Had the same issue twice on my long run today with Spotify stopping on my Forerunning 645 Music. Had to stop my run and stop and start the music once and then just gave up on the music after it happened the 2nd time. Haven't had this issue before and currently using version 6.50 (b23b9d3). Didn't appear to be anything wrong with my headphones. was very annoying. Hopefully it will be fix next patch.
How are you measuring your heart rate? I use a Garmin chest strap HR monitor (older "RUN" version).
When I went running, I noticed that my 645M would just stop playing music too - 15-20 minutes into a run over a period of 2-3 weeks. I looked at my run data and noticed that my chest rate monitor, after pairing with the watch at the beginning of the run would stop transmitting sometimes AND it forced the 645M to get heart rate data from the built-in optical HR reader (I can tell because the optical heart rate reader tends to read 15-20 bpm lower than my chest strap at the same moment during the run) - this happened again during a run and I noted that my heart rate data was zero bpm as it lost connection to my chest strop and picked up again as it switch to the optical HR reader.
I solved this problem by changing the battery in my chest strap HRM. For future runs, I intend to turn off the optical HR reader so the watch cannot switch to it if it loses connection with the chest strap HRM.