Heart with magnifying glass revealing a maze in a ventricle, alongside text reading 'ATTR-CM suspect & detect, uncover the clues for diagnosis'

Home > Diagnosis of ATTR-CM > Consider the clinical clues to identify ATTR-CM and the need for futher testing

 

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

 

The diagnosis of ATTR-CM may be delayed or missed. 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.1–4

 

HEART FAILURE WITH PRESERVED EJECTION FRACTION in patients typically over 605-7

 

  • 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 drops8,9
  • Imaging clues, such as reduced longitudinal strain with apical sparing (Figure 1 and 2), may help increase suspicion1,9

Examples of strain imaging showing apical sparing

Apical preservation of longitudinal strain (commonly referred to as apical sparing)1

Strain imaging with instances of apical sparing

Figure 1

Reprinted from Canadian Journal of Cardiology, 32, Narotsky DL, Castaño A, Weinsaft JW, Bokhari S, Maurer MS, Wild-type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging, 1166.e1–1166.e10, 2016, with permission from Elsevier. https://www.elsevier.com


Heart failure with preserved ejection fraction (HFpEF)

Prof. Perry Elliot of Bart’s Heart Centre summarises his symposium speech, identifying diagnostic clues and presents treatment guidance for HFpEF and other cardiomyopathies:

Professor Perry Elliott, Professor of Cardiovascular Medicine, University College London and Research Lead of the Inherited Cardiovascular Disease Unit, Bart’s Heart Centre

This symposium at the BCS Annual Conference 2019 was an educational symposium organised and sponsored by Pfizer.
The content of the symposium was developed and agreed by the faculty.

Bull's-eye plot of longitudinal strain showing apical sparing. This is often referred to as a "cherry on top" pattern1

Bull's-eye plot of longitudinal strain showing apical sparing

Figure 2

Reprinted from Canadian Journal of Cardiology, 32, Narotsky DL, Castaño A, Weinsaft JW, Bokhari S, Maurer MS, Wild-type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging, 1166.e1–1166.e10, 2016, with permission from Elsevier. https://www.elsevier.com

INTOLERANCE to standard HF therapies, i.e., ACEi/ARBs and beta blockers1,4,10

 

  • 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 therapies4,10

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

DISCORDANCE between QRS voltage on electrocardiography (ECG) and left ventricular (LV) wall thickness seen on echocardiography4,11-15

 

  • The classic ECG feature of ATTR-CM is a discordance between QRS voltage and LV mass ratio1,12,14
  • 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 hypertrophy1
    • Absence of a low QRS voltage does not, however, rule out ATTR-CM, as low voltage can vary among cardiac amyloidosis aetiologies12,13,16,17

ECG and echocardiography images showing discordance of limb lead QRS voltages and the degree of LV wall thickness in a patient with cardiac amyloidosis16

ECG and Echocardiography images showing discordance of limb lead QRS voltages and the degree of LV wall thickness in a patient with cardiac amyloidosis

Reproduced from Heart, Grogan M, Dispenzieri A, Gertz MA, 103, 10651072, 2017 with permission from BMJ Publishing Group Ltd.

Diagnosis of CARPAL TUNNEL SYNDROME or LUMBAR SPINAL STENOSIS4,15,17-23

 

  • Carpal tunnel syndrome and lumbar stenosis are often seen in ATTR-CM due to amyloid deposition in these areas4,16,17,19–24
  • Carpal tunnel syndrome in ATTR-CM often precedes cardiac manifestations by several years20,24,25

Echocardiography showing INCREASED LV WALL THICKNESS3,6,13,15,26,27

 

  • Increased wall thickness without a clear explanation (i.e. hypertension) should raise suspicion for cardiac amyloidosis3
  • Extracellular amyloid deposition results in an increased LV wall thickness that tends to be greater in ATTR-CM than in AL cardiac amyloidosis, with reported thicknesses for ATTR-CM often being more than 15 mm12,13,24,27

 

Transthoracic echocardiograms showing increased LV wall thickness:

Parasternal long-axis view5

Echocardiography image showing the parasternal long-axis view and increased LV wall thickness

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, European Heart Journal, 2015; 36 (38): 2585–2594, by permission of Oxford University Press on behalf of the European Society of Cardiology.

