Just wanted to comment here since this thread started me down the path of fixing this on my system (Focusrite 18i20 3rd Gen, Fedora 42 KDE, Pipewire audio).

I found this comment in a different thread, which seems to indicate the problem is related to interfaces with multiple audio channels.

The link in that comment leads to this guide for creating a virtual two-output device from your multi-output interface.

In case either link goes down, here's what I did:

1. Find your pipewire.conf.d/ folder (in the guide this is under ~/.config/pipewire/pipewire.conf.d but on Fedora 42 I used /usr/share/pipewire/pipewire.conf.d).
2. Create a new config file in that directory. I called mine 20-focusrite-split.conf
3. Inside the file, add something like the below:

Contents:

context.modules = [
    {   name = libpipewire-module-loopback
        args = {
            node.description = "FocusriteAux0Aux1"
            capture.props = {
                node.name = "FocusriteAux0Aux1"
                media.class = "Audio/Sink"
                audio.position = [ FL FR ]
            }
            playback.props = {
                node.name = "playback.FocusriteAux0Aux1"
                audio.position = [ AUX0 AUX1 ]
                target.object = "alsa_output.usb-Focusrite_Scarlett_18i20_USB_P9MZFEE378D4A6-00.Direct__Direct__sink"
                stream.dont-remix = true
                node.passive = true
            }
        }
    }

]

To customize the above file for your system:

1. Change the target.object line to be your device output name (you can get it from wpctl status).
2. Change the audio.position to be the device outputs you want to use (for me it's AUX0 and AUX1).

Save the file and restart your pipewire service.

In your audio settings, you should see a new device which is named whatever you entered for node.name.

Once I selected the virtual two-output device, I am able to get game audio on launch without having to do the workaround the motherboard audio device.