Originally published on CardiovascularBusiness.com in March 2019, this feature has been updated to include new data on transplanting hepatitis C-infected donor hearts. Through Penn Medicine, Tom Giangiulio Jr., shared that he is still doing well nearly three years after his transplant.
Not much of a choice
By the time three transplant physicians approached Tom Giangiulio Jr. about being the first patient in a clinical trial to accept a heart from a hepatitis C-positive donor, Giangiulio felt he didn’t have much of a choice. He had already been on the heart transplant waitlist for more than two years, he was a live-in at the Hospital of the University of Pennsylvania and he had a body size (6-foot-2, 220 pounds) and blood type (O-positive) that were difficult to match to a donor.
It took Giangiulio less than 24 hours to speak with his previous cardiologist and his family and decide to enroll in the program. The doctors at Penn explained to him that because of new antiviral medications that can cure hepatitis C, they were confident the virus could be eradicated post-transplant.
“There was no hesitation at all, not with me,” Carin Giangiulio, Tom’s wife of more than 30 years, told Cardiovascular Business in 2019. “Because I knew what the alternative was, and we didn’t have too much choice except for going on a VAD [ventricular assist device] … and he didn’t want to do that. I said, ‘If they have a cure, then it’s a no-brainer. Let’s just do it.’ And I’m glad we did because I don’t think he would’ve been here today.”
Tom, now 60, is set to celebrate his third anniversary with his new heart in June. He received the heart the day after Father’s Day in 2017 and subsequently contracted hepatitis C, which was wiped out with a 12-week regimen of elbasvir/grazoprevir (Zepatier; Merck Sharp & Dohme).
In early 2019, some of Giangiulio’s doctors at Penn published their experience with the first 10 patients in the clinical trial, called USHER, in the American Journal of Transplantation (19:2533-42). All nine patients who survived were cured of hepatitis C with the antiviral therapy.
‘We can do this safely’
The implications of the research are massive, says Rhondalyn McLean, MD, MHS, medical director of Penn’s heart transplant program and lead author of the study. For the past two decades, the U.S. has struggled to increase the number of heart transplants above about 3,000 per year. Every year, patients die waiting for a heart transplant or become too sick to handle a transplant surgery.
McLean estimates 700 hearts from donors with hepatitis C are discarded each year in the U.S. If even half of those are suitable for transplant, it would increase by 10 percent the number of organs that are available for implantation. “There are so many people who have end-stage heart failure who die waiting for transplant, so anytime that we can increase our access to organs, then I think we’re all going to be happy about that,” she says. “I think the people believe in the medicine, they believe that hepatitis C is curable, so the risk to these folks is low. With the results of the study, I think we’ve proven that we can do this safely and the medications have great efficacy.”
Transplanting hepatitis C-positive hearts isn’t a new idea, McLean explains. “We used to do this all the time [with] the thinking that hepatitis C usually doesn’t cause a problem for many, many years, so if hearts are only going to last 13 years or so and hepatitis C doesn’t usually cause a problem for 30 years in someone, it should be an OK thing to do,” she says.
But then a study published in the 1990s found hepatitis C-negative patients who accepted a heart from a donor with hepatitis C actually had an increased risk of death compared to those who received normal hearts, and the practice of using these organs ceased.
However, with the new medications—the first commercially available treatment for hepatitis C was approved by the FDA in 2014—McLean and her team are among researchers studying the safety of implanting these hearts and then wiping out the virus once it’s contracted.
McLean is optimistic about the program, which showed the first 10 patients had no evidence of the virus after their 12-week medication regimens. “That met the criteria for sustained virologic response, and those patients are deemed to be cured,” McLean says. “There’s no reason to think that this population would be any different than your normal, non-transplant population [in terms of hepatitis C reappearing] so I think it was a pretty successful study.”
Penn researchers also are studying a similar approach in kidney and lung transplant candidates, which could help patients stuck on waitlists for those organs as well. McLean describes the increasing availability of these organs as an “unfortunate benefit” of the opioid epidemic. Through sharing needles, many opioid users are contracting hepatitis C and dying young. Organs from young donors tend to perform better and often have no other problems, so solving the hepatitis C issue through medication could have a huge impact if this strategy is eventually rolled out on a broader scale.
