Influence of a Third Extrastimulus in Deflning Effective Drug Therapy During Serial Electrophysioiogicai Testing

Many electrophysiology laboralories use three extrastimuli in all patients with ventricular tachyarrhythmias during antiarrhythmic drug testing, regardless of the mode of arrhythmia induction in the baseline state. The purpose of this study was to compare this pacing protocol (full protocol) with a protocol in which three extrastimuli were only used during drug tests, if they were required in the baseline state for arrhythmia induction (limited protocol). There were 181 electrophysiology lests performed on 69 patients with ventricular tachyarrhythmias that were retrospectively analyzed. In all studies the full protocol was used, but the results of stimulation were also analyzed assuming the limited protocol had been used. In the baseline state, sustained ventricular tachyarrhythmias were reproducibly inducible with one or two extrastimuli in 38 (55%) patients. Of these patients, six (16%) achieved a drug efficacy prediction using the full protocol versus 15 (39%) patients using the limited protocol (P < 0.001). In all 69 patients, the drug response rate increased from 25% to 38% (P < 0.01) using the limited protocol. Overall, the cycle length of induced ventricular tachycardia during drug testing was longer than during baseline testing (352 ± 8vs 296 ± 7 msec, P < 0.001); however, the cycle length of ventricular tachycardia induced by three extrastimuli during drug restudies in patients in whom tachycardia had only required one or two extrastimuli to induce in the baseline state was not significantly different from the baseline tachycardia cycle length (303 ± 15 vs 318 ±11 msec, P = NS). and was significantly shorter than the cycle length of tachycardia induced by one or two extrastimuli during drug testing (303 ± 15 vs 385 ± 15 msec, P < 0.01). Using three extrastimuli in all patients during drug testing decreases the yield of drug efficacy predictions, but whether predictive value is improved or made worse cannot be answered from this study.     

Promotion of Ventricular Tachycardia Induction by Procainamide in Dogs with Inducible Ventricular Fibrillation Late After Myocardial Infarction

The influence of procainamide on inducible ventricular tachyarrhythmias was evaluated in 35 dogs with experimental myocardial infarction, and 9 normal dogs. Programmed stimulation was performed from the right ventricular apex via a percutaneously positioned electrode catheter, using up to five extrastimuli before and after intravenous administration of procainamide (15 mg/kg). Procainamide levels in postinfarct dogs were 8.5 +/- 0.7 micrograms/mL (range 5.3-13.6 micrograms/mL). Procainamide exerted its greatest effect in postinfarct dogs with reproducible baseline ventricular fibrillation. Six of nine dogs (P less than 0.05) with ventricular fibrillation had sustained monomorphic ventricular tachycardia (cycle length: 147 +/- 4 msec) induced after procainamide administration. This ventricular tachycardia required significantly more extrastimuli than baseline ventricular fibrillation (3 +/- 0.3 extrastimuli before vs 4 +/- 0.3 extrastimuli after procainamide). Procainamide never converted ventricular fibrillation to ventricular tachycardia in normal dogs. Procainamide had minimal effect on inducible ventricular tachycardia after myocardial infarction. Ventricular tachycardia induction was abolished in only 2 of 17 dogs despite significant prolongation of electrophysiological parameters. Ventricular tachycardia cycle length, and the number of extrastimuli required were unchanged by procainamide in this subgroup. Conclusion: Ventricular tachycardia is insensitive to the antiarrhythmic properties of procainamide in this model. In contrast, procainamide is able to convert postinfarction ventricular fibrillation to ventricular tachycardia, presumably by promoting sustained, organized reentry. This previously undescribed action is an unusual form of proarrhythmic effect, and suggests that this drug should be used cautiously in patients after myocardial infarction.     

