Safety and efficacy of oral sotalol for sustained ventricular tachyarrhythmias refractory to other antiarrhythmic agents.

The safety and efficacy of oral sotalol were evaluated in 481 patients with drug-refractory sustained ventricular tachyarrhythmias (VT) in an open-label multicenter study. After drug-free baseline evaluations, therapy was initiated at 80 mg every 12 hours, with upward dose titrations of 160 mg/day being allowed at intervals of 72 hours to a maximum dose of 480 mg every 12 hours. Efficacy determinations were made by either programmed electrical stimulation (PES) or Holter monitoring responses. Of the 481 patients enrolled, 473 underwent acute-phase titration. Of the 269 patients assessable by PES, 94 (34.9%) exhibited complete response (suppression of inducible VT), with an additional 67 patients (24.9%) exhibiting partial response. Of the 109 patients assessable by Holter monitoring, 43 (39.4%) exhibited a complete response. There were no significant differences between responders and nonresponders with regard to left ventricular ejection fraction. Although response rates tended to improve as the sotalol dose was increased to 640 mg/day, efficacy was most commonly achieved at a sotalol dose of 320 mg/day. Sotalol was discontinued because of adverse effects in 42 (8.9%) of the acute-phase patients. The most common adverse effect was proarrhythmia, which was observed in 23 patients (4.9%). Proarrhythmia took the form of torsades de pointes in 12 patients and an increase in VT episodes in 11. In 3 acute-phase patients (0.6%), sotalol was discontinued because of the emergence of congestive heart failure. A total of 286 patients entered the long-term phase. Life-table estimates of the proportion of patients who remained free of recurrence of arrhythmia at 12, 18, and 27 months were 0.76, 0.72, and 0.66, respectively. There were no significant differences in time to recurrence of arrhythmia as related to PES response, Holter monitor response, baseline left ventricular ejection fraction, or history of congestive heart failure. Among the 70 patients (24.5%) in whom there was recurrence of arrhythmia, sudden death occurred in 17 and sustained VT in 41. Sotalol was discontinued owing to presumed adverse effects in 21 (7.3%) of the long-term patients, including 8 with proarrhythmia; proarrhythmia consisted of torsades de pointes in 3 patients and increased episodes of VT in 5. These findings suggest that sotalol is an effective drug for the long-term treatment of patients with drug-refractory sustained VT. Proarrhythmia was observed in only 6.4% of the study population and tended to occur during the acute titration phase. The need to discontinue therapy because of congestive heart failure was uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

Case report: nuclear magnetic resonance imaging in a patient with a pacemaker.

The presence of a pacemaker has been considered a contraindication for magnetic resonance imaging (MRI) examination. The authors describe a patient with a pacemaker who underwent MRI of the head without sequelae. Spine-echo MRI was preformed with 1.5 Tesla imager using head coil only. Prior to imaging, the pacemaker was programmed to the OOO mode. In carefully selected pacing-independent patients, with a pacemaker in a bipolar configuration, MRI of the head appears to be safe provided the pacemaker is programmed to OOO and enough scar tissue has developed to prevent pacemaker or lead movement.

Carotid sinus hypersensitivity in patients with unexplained syncope: clinical, electrophysiologic, and long-term follow-up observations.

To assess the incidence and clinical characteristics of carotid sinus hypersensitivity and the relationship to electrophysiologic findings, 76 patients with unexplained syncope underwent carotid sinus massage during electrophysiologic studies for syncope evaluation. Twenty-one patients (28%) were found to have carotid sinus hypersensitivity. Of these 21 patients, 11 (52%) had coronary artery disease, two (10%) had hypertensive heart disease, and eight (38%) had no organic heart disease. During electrophysiologic studies, abnormal sinus node function was found in three patients (14%), abnormal atrioventricular (AV) node function was noted in four (19%), and combined abnormal sinus node and AV node functions were seen in three (14%). Eleven patients (53%) had a normal electrophysiologic study. During carotid sinus massage, sinus arrest alone was observed in 12 patients (57%), and combined sinus arrest and AV nodal block was seen in nine (43%). Thirteen patients were treated with a permanent pacemaker, in whom either carotid sinus massage reproduced the symptom or concomitant sinus node or AV node abnormality, or organic heart disease was present. With a mean follow-up of 42 +/- 19 months, none of these 13 patients had recurrent syncope. However, one of eight patients (13%) who did not receive a pacemaker had recurrence of syncope. Subsequently, this patient has done well after implantation of a pacemaker. These observations suggest that there is a significant incidence of carotid sinus hypersensitivity in patients with unexplained syncope. Permanent pacing appears to be beneficial in selected patients based on clinical and electrophysiologic findings.

