Modification of the circadian pattern of ventricular tachyarrhythmias by beta-blocker therapy

Background: Sudden cardiac death exhibits a circadian variation and predominantly occurs during morning hours. Beta-adrenergic antagonists have shown to blunt this morning peak. However, previous reports studying the effects of beta blockers on the circadian variation did not analyze the underlying cause of sudden cardiac death. It thus remains unclear whether ventricular tachyarrhythmias are influenced by beta-blocker therapy. Hypothesis: This study tested the hypothesis that beta-blocking agents blunt the morning peak of life-threatening ventricular tachyarrhythmias. Methods: In 87 patients who were treated and monitored with an implantable cardioverter defibrillator, the circadian distribution of ventricular tachyarrhythmias terminated by appropriate shocks was analyzed and compared in those receiving beta blockers versus those not receiving beta-blocker therapy. Results: Tachyarrhythmic episodes in the absence of beta-blocker therapy (n = 344) exhibited a circadian variation with a distinct morning peak (16, 38, 28, and 18% of episodes at 0–6, 6–12, 12–18, and 18–24 h, respectively, p<0.001). In contrast, tachyarrhythmic episodes during beta-blocker therapy (n = 104) were equally distributed over time (22, 27, 24, and 27% of episodes at 0–6, 6–12, 12–18, and 18–24 h, respectively, p = 0.95). The circadian distribution of episodes was significantly different in patients with and those without beta blockade (p<0.05). Conclusion: Beta-adrenergic antagonists influence the circadian distribution of malignant ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. The blunted morning peak of tachyarrhythmic events during beta blockade supports the hypothesis that a sympathetic surge is involved in the circadian pattern of malignant arrhythmias.     

Nonsustained ventricular tachycardia in dilated cardiomyopathy

In patients with structural heart disease, ventricular arrhythmias are associated with an increased risk of overall mortality and sudden cardiac death (SCD). Nonsustained ventricular tachycardia (NSVT) is common in patients with dilated cardiomyopathy of both ischemic and nonischemic origin. Recent studies suggest that NSVT may be a marker, but not a significant predictor, of mortality and SCD in that suppression of NSVT in these patients using antiarrhythmic drugs is of questionable benefit. Additionally, indications for implantable cardioverter defibrillator implantation do not include NSVT. This article focuses on the prognostic significance and treatment of patients with NSVT and ischemic or nonischemic dilated cardiomyopathy.     

Analysis of the pattern of initiation of sustained ventricular arrhythmias in patients with implantable defibrillators

INTRODUCTION: The purpose of this study was to analyze the pattern of initiation of sustained ventricular arrhythmias in patients with varying types of underlying structural heart disease. METHODS AND RESULTS: The study group consisted of 90 patients with an implantable cardioverter defibrillator. Cardiovascular diagnoses included coronary artery disease in 64 patients (71%). The patients were divided into four groups based on the type and severity of structural heart disease. Two hundred sixty episodes of sustained ventricular arrhythmias were analyzed. The mean coupling interval of the initiating beat of all ventricular arrhythmias was 523 +/- 171 msec. The coupling interval of the initiating beat was longer in patients with impaired ventricular function, particularly those with nonischemic dilated cardiomyopathy. The prematurity index was similar regardless of the type of underlying structural heart disease. However, the prematurity index was shorter in patients with polymorphic ventricular tachycardia (VT) compared to those with monomorphic VT. A pause was observed more commonly before the onset of polymorphic VT/ventricular fibrillation than sustained monomorphic VT. Two hundred twenty-two (85%) of the arrhythmia episodes were initiated by a late-coupled premature beat, 33 (13%) were initiated by an early-coupled premature beat, and 5 episodes (2%) were initiated with a short-long-short sequence. The pattern of initiation of the ventricular arrhythmias was similar in all patient groups and for both monomorphic and polymorphic tachycardias. CONCLUSION: These findings demonstrate that sustained ventricular arrhythmias typically are initiated by late-coupled ventricular premature depolarizations, regardless of the type or severity of underlying structural heart disease or resultant arrhythmia.     

