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.     

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.     

Are Electrophysiological Studies Needed Prior to Defibrillator Implantation?

At present, patients with documented sustained VT or resuscitated cardiac arrest (CA) are treated with ICDs. The aim of this study was to retrospectively evaluate if a routine electrophysiological study should be recommended prior to ICD implantation. In 462 patients referred for ICD implantation because of supposedly documented VT (n = 223) or CA (n = 239), electrophysiological study was routinely performed. In 48% of the patients with CA, sustained VT or VF was inducible. Electrophysiological study suggested conduction abnormalities (n = 11) or supraventricular tachyarrhythmias (n = 3) in conjunction with severely impaired left ventricular function to have been the most likely cause of CA in 14 (5.9%) of 239 patients. Likewise, sustained VT was only inducible in 48% of patients with supposedly documented VT. Of these inducible VTs, nine were diagnosed as right ventricular outflow tract tachycardia or as bundle branch reentry tachycardia. Supraventricular tachyarrhythmias judged to represent the clinical event were the only inducible arrhythmia in 35 (16%) patients (AV nodal reentrant tachycardia [n = 7], AV reentry tachycardia [n = 4], atrial flutter [n = 19], and atrial tachycardia [n = 5]). Based on findings from the electrophysiological study, ICD implantation was withheld in 14 (5.9%) of 239 patients with CA and in 44 (19.7%) of 223 patients with supposedly documented VT. During electrophysiological study, VT or VF was only reproducible in about 50% of patients with supposedly documented VT or CA. Electrophysiological study revealed other, potentially curable causes for CA or supposedly documented VT in 12.6% (58/462) of all patients, indicating that ICD implantation can potentially be avoided or at least postponed in some of these patients. Based on these retrospective data, routine electrophysiological study prior to ICD implantation seems to be advisable.     

Electrophysiological Evaluation of Sustained Ventricular Tachyarrhythmias in Idiopathic Dilated Cardiomyopathy

Sustained ventricular tachyarrhythmias and sudden death are particularly prevalent in patients with idiopathic dilated cardiomyopathy (IDC). In contrast to patients with ischemic heart disease, the value of electrophysiological stimulation (EPS) in patients with IDC has not yet been established. To clarify the role of EPS in these patients, we studied 19 patients (58 +/- 11 years) with IDC who had symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF). The mean left ventricular ejection fraction was 26 +/- 9%. Ten patients had survived out-of-hospital cardiac arrest, eight had documented sustained monomorphic VT and one patient had non-sustained VT associated with syncope. Thirteen of the 19 patients (68%) had their clinical ventricular tachyarrhythmias induced at EPS (12 VT, 1 VF). In nine of 13 patients (69%), the arrhythmias were subsequently suppressed during serial electrophysiological drug testing. During 17 +/- 11 months of follow-up, 10/19 (53%) patients experienced recurrence of their arrhythmias and nine out of 19 (47%) patients died; six died suddenly and three secondary to heart failure. There was no difference in arrhythmia recurrence between patients with and without inducible ventricular tachyarrhythmias at initial study. Furthermore, suppression of arrhythmia during serial testing did not predict outcome; recurrences were observed in five out of nine patients whose arrhythmias were suppressed.(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.     

The Role of Combination Therapy with Mexiletine and Procainamide in Patients with Inducible Sustained Ventricular Tachycardia Refractory to Intravenous Procainamide

This study evaluated the role of serial electropharmacological testing on combination therapy with mexiletine and procainamide in 20 patients with inducible sustained ventricular tachycardia (VT) refractory to intravenous procainamide. The clinical arrhythmias were cardiac arrest in five patients, sustained VT in 11 patients, and recurrent syncope of presumably arrhythmic origin in four patients. The mean left ventricular ejection fraction (LVEF) was 0.40 +/- 0.12 (mean +/- SD). All patients had inducible sustained VT at baseline and after administration of intravenous procainamide. All 20 patients underwent electropharmacological testing on combination therapy with mexiletine and procainamide. The mean cycle length of inducible sustained VT was 251 +/- 48 ms at baseline, 324 +/- 81 ms on intravenous procainamide (P less than 0.014 vs baseline), and 365 +/- 82 ms on combination therapy (P less than 0.0001 vs baseline, P = NS vs intravenous procainamide). Combination therapy did not suppress VT inducibility, nor did it make VT more difficult to induce in 19 of 20 patients. The remaining one patient had a partial response (runs of nonsustained VT, longest 10 seconds). Furthermore, combination therapy did not significantly prolong the VT cycle length over and above that observed during testing with intravenous procainamide. Therefore, in patients with inducible sustained VT refractory to procainamide during initial electropharmacological testing, mexiletine in combination with procainamide appears to be of little or no value and serial electropharmacological testing on these drugs is of limited usefulness. Early initiation of alternative therapy may be the preferred clinical option.     

