Electrophysiologic testing in patients at high risk for sudden cardiac death. I. Nonsustained ventricular tachycardia and abnormal ventricular function

Nonsustained ventricular tachycardia, although usually asymptomatic, is associated with a high risk of sudden cardiac death in patients with depressed left ventricular function. To test the vulnerability of such patients to symptomatic and potentially life-threatening arrhythmias, complete electrophysiologic studies were performed in 58 patients with clinically documented nonsustained ventricular tachycardia (greater than or equal to three complexes but less than 15 seconds of self-terminating ventricular tachycardia by 24 hour ambulatory electrocardiographic [Holter] or telemetric monitoring) and abnormal left ventricular function (ejection fraction less than 50% by radionuclide angiography). All patients had nonsustained ventricular tachycardia in the absence of antiarrhythmic drugs, acute ischemia, long QT syndrome, recent infarction or electrolyte abnormalities. The stimulation protocol for each patient included the introduction of single, double and triple ventricular extrastimuli at three cycle lengths (sinus, 600 and 450 ms) and two right ventricular sites (apex and outflow tract). A sustained ventricular tachyarrhythmia was induced in 23 patients (40%) and a nonsustained ventricular tachycardia in 14 patients (24%). Induction of sustained tachycardia correlated with the presence of akinesia or aneurysm, or both, by radionuclide angiography, but not with ejection fraction or presence or absence of coronary artery disease. These results indicate that: 1) patients with clinical nonsustained ventricular tachycardia and chronic left ventricular dysfunction have a high incidence of inducible sustained ventricular tachycardia or ventricular fibrillation; and 2) electrophysiologic testing may allow further substratification of risk of sudden cardiac death in high risk patients with nonsustained ventricular tachycardia.     

Development of arrhythmias in the patient with congestive heart failure: pathophysiology, prevalence and prognosis

While the number of deaths from coronary artery and cerebrovascular disease is clearly decreasing in the U.S., the prevalence of congestive heart failure (CHF) seems to be increasing. Many studies have found that more than half of the CHF-related deaths are sudden, and presumably are due to ventricular arrhythmias. Knowledge of the pathophysiology of arrhythmias in the patient with CHF is limited, but left ventricular mechanical abnormalities, diuretic-induced hypokalemia, hypomagnesemia and inotropic therapy may play a role. The prevalence of couplets, multiformed ventricular premature complexes or both is very high, averaging 87% in 8 different studies. The prevalence of nonsustained ventricular tachycardia, determined by ambulatory electrocardiographic recordings, is also quite high; it is approximately 54% in these same studies. Although still unclear, some data now suggest that ventricular arrhythmias may independently influence prognosis in patients with CHF. Future research is obviously necessary to evaluate the influence of antiarrhythmic therapy on survival. However, preliminary findings appear to indicate that treatment may not affect long-term survival in these patients.     

Ventricular arrhythmia in congestive heart failure.

