1.
Moss AJ, Zareba W, Hall WJ, et al.
Effectiveness and limitations of beta-blocker therapy in congenital long-QT
syndrome
Circulation 2000; 101 616-23
BACKGROUND: beta-blockers are routinely prescribed in congenital long- QT
syndrome (LQTS), but the effectiveness and limitations of beta- blockers in
this disorder have not been evaluated. METHODS AND RESULTS: The study
population comprised 869 LQTS patients treated with beta- blockers.
Effectiveness of beta-blockers was analyzed during matched periods before and
after starting beta-blocker therapy, and by survivorship methods to determine
factors associated with cardiac events while on prescribed beta-blockers.
After initiation of beta- blockers, there was a significant (P<0.001)
reduction in the rate of cardiac events in probands (0.97+/-1.42 to
0.31+/-0.86 events per year) and in affected family members (0. 26+/-0.84 to
0.15+/-0.69 events per year) during 5-year matched periods. On-therapy
survivorship analyses revealed that patients with cardiac symptoms before
beta-blockers (n=598) had a hazard ratio of 5.8 (95% CI, 3.7 to 9.1) for
recurrent cardiac events (syncope, aborted cardiac arrest, or death) during
beta- blocker therapy compared with asymptomatic patients; 32% of these
symptomatic patients will have another cardiac event within 5 years while on
prescribed beta-blockers. Patients with a history of aborted cardiac arrest
before starting beta-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7
to 35.5) for aborted cardiac arrest or death while on prescribed beta-blockers
compared with asymptomatic patients; 14% of these patients will have another
arrest (aborted or fatal) within 5 years on beta-blockers. CONCLUSIONS:
beta-blockers are associated with a significant reduction in cardiac events in
LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related
death continue to occur while patients are on prescribed beta-blockers,
particularly in those who were symptomatic before starting this therapy.

2.
Moss AJ, Robinson JL, Gessman L, et al.
Comparison of clinical and genetic variables of cardiac events associated with
loud noise versus swimming among subjects with the long QT syndrome
Am J Cardiol 1999; 84 876-9
Acute auditory stimuli and swimming activities are frequently associated with
syncope, aborted cardiac arrest, and death in the long QT syndrome (LQTS). We
investigated the clinical and genetic findings associated with cardiac events
precipitated by these arousal factors. The study population involved 195
patients with an index cardiac event associated with a loud noise (n = 77) or
swimming activity (n = 118). Patients with events associated with loud
auditory stimuli were older at their index event and were more likely to be
women than patients who experienced events during swimming-related activities.
Patients with an index event associated with loud noise were likely to have
subsequent events related to auditory stimuli; patients with an index event
associated with swimming were likely to have recurrent events related to
swimming or physical activities. Family patterning of auditory and swimming
and/or physical activity-related events was evident. Genotype analyses in 25
patients revealed a significant difference in the distribution of index
cardiac events by genotype (p <0.001), with all 19 patients with
swimming-related episodes associated with LQT1 genotype and 5 of 6 patients
with auditory-related events associated with LQT2 genotype. The clinical
profile and genotype findings of patients with LQTS who experience cardiac
events related to acute auditory stimuli are quite different from those who
experience events accompanying swimming activities.

3.
Schwartz PJ, Stramba-Badiale M, Segantini A, et al.
Prolongation of the QT interval and the sudden infant death syndrome [see
comments]
N Engl J Med 1998; 338 1709-14
BACKGROUND: The sudden infant death syndrome (SIDS) is multifactorial in
origin, but its causes remain unknown. We previously proposed that
prolongation of the QT interval on the electrocardiogram, possibly resulting
from a developmental abnormality in cardiac sympathetic innervation, may
increase the risk of life-threatening ventricular arrhythmias and contribute
to this devastating disorder. We prospectively tested this hypothesis.
METHODS: Between 1976 and 1994, we recorded electrocardiograms on the third or
fourth day of life in 34,442 newborns and followed them prospectively for one
year. The QT interval was analyzed with and without correction for the heart
rate. RESULTS: One-year follow-up data were available for 33,034 of the
infants. There were 34 deaths, of which 24 were due to SIDS. The infants who
died of SIDS had a longer corrected QT interval (QTc) than did the survivors
(mean [+/-SD], 435+/-45 vs. 400+/-20 msec, P<0.01) and the infants who died
from causes other than SIDS (393+/-24 msec, P<0.05). Moreover, 12 of the 24
SIDS victims but none of the other infants had a prolonged QTc (defined as a
QTc greater than 440 msec). When the absolute QT interval was determined for
similar cardiac-cycle lengths, it was found that 12 of the 24 infants who died
of SIDS had a QT value exceeding the 97.5th percentile for the study group as
a whole. The odds ratio for SIDS in infants with a prolonged QTc was 41.3 (95
percent confidence interval, 17.3 to 98.4). CONCLUSIONS: Prolongation of the
QT interval in the first week of life is strongly associated with SIDS.
Neonatal electrocardiographic screening may permit the early identification of
a substantial percentage of infants at risk for SIDS, and the institution of
preventive measures may therefore be possible.