Sudden death in idiopathic dilated cardiomyopathy.

Approximately 30% of deaths among patients with IDCM are sudden. Although ventricular tachyarrhythmias are responsible for many of these deaths, bradyarrhythmias may also play a significant role. Patients with a previous history of sustained ventricular arrhythmias are at high risk for sudden death. In patients without prior symptomatic ventricular arrhythmias a history of unexplained syncope, severely impaired right ventricular hemodynamics, frequent spontaneous ventricular ectopy or NSVT, and inducible SMVT may help identify those at greatest risk of dying suddenly. With the exception of angiotensin-converting enzyme inhibitor therapy, attempts at pharmacologic prevention of sudden death have had limited efficacy. The implantable defibrillator offers promising results in survivors of previous sustained ventricular arrhythmias; its prophylactic use in other high-risk subgroups is the subject of active investigation.     

Prognostic factors in nonsustained ventricular tachycardia

Electrophysiologic studies were performed in 83 consecutive patients with spontaneous nonsustained ventricular tachycardia (VT). VT was inducible in 52 patients (nonsustained VT only in 37 patients, nonsustained and sustained VT in 13 and sustained VT only in 2). During a follow-up of 3 to 111 months (mean 33), 10 patients died suddenly, 5 with coronary artery disease (CAD) and 5 with dilated cardiomyopathy. All patients with sudden death had an ejection fraction ≤0.40. Sudden death occurred in 4 of 15 patients with inducible sustained VT, 2 of 37 patients with only nonsustained VT and 4 of 31 patients without inducible VT. One patient with dilated cardiomyopathy and VT inducible only by isoproterenol died suddenly. Three of 5 patients with CAD who had sudden death had had inducible sustained VT, but 3 of 5 patients with cardiomyopathy who had sudden death had no inducible VT. Multivariate analysis revealed that patients with inducible sustained VT or an ejection fraction ≤0.40 had a 3-fold increased risk of sudden death, and patients with both factors had a 7-fold increased risk of sudden death. This study demonstrates that patients with nonsustained VT with an ejection fraction > 0.40 have an uncomplicated course; however, noninducibility does not predict such a course, particularly in patients with cardiomyopathy. The most powerful predictor of risk for sudden cardiac death is a left ventricular ejection fraction ?0.40, but the presence of inducible sustained VT is an independent risk factor for sudden death.     

Long-term reproducibility of responses to programmed cardiac stimulation in spontaneous ventricular tachyarrhythmias

Programmed electrical stimulation (PES) of the heart has been used to initiate and terminate ventricular tachyarrhythmias under controlled conditions in patients in whom these arrhythmias have occurred spontaneously. The long-term reproducibility of the response to programmed cardiac stimulation in patients with ventricular arrhythmias is unknown. Seventeen patients with previously documented spontaneously occurring ventricular tachyarrhythmias were evaluated: 5 with nonsustained ventricular tachycardia (VT), 10 with sustained VT and 2 with ventricular fibrillation. The underlying cardiac diagnosis was atherosclerotic coronary heart disease (CAD) in 11 patients, dilated cardiomyopathy in 2 patients, congenital heart disease in 1 patient and no structural heart disease in 3. All patients underwent PES in the absence of antiarrhythmic drug treatment, and patients with inducible VT underwent serial electrophysiologic-pharmacologic testing in an attempt to suppress the arrhythmia. All 17 patients were reexamined with PES at a mean of 18 months (range 2 to 42) after their initial electrophysiologic study, during which time none had a myocardial infarction or intervening cardiac surgery. Repeat electrophysiologic studies, performed in the absence of antiarrhythmic agents, were undertaken because of drug intolerance, availability of new drugs, recurrent arrhythmia or preoperative reevaluation. All 11 patients with CAD had inducible VT on both the first and second electrophysiologic evaluation. Of the 6 patients with no CAD, only 1 had inducible VT on both occasions. Thus, long-term reproducibility of PES-induced VT in patients with stable CAD appears to be high.     

