I'm not aware of any substantive changes to the transaction handling code between AS 4.2.1.GA and AS 4.2.2.GA. We have corrected some minor issues with timeout handling, but high CPU on the db server sounds more like a db issue than something relating to the AS itself. Did you change the db drivers or any other 3rd party component as part of the upgrade?
jhalliday, do you have JIRA tickets handy describing the timeout problems in 4.2.1? I'm trying to diagnose some connection weirdness in that version.