ATTR is an often-overlooked cause of heart failure1-4

Time to diagnosis is typically delayed by an average of ~6 years, in part because symptoms of ATTR-CM overlap with other common conditions.1-5*

Prevalence of ATTR-CM in screening studies

HFpEF ~1 in 8 people aged 60 or older with HFpEF had an underlying cause of ATTR‑CM6-8

CARPAL TUNNEL SYNDROME ~6 in 10 patients with ATTR-CM had carpal tunnel syndrome 5 to 10 years before a diagnosis of ATTR-CM9-13

AORTIC
STENOSIS ~1 in 6 older adults with AS undergoing TAVR may have ATTR-CM. For those with low-flow, low-gradient AS, that number may be ~2x higher14†

HYPERTROPHIC CARDIOMYOPATHY ~1 in 5 patients aged 50 or older diagnosed with HCM had ATTR-CM8

ATTR-CM & As Differential Diagnosis Flashcard
ATTR-CM vs HCM Differential Diagnosis Flashcard
*In a targeted literature review, mean time to diagnosis ranged from 1.3 to 7.2 years.5
†From a study of 151 patients (mean age 84 years ± 6 years) with degenerative AS.14
AS=aortic stenosis; ATTR=transthyretin-mediated amyloidosis; ATTR-CM=cardiomyopathy of transthyretin-mediated amyloidosis; HCM=hypertrophic cardiomyopathy; HFpEF=heart failure with preserved ejection fraction; TAVR=transcatheter aortic valve replacement.

Identifying Patients with ATTR

ClickTap on the flashcards below to follow the diagnostic journey for these hypothetical patients.*
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*Not actual patients.
A1c=hemoglobin A1c; ACE=angiotensin-converting enzyme; AFib=atrial fibrillation; AL=light chain amyloidosis; CAD=coronary artery disease; cMRI=cardiac magnetic resonance imaging; CTS=carpal tunnel syndrome; ECG=electrocardiogram; Echo=echocardiogram; ECV=extracellular volume; GI=gastrointestinal; GLS=global longitudinal strain; HF=heart failure; HTN=hypertension; IFE=immunofixation electrophoresis; IHD=ischemic heart disease; LGE=late gadolinium enhancement; LV=left ventricular; NT-proBNP=N-terminal prohormone of brain-type natriuretic peptide; NYHA=New York Heart Association; sFLC=serum free light chain; SPIE=serum protein electrophoresis with immunofixation; QRS=Q wave, R wave, S wave; T2D=type 2 diabetes; TAVR=transcatheter aortic valve replacement; UPIE=urine protein electrophoresis with immunofixation.

Echo, ECG, and cMRI are essential screenings for patients with red-flag symptoms

Echocardiography7,16,19,22,31,42,43

2D echocardiogram
A) LV septum (19 mm); B) Posterior wall (19 mm); C) RV free wall (8 mm)
Look for:
  • LV wall thickness ≥12 mm
  • Thickening of valves/septum
  • Refractile myocardium (granular sparkling)
  • Biatrial enlargement
  • Pericardial effusion
Longitudinal strain bull's-eye map
Look for:
Reduction in longitudinal strain with relative apical sparing
  • Presents in a "cherry-on-top" pattern
  • Red indicates normal longitudinal strain at apex
  • Pink and blue indicate abnormal longitudinal strain at mid/basal LV
Doppler echocardiography
Look for:
Diastolic dysfunction
  • Abnormal E/A ratio, E/e' ratio, and TDI lateral e'
  • 5-5-5 pattern in TDI tracings is seen in more advanced cardiac amyloidosis
While echocardiography findings can raise clinical suspicion, echocardiography alone is not sufficient to confirm ATTR-CM diagnosis.

ELECTROCARDIOGRAPHY13,18,19

Atrial fibrillation (HR 70), low voltage (limb leads), septal pseudo-infarct
Sinus rhythm, low voltage (limb leads), low voltage P waves, inferior pseudo-infarct
Look for:
  • Low QRS voltage relative to LV wall thickness
  • Pseudo-infarct pattern
  • AV conduction block
  • Arrhythmias (e.g., atrial fibrillation)
While electrocardiography findings can raise clinical suspicion, electrocardiography alone is not sufficient to confirm an ATTR-CM diagnosis.

CARDIAC MRI15,19,32,33,44

VIEW 1
A) Transmural septal LGE (green);
B) Diffuse subendocardial LGE (orange)
VIEW 2
  • Concentric LV thickening (greatest in the basal inferoseptum) with a posterior thickness of >12 mm
  • Increased RV wall thickness (>6 mm)
LOOK FOR:
  • Diffuse subendocardial or transmural late gadolinium enhancement
  • Left ventricular hypertrophy
  • ECV expansion (≥30%)

While cMRI findings can raise clinical suspicion, cMRI alone is not sufficient to confirm ATTR-CM diagnosis.

2D=2-dimensional; A=late (atrial) mitral inflow velocity; AV=atrioventricular; cMRI=cardiac magnetic resonance imaging; E=early mitral inflow velocity; e'=early diastolic mitral annulus velocity; hATTR-PN=polyneuropathy of hereditary transthyretin-mediated amyloidosis; HR=heart rate; LGE=late gadolinium enhancement; MRI=magnetic resonance imaging; QRS=Q wave, R wave, S wave; RV=right ventricle; TDI=tissue doppler imaging.

Neurologic assessments can help raise clinical suspicion of hattr-pn

Neurologic Assessments16,45,46

sensory-motor assessments

  • Electromyography (EMG)*
  • Nerve conduction study (NCS)*
  • Quantitative sensory testing (QST)

AUTONOMIC assessments

  • Heart rate deep breathing
  • Tilt table
  • Sympathetic skin response (SSR)
  • Quantitative sudomotor axon reflex testing (QSART)
  • Electrochemical skin conductance (ESC) measurement
*EMG and NCS may be normal in early stages of the disease.

Neurologic findings8,16,17,22,47,48

  • Axonal length-dependent sensory-motor neuropathy
  • Small-fiber sensory neuropathy may progress to large-fiber sensory and motor neuropathy
  • Bilateral carpal tunnel syndrome
  • Abnormal hemodynamic response and reduced heart rate variability in autonomic testing (e.g., orthostatic hypotension)
  • A length-dependent pattern of sweat reduction
Not all of the above assessments are required to raise suspicion of hATTR-PN.
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