Update of implantable cardioverter/defibrillator and cardiac resynchronization therapy in heart failure

PURPOSE OF REVIEW: Heart failure prevalence is reaching epidemic proportion in the United States and is associated with significant morbidity and mortality. A large proportion of the mortality is the result of sudden cardiac death (SCD). Clinical trials have demonstrated the superiority of the implantable cardioverter/defibrillator (ICD) compared with antiarrhythmic drugs for secondary prevention of sudden cardiac death. RECENT FINDINGS: Recently, several clinical trials in primary prevention of sudden cardiac death in both ischemic and nonischemic heart failure have been completed. The 2002 guidelines for implantable cardioverter/defibrillator implantation were recently released as well. Adjunct therapy consisting of antiarrhythmic drugs or radiofrequency ablation is necessary in the subset of patients with implantable cardioverter/defibrillator that have frequent or intractable ventricular arrhythmias. An emerging new therapy in the heart failure population is cardiac resynchronization therapy, which coordinates right and left ventricular pacing in a subset of patients with interventricular conduction delay. SUMMARY: Several randomized clinical trials have demonstrated improvements in heart failure-related symptoms, exercise tolerance, and reversal of ventricular remodeling. Meta-analysis of these trials has also demonstrated mortality benefit. Patient selection, left ventricular pacing site, and optimal device programming are issues that need further investigation. Recent trials have also studied the compatibility between cardiac resynchronization therapy and implantable cardioverter/defibrillator as a single device. Finally, the DAVID trial has raised concerns of conventional right ventricular pacing and the risk of heart failure in a subset of patients.     

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population

INTRODUCTION: Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. METHODS AND RESULTS: Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. CONCLUSION: Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.     

Circadian pattern of ventricular tachycardia episodes in patients with Chagas heart disease

Chronic Chagas' cardiomyopathy (CCM) causes ventricular arrhythmias and sudden death, and constitutes the most frequent cause of death in many endemic areas. The circadian variation in the incidence of ventricular arrhythmias and sudden death differs according to the substrate (e.g., morning and evening peaks in ischemic heart disease and non-Chagasic dilated cardiomyopathy). Third generation implantable cardioverter defibrillators (ICDs) have the ability to store the time and date of each ventricular tachycardia (VT) episode, enabling the patterns of ventricular tachyarrhythmia occurrence to be analyzed. The aim of our study was to evaluate the circadian variation of spontaneous VT in recipients of an ICD with CCM.     

Troponin-I elevation in a young man with arrhythmogenic right ventricular dysplasia/cardiomyopathy

Ventricular arrhythmias occur frequently in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) as well as those with ischemic heart disease. We present the case of a 29-year-old man with ARVD/C and multiple episodes of symptomatic ventricular tachycardia terminated by implantable cardioverter defibrillator (ICD) discharges. Phasic elevation of troponin-I prompted repeated coronary angiograms, all of which were normal. The patient was successfully treated with radiofrequency ablation. This case illustrates that ARVD/C may result in elevated cardiac enzymes in the absence of coronary artery disease.     

Annual distribution of ventricular tachycardias and ventricular fibrillation

Background

Ischemic events and coronary deaths show seasonal variability with a peak during December and January. It remains unclear whether ventricular tachycardias (VT) and ventricular fibrillation (VF) follow a similar pattern. The purpose of this study was to investigate the annual distribution of malignant ventricular arrhythmias.

Methods

Over a period of 11 years, all appropriate shock episodes (SE) after VT and VF in patients with an implantable cardioverter defibrillator (lCD) were analyzed with respect to the month of occurrence. An appropriate SE was defined as out-of-hospital VT/VF terminated by lCD shocks. Multiple shocks within 1 week were defined as 1 SE.

