Diagnosis guide for clinicians

Transthyretin (ATTR) amyloidosis: when to suspect it and what to test

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a restrictive cardiomyopathy caused by deposits of transthyretin, a liver-made transport protein, in the heart; it occurs as a hereditary variant form (ATTRv) or a wild-type form (ATTRwt).2020 AHA scientific statement

GeneReviews describes hereditary ATTR amyloidosis as a slowly progressive sensorimotor and/or autonomic neuropathy that can also involve the heart, eyes, kidneys and central nervous system.GeneReviews

The 2020 AHA scientific statement says ATTR-CM is frequently underrecognized because its signs are attributed to aging, hypertension, hypertrophic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF).2020 AHA scientific statement

Autosomal dominantInheritance of hereditary ATTR; each child of a heterozygous parent has a 50% risk of inheriting the TTR variantGeneReviews

13% to 17%Share of patients with HFpEF found to have ATTR, as cited in the 2020 AHA statement2020 AHA scientific statement

Up to 16%Patients with degenerative aortic stenosis who show ATTR deposition, as cited in the same statement2020 AHA scientific statement

3.0% to 3.9%Frequency of the TTR p.Val142Ile (V122I) variant in African Americans, per GeneReviewsGeneReviews

E85.82ICD-10-CM code, wild-type transthyretin-related (ATTR) amyloidosisNLM ICD-10-CM lookup

Orphanet record ORPHA:271861 · Inheritance: Autosomal dominant · Prevalence: 1-9 / 1 000 000 (point prevalence, Worldwide) · Also called: ATTRv amyloidosis, Familial TTR-related amyloidosis, Familial transthyretin-related amyloidosis, Hereditary TTR amyloid polyneuropathy, Hereditary TTR amyloidosis, Hereditary transthyretin amyloid polyneuropathy, hATTR

Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.

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Red flags Often mistaken for What to test Family screening ICD-10 codes Once confirmed For the patient

Red flags for Transthyretin (ATTR) amyloidosis

What the cited sources describe, grouped by life stage and organ. Each line links to its source.

Heart: imaging, ECG and laboratory clues

Unexplained left ventricular wall thickening, right ventricular thickening or atrial wall thickening, listed among cardiac clues in the 2020 AHA statement.2020 AHA scientific statement
The AHA statement says wall thickness of 14mm or more should trigger consideration of ATTR-CM, especially when it is discordant with QRS voltage on the ECG.2020 AHA scientific statement
The ESC position statement uses unexplained LV wall thickness of 12mm or more as the entry point of its echocardiographic criteria.ESC position statement
Low QRS voltage for the degree of LV thickness, a pseudoinfarct pattern and atrioventricular conduction disease are cardiac red flags in the ESC position statement.ESC position statement
Persistently elevated troponin, and NT-proBNP that is disproportionately high for the degree of heart failure.ESC position statement
The ACC summary of its 2023 decision pathway lists echo findings including thickening of the atrioventricular valves, right ventricular free wall and interatrial septum, biatrial enlargement and decreased global longitudinal strain with apical sparing.ACC summary of the 2023 decision pathway
GeneReviews describes a pseudoinfarction pattern with prominent Q waves and a thickened LV wall with a granular sparkling appearance and preserved systolic function.GeneReviews

Heart: clinical course

Intolerance of antihypertensive or heart failure medicines because of symptomatic hypotension or orthostasis.2020 AHA scientific statement
Low blood pressure, or normal blood pressure in a patient who was previously hypertensive.ESC position statement
Unexplained atrioventricular block or a prior pacemaker implantation.2020 AHA scientific statement
Atrial fibrillation and conduction system disease, which the ACC summary lists alongside heart failure symptoms, diastolic dysfunction and raised cardiac biomarkers.ACC summary of the 2023 decision pathway
The AHA statement says older patients presenting with HFpEF and even milder degrees of increased wall thickness also warrant scrutiny.2020 AHA scientific statement
The 2021 multisociety imaging consensus lists people over 60 with low-flow, low-gradient aortic stenosis among scenarios for imaging evaluation.2021 multisociety imaging consensus
The ESC group recommends looking for cardiac amyloidosis in people with increased wall thickness and heart failure, aortic stenosis or red flags, particularly if older than 65.ESC position statement

