In my office at work, I have the following setup:
1. Vanatoo Transparent One speakers, connected via USB to an ...
2. iMac (about 10 years old, running 10.13.6, no core audio kernel extension replacement)
3. Audirvana 3700 (older non-MQA version) for playback software.
The volume can be controlled either from Audirvana or from the system's master volume control menu item (assuming the Vanatoo speakers are turned on and are the default system output).
I've noticed if I turn the volume down in Audirvana, and then raise it up again, one of the speakers will be significantly quieter than the other, and this is reflected in Audio Midi Setup.
If I control the volume via the system control, all works correctly as one would expect (so my workaround is to use this, but I would prefer to route system audio through the internal speakers).