Electrophysiologic Testing to Identify Patients at Risk for Sudden Death
abstract & commentary
Synopsis: Electrophysiologic testing can be used to assess the prognosis of patients with coronary disease, left ventricular dysfunction, and nonsustained VT.
Source: Buxton AE, et al. N Engl J Med 2000:342: 1937-1945.
This provides further information from the multicenter Unsustained Tachycardia Trial (MUSST). The primary objective of MUSST was to determine if electrophysiologically guided drug therapy improved survival in patients with coronary artery disease (CAD), prior myocardial infarction (MI), left ventricular dysfunction, and spontaneous unsustained and inducible sustained ventricular tachycardia (VT). The primary objective implicitly assumed that induction of sustained VT was a marker for high risk. A secondary objective of MUSST was to evaluate the validity of that assumption.
In MUSST, patients who met the clinical criteria listed above underwent electrophysiologic testing using a standard protocol. If sustained monomorphic VT or sustained ventricular fibrillation with a protocol limited to two extrastimuli was induced, a consenting patient was randomly assigned to either electrophysiologically guided drug or device therapy or to no antiarrhythmic therapy. If an arrhythmia was not induced, the patient was followed without antiarrhythmic therapy in a registry. A comparison between these two untreated groups provided the data to test the secondary hypothesis that the baseline electrophysiologic study could be used to define a high-risk subgroup.
This paper provides data from 353 patients with inducible VT randomly assigned to no antiarrhythmic therapy and 1397 registry patients. There were several differences between the two groups. Registry patients were more likely to be women (16% vs 10%) and to have undergone coronary bypass surgery (63% vs 56%). The patients with induced VT were more likely to have a clinical history of MI (94% vs 87%). At the time of hospital discharge, 51% of the patients with inducible VT were receiving a beta-blocker vs. only 35% of the registry patients.
At discharge, among the patients with the inducible VT, 2% were receiving an antiarrhythmic drug and 2% had received an implantable cardioverter defibrillator (ICD). The corresponding values for the registry patients were 3% and 0.2%.
The primary end point in MUSST was cardiac arrest or arrhythmic death. After two and five years, the rates for the primary end points were 12% and 24% in the registry vs. 18% and 32% in the inducible VT group (unadjusted P = 0.005). Total mortality rates after two and five years were 21% and 44% in the registry vs. 28% and 44% in the inducible VT group.
The electrophysiologic findings in the registry group were analyzed to see if induced arrhythmias other than sustained monomorphic VT had prognostic significance. In the registry group, 661 patients had no VT of any type induced, 531 patients had nonsustained VT induced, and 205 patients had sustained polymorphic VT or ventricular fibrillation induced with triple extrastimuli. There were no significant differences in outcome when registry patients were subclassified based on these responses to stimulation.
Buxton and associates conclude that electrophysiologic testing can be used to assess the prognosis of patients with CAD, left ventricular dysfunction, and nonsustained VT.
Comment by John P. DiMarco, MD, PhD
The results of the randomized portion of MUSST were published last year (N Engl J Med 1999;341:1882-1890). The two most important observations were that electrophysiologically guided therapy decreased cardiac arrest and arrhythmic death in the randomized group and that all the benefit was observed in patients who received an ICD rather than antiarrhythmic drugs.
This paper deals with the prognostic value of the electrophysiologic study performed in patients with CAD, left ventricular dysfunction, and nonsustained VT. Although Buxton et al are technically correct in their claim that electrophysiologic study results are a predictor of outcome in this patient population, the results are of only limited clinical value.
When electrophysiologic testing was first introduced for patients with ventricular arrhythmias more than 25 years ago, it was observed that a higher proportion (> 90%) of patients with recurrent, sustained monomorphic VT could have their arrhythmia replicated during an electrophysiologic study. Many of these early patients had a long history of VT, had large aneurysms or scars, and could have their VT reproduced by relatively simple stimulation protocols. Limited control data showed that monomorphic VT was a rare response to programmed stimulation among patients without a history of VT. The early hope was that induction of sustained VT by stimulation would be a sensitive and highly specific finding. When cardiac arrest survivors were tested with the same stimulation protocols, a much lower proportion, only 50-70%, had an inducible sustained arrhythmia and, in many cases, polymorphic VT or ventricular fibrillation was the arrhythmia induced. As therapy for acute MI has improved, the characteristics seen in a contemporary VT population have changed. Large discrete aneurysms are less commonly found, more aggressive stimulation protocols are required to induce VT, and the arrhythmias are often more rapid and less well tolerated. However, it was still hoped that failure to induce VT would be a good prognostic sign. In this paper, Buxton et al note that 88% of patients without inducible monomorphic VT have been free of cardiac arrest or arrhythmic death after two years. However, 82% of the untreated patients with inducible VT were also doing well. Although the proportions are statistically different due to the power conferred by the large study group, this difference is too small to be useful for clinical decisionmaking. Rather, given the five-year mortalities of 44% and 48%, both groups should be considered to be at high risk. The electrophysiologic findings become just another risk factor of modest significance.
Prevention of CAD and early treatment of MI remain the most promising approaches for lowering the sudden death rate in the general population. Once MI has occurred and severe left ventricular dysfunction is present, the MUSST data indicate that general strategies that can be applied to all patients offer more hope than a strategy based on electrophysiologic testing. Hopefully, ongoing studies on the use of drugs and ICD therapy for patients with low ejection fractions and heart failure will provide new data that can guide clinicians dealing with these patients.
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