By the end of Season 3, the formulaic comfort of House was showing hairline fractures. The procedural rhythm of Gregory House (Hugh Laurie) berating Chase (Jesse Spencer), Cameron (Jennifer Morrison), and Foreman (Omar Epps) had run its course. The writers made a drastic choice: Chase was fired, Cameron resigned, and Foreman walked away.
The puzzle locks into place in "Wilson's Heart." House remembers that the dying person was Amber, who had come to pick him up from a bar because Wilson was working. The crash caused her kidneys to fail, preventing her body from filtering the toxic levels of amantadine (a flu medication) she had taken earlier. House MD - Season 4