Transthyretin amyloid cardiomyopathy (ATTR-CM) should be considered in patients presenting with red flags — for more information on ATTR-CM red flags, you can find resources here. When these features are present, the first step is diagnostic imaging; including an echocardiogram, which is widely available across secondary care settings as an inpatient or outpatient, an electrocardiogram (ECG), and, if available, cardiac magnetic resonance (CMR) .
Investigations that referring hospitals should complete
Before referring to a NAC or Regional Amyloidosis Centre, referring hospitals should aim to complete the following:
- Echocardiogram — assess LV wall thickness and LV strain patterns consistent with cardiac amyloidosis .
- Cardiac MRI — where DPD is unavailable or delayed, CMR may be used to support the diagnosis; local availability and timing should inform the sequencing of these investigations .
- Serum immunofixation and urine immunofixation — essential to exclude a monoclonal protein (AL amyloidosis); must not be substituted with serum protein electrophoresis alone, which lacks sufficient sensitivity to rule out a subtle clone
- Serum free light chains — required alongside immunofixation as part of the haematological screen
- DPD scintigraphy (if available) — a Grade 2 or 3 DPD scan in the absence of a monoclonal protein is consistent with ATTR-CM without the need for biopsy, in line with the non-invasive diagnostic algorithm
Electrophoresis alone is not sufficient — serum and urine immunofixation must be performed. Without this, it is not possible to follow the non-biopsy diagnostic pathway, as a subtle clonal protein may be missed, which could indicate AL amyloidosis.
What to include in the referral
All blood and urine test results should be included and dated with the referral letter. Specialist centres frequently receive referrals noting that tests have been performed but without the results — this delays diagnosis and the initiation of care. Where imaging has been completed, the full report, dated, should be included. Where investigations such as DPD scintigraphy or CMR have not yet been completed, referral can still be made; the specialist centre will complete the remaining workup as part of a one-stop-shop style clinic
What the NAC/Regional Centre can do
If a patient has been fully worked up — echocardiogram, CMR, serum and urine immunofixation, serum free light chains, and a Grade 2 or 3 DPD scan consistent with ATTR-CM — the specialist centre can confirm the diagnosis and initiate treatment without requiring the patient to travel in person. A telephone or video consultation can be used to explain and confirm the diagnosis, and medication can be arranged for delivery directly to the patient. This is particularly beneficial for patients who live a significant distance from a specialist centre.
Where investigations such as DPD scintigraphy or CMR have not yet been completed or are not available at the referring centre, referral can still be made; the specialist centre will complete the remaining workup.
