Sotalol in patients with life-threatening ventricular tachyarrhythmias

Summary To assess the antiarrhythmic efficacy of oral d,l-sotalol, 68 patients with sustained monomorphic ventricular tachycardia (SMVT) (n=62) or ventricular fibrillation (VF) (n=6) were studied by programmed ventricular stimulation (PVS). Fifty-one patients had coronary artery disease with a previous myocardial infarction and there were 17 patients without coronary disease: 11 patients had right and/or left ventricular dysplasia, one patient an aortic-valve replacement, and five patients had no visible heart disease. Prior to sotalol patients were treated with a mean of 3.6±1.3 antiarrhythmic class I drugs. None of these drugs prevented SMVT or VF. During control PVS (PVS 1), VF was induced in 8 patients (12%), SMVT in 47 patients (69%), and nonsustained ventricular tachycardia (NSVT) in 13 patients (19%). After loading with oral d,l-sotalol (320 mg/day), PVS (PVS 2) was repeated 4.2±3.3 weeks after PVS 1. In one of the patients (1%) VF was inducible, in 15 patients (22%) SMVT was induced, and in 18 patients (26%) NSVT was induced. In 34 patients (50%) either no or a short ventricular response was inducible. Our data show that oral d,l-sotalol is an effective antiarrhythmic agent in patients with SMVT or VF.     

Long-term reproducibility of electrophysiologically guided therapy with sotalol in patients with ventricular tachyarrhythmias

OBJECTIVES

Goal of this study was to assess the long-term reproducibility of electrophysiologic drug testing in patients with ventricular tachyarrhythmias (VT/VF).

BACKGROUND

Programmed ventricular stimulation (PVS) is still widely used to guide antiarrhythmic therapy in patients with sustained ventricular tachycardia/fibrillation (VT/VF). Sotalol is considered as one of the most effective drugs for VT/VF. Because there is no proof of long-term reproducibility of a successful drug test with sotalol, we investigated the long-term reproducibility of drug testing with sotalol.

METHODS

Thirty patients with VT/VF (age: 57 ± 11 years, 20 patients with coronary heart disease, 7 patients with no structural heart disease, 3 with others) and reproducible induction of VT/VF (28 patients VT, two patients VF) in a baseline PVS, were suppressible with sotalol (mean dosage 395 ± 137 mg) in a subsequent PVS. After a mean follow-up of 13 ± 10 months a PVS was again performed in patients, who had no evidence of progressive cardiac disease, who did not experience any arrhythmia recurrences or who were drug compliant. Irrespective of the inducibility after long-term therapy with sotalol, all patients were kept on the initial sotalol regimen. All 30 patients had a stable cardiac condition, were free of VT/VF recurrences and were drug compliant.

RESULTS

Despite the clinical efficacy of sotalol, in 12 patients (40%) VT/VF could again be induced after 13 ± 10.2 months. Inducibility was independent of age, heart disease, ejection fraction and follow-up time. During a further follow-up of 22.1 ± 10.9 months, five patients experienced nonfatal VT recurrences independently of the prior inducibility.

CONCLUSIONS

This study shows a lacking long-term reproducibility of an initial effective PVS with sotalol. Despite an uneventful clinical follow-up, late electrophysiologic testing showed a VT/VF inducibility in a high portion of patients. Hence, electrophysiologic testing performed late after the initial drug test may no longer be predictive of outcome.     

Contemporary Clinical Trials in Ventricular Tachycardia and Fibrillation: Implications of ESVEM, CASCADE, and CASH for Clinical Management

Trials in Ventricular Tachycardias. Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Hotter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N = 486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I (conduction slowing) effects, even when guided by EPS or HM.     

