Early subclinical systolic dysfunction detected by two-dimensional speckle tracking systolic strain in patients with hereditary TTR amyloidosis

Abstract Background Transthyretin Amyloidosis (ATTR) is a rare genetic cause of potentially fatal infiltrative cardiomyopathy. This is the commonest form of inherited restrictive cardiomyopathy. The Transthyretin (TTR) gene is located on chromosome 18q12.1 with autosomal dominant inheritance and variable penetrance. The availability of genetic testing has identified a carrier population without cardiac amyloidosis. 2-dimensional speckle-tracking echocardiography (2D-STE) has been the mainstay of screening and disease surveillance. However, utility of echocardiography for the comprehensive analysis of biventricular strains are not reported in a carrier population without cardiac amyloidosis. We sought to study the global and regional indices of biventricular strain in genotyped cases of ATTR. Purpose To assess whether individuals with a family history of TTR amyloidosis associated with a positive genetic study for transthyretin mutation can develop cardiac abnormalities even before the clinical manifestation of the disease, which may early clarify the cardiovascular risk of this pathology. Methods Patients with genotype TTR positive (TTR+) without cardiovascular symptoms were identified and matched with healthy controls. All patients underwent a full echocardiogram using a standardized protocol: 2D dimensions, tissue Doppler (TDI) and 2D-STE parameters were analyzed. Data are reported as means with standard deviation (±SD) or median with interquartile range [IQR]. Statistics performed were parametric and non-parametric tests, with a p value of <0.05 accepted as significant. In order to identify variables that could be associated with patients TTR genotype positive, an analysis of multiple logistic regression was proposed. Results 31 individuals in TTR+ and 34 controls were studied. Demographic and echocardiography parameters characteristics are detailed in Table. There was no significant difference in chamber dimensions, length, or ejection fraction between groups. Compared with controls, left ventricular (LV) wall thickness and mass index was higher in TTR+ (Table). Average E/e' tended to be higher in TTR+ (table). LV global circumferential and longitudinal strain were significantly lower in TTR+ (−28±4% vs. −21±4%, −25±2% vs. −19±3%, p<0.001 for all). Bull's eyes of the peak Longitudinal Strain are showed in Figure 1. RV strain was also lower in the TTR+ group (−25±5% vs. −18±4%, p<0.005). Additionally, there was a significant reduced in longitudinal strain basal, mid, and apical in TTR+ group (Table). The predictors of positive genetic testing were global longitudinal strain (adjusted odds ratio [95% CI], 2.46 [1.30–4.62]; p=0.005) and average E/e' (2.04; [1.09–3.91]; p=0.025). Conclusion Global and regional biventricular strain is lower in individuals with genetically proven TTR prior to development of cardiac amyloidosis. The impact of these variables as a component of a screening. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq)