Rejection involves cell- or antibody mediated cardiac injury resulting from recognition of the cardiac allograft as non-self. Risk factors for early rejection include younger recipient age, female sex, female donor, positive cytomegalovirus and EB serologic test results, prior infections, black recipient race, and number of HLA mismatches

• Acute cellular rejection or cell-mediated rejection is a mononuclear inflammatory response, predominantly lymphocytic, directed against the donor heart; It is most common from the first week to several years after transplantation, and it occurs in up to 40% of patients during the first year after surgery

• Antibody-mediated rejection (AMR): patients at greatest risk for antibody-mediated rejection are women and patients with positive crossmatch. It is estimated that significant antibody-mediated rejection occurs in about 7% of patients, but the rate may be as high as 20%
• Chronic rejection
  • Late graft failure is an irreversible gradual deterioration of graft function that occurs in many allografts months to years after transplantation
  • The current concept suggests that donor heart dysfunction in the chronic stages of maintenance immunosuppression is either related to chronic rejection mediated by antibodies, or a result of progressive graft loss from ischemia

REJECTION ASSESSMENT

• Clinical changes (fever, feeding refusal, fatigue, vomiting, etc.)
• Chest X-ray: Cardiomegaly, evidence of pulmonary congestion/edema
• ECG: Low voltage, arrhythmias (Bradyarrhythmias, heart block, tachyarrhythmias), changes from previous ECG
• Laboratory evaluation: CBC with diff (rising WBC or eosinophilia can indicate rejection), Comprehensive metabolic panel: kidneys/ liver profile, electrolytes, sugar level and acid/base balance (CMP), Nt-proBNP, drug levels (if the timing is appropriate)
• Right/Left heart cath (hemodynamics) and biopsy: need to be determined by treating Transplant MD (particularly helpful when discrepancy between clinical scenario, echocardiographic, ECG abnormalities; and/or when patient’s rejection course is complex, atypical, or not responding to current anti-rejection therapies … after 1 year Chronic Rejection (coronariography to r/o CAV)
• Echocardiography: “remember the donor age”. Data of rejection by Echo:
  • Pericardial effusion
  • Left ventricular hypertrophy
  • Rapidly increasing LV posterior wall and septal wall thickness
  • New tricuspid or mitral valve insufficiency
  • Decreasing posterior wall and septal systolic and diastolic function
  • Decreasing LV shortening fraction
  • Decreasing LV volume (may increase with severe rejection).
  • Mitral flow and DTI mitral (ratio E/e’) **
  • Impairment GLS

** Ambrosi et al. Predictive value of E/A and E/E’ Doppler indexes for cardiac events in heart transplant recipients. Clin Transplant 2016:30(8):959-63.