Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.

The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period.

Catheter ablation of sinoatrial node reentrant tachycardia.

OBJECTIVES: This study evaluates 1) the safety and efficacy of catheter delivery of radiofrequency current to eliminate sustained sinoatrial node reentrant tachycardia; 2) the incidence of sinoatrial node reentrant tachycardia in the current group of patients undergoing electrophysiologic study for paroxysmal supraventricular tachycardia; and 3) the association of sinoatrial node reentrant tachycardia with other tachyarrhythmias. BACKGROUND: Sustained sinoatrial node reentrant tachycardia is an uncommon cause of paroxysmal supraventricular tachycardia that is reported to occur infrequently in conjunction with other arrhythmias. Although pharmacologic and surgical therapies are available, there is limited information with regard to catheter ablation of sinoatrial node reentrant tachycardia. METHODS: Ten patients with sustained sinoatrial node reentrant tachycardia underwent electrophysiologic study and radiofrequency current ablation. Patients were followed up for 9.2 +/- 6.0 months. RESULTS: Of 343 consecutive patients referred for electrophysiologic evaluation of paroxysmal supraventricular tachycardia, 11 (3.2%) were found to have inducible sustained sinoatrial node reentrant tachycardia. Nine of the 11 patients had other associated arrhythmias, including atrioventricular (AV) node reentrant tachycardia (6 patients), AV reciprocating tachycardia (2 patients), ectopic atrial tachycardia (2 patients) and bundle branch reentrant tachycardia (1 patient). In 10 patients, direct ablation of sinoatrial node reentrant tachycardia was attempted and was successful in all (confidence interval for failure 0-0.26). Sinoatrial node reentrant tachycardia was eliminated with a median of four radiofrequency current applications (range 1 to 10) at 20 to 30 W. Successful ablation site characteristics during sinoatrial node reentrant tachycardia included 1) atrial activation > or = 35 ms (mean 44 +/- 8 ms) before the onset of the surface P wave, 2) atrial activation > or = 20 ms (mean 28 +/- 6 ms) before the onset of high right atrial activation, and 3) significantly prolonged and fractionated electrograms (mean duration 87 +/- 21 ms). No complications were encountered, and there have been no recurrences of sinoatrial node reentrant tachycardia. CONCLUSIONS: Sinoatrial node reentrant tachycardia may be effectively and safely treated with radiofrequency current ablation at the site of earliest atrial activation.

Radiofrequency catheter ablation of supraventricular tachycardia substrates after mustard and senning operations for d-transposition of the great arteries.

OBJECTIVES: The purpose of this study was to determine the efficacy and risks of radiofrequency ablation of various forms of supraventricular tachycardia after Mustard and Senning operations for d-transposition of the great arteries. BACKGROUND: In this patient group, the reported success rate of catheter ablation of intraatrial reentry tachycardia is about 70% with a negligible complication rate. There are no reports of the use of radiofrequency ablation to treat other types of supraventricular tachycardia. METHODS: Standard diagnostic criteria were used to determine supraventricular tachycardia type. Appropriate sites for attempted ablation included 1) intraatrial reentry tachycardia: presence of concealed entrainment with a postpacing interval similar to tachycardia cycle length; 2) focal atrial tachycardia: a P-A interval < or =-20 ms; and 3) typical variety of atrioventricular (AV) node reentry tachycardia: combined electrographic and radiographic features. RESULTS: Nine Mustard and two Senning patients underwent 13 studies to successfully ablate all supraventricular tachycardia substrates in eight (73%) patients. Eight of eleven (73%) patients having intraatrial reentry tachycardia, 3/3 having typical AV node reentry tachycardia, and 2/2 having focal atrial reentry tachycardia were successfully ablated. Among five patients having intraatrial reentry tachycardia (IART) and not having ventriculoatrial (V-A) conduction, two suffered high-grade AV block when ablation of the systemic venous portion of the medial tricuspid valve/inferior vena cava isthmus was attempted. CONCLUSIONS: Radiofrequency catheter ablation can be effectively and safely performed for certain supraventricular tachycardia types in addition to intraatrial reentry. A novel catheter course is required for slow pathway modification. High-grade AV block is a potential risk of lesions placed in the systemic venous medial isthmus.

Ventricular defibrillation using biphasic waveforms: the importance of phasic duration.

