Genetic architecture of dilated cardiomyopathy in Poland: variant distribution, clinical characteristics, and prognosis.

Introduction:  Genetic variants are the leading cause of dilated cardiomyopathy (DCM). Data on genetic testing in DCM from Central European populations are scarce.

Objectives:  We sought to determine the genetic architecture of DCM in Poland and to assess its influence on patient clinical characteristics and prognosis.

Patients and methods:  The study included 280 DCM patients (mean [SD] age, 39 [13] y; 68% men) who underwent next‑generation sequencing or in whom disease‑causing variants were identified using single‑gene testing.

Results:  DCM‑related variants were identified in 46% of the patients. Variants in titin (TTN) and lamin A/C (LMNA) genes were the most frequent (18% and 8% of the study cohort, respectively). Other genes with variant frequency equal to or above 2% included desmoplakin (DSP), myosin heavy chain 7 (MYH7), sodium voltage‑gated channel α subunit 5 (SCN5A), filamin C (FLNC), BCL2‑associated athanogene 3 (BAG3), and dystrophin (DMD). Positive family history, atrioventricular block, or atrial arrhythmias were found more often in the causative variant carriers, whereas the frequency of left bundle branch block or hypertension was lower. Severe DCM and a composite end point (cardiovascular death, heart transplantation, left ventricular assist device implantation) occurred with similar frequency in gene‑negative DCM and TTN‑related DCM, whereas the prognosis was worse in the remaining variant carriers. The risks of severe DCM and the composite end point were 2.4- and 3‑fold higher, respectively, for LMNA‑related DCM and 2.3- and 2‑fold higher for variants in the other genes.

Conclusions:  The distribution of causative genetic variants in Polish DCM patients is similar to that in Western European cohorts. The presence of the causative variants in the genes other than TTN is associated with a poorer prognosis.