Pregnancy in the broad phenotype and genotype spectrum of disease-causing desmosomal variant-positive women

Pregnancy is generally well tolerated in patients with arrhythmogenic cardiomyopathy (AC), but there are limited data comparing right-dominant AC (ARVC) and left-dominant AC (ALVC), as well as gene-positive but phenotype-negative (G+/P-) individuals. Recent guidelines have also introduced the non-dilated left ventricular cardiomyopathy (NDLVC).

This study examines disease expression in pregnant women with AC and family members with pathogenic genetic variants but a negative phenotype (G+/P-). We also included those with NDLVC.

We reviewed data from 22 patients diagnosed with definite AC and 9 G+/P- patients. Four patients meeting criteria for NDLVC were also analyzed. Each underwent at least one cardiovascular evaluation during pregnancy, which included a 12-lead ECG, echocardiography, and 24-h ambulatory monitoring. Events were defined as new or worsening arrhythmias, heart failure, or thromboembolic events.

All AC patients, including those with ARVC and ALVC, tolerated pregnancy well. None of the G+/P- patients was diagnosed with AC during pregnancy. One G+/P- patient had ECG changes, while three with PKP2 mutations experienced mild left ventricular dysfunction but fully recovered postdelivery. Among the four NDLVC patients, only one developed left ventricular dysfunction. There was no increase in arrhythmias, and 31% of the cases required caesarean sections. All pregnancies resulted in live births, and no major maternal complications were reported.

Pregnancy is typically safe for women with AC and G+/P- individuals, provided that they are hemodynamically stable. Patients with NDLVC also manage pregnancy well. However, careful monitoring during and after pregnancy is essential, even without obvious clinical signs of the disease.