Soluble fms-like tyrosine kinase-1 and peripartum cardiomyopathy: an exploratory meta-analysis of association and diagnostic performance

Introduction Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure in late pregnancy and early postpartum, and biomarkers for risk stratification are lacking. Soluble fms-like tyrosine kinase-1 (sFlt-1), implicated in PPCM and pre-eclampsia, may be associated with PPCM and may have potential diagnostic relevance. This study aimed to evaluate the association between circulating sFlt-1 levels and PPCM and to provide an exploratory assessment of the diagnostic performance of sFlt-1 overall and according to pre-eclampsia status. Methods We searched PubMed, Europe PMC, and ScienceDirect from inception to 15th February 2026 for studies reporting sFlt-1 in PPCM cases and pregnant or postpartum controls. Given the rarity of PPCM and the limited number of eligible studies, this review was designed as an exploratory meta-analysis. Random-effects models pooled odds ratios (ORs) for PPCM comparing high vs. low sFlt-1 and enabled subgroup analyses by pre-eclampsia. I Diagnostic performance was summarised using pooled sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Results Three studies ( n = 226) met the criteria. High sFlt-1 levels were associated with increased PPCM risk [pooled OR 1.79; 95% confidence interval (CI) 1.22–2.64], although substantial heterogeneity was present across studies. In exploratory diagnostic analyses, performance was modest, with sensitivity 72% (95% CI 64%–80%), specificity 57% (95% CI 44%–68%), and AUC 0.71 (95% CI 0.67–0.75). In women with pre-eclampsia, the association with PPCM was stronger (OR 2.11; 95% CI 1.45–3.09) than in those without pre-eclampsia (OR 1.36; 95% CI 1.03–1.80), with higher sensitivity and specificity. Conclusion Elevated sFlt-1 was associated with PPCM, with exploratory analyses suggesting somewhat better diagnostic discrimination in women with pre-eclampsia. However, because all included studies measured sFlt-1 in the postpartum period, these findings should not be interpreted as evidence for antepartum screening utility. Larger prospective studies with measurements during pregnancy and serial peripartum follow-up are needed before any clinical application can be considered. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42024535557 , identifier (CRD42024535557).