Now with the prevalence of no FTF available, even with no AF, it is still a game of averages. Even in the US, large merchants and certain types pay a much different interchange fee (below 2%) versus other merchants.
I have never seen a US issuer close a customer because of it, but I guess it is possible. It seems like the dream to have a great US card to use in EU, but I suspect it is still a small number who can profit so much.