High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment "failures".

BACKGROUND: Beta-blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite beta-blocker therapy have not been ascertained. METHODS AND RESULTS: This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with beta-blocker and followed up for a median time of 10 years. Before beta-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After beta-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22; P=0.001). None of the 26 patients with CA before beta-blocker had CA/sudden death on beta-blockers. CONCLUSIONS: beta-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. beta-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "beta-blocker failures." beta-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or beta-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.

[Cardiac syncope in children]. / Malaises et syncopes d'origine cardiaque chez l'enfant.

Syncope is a frequent and usually benign problem in childhood. Vasovagal syncope is the most likely etiology and is well recognized. However, syncope can herald a potentially lethal problem, so that routine evaluation including a 12-lead standard ECG should be performed in all cases. Worrying features requiring further investigations include syncope during emotion or exercise, history of familial syncope or sudden death in the young, and any abnormality on clinical exam or ECG tracings. Structural cardiac abnormalities that may cause syncope include cardiac obstructions, pulmonary hypertension, and myocardiopathy. Children with congenital heart disease who experienced syncope should always be referred to a specialist. Primary arrhythmias which are easily diagnosed on ECG are complete atrio-ventricular block and Wolff-Parkinson-White syndrome. "Channelopathies" such as the long OT syndrome and catecholaminergic ventricular tachycardia are increasingly recognized in children, carry a high risk of sudden death and deserve a complete work up, including familial screening and lifelong treatment with beta-blockers.

Patients operated for tetralogy of fallot and with non-sustained ventricular tachycardia have reduced heart rate variability.

BACKGROUND: To study heart rate variability (HRV) in patients operated for tetralogy of Fallot (ToF) and to identify any correlation between HRV and ventricular tachycardia (VT). PATIENTS AND METHODS: We studied HRV in 23 consecutive patients operated for ToF (mean age 14 +/- 6.6 years; mean follow-up 10.6 +/- 5.2 years). Seven patients had non-sustained VT on Holter monitoring. Two control groups were included: 18 healthy subjects and 15 patients operated for other congenital heart disease. There were no differences in age, age at surgery (in the operated groups), follow-up, and mean heart rate between the three groups. Four time and four frequency domain indices were calculated: mean duration of RR intervals, standard deviation of all RR intervals (SD), square root of the mean squared differences of successive RR intervals (r-MSSD), percent of differences between adjacent RR intervals (pNN50), total power (TP), low frequency (LF), high frequency (HF), and LF/HF ratio. RESULTS: HRV indices were identical in the two control groups but were significantly reduced in patients with ToF. Within the patients who had been operated on for ToF, HRV indices were significantly lower in the seven with non-sustained VT than in those without arrhythmias: SD (95 +/- 15 vs. 135 +/- 54 ms; p = 0.01), r-MSSD (26 +/- 9 vs. 45 +/- 20 ms; p = 0.03), pNN50 (4.4 +/- 3.4 vs. 16.5 +/- 12.5%; p = 0.001) and HF (111 +/- 97 vs. 352 +/- 291 ms(2); p = 0.009). Using stepwise multivariate regression analysis, pNN50, age at surgery, degree of pulmonary regurgitation and higher right/left ventricular ratio were independent predictive variables for VT (p < 0.0001; r(2) = 0.85). CONCLUSIONS: ToF patients, particularly those with ventricular arrhythmias, have significant impairment of sympatho-vagal balance, characterized by a reduction of vagal drive.

Can we predict 22q11 status of fetuses with tetralogy of Fallot?

OBJECTIVE: To determine if chromosome 22q11 deletion status can be predicted in fetuses with tetralogy of Fallot as regards additional phenotypic anomalies. METHODS: One hundred and fifty-one consecutive fetuses with tetralogy of Fallot without or with pulmonary atresia were screened for 22q11 deletion. Additional echographic features [increased nuchal translucency (NT), intrauterine growth retardation (IUGR), polyhydramnios, extracardiac malformations, pulmonary arteries abnormalities] were noted. RESULTS: Twenty-five fetuses had a 22q11 deletion (16.6%). Increased NT, polyhydramnios and IUGR were more frequent in fetuses with 22q11 deletion as well as pulmonary arterial abnormalities. When these different features were present in the same fetus with tetralogy of Fallot, 22q11 deletion can be predicted with a sensitivity of 88%. CONCLUSION: Simple echographic features can help to predict 22q11 status in fetuses with tetralogy of Fallot. This may improve the efficiency of prenatal screening for this defect.