Cardiac Tc99m-Pyrophosphate uptake may present variable correlation with transthyretin cardiac amyloidosis severity depending on the genotype
M Simoes, G Jadan, E B Correia, A A S Carvalho, A V S Macedo, P V Schwartzmann, P Scheinberg, M O Antunes, O R Coelho-Filho, S Mangini, D M Tanaka, F FernandesAbstract
Abstract
Rationale: Cardiac scintigraphy with Tc99m-Pyfophosphate (PYP) is largely used for transthyretin cardiac amyloidosis (TTR-CA) diagnosis and has potential use for cardiac disease severity assessment. However, cardiac PYP uptake may vary in different mutations causing hereditary TTR-CA.
Objective
We aimed at assessing the correlation between PYP cardiac uptake and extent of structural TTR-CA disease in patients with different genotypes.
Methods
We analyzed data from the REACT/SP (Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil), and among the 642 patient records, we identified 283 patients that underwent PYP: 85% were male, age of 73+/-8 years old, 215 were hereditary (79 were p.Val50Met, 86 were p.Val142Ile, 50 had other mutations) and 68 were wildtype. We performed a regression and correlation analysis between the heart and contra-lateral (H/CL) ratio obtained in planar PYP images and the interventricular septum thickness (IVS) measured on echocardiogram. This correlation was applied to the entire patient group and also in groups according to the genotype.
Results
The correlation between H/CL and IVS thickness was moderate, significant and positive when the whole group of patients were included in the analysis (n=283, R = 0.6, P<0.0001 - figure 1A). When only patients with p.Val142Ile were selected, a positive and moderate significant correlation was also found (R = 0.7, p<0.0001 - figure 1B). In the p.Val50Met group, there was different distribution of the correlation according to the clinical presentation. In the late-onset p.Val50Met patients (n=35), we found a positive moderate significant correlation (R=0.4, p = 0.02 - figure 1C), but we found no significant correlation (p=0.7) in the early-onset p.Val50Met patients (n=44 - figure 1D). Noteworthy, among the 10 patients with p.Val50Met presenting increased IVS thickness (>12 mm), only 2 patients presented simultaneously increased cardiac PYP uptake with H/CL ratio above 1.3. We also found positive weak correlations in the wildtype (R = 0.2, p=0.0478) and patients with other mutations (R=0.3, p = 0.0484).
Conclusions
The correlation between cardiac PYP uptake and severity of ATTR-CA, estimated by the IVS thickness, is stronger in p.Val142Ile patients, while patients with early onset p.Val50Met mutation present no significant correlation. These findings suggest that genotyping should be taken in consideration before analyzing PYP for diagnostic and prognostic purposes in patients with ATTR-CA.Scatter plots illustrating the correlations