L.Bing Liem

Relation Between Repolarization and Refractoriness in the Human Ventricle: Cycle Length Dependence and Effect of Procainamide

The cycle length dependence of the action potential duration and the effective refractory period of the right ventricular endocardium were investigated in 24 patients undergoing electrophysiologic studies for suspected ventricular tachycardia. The action potential duration at 90% repolarization and the effective refractory period at twice diastolic threshold strength were measured at the same catheter site at steady state cycle lengths of 350 to 600 ms. Both measurements decreased linearly with decreasing cycle length, maintaining a parallel relation. When the relation between action potential duration and effective refractory period was expressed as the effective refractory period-action potential duration difference, nearly constant values (range -12 to -15 ms) were obtained at all cycle lengths. To determine whether sodium channel blocking drugs influence the effective refractory period-action potential duration relation in humans, measurements of these two variables were obtained in 15 patients before and during the infusion of procainamide. Procainamide prolonged the action potential duration at each cycle length by a near constant amount over baseline values (p less than 0.001). Procainamide also increased the effective refractory period at each cycle length but with a greater incremental increase at the shorter cycle lengths. The rate-dependent increase in the effective refractory period-action potential duration difference became significant at cycle lengths less than or equal to 400 ms; at these high rates, the effective refractory period-action potential duration difference became positive (1.6 ms, p less than 0.01 compared with baseline). Thus, in the human ventricle, the action potential duration and the effective refractory period have a close relation that remains fixed over a wide range of cycle lengths.(ABSTRACT TRUNCATED AT 250 WORDS)

Implantable cardioverter-defibrillator therapy in survivors of out-of-hospital sudden cardiac death without inducible arrhythmias

OBJECTIVES The aim of this study was to determine the efficacy of implantable cardioverter-defibrillator (ICD) therapy in survivors of sudden cardiac death in whom no ventricular arrhythmias can be induced with programmed electrical stimulation. BACKGROUND Survivors of sudden cardiac death in whom ventricular arrhythmias cannot be induced with programmed electrical stimulation remain at risk for recurrence of serious arrhythmias. Optimal protection to prevent sudden death in these patients is uncertain. This study compares survival in the subset of survivors of sudden cardiac death with that of patients treated with or without an ICD. METHODS A retrospective study was performed on 194 consecutive survivors of primary sudden death who had < or = 6 beats of ventricular tachycardia induced with programmed electrical stimulation with at least three extrastimuli. Ninety-nine patients received an ICD and 95 did not. RESULTS There were no significant differences between the two groups in presenting rhythm, number of prior myocardial infarctions or use of antiarrhythmic agents. Patients treated with an ICD were younger (55 +/- 16 vs. 59 +/- 11 years, p = 0.03) and had a lesser incidence of coronary artery disease (48% vs. 63%, p = 0.04) and a lower ejection fraction (0.43 +/- 0.16 vs. 0.48 +/- 0.18, p = 0.04). There were no significant differences between the groups in the use of revascularization procedures or antiarrhythmic agents after the sudden cardiac death. Patients treated with an ICD had an improvement in sudden cardiac death-free survival (p = 0.04) but the overall survival rate did not differ from that of the patients not so treated (p = 0.91). A multivariate regression analysis that adjusted for the observed differences between the groups did not alter these results. CONCLUSIONS Survivors of sudden cardiac death in whom no arrhythmias could be induced with programmed electrical stimulation remained at risk for arrhythmia recurrence. Although the proportion of deaths attributed to arrhythmias was lower in the patients treated with an ICD, this therapy did not significantly improve overall survival.

Spectrum off electrophysiologic and electropharmacologic characteristics of verapamil-sensitive ventricular tachycardia in patients without structural heart disease

