Specificities of amyloid cardiomyopathy caused by transthyretin V30 mutation

Transthyretin-related amyloid cardiomyopathy (ATTR-CM) results from mutations in the TTR gene (vATTR) or conformational changes in wild-type TTR protein (wtATTR). The aim of this study was to characterize the specificities of cardiac involvement in patients with TTR V30M mutation.

This retrospective study included patients diagnosed with TTR V30M that were referred to a cardiology appointment during 2019 (median follow-up of 57 months). Data on cardiomyopathy (CM), conduction abnormalities, aortic stenosis, and atrial fibrillation (Afib) were collected. V30M ATTR-CM patients were compared to a contemporary cohort with wtATTR-CM.

A total of 238 TTR V30M patients were enrolled: mean age 54 years old, 52 % male, and 69 % with early onset disease. vATTR-CM occurred in 20 % of patients and was associated with male gender, older age at presentation, liver transplantation, ophthalmologic manifestations, and lower creatinine clearance. Age at presentation, male gender, liver transplant, and ophthalmologic manifestations were independent predictors of CM. vATTR-CM was associated with worse outcomes. Significant electric conduction disease was present in 32 % of patients and AFib in 11 %. Patients with vATTR-CM, compared to those without CM, had a higher prevalence of significant electric conduction changes, pacemaker implantation, and AFib when compared to those without CM. Most patients with electric disease had neuropathy and more than 12 years of symptoms. Significant aortic stenosis was rare. Compared to patients with wtATTR-CM, patients with vATTR-CM had a higher prevalence of significant conduction disease, a lower prevalence of AFib, and less severe hypertrophy. In vATRR-CM, age at presentation and male predominance were lower and orthostatic hypotension was more prevalent.

Our findings highlight the need for thorough cardiovascular evaluation in TTR V30M patients due to common conduction issues and the significant impact of CM on outcomes.