Electrocardiographic abnormalities in infants born from mothers with autoimmune diseases--a multicentre prospective study.

OBJECTIVES: To assess the prevalence of congenital heart block (CHB) and electrocardiographic (ECG) abnormalities in infants of anti-Ro/SSA-positive women. METHODS: Sixty anti-Ro-positive and 36 anti-Ro-negative patients were prospectively followed before/during pregnancy and underwent weekly fetal echocardiography from 18th to 26th weeks of gestational age. Infants' ECG and/or ECG-Holter were performed at 1, 3, 6 and 12 months. ECG of 200 consecutive neonates were used as a healthy control group. RESULTS: One of 61 fetuses of anti-Ro-positive mothers developed CHB (20th week); another anti-Ro-positive baby developed second degree atrioventricular (AV) block (30th week). The prevalence of transient first degree AV block detected post-natally was significantly higher in the anti-Ro-positive group, in comparison with healthy controls (P = 0.002). No differences in corrected QT (QTc) interval prolongation prevalence (>/=440 ms) was observed between the anti-Ro-positive and -negative groups, but both were significantly higher than that of the control population (P < 0.001). ECG-Holter showed QTc prolongation in 59% of infants of anti-Ro-positive and in 60% of infants of anti-Ro-negative mothers. Holter QTc was >/=470 ms in four infants of anti-Ro-positive group and two of anti-Ro-negative group. Known acquired causes of QTc prolongation were excluded. CONCLUSIONS: This prospective study confirms the low occurrence of CHB in newborns from anti-Ro-positive mothers. ECG abnormalities (first degree AV block and QTc interval prolongation) are frequent in infants of mothers with autoimmune diseases, independently of maternal disease, autoantibody profile and treatment during pregnancy.

Gene-specific differences in the circadian variation of ventricular repolarization in the long QT syndrome: a key to sudden death during sleep?

BACKGROUND: In the long QT syndrome (LQTS) most life-threatening cardiac events occur in association with physical or emotional stress. However, a minority of patients dies suddenly during sleep; intriguingly, these sleep-related sudden deaths tend to cluster in families. The mechanism(s) underlying this phenomenon and the reason why it occurs in few selected families are unknown. Recently, some of the LQTS genes have been identified leading to three main subgroups (LQT1, LQT2, LQT3) associated respectively with mutations affecting the following ionic currents involved in the control of ventricular repolarization: I(Ks), I(Kr), I(Na). We have recently observed that cardiac events nighttime are rare in LQT1 and frequent in LQT3 patients. METHODS: We studied 26 LQTS patients all genotyped (11 LQT1, 9 LQT2, 6 LQT3) and 26 healthy controls matched by age and gender. Using a specific software, 24-hour ambulatory ECG recordings were performed and the QT interval was measured in order to allow comparison between QTc nighttime and daytime. RESULTS: The main finding is that while LQT1 patients show a trend for modest QTc shortening and LQT2 patients a trend for modest lengthening nighttime versus daytime, LQT3 patients show clear lengthening of the QTc nighttime. These changes are not explained by heart rate changes or by the use of beta-blockers. CONCLUSIONS: The marked tendency for further QT prolongation nighttime, which clearly increases arrhythmic risk, present among LQT3 patients and absent among LQT1 patients, provides an explanation for the gene-specific higher risk for sudden death during sleep for LQT3 compared to LQT1 patients.

Effects of beta-adrenergic blockade on dispersion of ventricular repolarization in newborn infants with prolonged QT interval.

A prolonged QT interval in the neonatal period and during infancy is associated with higher mortality rates, independently of the appearance of symptoms. This suggests the opportunity of a prophylaxis with beta-blockers in this population. QT interval dispersion is a useful clinical tool to predict the efficacy of antiadrenergic therapy. However, the effects of antiadrenergic interventions on QT interval and QT interval dispersion in newborns are not known. Standard 12-lead electrocardiograms were recorded in 14 newborns with prolonged QT interval, before and after oral administration of 2 mg/kg propranolol. Two electrocardiograms were also recorded in 14 newborns with normal QT intervals, matched for age and sex. In the control group no differences in heart rate, mean QTc, and QTc dispersion between the two recordings were observed. In the newborns with prolonged QT interval, propranolol did not change mean Qtc (from 467 +/- 21 to 451 +/- 26 msec; difference not significant), whereas it decreased spatial QTc dispersion, measured as the difference between the longest and shortest QTc in 12 different leads (from 69 +/- 23 to 42 +/- 13 msec; -39%; p = 0.001). This reduction was explained mainly by a shortening of the maximum QTc (from 504 +/- 25 to 476 +/- 18 msec; p = 0.005), with no change in the minimum QTc, and was not dependent on the slight change in mean QTc, as shown by the decrease in the coefficient of variation of QTc (standard deviation of QTc/mean QTc x 100) from 6.0 +/- 2.2 to 3.3 +/- 0.8 (p = 0.002). Of note, after propranolol, both measures of QTc dispersion reached the same levels observed in the control newborns. During the follow-up (> 2 years for nine of 14 infants), none of the infants had symptoms or arrhythmias. These results suggest that beta-adrenergic blockade with propranolol slightly affects mean QTc, but it significantly decreases the spatial dispersion of ventricular repolarization in newborn infants with a prolonged QT interval. This effect might modify the arrhythmogenic substrate, leading to a reduction of the susceptibility to life-threatening arrhythmias.