Formononetin alleviates no reflow after myocardial ischemia-reperfusion via modulation of gut microbiota to inhibit inflammation.

Gut microflora plays an important role in relieving myocardial no-reflow (NR), formononetin (FMN) has potential effects on NR, however, the relationship between this effect and gut microflora remains unclear. This study aimed to evaluate the role of FMN in alleviating NR effects by regulating gut microflora. We used a myocardial NR rat model to confirm the effect and mechanism of action of FMN in alleviating NR. The rats were randomly divided into sham operation group (Sham), NR group, FMN group and sodium nitroprusside (SNP) group. Thioflavin S staining, Hematoxylin Eosin (HE), myocardial enzyme activity, ultrasonic cardiogram and RT-PCR detection showed that FMN could effectively reduce inflammatory cell infiltration, NR and ischemic area, improve cardiac structure and function and reduce TNF-α and NF-κB gene expression in NR rats. The results of 16S rRNA high-throughput sequencing showed that FMN could increase the abundance of anti-inflammatory bacteria such as Ligilaculum, Coprococcus, Blautia and Muribaculaceae and decrease the abundance of pro-inflammatory bacteria such as Treponema in Spirochaetota and Campylobacterota. The correlation between the differential bacteria in the gut microflora(anti-inflammatory bacteria and pro-inflammatory bacteria) and TNF-α and NF-κB, show that they had a strong correlation. Therefore, the anti-NR mechanism of FMN may be related to increasing the abundance of anti-inflammatory bacteria and reducing the abundance of pro-inflammatory bacteria to inhibit inflammation. This study provides innovative mechanistic insights into the relationship between gut microbiota and myocardial protection, suggesting potential strategy for future treatment of NR.

Cerebral blood flow from arterial spin labeling as an imaging biomarker of outcome after endovascular therapy for ischemic stroke.

Arterial spin labeling (ASL) is a contrast agent-free magnetic resonance imaging (MRI) technique to measure cerebral blood flow (CBF). We sought to investigate effects of CBF within the infarct on outcome and risk of hemorrhagic transformation (HT). In 111 patients (median age: 74 years, 50 men) who had undergone mechanical thrombectomy (MT) for ischemic stroke of the anterior circulation (median interval: 4 days between MT and MRI), post-stroke %CBF difference from pseudo-continuous ASL was calculated within the diffusion-weighted imaging (DWI)-positive infarct territory following lesion segmentation in relationship to the unaffected contralateral side. Functional independence was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days post-stroke. %CBF difference, pre-stroke mRS, and infarct volume were independently associated with functional independence in a multivariate regression model. %CBF difference was comparable between patients with and without HT. A subcohort of 10 patients with decreased infarct-CBF despite expanded Treatment in Cerebral Infarction (eTICI) 2c or 3 recanalization was identified (likely related to the no-reflow phenomenon). Outcome was significantly worse in this group compared to the remaining cohort. In conclusion, ASL-derived %CBF difference from the DWI-positive infarct territory independently predicted functional independence, but %CBF difference was not significantly associated with an increased risk of HT.

Glycoprotein IIb/IIIa Inhibitors in Acute Myocardial Infarction and Angiographic Microvascular Obstruction: The REVERSE-FLOW Trial.