Nonsustained ventricular tachycardia in patients with coronary artery disease: role of electrophysiologic study

Sixty-two consecutive patients with chronic coronary artery disease referred for evaluation of nonsustained ventricular tachycardia (VT) underwent electrophysiologic studies. Sustained VT was induced by one to three ventricular extrastimuli in 28 patients (45%). Therapy was guided by the results of electrophysiologic testing in 44 patients: 19 patients without inducible sustained VT received no antiarrhythmic therapy, and 25 patients with inducible sustained or symptomatic nonsustained VT received therapy guided by the results of electrophysiologic studies. The results of electrophysiologic studies were ignored by physicians for a second group of 18 patients: four had inducible sustained VT but received no antiarrhythmic therapy, and 14 had inducible sustained or nonsustained VT and received antiarrhythmic therapy not guided by results of electrophysiologic testing. After a mean follow-up period of 28 months, 11 patients had died suddenly. Seven of the 11 patients who died suddenly had inducible sustained VT. Three of 44 patients in the group receiving therapy guided by electrophysiologic studies died suddenly versus eight of 18 in the group receiving therapy not guided by electrophysiologic studies (p = .001). Only one of 19 patients without inducible sustained VT who were not treated experienced sudden death. Two of four patients with inducible sustained VT who did not receive antiarrhythmic therapy died suddenly. Multivariate analysis of the relationship of induced arrhythmias, left ventricular ejection fraction, site of myocardial infarction, history of syncope, or type of antiarrhythmic therapy to outcome revealed a greater than twofold increased risk for sudden cardiac death in patients whose therapy was not guided by results of electrophysiologic study.(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.     

Cardiac arrest recorded on ambulatory electrocardiograms

To characterize the events that precede and precipitate sudden cardiac death (SCD), the long-term electrocardiograms of 27 patients who had SCD while being monitored were analyzed. In 20 patients, SCD was associated with ventricular tachyarrhythmias (ventricular tachyardia [VT]/ventricular fibrillation [VF]) and in 7 it was associated with bradyarrhythmias. Seventeen of the patients were men and 10 were women. Twenty-one patients had coronary artery disease, 2 had idiopathic dilated cardiomyopathy, 2 had mitral stenosis and 1 patient had mitral valve prolapse. Four patients with VT/VF had a previous nonfatal cardiac arrest. In the 20 patients with tachyarrhythmia-related SCD, 3 or more VT beats always preceded degeneration to VF. In 5 patients, the frequency or complexity of ventricular arrhythmias increased in the hour before SCD. In 11 of 20, there was a 20% or greater increase in underlying heart rate in the hour before SCD. The R-on-T phenomenon was observed in 4 patients. The long-short phenomenon initiated VT/VF in 2 patients. Only 2 patients with VT/VF were resuscitated. No patient with bradyarrhythmia-related SCD had manifest atrioventricular block or bundle branch block. Two of 7 patients had an episode of nonsustained bradycardia in the hour before arrest. No patient was resuscitated. In conclusion, VT that degenerates into VF is the most common arrhythmia associated with SCD. VT/VF is frequently preceded by an increase in heart rate and complex ectopy. VT is most often initiated by late ventricular premature complexes. Twenty-five percent of patients who have SCD have associated bradyarrhythmias that may occur without premonitory events.     

Electropharmacology of nonsustained ventricular tachycardia: effects of class I antiarrhythmic agents, verapamil and propranolol

Forty-seven patients with spontaneous and inducible nonsustained ventricular tachycardia (VT) underwent serial electrophysiologic studies to evaluate the effects of antiarrhythmic agents on inducible arrhythmias, the role of electrophysiologic testing in the evaluation of pharmacologic therapy for these arrhythmias, and potential mechanisms underlying these arrhythmias. Type I antiarrhythmic agents prevented induction of VT by programmed stimulation in 18 of 37 patients and by isoproterenol in 9 of 11 patients. Verapamil and propranolol did not prevent or alter the mode of induction of VT by programmed stimulation, nor did they slow the induced tachycardias. Propranolol prevented induction of VT by isoproterenol in all 14 patients tested. Type I antiarrhythmic agents converted nonsustained into sustained VT in 2 of 37 patients. Inducible VT was prevented in 88% of patients without underlying heart disease, in contrast to only 38% of patients with associated cardiac disease (p less than 0.02). This study demonstrates that electrophysiologic studies may be used to identify antiarrhythmic agents with both beneficial and potentially harmful effects in patients with nonsustained VT. The responses of inducible tachycardias to antiarrhythmic agents in this group of patients with spontaneous nonsustained VT are similar to those previously observed in patients with sustained VT. Finally, the results suggest that VT induced by isoproterenol may frequently respond to type I antiarrhythmic agents in addition to beta blockers.     

