Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype.

Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V.

The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues.

Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.