A Change of Heart

Clark lived for 112 days, eventually succumbing to complications that led to multiple organ failure. DeVries talked with Una and agreed that it was time to turn off his still perfectly functioning artificial heart.

Although doctors rarely go to patients’ funerals, in Clark’s case, he had asked them to attend, and they did. DeVries said Clark was “a remarkable man, a pioneer to match these western lands.”

In the years after the first in-human, long-term use of the total artificial heart, scientists across the country made improvements in technology that led to the more widespread use of a partial artificial heart.

The left ventricular assist device (LVAD) is a heart pump that helps the failing organ work better rather than replacing it entirely.

This advance, and its potential, captured the imagination of Drakos and Selzman early in their careers, from opposite sides of the world. Today, the two physician-scientists are leading efforts in leveraging the LVAD in completely new ways to improve patients’ prospects.

After Drakos finished his MD/PhD in Athens, Greece, in 2001, the former chief of cardiology at the University of Athens summoned him to the University of Utah. For decades, U of U Health had served as a training ground for Athens’ cardiologists, and Drakos followed in the esteemed footsteps of the many who had come before him. For two years, Drakos learned how to manage the complex care of patients living with LVADs so he could bring that training and heart failure therapeutic option back to Greece and Europe.

When he saw how LVADs were supporting “sick-like-a-dog patients that would have been dead otherwise, I was shocked.” Within a handful of years, U of U Health asked Drakos to return and join its faculty.

Meanwhile, Selzman pursued medicine as a student at Baylor College of Medicine in Houston, where one of the world’s greatest heart surgeons, Michael E DeBakey, MD, pioneered operations in the 1950s and implanted the world’s first LVAD in 1966. During Selzman’s first year at U of U Health in 2008, there was only one LVAD patient, he recalled, and that man could not leave the hospital because the pump was extracorporeal—it sat outside the body.

His goal is to use this knowledge to develop new therapeutics that heal the human heart, therefore limiting the need for mechanical circulatory support.

Indeed, in 2021, they published in top-tier scientific journals their research findings identifying novel therapeutic targets such as MCT4 and VDAC2 that are now being pursued as new, groundbreaking therapies for heart failure.

With Shaw’s arrival in 2019 to take the reins of running CVRTI, the emphasis of the institute has shifted toward bench-to-bedside research. This includes Shaw’s own passionate commitment as a physician-scientist to a molecule called cardiac BIN1 and the role it may play in healing a damaged heart muscle through gene therapy.

Shaw’s scientific partner in that work is TingTing Hong, MD, PhD, an independent investigator at CVRTI who grew up on the southeast coast of China, three hours south of Shanghai. Members of her family had histories of stroke and coronary artery disease, but it was her adored 72-year-old grandfather’s death that particularly troubled her. He had been diagnosed with heart failure but refused to attend the nearest hospital. Instead, each time he had an episode, he went to a local rural clinic with few resources. Impatiently, he accelerated the IV drip speed of his medication, which led to his demise.

Hong started her own research lab in 2013, continuing her long-time collaboration with Shaw and his team to answer the question: Could they restore the function of heart muscle cells during heart failure by repairing the architecture of those cells?

What drives Shaw is the tragic reality he often witnessed daily in the ICU. Patients who, because they couldn’t get a heart transplant—whether for lack of availability or medical complications—were essentially stranded in their beds, such as one man who is never far from his mind.

The patient was in heart failure in one of the top CVICUs in the country, where he had spent several months tethered to machinery keeping him alive. He knew he was a burden on his family and that he would not improve. Medical staff had put in a new type of temporary LVAD and waited for the next step.

But if staff hadn’t given up, the patient had. He did not want to burden his family further, economically or emotionally. He looked into Shaw’s eyes. “They need to move on with their lives,” he said. “I’ve had enough. Thank you. Stop the therapies.”

His family disagreed with him but respected his decision. Therapy was discontinued, and he died the next morning. “Damn it, we suck!” Shaw thought afterward. Shaw had nothing in his medical arsenal he could offer to either improve his heart or dissuade him from his decision. “We have to nod our heads in sage agreement that it’s enough and that’s a rational decision,” he said.

In summer 2022, Shaw and Hong were in the midst of the next step after their successes with mice to move their gene therapy forward, running a test with three pigs. Two had been treated with cBIN1 gene therapy; the third, a negative control that had simply been given saline. Shaw was traveling to visit family when Hong called to consult on the control animal whose heart was failing.

“How are the other pigs doing?” he asked.

She had recently checked their echocardiograms. Their hearts had normalized in size, as had the rate at which blood pumped from their hearts. “Oh, they’re normal,” she said.

Shaw was silent for a moment. They had been expecting some reversal of the condition but certainly not normalizing of the heart. He was almost as shocked by how casual Hong had been in delivering the news as he was by the news itself.

“Do you understand what you’re saying?” Shaw said. “Do you realize how important this data is?”

“Of course,” Hong said. “It works.” She had always had faith the project would work.

After they hung up, Shaw sat in silence for an hour in the lengthening shadows of the bedroom, sifting through the enormity of what he had just learned after 15 years of working toward this one, priceless moment.

Perhaps they could one day treat heart failure in the ICU—and perhaps treat early-stage heart failure so patients wouldn’t have to even enter the ICU. The gene therapy that Hong and Shaw are developing would be far less invasive—and could be much more effective—than machines like the artificial heart and LVAD.

“It sounds remarkable, but that’s what the animals are telling us,” Shaw said. “People will walk out of the ICU.” As much as he knew that further testing needed to be done—and how careful he had to be about wildly over-emphasizing their initial findings—he felt that same sense of faith that Hong felt. Perhaps he’d always had it—but hadn’t articulated it to himself of late.

Forty years on from Barney Clark’s life-changing operation, the legacy that was the gift of his own life for the furtherance of medical science remained as vibrant as ever. It was a gift that, four decades ago, former University of Utah President Chase Peterson told reporters stemmed from Clark’s faith that something good would come out of it for patients with failing hearts. “If other people do get a quality of life that is more obviously satisfactory,” Peterson said, “they better thank Barney Clark.”

That same faith continues today, whether in the confident hands and hearts of Selzman, Drakos, Shaw, and Hong or all the other heart researchers, physicians, and support staff at U of U Health over the decades.

A faith that their interdisciplinary efforts in cardiovascular research—to gain a deeper understanding of the heart and use that knowledge to create new tests and treatments—will indeed change people’s lives for the better.