A Comparison of Ventricular Arrhythmias Induced with Programmed Stimulation Versus Alternating Current

In patients undergoing implantation and testing of the implantable cardio-verter defibrillator (ICD), alternating current (AC) may be used to induce ventricular tachyarrhythmias in a prompt, safe, and efficient manner. These arrhythmias have been previously reported to be similar to those induced during programmed electrical stimulation (PES). We compared the ventricular tachyarrhythmias induced by both methods in 14 patients: 8 male, 6 female; mean age 61 years; coronary disease in 10, cardiomyopathy in 4; mean ejection fraction 31%. The presenting arrhythmia was nonsustained ventricuiar tachycardia (VT) in four, sustained monomorphic ventricular tachycardia (SMVT) in five, ventricular fibrillation (VF) in four, and unknown in one patient with syncope. PES (single, double, triple extrastimuli; burst pacing) and AC (1–2 sec application) stimulation via right ventricular endocardial electrode catheter was performed off antiarrhythmic drugs in the nonsedated state. PES induced SMVT in nine, polymorphic VT in two, and VF in three. AC induced VF in all patients. Although AC can reliably induce ventricular tachyarrhythmias during de/ibrillation threshold and ICD testing, there is poor correlation to PES induced tachyarrhythmias.     

Phenytoin in the Treatment of Inducible Ventricular Tachycardia: Results of Electrophysiologic Testing and Long-Term FoUow-Up

Phenytoin treatment of inducible ventricular tachyarrhythmias was assessed by serial electrophysiologic studies (EPS) in 64 patients with spontaneous ventricular tachycardia, cardiac arrest, or symptoms compatible with a ventricular tachyarrhythmia. Coronary artery disease was the primary cardiac disease in 75% of the patients. All subjects had either inducible ventricular tachycardia (greater than or equal to 10 repetitive beats) or ventricular fibrillation at electrophysiologic study. Phenytoin was administered intravenously in 38 studies and orally in 31 studies. The mean serum phenytoin level was 19.5 +/- 4.7 mcg/ml. Only seven patients (11%) had a negative electrophysiologic study (less than or equal to 10 repetitive beats) after the administration of phenytoin and were classified as phenytoin responders (group I). The remaining 54 patients (89%) were classified as nonresponders (group II). For the nonresponders, phenytoin increased the cycle length of identical monomorphic ventricular tachycardias from a mean of 31 ms to a mean of 327 ms (p less than 0.001). For the four patients tested receiving both intravenous and oral phenytoin, the intravenous response always predicted the oral response. For the seven patients in whom electrophysiologic study indicated phenytoin efficacy, two are alive and arrhythmia-event free, two had sudden death when the regimen was changed (one case, quinidine added; one case, subtherapeutic serum level), and three died from nonarrhythmic causes. For the 10 patients treated empirically with phenytoin, either alone (seven patients) or in combination with another antiarrhythmic agent (three patients), four died secondary to an arrhythmic event.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sotalol: Current Status and Expanding Indications

BACKGROUND: The role of antiarrhythmic drug therapy continues to undergo major changes. The change is necessitated by the advent of invasive interventional procedures, such as catheter ablation of arrhythmias and the use of implantable devices for sensing and terminating life-threatening ventricular arrhythmias and symptomatically traublesome supraventricular arrhythmias. Many conventional and time-honored drugs, such as sodium channel blockers, have been found either to be ineffective or to have the potential to produce serious proarrhythmic reactions. Attention is therefore focused on compounds that prolong repolarization and reduce sympathetic stimulation. Two compounds, amiodarone and sotalol, have emerged as prototypes of drugs of the future. METHODS AND RESULTS: This review focuses on sotalol for controlling supraventricular and ventricular tachyarrhythmias. Sotalol is a major antiarrhythmic agent that combines potent class III action with nonselective beta-blocking properties. The drug's pharmacokinetics is simple. Its elimination half-life is 10-15 hours, the drug being excreted almost exclusively by the kidneys. Sotalol's pharmacokinetics allows development of optimal dosing for initiation of therapy relative to changes in creatinine clearance with further dose adjustment by monitoring the QT interval on the surface electrocardiogram. The compound exerts broad-spectrum antiarrhythmic actions in supraventricular and ventricular arrhythmias. It prevents inducible ventricular tachycardia (VT) and ventricular fibrillation (VF) in approximately 30% of patients with a higher figure for the suppression of spontaneously occurring arrhythmias documented on Holter recordings. CONCLUSIONS: The major role of sotalol is in the management of VT/VF often in conjunction with an implantable cardioverter/defibrillator, in which context it lowere the defibrillation threshold. Sotalol is superior to class I agents, especially in VT/VF and in survivors of cardiac arrest. Sotalol has emerged as a major antifibrillatory compound for the control of life-threatening ventricular arrhythmias as the main indication. Data have indicated its potential for the maintenance of stability of sinus rhythm in patients with atrial fibrillation and flutter after electrical conversion and in preventing their occurrence in a variety of clinical settings.     

