Unexpected ICD pulse generator failure due to electronic circuit damage caused by electrical overstress.

Because it is a lifesaving device, the unexpected failure of an ICD can be catastrophic. We report ICD electronic circuit failure due to electrical overstress damage (EOS) to the high voltage hybird circuit and other electronic components in a series of ICD pulse generator models. Data were obtained from the Multicenter Registry of Pacemaker and ICD Pacemaker and Lead Failures, and from the manufactures' adverse event reports, that were in the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. Of 16 nonbattery Guidant/CPI ICD pulse generator failures reported to the registry, 6 (38%) have been confirmed by the manufacturer to be EOS related, and Guidant/CPI has reported 273 such failures to the FDA as of 12/29/00. The signs of failure included loss of telemetry and inability to deliver therapy, and some patients have experienced serious adverse events. Hybrid circuit damage may have occurred during capacitor charging or reform, and the majority appears to have happened during normal ICD function. While the incidence of this problem is unknown, a management strategy should be adopted that includes routine follow-up every 3 months and device evaluation after a shock or exposure to external defibrillation or electrosurgical devices. This study suggests that additional data are needed to determine the incidence of this problem, and that our present methods for monitoring the performance of ICD's following market release are inadequate.

"Stable" ventricular tachycardia is not a benign rhythm : insights from the antiarrhythmics versus implantable defibrillators (AVID) registry.

BACKGROUND: Sustained ventricular tachycardia (VT) can be unstable, can be associated with serious symptoms, or can be stable and relatively free of symptoms. Patients with unstable VT are at high risk for sudden death and are best treated with an implantable defibrillator. The prognosis of patients with stable VT is controversial, and it is unknown whether implantable cardioverter-defibrillator therapy is beneficial. METHODS AND RESULTS: Screening for the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial identified patients with both stable and unstable VT. Both groups were included in a registry, and their clinical characteristics and discharge treatments were recorded. Mortality data were obtained through the National Death Index. The mortality in 440 patients with stable VT tended to be greater than that observed in 1029 patients presenting with unstable VT (33.6% versus 27.6% at 3 years; relative risk [RR]=1.22; P:=0.07). After adjustment for baseline and treatment differences, the RR was little changed (RR=1.25, P:=0.06). CONCLUSIONS: Sustained VT without serious symptoms or hemodynamic compromise is associated with a high mortality rate and may be a marker for a substrate capable of producing a more malignant arrhythmia. Implantable cardioverter-defibrillator therapy may be indicated in patients presenting with stable VT.

A comparison of biphasic and monophasic shocks for external defibrillation. Physio-Control Biphasic Investigators.

BACKGROUND AND OBJECTIVE: The ability of a shock to defibrillate the heart depends on its waveform and energy. Past studies of biphasic truncated exponential (BTE) shocks for external defibrillation focused on low energy levels. This prospective, randomized, double-blind clinical trial compared the first-shock efficacies of 200-joule (J) BTE, 130-J BTE, and 200-J monophasic damped sine wave shocks. METHODS: Ventricular fibrillation (VF) was induced in 115 patients during evaluation of implantable cardioverter-defibrillator function and 39 patients during electrophysiologic evaluation of ventricular arrhythmias. After 19 +/- 10 seconds of VF, a randomized transthoracic shock was administered. Mean first-shock success rates of the three groups were compared using a "Tukey-like" statistical test, adjusting for multiple comparisons. Blood pressures and arterial oxygen saturations were measured before VF induction and 30, 90, and 150 seconds after successful defibrillation. RESULTS: First-shock success rates were 61/68 (90%) for 200-J monophasic, 39/39 (100%) for 200-J biphasic, and 39/47 (83%) for 130-J biphasic shocks. The 200-J biphasic shocks were simultaneously superior in first-shock efficacy to both 200-J monophasic and 130-J biphasic shocks (experimentwise error rate, alpha < 0.01). There was no significant difference between the efficacies of 200-J monophasic and 130-J biphasic shocks, nor was there any significant difference between the three groups in hemodynamic parameters after successful shocks. CONCLUSIONS: Biphasic shocks of 200 J provide better first-shock defibrillation efficacy for short-duration VF than 200-J monophasic and 130-J biphasic shocks and thus may allow earlier termination of VF in cardiac arrest patients.

Large clinical trials in the management of ventricular arrhythmias. Applying group results to individual cases.

