Cardiac Transplantation Complications

Basics

Description

  • Cardiac transplant recipients may present with acute or chronic graft rejection, serious infections, coronary allograft vasculopathy (CAV), dysrhythmias, and “painless” and subtle acute coronary syndromes
  • Nearly 4000 cardiac transplants performed per year in the US, including more than 400 pediatric.
  • Transplants, along with left ventricular assist devices, are well-established therapy for end-stage heart failure
  • If the patient survives the 1st critical year, they can expect to live 15 yr on average
  • Typical immunosuppressive therapy to control rejection is a “triple-drug” regimen often including steroids
  • Acute rejection remains most frequent cause of morbidity and rehospitalizations:
    • Most common in 1st yr and especially 1st 3 mo after transplantation
    • Immunosuppression thus highest then, and thus infection risk also simultaneously high
    • Rejection often diagnosed by biopsy

Geriatric Considerations

  • The proportions of elderly patients on the transplant list, and those receiving transplants, are increasing
  • Elderly transplant recipients are at increased risk of both life-threatening infection and acute rejection

Pregnancy Considerations

  • Pregnancy after a heart transplant carries risks to both mother and fetus
  • Some immunosuppression, especially mycophenolate, is teratogenic; also increases risk for fetal cytomegalovirus (CMV) and other infections
  • Immunologically, pregnancy is a chimeric state. Paternal cells, maternal cells, and donor organ cells all interact, increasing risk for graft rejection
  • The Transplant Pregnancy Registry annual report in 2016 reported 147 pregnancies in 86 female recipients:
    • Nearly half were unintentional
    • Maternal mortality was 31%
    • Miscarriage rate was 27%
    • High incidence of preeclampsia (24%) and rejection (10%)

Etiology

  • Rejection:
    • Hyperacute rejection:
      • Occurs within minutes of transplantation.
      • Rare, aggressive, and immediately fatal to graft
    • Acute rejection:
      • Lymphocyte infiltration and myocyte destruction
      • Most common in the 1st 6 wk
      • May occur at any time
      • Treated with escalating immunosuppression
    • Chronic rejection:
      • Fibrosis and graft vascular disease
      • Long-term complication
      • Can be antibody or T-cell mediated
      • Therapeutic approaches are evolving
  • Cardiac allograft vasculopathy:
    • Analogous to accelerated coronary artery disease in native hearts: Immune-inflammatory response causes diffuse, concentric narrowing of allograft coronaries
    • Most common cause of mortality in transplant patients who survive the 1st yr
  • Immune-mediated atherosclerosis:
    • Form of chronic rejection
  • Infections:
    • 1st mo:
      • Bacterial infections are most common cause of mortality during this high-risk time
      • Pneumonia (Pseudomonas, Legionella, other gram-negative organisms)
      • Mediastinitis
      • Wound infection
      • UTI
    • 1st yr:
      • Opportunistic and conventional infections
      • CMV
      • Herpes simplex virus (HSV)
      • Legionella
      • Fungal infections
      • Pneumocystis carinii
  • Medication toxicity:
    • Cyclosporine, neoral (2nd-generation cyclosporine), tacrolimus:
      • Nephrotoxicity (30% incidence)
      • Hepatotoxicity
      • Neurotoxicity
      • Hyperlipidemia, diabetogenic
    • Azathioprine, mycophenolate mofetil:
      • Lower body temperature
      • Leukopenia
    • Sirolimus:
      • Hyperlipidemia
      • Poor wound healing
    • Steroids:
      • Osteoporosis
      • Cushing disease
  • Neoplasms:
    • Secondary to immunosuppression
    • 10-100x more common vs general population
    • Skin and lip cancer
    • Lymphomas
    • Kaposi sarcoma
    • Solid organ neoplasms

Pediatric Considerations

  • If the patient is not on steroids, bacteremia risk is similar to that in the general population
  • High incidence of pneumonia
  • Patients on steroids may not show meningeal signs

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