Results of Electrophysiological Testing and Long-Term Follow-Up in Patients Sustaining Cardiac Arrest Only While Receiving Type IA Antiarrhythmic Agents

Therapeutic management of patients sustaining a cardiac arrest while receiving antiarrhythmic agents can be difficult since the role of the drug in possibly facilitating the arrhythmia is often difficult to define. To determine if the response to programmed stimulation could give insight into which patients may have experienced a drug-induced cardiac arrest, we studied 29 patients (61 +/- 9 years) with no prior history of sustained ventricular tachyarrhythmias (VT) who suffered a cardiac arrest only while receiving type Ia antiarrhythmic agents. Patients with documented myocardial infarction, acute ischemia, electrolyte abnormalities, or torsade de pointes were excluded from the study. Twenty-four patients had coronary artery disease with prior myocardial infarction (ejection fraction 28% +/- 9%) and five patients had idiopathic dilated cardiomyopathy (ejection fraction 31% +/- 6%). During baseline electrophysiological testing, 19 patients (66%) had inducible sustained ventricular arrhythmias: uniform VT, n = 14 (group I), polymorphic VT or ventricular fibrillation, n = 5 (group II). Ten patients (group III) had no inducible sustained ventricular arrhythmias. To determine if rechallenge with a type Ia agent could facilitate induction of a sustained ventricular arrhythmia in group III, eight patients underwent ten electrophysiological studies during therapy with either procainamide or quinidine. Only two patients developed sustained VT in response to programmed stimulation. Patients in groups I and II received therapy guided by electrophysiological testing, including antiarrhythmic agents alone (n = 8), subendocardial resection (n = 4), or an implantable cardioverter defibrillator (n = 7). Patients in group III received antiarrhythmic agents empirically (n = 3), or for treatment of atrial tachyarrhythmias (n = 2) or nonsustained VT (n = 1). In addition, four patients in group III received an implantable cardioverter defibrillator. During a mean follow-up of 28 +/- 27 months (range: 1 day-84 months) 13 patients died suddenly or received a defibrillator shock preceded by syncope or presyncope: group I: n = 5; group II: n = 2; group III: n = 6. In conclusion: (1) most patients sustaining a cardiac arrest only in the presence of type Ia antiarrhythmic agents have inducible sustained VT in the absence of antiarrhythmic agents, and (2) the risk of recurrent VT persists in patients without inducible sustained arrhythmias in the drug-free state, regardless of whether they manifest inducible arrhythmias after rechallenge with a type Ia agent.     

Value of Serial Electropharmacological Testing in Managing Patients Resuscitated from Cardiac Arrest

Electrophysiologic studies were performed in 11 patients (9 men, 2 women; mean age: 59.9 yrs) who had survived an episode of cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation. The purpose of the studies was to evaluate the usefulness of serial acute drug testing in selecting an effective chronic antiarrhythmic regimen. Ten of the patients were suffering from chronic ischemic heart disease with one or more previous myocardial infarctions while one had no evidence of structural heart disease. A ventricular aneurysm was present in four of them. During control electrophysiologic study, a sustained VT was induced by ventricular stimulation (single and double extrastimuli at various paced ventricular cycle lengths plus bursts of rapid ventricular pacing) in nine of the ten patients (90%) who were studied while not receiving antiarrhythmic drugs; a non-sustained VT was induced in one of them (10%). In three patients (30%) VT could be initiated only by right ventricular stimulation at a side different from the apex (outflow tract). No arrhythmia was observed in the only patient who was studied while taking amiodarone orally (400 mg/day for more than three months). During serial acute drug testing a totally effective drug regimen (successful in preventing the induction of any ventricular arrhythmia) was found in seven of the ten patients (70%) who underwent this procedure and a partially effective drug regimen (a sustained VT was no longer inducible; it was easier to interrupt and it was considerably slower) was found in two patients (20%). None of the nine patients who received chronic antiarrhythmic therapy based on the results of serial acute drug testing died suddenly during a mean follow-up of 14 months (range: 3-28) and only one had a recurrence of cardiac arrest. The latter, however, was taking antiarrhythmic drugs at a dosage less than that proved to be effective during electropharmacological testing. The only patient who refused serial acute drug testing and received an empiric antiarrhythmic therapy died suddenly at the 21st month of follow-up. These results indicate that serial electropharmacological testing is useful in selecting an effective long-term drug regimen in survivors of cardiac arrest.     

Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses

Clinical cardiac electrophysiologic testing has evolved rapidly since 1968, when the technique was first described. In an electrophysiologic study, electrode catheters are positioned within the heart to record electrical activity from the atrium, atrioventricular conduction tissue, and ventricle. Programmed stimulation is then performed, which involves pacing of the atrium or ventricle and introducing critically timed premature stimuli during sinus rhythm or paced rhythm. The use of programmed stimulation in conjunction with intracardiac recordings in electrophysiologic studies has facilitated the diagnosis of mechanisms of arrhythmias and the assessment of therapy. Electrophysiologic testing is useful in selected patients with sinus node dysfunction, conduction system disorders, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation and in survivors of out-of-hospital cardiac arrest and patients with symptomatic but unsubstantiated rhythm disturbances. Therapeutic approaches that can be assessed by electrophysiologic testing include serial drug testing to determine the effectiveness of antiarrhythmic agents, antitachycardia pacing, the implantable defibrillator, transcatheter ablation, and electrophysiologically guided surgical procedures. In this review, we discuss the methods of electrophysiologic testing, its clinical applications in diagnosing the various cardiac rhythm disturbances, and its use in assessing various therapeutic modalities.     

Ventricular fibrillation/tachycardia

Ventricular fibrillation and rapid ventricular tachycardia called as pulseless tachycardia are both fetal and need immediate therapy to respore sinus rhythm. Sustained monomorphic ventricular tachycardia is also known to have a poor prognosis. Diagnosis of these arrhythmias should be followed by electrophysiologic study for risk stratification. The efficacy of the antiarrhythmic drug therapy is known to be limited. Catheter ablation can cure the arrhythmia but the success rate is limited: 50-70% in selected patients. Though symptomatic, ICD is the most reliable therapy so far. Antiarrhythmic drugs or catheter ablation should be tried as adjunctive therapy in fatal ventricular arrhythmias.     

Idiopathic Ventricular Fibrillation in Out-of-Hospital Cardiac Arrest Survivors

This study examined diagnostic and therapeutic roles of electrophysiological testing and long-term clinical outcome after out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation. This is defined as ventricular fibrillation occurring in the absence of detectable underlying heart disease or metabolic or electrolyte disturbance. Out-of-hospital cardiac arrest resulting from idiopathic ventricular fibrillation is uncommon. Records of all patients who underwent electrophysiological testing between June 1979 and June 1992 were reviewed. Patients with out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation were identified. Follow-up information was obtained by telephone interview in June 1992. Of 194 patients who underwent electrophysiological study after out-of-hospital cardiac arrest not associated with acute myocardial infarction, only six (4 male and 2 female) had idiopathic ventricular fibrillation. It was induced in only two patients by programmed ventricular stimulation. No sustained ventricular arrhythmias were induced in the remaining four patients. Four patients received implantable cardioverter defibrillators, one was treated with a β-adrenergic blocker, and one received no treatment. All patients were alive at a mean follow-up of 50 months. Two of the four patients without inducible sustained ventricular arrhythmias had events during follow-up. Of the two patients with inducible ventricular fibrillation, one experienced a cardiac arrest and documented ventricular fibrillation at 41 months after the index event and the other had had no recurrence at 15-month follow-up. All four patients with implantable cardioverter defibrillators were alive at last follow-up, and two had device discharges. In survivors of out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation: (1) programmed electrical stimulation is of limited value for evaluating cause and guiding therapy; (2) a high rate of recurrent events is observed (50%); and (3) an implantable cardioverter defibrillator is effective for preventing a fatal outcome.     