The Role of EP-Guided Therapy in Ventricular Arrhythmias: Beta-Blockers,Sotalol, and ICD's

Arrhythmic death can be reduced by antiarrhythmic drugs to a range of 2—4%. Electrophysiologic study by testing noninducibility of ventricular arrhythmia represents the classic method for evaluating the effectiveness of drug therapy.Several clinical studies have shown thaat sotalol suppresses VT induction and prevents arrhythmias recurrences at long term follow-up in 23% to 67% of patients. The efficacy of sotalol EP guided therapy in preventing VT/VF is not necessarily related to prevention of sudden death. In the ESVEM study the superiority of d,l-sotalol to other antiarrhythmic drugs was confirmed. The response to programmed ventricular stimulation was found to be strongly predictive for arrhythmia free state while the failure of sotalol therapy to suppress VT at the EP study was associated with an high recurrence rate (40%). However, EP study failes to predict freedom from sudden death. The beta-blocking activity of racemic sotalol may account for some of the observed survival benefit.Beta-blockers therapy reduces mortality in patients after myocardial infarction primarily by a reduction of sudden death. A reduction of death, worsening heart failure and life threatening ventricular arrhythmias was shown in a recent study on carvedilol. In the prospective study of Steinbeck the EP guided-therapy did not improve the overall outcome when compared to metoprolol. Suppression of inducible arrhythmias by antiarrhythmic drugs was associated with a better outcome. The effectiveness of defibrillator therapy in reducing overall mortality, has been uncertain since great clinical trials have been concluded. MADIT, AVID and CASH trials confirmed the superiority of ICD therapy over antiarrhythmic drugs therapy: ICD should be considered the first choice therapy in post-cardiac arrest patients.The ongoing BEST Trial will give us further responses about the interaction between EP study and metoprolol effect compared to ICD in patients post myocardial infarction also focusing on tolerability and compliance of the beta-blocking therapy in patients with low ejection fraction. In this study will be useful to optimize therapy in patients at high risk of sudden death     

Clinical and electrophysiologic predictors of ventricular tachyarrhythmia recurrence in patients with implantable cardioverter defibrillators

INTRODUCTION: Not all patients experience recurrent sustained ventricular tachyarrhythmias after placement of an implantable cardioverter defibrillator (ICD). We evaluated the clinical and electrophysiologic predictors of ventricular tachycardia (VT) and ventricular fibrillation (VF) recurrence following ICD implantation. METHODS AND RESULTS: Consecutive patients (n = 133) underwent 4 +/- 3 serial electrophysiologic studies (EPS) over 50 +/- 26 months following ICD implantation. Sustained VT/VF could always be induced during follow-up EPS in 49 patients; sustained VT/VF was sometimes induced during follow-up EPS in 47 patients; and sustained VT/VF could never be induced during follow-up EPS in 37 patients. Spontaneous VT/VF requiring ICD therapy occurred in 107 patients during follow-up. Patients with sustained VT/VF that was always inducible or sometimes inducible during follow-up experienced more frequent episodes of VT/VF following ICD implant (20.5, 95% CI 12.7-33.0; and 17.8, 95% CI 11.3-28.1 episodes/patient respectively; vs 3.0, 95% CI 2.0-4.6 episodes/patient for patients with VT/VF never induced, P < 0.001). Inducibility of sustained VT/VF post-ICD implant (P < 0.001) and sustained VT as the presenting arrhythmia (P = 0.02) were independent predictors of spontaneous VT/VF recurrence. CONCLUSION: Reproducibly inducible VT/VF following ICD implantation predicts a high probability of VT/VF recurrence and identifies a cohort of patients who experience frequent episodes of VT/VF over time. Persistent noninducibility of sustained VT/VF identifies a group of patients who experience no or very few episodes of VT/VF recurrence.     