The importance of ventricular arrhythmia is based on its association with sudden death. In certain groups of patients, ventricular arrhythmia--primarily runs of nonsustained ventricular tachycardia (NSVT)--is associated with an increased risk for sudden death. Although this relationship has been most often reported in patients with recent myocardial infarction, it has also been recognized in patients with dilated cardiomyopathy, regardless of etiology. Therefore, ventricular arrhythmia is common in patients with CHF due to cardiomyopathy. A number of studies have reported that 70-95% of patients with cardiomyopathy and congestive heart failure (CHF) have frequent ventricular premature beats, and 40-80% will manifest runs of NSVT. Many factors are responsible for ventricular arrhythmia in such patients, including structural abnormalities, electrolyte imbalance, hemodynamic impairment, activation of neurohormonal mechanisms, and pharmacologic therapy. Many studies have reported a high yearly mortality in patients with cardiomyopathy and CHF; greater than 40% of deaths are sudden, most often the result of sustained ventricular tachyarrhythmia. Most studies have noted an association between presence (and frequency) of NSVT and risk of sudden cardiac death in these patients. Unfortunately, other techniques--such as the signal-averaged electrocardiogram and electrophysiologic testing--are not helpful in identifying the individual at risk. Although several drug interventions will reduce mortality from progressive CHF, these drugs have not been shown to reduce sudden death and, indeed, have a variable effect on ventricular arrhythmia. Although NSVT is a marker for increased risk for sudden death, it is uncertain if antiarrhythmic drugs will prevent this outcome. Antiarrhythmic drugs have not been shown to be effective for preventing sudden death, although there are as yet no well-controlled randomized trials. Several studies suggest that amiodarone and beta blockers are beneficial, but this requires confirmation. For patients who have been resuscitated following an episode of sudden death due to a sustained ventricular tachyarrhythmia, antiarrhythmic therapy guided by invasive and noninvasive techniques appears to reduce risk of recurrent arrhythmia. However, the response rate to antiarrhythmic agents is low and side effects are common in patients with CHF. Especially important is the increased risk of precipitating CHF and aggravating the arrhythmia being treated. For many such patients who have had serious ventricular tachyarrhythmia, the automatic implantable cardioverter defibrillator may prove a better option. Other drugs used for management of CHF reduce overall mortality, but not risk of sudden death.     

Arrhythmias in Patients with Heart Failure

Opinion statement Both atrial and ventricular arrhythmias are very common in patients with congestive heart failure, and their presence is associated with symptoms, significant morbidity, and mortality. Studies have attempted to determine the prognostic significance of atrial and ventricular arrhythmias in patients with heart failure. Whether atrial fibrillation is an independent risk factor of mortality remains controversial. The presence of ventricular arrhythmias in patients with ischemic cardiomyopathy identifies patients at high risk for sudden death. However, in patients with nonischemic cardiomyopathy there is not a strong correlation between ventricular arrhythmias and increased risk for sudden death. Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients 1) post-myocardial infarction; 2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and 3) with sustained ventricular tachycardia and those who have survived an out-of-hospital cardiac arrest. The purpose of this article is to present an overview of arrhythmias in patients with heart failure and discuss the prevalence, prognostic significance, complications, mechanisms, and trials that have formed the current therapies presently used.     

Long-term outcome of pharmacological and nonpharmacological treatment for ventricular arrhythmias

Recent advances of nonpharmacological therapy such as catheter ablation and implantable cardioverter defibrillator and lessons from the Cardiac Arrhythmia Suppression Trial(CAST) have changed the strategy for ventricular arrhythmias. The safety and efficacy of radiofrequency catheter ablation of symptomatic sustained monomorphic ventricular tachycardia without structural heart disease has made ablation the firstline curative therapy. In idiopathic ventricular fibrillation such as Brugada syndrome, an implantable cardioverter defibrillator is the most effective treatment to prevent sudden cardiac death. In patients with asymptomatic ventricular tachyarrhythmias in heart failure, class I antiarrhythmic drugs should be avoided due to proarrhythmic and negative inotropic effects that may be responsible for increased mortality in some trials. In such patients, amiodarone and beta-blocker may reduce sudden cardiac death. For patients with sustained ventricular tachycardia or ventricular fibrillation in heart failure, amiodarone or implantable cardioverter defibrillator should be considered. In comparison with amiodarone, implantable cardioverter defibrillator markedly reduced sudden death in ventricular tachycardia and ventricular fibrillation survivors in Antiarrhythmics Versus Implantable Defibriltors(AVID). Although better patient selection and clarification of mapping criteria improved the successful ablation rate in patients with structural heart disease, candidates of ablation are few. In patients with extensive structural heart disease, multiple ventricular tachycardias are often present. Catheter ablation of a single ventricular tachycardia may be only palliative. Therefore, implantable cardioverter defibrillator is the most effective treatment to prevent sudden cardiac death, with amiodarone and ablation as the adjunctive therapy to prevent frequent ventricular tachycardia. Furthermore, an implantable cardioverter defibrillator improved survival in selected patients with depressed ventricular function after myocardial infarction, who also have nonsustained and inducible sustained ventricular tachycardia in Multicenter Automatic Defibrillator Implantation Trial(MADIT) and Multicenter Unsustained Tachycardia Trial(MUSTT).     

Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride by propranolol

The use of membrane-active antiarrhythmic agents may be complicated by aggravation of existing arrhythmias or development of new drug-induced arrhythmias. Four patients, referred because of out-of-hospital cardiac arrest or symptomatic sustained ventricular tachycardia, were receiving class IC antiarrhythmic agents in an attempt to prevent inducibility of sustained ventricular tachycardia. New or worsening spontaneous arrhythmias developed while they were on flecainide acetate (n = 3) or encainide hydrochloride (n = 1) therapy. Spontaneous runs of rapid nonsustained and sustained ventricular tachycardia developed in two. Increased frequency of premature ventricular contractions and repetitive forms of ventricular ectopic activity developed in one, despite the fact that inducibility of sustained ventricular tachycardia had been prevented. Salvos and nonsustained ventricular tachycardia developed in the fourth patient. Propranolol had failed to prevent inducibility of sustained ventricular tachycardia during previous programmed stimulation studies in three of the four patients, but it reproducibly suppressed drug-induced arrhythmias that appeared only after administration of the IC agents in each patient. Suppression of the proarrhythmic effects by beta-adrenergic blockade suggests a possible interaction of these drugs with autonomic function in the genesis of the observed proarrhythmic effects. Direct pharmacologic control of proarrhythmic drug effects has not previously been reported.     

Significance and control of cardiac arrhythmias in patients with congestive cardiac failure

A wide spectrum of ventricular and supraventricular tachyarrhythmias occurs in the setting of congestive cardiac failure. However, the two most clinically significant are atrial fibrillation and ventricular tachycardia and fibrillation.In the past there has been much emphasis on premature ventricular contractions and more recently, on nonsustained ventricular tachycardia. For the most part, these arrhythmias are asymptomatic in heart failure. They are markers of sudden arrhythmic death but their suppression by antiarrhythmic drugs have not resulted in a reduction of total mortality. Two approaches have been used to this end. The first is the use of beta-adrenergic blocking drugs and antiarrhythmic agents such as amiodarone. Beta-blockers have been shown to significantly reduce sudden death as well as total mortality, while the effects of amiodarone have been less decisive. The prospective role of the implantable cardioverter defibrillator (ICD) is undergoing critical evaluation in patients with cardiac failure at high risk for sudden death. The elective role of the ICD is well established as first-line therapy in patients with heart failure resuscitated from sudden death and in those with sustained ventricular tachycardia in conjunction with conventional therapies for cardiac decompensation.The prevalence of atrial fibrillation rises as a function of severity of cardiac failure, but it is also in known that persistent atrial fibrillation with an uncontrolled ventricular response may induce heart failure. Controlled ventricular response may prevent congestive heart failure and improve left ventricular function. The two most common causes of atrial fibrillation in cardiac failure in Europe and America are ischemic heart disease and hypertension, while mitral valve disease remains the prevalent cause elsewhere. The choice of antiarrhythmic drugs for maintaining sinus rhythm is critical in the prevention of heart failure aggravation and proarrhythmic reactions of antiarrhythmic drugs. Amiodarone and dofetilide are most widely used in this context.     