BACKGROUND AND AIMS: Glycoprotein (GP) IIb/IIIa inhibitors are recommended in acute myocardial infarction (AMI) for bailout treatment in case of angiographic microvascular obstruction (MVO), also termed no-reflow phenomenon, after percutaneous coronary intervention (PCI) with, however, lacking evidence (class IIa, level C). METHODS: The investigator-initiated, international, multicenter REVERSE-FLOW trial randomized 120 patients with AMI and Thrombolysis In Myocardial Infarction flow grade ≤2 after primary PCI to optimal medical therapy with or without GP IIb/IIIa inhibitor. The primary endpoint was infarct size (%LV) assessed by cardiac magnetic resonance (CMR). Secondary endpoints included CMR-derived MVO and 30-day adverse clinical events. The trial is registered with ClinicalTrials.gov: NCT02739711. RESULTS: The population was predominantly male (76.7%) with a median age of 66 years and ST-elevation myocardial infarction in 73.3% of patients. Clinical and angiographic characteristics were well balanced between the cohorts. Patients in the treatment group (n=62) received eptifibatide (n=41) or tirofiban (n=21). Infarct size assessed by CMR imaging was similar in both study groups (25.4% of left ventricular mass [LV] vs. 25.2%LV; p=0.386). However, the number of patients with evidence of CMR-derived MVO (74.5% vs. 92.2%; p=0.017) and the extent of MVO (2.1%LV vs. 3.4%LV; p=0.025) were significantly reduced in the GP IIb/IIIa inhibitor group compared to controls. Thirty-day outcome showed an increased bleeding risk after GP IIb/IIIa inhibitor administration restricted to non-life-threatening bleedings (22.6% vs. 6.9%; p=0.016) without differences in all-cause mortality (4.8% vs. 3.4%; p=0.703). CONCLUSIONS: Bailout GP IIb/IIIa inhibition in AMI patients with angiographic MVO failed to reduce the primary endpoint infarct size but decreased CMR-derived MVO and led to an increase in non-fatal bleeding events.

Collateral is brain: Low perfusion triggers spreading depolarization and futile reperfusion after acute ischemic stroke.

Futile reperfusion is a phenomenon of inadequate perfusion despite successful recanalization after acute ischemic stroke (AIS). It is associated with poor patient outcomes and has received increasing interest due to its clinical diagnosis becoming more common. However, the underlying mechanisms remain elusive, and experimental studies are focused on the pathological background of futile reperfusion. Our recent study has confirmed that poor primary collateralization plays a crucial role in the insufficiency of reperfusion after AIS in mice. Specifically, the absence of primary collaterals in the circle of Willis (CoW) promoted the development of spreading depolarizations (SDs) during AIS. In our experimental stroke model, the occurrence of SDs during ischemia always predicted futile reperfusion. Conversely, in mice with a complete CoW, no SDs were observed, and reperfusion was complete. Importantly, the human CoW displays variation in the primary collaterals in approximately 50% of the population. Therefore, futile reperfusion may result from SD evolution in AIS patients. Our purpose here is to emphasize the crucial role of SD in the development of futile reperfusion. We propose that adequate collateral recruitment can prevent SD occurrence, leading to improved reperfusion and AIS outcomes.

Analysis of risk factors for PCI no-reflow in coronary heart disease and construction of related prediction models.

OBJECTIVE: To analyze the risk factors of percutaneous coronary intervention (PCI) no-reflow in patients with coronary heart disease (CHD) and construct a predictive nomogram model. METHODS: This retrospective study included 260 patients with CHD who underwent PCI in the Third Affiliated Hospital of Chongqing Medical University from January 2022 to December 2023. The subjects were divided into a PCI no-reflow group (n = 86) and normal reflow group (n = 174) based on thrombolysis in myocardial infarction (TIMI) blood flow grading. General data, PCI related data and laboratory indexes of patients were collected. Logistic regression was used to analyze the risk factors of no-reflow after PCI in CHD patients. Based on the significant variables from regression analysis, a nomogram prediction model was constructed by using R language. The accuracy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the decision curve was drawn to clarify the clinical utility of the model. Model performance metrics included area under the curve (AUC), accuracy, sensitivity and specificity. RESULTS: Multivariate logistic regression analysis showed that hypertension, cystatin C (Cys-C), hypersensitive c-reactive protein (hs-CRP) and platelet-to-lymphocyte ratio (PLR) were risk factors for no-reflow after PCI in CHD patients (OR > 1, P < 0.001), while ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS-13) and lymphocyte (LYM) were protective factors (OR < 1, P < 0.001). The nomogram prediction model based on the above risk factors showed good predictive value. The AUC of the nomogram prediction model in the training set was 0.967 (95% CI: 0.946-0.989), with a specificity of 0.923 and a sensitivity of 0.908. In the validation set, the AUC was 0.894 (95% CI: 0.817-0.971), with a specificity of 0.807 and a sensitivity of 0.857. The calibration curve indicated good agreement between the predicted and actual probabilities, and the decision curve showed clinical benefit across a range of threshold probabilities in both the training and validation sets (0.0-0.99). CONCLUSION: The risk factors affecting the occurrence of no-reflow after PCI in patients with CHD include hypertension, serum Cys-C, hs-CRP, PLR, ADAMTS-13 and LYM levels. The nomogram risk prediction model based on the above factors is valuable for identifying patients with high risk of no-reflow after PCI.

