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The present investigation also offers a number of conceptual and practical advantages of ambulatory ECG-based risk assessment using TWA and HRT. Specifically, the authors demonstrated that valuable data on cardiac risk can be obtained without an exercise protocol in patients who have physical limitations or in whom it is difficult to increase heart rate because of medications. The inability to raise heart rate as a result of β-blockade therapy accounts for half of the indeterminate test results in studies using the Spectral Method of TWA analysis. In a meta-analysis, Chan et al determined that the predictive capacity of TWA for ventricular arrhythmic events was significantly weaker in TWA studies in which β-blockade therapy was withheld than in studies performed on current medications.8 Washout of β-blockade therapy at the time of TWA testing using the Spectral Method has been proposed as a major factor accounting for the negative outcomes of the Microvolt T-wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients (MASTER) trial and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) TWA substudy.5 Thus, the capacity to perform MMA-TWA testing without withdrawal of medications, as in the present investigation, constitutes a major advantage. We would like to raise 2 questions for the authors’ consideration. First, we would like to learn more specifics about the time of ECG monitoring following MI. They mentioned that the tests were performed >2 weeks after the event. It would be valuable to know the precise time period in terms of mean and range of weeks when the HRT and TWA measurements were made. This is a contemporary question of considerable debate. Exner and coworkers6 found no predictivity by any of the noninvasive risk stratifiers in current use, including HRT and TWA, when assessed at 2 to 4 weeks after MI. Only when the measurements were made at 10–14 weeks was prediction found. Alternatively, do the authors believe that it would be valuable to obtain these measurements both early after MI, to identify individuals who are at risk during the recovery phase, and later, after cardiac and neural remodeling occurs, when the substrate is more stable and longterm risk can be assessed? The second question relates to the status of the utility of HRT and TWA in guiding medical and device therapy. What information have the authors gathered to date with respect to the usefulness of these markers as therapeutic targets? Do they believe that these measurements can potentially guide rehabilitation during post-MI recovery? We commend the authors for this landmark investigation and look forward to learning about their experience and perspective regarding the issues we have raised.

circulation journal

Independent and Complementary Utility of Ambulatory Electrocardiogram-Based T-Wave Alternans and Heart Rate Turbulence for Predicting Major Cardiac Events in Patients After Myocardial Infarction