The implantable cardioverter-defibrillator

Ventricular arrhythmias remain a major cause of cardiovascular mortality. Therapy for serious ventricular arrhythmias has evolved over the past decade, from treatment primarily with antiarrhythmic drugs to implanted devices. The implantable cardioverter-defibrillator (ICD) is the best therapy for patients who have experienced an episode of ventricular fibrillation not accompanied by an acute myocardial infarction or other transient or reversible cause. It is also superior therapy in patients with sustained ventricular tachycardia (VT) causing syncope or hemodynamic compromise. Controlled clinical trials have confirmed the utility of these devices. As primary prevention, the ICD is superior to conventional antiarrhythmic drug therapy in patients who have survived a myocardial infarction and who have spontaneous, nonsustained ventricular tachycardia, a low ejection fraction, inducible VT at electrophysiologic study, and whose VT is not suppressed by procainamide. The effect of the ICD on survival of other patient populations remains to be proven. The device is costly, but its price is generally accepted to be reasonable. The ICD has been a major advance in the treatment of ventricular arrhythmias.     

Role of electrophysiologic testing in managing patients who have ventricular tachycardia unrelated to coronary artery disease

This study examined the usefulness of programmed electrical stimulation in managing 83 patients who had ventricular tachycardia not due to coronary artery disease. Among 39 patients with a history of sustained ventricular tachycardia, programmed stimulation induced ventricular tachycardia in 14 of 14 patients with mitral valve prolapse or primary electrical disease (arrhythmias without evidence of structural heart disease) and in 13 of 25 with cardiomyopathy (total 27 of 39, 69 percent). Programmed stimulation induced nonsustained ventricular tachycardia in 15 (34 percent) of 44 patients with a history of nonsustained tachycardia (5 of 13 with mitral valve prolapse, 6 of 19 with primary electrical disease and 4 of 12 with cardiomyopathy). Seventy-three of the 83 patients were treated with antiarrhythmic drugs and then followed up for 14.4 ± 11.4 months (mean ± standard deviation). Drug therapy was determined with serial electrophysiologic testing in 31 patients. Twenty-four of these 31 patients had a history of sustained ventricular tachycardia, and drugs prevented induction of ventricular tachycardia in 9 (none of whom manifested symptomatic events) but did not prevent it in 15 (6 of whom had symptomatic events). Among seven patients with a history of nonsustained ventricular tachycardia, drugs prevented induction of ventricular tachycardia in five (none of whom had symptomatic events) and did not prevent it in two (none of whom had symptomatic events). Forty-two patients were treated using the results of noninvasive testing. Drugs suppressed spontaneous ventricular tachycardia in 15 of 15 patients with a history of sustained tachycardia (7 of whom had symptomatic events including one sudden death), and in 26 of 27 with a history of nonsustained tachycardia (6 of whom had symptomatic events including one sudden death).Thus, in patients with ventricular tachycardia unrelated to coronary artery disease: (1) programmed electrical stimulation induced ventricular tachycardia less often than in patients whose tachycardia was due to coronary artery disease; (2) programmed stimulation induced ventricular tachycardia less often in patients with a history of nonsustained versus sustained tachycardia; and (3) suppression of inducible ventricular tachycardia appeared to predict effective drug therapy but drug therapy predicted with noninvasive testing appeared to be unreliable.     

Ventricular tachycardia in a young population without overt heart disease

Since 1974, 24 young patients presenting with ventricular tachycardia and without clinical evidence of heart disease were evaluated and followed. Sixteen patients (67%) were symptomatic. Clinical episodes of ventricular tachycardia were sustained in 18, incessant in four, and nonsustained in two patients. The rate of tachycardia ranged from 130 to 300 beats/min (mean = 200 beats/min). Subtle abnormalities of cardiac size or function were present at cardiac catheterization in 16 of 23 patients (70%). During electrophysiologic studies, spontaneous ventricular tachycardia was present in six patients. The clinical ventricular tachycardia was inducible by programmed stimulation in 13 of 18 patients. The site of origin of tachycardia based on endocardial mapping in 17 patients was the right ventricle in 14, the ventricular septum in one, and indeterminate in two patients. Seventeen patients were treated based on results of short-term drug testing. During a mean follow-up period of 7.5 years, three patients died suddenly; none of these patients were receiving antiarrhythmic medication at the time of death. We conclude that in a young population without clinical evidence of heart disease, ventricular tachycardia may be the first manifestation of cardiomyopathy, since at least two-thirds of these patients have abnormalities at cardiac catheterization. Without treatment mortality in this population may be as high as 13% over an 8 year period. Presently we recommend treatment of ventricular tachycardia in any symptomatic patient, with therapy guided by electrophysiologic and treadmill testing. In addition, we recommend treatment for any asymptomatic patient with exercise-related tachycardia, since this group appears to be at increased risk for sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arrhythmias in heart failure: current concepts of mechanisms and therapy

