So resume where Eye of Terror left off, with the Imperium doing damage control for a major chaos incursion and armies being recalled from important warzones across the galaxy to help out with that.
Another thing: Eldrad is dead. He's dead. He's watched the galaxy since before the Imperium existed, and guided it, and now he's dead. How do we know that without him things won't get a whole lot worse really fast? What if his actions have been keeping Bjorn and Dante and the other long-lived characters alive for so long? The plan has gone off the rails, gentlemen. Everyone is at risk.
Another thing: Imperials and Eldar collaborated pretty extensively during the campaign. Dark Angels and Space Wolves fought side-by-side. On the other hand, so did Orks and Orks. Dun dun dun.
And the millennium turns and the doomsday cults surge like they do every thousand years.
But really, nothing has changed. Some worlds are made up and destroyed. Eldrad has died, but he is the character with the longest lifespan of all and you can play infinite history games with him. The Imperium is *still* on the edge of collapse, where it's always been. It's still a bunch of screaming, heavily-armed bald guys surrounded my menacing aliens and being picked off one by one.