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Few stories encapsulate the times we live in as well as the story of college football, heart damage, and COVID. Right now, as the college football season should be shifting into high gear, multiple conferences have postponed the start of the season or will skip this season altogether. As reported by Sports Illustrated, one concern weighing on the minds of the decision-makers is that the novel coronavirus has a particular proclivity for hearts.
"That's what has been the final straw," says a team doctor at a prominent college football program.
But a closer look at the evidence behind the assertions made by some in the medical community says it's less than credible.
Viral Videos of COVID Collapse
The initial rumors of cardiac involvement in COVID trace back to videos of individuals from other countries lying unconscious on the ground.
This would be unusual behavior for a respiratory virus, but with novel pathogens there is little that can be deemed implausible. The arrival of SARS-CoV-2 in the United States quickly allowed this particular myth to be busted. There are no viral videos of Americans passed out in public venues in the middle of cities with raging epidemics, because it never happened. Not only was there seemingly no increase in heart attacks, but the incidence was actually lower relative to what would be expected on the basis of prior years.
The unfortunate crush of patients in hospitals gave the medical community a bird's-eye view of how COVID-19 affects the heart. It quickly became clear that many sick patients with COVID admitted to the hospital manifested evidence of myocardial injury. The problem is that many, if not most, very sick patients, regardless of the cause, manifest myocardial injury when assessed by highly sensitive cardiac markers.
The accumulating data also confirmed that the sicker patients are, the more likely myocardial injury coexists. While some cardiologists inexplicably take this to mean that "acute myocardial injury is commonly observed in COVID-19 and is prognostic for worse outcomes," the data are horribly confounded by indication bias. Essentially, the patients most often tested for cardiac injury are those who are very sick with COVID-19. This is suggestive of correlation, not causation.
Of note no studies to date have been able to establish a direct mechanism of cardiac cell injury by the virus. There are a number of case reports and anecdotes that have received widespread coverage, but the published reports don't stand up to closer scrutiny.
Cardiac MRI vs Endomyocardial Biopsy
A definitive diagnosis of myocarditis requires a heart biopsy, a procedure that has rarely been done in many of the "diagnosed" patients. Endomyocardial biopsy is rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis. To date, only one case report, from Brazil, in a child who died with multisystem inflammatory syndrome in children (MIS-C), has shown viral particles consistent with the coronavirus within myocardial cells on autopsy. While reports like this are sure to spawn viral tweets, it's vital to understand that it's not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in. It took high PCR cycle threshold values to isolate virus from the lung and heart samples in the Brazilian patient. This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs.
The story of kidney injury in COVID-19 is analogous in this regard. A large number of patients hospitalized with COVID-19 developed acute kidney injury, but the mechanism was almost entirely via acute tubular necrosis, a frequent manifestation of severe sepsis and septic shock. Virus particles can be found in the kidney, but it is far from conclusive that SARS-CoV-2 is causing important kidney damage.
So how, then, does one explain the many reports of myocarditis? The path to the current spate of diagnoses involves some very highly sensitive tests for heart injury. The first step involves demonstration of myocardial injury using high-sensitivity troponin assays. These tests, unfortunately, are so sensitive that they turn positive even in healthy endurance athletes after a long run. The next step involves demonstrating cardiac involvement. Usually this is done by snaking a catheter through a patient's neck into the heart to take a bite out of cardiac muscle, but recently cardiac MRI has made the case for demonstrating cardiac involvement without the need for a biopsy.
The weakness of this completely noninvasive approach to diagnosing myocarditis is best demonstrated by a recent paper from Germany. Based on the premise that COVID may affect the heart to a greater degree than the medical community is aware of because we simply aren't looking hard enough, German investigators performed cardiac MRI on 100 patients who had recently recovered from COVID-19. Their stunning conclusion: 78% of these patients demonstrated abnormalities in their heart. The paper was published by a well-respected journal and is believed to have played a part in the decision made by at least one major college football conference to postpone the start of the season.
But almost immediately after publication of the paper, a cardiologist team in Britain noted significant irregularities in how the results were reported. The parameters studied in the paper are not normally distributed in a population.
Similar to the distribution of income in a population, most quantitative markers of cardiac injury and stretch, such as cardiac troponin I (CTNI) and brain natriuretic peptide (BNP), are low. Very high levels of CTNI or BNP are about as frequent as incomes over $400,000 in the population. When data are not normally distributed, they can't be described easily using averages with surrounding symmetric standard deviations.
