Immune cell abundance was normal in left ventricular myocardium of HFpEF patients (0.90% Stage B, 0.78% Stage C vs 0.68% controls; P=NS), challenging immune infiltration as a driver.
Spatially resolved human myocardial profiling demonstrates no increase in immune lineage cells in preclinical or overt HFpEF, challenging the hypothesis that local immune cell infiltration is a major driver of the disease.
Absolute Event Rate: 0% vs 0%
Abstract Aims Myocardial inflammation has been proposed as a central mechanism in heart failure with preserved ejection fraction (HFpEF), supported by experimental work suggesting immune cell-mediated activation of profibrotic signaling. However, bulk transcriptomic analyses of human HFpEF myocardium did not demonstrate an activation of pro-inflammatory mediators or pathways. Here we investigated whether immune cell enrichment is present in human HFpEF myocardium. Methods and Results We analysed left ventricular (LV) epicardial biopsies from 28 adults undergoing elective coronary artery bypass grafting with preserved LV ejection fraction (≥50%). Participants were classified as referent controls (n=10), preclinical HFpEF Stage B (n=10), or overt HFpEF Stage C (n=8). High-resolution spatial transcriptomics and quantitative immunofluorescence for CD45, CD68, and CD3G were used to determine the abundance and phenotypic composition of immune lineage cells. HFpEF patients were older and more obese when compared to control subjects. Spatial transcriptomic profiling revealed normal immune cell abundances across all groups (mean 0.68±0.52% in controls, 0.90±0.49% in HFpEF Stage B, and 0.78±0.29% in HFpEF Stage C; P=NS), without differences in immune cell subsets or adaptive immune cell signatures. Immunofluorescence confirmed the absence of differences. Conclusion Spatially resolved human myocardial profiling did not demonstrate an increase in immune lineage cells in preclinical or overt HFpEF, challenging the concept that myocardial immune cell infiltration is a major driver of HFpEF. These findings support a model in which haemodynamic load and systemic factors, rather than local immune cell expansion, drive myocardial hypertrophy and fibrosis in HFpEF.
Ye et al. (Sat,) reported a other. Immune cell abundance was normal in left ventricular myocardium of HFpEF patients (0.90% Stage B, 0.78% Stage C vs 0.68% controls; P=NS), challenging immune infiltration as a driver.