If—Then

By Zach Nichols

Jennifer White, MD’s path to Jefferson began in 2012 when her heart stopped.

A dedicated runner balancing motherhood and emergency medicine with weekly mileage goals, she was the picture of vitality. Always able to keep pace on the race course and in the hospital, White became alarmed when she had a fainting episode in the middle of an exercise class.

Some might dismiss a few seconds’ lapse as exhaustion or dehydration, but she was suspicious and went to see a cardiologist, who put White through her paces with a stress test.

“They were like, ‘You’re the healthiest person I know.’ I’m like, ‘I know!’” she says. “But I looked at my own readings, and it looked really weird. I realized I was missing something.”

The cardiologist prescribed beta blockers to help keep White’s heart in rhythm. But with a naturally low resting heart rate, she didn’t tolerate them, so she and her doctors decided on a pacemaker. During the procedure, she went into cardiac arrest and had to be shocked back into rhythm. An implantable cardioverter defibrillator (ICD) was added to the hardware in her chest, and life started to look like one of the clinical riddles she had to solve each day in the emergency room. The fresh question mark in her chest inspired her to seek answers, which led her to get tested and find out that she carried a gene for Long QT syndrome and—because the trait is 50 percent heritable—so did her two sons.

Long QT is part of a family of congenital diseases called channelopathies, which affect the ion channels of the heart’s nervous system, our inborn pacemaker. Because it affects function instead of structure, the malady of misfires can be detected only through genetic testing or telltale signatures on an electrocardiogram (EKG).

The QT interval, or QTc, is the part of an EKG’s line reading that measures the “reset” period of the heart when its nervous system “recharges” and prepares to fire again. A QTc that is too long can cause overlap between heartbeats, with one beginning before the previous one ends, resulting in a dangerous arrhythmia. These can be triggered by fever, exercise, sleep, excitement, certain medicines, and everything in between.

“For kids, sudden cardiac death occurs at a higher rate than death from cancer,” White says, and that is likely an underestimation.

Two years ago, she was recruited to Jefferson. She was looking for a place that would help her advance her life’s work of tackling the condition her family faces, along with the many other causes of childhood sudden death.

“It was between Jefferson and a New York hospital,” she says. “They said, ‘We’ll see,’ and Jefferson said, ‘Let’s do it.’”

Historically, resistance to detection has made channelopathies appear as a pall of bad luck that falls over a family with a litany of premature deaths, miscarriages, and unexplained car- and swimming-related accidents. In the rush and swirl of the ER, it can be hard to suss out mischance from pathology.

From her vantage as the first provider seeing an undiagnosed patient, White sees the effects of this quiet complexity firsthand when caregivers focus too much on initial perceptions or information. This can lead to a premature conclusion of the diagnostic process. “The paramedics say that was a seizure,” she says. “They bring in ‘the seizure,’ and it gets put down as seizure as the chief complaint. The patient goes to neurology, but all the while they had a malignant rhythm and the seizure was really a near-death spell.”

Thomas Jefferson University Hospital’s emergency room, where White is associate medical director and assistant program director of the Emergency Medicine residency, treats an average of 200 patients each day. On a given shift, she sees 30 to 40 patients, treating, teaching, directing traffic, and making rapid-fire decisions: Are they “sick” or “not sick”? What do they have? What initial tests need to be completed? Can they go home or do they need to be hospitalized?

“I have to be mindful of all the cues, or I might miss a critical story or symptom,” White says. It helps to remember that the torrent of patients is made up of individuals, each manageable, and each interaction structured by teamwork, best practices, and well-honed clinical intuition.

There is specificity within the variety, dozens of eureka moments as new clues present themselves and diagnoses jump out from a CT scan or a simple conversation. “I do ‘if-then’ for a living,” she says of the context-sensitive pathways she takes from presentation to action.

This conditional sensibility follows her home from the ER, where there are four kids to look after: Harper (8), Logan (11), Sam (13), and Emma (15).

Unlike White, Logan and Sam don’t have ICDs or pacemakers, though they wear MedicAlert bracelets and take beta blockers. Instead of internal devices, the family relies on the buddy system and a web of contingency plans and subplans to cover any “if.”

They own two automatic external defibrillators (AED), one for home and one that travels to activities and sporting events because each of the White kids is an athlete. At school, the nurse knows that if Logan or Sam passes out at recess, then she should come running with the AED. When the kids were younger, the family hosted AED and CPR parties to familiarize neighbors and friends—potential first responders—with the lifesaving tools.

