Meta-Analysis on the Efficacy of High-Dose Statin Loading Before Percutaneous Coronary Intervention in Reducing No-Reflow Phenomenon in Acute Coronary Syndrome.

Currently, guidelines recommend the uptake of high-dose statins before and after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome. However, the association of high-dose statins with the incidence of the no-reflow phenomenon remains unclear. This study aimed to review the evidence of preprocedural high-dose statin therapy to reduce no-reflow incidence after PCI. PubMed, Embase, and Google Scholar were searched from inception until May 2022 for studies comparing high-dose statins with low-dose or no statin therapy before PCI. Studies reporting the no-reflow phenomenon were shortlisted. The National Institutes of Health tool for randomized and cohort studies was used to assess the quality of included studies. A random-effects model was used to derive odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). A total of 11 studies were included, with a population of 4,294 patients. The use of high-dose statins before PCI significantly reduced postprocedural no-reflow (OR 0.51, 95% CI 0.35 to 0.74, p = 0.0005, I2 = 32%). A total of 7 studies included patients who underwent PCI without previous use of statins. A significant decrease in overall no-reflow events was observed with high-intensity statin treatment versus low-intensity statin/placebo (OR 0.55, 95% CI 0.34 to 0.88, p = 0.01, I2 = 25%) among patients who were statin naive. Acute high-dose statin therapy before PCI significantly reduces the hazard of post-PCI no-reflow events in patients with acute coronary syndrome. Our results encourage the routine use of statins before PCI.

Administration of intracoronary adenosine before stenting for the prevention of no-reflow in patients with ST-elevation myocardial infarction.

Objectives: No-reflow phenomenon during the primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) is accompanied by a poor clinical outcome and mortality. We aimed to determine the effect of intracoronary adenosine in preventing the no-reflow phenomenon, as detected by three different methods, in patients who underwent primary (PCI). Design. In this single-blinded randomized controlled trial, patients with acute STEMI who presented to our center and underwent primary PCI were randomized to the intervention group who received intracoronary adenosine before stenting or the control group who received the standard treatment. No-reflow phenomenon was detected using thrombolysis in myocardial infarction (TIMI) flow grade, TIMI frame count, and myocardial blush grade (MBG). The incidence of the no-reflow phenomenon was then compared between the intervention and control groups. Results. The adenosine group consisted of 110 patients (age = 57 ± 11 years; 92 (84%) male) while 118 patients were in the control group (age = 59 ± 12 years; 89 (75%) male). There was no difference between the study groups in baseline characteristics. The frequency of no-reflow phenomenon was lower in the adenosine group as assessed by TIMI flow grade (15 [14%] vs. 41 [35%]), MBG (23 [21%] vs. 63 [53%]) and TIMI frame count (16 [14%] vs. 50 [42%]) (p < .001 for all). This effect remained significant after adjustment for confounding variables. Conclusion. Intracoronary adenosine could effectively prevent the no-reflow phenomenon in STEMI patients who underwent primary PCI.

Luteolin alleviates ischemia/reperfusion injury-induced no-reflow by regulating Wnt/ß-catenin signaling in rats.

The no-reflow phenomenon induced by ischemia-reperfusion (I/R) injury seriously limits the therapeutic value of coronary recanalization and leads to a poor prognosis. Previous studies have shown that luteolin (LUT) is a vasoprotective factor. However, whether LUT can be used to prevent the no-reflow phenomenon remains unknown. Positron emission tomography perfusion imaging, performed to detect the effects of LUT on the no-reflow phenomenon in vivo, revealed that LUT treatment was able to reduce the no-reflow area in rat I/R models. In vitro, LUT was shown to reduce the hypoxia-reoxygenation injury-induced endothelial permeability and apoptosis. The levels of malondialdehyde, reactive oxygen species and NADPH were also measured and the results indicated that LUT could inhibit the oxidative stress. Western blot analysis revealed that LUT protected endothelial cells from I/R injury by regulating the Wnt/ß-catenin pathway. Overall, we concluded that the use of LUT to minimize I/R induced microvascular damage is a feasible strategy to prevent the no-reflow phenomenon.

