Diagnostic utility of genetic testing in restrictive cardiomyopathy a single refferal centre experience. (14th October 2021)

• Record Type: Journal Article
• Authors: Szczygiel, J A; Michalek, P; Franaszczyk, M; Truszkowska, G; Ziarkiewicz, M; Gawor, M; Legatowicz-Koprowska, M; Walczak, E; Mazurkiewicz, L; Stawinski, P; Jedrzejczak, W W; Lutynska, A; Ploski, R; Bilinska, Z T; Grzybowski, J
• Is Part Of: European heart journal. Volume 42(2021)Supplement 1
• Publication Date: 2021-10-14
• Subjects: Restrictive Cardiomyopathy and Loeffler's Disease; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab724.1788
• Languages: English
• ISSNs: 0195-668X

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