Authors: Dylan Trujillo, DO, Felipe Medeiros, MD, Destiny F. Chau, MD; Arkansas Children’s Hospital/University of Arkansas for Medical Sciences, Little Rock, AR
An 8-year-old male child with history of an orthotopic heart transplantation six years prior due to dilated cardiomyopathy presents for laparoscopic appendectomy. The patient is compliant with transplant medications and the last cardiac catheterization demonstrated normal hemodynamics without rejection. The vital signs are as follows: BP 97/55, HR 108, SpO2 99% in room air, RR 21, and T 37.8oC. Laboratory results show: WBC 18 x 109 /L, Hb 13 g/dL, platelets 245 x 109 /L. At present, which of the following is the MOST likely cause of morbidity and mortality in this patient?
The primary causes of mortality following orthotopic heart transplantation (OHT) vary with the time elapsed since transplant. Common causes of death include acute rejection, infection, cardiac allograft vasculopathy (CAV) and malignancy. While acute rejection is the leading cause of death during the first 3 years following OHT, CAV predominates thereafter as the leading cause of mortality.
According to data from the International Society of Heart and Lung Transplantation, approximately 20% of OHT recipients have some degree of CAV at 5 years and 25% at 10 years post-transplant. The mortality rate after CAV diagnosis is high across all age groups. There is 25% 2-year mortality in patients with any severity of CAV and 50% 2-year mortality in patients with moderate-to-severe CAV. Infants have the worst survival rates with a median of 2 years after CAV diagnosis. The clinical symptom of chest pain from myocardial ischemia is typically absent due to denervation of the transplanted heart. Therefore, severe CAV manifests as progressive deterioration in graft function, heart failure, or sudden death. For this reason, transplant recipients are usually screened on a yearly basis for CAV using coronary angiography or dobutamine stress echocardiography. The histologic appearance of CAV is that of concentric intimal and medial proliferation that ultimately results in luminal occlusion, diastolic dysfunction, and graft failure. Treatment of CAV includes percutaneous revascularization procedures such as balloon angioplasty and coronary artery stenting, but the success rate is low due to the diffuse nature of the disease. Cardiac re-transplantation should be considered for those patients with moderate to severe CAV and graft dysfunction.
The rate of infection in OHT patients is highest in the first year after transplantation, accounting for approximately 16% of deaths, but declines thereafter. As immunosuppressive therapy can potentiate the severity of infections, early diagnosis and aggressive therapy of infection is imperative. In a 2006 single institution, retrospective review by Savar et al. of 8000 solid organ transplants (which included four OHTs and one heart-kidney transplant), 17 patients underwent appendectomy with an average age of 37 years (range 6yrs-73yrs). They reported no deaths, no episodes of acute organ rejection, and no intraoperative complications after appendectomy.
Acute rejection is the most frequent cause of death during the first year after OHT. Greater age at the time of transplantation increases the risk for acute rejection and is associated with lower survival. The risk of malignancy increases over time, with an incidence of approximately 10% at 10 years and 16% at 15 years post-transplant. Although post-transplant lymphoproliferative disorders account for the vast majority of malignancies and are associated with reduced survival, they are not one of the leading causes of mortality after OHT.
The patient’s cardiac status appears to be optimized given compliance with medications, normal cardiac catheterization data and negative biopsy results. As immunosuppression can exacerbate acute appendicitis, prompt treatment is imperative with good outcomes having been reported after surgical management. Perioperative continuation of the anti-rejection therapy is important for recovery. Obtaining a preoperative echocardiogram would be helpful to confirm cardiac function but should not delay surgery. As six years have elapsed since OHT, this patient’s risk for acute rejection and malignancy is lower than for CAV; thus, CAV would be the most likely cause of morbidity and mortality in this patient.
Dipchand AI, Laks JA. Pediatric heart transplantation: long-term outcomes. Indian J Thorac Cardiovasc Surg.2020; 36(Suppl 2):175-189.
Rossano JW, Dipchand AI, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Nineteenth pediatric heart transplantation report-2016; Focus theme: Primary diagnostic indications for transplant. J Heart Lung Transplant. 2016; 35(10):1185-1195.
Dipchand AI. Current state of pediatric cardiac transplantation. Ann Cardiothorac Surg. 2018; 7(1):31-55.
Savar A, Hiatt JR, Busuttil RW. Acute appendicitis after solid organ transplantation. Clin Transplant. 2006; 20(1):78-80.