Heart Transplant

Question 1

A 36-year-old male patient is listed for a laparoscopic appendicectomy. He has previously had a heart transplant. You are asked to assess him on the ward prior to his procedure.
Which conditions may lead to consideration of cardiac transplantation?

Answer 1

• Reasons for consideration of heart transplant include patients with chronic heart failure:
• Who despite maximal medical therapy, exhibit limiting symptoms, or require frequent hospital admissions, or exhibit
  rising natriuretic peptide levels.
• Who exhibit deteriorating renal function or intolerability to
  remove congestion without compromising renal function, or who require reduction or cessation of heart failure medication due to intolerable side effects e.g. hypotension and renal dysfunction.
• Urgent referral is indicated for patients dependent on intravenous inotropic therapy; those requiring mechanical support for cardiogenic shock; those requiring positive airway pressure ventilatory support for intractable pulmonary oedema; or those with refractory ventricular dysrhythmias.

Question 2

What are the contraindications to cardiac transplantation?

Answer 2

• Irreversible liver or renal failure.
• Diabetes: either poorly controlled or causing end-organ dysfunction.
• Obesity or other multi-system disease with poor long-term survival.
• Severe lung disease or pulmonary hypertension.
• Active or recent malignancy.
• Symptomatic cerebral or peripheral vascular disease.
• Active infection.
• Alcohol excess/drug abuse.
• Psychosocial factors such as non-compliance with medication, drug
  or alcohol misuse, current smoker and inadequate support.

Question 3

What are the long term consequences of cardiac transplantation?

Effect on organ systems:

Answer 3

• Immune-mediated coronary artery disease (CAV).
• The risk of organ rejection requires immunosuppression, long-term monitoring and surveillance cardiac biopsies.
• Persistence of any systemic disease processes that led to cardiac
  failure initially.
• Chronic graft dysfunction.
• Increased susceptibility to infection (including bacterial, viral, fungal
  and atypical) due to systemic immunosuppression.

Question 4

What are the long term consequences of cardiac transplantation?

Medication:

Answer 4

• Patients require lifelong immunosuppressive agents. For maintenance immunosuppression, a triple therapy regime is commonly used including a calcineurin inhibitor (ciclosporin or tacrolimus), an anti-metabolite (azathioprine or mycophenolate) and a corticosteroid (prednisolone or methylprednisolone).
  Over time, a significant proportion of patients can be weaned off steroids.
• As well as risk of infections, long-term consequences also include an increased risk of certain cancers.
• Therapeutic drug monitoring is required for some immunosuppressants, and careful avoidance of food or drug interactions that may potentiate or inhibit their effect. Some side effects include:

Question 5

Immunosuppressant side effects?

Answer 5

• Azathioprine – liver toxicity, pancreatitis, leukopenia and risk of infection.
• Mycophenolate – leukopenia, gastrointestinal symptoms, contraindicated in pregnancy due to the increased risk of miscarriage or congenital malformations.
• Ciclosporin or tacrolimus – renal toxicity, diabetes, hypertension, neurotoxicity and gingival hyperplasia (ciclosporin).
• Prednisolone – hypertension, hyperlipidaemia, diabetes, osteoporosis, Cushing’s syndrome and fuid retention.

Question 6

What is the commonest cause of pacemaker insertion in patients with a heart transplant?

Answer 6

• During cardiac transplantation, the donor atria are sutured to the recipient atria. Recipient atrial activity does not cross the suture line, so the donor heart rate is dependent on the denervated donor sino-atrial node.
• Bradycardia due to ineffective blood supply to the donor sino-atrial node, or AV conduction defects, are common reasons for permanent pacing.

Question 7

How would you assess this patient preoperatively?

1) History (remember to ask of symptoms of disease/disease progression in history)

Answer 7

• Ensure a thorough cardiac history including the reason for transplantation, any courses of treatment and disease progression. Explore symptoms suggestive of ischaemic heart disease or cardiac failure, bearing in mind that the patient is unlikely to experience angina due to the denervated heart.
• Take a full drug history including immunosuppressive agents and any side effects.
• Carry out a review of the patient’s notes and discuss with the specialist transplant team regarding the patient’s condition, including history of graft dysfunction, graft rejection, CMV status, and advice for peri-operative management such as therapeutic drug monitoring and antibiotic prophylaxis.
• Systematic review and other comorbidities should be considered, as well as previous anaesthetics, airway assessment and social history.
• History of the patient’s current illness.

Question 8

How would you assess this patient preoperatively?

Examination & Investigations:

Answer 8

Examination:
* Cardiovascular examination and airway assessment.

• Examine for signs of sepsis. Discuss with a microbiologist early given
  the risk of atypical infections.

