The Colin Tizzard-trained Thistlecrack will miss the rest of the season, including National Hunt racing's Blue Riband event, the Timico Cheltenham Gold Cup due to a stress fracture.
The 10-year-old son of Kayf Tara was a general 12/1 chance for the extended three-miles and two-furlong Grade One event but he will now miss the contest, won last season by Jessica Harrington's Sizing John, for the second successive year.
Rated as high as 174 over hurdles, Thistlecrack swept all before him over timber as he plundered five Grade One's including the 2015 Stayers' Hurdle by seven lengths and the Liverpool Stayers' Hurdle by the same margin at Aintree in 2015.
However, Sherborne handler Tizzard suggested the gelding's true ability would always manifest over fences and Thistlecrack highlighted that notion with an impressive four length victory at Chepstow on his chasing debut in October 2016, justifying prohibitive odds of 1/6.
Further success over the larger obstacles followed with Tizzard's charge landing victories at Cheltenham and Newbury, with the latter a Grade Two victory, before connections decided to target the novice at open company in the King George VI Chase.
Thistlecrack lived up to his billing, with a marvellous display of jumping under regular pilot Tom Scudamore, to land the Grade One event by three and a quarter-lengths with stable companion Cue Card back in second.
A head second to the ill-fated Many Clouds in the Grade Two Cotswold Chase at Cheltenham on Festival Trials Day was followed by the news that the gelding had incurred a tendon injury which ruled him out of the rest of the season.
Since returning from that injury, Thistlecrack was a bitterly disappointing fifth, beaten 13 lengths in the Grade Two Long Distance Hurdle at Newbury but shaped better than the bare result suggests when fourth next time out to Might Bite as he attempted to defend his King George crown at Kempton Park on Boxing Day.
However, connections will now have to go back to the drawing board once again with the chaser after it was announced that he had suffered a small stress fracture to his tibia, ruling him out of National Hunt racing's Blue Riband event and indeed the rest of the season.
Speaking to At The Races, Kim Tizzard, assistant trainer to her father Colin, said: "He has been off today for bone scans as he was stiff after the King George - he has a small hairline fracture and he misses the Gold Cup and probably the rest of the season."
In other news, Gordon Elliott's high-class novice chaser Death Duty has also been ruled out for the rest of the season after incurring a hind joint injury.
A Grade One winner over both hurdles and fences, the seven-year-old son of Shantou suffered a nasty fall at the final fence in the G1 Racing Post Novice Chase at Leopardstown on his latest outing behind ready winner Footpad.
However, connections believe the injury occurred before the fall, which has resulted in Death Duty, a prominent figure in the betting for both the G1 RSA Chase and JLT Novices' Chase now sadly being forced to miss the Cheltenham Festival and indeed the rest of the season.
However, he does remain a talented gelding with a bright future ahead of him over fences. Hopefully, the same can still be said for Thistlecrack.
Analysis by Danny Archer
The absence of both Thistlecrack and Death Duty from the National Hunt scene for the remainder of the season is a bitter pill to swallow for racing fans. One has to think whether Thistlecrack can really recapture his former talent. In two runs back from a tendon injury, in my opinion, he just hasn't looked the same horse despite a creditable run in the King George.
Two bad injuries in two successive seasons robs us of seeing Thistlecrack run in racing's Blue Riband event and it must now be argued whether he will ever be the same horse.
One long-term injury is enough of an obstacle to overcome, but two is a different story altogether. For the good of the sport, let's hope Thistlecrack can recapture his former glories.
As for Death Duty, I've always been a big fan of him and with hindsight, connections may think running him over two miles against Footpad was possibly not the best use of their charge. However, he is a young horse who still has the world at his feet and I fancy him to in the future run a huge race in a Cheltenham Gold cup, he has time on his side, Thistlecrack on the other hand, doesn't have the same luxury.