Welcome to readers from the Philippines looking to learn about the tragedies in the Condura Skyway Marathon and Half-Marathon on Sunday 7 February 2016. I originally wrote this post in 2014 after three marathon deaths in my region of North Carolina and in London on the same weekend. I focus here on a somewhat controversial disorder in exercise physiology, hypertropic obstructive cardiomyopathy. While we do not know the cause of death in Mr. Alfon and Major Lubang, they were both in the general age range–38 and 40, respectively–where such rare deaths occur. From the States, we send our deepest condolences to the Alfon and Lubang families and to all involved in the Condura Hero Foundation fundraiser.
Original post, 15 April 2014:
You've likely read the sad news from this weekend in the world of distance running: Three relatively young men died on Sunday while running in otherwise festive, long-distance races in London and Raleigh, North Carolina.
At the 34th London Marathon, where 36,000 runners participated on Sunday, the post-race death of a 42-year-old man was the event's second death in three years. In North Carolina, two men died, age 31 and 35, after collapsing at or near the end of the 13.1-mile, half-marathon of the capital city's inaugural Rock 'N' Roll Marathon. A combined 12,500 runners participated in the Raleigh events.
A pharmacology colleague and science writer, Bethany Brookshire, has a firsthand account and personal reflections from running the Raleigh Half Marathon.
While specific details beyond the runners' age and gender are not yet available, general reports on the three cases bear the hallmarks of sudden cardiac death. Each person collapsed late or at the end of the races and on-site resuscitation attempts were as prompt and aggressive as possible. But all three gentlemen were pronounced dead at the hospitals where they were taken.
Sudden death while running long distance races is rare phenomenon but is appearing to be more common due to the sheer number of runners participating across a racing calendar that continues to expand (the Raleigh race was the inaugural event there.).
While research shows that air temperature and race preparation are most likely to predict the best marathon finish times, sudden cardiac death is most often due to existing cardiovascular disease that is largely unrelated to the extent of physical conditioning. In many of these cases, the victims never had any previous problems or symptoms.
Rare events in large populations
Sudden deaths in marathon running have been the subject of much study in the cardiology and sports medicine fields because they are rare and somewhat unpredictable occurrences. Research estimates range from 0.5 to 2 deaths per 100,000 marathon runners in a given race, a far lower risk of death than in the majority of daily activities.
Dr. Dan Tunstall Pedoe, the London Marathon's Medical Director from 1981 to 2006, wrote in the journal, Sports Medicine, that an increase in marathon popularity as one contributor to the apparent increase in long-distance racing deaths.
Dr. Pedoe examined the records of documented sudden deaths across 650,000 marathon completions during that time, concluding that such risk in the London Marathon was 1 in 80,000 finishers. That's not far removed from London's two deaths in the last three years across about 105,000 runners (although the 2012 death of 30-year-old Claire Squiers has been primarily attributed to her use of a sports supplement containing the amphetamine-like drug, DMAA.).
A silent, genetic cause
These rare, tragic events deal a crushing blow to family members and the larger community, in part because even recreational marathoners are widely considered to be at their peak of physical conditioning.
But is there any way that sudden cardiac deaths in people under 40 or so could be prevented by detecting heart problems in advance? In older individuals, atherosclerosis or coronary artery disease is most often the cause of sudden death during athletic events but these situations will sometimes cause symptoms during training.
"When someone suddenly dies in an athletic event, particularly in teenagers and those in their 20s and 30s – the most common cause is hypertrophic obstructive cardiomyopathy," says Peter A. McCullough, M.D., M.P.H., a cardiologist at the Baylor University Medical Center at Dallas.
"This is a genetic abnormality of the proteins used by heart muscle cells. The heart becomes abnormally thick in one area and when the heart pumps, it has trouble ejecting blood past that thick point. The heart becomes very, very thick – two to three times as thick as normal," said Dr. McCullough.
This heart disorder, abbreviated HOCM or HCM, only starts to express itself around the time of puberty in boys and girls, so it can't be detected at birth.
You may already be familiar with the term, "athlete's heart," an adaptation where people who exercise frequently often develop a mild, generalized, and even-proportioned enlargement of the heart. But, HOCM is a distinctly different and pathological phenomenon. Here, the area of the heart where the unbalanced thickening (hypertrophy) occurs is in the walls of one chamber of the heart, the left ventricle, and particularly in the partition that separates the two ventricular chambers.