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).     

Effects of Coronary Artery Bypass Grafting on Ventricular Arrhythmias: Results with Electrophysiological Testing and Long-Term Follow-Up

Myocardial revascularization was performed in 56 patients with coronary artery disease who presented with ventricular tachycardia (VT) (n = 39) or ventricular fibrillation (n = 17). There were 46 men and 10 women, aged 65 ± 10 years. Three vessel (n = 42) or left main disease (n = 4) was present in 82%. Left ventricular ejection fraction averaged 36%± 11%. Electrophysioiogical studies were performed preoperatively in all patients; 50 (89%) had inducible ventricular arrhythmias. Sustained monomorphic VT was induced in 40 patients (cycle length 284 ± 61 msec). Reproducible symptomatic nonsustained VT was induced in four patients and ventricular fibrillation in six patients, while six patients had no inducible arrhythmia. Preoperatively the patients with inducible VT failed 3.3 ± 1.2 drug trials during electrophysiological studies. In addition to coronary bypass, 22 patients also received an automatic implantable cardioverter defibrillator (ICD), 26 patients received prophylactic ICD patches, and 1 patient had resection of a false aneurysm. There were no perioperative deaths. Postoperative electrophysiological studies were performed in all 56 surgical survivors. Ventricular tachyarrhythmia could not be induced in the six patients who had no inducible VT preoperatively and in 13 of 40 (33%) with preoperatively inducible sustained VT or in 19 of 50 (38%) patients with any previously inducible ventricular arrhythmia, thus a totaJ of 25 patients (45%) had no inducible VT postoperatively. Of the remaining, 11 patients were treated with antiarrhythmic drugs alone, 11 had already received an ICD (combined with drugs in 7), and another 9 received the ICD postoperatively (combined with drugs in 4). At a mean foJJow-up of 28 ± 21 months there were 11 deaths (20%): 2 sudden, 5 nonsudden cardiac, and 4 noncardiac deaths. There were 16 nonfatal VT recurrences (29%): 14 among patients with persistently inducible arrhythmias, and onJy 2 among those with no inducible arrhythmia postoperatively (P = 0.004); 13 occurred in patients with an ICD (P = 0.01). Thus among these patients with malignant ventricular arrhythmias who underwent revascuJarization, 45% had no inducible arrhythmia postoperatively with 33% of those with preoperatively inducible sustained VT apparently rendered noninducible by revascularization, while the majority (70%) remained free of major arrhythmic events during long-term follow-up. We conclude that myocardial revascularization alone can result in no ventricular arrhythmia induction in selected patients with VT inducible prior to surgery. Long-term follow-up of such patients indicates a low sudden death and arrhythmia recurrence rate. Furthermore, in patients with persistently inducible ventricular tachyarrhythmias after coronary revascuJarization, the sudden death rate is low despite a high frequency of nonfatal arrhythmia recurrence when antiarrhythmic medications are guided by programmed stimulation or an ICD is used.     

Selection of Patients with Recurrence of Ventricular Tachyarrhythmias for Electrical Studies

Clinical cardiac electrophysiologic testing has been employed in the evaluation and treatment of patients with tachyarrhythmias. In patients with recurrent supraventricular tachyarrhythmias, electrophysiologic study is indicated when the arrhythmia is life-threatening or significantly disruptive to lifestyle, when empiric therapy has failed to control the arrhythmia, or when supraventricular tachycardia complicates the Wolff-Piarkinson-White syndrome. In patients with ventricular tachyarrhythmias, electrophysiologic study should be undertaken when life-threatening sustained ventricular tachyarrhythmias are documented or where a substantial risk of developing these arrhythmias is noted.     