Abstract Verapamil-sensitive ventricular tachycardia (VT) is a well-recognized clinical entity that some authorities believe may result from triggered activity. Despite its uniform response to verapamil, however, there is evidence that this uncommon form of VT may not be as homogeneous as first believed. Standard intracardiac electrophysiologic techniques were used to study verapamilsensitive VT in 32 patients (aged 38 years ± 20 years) without evidence of structural heart disease. More than half of these patients (69%) exhibited VT with a right bundle branch block-type QRS pattern, with the remainder (31%) displaying VT with a left bundle branch block pattern. In 31% of the patients the VT could be induced by fixed-cycle length atrial pacing, whereas in 59% of patients fixed-cycle length ventricular pacing was necessary. A critical range of cycle lengths for VT induction was required in 66% of the patients. Ventricular tachycardia was initiated with single atrial premature extrastimuli in 16% of patients, single ventricular extrastimuli in 50% of patients, and double ventricular premature extrastimuli in 9% of patients. Ventricular tachycardia displaying cycle-length alternans was observed in 28% of patients. In only 19% of patients was it possible to entrain VT during pacing from the right ventricular apex. Isoproterenol infusion was required for tachycardia induction in 50% of patients, 44% of whom had VT with a left bundle branch block QRS pattern, with the remaining 56% exhibiting VT with a right bundle branch block pattern. Beta-adrenergic blockers suppressed 53% of verapamil-sensitive VT in patients tested, whereas adenosine terminated VT in 50% of patients, with 81 % of these patients exhibiting either a left bundle branch block QRS pattern or isoproterenol dependence. Ventricular tachycardia exhibiting a left bundle branch block pattern was more likely to be isoproterenol dependent (p 0.5). Verapamil-sensitive VT exhibits properties expected of both a reentrant and triggered arrhythmia, and it is inconsistently dependent on both exogenous catecholamines for induction and intravenous adenosine for termination. Verapamil-sensitive VT encompasses a heterogeneous group of tachycardias that may result from multiple cellular electrophysiologic mechanisms.

Localization of the origin of the atrioventricular junctional rhythm induced during selective ablation of slow-pathway conduction in patients with atrioventricular node reentrant tachycardia

During radiofrequency catheter ablation of slow atrioventricular node pathway conduction in patients with atrioventricular node reentrant tachycardia, an atrioventricular junction rhythm is frequently observed. The origin and relation to ablation success of this junctional rhythm was examined in this study. By using standard intracardiac electrophysiology techniques, we studied the radiofrequency energy-induced atrioventricular junctional rhythm in 43 consecutive patients with atrioventricular node reentrant tachycardia undergoing selective ablation of slow-pathway conduction. The frequency of atrioventricular junctional activity was correlated with successful and unsuccessful attempts at ablation of slow-pathway conduction. Also, we compared the sequence of retrograde atrial activation of radiofrequency energy-induced atrioventricular junctional beats in a subgroup of 22 patients with the retrograde activation sequence observed during pacing from the right ventricular apex and the site of successful ablation of slow-pathway conduction. A total of 201 radiofrequency-energy applications was delivered in 43 patients with > or = 5 atrioventricular junctional beat(s) induced during 110 (55%) of 201 ablation attempts. Atrioventricular junctional activity was noted during 98% of successful ablations but only 43% of the unsuccessful attempts (sensitivity, 98%; specificity, 57%; negative predictive value, 99%). The mean time to appearance of atrioventricular junctional beats was 8.8 +/- 4.1 sec (mean +/- SD) after the onset of radiofrequency-energy application. In 22 (100%) of 22 patients in whom detailed atrial mapping was performed, the retrograde atrial activation sequence of the radiofrequency-induced atrioventricular junctional beats was earliest in the anterior atrial septum, identical to that seen during pacing from the right ventricular apex. Earliest retrograde atrial activation was at the posterior septum in all patients during pacing from the successful ablation site, a markedly different activation pattern compared with that seen during either radiofrequency ablation or ventricular pacing. Whereas the occurrence of atrioventricular junctional activity during radiofrequency ablation does not necessarily herald a successful ablation of slow atrioventricular node pathway conduction, its absence strongly suggests that the energy is being applied in an unsuccessful fashion. Furthermore, it appears that radiofrequency energy-induced atrioventricular junctional beats originate not from the endocardium in contact with the ablating catheter tip but instead appear to exit remotely from the anterior atrial septal region. This finding supports the existence of specialized tissues in the atrioventricular junction that preferentially transmit the effects of radiofrequency energy to an anterior exit site, possibly identical to the atrial exit site of the retrograde fast atrioventricular node conduction pathway.

