Upgraded from 3.4.15 to 4.0.1 about 2 weeks ago.  Since then, database performance has decreased dramatically.  Prior to upgrading, SELECTs/sec were <50/sec (achieved by having a large InnoDB cache).  

Result:

After upgrading, SELECTs/sec is now a consistent 300-600/sec causing delayed writes and poor frontend performance:

• Active triggers will sometimes not resolve (have to manually close them)
• We use {ITEM.LASTVALUE} extensively in our trigger names.  After upgrading, many times the value displayed in the dashboard, as well as emails generated, will show the value prior to the one that would generate an alert, and no longer updates to show the current value (see screenshot.png).
• "Duration" column regularly shows negative numbers (see screenshot.png)
• "Problems by severity" widget take 5-7 seconds to refresh, every time it refreshes (constantly seeing the spinning circle; see screenshot2.png)