Predictors of Ventricular Tachvcardia Inducibility in Programmed Electrical Stimulation and the Effectiveness of Serial Drug Testing: Polish Multicenter Study

WNUK-WOJNAR, A.M., ET AL.: Predictors of Ventricular Tachycardia Inducibility in Programmed Electrical Stimulation and Effectiveness of Serial Drug Testing: Polish Multicenter Study. In 100 patients with IHD and complex ventricular arrhythmias, programmed electrical stimulation was performed using up to three extrastimuli at sinus rhythm, and paced 100, 120, and 140 beats/min delivered from the RV apex, outflow tract or the LV with ventricular mapping to evaluate late potentials (LP) in 41 patients. Sustained monomorphic VT (SMVT) was provoked in 91% of 42 patients with a history of VT/VF, p < 0.001, all five patients had SMVT in 24-hour ECG, p < 0.005, and 91% of 21 patients with LV dyskinesis, p < 0.01. After depolarizations were found in 62% of 21 patients with a history of VT, in 58% of 31 patients with inducible VT, p < 0.01 and in five of six patients with LV dyskinesis. In patients with inducible VT, LP had a higher amplitude (105 ± 35 vs 60 ± 47 µV) and were more delayed (202 ± 96 vs 133 ± 75 msec) than in noninducible patients. In 17 patients, serial drug testing was performed after oral administration using mexilitene, disopyramide, chinidine, propafenone, sotalol, and amiodarone. If one drug was tested, the therapy efficacy was 25% if two drugs-60%, and if three drugs-75%. In eight patients, VT was inducible in all tests, but in only one of these patients chronic antiarrhythmic therapy was not effective. We conclude that the most important predictors of VT inducibility are a history of VT or 24-hour ECG, and LV dyskinesis. Serial drug testing is efficient only when many drugs are tested, but even if VT is inducible, it does not exclude the possibility of a good clinical outcome in chronic therapy.     

Programmed Electrical Stimulation Protocols: Variations on a Theme

A series of prospective protocols were designed to determine the yield ratio (true positives vs. false positives = nonclinical) in various patient groups using a variety of programmed electrical stimulation (PES) variables. First, a PES protocol was used in 772 patients. Single, double, and triple extrastimuli were delivered in sequence (leaving each successive extrastimulus just beyond its refractory period before moving to the next extrastimulus) during sinus rhythm and two ventricular paced rates at the RV apex, before moving to the outflow tract and repeating the sequence and then moving on to isoproterenol infusion with the PES sequence repeated at the apex. This protocol met NASPE standards for induction of VT in patients with coronary artery disease and a history of VT, while failing to induce monomorphic VT in any control patient. The best yield ratios combined with the greatest likelihood of inducing clinical tachycardia were achieved with sinus rhythm and three extrastimuli, and pacing at the lower rate and three extrastimuli. Pacing at the faster rate and triple extrastimuli was highly inductive of clinical arrhythmias, but had a low yield ratio due to induction of more nonclinical arrhythmias than other steps. The next protocol was performed in 61 patients with inducible ventricular tachycardia. In each case, the protocol described above was completed at the RV apex, even if tachycardia was also induced at an earlier point in the protocol. This allowed for more accurate yield ratios to be established for each step in the protocol, since each patient was exposed to each of these steps. The results confirmed those of the first protocol described above. The next protocol compared extrastimuli delivered (1) in a straight sequential fashion (each extrastimulus decremented to its refractory period and then left just late enough to capture while the next extrastimulus was added and decremented in a similar fashion); versus (2) the tandem method, in which after reaching refractoriness, each extrastimulus was moved 50 msec beyond the refractory period and then decremented in tandem with the next extrastimulus. Preliminary analysis of this protocol in > 30 subjects indicates no significant difference in the number of clinical or nonclinical arrhythmias induced with these methods, although the tandem method was much more time consuming. We conclude that a simple sequential PES protocol, taken to refractoriness, is efficient and effective, and is not at a disadvantage compared to more complex or cumbersome protocols.     