Biphasic waveforms can be used to defibrillate the heart with less energy than that used by monophasic waveforms. In 14 anesthetized open chest dogs with large contoured defibrillation electrodes, the effect on defibrillation efficacy of varying the duration of the two phases of biphasic waveforms was studied. All combinations of 0, 1, 3.5, 6 and 8.5 ms duration were used for both the first and the second phase except for the meaningless case in which both durations were 0 ms. The 3.5-2 waveform (3.5 ms first phase and 2 ms second phase) was also tested. All the hearts were defibrillated with less than or equal to 5 joules using any of the 25 waveforms. However, biphasic waveforms with the second phase shorter than or equal to the first had significantly lower defibrillation thresholds than did those with the second phase longer than the first or than did monophasic waveforms of approximately the same total duration. A plot of defibrillation threshold current strength versus second phase duration for all biphasic waveforms with a 3.5 ms first phase did not produce a hyperbolic strength-duration curve as seen with monophasic waveforms. To verify these findings, defibrillation dose-response curves were obtained for the 3.5-2, 6-6 and 3.5-8.5 biphasic waveforms in another six dogs. The 50 and 80% successful voltage doses of the 3.5-8.5 waveforms were significantly higher than those of the other two waveforms, which were not different from one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy: results of a prospective multicenter study. Cooled RF Multi Center Investigators Group.

OBJECTIVES: The purpose of this multicenter study was to evaluate the safety and efficacy of a radiofrequency (RF) catheter ablation system with internal saline irrigation. BACKGROUND: Catheter ablation of ventricular tachycardia (VT) associated with structural heart disease is more difficult than ablation of idiopathic VT. The larger size of responsible reentrant circuits contributes to the difficulty in achieving an adequate ablation lesion with conventional techniques. Recently, cooling of the ablation electrode by saline irrigation has been shown to increase RF lesion size. METHODS: The patient population included 146 patients who participated in the Cooled RF Ablation System clinical trial and underwent an attempt at ablation of VT occurring in the presence of structural heart disease. The duration of follow-up was 243 +/- 153 days. RESULTS: Catheter ablation was acutely successful, as defined by elimination of all mappable VTs, in 106 patients (75%). In 59 patients (41%), no VT of any type was inducible after ablation. Twelve patients (8%) experienced a major complication. After catheter ablation, 66 patients (46%) developed one or more episodes of a sustained ventricular arrhythmia. CONCLUSIONS: The results of this study demonstrate that catheter ablation of all mappable forms of sustained VT can be performed with high initial success and a moderate incidence of major complications (8%).

Comparison of a novel rectilinear biphasic waveform with a damped sine wave monophasic waveform for transthoracic ventricular defibrillation. ZOLL Investigators.

OBJECTIVES: We compared the efficacy of a novel rectilinear biphasic waveform, consisting of a constant current first phase, with a damped sine wave monophasic waveform during transthoracic defibrillation. BACKGROUND: Multiple studies have shown that for endocardial defibrillation, biphasic waveforms have a greater efficacy than monophasic waveforms. More recently, a 130-J truncated exponential biphasic waveform was shown to have equivalent efficacy to a 200-J damped sine wave monophasic waveform for transthoracic ventricular defibrillation. However, the optimal type of biphasic waveform is unknown. METHODS: In this prospective, randomized, multicenter trial, 184 patients who underwent ventricular defibrillation were randomized to receive a 200-J damped sine wave monophasic or 120-J rectilinear biphasic shock. RESULTS: First-shock efficacy of the biphasic waveform was significantly greater than that of the monophasic waveform (99% vs. 93%, p = 0.05) and was achieved with nearly 60% less delivered current (14 +/- 1 vs. 33 +/- 7 A, p < 0.0001). Although the efficacy of the biphasic and monophasic waveforms was comparable in patients with an impedance < 70 ohms (100% [biphasic] vs. 95% [monophasic], p = NS), the biphasic waveform was significantly more effective in patients with an impedance > or = 70 ohms (99% [biphasic] vs. 86% [monophasic], p = 0.02). CONCLUSIONS: This study demonstrates a superior efficacy of rectilinear biphasic shocks as compared with monophasic shocks for transthoracic ventricular defibrillation, particularly in patients with a high transthoracic impedance. More important, biphasic shocks defibrillated with nearly 60% less current. The combination of increased efficacy and decreased current requirements suggests that biphasic shocks as compared with monophasic shocks are advantageous for transthoracic ventricular defibrillation.

The role of the autonomic nervous system in sudden cardiac death.

The autonomic nervous system exerts a modulating effect on the risk of sudden cardiac death (SCD) in the setting of ischemic heart disease. The mechanism by which sympathetic tone increases the risk of ventricular arrhythmias is not known, though regional sympathetic denervation at and apical to the site of transmural infarction may result in regional supersensitivity to circulating catecholamines and play a role in ventricular arrhythmogenesis. [(123)I]MIBG scintigraphy enables noninvasive determination of regional cardiac denervation and may be a useful tool for probing the role of sympathetic nervous system in SCD. Increased vagal tone is generally protective against SCD. Newer tests such as baroreflex slope testing and various techniques for determination of heart rate variability, which provide indices of vagal tone, may have greater predictive value and are powerful tools in assessing the role of autonomic nervous system in SCD.

Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Torsade de pointes during administration of pentamidine isethionate.

Pentamidine isethionate is a diamidine compound used in the treatment of a number of parasitic diseases, notably Pneumocystis carinii pneumonia. Although cases of sudden death have been reported during the administration of pentamidine, there have been no reported cases in the literature of pentamidine-associated arrhythmias. Reported in this study are two cases of torsade de pointes occurring during the prolonged administration of pentamidine. In addition, electrocardiographic changes of marked QT interval prolongation, pronounced precordial T wave abnormalities, and ST segment changes were shown in both patients. Mild hypomagnesemia coexisted in both cases, but torsade de pointes persisted in one patient and electrocardiographic changes remained in both cases despite magnesium replacement. QT interval prolongation and electrocardiographic abnormalities resolved slowly over several days to weeks, paralleling the known elimination kinetics of pentamidine. These data suggest a proarrhythmic effect of pentamidine isethionate.

Magnesium reversal of digoxin-facilitated ventricular rate during atrial fibrillation in the Wolff-Parkinson-White syndrome.

In patients with Wolff-Parkinson-White syndrome and atrial fibrillation, digoxin may increase the ventricular rate by facilitating conduction over the accessory pathway either directly by enhancing accessory pathway conduction and/or indirectly as a consequence of its effect on atrioventricular nodal conduction. Two cases are presented in which the intravenous administration of magnesium sulfate reversed digoxin facilitation of the ventricular rate to atrial fibrillation in the Wolff-Parkinson-White syndrome.

Treatment of supraventricular tachycardias with transcatheter delivery of radiofrequency current.

Medical therapy for the treatment of supraventricular tachycardias is frequently ineffective and associated with significant side effects, whereas curative surgical approaches have generally been limited by their considerable morbidity and cost. Greater understanding of the mechanisms underlying supraventricular tachycardias has improved our ability to precisely map endocardial areas critical to arrhythmogenesis. Advances in catheter ablation techniques and particularly the use of radiofrequency current to generate thermal energy for ablation have resulted in dramatic success rates for curative catheter ablation. This review examines the physics of radiofrequency current ablation and its application to the treatment of atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia, and arrhythmias associated with the Wolff-Parkinson-White syndrome. The limitations, risks, and cost-effectiveness of this technique relative to medical and surgical approaches are also evaluated.

Effect of continuous vagal enhancement on concealed conduction and refractoriness within the atrioventricular node.

This study examined the complex interaction between vagal enhancement and how a concealed atrial impulse alters atrioventricular (AV) nodal function. In theory, vagal augmentation could increase or decrease the effect that a premature atrial beat has on the subsequent beat. In 10 patients we established the AV nodal effective refractory period (ERP) without and with a conditioning atrial stimulus (Sc); the stimulation protocol was then repeated after enhancing reflex vagal tone with a continuous phenylephrine infusion. During phenylephrine infusion, the sinus cycle length prolonged from 827 +/- 99 to 1,029 +/- 223 ms (p < 0.001) and AV nodal ERP increased from 331 +/- 51 to 425 +/- 64 ms (p < 0.005). At control, AV nodal ERP in the presence of Sc prolonged to 536 +/- 69 ms (p < 0.001), and during phenylephrine infusion increased to 579 +/- 57 ms (p < 0.01), a change significantly less than during control (58 +/- 14% vs 31 +/- 14%, respectively, p < 0.01). Further experiments suggest that the effect of Sc was reduced because it occurred earlier relative to the vagally prolonged AV nodal ERP. In conclusion, this study demonstrates a complex relation between the timing of a premature atrial beat causing concealed conduction and the degree of vagal tone. The concealed beat, as related to the AV node ERP, has a substantial effect on subsequent AV nodal conduction. These data give insights into clinical AV nodal function.

Desmoplastic malignant melanoma: diagnosis of early clinical lesions.

Desmoplastic malignant melanoma (DMM) is an uncommon but potentially devastating malignancy that can be cured with early recognition and surgery. DMM has clinical as well as histological features that may be subtle and overlooked, or misdiagnosed as other benign or malignant lesions that would require less aggressive therapy for cure. We have reviewed the preliminary clinical diagnoses and histological features of 18 cases of desmoplastic malignant melanoma, defined as either an inapparent lesion clinically, or a papule or small nodule less than 0.7 cm, which proved histologically to be DMM. Nine of 18 cases (50%) were clinically pigmented. Histologically, early lesions were characterized by superficial tumor fascicles, and random diffuse hypercellularity in the upper dermis identified as elongated hyperchromatic pleomorphic spindle cells with stromal myxoid change. Neuroidal melanocytic structures, invasion of adventitial dermis, islands of inflammation, and epidermal lentiginous melanocytic hyperplasia were often present. The most reliable and characteristic features of an early lesion of DMM are aggregates of lymphocytes, tumor cell cytological atypia, stromal myxoid change, and poor circumscription of the dermal infiltrate. DMM is a disease best treated by complete excision at the time of initial surgery, but is also a lesion easily missed or misdiagnosed in the early stages. Features of early DMM are identified and illustrated to enable early diagnosis and cure of these lesions.

