Sudden Equine Deaths: “This is so frustrating for us”

News out of Churchill Downs last week that two of trainer Saffie Joseph Jr's horses had collapsed and died within days of each other has reignited talk around one of the most confounding–and by extension, frustrating–issues in racing: sudden equine death.

More than four years ago in response to the death of GI-placed Bobby Abu Dhabi (Macho Uno)–what was initially suspected a sudden cardiac-related event–the TDN took a lengthy dive into the issue.

In a nutshell, sudden cardiac deaths oftentimes leave no discernable physical sign for pathologists to piece together a clear diagnostic picture–no major lesions, faulty valves, ruptured arteries or damaged heart tissue for them to point to with authority and say this or that caused the heart to stop.

In a well-considered study published in 2011 looking at post-mortem findings from 268 Thoroughbred racehorses that suffered exercise-related sudden deaths, pathologists made a definite diagnosis in only 53% of cases, a presumptive diagnosis in 25% cases, while 22% of cases were left unexplained. In humans, coincidentally, about one-third of sudden deaths are presumed to be cardiovascular-related but don't actually have any concrete diagnosis.

Veterinary experts remain after all these years largely circumspect when pressed as to exactly what causes these events in racehorses, with fingers pointed towards electrical abnormalities like arrhythmias, genetic predispositions, drug use and faulty valves of the heart.

“We're asking better questions and we're asking more questions,” said Dionne Benson, chief veterinary officer for 1/ST Racing, when asked why progress has been slow in better understanding sudden death cases in racehorses. “But we've just started to ask those questions the last few years.”

Causes
Part of the reason is the infrequency with which these events occur. This paper pinned the number at roughly one sudden death per 10,000 individual starts.

Last Friday, the TDN asked the Horseracing Integrity and Safety Act (HISA)–mandated to record and report all equine fatalities at participating jurisdictions–how many sudden deaths have occurred since the law went into effect on July 1 last year. HISA did not provide an answer.

This study from last year found that sudden equine deaths were more likely during training than during racing, and horses with fewer lifetime starts were at higher risk.

“Exercise intensity appears not to be critically important in precipitating sudden cardiac death in horses,” the researchers summarized, before adding that typically, “sudden cardiac death occurred early in the careers of affected horses.”

A pivotal area of research surrounds so-called “electrical irregularities,” like arrhythmias (an irregular heartbeat), and heart murmurs (the presence of irregular heartbeat sounds).

Indeed, some 50% of racehorses experience cardiac arrhythmias when put under some kind of physical duress. That is one main reasons researchers out of the University of Minnesota are in the middle of a study of some 1,200 Thoroughbreds and Standardbreds with normal heart function at rest, but who develop arrhythmia during exercise.

“It's really hard to know for sure because when a horse dies, the electrical conductivity of the heart stops,” said Molly McCue, a professor and the associate dean for research at the University of Minnesota College of Veterinary Medicine, explaining why there still remains no concrete scientific proof that electrical irregularities cause sudden cardiac death, even though most experts agree that these issues are key to getting to the root of the problem.

In this regard, many veterinary experts bemoan the fact that in this scientific arena, horse racing is in some regards the medieval cousin of human athletics, which has already been closely monitoring and studying the heart's electrical capabilities for many decades, meaning so much of the dynamic possibility of a racehorse's heart remains shrouded in mystery.

Back in early 2015, in a study encompassing 30 racehorses in California, none of the horses suffered arrhythmias, but the authors noted a post-exercise increase in what is called valvular regurgitation, which is when heart valves don't close properly, allowing blood to flow backwards in the heart.

About 20% of healthy Thoroughbreds have some degree of valvular regurgitation when examined–but again, any clinical significance is currently unknown.

Despite the vast body of cardiac research in human athletes, the National Institutes of Health has its eye on the Grayson-Jockey Club funded arrhythmia study “as an interesting model for what happens in young human athletes,” McCue said, with the occurrence of sudden death in horses far higher than in humans.

“The frequency in horses, it's about 10 times more common than it is in people,” McCue said.

Another fast-evolving area of interest concerns genetics. Human science has found a genetic connection to a higher risk of heart disease. In racehorses, any potential genetic correlation with a higher likelihood of sudden death is still largely at lift-off.

McCue and her fellow researchers are taking DNA samples from the same 1200 horses in the arrhythmia study to see if any genetic pattern emerges. McCue calls these two studies “a two-pronged effort” to identify early horses at higher risk of experiencing sudden death.

“One is the genetics, figuring out who is high-risk and who we need to screen and look at really critically. And then two, developing tools that can identify the horses this is most likely to happen in,” said McCue.

“Our hope is that if we can develop computer models that can predict if a horse is more likely to experience severe arrhythmias today, we can then pull that horse from racing,” McCue added.

Some heart problems among horses that suffer sudden death are much easier to diagnose–but structural abnormalities are rare. A 2011 paper found that about 1% of horses who die suddenly suffer a ruptured aorta, which is the largest artery in the body.

Which brings the story around to the presumed connection between drugs and sudden cardiac death–the touchpaper of any high-profile sudden death in racing.

Drugs
“Here's the problem,” said Rick Arthur, former CHRB equine medical director. “People watch CSI and they see them taking a fingernail clipping and they can tell you what you had for lunch three days ago. Life doesn't work that way.”

In other words: Unlike an episode of CSI: NY, which typically wraps with a neat conviction, investigations into sudden racehorse death rarely conclude as tidily, even when a link emerges with a suspected substance.

