Experience on Genetic Testing for Primary Dilated Cardiomyopathy in a Single Austrian Genetic Center and the Role of...

Molecular genetic testing is increasingly offered to patients with dilated cardiomyopathy (DCM). The diagnosis of an inherited cardiomyopathy has major implications for medical care of patients and relatives. We report the results of a genotype-phenotype analysis of DCM investigated in Austria.

Overall, 194 patients with DCM underwent genetic testing over a period of 6 years. We analyzed the clinical and genetic characteristics of 105 DCM patients who showed a genetic variant and compared the genetic findings and outcome measures of patients with myocardial inflammation on endomyocardial biopsy and those without.

In 51.4% (54/105) patients, at least one likely pathogenic or pathogenic genetic variant (LP/P) was detected. Fifty one of 105 patients (48.6%) showed only variants of unknown significance (VUSs). Most LP/P variants (34.3%) were detected in the TTN gene. Clinical characteristics of the most prevalent genetic subgroups (TTN, LMNA, MYH7, MYH6, DMD, SCN5A) were not significantly different. DCM patients with inflammation had significantly higher frequency of memory of infection, left bundle branch block, mitral valve insufficiency but normal CK-MB levels. We added a case report where two family members initially were considered to have an inflammatory cardiomyopathy before a pathogenic variant in LMNA was found.

Cardiac features of DCM were not predictive of a specific genetic subgroup. We recommend applying multigene panels extensively since a large proportion of patients without a family history or with evidence of myocardial inflammation showed a genetic predisposition for DCM. However, the large number of VUS remains a challenge.