Applying the results of clinical trials to everyday practice in an appropriate manner can be difficult. Earlier clinical trials focused on the secondary prevention of ventricular arrhythmias. Studying patients at high risk of recurrent ventricular arrhythmias is important, but the overall impact on arrhythmic death is low. Recent arrhythmia trials have studied specific patient populations for the primary prevention of ventricular arrhythmias. New trials will expand the investigation to other populations. This article summarizes the results of large clinical trials in the management of ventricular arrhythmias and attempts to provide guidelines for applying their results to everyday clinical practice.

Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology.

Amiodarone has become an important drug for the treatment of supraventricular and ventricular arrhythmias, in short-term inpatient and outpatient settings. It may also have a role in affecting outcome in patients at high risk for arrhythmic events and sudden death; its place among available therapies is being established in clinical trials.

Determinants of outcome in patients with sustained ventricular tachyarrhythmias: the antiarrhythmics versus implantable defibrillators (AVID) study registry.

BACKGROUND: The prognosis of patients with sustained ventricular tachyarrhythmias varies according to clinical characteristics. We sought to identify predictors of survival in a large population of patients with documented sustained ventricular tachyarrhythmias not related to reversible or correctable causes included in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry. METHODS AND RESULTS: We analyzed the impact of 36 demographic, clinical, and discharge treatment variables on the outcome for 3559 patients. Survival status was assessed with the use of the National Death Index. Multivariate analyses were performed with the use of the Cox proportional hazards model. After a mean follow-up of 17 +/- 12 months, 631 patients died. Actuarial survival was 0.86 (95% confidence interval [CI] 0.85 to 0.88), 0.79 (95% CI 0.78 to 0.81), and 0.72 (95% CI 0.70 to 0.74) at 1, 2, and 3 years. Multivariate predictors of worse survival included older age, severe left ventricular dysfunction, lower systolic blood pressure, history of congestive heart failure, diabetes, smoking or atrial fibrillation, and preexistent pacemaker. The hemodynamic impact of the qualifying arrhythmia was not a predictor of outcome. Defibrillator implantation and hospital discharge while the patient was taking a beta-blocker or an angiotensin-converting enzyme inhibitor were associated with better prognosis. CONCLUSIONS: Despite therapeutic advances, the mortality rates of patients with sustained ventricular tachyarrhythmias remain high. Prognosis depends on the severity of underlying heart disease, as reflected by the extent of left ventricular dysfunction and the presence of heart failure. Well-tolerated ventricular tachycardia in patients with structural heart disease does not carry a significantly better prognosis than ventricular tachyarrhythmia with more severe hemodynamic consequences.

Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients. METHODS: We conducted a retrospective multicenter study of the efficacy of implantable cardioverter-defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death. RESULTS: At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [+/-SD], 40+/-16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the group of 43 patients who received defibrillators for secondary prevention (after cardiac arrest or sustained ventricular tachycardia), the devices were activated appropriately in 19 patients (11 percent per year). Of 85 patients who had prophylactic implants because of risk factors (i.e., for primary prevention), 10 had appropriate interventions (5 percent per year). The interval between implantation and the first appropriate discharge was highly variable but was substantially prolonged (four to nine years) in six patients. In all 21 patients with stored electrographic data and appropriate interventions, the interventions were triggered by ventricular tachycardia or fibrillation. CONCLUSIONS: Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in patients with hypertrophic cardiomyopathy. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias, indicating that these devices have a role in the primary and secondary prevention of sudden death.

Evaluation of antiarrhythmic drug efficacy in patients with an ICD: unlimited potential or replete with complexity and problems?

There are a number of novel ways in which implantable cardioverter defibrillator (ICD) endpoints can be used in clinical trials to evaluate antiarrhythmic drugs. The advances in ICD technology (storage, retrieval, and accurate interpretation of ICD electrograms) expand the potential to include the use of an ICD endpoint as a clinical surrogate for sudden death. The ICD also provides the necessary safety net to test new drugs. The frequent need for antiarrhythmic drugs in patients already fitted with an ICD (e.g., for atrial fibrillation) necessitates knowledge of the drugs' effect on defibrillator threshold. There are interpretative problems and challenges associated with all types of ICD trials. A particular difficult issue is the degree to which the results of data on antiarrhythmic drug efficacy and safety acquired in the context of an ICD endpoint trial might be extrapolated to patient populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpretation of clinical trials featuring ICD endpoints.

Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators.

