Prevention Of Sudden Arrhythmic Death Research Articles

Improving the appropriateness of sudden arrhythmic death primary prevention by implantable cardioverter-defibrillator therapy in patients with low left ventricular ejection fraction. Point of view.

It is generally accepted that the current guidelines for the primary prevention of sudden arrhythmic death, which are based on ejection fraction, do not allow the optimal selection of patients with low left ventricular ejection fraction of ischemic and nonischemic etiology for implantation of a cardioverter-defibrillator. Ejection fraction alone is limited in both sensitivity and specificity. An analysis of the risk of sudden arrhythmic death with a combination of multiple tests (ejection fraction associated with one or more arrhythmic risk markers) could partially compensate for these limitations. We propose a polyparametric approach for defining the risk of sudden arrhythmic death using ejection fraction in combination with other clinical and arrhythmic risk markers (i.e. late gadolinium enhancement cardiac magnetic resonance, T-wave alternans, programmed ventricular stimulation, autonomic tone, and genetic testing) that have been validated in nonrandomized trials. In this article, we examine these approaches to identify three subsets of patients who cannot be comprehensively assessed by the current guidelines: patients with ejection fraction of 35% or less and a relatively low risk of sudden arrhythmic death despite the ejection fraction value; patients with ejection fraction of 35% or less and high competitive risk of death due to evolution of heart failure or noncardiac causes; and patients with ejection fraction between 35 and 45% with relatively high risk of sudden arrhythmic death despite the ejection fraction value.

Device therapy for the management of cardiac tachyarrhythmias

Implantation of devices that can terminate cardiac arrhythmias has increased rapidly over recent years. This article looks at the evidence base for using such devices in the primary and secondary prevention of sudden arrhythmic death, discusses who should have a device and examines the issues surrounding implantation. Recent advances in technology and the future direction of therapy are also reviewed.

Pädiatrische Rhythmusstörungen

Diagnosis and therapy of cardiac dysrhythmia has become an important subspecialization in pediatric cardiology. The limited possibilities of antiarrhythmic drug therapy and antibradycardia pacing have been expanded by completely new and fascinating developments over the last 30 years. Curative treatment for the majority of tachyarrhythmias has been achieved by catheter ablation. Secondary as well as primary prevention of sudden arrhythmic death has become possible thanks to implantable defibrillators. Multiple hereditary life-threatening arrhythmia syndromes have been discovered and give a fascinating insight into the molecular genetic background of arrhythmogenesis. Cardiac resynchronization therapy has evolved into one of the few causal treatment strategies for heart failure and points toward intriguing remodeling processes at the cellular level. The following article provides practical as well as background knowledge of some of these developments.

Myocardial Ca2+handling and cell-to-cell coupling, key factors in prevention of sudden cardiac deathThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

Using whole-heart preparations, we tested our hypothesis that Ca(2+) handling is closely related to cell-to-cell coupling at the gap junctions and that both are critical for the development and particularly the termination of ventricular fibrillation (VF) and hence the prevention of sudden arrhythmic death. Intracellular free calcium concentration ([Ca(2+)](i)), ECG, and left ventricular pressure were continuously monitored in isolated guinea pig hearts before and during development of low K(+)-induced sustained VF and during its conversion into sinus rhythm facilitated by stobadine. We also examined myocardial ultrastructure to detect cell-to-cell coupling alterations. We demonstrated that VF occurrence was preceded by a 55.9% +/- 6.2% increase in diastolic [Ca(2+)](i), which was associated with subcellular alterations indicating Ca(2+) overload of the cardiomyocytes and disorders in coupling among the cells. Moreover, VF itself further increased [Ca(2+)](i) by 58.2% +/- 3.4% and deteriorated subcellular and cell-to-cell coupling abnormalities that were heterogeneously distributed throughout the myocardium. In contrast, termination of VF and its conversion into sinus rhythm was marked by restoration of basal [Ca(2+)](i), resulting in recovery of intercellular coupling linked with synchronous contraction. Furthermore, we have shown that hearts exhibiting lower SERCA2a (sarcoplasmic reticulum Ca(2+)-ATPase) activity and abnormal intercellular coupling (as in older guinea pigs) are more prone to develop Ca(2+) overload associated with cell-to-cell uncoupling than hearts with higher SERCA2a activity (as in young guinea pigs). Consequently, young animals are better able to terminate VF spontaneously. These findings indicate the crucial role of Ca(2+) handling in relation to cell-to-cell coupling in both the occurrence and termination of malignant arrhythmia.