Dofetilide reduces the frequency of ventricular arrhythmias and implantable cardioverter defibrillator therapies

Dofetilide Reduces VT/VF and ICD Therapies . Background: Patients with an implanted cardioverter defibrillator (ICD) and ventricular arrhythmias leading to ICD therapies have poor clinical outcomes and quality of life. Antiarrhythmic agents and catheter ablation are needed to control these arrhythmias. Dofetilide has only been approved for the treatment of atrial fibrillation. The role of dofetilide in the control of ventricular arrhythmias in patients with an ICD has not been established. Objective: Evaluate the safety and efficacy of dofetilide in a consecutive group of patients with an ICD and recurrent ventricular tachycardia (VT) and/ or ventricular fibrillation (VF) after other antiarrhythmic drugs have failed to suppress these arrhythmias. Methods: We studied 30 patients (age 59 ± 11; 5 women) with symptomatic VT or VF and ICDs for secondary prevention of sudden cardiac death. These patients had an average of 1.8 ± 4.5 episodes of VT/VF per month despite antiarrhymic therapy. Twenty‐one patients (70%) had recurrent appropriate ICD therapies prior to initiation of dofetilide, and 9 (30%) VTs below the programmed detection rate of the ICD. Twenty‐three patients (77%) had coronary artery disease. Mean ejection fraction was 30 ± 14% and 26/30 (87%) had congestive heart failure. All patients had previously failed 2 ± 1 antiarrhythmic drugs including amiodarone (n = 19) and sotalol (n = 10). Results: During the first month of treatment, 25 patients (83%) had complete suppression of VT/VF and of the 21 patients with ICD therapies 16 (76%) had no therapies during the first month of treatment. During a follow‐up period of 32 ± 32 months, dofetilide reduced the monthly episodes of VT/VF from 1.8 ± 4.5 to 1.0 ± 3.5 (P = 0.006). Monthly ICD therapies decreased from 0.9 ± 1.4 to 0.4 ± 1.7 (P = 0.037). In 9 patients that presented with slow VTs under the ICD detection zone, dofetilide reduced monthly VT/VF episodes from 0.7 ± 0.6 to 0.1 ± 0.1 (P = 0.01) and 6 (67%) had no further ICD therapies. Dofetilide was discontinued in 13 patients (43%) after 24 ± 30 months due to failure to control VT/VF (n = 7), placement of a left ventricular assist device (n = 3), catheter ablation (n = 1), heart transplantation (n = 1), and left ventricular restoration surgery (n = 1). There were 7 documented deaths (2 patients died suddenly; 3 patients of progressive heart failure; and 2 of non‐cardiac causes). Conclusions: In patients with an ICD and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD therapies even when other antiarrhythmic agents, including amiodarone, have previously been ineffective. Recurrences still occur in some patients requiring catheter ablation, mechanical support, or heart transplantation. (J Cardiovasc Electrophysiol, Vol. 23 p. 296‐301, March 2012.)     

Intravenous Procainamide for Predicting the Response of Sustained Ventricular Tachycardia to Type III Antiarrhythmic Drugs

The use of serial electrophysiology studies to guide antiarrhythmic drug therapy in patients with ventricular tachycardia is both costly and time consuming. Intravenous procainamide administered during of the initial electrophysiology study has previously been shown to be useful in predicting the efficacy of oral antiarrhythmic medications (type I and III). The purpose of this study is to confirm that ventricular tachycardia suppression after intravenous procainamide correlates with suppression on oral class III antiarrhythmic medications (amiodarone and sotalol). This study included all patients with sustained ventricular tachycardia who underwent an initial electrophysiology study including an acute suppression trial with intravenous procainamide and a subsequent restudy on oral amiodarone or sotalol. The response to intravenous procainamide was then compared with these type III antiarrhythmic medications. Between January 1993 and May 1995, 360 patients underwent electrophysiology studies for suspected or documented ventricular arrhythmias. One hundred patients (28%) had an inducible sustained ventricular tachycardia, and 26 patients received both intravenous procainamide and subsequently oral amiodarone or sotalol. Acute infusion of procainamide provided a highly specific method for predicting suppression of oral amiodarone and sotalol (82% and 100% respectively). However, several patients who were not suppressed by intravenous procainamide were suppressed by oral sotalol resulting in lower overall predictive accuracy 12/15 (80%) for amiodarone vs. 5/11 (45%) for sotalol treated group. We conclude that the acute infusion of procainamide may help to predict ventricular tachycardia suppression after oral amiodarone and sotalol. A larger prospective trial is warranted to confirm this finding.     

