharmacologic agent that maximizes efficacy while minimizing undesirable side effects, risks, and toxicities, as well as recommending and timing ablative therapy all hinge on identifying the probable mechanism of ventricular tachycardia. Much has been published regarding invasive electrophysiologic maneuvers that allow for correct diagnosis of ventricular tachycardia mechanism. The aim of this clinical review is to provide insight into VT mechanisms based on ECG clues of spontaneous arrhythmia events and the response to pharmacologic manipulation prior to invasive electrophysiologic evaluation.

Antifibrillatory and Proarrhythmic Effects of d,l-Sotalol Mediated by the Action Potential Duration Restitution Kinetics

Background and Objectives：The action potential duration (APD) restitution kinetics has been known to play a crucial role in the initiation and maintenance of ventricular tachycardia (VT)/fibrillation (VF). We hypothesized that “the anti-arrhythmic and proarrhythmic effects of d,l-sotalol are mediated by changing the APD restitution (APDR) kinetics”. Materials and Methods：The purposes of this study were: 1) to assess the effects of d,lsotalol on the APDR kinetics, and 2) to correlate the anti-arrhythmic and proarrhythmic action using the APDR kinetics. We recorded the transmembrane potentials (TMPs), using the microelectrode technique, in seven isolated perfused swine right ventricles, at the baseline, and with 1, 5, 10 and 20 mg/L of d,l-sotalol, with a washout period of 1 hour. The ventricular effective refractory periods (VERP), APD at 90% repolarization (APD90), spontaneous defibrillation rate and VF inducibility were measured at each concentration. We plotted APDR curves of S1-S2 pacing against VF, and calculated the maximal slopes (Smax) of the APDR. Results： Sotalol (10 mg/L) prolonged the APD90 (p<0.001) by reducing the Smax of the APDR (by S1-S2 pacing, p<0.01; during VF, p<0.05). Accordingly, 41.7% of the VT/VF was terminated spontaneously, and VT/VF inducibility reduced from 91.1% at the baseline to 25% with 10 mg/L sotalol. A higher dose of sotalol (20 mg/L) increased the Smax, despite continuous prolongation of the VERP and APD90, resulting in the increase in the VT/VF inducibility (36.4%). Conclusion：Sotalol produces its anti-fibrillatory effect by APD prolongation in parallel with a flattening of the Smax at therapeutic doses. However, a higher concentration of sotalol increased the Smax and VF inducibility in isolated swine ventricular tissue. (Korean Circulation J 2005;35:282-289)

Spatial Dispersion of Action Potential Duration Restitution Kinetics Is Associated with Induction of Ventricular Tachycardia/Fibrillation in Humans

Action potential duration restitution (APDR) plays a role in initiation and maintenance of ventricular tachycardia (VT)/ventricular fibrillation (VF). We hypothesized that the steeply sloped APDR and its spatial heterogeneity contribute to VT/VF inducibility in patients with ventricular arrhythmia. After programmed ventricular stimulation (PVS) for evaluation of clinically documented VT, patients (n = 20, 15 male, age 52.5 +/- 9.5 years) were divided into two groups: inducible sustained VT/VF (IVT, n = 10) and noninducible VT/VF (NVT, n = 10). Data were compared with the corresponding results obtained from normal controls (C, n = 10). Right ventricular (RV) monophasic action potential duration at 90% repolarization (APD90) and ventricular effective refractory period (VERP) in the right ventricular apex (RVA) and right ventricular outflow tract (RVOT) were determined. APDR was acquired by scanning diastole with premature ventricular beats during a pacing cycle length of 600 msec (S1-S2) in all patients and by rapid pacing at the cycle lengths that induced APD alternans in three patients. Maximal slopes (Smax) of the APDR curves and DeltaAPD90 (APD90 at S2 400 ms - APD90 at the shortest S2) were measured. VERP and APD90 at each RV site did not differ among the three groups. Smax obtained by S1-S2 (1.6 +/- 0.6) did not differ from Smax obtained by rapid pacing (1.2 +/- 0.7), with a significant correlation noted between these values (r = 0.92, P < 0.01). The IVT group had a higher spatial dispersion of Smax (Smax at RVOT - Smax at RVA) compared to the C group (P < 0.05), with no difference between the NVT group and the IVT or C groups. The IVT group had a higher spatial dispersion of DeltaAPD90 compared to the NVT and C groups (P < 0.01, respectively). Smax at the RVOT (2.7 +/- 1.9) was steeper than that at the RVA (1.9 +/- 1.2, P < 0.05). Inducibility of sustained VT/VF was greater at the RVOT (83.3%) than at the RVA (50.0%, P < 0.05). In patients with ventricular arrhythmia, VT/VF is highly inducible under conditions of greater spatial dispersion of ventricular refractoriness and APDR.

