BACKGROUNDThe Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study demonstrated that implantable cardioverter defibrillators (ICDs) significantly reduce the risk of sudden cardiac death in patients with nonischemic cardiomyopathy and an ejection fraction of 35% or less, with no statistically significant decrease in overall mortality. The impact of ICD placement and shock on health-related quality of life (HRQL) in this population is unknown.METHODSThe 12-Item Medical Outcomes Short-Form Health Survey and the Minnesota Living with Heart Failure Questionnaire were administered to 458 patients with nonischemic cardiomyopathy, an ejection fraction of 35% or less, and either nonsustained ventricular tachycardia or 10 or more premature ventricular depolarizations per hour at baseline, 1 month after randomization, and every 3 months thereafter throughout the trial. The subjects were randomized to an ICD or standard medical therapy. Outcomes were compared using hierarchical linear regression.RESULTSOverall, there were no significant differences in HRQL throughout the trial between patients randomized to an ICD or standard medical therapy. However, in patients with 1 or more ICD shocks, HRQL declined 0.5 +/- 0.2 (mean +/- SD) points per shock on the emotional scale of the Minnesota Living with Heart Failure Questionnaire (P = .04) and 1.0 +/- 0.5 points per shock on the mental component score of the 12-Item Medical Outcomes Short-Form Health Survey (P = .04).CONCLUSIONSOverall, HRQL was not affected by ICD implantation in patients in the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study. Implantable cardioverter defibrillator shock was associated with a reduction in some measures of HRQL, but the effects were unlikely to result in a clinically observable alteration until 5 or more shocks were experienced.

BACKGROUND The recent expansion of indications for prophylactic implantable cardioverter-defibritlator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy.OBJECTIVES The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement.METHODS This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (> 25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients.RESULTS The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN > 113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN < 81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN > 113 ms regardless of treatment assignment JCD vs control).CONCLUSION Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.

OBJECTIVES This study sought to determine whether the time from diagnosis to randomization was related to outcome in a clinical trial of implantable cardioverter-defibrillator (TCD) insertion in nonischemic cardiomyopathy.BACKGROUND Whether the duration of nonischemic cardiomyopathy is related to arrhythmic risk and the possible benefit of ICD insertion is unknown.METHODS The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial randomized 458 patients with nonischemic dilated cardiomyopathy and a left ventricular ejection fraction < 36% to receive standard medical therapy with or without an ICD. Patients were randomized regardless of the duration of known cardiomyopathy as long as a reversible cause of left ventricular dysfunction was not present. Patients were divided into recently and remotely diagnosed nonischemic cardiomyopathy groups based on the time from diagnosis of cardiomyopathy to randomization. To categorize patients, cut points of three and nine months were used.RESULTS Patients with recently diagnosed cardiomyopathy who received an TCD had better survival than those treated with standard therapy at both cut points. This difference in survival was significant at three months (p < 0.05) and was borderline significant at nine months (p = 0.058). Patients with remotely diagnosed cardiomyopathy did not have a significant survival benefit with ICD insertion, but there were no significant differences between ICD benefit in the recent and remote diagnosis groups (p = 0.17 and 0.25).CONCLUSIONS Patients who have a recent cardiomyopathy diagnosis do not have any less ICD benefit than those with a remote diagnosis. Thus, ICD therapy should be considered in such patients as soon as they are identified as long as a reversible cause of left ventricular dysfunction is excluded.

Background— Ventricular tachyarrhythmias long enough to cause implantable cardioverter defibrillator (ICD) shocks are generally thought to progress to cardiac arrest. In previous ICD trials, shocks have been considered an appropriate surrogate for sudden cardiac death (SCD) because the number of shocks has been thought to be equivalent to the mortality excess in patients without ICDs. The practice of equating ICD shocks with mortality is controversial and has not been validated critically. Methods and Results— The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective, randomized, multicenter trial of ICD therapy in 458 patients with nonischemic cardiomyopathy. Patients were randomized to receive standard medical therapy (STD) or STD plus an ICD. Shock electrograms were reviewed, and the cause of death was evaluated by a separate blinded events committee. There were 15 SCD or cardiac arrests in the STD group and only 3 in the ICD arm. In contrast, of the 229 patients randomized to an ICD, 33 received 70 appropriate ICD shocks. Patients in the ICD arm were more likely to have an arrhythmic event (ICD shock plus SCD) than patients in the STD arm (hazard ratio 2.12, 95% CI 1.153 to 3.893, P=0.013). The number of arrhythmic events when one includes syncope as a potential arrhythmic event was similar in both groups (hazard ratio 1.20, 95% CI 0.774 to 1.865, P=0.414). Approximately the same number of total events was noted in each arm when we compared syncope plus SCD/cardiac arrest in the STD arm with SCD plus ICD shocks plus syncope in the ICD arm. Conclusions— Appropriate ICD shocks occur more frequently than SCD in patients with nonischemic cardiomyopathy. This suggests that episodes of nonsustained ventricular tachycardia frequently terminate spontaneously in such patients.