Amiodarone: What have we learned from clinical trials?

Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This paper reviews clinical trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction trials include EMIAT and CAMIAT, both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In patients with congestive heart failure (CHF), amiodarone was associated with a neutral survival in CHF/STAT and improvement in survival in GESICA. In patients with nonsustained ventricular tachycardia, the MADIT trial demonstrated that therapy with an implantable cardioverter-defibrillator (ICD) improved survival compared with the antiarrhythmic drug arm in such patients, most of whom were taking amiodarone. In sustained VT/VF patients, the CASCADE trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared with other drugs guided by serial Holter or electrophysiologic studies. Several trials including AVID, CIDS, and CASH have demonstrated the superiority of ICD therapy compared with empiric amiodarone in improving overall survival. Clinical implications of these trials are discussed.     

Incidence and timing of recurrences of sudden death and ventricular tachycardia during antiarrhythmic drug treatment after myocardial infarction.

Incidence and timing of recurrences of sustained ventricular tachycardia (VT) or sudden death were studied in 206 patients who survived their first episode of ventricular fibrillation (VF; n = 52) or sustained VT (n = 154) after myocardial infarction. All patients were treated with (empirically selected) antiarrhythmic drugs; 49% received amiodarone. After a mean follow-up of 36 months, 64 patients (41%) in the VT group and 10 (19%) in the VF group had nonfatal VT recurrences. Sudden death occurred in 22 (14%) and 9 (17%) patients in the VT and VF groups, respectively. Incidence of sudden death had 2 peaks at approximately 3 and 12 months. Nonfatal VT recurrences were more frequent (most often occurring in first 6 months) in the VT than in the VF group. Sudden death occurred during the following 3 years in only 10% of patients who survived 1 year. There was a much higher incidence of sudden death in patients with left ventricular ejection fraction (LVEF) less than or equal to 40% than in those with LVEF greater than 40% (28 of 65 vs 3 of 141; p less than 0.0001), but no relation between LVEF and nonfatal VT recurrences.     

Usefulness of electrophysiologic testing in evaluation of amiodarone therapy for sustained ventricular tachyarrhythmias associated with coronary heart disease

The prognostic importance of electrophysiologic studies in patients with sustained ventricular tachyarrhythmias treated with amiodarone was prospectively studied in 100 consecutive patients. Sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) was inducible in all patients before amiodarone therapy. After amiodarone administration 2 groups of patients were identified. In group 1 patients the ventricular tachyarrhythmia was no longer inducible and in group 2 patients the arrhythmia remained inducible. In group 1, no recurrent arrhythmia occurred during a follow-up of 18 +/- 10 months. In group 2, 38 of 80 patients (48%) had arrhythmia recurrence during a follow-up of 12 +/- 9 months. The difference between group 1 and 2 could not be explained by clinical variables, amiodarone doses or plasma concentrations, or electrocardiographic variables. In patients in whom cardiovascular collapse or other severe symptoms where noted during electrophysiologic study after amiodarone treatment, recurrences caused sudden death (n = 12). However, in patients in whom the induced arrhythmia produced moderate symptoms, the recurrent arrhythmia was nonfatal VT (n = 26). Electrophysiologic testing provides clinical guidance and predicts prognosis in patients treated with amiodarone as it does for the evaluation of other antiarrhythmic agents.     

