Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.

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.