Spring/Summer 2002

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Finally a
Way to Get Rid of A-Fib

Hugh Calkins
Hugh Calkins in the midst of an ablation.

Eighteen months ago, David Erdman was sure he had climbed his last mountain. An avid backpacker, Erdman sat down during a group hike to catch his breath and felt the flutter of palpitations in his chest. As others in the group passed him by, Erdman knew exactly what was happening to him. His heart was racing out of control from a malady called atrial fibrillation just as it had done several times before. Doctors had given Erdman medications to control the condition, even tried electrically shocking his heartbeats back into sync with a process called cardioversion. But nothing got rid of the condition-he kept on flipping back into "A-Fib." At age 50, Erdman felt like an old man.

"I thought I was going to die," he confesses. "When I got to the top of that mountain I said I'm never going backpacking again."

But Erdman's cardiologist felt differently. He'd heard that electrophysiologist Hugh Calkins was offering a new technique to treat A-Fib at Hopkins and encouraged his patient to give it a try. Calkins would thread a catheter from Erdman's leg up to his heart and, using a high energy probe, burn the tissue that was causing the problem.

Hugh Calkins likes to greet his new patients with a description of what's wrong with them. To those like Erdman with A-Fib, he explains that the electrical signal that begins each beat in their heart's atrium has gone awry. The culprit is muscular tissue-located in veins that connect the heart and lungs-that diverts the signal from its normal pathway onto off-ramps where it spins continuously. This causes the upper chambers to beat faster and faster, out of sync with the lower ventricles. By destroying the off-ramps, with a process called ablation in which radio-frequency energy is used to cauterize the area causing the problem, Calkins makes the signal stay on course.

Results have been encouraging. The ablation has been able to cure 80 percent of the patients Calkins has treated for intermittent A-Fib and 50 percent of those with chronic A-Fib. The secret to success, Calkins says, is knowing how to use MRI and a special catheter-shaped like a branding iron and armed with some 20 electrodes-to zero-in on the disruptive tissues in the four pulmonary veins. "Target the active pulmonary vein and the success rate jumps to 90 percent," he says.

There are risks. The procedure causes the pulmonary vein to narrow in about one in 200 patients. To reduce that possibility, Calkins now ablates on the outer edge of the vein. He also uses cryotherapy on some patients to freeze and destroy the tissue. "The procedure is ready for prime-time," Calkins says. "Physicians and their patients should know about it."

Erdman, meanwhile, hasn't experienced A-Fib in a year and currently is planning a six-day backpacking trip to Mt. Whitney in California's High Sierras.

-Gary Logan

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Brain Stimulation Can Give Parkinson's Patients a Life

When banker John Kellerman's left hand shook as he carried a bag of groceries, his wife, a nurse practitioner, at first shrugged it off. Then, the tremor reappeared, and this time they both took notice. At 38, Kellerman found himself saddled with Parkinson's disease. His condition improved with medication, but declined again as the disease outran the drugs' ability to help.

Eight years later, Kellerman had learned to cram his living into dwindling "on" times while enduring "off" ones-periods of rigidity and slowness and terrible difficulty moving. Worse, his "on" times were increasingly disrupted by drug side-effects: "The dyskinesias are awful and unpredictable," says Kellerman, referring to involuntary twisting movements-the last straw in isolating Parkinson's patients from society.

Thus Kellerman became a candidate for deep brain stimulation (DBS), a technique the FDA approved last spring to diminish Parkinson's tremor, slowness and gait problems and also decrease the dyskinesia. Moreover, says neurosurgeon Frederick Lenz, the Hopkins specialist who's performed nearly 196 DBS surgeries, the technique whittles down many patients' drug needs: "One or two have even gone off drugs altogether."

In DBS surgery, Lenz and his team plot a path to the right spot in patients' brains to stimulate-usually the subthalamic nucleus, an island of nerve tissue deep in the brain. Locating the nucleus is a high-precision process, and the awake patient plays an active role in helping pinpoint the target. Then, with the patient anesthetized, Lenz inserts and anchors a small electrode connected to a pacemaker-size neurostimulator he implants below the clavicle. "The stimulation blocks the ability of target basal ganglia to fire," Lenz explains, "as though they're lesioned." Once patients recover from surgery, clinicians fine-tune the stimulation frequency, distribution and voltage.

"DBS is by no means a cure," explains neurologist Stephen Grill, who assesses patients for the surgery and fine-tunes the stimulator, "but it returns a rich measure of patients' lives. Some say it's like turning the clock back 10 years on their disease."

Kellerman, whose balance is much improved, concurs. "It's made a real difference in my life," he says.