Orthopedic and soft tissue

Carpal tunnel syndrome; GeneReviews notes that the majority of people with wild-type ATTR present with carpal tunnel syndrome.GeneReviews
Spinal stenosis and spontaneous biceps rupture, which the ACC summary calls findings unique to ATTR.ACC summary of the 2023 decision pathway
Hip or knee replacement and prior shoulder surgery, listed as extracardiac clues in the ACC summary.ACC summary of the 2023 decision pathway
The multisociety imaging consensus lists unexplained bilateral carpal tunnel syndrome after age 60, and heart failure with unexplained biceps tendon rupture after 60, among scenarios for imaging.2021 multisociety imaging consensus

Nerves and autonomic system (mainly hereditary ATTR)

Slowly progressive sensory neuropathy starting in the feet, with burning or shooting pain or numbness; temperature and pain sensation are impaired before vibration and position sense.GeneReviews
Autonomic dysfunction: orthostatic hypotension, constipation alternating with diarrhea, nausea and vomiting, delayed gastric emptying, impotence, anhidrosis, and urinary retention or incontinence.GeneReviews
GeneReviews says autonomic neuropathy may be the presenting manifestation, particularly in early-onset disease.GeneReviews
Heart failure with unexplained peripheral sensorimotor neuropathy is an imaging scenario in the multisociety consensus.2021 multisociety imaging consensus
The AHA statement names people with small-fiber polyneuropathy among groups with an increased prevalence of cardiac amyloidosis in whom more active ascertainment may be indicated.2020 AHA scientific statement

Eyes, kidneys, ears and brain

Vitreous opacities and glaucoma; GeneReviews reports vitreous opacification in about 20% of people with hereditary ATTR.GeneReviews
Proteinuria precedes kidney involvement; kidney failure occurs in about one third of Portuguese patients with early-onset p.Val50Met disease, but severe kidney dysfunction is rare in late-onset disease.GeneReviews
Deafness is listed as a red flag most often found in wild-type ATTR in the ESC red flag table.ESC position statement
Transient focal neurologic episodes from leptomeningeal amyloid, common with p.Val50Met and long-standing disease.GeneReviews

Ancestry, age and family history

GeneReviews puts the frequency of p.Val142Ile, historically called Val122Ile, at 3.0% to 3.9% in African Americans and says most heterozygotes develop late-onset cardiac amyloidosis.GeneReviews
The multisociety imaging consensus lists African American adults over 60 with unexplained heart failure or unexplained increased LV wall thickness among scenarios for imaging.2021 multisociety imaging consensus
The AHA statement lists Black race, a family history of polyneuropathy and a family history of cardiomyopathy among clues.2020 AHA scientific statement
A family history may include rapidly progressive polyneuropathy of unknown cause, heart failure, sudden cardiac death or arrhythmia; absence of a known family history does not preclude the diagnosis.GeneReviews
Large clusters of p.Val50Met, historically Val30Met, occur in Portugal, Sweden and Japan, where it is the most common variant.GeneReviews
The AHA statement gives an age at onset of 70 to 75 years for wild-type disease, with 80% to 90% of patients male.2020 AHA scientific statement

Often mistaken for

Diagnoses patients commonly carry first, and why the sources say they are confused.