Machine learning prediction of no reflow in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Background: No-reflow (NRF) phenomenon is a significant challenge in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Accurate prediction of NRF may help improve clinical outcomes of patients. This retrospective study aimed at creating an optimal model based on machine learning (ML) to predict NRF in these patients, with the additional objective of guiding pre- and intra-operative decision-making to reduce NRF incidence. Methods: Data were collected from 321 STEMI patients undergoing pPCI between January 2022 and May 2023, with the dataset being randomly divided into training and internal validation sets in a 7:3 ratio. Selected features included pre- and intra-operative demographic data, laboratory parameters, electrocardiogram, comorbidities, patients' clinical status, coronary angiographic data, and intraoperative interventions. Post comprehensive feature cleaning and engineering, three logistic regression (LR) models [LR-classic, LR-random forest (LR-RF), and LR-eXtreme Gradient Boosting (LR-XGB)], a RF model and an eXtreme Gradient Boosting (XGBoost) model were developed within the training set, followed by performance evaluation on the internal validation sets. Results: Among the 261 patients who met the inclusion criteria, 212 were allocated to the normal flow group and 49 to the NRF group. The training group consisted of 183 patients, while the internal validation group included 78 patients. The LR-XGB model, with an area under the curve (AUC) of 0.829 [95% confidence interval (CI): 0.779-0.880], was selected as the representative model for logistic regression analyses. The LR model had an AUC slightly lower than XGBoost model (AUC 0.835, 95% CI: 0.781-0.889) but significantly higher than RF model (AUC 0.731, 95% CI: 0.660-0.802). Internal validation underscored the unique advantages of each model, with the LR model demonstrating the highest clinical net benefit at relevant thresholds, as determined by decision curve analysis. The LR model encompassed seven meaningful features, and notably, thrombolysis in myocardial infarction flow after initial balloon dilation (TFAID) was the most impactful predictor in all models. A web-based application based on the LR model, hosting these predictive models, is available at https://l7173o-wang-lyn.shinyapps.io/shiny-1/. Conclusions: A LR model was successfully developed through ML to forecast NRF phenomena in STEMI patients undergoing pPCI. A web-based application derived from the LR model facilitates clinical implementation.

The triglyceride-glucose index is associated with no-reflow phenomenon in STEMI patients with type 2 diabetes after percutaneous coronary intervention.

Background: The relationship between the triglyceride-glucose (TyG) index and no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute ST-segment elevation myocardial infarction (STEMI) remains unclear. This study aimed to investigate the relationship between baseline TyG index and no-reflow phenomenon in STEMI patients with T2DM after PCI. Methods: This study enrolled 695 patients with T2DM and STEMI from the General Hospital of Ningxia Medical University (2014-2019). Patients were divided into tertiles according to the TyG index levels. The incidence of no-reflow phenomenon was recorded. A multivariate regression model was developed to analyze the association between the baseline TyG index and no-reflow phenomenon. The linear association between the baseline TyG index and no-reflow phenomenon was explored using smooth curve fitting with parallel subgroup analyses. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of the TyG index. Results: A multivariate logistic regression model revealed that the TyG index was an independent risk factor of no-reflow phenomenon [OR = 3.23, 95%CI: 2.15-4.86, P < 0.001], and the occurrence of no-reflow phenomenon increased gradually with the increase of TyG index tertile interval (P < 0.001). Smooth curve fitting showed that the TyG index was linearly related to the risk of no-reflow. Subgroup analysis showed that they participated in this positive correlation. The area under the ROC curve (AUC) of the TyG index for evaluating the occurrence of no-reflow was 0.710 (95% CI: 0.640-0.780; P < 0.01). Conclusions: The TyG index is independently associated with no-reflow phenomenon, suggesting that the simple index of the TyG index can be used for risk assessment of no-reflow phenomenon after PCI in STEMI patients with T2DM.