OBJECTIVES: We sought to assess the effect of baseline ejection fraction on survival difference between patients with life-threatening ventricular arrhythmias who were treated with an antiarrhythmic drug (AAD) or implantable cardioverter-defibrillator (ICD). BACKGROUND: The Antiarrhythmics Versus Implantable Defibrillators (AVID) study demonstrated improved survival in patients with ventricular fibrillation or ventricular tachycardia with a left ventricular ejection fraction (LVEF) < or =0.40 or hemodynamic compromise. METHODS: Survival differences between AAD-treated and ICD-treated patients entered into the AVID study (patients presenting with sustained ventricular arrhythmia associated with an LVEF < or =0.40 or hemodynamic compromise) were compared at different levels of ejection fraction. RESULTS: In patients with an LVEF > or =0.35, there was no difference in survival between AAD-treated and ICD-treated patients. A test for interaction was not significant, but had low power to detect an interaction. For patients with an LVEF 0.20 to 0.34, there was a significantly improved survival with ICD as compared with AAD therapy. In the smaller subgroup with an LVEF <0.20, the same magnitude of survival difference was seen as that in the 0.20 to 0.34 LVEF subgroup, but the difference did not reach statistical significance. CONCLUSIONS: These data suggest that patients with relatively well-preserved LVEF (> or =0.35) may not have better survival when treated with the ICD as compared with AADs. At a lower LVEF, the ICD appears to offer improved survival as compared with AADs. Prospective studies with larger patient numbers are needed to assess the effect of relatively well-preserved ejection fraction (> or =0.35) on the relative treatment effect of AADs and the ICDs.

In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival: results from the AVID Registry. Antiarrhythmics Versus Implantable Defibrillators.

OBJECTIVES: This study describes the outcomes of patients from the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study Registry to determine how the location of ventricular arrhythmia presentation influences survival. BACKGROUND: Most studies of cardiac arrest report outcome following out-of-hospital resuscitation. In contrast, there are minimal data on long-term outcome following in-hospital cardiac arrest. METHODS: The AVID Study was a multicenter, randomized comparison of drug and defibrillator strategies to treat life-threatening ventricular arrhythmias. A Registry was maintained of all patients with sustained ventricular arrhythmias at each study site. The present study includes patients who had AVID-eligible arrhythmias, both randomized and not randomized. Patients with in-hospital and out-of-hospital presentations are compared. Data on long-term mortality were obtained through the National Death Index. RESULTS: The unadjusted mortality rates at one- and two-year follow-ups were 23% and 31.1% for patients with in-hospital presentations, and 10.5% and 16.8% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted mortality rates at one- and two-year follow-ups were 14.8% and 20.9% for patients with in-hospital presentations, and 8.4% and 14.1% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted long-term relative risk for in-hospital versus out-of-hospital presentation was 1.6 (95% confidence interval [CI] 1.3-1.9). CONCLUSIONS: Compared with patients with out-of-hospital presentations of life-threatening ventricular arrhythmias not due to a reversible cause, patients with in-hospital presentations have a worse long-term prognosis. Because location of ventricular arrhythmia presentation is an independent predictor of long-term outcome, it should be considered as an element of risk stratification and when planning clinical trials.

Evaluation of antiarrhythmic drug efficacy in patients with an ICD. Unlimited potential or replete with complexity and problems?

A report from a Study group, proposed by A. J. Camm, London, of the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology; co-sponsored by the North American Society of Pacing and Electrophysiology. The Study Group was convened on 29 August 1997 at Saltsjöbaden, near Stockholm. The meeting was chaired by A. J. Camm, London, and C. M. Pratt, Houston. Based on the presentation and discussions, a first draft of the documents was prepared by C. Pratt and J. Camm which was then circulated to all members three times for their review. All members of the Study Group approved the final manuscript. This report represents the opinion of the members of this Study Group and does not necessarily reflect the official position of either society.The meeting of the Study Group was made possible by unrestricted educational grants from Medtronic, Guidant, Proctor & Gamble, Berlex and Sanofi.Also, presented, in part, at the Cardio-Renal Drugs Advisory Board meeting of the Food and Drug Administration, Bethesda, Maryland, on 30 April 1999.

Syncope and inducible ventricular fibrillation in a woman with hemochromatosis.

