After setting up your 4500 with Audyssey with your sub(s) connected go to the setup menu under Speakers: 2ch Playback. Make sure subwoofer is set to yes.
View attachment 42344
Thanks, that was it! I had not spotted this screen before.
It turns out that although Subwoofer was set as Yes, my Front was set as Large (in 2 channel mode, even though I had set them to Small in Audyssey setup). Also I noticed that the default crossover frequency is different here (40Hz) than what I had set manually.