Background: The parasympathetic nervous system has recently been implicated in the genesis of focal atrial fibrillation, with pronounced vagal reflexes having been demonstrated on pulmonary vein (PV) stimulation. However, the detailed autonomic profile of the PVs is not well understood.

Although many studies have shown that implantable cardioverter defibrillator (ICD) therapy improves the survival of patients with significant left ventricular dysfunction, the magnitude of effectiveness of ICD therapy in clinically defined subgroups remains uncertain. Similarly, although studies have shown an improvement in patients' hemodynamics and quality of life with cardiac resynchronization therapy (CRT), there is a continuing uncertainty about the effect of CRT on patients' survival and the magnitude of improvement in quality of life with this therapy. On August 24, 2004, an ad hoc group of experts representing clinical cardiovascular medicine, biostatistics, economics, and health policy were joined by representatives of the Food and Drug Administration, Centers for Medicare and Medicaid Services (Baltimore, Md), Agency for Healthcare Research and Quality (Rockville, Md), and the device industry for a 1-day round table to review the available clinical trial evidence on the effect of ICD therapy in the primary prevention of sudden cardiac death and the effect of CRT in patients with congestive heart failure. The meeting was organized by the Duke Clinical Research Institute, Durham, NC, and funded in part by the Agency for Healthcare Research and Quality. This document summarizes the evidence reviewed at that meeting and the discussions of that evidence.

HomeCirculationVol. 111, No. 24Heart Failure Devices Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBHeart Failure DevicesImplantable Cardioverter-Defibrillators and Biventricular Pacing Therapy Alan Kadish and Mandeep Mehra Alan KadishAlan Kadish From the Division of Cardiology and Bluhm Cardiovascular Institute, Feinberg School of Medicine, Chicago, Ill (A.K.), and the Division of Cardiology, University of Mayland, Baltimore (M.M.). Search for more papers by this author and Mandeep MehraMandeep Mehra From the Division of Cardiology and Bluhm Cardiovascular Institute, Feinberg School of Medicine, Chicago, Ill (A.K.), and the Division of Cardiology, University of Mayland, Baltimore (M.M.). Search for more papers by this author Originally published21 Jun 2005https://doi.org/10.1161/CIRCULATIONAHA.104.481267Circulation. 2005;111:3327–3335Although the age-adjusted mortality from heart disease has declined in the United States, cardiovascular disease remains the No. 1 cause of death.1,2 Patients with cardiac disease generally die of one of 2 causes: sudden, unexpected cardiac death or progressive heart failure. Chronic heart failure (CHF) has become an epidemic in the United States. Implantable cardioverter-defibrillator (ICD) therapy has had a major impact on the treatment of heart failure in the United States. The ICD has been shown to decrease mortality relative to the best medical therapy in patients who have survived an episode of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).3 Unfortunately, only a small minority of patients who experience an out-of-hospital cardiac arrest in the United States are successfully resuscitated.4 Thus, ICD therapy has been applied for the primary prevention of sudden death in patients at high risk of cardiac arrest. Once thought to be a “bystander” curiosity in the progression of heart failure, electrical-conduction disturbances are now recognized to be important causes of left ventricular (LV) dysfunction. Cardiac resynchronization therapy (CRT) can restore more-normal electrical contraction and, when combined with defibrillation (CRTD), can have a major impact on the mortality and morbidity of heart failure. Although there remain many limitations and challenges to the appropriate application of ICDs or CRTD, there is no question that device therapy has had a major impact on the management of patients with LV dysfunction.ICD TherapyThe ICD was developed in the 1970s as a device to detect and automatically terminate ventricular tachyarrhythmias.5,6 Early ICDs were large devices that required a thoracotomy to implant. Improvements in batteries, capacitors, and microprocessors7 have resulted in the rapid evolution of ICD technology. Current-generation ICDs are small enough to be easily implanted in the pectoral region and can perform a variety of sophisticated functions, including atrial8 and ventricular defibrillation,6 antitachycardia pacing (ATP),1 backup bradycardia pacing, electrogram storage, and biventricular pacing.9 ICDs can be implanted under local anesthesia and conscious sedation in a procedure that often lasts <1 hour.The development of the ICD was a revolutionary advance in the treatment of heart disease. Its development represented something of a paradox. It was the work of a small group of individuals, but its evolution has represented an extraordinary collaboration between technology, industry, and medicine. The ICD was conceived and developed by Dr Michel Mirowski (Figure 1) and Dr Morton Mower working in a small laboratory at a hospital affiliated with a major medical center. Dr Mirowski’s thoughts were widely criticized in the mainstream medical literature