Understanding and Managing Primary Graft Dysfunction After Heart Transplant

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• Overview of Heart Transplant Complications
• What is Primary Graft Dysfunction?
• Donor Factors: Age and Cause of Death
• Recipient Factors and ECMO Impact
• Managing Graft Dysfunction with Mechanical Support
• Full Transcript

Overview of Heart Transplant Complications

Dr. Pascal Leprince, MD, a leading heart transplant surgeon, categorizes post-transplant complications into three main types. The first category involves general surgical risks common to many major cardiac procedures. These include bleeding, which carries a higher risk if the patient has had previous chest surgeries, and cardiac arrhythmias. A less common but serious surgical complication is a cerebrovascular accident, or stroke.

What is Primary Graft Dysfunction?

A unique and critical complication specific to heart transplantation is primary graft dysfunction. Dr. Pascal Leprince, MD, describes this as the new heart failing to function properly immediately after the surgery. This occurs during the process of weaning the patient off the cardiopulmonary bypass machine, which requires a well-functioning graft. The incidence of this complication varies widely, between 5% to 25%, and is heavily influenced by the surgical team's expertise.

Primary graft dysfunction ranges in severity. Milder cases may only require temporary intravenous medications to support heart contraction. More severe cases necessitate prolonged mechanical circulatory support to keep the patient stable while the new heart recovers.

Donor Factors: Age and Cause of Death

The characteristics of the heart donor are a major determinant of primary graft dysfunction risk. Dr. Pascal Leprince, MD, highlights a significant international difference: the mean donor age in France is 44, compared to 33 in the United States. This age gap has profound implications because older donors often have different causes of death, primarily stroke.

Dr. Pascal Leprince, MD, explains that a donor death from stroke suggests underlying vascular problems, including the potential for atheroma, or cholesterol plaque, in the heart's own arteries. This can compromise the quality of the graft. In contrast, younger donors often die from trauma like car accidents or gunshot wounds, which may not directly affect heart tissue quality.

Recipient Factors and ECMO Impact

Remarkably, the condition of the transplant recipient is also a direct cause of graft dysfunction. Dr. Pascal Leprince, MD, notes that many recipients are critically ill before surgery, often spending over two weeks in the ICU, intubated, and with renal dysfunction. A large proportion, close to 50% in his experience, are stabilized on ECMO (Extracorporeal Membrane Oxygenation) before transplantation.

Dr. Pascal Leprince, MD, collaborated with researchers from Columbia University to study this phenomenon. Their laboratory research demonstrated that the serum from patients on pre-transplant ECMO can directly induce dysfunction in cardiac cells. This finding confirms that the recipient's severely inflamed and stressed physiological state is an independent aggressor to the fragile transplanted heart.

Managing Graft Dysfunction with Mechanical Support

Given the high prevalence of sick recipients and the use of older donors, managing primary graft dysfunction has become a central part of modern transplant care. Dr. Pascal Leprince, MD, states that his team proactively uses ECMO after transplantation as a mechanical circulatory support system. This device assists the patient's blood circulation, providing vital time and support for the new heart graft to recover from the immense stress of transplantation.

This approach is a direct response to the complex interplay of donor and recipient factors that lead to graft failure. By anticipating the need for support, Dr. Pascal Leprince, MD, and his colleagues aim to improve outcomes for the most challenging transplant cases.

Full Transcript

Dr. Anton Titov, MD: You are a leading heart transplant surgeon. What adverse effects and complications do you see after cardiac transplantation?

Dr. Anton Titov, MD: You co-authored the international guidelines on the problems with transplanted hearts.

Dr. Pascal Leprince, MD: There are three types of complications after cardiac transplantation. The first complication is related to the surgical operation. We can face the same complications as with regular surgery, for example, with coronary bypass grafting surgery. This complication is bleeding. Sometimes the patient already had many operations before, then the risk of bleeding is higher.

Other complications could be cardiac arrhythmias and CVA, cerebrovascular accident. Stroke is a low-risk complication, but it can happen.

