Decreased Cytokine Plasma Levels and Changes in T-Cell Activation Are Associated With Hemodynamic Improvement and Clinical Outcomes After Percutaneous Mitral Commissurotomy in Patients With Rheumatic Mitral Stenosis

Abstract

Mitral stenosis (MS) is a consequence of rheumatic heart disease that leads to heart failure requiring mechanical intervention. Percutaneous mitral commissurotomy (PMC) is the treatment of choice for the intervention, and currently there are no soluble markers associated with hemodynamic improvement after PMC. This study aims to determine the changes in cytokine/chemokine plasma levels, as well as T cell activation after PMC, and to investigate their association with immediate hemodynamic improvement and clinical outcomes. Plasma samples from eighteen patients with well-defined MS who underwent PMC and 12 healthy controls were analyzed using BioPlex immunoassay. We observed that 16 out of the 27 (60%) molecules assessed were altered in patients' plasma pre-PMC as compared to control group. Of those, IL-1β, IL-12, IL-6, IL-4, PDGF, and CCL11 showed significant decrease after PMC. Stratifying the patients according to adverse outcome after a 28-month median follow up, we detected a significant reduction of IL-1β, IL-12, IL-6, IL-4, IFN-γ, CXCL-10, VEGF, FGF and PDGF post-PMC in patients without events, but not in those who presented adverse events during the follow-up. Patients with adverse outcomes had lower IL-10 pre-PMC, as compared to the ones without adverse events. In addition, the frequency of CD8+ activated memory cells was increased after PMC, while the frequency of CD4+ activated memory cells did not change. Our results show an association between the decrease of specific cytokines and changes in T cell activation with hemodynamic improvement post-PMC, as well as with long-term outcomes, suggesting their possible use as soluble markers for hemodynamic recovery after MS intervention.

The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease

“…In heart tissue infiltrates from RHD patients, IFN-γ and TNFα expressing Th1 cells were found to be predominant and were considered to contribute to the valvular damage seen in RHD [358]. In patients with RHD-related mitral stenosis who underwent percutaneous mitral commissurotomy, IL-1β, IL-12, IL-6, and IL-4 were decreased [359]. Overall, the cytokines related to Th1 and Th17 cells appear to be important in the infiltration of valvular tissue in the heart in RHD.…”