Feature

50 years of heart transplant: Progress in immunosuppression, survival rates

The first heart transplant was performed by Christiaan N. Barnard, MD, a cardiac surgeon from South Africa, and his team 50 years ago in December 1967. Since then, although surgical techniques have evolved very little, effective pharmacotherapy has been developed to reduce rejection rates and improve quality of life for patients who have undergone the procedure, experts told Cardiology Today.

Michael J. Mack, MD, FACC, medical director of cardiovascular surgery at Baylor Health Care System in Dallas, chairman of the Heart Hospital Baylor Plano Research Center in Texas and Cardiology Today’s Intervention Editorial Board Member, was in the operating room in 1968 when the first heart transplant in St. Louis was taking place.

“What I remember that day ... is a sense of wonderment when you see a person alive without a heart sitting in their chest while the patient’s diseased heart has been removed and before the new donor heart is implanted; that person’s alive on a heart-lung machine without a heart,” Mack told Cardiology Today. “It was my first impression, and an impression that I’d never got over many hundreds of transplants on down the line.”

Progress in techniques

Frank Smart

The basic techniques used in heart transplantation have changed very little, but the biggest change has been bicaval anastomosis, which involves cutting the left atrium and sewing the inferior and superior vena cava back together, Frank Smart, MD, professor of medicine and chief of cardiology at Louisiana State University in New Orleans and Cardiology Today Editorial Board Member, said in an interview. This technique preserves the donor heart’s conduction system, avoids right atrial anastomosis and decreases long-term complications.

The greatest advancements in heart transplantation have been made in immunosuppression, experts said. When transplants were first performed, corticosteroids were predominantly used for widespread immunosuppression, though sometimes they would affect important processes such as the production of lymphocytes.

“The main reason people had so many problems and didn’t live long was because the pharmacotherapy for rejection was so problematic,” Smart said.

Targeted immunosuppression started to be used in the 1980s and helped improve survival rates. Steroids or prednisone can be given to patients in smaller doses or even eliminated completely to decrease complications without affecting the risk for rejection.

Mary Norine Walsh

“Many patients are now managed with tacrolimus as a single antirejection agent,” Mary Norine Walsh, MD, FACC, president of the American College of Cardiology, medical director of the heart failure and transplantation program at St. Vincent Heart Center in Indianapolis and a Cardiology Today Editorial Board Member, said in an interview. “This more-measured use of immunosuppression has decreased the long-term complications after transplant.”

The process of matching donor hearts to recipients has become more inclusive. Heart transplants were first performed using healthy hearts from young patients with no contraindications — including tattoos, HIV and hepatitis. Human leukocyte antigens typing has become more sophisticated in determining which hearts would be acceptable for a particular recipient, Walsh said.

“We started expanding the donor pool, taking smaller patients, taking older patients, taking patients from further away from the recipient hospital,” Smart said. “That expansion, we thought we were going to greatly improve the donor population and the donor pool, and it really didn’t.”

Over the last 15 years, the number of transplants in the United States and worldwide has not changed, Mack said. The number of hearts needed for the number of patients that are eligible for a heart transplant does not match. This is despite efforts at expanding the donor pool by extended criteria and by optimization of priorities on the waiting list of patients for transplant.

Improved survival rates

Survival rates and quality of life for patients continue to improve as a result of improved immunosuppression, individualized patient care and donor-recipient matching. According to an article published in the Journal of Thoracic Disease in 2015, data from the International Society of Heart and Lung Transplantation indicated a 1-year survival rate of 84.5% and a 5-year survival rate of 72.5%, which was an increase from survival rates from the 1980s (76.9% and 62.7%, respectively). The 20-year survival rate is 21%.

Michael J. Mack

“Heart transplantation is not a cure for anybody,” Mack told Cardiology Today. “It’s trading one disease for another disease. The disease that you’re trading away is heart failure, and the disease that you’re trading for is rejection and the risk of infection. The better than we are able to manage those competing risks, the better quality of life and survival rate is.”

When heart transplants were performed in the 1990s, patients’ quality of life was affected because of osteoporosis from steroids, having to wear a mask due to immunosuppression and numerous surveillance biopsies. Developments in targeted immunosuppression, reducing steroid doses and surveillance methods have increased these patients’ quality of life. Patients also undergo fewer procedures now that gene expression profiling has been used to assess for rejection.

Further research is needed to accommodate for the lack of donor hearts, including advanced organ transport for those located beyond the 4- to 6-hour window from removing the organ to transplanting it into the receiving patient. Unused donor hearts are often in countries outside the United States, but more research is needed regarding increased preservation and social, economic and ethical challenges associated with using the hearts.

Although progress has been made in antirejection drugs, a perfect therapy does not exist, Mack said.

The possibility of xenotransplantation, or transplanting organs from animals to humans, remains an area of interest regarding research, even if it has been largely unsuccessful, experts said. Scientific advancements are being made in growing new organs from a patient’s own tissue.

Even with the potential for progress in heart transplantation, organ donation remains a large concern in this area.

“The biggest challenge is the lack of ... donors for the number of patients who are listed for transplantation,” Walsh told Cardiology Today. “Public awareness of the importance of donation remains low. Also, in the very near future, changes will be made to the allocation system for hearts in the hope that the listed patient population will be better served.” – by Darlene Dobkowski

Disclosures: Mack, Smart and Walsh report no relevant financial disclosures.

