Ruey J. Sung

Electrophysiologic Testing in the Management of Survivors Of Out-of-Hospital Cardiac Arrest

Forty-five patients survived a cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF). Programmed ventricular stimulation was performed with the patients taking no antiarrhythmic medications. Sustained VT was induced in 26 patients (58%) and nonsustained VT in 8 (18%). With treatment aimed at the underlying heart disease (plus empiric antiarrhythmic therapy in 2 patients), the 11 patients who had no inducible VT have had no recurrence of symptomatic VT or cardiac arrest over a follow-up period of 19 +/- 9 months (mean +/- standard deviation). Conventional antiarrhythmic drugs suppressed the induction of VT and were used for chronic treatment in 9 of 34 patients (26%) with inducible VT. Three of these 9 patients had recurrent VT or sudden death, whereas 6 have had no recurrence over follow-up of 20 +/- 7 months. In the 25 of 34 patients in whom the induction of VT was not suppressed by conventional antiarrhythmic drugs, 23 were treated with amiodarone (daily dose 550 +/- 120 mg), and 2 underwent coronary artery bypass grafting with either aneurysmectomy or map-directed endocardial resection. One of the latter 2 patients died suddenly 12 months after surgery. Among the 23 patients treated with amiodarone, 2 had fatal VT or sudden death and 21 (91%) did not, over 18 +/- 14 months of follow-up. In survivors of a cardiac arrest, the chief value of electrophysiologic testing is in identifying patients without inducible VT, who appear to have a low risk of recurrent sudden death with treatment directed at the underlying heart disease. Serial electropharmacologic testing with conventional antiarrhythmic drugs is disappointing, with a low incidence of arrhythmia suppression.

Long-term follow-up of patients with recurrent unexplained syncope evaluated by electrophysiologic testing.

Electrophysiologic testing was performed in 53 patients with recurrent syncope that remained unexplained despite a thorough neurologic and noninvasive cardiac evaluation. Fifteen patients had no structural heart disease, 9 had mitral valve prolapse and 29 had structural heart disease other than mitral valve prolapse. Nonsustained ventricular tachycardia was induced in 15 patients (28%), sustained ventricular tachycardia was induced in 9 (17%), ventricular fibrillation was induced in 4 (8%) and sinus node function was abnormal in 2 (4%). Female sex and lack of structural heart disease were independently associated with a negative electrophysiologic study (p less than 0.001). Patients with inducible ventricular tachycardia or ventricular fibrillation were treated with drugs selected on the basis of the results of electropharmacologic testing. The recurrence rate of syncope was 43% over a 31 +/- 10 month period (mean +/- standard deviation) of follow-up in patients with a negative electrophysiologic study, 40% over a 22 +/- 6 month period in patients with inducible nonsustained ventricular tachycardia, 0% over a 30 +/- 12 month period in patients with inducible sustained ventricular tachycardia and 25% over a 21 +/- 10 month period in patients with inducible ventricular fibrillation. In patients with recurrent unexplained syncope undergoing electrophysiologic testing, a potential cause of syncope is least likely to be found in women without structural heart disease. The results of programmed ventricular stimulation must be interpreted with regard to the method of induction of ventricular tachycardia and the type of ventricular tachycardia induced. The excellent response rate in patients with inducible sustained ventricular tachycardia whose therapy is guided by the results of electropharmacologic testing suggests that sustained ventricular tachycardia is a clinically significant response.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of intravenous diltiazem for treatment of atrial fibrillation and atrial flutter

This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter. A double-blind, parallel, randomized, placebo-controlled protocol was used, and 6 large, urban hospitals, both university-affiliated and private, participated. The study involved 113 patients with atrial fibrillation or flutter, a ventricular rate greater than or equal to 120 beats/min and systolic blood pressure greater than or equal to 90 mm Hg without severe heart failure. The dose of intravenous diltiazem (or identical placebo) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective. If a patient did not respond, the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given. Of 56 patients, 42 (75%) randomized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg, for a total response rate of 52 of 56 patients (93%), whereas 7 of 57 patients (12%) responded to placebo (p less than 0.001). After the double-blind protocol, 49 of the 57 patients who received placebo were then given diltiazem; 47 of 49 responded, for an overall response rate of 99 of 105 patients (94%) with diltiazem. The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes. Side effects occurred in 14 patients, 7 of whom had asymptomatic hypotension not requiring intervention. Thus, intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter. Blood pressure decreased slightly. Side effects were mild.

Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity.