Results

Two hundred and thirty-three of 308 patients with an lCD had appropriate SE during follow-up. In these patients the seasonal variation of 753 SE was calculated. Most SE occurred during January (93 SE), and the fewest SE occurred during June (39 SE). The seasonal pattern was statistically significant with a peak during winter (P = .001). The seasonal pattern did not differ between patients with an ischemic and those with a nonischemic underlying cardiac disease.

Conclusion

Appropriate shock episodes due to out-of-hospital VT/VF in patients with an lCD show seasonal variation with a significant peak during winter. The pattern is similar in patients with ischemic and nonischemic cardiac disease.     

Triggers of Sustained Monomorphic Ventricular Tachycardia Differ Among Patients with Varying Etiologies of Left Ventricular Dysfunction

Background: The mechanisms underlying the initiation of sustained ventricular tachycardia (VT) have not been fully elucidated. The extent to which reentry, abnormal automaticity, and triggered activity play a role in VT differs depending on the etiology of left ventricular dysfunction. By analyzing electrograms from implantable cardioverter defibrillator (ICD), we sought to determine whether there were differences in VT initiation patterns between patients with ischemic and nonischemic cardiomyopathy. Methods: We analyzed ICD electrograms in patients with ejection fractions < 40% who had sustained VT over a 27‐month period. The trigger for VT onset was classified as a ventricular premature beat (VPB), supraventricular tachycardia, or of “sudden onset.” The baseline cycle length, VT cycle length, coupling interval, and prematurity ratio were recorded for each event. The prematurity ratio was calculated as the coupling interval of the VT initiator divided by the baseline cycle length. Results: Sixty‐three VT events in 14 patients met the inclusion criteria. A VPB initiated the VT in 58 episodes (92%), 1 episode (2%) was initiated by a supraventricular tachycardia, and 4 episodes (6%) were sudden onset. The prematurity ratio was significantly higher (P < 0.05) in patients with ischemic cardiomyopathy (0.751 ± 0.068) as compared to patients with nonischemic cardiomyopathy (0.604 ± 0.139). Conclusion: VPBs initiated most sustained VT episodes. A significantly higher prematurity ratio was observed in the ischemic heart disease group. This may represent different mechanisms of VT initiation in patients with ischemic versus nonischemic heart disease.     

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).     

Low recurrence of syncope in patients with inducible sustained ventricular tachyarrhythmias treated with an implantable cardioverter-defibrillator.

AIMS: To determine the effectiveness of the implantable cardioverter defibrillator (ICD) in preventing recurrence of syncope in patients with structural heart disease, previously unexplained syncope and inducible ventricular arrhythmias. METHODS: Thirty-eight patients with syncope, structural heart disease and inducible arrhythmias had an ICD implanted. All ICDs delivered antitachycardia pacing and shocks of adjusted energy. Detection and therapy were programmed according to uniform criteria. RESULTS: The mean age of the patients was 63+/-11 years and most of them were male (36/38). After a mean follow-up of 28+/-15 (4-61) months, six patients died and one underwent heart transplantation. Syncope recurred in three patients, but in none of them was it caused by an arrhythmic event. In 18 patients, 113 episodes of ventricular tachycardia/ventricular fibrillation were detected and appropriately treated by the ICD. The mean time from implant until first appropriate therapy was 18+/-14 months. The actuarial probability of receiving appropriate therapy was 20% and 42% at 12 and 24 months, respectively. CONCLUSIONS: In patients with unexplained syncope, structural heart disease and inducible arrhythmias, ICD prevents syncope associated with arrhythmic events. Frequent effective use of antitachycardia pacing and shocks of adjusted energy seem essential to this aim.     