T-Type Ca 2+ Channel Blockade Prevents Sudden Death in Mice With Heart Failure

Pharmacological interventions for prevention of sudden arrhythmic death in patients with chronic heart failure remain limited. Accumulating evidence suggests increased ventricular expression of T-type Ca(2+) channels contributes to the progression of heart failure. The ability of T-type Ca(2+) channel blockade to prevent lethal arrhythmias associated with heart failure has never been tested, however. We compared the effects of efonidipine and mibefradil, dual T- and L-type Ca(2+) channel blockers, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, on survival and arrhythmogenicity in a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor transgenic mice (dnNRSF-Tg), which is a useful mouse model of dilated cardiomyopathy leading to sudden death. Efonidipine, but not nitrendipine, substantially improved survival among dnNRSF-Tg mice. Arrhythmogenicity was dramatically reduced in dnNRSF-Tg mice treated with efonidipine or mibefradil. Efonidipine acted by reversing depolarization of the resting membrane potential otherwise seen in ventricular myocytes from dnNRSF-Tg mice and by correcting cardiac autonomic nervous system imbalance. Moreover, the R(-)-isomer of efonidipine, a recently identified, highly selective T-type Ca(2+) channel blocker, similarly improved survival among dnNRSF-Tg mice. Efonidipine also reduced the incidence of sudden death and arrhythmogenicity in mice with acute myocardial infarction. T-type Ca(2+) channel blockade reduced arrhythmias in a mouse model of dilated cardiomyopathy by repolarizing the resting membrane potential and improving cardiac autonomic nervous system imbalance. T-type Ca(2+) channel blockade also prevented sudden death in mice with myocardial infarction. Our findings suggest T-type Ca(2+) channel blockade is a potentially useful approach to preventing sudden death in patients with heart failure.

Remote monitoring for prevention of inappropriate implantable cardioverter defibrillator shocks: is there no place like home?

