Red Flags of ATTR-CMIdentifying these red flags, especially in combination, is key to early screening and diagnosis of ATTR-CM1
Unexplained HFpEF
2 Unexplained LV wall thickness
2 ≥ 12 mm
- LV wall thickness ≥12 mm on an echocardiogram3-6*†
- Reduction in longitudinal strain with apical sparing5-7‡
- Apical sparing on a bullseye strain map: the lack of amyloid deposition in the apex may result in a “cherry on top” pattern, in which a red circle at the apex (preserved strain) is surrounded by lighter shades of red or blue (reduced strain)
- Changes to the interatrial septum and valves5,7‡
- Thickening of interatrial septum (yellow arrow) and valves (white arrow) >0.5 cm5,7
Additional cardiac features to consider are5:
- Increased echogenicity of the myocardium (sparkling, hyper-refractile “texture” of the myocardium)
- Atrial enlargement and dysfunction
- Diastolic dysfunction of Grade 2 or worse with high E/A ratio (>1.5) and reduced E deceleration time (<150 ms)
- Increased pressures (>35 mmHg for PA, ≥10 mmHg for RA)
Per the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure, a left ventricular wall thickness of ≥14 mm, along with other clinical parameters, should heighten suspicion of ATTR cardiac amyloidosis.Illustrative representation.Reproduced with permission from ASNC. 2021 American Society of Nuclear Cardiology.ACC=American College of Cardiology; AHA=American Heart Association; HFSA=Heart Failure Society of America; PA=pulmonary artery; RA=right atrium.Electrocardiography suggestive of ATTR-CMElectrocardiography5- Discordance between LV wall thickness and QRS voltage on ECG5,6,8†
- Low QRS voltage not present in all cases
- Prevalence varies between ATTR cardiac amyloidosis (20%) and AL amyloidosis (60%)
AL=amyloid light chain.Illustrative representation.Other red flags of ATTR-CM:
 Clinical history1,3 |
Imaging results1,5,9 |
- Bilateral carpal tunnel syndrome
- Refractory to standard HF therapies (GDMT)
- Severe aortic stenosis
- Lumbar spinal stenosis
- Autonomic or sensory PN
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- Discordance between LV wall thickness and QRS voltage on ECG
- Dilated left atrium or bi-atrial enlargement
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While these patient characteristics may be suggestive of ATTR-CM, they are not exhaustive.
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Additional clinical findings suggestive of ATTR-CMCardiac magnetic resonance imaging (CMR)
- Marked ECV expansion, abnormal nulling time for the myocardium, or diffuse late gadolinium enhancement on CMR1
Biomarkers
- Elevated N-terminal pro B-type natriuretic peptide (NT-proBNP)1
- Elevated serum troponin levels1
ECV=extracellular volume.Cardiac symptoms suggestive of ATTR-CM
 |
- Refractory to standard HF therapies (eg, ACEi, ARB, and BB)10
- Cardiac arrhythmias (eg, atrial fibrillation)11
- Aortic stenosis12
- Atrioventricular block, in the presence of increased wall thickness7
- Mild increase in troponin levels on repeated occasions1
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ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=beta blocker.Noncardiac symptoms suggestive of ATTR-CMCertain noncardiac symptoms should also raise suspicion of ATTR cardiac amyloidosis
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Musculoskeletal/orthopedic
- Carpal tunnel syndrome13-15
- In observational studies of ATTR amyloidosis populations, including ATTR cardiomyopathy, between 29% (n=16/55) and 68% (n=21/31) of patients have been reported to have a history of carpal tunnel syndrome
- Lumbar spinal stenosis16
- One study of 47 patients identified the presence of TTR amyloid on surgical spine specimens in 21% of patients (n=10/47) undergoing LSS surgery17
- Biceps tendon rupture1,18,19
- Hip/knee arthroplasty20
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Nervous system
Autonomic
- GI complaints21
- In an observational registry, 15% of patients with wtATTR-CM reported experiencing gastrointestinal symptoms
- Autonomic neuropathy19
- Unexplained weight loss22
- Orthostatic hypotension19
- Sexual impotence19
Peripheral
- Peripheral sensory motor dysfunction19
- Peripheral neuropathy19
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Renal14,23
- Renal impairment
- Cardiorenal syndrome
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Ocular19
- Vitreous opacity
- Glaucoma
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GI=gastrointestinal; LSS=lumbar spinal stenosis; TTR=transthyretin; wtATTR-CM=wild-type transthyretin
amyloid cardiomyopathy.Next: Suspect ATTR cardiac amyloidosis? See how diagnosis is confirmed Continue LoadingACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=beta blocker; CMR=cardiac magnetic resonance; ECV=extracellular volume.ACC=American College of Cardiology; AHA=American Heart Association; ATTR=transthyretin amyloidosis; ATTR-CM=transthyretin amyloid cardiomyopathy; ECG=electrocardiogram; GDMT=guideline-directed medical therapy; HF=heart failure; HFpEF=heart failure with preserved ejection fraction; HFSA=Heart Failure Society of America; LV=left ventricular; PN=polyneuropathy.
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