PROGRESSION IS FAST,

TIMELY DIAGNOSIS
IS KEY1-3

An analysis from a clinical study showed that patients with ATTR-CM in NYHA Class I/II lost functional capacity at similar rates as those in Class III, as measured by 6‑MWT. Clear diagnostic guidelines and hallmark signs and symptoms can aid in diagnosis.2,4

ASSESSING FOR ATTR

Adults presenting with red-flag symptoms should be screened for ATTR.
Men aged 60 and older are particularly at risk.1,2,5

SCREENING METHODS FOR ATTR‑CM2,6-9:

  • Echocardiography:

    Look for LV wall thickness ≥12 mm and thickening of valves/septum in addition to reduction in longitudinal strain with relative apical sparing, which is more likely to indicate that ATTR-CM is the cause of LV hypertrophy. Also look for refractile myocardium—granular speckling.

  • Electrocardiography:

    Look for low QRS voltage in combination with increased LV wall thickness.

  • Cardiac MRI:

    Look for diffuse subendocardial or transmural LGE or increased ECV fraction. Amyloid deposits in the myocardium can lead to abnormal gadolinium kinetics.

Not a comprehensive list of diagnostic tools.

A single screening result cannot establish a diagnosis, but may be a warning sign of ATTR-CM.2

establish a diagnosis1,2:

1
Rule out AL
amyloidosis with simple monoclonal
light-chain assays
2
Detect amyloid
deposition in
myocardial tissue
with Tc scintigraphy
(eg, 99mTc-PYP) or
cardiac biopsy
3
Once ATTR-CM is
confirmed, genetic
testing to determine
if it is hereditary
(hATTR) is important,
given the possibility
that family members
may be affected
4
Refer to AHA
diagnostic guidelines
on amyloidosis and
HF for further details

diagnostic algorithm for ATTR-CM1,2

A chart showing a diagnostic algorithm for ATTR amyloidosis A chart showing a diagnostic algorithm for ATTR amyloidosis

Diagnosis is based on the independent medical judgment of the healthcare professional.

NEXT Stay up to date on ATTR

aBased on signs, symptoms, and initial findings consistent with hATTR amyloidosis.

bThe 2023 ACC Expert Consensus recommends serum and urine immunofixation electrophoresis and serum free light chain assay to exclude AL amyloidosis in the initial diagnostic workup.2

cConsider biopsy if scan is negative/equivocal but clinical suspicion is high.1,2

dSensitivity of a non-endomyocardial biopsy varies by site; negative fat-pad biopsy is not sufficient to exclude ATTR amyloidosis.1,2

eGrade 2: cardiac=rib uptake; Grade 3: cardiac>rib uptake with mild/absent rib uptake.1

6-MWT=6-minute walk test; 99mTc‑PYP=technetium-99m-pyrophosphate; ACC=American College of Cardiology; AHA=American Heart Association; AL=amyloid light chain; ATTR=transthyretin-mediated amyloidosis; ATTR‑CM=cardiomyopathy of transthyretin-mediated amyloidosis; DPD=3,3-diphosphono-1,2-propanodicarboxylic; ECV=extracellular volume; hATTR=hereditary transthyretin-mediated amyloidosis; HF=heart failure; HFpEF=heart failure with preserved ejection fraction; HMDP=hydroxymethylene diphosphonate; LGE=late gadolinium enhancement; LV=left ventricle; MRI=magnetic resonance imaging; NT‑proBNP=N-terminal prohormone of brain natriuretic peptide; NYHA=New York Heart Association; PYP=pyrophosphate; SPECT=single-photon emission computed tomography; TTR=transthyretin; wtATTR=wild-type transthyretin-mediated amyloidosis.

References:

  1. Kittleson MM, Maurer MS, Ambardekar AV, et al. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2020;142(1). doi:10.1161/cir.0000000000000792
  2. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC Expert Consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis. J Am Coll Cardiol. 2023;81(11):1076‑1126. doi:10.1016/j.jacc.2022.11.022
  3. Lane T, Fontana M, Martinez-Naharro A, et al. Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation. 2019;140:16-26. doi: 10.1161/CIRCULATIONAHA.118.038169
  4. Nativi-Nicolau J, Judge DP, Hoffman JE, et al. Natural history and progression of transthyretin amyloid cardiomyopathy: insights from ATTR-ACT. ESC Heart Fail. 2021;8(5):3875‑3884.
  5. Nativi-Nicolau JN, Karam C, Khella S, Maurer MS. Screening for ATTR amyloidosis in the clinic: overlapping disorders, misdiagnosis, and multiorgan awareness. Heart Fail Rev. 2021;27(3):785‑793. doi:10.1007/s10741‑021‑10080‑2
  6. Maurer MS, Bokhari S, Damy T, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12(9). doi:10.1161/circheartfailure.119.006075
  7. Witteles RM, Bokhari S, Damy T, et al. Screening for transthyretin amyloid cardiomyopathy in everyday practice. JACC Heart Fail. 2019;7(8):709‑716. doi:10.1016/j.jchf.2019.04.010
  8. Dharmarajan K, Maurer MS. Transthyretin cardiac amyloidoses in older North Americans. J Am Geriatr Soc. 2012;60(4):765‑774. doi:10.1111/j.1532‑5415.2011.03868.x
  9. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. doi:10.1161/CIRCULATIONAHA.116.024438
  10. Baptista, P., Moura de Azevedo, S., Alexandre, A., & Dias-Frias, A. (2023). Case report and literature review of cardiac amyloidosis: A not-so-rare cause of heart failure. Cureus. https://doi.org/10.7759/cureus.33364
  11. Oda S, Kidoh M, Nagayama Y, et al. Trends in diagnostic imaging of cardiac amyloidosis: emerging knowledge and concepts. Radiographics. 2020;40(4):961-981. doi: 10.1148/rg.2020190069