TAMPA — The Tampa surgeon who conducted Florida's first heart transplant, a radical procedure at the time, had confidence it would help improve his patients' quality of life.
He's pushing ahead with the same confidence in a new arena now — only this time, much of the work is being done outside the United States because it's deemed too risky here.
Heart patients, again, are among those who stand to benefit from the new procedure — boosting and injecting adult stem cells to help repair damaged parts of the body.
“It works,” said the surgeon, Raghavendra Vijaynagar. “It is only a start. Perhaps one day stem cells can do much more for someone's heart.”
Stephen Carre is a believer. The 63-year-old Sun City man had a history of heart problems — just walking across the room brought on chest pains and shortness of breath — but he didn't rate a top spot on the list of heart transplant candidates. He underwent the new procedure in the Bahamas and now is playing softball again.
“I felt like a guinea pig,” Carre said. “But I was desperate, and I trusted Dr. Vijay.”
The Food and Drug Administration requires more than that, including extensive sanctioned clinical studies to prove the procedure is safe for patients.
Anything less raises questions among skeptics such as Dr. Charles Lambert, of Tampa, medical director of the Florida Hospital Pepin Heart Institute and Dr. Kiran Patel Research Institute.
Hundreds of clinical studies are taking place throughout the United States, Lambert noted, to determine whether stem cells are safe and effective for Alzheimer's disease, diabetes, spinal problems, heart conditions and more. He said he doesn't believe the studies have proved anything.
“There is a reason there is currently no FDA-approved products on the market,” Lambert said.
Carre was the first stem cell patient of Advanced Innovative Medicine, a company founded by Vijaynagar in 2009 to seek the cures of tomorrow for today's ailments and focus on stem cell technology for the heart.
Carre had undergone two bypasses to reverse damage from repeated heart attacks, yet in 2012 he was told that most of his arteries again were blocked.
The amount of blood pumping from his heart, known as the ejection fraction, had dropped to about 38 percent; a healthy percentage is 55 to 70. Cardiologists wondered whether his heart could handle another bypass. He needed a heart transplant but might not have been able to get one until his condition grew even worse. Hearts are in high demand. Patients with lower ejection fractions would be higher on the list.
He sought another option. In October 2012, from its FDA-approved lab in Orlando, Advanced Innovative Medicine used technology it licensed from the Canada-based medical research company Hemostemix to grow tens of millions of stem cells from blood extracted from Carre.
These adult stem cells, found in the organ tissues of children as well as adults, are not the same as embryonic stem cells, which are extracted from human embryos.
When an organism is injured, stem cells travel to the troubled area and repair it.
“The heart does not always get enough stem cells to repair damage following a heart attack,” Vijaynagar said. “So what we do is give it enough to fix itself.”
In the AIM procedure, new stem cells grown from the patient's blood are injected directly into the heart, forming new blood vessels to pump the necessary blood into the heart. It's a kind of natural bypass procedure.
Growing adult stem cells in the United States is legal in an FDA-approved lab. But because the FDA considers the cells to be a drug, requiring further testing, administering them to a patient is illegal unless done through an FDA-approved clinical study.
Advanced Innovative Medicine has not sought FDA approval for a study. The procedure has been approved in the Bahamas, where Carre was treated a few days after the new cells were grown.
A year after the stem cells were grown from his blood, the man who could once barely make it around his home was doing yard work and taking batting practice with his softball team.
Carre said his cardiologist told him his ejection fraction had risen to about 45 percent. The cardiologist would not respond to requests for an interview.
Though the procedure did improve Carre's quality of life, Vijaynagar stressed that he did not “cure” his patient. Carre's heart, Vijaynagar said, will never be fully healthy again.
Dr. Mark Zucker, director of the Heart Failure Treatment and Transplant Program at Newark Beth Israel Medical Center in New Jersey and a member of Hemostemix's scientific advisory board, agreed with that assessment.
“A patient of ours followed by me for many years wound up going to Thailand for the stem cell therapy,” Zucker said. “Her ejection fraction prior to treatment was about 14 percent. A few months after treatment it was up to 40 percent, a marked improvement. Then a few years later, however, she ended up getting a heart transplant.”
This shows the treatment to be a quality of life option for patients such as Carre, Vijaynagar said — those who cannot live comfortably in their condition but cannot get a new heart soon enough. It's a Band-Aid for the heart.
AIM treated its second patient a few weeks ago, and the company says it is confident the results will be similar to Carre's. A third patient, whom Vijaynagar described only as a “Tampa VIP,” may soon undergo the procedure as well.
Pepin Heart in Tampa conducted two FDA-approved clinical studies on injecting stem cells grown from a patients' bone marrow into their damaged hearts.
“Both studies showed minimal benefits to the patients,” Lambert said. “There were some who got better and some who stayed the same. Some actually deteriorated.”
Lambert added that any medical study conducted in the Bahamas should be met with skepticism. In his opinion, he said, the island nation is among the least regulated in the world.
“The FDA is strict on research on people,” he said. “This is good because there is better patient protection here.”
Vijaynagar said technology AIM licensed to grow stem cells is different from the Pepin Heart procedure that Lambert described. Using blood rather than bone marrow is one example of how it differs.