First diagnosis	Why it is confused
Heart failure with preserved ejection fraction	Dyspnea, fatigue and edema are nonspecific; the AHA statement says they are often misdiagnosed as nonamyloid HFpEF.2020 AHA scientific statement
Hypertensive heart disease	The AHA statement says patients with HFpEF and moderate to severe wall thickening are often mislabeled as having hypertensive cardiomyopathy.2020 AHA scientific statement
Hypertrophic cardiomyopathy	LV thickening can look like HCM; GeneReviews notes that hereditary HCM lacks peripheral and autonomic neuropathy.GeneReviews
Normal aging	The AHA statement names attribution of presenting signs to aging as one reason ATTR-CM is underrecognized.2020 AHA scientific statement
Aortic stenosis alone	ATTR deposition is reported in up to 16% of patients with degenerative aortic stenosis, according to the AHA statement.2020 AHA scientific statement
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)	GeneReviews calls CIDP the most common misdiagnosis in hereditary ATTR without a family history; one series found 18 of 90 such patients misdiagnosed.GeneReviews
Diabetic neuropathy	Both cause peripheral neuropathy; GeneReviews separates them by a history of diabetes and high blood sugar.GeneReviews
Charcot-Marie-Tooth neuropathy	Both cause hereditary peripheral neuropathy; GeneReviews notes Charcot-Marie-Tooth has no cardiomyopathy and progresses more slowly.GeneReviews
AL (light chain) amyloidosis	AL can cause neuropathy, carpal tunnel syndrome, cardiomyopathy and kidney failure; GeneReviews says it may be difficult to distinguish clinically.GeneReviews
Fabry disease	Fabry disease also causes cardiomyopathy, nephropathy and peripheral neuropathy, but usually starts in youth and shows angiokeratoma and low alpha-galactosidase A activity.GeneReviews
Cardiac sarcoidosis	Both can cause cardiomyopathy with variable neuropathy or nephropathy; uveitis, hilar lymphadenopathy and a high serum ACE level point to sarcoidosis.GeneReviews

Codes patients often carry before this diagnosis

For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.

Diastolic (congestive) heart failure I50.30, I50.31, I50.32, I50.33

ATTR has been found in 13% to 17% of patients with HFpEF, and symptoms are often attributed to nonamyloid HFpEF.2020 AHA scientific statement

Nonrheumatic aortic (valve) stenosis I35.0

ATTR deposition is reported in up to 16% of patients with degenerative aortic stenosis.2020 AHA scientific statement

Obstructive or other hypertrophic cardiomyopathy I42.1, I42.2

LV thickening from ATTR can be labeled hypertrophic cardiomyopathy.2020 AHA scientific statement

Carpal tunnel syndrome G56.00, G56.01, G56.02, G56.03

GeneReviews says the majority of people with wild-type ATTR present with carpal tunnel syndrome.GeneReviews

Spinal stenosis, lumbar region M48.061, M48.062

Lumbar spinal stenosis is an orthopedic clue to ATTR-CM in the AHA statement.2020 AHA scientific statement

Atrial fibrillation (selected codes) I48.0, I48.11, I48.19, I48.20, I48.21, I48.91

Atrial fibrillation is among the cardiac clues listed in the ACC summary.ACC summary of the 2023 decision pathway

Atrioventricular block I44.0, I44.1, I44.2, I44.30, I44.39

Unexplained atrioventricular block or prior pacemaker implantation is a cardiac clue in the AHA statement.2020 AHA scientific statement

Orthostatic hypotension I95.1

GeneReviews lists orthostatic hypotension among the findings of autonomic neuropathy in hereditary ATTR.GeneReviews

Polyneuropathy, unspecified G62.9

GeneReviews says hereditary ATTR is characterized by a slowly progressive peripheral sensorimotor and/or autonomic neuropathy.GeneReviews

What to test, step by step

The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.

