Luca,
EM Description:
What version of APM are on the EM?
Is the EM a collector or a MOM?
What is the -Xms -Xmx in the Introscope_Enterprise_Manager.lax?
What version of Java is the EM running under?
Environment Description:
Is the EM part of an EM Cluster?
If you do have an EM cluster, how many EMs and are you using the loadbalance.xml to direct agents to specific enterprise managers?
Load:
How many agents, application and metric is the EM gathering?
My first guess is that your EM is overloaded and does not have enough resources for the application/metric/trace load.
You may need to trim your metrics, see if there are any agents that are metric/historic metric clamped.
Second guess would be the same as the others, is the memory settings for JVM 1.8 G1GC to optimize the memory a bit better than the default garbage collection for how APM uses memory.
Hope this helps,
Billy