Familiars that follow behind Isaac have a certain priority in how close their position is to him over other familiars, with The Relic having the lowest priority at 6th and thus being farther from Isaac than familiars of different priorities.
Having multiple copies of The Relic, such as duplication through Diplopia, will have each copied familiar paying out with soul hearts. (Lilith) can make use of this during Boss Rush, having the ability to duplicate the relic using the Box of Friends.
Synergies
BFFS!: The familiar requires one less room clear to drop a soul heart.
Soul Heart alternatingly:
Every 5 or 6 
Familiars that follow behind Isaac have a certain priority in how close their position is to him over other familiars, with The Relic having the lowest priority at 6th and thus being farther from Isaac than familiars of different priorities.
Diplopia, will have each copied familiar paying out with soul hearts. ( 
Lilith) can make use of this during 
Boss Rush, having the ability to duplicate the relic using the 
Box of Friends.
BFFS!: The familiar requires one less room clear to drop a soul heart.
Magdalene Unlocks 
Isaac (Boss) Unlocks 
The Binding of Isaac: Rebirth