BACKGROUND: Hemochromatosis has been associated with atrial tachyarrhythmias and congestive heart failure as a consequence of dilated or restrictive cardiomyopathy. Inducible ventricular fibrillation has not been previously described. METHODS AND RESULTS: An electrophysiologic study was conducted in a woman after two episodes of syncope. Polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) were induced with ventricular programmed stimulation. Magnetic resonance imaging demonstrated signal loss in the liver consistent with hemochromatosis, but normal cardiac size and function. Hematologic studies supported a diagnosis of hemochromatosis. CONCLUSION: Cardiac hemochromatosis may be associated with serious ventricular arrhythmias.

Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial.

OBJECTIVES: To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT). BACKGROUND: The ability of beta-blockers to alter the mortality of patients with VF or VT receiving contemporary medical management is not well defined. METHODS: Survival of 1,016 randomized and 2,101 eligible, nonrandomized patients with VF or symptomatic VT followed in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial through December 31, 1996 was assessed using Cox proportional hazards analysis. RESULTS: The 817 (28%) patients discharged from hospital receiving beta-blockers had less ventricular dysfunction, fewer symptoms of heart failure and a different pattern of medication use compared with patients not receiving beta-blockers. Before adjustment for important prognostic variables, beta-blockade was not significantly associated with survival in randomized or in eligible, nonrandomized patients treated with specific antiarrhythmic therapy. After adjustment, beta-blockade remained unrelated to survival in randomized or in eligible, nonrandomized patients treated with amiodarone alone (n = 1142; adjusted relative risk [RR] = 0.96; 95% confidence interval [CI] 0.64-1.45; p = 0.85) or a defibrillator alone (n = 1347; adjusted RR = 0.88; 95% CI 0.55 to 1.40; p = 0.58). In contrast, beta-blockade was independently associated with improved survival in eligible, nonrandomized patients who were not treated with specific antiarrhythmic therapy (n = 412; adjusted RR = 0.47; 95% CI 0.25 to 0.88; p = 0.018). CONCLUSIONS: Beta-blocker use was independently associated with improved survival in patients with VF or symptomatic VT who were not treated with specific antiarrhythmic therapy, but a protective effect was not prominent in patients already receiving amiodarone or a defibrillator.

Nonpharmacologic validation of the intrinsic heart rate in cardiac transplant recipients.

BACKGROUND: The maximum sinus rate during exertion in humans is inversely related to age. However, the sinus rate at rest is quite variable. The intrinsic heart (IHR) following pharmacologic blockade of autonomic tone with propranolol and atropine has been proposed as a test of sinus node function and is related to age by the linear regression equation: IHR = 118.1 - (0.57 x age). Whether this relationship exists for transplanted hearts for which the donor sinus node is denervated has not been determined. METHODS: The relationship between the resting heart rate and the age of the donor heart was examined in 103 patients 1 year following orthotopic cardiac transplantation in the absence of rejection or intercurrent illness. Patients receiving beta-blockers, calcium blockers, antiarrhythmic drugs, digitalis, theophylline, or with biopsy evidence of rejection or abnormal coronary arteriograms were excluded from analysis. RESULTS: The recipient age, left ventricular ejection fraction, pulmonary capillary pressure, cardiac index, donor heart ischemic time and cardiopulmonary bypass time did not correlate with the rate of the resting donor sinus node. The resting heart rate was inversely related to age of the donor heart by the linear regression equation: HR = 112.0 - (046 x age). CONCLUSION: The resting rate of the denervated sinus node is related to donor age with a regression equation that is similar, though slightly slower, than that predicted after pharmacologic autonomic blockade.

Design and results of the antiarrhythmics vs implantable defibrillators (AVID) registry. The AVID Investigators.

BACKGROUND: The Antiarrhythmics Versus Implantable Defibrillators (AVID) Study compared treatment with implantable cardioverter-defibrillators versus antiarrhythmic drugs in patients with life-threatening ventricular arrhythmias (VAs). AVID maintained a Registry on all patients, randomized or not, with any VA or unexplained syncope who could be considered for either of the treatment strategies. Trial-eligible arrhythmias were the categories of VF cardiac arrest, Syncopal VT, and Symptomatic VT, below. METHODS AND RESULTS: Of 5989 patients screened, 4595 were registered and 1016 were randomized. Mortality follow-up through 1996 was obtained on the 4219 Registry patients enrolled before 1997 through the National Death Index. Crude mortality rates (mean+/-SD, follow-up, 16.9+/-11.5 months) were: VF cardiac arrest, 17.0% (n=1399, 238 deaths); Syncopal VT, 21.2% (n=598, 127 deaths); Symptomatic VT, 15.8% (n=1065, 168 deaths); Stable (asymptomatic) VT, 19.7% (n=497, 98 deaths); VT/VF with transient/correctable cause, 17.8% (n=270, 48 deaths); and Unexplained syncope, 12.3% (n=390, 48 deaths). CONCLUSIONS: Patients with seemingly lower-risk or unknown-risk VAs (asymptomatic VT, and VT/VF associated with a transient factor) have a (high) mortality similar to that of higher-risk, AVID-eligible VAs. The similar (and poor) prognosis of most patients with VT/VF suggests the need for reevaluation of a priori risk grouping and raises the question of the appropriate arrhythmia therapy for a broad range of patients.