This editorial refers to ‘Potential role of home monitoring to reduce inappropriate shocks in implantable cardioverter-defibrillator patients due to lead failure’ by S. Spencker et al., on page 483 Although the implantable cardioverter defibrillator (ICD) has made a significant impact on prevention of sudden arrhythmic death, important limitations of this therapy remain. Chief among these is the risk of inappropriate shocks, which have been reported in 10‐25% of patients in randomized trials and case registries over 2‐4 years of follow-up. 1 Inappropriate shocks may cause pain, proarrhythmia, and even death in rare cases. Delivery of inappropriate shocks has also been associated with increased late mortality in several large ICD trials. Patients who experience multiple shocks may develop anxiety and other signs of psychological distress, and concern about this complication is commonly expressed by patients. The most common cause of inappropriate shocks is atrial fibrillation, followed by other supraventricular tachycardias, and leadsensing abnormalities. The latter category includes conductor fracture, insulation failure, T-wave oversensing, and myopotential oversensing. 2 A recent study examined 990 patients implanted with a variety of ICD lead models between 1992 and 2005 and found lead failure rates of 15% at 5 years and 40% at 8 years, with a pattern of accelerating annual failure rates over time. 3 One-third of ICD lead failures in this study presented with inappropriate shocks. In patients dependent upon ventricular pacing, ICD lead failure may also lead to symptoms from inhibition of pacing or failure to capture. Concern regarding ICD lead failure has increased recently with the recall of a widely used lead. 4 Manufacturers’ product performance reports suggest early annual lead failure rates of 0.5‐1% of latest generation of ICD leads, while the failure rate of the Sprint Fidelis family is approximately two- to three-fold higher. A 2007 review of the US Food and Drug Administration’s Manufacturer and User Facility Device Experience database found 679 reports of failed Sprint Fidelis leads, 33% of which were associated with inappropriate shocks. 4 Strategies to minimize the risk of inappropriate shocks include using high ventricular tachycardia/ventricular fibrillation rate cutoffs, multiple tachycardia detection zones, longer time to detection, anti-tachycardia pacing, supraventricular tachycardia discrimination algorithms, and medical therapies such as b-blockers and anti-arrhythmic drugs. 5 These strategies are less useful for the prevention of inappropriate shocks caused by ICD lead failure. For this purpose, algorithms have been devised to trigger device alert tones, device vibration, or automatic change in tachycardia detection criteria. 6 None of these algorithms, however, has been prospectively shown to reduce the risk of inappropriate shocks, and improved strategies to prevent inappropriate shocks are clearly needed. Spencker et al. report on their single-centre experience using an automatic wireless remote monitoring system for surveillance of ICD systems. 7 They retrospectively examined 54 patients who underwent ICD lead revision for the failure of the lead over a 6-year period. The 11 patients who had been undergoing daily remote wireless assessment were compared with the 43 patients who had been followed only with quarterly in-office visits. They found that fewer patients undergoing remote monitoring (27.3%) experienced ICD shocks for sensing failure prior to lead revision than those with standard in-office follow-up (46.5%). This trend reached statistical significance when symptomatic pacemaker inhibition was added to the endpoint (27.3% in remote monitoring group vs. 53.4% in the standard follow-up group, P ¼ 0.04). In addition, the authors found that in the standard follow-up patients, evidence of non-sustained oversensing was detected by the ICD a mean of 16 days prior to the onset of symptoms, suggesting that inappropriate shocks could have been avoided in most of these patients, had they been followed with remote monitoring and contacted in a timely fashion.

Secondary prevention of sudden arrhythmic death: the role of the implantable cardioverter-defibrillator

Patients with a history of sudden arrhythmic cardiac death (SACD) have a known significant recurrence rate ranging from 30% to 42% at one year. Because of this substantial number, secondary prevention of SACD has been advocated for a long time. Nevertheless, ongoing debate seems to be put to rest by recently published results of several well-designed randomized studies. The results of these secondary prevention trials consistently demonstrated that the implantable cardioverter-defibrillator is the first-choice therapy for secondary prevention of sudden arrhythmic cardiac death or hemodynamically compromising ventricular tachycardia. Thus, it is not very astonishing that these results have led to significant changes in the treatment of patients who have survived sudden cardiac death. Another message, which is supported by recent findings of the MUSST study, derives from the results of the secondary prevention trials: serial electrophysiologic drug testing now seems obsolete.

