Multicenter UnSustained Tachycardia Trial - MUSTT

Description:

EP testing vs signal averaged ECG for mortality in sudden death.

Hypothesis:

Whether electrocardiographic characteristics of spontaneous nonsustained ventricular tachycardia can predict the inducibility of sustained ventricular tachycardia by programmed electrical stimulation in patients with coronary artery disease having abnormal ventricular function.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 2202
Mean Follow Up: 2 years
Mean Patient Age: 67
Female: 10

Patient Populations:

Coronary artery disease documented by cardiac catheterization or a clearly documented myocardial infarction (MI).
The most recent MI must have occurred at least four days before enrollment.
Left ventricular ejection fraction at or below .40, documented within one year of entry into the study
Nonsustained ventricular tachycardia not associated with symptoms (documented within six months of enrollment, and at least four days after the most recent infarction or revascularization procedure).
Complete a symptom-limited exercise test within six months.

Exclusions:

Nonsustained ventricular tachycardia attributable to antiarrhythmic drugs, myocardial ischemia, or other metabolic derangements.
History of syncope.
Sustained ventricular tachycardia or fibrillation more than 48 hours after the onset of acute MI
Systemic disease likely to be fatal in less than two years.
>80 years old.

Primary Endpoints:

Arrhythmic death or cardiac arrest.

Secondary Endpoints:

Overall mortality and cardiac mortality.
Reproducible (at least twice) induction of sustained uniform ventricular tachycardia, completion of the stimulation protocol. If more than 15 complexes of polymorphic ventricular tachycardia or flutter is reproducibly (at least twice) initiated with three extrastimuli, stimulation was stopped.

Drug/Procedures Used:

Either electrophysiologically guided therapy or no therapy. Drugs to be used are procainamide, quinidine, disopyramide, propafenone, sotalol, amiodarone as monotherapy, or in combinations of quinidine or disopyramide plus mexiletine and procainamide or qu

Concomitant Medications:

All patients in the conservative group and EP-guided group received ACE inhibitors and beta-blockers

Principal Findings:

Eligible patients with nonsustained ventricular tachycardia, left ventricular ejection fraction <40%, and coronary artery disease all had an EP study to determine whether they had inducible sustained ventricular tachycardia. If they had inducible ventricular tachycardia, they were randomized to either conservative treatment (with an ACE inhibitor and/or beta-blocker) or EP-guided treatment using the following drug sequence: (Round 1) propafenone or sotalol; (Round 2) Type IA agent and mexiletine or ICD or another round 1 agent; (Round 3) amiodarone, ICD, or another round 1 or 2 agent. Patients proceeded to the next round if a repeat electrophysiology test induced ventricular tachycardia, until ventricular tachycardia could not be induced.

A total of 2202 patients were enrolled in the study; EP study revealed 767 subjects with inducible ventricular tachycardia, from which 704 patients were randomized to the conservative group (n=353) and antiarrhythmic therapy group (n=351), and the two groups were well-balanced, with the following characteristics: age 67 years, men 90%, Caucasian 90%, duration of nonsustained VT 5 beats, left ventricular ejection fraction (LVEF) 30%, NYHA Class II/III 63%, history of myocardial infarction 95%, history of CABG 56%, beta-blocker use 45%, and ACE inhibitor use 70%. In the antiarrhythmic therapy group, 45% of patients received antiarrhythmic drugs, 46% received an ICD, and 7% received no therapy.

The mortality rate at 24- and 60-month follow-up showed that the antiarrhythmic therapy group (12% and 25%, respectively) performed significantly better than the conservative group (18% and 32%, respectively, P=0.043). This translated to a hazard ratio of 0.73 and a 23% relative risk reduction. Analyzing the secondary endpoint of all-cause mortality, there was a trend toward better performance in the antiarrhythmic therapy group; however, this did not reach statistical significance. In subgroup analysis, the patients who received an ICD clearly performed better than any other group, with 92% being alive at 60 months. In fact, when the ICD patients were removed from the antiarrhythmic therapy group, there was no significant difference between the conservative group and the antiarrhythmic drug group.

Conclusion

No statistically significant difference in the frequency or duration of spontaneous nonsustained ventricular tachycardia was seen between patients with and those without inducible sustained ventricular tachycardia. Rates of spontaneous tachycardia were slightly slower in patients with inducible ventricular tachycardia than in patients without inducible ventricular tachycardia (P = 0.047), but the difference was not clinically significant.

Interpretation:

In patients with asymptomatic nonsustained ventricular tachycardia, coronary artery disease, left ventricular ejection fraction <40%, and sustained inducible ventricular tachycardia, ICD devices appear to confer a mortality benefit and reduce the risk of arrhythmic death and cardiac arrest. Given the high cost of EP testing and the enormous number of patients with coronary artery disease, left ventricular systolic dysfunction, and asymptomatic nonsustained ventricular tachycardia, it is unclear whether the healthcare system will be able to shoulder this additional financial burden if all these patients were to be studied and treated. Electrocardiographic characteristics of spontaneous nonsustained ventricular tachycardia do not predict which patients with coronary artery disease will have inducible sustained ventricular tachycardia.

References:

1. Prog Cardiovasc Dis 1993;36:215-226. Study design.
2. Ann Intern Med 1996;125:35-39. NSVT and inducible VT.
3. Presented at the ACC 48th Annual Scientific Session, New Orleans, LA, 1999

Clinical Topics: Arrhythmias and Clinical EP, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents, Statins

Keywords: Risk, Coronary Artery Disease, Procainamide, Myocardial Infarction, Follow-Up Studies, Quinidine, Cardiac Catheterization, Electrocardiography, Cost of Illness, Electrophysiology, Tachycardia, Ventricular, Disopyramide, Electric Stimulation, Stroke Volume, Ventricular Function, Propafenone, Sotalol, Death, Sudden, Cardiac, Mexiletine, Exercise Test


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