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CLINICAL RESEARCH: HEART RHYTHM DISORDERS

Post-Exercise Assessment of Cardiac Repolarization Alternans in Patients With Coronary Artery Disease Using the Modified Moving Average Method

Michael P. Slawnych, MD, PhD^_*, Tuomo Nieminen, MD, PhD^,||, Mika Kähönen, MD, PhD^,, Katherine M. Kavanagh, MD^_*, Terho Lehtimäki, MD, PhD^,¶, Darlene Ramadan, RN^_*, Jari Viik, PhD, Sandeep G. Aggarwal, MD^_*, Rami Lehtinen, PhD^,,, Linda Ellis, BSc^_*, Kjell Nikus, MD^_**, Derek V. Exner, MD, MPH^_*,_* REFINE (Risk Estimation Following Infarction Noninvasive Evaluation) FINCAVAS (Finnish Cardiovascular Study) Investigators

^_* Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere, Finland
Department of Clinical Physiology and Medical School, University of Tampere, Tampere, Finland
Medical School, University of Tampere, Tampere, Finland
^|| Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
^¶ Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
^_** Heart Centre, Department of Cardiology, Tampere University Hospital, Tampere, Finland
Tampere University Hospital, Tampere, Finland
Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland
Tampere Polytechnic, University of Applied Sciences, Tampere, Finland

Manuscript received March 24, 2008; revised manuscript received December 1, 2008, accepted December 23, 2008.

^_* 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: We sought to evaluate the utility of T-wave alternans (TWA) assessment in the immediate post-exercise period to identify and validate cutpoints for the modified moving average (MMA) assessment method.

Background: The presence of TWA is associated with an increased risk of cardiovascular death (CVD). The immediate post-exercise period, where increased physiologic stress and minimal surface artifact coexist, appears ideal to implement the MMA method.

Methods: A test (n = 322) and validation cohort (n = 681) provided 1,003 patients with coronary artery disease (CAD). We assessed TWA immediately after exercise. The outcomes, CVD and mortality, were adjudicated independent of the TWA results.

Results: During 48 months of follow-up 85 deaths, 54 categorized as CVD (64%), were observed. A linear relationship between the magnitude of TWA and the risk of CVD was identified. As a continuous measure TWA voltage was equivalent to ejection fraction in predicting the risk of CVD. To facilitate clinical application, a sensitive, modest predictive accuracy (20 µV) and a specific, greater predictive accuracy MMA cutpoint (60 µV) were identified and validated. Each cutpoint was associated with a 2.5-fold greater risk of CVD, independent of other important variables, including ejection fraction.

Conclusions: Post-exercise assessment of TWA using the MMA method is a strong, independent predictor of risk in patients with CAD. The 20-µV cutpoint (87% sensitivity) appears to be most suitable in higher-risk patients, whereas the 60-µV cutpoint (95% specificity) appears more appropriate when TWA is used as a single screening test in those at lower risk. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; NCT00399503)

Key Words: myocardial infarction • repolarization • stress testing • ambulatory ECG • risk stratification

Abbreviations and Acronyms   CAD = coronary artery disease   CI = confidence interval   CVD = cardiovascular death   EF = ejection fraction   HR = hazard ratio   IQR = interquartile range   MMA = modified moving average   MI = myocardial infraction   ROC = receiver-operating characteristic   TWA = T-wave alternans

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