Just take the case of a Standardbred that died suddenly at Cal Expo in early 2014. The horse, Arthur said, was subsequently found to have abnormally high levels of cobalt (a naturally occurring element) in its system.

The trainer faced no punitive actions because the death occurred before the CHRB passed rules instituting cobalt thresholds in test samples, said Arthur, who equivocated on whether the horse's death could have been definitively linked to an administration of cobalt.

“The cobalt was so high that it could have been associated with it,” Arthur said. “But again, that's when we were suspicious of cobalt–we might have over-interpreted it. But it certainly was very high.”

A recent limited study on six Standardbreds found a possible connection between cardiac arrhythmias (including atrial fibrillation) and levothyroxine–a thyroid supplement linked to the sudden deaths of seven Bob Baffert trained horses between 2011 and 2013.

A subsequent CHRB report noted that the horses had been administered thyroxine, and that use of thyroxine is “concerning in horses with suspected cardiac failure.” However, the report also noted that, because the drug had been administered to all horses in Baffert's care, the use of thyroxine “does not explain why all the fatalities occurred.”

Arthur co-authored a paper finding a “very strong” connection between anticoagulant rodenticide exposure and an increased risk of sudden death during exercise from unusual hemorrhaging. Strong suspicions surround the bronchodilator clenbuterol, which has been proven to increase heart muscle. Iodine–commonly found in seaweed-based supplements—has also been linked to arrhythmia.

“Certainly there are other things. Horses can build up levels of selenium [a naturally occurring mineral] which can cause sudden death,” Benson said. “You can also have things in the feed like monensin [a polyether antibiotic toxic to horses].”

In human sports the rise of erythropoietin [EPO]–a synthetic form of a natural metabolic product that thickens the blood–was linked to the deaths of multiple young professional cyclists and other athletes. Has illicit EPO use in horseracing ever been linked to any sudden equine deaths?

“No–at least not in California,” said Arthur, who said that EPO would have the same effect in horses' blood by thickening it though increased blood cell count, a process called polycythemia.

But a diagnostic complication in this issue, Arthur added, is how horses are “natural blood-dopers because of their huge spleens.”

Virus
 Springtime, of course, is equine virus hunting season. And viral infections are known to cause myocarditis, inflammation of the heart muscle.

“It's always a possibility,” said Francisco Uzal, coordinator of the California Animal Health and Food Safety Laboratory post-mortem program for the CHRB, when asked if a viral infection could explain the two recent Joseph-trained sudden deaths.

Uzal added, however, that while he has never seen during any sudden death necropsy instances of severe myocarditis–which would show up under the under the microscope as large lesions–“we've found in a number of sudden-death horses really, really mild and minor myocarditis.”

More tellingly, said Uzal, is how the same minor heart lesions appeared in horses that didn't suffer sudden death events. “You see it in normal horses, too. So, what does it mean? Probably nothing,” he said.

“This is so frustrating for us,” Uzal added. “We go home empty-handed most of the time.”

Which leads to the finer points of the actual necropsy process. Even if a substance suspected of increasing the likelihood of sudden equine death shows up at what are presumed elevated levels during the necropsy process, it doesn't necessarily indicate a smoking gun.

Take thyroxine, an endogenous substance, meaning it's produced naturally inside the body and therefore harder to evaluate than a medication with its own specific pharmacological signature.

“When you do a test, you compare what you find with the normal values in a normal animal in a living horse. There are no normal values for dead horses,” said Uzal, highlighting how difficult it is to determine baseline levels for endogenous substances like thyroxine.

“But having said that, we have compared the thyroxine found in postmortem blood in sudden death horses with the same in normal horses, and we found no difference,” he said.

Helpful to better understanding the underlying causes of sudden cardiac death in racehorses would be if all necropsies were made equal.

Uzal co-authored a 2017 paper highlighting how “autopsy technique” varies depending on personnel and “institutional preferences.”

As Uzal puts it, “pathology is a science as well as an art. You talk to 10 different pathologists, you hear 10 different stories. We have tried very hard to standardize, and we are still fighting for it.” In this regard, could federal intervention be on its way?

HISA's racetrack safety rules require all horses that die or are euthanized on licensed grounds at all participating jurisdictions undergo a necropsy. But the rules appear broad and fail to mandate more specific uniform rules on necropsy protocols.

HISA did not respond to a series of questions on the issue of necropsies. This includes whether every horse that has died during racing and training at jurisdictions under HISA's oversight have undergone necropsy examinations, and whether HISA has indeed instituted uniform protocols or guidelines for the actual necropsy process.

Future
In a bid to fill in some of the glaring blanks surrounding sudden death, UC Davis has begun storing necropsy samples taken from sudden death horses in a large freezer to be retrieved and re-tested in the advent of more sophisticated analytical technologies.

“The other thing we do from each horse, we have multiple different containers. So, the idea is we can provide it to different people,” said Uzal.

More contemporaneously, Uzal and his team are poised to begin studying the training records of horses that suffer sudden cardiac deaths for any possible explanatory patterns.

“We want to see if there's something in the training that could give us a clue of what's happening,” said Uzal. “We want to see if it's possible–and I don't know if that's the right expression–but see if it's possible that some horses are trained to the point of exhaustion.

“I don't know the answer–it's pure speculation,” Uzal added. “It could be nothing, or it could be something.”