To the Editor:

Abstract

in the Journal 1 rekindles a lingering ambivalence about 2 points: (1) whether or not one should study patients for microvolt T-wave alternans (MTWA) after discontinuing b-adrenergic blockade (BB); and (2) whether perturbations of the T-wave attributes, including T-wave amplitude, impact the magnitude of the MTWA. If one considers the known effects of BB on T-wave amplitude, "a triangle of concerns" inevitably emerges. The well-meaning motivation of discontinuing BB prior to assessing patients for MTWA is rooted in the worry that patients on such therapy will not attain the necessary rise of heart rate during exercise stress testing, leading thus to an indeterminate MTWA test. However, while a negative MTWA test leaves one reassured that a patient, even in the absence of presumably "protective" BB, tests negative, a positive test is associated with a disturbing afterthought that, had the patient been tested while on his/her maintenance BB therapy, the test would turn out to be negative. There is literature after all attesting to this, cited by the authors. The other issue of the effect of BB on the T-wave amplitude, not tackled by the authors, relates to a speculation that MTWA magnitude is T-wave amplitude dependent, and thus the former should be normalized to the latter. 2 Chan et al. in their meta-analysis from studies spanning 28 years and involving almost 4,000 patients found heterogeneity in the predictive value for arrhythmic events of a positive and indeterminate MTWA test in their assembled study population, in the sense that a "stronger" predictive value was found in the patients who underwent testing without their BB therapy being previously withheld (pooled RR = 5.39, 95% CI: 2.68-10.84; P < 0.001), as compared to the patients who had the test after BB was stopped (pooled RR = 1.40, 95% CI: 1.06-1.84; P = 0.02). The authors concluded that this large difference in predictability of the test in these two subpopulations could be explained by the modulation of MTWA testing result exerted by BB. This makes a lot of sense, as per reasoning that if a patient tests MTWA positive, "in-spite" of the ameliorating effect of BB, he/she must be at high risk for future arrhythmic outcome; thus BB cuts down on the false positive MTWA results in patients "unprotected" by BB, and thus enhances specificity of the test. One point that remains untested is whether BB alters the T-wave amplitudes and thus exerts an effect on the magnitude of MTWA which in turn influences "partially" the characterization of the test as positive or negative, based on the 1.9 μV threshold. This could not be tested by the authors of the present study since they did not have patient-level data. However, their conclusions could be corroborated in future prospective studies, where the effect of T-wave amplitude on the magnitude of MTWA, independent of the underlying electrophysiologic derangement, could also be ascertained. This needs to be clarified in light of previous studies showing that BB alters the amplitude of T-waves in normal subjects, a...