UNASSIGNED: Supersaturated oxygen (SSO2) delivered into the left anterior descending coronary artery after percutaneous coronary intervention (PCI) for anterior ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size, but its effects on microvascular obstruction (MVO) are unknown. The aim of this study was to compare MVO in patients with anterior STEMI treated with SSO2 after successful primary PCI from 2 studies (the optimized SSO2 pilot and IC-HOT) with similar patients from 7 randomized trials who underwent primary PCI without SSO2 treatment.
UNASSIGNED: A total of 874 patients with anterior STEMI who underwent MVO assessment using cardiac magnetic resonance imaging within 10 days after primary PCI were included, of whom 90 patients (10.3%) were treated with SSO2. The primary end point was the extent of MVO as a continuous measure in a weighted multivariable model. The secondary end point was the presence of MVO.
UNASSIGNED: SSO2 therapy was independently associated with a lower extent of MVO compared with no SSO2 therapy (coefficient, -1.35; 95% CI, -2.58 to -0.11; P = .03). SSO2 therapy was also associated with a borderline lower risk of any MVO (adjusted odds ratio, 0.56; 95% CI, 0.31-1.00; P = .051).
UNASSIGNED: In the present individual patient data pooled analysis from 9 studies, SSO2 therapy was associated with less MVO after successful primary PCI for anterior STEMI.

UNASSIGNED: Intramyocardial hemorrhage (IMH) occurs after ST-elevation myocardial infarction (STEMI) and has been documented using cardiac magnetic resonance imaging. The prevalence and prognostic significance of IMH are not well described, and the small sample size has limited prior studies.
UNASSIGNED: We performed a comprehensive literature search of multiple databases to identify studies that compared outcomes in STEMI patients with or without IMH. The outcomes studied were major adverse cardiovascular events (MACE), infarct size, thrombolysis in myocardial infarction (TIMI) flow after percutaneous coronary intervention (PCI), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and mortality. Odds ratios (ORs) and standardized mean differences with corresponding 95% CIs were calculated using a random effects model.
UNASSIGNED: Eighteen studies, including 2824 patients who experienced STEMI (1078 with IMH and 1746 without IMH), were included. The average prevalence of IMH was 39%. There is a significant association between IMH and subsequent MACE (OR, 2.63; 95% CI, 1.79-3.86; P < .00001), as well as IMH and TIMI grade <3 after PCI (OR, 1.75; 95% CI, 1.14-2.68; P = .05). We also found a significant association between IMH and the use of glycoprotein IIb/IIIa inhibitors (OR, 2.34; 95% CI, 1.42-3.85; P = .0008). IMH has a positive association with infarct size (standardized mean difference, 2.19; 95% CI, 1.53-2.86; P < .00001) and LVEDV (standardized mean difference, 0.7; 95% CI, 0.41-0.99; P < .00001) and a negative association with LVEF (standardized mean difference, -0.89; 95% CI, -1.15 to -0.63; P = .01). Predictors of IMH include male sex, smoking, and left anterior descending infarct.
UNASSIGNED: Intramyocardial hemorrhage is prevalent in approximately 40% of patients who experience STEMI. IMH is a significant predictor of MACE and is associated with larger infarct size, higher LVEDV, and lower LVEF after STEMI.

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.

Primary percutaneous coronary intervention (PCI) is the current class I therapeutic approach to treat acute ST-elevation myocardial infarction (STEMI). While primary PCI can restore adequate flow in the infarcted artery in the majority of cases, some patients experience the \'no-reflow\' phenomenon, i.e., an abnormal myocardial reperfusion occurring even after the occluded coronary artery has been opened. No-reflow occurs when microvascular obstruction arises from embolization of thrombus or components of the atheromatous plaques. These embolic materials travel downstream within the infarct-related artery at time of primary PCI, leading to compromised blood flow. Currently, no expert consensus documents exist to outline an optimal strategy to prevent or treat no-reflow. Interventional cardiologists frequently employ intracoronary adenosine, calcium channel blockers, nicorandil, nitroprusside or glycoprotein IIb/IIIa inhibitors. However, evidence suggests that these interventions consistently enhance myocardial blood flow in only a specific subset of patients experiencing no-reflow. A recent and innovative therapeutic approach gaining attention is low-dose fibrinolysis during primary PCI, which offers the potential to augment coronary flow post-myocardial revascularization.

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.

This systematic review will provide a comprehensive assessment of the evidence on PICSO in STEMI patients, and it will help to determine the role of this novel technique in the management of STEMI. The review searched for the relevant articles in the PubMed, Embase, Cochrane Library, and Web of Science databases regarding PC-ICSO. Four cohort studies were eligible to be included in the quantitative analysis. In the pooled analysis, the use of PICSO was associated with a significant reduction in infarct size (SMD = -0.44, 95% CI = -0.76,-0.13, p = 0.004). PICSO administration was associated with a reduced risk of developing microvascular resistance (RR = 0.75, 95% CI = 0.62,0.92, p = 0.0051). The post-procedural Index of Microvascular Occlusion (MVO) was lower in the PICSO treated compared to the control group and this result was homogenous and statistically significant (SMD = -0.35, 95% CI = -0.68-0.01, p = 0.03, I2 = 0%). Compared to matched controls, the use of PICSO was associated with higher Left Ventricular Ejection Fraction (LVEF) at the longest follow-up (SMD = 0.328, 95% CI = 0.03, 0.06, p = 0.03, I2 = 0%). This review suggested that PICSO can be used during PPCI in STEMI with improved outcomes of infarct size, LVEF, and microvascular perfusion.

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.

BACKGROUND: Sonothrombolysis is a therapeutic application of ultrasound with ultrasound contrast for patients with ST elevation myocardial infarction (STEMI). Recent trials demonstrated that sonothrombolysis, delivered before and after primary percutaneous coronary intervention (pPCI), increases infarct vessel patency, improves microvascular flow, reduces infarct size, and improves ejection fraction. However, it is unclear whether pre-pPCI sonothrombolysis is essential for therapeutic benefit. We designed a parallel 3-arm sham-controlled randomized controlled trial to address this.
METHODS: Patients presenting with first STEMI undergoing pPCI within 6 hours of symptom onset were randomized 1:1:1 into 3 arms: sonothrombolysis pre-/post-pPCI (group 1), sham pre- sonothrombolysis post-pPCI (group 2), and sham pre-/post-pPCI (group 3). Our primary end point was infarct size (percentage of left ventricular mass) assessed by cardiac magnetic resonance imaging at day 4 ± 2. Secondary end points included myocardial salvage index (MSI) and echocardiographic parameters at day 4 ± 2 and 6 months.
RESULTS: Our trial was ceased early due to the COVID pandemic. From 122 patients screened between September 2020 and June 2021, 51 patients (age 60, male 82%) were included postrandomization. Median sonothrombolysis took 5 minutes pre-pPCI and 15 minutes post-, without significant door-to-balloon delay. There was a trend toward reduction in median infarct size between group 1 (8% [interquartile range, 4,11]), group 2 (11% [7, 19]), or group 3 (15% [9, 22]). Similarly there was a trend toward improved MSI in group 1 (79% [64, 85]) compared to groups 2 (51% [45, 70]) and 3 (48% [37, 73]) No major adverse cardiac events occurred during hospitalization.
CONCLUSIONS: Pre-pPCI sonothrombolysis may be key to improving MSI in STEMI. Multicenter trials and health economic analyses are required before clinical translation.

BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.
METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.
RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.
CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

OBJECTIVE: This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure.
BACKGROUND: More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear.
METHODS: The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of 2 treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for 6 months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total.
CONCLUSIONS: This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.