RYR2 and cardiac arrhythmia: In conclusion, our clinical and experimental data, as well as computational modelling, show that increased heart rate and heart rate-independent effects of βAR stimulation on ventricular cardiomyocytes combine to increase the risk of arrhythmias, with βAR stimulation being the necessary factor to reveal the CPVT1 phenotype in RyR2-R2474S.