It is sad, but inevitable as written. They've been emphasizing from the beginning that they didn't have much in common, that Cuddy expected House to be other than he was, and that House basically has been clinging to her as an alternative to the drugs he would have swallowed if she hadn't shown up just in time. It was just a question of when and how, not if, it would end. Although I'm also feeling a bit jerked around by the way in which the writers chose to handle it.