Correspondence

Prolongation of the QT Interval and SIDS

N Engl J Med 2000; 343:1896-1897December 21, 2000

Article

To the Editor:

In 1998, Schwartz et al. presented strong clinical evidence of an association between the sudden infant death syndrome (SIDS) and the long-QT syndrome.1 In a recent article, the same group describes an infant who nearly died of SIDS and in whom the long-QT syndrome was diagnosed (July 27 issue).2 On the basis of the 1998 study, routine electrocardiographic screening of all newborns was not recommended, but there is agreement that screening of infants at high risk is appropriate and justified.3

In 1997, we described the prenatal findings in infants who had a prolonged QT interval after birth; seven of nine had had fetal bradycardia.4 Persistent fetal sinus bradycardia (base-line fetal heart rate, <120 beats per minute) occurs in fewer than 3 percent of all infants born at term (unpublished data) and in 5 percent of those born after term.5 In our pediatric cardiology unit, we identified 18 singleton infants born between 1987 and 1999 who had familial long-QT syndrome (12 infants) or sporadic long-QT syndrome (6 infants) and a corrected QT interval (QTc) longer than 440 msec. Twelve of the infants had severe prolongation, with a QTc of 500 msec or more. All the infants had been born after 36 weeks of gestation, and none had malformations or signs of perinatal asphyxia. The results of cardiotocography were available for 17 of these infants and showed that there had been persistent fetal sinus bradycardia in 12 (71 percent).

Bradycardia in newborns was not an independent significant predictor of the long-QT syndrome in the 1998 study by Schwartz et al.1 However, in that study, both of the newborns who had a QTc greater than 500 msec and who died of SIDS had bradycardia on the postpartum electrocardiogram. We speculate that sinus bradycardia occurs most frequently in fetuses with severe prolongation of the QTc.

Ernst Beinder, M.D.
Tomas Grancay
Michael Hofbeck, M.D.
University Hospital of Erlangen–Nuremberg, 91054 Erlangen, Germany

5 References

1
Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998;338:1709-1714
Full Text | Web of Science | Medline

2
Schwartz PJ, Priori SG, Dumaine R, et al. A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med 2000;343:262-267
Full Text | Web of Science | Medline

3
Towbin JA, Friedman RA. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998;338:1760-1761
Full Text | Web of Science | Medline

4
Hofbeck M, Ulmer H, Beinder E, Sieber E, Singer H. Prenatal findings in patients with prolonged QT interval in the neonatal period. Heart 1997;77:198-204
CrossRef | Web of Science | Medline

5
Sherer DM, Onyeije CI, Binder D, Bernstein PS, Divon MY. Uncomplicated baseline fetal tachycardia or bradycardia in postterm pregnancies and perinatal outcome. Am J Perinatol 1998;15:335-338
CrossRef | Web of Science | Medline

To the Editor:

Schwartz et al. make the interesting observation that a 44-day-old infant who nearly died of cardiac causes had a mutation in the SCN5A gene, causing the long-QT syndrome. However, they then make a quantum leap and suggest that SIDS might be prevented by early detection of a prolonged QT interval. They state that, in this infant, “undeniably, neonatal electrocardiography would have led to a much earlier diagnosis and institution of therapy and almost certainly would have prevented the life-threatening episode.”

This statement is based on two assumptions that have yet to be proved. The first is that an electrocardiogram obtained earlier would also have shown a prolonged QT interval. This has not been established. We do not know that this child had an abnormally long QT interval. The second assumption is that therapy would have prevented the life-threatening episode. The authors argue that the mutation in the SCN5A sodium-channel gene (the mutation responsible for the LQT3 subtype of the long-QT syndrome) is a good candidate as a cause of SIDS because death classically occurs during sleep, in association with bradycardia. This makes sense, but they fail to point out that data from the international long-QT registry, according to a study of which Schwartz is an author, showed that beta-blockers in the SCN5A type of long-QT syndrome “did not eliminate aborted cardiac arrest or long-QT syndrome related sudden death.”1

Jon Skinner, M.D.
Green Lane Hospital, Auckland 1030, New Zealand

1 References

1
Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000;101:616-623
Web of Science | Medline

To the Editor:

Schwartz and colleagues are to be congratulated on their important studies of SIDS and QT-interval prolongation. However, as acknowledged by the authors, the high rate of false positives in screening for QT prolongation is problematic. In their recent report, the authors state that the number of false positives may be decreased by postponing electrocardiographic screening until the second or third week of life. However, since the definition of QT-interval prolongation is statistical (2.5 percent of the “normal” population has a prolonged QT interval), I am not sure how merely postponing electrocardiography will help reduce the rate of false positives. Moreover, are there any data indicating that a “normal” QT interval on a follow-up electrocardiogram is reassuring?