as being unrealistic. Dr Mirowski’s vision and perseverance in the face of criticism were remarkable, and the ICD represented the culmination of the work of lone visionaries. In contrast, the development of the ICD has also been emblematic of the tremendous change that advanced technology has produced in medical care. The ICD incorporates technological advances, such as tiny microprocessors with hundreds of programmable features, batteries, and capacitors specifically designed for the ICD and novel miniaturization techniques. These advances would have been completely unimaginable 2 decades ago and exemplify the role that industry and technology play in modern medical care. Download figureDownload PowerPointFigure 1. Dr Michel Mirowski, inventor of ICD.Basic ICD Components and FunctionThe basic components of ICDs have not changed in the past 20 years.7,9 ICDs contain batteries, capacitors, a microprocessor, and a “header” that contains a site to attach leads. Although ICDs have millions of programmable features, advanced microprocessor technology has allowed these features to be seamlessly incorporated without an increase in device size. ICD leads are constructed in a fashion similar to pacemaker leads, except that a shocking coil or coils are also included. In a single-chamber ICD, one lead is placed in the right ventricle at a site that can pace and also defibrillate the heart. The ICD generator and microprocessors are encased in a titanium can that may be as small as 30 cm3 and can weigh as little as 50 g.The essential features of ICD function include detecting tachyarrhythmia, classification of a tachyarrhythmia as a treatable arrhythmia, delivering therapy, monitoring of heart rhythm after treatment, and storage of diagnostic results from the episode. Sensing of tachyarrhythmias occurs via a dedicated bipole of small electrodes near the catheter tip (dedicated sensing) or via a bipole from a tip electrode to a coil electrode that is also used to deliver defibrillation shocks (integrated sensing). After appropriate detection, ATP may be initiated for appropriate rhythm disturbances, or a defibrillation shock may be delivered between 2 coil electrodes or between a coil and the ICD generator box (active can). Arrhythmia detection can be based purely on heart rate, as in early-generation devices, or on more sophisticated algorithms. An example of appropriate arrhythmia detection is shown in Figure 2. After arrhythmia detection and fulfillment of appropriate diagnostic criteria (A), therapy is initiated. In B, ATP was used in an attempt to terminate an episode of VT. ATP was not successful. In C, electrical cardioversion occurred after the failure of ATP to terminate the arrhythmia. Download figureDownload PowerPointFigure 2. Electrograms recorded during interrogation of ICD from patient who had sustained arrhythmia episode. Each of 3 panels is similarly organized. Top trace shows atrial electrogram. Second trace shows ventricular electrogram from rate-sensing lead. Third panel shows marker channel. In A, tachycardia is detected as indicated by markers labeled TS (tachycardia sense). VT is present at cycle length of 370 ms, which is in VT detection zone. Note that diagnosis is confirmed by presence of ventriculoatrial dissociation and sinus rhythm in atrium. In B, multiple trains are delivered but fail to terminate VT. ICD is programmed to deliver cardioversion shock after failed ATP events. C shows cardioversion shock, resulting in delayed VT and atrioventricular paced rhythm that follows. Abbreviations are as defined in text.ICD Features and TypesICDs can be divided into 3 broad categories: single-chamber ICDs, dual-chamber ICDs, and CRT ICDs. Single-chamber ICDs have only a right ventricular lead, dual-chamber ICDs have a right atrial and a right ventricular lead, and CRTDs also have an LV lead that is placed via the coronary sinus (Figure 3) or epicardially. At present, no firm guidelines exist for implantation of single-versus dual-chamber ICDs. Although several clinical trials have compared single-chamber with dual-chamber pacemakers,10 few trials have examined comparisons between single-chamber and dual-chamber defibrillators. Although dual-chamber defibrillators provide additional flexibility when added to old diagnostic information,11 clear clinical benefit has not been demonstrated in prospective, randomized trials, except for patients who have bradycardia pacing indications.12 It has also become clear that electrical disturbances may be a cause of CHF, rather than just an effect of CHF. This results in progressive LV dysfunction, not due to permanently necrotic myocardium but due rather to electrical dyssynchrony.13,14 CRT, by restoring mechanical synchrony, can reverse signs and symptoms of heart failure and in some patients improve ejection fraction.15,16Download figureDownload PowerPointFigure 3. Fluoroscopic images of CRT device insertion. Both images are right interior oblique images. In both panels, right ventricular ICD lead has already been placed in right ventricular apex. Figure 3A shows angiogram of coronary sinus obtained with balloon occlusion catheter. Anterolateral branches of coronary sinus are identified. Figure 3B shows LV lead placed within anterolateral coronary sinus branch. Abbreviations are as defined in text.ComplicationsA