Cardio- and Vasoprotective Effects of Quinacrine in an In Vivo Rat Model of Myocardial Ischemia/Reperfusion Injury.

This study aimed to investigate the cardioprotective effect of quinacrine in an in vivo model of myocardial ischemia/reperfusion injury. A 30-min regional myocardial ischemia followed by a 2-h reperfusion was modeled in anesthetized Wistar rats. Starting at the last minute of ischemia and during the first 9 min of reperfusion the rats in the control (n=8) and experimental (n=9) groups were injected with 0.9% NaCl and quinacrine solution (5 mg/kg), respectively. The area at risk and infarct size were evaluated by "double staining" with Evans blue and triphenyltetrazolium chloride. To assess vascular permeability in the area at risk zone, indocyanine green (ICG) and thioflavin S (ThS) were injected intravenously at the 90th and 120th minutes of reperfusion, respectively, to assess the no-reflow zone. The images of ICG and ThS fluorescence in transverse sections of rat hearts were obtained using a FLUM multispectral fluorescence organoscope. HR tended to decrease by 13% after intravenous administration of quinacrine and then recovered within 50 min. Quinacrine reduced the size of the necrotic zone (p=0.01), vascular permeability in the necrosis region, and the no-reflow area (p=0.027); at the same time, the area at risk did not significantly differ between the groups. Intravenous administration of quinacrine at the beginning of reperfusion of the rat myocardium reduces no-reflow phenomenon and infarct size.

Growth differentiation factor-15 as a biomarker of coronary microvascular dysfunction in ST-segment elevation myocardial infarction.

Background: The predictive value of growth differentiation factor-15 (GDF-15) in coronary microvascular dysfunction (CMD) following primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) patients is unclear. Methods: This study continuously recruited STEMI patients treated with PPCI at the Chest Pain Center of Qilu Hospital of Shandong University from April 2023 to December 2023. Blood samples were taken before PPCI and the level of circulating GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the patients were divided into CMD and Control group according to angiographic microvascular resistance (AMR) (cut-off value 2.50 mmHg*s/cm). The differences in GDF-15 expression levels between the two groups were compared, and the predictive value of GDF-15 for CMD was systematically evaluated. Results: A total of 134 patients, with an average age of 59.78 ± 12.69 years and 75.37 % being male, were included in this study. Multivariable logistic regression revealed a significant association between GDF-15 and CMD (adjusted OR = 2.505, 95 % CI: 1.661-3.779, P < 0.001). The area under the curve (AUC) of GDF-15 for CMD was 0.782 (95 % CI: 0.704-0.861), with a sensitivity of 0.795 and specificity of 0.643 in predicting CMD in PPCI. The AUC of the GDF-15 model (Model With GDF-15) was 0.867 (95 % CI: 0.806-0.928), significantly outperforming the clinical baseline model (Model Without GDF-15) (Δ AUC = 0.079, 95 % CI: 0.020-0.138, P = 0.009). Furthermore, the net reclassification improvement (NRI) was 0.854 (95 % CI: 0.543-1.166, P < 0.001), and the integrated discrimination improvement (IDI) was 0.151 (95 % CI: 0.089-0.213, P < 0.001). Conclusions: GDF-15 can serve as a biomarker for predicting the development of CMD in STEMI patients undergoing PPCI.

The assessment of no-reflow phenomenon incidence in early versus delayed percutaneous coronary intervention following a primary fibrinolysis.

