Long-term outcome of survivors of cardiac arrest whose therapy is guided by electrophysiologic testing.

The long-term outcome of 217 consecutive survivors of cardiac arrest whose therapy was guided by electrophysiologic testing was analyzed. After electrophysiologic testing, 81 patients (37%) were classified as having no inducible arrhythmia and were treated without antiarrhythmic drugs; 23 received an implantable defibrillator. Of the 136 patients with inducible arrhythmia, the 51 (38%) who responded to serial drug testing were treated with the successful drug and the 85 (62%) with unsuccessful drug testing were treated with an implantable defibrillator (47 patients), amiodarone (36 patients) or drugs that were unsuccessful during testing (2 patients). The mean follow-up interval for all patients was 35 +/- 23 months. The actuarial incidence of sudden death and overall death was similar for patients whose arrhythmias were not inducible, drug responders and nonresponders. The actuarial incidence rate of recurrent arrhythmic events in nonresponders was 35 +/- 5% and 53 +/- 7% at 2 and 5 years, respectively. These values were significantly lower (and statistically similar to each other) in the other two patient groups: patients with noninducible arrhythmia (19 +/- 5% and 31 +/- 7%, respectively, p less than 0.05) and drug responders (13 +/- 5% and 23 +/- 8%, respectively, p less than 0.01). Patients with an implantable defibrillator who had recurrent arrhythmic events were significantly less likely to die suddenly than were patients without a defibrillator who had recurrent events (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease.

The ability of the automatic implantable cardioverter-defibrillator to prolong overall survival, particularly in patients with significantly depressed cardiac function, has not been well documented. Of 119 patients who received the implantable defibrillator in this institution, 40 had a left ventricular ejection fraction less than 30% (Group A) and 79 had an ejection fraction greater than or equal to 30% (Group B). For each group, cumulative survival was compared with the projected survival if the implantable defibrillator had not been used. Projected survival was based on the assumption that the first appropriate shock would have resulted in death without the defibrillator. For Group A, the 3 year cumulative survival rate was 67 +/- 12% versus a projected survival rate of 6 +/- 15% (p less than 0.001). For Group B, the 3 year cumulative survival rate was 96 +/- 3% versus a projected survival rate of 46 +/- 8% (p less than 0.001). Both the cumulative and projected survival rates for patients in Group A were significantly worse than for patients in Group B (p less than 0.01). The projected survival rates for both Groups A and B were comparable with the observed survival rate in similar patients treated without the implantable defibrillator. In summary, the implantable cardioverter-defibrillator significantly prolonged overall survival, even in patients with poor cardiac function. The technique of estimating projected survival appears to allow a realistic estimate of the reduction in mortality achieved by the defibrillator.

Classification of death in antiarrhythmia trials.

OBJECTIVES: We sought to develop and apply a new scheme for the classification of death to be used in trials of antiarrhythmia treatments. BACKGROUND: Because presently accepted classifications of death do not fully describe or tabulate all significant aspects of terminal events, nor do they consider unique aspects of arrhythmia investigations, a new classification scheme that addresses these issues is desirable. METHODS: A classification scheme of deaths that occur in antiarrhythmia trials was developed using the following categories: 1) primary organ cause (cardiac [arrhythmic, nonarrhythmic or unknown], noncardiac or unknown); 2) temporal course (sudden, nonsudden or unknown); 3) documentation (witnessed, monitored [yes, no or unknown]); 4) operative relation (preoperative, perioperative or postoperative); and 5) system relation (procedure related, pulse generator related and lead related [yes, no or unknown]). RESULTS: The classification scheme was used in a clinical trial of a new implantable cardioverter-defibrillator (1,250 patients, of whom 79 died) and used in an application for device market approval. Application of the classification to data reported using an older classification scheme is demonstrated. CONCLUSIONS: We propose a descriptive classification scheme that 1) fully describes and tabulates all significant aspects of terminal events; 2) incorporates previously used categorizations of death and new categorizations that address unique aspects of arrhythmia investigations; and 3) tabulates sufficient data to allow comparison with other studies. Events in a clinical trial of implantable defibrillator therapy were classified using the new classification scheme.