Clinical outcomes of nicorandil administration in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary percutaneous coronary intervention is the treatment of choice in ST-segment elevation myocardial infarction and no-reflow phenomenon is still an unsolved problem. METHODS: We searched PubMed, EmBase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials. The primary endpoint was the incidence of major adverse cardiac events and the secondary endpoint was the incidences of no-reflow phenomenon and complete resolution of ST-segment elevation. RESULTS: Eighteen randomized controlled trials were enrolled. Nicorandil significantly reduced the incidence of no-reflow phenomenon (OR, 0.46; 95% CI, 0.36-0.59; P < 0.001; I2 = 0%) and major adverse cardiac events (OR, 0.42; 95% CI, 0.27-0.64; P < 0.001; I2 = 52%). For every single outcome of major adverse cardiac events, only heart failure and ventricular arrhythmia were significantly improved with no heterogeneity (OR, 0.36; 95% CI, 0.23-0.57, P < 0.001; OR, 0.43; 95% CI, 0.31-0.60, P < 0.001 respectively). A combination of intracoronary and intravenous nicorandil administration significantly reduced the incidence of major adverse cardiac events with no heterogeneity (OR, 0.24; 95% CI, 0.13-0.43, P < 0.001; I2 = 0%), while a single intravenous administration could not (OR, 0.66; 95% CI, 0.40-1.06, P = 0.09; I2 = 52%). CONCLUSIONS: Nicorandil can significantly improve no-reflow phenomenon and major adverse cardiac events in patients undergoing primary percutaneous coronary intervention. The beneficial effects on major adverse cardiac events might be driven by the improvements of heart failure and ventricular arrhythmia. A combination of intracoronary and intravenous administration might be an optimal usage of nicorandil.

Mechanism and potential treatment of the "no reflow" phenomenon after acute myocardial infarction: role of pericytes and GPR39.

The "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments, we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, before reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared with controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39-knockout and VC43-treated mice compared with controls. We conclude that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI and that smaller no reflow zones in GPR39-knockout and VC43-treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI, as well as providing a therapeutic pathway for the condition.NEW & NOTEWORTHY The mechanism of "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction but tissue perfusion is not restored, is unknown. This condition is associated with worse outcome. Here, we show that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow. Smaller no-reflow zones in GPR39-knockout animals and those treated with a GPR39 inhibitor are associated with smaller infarct size. These results could have important therapeutic implications.

Prophylactically injection of Nicorandil to reduce no-reflow phenomenon during PCI in acute STEMI patients: Protocol of a double-blinded, randomized, placebo-controlled trial.

INTRODUCTION: An acute ST-elevation myocardial infarction (STEMI) is a very serious type of heart attack and a profoundly life-threatening medical emergency, and percutaneous coronary intervention (PCI) is the preferred strategy. However, in patients undergoing primary PCI, 30% to 40% may suffer the no-reflow phenomenon (NRP), and it could expand the myocardial infarction area and accompanied with high rehospitalization rate and fatality rate. In this study, we try to conduct a double blinded, randomized, placebo-controlled trial to observe whether the prophylactically intracoronary administration of Nicorandil could reduce the occurrence of NRP in STEMI patients undergoing PCI. METHODS: Simple randomization in a 1:1 ratio will be made in blocks of variable size according to a random numbers generated by Excel 2010 to divide the patients to treatment group (Nicorandil) and control group (Saline). The outcomes are the occurrence of NRP, levels of interleukin-6 and HS-CRP, cTnT, and CK-MB before, and every 4 hours following PCI, and major adverse cardiovascular events at day 30. SPSS 23.0 (IBM, Chicago, IL) will be used, and P-value < .05 will be considered statistically significant. CONCLUSIONS: The findings will determine the efficacy of prophylactically intracoronary administration of Nicorandil to reduce the occurrence of NRP during PCI in acute STEMI patients. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/QPF3V.

