Age- and genotype-specific triggers for life-threatening arrhythmia in the genotyped long QT syndrome

Age and Long QT Syndrome. Introduction: Patients with long QT syndrome (LQTS) become symptomatic in adolescence, but some become at age of ≥20 years. Since it remains unknown whether clinical features of symptomatic LQTS patients differ depending on the age of onset, we aimed to examine whether triggers for cardiac events are different depending on the age in genotyped and symptomatic LQTS patients. Methods and Results: We identified 145 symptomatic LQTS patients, divided them into three groups according to the age of first onset of symptoms (young <20, intermediate 20-39, and older ≥40 years), and analyzed triggers of cardiac events (ventricular tachycardia, syncope, or cardiac arrest). The triggers were divided into three categories: (1) adrenergically mediated triggers: exercise, emotional stress, loud noise, and arousal; (2) vagally mediated triggers: rest/sleep; and (3) secondary triggers: drugs, hypokalemia, and atrioventricular (AV) block. In the young group, 78% of the cardiac events were initiated by adrenergically mediated triggers and 22% were vagally mediated, but none by secondary triggers. In contrast, the adrenergically mediated triggers were significantly lower in the intermediate group. The percentage of secondary triggers was significantly larger in the older group than in the other two groups (0% in young vs 23% in intermediate vs 72% in older; P < 0.0001). Concerning the subdivision of secondary triggers on the basis of genotype, hypokalemia was only observed in LQT1, drugs mainly in LQT2, and AV block only in LQT2. Conclusion: Arrhythmic triggers in LQTS differ depending on the age of the patients, stressing the importance of age-related therapy for genotyped LQTS patients.