Non-Cardiac Amyloidosis Findings Are Not Increased in African American Carriers of TTR V142I with Heart Failure and/or Arrhythmia

TL;DR

African American carriers of a specific TTR gene variant do not show higher rates of non-cardiac amyloidosis despite heart issues.

Contribution

This study clarifies that TTR V142I carriers in African Americans are not more likely to have undiagnosed non-cardiac amyloidosis.

Findings

AA patients with TTR V142I and heart issues were not diagnosed with amyloidosis more frequently than non-carriers.

Genetic testing revealed no additional TTR variants in patients with amyloid-related diagnoses.

Carriers of TTR V142I showed no clinical distinction in non-cardiac amyloid diagnoses.

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive systemic disease involving the extracellular deposition of misfolded transthyretin protein. The hereditary subtype is caused by mutations in the transthyretin (TTR) gene. An estimated 2–3% of individuals of African American (AA) ancestry carry the p.Val142Ile (V142I, also referred to as V122I) TTR pathogenic variant. The non-specific clinical nature of ATTR-CM makes it challenging to diagnose clinically, and the high allele frequency of TTR V142I suggests that many patients with hereditary ATTR-CM may not have been tested. An analysis of electronic health record data from over 13,000 AA patients with a diagnostic code for heart disease or arrhythmia who also had additional amyloid-related findings were not diagnosed with amyloidosis at higher rates than those with heart failure or arrhythmia who did not have additional amyloid-related clinical diagnoses. Similarly, after genotyping 666 AA patients with heart failure or arrhythmia, TTR V142I carriers appeared to be clinically indistinguishable based on amyloid-related non-cardiac diagnoses from those who did not carry the allele. No additional TTR gene sequence variants were found in the TTR wildtype V142V patients with heart failure or arrhythmia who had additional amyloid-related diagnoses. Genetic testing for ATTR-CM may be important for timely diagnosis.

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