Long-term multicenter experience with a second-generation implantable pacemaker-defibrillator in patients with malignant ventricular tachyarrhythmias. The Guardian Multicenter Investigators Group.

A second-generation implantable pacemaker-cardioverter-defibrillator was evaluated in 200 patients with sustained ventricular tachycardia, ventricular fibrillation or prior cardiac arrest. The device permits demand ventricular pacing for bradyarrhythmias and for long QT interval or tachycardia suppression, uses programmable (3 to 30 J) energy shocks for conversion of ventricular tachycardia and ventricular fibrillation and is used with conventional pacing and defibrillation leads. Ventricular tachycardia/fibrillation recognition is based on the ventricular electrogram rate and requires reconfirmation before shock delivery. Two hundred patients (mean age 62 years, mean left ventricular ejection fraction 36%) were enrolled and followed up for 0 to 23 months (mean 12). Epicardial lead system implantation was performed with use of an anterolateral thoracotomy (38%), median sternotomy (26%) and subxiphoid (20%) or subcostal (16%) approach. Perioperative mortality rate was 5.5% (all nonarrhythmic deaths). Implant defibrillation threshold ranged from 3 to 30 J (mean 15), with initial programmed shock energy ranging from 3 to 30 J (mean 22). Ventricular tachycardia/fibrillation sensing threshold ranged from 0.7 to 1.8 mV (median 1) and the tachycardia detection interval from 288 to 416 ms (median 320). Reprogramming of implant variables was necessary for reliable electrographic sensing (54 patients), programmed shock therapy (61 patients) and tachycardia detection rate (63 patients). Device activation for potential shock delivery occurred in 111 patients (55.5%) with actual shock delivery after ventricular tachycardia/fibrillation reconfirmation in 66 patients (33%). During follow-up study, there was a 1% arrhythmia mortality rate, 6.5% cardiac mortality rate and 10.5% total mortality rate. This study demonstrates that the programmable implantable pacemaker-cardioverter-defibrillator is effective in preventing arrhythmic death, yet reduces patient exposure to repeated shock therapy. Reprogramming is usually necessary during follow-up for optimal function.

Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study was undertaken to characterize the outcome of survivors of ventricular fibrillation with no or minimal structural heart disease who received an implantable cardioverter-defibrillator. BACKGROUND: The prognosis among survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities remains unclear. Since the advent of implantable cardioverter-defibrillators, this question takes on added importance. METHODS: This 10-center retrospective study provided information on 28 survivors of ventricular fibrillation (mean age 42 years) with minimal or no structural abnormalities who were treated with an implantable cardioverter-defibrillator. RESULTS: Ventricular tachyarrhythmias (polymorphic in all but one patient) were induced during baseline programmed stimulation in 39% of patients. During a median 30.6-month follow-up period after implantable cardioverter-defibrillator implantation, there were no cardiac deaths and two noncardiac deaths. Sixteen patients experienced 36 shock episodes (total 88 shocks). The majority of shocks were classified as "indeterminate"; one patient received 47 "spurious" shocks during one shock episode and each of four patients received one "appropriate" shock. Ventricular arrhythmias were not inducible in any of these latter four patients. CONCLUSIONS: Survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities receiving an implantable cardioverter-defibrillator have an excellent 3-year survival rate. The occurrence, albeit infrequent, of appropriate implantable cardioverter-defibrillator shocks in this group suggests that these patients have a potential risk of recurrent cardiac arrest whose fatal outcome may be avoided by implantable cardioverter-defibrillator therapy.

Impact of the implantable defibrillator on mortality: the axiom of overall implantable cardioverter-defibrillator survival.