“It’s hard when you have single-center studies,” McLean says. “They’re always promising, but in order to get a better assessment of what we’re doing and how the drug is doing I think you need to combine numbers so there has to be a registry that looks at all of the patients who have received these drugs and then using numbers to determine whether this is a successful strategy for us. And I believe that it will be.”
Indeed, studies published after McLean spoke with CVB are examining the strategy. In early 2020, for example, researchers at the University of Pittsburgh Medical Center studied 7,889 patients from 128 medical centers who had severe heart failure and received heart transplants between 2016 and 2018. Slightly more than 4 percent of the patients received hepatitis C-infected hearts. In the Journal of the American Heart Association, the researchers reported that one-year post-transplant survival, rejection rates and complications were similar between the patients receiving non-infected vs. infected donor hearts (2020;9:e014495).
Among centers performing heart transplants, 28 percent are currently using hepatitis C-positive donors, the authors wrote. They called for more research to assess longer-term results and noted that protocols for transplanting hearts from infected donors should be refined as part of a plan for alleviating the national donor shortage.
Those are some of the large-scale implications of research into using hepatitis C-infected donor hearts. Tom Gangiulio told CVB about the personal side.
‘Patient No. 1’ shares his story
Giangiulio says he feels “extremely gifted” to be Patient No. 1 in the USHER program. He knows he might not be alive if he wasn’t.
He recalls going into ventricular tachycardia about a week before his transplant and said it “scared the daylights” out of him.
“The amount of red tape, meetings and research, technology and things that had to happen at a very precise moment in time for me to be the first … it’s mind-boggling to think about it,” he told CVB. “But for all that to happen and for it to happen when it happened—and for me to get the heart when I got it—there was a lot of divine intervention along with a lot of people that were involved.”
Giangiulio also has experienced some powerful moments since receiving the transplant. After a bit of written correspondence with his donor’s family, he met the young man’s family one weekend in December 2018.
He says riding to the meeting was probably the most tense he’s ever been, but once he arrived the experience far exceeded his expectations. “We were there for 2½ hours and nobody wanted to leave,” Giangiulio recalls.
The donor’s mother got Giangiulio a gift, a ceramic heart with a photograph of her son. A fellow transplant patient had told Giangiulio about a product called Enso, a kidney-shaped object you can hold in your hand that plays a recording of a user’s heartbeat.
Giangiulio decided to give it to her. “I was very cautious at the advice of the people here at Penn,” he says. “Nobody knew how she would react to it. It might bother her, she could be thrilled to death. And she was, she was thrilled to death with it and she sleeps with it every night. She boots up the app, and she listens to my heartbeat on that app every night.”
Another moment that sticks out to Giangiulio was meeting Patient No. 7 in the USHER program. They ran into each other while waiting to get blood work done and began talking about their experiences as transplant recipients. The clinical trial came up in their conversation, and Giangiulio slow-played his involvement, asking Patient No. 7 about the trial and not letting on that he was ultra-familiar with the program.
When Giangiulio finally shared that he was Patient No. 1, Patient No. 7 “came launching out of his chair” to hug him. “He said, ‘I owe you my life,’” Giangiulio recalls. Patient No. 7 had specifically asked how Patient No. 1 was doing when McLean first offered the program to him.
“She explained that I was going to be No. 7. … I didn’t care about 6, 5, 4, 3 or 2. I wanted to know how No. 1 was doing,” Giangiulio recalls of the conversation. “He said, ‘That was you. … They told me how well you were doing and that if I wanted you’d come here and talk to me, so I owe you.’”
Giangiulio feels strongly about giving back and reciprocating the good fortune he’s had. That’s why he talks to fellow patients and the media to share his story—because it could save other people’s lives, too.
He can’t do as much physical labor as he used to, but he remains involved in the excavating company he owns with his brothers and is the emergency management coordinator for New Jersey’s Waterford Township. He also serves on the township’s planning board and was previously director of public safety.
“To me, he’s Superman,” Carin Giangiulio says. “It was insane, completely insane, what the human body can endure and still survive.”
That now includes being given a heart with hepatitis C and then wiping out the virus with the help of modern medicine.