There are two possible reasons for this:
- the Couatl engine crashed in flight, usually because of issues with the Navdata API or the Navdata itself. With the "Disable GSX in cruise" option, combined with the fact the GSX menu is automatically Disabled, will prevent GSX from making any queries to the Navdata API during flight, so it's very unlikely it will crash in flight, since it's not doing anything, other than checking if you would eventually descend under 10k feet. However, even if the unlikely event the engine will crash in flight, the auto-restarter should restart it automatically.
- in some very rare occasions, Simconnect itself might get stuck, usually because you exceeded the maximum number of Simobjects during flight, so it just stops responding. Sometimes this is fixed by restarting the Couatl engine, but in some even more rare occasion, it's not, because the max number of objects has been exceeded by too much, so it won't come back until the next flight.