Comparison of analysis strategies to assess sex differences in microvascular reperfusion using near-infrared spectroscopy.

The near-infrared spectroscopy (NIRS) vascular occlusion test (VOT) assesses microvascular reperfusion. Two strategies have been used to quantify reperfusion following reactive hyperemia, but it is unclear whether both yield similar results when comparing biological sex. This study aimed to determine whether sex differences in NIRS-based microvascular reperfusion are similarly apparent using the 10-s reactive hyperemia slope of the tissue saturation index (StO2) signal (slope 2) and the halftime to maximal reperfusion (T ½). Healthy, recreationally active males (n = 31) and females (n = 31) between 18 and 82 years took part in this study. A NIRS VOT was performed on the tibialis anterior muscle, and reperfusion was quantified using slope 2 (% s-1) and T ½ (s). Adipose tissue thickness (ATT) was higher in females (P = 0.009), which was associated with a lower StO2 (P = 0.001) and oxygenated hemoglobin (O2Hb) (P = 0.05) signal range. The StO2 slope 2 was significantly steeper in males versus females (P = 0.001) but not after correcting for ATT (P = 0.295). There were no sex differences in StO2 T ½ (P = 0.067) or O2Hb T ½ (P = 0.197). In a subset of males (n = 26) and females (n = 21) with similar ATT, there were no sex differences in StO2 slope 2 (P = 0.068), StO2 T ½ (P = 0.491), or O2Hb T ½ (P = 0.899). An ATT-corrected StO2 slope 2 or the T ½ approach is recommended for analysis of NIRS-based microvascular reperfusion when differences in ATT are present between sexes.NEW & NOTEWORTHY Sex differences in near-infrared spectroscopy (NIRS)-based microvascular reperfusion have been previously reported. We found that greater adipose tissue thickness in females reduces kinetic measures of NIRS-based microvascular reperfusion. Sex differences are eliminated when performing an adipose tissue thickness correction, when the NIRS signal range is accounted for, or when adipose tissue thickness is similar between sexes. This highlights the importance of considering factors that affect NIRS signals, such as adipose tissue thickness, when drawing comparisons between groups.

Comparison of skeletal muscle oxidative function in young, middle-aged, and older males and females with similar physical activity levels.

Optimal skeletal muscle oxidative function (microvascular reactivity and mitochondrial capacity) is an integral part of healthy aging and is related to physical function and quality of life. We aimed to extend upon the understanding of skeletal muscle oxidative function with healthy aging in males and females across the adult life span. Younger (N = 22; 11 males), middle-aged (N = 19; 10 males), and older (N = 21; 10 males) adults completed this study. Time spent in moderate and vigorous physical activity was self-reported and similar among groups. Near-infrared spectroscopy was used to investigate skeletal muscle microvascular reperfusion [oxyhemoglobin-myoglobin (O2Hb+Mb) half-time to peak hyperemia (T½)], mitochondrial capacity [muscle oxygen consumption (mV̇o2) recovery rate constant], and walking tissue oxygen saturation ([Formula: see text]) of the tibialis anterior (TA) muscle at seven incremental walking speeds. Mitochondrial capacity was not significantly different across groups (P = 0.07). Younger adults exhibited significantly slower T½ compared with older adults (P = 0.006) and middle-aged adults (P = 0.025). There were no observed sex differences for mitochondrial capacity (P = 0.442) or T½ (P = 0.402). Older adults exhibited significantly lower [Formula: see text] across all walking speeds compared with younger adults (P = 0.003). Mitochondrial capacity and microvascular reperfusion are maintained in middle and older age, with no sex differences in either outcome. However, in older adults whole body functional movement, such as walking, may place an additional demand on the TA as a compensatory response to lower functional reserve not evident in distinct measures of mitochondrial capacity and microvascular reperfusion.NEW & NOTEWORTHY Compared with younger adults, mitochondrial capacity and microvascular reperfusion of the tibialis anterior (TA) muscle are well maintained in similarly physically active middle-aged and older adults, with no sex differences observed in either outcome. However, greater tissue oxygen utilization in older adults during walking highlights how whole body functional movement may place an additional demand on the TA that reveals a potential compensatory response to lower functional reserve not evident in distinct measures of mitochondrial capacity and microvascular reperfusion.