BACKGROUND: Percutaneous coronary intervention (PCI) is the gold standard approach to ST-Segment Elevation Myocardial Infarction (STEMI). Fibrinolysis followed by PCI has been recommended. The current study aims to investigate the no-reflow phenomenon incidence in patients undergoing post-thrombolytic therapy PCI. METHODS: This cross-sectional study was conducted on 250 patients with STEMI who primarily received fibrinolytic therapy followed by early (3-24 hours) (n=231) or delayed (> 24 hours) (n=19) PCI. They were also subcategorized into four intervals: <6 hours (n=98), 6-12 hours (n=93), 12-24 hours (n=38), and ≥24 hours (n=21). The demographic and medical data of the patients were retrieved. The Thrombolysis in Myocardial Infarction score (TIMI) was assessed at baseline and at the end of PCI. A TIMI score other than 3 was defined as no-reflow. RESULTS: The incidence of the no-reflow phenomenon was not associated with any of the underlying demographic and medical characteristics of the patients (P-value>0.05). Despite the significantly higher rate of improvement in TIMI grading among those undergoing early PCI (P-value=0.04), as well as within less than 6 hours after thrombolytic therapy (P-value=0.031), the rate of the no-reflow phenomenon did not differ between the groups, neither by sorting them as early versus delayed (P-value=0.518) nor by categorizing them into four intervals (P-value=0.367). CONCLUSION: Based on the findings of the current study, early PCI after fibrinolysis led to significantly improved TIMI flow. However, the incidence of no-reflow did not differ between the groups with early versus delayed post-fibrinolysis PCI.

A Prediction Nomogram for No-Reflow in Acute Myocardial Infarction Patients after Primary Percutaneous Coronary Intervention.

Background: The coronary no-reflow (NR) phenomenon is an independent predictor of major adverse cardiac events (MACEs). This study aimed to establish a clinical and comprehensive nomogram for predicting NR in acute myocardial infarction (AMI) patients after primary percutaneous coronary intervention (pPCI). Methods: The multivariable logistic regression analysis was performed to determine the NR-related factors. A nomogram was established via several clinical and biochemical factors, and the performance was evaluated via discrimination, calibration, and clinical factors. Results: The study consisted of 3041 AMI patients after pPCI, including 2129 patients in the training set (70%) and 912 patients in the validation set (30%). The NR event was 238 in the training set and 87 in the validation set. The level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP), basophil count (BASO), neutrophil count (NEUBC), D-dimer, hemoglobin (Hb), and red blood cell distribution width (RDW.CV) in NR patients showed statistically significant differences. In the training set, the C-index was 0.712, 95% CI 0.677 to 0.748. In the validation set, the C-index was 0.663, 95% CI 0.604 to 0.722. Conclusions: A nomogram that may predict NR in AMI patients undergoing pPCI was established and validated. We hope this nomogram can be used for NR risk assessment and clinical decision-making and significantly prevent potentially impaired reperfusion associated with NR.

The Role of Microvascular Obstruction and Intra-Myocardial Hemorrhage in Reperfusion Cardiac Injury. Analysis of Clinical Data.

Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41-50% of patients with ST-segment elevation myocardial infarction and PCI. The occurrence of IMH is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO. The appearance of MVO is associated with infarct size, the duration of ischemia of the heart, and myocardial edema. However, there is no conclusive evidence that myocardial edema plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca 2 + overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell damage in MVO formation remains unclear in patients with AMI and PCI. It is unclear whether nitric oxide production is reduced in patients with MVO. Only indirect evidence on the involvement of inflammation in the development of MVO has been obtained. The role of reactive oxygen species (ROS) in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied. The significance of the balance of thromboxane A2, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is currently unknown. Conclusive evidence regarding the role of coronary artery spasm in the development of MVhasn't been established. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI has not previously been performed. It is unclear whether epinephrine aggravates reperfusion necrosis of cardiomyocytes. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca 2 + channel blockers result in the long-term improvement of coronary blood flow in patients with MVO.

Electroacupuncture for slow flow/no-reflow phenomenon in patients with acute myocardial infarction undergoing percutaneous coronary intervention: protocol for a pilot randomized controlled trial.

