Taken from the now-retired Discord channel for speed tech:

1. Not picking up a gun on the floor makes the boss guarantee a gun from it's reward.
2. Dropping a gun and picking it back up instantly reloads it.
3. If shrine rooms have a way out, it usually leads to the boss or the shop.
4. Don't pick up Heavy Boots as the Bullet.
5. On Floor 2-3: the boss is usually through the shop (~70%).
6. On Floor 4: the asymmetric / oddly-shaped rooms with icicles means you are on path.
7. On Floor 6: long hallways leaving the 3-way split rooms are almost always the correct path.