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CLINICAL RESEARCH: POST-INFARCTION RISK

Noninvasive Risk Assessment Early After a Myocardial Infarction

The REFINE Study

Derek V. Exner, MD, MPH^_*,,1,_*, Katherine M. Kavanagh, MD^_*,, Michael P. Slawnych, MD, PhD^_*, L. Brent Mitchell, MD^_*, Darlene Ramadan, BSN^_*, Sandeep G. Aggarwal, MD^_*, Catherine Noullett, RN^_*, Allie Van Schaik, RN, Ryan T. Mitchell, BSc^_*, Mariko A. Shibata, BSc^_*, Sajad Gulamhussein, MD, James McMeekin, MD^_*, Wayne Tymchak, MD, Gregory Schnell, MD^_*, Anne M. Gillis, MD^_*,2, Robert S. Sheldon, MD, PhD^_*, Gordon H. Fick, PhD, Henry J. Duff, MD^_*,2 for the REFINE Investigators

^_* Libin Cardiovascular Institute of Alberta, Calgary, Canada
Department of Community Health Sciences, University of Calgary, Calgary, Canada
Department of Medicine, University of Alberta, Edmonton, Canada.

Manuscript received May 23, 2007; revised manuscript received August 3, 2007, accepted August 13, 2007.

^_* Reprint requests and correspondence: Dr. Derek V. Exner, 3330 Hospital Drive NW, Room G208, Calgary, Alberta, Canada T2N 4N1. (Email: exner{at}ucalgary.ca).

Objectives: This study sought to determine whether combined assessment of autonomic tone plus cardiac electrical substrate identifies most patients at risk of serious events after myocardial infarction (MI) and to compare assessment at 2 to 4 weeks versus 10 to 14 weeks after MI.

Background: Methods to identify most patients at risk of serious events after MI are required.

Methods: Patients (n = 322) with an ejection fraction (EF) <0.50 in the initial week after MI were followed up for a median of 47 months. Serial assessment of autonomic tone, including heart rate turbulence (HRT), electrical substrate, including T-wave alternans (TWA), and EF was performed, interpreted blinded, and categorized using pre-specified cut-points where available. The primary outcome was cardiac death or resuscitated cardiac arrest. All-cause mortality and fatal or nonfatal cardiac arrest were secondary outcomes.

Results: Mean EF significantly increased over the initial 8 weeks after MI. Testing 2 to 4 weeks after MI did not reliably identify patients at risk, whereas testing at 10 to 14 weeks did. The 20% of patients with impaired HRT, abnormal exercise TWA, and an EF <0.50 beyond 8 weeks post-MI had a 5.2 (95% confidence interval [CI] 2.4 to 11.3, p < 0.001) higher adjusted risk of the primary outcome. This combination identified 52% of those at risk, with good positive (23%; 95% CI 17% to 26%) and negative (95%; 95% CI 93% to 97%) accuracy. Similar results were observed for the secondary outcomes.

Conclusions: Impaired HRT, abnormal TWA, and an EF <0.50 beyond 8 weeks after MI reliably identify patients at risk of serious events. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; http://www.clinicaltrials.gov/ct/show/NCT00399503?order=1; NCT00399503 [ClinicalTrials.gov] )

Abbreviations and Acronyms   AUC = area under the receiver-operator characteristic curve   BRS = baroreflex sensitivity   CI = confidence interval   ECG = electrocardiograph/electrocardiographic   HRT = heart rate turbulence   HRV = heart rate variability   ICD = implantable cardioverter-defibrillator   LV = left ventricular   LVEF = left ventricular ejection fraction   MI = myocardial infarction   TWA = T-wave alternans   VPB = ventricular premature beats

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