I had hella issues using 4cm with the OG Helix floor and HXFX. The HXFX would hiss uncontrollably with certain amps or gain structures, and both devices seemed to change the way the guitar was hitting the front of the amp no matter how attentive I was to levels and routing.
The majority of my effects go through the front of the amp so I lived with it for a couple years without 4CM. I think if I needed heavy post FX at this point I’d either proxy my amp’s preamp and run Stadium into the FX return, or just go full digital and grab a matrix amp.