The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.

Background/Objectives: Cardiac magnetic resonance (CMR) imaging provides a comprehensive assessment of myocardial injury after ST-segment elevation myocardial infarction (STEMI), yet the relative prognostic value of segmental infarct zone parameters compared with global indices for predicting left ventricular (LV) functional recovery remains incompletely defined. This study aimed to determine whether segmental infarct zone functional and structural CMR parameters provide prognostic information for LV functional recovery after a first STEMI treated with primary percutaneous coronary intervention (PCI). Methods: In this prospective single-center study, 93 patients with a first STEMI (median age 61 years; 77% male) underwent CMR at baseline (median 3 days post-PCI) and at a 6-month follow-up. The comprehensive CMR assessment included cine imaging for volumetric and feature-tracking strain analysis, T1 and T2 mapping, and late gadolinium enhancement (LGE) for infarct size (IS) and microvascular obstruction (MVO) quantification. The myocardial segments were classified as infarcted, adjacent, or remote based on the LGE distribution. The primary outcome was unfavorable LV functional recovery, defined as failure to achieve an absolute increase of >10 percentage points in the LV ejection fraction (LVEF) or a follow-up LVEF ≤ 50%. Results: At the 6-month follow-up, significant reverse remodeling was observed: the LVEF improved from 49.0% [40.7–52.4] to 55.8% [47.9–59.9] (p < 0.001), the LV end-systolic volume decreased from 91.8 mL [75.1–113.8] to 80.8 mL [61.9–108.3] (p = 0.005), and the relative IS decreased from 30.9% [18.9–45.5] to 19.0% [11.1–31.3] of LV mass (p < 0.001). At the follow-up, MVO was no longer detectable in any patient. Unfavorable functional recovery occurred in 17 patients (18.3%). In the multivariable analysis, the infarct zone circumferential strain (CS) was the strongest independent predictor of unfavorable recovery (OR 8.81; 95% CI 1.98–39.28; p = 0.004), followed by the relative IS (OR 4.02; 95% CI 1.03–15.73; p = 0.045) and a lower infarct zone post-contrast T1 (OR 4.40; 95% CI 1.12–17.36; p = 0.034). Conclusions: Segmental infarct zone characteristics—particularly circumferential strain, post-contrast T1, and infarct size—provide clinically relevant prognostic information for LV functional recovery after STEMI. The infarct zone CS offers incremental predictive value beyond its structural parameters, reflecting the residual contractile reserve and myocardial viability.

Background: Adverse left ventricular remodeling (ALVR) remains an important complication after ST-segment elevation myocardial infarction (STEMI) despite timely reperfusion therapy. Early circulating biomarkers reflecting thromboinflammatory and eicosanoid-related pathways may improve identification of patients at risk of unfavorable remodeling. Objectives: To investigate whether platelet count, 20-hydroxyeicosatetraenoic acid (20-HETE), 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], and NETosis activity measured on the morning after reperfusion therapy are associated with serial cardiac magnetic resonance (CMR)-defined ALVR after first STEMI. Methods: In this prospective single-center study, 93 patients with first STEMI treated with reperfusion therapy, including primary percutaneous coronary intervention (PCI) in 87 patients and thrombolysis followed by PCI underwent baseline CMR at a median of 4 days after PCI and repeat CMR at 6 months. ALVR was defined as a ≥12% increase in both left ventricular end-diastolic volume and left ventricular end-systolic volume at follow-up. Fasting blood samples obtained on the morning after PCI were used to measure platelet count, 20-HETE, 15(S)-HETE, and NETosis activity. Univariable and multivariable logistic regression and receiver operating characteristic analyses were performed. A secondary exploratory analysis evaluated predictors of absolute improvement in left ventricular ejection fraction (LVEF) of ≥10%. Results: ALVR occurred in 19 of 93 patients (20.4%). Patients with ALVR had lower platelet count and lower 20-HETE levels at baseline. In the multivariable model, lower platelet count (OR 0.981, 95% CI 0.965–0.996; p = 0.015) and lower 20-HETE (OR 0.985, 95% CI 0.970–1.000; p = 0.047) were independently associated with ALVR, whereas urea was not significant. In receiver operating characteristic analysis, 20-HETE showed the highest discriminatory ability for ALVR (AUC 0.713, 95% CI 0.594–0.833; p < 0.001), followed by platelet count (AUC 0.670, 95% CI 0.546–0.794; p = 0.007). By contrast, 15(S)-HETE and NETosis activity were not significant discriminators in the primary analyses. Overall LV function improved during follow-up, with LVEF increasing from 49.0% to 56.0% (p < 0.001). In secondary exploratory analysis, higher HDL was independently associated with LVEF improvement of ≥10% (OR 7.84, 95% CI 1.26–48.99; p = 0.028). Conclusions: Lower platelet count and lower 20-HETE measured on the morning after PCI were independently associated with subsequent CMR-defined ALVR after first STEMI. Platelet count may serve as a simple, clinically accessible marker of risk, while 20-HETE suggests a potential role of eicosanoid-related pathways in remodeling process.

The formation of extracellular traps (ETs) through ETosis has emerged as a key mechanism in immunothrombosis. However, the temporal dynamics and clinical significance of ETosis in coronary thrombi of ST-elevation myocardial infarction (STEMI) patients remain incompletely understood. We investigated whether ETosis burden increases with thrombus age and is associated with DNASE1 and TREX1 genetic variants as well as impaired myocardial reperfusion. Thrombus aspirates from 81 STEMI patients undergoing primary percutaneous coronary intervention were histologically classified as fresh (n = 41) or lytic (n = 40). ETosis was quantified by citrullinated histone H3 (CitH3) immunohistochemistry and digital image analysis, complemented by multiplex staining for myeloperoxidase (MPO), CD68, caspase 3, and CD61. Plasma ET-related markers and genotyping of DNASE1 (rs1053874) and TREX1 (rs11797) were also performed. CitH3-positive cells were present in all thrombi but were more abundant in lytic (older) thrombi compared with fresh thrombi (1348 vs. 591 cells/mm², p < 0.001). Increased ETosis was associated with neutrophil and macrophage infiltration, apoptosis, prolonged ischemia time, elevated systemic inflammation (neutrophil–lymphocyte ratio and C-reactive protein), and impaired myocardial reperfusion (lower TIMI flow grades). Moreover, the DNASE1 GG genotype was associated with higher densities of MPO- and CD68-positive cells, whereas the TREX1 CC genotype was associated with increased densities of CitH3-, MPO-, and CD68-positive cells. This study demonstrates that ETosis increases with coronary thrombus maturation and is associated with local inflammation and impaired reperfusion in STEMI. Genetic variants in DNASE1 and TREX1 may modulate inflammatory cell accumulation within thrombi. These findings suggest ETosis as a potential therapeutic target, particularly in patients with delayed presentation.