Programmed left ventricular stimulation in non-sustained ventricular arrhythmias

The presence of nonsustained ventricular arrhythmia (NSVA) is an independent factor of sudden rhythmic death. The primary objective of our study was to evaluate the correlation between inducibility during programmed ventricular stimulation (PVS) and the presence of ventricular late potentials, the ejection fraction, the grade of arrhythmia, and the underlying cardiopathy. The secondary objective was to evaluate the interest of PVS in patients with NSVA. Ninety eight patients with NSVA have been tested by PVS and 14 were inducible. During the mean follow up of 24 months, 8 patients died, 3 of them suddenly. A significative statistical correlation was found between ventricular late potentials and inducibility (negative predictive value = 91%; p = 0.03). No correlation was found between the ejection fraction, the grade of arrhythmia, the cardiopathy and inducibility. In patients with ischaemic cardiopathy, PVS has allowed to identify a subgroup of patients with high risk of sudden death. In this subgroup, serial PVS for drug testing has contributed to choose the therapeutic regimen supposed to be more effective for prevention of fatal arrhythmia. Multiple factors explain sudden death, even though the initial treatment has been chosen by electrophysiologic studies. For non inducible patients, empiric treatment is not proven to be reliable, and the best therapeutic regimen is still unidentified, especially in the subgroup of patients with low ejection fraction. In this subgroup, the implantable cardioverter defibrillator vives better protection against sudden rhythmic death.     

Programmed stimulation in patients with malignant ventricular arrhythmias. I: Diagnostic value

Sudden cardiac death is a leading cause of death in industrially developed countries and accounts for approximately 90 000 deaths yearly in the FRG. While the majority of victims have severe coronary heart disease, sudden cardiac death is infrequently caused by acute myocardial infarction (20%) but is predominantly related to malignant ventricular arrhythmias (i.e., ventricular fibrillation or sustained ventricular tachycardia). Patients with a history of such malignant ventricular arrhythmias are at high risk for sudden death. Spontaneous occurrence of sustained ventricular tachycardia and of ventricular fibrillation is critically related to two factors: 1. trigger-arrhythmias consisting usually of complex ventricular extrasystoles (Lown classification IV to V); 2. increased vulnerability of the myocardium representing the target organ for trigger-arrhythmias. While trigger-arrhythmias can be easily recorded by noninvasive techniques including Holter monitoring or exercise and stress ECG, ventricular vulnerability is more difficult to determine and often requires ventricular stimulation with intracardiac electrocatheters. In patients with documented spontaneous malignant ventricular arrhythmias, two aspects of programmed stimulation must be considered: 1. diagnostic, and more importantly, 2. therapeutic purposes of this method. Diagnostic purposes include determination of the mode of initiation and unequivocal ventricular localization of the tachycardia excluding other arrhythmias with broad QRS complex. In patients with spontaneous sustained ventricular tachycardia, programmed stimulation can reproducibly initiate the clinical arrhythmia in 85% (sensitivity and specificity of the method approximately 90%). In patients with cardiac arrest due to ventricular fibrillation, programmed stimulation is less reliable (50%). However, the main purpose of programmed stimulation in patients with documented clinical malignant arrhythmias is not diagnostic or prognostic evaluation but is serial electrophysiological studies for individual optimization of antiarrhythmic therapy.     

Programmed electrical stimulation, the signal-averaged electrocardiogram, and the implantable cardioverter-defibrillator in ventricular arrhythmias

In the last year the technique of programmed electrical stimulation has been further developed and more fully evaluated when used for the assessment of an individual's risk from ventricular arrhythmias. The method of recording and analyzing signal-averaged electrocardiograms has recently undergone considerable technical development, especially in the frequency and spectrotemporal domains. The importance of late potentials as a risk factor for arrhythmic events in the convalescent period following acute myocardial infarction is less clear in patients who have received thrombolytic therapy. The implantable cardioverter-defibrillator is now fitted to over 10,000 new patients each year, yet its true value has not yet been prospectively assessed. However, it is known that fitting the device is associated with a considerable operative mortality, and the device does not completely eradicate sudden death. Furthermore, the cost of this form of therapy is very high and its prophylactic use has not been established.     