Antiarrhythmic therapy in patients with heart failure

In patients with severe chronic heart failure, many deaths are sudden due to life-threatening ventricular arrhythmias. Supraventricular arrhythmias such as paroxysmal or chronic atrial fibrillation may also cause serious complications in those patients due to acute loss of atrial contraction, pump failure during rapid ventricular response and embolic events. Two therapeutic strategies are currently available for therapy and prevention of malignant ventricular arrhythmias and subsequent sudden arrhythmic death: antiarrhythmic drug therapy and implantable defibrillators. However, selection of the most beneficial strategy for the individual patient to reduce the risk of sudden death remains a major challenge in cardiology. Betablockers exert a favorable antiarrhythmic action without increasing proarrhythmia, thus betablockers may serve as a basic medication in patients at risk for sudden death. However, the general use of antiarrhythmic drug therapy for symptomatic ventricular arrhythmias is not recommended, as these drugs have been shown to increase mortality in patients with severe congestive heart failure due to proarrhythmic or negative inotropic effects (e.g. class Ia antiarrhythmics). Even class III antiarrhythmic drugs such as amiodarone, which has been studied sufficiently in patients with left ventricular dysfunction, is not effective enough for significant reduction of cardiac mortality in patients with symptomatic ventricular arrhythmias and depressed ventricular function (e.g. EMIAT, CAMIAT). But as a positive result of available studies, amiodarone does not increase mortality in those patients. Dofetilide has also not been shown to prolong life significantly by suppressing malignant ventricular arrhythmias (DIAMOND-Study). In patients with symptomatic ventricular arrhythmias or aborted sudden death, ICD therapy has been proven to be superior to antiarrhythmic drug therapy in cardiac mortality reduction as a secondary prevention strategy (e.g. AVID, CASH, CIDS). For primary prevention of sudden arrhythmic death in high risk patients, 2 studies (MADIT, MUSST) have already demonstrated favorable results, decreasing mortality by ICD therapy in selected patient populations with partly-reduced ventricular function and unsustained but inducible ventricular tachycardias. This topic is, however, undergoing further evaluation by ongoing trials (e.g. MADIT II, SCD-HeFT). From available data, antiarrhythmic drug therapy in high risk patients is not justified on a routine basis, whereas ICD therapy as a secondary and perhaps primary prevention strategy will significantly reduce cardiac mortality in patients with severe heart failure. Sotalol, a class III antiarrhythmic agent, has recently been shown to reduce ICD-shock delivery which indicates that concomitant drug therapy in patients with an ICD device already implanted may be beneficial in terms of reducing ICD discharges due to ventricular and supraventricular tachycardias. In patients with paroxysmal atrial fibrillation and congestive heart failure, restitution of sinus rhythm is the primary therapeutic goal which can be safely achieved by amiodarone and dofetilide (DIAMOND). In the latter, continuous monitoring of the patient is mandatory because of increased risk of torsade de pointes arrhythmias during the first days of drug administration. In patients with chronic atrial fibrillation rate control and anticoagulation with warfarin is the primary therapeutic option, which can be achieved with either drug treatment (Digoxin, betablockers, amiodarone) or by His bundle ablation with subsequent pacemaker insertion.

New primary prevention trials of sudden cardiac death in patients with left ventricular dysfunction: SCD-HEFT and MADIT-II

Primary prevention of sudden arrhythmic death in patients with organic heart disease with poor left ventricular function and/or heart failure is currently a major challenge in cardiology. Amiodarone (with or without β blockers) and the implantable cardioverter defibrillator (ICD) are considered the 2 major therapeutic tools to prevent sudden arrhythmic death in these patients. Two large trials have been launched to define the prophylactic benefit of the ICD or amiodarone on total mortality in patients that receive optimal heart failure and anti-ischemic treatment but remain at high risk of dying suddenly. The Sudden Cardiac Death in Heart Failure Trial (SCD-Heft) is designed to determine whether amiodarone or the ICD will decrease overall mortality in patients with coronary artery disease or nonischemic cardiomyopathy who are in heart failure New York Heart Association (NYHA) class II or III and have a left ventricular ejection fraction <35%. The primary endpoint is total mortality; secondary objectives are comparison of arrhythmic and nonarrhythmic mortality and morbidity in the 3 arms as well as quality of life, cost-effectiveness, and incidence of episodes of ventricular tachyarrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II is a follow-up study to the MADIT trial. It examines the prophylactic benefit in coronary artery disease patients with a left ventricular ejection fraction of <30%, who have had at least 1 myocardial infarction but require no further risk stratification. MADIT II is a sequential design trial that compares ICD versus no ICD therapy. Programmed electrical stimulation to test inducibility of ventricular tachycardia is performed during ICD implantation, and various noninvasive risk markers are tested after randomization. Primary endpoint is total mortality, and secondary objectives are quality-of-life issues as well as cost-effectiveness ratio.

Altering molecular mechanisms to prevent sudden arrhythmic death

Trials of drug treatment for prevention of sudden arrhythmic death have been disappointing, perhaps because suppressive therapy with arrhythmic agents fails to address the mechanisms leading to electrophysiological failure. We propose that preventive treatment should pay more attention to molecular mechanisms responsible for the progression of cardiac disease to electrophysiological failure. Most sudden cardiac deaths occur in people with atherogenic dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory-prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis include phospholipids and leucotrienes acting through the platelet-activating-factor and peroxisome proliferator-activated-receptor pathways. There are drugs available to test the hypothesis of dyslipidaemias-specific prevention of electrophysiological failure.

