Heart-Lung Transplant

The denervated heart

• SA node of recipient is retained but DOES NOT activate the grafted heart across the suture line
• The donor heart has its own SA node but this IS NOT innervated
• Can sometimes discern two P waves on ECG
• The donor SA node controls the graft heart rate
• Only drugs or maneuvres that directly affect the heart can control HR
• Still retains normal Frank-Starling response to volume normal conductivity and intact responses to adrenergic agents
• Coronary arteries retain response to nitrates and metabolic demands
• Patients suffer no angina with ischaemia or infarction
• Atypical response to exercise, hypovolaemia and hypotension
  • Any required increase in CO is due to volume or circulating catecholamines and is therefore delayed
  • Attention to preload is critical with any intercurrent illness

The denervated heart

• Atropine has no effect whatsoever
• Adenosine has four-fold increased effect in sinus and AV nodal blockade due to denervation hypersensitivity
• Digoxin has increased contractility effect but no effect on AV node
• Adrenaline and noradrenaline have increased effect due to denervation hypersensitivity
• Cardiac arrhythmias may be a sign of rejection

Rejection

• Experienced by the majority of recipients within first 3 months
• Biopsy is the gold standard
• May present as dyspnoea, arrhythmias, weight gain, malaise, low-voltage ECG, echo evidence of declining function

Infections

• Opportunistic infections (mostly of lung) occur in many patients
• 45% bacterial and <10% fungal but mortality 40% for fungal and 10% for bacterial

Malignancy

• 100x risk of malignancy (1-2% per year)
• Mostly skin cancers

Cardiac allograft vasculopathy

• Main cause of death in the long-term
• Diffuse obliterative coronary atherosclerosis
• Revascularisation made difficult by diffuse nature of illness

Heart-Lung Transplant

• Indications
  • Primary pulmonary HTN
  • Eisenmenger’s
  • End-stage suppurative pulmonary disease
  • End-stage bilateral lung disease with cardiac failure
• Patient then lacks bronchial arterial supply, pulmonary or cardiac innervation
• Lymphatic drainage to lungs is lost
• Bronchial arterial supply and lymphatic drainage regenerate after several weeks
• Denervation prevents reflex coughing of secretions below the anastamosis (usually at 5 tracheal rings above carina)
• Rejection manifests in lungs before heart usually
• 3x as many infections as heart transplant patients

Key history

• Recent temperature change
• Changes in exercise tolerance
• Date of transplant surgery
• Rejection history
• Recent changes in immunosuppressive regime
• Chronic infections e.g. CMV, EBV, HepB, HepC
• Recent exposure to infections e.g. varicella, CMV, tuberculosis
• Compliance with immunosuppressants
• Recent travel or exposure to travellers

Key examination

• Vital signs
• Eyes: CMV/toxoplasmosis retinitis, Listeria endophthalmitis
• Sinuses: S. aureus, mucormycosis, fungal
• Mouth: Candida, HSV
• Lymphadenopathy: CMV, EBV, hepatitis
• Lungs: S. pneumoniae, PCP, aspergillus, TB, coccidiomycosis and viral pneumonias
• Abdomen: Peritonitis without defined source, RUQ tenderness may suggest hepatitis, VZV pancreatitis
• Genitourinary: Pyelonephritis
• CNS: Cyclosporine/tacrolimus neurotoxicity, steroid psychosis, HSV encephalitis, Listeria meningitis/encephalitis and cryptococcal meningitis

Differential diagnosis

• Common medical problems with subsequently complicated management
• Complications of immunosuppression
• Infection
• Solid-organ rejection
• Graft-versus-host disease
• Fever may be absent in 50% of those with infections
• Fever in any transplant patient requires an aggressive workup, even if low-grade

Infections by date

• <1mo: MRSA, VRE, candida, aspiration, wound infection, C. difficile colitis, colonisation of transplanted organ (Aspergillus, Pseudomonas, Klebsiella, legionella)
• 1-6mo:
  • Patients on PCP and antiviral prophylaxis: Polyomavirus BK infection, C. difficile, HCV, adenovirus, influenza, Cryptococcus neoformans, TB
  • Patients not on prophylaxis: Pneumocystis, Herpesviruses, HBV, Listeria, Nocardia, Toxoplasma, Strongyloides, Leishmania, Trypanosoma cruzi
• >6mo: CAP, UTI, Aspergillus, mucor, Nocardia and late viral infections including CMV colitis/retinitis, HBV, HCV, HSV encephalitis, SARS, JC polyomavirus, skin cancer

Lung transplant presentations

• Fever, cough, increasing dyspnoea
• Signs of infection often overlap with rejection
• Drop in FEV1 by >10% warrants clinical investigation
• Bronchoscopy is required for specific diagnosis
• Commonly both infection and rejection are treated while awaiting definitive diagnosis
  • Empirical antibiotics
    • PipTaz 4.5g IV QID
    • Azithromycin 500g IV BD
    • Fluconazole 400mg IV
    • Aciclovir 10mg/kg IV TDS
  • Ensure to cover any previous colonisers and test samples broadly for bacterial/viral/fungal
  • Methylpred 1g IV stat in liaison with transplant team

Lung transplant complications by time

• 0-3 days:
  • Haemorrhage, reperfusion injury, dysrhythmia
• 3 days to 1 month
  • Infection: Bacterial, mycoplasma, community respiratory viruses
  • Rejection
  • Anastamotic failure
  • PE
  • Muscle weakness
  • Dysrhythmia
• >1mo
  • Rejection, obliterative bronchiolitis, infection (bacterial, fungal, community viral), mycoplasma (0-4mo) and mycobacteria (>4mo)
• Other
  • CMV and PCP can occur at any time, but more commonly if no prophylaxis (especially if prophylaxis recently discontinued)

Implantation syndrome

• Within hours of transplant get infiltrates on CXR with oedematous peribronchial cuffing
• In severe cases, looks like ARDS
• Management is supportive with fluid restriction as tolerated

Hyperacute rejection

• Rare but results in acute graft failure with very poor prognosis
• Management requires continued respiratory support and consideration of re-transplantation

Acute rejection

• Common and may occur 3-6 times in first post-operative year then reduces in frequency
• Seen in almost all patients within first 3 months
• Can occur for several years after transplant
• Signs of rejection: Cough, chest tightness, increase or decrease in baseline temperature by 0.28 degrees, hypoxaemia, FEV 1 drop by >10% and infiltrates on CXR
• After 6 weeks post-operatively, acute rejection may be ‘radiographically silent’
• If immunosuppressant regime has been tapered, usually increase dose back to pre-tapering level + high-dose corticosteroids methylprednisolone15mg/kg IV each day for 3 days
• Symptoms, spirometry, oxygenation and CXR (if abnormal) usually improves within 1-2 days
• Failure to improve suggests infectious aetiology

Indications for admission

• Pre-transplant
  • Respiratory failure
  • Infiltrates
  • Systemic infection
  • Decompensated CCF or PE
  • Pneumothorax
• Post-transplant
  • Respiratory failure
  • Acute rejection
  • FEV1 >10% drop over 48 hours
  • Infiltrate
  • Systemic infection
  • Febrile neutropaenia
  • Pneumothorax

Prognosis post-transplant

• 90% of heart recipients alive at 3 months vs. 75% of heart-lung and lung recipients
• 70% of heart recipients still alive at 5 years vs. <50% of heart-lung or lung recipients

Last Updated on October 28, 2020 by Andrew Crofton