Acute Hypokalemia and Inducibility of Ventricular Tachyarrhythmia in a Nonischemic Canine Model

Inducibility of sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) by programmed ventricular stimulation following acute hypokalemia was studied in 21 anesthetized dogs free of inducible ventricular tachyarrhythmias at baseline. The control mean serum potassium concentration of 3.65 mEq/L was decreased to 2.14 mEq/L by insulin and furosemide administration. Inducibility of arrhythmias was also assessed following isoproterenol infusion before and after induction of hypokalemia. None of the animals developed sustained VT. Only one animal developed VF following hypokalemia (p greater than 0.05). Two normokalemic animals and five hypokalemic animals developed VF following isoproterenol infusion; this difference was not significant (p greater than 0.05). In this study, hypokalemia did not predispose to the development of a substrate necessary for the genesis and maintenance of VT. The inducibility of VF following hypokalemia was not significantly enhanced and appears to be related to the "aggressive" stimulation protocol.

Mechanisms underlying the development of ventricular fibrillation during early myocardial ischemia.

The mechanisms underlying the development of ventricular fibrillation (VF) during early myocardial ischemia were assessed by use of a computerized three-dimensional mapping system capable of recording simultaneously from 232 intramural recording sites throughout the entire feline heart in vivo. Occlusion of the proximal left anterior descending coronary artery led to ventricular tachycardia (VT), which degenerated to VF in 1-5 minutes in four of 15 animals. Normal sinus beats immediately preceding the initiation of VT leading to VF demonstrated delayed activation (total activation time 133 +/- 14 msec), which was not significantly different from the activation time for normal sinus beats immediately preceding nonsustained VT (149 +/- 7 msec). Most of the conduction delay occurred in the subendocardial and midmyocardial regions in both groups. Initiation of VT leading to VF occurred by intramural reentry in three of the four cases. In one case, a mechanism responsible for the initiation of VT could not be assigned. The coupling interval of the initiating beats of VT ultimately leading to VF (210 +/- 15 msec) did not differ from that of nonsustained VT. Maintenance of the VT that led to VF was due primarily to intramural reentry (84% of cases) involving multiple activation sites in and around the border region of the ischemic zone. Nonreentrant mechanisms, arising in the subendocardium and subepicardium, also contributed to the maintenance of VT before development of VT. The transition from VT to VF was due exclusively to intramural reentry with initiation of the reentrant beats in the subendocardium and, occasionally, the subepicardium. Acceleration of the tachycardia by intramural reentry, along with very rapid and inhomogeneous recovery of excitability (as low as 50-60 msec), led to increased functional block and conduction delay. As a result, the total activation time for a given beat exceeded the coupling interval for that beat and led to the multiple reentrant circuits and multiple simultaneous activations characteristic of VF. Thus, the initiation and maintenance of VT leading to VF during early ischemia is due to intramural reentry, although nonreentrant mechanisms also contribute. However, the development of VF is due to continued intramural reentry and rapid recovery of excitability.

Reentrant and nonreentrant mechanisms contribute to arrhythmogenesis during early myocardial ischemia: results using three-dimensional mapping.

The present study assessed the mechanisms responsible for the initiation and maintenance of premature ventricular complexes (PVCs) and ventricular tachycardia (VT) during early ischemia using a unique computerized mapping system capable of recording simultaneously from 232 individual intramural sites. In the chloralose-anesthetized cat, during normal sinus rhythm prior to ischemia, ventricular activation was rapid with a total activation time of 25 +/- 2 msec. Five minutes after occlusion of the left anterior descending (LAD) coronary artery, activation was delayed during sinus rhythm (64 +/- 6 msec) (p less than 0.001 vs. control) and was characterized by slow conduction in the same plane and block in both the same plane and in the endocardial-to-epicardial direction. In 76% of cases (16 of 21), initiation of single PVCs and the first beat of VT occurred through intramural reentry. In all but one case, initiation occurred in the subendocardium, adjacent to the site of delayed subendocardial and midmyocardial activation of the preceding sinus beat. The activation time of the sinus beat preceding the PVC or VT was significantly prolonged (149 +/- 7 msec, p less than 0.001 vs. sinus beats during ischemia not followed by a PVC or VT) with most of the delayed activity occurring in the subendocardium and midmyocardium, a finding that would not have been apparent by epicardial mapping alone. The length of the reentrant pathway ranged from 1.8-3.0 cm. Marked delay was a necessary, but not a sufficient, condition for reentry to occur since, in some cases, delays as large as 220 msec was found without initiation of reentry or the occurrence of nonreentrant PVCs or VT. Maintenance of VT by intramural reentry arose in either the subendocardium or the subepicardium and was primarily dependent on the continued presence of marked transmural delay (159 +/- 8 msec). In contrast, in 24% of cases (5 of 21), initiation of the first beat of VT arose in either the subendocardium or subepicardium by a mechanism other than reentry as evidenced by the lack of intervening electrical activity between the end of the preceding sinus beat and the initiation of the ectopic beat. The preceding sinus beat was characterized by delay (129 +/- 12 msec) comparable to that of sinus beats preceding reentrant ectopic beats (p = NS), but the marked delay was distant from the site of nonreentrant initiation. Ventricular tachycardia could be initiated by one mechanism (reentrant or nonreentrant) and maintained or terminated by another mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium.