Adults with heart failure, wall thickening or the red flags above

Recognize the clinical clues
The AHA statement says the key to diagnosis is a high index of suspicion, and its testing algorithm begins with the cardiac and noncardiac clues in its Table 1.2020 AHA scientific statement

Anyone with suspected cardiac amyloidosis

Echocardiography
The AHA statement calls echocardiography not diagnostic, but lists effusions, a thick right ventricle, a small LV cavity and impaired global longitudinal strain with apical sparing as clues.2020 AHA scientific statement

Adults being evaluated with imaging

Echo and CMR criteria
The multisociety imaging consensus lists LV wall thickness above 12mm, relative apical sparing with an apical to mid plus basal strain ratio above 1, or grade 2 or worse diastolic dysfunction, with other causes reasonably excluded. Its CMR criteria include global ECV above 0.40 and diffuse LGE.2021 multisociety imaging consensus

Everyone with suspected cardiac amyloidosis

Monoclonal protein screen
The ACC summary calls this the first step in typing: serum free light chains plus serum and urine immunofixation. If all are negative, AL has been ruled out; if any are positive, it names biopsy of the involved organ with mass spectrometry as the next step.ACC summary of the 2023 decision pathway

Everyone screened for AL

Why immunofixation, not electrophoresis alone
The AHA statement cites about 70% sensitivity for serum protein electrophoresis against over 90% for serum immunofixation. Together, serum and urine immunofixation and serum free light chains are over 99% sensitive for AL.2020 AHA scientific statement

Suspected ATTR-CM, read alongside light chain results

Technetium bone scintigraphy
PYP, DPD or HMDP tracers are used; the AHA statement notes PYP is used in the United States. Uptake is graded against rib: grade 2 equals rib uptake and grade 3 exceeds it.2020 AHA scientific statement

Grade 2 or 3 uptake, no monoclonal protein and typical echo or CMR features

Nonbiopsy diagnosis
In a 2016 study of 1,217 patients with suspected cardiac amyloidosis referred to specialist centers, grade 2 or 3 uptake without a serum or urine monoclonal protein had a specificity and positive predictive value of 100% for cardiac ATTR in that cohort (PPV confidence interval 98.0 to 100). The authors reported that false positive scans came almost entirely from cardiac AL amyloidosis, and proposed noninvasive diagnostic criteria.Gillmore 2016 nonbiopsy diagnosis study

Every positive scan

Confirm uptake with SPECT
The ESC position statement says scintigraphy should always include SPECT to confirm that uptake is in the myocardium and not in the cardiac chambers.ESC position statement

Uptake plus any abnormal immunofixation, free light chain result or MGUS

Positive scan with abnormal light chain tests
The imaging consensus says the scan is then not diagnostic of ATTR-CM and recommends referral to a specialist amyloid center and consideration of biopsy.2021 multisociety imaging consensus

Positive scan with a monoclonal protein

Histology with amyloid typing
ESC notes that ATTR with MGUS, AL amyloidosis, or coexisting AL and ATTR amyloidosis are possible here, and diagnosis requires histology with amyloid typing, usually by endomyocardial biopsy.ESC position statement

Grade 1 uptake with negative monoclonal protein tests

Grade 1 uptake
ESC says grade 1 uptake does not allow a noninvasive diagnosis and histology is required, which may be extracardiac.ESC position statement

Equivocal scans

Equivocal scan
The imaging consensus says endomyocardial biopsy should be considered when a scan is equivocal.2021 multisociety imaging consensus

No uptake and normal light chain tests, but high clinical suspicion

Negative scan, persistent suspicion
ESC suggests CMR followed by cardiac or extracardiac biopsy, because bone scintigraphy can be negative with some TTR variants and in rare subtypes of cardiac amyloidosis.ESC position statement

Suspected infiltrative disease when ATTR-CM is less likely

Cardiac MRI
The AHA statement says CMR alone is not diagnostic of ATTR-CM. It names CMR as the appropriate test in younger patients or when sarcoidosis, hemochromatosis, Fabry disease, HCM, myocarditis or constrictive pericarditis is suspected.2020 AHA scientific statement

Everyone diagnosed with ATTR-CM

TTR gene sequencing
The AHA statement says sequencing is required to separate ATTRv from ATTRwt. It adds that age alone is not a valid way to tell the 2 apart.2020 AHA scientific statement

