Prosthetic heart valve devices for percutaneous replacement of native heart valves and associated systems and method are disclosed herein. A prosthetic heart valve device configured in accordance with a particular embodiment of the present technology can include a valve support having an upstream end and a downstream end extending around a longitudinal axis and having a cross-sectional shape. The valve support can have an outer surface and an inner surface, wherein the inner surface is configured to support a prosthetic valve. The device can also include an expandable retainer coupled to the upstream end of the valve support. The retainer can be configured to engage tissue on or near the annulus. In some embodiments, the valve support is mechanically isolated from the retainer such that the cross-sectional shape of the valve support remains sufficiently stable when the retainer is deformed in a non-circular shape by engagement with the tissue.