The first heart transplant was performed by Christiaan N. Barnard, MD, a cardiac surgeon from South Africa, and his team 50 years ago in December 1967. Since then, although surgical techniques have evolved very little, effective pharmacotherapy has been developed to reduce rejection rates and improve quality of life for patients who have undergone the procedure, experts told Cardiology Today.

Michael J. Mack, MD, FACC, medical director of cardiovascular surgery at Baylor Health Care System in Dallas, chairman of the Heart Hospital Baylor Plano Research Center in Texas and Cardiology Today’s Intervention Editorial Board Member, was in the operating room in 1968 when the first heart transplant in St. Louis was taking place.

“What I remember that day ... is a sense of wonderment when you see a person alive without a heart sitting in their chest while the patient’s diseased heart has been removed and before the new donor heart is implanted; that person’s alive on a heart-lung machine without a heart,” Mack told Cardiology Today. “It was my first impression, and an impression that I’d never got over many hundreds of transplants on down the line.”

Progress in techniques

Frank Smart

The basic techniques used in heart transplantation have changed very little, but the biggest change has been bicaval anastomosis, which involves cutting the left atrium and sewing the inferior and superior vena cava back together, Frank Smart, MD, professor of medicine and chief of cardiology at Louisiana State University in New Orleans and Cardiology Today Editorial Board Member, said in an interview. This technique preserves the donor heart’s conduction system, avoids right atrial anastomosis and decreases long-term complications.

The greatest advancements in heart transplantation have been made in immunosuppression, experts said. When transplants were first performed, corticosteroids were predominantly used for widespread immunosuppression, though sometimes they would affect important processes such as the production of lymphocytes.

“The main reason people had so many problems and didn’t live long was because the pharmacotherapy for rejection was so problematic,” Smart said.

Targeted immunosuppression started to be used in the 1980s and helped improve survival rates. Steroids or prednisone can be given to patients in smaller doses or even eliminated completely to decrease complications without affecting the risk for rejection.

Mary Norine Walsh

“Many patients are now managed with tacrolimus as a single antirejection agent,” Mary Norine Walsh, MD, FACC, president of the American College of Cardiology, medical director of the heart failure and transplantation program at St. Vincent Heart Center in Indianapolis and a Cardiology Today Editorial Board Member, said in an interview. “This more-measured use of immunosuppression has decreased the long-term complications after transplant.”

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The process of matching donor hearts to recipients has become more inclusive. Heart transplants were first performed using healthy hearts from young patients with no contraindications — including tattoos, HIV and hepatitis. Human leukocyte antigens typing has become more sophisticated in determining which hearts would be acceptable for a particular recipient, Walsh said.

“We started expanding the donor pool, taking smaller patients, taking older patients, taking patients from further away from the recipient hospital,” Smart said. “That expansion, we thought we were going to greatly improve the donor population and the donor pool, and it really didn’t.”

Over the last 15 years, the number of transplants in the United States and worldwide has not changed, Mack said. The number of hearts needed for the number of patients that are eligible for a heart transplant does not match. This is despite efforts at expanding the donor pool by extended criteria and by optimization of priorities on the waiting list of patients for transplant.

Improved survival rates

Survival rates and quality of life for patients continue to improve as a result of improved immunosuppression, individualized patient care and donor-recipient matching. According to an article published in the Journal of Thoracic Disease in 2015, data from the International Society of Heart and Lung Transplantation indicated a 1-year survival rate of 84.5% and a 5-year survival rate of 72.5%, which was an increase from survival rates from the 1980s (76.9% and 62.7%, respectively). The 20-year survival rate is 21%.

Michael J. Mack

“Heart transplantation is not a cure for anybody,” Mack told Cardiology Today. “It’s trading one disease for another disease. The disease that you’re trading away is heart failure, and the disease that you’re trading for is rejection and the risk of infection. The better than we are able to manage those competing risks, the better quality of life and survival rate is.”

When heart transplants were performed in the 1990s, patients’ quality of life was affected because of osteoporosis from steroids, having to wear a mask due to immunosuppression and numerous surveillance biopsies. Developments in targeted immunosuppression, reducing steroid doses and surveillance methods have increased these patients’ quality of life. Patients also undergo fewer procedures now that gene expression profiling has been used to assess for rejection.

PAGE BREAK

Further research is needed to accommodate for the lack of donor hearts, including advanced organ transport for those located beyond the 4- to 6-hour window from removing the organ to transplanting it into the receiving patient. Unused donor hearts are often in countries outside the United States, but more research is needed regarding increased preservation and social, economic and ethical challenges associated with using the hearts.

Although progress has been made in antirejection drugs, a perfect therapy does not exist, Mack said.

The possibility of xenotransplantation, or transplanting organs from animals to humans, remains an area of interest regarding research, even if it has been largely unsuccessful, experts said. Scientific advancements are being made in growing new organs from a patient’s own tissue.

Even with the potential for progress in heart transplantation, organ donation remains a large concern in this area.

“The biggest challenge is the lack of ... donors for the number of patients who are listed for transplantation,” Walsh told Cardiology Today. “Public awareness of the importance of donation remains low. Also, in the very near future, changes will be made to the allocation system for hearts in the hope that the listed patient population will be better served.” – by Darlene Dobkowski

Disclosures: Mack, Smart and Walsh report no relevant financial disclosures.