Restoration of Circulating Myeloid Dendritic Cells Following Mitral Valve Transcatheter Edge-to-Edge Repair Suggests Immune Involvement in Volume Overload Heart Failure

R. J. Sauter (Mannheim)¹, Y. Zhang (Tübingen)², J. Patzelt (München)³, F. Emschermann (Tübingen)⁴, H. Magunia (Tübingen)⁵, P. Rosenberger (Tübingen)⁵, C. Schlensak (Tübingen)⁶, J. Schreieck (Tübingen)², K. Stellos (Mannheim)⁷, T. Geisler (Tübingen)², M. Gawaz (Tübingen)², H. Langer (Mannheim)^1
1Universitätsklinikum Mannheim GmbH I. Medizinische Klinik Mannheim, Deutschland; ²Universitätsklinikum Tübingen Innere Medizin III, Kardiologie und Kreislauferkrankungen Tübingen, Deutschland; ³Augustinum Klinik München Kardiologie und Intensivmedizin München, Deutschland; ⁴Universitätsklinikum Tübingen Innere Medizin III, Kardiologie und Angiologie Tübingen, Deutschland; ⁵Universitätsklinikum Tübingen Klinik für Anästhesiologie und Intensivmedizin Tübingen, Deutschland; ⁶Universitätsklinikum Tübingen Klinik für Thorax-, Herz- Gefäßchirurgie Tübingen, Deutschland; ⁷Universitätsmedizin Mannheim der Universität Heidelberg Institut für Herz-Kreislaufforschung Mannheim, Deutschland

Aim:
Mitral valve transcatheter edge-to-edge repair (M-TEER) results in positive left ventricular (LV) remodelling in mitral regurgitation (MR) with heart failure (HF). Dendritic cells (DCs) are known to play a vital role in left ventricular (LV) remodelling following myocardial ischemia and myocarditis. However, their immune-modulating role in heart failure (HF), particularly in mitral regurgitation (MR), remains unclear. Here, we investigated the number and phenotype of circulating DC precursors in patients undergoing M-TEER to uncover potential crosstalk between HF and immune regulation.

Methods:
Using flow cytometry, we quantified circulating myeloid (mDC) and plasmacytoid (pDC) dendritic cells, along with surface expression of the co-stimulatory molecules CD40, CD86, and HLA-DR, and the adhesion molecule CD11a, in healthy controls (n=11) and patients with MR at baseline (n=80) and at 6-month follow-up. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and CXCL5 were measured by ELISA/multiplex assay. Echocardiographic parameters including left ventricular end-diastolic diameter (LVEDD) and functional capacity by 6-minute walk test (6MWT) were assessed before M-TEER and at follow-up.

Results:
Compared to controls (mDC 10.38±1.07/µl and pDC 5.44±0.69/µl), MR patients showed significantly reduced circulating mDC precursors (7.05±0.47/µl, P<0.01) but no significant difference in pDC precursors (5.10±0.4/µl). Surface expression of CD11a on mDCs was significantly increased in MR patients compared to controls (mean fluorescence intensity [MFI] 160 vs. 130, P<0.05). At 6 months after M-TEER, mDC and pDC numbers increased significantly (8.93±0.54/µl and 7.04±0.65/µl, respectively, P<0.01), accompanied by decreased CD11a expression. M-TEER was associated with reductions in inflammatory markers, including CRP, IL-6, and CXCL5, decreased LVEDD, and improved 6MWT distance. Notably, changes in mDC numbers positively correlated with functional improvement and inversely correlated with CRP and IL-6 levels.

Conclusions:
Our findings suggest that circulating DC precursors and CXCL5 are involved in the inflammatory response associated with MR-related HF and that M-TEER modifies their levels and phenotype alongside clinical improvement. This highlights a novel immune dimension in the pathophysiology of MR and HF.