Limited clinical utility of endomyocardial biopsy in patients presenting with ventricular tachycardia without apparent structural heart disease.

To determine the cardiac pathology underlying ventricular tachyarrhythmias, endomyocardial biopsy was performed in 14 patients, 10 men and 4 women, with a mean age of 40 years (range 17-63) and no apparent structural heart disease, presenting with high-density symptomatic nonsustained ventricular tachycardia (VT) (n = 4), sustained VT (n = 6), and ventricular fibrillation (n = 4). The absence of coronary or valvular heart disease was documented by cardiac catheterization. The mean left ventricular ejection fraction was 56 +/- 10%. Noninvasive assessment of the ventricular arrhythmia was made in all patients with Holter monitoring and/or exercise testing, while invasive evaluation with programmed electrical stimulation was performed in 13 patients. Biopsy findings included subendocardial and interstitial fibrosis in 7 patients, and monocytes containing periodic acid Schiff (PAS) positive vacuoles in 1 patient; biopsy was normal in 6 patients. There was no relationship between the presence or absence of pathologic abnormalities on biopsy and left ventricular ejection fraction, presenting or induced arrhythmias, or prognosis. Pathologic evidence supporting a specific treatable diagnosis was not present in any biopsy. Drugs to suppress spontaneous (3 patients) or induced (8 patients) VT were instituted, while 2 patients were not treated. In 1 patient who was resuscitated from out-of-hospital cardiac arrest an automatic defibrillator was implanted. In 24.6 months of mean follow-up there was 1 nonfatal arrhythmia recurrence, 1 noncardiac death, and 1 sudden death in a patient with fibrosis on biopsy, an ejection fraction of 45%, and both inducible and spontaneous sustained VT suppressed with an antiarrhythmic agent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Results of signal-averaged electrocardiography and electrophysiologic study in patients with nonsustained ventricular tachycardia after healing of acute myocardial infarction

Programmed stimulation and signal-averaged electrocardiography were performed in 43 consecutive patients with nonsustained ventricular tachycardia (VT) after healing of inferior (29 patients) or anterior wall (14 patients) acute myocardial infarction. Twenty-two patients had inducible sustained VT. Patients with inferior infarction and inducible sustained VT had significantly longer filtered QRS durations (125 +/- 19 vs 112 +/- 15 ms, p less than 0.01) and significantly lower voltage in the last 40 ms of the filtered QRS complex (19 +/- 5 vs 30 +/- 14 microV, p less than 0.05) than those without inducible sustained VT. In contrast, the signal-averaged electrocardiographic measurements in patients with anterior infarction and inducible sustained VT did not differ significantly from those without inducible sustained VT. The results of these studies were compared with those of 2 control groups: 45 patients without ventricular arrhythmias after myocardial infarction and 95 patients with spontaneous and inducible sustained VT after myocardial infarction. The signal-averaged electrocardiographic measurements in patients with spontaneous nonsustained VT after inferior infarction were intermediate between the control group without arrhythmias and the control group with sustained VT. The signal-averaged electrocardiograms in patients with nonsustained VT after anterior infarction were not significantly different from those in patients without ventricular arrhythmias. The study shows that the site of infarction influences the signal-averaged electrocardiogram in patients with VT after myocardial infarction. The signal-averaged electrocardiogram may be useful in identifying patients with nonsustained VT after a remote inferior myocardial infarction who have inducible sustained VT.     

Evidence-based medicine and the implantable defibrillator

Evidence from recent randomized clinical trials now strongly supports the use of the implantable defibrillator, as treatment of first choice, in patients who have experienced symptomatic, sustained ventricular tachyarrhythmias. Little or no controversy remains on this question, either among physicians or third-party players. The evidence-based use of the defibrillator as primary preventative therapy (that is, for patients who have an increased risk for lethal arrhythmias, but who have not yet experienced them) is far more limited. Two randomized trials have now demonstrated a survival benefit with the defibrillator in patients who have ichemic heart disease; reduced left ventricular ejection fraction; documented nonsustained ventricular tachycardia; and inducible sustained ventricular tachycardia during electrophysiologic testing that is not suppressed by at least one drug trial. Based on the strength of this recently available information, the screening of appropriate patients, while admittedly inconvenient, ought to be strongly considered. The broader use of the implantable defibrillator in the primary prophylaxis of arrhythmic sudden death will have to await the results of future trials.     

Programmed electrical stimulation to determine the need for antiarrhythmic therapy in patients with complex ventricular ectopic activity

Patients with complex ventricular ectopy (greater than or equal to Lown grade III) and organic heart disease (OHD) are at increased risk for sudden cardiac death. Despite this fact, many such patients will remain free of symptomatic ventricular arrhythmia and thus are unnecessarily exposed to antiarrhythmic drug toxicity and arrhythmic potentiation. Programmed stimulation (PS) was used to direct therapy in 88 patients with asymptomatic ventricular ectopy complicating OHD. Thirty-three had inducible ventricular tachycardia (VT) and underwent treatment. The 55 patients without inducible VT (less than or equal to 6 repetitive ventricular responses) are the focus of this study. Three patients required treatment for persistent cardiac awareness. The remaining 52 have been followed for 22 months off antiarrhythmic drugs and all have remained free of subsequent major arrhythmic events. Therefore, in patients with complex ventricular ectopy, OHD, and absence of prior symptomatic ventricular arrhythmia, PS identifies patients at low risk for future disabling or life-threatening arrhythmic episodes and patients with absence of inducible VT can usually be managed without antiarrhythmic drugs.     

Programmed ventricular stimulation for arrhythmia risk prediction in patients with idiopathic dilated cardiomyopathy and nonsustained ventricular tachycardia

Objectives. This study investigated the role of programmed ventricular stimulation (PVS) for arrhythmia risk prediction in patients with idiopathic dilated cardiomyopathy (IDC) and spontaneous nonsustained ventricular tachycardia (VT).Background. Nonsustained VT in patients with IDC has been associated with a high incidence of sudden cardiac death.Methods. Over the course of 4 years, 34 patients with IDC, a left ventricular (LV) ejection fraction ≤35%, and spontaneous nonsustained VT underwent PVS. All patients were prospectively followed for 24 ± 13 months.Results. Sustained ventricular arrhythmias were induced in 13 patients (38%). Sustained monomorphic VT was induced in three patients (9%), and polymorphic VT or ventricular fibrillation (VF) in another 10 patients (29%). No sustained ventricular arrhythmia could be induced in 21 study patients (62%). Prophylactic implantation of third-generation defibrillators (ICDs) with electrogram storage capability was performed in all 13 patients with inducible sustained VT or VF, and in nine of 21 patients (43%) without inducible sustained VT or VF. There were no significant differences between the additional use of amiodarone, d,I-sotalol, and beta-blocker therapy during follow-up in patients with and without inducible VT or VF. During 24 ± 13 months of follow-up, arrhythmic events were observed in nine patients (26%) including sudden cardiac deaths in two patients and ICD shocks for rapid VT or VF in seven patients. Arrhythmic events during follow-up occurred in four of 13 patients with inducible ventricular arrhythmias compared with five of 21 patients without inducible ventricular arrhythmias at PVS (31% vs. 24%, p = NS).Conclusion. PVS does not appear to be helpful for arrhythmia risk stratification in patients with IDC, a left ventricular ejection fraction ≤35%, and spontaneous nonsustained VT. Due to the limited number of patients, however, the power of this study is too small to exclude moderately large differences in outcome between patients with IDC with and without inducible VT or VF.     

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).     

