We present our computational methods for and results from aorta flow analysis and heart valve flow and structure analysis. In flow analysis, the core method is the space–time Variational Multiscale (ST-VMS) method. The other key methods are the ST Slip Interface (ST-SI) and ST Topology Change (ST-TC) methods and the ST Isogeometric Analysis (ST-IGA). The ST framework, in a general context, provides higher-order accuracy. The VMS feature of the ST-VMS addresses the computational challenges associated with the multiscale nature of the unsteady flows in the aorta and heart valve. The moving-mesh feature of the ST framework enables high-resolution computation near the valve leaflets. The ST-SI connects the sectors of meshes containing the leaflets, enabling a more effective mesh moving. The ST-TC enables moving-mesh computation even with the TC created by the contact between the leaflets. It deals with the contact while maintaining high-resolution representation near the leaflets. Integration of the ST-SI and ST-TC enables high-resolution representation even though parts of the SI are coinciding with the leaflet surfaces. It also enables dealing with leaflet–leaflet contact location change and contact sliding. The ST-IGA provides smoother representation of aorta and valve surfaces and increased accuracy in the flow solution. With the integration of the ST-IGA with the ST-SI and ST-TC, the element density in the narrow spaces near the contact areas is kept at a reasonable level. In structure analysis, we use a Kirchhoff–Love shell model, where we take the stretch in the third direction into account in calculating the curvature term. The computations presented demonstrate the scope and effectiveness of the methods.