Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction.

Circulating monocytes have different subsets, including classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2-14.8, p = 0.02), for CD14+/CD16++/CCR2+ cells was 3.82 (95% CI 1.06-13.7, p = 0.04), for CD14+/CD16++/CD42b+ cells was 3.37 (95% CI 1.07-10.6, p = 0.03), for CD14+/CD16++/CD11b+ was 5.17 (95% CI 1.4-18.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0-28.5, p = 0.002). CD14++CD16-, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings.

Regional end-systolic circumferential strain demonstrates compensatory segmental contractile function in patients with ST-segment elevation myocardial infarction.

Myocardial strain has shown tremendous promise as a potential diagnostic tool for characterizing ventricular function. With regards to myocardial infarction, global circumferential strain (CS) can be used to assess overall function, while regional CS can identify local alterations in contractility. Currently, there is a lack of data related to regional strain in patients with ST-segment elevation myocardial infarction (STEMI). Thus, the goal of this study was to quantify regional strain patterns in STEMI and normal control patients, measuring both peak CS and end-systolic (ES) CS in the mid-ventricular region. This was done by conducting cardiac magnetic resonance (CMR) imaging acutely after STEMI patients underwent primary percutaneous coronary intervention. The CMR datasets were then analyzed using feature-tracking of the cine images. The patients were broken into three groups: (1) control patients (N = 18), (2) STEMI patients with ejection fraction (EF) ≥ 50% (N = 20), and (3) STEMI patients with EF < 50% (N = 20). The key result of the analysis was that ES CS detected a significant increase in the magnitude of strain in the non-infarcted tissue of STEMI patients with EF ≥ 50% when compared to STEMI patients with EF < 50%, whereas peak CS did not detect any differences. This implies that the tissue in this region is contracting more strongly compared to non-infarcted tissue in STEMI patients with EF < 50%. Thus, regional ES CS could potentially be utilized as a diagnostic tool for assessing STEMI patients, by detecting regional changes in contractility after PCI, which could assist in treatment planning.

Comparative Effectiveness of Anti-Inflammatory Drug Treatments in Coronary Heart Disease Patients: A Systematic Review and Network Meta-Analysis.

METHODS: We conducted a network meta-analysis of randomized controlled trials that studied the effects of anti-inflammatory medications on cardiovascular outcomes of coronary artery disease patients. We searched the electronic database until March 2020 for relevant studies. RESULTS: Nineteen trials examining the efficacy of eight anti-inflammatory medications (pexelizumab, anakinra, colchicine, darapladib, varespladib, canakinumab, inclacumab, and losmapimod) were selected for analysis. Overall, there is no statistically significant difference in all-cause mortality, cardiovascular mortality, revascularization, and major cardio and cerebrovascular events (MACCE) with the use of anti-inflammatory drugs. However, we found the use of colchicine significantly reduces the odds of developing stroke by approximately 75% (OR 0.26, CI 0.10-0.63). Colchicine use was also associated with a lower risk of revascularization and MACCE compared to the other agents. Our subgroup analyses comparing the timing of medication initiation (within 7 days vs. >7 days) and clinical presentation (ACS vs. non-ACS) revealed a significant reduction in the risk of recurrent MI in the group that received medication after seven days (OR 0.92, CI 0.86-0.99) and the non-ACS group (OR 0.88, CI 0.80-0.98). CONCLUSION: Although many anti-inflammatory medications have failed to reduce adverse cardiovascular outcomes in the CAD population, selected medications show promise among subgroups of patients without ACS or after the first week following an acute ischemic event. Future studies examining the proper timing and targetable anti-inflammatory pathways are warranted.

Cangrelor in addition to standard therapy reduces cardiac damage and inflammatory markers in patients with ST-segment elevation myocardial infarction.

Although P2Y12 receptor blockers have become a standard, adjunctive therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the optimal regimen has not been established. We performed a prospective, open-label, randomized study to investigate the effect of cangrelor administration on platelet function and inflammation in patients with primary PCI (PPCI). Twenty-two patients were randomized to receive either cangrelor and ticagrelor or ticagrelor alone (standard group) before PPCI. Platelet reactivity was evaluated at baseline (before PCI), 10 min and the end of the procedure. At baseline, there was no significant difference in platelet reactivity between both groups, whereas platelets were significantly inhibited at 10 min after initiating cangrelor vs. standard (adenosine-diphosphate-induced aggregation 102.2 ± 24.88 vs. 333.4 ± 63.3, P < 0.05 and thrombin-receptor-activating-peptide-induced aggregation 285.8 ± 86.1 vs. 624.8 ± 106.0, P < 0.05). Lower platelet aggregation in the cangrelor group persisted but the difference was reduced by the end of the procedure. Circulating inflammatory cells, pro-inflammatory cytokines, total elastase, and surrogates of neutrophil extracellular traps (total elastase-myeloperoxidase complexes) were significantly lower in the cangrelor compared to the standard therapy group at 6 h after randomization. There was a trend towards reduction in cardiac damage in the cangrelor group as reflected by the changes in late gadolinium enhancement between 48 h and 3 months after STEMI. Early administration of cangrelor in STEMI patients was associated with more effective platelet inhibition during PPCI and significantly dampened the deleterious inflammatory response compared to standard therapy (NCT03043274).

Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction.

OBJECTIVE: Acute myocardial infarction (AMI) initiates pathological inflammation which aggravates tissue damage and causes heart failure. Lysophosphatidic acid (LPA), produced by autotaxin (ATX), promotes inflammation and the development of atherosclerosis. The role of ATX/LPA signaling nexus in cardiac inflammation and resulting adverse cardiac remodeling is poorly understood. APPROACH AND RESULTS: We assessed autotaxin activity and LPA levels in relation to cardiac and systemic inflammation in AMI patients and C57BL/6 (WT) mice. Human and murine peripheral blood and cardiac tissue samples showed elevated levels of ATX activity, LPA, and inflammatory cells following AMI and there was strong correlation between LPA levels and circulating inflammatory cells. In a gain of function model, lipid phosphate phosphatase-3 (LPP3) specific inducible knock out (Mx1-Plpp3Δ) showed higher systemic and cardiac inflammation after AMI compared to littermate controls (Mx1-Plpp3fl/fl); and a corresponding increase in bone marrow progenitor cell count and proliferation. Moreover, in Mx1- Plpp3Δ mice, cardiac functional recovery was reduced with corresponding increases in adverse cardiac remodeling and scar size (as assessed by echocardiography and Masson's Trichrome staining). To examine the effect of ATX/LPA nexus inhibition, we treated WT mice with the specific pharmacological inhibitor, PF8380, twice a day for 7 days post AMI. Inhibition of the ATX/LPA signaling nexus resulted in significant reduction in post-AMI inflammatory response, leading to favorable cardiac functional recovery, reduced scar size and enhanced angiogenesis. CONCLUSION: ATX/LPA signaling nexus plays an important role in modulating inflammation after AMI and targeting this mechanism represents a novel therapeutic target for patients presenting with acute myocardial injury.