If Isaac has less than one full Red Heart after taking damage, he will be immediately teleported to a random room.
The teleportation happens only at half a heart or less left, regardless of health type. Empty Bone Hearts are not counted as health even if they can absorb a hit.
Synergies
Golden Trinket / Mom's Box: Having either teleports Isaac to a random special room instead. Having both activates if Isaac has 1 full heart or less after taking damage.
Interactions
Scapular: Provided Scapular can always trigger, grants effective immortality, as the soul heart is always given before the teleport takes place.
+The Wafer: Grants true immortality, plus one hit on the soul heart, allowing the player to get hit once before teleporting.
Notes
Does not affect The Lost, as being hit with Holy Mantle does not count as taking damage.
It will affect Isaac with Spirit Shackles, teleporting the player out of the room and restoring the Holy Mantle charge.
It is not recommended to have this item equipped during a boss fight as the boss's health will be restored to 100% if the player is teleported out of the room and returns, placing the player at a disadvantage.
Red Heart after taking damage, he will be immediately teleported to a random room.
The teleportation happens only at half a heart or less left, regardless of health type. Empty 
Bone Hearts are not counted as health even if they can absorb a hit.
Golden Trinket / 
Mom's Box: Having either teleports Isaac to a random special room instead. Having both activates if Isaac has 1 full heart or less after taking damage.
Scapular: Provided Scapular can always trigger, grants effective immortality, as the soul heart is always given before the teleport takes place.
The Wafer: Grants true immortality, plus one hit on the soul heart, allowing the player to get hit once before teleporting.
The Lost, as being hit with 
Holy Mantle does not count as taking damage.
It will affect Isaac with 
Spirit Shackles, teleporting the player out of the room and restoring the Holy Mantle charge.
Bones 