Microvascular reperfusion of fibrinolysis followed by percutaneous coronary intervention versus primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction.

Background: Primary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI. Methods: STEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022. Results: In total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups. Conclusions: In eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.

Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment.

OBJECTIVES: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. MATERIALS AND METHODS: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. RESULTS: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. CONCLUSIONS: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Quantitative 3D analysis of tissue damage in a rat model of microembolization.

There is a discrepancy between successful recanalization and good clinical outcome after endovascular treatment (EVT) in acute ischemic stroke patients. During removal of a thrombus, a shower of microemboli may release and lodge to the distal circulation. The objective of this study was to determine the extent of damage on brain tissue caused by microemboli. In a rat model of microembolization, a mixture of microsphere (MS) sizes (15, 25 and 50 µm diameter) was injected via the left internal carotid artery. A 3D image of the left hemisphere was reconstructed and a point-pattern spatial analysis was applied based on G- and K-functions to unravel the spatial correlation between MS and the induced hypoxia or infarction. We show a spatial correlation between MS and hypoxia or infarction spreading up to a distance of 1000-1500 µm. These results imply that microemboli, which individually may not always be harmful, can interact and result in local areas of hypoxia or even infarction when lodged in large numbers.

Novel Biomarkers, ST-Elevation Resolution, and Clinical Outcomes Following Primary Percutaneous Coronary Intervention.

Background Despite restoration of epicardial flow following primary percutaneous coronary intervention (PPCI), microvascular reperfusion as reflected by ST-elevation resolution (ST-ER) resolution remains variable and its pathophysiology remains unclear. Methods and Results Using principal component analyses, we explored associations between 91 serum biomarkers drawn before PPCI clustered into 14 pathobiologic processes (including NT-proBNP [N-terminal pro-B-type natriuretic peptide] as an independent cluster), and (1) ST-ER resolution ≥50% versus <50%; and (2) 90-day composite of death, shock, and heart failure. Network analyses were performed to understand interbiomarker relationships between the ST-ER groups. Among the 1160 patients studied, 861 (74%) had ST-ER ≥50% at a median 40 (interquartile range, 23-70) minutes following PPCI, yet both groups had comparable post-PPCI TIMI (Thrombolysis in Myocardial Infarction) grade 3 flow (86.6% versus 82.9%; P=0.25). ST-ER ≥50% was associated with significantly lower pre-PPCI concentrations of platelet activation cluster (particularly P-selectin, von Willebrand factor, and platelet-derived growth factor A) and NT-proBNP, including after risk adjustment. Across both ST-ER groups, strong interbiomarker relationships were noted between pathways indicative of myocardial stretch, platelet activation, and inflammation, whereas with ST-ER <50% correlations between iron homeostasis and inflammation were observed. Of all 14 biomarker clusters, only NT-proBNP was significantly associated with the 90-day clinical composite. Conclusions Suboptimal ST-ER is common despite achieving post-PPCI TIMI grade 3 flow. The cluster of platelet activation proteins and NT-proBNP were strongly correlated with suboptimal ST-ER and NT-proBNP was independently associated with 90-day outcomes. This analysis provides insights into the pathophysiology of microvascular reperfusion in ST-segment-elevation myocardial infarction and suggests novel pre-PPCI risk targets potentially amenable to enhancing tissue-level reperfusion following PPCI.

Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction.

