[source]
pmid = PMID:27861123
title = TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT
[diagnosis]
disease_id = OMIM:614021
disease_label = Ventricular tachycardia, catecholaminergic polymorphic, 3
[text]
Patient 1 is a French Canadian female, who presented with ventricular fibrillation and cardiac arrest during walking at age 22, without prior history of syncope or documented arrhythmia. Coronary angiography, transthoracic echocardiography, and invasive electrophysiological (EP) testing, including ventricular premature stimulation, were normal. The resting ECG showed a normal QT interval, but isoproterenol infusion resulted in QT prolongation. During follow‐up, the patient presented with recurrent episodes of exercise‐ or emotion‐induced atrial and ventricular arrhythmias resulting in multiple shocks from an implantable cardioverter–defibrillator (ICD). Arrhythmia was refractory to standard beta‐blockers (metoprolol and bisoprolol) but was finally suppressed by high doses of nadolol. During further follow‐up, repeat echocardiography remained normal but significant repolarization abnormalities with QT prolongation (QTc range: 451–494 ms) during follow‐up were occasionally seen on the resting ECG (Fig 1A); the patient was therefore diagnosed with LQTS. The parents were not known to be consanguineous but came from the same town. No family member was available for genetic testing.
[text]
Patient 2 is also a French Canadian female. She presented initially at age 18 with numerous syncopal episodes triggered by emotional stress, with documentation of non‐sustained VT during exercise stress testing. Despite beta‐blocker therapy, she had an aborted cardiac arrest during emotional stress at the age of 31. At rest, the QTc was 437 ms with repolarization abnormalities (Fig 1B). Coronary angiography and cardiac magnetic resonance imaging were unremarkable. Sustained polymorphic VT was inducible with one ventricular extrastimulus during isoproterenol infusion. Epinephrine challenge resulted in a 57 ms paradoxical QT prolongation with appearance of ventricular bigeminy, suggesting a low repolarization reserve compatible with LQTS (Fig 1C). During follow‐up, the patient had multiple episodes of adrenergic atrial and ventricular arrhythmia resulting in numerous ICD shocks. Electrophysiological mapping showed an extensive low‐voltage area along the interatrial septum and multiple foci of atrial tachycardia (AT) was ablated. The combination of AT ablation and nadolol significantly decreased arrhythmia recurrence in this patient.
[text]
Patient 3 (Subject 1V:13 of Fig 1D) is a Sudanese male who presented with cardiac arrest at age 4 while running. ECG recording during successful resuscitation showed ventricular fibrillation and TdP, which was reversed to sinus rhythm following DC shock. ECG showed a QTc interval of 450 ms (Fig 1E). He had a second attack while in hospital but was in sinus rhythm between the two attacks with a normal QRS axis, aQTc interval of 450 ms, and no ST changes. He later received an ICD and has had no further syncope or cardiac arrest. However, ICD interrogation occasionally revealed a fast rhythm around 193 beats/min (cycle length 310 ms) with polymorphic ventricular ectopy (Fig 1F). The parents of patient 3 are first‐degree cousins and seven of 13 children in the family presented exertion‐induced arrhythmias and/or SCD during early childhood. In five of these children, an arrhythmic episode was fatal. Two children (IV:9 and IV:13) survived an arrhythmic attack.