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About ATTR-CMAbout

Learn about ATTR-CM and uncover the differences between hereditary and wild-type ATTR-CM

About ATTR-CMWhat is ATTR-CM?The different types of ATTR-CM




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Diagnosis of ATTR-CMSigns and symptomsClinical cluesFormal diagnosis
Emerging treatmentsEducational resourcesEducational resources

Explore a range of educational resources to support the diagnosis of ATTR-CM

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Click here for Vyndaqel®▼ (tafamidis) Prescribing Information. Adverse event reporting information can be found at the bottom of the page.

Consider the clinical clues to identify ATTR-CM and the need for further testing

The diagnosis of ATTR-CM may be delayed or missed. Therefore, having a high awareness of the red flags in important to facilitate an early diagnosis. Routine heart failure assessments, such as echocardiography and electrocardiography (ECG), along with advanced imaging techniques, can help you identify patients who may require further testing to make a diagnosis.1,2,3

HEART FAILURE WITH PRESERVED EJECTION FRACTION in patients typically 60 years old4-6
  • In ATTR-CM, diastolic function is impaired due to amyloid fibril deposition in the myocardium, resulting in thicker and inelastic ventricles, thereby decreasing stroke volume. It is not until the later stages of ATTR-CM disease that ejection fraction drops7,8
  • Imaging clues, such as echo showing reduction in longitudinal strain with relative apical sparing (Figure 1 & 2) can help to differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy.2
Examples of strain imaging showing relative apical sparing:​​​​​​​ Apical preservation of longitudinal strain (commonly referred to as apical sparing)9

Figure 1
Illustrative representation.

Bull's-eye plot of longitudinal strain showing apical sparing. This is often referred to as a "cherry on top" pattern9

Figure 2
​​​​​​​Illustrative representation.

POOR TOLERANCE to standard heart failure therapies, i.e., ACEi/ARBs and high dose beta blockers10​​​​​​​​​​​​​​
  • Patients can develop a decrease in stroke volume, which can lead to low blood pressure. As a result, they can develop an intolerance to blood pressure–lowering therapies​​​​​​​​​​​​​​

ACEi, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers.

​​​​​​​DISCORDANCE between QRS voltage on electrocardiography (ECG) and left ventricular (LV) wall thickness seen on echocardiography2
  • The classic ECG feature of ATTR-CM is a discordance between QRS voltage and LV mass ratio
  • The amplitude of the QRS voltage is not reflective of the increased LV wall thickness, because the increase is due to extracellular amyloid protein deposition rather than myocyte hypertrophy9
  • Absence of a low QRS voltage does not, however, rule out ATTR-CM, as low voltage can vary among cardiac amyloidosis aetiologies
ECG and echocardiography images showing discordance of limb lead QRS voltages and the degree of LV wall thickness in a patient with cardiac amyloidosis11 Figure 3

Illustrative representation.

  • Carpal tunnel syndrome and lumbar stenosis are often seen in ATTR-CM due to amyloid deposition in these areas
  • ATTR-CM frequently presents with a history of bilateral carpal tunnel syndrome and lumbar spinal stenosis. Bilateral carpal tunnel syndrome may manifest up to 10 years prior to diagnosis.​​​​​​​12
Echocardiography showing INCREASED LEFT VENTRICULAR WALL THICKNESS not attributed to another cause (e.g. hypertension)2,13
Scroll left to view table
Parasternal long-axis view5 Parasternal short-axis view7
Helix Image​​​​​​​ Helix image​​​​​​​

Figure 4
Illustrative representation.​​​​​​​

Figure 5
Illustrative representation.​​​​​​
AUTONOMIC NERVOUS SYSTEM dysfunction, including gastrointestinal complaints (e.g. diarrhoea or constipation)2,14​​​​​​​
  • Gastrointestinal complaints due to autonomic dysfunction include diarrhoea and constipation
  • Orthostatic hypotension due to autonomic dysfunction is another symptom that may occur with ATTR-CM15,16
Additional key considerations

There are several additional signs/symptoms that could be clues for cardiac amyloidosis and ATTR-CM, which include:

  • Strain imaging showing apical sparing or apical preservation​​​​​​​
    • Longitudinal strain seen on echocardiography is reduced in the basal and midwall area; however, the apical strain is spared or preserved9
  • A history of bicep tendon rupture in wild-type patients17
  • A diagnosis of hypertrophic cardiomyopathy after the sixth decade.18​​​​​​​
  • Arrhythmias such as atrial fibrillation or other conduction abnormalities, which may require a pacemaker4
  • Aortic stenosis (AS) and transthyretin cardiac amyloidosis may occur in elderly patients, notably those with a low-flow, low-gradient AS pattern19
  • Hip and knee arthroplasty20
Building the knowledge: The patient journey to diagnosis of ATTR-CM, a race against time

This is a series of animated, educational modules that outline key background information on ATTR amyloidosis. This video reviews the importance of an early diagnosis of ATTR-CM​.

Learn more about the formal diagnosis of ATTR-CM Learn more Loading See other educational resources available  Explore more Loading


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.Witteles RM, Bokhari S, Damy T et al.  Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice. JACC Heart Fail. 2019; 7(8): 709–716Gillmore JD, Maurer MS, Falk RH et al.  Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016; 133: 2404–2412Mohammed SF, Mirzoyev SA, Edwards WD, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014; 2(2): 113–122.González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015; 36(38): 2585–2594.Maurer MS, Hanna M, Grogan M, et al. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis. J Am Coll Cardiol. 2016; 68(2): 161–172.Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018; 28(1): 10–21.Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011; 2(6): 670–679.Narotsky DL, Castaño A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016; 32(9): 1166.e1–1166.e10.Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail 2016;22:996– 1003.Grogan M, Dispenzieri A, Gertz MA. Light-chain cardiac amyloidosis: strategies to promote early diagnosis and cardiac response. Heart. 2017; 103(14): 1065–1072Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release. J Am Coll Cardiol. 2018; 72(17): 2040–2050.Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart 2012;98:1442-8.Nativi-Nicolau J, Maurer MS. Amyloidosis cardiomyopathy: update in the diagnosis and treatment of the most common types. Curr Opin Cardiol 2018;33:571-9.Rapezzi C, Merlini G, Quarta CC et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009; 120(13): 1203–1212.Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013; 29(1): 63–76.Geller HI, Singh A, Alexander KM et al. Association between ruptured distal biceps tendon and wild-type transthyretin cardiac amyloidosis. JAMA. 2017; 318(10): 962–963Rapezzi C, Lorenzini M, Longhi S et al. Cardiac amyloidosis: the great pretender. Heart Fail Rev. 2015; 20(2): 117–124.Treibel TA, Fontana M, Gilbertson JA et al. Occult transthyretin cardiac amyloid in severe calcific aortic stenosis: prevalence and prognosis in patients undergoing surgical aortic valve replacement. Circ Cardiovasc Imaging. 2016;9(8). doi: 10.1161/CIRCIMAGING.116.005066.Rubin J, Alvarez J, Teruya S et al. Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloid diagnosis: can we identify affected patients earlier? Amyloid. 2017; 24(4): 224–228.
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