Older patients with apparent wild-type disease

Genetic testing in older adults
ESC says genetic counselling and testing should be performed even in elderly patients, as a significant number can have TTR variants.ESC position statement

Suspected hereditary ATTR with polyneuropathy

Diagnosis in neuropathy-led presentations
GeneReviews says the diagnosis is established by suggestive findings, including imaging or histology showing amyloid, plus a heterozygous pathogenic or likely pathogenic TTR variant.GeneReviews

When histology is needed outside the heart

Tissue biopsy sites
GeneReviews lists abdominal fat, skin, gastric or rectal mucosa, sural nerve, endocardium and tissue from carpal tunnel surgery. It puts GI mucosal biopsy sensitivity at about 85%, and calls sural nerve biopsy less sensitive because deposits are patchy.GeneReviews

Molecular testing

Which TTR test
GeneReviews says TTR sequencing detects 100% of reported pathogenic variants. Deletion/duplication testing is unlikely to help because the disease acts through gain of function.GeneReviews

ATTRv, or neuropathy present or suspected

Neurology input
The AHA statement says neurological consultation should be pursued when neurological involvement is present or suspected, or when the variant is associated with it.2020 AHA scientific statement

Adults with confirmed ATTR-CM

Label scope: tafamidis
The Vyndaqel and Vyndamax label covers the cardiomyopathy of wild-type or hereditary ATTR in adults, to reduce cardiovascular mortality and cardiovascular-related hospitalization.Vyndaqel and Vyndamax label
Label scope: acoramidis
The Attruby label covers the cardiomyopathy of wild-type or variant ATTR in adults, to reduce cardiovascular death and cardiovascular-related hospitalization.Attruby label

Adults with ATTR-CM or hereditary ATTR polyneuropathy

Label scope: vutrisiran
The Amvuttra label covers the polyneuropathy of hereditary ATTR and the cardiomyopathy of wild-type or hereditary ATTR in adults.Amvuttra label

Adults with hereditary ATTR polyneuropathy

Label scope: eplontersen
The Wainua label covers only the polyneuropathy of hereditary ATTR in adults.Wainua label
Label scope: patisiran
The Onpattro label likewise covers only the polyneuropathy of hereditary ATTR in adults.Onpattro label

Where testing goes wrong

The AHA statement says a bone scan alone, without light chain testing, is neither appropriate nor valid for telling ATTR-CM from AL cardiomyopathy.2020 AHA scientific statement
Serum and urine protein electrophoresis should not be used to rule out a monoclonal protein because they are less accurate than immunofixation, according to the ACC summary.ACC summary of the 2023 decision pathway
Planar images alone can mistake blood pool for myocardial uptake; ESC lists blood pool, rib fractures, valve calcification and recent infarction as false positives that SPECT helps resolve.ESC position statement
Other false positives in the ESC table include AL amyloidosis, hydroxychloroquine cardiac toxicity, apolipoprotein AI, AII and AIV amyloidosis, and beta-2 microglobulin amyloidosis after over 9 years of dialysis.ESC position statement
False negatives in the ESC table include the Phe84Leu and Ser97Tyr TTR variants, very mild disease, and images acquired too early or too late.ESC position statement
GeneReviews notes that bone scintigraphy is negative in young people with the p.Val50Met variant.GeneReviews
Mild kappa to lambda ratio rises are common in kidney disease; ESC says that in moderate CKD with eGFR below 45 (its Table 3 footnote says 45 or less), a Freelite ratio up to 2.0, or 3.1 on dialysis, can typically be considered normal if serum and urine immunofixation are normal.ESC position statement
A negative fat pad biopsy does not rule out AL or ATTR, and the ACC summary says biopsy of the involved organ should be considered.ACC summary of the 2023 decision pathway
The ACC summary names macroglossia, periorbital purpura and acquired factor X deficiency as pathognomonic extracardiac findings for AL amyloidosis.ACC summary of the 2023 decision pathway
Under 40% of patients with biopsy-proven ATTR-CM have low ECG voltage, so the AHA statement says its absence should not dissuade clinicians.2020 AHA scientific statement
The AHA statement notes that grade 2 or 3 uptake is highly specific in amyloid centers with a high disease prevalence, but test performance in lower-prevalence populations is unknown.2020 AHA scientific statement
The AHA statement says AL and ATTR cardiomyopathy may very rarely occur together, and that patients with biopsy-proven AL, especially if older, may also have superimposed wild-type ATTR deposits.2020 AHA scientific statement
In one series cited by GeneReviews, 13 of 102 people with hereditary ATTR met definite electrodiagnostic criteria for CIDP.GeneReviews
Older papers number TTR variants from the mature protein, 20 amino acids lower than standard numbering, so p.Val50Met appears as Val30Met.GeneReviews
A TTR variant of uncertain significance neither establishes nor rules out the diagnosis.GeneReviews