number of complications have been described with the use of ICD therapy, and these need to be carefully considered in evaluating the risk-benefit ratio of ICD implantation for individual patients. The most common complication of ICD therapy in almost all series is inappropriate ICD shocks that range from 21% to 25%.17,18 The most common cause of these shocks is atrial fibrillation, other supraventricular tachyarrhythmias, or sinus tachycardia. Although atrial fibrillation is not a contraindication to ICD implantation, a careful assessment of heart rate during fibrillation should be performed to minimize the incidence of inappropriate shocks. Inappropriate ICD shocks due to oversensing can also occur but are less frequent in current ICDs. Although the effects of inappropriate shocks can be psychologically devastating in individual patients, in most cases, changes in ICD programming or adjustment of medical therapy can eliminate or decrease the incidence of inappropriate shocks. More serious complications can occur during ICD implantation, such as pneumothorax, hemothorax, infection, lead dislodgment, and cardiac tamponade.17–21 The overall incidence of significant complications, with the exception of inappropriate ICD shocks, should be well under 5%. Unless patients are acutely ill, have severe CHF, or are undergoing lead extraction, death from ICD implantation should be uncommon.Cost-EffectivenessHealthcare costs in the United States have risen at a rate faster than inflation for the past 20 years. Although ICD therapy accounts for only a very small percentage of current healthcare costs, the cost of ICD implantation including the device, lead or leads, and hospitalization for ICD implantation may be as high as $30 000 to $40 000. Thus, careful analysis of ICD cost-effectiveness is appropriate. At present, there are no hard guidelines for cost-effectiveness application of medical therapy. However, a carefully thought-out, case-by-case approach should be utilized when considering expanding ICD indications to patients in whom the clinical benefit may be small.22–25 If ICD costs can be decreased, it will allow the therapy to be applied to larger numbers of patients without dramatic increases in healthcare expenditures for ICDs.ICD Therapy for Secondary Prevention of Sudden Cardiac DeathInitial observational studies suggested that the ICD was effective in preventing recurrent cardiac arrest in survivors of sudden arrest.26,27 However, no comparative trials validating the relative effectiveness of ICD therapy compared with other forms of therapy were performed until the late 1990s. Three randomized, controlled trials compared the best antiarrhythmic therapy with ICD therapy for the treatment of ventricular tachyarrhythmias in patients resuscitated from a cardiac arrest.28,29 Although the trials differed slightly in inclusion criteria and study design, the major results were similar. In the Antiarrhythmic versus Implantable Defibrillator trial (AVID), 1016 patients with life-threatening arrhythmias were randomized to receive an ICD or antiarrhythmic therapy.19 More than 75% of the patients who were randomized to receive antiarrhythmic therapy were treated with amiodarone.29 There was an ≈30% relative decrease in overall mortality in the group who received the ICD compared with antiarrhythmic drugs. Absolute mortality at 2 years was 25.3% in the control (drug) group and 18.4% in the ICD group. The Canadian Implantable Defibrillator trial (CIDS) randomized 328 patients to receive an ICD and 331 to receive amiodarone. There was a 20% relative risk reduction and a 2% absolute annual mortality benefit in the group who received an ICD. However, this difference did not reach significance. In the Cardiac Arrest Study Hamburg (CASH), patients were randomized to receive an ICD, amiodarone, or metoprolol.30 Two hundred twenty-eight patients were included in the study. There was an ≈30% reduction in mortality in the group who received the ICD. The absolute mortality benefit was difficult to calculate because the primary end point of the study was sudden death mortality rather than total mortality. There was no significant difference between the effect of amiodarone and that of metoprolol. Although the results of the study were of borderline significance, the patient population was small. Taken together and evaluated in a meta-analysis, the results suggest that ICDs are superior to medical therapy for the treatment of patients who have experienced a cardiac arrest.3 Subgroup analysis has suggested that some patients who have survived a cardiac arrest, such as those >65 years or with well-preserved ventricular function, may not have as great a benefit from ICD therapy.31–36 However, trials that are adequately powered to detect differences among such subgroups have not been completed.36 Although the data suggesting lower mortality in patients who receive an ICD are clear, there are many patients who experience a cardiac arrest in whom less-aggressive medical therapy may be appropriate because of an overall poor prognosis or comorbid conditions.ICD Therapy for Primary Prevention of Sudden Cardiac DeathRisk StratificationA multifactorial approach to the prevention of sudden cardiac death is clearly needed. Components of this approach include modifying risk factors for coronary