Edward L.C. Pritchett

Ventricular fibrillation in the Wolff-Parkinson-White syndrome.

To examine the risk of ventricular fibrillation in patients with the Wolff-Parkinson-White syndrome, we compared patients who had this syndrome and a history of ventricular fibrillation related to preexcitation with patients who had the syndrome without this history. Ventricular fibrillation occurred during atrial fibrillation, with rapid conduction over the accessory pathway, and these patients had a higher prevalence of both reciprocating tachycardia and atrial fibrillation (14 of 25 vs. 18 of 73, P = 0.004) and multiple accessory pathways (five of 25 vs. four of 73, P = 0.012). The shortest preexcitation R-R interval during atrial fibrillation was less in the group with ventricular fibrillation (mean shortest R-R, 180 vs. 240 milliseconds, P less than 0.0001) as was the average R-R interval (mean average R-R, 269 vs 340 milliseconds, P less than 0.0001). Patients with Wolff-Parkinson-White syndrome who are most susceptible to ventricular fibrillation have a history of atrial fibrillation and reciprocating tachycardia, demonstrate rapid conduction over an accessory pathway during atrial fibrillation and have multiple accessory pathways.

Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia.

BACKGROUND Paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown. METHODS AND RESULTS Twenty-two patients with paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for all 29 days of the study. In the group of patients with paroxysmal atrial fibrillation, asymptomatic arrhythmia events occurred significantly more frequently than symptomatic arrhythmia events; the mean rates, expressed as events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2 (2.7, 9.0) (P < .01); the ratio of the mean rates was 12.1 (5.8, 26.4). In contrast, in the group of patients with paroxysmal supraventricular tachycardia, asymptomatic arrhythmia events were significantly less frequent than symptomatic arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P = .02). The ratio of the mean rates was 0.0 (0.0, 0.8). CONCLUSIONS In a group of patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial fibrillation occurs far more frequently than symptomatic atrial fibrillation. However, it is not known whether asymptomatic atrial fibrillation is a potential risk factor for stroke even when patients are not having symptomatic arrhythmias.

The preexcitation syndromes

Current methodology permits one to define the functional basis of the preexcitation syndromes with reasonable certainty and to develop a rationale for instituting trials of medical therapy. Future studies will hopefully result in a more exact definition of the anatomic substrates of preexcitation and their relationship to the pathophysiology of the associated syndromes. New antiarrhythmic agents must also be developed to add to the relatively small number of available drugs. Important questions still remain. Should asymptomatic patients with preexcitation be studied? If found to demonstrate potential for malignant arrhythmias, should they be treated prophylactically? The answers to these questions will require study and long-term follow-up of nonhospital referral patients. Surgery offers a feasible therapeutic alternative for patients with life-threatening or disabling arrhythmias but demands a team equipped to perform precise preoperative and intraoperative mapping studies to define the type and location of underlying anatomic substrates.

Vernakalant Hydrochloride for Rapid Conversion of Atrial Fibrillation. A Phase 3, Randomized, Placebo-Controlled Trial

Background— The present study assessed the efficacy and safety of vernakalant hydrochloride (RSD1235), a novel compound, for the conversion of atrial fibrillation (AF). Methods and Results— Patients were randomized in a 2:1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n=220; long duration, n=116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm (median time, 11 minutes) compared with 3 of the 75 placebo patients (4.0%; P<0.001). Overall, in the short- and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients (2.6%; P<0.001). Transient dysgeusia and sneezing were the most common side effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [2 events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. Conclusion— Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.

Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope

The Holter monitor, the most frequently used diagnostic test in patients with syncope, is nondiagnostic in over 90% of cases. This study sought to determine the impact of a new noninvasive device, the cardiac loop electrocardiographic (ECG) recorder, after Holter monitoring in 57 patients with unexplained syncope. All patients underwent a standardized evaluation protocol and were the monitor for up to 1 month. In 14 patients, loop recording definitively determined whether an arrhythmia was the cause of symptoms (diagnostic yield 25%; 95% confidence intervals 14 to 38%). Diagnoses included unsuspected ventricular tachycardia (1 patient), high grade atrioventricular block (2 patients), supraventricular tachycardia (1 patient), asystole or junctional bradycardia from neurally mediated syncope (3 patients) and normal cardiac rhythms (the remaining 7 patients). Follow-up of all patients diagnosed as having nonarrhythmic syncope by loop recording showed that none of these patients died suddenly. Cardiac loop ECG recording is an important new diagnostic test in patients with syncope unexplained by Holter monitoring.

Atrial Fibrillation in the Preexcitation Syndrome

One hundred patients with proved accessory pathways of the Kent bundle type were studied with multiple intracardiac catheters. During the procedure 16 had atrial fibrillation. Two patterns of induction of atrial fibrillation were noted. In most patients an earlier than expected atrial deflection appeared in one of the atrial recordings and was followed by atrial flutter (cycle length less than 220 msec) or atrial fibrillation either immediately or after a brief period of acceleration of atrial rate. In a few patients, intraatrial conduction delay, manifested as 2:1 block or Wenckebach block from the right to the left atrium or vice versa, occurred before the onset of atrial fibrillation. The incidence of atrial fibrillation was not statistically related to any associated cardiac abnormalities. A significantly large incidence of ventricular fibrillation was recorded in patients who had documented atrial fibrillation either before admission or during the catheter study.