If universal screening were implemented, 98 or 99 infants would require treatment for each baby saved. Schwartz and colleagues never discuss the potentially enormous emotional toll on the families of the infants who would be treated but who would ultimately not die of SIDS: 98 to 99 percent of families would be expecting a time bomb when none was present.

Finally, the use of beta-blocker therapy in approximately 100,000 babies annually (2.5 percent of the approximately 4 million babies born annually in this country) might well magnify uncommon adverse effects and problems. We can justify the medical treatment of 98 or 99 infants to save 1 only if the risks of treatment are extremely low. Only a well-designed clinical trial can answer this question adequately. Unfortunately, genetic testing, though more specific than electrocardiographic screening, remains a research tool at present.1

Colin K. Phoon, M.D.
New York University School of Medicine, New York, NY 10016

1 References

1
Towbin JA, Friedman RA. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998;338:1760-1761
Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: In response to Beinder and colleagues: a lower-than-normal heart rate in children is indeed one of the (minor) diagnostic criteria for the diagnosis of the long-QT syndrome.1,2 It is indeed likely that sinus bradycardia in fetuses might often be associated with a markedly prolonged QT interval; it may alert physicians early on to the possible presence of the long-QT syndrome and warrant postpartum electrocardiography. However, a normal heart rate does not rule out the long-QT syndrome.

In response to Skinner: day-to-day variability in the QT interval in the long-QT syndrome is well known,3 but not to the extent of oscillation between a QTc of 650 msec and normal values. During five years of follow-up in the child we described, every electrocardiogram showed that the QTc was greater than 500 msec. Our experience with thousands of patients with the long-QT syndrome suggests that it is very unlikely that an earlier electrocardiogram might have been normal.

We did not argue that the sodium-channel gene SCN5A is a good candidate as a cause of the long-QT syndrome; we simply mentioned some interesting features that are consistent with typical deaths due to SIDS. We have evidence that mutations on the genes that are associated with the long-QT syndrome and that encode potassium channels can also cause SIDS. Skinner also misquotes our collaborative study on beta-blockers.4 The statement quoted refers to the entire population and not specifically to the group with the LQT3 subtype of the syndrome. Furthermore, only one (3.5 percent) of the patients with the LQT3 subtype who were receiving treatment with beta-blockers died. Beta-blockers are much more effective in patients with the LQT1 or LQT2 subtype than those with the LQT3 subtype.5

In response to Phoon: given the skewed distribution of the QT interval, most of the 2.5 percent of QT intervals that are “prolonged” become close to 440 to 450 msec as time passes after birth. As with any other disease, the finding of moderate abnormalities should prompt a reassessment of the measurement and not the immediate initiation of therapy.

To treat more people than necessary is unavoidable and well accepted in preventive medicine (as in the case of cholesterol-lowering drugs, antihypertensive agents, and even thrombolysis), despite potential adverse effects.

The “emotional toll” is largely dependent on what the physician tells the parents: discussion of a safety measure against an unlikely possibility seems preferable to the devastating tragedy of a death that could have been prevented.

Peter J. Schwartz, M.D.
Policlinico San Matteo, 27100 Pavia, Italy

Silvia G. Priori, M.D., Ph.D.
Fondazione Salvatore Maugeri, 27100 Pavia, Italy

Marco Stramba-Badiale, M.D., Ph.D.
Istituto Auxologico Italiano, 20149 Milan, Italy

5 References

1
Schwartz PJ. Idiopathic long QT syndrome: progress and questions. Am Heart J 1985;109:399-411
CrossRef | Web of Science | Medline

2
Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome: an update. Circulation 1993;88:782-784
Web of Science | Medline

3
Schwartz PJ. The long QT syndrome. Armonk, N.Y.: Futura Publishing, 1997.

4
Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000;101:616-623
Web of Science | Medline

5
Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation (in press).

Citing Articles (3)

Citing Articles

1
Silvia Comani, Peter Van Leeuwen, Silke Lange, Daniel Geue, Dietrich Grönemeyer. (2009) Influence of gestational age on the effectiveness of spatial and temporal methods for the reconstruction of the fetal magnetocardiogram. Biomedizinische Technik/Biomedical Engineering 54:1, 29-37
CrossRef
2
Silvia Comani, Giovanna Alleva. (2007) Fetal cardiac time intervals estimated on fetal magnetocardiograms: single cycle analysis versus average beat inspection. Physiological Measurement 28:1, 49-60
CrossRef
3
Uwe Schneider, Jens Haueisen, Markus Loeff, Nikolai Bondarenko, Ekkehard Schleussner. (2005) Prenatal diagnosis of a long QT syndrome by fetal magnetocardiography in an unshielded bedside environment. Prenatal Diagnosis 25:8, 704-708
CrossRef