Value of Electropharmacologic Testing in Idiopathic Dilated Cardiomyopathy and Sustained Ventricular Tachyarrhythmias

Electrophysiologic studies in 64 patients with idiopathic dilated cardiomyopathy who had sustained ventricular tachycardia or ventricular fibrillation were performed. A sustained ventricular tachyarrhythmia was induced in 43 patients (67%). Electropharmacologic testing predicted an antiarrhythmic drug effective in 15 of 35 patients in whom sustained monomorphic ventricular tachycardia could be induced reproducibly (43% of tested patients, 23% of all patients). During median follow-up of 1.6 years, there were 32 arrhythmia recurrences and 24 cardiac arrests. Multivariate regression analysis identified treatment with a drug predicted to be effective at electropharmacologic testing as the only predictor of freedom from arrhythmia recurrence (p = 0.01); and treatment with a drug predicted to be effective at electropharmacologic testing and lower New York Heart Association functional class as independent predictors of freedom from cardiac arrest (p = 0.03 and p = 0.02, respectively). At median follow-up, the incidences of freedom from arrhythmia recurrence and from cardiac arrest were both 100% during treatment with a drug predicted to be effective at electropharmacologic testing versus 54 +/- 8% and 62 +/- 7%, respectively, during other treatments. These findings indicate that results of electropharmacologic testing accurately predict freedom from arrhythmia recurrence and cardiac arrest in patients with idiopathic dilated cardiomyopathy and sustained ventricular tachyarrhythmias.

Frequency-dependent effect of quinidine, mexiletine, and their combination on postrepolarization refractoriness in vivo

Summary: Combination therapy with mexiletine and quinidine has been shown to enhance antiarrhythmic efficacy. To assess further the underlying electrophysiological mechanism, the effect of therapeutic concentrations of mexiletine and quinidine, and of their combination, on action potential duration (at the level of 90% repolarization, APD90), effective refractory (ERP), and the relationship between these two parameters (ERP-APD90) was determined in 21 in vivo canine hearts. The frequency dependence of these effects was assessed over a range of paced steady-state cycle lengths from 250–600 ms. A modified contact electrode technique allowed measurements of both APD90 and ERP simultaneously and at the same ventricular site. In the drug-free state, both APD90 and ERP shortened linearly with shorter cycle lengths, maintaining a constant relationship (ERP–APD90 difference = −9 ± 2 ms) at all cycle lengths. Quinidine prolonged APD90 by a near constant amount of 11 ± 1 ms over the entire range of cycle lengths, while mexiletine tended to shorten it. Both mexiletine and quinidine increased ERP and ERP-APD90 in a rate-dependent fashion, the effect increasing with shorter cycle lengths. When used in combination, mexiletine attenuated the lengthening effect of quinidine on APD90 but augmented the rate-dependent increase in ERP, thereby producing greater postrepolarization refractoriness than either drug alone. This effect may explain the clinically favorable antiarrhythmic efficacy of mexiletine and quinidine combination therapy.

Ventricular fibrillation induced by low-energy shocks from programmable implantable cardioverter-defibrillators in patients with coronary artery disease

Many of the newest implantable cardioverter-defibrillators (ICDs) provide the option of programmable low-energy cardioversion for monomorphic ventricular tachycardia (VT). Whereas these devices may provide less myocardial damage and increased comfort in patients receiving frequent shocks for VT, the proarrhythmic effects of low-energy cardioversion from ICDs in patients with structural heart disease are not clear. The purpose of this study was to determine prospectively the per-patient incidence of ventricular fibrillation (VF) induction after low-energy cardioversion of VT by ICDs in patients with coronary artery disease. The estimated cardioversion energy requirement was determined during the course of routine predischarge ICD testing in 40 patients with newly implanted ICDs. Two groups of patients were identified during determination of the cardioversion energy requirement: (1) a non-VF group consisting of 26 of 40 patients (65%) without VF induced by low-energy shock and, (2) a VF group consisting of 14 of 40 patients (35%) who developed VF during low-energy cardioversion. There was no difference between the 2 groups in terms of patient age, sex, concurrent antiarrhythmic drug therapy, VT cycle length, or type of ICD system implanted. Compared with the non-VF group, the VF group was more likely to have both a lower ejection fraction (25 +/- 5% vs 33 +/- 8%; p = 0.005) and a cardioversion energy requirement > 2 J (79 vs 27%; p = 0.005). Our results suggest that low-energy cardioversion is associated with a high per-patient risk of VF induction, and the risk is higher in patients with poorer left ventricular function and, possibly, higher cardioversion energy requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Microwave Linear Ablation of the Isthmus Between the Inferior Vena Cava and Tricuspid Annulus