Clinical predictors of electrophysiologic findings in patients with syncope of unknown origin.

Unexplained syncope is a common medical problem. Intracardiac electrophysiologic studies (EPS) have been used to uncover the underlying arrhythmic mechanisms. Electrophysiologic studies are especially helpful in the management of patients with inducible tachyarrhythmias, but is of limited usefulness in those with normal EPS findings. We investigated whether clinical and noninvasive laboratory variables can predict the results of EPS in 89 patients with unexplained syncope. The prevalence of inducible ventricular tachycardia (VT) was 15%; supraventricular tachycardia, 15%; bradyarrhythmias, 41%; and normal EPS, 29%. We used multivariate discriminant function analysis to predict the results of EPS. The variables selected for identification of patients with inducible VT by this analysis include New York Heart Association (NYHA) functional class, gender, digitalis use, nonsustained VT, and atrial fibrillation. Based on our statistical model, performing EPS on 45% of the patients with unexplained syncope would result in a 90% sensitivity in detecting patients with inducible VT. The variables selected for identification of patients with normal EPS findings include: New York Heart Association functional class, heart disease, digitalis use, and intraventricular conduction. Based on this model, it would require that all but 12% of patients with unexplained syncope be studied to achieve a 90% predictive accuracy for identification of patients with normal EPS. During follow-up, recurrence rates for the different EPS categories did not differ significantly. The five-year cumulative survival among the EPS groups were as follows: VT, 37% +/- 28%; SVT, 90% +/- 9%; bradyarrhythmias, 71% +/- 10%; and normal EPS, 96% +/- 4%. Survival of the VT group differed significantly from that of the normal group. In patients with unexplained syncope, EPS findings can be predicted from clinical and noninvasive laboratory data. Mortality during follow-up relates to EPS findings.

"Quinidine syncope" without lengthening of Q-Tc interval in the presence of left bundle branch block. Role of programmed ventricular stimulation studies.

Idiosyncratic and proarrhythmic reactions to antiarrhythmic drugs are a well-recognized phenomenon and appear to correlate poorly with Q-T prolongation or with the serum concentration of the drug. It therefore becomes difficult to identify patients clinically with an underlying electrophysiologic substrate for ventricular tachycardia which was made manifest by an antiarrhythmic drug, or to determine whether the drug is causing an idiosyncratic reaction (the classic "long Q-T syndrome"). We recently studied a patient with ischemic heart disease and a prolonged corrected Q-T interval (Q-Tc) due to chronic left bundle-branch block. She developed "quinidine syncope," and the Q-Tc was unchanged despite stopping administration of the drug; however, electrophysiologic studies demonstrated reproducibly inducible "torsade de pointes" while the patient was being rechallenged with quinidine, while no inducible arrhythmia was seen during control studies. We conclude that electrophysiologic studies are of clinical value in the clarification of possible drug-induced arrhythmias.

Worsening of ventricular tachycardia by amiodarone.

The details of worsening of ventricular tachycardia in 8 (4.1%) of 194 patients receiving treatment with amiodarone are reported. Two forms of amiodarone-induced tachycardia were recognized: first, the development of new tachycardias (three patients) and second, a change in the pattern of recurrence of clinical tachycardia (five patients). In retrospect, the time from the initiation of amiodarone to the initial documentation of worsening ranged from 1 to 23 days (mean +/- SD, 9.4 +/- 8.2 days) and the time from the initiation of therapy to the recognition of worsening ranged from 6 to 26 days (14.6 +/- 10.1 days). Seven patients survived the worsening of tachycardia and one died. The total dose of amiodarone received and the duration of administration did not correlate with time to manifestation or time to resolution of worsening. This report emphasizes that worsening of ventricular tachycardia as a result of amiodarone is often difficult to differentiate from inadequate drug loading or early recurrence of 2 patient's clinical tachycardia. Further, because of the pharmacokinetics of the drug, the manifestations of worsening may be prolonged. In the cases reported, it ranged from 2 to 26 days (7.9 +/- 8.3 days), which is longer than previously reported. Because of the potential for amiodarone to cause life-threatening worsening of ventricular tachycardia and in accordance with current results, a period of in-hospital monitoring of at least 10 days at the start of therapy with amiodarone is recommended.

Correlation between the signal-averaged electrocardiogram and electrophysiologic study findings in patients with coronary artery disease and sustained ventricular tachycardia.