-Marjorie Centofanti

A DBS Photolog  
The transplant surgeon: Robert Montgomery; the patient: Alan Goody. 7:45 a.m. Using MRI, neurosurgeon Lenz (center) and DBS team mem-bers work out the location of their deep-brain target.
9 a.m. Lenz superimposes his proposed route for the recording microelectrode on
a brain map.
9:30 a.m. The electrode is eased into position in tiny 0.2 mm steps. The image of neuron firing-on an oscilloscope- tells the team how close they are.
12:40 p.m. The microelectrode enters the target site in the brain. Then, the
surgical team withdraws it and fixes a permanent stimulator in that same brain spot. Patient reactions tell Lenz if they're on target.
Three weeks later. Neurologist Stephen Grill programs the "business end" of the stimulator, implanted beneath the skin. He videotapes a baseline measure of its abilities.

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Joy Yang's Powerful Flecks of Lint

Joy Yang

In 1995, as a postdoctoral fellow at M.I.T., Joy Yang made a fascinating discovery. She deleted a protein called alpha 4 integrin from mouse embryos and discovered that the embryos developed hemorrhaged hearts and died before reaching maturity. Death came, she determined, because the embryos were lacking the topmost layer of the heart, the epicardium, and therefore couldn't grow coronary vessels to circulate life-supporting blood.

Why, Yang wondered, is alpha 4 integrin necessary to develop an epicardium? To find out, in 1996, when she joined Hopkins' Department of Cell Biology, she went right on studying the same mouse-embryo protein. Now she's come up with another discovery-it turns out that the alpha 4 integrin helps the cells destined to form the epicardium and coronary vessels attach to the surface of the heart.

Yang and her lab group made their discovery by cutting out pieces of embryonic tissue-tiny flecks that looked like lint floating in a petri dish-and letting them crawl across a chamber coated with a protein called fibronectin that is known to bind to alpha 4 integrin. What soon became clear is that cells missing alpha 4 integrin had trouble attaching to the fibronectin. Those that did manage to stick remained huddled where they landed and couldn't move across the heart to form the epicardium.

Yang knows just this much so far. Now she is pressing ahead with her next question: Does alpha 4 integrin continue to play a key role in helping the epicardium build the coronary vessels?

And what if it does, you might ask. Would knowing this contribute anything to medicine? Yang is still some distance from that step. That's the way basic science works. But she has some ideas. People who develop congenital heart disease, she speculates, might have mistakes in alpha 4 integrin. If that were the case, understanding how the protein works certainly would help physicians have a better grasp of the condition-and how to deal with it.

- Raj Mukhopadhyay

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The Neurosurgeon's a Woman

Judy Huang

Judy Huang breaks the stereotype about women not wanting to become neurosurgeons. To hear her talk, she charted a course in elementary school and rolled right into the OR at Johns Hopkins Bayview several decades later, scalpel in hand.

"Being a woman is a non-issue," says Hopkins' first female attending neurosurgeon. "There are two women neurosurgery residents at Hopkins. Along the way, I've had fine role models who didn't care about my gender as long as I was good at what I did."

Huang, who arrived here this summer, specializes in degenerative spinal disorders and brain tumor surgery. Her main interest, however, lies in performing the operation known as a carotid endarterectomy. She shares a philosophy with her colleague Rafael Tamargo in the usefulness of removing the buildup of fatty tissue in the carotids, the main arteries of the neck and head, to prevent a stroke.

"And even though that surgery's short-under two hours-it's elegant. It's like a ballet when things go well," she explains.

Huang has published widely on stroke and does bench research on inflammatory mechanisms underlying brain damage after stroke. She's also interested in why ruptured cerebral aneurysms are more common in women than men.

A graduate of Brown University and of Columbia University College of Physicians and Surgeons, where she did her internship and residencies, Huang's never doubted her course: "There's nothing else I'd be happy doing," she says.

-Marjorie Centofanti

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A Driven Surgeon Moves in on the Diabetic Foot
Lee Dellon gets his intellectual kicks from pioneering new techniques.

Two months post-op, Dellon takes a look at his patient's now pain-free foot.

Lee Dellon is back in the news. This time, it's for an unusual procedure he's developed to treat the most common complication of advanced diabetes-the agonizing tingling and numbness of the feet.

Dellon, a 1970 graduate of the School of Medicine. has always been what you might call, well, driven. A plastic surgeon who maintains two practices on opposite sides of the country-one in Baltimore, one in Tucson-he's written three books and some 300 articles on everything from cleft-palate surgery to reconstruction of the fingertip. He also gained wide recognition for pain-relieving peripheral nerve surgeries-a specialty that blends neuro and plastic surgery. "I like developing techniques that are unique," Dellon says. "I enjoy that intellectual thrill. It's the spirit of a Hopkins education."