disease, identifying genetic predispositions to sudden death, improving community-based cardiopulmonary resuscitation training, and using technological advances, such as the automatic external defibrillator37 and the wearable defibrillator. Despite substantial efforts, however, survival rates from cardiac arrest in the United States remain low.1 Although survival rates >30% were briefly achieved in some local areas such as Seattle and continue to be achieved in areas such as casinos and airports, the overall survival rate from cardiac arrest in the United States is probably <10%.38 Thus, identifying patients at high risk for cardiac arrest and treating them with pharmacological or nonpharmacological therapy to prevent cardiac arrest is appropriate.The most important risk factor for determining the risk of cardiac arrest in patients with acquired heart diseases is the extent of myocardial damage.39 The risk of cardiac arrest increases moderately with ejection fractions <40% and more significantly with ejection fractions <30%. Other factors that have been shown to be associated with the risk of sudden cardiac death include the extent of heart failure, QRS width, and neurohormone levels. Some studies have suggested that the inducibility of ventricular arrhythmias at electrophysiological testing, heart rate variability, signal-averaged ECGs, and T-wave alternans may provide independent prognostic information. However, for many of these risk-stratification tests, high positive and negative predictive values have not been consistently obtained. A multifactorial model40 may be scientifically most appropriate to determine the risk of cardiac arrest, but it is unclear whether such a model can be widely applied clinically. Thus, selection of patients for trials examining the efficacy of the ICD in the primary prevention of sudden death has typically been based on ejection fraction and, at most, 1 or 2 other risk-stratification tests.Clinical TrialsSeveral recently completed, large-scale trials have examined the use of ICD therapy in patients with underlying structural heart disease at risk for sudden death. Six large trials have examined the use of the ICD in patients with coronary artery disease. The CABG-PATCH trial41 randomized 900 patients who were undergoing cardiac surgery for adjunctive epicardial ICD placement. The inclusion criteria for the CABG-PATCH trial were the presence of LV dysfunction and an abnormal signal-averaged ECG. There was no difference in survival between the patients who received the epicardial ICD and those who did not. The negative results of this study could potentially be attributed to deleterious effects of epicardial ICD implantation or to improvements in ventricular function occurring as a result of bypass surgery. In contrast, 4 other trials that used the ICD for the primary prevention of sudden death in patients with chronic coronary disease and LV dysfunction all showed benefits of the ICD. The MADIT-I study, published in 1996, randomized patients with an LV ejection fraction of ≤35%, coronary artery disease, nonsustained VT, and inducible VT to receive an ICD or standard therapy.42 Only 196 patients were enrolled. There were 15 deaths in the ICD arm and 39 in the conventional-therapy arm. The hazard ratio for overall mortality was 0.46 (P=0.009). Although the study was small and limited by an imbalance in β-blocker use in the 2 groups, the dramatic clinical benefit of the ICD in this patient population led to approval of ICD use for this indication. The Multi-center, Unsustained Tachycardia Trial (MUSTT) had a complex study design.43 Two thousand two hundred two patients were screened and 704 were randomized to be treated with an electrophysiology-guided approach or a medical approach. No difference was seen between the 2 arms. However, a subpopulation who was randomized to the electrophysiologically guided approach received an ICD. The risk of cardiac arrest or death from arrhythmia among patients who received the ICD was significantly lower than in those without the ICD (hazard ratio, 0.24; P<0.001). Analyzing the effect of the ICD in a trial that was designed to compare an electrophysiologically to a nonelectrophysiologically guided approach is complex. However, the dramatic reduction in mortality seen and the consistency with the results of the MADIT-I trial were important observations that the ICD would benefit patients with coronary disease and LV dysfunction. The MADIT-II trial did not use electrophysiological testing or signal-averaged ECGs to stratify patients for enrollment.18 Patients were randomized if they had a prior myocardial infarction and an LV ejection fraction ≤30%. The crude mortality rate was 19.8% in the control arm and 14.2% in the ICD arm. The hazard ratio for reduction of all-cause mortality was 0.69 (P=0.016). These results confirmed that patients with coronary disease and LV dysfunction would benefit from the ICD for the primary prevention of sudden death. One limitation to these trials is that in some, medical therapy was not optimal by current standards. The most recent trial examining the effectiveness of the ICD in the primary prevention of sudden death in patients without coronary artery disease was the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which has been presented in abstract form.44 This