Ventricular late potentials at the end of the surface QRS, detected on the signal-averaged electrocardiogram (SAECG) have been shown to be markers for spontaneous and/or inducible ventricular tachycardia (VT) in patients with coronary artery disease (CAD). We examined the correlations between electrophysiologic study (EPS) findings and SAECG indexes in 50 patients with chronic CAD with documented spontaneous VT/ventricular fibrillation (VF), who had either syncope (24 patients) or aborted sudden cardiac death (SCD). The prevalence of late potentials was significantly higher in the syncope patients (75%) compared with the SCD group (46%) (p less than 0.05). No correlation was found between the ventricular refractoriness and the SAECG indexes. There was a significant difference in quantitative SAECG indexes comparing the induction mode of the sustained VT/VF by single and double versus triple extrastimuli; the types of the induced VT (sustained monomorphic, sustained pleomorphic or VF, noninducible); and the cycle length of the induced sustained monomorphic VT with the high frequency QRS duration (QRSD). In conclusion, differences in prevalence and characteristics of ventricular late potentials were found between patients with syncope and with SCD. The degree of abnormality of SAECG indexes correlated with the type and the mode of induction of sustained VT. The magnitude of QRSD of the SAECG correlated with the cycle length of monomorphic VT. The above findings suggest that in patients with CAD and sustained VT/VF the SAECG variables are related to the area of reentry.

The automatic implantable cardioverter-defibrillator. Clinical experience, complications, and follow-up in 25 patients.

Twenty-five patients with recurrent ventricular tachyarrhythmias underwent implantation of an automatic implantable cardioverter-defibrillator. The mean length of follow-up was 11.9 +/- 10.8 months. Before the implantation, the patients had survived one or more cardiac arrests (mean, 1.7; range, 1 to 4) and episodes of syncope (mean, 2.2; range, 2 to 3) and had received 6.0 +/- 1.0 antiarrhythmic drug trials. The in-hospital complications included death (two patients), reoperation (one patient), intraoperative myocardial infarction (one patient), sensing-failure (one patient), infection (five patients), and pocket seroma (two patients). The posthospital complications included device failure (four patients), device deactivation (one patient), and inappropriate discharge (two patients). The device discharged appropriately in seven patients due to sustained ventricular tachycardia. During electrophysiologic measurements, the energy requirement for successful cardioversion-defibrillation was related to the type of ventricular arrhythmia induced (monomorphic or pleomorphic ventricular tachycardia or fibrillation). Ventricular tachycardia acceleration occurred in ten patients (40%). No significant changes were found in the size of the electrograms or in the cardioversion threshold during early and late follow-up measurements. Life table analysis showed a 12-month survival rate of 86% and an arrhythmic death survival rate of 100%. We confirm the improved rate of survival in this high-risk group of patients, despite significant complications.

Cardiac arrhythmias--update 1987.

Arrhythmias may result from abnormalities of impulse initiation (automaticity), conduction (slow conduction, block, reentry), or a combination. The central and peripheral nervous systems have an important influence on the genesis of cardiac arrhythmias. Sympathetic and parasympathetic fibers innervate both atria and ventricle. The study of clinical cardiac arrhythmias includes the use of invasive and noninvasive testing procedures. The ECG, ambulatory monitoring, esophageal recording, exercise testing, and signal averaging techniques are the currently used noninvasive tests. Intracardiac electrophysiologic studies and endocardial catheter mapping are invasive techniques. The treatment of cardiac arrhythmias includes the use of antiarrhythmic drugs, cardiac pacing (antibradycardia, antitachycardia), implantable automatic defibrillator, cardiac fulguration, and antitachycardiac surgery. Clinical cardiac arrhythmias are of two types, the bradyarrhythmias and the tachyarrhythmias. The tachyarrhythmia, in turn, may be supraventricular or ventricular. There are clinical syndromes specifically related to arrhythmias: preexcitation syndromes are associated with supraventricular tachyarrhythmias, long Q-T syndromes with ventricular tachyarrhythmias, and sick sinus syndrome with bradyarrhythmias. The "tachycardia-bradycardia syndrome" is a combination of atrial tachyarrhythmias and sinus node dysfunction (some of the patients may also have ventricular tachyarrhythmias). Specific arrhythmias are recognized by their ECG characteristics. These arrhythmias also have specific electrophysiologic features which can be defined during invasive electrophysiologic studies. Cardiac arrhythmias may or may not be accompanied by underlying organic heart disease. Their treatment is related to the specific diagnosis and mechanism of the rhythm disturbance. The presence and extent of underlying organic heart disease is an important factor in the selection of antiarrhythmic therapy (drug, pacemaker, or surgery).

