Background Transthyretin Cardiac amyloidosis (ATTR) presents with diffuse deposition of amyloid fibrils in the heart. Biomarkers of cardiac involvement such as troponins are often elevated even in early disease stages, reflecting direct cardiomyocyte damage and coronary microvascular dysfunction by amyloid deposits. Objectives Evaluate global and segmental coronary flow reserve (CFR) by PET 13N-ammonia in patients with hereditary Transtirretina Amyloidosis with and without cardiac involvement. Methodology Thirty-eight ATTR mutation carrier patients (18 with cardiac amyloidosis and 20 without cardiac amyloidosis underwent CFR study by PET 13N-ammonia. Cardiac involvement was defined by means of echocardiography, with an end-diastolic interventricular septal wall thickness ≥12 mm or positive endomyocardial biopsy or grade II or III nuclear scintigraphy using bone avid radiotracers. The Mann-Whitney test was used to compare the values of coronary flow reserve between the groups. The effect size was calculated using the Wilcox method and 95% confidence intervals, obtained by bootstrapping. A multivariate linear regression model was applied to identify the main determinants of global coronary flow reserve. Results Compared with patients without cardiac involvement, patients with cardiac involvement were older (69±8 vs. 41±11 years old; p<0,001), had worse NYHA functional classification, higher left ventricular mass index (198±51 g/m2 x 75±19 g/m2; p<0,001), thicker interventricular septum (17,9±3,4 mm vs. 8,7 ± mm; p<0,001]. Coronary flow reserve values were significantly lower in the cardiac amyloidosis group globally (1,8±0,4 vs. 2,9±0,7; p<0,001) and in all analyzed segments (p<0.01). The apical segments were also affected when comparing group with and without cardiac involvement (2,0±1 vs. 3,0±0,7; P=0,002), suggesting absence of microvascular apical preservation. In multivariable linear regression analyses, age and BNP were the main factors associated to coronary reserve flow. The reduction in global CRF was 0,25, 0,08 and 0,17 points, on average, for each decade of life, for each 100 mg/dl of serum BNP and for each 0,1 heart to contralateral lung ratio uptake in 3-hour caption on TcPYP scintigraphy respectively. Conclusion Patients with cardiac amyloidosis present lower coronary flow reserve both globally and segmental compared to mutation carrier without cardiac amyloidosis. The evaluation of Coronary flow reserve by PET 13N-ammonia may be a worthwhile tool in cardiac involvement in TTR patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer
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