Direct Current Shock Ablation: Quantitative Assessment of Proarrhythmic Effects

Catheter ablation using direct current (DC) shock has proved invaluable in the management of a variety of tachycardias. However, sporadic reports of fatal arrhythmias following ablation have raised the question of the proarrhythmic potential of DC shock ablation. The present study was undertaken in 45 patients to assess prospectively any proarrhythmia related to DC shock ablation, using matched pre- and postablation Holter monitors and programmed electrical stimulation (PES). Nineteen of these patients had Holter monitors for three successive postablation days to observe trends. There was unmatched data in 11 additional patients. All 56 patients provided prospective follow-up for clinical events. There was no immediate sustained VT/VF at the time of the ablation. Four patients had sustained VT in the first 72 hours after ablation; three episodes were similar to the preablation clinical arrhythmias; one patient had torsades de pointes interrupting bradycardia. Twelve patients met Holter, PES, or clinical criteria for proarrhythmia; none were treated on the basis of these findings. On Holter monitoring, there were significant increases in VPCs/hour and couplets/hour in patients undergoing atrial or atrioventricular junctional ablations; and an increase in couplets after accessory pathway ablations. Increases in these categories were not significant for VT patients; nor were increases in episodes of VT/hour or atrial arrhythmias significant in any group. Patients were followed for 44 +/- 33 months, with an actuarial survival of 95% at 1 year, 88% at 3 years, and 85% at 4 years. There were six deaths during follow-up. Two patients had sudden death: one at 2 months had early evidence of proarrhythmia; the other at 32 months may have represented later myocardia deterioration. One patient died of heart failure at 77 months; and there were three noncardiac deaths. DC shock ablation in humans is much less proarrhythmic than in dogs. The low incidence of clinical proarrhythmic events during prolonged follow-up after discharge resulted in low sensitivity, specificity, and positive predictive values for Holter and PES, although the negative predictive values of these tests were greater than 90%. Only one of 12 patients who met criteria for proarrhythmia in the days immediately following ablation had subsequent clinical events consistent with proarrhythmia. These results may be useful as standards for comparison with results of radiofrequency or other ablation modalities.     

The Value of Exercise Test, Hotter Monitoring, and Programmed Electrical Stimulation in Detection of Ventricular Arrhythmias in Patients with Hypertrophic Cardiomyopathy

To determine the best way to detect serious ventricular arrhythmia in patients with hypertrophic cardiomyopathy (HCM), 15 patients with HCM performed an exercise test, had Holter monitoring during 24 hours, and programmed electrical stimulation (PES) in a randomized order, and the presence and type of ventricular arrhythmia was noted. During exercise testing, only one patient demonstrated ventricular tachycardia (VT) just prior to the test. By Holter monitoring, four patients had short episodes of asymptomatic VT. PES, using up to three extrastimuli induced VT or ventricular fibrillation (VF) in ten patients including those with VT during exercise testing and Holter monitoring. There were no differences between patients with and without ventricular arrhythmia during PES regarding age, left ventricular outflow obstruction, thickness of interventricular septum, interventricular septum/posterior wall thickness ratio, corrected QT interval, or the amplitude of the R wave in lead aVR in electrocardiography. Our results indicate that inducible VT/VF during PES is a common finding in patients with HCM. Twenty-four hour Holter monitoring was superior to exercise testing in revealing serious ventricular arrhythmia in those patients.     

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.     

Efficacy and Safety of Combination Therapy with Amiodarone and Type I Agents for Treatment of Inducible Ventricular Tachycardia

In a prospective study the efficacy of amiodarone in combinalion with the three Class I drugs mexiletine, fiecainide, orencainide was evaluated consecutively in 12 patients with recurrent venlriculav tachycardias (VT) by programmed stimulation. None of the tested drug combinations suppressed induction of sustained VT. The combination of amiodarone with Class IC drugs fJecainide and encainide prolonged the cycle length of VT significantly, whereas the combination with mexiletine did not hove the same degree of slowing on the VT cycle length. Several proarrhythmic effects occurred during the combination therapy with encainide: (1) frequent, spontaneous recurrences of hemodynamically well tolerated VT in four patients; (2) enhanced inducihilily of VT in three patients; (3) impaired termination of VT in three patients. Though a marked increase in QRS and QTc intervals was observed by combined treatment with encainide, no significant correlation could be established between aggravation of arrhythmia and plasma levels of encainide, degree of QRS widening, JT or QTc prolongation. The only predictor for the occurrence of proarrhythmic events was found in left ventricular ejection fraction. These findings suggest that in patients refractory to amiodarone alone or a combination with mexiletine, the combined treatment of amiodarone with other Class IC drugs prolongs the VT cycle length but does not suppress induction of VT during programmed stimulation. Combination therapy of amiodarone with encainide was associated with a high incidence of proarrhythmic effects.     

