Figure 4.

Prediction of TdP risk from model simulations. (A) Baseline ORd model with epicardial myocyte parameter settings (the epicardial configuration is shown here as it was determined to give the best classification in Lancaster and Sobie, 2016. Using the endocardial baseline model yields very similar results). (B) APD_LQT±βAdr optimized model. (C) Multi-variable optimized model. (D) APD_LQT optimized model. Dotted lines indicate no-drug control values of APD₅₀ and diastolic [Ca²⁺]_i. Colors for the different models correspond to the color scheme in Figure 3. Solid lines give decision boundaries between torsadogenic (open circles) and non-torsadogenic drugs (filled circles). Dashed lines demarcate regions within which the categorization error remains below a threshold value (E^*). Using the multi-variable optimized model, all drugs that prolong APD₅₀ by more than 5 ms are known TdP risk drugs. Verapamil (marked by black dot) is an example of a TdP negative drug that significantly prolongs the AP in the baseline and APD-optimized models but not in the multi-variable optimized model.