trial randomized patients with all types of LV dysfunction to an ICD, placebo, or conventional therapy. The results in patients with nonischemic cardiomyopathy are discussed in the next section. Approximately 1300 patients with coronary disease were randomized. Amiodarone had no effect on mortality. The ICD reduced overall mortality by 23%. The ICD had a significant benefit in the overall patient population. In patients with coronary disease, the hazard ratio crossed 1, but an impressive trend to reduction in overall mortality was seen.One study on ICD therapy soon after infarction failed to show a benefit. In the Defibrillator in Acute Myocardial infarction Trial (DINAMIT), 675 patients were randomized to receive an ICD or standard medical therapy.45 Patients were randomized 4 to 40 days after myocardial infarction and had LV dysfunction and abnormal heart rate variability. Survival was similar in the 2 groups. The reasons for the failure to demonstrate benefits of prophylactic ICD implantation are not yet fully apparent but suggest that ICD implantation soon after myocardial infarction does not yield dramatic clinical benefit. Taken together, the results of these trials suggest that the transvenous ICD substantially reduces mortality in patients with chronic coronary disease and severe LV dysfunction.Although small trials failed to show ICD benefit in patients with nonischemic dilated cardiomyopathy,30,46 2 large, multicenter, randomized trials have been performed. The Defibrillators in Non Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) study randomized 458 subjects with nonischemic dilated cardiomyopathy and LV ejection fractions <36% to receive the best medical therapy or the best medical therapy plus an ICD.17 After 2 years, 14.1% of the patients in the standard-therapy group and 7.9% of the patients in the ICD group had died of all causes (6.2% absolute mortality reduction, P=0.08). Although statistical significance was not reached in the primary end point, the results of the study did suggest that the ICD might have utility in selected patients with nonischemic dilated cardiomyopathy. In the SCD-HeFT trial, >1100 patients with nonischemic cardiomyopathy were randomized into 3 arms.44 There was a 27% relative risk reduction in patients who received an ICD. The difference in patients with nonischemic cardiomyopathy did not quite reach significance, but a strong trend to mortality reduction was observed.The results of these studies suggest that in judiciously selected patients with significant LV dysfunction that persists despite optimal medical therapy, ICD implantation may be appropriate. A group with moderately high risk for cardiac arrest in whom ICD implantation may be justified is probably defined by those patients with ejection fractions ≤35%. In patients with less severe ventricular function, additional assessments such as electrophysiological or noninvasive testing may be appropriate to further risk-stratify patients.Primary Prevention of Sudden Death in Other DiseasesA number of diseases other than dilated cardiomyopathy have been associated with an increased incidence of sudden cardiac death. These include inherited diseases of ion channels, such as long-QT syndrome,47 Brugada syndrome,48 and catecholaminergic VT.49 In addition, other structural heart diseases, such as right ventricular dysplasia,50 hypertrophic cardiomyopathy,51 and certain types of congenital heart disease, may be associated with an increased risk of sudden death. The frequency of these conditions is not as high as that of ischemic or nonischemic dilated cardiomyopathy, making prospective, randomized, control trials difficult to perform. Nonrandomized, observational studies suggest that subgroups of high-risk patients may benefit from ICD therapy. One randomized trial was performed in Thailand on patients with an inherited risk of sudden cardiac death (DEBUT).52 In that trial, patients with an inherited syndrome of sudden death that probably represents the Brugada syndrome were randomized to receive β-blockers or an ICD. Patients who received an ICD had better survival.In the absence of large-scale trials for most of these conditions, risk-stratification algorithms based on retrospective studies have been created in an attempt to help select appropriate patients for ICD therapy. Although criteria suggesting an increased risk differ among different conditions, a family history of sudden death in almost all of the diseases mentioned earlier appears to be associated with an increased risk of sudden death. In addition, there are disease-specific markers, such as septal wall thickness in hypertrophic cardiomyopathy,51 the length of the QT interval in the inherited long-QT syndrome,47 and the presence of persistent rather than intermittent right precordial ST-segment elevation in Brugada syndrome,48 that appear to portend an increased risk of sudden death and may make aggressive use of the ICD for the primary prevention of sudden death appropriate.Cardiac Resynchronization TherapyPhysiologically, the presence of electrical-conduction defects in heart failure is associated with a decrease in contractile performance, development or prolongation of mitral regurgitation, and wasted cardiac work as a result of development of mechanical asynchrony.53 Intraventricular