Ken-ichi Kurosaki, Hiroshi Hosoda, Naoto Minamino, Kunihiro Nishimura, Isao Shiraishi, Takekazu Miyoshi, Mikiya Miyazato, Michikazu Nakai, Kenji Kangawa, Takashi Asada, Tomoaki Ikeda, Takashi Umekawa, Akihiro Fujiwara, Jun Yoshimatsu
Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established marker of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with congenital heart defect (CHD) and arrhythmia.
This was a prospective observational study at a tertiary pediatric cardiac center. A total of 129 singletons with CHD, arrhythmia, or both and 127 controls from 2012 to 2015 were analyzed. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure such as a cardiovascular profile (CVP) score and morphological characteristics.
Fetuses with CHD, arrhythmia, or both had higher NP levels than controls (P<0.01). NP levels of fetuses with CHD, arrhythmia, or both were inversely correlated with CVP score (P for trend <0.01). No differences were found in NP levels between fetuses with CHD or arrhythmia and a CVP score of ≥8 versus controls. Multivariate analysis showed that a CVP score of ≤5, tachy- or bradyarrhythmia at birth, preterm birth, and umbilical artery pH <7.15 are independently associated with high NP levels (P<0.01). Among fetuses with a CVP score of ≤7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than those with CHDs, and fetuses with tachy- or bradyarrhythmia had higher NP levels than those with CHDs (P=0.01). Fetuses with right heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than fetuses with other types of CHD (P<0.01).
Plasma NP levels in fetuses with CHD, arrhythmia, or both are correlated with the severity of fetal heart failure. Elevated NP levels are mainly attributed to increases in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to a CHD, rather than the morphological abnormality itself.