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.

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.

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.

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.

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.

Implantable cardioverter-defibrillator therapy in 300 patients with coronary artery disease presenting exclusively with ventricular fibrillation.

To determine outcomes of implantable cardioverter-defibrillator (ICD) therapy in a uniform population of survivors of sudden cardiac death, we used epicardial defibrillation lead systems to study 300 patients with coronary artery disease (CAD) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Operative (30-day) mortality, 2.7% overall, was lower (0.6%) in patients with ejection fractions (EF) > or = 0.30. Over a median follow-up of 1.9 years, cumulative actuarial shock incidence was similar in patients who underwent concomitant coronary artery bypass graft (CABG) surgery (38%) and in those who did not. The 2-year cumulative actuarial incidences of any or appropriate shocks were 65% and 38%, respectively. Sudden death survival at 2 years was 92.5% and 99.3% for patients with EFs < or = 0.30 and > 0.30, respectively. The total mortality rate was similar in shocked and in unshocked patients. Multivariate analysis identified EF and female gender as significant predictors of any and appropriate shock occurrence (all p values < or = 0.05) and EF as a significant predictor of sudden, cardiac, and total mortality (all p values < 0.03). We conclude that in CAD patients presenting exclusively with VF unassociated with acute myocardial infarction and treated with thoracotomy-requiring ICD therapy: (1) operative (30-day) mortality is minimal for patients with an EF > or = 0.30; (2) device use is high and sudden death rates low regardless of concomitant CABG; (3) low EF is a significant predictor of cumulative shock occurrence and mortality (sudden, cardiac, and total); (4) female gender may be a predictor of shock occurrence; and (5) similar mortalities and low sudden-death rates in shocked and nonshocked ICD patients imply that ICD therapy improves survival in shocked patients to a level observed in comparable patients in whom ventricular tachyarrhythmia does not recur.

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.

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.

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.

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)

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.

Reproducibility of successful drug trials in patients with inducible sustained ventricular tachycardia.

Patients whose inducible sustained ventricular tachycardia is suppressed during serial electrophysiological testing have a small but gradually increasing actuarial incidence of recurrent arrhythmias despite therapy with the "successful" drug. In an effort to improve the predictive value of a drug response, in 1990 we began to require that our full stimulation protocol be repeated successfully several times before considering a drug to be effective. In 23 consecutive patients who had inducible sustained ventricular tachycardia which was suppressed by at least one drug during invasive serial drug testing using a standard stimulation protocol, the identical stimulation protocol was performed six times during therapy with the initially successful drug (three trials on Day 1 and three trials on Day 2). Repeat trials were completed (i.e., either all six trials were successfully finished or sustained tachycardia was induced) for 29 initially successful drugs in these 23 patients. With 18 of these 29 initially successful drugs (62%), sustained ventricular tachycardia was eventually induced during repeat trials. The eventual drug failures could not be correlated with specific drugs tested, subtherapeutic or falling serum drug levels, marked fluctuations in autonomic tone, or changes in anatomic substrate. The proportion of patients failing each repeat trial was relatively constant: 4/29 (14%) failed Trial 2, 2/25 (8%) failed Trial 3, 7/23 (30%) failed Trial 4, 2/16 (13%) failed Trial 5, and 3/14 (21%) failed Trial 6. The increase in the cumulative incidence of drug failure during repeat trials was nearly linear. Inducibility of ventricular tachycardia appears to be a probability function; a successful drug study should not be regarded as an absolute phenomenon.

Long-term efficacy of an antitachycardia pacemaker and implantable defibrillator combination.

Antitachycardia pacemakers and implantable cardioverter defibrillators (ICD) were implanted in 14 patients to control recurrent hemodynamically stable ventricular tachycardia (VT). All patients underwent extensive preimplant testing in the electrophysiology laboratory documenting that in each patient at least 50 episodes of VT could be reliably terminated by an external model of the antitachycardia pacemaker. The burst scanning mode of antitachycardia pacing was used in all patients. ICDs were implanted solely as a back up should acceleration of VT occur, and all had high nonprogrammable rate cutoffs (mean 191 +/- 12 beats/min). During a mean follow-up of 25 +/- 6 months, 6,029 episodes of VT were treated in the 14 patients. Only 103 ICD discharges were required (approximately one discharge per 60 episodes of VT). Ten of the 14 patients received discharges from their ICDs. No deaths have occurred. All devices remain active and in the automatic mode. Thus, an antitachycardia pacemaker and ICD combination can safely and effectively terminate VT in highly selected patients who are subjected to extensive preimplant testing. In such patients, the vast majority of episodes of VT can be terminated with antitachycardia pacing, and only rarely is a discharge required from the ICD.