The actress who played Camille (Tessa Thompson), the chief's niece, in season 2 is replaced by Camille Winbush this season
Every episode of the show is named after a famous song. "The Heart of the Matter" is a song by Don Henley.
When they call Lexi "3", Dr. Shepherd says: "Is that a sort of nickname?" Around the same time on House MD they have an intern named 13.