Left Ventricular Unloading by Microaxial Flow Pump Promotes Cardiac Recovery in Patients Undergoing Myocardial Infarction Through Limiting the Induction of Cellular Senescence

All articles of this category (opens in new window) Background: Cardiogenic shock (CS) following myocardial infarction (MI) in patients undergoing primary coronary intervention is characterized by ischemia–reperfusion injury, which leads to induction of cellular senescence in the myocardium. Senescent cells release pro-inflammatory/fibrotic mediators, compiled as the senescence-associated secretory phenotype (SASP), which drive adverse remodeling. Mechanical circulatory support with temporary microaxial flow devices (Impella) is often applied in CS after MI. Notably, several patients show sustained recovery after Impella-explantation, suggesting that left ventricular (LV) unloading may attenuate senescence induction and enhance functional recovery. Methods: Serum samples from 14 patients with CS after MI treated with Impella support were analyzed at baseline, and on days 1, 3, and 7 after implantation. Patients were stratified according to their degree of cardiac functional improvement: moderate recovery was defined as an improvement of 10 to 20% in LV ejection fraction (LVEF), and strong recovery as an LVEF improvement of > 20%. To assess senescence induction, Multi- and Single-ELISA were performed to quantify SASP factors. Moreover, DPP4-expression was assessed, a novel senescence biomarker expressed on extracellular vesicles (EVs) deriving from senescent cells, thus correlating with their abundance in tissues. Therefore, E vs. were isolated from serum samples, lysed, and DPP4 expression assessed using ELISA. Results: Impella therapy was associated with a reduction in circulating pro-inflammatory SASP-factors, including MCP-1, IL-1β, IL-1α, and TNF-α ( p < 0.1), with a more pronounced decrease in patients with greater functional recovery ( p < 0.05). Consistently, the cardiomyocyte-specific SASP-factor GDF15, implicated in fibrosis and heart failure following MI, declined more profoundly in patients exhibiting strong recovery ( p < 0.01). Pro-fibrotic SASP-factors, including VEGF, IL-17, and sCD40L, followed a similar trend ( p < 0.05). Most importantly, the expression of DPP4 declined significantly more in patients showing strong recovery after 3 days of Impella support ( p < 0.01), indicating diminished senescence induction. Conclusion: Our data provide novel mechanistic insights suggesting that Impella support in patients experiencing CS after MI promotes myocardial recovery through limiting senescence induction. Evaluating senescence biomarkers during Impella therapy may support the identification of patients with cardiac recovery. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany