Analysis of the left ventricular involvement in patients with a biventricular phenotype of arrhythmogenic ardiomyopathy: a case series description

Aim. To assess the prevalence of the left ventricle involvement and the features of the biventricular phenotype of arrhythmogenic cardiomyopathy in patients with pathogenic mutations in the PKP2 and DSP genes.Material and methods. Three unrelated probands underwent a comprehensive molecular-genetic, clinical and instrumental examination, which included a 12-lead ECG, 24-hour ECG monitoring, transthoracic echocardiography, and cardiac magnetic resonance imaging with late gadolinium enhancement.Results. The results of our clinical observations showed that in three studied patients with arrhythmogenic cardiomyopathy left ventricle involvement of various degree was found. The left ventricle damage was characterized by fibrous or fibro-fatty infiltration of the myocardium, as well as regional or global systolic dysfunction of different severity. The patients had pathogenic mutations c.1912C > T (p.Gln638*, rs397517012, rs397517012); c.1237C > T (p.Arg413*, rs372827156) in the PKP2 gene and a new probably pathogenic variant in the form of a c.3494delA deletion in the DSP gene. It was found that the mutation in the DSP gene was associated with a more pronounced systolic dysfunction and a greater percentage of fibrous replacement of the left ventricular myocardium compared with carriers of mutations in the PKP2 gene. All patients had life-threatening ventricular arrhythmias with the need for implantation of a cardioverter-defibrillator.Conclusion. Our clinical observations have shown that in patients with biventricular arrhythmogenic cardiomyopathy, the detection of a mutation in the DSP gene is associated with a more pronounced systolic dysfunction and a higher percentage of fibrous replacement of the left ventricle myocardium compared with carriers of mutations in the PKP2 gene.