Tongmai Yangxin pill reduces myocardial no-reflow by regulating apoptosis and activating PI3K/Akt/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty and was further improved by Professor Ruan Shiyi, a cardiovascular expert at Tianjin University of Traditional Chinese Medicine. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease and can improve vascular endothelial function in patients with angina pectoris or coronary heart disease by up-regulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial no-reflow by up-regulating NO activity and then dilating blood vessels remains unclear. AIM OF THE STUDY: This study aimed to reveal whether TMYX can further improve myocardial NR by up-regulating NO activity and then dilating blood vessels. The mechanism underlying PI3K/Akt/eNOS pathway activation and apoptosis regulation is also explored. MATERIALS AND METHODS: The left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish a NR model. The rats were assigned to 14 groups: control, sham, NR, TMYX (4.0 g/kg), sodium nitroprusside (SNP), Tongxinluo capsule (TXL), PI3K blocker (LY), TMYX + LY, SNP + LY, TXL + LY, eNOS blocker (L-NAME), TMYX + L-NAME, SNP + L-NAME, and TXL + L-NAME groups. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were adopted to evaluate NR and ischemic areas. Cell inflammation degree and edema were assessed by hematoxylin-eosin staining. Automated biochemical analyzer and kit were used to detect the activities of myocardial oxidants, including reactive oxygen species, super oxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins in the PI3K/Akt/eNOS signaling pathway and apoptosis were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was adopted to detect coronary artery diastolic function in vitro. RESULTS: TMYX reduced NR and ischemic areas; suppressed LV-mass; enhanced EF, FS, LVOT peak, and LVSV; and improved cardiac structure and function. Moreover, it decreased creatine kinase (CK), CK-MB, and lactic dehydrogenase activities. TMYX increased NO and super oxide dismutase activities; inhibited malonaldehyde activity; reduced muscle fiber swelling and inflammatory cell infiltration; and improved vasodilation in vitro. In the NR myocardium, TMYX stimulated myocardial PI3K activities and PI3K (Tyr458) phosphorylation and enhanced Akt activities and Akt phosphorylation at Tyr315. TMYX increased the activities of eNOS and the phosphorylation of eNOS at Ser1177 in the NR myocardium and attenuated cardiomyocyte apoptosis by increasing the expression of Bcl-2 and decreasing that of caspase-3 and Bax. All these effects of TMYX were abolished by the specific inhibitors of PI3K (LY) and eNOS (L-NAME). CONCLUSIONS: TMYX attenuates myocardial NR after ischemia and reperfusion by activating the PI3K/Akt/eNOS pathway and regulating apoptosis, further up-regulating NO activity and relaxing coronary microvessels.

Randomized trial of intracoronary adenosine as adjunctive therapy for prevention of the no-reflow phenomenon.

No-reflow phenomenon as a serious complication following percutaneous coronary intervention, deteriorates clinical outcomes. Intracoronary (IC) Adenosine, seems to be a way to deal with it. One hundred four consecutive patients with ST-segment elevation myocardial infarction were randomized into two groups. Each group consisted of 52 patients who managed with two bolus doses of IC Adenosine (Adenosine group) or two bolus doses of IC normal saline (placebo group) administered before and after stenting. Thrombolysis in myocardial infarction (TIMI) grade flow, ST-segment resolution (STR) and post-procedural clinical outcomes were used as endpoints. IC adenosine led to lower rates of no-reflow based on TIMI grade flow scaling (15.4% vs. 44.3%; P-value: 0.02). STR classified as complete, partial and no resolution was similar between two groups (P-value: 0.748). Also, post-interventional clinical outcomes, including arrhythmia, left ventricular ejection fraction, hospitalization time, and 30 days mortality were similar between Adenosine and placebo groups.

Pathophysiology, Diagnosis, and Management of the No-Reflow Phenomenon.

Successful reperfusion of an infarct-related coronary artery by primary percutaneous intervention or fibrinolysis during acute ST-elevation myocardial infarction (STEMI) does not always restore myocardial tissue perfusion, a phenomenon termed "no-reflow." Herein we discuss the pathophysiology of this highly prevalent phenomenon and highlight the most salient aspects of its clinical diagnosis and management as well as the limitations of presently used methods. There is a great need for understanding the dynamic nature of no-reflow, as its occurrence is associated with poor cardiovascular outcomes. The no-reflow phenomenon may lend an explanation to the lack of further improvements in in-hospital mortality in STEMI patients despite decreases in door-to-balloon time. Hence, no-reflow potentially presents an important target for investigators interested in improving outcomes in STEMI.

Cardiovascular events associated with nicorandil administration prior to primary percutaneous coronary intervention in patients with acute ST-segment elevated myocardial infarction: a systematic review and meta-analysis.