Effects of sotalol on ventricular tachycardia and fibrillation produced by programmed electrical stimulation: comparison with other antiarrhythmic agents

Sotalol, a beta blocker, is now recognized as an important class III agent. The drug lengthens the action potential in most cardiac tissues without affecting conduction. Several studies have shown that sotalol is very effective in treating life-threatening arrhythmias. One hundred thirty-eight patients with inducible and clinically sustained tachycardia were retrospectively analyzed. With the use of the S1S2S3 stimulation protocol for ventricular tachycardia (VT) induction, sotalol prevented VT/ventricular fibrillation (VF) induction in 45% of the patients; other class I agents prevented VT/VF induction in only 15 to 22%. Data were also analyzed from a prospective multicenter study comparing sotalol with procainamide in suppressing sustained VT in 153 patients with symptomatic sustained VT/VF. With the use of the S1S2S3S4 stimulation protocol, sotalol prevented VT/VF induction in 35% of the patients, whereas procainamide prevented VT/VF induction in only 22% (difference not significant). When patients whose VT induced by the triple-stimuli protocol were excluded, sotalol prevented VT induction in 53%. These findings indicate that the antiarrhythmic effects of sotalol are comparable to those of class I agents in treating malignant arrhythmias. Although more data are needed on the comparative effects of sotalol, available data establish sotalol as an important addition to available antiarrhythmic agents.     

Predicting the Recurrence of Ventricular Tachyarrhythmias from T‐Wave Alternans Assessed on Antiarrhythmic Pharmacotherapy: A Prospective Study in Patients with Dilated Cardiomyopathy

Background: Microvolt T‐wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. Methods: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow‐up period. Results: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow‐up of 13 ±; 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow‐up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan‐Meier event‐free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. Conclusions: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias. A.N.E. 2001; 6(3):203–208     

Implantable defibrillators are preferable to pharmacologic therapy for patients with ventricular tachyarrhythmias: An antagonist's viewpoint

Despite their intuitive appeal, implantable cardioverter defibrillators (ICDs) will require testing in randomized studies to establish their relative value as compared with antiarrhythmic drugs in patients with-life-threatening ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]). In these studies, only total mortality is an acceptable primary end point. Lessons from recent drug studies (CAST, ESVEM, CASCADE) have shown that class-III/β-receptor antagonist therapy is superior to class-I drugs selected by electrophysiologic or Holter monitor testing. Thus, sotalol or amiodarone should now be considered first-line drugs for VT/VF therapy. Advantages of contemporary drug therapy for VT/VF include wide experience among clincians, progressively better drugs, lower cost, universal availability, greater flexibility in use (easy to start, titrate, and stop), ability to suppress (not just terminate) events, and favorable effect on disease progression (eg, β-blockade effects in cardiomyopathy and ischemic heart disease). Recent matched observational studies and a small randomized experience (CASH) suggest near equivalence in total mortality in ICD and drug-treated groups. Until or unless modified by the results of large, ongoing, randomized trials (AVID, CIDS), contemporary antiarrhythmic drug therapy has much to be recommended as first-line, standard treatment for patients with VT/VF. Even in patients receiving ICDs, added drug therapy is frequently indicated.     

Japanese randomized trial for investigation of a combined therapy of amiodarone and implantable cardioverter defibrillator in patients with ventricular tachycardia and fibrillation: the Nippon ICD Plus Pharmachologic Option Necessity study design.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are the most effective therapy in reducing the mortality of patients with life-threatening ventricular tachyarrhythmias. However, the ICD cannot prevent the recurrence of tachycarida attacks and that limits the clinical usefulness of them. The Nippon ICD Plus Pharmachologic Option Necessity (NIPPON) trial was designed as the first prospective randomized study to test the hypothesis whether amiodarone could improve the patient's clinical outcome by reducing the amount of ICD therapy in the Japanese patient population. METHODS AND RESULTS: Approximately 400 patients with organic heart disease and spontaneous episode(s) of sustained ventricular tachycardia/fibrillation (VT/VF) will be randomly assigned to one of 2 groups; the amiodarone group and non-amiodarone group. Both groups of patients will be followed at least for 24 months. The end-point committee will adjudicate events in a blinded fashion. The primary end-points of this study are determination of the appropriate therapy from the ICD and alteration of the assigned treatment because of its harmful effects and/or frequent ICD therapies. CONCLUSION: The NIPPON study is expected to confirm our understanding of the prognostic and therapeutic usefulness of adjuvant amiodarone therapy for patients with an ICD and with a history of sustained VT/VF.     

