Diagnostic utility of genetic testing in restrictive cardiomyopathy a single refferal centre experience

Abstract

Abstract Introduction Restrictive cardiomyopathy (RCM) is considered to have a genetic background in approximately 50–60% of patients (pts) [1,2,3]. Purpose The aim of the study was to assess the frequency of pathogenic gene variants in Polish patients with RCM. Methods Restrictive cardiomyopathy was diagnosed by transthoracic echocardiography. The analysis included all consecutive unrelated pts with RCM admitted to the cardiology department from January 2015 to December 2016. Light-chain (AL) amyloidosis was diagnosed using tissue biopsy, concentration of serum free light chains and bone marrow biopsy. A genetic test was offered to every patient without AL amyloidosis. In 4 pts coding regions of TTR or GLA genes were screened by Sanger sequencing. Next Generation Sequencing (NGS) was performed: a panel covering coding regions of >4800 disease-associated genes in 18 pts and Whole Exome Sequencing (WES) in 2 pts. Classification of rare variants was made according to ACMG criteria [4]. Results Forty-four pts were enrolled. Eighteen pts were diagnosed with AL amyloidosis. One patient was diagnosed with histologically-proven myocarditis and one patient with transthyretin (ATTR) amyloidosis declined genetic test. The other 24 pts (median age 48 yrs, 6 males) underwent genetic testing, their median values (interquartile ranges) of the following parameters were: NT-proBNP, 2508 (995–5895) pg/mL; hs-TnT, 25 (18–46) ng/L; E/A ratio, 2.5 (1.8–4.5); E wave deceleration time, 135 (98–167) ms; E/e' ratio, 16 (12–19); left ventricular (LV) posterior wall, 13 (12–14.5) mm; interventricular septum, 14 (13–17) mm and LV end-diastolic dimension, 48 (43–49) mm. Pathogenic or likely pathogenic variants were detected in 16 probands: 5 in MYH7 gene, 3 in TNNI3 gene, 2 in MYBPC3 gene, 1 in BAG3 gene, 1 in PRAKG2 gene, 2 in GLA gene and 2 in TTR gene. Conclusions Genetic testing is justified in every patient with RCM, in whom AL amyloidosis is excluded. The molecular diagnosis in RCM may result in causal treatment of Anderson-Fabry disease and ATTR amyloidosis or improve disease management in other types of RCM. MYH7 gene is the most common causative gene in Polish patients with RCM. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institute of Cardiology