I did some experimenting to test this out (now that I have the program in front of me, I can use real numbers).
First, I ran the optimizer and equipped exactly what it suggested, to avoid any discrepancy. This removed the first oddity I mentioned above, as you said it would.
My optimized gear had an overall value of 347664.7 points. I still had the same strangeness with Heart of Iron. It was a minor upgrade to my first trinket slot, and a huge upgrade to my second trinket slot. "Build Upgrade List"
showed it as an upgrade value of 508.
I marked it as "available" and equipped it. My new overall point value became 353678.9, an increase of 6014.2. To test further, I re-equipped my Alchemist Stone and ran the Optimizer again. The only change the Optimizer suggested
was to equip the Heart of Iron in place of the Alchemist Stone, and came up with the same overall point value.
I think what is happening is the Upgrade List isn't properly comparing both trinket slots. The 508 number is approximately what I would get if I replaced my DMC:G with the Heart of Iron (slot 1) and left the second slot as the Alchemist Stone.
In fact, when I mouse-over the Heart of Iron in the Upgrade List, this is what it is suggesting I do, despite the fact that I would get a much bigger boost by replacing the Alchemist Stone.
DMC:G + Alchemist Stone: 347664.7
Heart of Iron + Alchemist Stone: 348167.5 (+502.8, approximately what is shown in Upgrade List)
DMC:G + Heart of Iron: 353678.9 (+6014.2, significantly better than the Upgrade List suggests)