Emergency treatment of tachyarrhythmias.

The diagnosis, clinical aspects, and emergency treatment of the most common cardiac arrhythmias, including atrial flutter and fibrillation, paroxysmal supraventricular tachycardia, the Wolff-Parkinson-White syndrome, ventricular tachycardia, and torsades de pointes, are discussed. The use of the antiarrhythmic drugs most frequently utilized in clinical practice is described.

Unexpected coexistence of supraventricular and ventricular tachycardia in patients with syncope.

The incidence of multiple, inducible sustained arrhythmias during electrophysiologic studies is unknown. We have identified five patients who had several sustained tachycardias, some of which were not previously recognized clinically. Three patients had documented sustained supraventricular tachycardia (one of these also had nonsustained ventricular tachycardia) and two had documented sustained ventricular tachycardia. The clinically documented tachycardia was successfully reproduced in all cases; however, the three cases of supraventricular tachycardia also had sustained ventricular tachycardia initiated, and the two cases of ventricular tachycardia also had sustained supraventricular tachycardia, which had not previously been seen. The underlying common denominators for all five patients were poor left ventricular function due to ischemic heart disease and a history of syncope. In one case of clinical supraventricular tachycardia, the second sustained tachycardia appeared following drug therapy (procainamide), which seemed to convert nonsustained to sustained ventricular tachycardia. In another patient with clinical ventricular tachycardia, the supraventricular tachycardia was also initiated following drug therapy (indecainide). We conclude that: (1) patients with syncope may have multiple arrhythmic etiologies and (2) complete electrophysiologic evaluation, during control studies as well as serial drug studies, are important in the management of these patients.

The role of electrophysiologic studies in the management of patients with unexplained syncope.

We evaluated the frequency and type of electrophysiologic abnormalities in an unselected population of consecutive patients with unexplained syncope. Fifty patients were entered in the study; all had 24-hour dynamic electrocardiographic (Holter) recordings and underwent complete electrophysiological studies. An abnormal electrophysiologic study was found in 74% of the patients. Sinus node abnormality was observed in 30%, abnormal AV node function in 14%, long HV in 10%, block distal to H during rapid atrial pacing in 6%, paroxysmal supraventricular tachycardia in 12%, ventricular tachycardia/fibrillation in 8%, and hypersensitive carotid sinus syndrome in 24%. There was no correlation between Holter and electrophysiologic study findings except for the presence of paroxysmal sustained supraventricular tachycardia. Based on clinical, Holter monitoring, and electrophysiologic findings, 38% were treated by antiarrhythmic drugs, 40% received permanent pacemakers, and 22% were not treated at all. During follow-up (23 +/- 13 months), 9 patients (18%) experienced recurrent syncope or death.

Significance of ventricular pauses of three seconds or more detected on twenty-four-hour Holter recordings.

The natural history of patients with asymptomatic prolonged ventricular pauses and the indications for permanent pacing are controversial. To examine this problem, 6,470 consecutive 24-hour Holter recordings were reviewed between 1979 and 1983 for the presence of ventricular pauses of at least 3 seconds. Fifty-two patients (0.8% of total), 22 men and 30 women, were identified with an average longest pause duration of 4.1 seconds. Holter recordings were requested to evaluate syncope in 14 patients (27%), dizziness in 9 (17%) and other reasons in 29 (56%). Causes of the pauses were sinus arrest in 22 patients, atrial fibrillation with slow ventricular response in 18 patients and atrioventricular block in 12. Holter recordings were also evaluated for the presence of tachyarrhythmias. Six patients had nonsustained ventricular tachycardia and 7 had supraventricular tachycardia. Five of the 52 patients (10%) had dizziness or syncope during pauses. Twenty-six patients (50%) received permanent pacemakers. The paced (26 patients) and unpaced (26 patients) groups were similar in the length and etiology of pause, associated tachyarrhythmias, presence of bradycardia-related symptoms, prevalence of organic heart disease, medications and length of follow-up. Four patients in the paced group and 2 in the unpaced group died, yielding 3-year actuarial survival probabilities of 78% and 85%, respectively. It is concluded that ventricular pauses of 3 seconds or longer are uncommon, these pauses usually do not cause symptoms, and the presence of these pauses does not necessarily portend a poor prognosis or the need for pacing in asymptomatic patients.

The role of Holter monitoring in patients with recurrent sustained ventricular tachycardia: an electrophysiologic correlation.