The yield of programmed ventricular stimulation in mitral valve prolapse patients with ventricular arrhythmias

A high-risk subset of patients with mitral valve prolapse (MVP) and a predisposition to sudden cardiac death (SCD) has been proposed. We analyzed the results of programmed ventricular stimulation (PVS) in 20 patients with MVP and ventricular arrhythmias (ventricular premature depolarization in 6, ventricular couplets in 2, nonsustained ventricular tachycardia [VT] in 7, ventricular fibrillation [VF] in 5) and in 12 "normal" control subjects. With the use of an identical stimulation protocol from the right ventricular apex (twice diastolic threshold, three extrastimuli), 9 of 20 MVP patients and 1 of 12 normal subjects had inducible ventricular arrhythmias (p less than 0.05). When more aggressive attempts at ventricular stimulation were used, an additional five MVP patients had positive responses to PVS while no normal subjects did. In the MVP group, the following arrhythmias were induced: nonsustained polymorphic VT in 10, VF in three, and ventricular flutter in one. In all but two patients, triple ventricular extrastimuli were required to elicit this response. Two of the 10 MVP patients undergoing electropharmacologic testing had a successful antiarrhythmic regimen identified, while 13 patients were discharged on empiric antiarrhythmic therapy. At a follow-up of 19.8 +/- 13.1 months, all 19 MVP patients who could be contacted were alive. Five patients had symptomatic recurrences at follow-up including two SCD survivors (VT in one and VF in one). In conclusion, it was found that the majority of MVP patients with ventricular arrhythmias have inducible ventricular tachyarrhythmias during PVS and are more susceptible to this than patients without structural heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic studies in nonsustained ventricular tachycardia: Relation to underlying heart disease

Electrophysiologic studies were performed in 83 patients with spontaneous episodes of nonsustained ventricular tachycardia (VT). The clinical arrhythmia was reproduced in 63% (in 42 patients by programmed stimulation and in 10 by isoproterenol infusion). In 15 patients sustained VT could be reproducibly induced by programmed stimulation. Inducibility was related to the associated heart diseases: programmed stimulation induced VT in 25 of 33 patients (75%) with coronary disease, 6 of 18 patients (33%) with cardiomyopathy (dilated in 16, hypertrophic nonobstructive in 2), in 4 of 8 patients (50%) with mitral valve prolapse and in 7 of 24 patients (29%) without structural heart disease. Isoproterenol infusion induced VT in no other patient with coronary artery disease, 1 other patient with mitral valve prolapse, 3 patients with cardiomyopathy, and in 6 of 24 patients without structural heart disease. Sustained VT was induced only in patients with structural heart disease, and correlated with the presence of left ventricular aneurysms: Sustained VT was induced in 9 of 13 patients with left ventricular aneurysms. The study demonstrates that electrophysiologic techniques can reproduce episodes of nonsustained VT in most patients with spontaneous arrhythmias. Some patients who demonstrate only nonsustained VT spontaneously have inducible, sustained VT, most often in the setting of coronary artery disease and left ventricular aneurysms.     

Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease

Objectives. The aim of this study was to determine the relation between autonomic control of heart rate and the spontaneous occurrence and inducibility of ventricular arrhythmias in patients with coronary artery disease.Background. Low heart rate variability increases the risk of arrhythmic events. It is not known whether impaired autonomic heart rate control reflects alterations in functional factors that contribute to the initiation of spontaneous arrhythmias or whether it is the consequence of an anatomic substrate for reentrant tachyarrhythmias.Methods. Fifty-four patients with coronary artery disease with a history of sustained ventricular tachycardia (n = 25) or cardiac arrest (n = 29) were studied by 24-h ambulatory electrocardiographic recording and by programmed electrical stimulation. Heart rate variability was compared among the patients with and without spontaneous ventricular arrhythmias and with and without inducibility of sustained ventricular tachyarrhythmias.Results. Eight patients had a total of 21 episodes of sustained ventricular tachycardia on Holter recordings. Standard deviation of RR intervals and low frequency and very low frequency components of heart rate variability were significantly blunted in patients with sustained ventricular tachycardias compared with those without repetitive ventricular ectopic activity (p < 0.05, p < 0.01 and p < 0.05, respectively). However, no significant alterations were observed in heart rate variability before the onset of 21 episodes of sustained ventricular tachycardia. Heart rate variability did not differ between the patients with or without nonsustained episodes of ventricular tachycardia. In patients with frequent ventricular ectopic activity, low frequency and very low frequency power components were significantly blunted compared with those with infrequent ventricular ectopic activity (p < 0.01 and p < 0.001, respectively). Heart rate variability did not differ significantly between the patients with and without inducible sustained ventricular tachyarrhythmias.Conclusions. Impaired very low and low frequency oscillation of heart rate reflects susceptibility to the spontaneous occurrence of ventricular arrhythmias but may not reflect the instantaneous triggers for life-threatening arrhythmias or a specific marker of the arrhythmic substrate for ventricular tachyarrhythmias.     

