"After a complete evaluation from a number of different physicians and experts associated with this condition, we decided that this was the best and only alternative for me," Konowalchuk said in a written statement.
"As much as I'll miss the game of hockey and all that it's provided for my family and I, my health was the number one priority."
The team said the 33-year-old Konowalchuk has Long QT Syndrome, a genetic disorder that can lead to irregular heart rhythms.
Team captain Joe Sakic said Konowalchuk's retirement was hard to believe after the work he invested in getting ready for the season.
"On the other hand, it's better to find it now. Safety comes first and your family comes first and it is a decision we support and respect," he said.
Sakic said many of Konowalchuk's teammates knew he was undergoing tests but did not expect such a drastic outcome.
"We had seen him work out and work hard," winger Ian Laperriere said. "We were holding out hope he would play."
Laperriere said Konowalchuk would be missed. "He was good to the team on and off the ice," he said.
Defenceman John-Michael Liles said teammates understood Konowalchuk's move.
"I don't think anybody disagrees with his decision," he said. "He has to think about himself and the well-being of his family. We want him to live a long and healthy life."
Konowalchuk had 171 goals and 225 assists in 790 games over 13 seasons. He played in 52 playoff games, recording nine goals and 12 assists. He was drafted by the Washington Capitals in 1991 and acquired by the Avalanche in 2003.
The Avalanche also said forward Brad May would be out four to six months after reconstructive shoulder surgery on Thursday. May was injured in a pre-season game Monday.
"It was a freakish injury," coach Joel Quenneville said. "He brought us grit and toughness and now someone else is going to have to step up and provide it."