Introduction: Nicorandil may exert cardioprotective effects in ischemic heart disease. However, its efficacy in combination with early reperfusion is uncertain. The authors performed a meta-analysis of the short- and long-term clinical outcomes of nicorandil administration at the time of primary percutaneous coronary intervention (PCI) in patients with ST-elevated myocardial infarction (STEMI). Methods: PubMed, MEDLINE, Embase, and the Cochrane Library databases were systematically searched for eligible randomized controlled studies. The primary endpoint was major adverse cardiovascular events (MACE), both in-hospital and post-discharge. The secondary endpoint was the incidence of no-reflow phenomenon. Results: Ten studies were included (n = 1105). Mean patient age was 63.0 ± 10.0 years; 76.6% of patients were male. Compared with controls who received primary PCI, combined nicorandil/primary PCI significantly reduced in-hospital MACE (pooled odds ratio [OR] 0.16; 95% confidence interval [CI] 0.09-0.27), follow-up MACE (pooled OR 0.53; 95% CI 0.37-0.75), and total MACE (pooled OR 0.27; 95% CI 0.15-0.49). The combined treatment also reduced the incidence of no-reflow phenomenon (pooled OR 0.34; 95% CI 0.23-0.50). Conclusion: Nicorandil administration at the time of primary PCI is associated with reduced MACE (both short- and long-term) and no-reflow phenomenon in patients with STEMI.

Is Atherothromboaspiration a Possible Solution for the Prevention of No-Reflow Phenomenon in Acute Coronary Syndromes? Single Centre Experience and Review of the Literature.

BACKGROUND: Intracoronary thrombus in acute Myocardial Infarction (MI) confers higher rates of no-reflow with attendant adverse consequences. Earlier Randomized-Controlled-Trials (RCTs) of routine thromboaspiration during Percutaneous Coronary Intervention (PCI) indicated a clinical benefit, but more recent RCTs were negative. However, data of selective use of this adjunctive approach remain scarce. OBJECTIVE: The aim of this single-centre prospective study was to report the results of selective thromboaspiration during PCI in patients with intracoronary thrombi, and also to provide an extensive literature review on current status of thromboaspiration. METHODS: The study included 90 patients (77 men; aged 59.3±12.7 years) presenting with acute MI (STElevation MI (STEMI) in 74, non-STEMI in 16) who had intracoronary thrombi and were submitted to thromboaspiration. RESULTS: Total (n=67) or subtotal (n=18) vessel occlusions were present in 85 (94%) patients. Thromboaspiration and subsequent PCI were successful in 89/90 (98.9%) patients, with coronary stenting in 86 (96.6%). In 4 patients with residual thrombus, a mesh-covered stent was implanted. IIb/IIIa-inhibitors were administered in 57 (63.3%) patients. No-reflow occurred in only 1 (1.1%) patient. The postprocedural course was uneventful. Review of the literature revealed several early observational and RCTs and meta-analyses favouring manual, not mechanical, thrombectomy. However, newer RCTs and meta-analyses significantly curtailed the initial enthusiasm for the clinical benefits of routine use of thromboaspiration. CONCLUSION: Selective thromboaspiration for angiographically visible thrombi in MI patients undergoing PCI, as an adjunct to mechanical reperfusion and to IIb/IIIa-inhibitors, may be an option since this manoeuvre may improve procedural and clinical outcome.

Intracoronary or intravenous abciximab after aspiration thrombectomy in patients with STEMI undergoing primary percutaneous coronary intervention.

OBJECTIVE: To test whether aspiration thrombectomy with intracoronary (IC) instead of intravenous (IV) administration of abciximab could reduce the no-reflow phenomenon in patients undergoing primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: Despite recanalisation with PCI, failure to restore microvascular flow may affect the prognosis of patients with STEMI. A combination of aspiration thrombectomy with IC abciximab may improve distal perfusion. METHODS: After aspiration thrombectomy during primary PCI for STEMI, 160 patients were randomly assigned to either an IV or IC abciximab bolus delivered through the aspiration catheter, both followed by a 12-hour IV abciximab infusion. RESULTS: ST-segment resolution ≥ 70% was achieved in 36 of 78 patients with IC versus 30 of 82 patients with IV abciximab (46.1 vs 36.6%, p = 0.368), and partial resolution in 28 of 78 versus 31 of 82 patients (35.9 vs 37.8%, p = 0.368). Postprocedural myocardial blush grade (MBG) 3 was obtained in 62.8 vs 63.4% (p = 0.235) and MBG ≥ 2 in 89.7 vs 81.7% (p = 0.148) of patients given IC and IV abciximab, respectively. There were three deaths in each group (3.8%). Major adverse cardiac events occurred in six of 78 patients given the IC and seven of 82 patients given the IV abciximab bolus (7.6 vs 8.5%, p = 0.410). One stroke occurred in each group, and two patients in the IC and nine in the IV group developed renal failure (2.5 vs 10.9%, p = 0.414). CONCLUSIONS: IC versus IV abciximab did not enhance myocardial reperfusion in non-selected patients with STEMI undergoing primary PCI after aspiration thrombectomy had successfully been performed.