About one half of deaths in patients with heart failure are sudden, mostly due to ventricular tachycardia (VT) degenerating to ventricular fibrillation or immediate ventricular fibrillation. In severe heart failure, sudden cardiac death also may occur due to bradyarrhythmias. Other dysrhythmias complicating heart failure include atrial and ventricular extrasystoles, atrial fibrillation (AF), and sustained and nonsustained ventricular tachyarrhythmias. The exact mechanism of the increased vulnerability to arrhythmias is not known. Depending on the etiology of heart failure, different preconditions, including ischemia or structural alterations such as fibrosis or myocardial scarring, may be prominent. Reentrant mechanisms around scar tissue, afterdepolarizations, and triggered activity due to changes in calcium metabolism significantly contribute to arrhythmogenesis. Furthermore, alterations in potassium currents leading to action potential prolongation and an increase in dispersion of repolarization play a significant role. Treatment of arrhythmias is necessary either because patients are symptomatic or to reduce the risk for sudden cardiac death. The individual history, left ventricular function, electrophysiologic testing, and the signal-averaged ECG give useful information for identifying patients at risk for sudden cardiac death. The implantable cardioverter defibrillator (ICD) has evolved as a promising therapy for life-threatening arrhythmias. A potential role may exist for antiarrhythmic drugs, mainly amiodarone. There is growing evidence that patients with sustained VT or a history of resuscitation have the best outcome with ICD therapy regardless of the degree of heart failure. Many of these patients require additional antiarrhythmic therapy because of AF or nonsustained VTs that may activate the device. Catheter ablation or map-guided endocardial resection are additional options in selected patients but seldom represent the only therapeutic strategy.     

Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without ventricular tachycardia

The proarrhythmic effects of class IA antiarrhythmic drugs were prospectively evaluated during programmed ventricular stimulation in 24 consecutive patients with frequent ventricular premature beats whose baseline study, performed while no antiarrhythmic drugs were being taken, showed no inducible sustained ventricular arrhythmias. No patient had nonsustained (greater than 5 beats) or sustained ventricular tachycardia by history or baseline 24 hour ambulatory electrocardiographic monitoring. Sequential stimulation studies using up to three extra-stimuli were performed after administration of procainamide, quinidine and disopyramide on different days. Proarrhythmic response was defined as induction of one or more of the following: sustained monomorphic ventricular tachycardia; sustained polymorphic ventricular tachycardia; ventricular fibrillation; reproducibly inducible nonsustained monomorphic ventricular tachycardia. During 55 antiarrhythmic drug trials (24 of procainamide, 21 of quinidine, 10 of disopyramide) in the 24 patients, 6 patients had a proarrhythmic response: sustained monomorphic ventricular tachycardia in 3, ventricular fibrillation in 2, nonsustained monomorphic ventricular tachycardia in 1. Thus, 11% of drug trials resulted in a proarrhythmic response and 25% of patients had a proarrhythmic response to one of the drugs tested. A proarrhythmic response to one drug did not predict a similar response to another drug of the same class. The 6 patients with a proarrhythmic response did not differ significantly from the other 18 patients with regard to underlying heart disease, electrocardiographic or baseline 24 hour ambulatory electrocardiographic characteristics; however, they did have a higher incidence of digoxin usage (p less than 0.02), a shorter baseline right ventricular effective refractory period (p less than 0.01) and a smaller increment in effective refractory period during antiarrhythmic drug testing (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exacerbation of ventricular tachycardia by tocainide