Parents of children with channelopathies are often shocked to find out how much White does with her kids. As avid skiers, there’s not much they don’t do. “It’s probably one of the things that makes me the most nervous,” she says, citing the remote locations and the layers of clothing she’d have to go through to access her kids’ chests.

“Understandably, many [parents] won’t let their kids do much,” she says. “But I’m thinking pretty practically about what my family does. It’s all about time to AED placement.” She knows how to avoid potential triggers, the fevers and meds that could send the boys’ hearts offbeat. She also knows there are plenty of startles that are impossible to plan for—because they are by definition a surprise.

Once, when Sam was younger, White let him go down a big waterslide by himself. From the bottom, she watched him enter the tube, then waited for him to come out. Only he didn’t. “I was asking myself, ‘Do I run up the eight flights to the top?’” says White. “It turned out the slide wasn’t wet enough, and his suit had gotten stuck, so a lifeguard had to help him out.”

It is these moments of terror that drive White to learn more and share what she’s found. They’re also what inspired her to seek out Roy Hoffman, MD, MPH, medical director for the Philadelphia Department of Public Health’s Fatality Review Program and a pediatrician at one of the city’s district health centers.

Distinct from autopsies, death reviews offer insight into the context of fatalities and are a way to keep in touch with the health of vulnerable groups like the homeless, mothers, children, and infants. “One of the most important things in public health is surveillance,” Hoffman says. “You can’t see if something is a trend or if something is getting better or worse unless you know what the underlying rate is.”

Together, White and Hoffman want to better understand children who are dying unexpectedly in Philadelphia—where two to three infants die each month from a sleep-related death—and what they can do about it.

The United States has startlingly little data on rates of sudden death of children, which is why the Centers for Disease Control and Prevention launched the Sudden Death in the Young (SDY) Case Registry study. Now in its second five-year round of grantmaking, it aims to create a national database of demographic and genetic information, a long-term plan designed to set a benchmark against which local interventions can be compared.

Philadelphia is one of about a dozen sites in the country that recently have been awarded the latest grant to closely track sudden deaths in children and youth. The Philadelphia Department of Public Health is now expected to identify and investigate all child medical deaths that are “unexpected.” A child who dies from a previously undiagnosed brain aneurysm would qualify, as would a 5-month-old who dies in a crib. SDY doesn’t look at homicides, suicides, or most accidental deaths. These extenuating circumstances raise the question of what caused the mishap in the first place. Was it bad luck or some underlying, unknown medical issue? Hoffman estimates that more than 60 Philadelphians per year meet the SDY criteria.

White anticipates about 30 percent of these cases will be the result of cardiac channelopathies, which are typically diagnosed through a molecular autopsy, essentially a postmortem genetic test.

Physicians and public health officials can identify the genetic causes for many varieties of channelopathies, including Long QT, but there are likely other genetic factors that SDY will help to uncover. This is the study’s long view: To establish patterns and develop a picture of what “normal” looks like, so the work of managing a coordinated approach can begin.

“In the clinic, it’s very direct because my typical intervention with a child who presents with a problem is asking, ‘What’s wrong and what can I do right now?’” Hoffman says. “But when I put on my public-health hat, my ‘patient’ is a whole population, so I’m typically looking ahead to see what I can prevent.” This can be as simple as White’s AED parties or as complex as making family genetic testing more widely available to at-risk populations.

Hoffman and White are working to synthesize these distinct medical realms, the populations, and the individual patient. Their plan is to use molecular autopsies not only as a research tool but as a way to stop tragedies in the making. By working backward from the “index case,” the first documented patient, clinicians can rapidly test the rest of the immediate and extended family to determine who has the trait.

White has seen this if-then process in Jefferson’s ER. An 80-year-old patient came in with a facial fracture he sustained in a fall. While the patient was being treated, he went into torsades de pointes, a kind of tachycardia that often accompanies Long QT. After resuscitation, White says, “We took a history and found a couple of sudden deaths, which initiated cascade testing for his entire family.”

For White, knowing why a patient dies—or could die—suddenly is more than closure: It’s an opening. Here, knowing is the battle, taking the “sudden” out of “sudden death,” and transmuting it into an identifiable medical condition with a definite treatment plan.

Says White, “This is why I’m in emergency medicine.”