DOI: 10.3390/jpm16110541 ISSN: 2075-4426

Pregnancy-Associated HFpEF: A Window into Future Cardiovascular Risk? A Narrative Review of Current Evidence, Diagnostic Challenges, and Future Directions

Radha Gopalan, Mahmoud Elbsiony, Jamal Mahar, Anusha Sunkara, Anantharam Kalya, Mohamed Reyad Mohamed, Marc A. Silver

This narrative review synthesizes the available evidence on pregnancy-associated heart failure with preserved ejection fraction (HFpEF) and presents an operational definition and hypothesis-generating conceptual framework for this underrecognized cardio-obstetric phenotype that extends the traditional reduced-ejection-fraction framework of pregnancy-associated heart failure. Pregnancy-associated HFpEF refers to heart failure occurring during pregnancy or postpartum in patients with preserved left ventricular ejection fraction and objective evidence of congestion, elevated cardiac filling pressures, or impaired diastolic function, after consideration of alternative causes. Although peripartum cardiomyopathy has historically shaped the understanding of pregnancy-associated heart failure, limited observational studies and case reports have described heart-failure presentations during pregnancy or postpartum despite preserved left ventricular systolic function. Whether these presentations represent a distinct pregnancy-associated HFpEF phenotype after exclusion of alternative causes remains uncertain. This phenotype is closely linked to hypertensive disorders of pregnancy, obesity, diabetes, renal dysfunction, advanced maternal age, and social vulnerability, and may overlap mechanistically with preeclampsia through shared pathways of endothelial dysfunction, increased afterload, elevated filling pressures, and pulmonary congestion. Diagnosis remains challenging because normal pregnancy can mimic HFpEF symptoms and alter biomarkers and echocardiographic parameters, while existing HFpEF algorithms have not been validated in pregnant populations. Recognition requires integration of clinical evidence of congestion, natriuretic peptide levels, echocardiographic evidence of diastolic dysfunction or elevated filling pressures, assessment of pulmonary hypertension and right ventricular involvement, and the postpartum clinical trajectory. Given the heterogeneity of this phenotype, a personalized-medicine approach may be particularly relevant, integrating maternal risk factors, obstetric context, biomarkers, and cardiac imaging rather than relying on preserved LVEF alone. Although hypertensive disorders of pregnancy are associated with increased long-term cardiovascular and HFpEF risk, whether pregnancy-associated HFpEF itself independently predicts future heart failure remains unknown. The operational definition, conceptual framework, and postpartum considerations presented in this narrative review are intended to organize the available evidence and generate hypotheses rather than serve as a formal diagnostic or management protocol, and they require prospective validation before routine clinical adoption.

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