Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study

Abstract

Background

Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.

Material and Methods

This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.

Results

Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63–71] years vs 76[70–79] years, p < .001), age at first cardiac symptom (66[61–71] years vs 74[68–78] years, p < .001) and age at first extracardiac symptom (59[52–70] years vs 69[62–75] years, p = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67–74] vs 78[76–79] years, p = .018).

Conclusion

This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.

Keywords:

• Cardiac amyloidosis
• hereditary amyloidosis
• hereditary transthyretin amyloidosis
• homozygote
• p.Val142Ile; V122I mutation

Acknowledgments

The authors thank all patients and physicians involved in the Mondor Amyloidosis Network and Amy Whereat for medical writing assistance.

Disclosure statement

Silvia Oghina received honoraria and consultancy fees from Pfizer. Thibaud Damy received research and/or consultancy fees from GlaxoSmithKline, Alnylam, Pfizer, Prothena, Ionis, Akcea, and Janssen.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.