Relation of T-wave alternans to mortality and nonsustained ventricular tachycardia in patients with non-ST-segment elevation acute coronary syndrome from the MERLIN-TIMI 36 trial of ranolazine versus placebo

Am J Cardiol. 2014 Jul 1;114(1):17-23. doi: 10.1016/j.amjcard.2014.03.056. Epub 2014 Apr 16.

Abstract

We explored the utility of T-wave alternans (TWA) in predicting mortality in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Maximum TWA was calculated using Modified Moving Average method from continuous electrocardiographic recordings in patients with left ventricular ejection fraction <40% and ventricular tachycardia (VT) ≥4 beats during index hospitalization or sudden cardiac death during the follow-up year and age- and sex-matched controls in the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction (MERLIN-TIMI) 36 trial. All patients received standard therapy for NSTEACS plus ranolazine (n = 109) or placebo (n = 101). Median follow-up was 1 year. Baseline clinical characteristics did not differ between patients with elevated TWA (≥47 μV) compared with lower levels. Patients with TWA ≥47 μV at admission had increased risk of total mortality (adjusted odds ratio [ORadj] 2.35, p = 0.04) during follow-up and VT ≥4 beats (ORadj 2.70, p = 0.01) during hospitalization with a trend toward increased cardiovascular death risk (ORadj 2.18, p = 0.07) during follow-up. In patients receiving placebo, TWA ≥47 μV on day 6 was associated with increased risk of total mortality (OR 4.12, 95% confidence interval 1.25 to 13.64, p = 0.02) and cardiovascular death (OR 4.73, p = 0.01) during follow-up. No deaths occurred among patients with TWA ≥47 μV assigned to ranolazine. In conclusion, in patients with NSTEACS and left ventricular ejection fraction <40%, TWA ≥47 μV early after admission is associated with increased risk of mortality at 1 year and with nonsustained VT during hospitalization. TWA may be useful in risk estimation in patients with NSTEACS. The possibility that TWA may serve as a therapeutic target deserves further exploration.

Trial registration: ClinicalTrials.gov NCT00099788.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / therapeutic use
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / mortality*
  • Acute Coronary Syndrome / physiopathology*
  • Aged
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / mortality*
  • Arrhythmias, Cardiac / physiopathology*
  • Brugada Syndrome
  • Cardiac Conduction System Disease
  • Death, Sudden, Cardiac
  • Electrocardiography
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Heart Conduction System / abnormalities*
  • Heart Conduction System / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Piperazines / therapeutic use
  • Placebos
  • Predictive Value of Tests
  • Ranolazine
  • Risk Factors
  • Tachycardia, Ventricular / drug therapy
  • Tachycardia, Ventricular / mortality*
  • Tachycardia, Ventricular / physiopathology*
  • Treatment Outcome

Substances

  • Acetanilides
  • Enzyme Inhibitors
  • Piperazines
  • Placebos
  • Ranolazine

Associated data

  • ClinicalTrials.gov/NCT00099788