Pregnancy as a risk factor for decompensated heart failure in carriers of truncating titin gene variants: two case reports

Abstract

Aim . To characterize the pregnancy and postpartum period in carriers of truncating TTN gene variants with a phenotype of dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) with increased left ventricular (LV) trabeculation, and to evaluate the potential role of pregnancy as a trigger for decompensation of inherited cardiomyopathies. Material and methods. Two cases of patients with DCM and HCM with increased LV trabeculation are presented. We analyzed medical history data, echocardiographic changes, Holter ECG monitoring and cardiac magnetic resonance imaging data, and pathological examination of the cardiac explant. In addition, nextgeneration sequencing using a targeted cardiac panel, including genes associated with cardiomyopathies, as well as phenotypically similar conditions, was performed. R e sults . A patient with a heterozygous truncating variant of TTN (chr2:178581583, NM_001267550.2: c.66685C>T; p.Gln22229Ter) developed fulminant dilated cardiomyopathy in the early postpartum period. A patient with a HCM phenotype and increased LV trabeculation and a heterozygous truncating variant of TTN (chr2:178552954, NM_001267550.2: c.89943_89946del; p.Val29982CysfsTer12) also developed a significant decrease in ejection fraction in the postpartum period. Conclusion . The presented cases demonstrate that pregnancy and the early postpartum period can act as a hemodynamic and neurohumoral trigger, contributing to the clinical manifestation or decompensation of inherited cardiomyopathies in carriers truncating TTN variants. However, given the isolated nature of these observations and the lack of a comprehensive family survey, the data obtained should be considered a hypothesis requiring confirmation in larger case series.