asynchrony, characterized by regional contractile phase delay in the anteroseptal and posterolateral walls of the LV, and interventricular asynchrony, characterized by a phase delay in contraction between the right and left ventricles, are the typical manifested consequences of electrical remodeling in the cardiac conduction system. These electrical alterations translate into abnormal myocardial metabolism, redirection of regional coronary perfusion, and cellular changes characterized by abnormalities in cellular calcium handling and upregulation of stress kinases.54,55 Thus, restoring electrical synchrony could potentially improve cardiac function by reversing these cellular, physiological, and hemodynamic aberrations.Resynchronization Pacing in Heart FailureThe first clinical report of biventricular pacing is credited to Cazeau et al56 in 1994. That study was followed by a series of uncontrolled studies demonstrating marked short-term improvements in hemodynamics and symptoms with biventricular stimulation.57,58The European and Canadian InSync Study was designed to test the safety and efficacy of a multisite pacemaker (Medtronic InSync) in the treatment of refractory heart failure. The trial was conducted without a control group and thus, was observational. Significant improvements in exercise capacity, New York Heart Association (NYHA) functional class, and quality-of-life score were also noted at each of these time points.59 The MIRACLE (Multicenter InSync Randomized Clinical Evaluation) trial randomized 453 patients to activation or nonactivation of cardiac resynchronization in a double-blind study design.60 Inclusion criteria were NYHA class III/IV, QRS >130 ms, ejection fraction <35%, and LV end-diastolic dimension >55 mm (echocardiographic). Resynchronization improved symptoms, quality of life, and exercise capacity (6-minute walk test increased by 39 m and V̇o2 increased by 1 mL · min−1 · kg−1) while reducing LV dimension (LV end-diastolic dimension decreased by 5 mm) and improving ejection fraction. There were also improvements in the numbers of patients requiring hospitalization (8% versus 15%) or intravenous medications (7% versus 15%) for the treatment of heart failure (P<0.05). The biggest drawback of that study is that it was not subjected to an intention-to-treat analysis, because randomization assignment was made only after initial successful device implantation was secured.Long-Term Studies of Multisite Pacing (With ICD)The CONTAK CD trial61 enrolled 581 patients, who also met conventional indications for ICD implantation, to active CRT or not. Initially, patients were randomized (in a double-blind design) to either biventricular or no pacing for 3 months and then crossed over to the opposite assignment for the next 3 months (n=248), but the scheme was later changed to a 6-month parallel control design (n=333). The primary end point was a composite of mortality, heart failure hospitalizations, and episodes of ventricular arrhythmias. The primary end point favored CRT but was not statistically significant. However, the 6-minute walk test, NYHA class, and peak aerobic capacity were significantly improved with CRT, particularly in patients with NYHA III/IV heart failure.The MIRACLE ICD trial was designed in a similar manner to the original MIRACLE study, the only exception being that all patients were to have an indication for ICD.62 In addition to the primary heart failure–related efficacy variables, this trial also assessed the efficacy of ICD function in the presence of CRT. At 6 months, significant improvements in NYHA class and peak aerobic capacity (but not in the 6-minute walk test) were noted. Furthermore, no significant differences were noted in overall heart failure status, LV size or function, hospitalizations, or survival. More important, this study demonstrated that arrhythmia recognition and ICD function were preserved, and no proarrhythmia was noted. The CRTD trials as a group showed functional improvement after biventricular pacing.Morbidity and Mortality Studies of Multisite PacingCOMPANION (comparison of medical therapy, pacing, and defibrillation in CHF) enrolled patients with CHF and NYHA class III or IV symptoms, despite maximized medical therapy.15 Inclusion criteria included a QRS duration >120 ms and a PR interval >150 ms. The trial had 3 treatment arms: One of 5 patients was to receive optimal pharmacological therapy, 2 of 5 were to receive optimal pharmacological therapy plus biventricular pacing, and the remaining 2 of 5 were to receive biventricular pacing plus backup ICD therapy. In contrast to all others, this study was sufficiently powered to eva

Most patients who have an out-of-hospital cardiac arrest do not survive. Thus, the use of a prophylactic implantable cardioverter–defibrillator (ICD) for the primary prevention of sudden death is a conceptually attractive option for high-risk patients. Several clinical trials have previously shown that ICDs reduced mortality in patients with coronary artery disease who had not yet had a life-threatening arrhythmia and who were selected on the basis of either the results of electrophysiological testing or left ventricular dysfunction.1–4 In the past year, four multicenter clinical trials have helped refine the selection of appropriate patients for ICD therapy. In addition to . . .