The significance of spontaneous ventricular premature depolarization (VPD) frequency and severity in patients with sustained ventricular tachycardia undergoing serial electrophysiologic studies (EPS) are unknown. Nineteen patients with sustained ventricular tachycardia were studied with 24-hour Holter recordings prior to control EPS and prior to each drug trial. Successful drug or surgical treatment (with the exception of amiodarone) was based upon noninducibility of ventricular tachycardia in the laboratory. Among the eight noninducible and nonamiodarone medically treated patients, two (25%) had significant VPD reduction and/or Lown class improvement. The remaining six (75%) had no change or worsening of Holter findings, despite noninducibility of sustained VT. Among the six amiodarone-treated patients, five of whom were persistently inducible prior to discharge, four (66%) had improved and two (33%) had worsened Holter findings compared to control. None of the five (100%) surgically managed patients were inducible postoperatively, and three of the five (60%) had no change or worsening of Holter findings. We conclude that (1) EPS are superior to Holter findings in assessing successful management; and (2) Holter findings may be concordant or discordant during EPS serial drug trials or following surgery and therefore cannot predict the success or failure of the intervention.

Normal electrophysiological findings in a patient with symptomatic intermittent advanced atrioventricular block.

This report describes an otherwise healthy young woman who presented with syncope during episodes of advanced atrioventricular (AV) block. The His bundle recordings during normal sinus rhythm and atrial and ventricular pacing were normal. Carotid sinus massage produced no abnormality. Subsequently, the patient received a permanent pacemaker and has been free of symptoms. Intermittent advanced AV block has been observed on follow-up electrocardiograms. This unique case demonstrates a potential limitation of routine electrophysiologic investigation.

Dual AV nodal pathways--vagal influences on AV nodal conduction.

This 52-year-old male presented with syncope and demonstrated two distinct PR intervals on the electrocardiogram. Electrophysiologic studies showed dual AV nodal pathways. Right-sided carotid sinus massage induced prolonged periods of sinus arrest with no change in AH interval. Left-sided carotid sinus massage produced long AH intervals (slow pathway conduction) with some slowing of sinus rate. Whenever sinus rhythm with slow pathway conduction was observed (long AH) a 20-30 mmHg drop systolic pressure was seen. Following implantation of an AV sequential pacemaker, the patient has been asymptomatic.

Electrophysiologic effects of intravenous timolol.

We evaluated the electrophysiologic effects and dose response of the long-acting beta-blocking drug timolol given intravenously to 12 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured during control and immediately, 30 minutes, and 48 hours following infusion. Significant changes in electrophysiologic parameters were only observed in the five patients (Group B) who received 0.05 mg/kg and not in the seven patients who received 0.02 mg/kg (Group A). In Group B patients immediately after timolol infusion sinus cycle length increased from 840 +/- 254 msec to 1048 +/- 63 msec (P less than 0.01), A-H interval during normal sinus rhythm increased from 94 +/- 42 msec to 101 +/- 45 msec (P less than 0.05), paced cycle length to A-V nodal Wenckebach increased from 370 +/- 45 msec to 430 +/- 76 msec (P less than 0.05), and A-V nodal effective refractory period increased from 284 +/- 63 msec to 360 +/- 83 msec (P less than 0.01). Significant increases in these electrophysiologic parameters were also noted at 30 minutes following timolol infusion. Other conduction times, atrial and ventricular refractory periods, and corrected sinus node recovery. time were unaltered by timolol. All electrophysiologic parameters returned to control in 48 hours. No adverse effects were observed. We conclude that intravenous timolol in doses of 0.05 mg/kg significantly increases sinus cycle length and prolongs A-V nodal conduction and refractoriness, demonstrates peak effects immediately after intravenous administration, and is well tolerated.

Clinical electrophysiology--a decade of progress.

During the past 14 years there have been major advances in the field of clinical electrophysiology. This progress is a result of a more extensive use of intracardiac electrode catheters with recordings from multiple sites in the right and left cardiac chambers, the introduction of programmed electrical stimulation techniques and the use of antiarrhythmic drugs for diagnostic and therapeutic purposes during acute electrophysiologic testing. This article examines the pioneering studies and the subsequent developments in the field of clinical electrophysiology. The specific topics that are reviewed include the sinus node and atrium, atrioventricular conduction, supraventricular tachycardia and ventricular tachycardia. The therapeutic implications of each topic are also discussed. Clinical electrophysiology in its initial stages was a descriptive technique, but has since become an important diagnostic and therapeutic tool. However, electrophysiologic testing is an intensive process, requiring specialized training and a substantial commitment of human and physical resources.