For such accomplishments, plus the fact that since 1978 he's helped train Hopkins plastic surgery residents, Dellon received a singular nod from the School of Medicine. Johns Hopkins made him a full professor even though he's always practiced outside of Hopkins Hospital.

Dellon's interest in restoring function to damaged nerves began back in his third year of medical school. About 15 years ago he began focusing on the diabetic foot problem. Caused by nerve compression, the condition feels like rubber bands wound around the toes, according to some patients. Many with the "neuropathy" can't sense when a bath is too hot or even feel the pain when they unwittingly step on a sharp object. The ulcerations, even huge holes, that result on the soles of their feet often end in amputation.

The foot complication, Dellon knew, occurs when diabetes causes nerves to swell, decreasing the blood flow in tight anatomic areas. What he wasn't sure of at first was the exact nerves involved. Finally, he examined enough cases to figure out that the main compressions were at the outside of the knee, the top of the foot and the inside of the ankle. If he used a technique similar to carpal tunnel surgery, Dellon reasoned that he should be able to open the small canals in which the nerves travel and restore the blood flow.

He tested his hypothesis on diabetic rats and monkeys, dividing the ligament across the tarsal tunnel nerves in their feet to open the tight area. When the procedure improved nerve-function and restored sensation, Dellon moved on to humans. Today he has operated on some 400 patients for the painful foot condition, and 80 percent of them no longer suffer the distress and numbness. People from all over the nation, in fact, now flock to Dellon's Institute for Peripheral Nerve Surgery for the operation or make an appointment with one of 98 other surgeons around the world he's trained in the technique.

"The surgery doesn't cure anyone's metabolic neuropathy," Dellon makes clear. But it does relieve their symptoms. No one who's had it has developed a foot infection or ulcer or had a foot amputation. That's a pretty big step forward."


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The Stroke-inducing Hole in the Heart

Everything about repairing a PFO can be tricky, even finding it.

Cardiologists Jon Resar, left, and Richard Ringel, with the device they use to close the hole in the septum.

The physician was puzzled. His patient, a 54-year-old Baltimore woman, had suffered a severe stroke and was paralyzed on the right side of her body. But the doctor couldn't discover what had caused the stroke. Tests didn't show bleeding in the brain or narrowing in her carotid neck arteries, the usual culprits. It took a referral to Hopkins, in fact, and an extensive examination to determine that the problem had been a much less-common but remarkably dangerous stroke-inducer, a small hole called a patent foramen ovale (PFO) in the septum between the upper chambers of the heart.

All fetuses have a PFO in their developing hearts. The minuscule hole closes naturally in 85 percent of newborns. But in about 15 percent it remains open. And it can act like a time bomb. A single clot passing from the left to the right atrium can go straight to the brain. "Usually such clots are small enough that they just lodge in the lung and dissolve," says pediatric cardiologist Richard Ringel. "But those that move into the brain and block a blood vessel cause drastic problems."

When specialists conclude that a stroke has been caused by a PFO, there is only one way to make certain it doesn't happen again-and with potentially lethal consequences. The hole must be closed. But everything about the repair can be tricky, even locating the PFO with X-ray imaging. Ringel, a specialist in correcting congenital heart disorders in children, and Jon Resar, an adult cardiologist who specializes in catheter approaches, work together to repair these anomalies.

To pinpoint the exact location of the PFO, the duo performs a special "bubble study," in which they inject agitated saline rapidly into the patient's vein. These show up in image studies as whirlpools within the blood system. Ringel asks the patient to bear down. Any PFO remains closed at least 90 percent, but straining causes a change of pressure in the two chambers and pushes the hole open. If the imaging shows the whirlpools passing through the septum, it's likely because of a PFO.

Once they've found the hole, Ringel and Resar don't open the patient's chest to do the repair. Instead, they make one tiny incision in the leg and feed a catheter up to the heart's right atrium through the PFO into the left atrium. By inflating a balloon-which takes on an hourglass shape as it expands on both sides of the PFO-the physicians determine the size of the device they'll need to seal the hole. They then insert the umbrella-like sealing device, until it feels "nice and tight" against the septum and release it by pulling the catheter back into the right atrium. They deploy the identical other half of the sealing device on the other side of the hole, and they make sure there aren't any leaks, by injecting a dye. The patient is usually out of the hospital by the next day.

"After three months the device will be covered with body tissue and incorporated into the wall of the heart," Ringel says. "The risk of clot and stroke is gone."

-Gary Logan