As soon as it was established that the implantable cardioverter-defibrillator (ICD) effectively prevents sudden death, it became axiomatic that whether the ICD will prolong overall survival depends entirely on the population of patients to which it is applied. This axiom of overall ICD survival immediately reveals the only vital question that remains regarding usage of the ICD; namely, How does one select those patients in whom prevention of sudden death by the ICD will also prolong life? This axiom also reveals the essential futility of randomized trials now being conducted for the purpose of discerning the true efficacy of the ICD. Claims to the scientific high ground notwithstanding, if a study asks the wrong question from the beginning, then the design of that study (including whether the study is randomized or nonrandomized), is completely irrelevant. Ideally, funds now being spent on these randomized trials should be diverted to the design and initiation of more appropriate trials, trials that will teach us to select patients for the ICD more effectively. At the very least, however, we should recognize the problems inherent in the ongoing trials, so that when their results are finally published (and are loudly touted by whichever faction feels vindicated by them), we will not be carried away into inappropriate clinical behavior.

Long-term prognosis of patients undergoing electrophysiologic studies for syncope of unknown origin.

Long-term prognosis was determined in 70 patients with unexplained syncope who underwent electrophysiologic testing between April 1981 and April 1986. The electrophysiologic study had positive results in 37 patients--31 with ventricular tachycardia, 3 with supraventricular tachycardia and 3 with abnormal conduction. There was no significant difference in the 3-year actuarial recurrence rate between the positive and negative outcomes (32 vs 24%, respectively). At 3 years, patients with positive outcomes had higher rates of sudden death than patients with negative results (48 vs 9%, respectively, p less than 0.002). The 3-year total mortality rate was also markedly higher in patients with positive results than among those with negative outcomes (61 vs 15%, respectively, p less than 0.001). Multivariate analyses showed mortality to be independently associated with unsustained ventricular tachycardia on prolonged electrocardiographic monitoring. It was concluded that patients with electrophysiologically positive results had high rates of sudden death and total mortality that have not been previously well recognized.

Pharmacokinetics of moricizine HCl.

Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.

Outcome with implantable cardioverter-defibrillator therapy for survivors of ventricular fibrillation secondary to idiopathic dilated cardiomyopathy or coronary artery disease without myocardial infarction.

Patients with idiopathic dilated cardiomyopathy (IDC) constitute a minority among implantable cardioverter-defibrillator (ICD) recipients; how these patients fare versus those with coronary artery disease (CAD) is not well defined, nor is the mechanism of cardiac arrest recurrence, which may involve a more significant role of bradyarrhythmias. A retrospective multicenter study regarding outcome of ICD therapy was conducted in 224 patients with either IDC (n = 69; 31%) or CAD (n = 155; 69%) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Patients with IDC were significantly younger (mean age 57 vs 61 years in patients with CAD, p < 0.04) and less male predominant (64 vs 79% in patients with CAD, p < 0.02). There was no significant difference in mean left ventricular ejection fraction (0.27 in IDC patients vs 0.29 in CAD patients), but sustained ventricular tachycardia was induced less often in patients with IDC (21 vs 58% in CAD patients, p < 0.001). Bradycardia pacing, either by an ICD with bradycardia pacing ability or a separate bradycardia pacemaker, was available in only 15% of ICD implantees. During a median follow-up duration of 1.7 years for patients with IDC and 1.9 years for patients with CAD, estimated cumulative event rates were similar for any type shock (2-year incidence of 74% in IDC patients, 69% in CAD patients) as well as for appropriate shock (2-year incidence of 46% in IDC patients, 40% in CAD patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac arrhythmias. Syncope and stroke.

Cardiac arrhythmias are an important cause of neurologic symptoms. Bradyarrhythmias and tachyarrhythmias, by disrupting blood flow to the brain and causing cerebral hypoxia, can lead to loss of consciousness (and ultimately to cerebral necrosis or death). Thus cardiac arrhythmias must be considered as a potential cause in any patient presenting with syncope. For syncopal patients in whom the substrate for reentrant ventricular arrhythmias is found (that is, patients with ventricular dysfunction), management must be extremely aggressive because their near-term risk for sudden death is high, and conservative therapy is ineffective. Embolic stroke is a common result of atrial fibrillation. Several randomized trials now indicate that anticoagulation with low-dose warfarin is necessary, whenever possible, in patients with atrial fibrillation even in the absence of underlying valvular heart disease. Ongoing studies are evaluating the efficacy of aspirin in preventing embolic events.