Invasive and Noninvasive Methods to Predict the Long-Term Efficacy of Amiodarone: A Compilation of Clinical Observations Using Meta-Analysis

Background: The method of choice to predial the long-term efficacy of amiodarone in the treatment of complex ventricular arrhythmias is unknown. Whether electrophysiological testing or Holter monitoring better predicts long-term outcome is controversial. Methods and Results: We performed a meta-analysis of trials using electrophysiological testing or electrocardiographic monitoring to predict the efficacy of amiodarone in patients with sustained ventricular tachycardia. Arrhythmia recurrence data were combined after homogeneity testing across trials. Bayesian estimates and 95% credibility intervals were constructed to compare the arrhythmia-free probability among groups. Nine studies using electrophysiological testing (351 patients) and three using Holter monitoring (167 patients) met criteria for inclusion determined a priori. The combined arrhythmia-free probability estimate and credibility intervals were 0.86 (0.78–0.92) for patients rendered noninducible and 0.81 (0.73–0.87) for patients with abolition of ventricular tachycardia during Holter monitoring on amiodarone. With this primary analysis, there was no significant difference between the predictive value of noninducibility during electrophysiological testing and abolition of ventricular tachycardia with Holter. However, if only those electrophysiological studies using at least triple extrastimuli were included, arrhythmia-free probability for patients rendered noninducible increased to 0.96 (0.88–0.99), significantly better than noninvasive testing. Conclusions: Noninducible ventricular tachycardia during electrophysiological testing and abolition of ventricular tachycardia during electrocardiographic monitoring on amiodarone appear equally predictive of long-term amiodarone success, but this conclusion seems dependent on the stimulation protocol used. Although the vield is lower (compared to Holter monitoring), ventricular tachycardia rendered noninducible with a stimulation protocol using triple extrastimuli is the most highly predictive test of long-term amiodarone efficacy.     

Role of Programmed Electrical Stimulation of the Heart in Risk Stratification Post-Myocardial Infarction

Programmed electrical stimulation (PES) of the heart was evaluated as a method of identifying patients at risk of sudden death post-myocardial infarction (post-MI). Eighty-four patients (mean age, 56 +/- 10 years) underwent PES 6 to 8 weeks post-MI. PES was performed at the right ventricular apex at twice diastolic threshold. Prior to stimulation patients were studied with exercise stress testing, 24-hour Holter monitoring and radionuclide ejection fraction. The patients were placed into two groups, according to their responses to electrical stimulation. Group 1:65 patients in whom no arrhythmias were induced or who had repetitive responses that lasted less than six cycles; Group 2:19 patients in whom ventricular tachycardia was induced. At the end of follow-up (20 +/- 9 months) six patients from Group 1 had died. Complex ventricular ectopy and ventricular tachycardia were more frequently detected on Holter in Group 2 (9/19) than in Group 1 (14/65) (p less than 0.03). The results of exercise testing and radionuclide ejection fraction did not correlate with the response to PES. However all but one of the patients who died had a left ventricular ejection fraction (LVEF) under 40% and four out of six patients had ventricular tachycardia on Holter monitor. We draw the conclusion that PES did not contribute to the identification of high-risk patients post-MI, as none of the 19 patients in whom ventricular tachycardia was induced died during follow-up. In addition, high-risk patients were characterized by poor ventricular function and complex ventricular arrhythmias on Holter recording.     

