For example, severe aortic stenosis (AS)*, arrhythmias, in patients typically over the age of 60^6,7,8

• 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 drops^9,10
• Imaging clues, such as echo showing reduction in longitudinal strain with relative apical sparing (Figure A & B) can help to differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy.³

Examples of strain imaging showing relative apical sparing:
 

(A): Apical sparing of longitudinal strain (commonly referred to as apical sparing)¹¹
(B): Bull’s-eye plot of longitudinal strain showing apical sparing. This is often referred to as a “cherry on top” pattern¹¹


 

For example, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta blockers¹²

• 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.

• The classic ECG feature of ATTR-CM is a discordance between QRS voltage and LV mass ratio³
• 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 hypertrophy¹¹
• Absence of a low QRS voltage does not, however, rule out ATTR-CM, as low voltage can vary among cardiac amyloidosis aetiologies.

Including carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, and/or hip and knee arthroplasty¹⁴

• 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.¹⁴

Using echocardiography to suspect ATTR-CM^3,15

Echocardiography (echo), including tissue Doppler imaging (TDI) and strain analysis, can play a role in the noninvasive diagnosis of ATTR-CM due to its:¹⁶

• Widespread availability and portability
• Capacity to assess structure and diastolic function. 

Echo can help identify characteristics related to amyloid infiltration but cannot distinguish between ATTR-CM and other types of cardiac amyloidosis.¹⁶
 

Parasternal long-axis view¹⁶

Illustrative representation

Characteristic appearance of cardiac amyloidosis on echo¹⁶

Transthoracic echocardiography, parasternal long-axis view, left ventricular hypertrophy with preserved ejection fraction. Image courtesy of Filiale d'Imagerie Cardiovasculaire.
Echo findings that are strongly suggestive of cardiac amyloidosis and should be reported include:¹⁶

• Increased LV wall thickness
• Increased LV mass
• Typical LV longitudinal strain pattern
• Mitral annular TDI <5 cm/s
• Biatrial enlargement
• Small A wave in sinus rhythm
• Small pericardial and/or pleural effusions
   

Including gastrointestinal complaints (e.g., diarrhoea or constipation)^3,17

• Gastrointestinal complaints due to autonomic dysfunction include diarrhoea and constipation.
• Orthostatic hypotension due to autonomic dysfunction is another symptom that may occur with ATTR-CM^17,18

Using CMR to suspect ATTR-CM

CMR may raise suspicion of disease in two scenarios:¹⁶

• Differentiation between cardiac amyloidosis and other cardiomyopathic conditions with increased wall thickening
• Detection of early cardiac involvement in patients presenting with symptoms of systemic amyloidosis

CMR may be advantageous in the following scenarios if echocardiographic acoustic windows are poor:¹⁶

• To characterise the right ventricle 
• To characterise tissue based on the contrast-enhanced patterns of myocardial infiltration.
• To precisely quantify cardiac chamber volumes and ventricular mass

Patient A: Normal heart 

Patient B: Heart shows a significantly high amyloid burden (elevated native T1, transmural late gadolinium enhancement, and increased extracellular volume)

Adapted from Dorbala et al. Expert consensus recommendations for multimodality imaging in cardiac amyloidosis. J Nucl Cardiol. 2019
 

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 preserved³
• A history of bicep tendon rupture in wild type patients¹⁹
• A diagnosis of hypertrophic cardiomyopathy after the sixth decade²⁰
• Arrhythmias such as atrial fibrillation or other conduction abnormalities, which may require a pacemaker²¹
• Aortic stenosis (AS) and transthyretin cardiac amyloidosis may occur in elderly patients, notably those with a low-flow, low-gradient AS pattern²¹
• Hip and knee arthroplasty²²

Common signs and symptoms in wild-type ATTR-CM and hereditary ATTR-CM^3,8,17,23-28

European Society of Cardiology (ESC) recommendations¹

The ESC Working Group recommends screening for ATTR-CM if LV wall thickness is ≥12 mm + the presence of ≥1 red flag or clinical scenario.