Early mechanical reperfusion of the epicardial coronary artery by primary percutaneous coronary intervention (PCI) is the guideline-recommended treatment for ST-elevation myocardial infarction (STEMI). Successful restoration of epicardial coronary blood flow can be achieved in over 95% of PCI procedures. However, despite angiographically complete epicardial coronary artery patency, in about half of the patients perfusion to the distal coronary microvasculature is not fully restored, which is associated with increased morbidity and mortality. The exact pathophysiological mechanism of post-ischaemic coronary microvascular dysfunction (CMD) is still debated. Therefore, the current review discusses invasive and non-invasive techniques for the diagnosis and quantification of CMD in STEMI in the clinical setting as well as results from experimental in vitro and in vivo models focusing on ischaemic-, reperfusion-, and inflammatory damage to the coronary microvascular endothelial cells. Finally, we discuss future opportunities to prevent or treat CMD in STEMI patients.

Fragmented QRS complex is a prognostic marker of microvascular reperfusion and changes in LV function occur in patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

The present study aimed to investigate the in-hospital and long-term prognostic value of fragmented QRS complex (fQRS) for microvascular reperfusion and changes in left ventricular (LV) function in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). A total of 216 patients with STEMI undergoing primary PCI were included in the current study. Patients were divided into two groups based on the presence (n=126) or absence (n=90) of fQRS following electrocardiograms (ECGs) on admission. Following primary PCI and follow up, patients were divided into four groups based on new onset, resolution, persistence and absence of fQRS. Major adverse cardiac events were defined to include cardiovascular death, arrhythmia, heart failure, reinfarction and target vessel revascularization. The percentage of patients with heart failure and microvascular reperfusion differed significantly between the fQRS(+) and fQRS(-) groups. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), Peak creatine kinase-MB (CK-MB) and Troponin I levels were observed to be significantly higher in the fQRS(+) group compared with the fQRS(-) group. In univariate logistic regression analysis, left ventricular ejection fraction (LVEF), NT-proBNP, Troponin I, Peak CK-MB and microvascular reperfusion were found to be associated with fQRS. Multivariate analysis identified that LVEF, NT-proBNP, Troponin I and microvascular reperfusion may be independent predictors of fQRS. The presence of fQRS was demonstrated to be associated with left ventricular dysfunction at follow up assessments. The presence of fQRS was not only significantly associated with myocardial microvascular reperfusion and left ventricular function, but was also a prognostic marker in STEMI.

Effect of Hematologic Parameters on Microvascular Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

OBJECTIVES: Despite the significant role of certain hematologic parameters in reperfusion injury, their relationship with microvascular reperfusion remains not well understood. Therefore, our objective was to evaluate the relationship between hematologic parameters at admission and microvascular reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (primary PCI). METHODS: A total of 213patients (mean age: 57.5 ± 11 years) with STEMI were included. Blood samples were obtained from all patients prior to primary PCI. Electrocardiographic recordings were made for the evaluation of ST-segment resolution (STR) before and after primary PCI. Angiographic assessment in the infarct-related artery was performed using the myocardial blush grade (MBG) and thrombolysis in myocardial infarction (TIMI) flow. Patients were categorized into 2 groups as those with impaired microvascular reperfusion (STR <70%, TIMI: 0-1, and MBG: 0-1) and those with normal microvascular reperfusion (STR >70%, TIMI: 2-3, and MBG: 2-3). RESULTS: Of the overall study group, 139, 105, and 69 patients had an STR of <70%, MBG of 0-1, and TIMI of 0-1, respectively. Demographic parameters in both groups are shown in the tables. Patients with impaired microvascular reperfusion were found to have higher white blood cell (WBC) count, neutrophil count, lymphocyte count, and mean platelet volume (MPV). Neutrophil-lymphocyte ratio and platelet count were similar between the 2 groups. Correlation analysis showed a negative correlation between lymphocyte count and STR (r: -.195, P: .004), lymphocyte count and TIMI flow(r: -.09, P: .14), and lymphocyte count and MBG (r: -.211, P: .002). CONCLUSION: Our results suggest that higher WBC count and MPV at admission are independent predictors of impaired microvascular perfusion in patients with STEMI. On the other hand, a negative correlation was found between lymphocyte count and impaired microvascular perfusion. Specifically, elevated lymphocyte count seemed to indicate the presence of impaired microvascular reperfusion in patients with STEMI.