Excellent Long‐Term Reproducibility of the Electrophysiologic Efficacy of Quinidine in Patients with Idiopathic Ventricular Fibrillation and Brugada Syndrome

Background: Quinidine is very effective in preventing the reinduction of sustained ventricular fibrillation (VF) during electrophysiologic study (EPS) in patients with idiopathic VF and Brugada syndrome. However, there are no data on the long‐term reproducibility of this EP efficacy. Methods and Results: Nine patients (seven males and two females, aged 21–72 years), who suffered from aborted cardiac arrest (n = 8) or recurrent syncope (n = 1) due to Brugada syndrome (n = 5) or idiopathic VF (n = 4), comprised the study. All patients had inducible sustained VF at baseline that was prevented by quinidine therapy and underwent another EPS on medication after 1.7–23.6 (9.8 ± 6.8) years (>5 years in eight patients). Two patients underwent two late EPS on quinidine. The goal of repeat EPS on quinidine was to ensure persistent long‐term drug efficacy (n = 6) or to elucidate the reason of syncopal episodes during therapy (n = 3). The EPS protocol significantly evolved over the years as it became more aggressive (more pacing sites and/or more ventricular extrastimuli). All nine patients tolerated the medication well and had no recurrent documented arrhythmic events during long‐term follow‐up (mean 15 ± 7 years). No sustained ventricular tachyarrhythmias could be induced in any patient during repeat late EPS. In six patients, a more aggressive stimulation protocol could be tested at repeat EPS. Conclusion: The long‐term reproducibility of the EP efficacy of quinidine in patients with idiopathic VF and Brugada syndrome is excellent. EP‐guided quinidine therapy represents a valuable long‐term alternative to ICD therapy in these patients.     

Frequency of spontaneous and inducible atrioventricular nodal reentry tachycardia in patients with idiopathic outflow tract ventricular arrhythmias

OBJECTIVES: We sought to assess the frequency of spontaneous or inducible atrioventricular nodal reentry tachycardia (AVNRT) in patients referred for radiofrequency ablation (RFA) of idiopathic outflow tract ventricular arrhythmias. BACKGROUND: In patients with no obvious heart disease, AVNRT and outflow tract ventricular tachycardia (VT) are the most frequently encountered supraventricular and ventricular tachycardias, respectively. An increased coexistence of the two arrhythmias has been recently suggested. METHODS: In 68 consecutive patients referred for RFA of an idiopathic ventricular outflow tract arrhythmia, a stimulation protocol including repeated bursts of rapid atrial pacing, up to triple atrial extrastimuli during sinus rhythm and rapid ventricular pacing was performed before and after isoproterenol infusion following RFA of the ventricular arrhythmia. In patients with inducible AVNRT, RFA of the slow pathway was performed. RESULTS: Of the 68 study patients, 17 (25%) had either spontaneous AVNRT documented prior to RFA of the ventricular arrhythmia (n = 4) or inducible AVNRT at the time of RFA of the ventricular arrhythmia (n = 13). AVNRT was induced by atrial pacing in 15 (88%) of 17 patients: in 3 patients without isoproterenol and in 12 patients during isoproterenol infusion. Uncomplicated RFA of the slow pathway was successfully achieved in all patients with inducible AVNRT. CONCLUSION: Spontaneous or inducible AVNRT is relatively common in patients with idiopathic outflow tract ventricular arrhythmias. Atrial stimulation, especially when performed after isoproterenol infusion plays a major role in AVNRT inducibility. Although we performed RFA of the slow pathway in patients with inducible AVNRT and no prior tachycardia documentation, the question whether this is mandatory remains unsettled.     

Mexiletine-quinidine combination: enhanced antiarrhythmic and electrophysiologic activity in the dog

