When To Suspect

Suspect Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

ATTR-CM presents with heart failure symptoms. Learn how to recognize the
clues to make a diagnosis.1-3

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HIDDEN IN PLAIN SIGHT

SUSPECT ATTR-CM

The diagnosis of ATTR-CM is often delayed or missed. Routine heart failure assessments such as echo and electrocardiogram (ECG), along with advanced imaging techniques, can help identify clues on the diagnostic pathway. magnify-glass-mobBy increasing your suspicion of ATTR-CM, you can identify patients who may require further testing to make a diagnosis.1-4

magnify-glass

CONSIDER THE FOLLOWING CLINICAL CLUES, ESPECIALLY IN COMBINATION, TO RAISE SUSPICION FOR ATTR-CM AND THE NEED FOR FURTHER TESTING

heart failure with preserved ejection fraction in patients typically over 605

  • 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 drops6,7
  • Imaging clues, such as reduced longitudinal strain with apical sparing, may help increase suspicion7

Click here for a clue to look for on strain imaging

to standard heart failure therapies, ie, ACEi/ARBs and beta blockers8

  • 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 therapies8

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.

between QRS voltage and
left ventricular (LV) wall thickness9,10

  • The classic ECG feature of ATTR-CM is a discordance between QRS voltage and LV mass ratio11
  • 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 amyloidosis, as low voltage can vary among cardiac amyloidosis etiologies9,12-15

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

discordance_image

discordance_image

Adapted by permission from BMJ Publishing Group Limited. [Heart, Grogan M, Dispenzieri A, Gertz MA, 103, 1065-1072, 2017]

of carpal tunnel syndrome or
lumbar spinal stenosis17,18

  • Bilateral carpal tunnel syndrome and lumbar stenosis are often seen in ATTR-CM due to amyloid deposition in these areas17,18
  • Bilateral carpal tunnel syndrome in ATTR-CM often precedes cardiac manifestations by several years17,19

showing increased LV wall thickness9

  • Increased wall thickness without a clear explanation (ie, hypertension) should raise suspicion for cardiac amyloidosis3

Echo, echocardiography.

Transthoracic echocardiograms showing increased LV wall thickness

Parasternal long-axis view5

parasternal-long-axis

Reproduced from 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, by permission of Oxford University Press and the European Society of Cardiology.

Parasternal short-axis view7

parasternal-short-axis

Reprinted from Trends Cardiovasc Med, 28/1, Siddiqi OK, Ruberg FL, Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment, 10-21, 2018, with permission from Elsevier.

autonomic nervous system dysfunction,
including gastrointestinal complaints
or unexplained weight loss20

  • Gastrointestinal complaints due to autonomic dysfunction include diarrhea and constipation20
  • Orthostatic hypotension due to autonomic dysfunction is another symptom that may occur with ATTR-CM20

estimATTR logo

Evaluate clinical clues in a hypothetical patient with the estimATTR

A probability estimator for wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM)

This tool is only to be used by US health care professionals. It is for educational purposes only, and not to be used for the suspicion or diagnosis of wtATTR-CM in individual patients in a clinical setting.

estimATTR desktop and responsive layouttry it now

The wtATTR-CM estimATTR was developed based on an artificial intelligence/machine learning (AI/ML) algorithm using diagnosis codes from a large, real-world claims dataset comprising 1678 patients with wtATTR-CM.

Using hypothetical patient cases presenting with heart failure, the estimATTR can highlight the types of combinations of cardiac and noncardiac conditions that should raise suspicion for wtATTR-CM by:

  • Estimating the probability of wtATTR-CM based on combinations of clinical features known to be associated with the disease
  • Illustrating important features that help distinguish between wtATTR-CM and heart failure from other causes

The HIDDEN clinical clues of ATTR-CM

Discover how a cardiologist suspects ATTR-CM.

In the first video, a colleague asked Dr. Detective for help with a tough case. Watch to see how looking for certain signs and symptoms can point to ATTR-CM.

 

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 preservation21(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 preserved21
  • A history of bicep tendon rupture22
  • A diagnosis of hypertrophic cardiomyopathy3
  • Arrhythmias such as atrial fibrillation (most common) and conduction abnormalities, which may require a pacemaker11,13,23
  • Aortic stenosis (AS) and ATTR-CM may occur in elderly patients, notably those with a low-flow, low-gradient AS pattern24
  • Hip and knee arthroplasty25

 

EXAMPLES OF STRAIN IMAGING SHOWING APICAL SPARING

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

ex-apical-sparing

Reprinted from Can J Cardiol, 32/9, 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.

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

ex-cherry-on-top

Reprinted from Can J Cardiol, 32/9, 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.

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