Cardiac Response to Enzyme-Replacement Therapy in Gaucher's Disease

Abstract

The New Eng land Jour nal of Medicine ond, this finding might represent a gain in specificity-that is, it might not be mistakenly positive in 1 of 40 infants who survived. Third, this finding might corroborate other research on QTc dispersion as a means of predicting arrhythmias in adults. 2-4 These hypotheses could be tested quite quickly with use of the available data. 1. Day CP, McComb JM, Campbell RW. QT dispersion: an indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990;63: 342-4. 2. Hii JT, Wyse DG, Gillis AM, Duff HJ, Solylo MA, Mitchell LB. Pre-cordial QT interval dispersion as a marker of torsade de pointes: disparate effects of class IA antiarrhythmic drugs and amiodarone. Circulation 1992; 86:1376-82. 3. Manttari M, Oikarinen L, Manninen V, Viitasolo M. QT dispersion as a risk factor for sudden cardiac death and fatal myocardial infarction in a coronary risk population. Heart 1997;78:268-72. 4. Goldner B, Brandspiegel HZ, Horwitz L, Jadonath R, Cohen TJ. Utility of QT dispersion combined with the signal-averaged electrocardiogram in detecting patients susceptible to ventricular tachyarrhythmia. Am J Car-diol 1995;76:1192-4. To the Editor: The study by Schwartz et al. raises important methodologic and editorial questions. Although the study is described as prospective, it appears that the elec-trocardiograms were analyzed on a retrospective basis. It is not stated when the retrospective electrocardiographic analysis was performed and by whom, or whether all the observers were unaware of the clinical data on the subjects-an essential prerequisite to avoid bias. Was the repro-ducibility of the measurements tested, given the subjective nature of measuring the QT interval? E RIC R OSENTHAL , M.D., M.R.C.P. Guy's Hospital London SE1 9RT, United Kingdom To the Editor: The study by Schwartz et al. has clearly advanced our knowledge of cardiac culprits in SIDS. However , the engineer in me is troubled each time the unit milliseconds is used with the QTc. The teaching of Bazett's formula (QTc equals the QT interval in seconds divided by the square root of the RR interval in seconds) to students and residents would be enhanced by using the correct units (seconds 1/2) and by not moving the decimal point. 1. Towbin JA, Friedman RA. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998;338:1760-1. The authors reply: To the Editor: Drs. Guntheroth and Spiers mention four prospective studies that found no increase in the QTc of infants who died of SIDS but do not give specific citations. We are unaware of any other prospective study with adequate statistical power to demonstrate or disprove differences between groups, nor did we criticize the study by Southall et al. 1 Why should infants who die of SIDS because of respiratory or other problems have a prolonged QT interval? A prolonged QT interval can be expected only in those who die of cardiac arrhythmia. Thus, one has to calculate whether the number of infants with a prolonged QT interval who died of SIDS exceeds that expected by chance alone according to the normal distribution of values for the QT interval. This is what happened in the study by Southall et al., as we discussed in our article. That "independent confirmation of [our] conclusions is still lacking" is a consequence of the fact that no one else has carried out a study with numbers comparable to ours. Of course we did not provide data on arrhythmias in the infants with a prolonged QT interval who died of SIDS; we only recorded a standard electrocardiogram for 30 seconds. The fact that thousands of infants have been monitored without evidence of arrhythmias means nothing if they were not at risk for death from cardiac causes. The statement by Guntheroth and Spiers that patients with the long-QT syndrome have multiple episodes of ar-rhythmia is irrelevant because it refers to children and adults. Our most recent data 2 indicate that the risk of death as a first cardiac event ranges between 2 and 20 percent according to the genotype and, a fact that is highly relevant here, is particularly high in the first year of life. 3 A child or adult who has an arrhythmic syncope loses consciousness and falls to the ground, whereas if an infant has a transient syncopal arrhythmia, where can he or she fall, since he or she is lying in a crib? A nonlethal episode could easily go unnoticed. Finally, the data from the International Long-QT Syndrome Registry indicate a very high degree of efficacy of beta-blockers in reducing life-threatening arrhythmias in patients with the long-QT syndrome. 3,4 If an infant is recognized to be at high risk for lethal arrhythmias because of a markedly prolonged QT interval, then prophylactic therapy with beta-blockers for at least several months is a safe and rational approach.