Arrhythmias in Hypertrophic Cardiomyopathy

Supraventricular and ventncular arrhythmias, particularly nonsustained ventricular tachycardia, and ventricular premature beats are a common finding in patients with hypertrophic cardiomyopathy. Several investigations have demonstrated that nonsustained ventricular tachycardia on Holter monitoring is associated with an increased risk of sudden cardiac death. It has been a long lasting controversial discussion whether suppression of these arrhythmias with drugs, such as amiodarone is capable to reduce the incidence of sudden cardiac death. While recent studies have indicated that nonsustained ventricular tachycardia in asymptomatic patients without additional risk factors, such as a positive family history of sudden cardiac death or syncope should not be treated prophylactically with amiodarone. Symptomatic patients with sustained ventricular tachycardias and/or syncope related to ventricular arrhythmias should undergo ICD implantation. The implantation of an ICD in asymptomatic patients should be limited to those who have several risk factors for sudden cardiac death. It is questionable whether other risk stratifiers, such as programmed electrical stimulation may be helpful to identify asymptomatic patients who are at risk to die suddenly. Moreover, whether the demonstration of electrocardiogram fractionation during electrophysiological study is superior to the induction of sustained ventricular arrhythmias for risk stratification, needs further investigation.     

Electrophysiologic studies of patients with hypertrophic cardiomyopathy presenting with syncope of undetermined etiology

Patients with hypertrophic cardiomyopathy (HC) have a high risk of sudden death. The best clinical predictors of sudden death from HC are young age, strong family history of sudden death, ventricular tachycardia (VT), and progression of symptoms such as syncope. We performed 24-hour Holter monitoring and electrophysiologic studies (EPS) on 26 patients with HC, some with the obstructive form of the disease and some with syncope, in order to predict their vulnerability to syncope and to potentially malignant arrhythmias. Holter monitoring demonstrated supraventricular tachycardia (SVT) in 9/26 patients whereas atrial programmed electrical stimulation induced SVT in 17/26 patients. Of the 17 patients, nine had symptomatic hypotension with SVT while lying supine. Holter monitoring demonstrated nonsustained VT in 7/26 patients whereas ventricular programmed electrical stimulation induced VT or ventricular fibrillation (VF) in 6/26 patients. The patient who had the longest run of nonsustained VT on Holter had VF induced by ventricular programmed electrical stimulation. He was cardioverted to normal sinus rhythm with no untoward effects. We found that atrial programmed electrical stimulation induced SVT with hypotension best predicted a history of syncope in these patients. Although one patient required direct current cardioversion, EPS was conducted safely in all patients. Further long-term studies are needed to demonstrate the value of clinical decisions based upon EPS in patients with HC.     

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)     

Therapy of Sustained Ventricular Arrhythmias With Amiodarone: Prediction of Efficacy With Serial Electrophysiologic Studies

BACKGROUND: Programmed electrical stimulation early during amiodarone therapy has poor prognostic capabilities; and persistent inducibility has been associated with a favorable outcome in a majority of patients. These observations result from studies that differed significantly in methodology. METHODS AND RESULTS: The authors prospectively enrolled 121 patients in a standardized amiodarone dosing protocol in which amiodarone was the only antiarrhythmic agent. Electrophysiologic testing was done after 2 and 6 weeks to determine noninducibility, predictive value, and the significance of drug-induced prolongation of tachycardia cycle length. The mean age of the patients in the study was 63.2 +/- 11.5 years, and their ejection fraction was 32.8 +/- 11.9%. Coronary artery disease was present in 103 (85%). At 2 weeks 17 patients (14%) were no longer inducible, whereas 104 patients (86%) remained inducible. Patients in these groups were similar in age and ejection fraction. During follow-up evaluation, recurrences (35% vs 24%; P =.44) and sudden death (12% vs 13.5%) were similar in the two groups. Thirty-five of 95 patients (32%) with sustained monomorphic ventricular tachycardia had more than 100 ms prolongation of their cycle length, which was hemodynamically well tolerated (partial response), but 60 did not (nonresponse). Patients with a partial response were older (66.5 vs 61.1 years; P =.02) and had longer QRS durations (143.2 vs 129.4 ms; P =.03). They also had increased recurrences (37% vs 17%; P =.01) and more sudden deaths (23% vs 8%; P =.02). At 6 weeks 11 of 76 patients studied were noninducible. They had a lower recurrence rate than those who remained inducible (8% vs 27%; P =.02) but a similar number of sudden deaths (8% vs 16%; P =.27). Thirty-two patients partially responded, and 31 patients did not respond. During follow-up examination these two groups had a similar number of recurrences (25% vs 29%; P =.76) and sudden deaths (16% vs 16%). CONCLUSIONS: Noninducibility at 2 or 6 weeks of amiodarone therapy did not identify patients at low risk of sudden death. In inducible patients, tachycardia cycle length prolongation, even when well tolerated, was not a marker for favorable outcome. Electrophysiologically guided therapy, therefore, offers little benefit over empiric amiodarone.     