Comparison of ventricular arrhythmia frequency in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy treated with implantable cardioverter defibrillators

Implantable cardioverter defibrillators have been shown to provide similar survival benefits for patients who have left ventricular dysfunction due to ischemic heart disease and for subsets of patients who have nonischemic cardiomyopathy. Findings in this study extend these observations by showing that patients who have ischemic or nonischemic heart disease and receive implantable cardioverter defibrillators not only have comparable mortality rates but also similar tachyarrhythmia frequencies during follow-up; further, mortality and tachyarrhythmia outcomes are independent of initial arrhythmia indication.     

Sudden Death Late After Doxorubicin Administration: Use of Electrophysiological Study and Treatment by Automatic Implantable Cardioverter Defibrillator

Two patients who survived cardiac arrest late after doxorubicin administration are described. Both patients had nonischemic, dilated cardiomyopathies and underwent electrophysiological studies during which no ventricular arrhythmias were induced. Their negative electrophysiological studies despite well documented cardiac arrests and subsequent clinical courses suggest that patients with cardiomyopathies after doxorubicin administra tion and dilated cardiomyopathies of other etiologies have similar natural histories. Treatment with an automatic implantable cardioverter defibrillator appears to be a reasonable therapeutic option for patients with anthracyline associated cardiac disease who have survived their malignancy but at the price of developing life-threatening arrhythmias.     

A comprehensive approach to management of ventricular arrhythmias

This review presents five cases that highlight the complexity of taking care of patients with ventricular arrhythmias. Three of the cases discuss management of patients with nonsustained ventricular tachycardia in the setting of structural heart disease: dilated cardiomyopathy, hypertrophic cardiomyopathy, and after myocardial infarction. A fourth case asks whether data from implantable cardioverter defibrillator (ICD) trials can be extrapolated to older patients, and the fifth case discusses management of recurrent ventricular arrhythmias in a patient with an ICD.     

Ventricular arrhythmias in the athlete

Life-threatening ventricular arrhythmias in the athlete nearly always occur in the presence of structural heart disease. In the last few years, 2 new causes of life-threatening arrhythmias have been described in patients with normal hearts-that of the Brugada syndrome and that of commotio cordis. Non-life-threatening premature ventricular beats and even nonsustained ventricular tachycardia are not rare, and although usually benign, can be secondary to cardiomyopathies. Athletes with symptoms of syncope, especially if exertional, warrant a complete evaluation. The treatment of athletes and other individuals with life-threatening ventricular arrhythmias has been revolutionized by the implantable cardioverter defibrillator, a device that affords excellent protection from sudden death. Defining those athletes who would benefit from the implantable defibrillator is not always clear. Furthermore, participation in competitive athletics for athletes with life-threatening arrhythmias or structural heart disease known to put the athlete at risk for life-threatening arrhythmias is usually prohibited.     

Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy.

BACKGROUND: The objective of this study was to determine the effects of a moderate exercise training program on functional capacity, quality of life, and hospital readmission rate in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy. METHODS AND RESULTS: We studied 52 men (mean age 55+/-10 years, ejection fraction 31+/-7%) in chronic heart failure II (n=29) and III (n=23) NYHA functional class with ischemic cardiomyopathy who received implantable cardioverter defibrillators with or without cardiac resynchronization therapy. Patients were randomized into two groups. Group T (n=30 patients, 15 implantable cardioverter defibrillator, 15 implantable cardioverter defibrillator+cardiac resynchronization therapy) underwent a supervised exercise training program at 60% of peak VO2 three times a week for 8 weeks. Group C (n=22 patients, 12 implantable cardioverter defibrillator, 10 implantable cardioverter defibrillator+cardiac resynchronization therapy) avoided physical training. At 8 weeks, only trained patients had improvements in peak VO2 (P<0.01 versus C), endothelium-dependent dilatation of the brachial artery (P<0.001 versus C) and quality of life (P<0.001 versus C). Among trained patients, those with cardiac resynchronization therapy had greater improvements in peak VO2 and quality of life. During the follow-up (24+/-6 months), eight controls had sustained ventricular tachycardia requiring hospital readmission, while no trained patients had adverse events (log rank 8.56; P<0.001). The improvement in peak VO2 was correlated with the improvement in endothelium-dependent dilatation (r=0.65). CONCLUSION: Moderate exercise training is safe and has beneficial effects after implantable cardioverter defibrillator implantation, especially when cardiac resynchronization therapy is present. These effects are associated with improvement in quality of life and outcome.     