In addition, cardiac muscle cells and the fibers within them that are responsible for coordinated contraction and relaxation of heart muscle appear microscopically to be quite disorderly, an arrangement appropriately called myofibril disarray. The faulty and inefficient organization of these fibers is most often due to mutations in one of the nine types of proteins that make up these fibers.
"This can be the setup for an abnormal, circular heart rhythm that can take off on its own, called a re-entrant arrhythmia, that can degenerate into full-blown cardiac arrest," says Dr. McCullough. "The reason why it happens with exertion, and, in particular with dehydration, is that there's a decrease in the blood volume."
With the ventricles already having trouble filling with blood and ejecting it out, the abnormal heart rhythm develops, potentially because of less oxygen delivery to the heart muscle.
As to why some deaths seem to occur at the end of the race, McCullough says, "There's still a lot of circulating adrenaline so the heart is pumping very, very hard, but there's relatively little blood to fill it."
Moreover, blood pools in the legs when you stop running because there's no longer the contraction of muscles that helps push the blood back up.
A 2012 study published in the New England Journal of Medicine by the multi-institutional research team, the Race Associated Cardiac Arrest Event Registry (RACER) Study Group, showed that nearly 80% of the non-survivors of cardiac arrest collapsed in the final 25% of the distance of marathons and half-marathons, or shortly after finishing.
The RACER study was exhaustive, examining 59 cardiac arrests among 10.9 million registrants for marathons and half-marathons between 2000 and 2010. One additional concern that arose from this study is that men had an increased rate of risk of cardiac events over the study period that averaged five times greater than that of women. The authors posited that distance racing might be attracting a greater proportion of men with unrecognized cardiac disease who seek the health benefits of exercise.
Most dramatically, the study showed that younger runners (under age 40) experiencing cardiac arrest were almost seven times less likely to survive than runners over 40 (7% vs. 47%). The reason, the authors stated, was that the underlying cardiac disease was distinctly different: In those cases under age 40, the predominant condition was hypertrophic cardiomyopathy whereas older runners had ischemic heart disease, a condition that's more responsive to resuscitation efforts.
Another contributing factor to the low survival rate of those patients under 40 is that the ventricular tachycardia that precedes cardiac arrest – heart rates of 220-240 beats per minute – can only be reversed by a portable cardiac defibrillator during the first minute or two. Once the condition progresses to ventricular fibrillation, where the heart is essentially quivering and doing no actually pumping – oxygen deprivation has already progressed toward the point of no return.
So even if a defibrillator was at each water station – usually spaced every two miles – even a five-minute miler wouldn't be able to get the apparatus to the victim in time.
Detection and prevention
But how do you know if you have HCOM? Dr. McCullough says that a heart murmur can be detected in 75% of cases. But the gold standard for diagnosis is a cardiac echogram, or echocardiogram, an external examination of the beating heart using ultrasound.
"The cardiac community is divided on this," says Dr. McCullough. "But I fall in the camp where I think that everyone involved in serious athletics should have a echocardiogram, just like every woman who gets pregnant has two or three ultrasounds."
But others feel that that the number needed to screen for this rare anomaly is so large that it's not cost-effective for the healthcare system to, essentially, prevent these relatively few deaths. The consumer health information site, iTriage, lists the average, U.S. out-of-network cost for an echocardiogram as about $1,960, or $402 for in-network.
"I'm embarrassed about cardiologists who are opposed to uniform screening," laments Dr. McCullough. "You'll find that even our position papers and guidelines in cardiology do not support getting an echocardiogram beginning with adolescents."
He added, "It's ironic that we aren't so concerned about costs with a pregnant woman or a fetus but we are when the child gets to 13 or 14."
What's striking about the pathology of this disease is that medical science has the capability to detect one major, albeit rare, risk of cardiac death years before one might consider training for long-distance events.
A sleek chassis does not always equal a healthy engine
But McCullough raised another type of contributing factor that he and cardiologist, Justin E. Truvax, M.D., discussed in a 2012 review in the journal, Clinical Cardiology. If hypertrophic cardiomyopathy, anomalous coronary arteries, and coronary atherosclerosis have been excluded the cause in a sudden death in athletic competitions, another type of disorder brought on by endurance training might be to blame.