How useful are implantable cardioverter-defibrillators?

When use of an implantable cardioverter-defibrillator (ICD) is being considered for a patient with life-threatening ventricular arrhythmias, the potential risks and benefits must be carefully weighed. The risks of implantation of an ICD should be minimal; however, a low risk is highly dependent on patient selection and other factors, and perioperative risk varies significantly from center to center. The referring physician should not hesitate to ask for perioperative mortality statistics from the referral center. The difficulty in successfully documenting the usefulness of the ICD is especially important today. As the ICD becomes more like the pacemaker, there will be a natural tendency to expand the use of this new technology to patients in lower-risk groups. Suboptimal methods were adequate to document the benefit of the ICD in high-risk patients, but similar methods may not be adequate for low-risk patients. Fortunately, the importance of performing adequate studies has been recognized, as evidenced by the several randomized controlled trials that have been undertaken to study the efficacy of the ICD in these new groups of patients.

The automatic implantable defibrillator.

The automatic implantable defibrillator is undergoing clinical trials in the United States. The device is a self-contained unit designed to detect malignant ventricular arrhythmias as they occur and to terminate them with a defibrillating current. Early clinical trials demonstrate its safety and effectiveness in terminating ventricular tachyarrythmias as well as its ability to reduce markedly the incidence of sudden cardiac death in high-risk patients. Continued refinements should further improve reliability and safety of the device.

An AVID dissent.

Despite declarations to the contrary, AVID appears to be a study that is seriously flawed. It is unfairly biased against the ICD; it entails unresolved ethical questions; and it poses a basic question that is inappropriate and subject to broad misinterpretation. Whatever the outcome of the study, harm is likely to follow unless the results are viewed very circumspectly. Rather than conducting such a study, we instead should be directing research funds toward identifying subsets of patients who might best benefit from the ICD. To optimize the use of the ICD, we need to do more patient selection, not less. We need to define subsets of patients in whom the prevention of sudden death by the ICD yields a prolonged overall survival, as well as subsets of patients in whom the device offers little or no benefit. AVID not only fails to do this, but it also threatens to inappropriately curtail (or less likely, to inappropriately expand) the proper use this efficacious tool, the ICD.

Evidence-based medicine and the implantable defibrillator.

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

Major clinical trials assessing the prophylactic use of amiodarone in patients with ventricular tachyarrhythmias.

The purpose of this article is to summarize and critique recently completed and ongoing clinical trials assessing the prophylactic use of amiodarone in patients with potentially life-threatening ventricular arrhythmias. Three of the trials compare amiodarone with an implantable cardioverter defibrillator.

Efficacy of phenytoin in suppressing inducible ventricular tachyarrhythmias.

We examined the efficacy of phenytoin in 69 of 87 consecutive patients undergoing serial electrophysiologic studies for inducible sustained ventricular tachycardia or fibrillation (VT/VF). In general, during the initial session lidocaine and procainamide were tested immediately after baseline electrophysiologic evaluation, followed by phenytoin and quinidine during the next two sessions, and then by additional drugs as needed. Once a successful drug was identified, all testing was stopped. Drugs that had failed in prior empiric trials were not tested. Twenty-five of the 87 patients (28.7%) had success in 258 serial drug tests. Sixty-nine patients were tested on phenytoin (mean serum level 13.4 +/- 5.0 mg/L), 52 after oral loading, and 17 after intravenous loading; the remaining 18 had either had prior successful testing with other drugs (9 patients) or had prior empiric failures with phenytoin (9 patients) or had prior empiric failures with phenytoin (9 patients). Nine of the 69 phenytoin trials were successful (13.0%), compared to 8 of 57 trials (14.0%) with procainamide, 4 of 37 trials (10.8%) with quinidine, and 0 of 41 trials (0%) with lidocaine. All nine patients who had successful phenytoin trials tolerated chronic doses adequate to maintain serum phenytoin levels equivalent to those measured during successful drug testing. For the 25 patients with successful drug trials, the mean follow-up was 14.5 +/- 9.8 months, and the actuarial incidence or recurrent VT/VF was 7 +/- 5% at 12 months. For the nine patients who had success with phenytoin the mean follow-up was 18.4 +/- 11.7 months, and the 12-month actuarial recurrence was 0%. Phenytoin is a well tolerated drug whose efficacy appears similar to most standard antiarrhythmic agents. If our results are confirmed in a larger, randomized study, routine testing with phenytoin should be considered.

