Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia caused by mutations in the ryanodine receptor type 2 (RyR2). Diagnosis of CPVT often occurs after a major cardiac event, thus posing a severe threat to the patient’s health.

Methods Publication databases, including PubMed, Scopus, and Embase, were searched for articles on patients with RyR2-CPVT mutations and their associated clinical presentation. Articles were reviewed by two independent reviewers and mutations were analyzed for demographic information, mutation distribution, and therapeutics. The human RyR2 cryo-EM structure was used to model CPVT mutations and predict the diagnosis and outcomes of CPVT patients.

Findings We present a database of 1008 CPVT patients from 227 papers. Data analyses revealed that patients most often experienced exercise-induced syncope in their early teenage years but the diagnosis of CPVT took a decade. Mutations located near key regulatory sites in the channel were associated with earlier onset of CPVT symptoms including sudden cardiac death.

Interpretation The present study provides a road map for predicting clinical outcomes based on the location of RyR2 mutations in CPVT patients. The study was partially limited by the inconsistency in the depth of information provided in each article, but nevertheless is an important contribution to the understanding of the clinical and molecular basis of CPVT and suggests the need for early diagnosis and creative approaches to disease management.

Funding The work was supported by grant NIH R01HL145473, P01 HL164319 R25HL156002, T32 HL120826.

Columbia University and ARM own stock in ARMGO, Inc., a company developing compounds targeting RyR and have patents on Rycals

: The work was supported by grant NIH R01HL145473, P01 HL164319 R25HL156002, T32 HL120826

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