Risk of Myocardial Ischemia in ICD Patients

Abstract & Commentary

By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.

Synopsis: Ischemia during stress echocardiography is an independent predictor of death and ICD therapy in patients with coronary heart disease at high risk of arrhythmic death.

Source: Elhendy A, et al. Association of Myocardial Ischemia with Mortality and Implantable Cardioverter-Defibrillator Therapy in Patients with Coronary Artery Disease At Risk of Arrhythmic Death. J Am Coll Cardiol. 2005;46:1721-1726.

In this paper, Elhendy and colleagues look at the value of inducible ischemia during stress echocardiography for predicting mortality and major ischemic events in ICD patients. Elhendy et al studied 90 consecutive patients with coronary artery disease who had received an ICD and underwent a stress echo exam. The stress echo was performed 3 ± 2 years after ICD implantation. The indications for stress testing were for the evaluation of chest pain in 50 patients, for a functional assessment after revascularization in 26 patients, and for investigation of reversible causes of heart failure in 14 patients. Most patients in the group had received an ICD for secondary prevention after an episode of aborted sudden cardiac death or sustained ventricular tachycardia (VT). Stress echocardiography was performed after beta blockers had been discontinued. ICDs were inactivated before the stress test in order to minimize the potential for shocks. Patients underwent either a symptom-limited exercise treadmill test or a graduated-dose dobutamine infusion. Images were acquired at rest, immediately after exercise/dobutamine stress, and in recovery. A 16-segment model was used for analysis of regional ventricular function, and an ejection fraction was calculated at each point. Ischemia was defined as new or worsened wall motion abnormalities during stress, associated with an increase in wall motion score > one grade in > one segment. Follow-up was obtained during scheduled visits to the ICD clinic. Patients who underwent surgical or percutaneous myocardial revascularization were censored at the time of recurrence. The end points of the trial were death or appropriate ICD therapy, which could include either antitachycardia pacing or shock for either ventricular tachycardia or ventricular fibrillation.

The study group included 90 patients, of whom 70% were men. The mean age was 65 ± 13 years. Most had a history of either cardiac arrest, syncope with inducible ventricular tachycardia, or sustained ventricular tachycardia. During the stress test, the target heart rate was reached in 81 of 90 patients. There were no episodes of death, myocardial infarction, ventricular fibrillation, or sustained VT during or shortly after the test. Ischemia was detected during the stress test in 44 of 90 patients.

During a mean follow-up of 2.8 ± 1.5 years, 5 patients died and 19 patients had appropriate ICD therapy. Thirteen patients underwent revascularization and were censored at that point. All of the 5 patients who died during follow-up had inducible ischemia, and 3 of these 5 deaths were classified as cardiac. Patients with events more often had a history of spontaneous sustained VT, inducible VT at electrophysiologic study, and inducible ischemia on stress echocardiograms. A Cox multivariate analysis model was used to assess independent predictors of events. Independent predictors of events in the Cox model included a history of spontaneous sustained VT (hazard ratio, 1.9), inducible VT in response to programmed stimulation (hazard ratio 1.7), and myocardial ischemia during stress echocardiography (hazard ratio, 2.1). Kaplan-Meier event-free survival curves in patients with or without ischemia showed a 3-year event-free survival above 90% in those without ischemia vs approximately 45% in those with ischemia.

Elhendy et al conclude that myocardial ischemia on stress echocardiography is associated with an increased risk of death and need for therapy in ICD patients. These data suggest, but do not prove, that aggressive treatment of ischemia can reduce the incidence of events in ICD patients.

Commentary

This paper highlights the important role of ischemia in the pathogenesis of sudden death in patients with coronary artery disease. When electrophysiologic studies were first introduced for the evaluation of patients with ventricular arrhythmias, much of the initial focus was on sustained monomorphic ventricular tachycardia in patients with large, fixed scars or aneurysms. In these patients, sustained VT could be easily reproduced with stimulation. However, a different pattern of electrophysiologic responses was seen in cardiac arrest survivors. Although some had inducible, sustained monomorphic VT, many had either no inducible arrhythmia or only polymorphic VT or ventricular fibrillation. Since those early studies used more aggressive treatment in patients with myocardial infarction and myocardial ischemia, it has decreased the numbers of patients with the large, dense scars likely to produce monomorphic ventricular tachycardia at random intervals. This has increased the importance of transient phenomena such as heart failure or ischemia as primary or contributing factors in sudden death.

A number of other observations support this concept. Among cardiac arrest victims in the community, ventricular tachycardia is now rarely documented by first responders, and either ventricular fibrillation or bradycardic rhythms are more commonly seen. In autopsy studies of cardiac arrest survivors, active coronary lesions are frequently seen, even in the absence of preceding chest pain. For example, in the ATLAS trial (Circulation. 2000;102:611-616), acute coronary findings were present in 54% of the patients with coronary artery disease who died suddenly. It has also been observed in the Coronary Artery Bypass Graft ICD Patch Trial that recently revascularized patients did not benefit from ICD therapy. Similar results were seen in the Multicenter Unsustained Tachycardia Trial in which patients who had their devices implanted shortly after surgical revascularization received no benefit from the ICD.

The data presented here emphasize that we need to provide comprehensive care to prevent sudden death. Although an ICD can reverse acute episodes, aggressive treatment to prevent both ischemia and heart failure is necessary for optimal patient outcomes.