ALLOGRAFT DIASTOLIC DYSFUNCTION AND CHRONOTROPIC INCOMPETENCE LIMIT CARDIAC-OUTPUT RESPONSE TO EXERCISE 2 TO 6 YEARS AFTER HEART-TRANSPLANTATION

Background: Because prolonged survival of heart transplant recipients is expected with the current immunosuppressive treatment, the function al capacity of these long-term survivors is of interest. Previous exer cise studies showed no objective improvement in exercise tolerance sev eral years after transplantation, but the extent to which chronotropic incompetence and allograft diastolic dysfunction observed early after transplantation may improve over time has not been defined. Methods: Thirteen untrained heart transplant recipients without symptoms, betwe en 27 and 70 months after transplantation, and 13 age-matched sedentar y normal controls underwent maximal upright bicycle exercise testing w ith simultaneous hemodynamic, radionuclide, and expired gas measuremen ts. Results: Systolic function as measured by ejection fraction was su pranormal at rest in the transplant group and normalized with exercise . Despite their maximal exercise effort, transplant recipients had a 6 0% reduction in their exercise capacity compared with nontransplant re cipients. Peak oxygen consumption was similarly reduced by 52%. Cardia c output response to exercise was 43% lower in the transplant group be cause of a 78% reduction in heart rate reserve and an 18% reduction in maximal stroke volume. Ventricular volumes were similarly reduced aft er transplantation, but filling pressures remained normal, indicating allograft diastolic dysfunction. Despite the significantly reduced max imal cardiac output, maximal arteriovenous oxygen difference was 25% l ower in the transplant recipients, suggesting a peripheral deficit in oxygen handling.Conclusions: Therefore, patients, 2 to 6 years after t ransplantation, continue to have a significant reduction in exercise t olerance as a result of a combination of severe chronotropic incompete nce, limited stroke volume reserve caused by a reduced ventricular siz e and allograft diastolic dysfunction, and an abnormality in periphera l oxygen delivery or use. Efforts aimed at improving these factors may further enhance the functional capacity of these long-term survivors of heart transplantation.