And Vijaynagar said he did seek to conduct FDA-approved studies but the only way he could afford it was to turn control over to a research institute, which he refuses to do. He said AIM's team is just as qualified as any institution's. He would work “with” a research institution but not “for” one, he said.
Vijaynagar understands the concerns, he said. Because he charges for the procedure and because it is not FDA-regulated, peers will always question the safety of the procedure and the authenticity of his results. He said he is aware of reports about ineffective or even dangerous stem cell procedures.
“I'm not an idiot,” Vijaynagar said with a laugh. “My résumé speaks for itself. I know what I am doing. And this is not the first time people have not believed in me.”
Vijaynagar was born in 1939 in Hospit, India, a town so small no one owned a camera. When he learned through books and magazines about doctors in the United States performing heart surgery, he declared this his dream career, even as he was mocked by those who knew him.
“It sounded more like science fiction than science to my friends. That provided me with more motivation. I've always been the type of guy who likes to prove people wrong.”
In 1983, when it was announced he would perform the first heart transplant in Florida, at Tampa General Hospital, he received hate letters. Hospitals in two other states had successfully done the procedure, but locals were not sold on the safety of the technology. Even his peers were doubtful, Vijaynagar said.
“I had done my due diligence. I knew it was safe. ”
By the time he retired from Tampa General in 2007, he said, he had done 200 heart transplants — nearly one-fifth of the heart transplants in the hospital's history.
The hospital could not confirm this number, but when asked about Vijaynagar's role there, this response came via email from Sjonne Mabbott, a heart transplant coordinator at the time the program started: “Dr. Vijay was one of the driving forces for the development of our heart transplant program.”
He was also the first to perform three other types of heart surgeries at Tampa General.
In a proclamation passed to honor Vijaynagar's career in 1998, then-state Sen. Charlie Crist wrote that the heart surgeon “helped put his city and state on the map, worldwide.”
And in 2003, then-Gov. Jeb Bush appointed Vijaynagar chairman of the Florida Board of Medicine.
Despite these credentials, Vijaynagar said he was not satisfied with his career.
The average heart transplant patient, he explained, survives an additional 10 years. He felt more could be done.
“I could have retired to the beach and been remembered for a good career. That is not who I am.
“A great doctor is not only one who saves lives, but also one who thrives on new discoveries that can save lives. I believe anything and everything is possible through science.”
This belief led him to stem cells. Vijaynagar researched a number of technologies before concluding that Hemostemix was the best option.
“I studied them for four years, talked to many experts and visited their labs. I was very impressed.”
Hemostemix conducted a clinical trial in Thailand from 2004 to 2006 on the impact of its stem cell technology on 24 patients suffering from angina pectoris — chest pain caused by poor blood flow.
Hemostemix founder Valentin Fulga said all 24 patients showed improvement. More importantly, the doctor said, none suffered adverse side effects from the stem cells. Valentin then conducted two studies, one in Thailand and one in Hungary, on his technology's effect on patients with critical limb ischemia, poor blood flow to the lower extremities.
Like the Bahamas, Thailand and Hungary are among the least medically regulated countries in the world. Studies conducted there carry little weight in the United States or Europe, said Lambert, of Pepin Heart.
Still, the impact of Fulga's technology's on critical limb ischemia was accepted for further studies in Health Canada — the federal health system of Canada.
Though Health Canada is less stringent in its regulation than the FDA, it is not far behind, Lambert said. Medical researchers often choose the United States' northern neighbor because its less stringent regulations mean the clinical studies are less expensive to perform.
“In general, the cost of doing a study in the U.S. to bring a product to market applies to drugs, devices and biologics,” Lambert said. “The FDA generally requires a higher level of evidence and safety than do other countries. All of this costs money.”
Researchers, he explained, who think they have a “home run” will sometimes conduct a study in Canada then later present their research to the FDA. If the findings are compelling, it might be “fast tracked” through the FDA process.
“I can't comment on if we will seek FDA approval,” said Fulga, of Hemostemix. “That is a long ways off.”
If he does, it would only be for critical limb ischemia; his research on stem cells as a treatment for heart problems is on hold.
“We are a small company so had to prioritize,” he said.
This is where Vijaynagar and Advanced Innovative Medicine stepped in. They licensed the technology for the Bahamas and the United States.
Vijaynagar says he is confident that once he successfully treats 20 patients in the Bahamas with stem cells grown using Hemostemix's technology, the island nation will allow him to commercialize the procedure. Then the FDA may have to take notice.
Lambert said heart patients should avoid taking part in such studies in a country with less regulation.
Vijaynagar scoffed at the warning.
“It's a drive and a passion to save somebody's life. This is what I have always wanted to do for a living — to help people, to do things no one else has done and to continue to discover new things. My job as a doctor is not to send people home to die, but to help them.”
Zucker, of Hemostemix, urged caution.
“People want to believe the cell therapy will work. Doctors want to believe the cell therapy will work. It is in circumstances such as this that you must take extra precaution.”
Carre, the patient, said he trusts Vijaynagar and is thankful for all he has done. If his heart begins to fail again and he can afford a second stem cell procedure, he said, he would do it.
“I feel good,” he said. “That's all that matters to me.”
Vijaynagar expects to hear that sentiment repeated again and again.
“I believe that heart transplants will one day be second to stem cells.”