https://doi.org/10.1007/s00392-024-02526-y
1Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; 2Deutsches Herzzentrum München München, Deutschland
Background: Acute myocardial infarction (MI) causes systemic inflammation. This leads to leukocyte accumulation inside the cardiac tissue, promoting inflammation and removing dead cells. On day 3 after MI the reparative phase is initiated, where cardiac macrophages adopt anti-inflammatory phenotypes, which supports scar formation and cardiac healing. Resolution of inflammation needs to occur in a timely and coordinated fashion and overzealous inflammation leads to adverse cardiac remodeling after MI.
Objective: To correlate persistent inflammation and delayed resolution of inflammation (as indicated by sustained elevated leukocyte counts on day 3 after MI) with infarct size and clinical outcome in patients presenting with acute ST-elevation myocardial infarction (STEMI).
Methods and Results: In this retrospective study, we analyzed data of STEMI patients treated with primary percutaneous coronary intervention (PPCI) from a historical cohort (1155 patients, 2002-2007) and a contemporary cohort (698 patients, 2014-2022). In both cohorts we grouped patients in tertiles according to leukocyte counts on day 3 after MI. Leukocyte count on day three was available in 976 (84,5%) and 468 (67%) respectively. In the historical cohort, groups were as follows: tertile 1 (T1, n=332; interquartile range [IQR] 0.81 – 7.70 [109/l]), tertile 2 (T2, n=319; IQR 7.71 – 9.70 [109/l]) and tertile 3 (T3, n=325; IQR 9.71 – 24.95 [109/l]). Serial single-photon emission computerized tomography imaging was available on admission and 7 to 14 days. Patients with elevated leukocyte counts after 72h (T3 group) showed greatest area at risk and infarct size: myocardial area at risk before PPCI (median) was 20.0% (IQR 11.0–36.0%) in T1, 25.0% (IQR 14.0–40.0%) in T2 and 27.4% (IQR, 15.0–51.0%) of the left ventricle in T3. The final infarct size in the 7 to 14 days scintigraphy (median) was 7.0% (IQR 1.0–17.0%) in T1, 12.0% (IQR 3.0–24.7%) in T2 and 13.0% (IQR 5.0–30.0%) of the left ventricle in T3. In line with these scintigraphic findings, peak creatine kinase myocardial band (CK-MB) values, as an enzymatic estimate of the infarct size, were also highest in T3. Additionally left ventricular ejection fraction (LV-EF) was lowest in the T3. One-year follow-up for all-cause mortality was available in 911 (78.9%) patients. At one year, 8 patients in T1, 7 patients in T2 and 22 patients in T3 had died (Kaplan–Meier estimates of 1-year mortality: 2,6%, 2.3% and 7.3%, respectively (log-rank test: T1 vs. T3: p=0.01; T2 vs. T3: p=0.03). In the contemporary cohort, groups were as follows: T1 (n=157; IQR 1.00 – 8.12 [109/l]), T2 (n=156; IQR 8.13 – 10.41 [109/l] and T3 (n=157; IQR 10.43 – 29.2 [109/l]. As in the historical cohort, we found that patients with elevated leukocyte counts after 72h (T3 group) showed greatest enzymatic infarct size, estimated by peak CK-MB values and reduced LV-EF. One-year follow-up for all-cause mortality was available in 468 (100%) patients. At one year, 6 patients in T1, 13 patients in T2 and 25 patients in T3 had died (Kaplan–Meier estimates of 1-year mortality: 3.8%, 8.3% and 15.9%, respectively (log-rank test: T1 vs. T3: p<0.005, T2 vs. T3: p=0.004).
Conclusion: Persistent inflammation, estimated by elevated leukocyte counts 72h after STEMI, is associated with poorer outcomes at one year in both cohorts. These findings highlight the importance of a timely resolution of inflammation following MI.