A Model of Drug Effects on Heart Failure and Hypertrophic Cardiomyopathy in Human Ventricular Cardiomyocytes

Heart failure (HF) and hypertrophic cardiomyopathy (HCM) are two cardiovascular diseases that increase the risk of arrhythmia due to their effects on cardiac electrical activity.However, there is no drug designed for treating the electrophysiological and arrhythmogenic consequences of HF and HCM considering their three stages of severity.In this work, computational modelling has been used to study the efficacy of several drugs against arrhythmogenic phenomena caused by HF and HCM.95 drugs have been taken into account, of which 28 have been considered as nonarrhythmogenic a priori due to their IC50 values.A modified version of the O'Hara-Rudy computational model has been used to simulate both, the pathologies and drugs effect and the influence of sex, cell type and heart rate.Considering the occurrence of early afterdepolarizations (EADs), results show that Diltiazem, Nifedipine and Nitrendipine are the most effective drugs to solve EADs, being Nitrendipine the most effective one without an overdose.Additionally, not only does tachycardia provoke a greater probability of the occurrence of EADs, but also the favourable response to some anti-arrhythmogenic drugs is lower.In conclusion, the risk of HF and HCM developing arrhythmias may be reduced with drugs as identified by our in-silico AP model.