 

Parasternal short-axis view9

Echocardiography image showing the parasternal short-axis view and increased LV wall thickness

Reprinted from Trends in Cardiovascular Medicine, 28, Siddiqi OK, Ruberg FL, Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment, 10-21, 2018, with permission from Elsevier. https://www.elsevier.com

AUTONOMIC NERVOUS SYSTEM dysfunction, including gastrointestinal complaints or unexplained weight loss6,15,28,29

 

  • Gastrointestinal complaints due to autonomic dysfunction include diarrhoea and constipation29
  • Orthostatic hypotension due to autonomic dysfunction is another symptom that may occur with ATTR-CM6,15,28

| 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 preservation1,3,9,13,27 (Click here to see an example)
    • Longitudinal strain seen on echocardiography is reduced in the basal and midwall area; however, the apical strain is spared or preserved1,3,9,13,27
  • A history of bicep tendon in wild-type patients30
  • A diagnosis of hypertrophic cardiomyopathy1,3,5
  • Arrhythmias such as atrial fibrillation (most common) or other conduction abnormalities, which may require a pacemaker5,6,31,32
  • Aortic stenosis (AS) and transthyretin cardiac amyloidosis may occur in elderly patients, notably those with a low-flow, low-gradient AS pattern33,34
  • Hip and knee arthroplasty35

 

NEXT SECTION: Formal diagnosis of ATTR-CM >

 


 

References

  1. 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.
  2. AlJaroudi WA, Desai MY, Tang WH, Phelan D; Cerqueira MD, Jaber WA. Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques. J Nucl Cardiol. 2014; 21(2): 27283.
  3. Rapezzi C, Lorenzini M, Longhi S et al. Cardiac amyloidosis: the great pretender. Heart Fail Rev. 2015; 20(2): 117–124. 
  4. Brunjes DL, Castaño A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016; 22(12): 996–1003. 
  5. 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.  
  6. Maurer MS, Hanna M, Grogan M et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016; 68(2): 161–172. 
  7. Mohammed 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. 
  8. Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011; 2(6): 670–679.
  9. Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018; 28(1): 10–21. 
  10. Castaño A, Drach BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015; 20(2): 163–178. doi:10.1007/s10741-014-9462-7.
  11. Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982; 49: 9–13. 
  12. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014; 114(7): 10891093. 
  13. Quarta CC, Solomon D, Uraizee I et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014; 129(18): 1840–1849. 
  14. Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012; 126(10): 12861300. 16. Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016; 133(3): 282–290.  
  15. 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. 
  16. Grogan M, Dispenzieri A, Gertz MA. Light-chain cardiac amyloidosis: strategies to promote early diagnosis and cardiac response. Heart. 2017; 103(14): 1065–1072.
  17. Connors LH, Sam F, Skinner M et al. Heart Failure Due to Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study. Circulation. 2016; 133(3): 282–290.
  18. Connors LH, Prokaeva T, Lim A et al. Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J. 2009; 158(4): 607–614. 
  19. Nakagawa M, Sekijima Y, Yazaki M et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016; 23(1): 58–63. 
  20. Sperry 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.  
  21. Sueyoshi T, Ueda M, Jono H et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011; 42(9): 1259–1264. 
  22. Yanagisawa A, Ueda M, Sueyoshi T et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015; 28(2): 201–207. 
  23. Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014; 119(3): 223–228. 
  24. Pinney JH, Whelan CJ, Petrie A et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013; 2(2): e000098. 
  25. Papoutsidakis N, Miller EJ, Rodonski A, Jacoby D. Time course of common clinical manifestations in patients with transthyretin cardiac amyloidosis: delay from symptom onset to diagnosis. J Card Fail. 2018; 24(2): 131–133. 
  26. 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(19): 1442–1448. 
  27. Ternacle J, Bodez D, Guellich A et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging. 2016; 9(2): 126–138. 
  28. 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. 
  29. Nativi-Nicolau J, Maurer MS. Amyloidosis cardiomyopathy: update in the diagnosis and treatment of the most common types. Curr Opin Cardiol. 2018; 33(5): 571–579. 
  30. Geller HI, Singh A, Alexander KM et al. Association between ruptured distal biceps tendon and wild-type transthyretin cardiac amyloidosis. JAMA. 2017; 318(10): 962–963.   
  31. Ng B, Connors LH, Davidoff R et al. Senile Systemic Amyloidosis Presenting With Heart Failure. Arch Intern Med. 2005; 165(12): 1425142.
  32. Castaño A, Narotsky DL, Hamid N et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017; 38(38): 2879–2887. 
  33. Galat A, Guellich A, Bodez D et al. Aortic stenosis and transthyretin cardiac amyloidosis: the chicken or the egg? Eur Heart J. 2016; 37(47): 3525–3531. 
  34. 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.
  35. 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.

PP-VYN-GBR-0184. March 2020

Click here for Vyndaqel ▼ (tafamidis) prescribing information