Where to test

NIH Genetic Testing Registry: hereditary transthyretin amyloidosis: Lists clinical TTR genetic tests submitted by laboratories for this condition, recorded in NIH's MedGen as Amyloidosis, hereditary systemic 1. NIH does not independently verify submissions or endorse any laboratory.NIH GTR
Light chain tests through a clinical laboratory: Serum free light chain assay with serum and urine protein electrophoresis with immunofixation, the panel the ESC statement uses to exclude a clonal disorder.ESC position statement
Bone scintigraphy through nuclear medicine: Technetium PYP, DPD or HMDP scans; the AHA statement notes PYP is used in the United States.2020 AHA scientific statement
NIH's Genetic Testing Registry listed 9 tests for a search of “Transthyretin (ATTR) amyloidosis” on November 9, 2026. NIH does not endorse or verify the labs it lists.

Family screening and referral

Who else in the family

Hereditary ATTR is autosomal dominant; each child of a heterozygous parent has a 50% chance of inheriting the TTR variant.GeneReviews
The AHA statement says confirming ATTRv should trigger genetic counseling and potential screening of family members.2020 AHA scientific statement
ESC recommends genetic testing for relatives of patients with an inheritable form, along with genetic counselling.ESC position statement
ESC discourages genetic testing of minors because all hereditary amyloidoses have adult onset, but says it could be offered in young adulthood for career or reproductive planning.ESC position statement
ESC recommends starting assessment of carriers about 10 years before the age of onset in affected relatives, or as soon as compatible symptoms develop.ESC position statement
Penetrance varies by variant and region: GeneReviews cites 80% by age 50 for p.Val50Met carriers in Portugal against 14% in France.GeneReviews
A family history can look negative because of unrecognized disease, early parental death or late onset in a parent.GeneReviews
Predictive testing of at-risk relatives and prenatal or preimplantation testing are possible once the family variant is known.GeneReviews

Who to refer to

The ACC summary of its 2023 decision pathway calls multidisciplinary care a requisite, because amyloid fibrils can deposit in multiple organs.ACC summary of the 2023 decision pathway
The imaging consensus recommends referral to a specialist amyloid center when a scan is positive alongside any abnormal light chain test or MGUS.2021 multisociety imaging consensus
ESC advises consultation with a haematologist when the free light chain ratio is abnormal beyond its kidney-adjusted ranges, and when a monoclonal protein test is abnormal without cardiac uptake on scintigraphy, where AL has to be ruled out promptly.ESC position statement
If the workup finds AL instead, ESC says treatment should be undertaken by multidisciplinary teams with oncohaematology and cardiology specialists, and patients referred to specialized centres whenever possible.ESC position statement
The AHA statement advises neurological consultation when neuropathy is present or suspected, or the variant is linked to neurological involvement.2020 AHA scientific statement
GeneReviews lists genetic counseling by genetics professionals after a hereditary ATTR diagnosis, to build a pedigree and inform the family.GeneReviews

Find a specialist by state

From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Transthyretin (ATTR) amyloidosis; patient organizations and academic centers can often name experienced clinicians.