Data that are not normally distributed can be better described as using median and interquartile ranges (IQR), which is exactly how the authors of the paper chose to present their data. The median in this case is used instead of the mean, precisely because outliers make the average of a dataset meaningless. It would be like taking the average net worth of parents at a birthday party where one of the parents is Elon Musk. Data that are asymmetric, or skewed, should lead to median and IQR values that are also skewed. Remarkably, the German cardiac MRI paper reports beautifully symmetric medians and IQRs. For example, the median BNP in COVID-recovered patients is 69 pg/mL, which is smack dab in the middle of the IQR from 53 to 82 pg/mL.
Suspicious Symmetry
These numbers, along with other irregularities, are implausible enough as to bring the veracity of the entire paper into question. But even if the mistakes in reporting are an innocuous clerical error, a cursory reading of the study suggests caution in drawing any strong conclusions. The investigators included a risk-factor–matched control group of patients who had never been infected with SARS-CoV-2, yet 16% of them also had signs of cardiac inflammation on cardiac MRI.
The authors made much of the fact that recovered COVID patients also had evidence of fibrosis on their MRI. This would appear to be even more concerning because fibrosis is typically an irreversible process; it suggests that healthy cardiac tissue is being replaced with scar tissue. But almost 20% of the risk-factor–matched controls showed evidence of fibrosis. If close to 20% of a control population is found to be abnormal, the real question relates to how the testing instrument is being calibrated.
It's quite possible that technological advancements are creating tests that are so sensitive that the word abnormal is losing its meaning. For instance, completely asymptomatic endurance athletes have been shown to have elevated biochemical markers of cardiac inflammation and injury as well as findings consistent with fibrosis on cardiac MRI. That's right — a proportion of completely healthy asymptomatic athletes, when subjected to the best tests available today, will be found to be "abnormal."
The dirty secret that some in the medical field are loath to inform the public of is that some advances in diagnostic testing have vastly outstripped doctors' abilities to make sense of the findings. To be fair, this is always true of the early experience with diagnostic tests. The ability to ultrasound the heart with great fidelity in the 1980s momentarily resulted in a rash of diagnoses of heart valve abnormalities. These were later attributed to cardiologists' limited understanding of how the normal heart valve moved. The cardiologists were in error, not the valve.
It is entirely possible that the German study's findings of myocarditis are a function of this same phenomenon. And even if it were to turn out that certain findings on an MRI increased the risk for a bad cardiac event by a factor of two, the very low baseline risk for cardiac death in elite athletes would make this increase in risk miniscule. The current upper bound of estimated risk for sudden cardiac death in athletes is around 1 in 40,000. Increasing the risk for death to 1 in 20,000 would hardly be grounds to prohibit athletic activity.
Seek and You Shall Find
Viral infections often cause myocarditis. Typically doctors don't go hunting for myocarditis unless the patient has symptomatic heart failure. A good medical sleuth needs a clinical basis to go fishing for a diagnosis. Using a bad MRI study that demonstrates findings of uncertain significance is no reason to recommend routine cardiac imaging of asymptomatic athletes prior to returning to play. A protocol-based approach to screening athletes, as some have recommended, is a self-fulfilling prophecy: Seek and you shall find. What would we even do with the information we may find? How could we tell if the cardiac MRIs from recovered COVID patients are any different from what we would see in a patient who recovered from influenza, or one who was in intensive care for any severe illness?
There are no convincing data that this particular coronavirus has any greater affinity for the heart than any other virus. Given the lack of convincing evidence to suggest a significant connection between COVID and heart injury, it is highly questionable for cardiologists or public health officials to make actionable recommendations regarding cardiac risk from COVID-19 to an asymptomatic healthy athlete, or to the college football community at large. Yet, somehow, COVID has seemingly broken the minds of enough people (perhaps we should be doing more brain MRIs?) that we are treated to the spectacle of the official Twitter account of the American Heart Association breathlessly quoting a Sports Illustrated article that in turn hypes the risk for "cardiac inflammation" that COVID may cause.
It's important to note that every year, some unfortunate individuals are stricken with fulminant severe myocarditis. Some of these individuals even happen to be athletes. But the wide experience to date does not suggest that the risk of this happening is higher in the COVID era than in any other season.
College football may very well have to be postponed for a multitude of reasons related to the pandemic, but concerns about heart damage in healthy athletes shouldn't be one of those reasons.
Anish Koka, MD, is a cardiologist in private practice in Philadelphia. He comments frequently on healthcare absurdities and on healthcare policy. He is also a co-host of the Accad & Koka Report Podcast. Follow him on Twitter @anish_koka
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Don't Let Dubious Science Cancel College Football - Medscape - Aug 21, 2020.
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