The purpose of this study is to assess the potential utility and practicality of microwave (MW) ablation in the creation of linear lesion for the treatment of atrial flutter. In the search for a more versatile form of energy for ablation of complex arrhythmias, MW, with its more direct form of heating, has been considered a potential alternative to radiofrequency. MW ablation is expected to offer an advantage in creating deeper or more uniform linear lesions but data on its usefulness remain lacking. Microwave ablation was applied to the inferior vena cava and tricuspid annulus isthmus in eight canines weighing 67.2 ± 4.8 lbs. We applied stationary ablations across the isthmus using 60–75 W power of 2,450–MHz MW energy delivered through a deflectable catheter with a 12‐or 18‐mm antenna, achieving 70.1±± 9.0±C antennas temperature. Ablations were made between the coronary sinus os and the low lateral right atrium. Bi‐directional block at the isthmus was accomplished in seven canines with an average of 2.7 ± 1.3 ablations while in one canine, only unidirectional block was achieved after five ablations. Gross pathological examination identified 16 transmural ovaloid and linear lesions measuring 9,4 ± 3.4 mm long, 4.9 ± 2.0 mm wide, and 2.1 ± 0.6 mm deep. In one canine the lesion extended to the surface of the tricuspid valve leaflet and in two other to the opposing anterior right ventricular wall. There were no coronary vascular or other structural damage. Histopathological examination showed hemolyzed blood on the surface, subendocardial hemorrhage and necrosis, and degeneration and fragmentation of the atrial myocardium. We concluded that single application ablation could achieve complete isthmus block using MW energy delivered through appropriately sized antenna. Such ablation may be useful for producing linear lesions for the treatment of atrial flutter.

In Vitro and In Vivo Results of Transcatheter Microwave Ablation Using Forward‐Firing Tip Antenna Design

This study was designed to test a microwave (MW) ablation system using approximately 2,450 MHz of energy and a deflectable catheter with forward‐firing tip antenna, an early clinical prototype system. In vitro three‐dimensional thermal mapping of single and double helix antenna designs was performed. Quantitative measurements of antenna radiation were recorded on tissue phantoms equipped with temperature sensors distributed radially and outwardly. In vivo testing consisted of closed‐chest AV junction ablation in three dogs. Thermal mapping showed hemispherical heat distribution from the tip antenna. For the double helix design, this distribution was measured at 8,4‐mm diameter with a maximum temperature of 61.62°C. As expected, the single helix design produced less heating with a measured diameter of 6.4 mm and maximum temperature of 55.90°C. The in vivo study produced lesions of geometry and size concordant with these heating patterns. MW ablation produced bundle branch block in one dog and complete AV nodal block in the remalning two, without transvalvular or other structural damage. The histopathology of the lesions was typical of a thermal burn showing hemorrhage and coagulative necrosis with clearly demarcated borders. We conclude that, using this early clinical prototype system with a deflectable catheter and a forward‐firing tip antenna design, MW heating can produce a moderate‐size lesion and is safe and effective for cardiac ablation.

Microwave Catheter Ablation Using a Clinical Prototype System with a Lateral Firing Antenna Design

Microwave has been considered a potentially more effective and more versatile form of energy than radiofrequency. Its feasibility has been tested using various prototype systems and catheter designs. This study assessed the safety and efficacy of a clinically‐suitable prototype microwave power supply and catheter system with a lateral‐firing antenna design for atrioventricular (AV) junction ahlation in canines and to correlate with tissue histopathology. The system consisted of a deflectable catheter with a 6‐mm antenna and a thermocouple; and a 2.45‐CHz frequency generator with power, time, and temperature controls. AV junction ablations were performed using 75 W energy for up to 60 seconds. Effective heating was confirmed hy a rise in catheter temperature to 69.3 ± 8.8°C. Complete AV nodal block was accomplished in all canines after an average of 4.1 ± 2.3 applications at 66.8 ± 7.7°C, and persisted after 28 days in all chronic animals. Lesions were consistent with thermal necrosis, were hemispherical to semi linear in shape and have distinct borders. Acute lesions were 3.4 ± 1.5 mm wide, 4.8 ±2.1 long, and 2.0 ± 0.9 deep. Chronic lesions showed typical healing and were smaller in size. Ablations did not cause any transvalvular, vascular or other cardiac structural damage, and no coagulum formation was noted on the antenna or catheter tip. Microwave AV junction ablation using this clinical prototype system specifically designed for it was safe and effective. Lesions depth was limited to 5 mm with 60‐second heating while its shape corresponded to the antennas length. Microwave energy may provide greater versatility for producing discrete or linear ablation.