Statins, ventricular arrhythmias and heart rate variability in patients with implantable cardioverter defibrillators and coronary heart disease

The aim of this study was to evaluate whether the incidence of ventricular arrhythmias and heart rate variability were influenced by statin treatment and lipid levels in patients treated with an implantable cardioverter defibrillator (ICD). Heart rate variability measurements were performed in 86 patients with coronary heart disease and an ICD implant. The number of events with ventricular fibrillation and ventricular tachycardia were recorded during a 12-month period. This study lends little support for an antiarrhythmic effect of statins or any relation between plasma lipids and lipoproteins and malignant ventricular arrhythmias in patients with an ICD.     

Recent primary prevention implantable cardioverter defibrillator trials

PURPOSE OF THE REVIEW: The aim of this article is to summarize the most relevant findings of recently published trials on prophylactic implantable cardioverter defibrillator therapy. RECENT FINDINGS: A number of important randomized clinical trials on the efficacy of prophylactic implantable cardioverter defibrillator therapy in patients deemed to be at high risk for ventricular tachyarrhythmias have recently reported their results. Patients with chronic ischemic cardiomyopathy, a long history of heart failure, and an ejection fraction of 0.30 or below benefit from preventive device therapy and are thus candidates for prophylactic defibrillator implantation. For this purpose, a single chamber device appears to be appropriate since there have been no prospective studies showing convincing clinical benefit by adding an atrial lead. Prophylactic implantable cardioverter defibrillator therapy should not be used in patients with recent myocardial infarction. There is convincing evidence from one trial that benefit from the defibrillator in coronary patients accrue after a considerable time has elapsed from the most recent infarct, presumably at least 6 months or perhaps longer. Finally, in patients with chronic dilated non-ischemic cardiomyopathy and a left ventricular ejection fraction of 0.35 or below, there is also benefit from prophylactic implantable cardioverter defibrillator therapy. SUMMARY: Taken together, these trials allow an evidence-based approach to primary prevention of sudden cardiac death in patients with both ischemic and non-ischemic cardiomyopathy.     

Do the spatial characteristics of myocardial scar tissue determine the risk of ventricular arrhythmias?

Sudden cardiac death is one of the main causes of mortality in patients with structural heart disease. Although an implantable cardioverter defibrillator significantly reduces the mortality rate, many patients never receive a shock. Identification of high-risk patients would reduce the costs associated with this therapy and prevent the deleterious effect of inappropriate discharges. As scar tissue is the substrate of ventricular arrhythmias in patients with structural heart disease, scar characterization could allow stratification of the risk. The objective of this article is to review the role of scar characteristics in the pathogenesis of ventricular arrhythmias in patients with structural heart disease.     

Use of traditional and biventricular implantable cardiac devices for primary and secondary prevention of sudden death

Sudden cardiac death is the leading cause of cardiac mortality, particularly among high-risk populations with known left ventricular systolic dysfunction. Multiple randomized clinical trials demonstrated a significant mortality benefit of the implantable cardioverter defibrillator (ICD) compared with antiarrhythmic drug therapy or standard medical care. Initial ICD trials showed a mortality improvement for patients who previously had experienced aborted sudden cardiac death or sustained ventricular tachycardia (secondary prevention). Primary prevention trials in selected high-risk patients who had both ischemic and nonischemic cardiomyopathy also demonstrated a mortality benefit associated with ICD treatment. More recently, cardiac resynchronization therapy with or without defibrillator capability has been shown to reduce morbidity and mortality among advanced heart failure patients with a prolonged QRS duration.