Christian Graesser, Johannes Krefting, Marius Schwab, Hendrik Scheidhauer, Sophie Novacek, Nicolás López Armbruster, Julia Hinterdobler, Svenja Rapelius, Amos Romer, Philipp M. Rumpf, Ferdinand Roski, Tobias Lenz, Felix Voll, Baiba Vilne, Teresa Trenkwalder, Moritz von Scheidt, Erion Xhepa, Michael Joner, Salvatore Cassese, Sabine Steffens, Christian Weber, Heribert Schunkert, Gjin Ndrepepa, Adnan Kastrati, Thorsten Kessler, Aldo Moggio, Hendrik B. Sager
AIMS: Acute myocardial infarction (MI) induces a systemic inflammatory response that usually resolves within days, but the prognostic impact of persistent inflammation is uncertain. We assessed whether sustained leukocytosis after ST-segment elevation myocardial infarction (STEMI) relates to infarct size, left ventricular function, and clinical outcomes. METHODS AND RESULTS: In >1,700 STEMI patients treated with primary percutaneous coronary intervention, leukocytes peaked on admission and typically normalized by day 3. Patients were stratified by leukocyte tertiles at admission and day 3. High day 3 leukocyte counts were associated with larger infarct size (scintigraphy; peak creatine kinase-myocardial band and troponin T), worse left ventricular function in hospital and at 6 months, and higher 1- and 5-year mortality. Patients whose leukocyte counts declined had better recovery, whereas persistent leukocytosis marked the poorest outcomes. Monocyte RNA sequencing showed post-MI transcriptomic reprogramming, and murine MI models recapitulated a similar systemic immune response. CONCLUSIONS: Persistent inflammation, particularly elevated leukocyte counts at day 3 post-MI, is associated with adverse remodeling and increased mortality after STEMI, identifying unresolved inflammation as a negative prognostic marker and potential therapeutic target.