Background: Three-dimensional (3D) mapping systems are commonly used for mapping and ablation of RVOT VT and PVCs. Newer catheters that are circular with multiple electrodes, such as the Lasso catheter, are capable of simultaneously recording from multiple points within a circumferential plane. Given the tubular structure of the RVOT these catheters could be used for mapping tachycardias from the RVOTMethods: A retrospective cohort study of patients undergoing radiofrequency (RF) ablation of RVOT VT or PVCs was performed. In group 1 (n = 7), mopping was performed with a single ablation catheter and fluoroscopy. In group 2 (n = 10), 3D mapping using ESI (n = 9) or CARTO (n = 1) was performed. In group 3 (n = 12), mopping was performed with a circular multielectrode catheter (n = 12). All ablations were performed with 4-mm tip catheters using RF energy.Results: Catheter ablation for RVOT VT (n = 15) or PVCs (n = 14) was performed on 29 cases in 26 patients, 9 moles. Mean age was 35.9 years. In groups 1, 2, and 3, the mean number of lesions was 17.7 +/- 7.7, 13.6 +/- 7.7, and 18.2 +/- 22.7 and the median number of lesions was 20, 13, and 5, respectively. There were no significant differences in the number of lesions, BF time, fluoroscopy time, procedure time, and acute success rate among the three techniques. There were three complications in group 2 and one in group 3.Conclusion: The use of a circular multielectrode catheteris as effective as the other standard available 3D mapping techniques, both in terms of procedural success and procedural characteristics. Additionally, because of the lower cost associated with using the circular multielectrode catheter approach, further evaluation should be performed to determine whether this is the most cost-effective approach to 3D mopping and ablation of RVOT tachycardias.

We hypothesized that myocardial infarction-related alterations in ventricular fibrillation (VF) cycle length (VFCL) would correlate with changes in local cardiac electrophysiological and anatomic properties. An electrophysiological study was performed in normal, subacute, and chronic infarction mongrel dogs. VF was induced by programmed electrical stimulation and mean and minimum early and late VFCL was determined and correlated with local electrophysiological and anatomic properties. Effective refractory period (ERP), activation recovery time (ART), ERP/ART ratio, threshold, and ERP and ART dispersion were determined at 112 sites on the anterior left ventricle. Wave front progression was analyzed over a 2-s period. The extent of local tissue necrosis and of myocardial fiber disarray was also evaluated. The early mean VFCL was significantly longer in the subacute infarction (149 +/- 35 ms) and chronic infarction dogs (129 +/- 18 ms) compared with control dogs (102 +/- 15 ms; P < 0.0001 for both comparisons) as was the early minimum VFCL with similar trends seen during late VF. Complete epicardial reentrant circuits were significantly more common in normal dogs (4.3 +/- 2.4, 22.4% of cycles) than in subacute (0.75 +/- 0.96, 5.3% of cycles, P < 0.05 vs. normal) and chronic infarction dogs (1.3 +/- 1.3, 7.5% of cycles, P < 0.05 vs. normal). There was a poor correlation between the mean and minimum early and late VFCL and local electrophysiological and anatomic properties (R(2) < 0.2 for all comparisons) with a much better correlation between average mean and minimum VFCL (over the entire plaque) and global ERP and ART dispersion during early and late VF. In conclusion, VFCL in normal and infarcted myocardium shows a poor correlation with local ventricular electrophysiological and anatomic properties measured in sinus rhythm. However, there was a much better correlation between the average VFCL with global dispersion of repolarization. The lack of correlation between local VFCL and refractoriness and the infrequent occurrence of epicardial reentry suggests that intramural reentry may be the primary mechanism of VF in this model.

BACKGROUND:Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes. However, the value of prophylactic implantation of an implantable cardioverter-defibrillator (ICD) to prevent sudden death in such patients is unknown.METHODS:We enrolled 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36 percent, and premature ventricular complexes or nonsustained ventricular tachycardia. A total of 229 patients were randomly assigned to receive standard medical therapy, and 229 to receive standard medical therapy plus a single-chamber ICD.RESULTS:Patients were followed for a mean (+/-SD) of 29.0+/-14.4 months. The mean left ventricular ejection fraction was 21 percent. The vast majority of patients were treated with angiotensin-converting-enzyme (ACE) inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28 in the ICD group, as compared with 40 in the standard-therapy group (hazard ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality rate at two years was 14.1 percent in the standard-therapy group (annual mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standard-therapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71; P=0.006).CONCLUSIONS:In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.

Journal of Cardiovascular ElectrophysiologyVolume 15, Issue 6 p. 665-666 Implantable Cardioverter Defibrillator Therapy for Ambulatory Ventricular Tachycardia: Are We Using an Elephant Gun? ALAN H. KADISH M.D., ALAN H. KADISH M.D. Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USASearch for more papers by this author ALAN H. KADISH M.D., ALAN H. KADISH M.D. Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USASearch for more papers by this author First published: 28 May 2004 https://doi.org/10.1046/j.1540-8167.2004.03662.x Address for correspondence: Alan H. Kadish, M.D., 251 E. Huron, Feinberg Pavilion, Suite 8-536, Chicago, IL 60611. Fax: 312-926-0607; E-mail: a-kadish@nwu.edu J Cardiovasc Electrophysiol, Vol. 15, pp. 665-666, June 2004. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue6June 2004Pages 665-666 RelatedInformation