Proarrhythmic Response to Antiarrhythmic Drug as a Risk Factor for Sudden Cardiac Death in Patients with Ischemic Heart Disease

The prognostic significance of arrhythmogenicc response to an antiarrhythmic drug was studied. In 782 palients with ischemic heart disease (IHD) and frequent and/or complex ventricular premature boats (VPBs), 1,041 drug tests guided by 24-hour Holter monitoring were conducted. The following drugs were assessed: beta blockers, disopyramide, mexiletine, amiodarone. Proarrhythmia was defined as: (1) > 4-fold increase in VPBs, (2) > 10-fold increase in repetitive forms, or (3) new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). During a follow-up of 1–49 months fmean 22) patients were treated with anfiarrhythmic drugs found to be safe in control Holter monitoring, Proarrhythmic effects were observed in 8.4% of patients. No drug was completely free of this type of reaction. In long-term observation, cardiac death and sudden death occurred in 5.3 and 32 patients, respectively. With actuarial analysis (Kaplan-Meier method, log-rank test) there was a significant difference in cardiac death (P < 0.01) and sudden death rate (P < 0.05) of proarrhythmia (+) compared with proarrhythmia (-) patients at 1 year (11% vs 4%, 7% vs 3%) and 3 years (24% vs 11%, 16% vs 7%). Proarrhythmic response was an independent risk factor apart from myocardial infarction, VT/VF, ejection fraction < 40% and QT_c > 440 msec. Arrhythmogenic response to antiarrhythmic drugs seems to be en additional predictor of sudden death in IHD.     

Predictive value of early electrophysiologic testing in determining long-term outcome with amiodarone treatment in patients with sustained ventricular tachycardia

This prospective study sought to determine whether programmed ventricular stimulation before hospital dismissal in patients who had received a loading dose of amiodarone would identify those at risk for recurrent ventricular arrhythmias. Between January 1985 and January 1989, 64 patients (55 men and 9 women; mean age, 64 years) with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation were referred to our institution for electrophysiologic testing. Of these patients, 52 had coronary artery disease, 11 had dilated cardiomyopathy, and 1 had hypertrophic cardiomyopathy. Of the 64 patients, 47 had baseline tests while no drugs were administered and repeated electrophysiologic testing after 10 days of amiodarone loading (1.2 g/day). The other 17 patients had no baseline study because of instability of their arrhythmias but underwent electrophysiologic testing after amiodarone loading. Follow-up ranged from 7 to 1,536 days (mean, 652 days). During the follow-up period, recurrent arrhythmias were detected in 22 patients. Of the 64 patients, 14 had suppression of VT. Of 43 patients in whom the cycle lengths of VT were determined both at baseline and after amiodarone therapy, 20 had an increase of 100 ms or more, and 23 had no substantial change. The mean ejection fraction was 31%. Of a total of 16 deaths in the series, 8 were sudden. Suppression of VT during amiodarone therapy suggested a lower rate of fatal and nonfatal recurrent arrhythmias, but the difference was not statistically significant. An increase in the cycle length of VT did not predict an improved outcome. The age of the patient and the presence of a left ventricular aneurysm were slightly predictive of mortality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amiodarone in the Management of Patients with Ventricular Tachycardia and Ventricular Fibrillation