The coronary circulation in acute myocardial ischaemia/reperfusion injury: a target for cardioprotection.

The coronary circulation is both culprit and victim of acute myocardial infarction. The rupture of an epicardial atherosclerotic plaque with superimposed thrombosis causes coronary occlusion, and this occlusion must be removed to induce reperfusion. However, ischaemia and reperfusion cause damage not only in cardiomyocytes but also in the coronary circulation, including microembolization of debris and release of soluble factors from the culprit lesion, impairment of endothelial integrity with subsequently increased permeability and oedema formation, platelet activation and leucocyte adherence, erythrocyte stasis, a shift from vasodilation to vasoconstriction, and ultimately structural damage to the capillaries with eventual no-reflow, microvascular obstruction (MVO), and intramyocardial haemorrhage (IMH). Therefore, the coronary circulation is a valid target for cardioprotection, beyond protection of the cardiomyocyte. Virtually all of the above deleterious endpoints have been demonstrated to be favourably influenced by one or the other mechanical or pharmacological cardioprotective intervention. However, no-reflow is still a serious complication of reperfused myocardial infarction and carries, independently from infarct size, an unfavourable prognosis. MVO and IMH can be diagnosed by modern imaging technologies, but still await an effective therapy. The current review provides an overview of strategies to protect the coronary circulation from acute myocardial ischaemia/reperfusion injury. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

Do We Need Potent Intravenous Antiplatelet Inhibition at the Time of Reperfusion During ST-Segment Elevation Myocardial Infarction?

Acute myocardial infarction (MI) is still a large source of morbidity and mortality worldwide. Although early reperfusion therapy has been prioritized in the modern era of percutaneous coronary intervention and thrombolysis, attempts at incremental improvements in clinical outcomes by reducing MI size have not been successful so far. Herein, we review the studies that have evaluated immediate-onset antiplatelet therapy as attempts to improve meaningful clinical outcomes in ST-segment elevation MI (STEMI). Unfortunately, many of the adjunctive pharmacotherapies have proven to be disappointing. Recent studies performed in the background of routine oral administration of P2Y12 adenosine receptor inhibitors, which may take several hours to take full effect, and aspirin have largely shown no improvement in outcomes, despite an earlier onset of antiplatelet activity of the investigative agents. Further progress in improving outcomes during STEMI may depend on exploring therapeutics that modulate the pathophysiology of microvascular damage during ischemia-reperfusion injury, a phenomenon whose effects evolve over hours to days. We speculate that the dynamic nature of the no-reflow phenomenon may be an explanation for these disappointing results with the intravenous antiplatelet agents. We hope that appreciation for what has not worked in this domain may direct future research efforts to focus on novel pathways. Myocardial ischemia and reperfusion injury are very much still a lingering issue. Despite significant improvements in door-to-balloon times, rates of in-hospital mortality for STEMI remain unchanged. Outcomes following successfully reperfused STEMI are likely determined by the initial size of myocardial necrosis (ie, cardiomyocyte death during the period of ongoing ischemia), patency of the infarct-related epicardial coronary artery, possible reperfusion injury, the microvascular no-reflow phenomenon, and adverse remodeling after infarction.

Effect of Intravascular Cooling on Microvascular Obstruction (MVO) in Conscious Patients with ST-Elevation Myocardial Infarction Undergoing Primary PCI: Results from the COOL AMI EU Pilot Study.

