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    Usefulness of preprocedural N-terminal pro-brain natriuretic peptide in predicting angiographic no-reflow phenomenon during stent implantation in patients with ST-segment elevation acute myocardial infarction. Hong Seo Na,Ahn Youngkeun,Hwang Sun Ho,Yoon Nam Sik,Lee Sang Rok,Moon Jae Youn,Kim Kye Hun,Hong Young Joon,Park Hyung Wook,Kim Ju Han,Jeong Myung Ho,Cho Jeong Gwan,Park Jong Chun,Kang Jung Chaee The American journal of cardiology The no-reflow phenomenon after primary percutaneous coronary intervention (PCI) is associated with larger infarct size, worse functional recovery, and higher incidence of complication after acute ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the relation between preprocedural N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and angiographic no-reflow phenomenon. We measured preprocedural serum NT-pro-BNP level in 159 consecutive patients with acute STEMI (aged 63 +/- 12 years; 72% men) before PCI. Angiographic no-reflow after PCI was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade <3. Baseline characteristics, including time from chest pain onset, between the no-reflow (n = 67) and normal-reflow groups (n = 92) were similar. NT-pro-BNP was significantly higher in the no-reflow group than the normal reflow group (1,982 +/- 3,314 vs 415 +/- 632 pg/ml; p = 0.005). Also, high-sensitivity C-reactive protein, monocytes, and troponin-T were significantly higher in the no-reflow group than the normal-reflow group. In the no-reflow group, NT-pro-BNP was much higher in patients with TIMI flow grade 0 (n = 41; 2,290 +/- 3,495 pg/ml) than those with TIMI grade 1 or 2 (n = 26; 1,575 +/- 2,340 pg/ml), but without significant difference. The area under the receiver-operating characteristic curve for NT-pro-BNP was 0.78, and the optimal cut-off value identified using receiver-operating characteristic curve analysis was 500 pg/ml. At the standard cut-off value of >500 pg/ml, increased NT-pro-BNP showed a high probability of no-reflow phenomenon (odds ratio 4.42, 95% confidence interval 1.15 to 17.00, p = 0.028). In conclusion, preprocedural NT-pro-BNP may be a strong predictor of the development of no-reflow phenomenon after PCI in patients with acute STEMI. 10.1016/j.amjcard.2007.03.075
    Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Ito H,Maruyama A,Iwakura K,Takiuchi S,Masuyama T,Hori M,Higashino Y,Fujii K,Minamino T Circulation BACKGROUND:Recent studies demonstrated that the "no reflow" phenomenon after coronary reflow implies the presence of advanced myocardial damage. In this study, we verified the prognostic value of the detection of this phenomenon by studying complications, left ventricular morphology, and in-hospital survival after acute myocardial infarction (AMI). METHODS AND RESULTS:The study population consisted of 126 patients with a first anterior AMI. All patients received coronary reflow within 24 hours of onset of symptoms and underwent myocardial contrast echocardiography (MCE) before and shortly after coronary reflow with an intracoronary injection of sonicated microbubbles. From contrast reperfusion patterns, patients were divided into two subsets: those with MCE no reflow (47 patients, 37%) and those with MCE reflow (79 patients). There was no difference in the frequency of arrhythmia or coronary events between the two subsets. Pericardial effusion and early congestive heart failure were observed more frequently in patients with MCE no reflow than in those with MCE reflow (26% versus 4%, P < .05; 45% versus 15%, P < .05, respectively). Congestive heart failure tended to be prolonged in those with MCE no reflow, and 3 patients (7%) of this subset died of pump failure. Left ventricular end-diastolic volume progressively increased in the convalescent stage in patients with MCE no reflow (early versus late, 145 +/- 43 versus 169 +/- 60 mL, P < .001), whereas it decreased in those with MCE reflow (154 +/- 42 versus 144 +/- 44 mL, P < .01). CONCLUSIONS:The substantial size of the MCE no reflow phenomenon at coronary reflow conveys useful information about an outcome of coronary intervention and left ventricular remodeling in individual patients with anterior wall AMI, although these are suggestive results in a limited number of patients. 10.1161/01.cir.93.2.223
