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Background Acute inflammatory responses during and after percutaneous coronary intervention (PCI) are associated with subsequent cardiovascular event risk, but limited data exist on acute immune cell responses regulating PCI-related inflammation. As an exploratory pilot study, our objective was to determine whether PCI acutely alters neutrophil-specific components of activation, maturity and chemotaxis in the coronary and peripheral circulation.Methods This prospective cohort study was conducted from October 2024 to January 2025 within an urban tertiary-care academic medical centre. Twenty-nine consecutive patients ≥18 years of age undergoing clinically indicated PCI were included. Paired blood samples were collected immediately pre-PCI and post-PCI from the peripheral arterial sheath (peripheral circulation) and coronary guide catheter (coronary circulation).Results The primary endpoints were pre-PCI to post-PCI changes in immature neutrophils (CD10 −CD16− subset as a total percentage of neutrophils) and neutrophil-specific expression of markers relevant for activation and degranulation (CD62L and CD63 expression). In the immediate pre-PCI to post-PCI period, there was an acute increase in CD10-CD16- neutrophil subset in the coronary blood (1.5±0.3% vs 3.4±0.8%, p=0.012) and a decrease in CD62L neutrophil expression in both the coronary (median fluorescence intensities (MFI)=1340.4±102.3 vs 1084.0±92.8, p=0.002) and peripheral circulation (CD62L MFI=1182.4±82.7 vs 1078.1±77.9, p=0.035). No differences were observed with neutrophil degranulation, chemotaxis or migration.Conclusions In patients undergoing PCI, we observed an acute increase in circulating neutrophil cell-specific activation and immaturity markers following PCI but no significant effects of PCI on neutrophil degranulation. Further research is needed to understand whether these effects contribute to long-term post-PCI outcomes and, if so, if neutrophil release and activation warrant targeting during PCI.