signs that tubes need to be replaced

I have a pair of Cary Audio Six pacs which i bought used about a year ago. They mate well with my tube preamp and i couldn't be more pleased with the setup i have.  I dont know the number of hours on the EL 34s that came with the amps. The previous owner may have replaced them at one time since they look like they were sourced from Tubeco.I have them biased at the recommended 220 ma. and put about 300 hrs/yr on them. Question is, what should I be looking for (sonically) besides obvious tube failure that would signify the tubes are nearing the end of their useful life? Will inability to maintain bias be any indication?

Thanks,
J.Chip