Original Article Personalized Perioperative Multi-scale, Multi-physics Heart Simulation of Double Outlet Right Ventricle TARO KARIYA, 1,5 TAKUMI WASHIO, 2 JUN-ICHI OKADA, 2 MACHIKO NAKAGAWA, 3 MASAHIRO WATANABE, 3 YOSHIMASA KADOOKA, 3 SHUNJI SANO, 4,6 RYOZO NAGAI, 1,7 SEIRYO SUGIURA, 2 and TOSHIAKI HISADA 2 1 Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan; 2 UT-Heart Inc, The University of Tokyo, Tokyo, Kashiwa-no-ha Campus Station Satellite #304, 178-4-4 Wakashiba, Kashiwa, Chiba 277-0871, Japan; 3 Next-Generation Healthcare Innovation Center, Fujitsu Ltd., Tokyo, Japan; 4 Department of Cardiac Surgery, Okayama University, Okayama, Japan; 5 Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6 Division of Pediatric Cardiothoracic Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA, USA; and 7 Jichi Medical University, Tochigi, Japan (Received 11 November 2019; accepted 2 March 2020) Associate Editor Aleksander S. Popel oversaw the review of this article. Abstract—For treatment of complex congenital heart dis- ease, computer simulation using a three-dimensional heart model may help to improve outcomes by enabling detailed preoperative evaluations. However, no highly integrated model that accurately reproduces a patient’s pathophysiol- ogy, which is required for this simulation has been reported. We modelled a case of complex congenital heart disease, double outlet right ventricle with ventricular septal defect and atrial septal defect. From preoperative computed tomography images, finite element meshes of the heart and torso were created, and cell model of cardiac electrophysi- ology and sarcomere dynamics was implemented. The parameter values of the heart model were adjusted to reproduce the patient’s electrocardiogram and haemody- namics recorded preoperatively. Two options of in silico surgery were performed using this heart model, and the resulting changes in performance were examined. Preopera- tive and postoperative simulations showed good agreement with clinical records including haemodynamics and measured oxyhaemoglobin saturations. The use of a detailed sarcomere model also enabled comparison of energetic efficiency between the two surgical options. A novel in silico model of congenital heart disease that integrates molecular models of cardiac function successfully reproduces the observed pathophysiology. The simulation of postoperative state by in silico surgeries can help guide clinical decision-making. Keywords—Congenital heart disease, Computer simulation, Double outlet right ventricle. INTRODUCTION Congenital heart disease (CHD) affects nearly 1% of all newborn babies, and represents a worldwide public health burden. 8 As CHD typically presents with various structural abnormalities, the main therapeutic approach for complex CHD is surgery, which requires a high level of technical expertise. Realistic three-di- mensional (3D) heart models have been developed to improve the clinical outcome of CHD surgery. 18,22 Such static morphological models help to design effi- cient surgical strategies by facilitating understanding of anomalous geometries, but do not provide functional information on the dynamically beating heart of the individual. Computer simulation using 3D models can reproduce cardiac function of an individual under various conditions, for use as a tool to explore differ- ent surgical scenarios. To date, however, their clinical application remains in the early investigational stage, and most studies have focused on the flow dynamics in rigid structural models of the heart or blood vessels. 3,6 Further, these models are unable to simultaneously account for multi-physics phenomena (e.g., metabo- lism, electrophysiology, muscle contraction, and blood flow) and multi-scale structures (e.g., molecules, cells, tissues, and organs), which are important for a com- Address correspondence to Seiryo Sugiura, UT-Heart Inc, The University of Tokyo, Tokyo, Kashiwa-no-ha Campus Station Satellite #304, 178-4-4 Wakashiba, Kashiwa, Chiba 277-0871, Japan. Electronic mail: sugiura@ut-heart.com Taro Kariya and Takumi Washio contributed equally to this work. Annals of Biomedical Engineering (Ó 2020) https://doi.org/10.1007/s10439-020-02488-y BIOMEDICAL ENGINEERING SOCIETY Ó 2020 Biomedical Engineering Society