Mtawarira, nicknamed 'The Beast', travelled with the Springboks squad from Dublin to Edinburgh on Sunday ahead of Saturday's EMC Test with Scotland, but will now return home.
Springbok coach Heyneke Meyer said on the South African rugby's website: "We've consulted with Beast and his cardiologist in Durban and although it's safe for him to play, we decided it would be best for him to return home and rest.
"The player's welfare is the most important consideration at this stage."
The 27-year-old, who has 41 caps, had an irregular heart rhythm, a hereditary condition, according to South Africa team doctor Craig Roberts.
Roberts said: "He has had this several times before and it's always been managed accordingly.
"This condition is not life threatening, but needs to be managed properly which is why we thought it would be in Beast's best interest to return to South Africa.
"He needs to have a repeat of the minor procedure he had in Cape Town earlier this year and it's important to notice that he is not at risk by playing with it, and his career is not in jeopardy."
A decision on a replacement will be taken in due course, with the Test at Murrayfield and against England to come.
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