Cardiac arrhythmias during theophylline toxicity. A prospective continuous electrocardiographic study

To examine the effects of theophylline toxicity on cardiac rhythm, patients underwent continuous ambulatory ECG recording during acute theophylline toxicity and recovery. The patients, who were recruited form inpatient wards, intensive care units, and emergency departments of a University Medical Center and a Veterans Administration Medical Center, had serum theophylline concentrations (STC) greater than 30 mg/L. There were 14 men and two women with a mean age of 66 years. Fourteen patients had COPD and developed toxicity following long-term theophylline overmedication. Two patients had asthma and ingested an intentional overdose. The STC at the onset of ECG recording ranged from 23 to 67 mg/L. The principal rhythm was sinus in 15 patients; one patient had atrial fibrillation. Sinus tachycardia (heart rate greater than 100/min) was common, and heart rate fell in proportion to STC as toxicity resolved. Supraventricular ectopic beats (SVEs) were noted in seven patients with multiple runs of SVE being present in four. One patient developed multifocal atrial tachycardia (MAT) during toxicity that resolved spontaneously. During the 11 +/- 8 hours of recording during toxicity (STC greater than 20 mg/L), 80 percent of patients had ventricular premature beats (VPBs), 44 percent had paired VPBs, and 25 percent had ventricular runs. One elderly patient with heart disease developed sustained ventricular tachycardia (VT) when STC = 66 mg/L. No other patient had ventricular ectopy that required intervention. During the 10 +/- 6 hours of recording during the "recovery phase" (STC less than 20 mg/L), all patients with VPBs continued to have ectopy; however, the number of VPBs declined significantly. A follow-up 24-hour ECG recording obtained one week after recovery from toxicity in the patient with sustained VT demonstrated marked reduction in the frequency and complexity of VPBs. Patients with frequent (greater than 10/h) or repetitive VPBs were older (p less than 0.05) than those without complex ectopy. There was a trend (p = 0.07) suggesting patients with underlying heart disease were at risk for having complex ventricular ectopy. We conclude that sinus tachycardia, SVE, and VPBs are common among patients with theophylline toxicity; however, sustained ventricular or supraventricular tachyarrhythmias that require antiarrhythmic therapy are uncommon.     

Electrophysiologic testing in the management of survivors of out-of-hospital cardiac arrest

Forty-five patients survived a cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF). Programmed ventricular stimulation was performed with the patients taking no antiarrhythmic medications. Sustained VT was induced in 26 patients (58%) and nonsustained VT in 8 (18%). With treatment aimed at the underlying heart disease (plus empiric antiarrhythmic therapy in 2 patients), the 11 patients who had no inducible VT have had no recurrence of symptomatic VT or cardiac arrest over a follow-up period of 19 +/- 9 months (mean +/- standard deviation). Conventional antiarrhythmic drugs suppressed the induction of VT and were used for chronic treatment in 9 of 34 patients (26%) with inducible VT. Three of these 9 patients had recurrent VT or sudden death, whereas 6 have had no recurrence over follow-up of 20 +/- 7 months. In the 25 of 34 patients in whom the induction of VT was not suppressed by conventional antiarrhythmic drugs, 23 were treated with amiodarone (daily dose 550 +/- 120 mg), and 2 underwent coronary artery bypass grafting with either aneurysmectomy or map-directed endocardial resection. One of the latter 2 patients died suddenly 12 months after surgery. Among the 23 patients treated with amiodarone, 2 had fatal VT or sudden death and 21 (91%) did not, over 18 +/- 14 months of follow-up. In survivors of a cardiac arrest, the chief value of electrophysiologic testing is in identifying patients without inducible VT, who appear to have a low risk of recurrent sudden death with treatment directed at the underlying heart disease. Serial electropharmacologic testing with conventional antiarrhythmic drugs is disappointing, with a low incidence of arrhythmia suppression.     

