Designation and distribution of events in the Multicenter UnSustained Tachycardia Trial (MUSTT).

Patients with coronary artery disease, depressed left ventricular ejection fraction, and nonsustained ventricular tachycardia (VT) have a high mortality rate due to arrhythmic (arrhythmic death/cardiac arrest) and other cardiac causes. The Multicenter UnSustained Tachycardia Trial (MUSTT) investigated whether electrophysiologic study (EPS) was helpful in choosing drug or defibrillator therapy in patients induced into sustained VT. The events committee attempted to categorize follow-up events in patients in MUSTT and to present a detailed breakdown of events. A derivative of the Hinkle-Thaler classification was used, incorporating lessons from other multicenter studies. The committee was blinded to results of EPS and implantable cardioverter-defibrillator (ICD) or other antiarrhythmic therapy status of patients. The primary end point was cardiac arrest or death from arrhythmia. Secondary end points were death from all causes, cardiac causes, and spontaneous sustained VT. Classifications were death and cardiac arrest. Each was similarly divided as arrhythmic with 14 subcategories, e.g., unwitnessed or related to EPS and nonarrhythmic with 10 subcategories, e.g., ischemia. Terminal VF in progressive heart failure was considered nonarrhythmic. Events were reviewed by 2 members. Disagreements were resolved by the 2 members or, if needed, by the full committee. Of the 2,202 patients in MUSTT, there were 902 deaths. Sustained VT requiring cardioversion occurred in 182 patients. An additional 94 patients had resuscitated cardiac arrests. Events occurred in 1,027 patients, and all were reviewed. The 3 leading events were deaths that were classed as sudden/unwitnessed (23% of 902), due to progressive heart failure (22%), or due to noncardiovascular causes (18%). Arrhythmic deaths or cardiac arrests were highest in inducible patients randomized to no antiarrhythmic therapy; next were inducible patients receiving an ICD; and lowest were in patients who were noninducible. In conclusion, the classification system provided a detailed breakdown of events in consistent categories, showing utility for event analysis and interpretation and development of therapeutic strategies. The classifications assigned by the committee were used in all MUSTT outcomes reports, thus affecting all reported outcomes and overall interpretations of the MUSTT.

Influence of gender on arrhythmia characteristics and outcome in the Multicenter UnSustained Tachycardia Trial.

INTRODUCTION: Previous studies have demonstrated gender differences in risk of sudden death in patients with ischemic heart disease. The Multicenter UnSustained Tachycardia Trial (MUSTT) evaluated the ability of therapy guided by electrophysiologic (EP) testing to reduce mortality in patients with coronary disease, ejection fraction < or =40%, and spontaneous nonsustained ventricular tachycardia. METHODS AND RESULTS: We analyzed the influence of gender on results of EP testing and outcome of patients enrolled in MUSTT. Women made up 14% of the overall MUSTT population and were less likely than men to have inducible sustained randomizable ventricular arrhythmias (24% vs 36%, P < 0.001). Baseline characteristics differed between men and women. In randomized patients, women were older, more likely to have had an infarction within 6 months, more likely to have a history of heart failure, and more likely to have recent angina prior to enrollment than men (P < 0.05). In the EP-guided therapy group, there was no difference in implantable cardioverter defibrillator implantation rate in men and women (45% vs 53%, P = 0.38). There also were no significant gender influences on risk of arrhythmic death or cardiac arrest (2-year event rate 9% in women and 12% in men, adjusted hazard ratio 0.88) or overall mortality (2-year event rate 32% in women vs 21% in men, adjusted hazard ratio 1.51). CONCLUSION: The outcome and benefit of EP-guided therapy in this trial did not appear to be influenced by gender. However, due to the small numbers of women in the trial, small differences in outcome may not be apparent. Plans for future primary prevention trials should include careful risk stratification of women who less often have inducible sustained ventricular arrhythmias and better left ventricular function despite more frequent heart failure.

Relation of ejection fraction and inducible ventricular tachycardia to mode of death in patients with coronary artery disease: an analysis of patients enrolled in the multicenter unsustained tachycardia trial.

BACKGROUND: Fifty percent of deaths in patients with coronary disease occur suddenly. Although many factors correlate with increased mortality, there is little information regarding the influence of these factors on mode of death. As such, optimum methods to determine patients most likely to benefit from implantable defibrillator therapy are unclear. METHODS AND RESULTS: We analyzed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in all 1791 patients enrolled in the Multicenter Unsustained Tachycardia Trial who did not receive antiarrhythmic therapy. Total mortality and arrhythmic deaths/cardiac arrests occurred more frequently in patients with ejection fraction <30% than in those with ejection fraction of 30% to 40%. The percentage of deaths classified as arrhythmic was similar in patients with ejection fraction <30% or > or =30%. The relative contribution of arrhythmic events to total mortality was significantly higher in patients with inducible tachyarrhythmia (58% of deaths in inducible patients versus 46% in noninducible patients, P=0.004). The higher percentage of events that were arrhythmic among patients with inducible tachyarrhythmia appeared more distinct among patients with an ejection fraction > or =30% (61% of events were arrhythmic among inducible patients with ejection fraction > or =30% and only 42% among noninducible patients, P=0.002). CONCLUSIONS: Both low ejection fraction and inducible tachyarrhythmias identify patients with coronary disease at increased mortality risk. Ejection fraction does not discriminate between modes of death, whereas inducible tachyarrhythmia identifies patients for whom death, if it occurs, is significantly more likely to be arrhythmic, especially if ejection fraction is > or =30%.

Prognostic significance of nonsustained ventricular tachycardia identified postoperatively after coronary artery bypass surgery in patients with left ventricular dysfunction.

INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) occurs frequently in the postoperative period (< or = 30 days) after coronary artery bypass graft (CABG) surgery, a setting where many factors may play a role in its genesis. The prognosis of NSVT in this setting in patients with left ventricular (LV) dysfunction is unknown. This study was designed to assess its significance. METHODS AND RESULTS: We compared the outcome of untreated patients enrolled in the Multicenter Unsustained Tachycardia Trial with coronary artery disease (CAD), LV dysfunction, and NSVT identified postoperatively after CABG (n = 228; mean age 67 years, 84% males) versus nonpostoperative settings (n = 1,302; mean age 66 years, 85% males). Sustained monomorphic ventricular tachycardia was induced in 27% and 33% (P = 0.046) of patients with postoperative and nonpostoperative NSVT, respectively. The 2- and 5-year rates of arrhythmic events were 6% and 16%, respectively, in postoperative patients versus 15% and 29% in nonpostoperative patients (unadjusted P = 0.0020, adjusted P = 0.0082). The 2- and 5-year overall mortality rates were 15% and 36%, respectively, for postoperative patients versus 24% and 47% for nonpostoperative patients (unadjusted P = 0.0005, adjusted P = 0.027). Patients whose NSVT was identified early (<10 days) versus late (10-30 days) after CABG had significantly lower 2- (13% vs 23%) and 5-year (30% vs 52%) mortality rates (unadjusted P = 0.024, adjusted P = 0.018). CONCLUSION: In this population of patients with CAD and LV dysfunction, the occurrence of postoperative NSVT, especially within 10 days after CABG, portends a far better outcome than when it occurs in nonpostoperative settings. This suggests that in a such setting, NSVT represents a less specific risk factor for future events and should be considered when assigning risk and treatment of similar patients.