Background: Slow flow/no-reflow (SF-NR) during percutaneous coronary intervention (PCI) is associated with poor prognosis of patients with acute myocardial infarction (AMI). Currently, effective treatment is not available for SF-NR. Electroacupuncture (EA) has shown significant efficacy as an adjuvant therapy for many cardiovascular diseases by improving microcirculation and reducing ischemia-reperfusion injury. However, its effects on SF-NR in the AMI patients during PCI are not clear. This pilot trial aims to determine the efficacy of intraoperative EA in alleviating SF-NR in AMI patients undergoing PCI. Methods: This prospective, single-center, randomized controlled, pilot trial will recruit 60 AMI patients scheduled for PCI at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, China. The patients will be randomized in a 1:1 ratio into the EA or the control groups. Patients in the control group will undergo standard PCI. Patients in the EA group will undergo intraoperative electroacupuncture while undergoing standard PCI. Incidence of SF-NR is the primary outcome for this study. This study will also assess secondary outcomes including cardiac biomarkers, inflammatory biomarkers, pain and anxiety scores, electrocardiography parameters, traditional Chinese medicine (TCM) symptom score, and major adverse cardiovascular and cerebrovascular events (MACCE). All the included patients will undergo laboratory tests including routine blood tests, levels of electrolytes, as well as liver and renal function tests. Patients will be followed up for 1 month after the procedure. Discussion: This pilot trial will provide evidence for the potential benefits of intraoperative EA in improving microvascular perfusion and preventing or alleviating SF-NR during PCI in patients with AMI. If proven effective, intraoperative EA will provide a new and effective strategy against SF-NR and provide evidence for subsequent multicenter trials. Clinical Trial Registration: ClinicalTrials.gov, identifier (ChiCTR2300072265). Registered on 8 June 2023.

Sonothrombolysis in Patients With ST-Elevation Myocardial Infarction With Electrocardiographic No-Reflow After Percutaneous Coronary Intervention: A Randomized Controlled Trial.

BACKGROUND AND AIMS: Approximately 50% of patients with ST elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) experience microvascular no-reflow. Pre- and post-PCI sonothrombolysis has been shown to decrease infarct size and improve left ventricular (LV) systolic function in STEMI patients receiving urgent PCI. The aim of this study was to investigate whether post-PCI sonothrombolysis alone in STEMI patients with persistent ST elevation could reduce no-reflow and infarct size. METHODS: Patients with STEMI with symptoms <12 hours who had persistent ST elevation (≤70% ST resolution) after primary PCI were randomized to sonothrombolysis or control. The primary end point was summed (Σ) ST elevation 60 minutes after study intervention. Secondary end points included infarct size, myocardial perfusion score, LV ejection fraction on cardiovascular magnetic resonance imaging at 2 months follow-up, and clinical outcome at 6-month follow-up. RESULTS: Sixty-seven STEMI patients with persistent ST elevation after PCI were randomized (49 left anterior descending, 18 right coronary/left circumflex artery). No difference was observed in Σ ST elevation 60 minutes after study intervention (mean difference, 0.6 mm; 95% CI, -1.1 to 2.2, P = .50). Complete ST resolution occurred in 14 (40%) of patients treated with sonothrombolysis compared to 6 (19%) of controls (P = .16). Myocardial perfusion score index (1.5 ± 0.3 vs 1.5 ± 0.3, P = .93), infarct size (18.0% ± 10% vs 16.8% ± 11%; P = .29) and LV ejection fraction on cardiovascular magnetic resonance (46% ± 8% vs 47% ± 11% in the control group; P = .86) were comparable. Incidence of all-cause death, acute coronary syndrome, and hospital admission for heart failure at 6-month follow-up was similar between the groups (sonothrombolysis, 2; control, 5). CONCLUSIONS: In STEMI patients with persistent ST elevation after PCI, post-PCI sonothrombolysis did not result in more ST resolution or smaller infarct size compared to control subjects. The incidence of the combined clinical end points was remarkably low in this high-risk patient population.

The effect of the systemic immune-inflammatory index on the no-reflow phenomenon in patients undergoing saphenous vein intervention.