Filtered QRS duration on signal-averaged electrocardiography predicts inducibility of ventricular tachycardia in arrhythmogenic right ventricle dysplasia

Treatment of arrhythmogenic right ventricular dysplasia (ARVD) is mostly based on the prevention of sudden cardiac death that results from arrhythmias. A clinical history suggestive of ARVD requires careful evaluation including electrophysiological study. The potential ability to identify those patients who will have inducible VT with electrophysiological study will enable better risk stratification and selection of vulnerable patients for electrophysiologically guided therapy. The purpose of the study was to evaluate the predictive ability of signal-averaged electrocardiography (SAECG) to predict inducibility of VT in patients with ARVD. The patient population consisted of 31 ARVD patients diagnosed with McKenna's criteria who underwent electrophysiological study. Electrophysiological study was considered positive if sustained monomorphic VT was induced. The sensitivity, specificity, and predictive accuracy of various SAECG criteria for inducibility of sustained monomorphic VT were also calculated. Twenty-one patients had inducible VT. The filtered QRS duration (fQRS), duration of signal <40 uV (LAS40), and root mean square voltage in the last 40 ms of QRS duration (RMS40) in ARVD patients induced versus noninduced were 122 +/- 21 and 103 +/- 8 ms (P=0.007), 45 +/- 20 and 28 +/- 14 ms (P=0.02), 19 +/- 19 and 32 +/- 22 uV (0.03), respectively. The ejection fractions were comparable in both groups. fQRS duration > or =110 ms had sensitivity of 91%, specificity of 90%, and a total predictive accuracy of 90% in predicting inducibility of VT in these patients. Filtered QRS duration on SAECG is predictive of electrophysiological study outcome in ARVD. Further studies will be needed to determine if SAECG results can predict the development of ventricular arrhythmias during follow-up.     

Results of Holter ECG Guided Therapy for Ventricular Arrhythmias: The ESVEM Trial

The Electrophysiological Study Versus Electrocardiographic Monitoring (ESVEM) trial randomized 486 patients with spontaneous sustained ventricular tachycardia (VT), ventricular fibrillation (VF) or unmonitored syncope, who manifested reproducibly inducible sustained ventricular arrhythmias by provocative stimulation and 10 or more premature ventricular contractions per hour on Holter monitoring, to two groups treated with pharmacotherapy guided by suppression of stimulation-inducible VT/VF or suppression of spontaneous or exercise induced ventricular arrhythmias. There was no difference over four years of follow-up in the rates of recurrence of arrhythmias, arrhythmic mortality, cardiac mortality, or mortality from any cause between the two groups of patients but more patients [77%) received pharmacotherapy in ihe group treated on the basis of suppression of spontaneous arrhythmias than the group treated on the basis of electrophysiological study. In this trial, rates of recurrence of arrhythmias were higher (37% at one year and 66% at four years) than generally reported, but cardiac and arrhythmia mortality were comparable or lower than generally reported. Of the seven agents tested, six were sodium channel blockers (imipramine, mexiletine, procainamide, propafenone, pirmenol, and quinidine) and the other was sotalol. Sotalol had a significantly higher rate of efficacy predictions by EPS (35%) than the others (15%) and a comparable rate by Holter monitor. Sotalol was significantly more efficacious in preventing recurrences, arrhythmic mortality, cardiac mortality, and total mortality than the other agents and it was better tolerated. Probability of successful long term therapy with a sodium channel blocker tested by electro-physiological study was low (5% at one year). These results indicate sotalol is a reasonable first option for pharmacotherapy io prevent recurrent VT/VF in patients comparable to the patients included in ESVEM and that Holter monitoring is an acceptable mode of guiding therapy.     