ICD-10-CM codes for Transthyretin (ATTR) amyloidosis

For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.

E85.0Non-neuropathic heredofamilial amyloidosisCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

E85.1Neuropathic heredofamilial amyloidosisCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

E85.2Heredofamilial amyloidosis, unspecifiedCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

E85.82Wild-type transthyretin-related (ATTR) amyloidosisCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

I43Cardiomyopathy in diseases classified elsewhereCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

Once the diagnosis is confirmed

ATTR amyloidosis with cardiomyopathy (ATTR-CM) drugs compared3 approved drugs side by side, with a prescribing guide for each: Amvuttra, Attruby, Vyndamax.Open trials: 39Screen a de-identified patient against every recruiting Transthyretin (ATTR) amyloidosis study on ClinicalTrials.gov.Patient and family pageThe plain-language Transthyretin (ATTR) amyloidosis page, with trials, treatments and help paying.

For the patient: why your doctor ordered this test

Plain language a patient can read or take home.

Your doctor ordered these tests to check for a condition called ATTR amyloidosis.

In ATTR amyloidosis, a protein called transthyretin folds the wrong way. It builds up in the heart, nerves and other tissues.

Some people inherit a gene change that causes it. In others, it comes with getting older.

Blood and urine tests look for an abnormal protein that causes a different type, called AL amyloidosis. Doctors check these tests along with the heart scan.

A heart scan uses a small amount of a tracer given in a vein. It shows whether the protein is in the heart.

If the scan points to ATTR, a gene test checks whether it runs in your family.

If you have the inherited type, your relatives may want genetic counseling and testing.

Questions clinicians ask about Transthyretin (ATTR) amyloidosis testing

What tests are used first when ATTR cardiomyopathy is suspected?

Published algorithms pair a monoclonal protein screen with technetium bone scintigraphy. The ACC summary of its 2023 decision pathway calls serum free light chains plus serum and urine immunofixation the first step in typing amyloid. The ESC position statement couples this panel with PYP, DPD or HMDP scintigraphy.

Can ATTR cardiomyopathy be diagnosed without a biopsy?

Yes, when grade 2 or 3 cardiac uptake on bone scintigraphy occurs with no monoclonal protein and typical imaging findings. In the 2016 Circulation study by Gillmore and colleagues of 1,217 patients with suspected cardiac amyloidosis referred to specialist centers, grade 2 or 3 uptake with no monoclonal protein had a specificity and positive predictive value of 100% for cardiac ATTR in that cohort. The AHA statement adds that test performance in lower-prevalence populations is unknown.

Why are light chain tests needed if the PYP scan is positive?

Because AL amyloidosis can also produce cardiac uptake. The AHA statement says a bone scan without light chain testing is neither appropriate nor valid for separating ATTR-CM from AL cardiomyopathy. The 2021 imaging consensus says a positive scan with any abnormal light chain test or MGUS is not diagnostic of ATTR-CM, and recommends referral to a specialist amyloid center and consideration of biopsy.

Should older patients with ATTR-CM have TTR genetic testing?

Yes, the AHA statement says TTR sequencing is required to separate variant from wild-type disease and that age alone is not a valid discriminator. ESC says testing should be performed even in elderly patients, as a significant number can have TTR variants.

What is the V122I (p.Val142Ile) TTR variant?

It is a TTR variant common in people of African ancestry, found in 3.0% to 3.9% of African Americans, per GeneReviews. GeneReviews says most heterozygotes develop late-onset cardiac amyloidosis, and that the variant partly explains why cardiac amyloidosis is 4 times more common in Black than White people over 60 in the US. V122I is the historical name; p.Val142Ile is standard numbering.

Which FDA labels cover ATTR cardiomyopathy?