Introduction: The systemic immune inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, has been shown to be an independent indicator of no-reflow phenomenon during percutaneous intervention. However, the relationship between SII and no-reflow phenomenon (NRP) that develops after the procedure of saphenous vein grafts is unknown. Aim: In this study, we aimed to investigate the relationship between no-reflow phenomenon and SII during percutaneous intervention on saphenous vein grafts. Material and methods: A total of 133 patients who underwent percutaneous intervention for saphenous vein grafts due to acute coronary syndrome between 2019 and 2022 were included in this study. The receiver-operating characteristics (ROC) curve was used to determine the cut-off value of SII to predict the no-reflow. The multivariate regression was used to analyse the correlation between no-reflow and SII. Results: The median value of SII was significantly higher in patients with no-reflow in comparison with normal reperfusion (543 (447, 717) vs. 861 (642, 1272), p < 0.001). The optimal threshold for SII in predicting the no-reflow phenomenon was 613, with sensitivity and specificity of 84% and 66%, respectively. The area under the ROC curve (AUC) was 0.80 (95% CI: 0.73-0.89, p < 0.001). In multivariate analysis, SII ≥ 613 showed an independent predictive value for the no-reflow (OR = 4.02, 95% CI: 1.40-11.57, p < 0.001). Conclusions: Our results showed that high SII levels were independently associated with the development of no-reflow phenomenon in patients presenting with acute coronary syndrome and undergoing percutaneous intervention to the SVG.

Prevalence and prognostic implications of the no-reflux phenomenon in patients undergoing primary percutaneous coronary intervention at a university center in a middle-income country.

OBJECTIVE: To analyze the prevalence of no-reflow and the 30-day mortality in a university center in a middle-income country. METHOD: We analyzed 2463 patients who underwent primary PCI from January 2006 to December 2021. The outcome measure was 30-day mortality. RESULTS: Of a total of 2463 patients, no-reflow phenomenon was found in 413 (16.8%) patients, 30-day mortality was 16.7 vs. 4.29% (p < 0.001). Patients with no-reflow were older 60 (53-69.5) vs. 59 (51-66) (p = 0.001), with a higher delay in onset of symptom to emergency department arrival 270 vs. 247 min (p = 0.001). No-reflow patients also had had fewer previous myocardial infarction, 11.6 vs. 18.4 (p = 0.001) and a Killip class > 1, 37 vs. 26% (p < 0.001). No-reflow patients were more likely to have an anterior myocardial infarction (55.4 vs. 47.8%; p = 0.005) and initial TIMI flow 0 (76 vs. 68%; p < 0.001). CONCLUSION: No-reflow occurred in 16.8% of STEMI patients undergoing primary PCI and was more likely with older age, delayed presentation, anterior myocardial infarction and Killip class > 1. No-reflow was associated with a higher mortality at 30-day follow-up.

OBJETIVOS: Analizar la prevalencia de no reflujo y la mortalidad a 30 días en un centro universitario de un país de ingresos medios. MÉTODO: Analizamos 2,463 pacientes que se sometieron a ICP primaria desde enero de 2006 hasta diciembre de 2021. La medida de resultado fue la mortalidad a los 30 días. RESULTADOS: Del total de 2,463 pacientes, se encontró fenómeno de no reflujo en 413 (16.8%), la mortalidad a los 30 días fue del 16.7 vs. 4.29% (p < 0.001). Los pacientes sin reflujo tenían mayor edad 60 (53-69.5) vs. 59 (51-66) (p = 0.001), con mayor retraso del inicio de los síntomas a la llegada a urgencias, 270 vs. 247 min (p = 0.001). Los pacientes sin reflujo también tenían menos infarto de miocardio previo, 11.6 vs. 18.4 (p = 0.001), y una clase Killip > 1, 37 vs. 26% (p < 0.001). Los pacientes sin reflujo tenían más probabilidades de tener un infarto de miocardio anterior (55.4 vs. 47.8%; p = 0.005) y flujo TIMI inicial 0 (76 vs. 68%; p < 0.001). CONCLUSIÓN: Ocurrió ausencia de reflujo en el 16.8% de los pacientes con IAMCEST sometidos a ICP primaria y fue más probable con la edad avanzada, presentación tardía, infarto de miocardio anterior y clase Killip > 1. El no reflujo se asoció con una mayor mortalidad a los 30 días de seguimiento.