The mechanisms responsible for malignant ventricular arrhythmias associated with reperfusion of ischemic myocardium were delineated with a computerized, three-dimensional mapping system, with simultaneous eight-level transmural recordings from 232 bipolar sites. In six chloralose-anesthetized cats, regional ischemia was induced for 10 min by occlusion of the left anterior descending coronary artery, followed by reperfusion. At 10 min after ischemia, just before reperfusion, total ventricular activation time during sinus rhythm was significantly delayed (63 +/- 8 vs 25 +/- 2 msec before ischemia, p less than .001). Ventricular tachycardia (VT) occurred within 15 sec after reperfusion and in three animals culminated in ventricular fibrillation. In 75% of cases of nonsustained VT, initiation occurred in the subendocardium, at the border of the reperfused zone via a mechanism not involving reentry, as determined by the fact that continuous activation was not apparent and the time from the end of the sinus beat to the beginning of VT (142 +/- 14 msec) was not associated with any intervening depolarizations. In the remaining 25% of cases of nonsustained VT, initiation of the VT resulted from intramural reentry in the subendocardium adjacent to the site of delayed midmyocardial activation from the preceding sinus beat (total activation time = 151 +/- 9 msec, p less than .001 vs just before reperfusion). This reentrant mechanism was similar to that responsible for the majority of cases of VT during ischemia without reperfusion. Maintenance of VT during reperfusion occurred by nonreentrant mechanisms as well as by intramural reentry, with most cases of VT involving both mechanisms. Ventricular tachycardia leading to ventricular fibrillation was initiated in the subendocardium at the border of the reperfused zone by a nonreentrant mechanism and was maintained by both nonreentrant and reentrant mechanisms, at times in combination in the same beat. The coupling interval of the first ectopic beat of VT leading to ventricular fibrillation was not significantly different from that of nonsustained VT (199 +/- 16 vs 189 +/- 9 msec, p = NS). However, during the transition from VT to ventricular fibrillation, nonreentrant mechanisms arising both in the subendocardium and subepicardium led to very rapid acceleration of the tachycardia to the coupling interval of 92 +/- 2 msec, resulting in enhanced functional block and further conduction delay, with the total activation time of the transition beats exceeding the coupling interval of the tachycardia.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical ablation of ventricular tachycardia in the dog

Sustained ventricular tachycardia was induced in dogs following occlusion-reperfusion of the left anterior descending coronary artery. While dogs were supported by cardiopulmonary bypass, the left ventricle was opened and the endocardium was mapped during electrically induced ventricular tachycardia to determine the earliest site of ventricular activation. Phenol (carbolic acid) application at that site necrosed myocardium to a depth of 1 to 3 mm and prevented electrical reinduction of ventricular tachycardia in 9 of 15 dogs. These data suggest that chemical ablation may be used as an alternate means to destroy areas of myocardium involved in the genesis or maintenance of ventricular tachycardia, particularly if these areas cannot be resected surgically because of their size or location.

Intramural reentry as a mechanism of ventricular tachycardia during evolving canine myocardial infarction.

We evaluated the contribution of intramural electrical events in initiation and maintenance of ventricular tachycardia in 15 dogs 3-8 days after either permanent (n = 2) or transient (n = 13) coronary artery occlusion. Seven of the dogs (47%) demonstrated eight distinct monomorphic ventricular tachycardia patterns which were mapped by means of a recently designed computerized system capable of simultaneously detecting, storing, and assessing information from 232 individual cardiac sites. Using both epicardial and intramural electrodes, we found definitive evidence for intramural reentry in seven of the eight monomorphic tachycardias analyzed. Furthermore, five of these animals (71%) demonstrated microreentry, in which small epicardial conduction loops exited intermittently into nonrefractory subendocardium to initiate succeeding beats, while, in the remaining two dogs, ventricular tachycardia was due to macroreentry, during which the broad subendocardial wavefronts depolarizing the ventricle constituted the proximal (fast) reentry limbs. Detailed anatomical analysis of the resultant infarcts demonstrated the thin surviving epicardial tissue rim to be the site of conduction delay necessary for reentry, whereas "preferred pathways" of exit into the subendocardial plane occurred at the infarct borders and were of variable configuration. Successful interruption of these rhythms should accompany interference with the process of exit into nonrefractory subendocardial tissue.

Recurrent sustained ventricular tachycardia. 1. Mechanisms.

The mechanism of recurrent sustained ventricular tachycardia (VT) was evaluated in 21 patients. Re-entry as the mechanism for VT was suggested by a) the reproducible initiation (19) and termination (15) of the arrhythmia by programmed stimulation. The rate, ventricle of origin, and stimulation site determined the method of termination. One VPD was usually required with VT rates less than 175/min and/or ventricle of origin ipsilateral to the stimulation site, while two VPDs were usually required for VT with faster rates originating in a contralateral ventricle. The proximal His-Purkinje system (HPS) was not required for initiation or maintenance of VT. Evidence localizing the site of re-entry to a small portion of the ventricles included: a) ventricular capture by ventricular premature depolarizations (VPDs) or pacing (VP) without terminating VT (5), b) sinus capture following VPDs and/or supraventricular fusions without terminating VT (12), and c) atrial pacing normalizing the QRS and H-V intervals without terminating VT (5).