Despite doing everything the Joker asked of him, Doctor Arkham watches helplessly as the bomb the Joker left behind in his house blows up, with his wife still inside.
While Mrs. Arkham didn't die in the blast, she was sent into a coma, which winds up being the basis of Doctor Arkham's actions in Season 2, desperately trying to bring his wife out of her coma.
Harley is presented with a rather Sadistic Choice near the end of "Near-Death Experience": she either can kill the representation of the Joker, and ultimately die from the hallucination brought upon by the Scarecrow's "Valley of Fear" toxin, or she can wake up... by killing the representation of her late fiance.
After all the abuse she experienced throughout the series, Pearl ultimately is killed, by Doctor Arkham of all people, in "Axes and Allies".
Why did this happen? Mrs. Arkham needed a new heart, and given the lockdown at Arkham Asylum, Tommy Elliot had no way of getting one on short notice.
