Prognostic impact of misdiagnosis of cardiac channelopathies as epilepsy

Abstract

Introduction: Cardiac channelopathies are a frequent cause of sudden cardiac death (SCD) and often manifest with convulsive syncope, leading to a misdiagnosis of epilepsy. We aim to evaluate the clinical impact of epilepsy misdiagnosis in a cohort of patients with cardiac channelopathies.

Methods: Fifty probands/families with a cardiac channelopathy were included. We retrospectively collected information from medical records to identify all patients who presented with convulsive syncope and were diagnosed with epilepsy after neurological evaluation. Clinical data and outcome were compared with those of patients without a previous epilepsy diagnosis.

Results: Eight patients had a previous diagnosis of epilepsy. At first episode, 3 of them presented a positive family history of SCD and 5 showed a pathological electrocardiogram; half presented with sudden cardiac arrest (SCA) and the rest with recurrent syncope despite treatment with 1 or more anti-epileptic drugs. Five patients had long QT syndrome, 2 had catecholaminergic polymorphic ventricular tachycardia, and 1 had Brugada syndrome. Epilepsy misdiagnosis was associated with an increased risk of SCA/SCD (OR 6.92, P = .04), a delay of 12 years (P = .047) in correct diagnosis, and a delay from first symptom to channelopathy diagnosis of 18.45 years (P < .0001).

Conclusion: Cardiac channelopathy patients can be misdiagnosed with epilepsy. This involves a delayed diagnosis, a delay from the first symptom to a correct diagnosis, and an increased risk of SCA/SCD.

Fig 1. Primary inherited arrhythmic syndromes and genotype distribution among all probands (panel A), probands without previous epileptiform diagnosis (panel B) and probands previously misdiagnosed (panel C).

Fig 2

Age at diagnosis in years in the two different groups showing a significantly delayed diagnosis in the previously misdiagnosed patients (Panel A). Compared distribution of primary inherited arrhythmic syndromes among probands (Panel B). Distribution of typical triggers within probands (Panel C). Percentage of patients presented with sudden cardiac arrest at time of diagnosis (Panel D). *number above bars represent the percentage among the group. †* means significance p value <0.05.

Fig 3. Representative ECG traces of misdiagnosed probands, showing typical LQTS features.

Panels A to C show basal ECG from three KCNH2 mutation carriers with extremely prolonged QT intervals and abnormal T-wave shape (A: notched T wave, B: inverted and wide T wave, and C: widened T wave). Panel D shows an ECG recording during one of the syncopal attacks with convulsive status suffered by the patient in panel A, who corresponds to patient II in Table 2, demonstrating a torsade de pointes episode that required external defibrillation.