To distinguish this type of damage from HCOM, the authors called this type of damage Phidippides cardiomyopathy, after the Greek herald who died after running 175 miles in two days. Here, the heart doesn't have asymmetric, localized thickening of the walls. Instead, the heart forms scar tissue that accumulates over time due to excessive and repetitive stretching of the heart ventricles pumping a remarkably large amount of blood during prolonged training and competitions.
For perspective, your heart is pumping about five liters of blood each minute as you're reading this article. But when running near one's maximal heart rate, you pump about 35 liters of blood per minute, a 700% increase in demand on the heart.
"If you go run for 20, 30, 40 minutes – that's fine. The body's kind of designed to do that," says Dr. McCullough. "But when you go run for four hours straight, the heart chambers of about a quarter of individuals can't tolerate it. The chambers start to dilate and the heart releases distress signals."
Unfortunately, detecting Phidippides cardiomyopathy requires a cardiac MRI in order to see the scar tissue in addition to the changes in bloodflow. This procedure is more expensive and more time-consuming that an echocardiogram.
John Mandrola, M.D., a cardiac electrophysiologist and competitive cyclist wrote last year at Medscape about his reticence to tell patients that too much exercise might be a bad thing. He cited one meeting report on a study of 93 senior citizens where those that had been competitive athletes did not show any scarring of the heart. But he aptly noted that drugs have a dose-response curve – medium doses are useful in treating diseases while higher doses can cause unwanted side effects. So why wouldn't "doses" of exercise exhibit the same spectrum of responses?
But Dr. Mandrola offered the following in closing:
Please don't ask where the upper limit of exercise is. I don't think there is just one threshold. Individuals differ in their tolerance for stress. As physicians, though, we can emphasize to our patients what we know:
It is possible to exercise enough to harbor an increased risk of arrhythmia and maybe even induce fibrosis. It's worth noting that "superfitness" does not inoculate against heart disease. Do not judge a book by its cover. The engine should not be assumed healthy because the chassis looks sleek.
Dr. McCullough has likely run more marathons than any cardiologist studying this area. Between age 42 and 49, he ran a marathon in each of the 50 U.S. states.
But now?
"I personally have retired from running marathons. I'm convinced there's sufficient enough concern here that I just don't want to pay the ultimate price of overdoing it. I'm enjoying the shorter races."
In fact, Dr. McCullough had just finished a three-mile run before our interview. He said, "I feel great and I think one can get that great feeling that exercise delivers without going two, three, and four hours."
Was weather a contributing factor?
Race authorities in both cities expressed that it was unlikely that weather contributed to the casualties at both races. But conditions in London and Raleigh on Sunday weren't exactly conducive to comfort, if such a thing exists in marathon running.
At London's 10 a.m. racetime start at Greenwich, the temperature was at 51°F and was 61°F at the three-hour mark as runners were finishing in St. James Park, just a tick above average for April 13.
The Raleigh race went off at 60°F and was 65°F two hours later, with a relative humidity of 78%, also about average for this time of year. But 30 miles away in Durham where I was merely walking briskly while nursing an injured Achilles tendon, I was uncomfortable enough from the sun and humidity to think that I was happy not to be running a marathon in such weather.
A 2012 study published in the journal, PLOS One, is suggestive that these normal temperatures are above ideal for most runners. These Paris-based researchers examined twelve marathons in the the U.S. and Europe, concluding that the optimal temperature for elite male and female marathoners was 39°F and 50°F, respectively. For recreational runners finishing in the top 25%, men and women raced optimally at 43-44°F, with little gender difference.
A lasting gesture of kindness
The 42-year-old marathoner who died Sunday in London, Robert Berry, was running the race in honor of his mother who developed debilitating osteoporosis at age 52. He had hoped to raise £1,700 for the U.K. National Osteoporosis Society. At the time of this writing, donations at his JustGiving page exceeded £51,000.
Mr. Berry had been training well and certainly took the challenge seriously, but was still light-hearted. Following a long, late January training run at an average heart rate of 191 bpm, he wrote:
Longest run yet at 20.35 miles and predicted time to break 03:30, assuming the last six miles don't kill me! Not quite as fast as Tony's 03:17 last year!!
