Patient-specific heart simulation can identify non-responders to cardiac resynchronization therapy

To identify non-responders to cardiac resynchronization therapy (CRT), various biomarkers have been proposed, but these attempts have not been successful to date. We tested the clinical applicability of computer simulation of CRT for the identification of non-responders. We used the multi-scale heart simulator "UT-Heart," which can reproduce the electrophysiology and mechanics of the heart based on a molecular model of the excitation-contraction mechanism. Patient-specific heart models were created for eight heart failure patients who were treated with CRT, based on the clinical data recorded before treatment. Using these heart models, bi-ventricular pacing simulations were performed at multiple pacing sites adopted in clinical practice. Improvement in pumping function measured by the relative change of maximum positive derivative of left ventricular pressure (%ΔdP/dt_max) was compared with the clinical outcome. The operators of the simulation were blinded to the clinical outcome. In six patients, the relative reduction in end-systolic volume exceeded 15% in the follow-up echocardiogram at 3 months (responders) and the remaining two patients were judged as non-responders. The simulated %ΔdP/dt_max at the best lead position could identify responders and non-responders successfully. With further refinement of the model, patient-specific simulation could be a useful tool for identifying non-responders to CRT.