Exacerbation of ventricular arrhythmias by antiarrhythmic drugs the lignocaine-type has not been reported previously. In this paper we describe three patients with a variety of ventricular arrhythmias who were treated with tocainide and developed worsening of the ventricular arrhythmias. In one patient, frequent ventricular ectopic beats were converted to sustained ventricular tachycardia (VT) in another, nonsustained VT was converted to sustained VT, and in a third, monomorphic VT was converted to multimorphic VT. These patients illustrate the need for careful supervision of antiarrhythmic therapy for VT, even when lignocaine-like drugs are being used.     

Short- and long-term experience with flecainide acetate in the management of refractory life-threatening ventricular arrhythmias

Thirty-eight patients with organic heart disease and history of sudden cardiac arrest or recurrent sustained ventricular tachycardia were treated with flecainide. Coronary artery disease was present in 33 patients. Previous antiarrhythmic therapy consisted of two to eight drugs (mean four). Fourteen patients were resuscitated from sudden cardiac death and 24 patients had chronic recurrent sustained ventricular tachycardia. Twenty-eight patients had electrophysiologic testing before and during flecainide treatment. Sustained ventricular tachycardia became noninducible in 5 patients, nonsustained in 5 patients and slowed in 13 patients (cycle length increased from 278 +/- 64 to 395 +/- 91 ms; p = 0.002). Three of the 14 patients with sudden cardiac death and 15 of the 24 patients with recurrent sustained ventricular tachycardia remained on long-term flecainide treatment. The mean left ventricular ejection fraction in 16 of these 18 patients was 37%. Nonlimiting side effects occurred in seven patients (18%). Proarrhythmic effects were seen in four patients (10%). At a mean follow-up time of 11 +/- 3 months, 15 patients (39%) had had no recurrence, including 5 who had inducible sustained ventricular tachycardia and 5 who did not on retesting during treatment. In the 18 patients who received long-term therapy, 3 late deaths occurred, 1 of which was of arrhythmic origin. These data suggest that flecainide is effective in about 40% of patients with severe refractory ventricular arrhythmias. Its value as a single drug in the treatment of sudden cardiac death remains to be defined.     

Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators

BACKGROUND: Ventricular arrhythmias are a frequent finding in congestive heart failure (CHF) patients and a cause of concern for physicians caring for them. Previous studies have reached conflicting conclusions regarding the importance of ventricular arrhythmias as predictors of sudden death in patients with CHF. This study examined the independent predictive value of ventricular arrhythmias for sudden death and all-cause mortality in PROMISE (Prospective Randomized Milrinone Survival Evaluation). METHODS AND RESULTS: Ventricular arrhythmias were analyzed and quantified by use of prespecified criteria on baseline ambulatory ECGs from 1080 patients with New York Heart Association (NYHA) class III/IV symptoms and a left ventricular ejection fraction 相似文献   

Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction

Programmed electrical stimulation of the heart was prospectively used in 160 patients with healed myocardial infarction to study the incidence and characteristics of ventricular arrhythmias induced. Thirty-five patients had neither documented nor suspected ventricular arrhythmias (Group A); 37 patients had documented nonsustained ventricular tachycardia (Group B); 31 patients had been resuscitated from ventricular fibrillation (Group C); and 57 patients had documented sustained monomorphic ventricular tachycardia (Group D). No electrophysiologic differences were found between patients in Group A and Group B, but patients in both groups differed significantly from patients in Group C and Group D. In the last two groups, sustained monomorphic ventricular tachycardia was more frequently induced, the cycle length of the induced ventricular tachycardia was slower and a lesser number of premature stimuli was required for induction. No differences were found in the incidence, rate or mode of induction of nonsustained monomorphic ventricular tachycardia, but nonsustained polymorphic ventricular tachycardia and ventricular fibrillation were more frequently induced in Groups A and B. It is concluded that the substrate for sustained ventricular arrhythmia is present in at least 42% of patients after myocardial infarction. The electrophysiologic characteristics of the substrate for ventricular tachycardia seem to be the major determinant of the clinical occurrence of sustained ventricular arrhythmia. Changes in the electrophysiologic properties of the substrate of ventricular tachycardia, either spontaneously with time or induced by ischemia or antiarrhythmic drugs, can contribute to the clinical occurrence of sustained ventricular arrhythmias in patients with an old myocardial infarction.     

