Arrhythmias in the ventricular chambers are a major cause of death in heart disease, but many mysteries remain concerning the mechanisms of arrhythmias, including the wide variability among patients and the poor efficacy of drugs intended to combat arrhythmias. Cardiac arrhythmias reflect not only the electrical properties of single cardiac muscle cells, but also properties arising from the three-dimensional cardiac tissue that includes cardiac muscle cells, fibroblasts and endothelial cells. The phenomena that initiate and propagate arrhythmias are patient-specific.

“Patient-Specific Ventricular Cardiac Tissue Units for Sudden Cardiac Death Prevention” will fashion human induced pluripotent stem (iPS) cells into micro-patterned structures containing all three of the above cell types to create functional ventricular cardiac tissue units (vCTUs). The tissue units will manifest properties of mature ventricular muscle and exhibit patient-specific arrhythmic behavior specific to the donor of the adult cells that became the source for the iPS cells. A second goal is to generate an optical imaging platform for rapid assessment of the vCTUs that allows testing of their response to anti-arrhythmia therapy. The project is designed to open new avenues for precision medicine-based diagnosis and treatment of lethal forms of heart disease, with concomitant improvements in drug development, toxicity testing and diagnostic assays.