To define the role of verapamil in the treatment of ventricular tachycardia (VT), we studied 21 patients with chronic recurrent VT. Electrophysiologic studies were performed before and during intravenous infusion of verapamil (0.15 mg/kg followed by 0.005 mg/kg per min). On the basis of the mode of VT initiation and termination, we identified three groups of patients: (a) 11 patients had VT suggestive of reentry, as VT could be initiated with ventricular extrastimulation and terminated with overdrive ventricular pacing. Verapamil did not affect the inducibility and cycle length of VT. (b) 7 patients had VT suggestive of catecholamine-sensitive automaticity as VT could not be initiated with programmed electrical stimulation but could be provoked by isoproterenol infusion. Moreover, the VT could not be converted to a sustained sinus rhythm with overdrive ventricular pacing and it resolved only with discontinuing isoproterenol infusion. Verapamil exerted no effects on VT. (c) 3 patients had VT with electrophysiologic characteristics suggestive of triggered activity related to delayed afterdepolarizations. Characteristically, after attaining a range of cycle lengths, the sinus, atrial or ventricular paced rhythm could initiate VT without ventricular extrastimulation. The first beat of VT invariably occurred late in the cardiac cycle with a premature coupling interval 0-80 ms shorter than the preceding QRS cycle length; the premature coupling interval gradually decreased as the sinus, atrial or ventricular paced cycle length progressively shortened. Of note, verapamil completely suppressed VT inducibility in these three patients. These observations lead us to suggest that verapamil does not affect VT caused by reentry and catecholamine-sensitive automaticity but is effective in suppressing VT caused by triggered activity related to delayed afterdepolarizations in humans.

Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation.

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.

Electrophysiologic mechanism of exercise-induced sustained ventricular tachycardia*

To elucidate electrophysiologic mechanism of exercise-induced ventricular tachycardia (VT), electrophysiologic studies were performed in 12 patients in whom sustained VT had developed during treadmill exercise testing. Six patients had arteriosclerotic coronary heart disease, 3 had cardiomyopathy, and 3 had no clinical evidence of organic heart disease. All patients had had documented episodes of sustained VT related to exertion and had experienced dizziness, syncope, or both. In addition, 3 patients had had nonfatal cardiac arrest. Electrophysiologic studies provoked paroxysms of sustained VT identical to those observed during treadmill exercise testing in 10 patients and provoked ventricular flutter/fibrillation in 1. Seven patients had VT suggestive of a reentrant mechanism, as the VT could be readily initiated with programmed ventricular extrastimulation or terminated by ventricular overdrive pacing, or both. Three patients had VT suggestive of catecholamine-sensitive automaticity. The VT could not be initiated with programmed electrical stimulation, but it could be provoked by intravenous isoproterenol infusion; furthermore, the VT could not be terminated with ventricular overdrive pacing, but it could be abolished by discontinuing isoproterenol infusion. Reproduction of VT in these 10 patients allowed serial pharmacologic testing in selecting an effective antiarrhythmic regimen. Thus (1) exercise-induced VT can be caused by either reentry or catecholamine-sensitive automaticity, and (2) electrophysiologic studies are of use in defining the underlying mechanism of exercise-induced sustained VT.

Electrophysiologic and hemodynamic effects of intravenous propafenone in patients with recurrent ventricular tachycardia.

Electrophysiologic and hemodynamic studies were performed before and after intravenous infusion of a new antiarrhythmic agent, propafenone, in 28 patients with recurrent ventricular tachycardia. Propafenone was given at a loading dose of 2 mg/kg in all patients. Subsequently, group A, the first 14 patients, received 1 mg/min and group B, the second 14 patients, received 2 mg/min continuous infusion. Propafenone exerted no effect on sinus nodal recovery time and sinoatrial conduction time, but significantly prolonged atrioventricular (AV) nodal and His-Purkinje conduction time and the QRS duration (respectively, 95 +/- 19, 48 +/- 10 and 120 +/- 23 ms before, and 110 +/- 28, 53 +/- 10 and 135 +/- 27 ms after; p less than 0.001). Propafenone did not change the mean arterial blood pressure but slightly increased right atrial, pulmonary artery and capillary wedge pressures resulting in mild depression of the cardiac index (2.6 +/- 0.8 liters/min per m2 before and 2.3 +/- 0.7 liters/min per m2 after; p less than 0.001). None of the patients were symptomatic from these changes. In group A, propafenone did not affect the inducibility of ventricular tachycardia except for one patient whose arrhythmia was sustained before and become nonsustained after propafenone. In group B, sustained ventricular tachycardia became noninducible in three patients and nonsustained in two patients, and nonsustained ventricular tachycardia became noninducible in one patient after propafenone. Therefore, an appropriate loading dose of intravenous propafenone such as 2 mg/kg followed by 2 mg/min infusion may be given safely and may suppress ventricular tachycardia. Propafenone may be a useful addition to currently available antiarrhythmic agents.