Investigations:
* Baseline observations.
* Baseline blood tests to include a full blood count, renal function and
electrolytes, and markers of infection.
* Baseline ECG, chest X-ray and recent echo.

Question 9

What are the anaesthetic implications and goals for this patient?

Implications:

Answer 9

• The heart is denervated at the time of donor retrieval. This significantly impacts its ability to alter heart rate following transplantation. The heart rate is usually maintained by donor sino-atrial activity between 90 and 100 bpm.
• In the denervated heart, there will be an absence of reflex autonomic heart rate changes to events such as laryngoscopy or traction to abdominal or pelvic viscera.
• Significant blood pressure fluctuations can occur due to the lack of heart rate compensatory responses to changes in systemic vascular resistance.
• Sympathetic stimulation to the denervated transplanted heart occurs through circulating catecholamines. This requires the use of direct-acting adrenergic sympathomimetic drugs including ephedrine, isoprenaline, noradrenaline or adrenaline.
• For brady-dysrhythmias, vagolytic drugs such as atropine and glycopyrrolate will be ineffective at increasing heart rate. Use direct-acting beta-adrenergic drugs to increase heart rate, or electrical
  pacing if necessary.
• For tachy-dysrhythmias, digoxin will be ineffective at reducing heart rate through its vagally mediated mechanism of action. Consider the use of amiodarone or verapamil.

Question 10

What are the anaesthetic implications and goals for this patient?

Implications….continued:

Answer 10

• Beware of denervation supersensitivity to drugs such as noradrenaline,
  adrenaline and adenosine.
• The Frank-Starling mechanism remains intact, facilitating preload-
  induced effects on stroke volume and thus cardiac output. The transplanted heart is particularly sensitive to preload changes and the subsequent effect on cardiac output, given the poor or absent autonomic heart rate response in denervated hearts.
• Due to denervation, patients may not experience angina despite the presence of myocardial ischaemia.
• There is evidence of a degree of sympathetic and/or parasympathetic re-innervation over time in some patients following cardiac transplantation, although this occurs to a variable extent. Regeneration of autonomic nerve fibres may, for example, improve the transplanted heart’s ability to vary heart rate or contractility, or to re-establish the patient’s ability to experience the sensation of angina.
• If the patient is CMV negative, they should receive CMV negative blood products.

Question 11

What are the anaesthetic implications and goals for this patient?

Goals:

Answer 11

• Take extra care during laryngoscopy or airway instrumentation as gingival hyperplasia may increase the risk of oral bleeding.
• Consider using cis-atracurium for neuromuscular blockade, given its favourable metabolism and elimination profile in the presence of hepatic or renal dysfunction. Neostigmine in combination with glycopyrrolate has been used safely in heart-transplanted patients, although cases of severe bradycardia or cardiac arrest following administration have been reported. Ensure immediate availability of direct-acting catecholaminergic drugs. Alternatively, rocuronium followed by sugammadex could be considered.
• Ensure a cardiostable anaesthetic. Be aware of the potential for exaggerated blood pressure variation, both with general anaesthetic or neuraxial blockade, due to the blunted heart rate response. Therefore, anticipate the effects of, and avoid, large swings in the systemic vascular resistance.
• Judicious use of fluids to maintain and optimise preload, given the preload dependence of the transplanted heart. Avoid hypovolaemia prior to induction.
• Maintain coronary perfusion pressures.

Question 12

What are the anaesthetic implications and goals for this patient?

Goals…continued:

Answer 12

• Use direct-acting chronotropic and inotropic agents and have external
  pacing readily available.
• Consider cardiac output monitoring or intra-operative echo for
  monitoring and guiding management.
• Ensure optimal oxygenation, temperature and pain control.
• Use strict aseptic techniques for venous/arterial line or urinary catheter insertion, or regional/neuraxial anaesthetic procedures, due
  to the increased risk of infection.
• Ensure meticulous patient positioning and padding as steroids can cause thin and fragile skin and increase the risk of pressure sores.
• Seek advice regarding additional stress-dose cover if the patient is
  taking significant doses of corticosteroids for immunosuppression.
• Postoperatively, remove lines or catheters at the first appropriate
  opportunity, given the increased risk of infection.
• Ensure immunosuppressant therapy is maintained and therapeutic
  drug monitoring as advised by the transplant team.
• Avoid NSAIDs if there is a possibility of worsening renal dysfunction.

Question 13

Heart transplant main points

Answer 13

• Indications/contraindications for a transplant
• CAV, organ effects, infections, malignancy
• Immunosuppression drugs and s/e’s
• Anaesthetic implications and goals
• Avoid vagolytic drugs, use direct sympathomimetic drugs (ephedrine, NA, adrenaline, isoprenaline)
• Preload dependent
• Cardiostable anaesthetic, CO monitoring
• Strict asepsis
• Avoid NSAIDs