OBJECTIVE: COOL AMI EU pilot was a multi-center, randomized controlled trial to assess feasibility and safety of rapid intravascular therapeutic hypothermia (TH) in conscious patients with anterior ST-elevation myocardial infarction (STEMI) undergoing primary PCI (PPCI). We report the effect of hypothermia upon microvascular obstruction (MVO). METHODS: Conscious patients with anterior STEMI and symptom duration <6 h were recruited and randomized to PPCI + TH or PPCI alone. TH was induced using the ZOLL® Proteus™ intravascular temperature management system and rapid infusion of 1 L of cold normal saline, with a target temperature of 32 °C. MVO was measured by cardiac magnetic resonance (CMR) at 4 to 6 days post-MI. MVO larger than 3.9% of LV was considered as extensive MVO. RESULTS: 50 patients were randomized; mean age was 58 years, and 86% were men. At reperfusion, mean intravascular temperature for the TH group was 33.6 ±â€¯1 °C. The presence of MVO was high and not different in both groups (74% vs. 77%, p = 0.79). The proportion of patients with extensive MVO was 11% in the TH group and 23% in the control group (OR 0.4 95%CI 0.07-2.35, p = 0.30). Patients with extensive MVO showed reduced EF at 4-6 days (34% versus 43%, p = 0.01). The percentage of patients with EF <35% at 30 days was 6% in the TH group versus 24% in the control group (p = 0.19). CONCLUSION: In the COOL-AMI Pilot Trial, the presence of MVO in both test groups was high and extensive MVO was related with reduced LVEF. The efficacy of therapeutic hypothermia (TH) in MVO reduction should be tested in a pivotal trial.

Reduction of No Reflow with a Loading Dose of Atorvastatin before Primary Angioplasty in Patients with Acute ST Myocardial Infarction.

BACKGROUND: No reflow defined as an altered myocardial reperfusion and failure at microvascular level is a frequent complication in acute myocardial infarction that attenuates beneficial effect of reperfusion therapy leading to poor outcomes. There is not enough evidence to support that previous use of statins improves coronary flow in patients undergoing primary percutaneous coronary intervention (PCI). AIM OF STUDY: To determine if a loading dose of 80 mg of atorvastatin before primary angioplasty reduces the frequency of no reflow, hs-CRP, IL6 intracoronary levels, and major combined cardiovascular events at 30 d. METHODS: In this controlled clinical trial, we randomly assigned 103 adult patients within the 12 h of acute ST-elevation myocardial infarction (STEMI) to receive 80 mg of atorvastatin additional to standard treatment (AST) before performing primary PCI versus standard treatment (ST) alone. The primary outcomes were the occurrence of no reflow and high sensitivity C-reactive protein (hs-CRP) and interleukin 6 levels and secondary outcomes were major adverse cardiovascular events at 30 d. RESULTS: 103 patients were analyzed, 49 (48%) received AST, 54 (52%) ST. Frequency of no reflow among groups was 27 vs. 63% respectively, p ≤0.0001. hs-CRP level was 2.69 mg/dL for AST vs. 2.2 mg/dL in ST, meanwhile IL-6 levels were 5.2 pg/mL vs. 6.35 pg/mL respectively, p = ns. Cox regression model demonstrated that the treatment assigned is an independent predictor for no reflow occurrence (HR 0.34 95%, CI 0.18-0.61, p ≤0.001). CONCLUSION: The administration of a loading dose of 80 mg atorvastatin before primary PCI is an effective strategy for prevention of no reflow improving also clinical outcomes and free survival rate for the presentation of major adverse cardiovascular events at 30 d.

A Randomized Study of Distal Filter Protection Versus Conventional Treatment During Percutaneous Coronary Intervention in Patients With Attenuated Plaque Identified by Intravascular Ultrasound.