Evaluation of antiarrhythmic therapy using Holter monitoring

Premature ventricular complexes and nonsustained ventricular tachycardia mark a person with structural cardiac disease as a high--risk candidate for sudden cardiac death. Such ventricular arrhythmias are considered potentially lethal and should be distinguished from both those that are benign and those that cause hemodynamic consequences (i.e., lethal or malignant arrhythmias). Noninvasive Holter monitoring is the principal technique for detecting and evaluating the presence of potentially lethal ventricular arrhythmias. These arrhythmias undergo a high degree of spontaneous variability. Thus, to define a therapeutic drug effect, a reduction in the frequency of premature ventricular complexes of at least 75% and a reduction in the frequency of nonsustained ventricular tachycardia by at least 90% are required to eliminate the likelihood of spontaneous variability as the cause of this change in the frequency of arrhythmia. To define proarrhythmia, a different algorithm must be applied. When using antiarrhythmic drugs, a quantitative ventricular arrhythmia baseline for both frequency and type of arrhythmia must be established so that after therapeutic intervention repeat Holter monitoring can determine whether efficacy, inefficacy or proarrhythmia had occurred. Holter monitoring clearly reveals differential antiarrhythmic response rates among classes of antiarrhythmic drugs in patients with benign or potentially lethal arrhythmias. However, preliminary data have not clearly defined the relation between antiarrhythmic pharmacotherapy and a reduction in sudden cardiac death. The results of large-scale clinical trials that have only recently been undertaken must be assessed to determine whether sudden cardiac death can be prevented by adequately suppressing potentially lethal ventricular arrhythmias.     

Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs

The protective effect of antiarrhythmic agents for patients with malignant ventricular arrhythmia (defined as noninfarction ventricular fibrillation or sustained hemodynamically compromising ventricular tachycardia) remains uncertain. We have analyzed survival among 123 such patients (98 males, 25 females, average age 53.6 years) dependent on the abolition of antiarrhythmic drugs of salvos of ventricular tachycardia and R-on-T ventricular premature beats (Lown grades 4B and 5). Over an average follow-up of 29.6 months there were 35 deaths (11.2 percent annual mortality rate) of whom 23 patients succumbed suddenly (8.2 percent annual mortality rate). Among 98 patients in whom antiarrhythmic drugs abolished grades 4B and 5 ventricular premature beats, only 6 sudden deaths occurred for a 2.3 percent annual mortality rate. Of the 25 patients in whom advanced ventricular premature beats were not controlled, 17 died suddenly. Seventy-nine patients had left ventricular studies suitable for analysis. Among 44 patients with left ventricular dysfunction, control of ventricular premature beats was a critical element predicting survival. The annual sudden death rate for the 12 noncontrolled patients with left ventricular dysfunction was 41 percent contrasting with only 3.1 percent for the 32 patients with similar abnormalities in ventricular function in whom advanced ventricular premature beats were abolished. It is concluded that antiarrhythmic drugs can protect against the recurrence of life-threatening arrhythmias in patients who have manifest ventricular fibrillation or ventricular tachycardia and that abolition of certain advanced grades of ventricular premature beats provides an effective therapeutic objective.     