The Vyndaqel and Vyndamax, Attruby and Amvuttra labels cover the cardiomyopathy of wild-type or hereditary (variant) ATTR in adults, per DailyMed labels checked November 8, 2026. The Onpattro and Wainua labels cover only hereditary ATTR polyneuropathy. GeneReviews (updated May 30, 2024) still calls tafamidis the only drug approved for cardiomyopathy and says acoramidis is not FDA approved; the current labels supersede that.

What are the ICD-10 codes for ATTR amyloidosis?

ICD-10-CM lists E85.82 for wild-type transthyretin-related (ATTR) amyloidosis, and E85.0, E85.1 and E85.2 for non-neuropathic, neuropathic and unspecified heredofamilial amyloidosis, per the NLM lookup checked November 8, 2026. I43 is cardiomyopathy in diseases classified elsewhere. The lookup does not say which code fits a given patient; that is a coding decision.

Sources

Hereditary Transthyretin Amyloidosis. GeneReviews, University of Washington, Seattle, via NCBI Bookshelf (NBK1194); Sekijima Y, Nakamura K, 2024-05-30.
Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation 2020;142(1):e7-e22 (Kittleson MM et al; AHA Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; corrected 2021), via AHA Journals, 2020-06-01.
2023 ACC Expert Consensus on Cardiac Amyloidosis: Key Points. American College of Cardiology, ACC.org (Shore S), summarizing Kittleson MM, Ruberg FL et al, J Am Coll Cardiol 2023;81:1076-1126, 2023-01-23.
Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. European Heart Journal 2021;42(16):1554-1568 (Garcia-Pavia P et al; author grants from Instituto de Salud Carlos III, the British Heart Foundation and NIH), via PubMed Central, 2021-04-21.
ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 2 of 2-Diagnostic Criteria and Appropriate Utilization. Circulation: Cardiovascular Imaging 2021;14:e000030 (Dorbala S et al; no funding statement in the published text; PubMed lists British Heart Foundation grant FS/18/21/33447), via AHA Journals, 2021-07.
Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation 2016;133:2404-2412 (Gillmore JD et al; British Heart Foundation grants listed in PubMed), via PubMed abstract, 2016-04-22.
VYNDAQEL (TAFAMIDIS MEGLUMINE) CAPSULE, LIQUID FILLED VYNDAMAX (TAFAMIDIS) CAPSULE, LIQUID FILLED [PFIZER LABORATORIES DIV PFIZER INC] (prescribing information, SPL version 15). Pfizer, via DailyMed, 2026-05-13.
ATTRUBY (ACORAMIDIS HYDROCHLORIDE) TABLET, FILM COATED [BRIDGEBIO PHARMA, INC.] (prescribing information, SPL version 8). BridgeBio Pharma, via DailyMed, 2026-07-03.
AMVUTTRA (VUTRISIRAN) INJECTION [ALNYLAM PHARMACEUTICALS, INC.] (prescribing information, SPL version 8). Alnylam Pharmaceuticals, via DailyMed, 2025-11-17.
ONPATTRO (PATISIRAN) INJECTION, LIPID COMPLEX [ALNYLAM PHARMACEUTICALS, INC.] (prescribing information, SPL version 11). Alnylam Pharmaceuticals, via DailyMed, 2025-09-29.
WAINUA (EPLONTERSEN) INJECTION, SOLUTION [ASTRAZENECA PHARMACEUTICALS LP] (prescribing information, SPL version 20). AstraZeneca Pharmaceuticals, via DailyMed, 2026-04-30.
GTR condition record for Amyloidosis, hereditary systemic 1 (MedGen C2751492, hereditary transthyretin amyloidosis). National Center for Biotechnology Information, NIH, 2026-11-08.
ICD-10-CM search results for "amyloid" (Clinical Table Search Service). National Library of Medicine, 2026-11-08.
ICD-10-CM search results for "I43" (Clinical Table Search Service). National Library of Medicine, 2026-11-08.

A reference for licensed professionals, checked against its sources on November 9, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.