Compound Mutations in Long QT Syndrome Assessed by a Computer Model

Long QT syndrome (LQTS) is an electrical disorder that predisposes affected individuals to sudden death from cardiac arrhythmias. Recently, it has been shown that compound mutations in LQTS are more common than expected and cause a severe phenotype. We used a mathematical model of rabbit ventricular myocyte (LabHEART) to investigate the simultaneous effects of three compound mutations reported in LQTS patients. Our results show that the mutations prolong the action potential (AP), being the impact of compound mutations stronger than the additive effects of single ones. The user-friendly characteristic of LabHEART allows combining easily different levels of current alterations to evaluate their outcome. This feature makes it an invaluable tool for researchers who want to explore the effects of channel mutations on the AP waveform.