Heart Rate Dynamics and Vulnerability to Ventricular Tachyarrhythmias

Sudden arrhythmic death is the most common mode of death in Western countries. An increased understanding of the pathophysiology and trigger mechanisms of life-threatening ventricular tachyarrhythmias in patients with structural heart disease can provide a logical basis for improved therapeutic strategies in the prevention of sudden death. Analysis of heart rate variability (HRV) from ambulatory electrocadiographic recordings can identify the patients at increased risk for arrhythmic death after an acute myocardial infarction. Despite the epidemiological evidence of an association between low HRV and sudden arrhythmic death, the pathophysiological link of this association has not been completely understood. An important approach to understand this association is to investigate the heart rate dynamics before the spontaneous onset of life-threatening arrhythmias. Analysis of heart rate behaviour preceding the spontaneous onset of ventricular tachyarrhythmias has shown that overall HRV is impaired in patients who develop spontaneous ventricular tachycardia during the Holter recording. Recently, quantitative analysis of Poincare plots of successive R-R intervals has shown that reduced long-term R-R interval variability, associated with episodes of beat-to-beat sinus alternans, is a specific sign of a propensity for spontaneous onset of ventricular tachycardia. These studies suggest that abnormal heart rate behaviour reflects an electrical instability favoring the onset of life-threatening arrhythmia and provide evidence that altered neurohumoral or autonomic regulation is an important trigger mechanism for the spontaneous onset of life-threatening arrhythmia. Future research in larger patient populations will reveal whether analysis of dynamic behaviour of cardiac electrical signals will give new insights into the mechanisms of life-threatening arrhythmias and help in the development of new therapeutic options for the prevention of sudden arrhythmic death.

Prevention of sudden arrhythmic death with implanted automatic defibrillators.

Editorials1 October 1982Prevention of Sudden Arrhythmic Death with Implanted Automatic DefibrillatorsM. MIROWSKI, M.D.M. MIROWSKI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-4-606 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptVentricular fibrillation and many ventricular tachycardias are medical emergencies needing immediate application of electrical countershock to prevent brain damage and death. Because the treatment involves trained personnel and specialized equipment, successful resuscitation from these arrhythmias is largely limited to coronary care units and other hospital facilities. It is estimated that ventricular tachyarrhythmias claim the lives of some 450 000 persons annually in the United States alone (1), an increasing number of whom can be identified prospectively as being at high risk for sudden arrhythmic death (2-8).The strategies for dealing with malignant ventricular rhythms outside of hospitals have been centered...

The automatic implantable defibrillator. New Modality for treatment of life-threatening ventricular arrhythmias.

The automatic implantable defibrillator continuously monitors cardiac rhythm, identifies ventricular fibrillation and then delivers corrective defibrillatory discharges when indicated; it weighs 250 grams and has a volume of 145 cc. When a suitable arrhythmia is detected, a 25 Joule pulse is delivered through a superior vena cava catheter electrode and another electrode placed over the cardiac apex. As of March 1981, sixteen survivors of multiple cardiac arrests refractory to antiarrhythmic therapy had undergone implantation of the automatic defibrillator. There was no operative mortality and the morbidity was minimal. Electrophysiologic studies were performed before and after surgery to confirm failure of drug therapy and to ensure the device's ability to terminate malignant arrhythmias. Eight spontaneous and fourteen of the seventeen induced malignant arrhythmias were properly recognized and corrected by the device. The discharges were well tolerated by awake patients. A number of problems including recycling delays and spurious discharges have been identified and corrected. There were three late deaths with pulmonary edema noted in two patients, and asystole in one. The autopsies revealed no myocardial damage attributable to the automatic defibrillator. Although the ultimate role of this approach to prevention of sudden arrhythmic death has yet to be determined, the results obtained to date are encouraging and indicate that a useful modality for treating malignant ventricular arrhythmias has been added to our armamentarium.