    Association between the Glu298Asp and 4b/4a polymorphisms of endothelial nitric oxide synthase and coronary slow flow in the North Indian population. Gupta Mohit D,Akkarappatty Cherian,Girish Meenahalli P,Kumar Rahul,Rain Manjari,Tyagi Sanjay,Qadar Pasha Mohammed A Coronary artery disease RATIONALE:Genetic variants in endothelial nitric oxide synthase gene (NOS3) leading to endothelial dysfunction may be predispose to the coronary slow-flow phenomenon (CSFP). METHODS AND RESULTS:In this study, we examined the relationship between Glu298Asp (894G/T) and 4b/4a polymorphisms of NOS3 and CSFP. A total of 27 patients with CSFP but otherwise normal coronary arteries (mean age 50.4±8.2 years) and 200 controls with a normal coronary angiogram (mean age 53.1±8.6 years) were screened for Glu298Asp and 4b/4a polymorphisms by restriction fragment length polymorphism and PCR, respectively. Nitric oxide levels were determined using Griess' enzymatic method for an association with the polymorphisms. The genotype distribution of the Glu298Asp polymorphism differed significantly between the CSFP patients and controls (P=0.004). The dominant genetic model showed that GT+TT was significantly prevalent in patients in comparison with controls (P=0.014) and the T allele was significantly prevalent in patients (P=0.002). The genetic distribution of 4b/4a differed significantly for the heterozygous genotype ba (P=0.047). The overdominant genetic model re-established that the ba genotype was significantly prevalent in patients (P=0.044). Nitric oxide level was higher in patients than in controls, the values being 144.51±43.25 and 129.64±29.47 μmol/l, respectively (P>0.05). The genotypes of Glu298Asp showed a trend of association with nitric oxide levels, which decreased linearly in the order of GG, GT, and TT (P>0.05). CONCLUSION:The Glu298Asp polymorphism of NOS3 associates with CSFP. 10.1097/MCA.0000000000000093
    HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism. Kong Qiuyue,Dai Leyang,Wang Yana,Zhang Xiaojin,Li Chuanfu,Jiang Surong,Li Yuehua,Ding Zhengnian,Liu Li Scientific reports Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. HSPA12B is an endothelial-cell-specifically expressed heat shock protein. However, the roles of HSPA12B in acute myocardial I/R injury is unknown. Here we reported that myocardial I/R upregulated HSPA12B expression in ventricular tissues, and endothelial overexpression of HSPA12B in transgenic mice (Tg) limited infarct size, attenuated cardiac dysfunction and improved cardiomyocyte survival compared with their wild type littermates. These improvements were accompanied with the diminished myocardial no-reflow phenomenon, decreased microvascular leakage, and better maintained endothelial tight junctions. The I/R-evoked neutrophil infiltration was also suppressed in Tg hearts compared with its wild type (WT) littermates. Moreover, Tg hearts exhibited the enhanced activation of PI3K/Akt//mTOR signaling following I/R challenge. However, pharmacological inhibition of PI3K abolished the HSPA12B-induced cardioprotection against myocardial I/R injury. The data demonstrate for the first time that the endothelial HSPA12B protected hearts against myocardial I/R injury. This cardioprotective action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Our study suggests that targeting endothelial HSPA12B could be an alternative approach for the management of patients with myocardial I/R injury. 10.1038/srep33636
    Mechanism of Enhanced MerTK-Dependent Macrophage Efferocytosis by Extracellular Vesicles. de Couto Geoffrey,Jaghatspanyan Ervin,DeBerge Matthew,Liu Weixin,Luther Kristin,Wang Yizhou,Tang Jie,Thorp Edward B,Marbán Eduardo Arteriosclerosis, thrombosis, and vascular biology OBJECTIVE:Extracellular vesicles secreted by cardiosphere-derived cells (CDC) polarize macrophages toward a distinctive phenotype with enhanced phagocytic capacity (M). These changes underlie cardioprotection by CDC and by the parent CDCs, notably attenuating the no-reflow phenomenon following myocardial infarction, but the mechanisms are unclear. Here, we tested the hypothesis that M are especially effective at scavenging debris from dying cells (ie, efferocytosis) to attenuate irreversible damage post-myocardial infarction. Approach and Results: In vitro efferocytosis assays with bone marrow-derived macrophages, and in vivo transgenic rodent models of myocardial infarction, demonstrate enhanced apoptotic cell clearance with M. CDC exposure induces sustained MerTK expression in M through extracellular vesicle transfer of microRNA-26a (via suppression of ); the cardioprotective response is lost in animals deficient in MerTK. Single-cell RNA-sequencing revealed phagocytic pathway activation in M, with increased expression of complement factor , a phagocytosis facilitator. CONCLUSIONS:Together, these data demonstrate that extracellular vesicle modulation of MerTK and C1qa expression leads to enhanced macrophage efferocytosis and cardioprotection. 10.1161/ATVBAHA.119.313115