OBJECTIVES: The aim of this study was to evaluate the utility of distal protection during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes at high risk for distal embolization. BACKGROUND: The results of previous clinical trials indicated that the routine use of distal protection in patients with ST-segment elevation myocardial infarction did not improve clinical outcomes. However, selective use of distal protection by means of a filter-based distal protection system has not been evaluated. METHODS: Two hundred patients with acute coronary syndromes who had native coronary artery lesions and attenuated plaque with longitudinal length ≥5 mm on pre-PCI intravascular ultrasound were randomly assigned to undergo PCI with distal protection or conventional treatment. RESULTS: The primary endpoint (no-reflow phenomenon) occurred in 26 patients (26.5%) in the distal protection group and 39 patients (41.7%) in the conventional treatment group (p = 0.026), and the corrected TIMI (Thrombolysis In Myocardial Infarction) frame count after revascularization was significantly lower in the distal protection group (23 vs. 30.5; p = 0.0003). The incidence of cardiac death, cardiac arrest, cardiogenic shock after revascularization requiring defibrillation, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation was significantly lower in the distal protection group than in the conventional treatment group (0% vs. 5.2%; p = 0.028). CONCLUSIONS: The use of distal embolic protection applied with a filter device decreased the incidence of the no-reflow phenomenon and was associated with fewer serious adverse cardiac events after revascularization than conventional PCI in patients with acute coronary syndromes with attenuated plaque ≥5 mm in length. (Assessment of Distal Protection Device in Patients at High Risk for Distal Embolism in Acute Coronary Syndrome [ACS] [VAMPIRE3]; NCT01460966).

Intracoronary Nicorandil and the Prevention of the No-Reflow Phenomenon During Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND This study aimed to investigate intracoronary nicorandil treatment on the no-reflow phenomenon (NRP) during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and to compare nicorandil with sodium nitroprusside. MATERIAL AND METHODS Patients with sustained acute STEMI who underwent primary PCI (N=120) were randomly assigned to three groups: the nicorandil-treated group (N=40) had 2 mg of nicorandil injected into the coronary artery at 2 mm beyond the occlusion with balloon pre-dilation; the sodium nitroprusside-treated group (N=40) underwent the same procedure, but with 200 µg of sodium nitroprusside; the control group (N=40) received PCI and balloon pre-dilation only. Coronary angiography, incidence of NRP, hypotensive episodes, ST-segment resolution (STR) rate, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), wall motion score index (WMSI), and left ventricular ejection fraction (LVEF) were measured before and after primary PCI. Major adverse cardiovascular events (MACEs) post-PCI and at three-month follow-up were recorded. RESULTS Patients in the sodium nitroprusside and nicorandil groups had significantly improved thrombolysis in myocardial infarction (TIMI) scores, TIMI myocardial perfusion grade (TMPG), and ST-segment elevation resolution (STR) (P<0.05), and a significantly lower incidence of NRP (P=0.013). The incidence of intraoperative hypotension in the sodium nitroprusside group was significantly greater than the nicorandil and control groups (P=0.035). CONCLUSIONS Patients with sustained acute STEMI undergoing primary PCI, treated with intracoronary nicorandil had a reduced incidence of the NRP, improved myocardial perfusion and cardiac function.

The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment.

OBJECTIVE: To investigate the mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic (T2DM) patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI) treatment. PATIENTS AND METHODS: 66 patients were randomly divided into control group and observation group, 33 cases in each group. According to the percutaneous coronary intervention (PCI) emergency treatment principle, patients from the control group were treated with an intracoronary injection of adenosine combined with a micro-pump intravenous infusion of tirofiban. Patients from the observation group were injected with exogenous adiponectin in addition to the adenosine and tirofiban treatments. RESULTS: There were no significant differences in gender, age, location of the target lesion, degree of stenosis, stent implantation number, length and the inner diameter between control and observation group (p > 0.05). Lower frequent of slow blood flow and no-reflow and shorter interventional procedures were observed in observation group compared with those of control group (p < 0.05). Moreover, the increase of plasma creatine kinase (CK-MB) in patients of observation group was lower than that of the patients in control group (p < 0.05). In addition, the levels of troponin-I (cTnI), IL-6, TNF- α, endothelin-1 (ET-1), vascular endothelial adhesion molecular I (VCAM-1) and bax/Bcl-2 were significantly lower in observation group than those in control (p < 0.05). Furthermore, the occurrence of major adverse cardiac events (MACE) during a 12-month follow-up was significantly lower in the observation group than that of control (p < 0.05). CONCLUSIONS: Exogenous adiponectin further reduced the no-reflow phenomenon during PCI treatment of the patients with T2DM combined with AMI. The function of exogenous adiponectin is associated with the reduced myocardial and endothelial cell injury and the inhibited inflammation and apoptosis. The application of exogenous adiponectin can significantly improve the clinical outcomes.