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Knowledge of red flags suggesting cardiac transthyretin amyloidosis is crucial for identifying at-risk patients and establishing the correct diagnosis.

Cardiac amyloidosis is caused by the extracellular deposition of misfolded proteins in cardiac tissue. Wild-type transthyretin amyloidosis (wtATTR) is the most common form of cardiac amyloidosis. It mostly affects elderly patients, who usually present with heart failure, atrial fibrillation, or stroke due to underlying ATTR-related cardiomyopathy. The disease is often recognized at a late stage and is still underdiagnosed. Recognizing the warning signs of ATTR is the key to timely diagnosis and treatment. A study published in the journal Praxis reviewed these warning signs.

Red Flags for Cardiac ATTR

As amyloidosis is a multisystem disease, red flags for cardiac amyloidosis include cardiac and extracardiac manifestations.

  1.   Cardiac Red Flags

These include signs and symptoms of cardiac failure (usually with preserved ejection fraction), elevated troponin levels, abnormal electrocardiograms (ECG), elevated N-terminal fragment of prohormone brain natriuretic peptide, and changes in echocardiogram and cardiac magnetic resonance imaging (CMR).

 ECG signs include Q waves (pseudo-infarction patterns), poor progression of R waves, high-grade atrioventricular block, bundle branch block, and sometimes, peripheral low voltage.

Dysfunction due to atrial amyloid increases the risk of thrombus formation and atrial tachycardia, atrial flutter, and atrial fibrillation. Typical echocardiogram findings include hypertrophied ventricular walls due to amyloid deposition and resultant diastolic dysfunction.

Strain analysis of left ventricular myocardial deformation shows apical sparing with marked impairment at the base. CMR shows the characteristic patchy delayed enhancement pattern.

Cardiac radiotracer uptake is seen on bone scintigraphy.

Intolerance to antihypertensive or cardiac failure medication, mainly due to orthostatic problems, is a typical finding in ATTR patients. This association is particularly true for beta blockers.

Another pattern that should arouse suspicion for ATTR is when patients who have been on antihypertensive medication for years start exhibiting normal or low blood pressure with advancing age due to the underlying development of cardiac dysfunction.

  1.   Extracardiac Red Flags
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These include musculoskeletal disorders and polyneuropathy.

More than 50% of wtATTR patients are affected by carpal tunnel syndrome. It is mostly bilateral and needs surgery. It usually precedes the onset of cardiac failure by approximately 8 years. In recent studies, carpal tunnel tissue samples revealed amyloid deposits, highlighting their potential role in early recognition of wtATTR.

Other musculoskeletal problems include lumbar spinal stenosis and biceps tendon rupture.

Furthermore, wtATTR patients require knee and hip arthroplasty earlier and more frequently than age- and sex-matched healthy controls.

Peripheral neuropathy is another manifestation of the disease, and is mostly sensory and symmetric.


Galuszka, O. M., & Stämpfli, S. F. (2023). Red Flags Suggesting Cardiac Transthyretin Amyloidosis (ATTR) in Clinical Practice. Praxis, 112(5–6), 357–361. https://doi.org/10.1024/1661-8157/a004001