Combination treatment with mexiletine and quinidine has been shown to be more effective than either monotherapy in the treatment of ventricular tachycardia in humans. The purpose of this study was to assess the electrophysiologic changes which correlated with enhanced antiarrhythmic activity during treatment with the monotherapies and this combination. Twenty-seven dogs with inducible sustained ventricular tachyarrhythmias (VT) late after ischemic injury were treated with mexiletine and quinidine, alone and in combination. Conscious but sedated animals were assigned randomly to receive serial drug treatments. Sustained VT was consistently inducible during serial placebo studies. In 13 dogs who received all four drug treatments (mexiletine, quinidine, combination and placebo) significantly greater antiarrhythmic efficacy was seen with combination therapy (8 of 13) than was seen with mexiletine alone (1 of 13), quinidine alone (3 of 13) and saline (0 of 13) (P less than .005). This enhanced antiarrhythmic activity was paralleled by greater prolongation of intraventricular conduction to the border zone and increase in excitability threshold at the border zone and increase in ventricular effective refractory period in the infarct zone. Serum concentrations of quinidine were 19 +/- 5 microM when given alone and 15 +/- 5 microM when given in combination. Mexiletine concentrations were 3.6 microM when given alone and 4.2 microM when given in combination. In conclusion, mexiletine and quinidine in combination produced enhanced antiarrhythmic activity which was paralleled by electrophysiologic changes occurring in the perinfarct zone. These electrophysiologic changes appear to be correlates of enhanced antiarrhythmic activity.     

Mechanism and Clinical Significance of Atrial Repetitive Responses in Man

We have studied the electrophysiological correlates of atrial repetitive responses, induced by single extrastimuli, in a group of 25 patients undergoing electrophysiologic studies for a variety of supraventricular and ventricular arrhythmias. The incidence of repetitive responses was not related to a previous history of atrial tachyarrhythmias. Repetitive responses were observed only when the extrastimulus elicited a significant intra-atrial conduction delay, as measured from the extrastimulus artifact, to two or three points in the atria. This condition was fulfilled only when the basic atrial rhythm was paced, and it was also facilitated by increasing atrial rate, which shortened the atrial effective refractory period. Atrial pacing thus seemed to facilitate the production of atrial repetitive responses by both promoting intra-atrial conduction delays during extrastimulation, and by shortening the atrial refractory period. Alrial repetitive responses are probably a nonspecific phenomenon, unrelated to a tendency towards atrial tachyarrhythmias; their mechanism is probably local re-entry, related to slow conduction of impulses during incomplete repoiarization, and under favorable conditions they may precipitate atrial flutter or fibrillation in predisposed patients.     

Data-driven Decisions: The Importance of Clinical Trials in Arrhythmia Management

As a result of clinical trials, the measurement of arrhythmias has evolved over the past three decades. In the late 1960s, customary teaching was that ventricular premature depolarizations were dangerous and antiarrhythmic therapy, in hopes of reducing fatal consequences, became common place; however, following clinical trials such as CAST, IMPACT, and SWORD, we learned that, at least in postinfarct patients, arrhythmia suppression may lead to increased rather than reduced mortality. Such trials have led to a marked reduction in therapy of indiscriminate ventricular ectopy and have led to ongoing testing of specific subgroups identified as having particularly higher adverse prognostic risk. With the advent of cardiac monitoring and the confirmation that ventricular tachyarrhythmias are the most common cause for sudden death, their therapy, too, has evolved and matured, again aided by clinical trials. The ESVEM study prospectively examined the role of monitor-guided versus electrophysiologically guided drug therapy of ventricular tachyarrhythmias and confirmed that both approaches may have a role in reducing arrhythmic deaths-though the specific benefits of each technique remain somewhat unsettled. Both the ESVEM and CASCADE studies suggested that the most effective drugs for ventricular tachyarrhythmias are the class II/III drugs, sotalol and amiodarone, both appearing more effective than our older class I agents. These should now be viewed as the first-line drugs for these arrhythmias. The relative benefits of these two agents with respect to each other and to implantable cardioverter defibrillators, however, remains to be determined by further clinical trials, such as AVID and CIDS. The therapy of atrial tachyarrhythmias has similarly evolved with the aid of clinical observations. While rate control is required in all patients with atrial fibrillation, we have come to realize that the applications of antiarrhythmic drugs for the purpose of maintaining sinus rhythm must be used only selectively rather than uniformly. Both a meta-analysis by Coplen and colleagues and a report by the SPAF investigators suggested that with atrial arrhythmias, too, antiarrhythmic drug therapy may result in enhanced rather than reduced mortality in some circumstances. Additional clinical trials are needed to further elucidate the role of antiarrhythmic therapy of atrial fibrillation.