I have noticed that you can choose between Normal and Hard at the start of a run in The Binding of Isaac: Rebirth. What changes when you choose Hard?
The Binding of Isaac Rebirth – Difference Between Normal and Hard Mode
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Best Answer
As mentioned here by Ed, some effects are no heart drops from bosses and curses being more prevalent.
I'd hazard to guess that less drops in general and higher HP enemies might play a part. Especially less drops.
And here's his general notes copied over from the linked post: