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Update on Disease-Specific Biomarkers in Transthyretin Cardiac Amyloidosis

  • Biomarkers of Heart Failure (W.H.W. Tang and J. Grodin, Section Editors)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial delay between initial symptoms and diagnosis. With the recent emergence of various targeted therapies proven to reduce morbidity and mortality, there is an imperative to diagnose subclinical disease. Biomarkers may be well-suited for this role.

Recent Findings

Conventional markers of heart failure, such as natriuretic peptides and cardiac troponins, and estimated glomerular filtration rate are associated with risk in ATTR-CM. Circulating transthyretin (TTR) levels parallel TTR kinetic stability, correlate with disease severity, and may serve as indirect markers of ATTR-CM disease activity and response to targeted treatment. There is also growing evidence for the correlation of TTR to retinol-binding protein 4, a biomarker which independently associates with this disease. The rate-limiting step for ATTR pathogenesis is dissociation of the TTR homotetramer, which may be quantified using subunit exchange to allow for early risk assessment, prognostication, and assessment of treatment response. The protein species that result from the dissociation and misfolding of TTR are known as nonnative transthyretin (NNTTR). NNTTR is quantifiable via peptide probes and is a specific biomarker whose reduction is positively correlated with improvement in neuropathic ATTR amyloidosis. Neurofilament light chain (NfL) is released into the blood after axonal damage and correlates with neuropathic ATTR amyloidosis, but its clinical use in ATTR-CM is uncertain.

Summary

Conventional markers of heart failure, transthyretin, retinol-binding protein 4, transthyretin kinetic stability, nonnative transthyretin, peptide probes, and neurofilament light chain have potential as biomarkers to enable early, subclinical diagnosis in patients with transthyretin cardiac amyloidosis.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Caleb J. Hood

  2. Parkland Health and Hospital System, Dallas, TX, USA

    Caleb J. Hood, Nicholas S. Hendren & Justin L. Grodin

  3. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Ste. E5.310F, Dallas, TX, 75390-8830, USA

    Nicholas S. Hendren, Lori R. Roth & Justin L. Grodin

  4. Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Rose Pedretti & Lorena Saelices

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Conflict of Interest

Justin Grodin received research funding from the Texas Health Resources Clinical Scholarship and the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R01HL160892 and receives consulting income from Pfizer and Eidos Therapeutics. Caleb Hood declares no conflict of interest. Nicholas Hendren declares no conflict of interest. Rose Pedretti declares no conflict of interest. Lorena Saelices declares no conflict of interest. Lori Roth has done consulting work with Eidos Therapeutics.

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Hood, C.J., Hendren, N.S., Pedretti, R. et al. Update on Disease-Specific Biomarkers in Transthyretin Cardiac Amyloidosis. Curr Heart Fail Rep 19, 356–363 (2022). https://doi.org/10.1007/s11897-022-00570-1

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