Usefulness of sotalol for life-threatening ventricular arrhythmias

Two trial designs have been used in evaluating sotalol in patients with sustained tachyarrhythmias: open-label dose escalation and randomized comparison with reference agents. At least 7 open-label studies (n = 16–65) have been reported from single centers in patients in whom trials of numerous other antiarrhythmic agents were unsuccessful. At the doses used, usually 320–640 mg/day, plasma concentrations were in the range associated with both β blockade and class III antiarrhythmic activity (2–3 μg/mL). These concentrations produced etectrophysiologic changes that were consistent across studies: 10–16% increase in right ventricular effective refractory period (ERP), 4–8% increase in corrected QT interval (QT_c), and 17–30% increase in sinus cycle length (corresponding to a 15–23% decrease in heart rate). In these open-label trials, sotalol suppressed inducible ventricular tachyarrhythmias in 20–72% of patients; the higher degrees of efficacy were reported when induction protocols were confined to double extrastimuli. Side effects leading to discontinuation of sotalol in patients with sustained ventricular tachycardia or fibrillation include fatigue (4.0%), marked bradycadia (3.0%), torsades de pointes (3.0%), and heart failure or pulmonary edema (1.0%). A multicenter randomized trial compared intravenous sotalol with intravenous procainamide in a double-blind prospective fashion. Sotalol suppressed ventricular tachyarrhythmias inducible with triple extrastimuli in 15 (30%) of 50 patients, whereas procainamide was effective in 10 (20%) of 50. In this and other series, responsiveness to sotalol was prospectively identified by a particularly fast tachycardia at baseline (e.g., cycle length of <270 msec), but not by the extent of changes in global indices of repolarization (QT_c, ERP). Several of these trials, at least 1 of which used implantable cardioverter/defibrillators as a backup, reported that initial suppression of inducible arrhythmias during sotalol therapy was predictive of a low incidence of arrhythmia recurrence during long-term treatment. These uncontrolled and controlled data indicate that, although side effects typical of combined class II and class III actions can occur during long-term therapy, sotalol appears to be at least as effective as, or slightly more effective than, currently available agents for the management of life-threatening ventricular arrhythmias.     

Programmed stimulation for the analysis of arrhythmias]

On the basis of the examination of a left bundle-branch heart block depending on frequency, of a paroxysmal tachycardia in functional conduction dissociation in the atrioventricular node and a WPW-syndrome of type A is shown that and how by means of programmed stimulation of the right atrium in order to establish the times of conduction and the refractory periods of all conduction sections of the conduction system of the heart also under influence of medicaments the diagnostic repertoire is enriched for the analysis of disturbances of the rhythm without comprehensively or finally estimating the clinical valency of the method.     

Bepridil hydrochloride for treatment of benign or potentially lethal ventricular arrhythmias

To define the efficacy and safety of a new once-a-day calcium antagonist, bepridil, 21 patients with frequent ventricular premature complexes (VPCs) underwent a 14-day inpatient monitored trial. After Holter monitoring during placebo administration, patients underwent 2 days of a loading dose of bepridil followed by 12 days of bepridil, 400 mg/day. Holter monitoring during therapy showed that 10 patients (48%) had more than a 70% reduction in VPC frequency and 8 of 16 patients (50%) at least a 95% reduction in frequency of nonsustained ventricular tachycardia. Gastrointestinal and central nervous system side effects considered to be mild occurred in 13 patients (62%). One patient had an asymptomatic increase in VPC frequency and another had sustained ventricular tachycardia associated with a loading dose of 900 mg of bepridil. Thus, bepridil has moderate antiarrhythmic efficacy in patients with ventricular arrhythmias, but further definition of its potential for causing proarrhythmia must be determined.     

Programmed ventricular stimulation in structural heart disease: Implications of patterns of ventricular arrhythmias induced to long-term outcomes

IntroductionCurrently available data gives some credence to utility of VT induction studies in patients with stable ischemic cardiomyopathy, there are some unresolved questions as to define sensitive threshold for low-risk and the prognostic relevance of ill sustained or non-specific tachycardia on induction study. We evaluated potential ability of VT inducibility to predict likelihood of SHD (Structural heart disease) patients for subsequent arrhythmic or adverse cardiac events.Material and MethodsAll consecutive patients with syncope/documented arrhythmia who had VT induction done were included and patients with VT storm, ACS,uncontrolled HF were excluded. We studied in 4 groups-monomorphic VT, sustained polymorphicVT, ill sustainedVT/VF and no VT/VF induced. The primary-endpoints were – Sudden death, all-cause mortality and secondary-endpoints were – MACE (AICD shock, death,HF, recurrence of VT). We screened 411 patients and included 169 within inducible (n = 79) and non-inducible group (n = 90).ResultsThere were a higher number of patients with coronary artery disease, LV dysfunction, patients on amiodarone in inducible group and no difference in usage of beta-blockers. Recurrence of VT, composite of MACE was significantly higher in inducible group (p < 0.05). Mortality was not different in 3 groups compared with no VT/VF group. We found that monomorphic VT group had significantly higher MACE as compared to others and also predicted recurrence of VT and AICD shock and showed a trend towards significance for prediction of mortality. Inducible patients on AICD had mortality similar to non-inducible group.ConclusionInduction of monomorphicVT/polymorphicVT with ≤3extrastimuli is associated with a higher number of MACE events on follow up. Induction of monomorphicVT predicts recurrence of VT/ICD shock.     

Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias

Classification of ventricular arrhythmias into those that are benign, potentially lethal and lethal is based on their associated risk for producing sudden cardiac death. This classification system is useful in defining indications for the treatment of ventricular arrhythmias and predicting differential rates of antiarrhythmic drug efficacy and toxicity. Whether the reduction of potentially lethal ventricular arrhythmias will prevent sudden cardiac death remains to be determined. The class II antiarrhythmic agents--the beta-adrenergic blocking drugs--have been shown to reduce sudden cardiac death in postmyocardial infarction patients, but the precise mechanism of their effect has not been defined. beta blockers are efficacious in approximately 50% of patients with benign or potentially lethal ventricular arrhythmias. This response is comparable to that seen with the class IA agent disopyramide or the class IB agents tocainide and mexiletine. beta blockers have favorable side-effect profiles including a low incidence of proarrhythmia and a lack of organ toxicity such as hepatitis, pulmonary fibrosis or agranulocytosis, which are concerns with class I and class III antiarrhythmic drugs. The proper dosage of the beta blocker is critical in limiting adverse effects. In a study of 23 patients with benign or potentially lethal ventricular arrhythmias, 11 (48%) of the patients responded to nadolol with a reduction of greater than 75% in arrhythmia frequency, and several patients responded at nadolol dosages as low as 10 mg daily. Thus, it is plausible to consider beta blockers as first-choice antiarrhythmic therapy, even in patients with left ventricular dysfunction when sympathetic tone is not required to maintain cardiac compensation.     

Psychosocial status predicts mortality in patients with life-threatening ventricular arrhythmias

BACKGROUND: Quality-of-life (QoL) instruments evaluate various aspects of physical, mental, and emotional health, but how these psychosocial characteristics impact long-term outcome after cardiac arrest and ventricular tachycardia (VT) is unknown. OBJECTIVE: The purpose of this study was to evaluate the relationship of baseline QoL scores with long-term survival of patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial. METHODS: Formal QoL measures included SF-36 mental and physical components, Patient Concerns Checklist, and Ferrans and Powers Quality-of-Life Index-Cardiac Version. Multivariate Cox regression was used to assess the association of survival and these measures, adjusting for index arrhythmia type, gender, race, age, ejection fraction, history of congestive heart failure, antiarrhythmic therapy, and beta-blocker use. RESULTS: During mean follow-up of 546 +/- 356 days, 129 deaths occurred among 740 patients. Higher baseline SF-36 physical summary scores (P <.001), higher baseline QoL Index summary scores (P = .015), and lower baseline Patient Concerns Checklist summary scores (P = .047) were associated with longer survival, even after adjustment for clinical variables. When QoL measures were examined simultaneously, only the SF-36 physical summary score remained significant (P = .002). CONCLUSION: During recovery after sustained VT or cardiac arrest, formal baseline QoL assessment provides important prognostic information independent of traditional clinical data.     

Role of invasive electrophysiologic testing in the management of life-threatening ventricular arrhythmias

Electrophysiologic studies are indicated in patients with sustained paroxysmal ventricular tachycardia, ventricular fibrillation or aborted sudden death. These studies allow determination of mechanism and reproducibility of initiation as well as pacing termination of ventricular tachycardia, against which the effects of pharmacologic or nonpharmacologic therapies can be tested. Such studies are also indicated in certain patients with syncope in whom a strong suspicion exists for an arrhythmic cause. The content and conduct of electrophysiologic testing in these patients require attention to the physiology of the conduction system and systematic programmed stimulation of the right ventricle. The stimulation protocol should include, if necessary, twice-threshold stimulation at 2 sites at 3 or more cycle lengths, with up to 3 extrastimuli. Sufficient variability exists in electrophysiologic testing as in other clinical methods calling for careful attention to the reproducibility of tachycardia induction in a given patient, lest chance alone mimic beneficial or deleterious effects of antiarrhythmic regimens. Mapping-directed surgery for ventricular tachycardia remains the most effective therapy in patients with sustained monomorphic ventricular tachycardia with a mortality similar to other forms of medical therapy.     

Incidence of proarrhythmic effects from quinidine in the outpatient treatment of benign or potentially lethal ventricular arrhythmias

To determine the prevalence and importance of proarrhythmic events secondary to the initiation of quinidine therapy in outpatients with benign or potentially lethal ventricular arrhythmias, the data from 360 patients treated with quinidine as part of 3 outpatient drug trials were retrospectively reviewed. These patients had at least 30 ventricular premature complexes per hour during placebo treatment and had no evidence of unstable clinical states, hypokalemia, digitalis toxicity, atrial fibrillation or a prolonged QT interval (longer than 0.50 second). The quinidine dose varied from 200 to 400 mg 4 times a day for 2 to 4 weeks. Proarrhythmic effect was defined on Holter monitoring as a 400% increase in frequency of ventricular premature complexes, the presence of new ventricular tachycardia not previously identified or a 10-fold increase in the number of beats of ventricular tachycardia. There was no difference in the demography, response to quinidine therapy or side effects on quinidine among the 3 trials. Six of 360 patients (2%) had a proarrhythmic response and none of these patients had hemodynamic symptoms, required hospitalization or died from the proarrhythmic event. Thus, quinidine can be safely initiated to outpatients who meet the inclusion criteria cited herein.