Electrophysiologic testing in the management of patients with the Wolff-Parkinson-White syndrome and atrial fibrillation

Twenty patients with the Wolff-Parkinson-White (WPW) syndrome and 1 or more episodes of symptomatic atrial fibrillation (AF) due to rapid anterograde bypass tract conduction underwent electrophysiologic testing. The mean ventricular rate during spontaneous AF was 242 +/- 56 beats/min (+/- standard deviation) and the shortest preexcited R-R interval was 194 +/- 40 ms. Six patients underwent surgical bypass tract ablation and 14 were treated medically, based on the results of electropharmacologic testing. Over a mean follow-up period of 35 +/- 19 months (+/- standard deviation), only 1 patient treated medically had a recurrence of minimally symptomatic AF. The successful chemoprophylaxis of symptomatic AF was associated with the inability to induce AF and atrioventricular reciprocating tachycardia during drug testing (7 patients) or with the induction of AF with a ventricular rate less than 200 beats/min and a shortest preexcited R-R interval of greater than 250 ms (7 patients). Electrophysiologic testing can identify a subgroup of patients with WPW and AF in whom medical therapy is a suitable alternative to bypass tract ablation.

Programmed ventricular stimulation in patients without spontaneous ventricular tachycardia

Programmed ventricular stimulation was performed in 52 patients who had not had a documented or suspected episode of spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF). Programmed stimulation with up to three extrastimuli was performed from the right ventricular (RV) apex in all patients and from the left ventricular (LV) apex in 14 patients. A maximum response of one to five intraventricular reentry beats was induced in 52% of patients. Nonsustained VT (six or more repetitive beats terminating spontaneously within 30 seconds) was never induced in the 16 patients without structural heart disease but was induced (usually with triple extrastimuli) in 45% of nine patients with mitral valve prolapse and in 37% of 27 patients with other types of heart disease. Sustained VT was never induced; however, sustained VF was induced in two patients. During programmed RV and LV stimulation with up to three extrastimuli (with 2 msec pulses, 5 mA in intensity), (1) a maximum response of one to five repetitive beats is a nonspecific finding of no predictive value; (2) nonsustained VT was not induced in patients without structural heart disease who had not had spontaneous VT; (3) nonsustained VT was frequently induced in patients with structural heart disease who had not previously been known to have had VT; (4) the induction of sustained VT appears to be a response specific to patients who have had spontaneous VT or VF; and (5) sustained VF can be induced infrequently in patients who have never had spontaneous VT or VF.

Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias.

To assess effects of beta-adrenergic blockade on ventricular tachycardia (VT) of various mechanisms, electrophysiology studies were performed before and after intravenous infusion of propranolol (0.2 mg/kg) in 33 patients with chronic recurrent VT, who had previously been tested with intravenous verapamil (0.15 mg/kg followed by 0.005 mg/kg/min infusion). In the verapamil-irresponsive group, 10 patients (group IA) had VT that could be initiated by programmed ventricular extrastimulation and terminated by overdrive ventricular pacing, and 11 patients (group IB) had VT that could be provoked by isoproterenol infusion (3-8 micrograms/min) but not by programmed electrical stimulation, and that could not be converted to a sustained sinus rhythm by overdrive ventricular pacing. Notably, in the group IA patients, all 10 patients had structural heart disease (coronary arteriosclerosis or idiopathic cardiomyopathy); beta-adrenergic blockade accelerated the VT rate in one patient but exerted no effects on the VT rate in the remaining 9 patients, and VT remained inducible in all 10 patients. By contrast, in the group IB patients, 7 of the 11 patients had no apparent structural heart disease; beta-adrenergic blockade completely suppressed the VT inducibility during isoproterenol infusion in all 11 patients. There were 12 patients with verapamil-responsive VT (group II). 11 of the 12 patients had no apparent structural heart disease. In these patients, the initiation of VT was related to attaining a critical range of cycle lengths during sinus, atrial-paced or ventricular-paced rhythm; beta-adrenergic blockade could only slow the VT rate without suppressing its inducibility. Of note, 14 of the total 33 patients had exercise provocable VT: two in group IA, five in group IB, and seven in group II. Thus, mechanisms of VT vary among patients, and so do their pharmacologic responses. Although reentry, catecholamine-sensitive automaticity, and triggered activity related to delayed afterdepolarizations are merely speculative, results of this study indicate that beta-adrenergic blockade is only specifically effective in a subset group (group IB) of patients with VT suggestive of catecholamine-sensitive automaticity.