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Points of attention after heart transplantation

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Points of attention after heart transplantation

Immunosuppression

Chronic immunosuppressive therapy is necessary to prevent rejection of the donor heart. This therapy consists of the combination of a calcineurin inhibitor (now always tacrolimus , formerly cyclosporine), a purine antimetabolite (now usually mycophenolate mofetil) and glucocorticoids.

The glucocorticoids are always reduced as much as possible and stopped during the 1st year after the transplant.

In chronic follow-up of these patients, it is very important to regularly measure the trough level, especially of the calcineurin inhibitor, by taking blood samples early in the morning, before taking the morning dose. This concentration must fluctuate between certain target values.

  • A level that is too high increases the risk of infections or side effects, progressive renal insufficiency (tacrolimus and cyclosporine),...
  • A level that is too low increases the risk of rejection and progressive dysfunction of the donor heart.

The therapy and target values are determined by the cardiologists of the transplant team.

The blood concentration of this therapy can fluctuate widely due to interactions with concomitant intake of other drugs and/or other disease conditions. Gastroenteritis and diarrhea may increase immunosuppressant levels with increased toxicity due to transient reduction in P-glycoprotein (P- gp) function due to damage to the brush border.

In the event of adjustments to the medication regimen or illness, it is best to monitor this trough level additionally, with urgent consultation with a cardiologist from the transplant team in the event of abnormal values to discuss adjusting the dose of this medication.

Interactions can be checked online, for example at: Drug Interaction Checker - For Drugs, Food, and Alcohol

Immunosuppressants should not be combined with intake of grapefruit juice, St. John's wort, etc.

 

1. Tacrolimus

  • Current standard therapy after heart transplantation.
  • Available products :
    • Prograft :
      • Tablets available of 0.5 mg, 1 mg or 5 mg.
      • To be taken twice a day with 12 hours in between.
    • Advagraf :
      • Tablets available of 0.5 mg, 1 mg, 3 mg or 5 mg.
      • To be taken once a day with 24 hours in between.
  • Target values
    • < 1 year after transplantation: 10 – 12 µg/L – after 6 months: 8 – 10 µg/L.
    • > 1 year after transplantation: 6 – 10 µg/L – in the long term more likely 6 – 8 µg/L, unless in monotherapy (rather 8 – 10 µg/L).
  • Possible side effects:
    • Headache
    •  Tremor
    • Renal insufficiency, hyperkalemia
    • Arterial hypertension, hypercholesterolemia, diabetes mellitus
    • Skin tumors
    • Hair loss
    • Constipation or diarrhea

2. Cyclosporine

  • This used to be the standard therapy, but not anymore. Many patients still take this after a heart transplant many years ago.
  • Practical: Neoral 
    • Tablets available in 10 mg, 25 mg, 50 mg and 100 mg.
    • To be taken twice a day with 12 hours in between.
  • Target values:
    • > 1 year after transplant: 100-150 ng / ml, sometimes lower (especially if significant renal insufficiency or many skin tumors).
  • Possible side effects:
    • Headache
    • Tremor
    • Renal insufficiency, hyperkalemia
    • Arterial hypertension, hypercholesterolemia, diabetes mellitus
    • Skin tumors
    • Gingival hypertrophy and bleeding
    • Hirsutism

3. Mycophenolate mofetil (Cellcept)

  • Tablets available in 250 mg and 500 mg.
  • To be taken twice a day with 12 hours in between.
  • Dose: 500 mg to 2 grams per day.
  • Possible side effects :
    • Diarrhea, constipation and GI discomfort (stomach discomfort).
    • Leukopenia and neutropenia, thrombopenia, anemia
    • Headache
    • Fatigue
    • Skin tumors

Possible complications after heart transplantation in the short and long term

 

1. Complications early after transplantation (especially during the first year after transplantation)

These complications can be serious and life-threatening. If suspicious symptoms are identified, it is best to consult urgently with the treating transplant team for quick and correct diagnosis and treatment, if necessary through urgent hospitalization.

 

  • Rejection of the donor heart
  • Symptoms of rejection:
    • None. Sometimes this is discovered incidentally on regular myocardial biopsies.
    • Echocardiography: thickened heart muscle, deterioration of LV function,...
    • Symptoms of heart failure, (ventricular) arrhythmias , hypotension,...
    • Malaise, chills, subfebrility , nausea, anorexia,...

 

  • Infections
    • There is a higher risk especially during the first year after the transplant.
    • Prevention:
      • Washing hands frequently and good hygiene.
      • Avoiding contact with sick people, avoiding places where many people are together.
      • Safe food:
        • Wash fruits and vegetables well.
        • Hygienic preparation.
        • Avoiding raw meat and eggs. Sufficiently heat, bake or cook food.
        • Only consume products with pasteurized milk.
        • ...
      • In case of an infection: rapid treatment with antibiotics, with or without hospitalization, best in consultation with the transplant team.
      • Annual flu and COVID vaccination.
      • Vaccination against pneumococcal disease.
      • Please note: live attenuated vaccines are contraindicated.
    • Consider opportunistic infections:
      • CMV (Cytomegalovirus) primo infection or reactivation : fever, diarrhea,...
      • Pneumcystis jerovecii pneumonia (PJP).
      • Funghi : invasive candidiasis, aspergillosis ,...

In the first months after the transplant, certain therapies are usually prescribed to prevent certain opportunistic infections. For example: co-trimoxazole (Bactrim), Nystatin mouthwash, valgancyclovir (Valcyte),...

2. Late complications (after months to years)

  • Diabetes mellitus.
  • Arterial hypertension.
  • Progressive chronic renal failure.
  • Higher risk of several malignancies, especially:
    • Skin tumors: exposure to the sun and UV radiation should be limited. Long-term dermatological follow-up.
    • Lymphomas (usually mediated by EBV, Epstein -Barr virus ).
  • Transplant vasculopathy (occurrence of coronary stenoses in the donor heart).
  • Osteoporosis.
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