Defective recovery of QT dispersion due to no-reflow following acute interventional therapy in patients with ST-segment elevation myocardial infarction.

Background: Previous studies have suggested that adequate myocardial reperfusion after percutaneous coronary intervention (PCI) can improve the inhomogeneity of myocardial repolarization. However, it remains unclear whether no-reflow (NR) following emergency PCI involves disadvantages related to ventricular repolarization indices. The present study aimed to determine the effect of NR on QT dispersion (QTd) in patients with ST-segment elevation myocardial infarction (STEMI) and to evaluate the prognostic value of the relative reduction of QTd on ventricular arrhythmia events (VAEs). Methods: A prospective case-control study was conducted. According to the inclusion criteria, 275 patients with STEMI who underwent primary PCI treatment at the First People's Hospital of Anqing affiliated to Anhui Medical University from January 2020 to May 2023 were enrolled. According to whether NR occurred during PCI, these patients were divided into two groups: an NR group and a non-NR group. Subsequently, the QT intervals were measured before and at 12 hours after PCI. Afterward, the QTd, corrected QTd (QTcd), and the relative reduction of QTd and QTcd 12 hours pre- and postprocedure (ΔQTd-R and ΔQTcd-R, respectively) were calculated. Finally, multivariable logistic regression analysis was performed to predict the risk of VAE occurrence. Results: In the non-NR group, there was a significant decrease from baseline in postprocedure QTd (48±17 vs. 73±22 ms; P=0.009) and QTcd (54±19 vs. 80±23 ms; P=0.01); in contrast, the NR group showed no significant difference in QTd (64±20 vs. 75±23 ms; P=0.58) or QTd (70±22 vs. 82±26 ms; P=0.45). Furthermore, the ΔQTd-R and ΔQTcd-R were both lower in the NR group than in the non-NR group (P<0.05); however, the rate of VAEs was higher in the NR group than in the non-NR group (15.2% vs. 6.2%; P=0.02). The multivariable logistic regression analysis results revealed that each increase of 12% in ΔQTcd-R was an independent predictor of VAEs (odds ratio: 0.547; 95% confidence interval: 0.228-0.976). Conclusions: The NR phenomenon following primary PCI in patients with STEMI leads to the defective recovery of QTd and QTcd. Furthermore, ΔQTcd-R can be viewed as an effective indicator for evaluating the myocardial repolarization inhomogeneity, and short-term clinical outcomes.

Efficiency and Safety of Intracoronary Epinephrine Administration in Patients With ST-Elevation Myocardial Infarction With Refractory Coronary No-Reflow.

Studies assessing the treatment of refractory no-reflow in patients with ST-elevation myocardial infarction (STEMI) are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary adrenaline administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after the initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in Group 1 received adrenaline, and 45 patients in Group 2 (control) received conventional treatments alone. After intracoronary drug administration, the adrenaline group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction grade 3 (56% vs 29% [p = 0.01]) and resolution of STEMI >50% after PCI (78% vs 36% [p <0.001]). Additionally, the adrenaline group showed a lower indexed microvascular obstruction (MVO) volume compared with the control group (0.9 [0.3; 3.1] % vs 1.9 [0.6; 7.9] % [p = 0.048]). A significant improvement in ejection fraction (EF) was observed in the adrenaline group (p = 0.025). Intracoronary adrenaline administration during PCI in patients with STEMI with refractory no-reflow is more effective compared with conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of STEMI, enhances EF, and reduces MVO volume. Intracoronary adrenaline administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary adrenaline administration during PCI could be an effective treatment strategy for patients with STEMI with refractory no-reflow.

Intracoronary adenosine compared with adrenaline and verapamil in the treatment of no-reflow phenomenon following primary PCI in STEMI patients.

BACKGROUND: no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). METHODS: 108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. RESULTS: The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. CONCLUSION: Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.