Energy levels for defibrillation: what is of real clinical importance?

Today, transthoracic and intracardiac defibrillation offer a well-accepted and widely used form of therapy for patients with life-threatening ventricular arrhythmias. Despite the wide clinical use of defibrillators, the mechanisms by which an electrical shock halts fibrillation are still not completely understood. During a shock, different amounts of current flow through the different parts of the heart and the current distribution is highly uneven. This current distribution is affected by changes in the shock potential gradient through the heart, changes in fiber orientation, and changes in myocardial conductivity caused by connective tissue barriers. It would be ideal if the potential gradient distribution throughout the ventricles could be measured directly for each individual patient during defibrillator implantation and follow-up and the shock strength could be programmed based on this measurement, but so far this is not possible. A more feasible approach is to determine, by trial and error, the magnitude of the shock strength delivered through the defibrillation electrodes for successful defibrillation. There is no distinct threshold value above which all shocks succeed and below which all shocks fail to defibrillate. Rather, increasing shock strength increases the likelihood the shock will succeed. Therefore, instead of a distinct defibrillation threshold, a probability of success curve exists. However, increasing the shock strength above an optimal range can actually decrease the success rate for defibrillation. One possible explanation is that the high voltage gradients caused by such large shocks damage cells and result in postshock arrhythmias that may reinitiate fibrillation. Another problem that can affect the probability of defibrillation success for a particular programmed energy setting is that the shock strength required for defibrillation may increase over time due to (1) the growth of fibrotic tissue around the defibrillation electrode; (2) migration of the lead; (3) acute ischemia; or (4) other changes in the underlying cardiac disease (e.g., worsening of heart failure). Such possible increases in the defibrillation shock strength requirement should be compensated for before they occur by adding a margin of safety to the shock strength needed for effective defibrillation. When programming an implantable defibrillator, it is important to keep in mind that the defibrillation shock should be (1) strong enough to defibrillate at least 98% of the time with the first shock; (2) weak enough not to cause severe post-shock arrhythmias or reinitiation of fibrillation; but (3) strong enough to compensate for changes of defibrillation energy requirements over time. This usually can be accomplished by setting the defibrillator 7-10 J higher than the defibrillation threshold determined by a standard step-down protocol.

The influence of ventricular fibrillation duration on defibrillation efficacy using biphasic waveforms in humans.

OBJECTIVES: The purpose of this study was to prospectively investigate the influence of ventricular fibrillation (VF) durations of 5, 10 and 20 s on the defibrillation threshold (DFT) during implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND: Although the DFT using monophasic waveforms has been shown to increase with VF duration in humans, the effect of VF duration on defibrillation efficacy using biphasic waveforms in humans is not known. METHODS: Thirty patients undergoing primary ICD implantation or pulse generator replacement were randomly assigned to have the DFT determined using biphasic shocks at two durations of VF each (5 and 10 s, 10 and 20 s or 5 and 20 s). RESULTS: There was no statistically significant difference in the mean DFT comparing VF durations of 5 s (9.5+/-6.0 J) and 10 s (10.8+/-7.0 J) (p=0.4). The mean DFT significantly increased from 10.9+/-6.1 J at 10 s of VF to 12.6+/-5.6 J (p=0.03) at 20 s of VF, and from 7.0+/-3.5 J at 5 s of VF to 10.5+/-6.3 J (p=0.04) at 20 s of VF. An increase in the DFT was observed in 14 patients as VF duration increased. There were no clinical characteristics that differentiated patients with and without an increase in the DFT. CONCLUSIONS: Defibrillation efficacy decreases with increasing VF duration using biphasic waveforms in humans. Ventricular fibrillation durations greater than 10 s may negatively affect the effectiveness of ICD therapy.