But there is one complication after heart transplantation. This side effect is not common with other diseases. It is heart graft failure. The primary heart graft failure in some newly transplanted patients happens right after the surgery.

A patient is on cardiopulmonary bypass during cardiac transplantation surgery. Then the heart restarts as soon as the blood is going through the coronary artery of the graft. The heart just restarts to beat. Then you start to wean the cardiopulmonary bypass off.

But to wean the patient off cardiopulmonary bypass, you need to have a well-functioning graft, the new heart. Once in a while, you have a problem. It is not so rare because it depends on surgical team quality. It is like somewhere between 5% to 25%.

Dr. Anton Titov, MD: You can face dysfunction of the new heart graft. It means the new heart graft at least will require some intravenous drips to get better heart contraction. This is okay. Sometimes a patient just requires intravenous drip with medications for a few days. I would say it is not a huge heart dysfunction.

But some patients with heart graft failure you have to keep on mechanical circulatory support. The primary heart graft dysfunction means that it is not due to another complication. That is just the heart graft that does not work well by itself.

This is interesting. Primary heart graft dysfunction can be related, of course, to the heart graft itself. Complication after heart transplantation can be related to the donor's heart. People have to understand that, for instance, in France, the mean age of the cardiac donor is 44. In comparison, in the United States, the mean age of the cardiac donor is 33. This makes a huge difference.

Because we know that with an older donor, the rate of primary heart graft failure is higher. It is so not only because heart donors in France are older, but because the cause of death for older heart donors is different in comparison to the cause of death of younger heart donors.

Sometimes you have a young heart donor. The main cause of death is gunshot or stab wound, or car accidents. On the other hand, it is suicide.

Dr. Anton Titov, MD: You can go through the causes of death of older heart donors. The main cause of death is mainly a stroke. This means that older heart donors have different vascular problems. They have a higher risk of getting atheroma not only in the brain but also in the heart. Atheroma is cholesterol plaque.

This might explain some differences we have to face between different countries in primary heart graft failure rates.

Dr. Pascal Leprince, MD: We are looking at different causes of death of the heart donors. This is one of the reasons for the cardiac graft dysfunction after heart transplantation. But there is another reason for heart graft failure. It is more interesting to me.

We have a collaboration with a colleague from Columbia University in New York. We have shown that the heart transplant recipient can be the cause of graft dysfunction. Because you just have to think if you want to tell a nice story: the heart graft by itself is very fragile. A transplanted heart is a fragile organ.

Because the heart was in the donor who was brain dead. Brain death is very aggressive for the tissues of the donor. Then the heart was harvested, cooled down, transported, transplanted. Then the heart got the blood from the recipient flowing into the coronary arteries. This is very aggressive for the graft. It is a big stress for the heart! This is very, very stressful for the heart.

But then if you have a recipient who spent 15 days in the ICU before the transplantation, the patient was intubated; he has renal dysfunction. A patient is on ECMO, for instance. ECMO is an extracorporeal circulation to stabilize the patient for a few days. This is a very aggressive condition as well. It is a difficult condition for the organ, for the heart graft.

Medical second opinion is important. This is why we showed with colleagues from Columbia University that the serum of the patients who were on ECMO before transplantation can bring some dysfunction of the cardiac cells. We showed that in laboratory experiments on a bench. That is very interesting to me.

Medical second opinion is important. Causes of heart graft failure are not only related to the history of the donor or the graft. It relates to the history of the recipient himself. Medical second opinion is important. That is quite very interesting.

Then we use more older donors. We have to transplant patients who are in bad shape. There are, in our experience, close to 50% of the patients on ECMO before heart transplantation. That means we have to face severe organ dysfunction, cardiac dysfunction after transplantation.

This is why, in our experience, we use more this ECMO system after transplantation. It is an extracorporeal mechanical circulatory support system. This is not an artificial lung. This is also a blood circulation device to help the blood circulation of the patient for the graft to recover.