# Percutaneous Coronary Intervention for Chronic Total Occlusions Modulates Cardiac Hypoxic and Inflammatory Stress

## TL;DR

This study shows that a heart procedure called CTO-PCI reduces heart stress and inflammation, which may improve heart function over time.

## Contribution

The study is the first to explore acute cardiac microenvironment changes and their link to long-term heart function improvement after CTO-PCI.

## Key findings

- CTO-PCI significantly reduced pro-angiogenic biomarkers like angiopoietin-1 and vascular endothelial growth factors.
- The procedure increased anti-inflammatory interleukin-10 and decreased pro-inflammatory interleukin-1β in the cardiac microenvironment.
- Interleukin-10 levels predicted improvement in left ventricular ejection fraction at 6-month follow-up.

## Abstract

Background/Objectives: The cardiac hypoxia- and inflammation-associated processes in patients with chronic coronary artery disease remain unknown. The coronary sinus (CS) can be used to explore changes in cardiac microenvironment. This study sought to evaluate acute changes in the CS concentration of hypoxia and inflammation-associated biomarkers after the percutaneous revascularization of chronic total occlusions (CTO-PCI). Additionally, we explored changes in systemic inflammation and the potential of CS biomarkers to predict left ventricular ejection fraction (LVEF) improvement on follow-up. Methods: Thirty-three patients undergoing CTO-PCI were included. Samples from CS were collected before and after the revascularization. Twenty-six protein biomarkers associated with hypoxia and inflammation were measured using proximity extension assay technology. Systemic inflammation markers and LVEF on cardiac magnetic resonance imaging were assessed at baseline and 6-month follow-up. Results: CTO-PCI yielded a significant decrease in the concentration of CS pro-angiogenic biomarkers (angiopoietin-1, vascular endothelial growth factors). In addition, there was a significant increase in the anti-inflammatory biomarker interleukin-10 and a decrease in several pro-inflammatory biomarkers like interleukin-1β. The acute response in cardiac microenvironment was followed by a mid-term reduction in systemic inflammatory markers, particularly high-sensitivity C-reactive protein. Notably, interleukin-10 showed good performance to identify patients achieving LVEF improvement on follow-up in our cohort. Conclusions: Our results suggest that CTO-PCI might attenuate cardiac hypoxic and inflammatory stress. These exploratory findings warrant confirmation in larger, controlled studies.