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

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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 (HFpEF) or other cardiac conditions (eg, severe aortic stenosis [AS],* arrhythmias) in patients typically over the age of 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
  • Prevalence among older HFpEF patients:
    • ~10% of patients referred to a dedicated center had ATTR-CM confirmed by EMB10†
    • ~13% of hospitalized patients with HFpEF and increased LV wall thickness had wtATTR-CM confirmed by scintigraphy5‡
  • In patients undergoing transcatheter aortic valve replacement for severe calcific AS, prevalence of ATTR-CM was 16% overall and 22% among men6

Reduced longitudinal strain with apical sparing should raise suspicion of ATTR-CM1,9

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Illustrative representation.

to standard heart failure therapies, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta blockers11

  • Intolerance to standard heart failure medications is common in patients with cardiac amyloidosis; such agents exacerbate symptomatic hypotension in the setting of concomitant autonomic dysfunction or by lowering heart rate and reducing cardiac output11

between QRS voltage on ECG and 
left ventricular (LV) wall thickness12,13

  • The classic ECG feature of ATTR-CM is a discordance between QRS voltage and LV mass ratio7
  • 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 etiologies12,14-17

Discordance between LV wall thickness and QRS voltage

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Illustrative representation.

of orthopedic conditions, including carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, and/or hip and knee arthroplasty18-21

Bilateral carpal tunnel syndrome and lumbar stenosis

  • Often seen in ATTR-CM due to amyloid deposition in these areas; lumbar spinal stenosis is principally seen in wtATTR-CM7,18,19
  • Bilateral carpal tunnel syndrome and lumbar spinal stenosis are known clinical predictors of ATTR-CM and may precede heart failure symptoms by several years7,19
  • Among patients undergoing carpal tunnel release surgery, 10.2% had amyloid deposits22

Biceps tendon rupture

  • Among patients with wtATTR-CM, biceps tendon rupture has been observed in 33% of patients, occurring in the dominant arm in 95% and bilaterally in 24% of patients20

Hip and knee arthroplasty

  • In a study of 313 patients (172 with ATTR-CM), hip and knee arthroplasty surgeries were more frequent than in the general population, and on average, arthroplasty occurred 7.2 years before ATTR-CM diagnosis21

showing increased LV wall thickness12

  • Unexplained increased LV wall thickness (eg, hypertension) should raise suspicion for cardiac amyloidosis3

Transthoracic echocardiograms showing increased LV wall thickness

Parasternal long-axis view

Parasternal short-axis view

ATTR amyloidosis heartparasternal-long-axisVideo courtesy of Filiale d'Imagerie Cardiovasculaire.

ATTR amyloidosis heartparasternal-short-axisIncreased LV end diastolic interventricular wall thickness

Normal heartparasternal heart

Illustrative representation.

dysfunction, including polyneuropathy and autonomic dysfunction, including gastrointestinal complaints and/or unexplained weight loss23

  • Gastrointestinal complaints due to autonomic dysfunction include chronic diarrhea, constipation, or both23
  • Orthostatic hypotension due to autonomic dysfunction is another symptom that may occur with ATTR-CM23

*Notably those with a low-flow, low-gradient AS pattern.6

A prospective analysis in 108 patients (61% women, age range: 57-74 years) seen at the Johns Hopkins University HFpEF Clinic who underwent EMB to evaluate myocardial tissue histopathology.10

A prospective, cross-sectional, single-center study at a tertiary university hospital in Madrid, Spain. Included 120 patients ≥60 years of age (59% women, mean age: 82 ± 8 years) admitted for HFpEF, with LV ejection fraction ≥50% and LV hypertrophy ≥12 mm. 99mtechnetium-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy used to confirm ATTR-CM.5

Echo, echocardiography.

DOWNLOAD HIDDEN MNEMONIC

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wtATTR-CM estimATTR: A TOOL DESIGNED TO EDUCATE ABOUT CLINICAL CONDITIONS COMMONLY ASSOCIATED WITH wtATTR-CM

A PROBABILITY ESTIMATOR FOR wtATTR-CM

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

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TRY 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 more than 1500 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 may 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.

 

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