Predictors and outcomes of amyloid cardiomyopathy caused by transthyretin V30 mutation

Abstract Background Transthyretin-related amyloid cardiomyopathy (ATTR-CM) results from mutations in the TTR gene (vATTR) or conformational changes in wild-type TTR protein (wtATTR). Regarding TTR mutations, a particular early-onset phenotype, presenting predominantly as a peripheral neuropathy (named Familial Amyloid Polyneuropathy) is endemic in Portugal, Sweden and Japan, with the V30M being the most common pathogenic variant. The aim of this study was to characterize the occurrence of V30M ATTR-CM, as well as its predictors and outcomes. Methods We conducted a retrospective study including patients diagnosed with TTR V30M mutation, with and without amyloid cardiomyopathy, consequently seen in Cardiology appointments in 2019 at our center at followed for at least 5 years. Diagnostic criteria for ATTR-CM were considered according to ESC recommendations. Multiple linear regression was used to identify independent predictors for ATTR-CM. Death rates were plotted as Kaplan-Meier curves. Results We enrolled a total of 248 TTR V30M patients, mean age of 54 years old, 53% males, 68% with early onset disease (50 years); 49 (21%) patients fulfilled the criteria for ATTR-CM diagnosis (with an additional 10% possibly having cardiomyopathy without fulfilling all diagnostic criteria). V30M ATTR-CM was associated with male gender (78% vs 46%, p0.001), older age (62.4±13.7 years vs 52.1±13.4 years, p0.001), late-onset disease (40% vs 18%, p=0.002), liver transplantation (49% vs 28%, p=0.004), orthostatic hypotension (55% vs 30%, p0.001), ophthalmologic manifestations (31% vs 16%, p=0.019), and lower creatinine clearance (81.5±25.3 ml/min vs 94.0±30.4 ml/min, p=0.009). There was no difference between groups regarding neurological involvement (present in 90% vs 82%) or GI, renal and urological manifestations. In multivariate analysis, male gender (OR 4,69; 95% CI 1.85–11.93; p0.001) and liver transplant (OR 6.41; 95% CI 1.93–21.24; p=0.002) were the only independent predictors of CM identified. Median follow-up time was 57 (5) months. ATTR-CM was associated with worse outcomes (survival 78.5% vs 91.3%, LogRank = 0.034) (Figure 1). Conclusion ATTR-CM affects more than one fifth of our TTR V30M patients and is independently predicted by male gender and liver transplantation. It is associated with worse outcomes, highlighting the need for early detection and management to improve prognosis.