Fifty-eight patients with symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF) were treated with amiodarone. All had clinical episodes of VT/VF or inducible VT during electropharmacologic testing despite treatment with maximumtolerated doses of conventional antiarrhythmic agents. Chronic treatment with amiodarone was begun at a dose of 800–1000 mg per day. Thirty-two patients were also treated with a previously ineffective conventional agent. Thirty patients underwent programmed ventricular stimulation after 2.6 ± 1.7 months (mean ± S. D.) of treatment with amiodarone at a mean daily dose of 588 ± 155 mg. VT was induced in 25 patients (sustained in 20, nonsustained in five). Seventeen patients had a recurrence of VT or VF after 0.5–9 months of treatment with amiodarone (fatal in seven, non-fatal in 10). Forty-one patients (71%) had no recurrence of symptomatic VT or VF while being treated with amiodarone (mean follow-up period, 17.1 ± 12.4 months). Among the 25 patients who had inducible VT with programmed ventricular stimulation while being treated with amiodarone, 19 patients (76%) have had no recurrence of symptomatic VT or VF overa follow-up period of 21.5 ± 7.3 months. Ambulatory electrocardiographic recordings obtained after one week of treatment with amiodarone were not helpful in predicting clinical response. Twenty-two patients (38%) developed ataxia and/or an intention tremor which improved with a decrease in the amiodarone dose. Amiodarone, either by itself or in combination with conventional antiarrhythmic drugs, has a significant therapeutic effect in high risk patients with refractory VT. The finding of inducible VT during electropharmacologic testing in patients taking amiodarone does not preclude a favorable clinical response. Neurologic toxicity is common in patients treated with 600–800 mg per day of amiodarone.     

The Signal Averaged Electrocardiogram and Programmed Stimulation in Patients with Complex Ventricular Arrhythmias

TURITO, G., ET AL.: The Signal Averaged Electrocardiogram and Programmed Stimulation in Patients with Complex Ventricular Arrhythmias. The signal averaged electrocardiogram (SA-ECG), programmed electrical stimulation (PES), and left ventricular ejection fraction (EF) studies were utilized for risk stratification and management of patients with complex ventricular arrhythmias and nonsustained ventricular tachycardia (VT). The study population included 90 patients (63 with coronary artery disease and 27 with dilated cardiomyopathy). Sustained monomorphic VT was induced in 22 cases (24%), ventricular fibrillation (VF) in 10 (11%), and no sustained VT/VF in 58 (64%). An abnormal SA-ECG was recorded in 23 patients (26%) and was more common in patients with than in those without induced sustained VT (68% vs 12%, p < 0.0001). None of 33 patients with normal SA-ECG and EF ≥ 40% had induced VT. Patients were followed-up for 2.5 ± 0.8 years off antiarrhythmic therapy, unless they had induced sustained VT. The 3-year sudden death rate was 19% in the group with induced sustained VT, 0 in that with induced VF, and 9% in that without induced VT/VF (P = NS). The 3-year total cardiac mortality was higher in patients with than in those without EF < 40% (27% vs 7%, p < 0.05). It is concluded that patients with organic heart disease and spontaneous nonsustained VT may not need PES or antiarrhythmic therapy if SA-ECG is normal and EF is ≥ 40%, since their risk of induced VT and sudden death is low. On the other hand, patients with abnormal SA-ECG and/or EF < 40% may require PES, since their risk for induced VT is high. Antiarrhythmic therapy may also be considered in these patients. (PACE, Vol. 13, December, Part II 1990)     

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.     

Late Ventricular Potentials and Spontaneous and Induced Ventricular Arrhythmias in Dilated or Hypertrophic Cardiomyopathies. A Prospective Study About 83 Patients

In a series of 83 patients with dilated (DCM) (n = 56) or hypertrophic cardiomyopathies (HCM) (n = 27), were performed 24-hour-Holter monitorings, exercise stress testings, noninvasive recordings of late ventricular potentials (LVP), and programmed ventricular stimulations (PVS) (sinus rhythm and three cycles of stimulation, two extrastimuli, two right ventricle sites) (n = 53). in order to appreciate the frequency of ventricular premature depolarisations (VPDs), to correlate these results with myocardial vulnerability to TV induction, and to compare electrophysiologic and hemodynamic results. Holter monitoring showed that 80% of group A patients had VPDs (75% Lown's grade 3 or over) and 63% in group B (37%≥ grade 3). LVP were found in 15/56 DCM, and 2/27 HCM; in comparison with a control group of 32 normal subjects, the prevalence of LVP was only significant for DCM group. LVP were more frequent in cases of VPD's ≥ Lown's grade 3 at Holter monitoring in DCM group, (33% versus 7% if VPDs ≤ Lown's grade 3) and HCM group (20% versus 0) but the correlation was not significant. Exercise stress testing, conducted only in group E, revealed about 20% of VPDs. PVS provoked ventricular arrhythmia (>5 QRS) in 13 out of 33 cases in group A and in 2 out of 20 cases in group B. There was no significant correlation between the results of these methods of study and those of hemodynamic or echocardiographic explorations except for cardiac index in group A flower when LVP were present, and VPDs ≥ grade 3 during Holter) and end diastolic diameter (larger when PVS provoked fewer ventricular arrhythmias). In group B, PVS induced monomorphic VT in 2/3 patients with syncopes. Thus: (1) ventricular arrhythmias are frequent in cardiomyopathies but LVP had a significant prevalence only in dilated forms; (2) in DCM monomorphic induced VT reproduce spontaneous crisis, whereas in HCM it is possible to provoke VT in patients with syncopes but without this clinical arrhythmia; (3) in DCM as in HCM, ventricular arrhythmia can be independent from hemodynamic disorders.     