Actuarial incidence and pattern of occurrence of shocks following implantation of the automatic implantable cardioverter defibrillator.

The actuarial incidence and pattern of occurrence of shocks were analyzed in 65 patients after implantation of the automatic implantable cardioverter defibrillator. During a mean follow-up of 25 +/- 21 months only one patient died suddenly, and this patient had a nonfunctioning device at the time of death. The long-term actuarial risk of death from any cause in the patients who received appropriate shocks was not significantly different than for the entire group. The 1- and 4-year cumulative risk of receiving any shock was 51 +/- 7% and 81 +/- 11%; of receiving an appropriate shock was 33 +/- 7% and 64 +/- 10%; of receiving a spurious shock was 17 +/- 5% and 21 +/- 6%; and of receiving an "indeterminate" shock was 19 +/- 6% and 52 +/- 10%. In 14 patients who were followed for 24 months without receiving an appropriate shock, the actuarial risk of receiving an appropriate shock was 29 +/- 14% during the next 24 months. The mean number of shocks delivered during appropriate episodes was 1.6 +/- 0.9, which was significantly lower than the mean of 4.0 +/- 2.0 shocks during spurious episodes (P less than 0.02). The mean number of shocks during indeterminate episodes was 1.7 +/- 1.5. Our data confirms the efficacy of the implantable defibrillator in preventing sudden death. The majority of patients with this device receive appropriate shocks during long-term follow-up, and the cumulative incidence of appropriate shocks increases steadily for at least 4 years. In contrast, the cumulative incidence of spurious shocks plateaus at about 12 months. Our data suggests that many "indeterminate" shocks actually appear to be appropriate.

The automatic implantable cardioverter-defibrillator in drug-refractory ventricular tachyarrhythmias.

STUDY OBJECTIVE: To assess the efficacy of the automatic implantable cardioverter-defibrillator in preventing sudden death in high-risk patients. DESIGN: Nonrandomized cohort study. SETTING: A university teaching hospital with 500 beds. PATIENTS: Consecutive sample of 78 patients with symptomatic, sustained ventricular tachyarrhythmias that were previously drug-refractory. INTERVENTIONS: Before February 1985, patients received treatment with the defibrillator and amiodarone if they presented with loss of consciousness (group A) and amiodarone alone if they did not lose consciousness (group C). After February 1985, because the availability of the defibrillator was severely curtailed, patients who lost consciousness received treatment with amiodarone alone (group B). MEASUREMENTS AND MAIN RESULTS: The risk for recurrent arrhythmias was similar between groups. The actuarial risk for sudden death in group B was 31% (95% confidence interval, 11% to 51%) at 1 and 2 years, a value that was significantly higher than that for group A (p less than 0.003) or group C (p less than 0.03). The risk for dying suddenly with the first recurrence was 0.78 in group B, a value that was significantly higher than that for group A (p less than 0.003) or group C (p less than 0.002). CONCLUSION: The defibrillator is highly effective in preventing sudden death in patients whose presenting arrhythmias caused loss of consciousness (group A). In patients whose presenting arrhythmias did not result in loss of consciousness (group C), initial treatment with the defibrillator appears unnecessary.