Should Electrophysiological Studies Be Performed in Asymptomatic Patients Following Myocardial Infarction? A Pragmatic Approach

We analyze the arguments commonly afforded by advocates of electrophysiological evaluation for patients with recent myocardial infarction. These argu ments are: (1) electrophysiological evaluation is useful for risk stratification of infarct survivors; and (2) it may be used for guiding drug therapy or to identify a group of asymptomatic patients who will benefit from implantation of an automatic cardioverter defibrillator. A positive electrophysiological study is ap parently the single best predictor of future arrhythmic events in infarct survivors. However, several nonin-vasive tests combined may provide just as valuable information. Therefore, electrophysiological evalua tion should not be advised, to the majority of infarct survivors, for the mere purpose of risk stratification. Nevertheless, electrophysiological evaluation may be proposed to patients with impaired left ventricular function or high grade ventricular arrhythmias. Patients without inducible arrhythmias have a good prog nosis and may be spared the risk of long-term treatment with antiarrhythmic drugs. However, before proceeding with invasive electrophysiological evaluation, both physician and patient should ask them selves if they are willing to go ahead with defibrillator implantation in case sustained monomorphic ventricular tachycardia is induced.     

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.     

Long-Term Outcome Following Programmed Electrical Stimulation in Patients with High-Grade Ventricular Ectopy

To determine if programmed electrical stimulation (PES) could be utilized to identify patients with high-grade ventricular ectopy at low- or high-risk for sudden cardiac death, we performed PES in 40 patients with high-grade ventricular ectopy refractory to conventional antiarrhythmic agents. Twenty-one patients had a previous myocardial infarction, five had cardiomyopathy, six had hypertension, three had valvular heart disease and five had no known structural heart disease. The mean age was 50 years (range, 18 to 76). During programmed ventricular stimulation, eight patients had inducible sustained (more than 30 seconds) monomorphic ventricular tachycardia (Group I) but in 32 patients sustained ventricular tachycardia was not inducible (Group II). None of the five patients without structural heart disease were inducible while seven out of 21 (33%) patients with previous myocardial infarction had inducible ventricular tachycardia (VT). Antiarrhythmic therapy was instituted in patients with inducible VT; patients without inducible VT did not receive antiarrhythmic agents. In Group I, seven of the eight patients are alive (mean follow-up, 16 months) and in Group II, 28 of the 32 patients are alive (mean follow-up, 17 months). None of the five deaths were sudden. We conclude that in the absence of antiarrhythmic therapy, the incidence of sudden cardiac death is very low in patients with high-grade ventricular ectopy who do not have inducible monomorphic ventricular tachycardia during programmed ventricular stimulation.     

Retrospective Analysis of Patients Undergoing One- or Two-Stage Strategies for Myocardial Revascularization and Implantable Cardioverter Defibrillator Implantation

Internal defibrillation leads were placed at time of coronary revascularization in 79 patients. In 34, an implantable cardioverter defibrillator (ICD) was placed simultaneously (group I). A two-stage strategy (selective implantation of the ICD in patients with postoperative spontaneous or inducible ventricular tachycardia [VT]) was followed in 45 patients (group II). Group I patients had failed more antiarrhythmic drug trials (2.9 +/- 1.6 vs 1.5 +/- 1.6; P = 0.02), including amiodarone (62% vs 20%; P less than 0.001). There were four operative deaths in each group. Postoperatively, VT was present in 27 group II patients (60%), 25 of whom received an ICD (two refused device implantation). Patients with postoperative VT had a lower left ventricular ejection fraction than those without VT (33 +/- 9 vs 47 +/- 16; P = 0.01). Actuarial survival at 1, 2, and 3 years was 88 +/- 6, 88 +/- 7, and 88 +/- 10 in group I; and 83 +/- 6, 76 +/- 7, and 76 +/- 11 in group II (NS). No patient without an ICD (based on the postoperative electrophysiological study [EPS]) died suddenly. Five patients (6%) had ICD system infection. Sudden death was largely prevented by either strategy, but relatively high rates of operative mortality and ICD system infection were observed. Prospective studies should identify patients more likely to benefit from one or another strategy.     