Comparison of event rates and survival in patients with unexplained syncope without documented ventricular tachyarrhythmias versus patients with documented sustained ventricular tachyarrhythmias both treated with implantable cardioverter-defibrillators

Patients with unexplained syncope and inducible ventricular tachyarrhythmias during electrophysiologic testing have an increased cardiac mortality rate. We compared event rates and survival of 178 patients with unexplained syncope and no documented ventricular arrhythmias (syncope group) versus 568 patients with documented sustained ventricular tachycardia (VT or fibrillation (VF) (VT/VF group) treated, as part of a lead (Ventritex TVL) investigation, with similar implantable cardioverter-defibrillators (ICDs) capable of extensive data storage. The 2 groups shared similar clinical characteristics. The mean follow-up was 11 months for the syncope group and 14 months for the VT/VF group. The mean time from device implantation to first appropriate therapy was similar in the 2 groups (109 +/- 140 vs 93 +/- 131 days, p = 0.40). Actuarial probability of appropriate ICD therapy was 49% and 55% at 1 and 2 years, respectively, in syncope group and 49% and 58% in VT/VF group (p = 0.57). Recurrent syncope was associated with ventricular tachyarrhythmias in 85% and 92% of the syncope group and VT/VF group, respectively (p = 0.54). At 2 years, actuarial survival was 91% in the syncope group and 93% in VT/VF group (p = 0.85). We conclude that patients treated with ICD with unexplained syncope and induced VT/VF have an equally high incidence of appropriate ICD therapy and low mortality compared with similar patients with documented VT/VF. These findings, plus the high association between recurrent syncope and ventricular arrhythmias, indicate that VT/VF are likely etiologies in selected patients with unexplained syncope and support ICD therapy in such cases.     

Electrophysiologic study-guided amiodarone for sustained ventricular tachyarrhythmias associated with structural heart diseases.

BACKGROUND: Although an electrophysiologic study (EPS) and Holter-monitoring are often helpful in evaluating the efficacy of antiarrhythmic drugs in patients with ventricular tachyarrhythmias (ventricular tachycardia/fibrillation (VT/VF)), the efficacy of EPS- or Holter-guided oral amiodarone therapy in Japanese patients is still unclear. METHODS AND RESULTS: EPS was performed 1 month after starting amiodarone, and Holter-monitoring was recorded before and 1 month after amiodarone in 188 patients with sustained VT/VF because of structural heart diseases. In spite of the judgment of EPS (n=89) or Holter (n=75), all patients continued amiodarone. Patients were followed up to 3 years and the primary endpoint was VT/VF recurrence and secondary endpoint was death by all cause. Kaplan-Meier estimated the risk of VT/VF recurrence was significantly smaller with EPS-guided amiodarone (p<0.01) but not with Holter-guided amiodarone. Multivariate Cox hazard analysis revealed that EPS-guided amiodarone was an independent factor suppressing the recurrence of VT/VF (p<0.05, 95% confidence interval =0.15 to 0.96). In the subgroup analysis, EPS-guided amiodarone was effective in patients with relatively well-preserved left ventricular ejection fraction (LVEF > or =0.30) but not in patients with lower LVEF (LVEF <0.30). CONCLUSION: EPS-guided amiodarone was useful for preventing recurrence of VT/VF in patients with a relatively well-preserved LVEF, but not always beneficial in patients with a lower LVEF.     

Prospective clinical evaluation and follow-up of a cohort of consecutive VT/VF patients, using a staged-care protocol, including coronary arteriography, programmed electrical stimulation and cardiac surgery.

