Diabetes Alone Does Not Rule Out Heart Transplants

NEW YORK, Nov. 7 -- Diabetes should not be an automatic barrier to heart transplantation, said researchers here.

Patients with uncomplicated diabetes who had a heart transplant survived just as long as non-diabetic recipients over 10 years, found Yoshifumi Naka, M.D., Ph.D., of Columbia, and colleagues. But patients with diabetes-related renal disease or stroke had significantly lower survival rates.

Among patients with diabetes-related complications, each additional complication was associated with a significantly shorter post-transplant survival, the investigators reported online in Circulation, Journal of the American Heart Association.

"The question is not whether a person has diabetes but how much damage the diabetes has done," said Mark J. Russo, M.D., a co-author. "A person should not be disqualified from transplantation solely because of diabetes."

Some transplant centers view diabetes as a relative contraindication to heart transplantation, because of increased risk of renal failure, peripheral vascular disease, and thrombotic events, including stroke, the investigators noted.

"In addition, the hyperglycemic effect of immunosuppressant steroid therapy further complicates the post-transplantation management of their disease," they wrote. "Moreover, there is concern for a multiple-hit phenomenon in which the use of nephrotoxic immunosuppressant drugs further increases the likelihood of renal disease in patients already at risk. Finally, although still unproven, a higher incidence of post-transplantation infection, rejection, and transplant coronary artery disease is hypothesized."

To determine whether some transplant centers were justified in rejecting patients with diabetes as heart transplant candidates, the authors conducted a retrospective study of long-term survival among diabetic versus non-diabetic heart transplant recipients. They also evaluated transplant-related morbidity among recipients with diabetes, including post-transplantation renal failure, infection, rejection, and transplant coronary artery disease.

They used patient data, stripped of its personal identification, from the United Network for Organ Sharing database. For their primary analysis, they looked at 20,412 first-time heart graft recipients ages 18 years and older who underwent surgery from the beginning of 1995 through the end of 2005.

They stratified diabetic recipients according to severity based on the number of complications, which included pre-transplantation history of renal failure, peripheral vascular disease, cerebrovascular accident, and severe obesity (body mass index > 35 kg/m²).

The primary study outcome was median post-transplant survival in years. The authors also looked at survival free of transplant coronary artery disease, post-transplant renal failure, acute rejection, or severe infection.

They defined renal failure as post-transplantation creatinine > 2.5 mg/dL or the need for dialysis, severe infection as the need for hospitalization because of infection, and acute rejection as an episode of rejection required medical treatment.

They also looked at deaths by infection, cerebrovascular or cardiovascular disease, renal failure, or rejection, and analyzed patient functional status according to whether the patient required total assistance for activities of daily living (score of 3) or no assistance (score of 1).

They found that overall post-transplantation survival was significantly better among patients without diabetes (median survival 10.1 years) compared with all patients with diabetes (9.0 years, P<0.001).

But when they looked at those diabetics with no diabetes-related complications, they found that there were no significant differences in survival compared with patients without diabetes. Median survival among diabetic patients with no complications was 9.3 years, compared with 10.1 years for non-diabetics (P=0.08).

When the investigators looked at diabetics with complications, that survival decrease with each additional complication. Compared with the 9.3 year median survival without complications, patients with one complication had a 6.7-year median survival, and those with two or more diabetes-relate complications had a median survival of 3.6 years.

In a multivariable Cox proportional hazards regression model, history of diabetes, increasing donor age, increasing recipient age, increasing ischemic time, ischemic cause of heart failure, and UNOS status 1/1A/1B at transplantation were all associated with significantly worse survival, but these associations did not alter the similarity between survival rates among non-diabetics and diabetics with no complications.

Although there were no between-group differences in either acute rejection or survival free of transplant coronary artery disease, both renal failure and survival free of severe infection were worse in patients with diabetes, and were inversely related to the number of diabetes-related complications.

"In the pre-transplant screening, we must identify diabetic patients who have severe end-organ damage," said Dr. Naka, "Those patients do not do as well after transplantation; so we must consider alternative treatment strategies for these patients. However, diabetics with only minimal damage should be considered for transplant."

For patients with severe heart failure and severe diabetes, alternatives might include left ventricular assist devices (destination therapy), or the use of high-risk transplant lists, the authors recommended.