Early post-reperfusion inflammatory trajectories and 6-month mortality after acute myocardial infarction: insights from the TIRANA-ACS prospective registry

Background/Introduction Inflammation plays a central role in myocardial healing and ventricular remodelling after acute myocardial infarction (AMI). Current post-AMI risk stratification relies predominantly on infarct severity and left ventricular function, while the prognostic significance of early temporal inflammatory changes following reperfusion remains uncertain. Purpose To determine whether early post-reperfusion inflammatory trajectories, assessed by serial neutrophil-to-lymphocyte ratio (NLR) measurements within the first 48 hours after percutaneous coronary intervention (PCI), are associated with mortality and cardiovascular events. Methods The TIRANA-ACS registry prospectively enrolled 900 consecutive patients aged 18–85 years presenting with ST / non–ST-segment elevation myocardial infarction (STEMI / NSTEMI) treated with PCI. NLR was measured at admission, 24h, and 48h and a validated cut-off of ≥4 was applied. Patients were classified into four predefined inflammatory trajectories: (1) persistently normal (<4 at all times), (2) progressive activation (≥4 with rising trend), (3) resolving (≥4 with decreasing trend), and (4) biphasic (rise at 24h followed by fall at 48h). The primary endpoint was 6-month all-cause mortality; secondary endpoints included in-hospital mortality, cardiovascular death, major adverse cardiovascular events (MACE: death, recurrent MI, or unplanned revascularization), and heart failure hospitalization. Multivariable logistic regression was adjusted for prespecified clinically relevant confounders: age, STEMI presentation, peak troponin, baseline LVEF, cardiogenic shock, and CRP. Results Complete serial data were available for 892 patients (67.3±10.7 years; 23.3% female; 49.7% STEMI; median LVEF 45% [IQR 40–50]). Trajectory distribution: persistently normal 28.4%, progressive activation 18.9%, resolving 28.7%, biphasic 24.0% . Among 758 patients with follow-up, 6-month mortality was 8.7%, varying significantly across trajectories (p<0.001): persistently normal 1.9%, progressive activation 18.2%, resolving 7.8%, biphasic 10.1% (Figure 1). After multivariable adjustment, progressive activation was independently associated with higher mortality versus persistently normal (adjusted OR 4.60, 95% CI 1.32–16.08; p=0.017). Resolving (adjusted OR 2.40, 95% CI 0.66–8.75; p=0.185) and biphasic (adjusted OR 2.80, 95% CI 0.78–10.04; p=0.114) trajectories were not significant. Similar trends were observed for secondary endpoints, including MACE and heart failure hospitalization. Conclusions Early post-reperfusion inflammatory trajectories, assessed by serial NLR measurements, are independently associated with 6-month mortality after AMI. Progressive inflammatory activation identifies a high-risk phenotype, indicative of impaired inflammatory resolution. Serial inflammatory assessment may facilitate early phenotypic risk stratification and guide interventions targeting residual inflammatory risk.