P Coumel

BACKGROUND: The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific. METHODS AND RESULTS: We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with ss-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. CONCLUSIONS: Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches.

BACKGROUND: Primary ventricular tachyarrhythmias are rarely seen in children. Among them, catecholaminergic polymorphic ventricular tachycardia has a poor spontaneous outcome. Its diagnosis is often delayed after the first symptoms, which is unacceptable because treatment with the appropriate beta-blocker prevents sudden death. METHODS AND RESULTS: We observed 21 children (mean +/- SD age, 9.9 +/- 4 years) at the time of the diagnosis who had no structural heart disease and a normal QT interval on routine ECG. They were referred for stress- or emotion-induced syncope related to ventricular polymorphic tachyarrhythmias. The arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvoes of bidirectional and polymorphic tachycardia susceptible to degeneration into ventricular fibrillation, was reproducibly induced by any form of increasing adrenergic stimulation. There was a familial history of syncope or sudden death in 30% of our patients. On receiving therapy with the appropriate beta-blocker, the patients' symptoms and polymorphic tachyarrhythmias disappeared. During a mean follow-up period of 7 years, three syncopal events and two sudden deaths occurred, probably due to treatment interruption. CONCLUSIONS: The entity of adrenergic-dependent, potentially lethal tachyarrhythmia with no structural heart disease deserves to be individualized. It may form a variant of the congenital long QT syndrome in which the ECG marker is lacking; this primary ventricular arrhythmia must be looked for in a pediatric patient with stress- or emotion-induced syncope because only beta-blocking therapy can prevent sudden death and therefore must be given for the patient's lifetime.

BACKGROUND: The clinical presentation and causes of atrial fibrillation (AF) in the 1990s may differ from AF seen 2 to 3 decades ago. It was the objective of this prospective study to characterize various clinical presentations and underlying conditions of patients with AF observed in general practice in France. METHODS AND RESULTS: The study population comprised 756 patients (19 to 95 years of age) with electrocardiographically documented AF subdivided into paroxysmal (<7 days), chronic (last episode >1 month) and recent onset AF(persistent >7 days and<1 month). Symptoms were present in 670 patients (88.6%). The relative prevalences of paroxysmal, chronic, and recent onset AF were 22.1%, 51.4%, and 26.4%, respectively. Cardiac disorders, present in 534 patients (70.6%), included hypertension (39.4%), coronary artery disease (16.6%), and myocardial diseases (15.3%) as the most common. Rheumatic valvular disease represented a common cause in women (25. 0%) but not in men (8.0%). The paroxysmal group differed by a high percentage of palpitations (79.0%) and a low percentage of underlying heart disease (53.9%). With a mean follow-up of 8.6+/-3.7 months, 28 patients (3.7%) died, including 6 fatal cerebrovascular accidents. Among the 728 patients who survived, congestive heart failure occurred in 30 patients (4.1%), and embolic complications occurred in 13 patients (1.8%). In the paroxysmal AF group, 13 patients (8.0%) developed chronic AF and 51 (31.3%) had AF recurrences. At the time of follow-up, 53 patients (14.3%) from the chronic AF group and 108 patients (55.7%) from the recent onset AF group were in sinus rhythm. CONCLUSIONS: This large-scale study establishes the current demographic profile of out-of-hospital patients with AF and highlights some of the changes that have occurred in the past decades, including a particular shift in cardiac causes toward nonrheumatic AF. This study also demonstrates significant differences between various subsets of AF.