Patients with late-onset hereditary transthyretin amyloidosis (hATTR) who have a predominant p.A117S mutation tend to develop cardiomyopathy regardless of the clinical severity of polyneuropathy, according to a recently published study in Annals of Clinical and Translational Neuropathy.

Although neurologic symptoms secondary to polyneuropathy constitute the hallmark presentation of hATTR, the presence of cardiomyopathy represents the main prognostic marker. However, many authors agree that cardiomyopathy is currently underdiagnosed in patients with hATTR because several heart failure symptoms, such as dyspnea and edema, can be masked by polyneuropathy symptoms.

Fortunately, new imaging techniques, such as repurposed bone scintigraphy and cardiac magnetic resonance (CMR) imaging, have facilitated diagnosis without the need to perform a tissue biopsy and expose patients to the risks involved in the procedure.

“CMR can provide accurate and detailed information about the changes in cardiac tissue and morphology by demonstrating late gadolinium enhancement and measuring the myocardial T1 time, extracellular volume (ECV), and left ventricular mass index,” the authors wrote.

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The study aimed to assess cardiac involvement in patients with late-onset hATTR and a predominant p.A117S genotype and correlate it with the presence of polyneuropathy. The study involved 50 patients with a median age of approximately 65 years who had experienced symptoms of polyneuropathy for 3 to 5 years.

Approximately 70% of patients involved in the study presented with ventricular hypertrophy, according to CMR findings. Furthermore, over 50% of patients had either hypokinesia or akinesia in the left ventricle, and 80% had subendocardial delayed enhancement in the left ventricular myocardium or biventricular myocardium.

Myocardial native T1 and ECV values revealed a considerable degree of myocardial amyloidosis. Technetium-pyrophosphate single-photon emission computed tomography (Tc-PYP SPECT) imaging revealed that hATTR patients had increased radioactive uptake.

The authors used a linear regression model to correlate cardiopathy findings with polyneuropathy findings, concluding that cardiac changes were correlated with neuropathic changes and could reflect overall severity in patients with hATTR.

“In conclusion, our observations-based concomitant survey of polyneuropathy and cardiomyopathy suggested that patients with late-onset [hATTR with polyneuropathy] and predominant p.A117S mutation invariably manifested cardiomyopathy regardless of the clinical severity of polyneuropathy,” the authors wrote.


Lin YH, Hsueh HW, Su MY, et al. Cardiomyopathy correlates to nerve damage in p.A117S late‐onset transthyretin amyloid polyneuropathy. Ann Clin Transl Neurol. Published online August 9, 2022. doi:10.1002/acn3.51635