Trazodone-related exercise-induced nonsustained ventricular tachycardia.

A 79-year-old woman in the course of a syncope evaluation is shown to have a trazodone-related cardiac arrhythmia confirmed by drug rechallenge. This nontricyclic antidepressant should be considered as potentially arrhythmogenic despite its generally favorable cardiovascular profile.

Activation in unipolar cardiac electrograms: a frequency analysis.

We have developed and tested several detectors of local activations in unipolar cardiac electrograms; the detectors are based on the frequency content of the waveforms. For this study, myocardial regions with no local electrical activity were created with cryoablation in canine ventricles, so that the characteristics of electrograms reflecting local activation could be compared with those with only distant electrical activity. For each electrogram, representations of the original signal were created using the output of bandpass filters; for each representation, the value of the maximum amplitude was taken as a measurement of the frequency content of the electrogram in that frequency band. The content of each frequency band and the first derivative of the signal were tested as discriminators between local and distant electrical activity. Combinations of frequency bands were also tested using a logistic regression technique; certain combinations provided better detection than any of the individual frequencies or the first derivative. The inclusion of frequencies between 500 and 1000 Hz improved the detection performance, suggesting that sampling rates of 1000 samples per second or less may not be adequate for optimal discrimination. A detector based on multivariate analysis of different frequency components of a signal may be more effective than single-band filtering in discriminating between local and distant electrical activity in the heart, especially when those components have very different magnitudes.

Prophylactic implantable defibrillator patches in patients at high risk for malignant ventricular dysrhythmias.

The indications for prophylactically placing implantable cardioverter defibrillator (ICD) patches at cardiac surgery are unclear. Over the past 4 years, 25 patients have undergone placement of prophylactic ICD patches at the authors' institution. Indications were severe coronary artery disease with ventricular tachycardia (VT) (n = 14) or ventricular fibrillation (VF) (n = 2), and left ventricular aneurysmectomy and/or subendocardial resection (SER) (n = 9). Four patients died in-hospital, three from refractory VT (which could be transthoracically cardioverted until recurrence was unremitting), and one from congestive heart failure (CHF). All of the remaining 21 patients underwent post-operative electrophysiologic studies (EPS), and 12 had inducible VT (8/14 CABG, 4/7 SER). Eight of the 12 inducible patients had generators implanted, whereas 3 patients were controlled medically. One patient refused generator implantation and died at home from sudden cardiac death, and one initially non-inducible patient required late ICD generator placement, yielding a total of nine patients who received generators. All nine of these patients are currently alive at 14 +/- 7 months follow-up, and five have subsequently received appropriate ICD discharges. In patients undergoing cardiac surgery considered preoperatively or intraoperatively to be at increased risk for VT/VF and too unstable for preoperative EPS, prophylactic ICD patches should be considered.

Ventricular fibrillation resulting from synchronized internal atrial defibrillation in a patient with ventricular preexcitation.

This case describes ventricular proarrhythmia as a result of a synchronized internal atrial defibrillation shock in a 29-year-old man with Ebstein's anomaly referred for radiofrequency ablation of a right posterior accessory pathway. During the electrophysiologic study, atrial fibrillation was induced and 3/3 msec shocks of various strengths were delivered between two decapolar defibrillation catheters in the coronary sinus and right atrial appendage. A 2.0-J biphasic shock synchronized to an R wave after a short-long-short ventricular cycle length pattern with a preshock coupling interval of 245 msec induced ventricular fibrillation, which was externally defibrillated with 200 J. This observation has implications for the development of implantable atrial defibrillators.

Ventricular tachycardia and fibrillation in normal hearts.

Although ventricular tachyarrhythmias usually occur in the setting of definable heart disease, up to 15% of ventricular tachycardias and 10% of ventricular fibrillation occur in patients without heart disease. Of the various clinical entities comprising these idiopathic ventricular tachyarrhythmias, a few well-defined clinical syndromes have been described, such as idiopathic right ventricular outflow tract tachycardia, idiopathic left posterior fascicular ventricular tachycardia, and the right bundle branch block and ST segment elevation syndrome of idiopathic ventricular fibrillation. Many advances have been made in the past few years in our understanding and treatment of idiopathic ventricular tachyarrhythmias, and these advances are the subject of this review.