Is long QT syndrome a cardioneurologic or neurocardiologic disorder?

Abstract

Although most long QT syndromes (LQTSs) are associated with ion channel gene mutations, the phenotype of the disease cannot be completely explained by what happens in the heart alone. Moss and McDonald reported a 39-year-old woman with abrupt and transient episode of syncope who received a unilateral cervicothoracic (stellate) sympathetic ganglionectomy. One year after surgery, the patient remained asymptomatic and was off medications. The QT interval shortened from 0.64 to 0.44 seconds or less. This case supports a hypothesis popular at that time that LQTS has a neurogenic etiology. The neurocardiogenic hypothesis of LQTS remains alive today because of the discovery of an association between LQTS and vasovagal syncope as well as between LQTS and seizure disorders. In our own experience at a new genetic clinic at the Krannert Institute of Cardiology, 1 of 4 (25%) patients with confirmed type 1 or 2 LQTS had a family history of seizure disorder. That patient had a pathogenic mutation in KCNH2 and documented torsades de pointes ventricular tachycardia and ventricular fibrillation. The mother died of sudden death during a seizure episode, which is consistent with sudden unexpected death in epilepsy. A niece with the same mutation had epilepsy and continued to receive antiepileptic treatment by her neurologist in spite of positive genetic testing results. It is possible that this family has 2 different diseases that negatively affect each other. However, it is also known that epilepsy can be misdiagnosed as LQTS and vice versa in some patients. Whether the symptoms associated with LQTS are neurocardiogenic, cardioneurogenic, or both may vary among patients. It remains an important topic of investigation. In this issue of HeartRhythm, Haugaa reports abnormal electroencephalographic (EEG) activity in 71% (12 of 17) of the individuals with LQTS mutation. All 12 patients had