Induced Sustained Ventricular Tachycardia in Nonischemic Dilated Cardiomyopathy: Dependence on Clinical Presentation and Response to Antiarrhythmic Agents

Thirty-one patients with nonischemic dilated cardiomyopathy either idiopathic or due to regurgitant valvular disease were studied in the cardiac electrophysiology lab. The indications for study were sustained ventricular tachycardia (VT) in 26, ventricular fibrillation (VF) in 11, and syncope of unknown etiology in 4. Sustained VT was reproducibly induced in 17 patients, including 12 with a history of sustained VT, 2 with VF and 3 with syncope. Of 15 patients undergoing serial antiarrhythmic drug studies, sustained VT was rendered noninducible or nonsustained in 23. Three had recurrent arrhythmic events while on therapy predicted to be effective. One of 2 patients discharged on a regimen predicted to be ineffective had a recurrence of sustained VT that resulted in cardiac arrest. Of 14 patients in whom sustained VT could not he reproducibly induced, 2 subsequently had spontaneous occurrences of sustained VT, and 2 experienced aborted sudden death. These results suggest the following; (1) the induction of sustained VT in the setting of nonischemic dilated cardiomyopathy is dependent on the clinical presentation; (2) antiarrhythmic drugs frequently render sustained VT noninducible or nonsustained; (3) antiarrhythmic drug suppression of inducible sustained VT predicts long-term prevention of spontaneous recurrences; and (4) noninducibility of sustained VT in the baseline state does not predict freedom from subsequent episodes of VT or sudden death.     

Sustained polymorphic arrhythmias induced by programmed ventricular stimulation have prognostic value in patients receiving defibrillators

BACKGROUND: Patients with ischemic cardiomyopathy (ICM) who have monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation (PVS) are at increased risk of sudden cardiac death (SCD). Among a primary prevention population, the prognostic significance of induced polymorphic ventricular arrhythmias is unknown. METHODS: A total of 105 consecutive patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention of SCD in the setting of ICM and non-sustained VT were retrospectively evaluated. Seventy-five patients (group I) had induction of monomorphic VT and 30 patients (group II) had a sustained ventricular arrhythmia other than monomorphic VT (ventricular flutter, ventricular fibrillation, and polymorphic VT) induced during PVS. RESULTS: Baseline characteristics were similar between group I and group II except for ejection fraction (25% vs. 31%, P = 0.0001) and QRS duration (123 milliseconds vs. 109 milliseconds, P = 0.04). Sixteen of 75 (21.3%) patients in group I and 6 of 30 (20%) patients in group II received appropriate ICD therapy (P = 0.88). Survival free from ICD therapy was similar between groups (P = 0.54). There was a trend toward increased all-cause mortality among patients in group I by Kaplan-Meier analysis (P = 0.08). However, when adjusted for age, EF, and QRS duration mortality was similar (P = 0.45). CONCLUSIONS: There is no difference in rates of appropriate ICD discharge or mortality between patients dichotomized by type of rhythm induced during PVS. These results suggest that patients in this population who have inducible VF or sustained polymorphic VT have similar rates of subsequent clinical ventricular tachyarrhythmias as those with inducible monomorphic VT.     

Risk Factors for Tachycardia Events Caused by Antiarrhythmic Drugs: Experience From the ESVEM Trial

