Van de Ven did train with Tottenham last week but was not included in their matchday squad for Sunday's Premier League loss at Newcastle United.
In Spurs' previous match, a 4-0 home win over Everton on August 24th, he appeared to have hurt his knee after a tackle and was in some discomfort but able to continue.
The Dutch football association (KNVB) said Van de Ven was not match fit and therefore being replaced by the 24-year-old Van Hecke.
The Netherlands host Bosnia & Herzegovina in Eindhoven on Saturday and then Germany at the Johan Cruyff Arena in Amsterdam three days later at the start of the new Nations League campaign.