AAN Supportive Care guidelines
While the elimination, stabilisation and/or removal of amyloid is key to improving organ function, all patients require effective supportive care to make disease altering therapy possible. Supportive treatment is challenging and requires a multidisciplinary approach which may include allied health specialists, palliative care, social work, psychological/spiritual support and specialist medical management. Below are suggestions for optimising common patient symptoms. These suggestions are generally supported by only low-quality evidence (level IV-V). Trial and error of different approaches in partnership with patients is required and encouraged.
AL Cardiac Amyloidosis
- Diuretics (loop and aldosterone antagonists) are the cornerstone of treatment for volume overload in the setting of heart failure, nephrotic syndrome or treatment.
- Checking body weight regularly, reducing dietary salt intake and fluid restriction are fundamental to maintaining appropriate volume status.
- Neurohormonal blockade with ACE inhibitors, angiotensin receptor blockers, and beta-blockers are generally poorly tolerated in amyloid cardiomyopathy and there is no established mortality benefit [1,2].
- While the ejection fraction is often preserved in cardiac amyloid, stroke volume is reduced secondary to restrictive filling. Patients with cardiac amyloid often depend on a high heart rate to maintain output. As such, beta blockers can cause profound hypotension, worsen cardiac output and should be avoided.
- Afterload reduction also tends to be poorly tolerated, especially in patients who have existing postural hypotension.
- AF is the commonest arrhythmia in patients with cardiac amyloidosis. Its prevalence increases with stage of the disease (stage 1 – 61%, stage 3 – 76%). The presence of AF is associated with worse outcomes.
- Rate control:
- Atrial arrhythmias are common in cardiac amyloid, and rate control with conventional agents such as beta blockers are often poorly tolerated [1].
- In majority of patients with cardiac amyloidosis adequate rate control should be achieved by low dose beta blockers or Amiodarone [2].
- Calcium channels blockers are contraindicated.
- Historical evidence of digoxin binding to amyloid fibrils has meant it is used sparingly [3]. But judicious use of low dose Digoxin could be tried in those with low blood pressure and no alternative.
- Rhythm control.
- As the freedom from recurrent AF varies between the stages (~90% at 30 days in stage 1, <50% at 30 days for stage 3), in general the attempt at restoring sinus rhythm (with Direct Current CardioVersion DCCV + oral amiodarone) is not recommended in advanced cardiac amyloid.
- TOE should guide any attempt at DCCV with adequate provision of therapeutic anticoagulation in view of high risk of atrial thrombi formation and stroke.
- AF ablation is generally not recommended due to its low efficacy. However if Aflutter is the dominant atrial rhythm leading to hemodynamic instability an Aflutter ablation could be considered.
- Anticoagulation
- In AL, Anticoagulation should be considered for atrial fibrillation or flutter, recognizing that life-threatening bleeding is a potential risk.
- Cardiac amyloidosis is a risk factor for atrioventricular block, leading to severe bradycardia and cardiac arrest. Syncope in these patients should be investigated promptly, and pacemaker placement is indicated in such patients
- Defibrillator placement is controversial, with both successes and failures reported [4,5]. Patients with cardiac amyloidosis appear to have inferior outcomes following defibrillator placement compared to individuals with other non-ischaemia cardiomyopathies [6-8]
- In general, there is limited benefit from primary prevention ICD but use of device in survivors of SCD is generally accepted.
- Heart transplantation can be considered in very select cases for AL amyloidosis.
- The largest series examining heart transplantation in AL amyloidosis, found median OS of 3.5 years with 1-year survival of 77% [9]. Progressive amyloidosis was the cause of death in 60% of cases, and the best outcomes were observed in those who obtained a haematologic CR.
- Patients with extensive multiorgan involvement are generally not candidates.
Renal Amyloidosis
- Kidney transplantation is feasible in selected patients with end stage renal failure. Data from the Mayo group found 1-, 3-, and 10-year renal graft survival rates with 98.6%, 96.7% and 88.5%, respectively [10]. With the best outcomes observed in patients who were able to obtain a haematological complete response.
- Post renal transplantation the use of IMIDs has been associated with transplanted organ rejection [11].
Nervous System Amyloidosis
- Midodrine (up to 30mg/day, i.e. 5-10mg PO TDS), Droxidopa and pyridostigmine can help with postural hypotension related to autonomic dysfunction.
- Reverse Trendelenburg supine positioning (head up) can be helpful to improve daytime blood pressure and supine hypertension.
- Compression stockings or an abdominal binder may also be helpful and are a low-risk intervention.
- In patients without cardiac involvement, increased salt intake, hydration and fludrocortisone may be considered.
- A slowly graded exercise program should be encouraged, using recumbent bicycles if necessary, to improve venous return and vascular tone.
- Painful neuropathy may be treated symptomatically with gabapentin, pregabalin, or duloxetine. Amitriptyline or nortriptyline can be considered if there is no significant arrythmia.
- Topical preparations of lignocaine, amitriptyline or capsaicin may also provide relief.
- If neuropathy is secondary to carpal tunnel syndrome, then splints or carpal tunnel release are effective.
- Consider pre-emptive dose reduction of bortezomib and other plasma cell therapies associated with neuropathy. Bortezomib should be avoided in patients with baseline severe peripheral neuropathy.
- Appropriate footwear, regular visual inspection of the feet and podiatry assessments should be undertaken for significant sensory deficits of the lower limbs.
Gastrointestinal Amyloidosis
- Domperidone or metoclopramide may be used in patients with nausea and early-satiety.
- Loperamide or codeine may be used in the management of diarrhoea once infection has been excluded.
Patient Support and Education
Amyloidosis is a debilitating group of diseases.
The psychological aspect of being diagnosed with one of these diseases can be profound due to disease burden, chronicity, and life expectancy. A 2022 study from a French national survey of amyloidosis patients showed that 69% of patients believed that amyloidosis severely affected their quality of life. [12]
Amyloidosis continues to be under recognized and misdiagnosed. Patient have often seen several specialists before receiving a definitive diagnosis of amyloidosis, which can leave them confused, exhausted, anxious and sick. Support and education is extremely important in the amyloidosis journey, particularly at diagnosis, treatment initiation or when treatment is changed.
Patient Information Record
The AAN Patient’s and Family Advisory Committee (PFAC) recommends that amyloidosis patients carry with them a complete and up-to-date Amyloidosis Patient Information Record. It asks that you introduce the document to the patient and encourage them to fill it in. This document would contain a record of their amyloidosis journey including amyloidosis type, impact, treatment and medications and include the names and contact details for all medical professionals involved in their care. It is seen as an effective and efficient communication catalyst between patient and medical professionals as well as ensuring all medical professionals treating them, including emergency responders, are fully informed of the patient’s condition and the others involved in their care. It has the potential to increase the patient’s understanding, involvement and ownership of their care leading to better treatment outcomes.
Many patients wish to find ways to help themselves. See the downloadable pamphlets on [LINKS TO BE ESTABLISHED]:
- Support services.
- Complimentary treatments
- Diet
- Exercise
- Dealing with anxiety
Referral to Supportive Care/Palliative Care
Patients’ wishes must be sought and respected, but this can only happen if they fully understand their disease and treatment. Though several disease-modifying therapies are now available for the main types of amyloidosis they are not without issues such as side effects, travel time, hospital visits and costs.
Many patients are often diagnosed late in life and may opt for conservative treatment. Supportive and palliative care can help with symptom control, particularly breathlessness and postural symptoms. In addition, it can help support patients with end-of-life planning and comfort measures.
More information on Palliative Care can be found using the link below.
