"LINE OUTPUTS: LEFT and RIGHT – 2 x ¼” (6.35 mm) TRS jack sockets; +10 dBu output level (variable), electronically balanced. Either ¼” TRS (balanced connection) or TS (unbalanced connection) jack plugs can be used." With the S501 amp the TS cables are better because they are now unbalanced, and the cable downgrades the balanced connection to unbalanced to better interface with the amp.
If the documentation on the Focusrite interface says that the 1/4" outputs can be used with either balanced TRS or unbalanced TS cables, then you're probably ok.
The unbalanced inputs on your S501 amp are most likely designed for a somewhat lower signal level than +10 dBu though. And I'm not sure how using the TS cable might effect that. You can read a little more about the different signals here though...
https://en.wikipedia.org/wiki/Line_level
I believe that balanced pro audio connections normally us a +4 dBu line level. And unbalanced consumer audio connections use -10 dBV line level. Which is one of the reasons it's not generally a good idea to try to interconnect them without an appropriate signal converter or transformer. The volume control on your interface may be sufficient for that though. (?)
If the 1/4" outputs on the interface support TS, then you could probably also try connecting them to the unbalanced RCA inputs on the Heresy amp as well, using unbalanced 1/4" TS to RCA adapter cables. Just be aware that your Heresy amp may also be expecting a lower signal level than your interface is capable of putting out. More on the order of -10 dBV.
It appears that though 100% not technically ideal, in the real world this balanced > unbalanced set-up just results in an unbalanced signal, which the S501 is designed around. I don't see any downside besides theoretical arguments that they aren't a mated pair, but I have read extensively this type of set-up is very often used, and with a cable run of 3' shouldn't have any issues whatsoever.
I can't explain the differences in a way that an engineer could understand. I just know from using alot of different gear that going balanced <-> unbalanced is generally a bad idea. And that there's more involved than simply dropping a wire or pin. If the docs for your device says it's ok though, then you're probably in the clear.
The balanced connections that are sometimes used on
consumer audio gear are also not well standardized. Which would make me even more cautious about the type of cabling I'd use with them. When in doubt, RTFM. (And say a little a prayer to your favorite audio deity!)