🫀 Chapter 492: Pediatric Heart and Heart-Lung Transplantation
Nelson's Textbook of Pediatrics 22e | Indications · Listing criteria · Immunosuppression · Rejection (cellular, antibody-mediated) · CAV · PTLD · Survival · Transition · Heart-lung transplant · Lung transplant
📚 Reference: www.paeds.online — Paediatric Resource Hub
📌 Heart Transplantation – IndicationsEnd-stage cardiomyopathy (DCM, HCM, RCM) refractory to medical therapy. Complex congenital heart disease (HLHS, pulmonary atresia with coronary sinusoids). Failed Fontan. Retransplantation. Survival: 1-year ~90%, 5-year ~80%.
📌 ContraindicationsFixed elevated PVR >6 Wood units (relative). Active infection. Malignancy with poor prognosis. Severe irreversible multiorgan failure. Non-adherence risk. Severe pulmonary hypertension may require heart-lung transplant.
📌 Listing & AllocationUNOS status 1A (highest urgency): VAD, ECMO, mechanical ventilation, inotropes with high PVR, life-threatening arrhythmias. ABO-incompatible transplantation in infants <2 years (immune immaturity).
📌 Immunosuppression – InductionAntithymocyte globulin (ATG) or basiliximab (anti-IL-2 receptor) in first 5-7 days. Steroids tapered early.
📌 Maintenance ImmunosuppressionTriple therapy: calcineurin inhibitor (tacrolimus > cyclosporine) + antiproliferative (mycophenolate mofetil MMF, azathioprine) + prednisone (tapered off in many). mTOR inhibitors (sirolimus, everolimus) for renal sparing or CAV prevention.
📌 Acute Cellular Rejection (ACR) – ISHLT grading0R: no rejection. 1R: mild. 2R: moderate (myocyte necrosis). 3R: severe. Surveillance endomyocardial biopsy. Treatment: corticosteroids (IV methylprednisolone). Refractory: ATG, plasmapheresis.
📌 Antibody-Mediated Rejection (AMR)Donor-specific antibodies (DSA) + C4d staining. Hemodynamic compromise. Treatment: plasmapheresis, IVIG, rituximab, bortezomib.
📌 Cardiac Allograft Vasculopathy (CAV)Diffuse coronary intimal thickening. Surveillance: coronary angiography, IVUS. Risk factors: donor age, rejection episodes, CMV infection. Treatment: everolimus, revascularization (rare), retransplantation.
📌 Post-transplant Lymphoproliferative Disease (PTLD)EBV-associated (EBV-naive recipients). Reduce immunosuppression, rituximab, chemotherapy. High mortality.
📌 Heart-Lung TransplantationIndications: Eisenmenger syndrome with irreversible PAH, complex CHD + lung disease, cystic fibrosis (lung transplant alone if normal heart). 5-year survival ~50%. Double-lung transplant + CHD repair vs heart-lung.
🔍 Step 1: Recognize symptoms of rejection
Fatigue, poor feeding, irritability (infants). Fever, malaise, dyspnea, decreased exercise tolerance (older children). May mimic viral illness. Gallop rhythm, new murmur (MR).
📈 Step 2: Signs of advanced rejection
Heart failure (hepatomegaly, edema, pulmonary congestion). Arrhythmias (atrial fibrillation, VT). Cardiogenic shock (hypotension, low output).
🩺 Step 3: Diagnostic tests
Endomyocardial biopsy (gold standard for cellular rejection). Troponin, BNP elevated. Echocardiogram: ↓EF, new pericardial effusion, wall motion abnormality. Donor-specific antibodies (DSA).
🔄 Step 4: Surveillance (routine)
Protocol biopsies: frequently first year (every 1-3 months), then annually. Gene expression profiling (AlloMap) – not validated in children.
🚨 Step 5: Complications
CAV: silent ischemia (denervated heart). PTLD: fever, lymphadenopathy, GI bleeding, CNS symptoms. Infections (CMV, EBV, PJP).
1️⃣ Pre-transplant evaluation
▪ Cardiac catheterization: PVR (fixed >6 Wood units → heart-lung).
▪ Echocardiogram, cardiac MRI.
▪ HLA typing, panel reactive antibodies (PRA).
▪ Social work: adherence assessment.
▪ Vaccinations (avoid live vaccines post-transplant).
2️⃣ Listing – UNOS status
▪ Status 1A: VAD, ECMO, inotropes with high PVR, mechanical ventilation.
▪ Status 1B: inotropes only.
▪ Status 2: stable outpatient.
▪ ABO-incompatible transplantation in infants (<2 years) – reduced wait times.
3️⃣ Immediate post-transplant (ICU)
▪ Induction immunosuppression (ATG, basiliximab).
▪ Start tacrolimus + MMF + steroids.
▪ Monitor for primary graft dysfunction (ECMO if needed).
▪ Prophylaxis: anti-CMV (ganciclovir), PJP (TMP-SMX), antifungal.
4️⃣ Acute rejection – Cellular
▪ Grade 1R (mild): observe or treat with oral prednisone.