The prospective evaluation and follow-up of 39 consecutive subjects with VT/VF, 6 of whom, with cardiac arrest (CA), are reported. Patients were enrolled in a specific staged-care approach protocol, which included coronary arteriography (CAR) and ventriculography (VC), in order to exclude the need of cardiac surgery, including coronary artery bypass graft (CABG), with and without left ventricular aneurysmectomy (LVA). The protocol included inducibility of VT/VF, which was verified by programmed electrical stimulation (PES) in control conditions and after antiarrhythmic therapy (ADT), to assess persistent inducibility and mainly to verify the hemodynamic sequelae of VT. VT that showed poor hemodynamic tolerance was treated with ICD, while well-tolerated VT was treated by ADT or ablation when indicated. Furthermore, PES was obtained after surgical procedures. As a first step, the patients were assigned to receive amiodarone (AMIO) (200-400 mg/daily) in the presence of EF% < 30% or contraindication to sotalol, (Group A), or sotalol (SOT) (80-140 mg/daily) in the presence of EF > or = 31%. (Group C). Conversely, in case of recurrences, patients were assigned to receive AMIO (200-300 mg/daily) plus metoprolol (MET) (20-100 mg/daily), (Group B) or, in case of intolerance to beta-blockers, to AMIO plus mexiletine (MEX) (200 mg/daily) (Group D). The four groups were similar for the type of VA, with recurrent ventricular tachycardia (RVT) being the most frequent one. The most frequent underlying cardiac disease of VA in this study was post-AMI CAD, with a rate of over 60% in all four groups. Single- and two-vessel lesions were found at CAR in various patients in all four groups, in 5/13 (38%) in Group A, in 8/14 (57%) in Group B, in 5/7 (71%) in Group C, and in 3/5 (60%) in Group D. Cardiac surgery was performed in a similar and limited number of patients in all four groups, in 4/13 (30%) in Group A, in 4/14 (35%) in Group B, in 2/7 (28%) in Group C, and in 2/5 (40%) in Group D. In 8/39 (20.5%) of the patients who underwent CABG, there was no operative or late mortality; 4/39 (10.2%) received CABG and LVA, and two died. For the amiodarone plus metoprolol and sotalol patients only, PES showed a lower residual inducibility, in comparison to the amiodarone and amiodarone + mexiletine groups. In the entire group, 7 out of 26 (27%) were still inducibile at PES while in 19/26 (64%) of the patients, an apparently effective treatment could be found, documenting the relative usefulness of PES. Recurrence rate was the highest in the amiodarone + mexiletine group and in patients with previous CA. Our data show the potential utility and limitations of ADT, even using the most effective antiarrhythmic drugs and association of drugs, mainly because of the high recurrence rate of VT observed in the present study, even in non-inducible patients [14/39 (36%)]. In conclusion, in a prospective and staged-care approach protocol of management of VT/VF patients, only a few patients with VT/VF benefited from cardiac surgery. PES could still play a role in the evaluation of the most effective ADT. Amiodarone + metoprolol seems to be the most effective ADT in these patients. Nevertheless, a high recurrence rate was observed in this patient population, even with an aggressive protocol, in the short follow-up period of 12 +/- 8 months, confirming recent data on the superiority of ICD to ADT, in patients with frequent recurrences or hemodynamically poorly-tolerated VT. In these patients, ICD therapy should definitively be preferred to ADT.     

Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to evaluate the survival of patients with hypertrophic cardiomyopathy (HCM) after resuscitated ventricular fibrillation or syncopal sustained ventricular tachycardia (VT/VF) when treated with low dose amiodarone or implantable cardioverter defibrillators (ICDs). BACKGROUND: Prospective data on clinical outcome in patients with HCM who survive a cardiac arrest are limited, but studies conducted before the widespread use of amiodarone and/or ICD therapy suggest that over a third die within seven years from sudden cardiac death or progressive heart failure. METHODS: Sixteen HCM patients with a history of VT/VF (nine male, age at VT/VF 19 +/- 8 years [range 10 to 36]) were studied. Syncopal sustained ventricular tachycardia/ventricular fibrillation occurred during or immediately after exertion in eight patients and was the initial presentation in eight. One patient had disabling neurologic deficit after VT/VF. Before VT/VF, two patients had angina, four had syncope and six had a family history of premature sudden cardiac death. After VT/VF all patients were in New York Heart Association class I or II, three had nonsustained VT during ambulatory electrocardiography and 11 had an abnormal exercise blood pressure response. After VT/VF eight patients were treated with low dose amiodarone and six received an ICD. Prophylactic therapy was declined by two patients. RESULTS: Mean follow-up was 6.1 +/- 4.0 years (range 0.5 to 14.5). Cumulative survival (death or ICD discharge) for the entire cohort was 59% at five years (95% confidence interval: 33% to 84%). Thirteen (81%) patients were alive at last follow-up. Two patients died suddenly while taking low dose amiodarone, and one died due to neurologic complications of his initial cardiac arrest. Three patients had one or more appropriate ICD discharges during follow-up; the times to first shock after ICD implantation were 23, 197 and 1,124 days. CONCLUSIONS: This study shows that patients with HCM who survive an episode of VT/VF remain at risk for a recurrent event. Implantable cardioverter defibrillator therapy appears to offer the best potential benefit regarding outcome.     

Management of refractory sustained ventricular tachycardia with amiodarone: a reappraisal

We examined the value of clinical variables, chronic 24-hour ambulatory ECG monitoring, and chronic electrophysiologic (EP) testing in 49 patients with recurrent and refractory sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) treated with chronic oral amiodarone in order to develop a prospective approach to the management of these patients. All patients underwent control EP studies followed by continuous telemetric cardiac monitoring during oral amiodarone administration (mean duration 29 +/- 6 days, mean dose 739 +/- 230 mg). Follow-up 24-hour ambulatory ECG monitoring and EP studies were performed. Thirty VT recurrences occurred in the first 4 weeks of amiodarone therapy (total incidence, 61%), with the majority (55%) in the first 3 weeks of treatment. During long-term follow-up (1 to 42, mean 15 +/- 12 months), there were 12 symptomatic VT/VF recurrences (incidence 24%). There was a higher incidence of VT recurrences if patients had inducible sustained or nonsustained VT at chronic EP study (p less than 0.01), or complex ventricular arrhythmias on ambulatory ECG monitoring (p less than 0.05). The sensitivity, specificity, and predictive accuracy of chronic EP testing and 24-hour ambulatory ECG monitoring were 100%, 35%, and 51%, and 58%, 84%, and 78%, respectively. Chronic EP testing correctly identified all patients who had their arrhythmia suppressed by amiodarone on long-term follow-up, while 42% of all VT recurrences occurred in patients without complex ventricular arrhythmias on 24-hour ambulatory ECG monitor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous sustained ventricular tachyarrhythmias during treatment with type IA antiarrhythmic agents

Twenty-six patients who developed their first clinical episode of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) while taking type IA antiarrhythmic agents for more benign rhythm disturbances were rechallenged with the identical drug during electrophysiologic testing. Patients with these new drug-associated spontaneous ventricular arrhythmias often manifested a preexisting substrate for such arrhythmias: sustained VT or VF was induced in 65% of patients at baseline, and in 58% of patients when tested with their previously taken antiarrhythmic drug. Among those without inducible sustained ventricular arrhythmias in the drug-free state, 78% remained free of inducible sustained arrhythmias when tested with the same drug they had been taking at the time of the clinical arrhythmia. Even patients without a definable electrophysiologic substrate for sustained VT or VF remained at risk for arrhythmia recurrence if treated with alternative antiarrhythmic medications: 40% of such patients who continued to receive an antiarrhythmic agent different from that being administered when their clinical VT or VF occurred had recurrent spontaneous ventricular tachyarrhythmias during follow-up. Thus, patients with drug-associated clinical sustained ventricular tachycardias form a heterogenous group that should be evaluated individually and not empirically managed for a "proarrhythmic effect" simply by antiarrhythmic drug withdrawal or drug substitution.