Multidisciplinary Approaches for Diagnosing Underrecognized Transthyretin Amyloidosis in Real-World Practice

Transthyretin amyloidosis (ATTR) is a rare but progressive disease. Its heterogeneous clinical presentation often leads to a delayed diagnosis. This study aimed to review the clinical manifestations of ATTR at diagnosis across cardiology and neurology subspecialties and to identify common red-flag symptoms in real-world practice.

We analyzed consecutive patients diagnosed with ATTR between March 2018 and December 2024. Variant ATTR (ATTR-v) was confirmed by genetic testing, while wild-type ATTR (ATTR-wt) was diagnosed based on the absence of monoclonal protein, a positive ^99mtechnetium-pyrophosphate scan, and no transthyretin gene mutations. All patients underwent clinical assessments, electrocardiography (ECG), and comprehensive echocardiography at diagnosis.

Among the 63 enrolled ATTR patients (median age 64 years, 66.7% men), 27% were diagnosed in cardiology clinics and 73% in neurology clinics. Six had ATTR-wt (all diagnosed by cardiologists), while 57 had ATTR-v (94.7% with the Ala97Ser mutation), predominantly diagnosed by neurologists. Some patients presenting to cardiology clinics had considerable neurological symptoms or a history of bilateral carpal tunnel syndrome in addition to prominent cardiac involvement. Conversely, patients presenting to neurology clinics had significant cardiac involvement comparable to those diagnosed in cardiology clinics. Peripheral neuropathy was the most prevalent red flag, followed by autonomic dysfunction, discordant QRS voltages on ECG, and a history of bilateral carpal tunnel syndrome. Notably, the absence of low-voltage QRS or the presence of left ventricular hypertrophy on ECG did not necessarily exclude ATTR.

Recognizing red-flag symptoms remains the key to identifying ATTR. Early detection of ATTR requires clinical vigilance and multidisciplinary collaboration across subspecialties.