BACKGROUND: In the Electrophysiology Study versus Electrocardiographic Monitoring (ESVEM) trial, up to seven antiarrhythmic drugs were randomly assigned to 486 patients with a history of sustained ventricular arrhythmia. At baseline, all the patients had inducible sustained ventricular tachycardia (VT) and had >/=10 premature ventricular beats (PVBs) per hour on 48-hour Holter monitoring. A total of 1,229 drug trials were performed. Antiarrhythmic drugs were discontinued during hospitalization because of ventricular tachyarrhythmias thought to be a proarrhythmic effect of the antiarrhythmic drugs in 96 of 479 patients (20%) who received drugs. Proarrhythmic effects were defined as sustained VT, ventricular fibrillation or arrhythmic death, torsade de pointes, or distinct intolerable worsening of the baseline arrhythmia after at least three doses of the drug. METHODS AND RESULTS: Eighteen baseline characteristics were analyzed for factors that would predict a higher incidence of proarrhythmia. These included type of heart disease, previous myocardial infarction, symptom activity scale, gender, type of arrhythmia, VT/ventricular fibrillation, age, left ventricular ejection fraction (LVEF), PVB frequency, heart rate, QRS duration, and QT interval. Multiple logistic regression analysis identified increased mean PVB frequency (P =.003) and increased heart rate (P =.026) as significant predictors of proarrhythmia. Decreased LVEF (<25%) exhibited only a trend toward significance (P =.073). When proarrhythmia was redefined as sustained VT, cardiac arrest of arrhythmic death, or torsade de pointes (n = 59), PVB frequency (P =.003) and heart rate (P =.034) were still the only significant baseline predictors. CONCLUSIONS: In the ESVEM study, higher PVB frequency and higher heart rate were significant predictors of drug-induced proarrhythmia.     

Abnormal heart rate turbulence predicts the initiation of ventricular arrhythmias

BACKGROUND: Abnormal heart rate turbulence (HRT) reflects autonomic derangements predicting all-cause mortality, yet has not been shown to predict ventricular arrhythmias in at-risk patients. We hypothesized that HRT at programmed ventricular stimulation (PVS) would predict arrhythmia initiation in patients with left ventricular dysfunction. METHODS: We studied 27 patients with coronary disease, left ventricular ejection fraction (LVEF) 26.7 +/- 9.1%, and plasma B-type natriuretic peptide (BNP) 461 +/- 561 pg/mL. Prior to arrhythmia induction at PVS, we measured sinus cycles after spontaneous or paced premature ventricular contractions (PVCs) for turbulence onset (TO; % cycle length change following PVC) and slope (TS; greatest slope of return to baseline cycle). T-wave alternans (TWA) was also measured during atrial pacing. RESULTS: At PVS, abnormal TO (> or =0%) predicted inducible ventricular tachycardia (VT; n = 10 patients; P < 0.05). TO was greater in inducible than in noninducible patients (2.3 +/- 3.1% vs -0.02 +/- 2.8%, P < 0.05) and correlated with LVEF (P < 0.05) but not with BNP. TS did not differ between groups. Conversely, ambulatory HRT differed significantly from HRT at PVS (TO -0.55 +/- 1.08% vs 0.85 +/- 3.02%, P < 0.05; TS 2.63 +/- 2.09 ms/RR vs 8.70 +/- 6.56 ms/RR, P < 0.01), and did not predict inducible VT but trended (P = 0.05) to predict sustained VT on 739 +/- 179 days follow-up. TWA predicted inducible (P < 0.05) and spontaneous (P = 0.0001) VT but did not co-migrate with HRT. CONCLUSIONS: Abnormal HRT measured at PVS predicted the induction of sustained ventricular arrhythmias in patients with ischemic cardiomyopathy. However, HRT at PVS did not correlate with ambulatory HRT, nor with TWA, both of which predicted spontaneous ventricular arrhythmias. Thus, HRT may reflect the influence of autonomic milieu on arrhythmic susceptibility and is likely complementary to traditional arrhythmic indices.     

Long-term reproducibility of ventricular tachycardia induction with electrophysiological testing in patients with coronary heart disease and depressed left ventricular ejection fraction