Cryosurgical ablation of accessory atrioventricular connections: a method for correction of the pre-excitation syndrome.

Cryothermia, a new technique for definitive treatment of the pre-excitation syndrome, is described in two patients. The first patient presented with a normal P-R interval with a delta wave and reciprocating tachycardia. Preoperative electrophysiologic study suggested a free-wall atrioventricular connection on the left posterior atrioventricular (A-V) groove. At surgery, epicardial mapping confirmed the site of pre-excitation on the posterior left ventricular (LV) wall. An electrogram arising from the accessory pathway (AP) was recorded at the site of earliest ventricular activation. Interatrial delay combined with an apparently long accessory pathway to the ventricle caused the P-R interval to appear normal. Local pressure abolished pre-excitation. The site of early ventricular activation was cooled to −60°C with a specially designed cryoprobe. All evidence of pre-excitation and arrhythmias disappeared. The second patient presented with a refractory reciprocating tachycardia and was found to have an AP in the septum capable of only retrograde conduction. Retrograde conduction was abolished by applying a temperature of 0°C to the anulus at this site during tachycardia. Conduction over the AP and reciprocating tachycardia returned with rewarming. Ablation of the AP was obtained by applying a temperature of −60°C for 90 seconds on two occasions to the same area. The His bundle was not injured.

Ventriculoatrial intervals: diagnostic use in paroxysmal supraventricular tachycardia.

Reciprocating tachycardias due to reentry either within the atrioventricular (AV) node or using an accessory AV pathway are a common cause of paroxysmal supraventricular tachycardia in humans. Unfortunately, although of potential therapeutic value, differentiation of these forms of reciprocating tachycardia may be difficult and require detailed electrophysiologic study. To develop diagnostic criteria that permit exclusion of participation of an accessory AV pathway in reciprocating tachycardia without extensive laboratory testing, results of electrophysiologic studies were examined in 50 patients with Wolff-Parkinson-White syndrome, 15 patients with accessory AV pathways that conducted only in the ventriculoatrial direction, and 15 patients with reentry within the AV node. The interval between onset of ventricular activation and both earliest recorded atrial activity (V-Amin) and high lateral right atrial electrogram (V-HRA) was measured during tachycardia. A V-Amin of 61 ms or less or V-HRA of 95 ms or less did not occur in patients with accessory AV pathways, but occurred frequently (12 of 15 and seven or eight, respectively) in patients with reentry within the AV node. Therefore, in patients with paroxysmal reciprocating tachycardias, V-A interval measurements provide a screening test capable of excluding participation of an accessory AV pathway.

Pharmacokinetic and pharmacodynamic effects of diltiazem

Abstract The pharmacokinetic and pharmacodynamic effects of diltiazem were studied in 8 patients after a short intravenous infusion (20 mg over 10 minutes), a single oral dose (60 or 90 mg), and repeated oral administration (60 or 90 mg every 6 hours for 16 doses). Diltiazem levels decreased in a triexponential manner after intravenous infusion. Terminal half-lives after intravenous, single oral, and repeated oral administration were not significantly different (4.5 ± 1.3, 3.7 ± 0.6, and 4.9 ± 0.4 hours, respectively). The kinetic effects of oral diltiazem were nonlinear. With repeated oral administration, there was accumulation of both diltiazem and its metabolite, deacetyldiltiazem. The diltiazem area under the time versus concentration curve increased by a factor of 2.39 ± 0.42 (p = 0.00002). Most patients showed a double peaked time versus concentration curve after oral administration, indicating possible enterohepatic recirculation. After intravenous administration, there was a substantial increase in the P-R interval (14.3 ± 5.4%). Although only small changes in P-R interval were seen with a single oral dose, with chronic administration there was persistent P-R interval prolongation, peaking at 17.3 ± 5.6% over control. Counterclockwise hysteresis was present in the P-R interval versus plasma diltiazem concentration curve after intravenous administration. Only small changes were seen in heart rate and blood pressure.

Epicardial mapping in the Wolff-Parkinson-White syndrome.

Epicardial mapping provides a method for defining antegrade and retrograde sites of pre-excitation. It is best undertaken only after a careful, detailed preoperative electrophysiological study has been performed. The potential pitfalls of the technique are many and technical expertise must be constantly available to maintain a functioning system. For these reasons, it is not likely to lend itself to widespread application. The same techniques can be applied to localization of the site of origin of atrial or ventricular dysrhythmias, localization of myocardial ischemia and infarction, as well as to differentiate between epicardial delays due to conduction delay and those caused by intramural myocardial delay.