Complex ventricular extrasystole. Value of programmed electric stimulation for evaluating the risk of sudden death]

A prospective study was carried out from May 1984 to July 1987 to determine the prognostic value of the results of programmed electrical stimulation (PES) in patients with complex ventricular ectopy. The study population comprised 118 patients, 80 with and 38 without apparent underlying cardiac disease. The PES consisted in at most 3 extrastimuli delivered to the right ventricular apex during 2 imposed basal rhythms. Two groups of patients were identified: Group I (n = 35; 29.6%) in which a significant ventricular arrhythmia was induced (sustained ventricular tachycardia (11 cases), non-sustained VT (21 cases) and ventricular fibrillation (3 cases); and Group II (n = 83; 70.3%) in which no significant arrhythmia could be induced. During follow-up (average 28.7 +/- 11.7 months, range 6 to 48 months) there were 10 cardiac deaths, 8 of which occurred suddenly. Sudden death only occurred in patients with cardiac disease and usually with LV ejection fraction of less than 0.40; the prevalence of sudden death in Group I (11.5%) was higher than in Group II (4.8%) but the difference was not statistically significant. The prognosis of patients in Group II was the same as that of the general population. The results of this study suggest that PES enables identification of a subgroup of patients with complex ventricular ectopy in which ventricular tachyarrhythmias cannot be induced and the risk of sudden death is low; the management of patients with inducible ventricular tachyarrhythmias and normal LV function has to be determined case by case.     

Implantable defibrillator event rates in patients with unexplained syncope and inducible sustained ventricular tachyarrhythmias: a comparison with patients known to have sustained ventricular tachycardia

OBJECTIVES

To assess the clinical significance of inducible ventricular tachyarrhythmias among patients with unexplained syncope.

BACKGROUND

Induction of sustained ventricular arrhythmias at electrophysiology study in patients with unexplained syncope and structural heart disease is usually assigned diagnostic significance. However, the true frequency of subsequent spontaneous ventricular tachyarrhythmias in the absence of antiarrhythmic medications is unknown.

METHODS

In a retrospective case-control study, the incidence of implantable cardiac defibrillator (ICD) therapies for sustained ventricular arrhythmias among patients with unexplained syncope or near syncope (syncope group, n = 22) was compared with that of a control group of patients (n = 32) with clinically documented sustained ventricular tachycardia (VT). Sustained ventricular arrhythmias were inducible in both groups and neither group received antiarrhythmic medications. All ICDs had stored electrograms or RR intervals. Clinical variables were similar between groups except that congestive cardiac failure was more common in the syncope group.

RESULTS

Kaplan-Meier analysis of the time to first appropriate ICD therapy for syncope and control groups produced overlapping curves (p = 0.9), with 57 ± 11% and 50 ± 9%, respectively, receiving ICD therapy by one year. In both groups, the induced arrhythmia was significantly faster than spontaneous arrhythmias, but the cycle lengths of induced and spontaneous arrhythmias were positively correlated (R = 0.6, p < 0.0001). During follow-up, three cardiac transplantations and seven deaths occurred in the syncope group, and two transplantations and five deaths occurred in the control group (36-month survival without transplant 52 ± 11% and 83 ± 7%, respectively, p = 0.03).

CONCLUSIONS

In patients with unexplained syncope, structural heart disease and inducible sustained ventricular arrhythmias, spontaneous sustained ventricular arrhythmias occur commonly and at a similar rate to patients with documented sustained VT. Thus, electrophysiologic testing in unexplained syncope can identify those at risk of potentially life-threatening tachyarrhythmias, and aggressive treatment of these patients is warranted.