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) has recently confirmed the role of programmed ventricular stimulation (PVS) to identify the high risk patients of sudden death after myocardial infarction and to prevent this risk. The purpose of this study was to evaluate the long-term reproducibility of PVS in these patients. Thirty patients with coronary heart disease without spontaneous documented sustained ventricular tachycardia (VT) underwent two programmed stimulations in the absence of antiarrhythmic drug treatment between 2 and 6 years (mean 4 years). No patient had a myocardial infarction or intervening cardiac surgery during this period. The protocol of study was similar using up to three extrastimuli in two sites of the right ventricle, delivered in sinus rhythm and driven rhythm (600 ms, 400 ms, respectively). On the first PVS, 17 patients had inducible sustained VT (group I). Thirteen patients did not have inducible VT (group II). On the second PVS all group I patients but one had inducible VT, but the cycle length was significantly modified in 11. In group II, five patients had inducible VT and in the other patients the PVS remained negative. In conclusion, in patients with coronary heart disease, but without documented VT, the long-term reproducibility of PVS was excellent in those with inducible VT (94%); the patients remain at risk of VT and a prophylactic implantable cardioverter defibrillator could be considered. In patients with initially negative study, reproducibility of PVS was lower (61.5%), probably because of the progressive remodeling after myocardial infarction. Therefore, the occurrence of new symptoms in patients with previously negative study requires a second programmed ventricular stimulation.     

Dispersion in ventricular repolarization in patients with severe intraventricular conduction disturbances

Increased dispersion of repolarization, measured invasively or by QT interval measurements, is associated with an increased risk for ventricular arrhythmias and sudden death. Most studies on this issue have included patients with normal intraventricular conduction, and it is not known if this finding has a predictive value also in patients with intraventricular conduction disorders. An invasive electrophysiological study, including programmed ventricular stimulation and assessment of effective refractory periods at two RV sites, was performed in 103 patients with bifascicular block (mean age 67 +/- 12 years). QT dispersion was measured from standard 12-lead ECGs. In patients with inducible sustained polymorphic VT or VF the dispersion in refractoriness between the two RV sites was significantly greater (46 +/- 11 ms, n = 13) than in noninducible patients (14 +/- 14 ms, n = 84) and in patients with inducible sustained monomorphic VT (16 +/- 5 ms, n = 6) (P < 0.01). Similarly, QT dispersion was 104 +/- 46 ms, 66 +/- 31 ms, and 77 +/- 33 ms, respectively, in the three groups (P < 0.05). Dispersion in repolarization, neither measured invasively nor by QT interval measurements, predicted sudden death, all cause mortality, or ventricular arrhythmia during a mean follow-up period of 3 years. In patients with bifascicular block, there is a relation between the degree of dispersion of ventricular repolarization and the inducibility of polymorphic ventricular arrhythmia, but this outcome did not occur during follow-up.     

Heart failure

Survival of patients with heart failure has improved over the past decade due to advances in medical therapy. However, sudden cardiac death continues to cause 35 to 65% of death. Ventricular arrhythmias are important causes of sudden cardiac death in patients with heart failure. The risks of antiarrhythmic drugs are increased in patients with heart failure. Therefore, in the absence of a clear indication, antiarrhythmic drug therapy should be avoided. A number of recent randomized trials have provided evidence that beta-adrenergic blockers, angiotensin-converting enzyme(ACE) inhibitors and angiotensin II receptor blockers(ARB) significantly reduces the risk of sudden death in patients with chronic congestive heart failure. For patients who have a history of sustained ventricular tachycardia(VT) or ventricular fibrillation(VF) amiodarone or an implantable cardioverter defibrillator(ICD) should be considered, and these therapy may benefit some high risk patients who have nonsustained VT.     

The Interaction of Antiarrhythmic Drugs and the Energy for Cardioversion of Chronic Atrial Fibrillation

Antiarrhythmic drugs may alter the energy for cardioversion of ventricular arrhythmias. This study compares the energy necessary for cardioverting chronic atrial fibrillation in 57 patients taking type Ia, Ic, or type III antiarrhythmic drugs. Patients taking Ia (n = 22) or III (n = 14) drugs had a median energy for cardioversion of 100 joules, while the patients taking Ic (n = 17) drugs had a median energy of 200 joules (P = 0.03). There were no differences in the frequency of unsuccessful cardioversion. There were no serious adverse events in any of the three groups, although three patients in the Ic group had greater than 3 second pauses after the shock. The data suggest that the use of Ic antiarrhythmic drugs results in a higher energy for cardioversion of atrial fibrillation. However with higher energies, conversion is as successful as for type Ia and type III.