Electrophysiological testing and nonsustained ventricular tachycardia. Use and limitations in patients with coronary artery disease and impaired ventricular function

Electrophysiological testing was performed in 100 consecutive patients with spontaneous asymptomatic nonsustained ventricular tachycardia, chronic coronary artery disease, and ejection fraction of less than 40%. Fifty-seven patients without inducible sustained ventricular arrhythmias were discharged on no antiarrhythmic therapy. Sustained monomorphic ventricular tachycardia was induced in 37 patients, and polymorphic ventricular tachycardia or ventricular fibrillation was induced in six patients. Of the 43 patients with inducible sustained ventricular arrhythmias, three had spontaneous cardiac arrest during serial drug testing and were excluded from further analysis. Twenty patients were discharged on drug therapy, resulting in suppression of inducible sustained ventricular arrhythmias. The remaining 20 patients with persistently inducible sustained arrhythmias were discharged on drug therapy, resulting in maximal rate slowing of the induced tachycardia. During a mean follow-up of 16.7 months, there were 10 recurrent cardiac arrests or sudden deaths. The 1- and 2-year actuarial incidence of these events was 2% and 6%, respectively, in patients without inducible sustained ventricular arrhythmias; 0% and 11%, respectively, in patients in whom inducible arrhythmias were suppressed; and 34% and 50%, respectively, in patients with persistently inducible sustained ventricular arrhythmias. Multivariate Cox analysis identified only the persistence of inducible sustained ventricular arrhythmias as a significant independent predictor of sudden death or recurrent sustained arrhythmias (p less than 0.001; relative risk, 3.5; 95% confidence intervals, 2.1-4.9). In this population, therapeutic intervention to prevent sudden death is unnecessary in patients without inducible sustained ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tachycardias of right ventricular origin.

Ventricular tachycardia arising from the right ventricle usually has a left bundle branch morphology and occurs in a variety of disorders. Uhl's anomaly and right ventricular dysplasia may represent a spectrum of one disorder and are a cause of right heart dilatation, failure, and premature sudden death due to ventricular arrhythmias. Familial forms of the disorder may account for focal clustering in some geographic areas. Management should involve aggressive stratification of arrhythmia risk and may include medical, surgical, or device therapy. In contrast, the syndrome of right ventricular outflow tract tachycardia, including nonischemic exercise-induced and repetitive monomorphic ventricular tachycardia, is a more benign entity. Management often involves beta- and calcium channel blocking drugs or type IC antiarrhythmic drugs. Catheter ablation of the arrhythmia focus in the right ventricular outflow tract has been used in selected patients. In this syndrome the right ventricle is normal, and noninvasive testing as well as electrophysiologic studies can be helpful in distinguishing it from the more malignant right ventricular dysplasia. Ventricular arrhythmias may also be seen after right ventricular incision, as in surgical repair of tetralogy of Fallot and ventricular septal defects. Significant ventricular ectopy associated with an abnormal right ventricle (enlarged or depressed systolic function) is associated with an increased risk for sustained arrhythmia and sudden cardiac death in this group. The optimal indicator(s) of highest risk in these patients remains under investigation but will likely include electrophysiologic testing. Bifascicular block occurs commonly after repair of tetralogy of Fallot, but is usually benign. Isolated right ventricular infarction is rare. Most right ventricular arrhythmias associated with ischemia occur in the setting of iatrogenic catheter manipulation for pacing or hemodynamic monitoring. In conclusion, right ventricular arrhythmias involve an unusual and interesting group of clinical entities and appear to span the spectrum of arrhythmias mechanisms. A macroreentrant activation ring around the ventriculotomy scar may account for the arrhythmias following repair of tetralogy of Fallot. Microreentry at sites of morphologic abnormalities results in the arrhythmias associated with right ventricular dysplasia and ischemia. Triggered activity related to DADs or, less likely, abnormal automaticity, produce repetitive monomorphic ventricular tachycardia and nonischemic exercise-induced ventricular tachycardia, both of which usually originate from the right ventricular outflow tract. Iatrogenic ventricular tachycardia associated with catheter manipulation is especially likely to occur in the presence of right ventricular ischemia and infarction. It is important to recognize these clinical entities because treatment is specific.(ABSTRACT TRUNCATED AT 400 WORDS)