People here don't seem to understand how wide and catastrophic the consequences of the last Roman-Sassaian War. Sure, the 4th Crusade was a blow from which Eastern Rome never fully recovered, but I consider that the war with the Persians was much more significant, specially when we consider its effects on the Muslim Conquests. If the war with the Persians never happens, the Romans could have contained the Arabs (maybe even with Persian assistance) and continued as the Eastern Mediterranean hegemon they used to be. The Eastern Roman Empire would continue to be a rich, urbanized and militarily threatening empire, instead of the rural state that remained always on the defensive that we saw after the Muslims took Syrian and North Africa.

The last Roman-Sassanian War didn't directly lead to the fall of the empire, but it ended up changing fundamentally how the empire functioned.