Pathogenic variants in the PKP2 gene were associated with a significantly lower rate of death or heart transplant (11% vs 39%, p=0.03) compared to ARVC patients without PKP2 mutations.
Cohort (n=56)
No
Does the presence of pathogenic variants in the PKP2 gene improve survival and reduce heart failure progression in patients with arrhythmogenic right ventricular cardiomyopathy?
In patients with ARVC, the presence of PKP2 pathogenic variants is associated with a more classical phenotype but better long-term survival and less left ventricular involvement compared to those without PKP2 mutations.
Absolute Event Rate: 11% vs 39%
p-value: p=0.03
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is mainly caused by mutations in genes encoding desmosomal proteins. Variants in plakophilin-2 gene (PKP2) are the most common cause of the disease, associated with conventional ARVC phenotype. The study aims to evaluate the prevalence of PKP2 variants and examine genotype-phenotype correlation in Polish ARVC cohort. All 56 ARVC patients fulfilling the current criteria were screened for genetic variants in PKP2 using denaturing high-performance liquid chromatography or next-generation sequencing. The clinical evaluation involved medical history, electrocardiogram, echocardiography, and follow-up. Ten variants (5 frameshift, 2 nonsense, 2 splicing, and 1 missense) in PKP2 were found in 28 (50%) cases. All truncating variants are classified as pathogenic/likely pathogenic, while the missense variant is classified as variant of uncertain significance. Patients carrying a PKP2 mutation were younger at diagnosis (p = 0.003), more often had negative T waves in V1-V3 (p = 0.01), had higher left ventricular ejection fraction (p = 0.04), and were less likely to present symptoms of heart failure (p = 0.01) and left ventricular damage progression (p = 0.04). Combined endpoint of death or heart transplant was more frequent in subgroup without PKP2 mutation (p = 0.03). Pathogenic variants in PKP2 are responsible for 50% of ARVC cases in the Polish population and are associated with a better prognosis. ARVC patients with PKP2 mutation are less likely to present left ventricular involvement and heart failure symptoms. Combined endpoint of death or heart transplant was less frequent in this group.
Biernacka et al. (Wed,) conducted a cohort in Arrhythmogenic right ventricular cardiomyopathy (ARVC) (n=56). Pathogenic variants in plakophilin-2 gene (PKP2) vs. PKP2 mutation-negative was evaluated on Combined endpoint of death or heart transplant (p=0.03). Pathogenic variants in the PKP2 gene were associated with a significantly lower rate of death or heart transplant (11% vs 39%, p=0.03) compared to ARVC patients without PKP2 mutations.