I had the same issue and found a working solution in the thread Qubes 4.2 audio issues - Need to reset audio output for each new Qube audio use
It’s not perfect, as I can boot up and if I don’t plug in headphones initially for some reason it fails to register that there is an audio device and needs to be restarted. It fixed the issue for me though and I have had no repeats of the problem aside from what I just described, which relative to the original issue is minor.
Clearly this is a bug with 4.2
I was also running KDE so maybe that is the common thread?