More Of That (right) winning last year© Photo Healy Racing
More Of That will not defend his Ladbrokes World Hurdle crown and will miss the rest of this season.
Having lost his unbeaten record on his only run of the current campaign at Newbury, the seven-year-old then underwent a breathing operation.
More Of That had been on the comeback trail but it emerged two weeks ago that he had bled following a piece of work, putting his Cheltenham Festival participation in doubt.
Connections have now ruled out a return trip to Prestbury Park for Jonjo O'Neill's charge.
Frank Berry, racing manager to owner JP McManus, said: "The writing was on the wall a few weeks ago to be fair."
More Of That appeared to have the world at his feet following his win in last year's World Hurdle.
In fending off another previously unbeaten contender in Annie Power O'Neill appeared to have a potential staying star on his hands.
The decision was made to keep him over hurdles this season but he did not reappear until the end of November and looked leg-weary when only third to Medinas in the Long Distance Hurdle.
That came at a time O'Neill's yard were in a quiet spell, but the consensus was that he had a problem with his wind and after his operation, hopes were high he could return to his best.
Having overlooked More Of That in favour of At Fishers Cross who finished third in the World Hurdle, Tony McCoy had been looking forward to riding him at the Festival, particularly as this will be his final Cheltenham before retirement.
Unfortunately for McCoy, the next time More Of That runs, someone else will be riding him.
"When he burst a few weeks ago we feared the worst," said Berry.
"He's back in good form again with himself, but the Festival is just going to come too quick.
"So, we'll give him a nice long break and bring him back refreshed in the autumn."