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Almost 2 weeks after Damar Hamlin suffered a cardiac arrest during a Monday Night Football game, the underlying cause that triggered his condition has yet to be revealed -- but that's because his doctors have to conduct an extensive workup involving several possibilities.

Cardiologists and electrophysiologists who were not involved in Hamlin's care outlined those possibilities in interviews with MedPage Today.

Since Hamlin's case was witnessed by so many people, that helps narrow the diagnoses a bit, said Zian Tseng, MD, a cardiologist and cardiac electrophysiologist at the University of California San Francisco. Hamlin had a "documented rhythm of ventricular fibrillation and was then shocked for it, that really does help narrow it down that it was an arrhythmia-related cardiac arrest," he said.

In a case like this, doctors would take a complete history and physical, noting whether the patient had any prior symptoms, such as chest pain, shortness of breath, or fainting. Doctors would also determine if the patient was taking any medications or supplements.

Meagan Wasfy, MD, MPH, a sports cardiologist at Massachusetts General Brigham in Boston, said an analogy for how physicians would approach a case like this would be to think of the heart as a house. They must check the plumbing (the arteries), structural issues, and the electrical system.

"The evaluation really has to look at all the potential systems that can contribute to a sudden cardiac arrest event," Wasfy said.

Physicians might first consider ischemic heart disease, such as a myocardial infarction, as a potential cause, as well as dissection or spasm of the arteries or some other kind of congenital anomaly in the heart's blood vessels.

"Any coronary artery-related or ischemic heart disease would be one big thing to rule out," Tseng said.

Next, doctors would look for structural problems, such as hypertrophic cardiomyopathy or any increased thickness or dilation of the heart, along with any valvular problems.

"Sometimes that may require not just an echocardiogram, but an MRI, to rule out more subtle things like myocarditis, or cardiac sarcoidosis, or any kind of infiltrative disease," Tseng said.

If those tests don't reveal anything, then electrical problems need to be considered, he said.

A baseline electrocardiogram (ECG) can reveal conditions that may predispose someone to sudden cardiac arrest, such as Wolff-Parkinson-White (WPW) syndrome, long QT syndrome, or Brugada syndrome, he said.

If the patient is negative for all of those conditions, "then we go down the pathway of looking for rare electrical causes," he said, which involves an exercise test or an electrophysiology study "where we do programmed electrical testing ... to try to reproduce the ventricular fibrillation or the ventricular tachycardia."

It's possible that some patients may have genetic testing to find something extremely unusual, such as an "unrecognized channelopathy," Tseng said, but doctors tend to be cautious about these results.

Kiran Musunuru, MD, PhD, MPH, a cardiologist and cardiovascular genetics expert at the University of Pennsylvania, said the challenge with genetic testing is that it could yield false-positive results or variants of uncertain significance.

That "could lead to unnecessary testing and to undue stress for the patient and their family members," Musunuru said.

Nonetheless, it's unlikely an NFL player would be allowed to return to play unless every diagnosis has been ruled out, Tseng added.

If all of these pathways are explored and nothing turns up a positive finding, then doctors can consider concluding that Hamlin's cardiac arrest was indeed caused by commotio cordis, that rare condition in which cardiac arrest occurs after a blunt force trauma to the chest at a specific time during the heart's beating cycle.

Tseng said the episode did look "very consistent with chest wall trauma."

"If everything is negative and all you're left with is, he collapsed on the field and had ventricular fibrillation, and right before that he had this really violent tackle -- I think that would be consistent with commotio cordis," Tseng said.

Yet he warned that it's a "tall order" to rule out all possibilities; to make sure Hamlin hasn't had previous chest pain or fainting, that the ECG is completely normal; that a full electrical study yields no abnormalities. It would also be "dangerous" to conclude commotio cordis and "miss something else that might be able to recur and cause another cardiac arrest."

Wasfy echoed those sentiments. She said that going into an evaluation with any type of bias "leaves you at risk for not recognizing any other potential contributors. You have to keep an open mind and be thorough, thoughtful, and methodical about the evaluation."

She noted that "being able to rest on a diagnosis of exclusion is extremely nuanced ... and is up to the medical team that knows all the details."

If it is indeed commotio cordis, only a "perfect storm" could have led to the event, Tseng said. "There's a small window in your electrical activation and recovery period where your heart is particularly vulnerable to inducing [ventricular fibrillation], and that's at the peak of the T wave. It's something like 20 milliseconds out of a typical 1,000 milliseconds of your heartbeat."

"You have to time it to that 2% of your heart cycle, and the force has to be enough to reach the heart, and it has to be right over the heart," he said. That's probably why it's not commonly seen in football, he said.

And even if the diagnosis ends up being commotio cordis, said Tseng, that doesn't mean there isn't something else going on with the heart that could have increased susceptibility to another event.

"Any sort of underlying condition could make somebody more prone to commotio cordis events," he said. "It doesn't mean that they can't both be true."

Tseng is the founder and primary investigator of the NIH-funded "postmortem systematic investigation of sudden cardiac death" (POST SCD) study, which investigates the underlying cause of every single sudden cardiac death in the county of San Francisco. Among its most is that nearly half of presumed cardiac deaths were not indeed cardiac-related on autopsy.

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