While the Chockalingham et al. (7) deserve recognition for their important observations, several limitations must be emphasized. First, owing to the nonrandomized nature of this retrospective analysis, there were significant differences in baseline clinical characteristics between the different treatment groups, including sex, history of syncope, baseline QTc, age at which therapy was started, and on-therapy heart rate. Three other aspects of the patient population need to be emphasized: 1) the baseline mean QTc for the study population was 472 ms, indicating that a significant proportion of the patient population (64%) had a normal or borderline QTc; 2) only 27% of the study population had had symptoms before therapy, roughly correlating with the number of patients with a prolonged QTc; and 3) a significant number of patients switched beta-blockers during follow-up, an observation capitalized upon by the investigators, as noted. Next, caution is needed in generalizing about preferred therapy for LQTS, as LQT1, 2, and 3 (and other subtypes) represent multiple syndromes with unique characteristics. Even within subtypes, risk and beta-blocker benefit may vary by mutation site, type, and other factors (5). For example, LQTS1 patients harboring C-loop mutations appear to respond more favorably to beta-blockers (5). Intriguingly, mutation of the sodium-channel blocker binding site can affect the ability of propranolol to block sodium current (13).