ATTR amyloidosis often presents with multisystem manifestations years before diagnosis. Test your knowledge of key red flags, common mimicking conditions, and clinical patterns that may support earlier recognition.
6 questions
A 72-year-old man with heart failure with preserved ejection fraction (HFpEF) reports progressive exertional dyspnea and bilateral carpal tunnel syndrome that required surgery 6 years earlier. Which additional finding would most strongly raise suspicion for ATTR amyloidosis?
Correct Answer: C
ATTR amyloidosis is increasingly recognized as a multisystem disease with extracardiac manifestations that may precede cardiac involvement by years. Bilateral carpal tunnel syndrome and lumbar spinal stenosis are recognized orthopedic “red flags,” particularly in older adults with HFpEF or unexplained ventricular thickening. Identifying these findings together may support earlier recognition of ATTR amyloidosis.
https://link.springer.com/article/10.1007/s12170-025-00771-y
Correct Answer: B
Hereditary ATTR amyloidosis commonly presents with progressive sensory-motor polyneuropathy accompanied by autonomic manifestations such as orthostatic hypotension, gastrointestinal dysfunction, erectile dysfunction, or urinary symptoms. These findings are frequently mistaken for diabetic neuropathy or other neurologic disorders, contributing to delays in diagnosis.
https://www.sciencedirect.com/science/article/pii/S0929664626000410
A patient with progressive peripheral neuropathy, chronic diarrhea, and unexplained weight loss has been treated for years for chronic inflammatory demyelinating polyneuropathy (CIDP) without improvement. What is the most appropriate next step?
ATTR amyloidosis may mimic CIDP and other neuropathic disorders. Lack of response to immunomodulatory therapy—particularly in the presence of autonomic or gastrointestinal symptoms—should prompt evaluation for alternative etiologies, including amyloidosis.
https://link.springer.com/article/10.1007/s00415-025-13218-6
Which echocardiographic finding is commonly associated with cardiac ATTR amyloidosis and may warrant additional diagnostic evaluation?
Cardiac ATTR amyloidosis often presents with increased left ventricular wall thickness despite preserved or mildly reduced ejection fraction. In older adults with HFpEF, unexplained ventricular thickening should prompt consideration of infiltrative cardiomyopathy and further diagnostic evaluation.
https://www.sciencedirect.com/science/article/pii/S0735109725077198
ATTR amyloidosis is commonly underrecognized because manifestations may involve orthopedic, neurologic, autonomic, gastrointestinal, and cardiac systems over many years. Patients frequently present across multiple specialties before diagnosis, underscoring the importance of recognizing multisystem clinical patterns.
https://www.sciencedirect.com/science/article/pii/S1050173825000349
Correct Answer: D
Wild-type ATTR amyloidosis is increasingly recognized in older adults with HFpEF, atrial fibrillation, and orthopedic manifestations such as bilateral carpal tunnel syndrome. Recognition of these clinical clusters may support earlier diagnosis and referral for confirmatory evaluation.
https://pubmed.ncbi.nlm.nih.gov/41907036/