The helicopter crashed at 5:53 a.m. Monday, according to Federal Aviation Administration spokeswoman Kathleen Bergen.
Bergen said no flight plan was filed for the helicopter, which was headed to a Gainesville hospital, Shands at the University of Florida.
Clay County Sheriff's Office spokesman Russ Burke told The Florida Times-Union the helicopter originally left the St. Augustine airport.
The helicopter was carrying heart surgeon Dr. Luis Bonilla and procurement technician David Hines of the Mayo Clinic in Jacksonville. Sheriff's officials say the name of the pilot has not been released.
Mayo Clinic spokesman Layne Smith said the heart they were to pick up could not be used in another transplant because its viability expired. The patient is back on the waiting list for a new organ.
Kathy Giery, a spokeswoman for Shands' LifeQuest Organ Recovery Service, told The Gainesville Sun that finding a new match for that heart would have taken longer than the roughly four-hour window between the harvest and transplant operations.
"In a last-minute situation like this one, there is no time, actually, to regroup and start over," Giery said.