Early and accurate diagnosis is key to improving survival outcomes1–4
Patients with ATTRv amyloidosis face a diagnostic delay of
3–4 years5
50% of patients with ATTRv amyloidosis saw
≥3 physicians
before receiving the correct diagnosis*6
Patients with ATTR amyloidosis are missed among a broader population
*Survey created by Amyloidosis Research Consortium Cardiac Amyloidosis, including patients with AL and ATTR amyloidosis and their caregivers. 745 responses were captured across Asia-Pacific (7%), European Union (22%) and North America (71%) regions; 17% of responses (n=123) pertained to ATTRv amyloidosis;6
†Pooled incidence from four publications, published between 2011 and 2018. Individual incidences are not reported;7
‡Pooled incidence from three articles, published between 2011 and 2019. Individual incidences are not reported;7
§From a systematic review of 164 publications in Medline and EMBASE about musculoskeletal manifestations associated with ATTR amyloidosis;8
¶Prospective, cross-sectional, and unicentric study in which 99mTc-DPD scintigraphy was performed on 120 patients ≥60 years old admitted due to HFpEF with LV hypertrophy, to screen for and determine the prevalence of ATTRwt.9
The steps to diagnose ATTR amyloidosis in practice
Diagnosing ATTRv-PN
Suspicion index for diagnosing ATTRv-PN in endemic (A) and non-endemic (B) areas5,10
ATTRv-PN should be suspected in patients with progressive and disabling polyneuropathy, particularly in elderly patients. The disease should also be considered in patients with neuropathy and >1 red flag symptom suggestive of multisystemic involvement
*No diabetes, no alcohol abuse, vitamin B12 deficiency.5,10
Adapted from Conceição I, et al. J Periph Nerv Syst. 201610 and Adams D, et al. J Neurol. 20215
Expert consensus recommendations to improve diagnosis of ATTRv-PN5
Clinical suspicion of amyloid neuropathy5
Electrophysiological tests are useful in demonstrating large fibre neuropathy:11
- Nerve conduction studies (NCS)
- Electromyelography
Confirmation of ATTRv amyloidosis5
Biopsy of amyloid deposition
- Possible biopsy sites: labial salivary gland, subcutaneous fatty tissue of abdominal wall, skin, kidney, nerve and gastrointestinal tract (including submucosa)
- Congo red staining with characteristic green birefringence under polarised light
Amyloid typing
- Immunohistochemistry or mass spectrometry
DNA sequencing
- Analysis of the amyloidogenic TTR variant
- Can support or exclude a diagnosis of ATTRv amyloidosis
Figure adapted from Adams D, et al. J Neurol. 20215
Diagnosing ATTR-CM12
2023 ESC Guidelines: Diagnosis of cardiac amyloidosis12
According to the 2023 ESC Guidelines for the management of cardiomyopathies, ATTR-CM should be suspected in patients with increased LV wall thickness in the presence of cardiac or extracardiac red flags and/or in specific clinical situations, particularly in patients >65 years of age12
Left ventricular wall thickness ≥12 mm + ≥1 of
Adapted from the 2023 ESC Guidelines on the management of cardiomyopathies12
2023 ESC Guidelines: Diagnosis of cardiac amyloidosis12
Signs and symptoms, ECG, ECHO or CMR suggestive of cardiac amyloidosis
ECG: Discordant QRS voltage for degree of increased LV wall thickness on imaging, conduction abnormalities, and rhythm disturbances13-15
ECHO: Increased LV wall thickness, Grade 2 or worse diastolic dysfunction, and decreased global longitudinal strain with relative apical sparing13-15
CMR: Expansion of extracellular volume and diffuse subendocardial or transmural late gadolinium enhancement13-15
Consider biopsy if cardiac scintigraphy is negative or equivocal and clinical suspicion is high13,15
Light-chain cardiac amyloidosis (AL-CM) may present similarly in ATTR-CM but is caused by a plasma cell dyscrasia; it should be ruled out by screening for monoclonal protein with sFLC, SIFE, and UIFE13,15
Consider biopsy if cardiac scintigraphy is negative or equivocal and clinical suspicion is high13,15 Light-chain cardiac amyloidosis (AL-CM) may present similarly in ATTR-CM but is caused by a plasma cell dyscrasia; it should be ruled out by screening for monoclonal protein with sFLC, SIFE, and UIFE13,15
Adapted from the 2023 ESC Guidelines on the management of cardiomyopathies12
Watch this video to learn about diagnosing ATTR amyloidosis
It is important to suspect ATTR amyloidosis signs and symptoms to facilitate earlier diagnosis and treatment1
Early intervention for ATTR amyloidosis may improve quality of life1,2,4,10,16–19
GB-77262 | August 2026
