Targeted Serum Organic-Acid Profiling Identifies Candidate Metabolic Signatures in Peripartum Cardiomyopathy: A Case-Control Study

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening form of heart failure that occurs toward the end of pregnancy or in the months following delivery. Biomarkers that may support the recognition and characterization of PPCM remain limited. We investigated whether targeted serum organic-acid profiling could identify candidate metabolites associated with PPCM. In this case–control study, serum samples from women with PPCM (n = 40) and healthy controls (n = 40) were analyzed using a targeted organic-acid panel. Log2-transformed metabolite abundances were compared using Welch’s t-test, with Benjamini–Hochberg false discovery rate (FDR) correction correction and Hedges’ g effect sizes. Distributional assumptions were assessed using group-specific Shapiro–Wilk tests, and Mann–Whitney U tests were performed as a non-parametric sensitivity analysis. Homogentisic acid was increased in PPCM (log2fold change (log2FC) = 0.696; FDR q = 9.8 × 10−6), whereas lactic acid was decreased (log2FC = −0.701; FDR q = 0.00773). Both findings remained significant in the Mann–Whitney U sensitivity analysis (BH-FDR q = 5.63 × 10−5 and q = 0.0114, respectively). The best-performing single metabolite showed an area under the receiver operating characteristic curve(AUC) of 0.818 (95% CI, 0.723–0.899). The multivariable model achieved a cross-validated AUC of 0.708 (95% CI, 0.590–0.813), with a sensitivity of 0.800 and a specificity of 0.550. Targeted organic-acid profiling revealed a distinct metabolic signal in PPCM, highlighted by higher homogentisic acid and lower lactic acid levels. These exploratory findings warrant confirmation in larger prospective studies with external validation.