Cumulative Effects of Amiodarone on Inducibility of Ventricular Tachycardia: Implications for Electrophysiological Testing

To determine whether the slow onset of action of amiodarone might result in a delayed effect on the inducibility of sustained ventricular arrhythmias, 45 patients with ischemic heart disease and inducible sustained monomorphic ventricular tachycardia were prospectively studied. Each patient had at least one initial repeat study on amiodarone and those with persistently inducible arrhythmias were rescheduled for further studies over the following 24 weeks. After 2-3 weeks of amiodarone therapy, nine patients no longer had inducible tachycardias, and tachycardia in another eight patients (18%) later became noninducible. Using life-table methods, analysis based on the results of the first re-study showed 18-month recurrence rates of 43% in the inducible vs 17% in the noninducible groups (p = 0.056). When the results of additional testing were then used to reclassify patients, the recurrence rates for these two groups were 50% and 17%, respectively (p = 0.004). Observation of blood pressure and level of consciousness during induced arrhythmias was also predictive of clinical tolerance in patients having recurrences; 16 of 19 patients experienced symptoms of similar severity to those produced during testing. We conclude: (1) early testing of amiodarone may result in misclassification of some patients as remaining inducible; (2) re-testing at a later time more accurately predicts tachycardia recurrence; (3) observation of hemodynamic response also provides important prognostic information.     

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.     

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.     

Efficacy and Safety of Low Doses of Beta-Blocker Agents Combined with Amiodarone in Refractory Ventricular Tachycardia

Twenty patients aged 55 ± 16 years with 40 chronic ventricular tachycardias (VT) refractory to 4.6 ± 1.9 antiarrhythmic drugs, used alone or in combination, were managed by low doses of beta-blocker agents combined with oral amiodarone (Am), either after loading (1.2 g for 7 days, n: 5) or reloading (1.2 g for 4 days, n: 15) of Am. All patients proved refractory to Am alone. Seven VT were also refractory to endocardial catheter fulguration in six patients. Thirteen patients had coronary artery disease, three had arrhythmogenic right ventricular dysplasia, two had dilated cardiomyopathy, one had valvular disease, and one had no structural heart disease. Ten patients had an EF <30%. Ten patients were in NYHA functional class three. VT was permanent in three patients, daily in three, weekly in seven, paroxysmal in seven. In 11 patients, VT occurred both at day and night. In 11 patients, decrease of the sinus cycle preceeded VT. Oral administration of a daily low dose of a beta blocker agent (acebutolol 100 mg, betaxolol 5–10 mg, metoprolol 50 mg, nadolol 20–40 mg, pindolol 2.5 mg, propanolol 30 mg, sotalol 80–160 mg, terta-tolol 2.5 mg) combined with 400 mg/day of Am suppressed VT episodes in all patients. None presented heart failure or collapse. The mean reduction of the heart rate was 15% (65 to 55/min). At discharge, exercise ECG (n: 14) induced non sustained VT in two patients. At programmed electrical stimulation (PES) (n: 15), VT was no longer inducible in 4 patients, was slower, well-tolerated in nine patients, and remained inducible at the same rate in only two patients. Chronic treatment prevents recurrence of VT in 19 patients during a follow-up of 14 ± 9 months (range 2 to 33). Conclusions: (1) beta blockers agents and Am have strong synergistic effects; (2) antiarrhythmic treatment with low doses of beta blockers could be managed by PES; (3) at the doses used in (his study, all beta blockers presented the same safety; (4) combination of low doses of beta blockers agents with chronic Am therapy inhibit VT.