▪ Grade 2R (moderate): IV methylprednisolone 10-20 mg/kg/day ×3 days.
▪ Grade 3R (severe): IV steroids + ATG or plasmapheresis.
5️⃣ Antibody-Mediated Rejection (AMR)
▪ Plasmapheresis + IVIG + rituximab.
▪ Bortezomib for refractory AMR.
6️⃣ Long-term complications
▪ CAV: treat with everolimus (mTOR inhibitor), revascularization rare. Retransplantation.
▪ PTLD: reduce immunosuppression, rituximab, chemotherapy.
▪ Hypertension, renal dysfunction (CNI toxicity).
▪ Growth retardation (steroid-sparing protocols).
7️⃣ Transition to adult care
▪ Lifelong immunosuppression, surveillance biopsies.
▪ Pregnancy: high-risk, teratogenicity of MMF (switch to azathioprine).
▪ Transition to adult transplant cardiologist.
❓ Reflex prompt 1: A 5-year-old post-heart transplant (1 month) presents with fever, fatigue, and poor feeding. Echocardiogram shows EF 45% (previous 65%). Next step?
✅ Answer: Endomyocardial biopsy for rejection. IV methylprednisolone if moderate rejection.
❓ Reflex prompt 2: A 12-year-old post-heart transplant (3 years) has persistent fatigue. Coronary angiography shows diffuse narrowing. Diagnosis?
✅ Answer: Cardiac allograft vasculopathy (CAV). Treat with everolimus, consider retransplantation.
❓ Reflex prompt 3: A 2-month-old infant with HLHS is listed for heart transplant. ABO-incompatible donor is available. Is this feasible?
✅ Answer: Yes, ABO-incompatible heart transplantation is safe in infants <2 years due to immune immaturity (low isohemagglutinins).
❓ Reflex prompt 4: A 10-year-old post-heart transplant develops fever, cervical lymphadenopathy, and EBV PCR positive. Diagnosis?
✅ Answer: Post-transplant lymphoproliferative disease (PTLD). Reduce immunosuppression, rituximab.
❓ Reflex prompt 5: A 15-year-old with Eisenmenger syndrome (PAH) and fixed PVR 10 Wood units is referred for transplantation. Which type?
✅ Answer: Heart-lung transplantation. Isolated heart transplant would fail due to high PVR.
❓ Reflex prompt 6: A 14-year-old post-heart transplant (3 months) develops new-onset donor-specific antibodies (DSA) but normal biopsy. What is the risk?
✅ Answer: Risk of antibody-mediated rejection and CAV. Surveillance, consider treatment with IVIG/rituximab.
📌 Pediatric Heart and Heart-Lung Transplantation – Core Concepts (Nelson 22e, Chapter 492)

1. Indications for heart transplant: End-stage cardiomyopathy (DCM, HCM, RCM) refractory to medical therapy; complex CHD (hypoplastic left heart syndrome, pulmonary atresia with coronary sinusoids, failed Fontan); retransplantation. ~400 pediatric heart transplants/year in US.
2. Contraindications: Fixed elevated PVR >6 Wood units (requires heart-lung transplant). Active malignancy, severe irreversible multiorgan failure, non-adherence risk.
3. Listing (UNOS status):
- Status 1A: VAD, ECMO, mechanical ventilation, inotropes with high PVR, life-threatening arrhythmias.
- Status 1B: inotropes only.
- Status 2: stable outpatient.
- ABO-incompatible transplantation in infants <2 years (immune immaturity).
4. Immunosuppression:
- Induction: ATG or basiliximab (anti-IL-2 receptor).
- Maintenance: calcineurin inhibitor (tacrolimus preferred) + MMF (or azathioprine) + steroids (tapered).
- mTOR inhibitors (sirolimus, everolimus) for CAV prevention or CNI renal toxicity.
5. Acute rejection:
- Cellular (ISHLT grade 1R-3R): surveillance endomyocardial biopsy. Grade 2R/3R: IV methylprednisolone.
- Antibody-mediated (AMR): donor-specific antibodies + C4d. Plasmapheresis, IVIG, rituximab.
6. Cardiac allograft vasculopathy (CAV): Diffuse coronary intimal thickening. Surveillance: angiography, IVUS. Everolimus, retransplantation.
7. Post-transplant lymphoproliferative disease (PTLD): EBV-associated. Reduce immunosuppression, rituximab, chemotherapy.
8. Infections: CMV (ganciclovir prophylaxis), PJP (TMP-SMX), EBV, fungal.
9. Heart-lung transplantation: Indications: Eisenmenger with irreversible PAH, complex CHD + lung disease. 5-year survival ~50%.
10. Survival: Pediatric heart transplant: 1-year ~90%, 5-year ~80%.
💡 Clinical pearls:
➤ ABO-incompatible transplantation in infants reduces waitlist mortality.
➤ Endomyocardial biopsy remains gold standard for rejection surveillance.
➤ CAV is a leading cause of late graft loss; everolimus reduces progression.
➤ PTLD is a major cause of late mortality; EBV-naive recipients at highest risk.
➤ Transition to adult care: adherence crucial; pregnancy high-risk (MMF teratogenic).