    miR-30e-5p Mitigates Hypoxia-Induced Apoptosis in Human Stem Cell-Derived Cardiomyocytes by Suppressing Bim. Mo Binhai,Wu Xiaodan,Wang Xiantao,Xie Jian,Ye Ziliang,Li Lang International journal of biological sciences Coronary microembolization can cause slow or no reflow, which is one of the crucial reasons for reverse of clinical advantage from cardiac reperfusion therapy. miRNAs and apoptosis are dramatically involved in the occurrence and process of cardiovascular diseases. Fortunately, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as an appealing model for the evaluation of cardiovascular diseases. Therefore, our study was designed to explore the role of miR-30e-5p and apoptosis in a hypoxia-induced hiPSC-CM injury model. Our results showed that the expression levels of miR-30e-5p were overtly downregulated in a time-dependent manner under hypoxic conditions. Expression of miR-30e-5p was significantly downregulated after 24 hours of hypoxia, hypoxia treatment dramatically induced apoptosis. Calcium handling capability significantly decreased after 24 hours of hypoxia treatment. miR-30e-5p overexpression partially mitigated hypoxia-induced apoptosis and rescued hypoxia-induced calcium handling defects in hiPSC-CMs. The luciferase reporter assay showed that miR-30e-5p can directly target the 3'-UTR of Bim, which is an apoptosis activator and autophagy suppressor. The mRNA and protein of Bim remarkably increased after hypoxia treatment and reduced with miR-30e-5p overexpression. Moreover, downregulation of Bim mitigated hypoxia-induced apoptosis and activated autophagy. These results demonstrated that miR-30e-5p mitigated hypoxia-induced apoptosis in hiPSC-CMs at least in part via Bim suppression and subsequent autophagy activation. Our study suggested miR-30e-5p may act as a potential therapeutic target for coronary microembolization. 10.7150/ijbs.31099
    The Relationship between Interleukin-6 Promotor Polymorphisms and Slow Coronary Flow Phenomenon. Liu Chun-Ling,Xue Zong-Qian,Gao Shu-Ping,Chen Chu,Chen Xiao-Hu,Pan Min,Wang Zhen-Xing Clinical laboratory BACKGROUND:Several lines of evidence suggest that slow coronary flow (SCF) phenomenon seems to be an early form of atherosclerosis and low-grade inflammation plays a role in the development of SCF. Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response, and has both pro-inflammatory and anti-inflammatory properties. The aim of the present study is to investigate the relationship between IL-6 -634C/G polymorphism and SCF in Han Chinese. METHODS:250 subjects who underwent coronary angiography and had normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. 41 patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and 209 subjects within normal limits served as normal coronary flow (NCF) group. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes. RESULTS:The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 56.94%, 37.80%, and 5.26% in the NCF subjects, and 36.59%, 48.78%, and 14.63% in the SCF group, respectively (p = 0.0173). The frequency of the G allele in the SCF (39.02%) group was significantly higher than that in the NCF (24.16%) group (p = 0.0054). Compared with the CC genotype, the G allele carriers (CG + GG genotypes) had increased risk of SCF in both unadjusted and adjusted analyses. In SCF patients, the average serum IL-6 levels (pg/mL) in CG + GG genotype (4.78 ± 0.42) were statistically higher than in CC genotype (3.93 ± 0.36) (p = 0.0000). CONCLUSIONS:Our data support that IL-6 -634C/G polymorphism is associated with SCF and the G allele has increased risk for SCF in Han Chinese. 10.7754/clin.lab.2015.151021
    The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1. Su Qiang,Lv Xiangwei,Ye Ziliang,Sun Yuhan,Kong Binghui,Qin Zhenbai,Li Lang Cell death & disease Coronary microembolization (CME) is a common complication seen during primary percutaneous coronary intervention (pPCI). CME-induced myocardiac inflammation is the primary cause of myocardiac injury. Dysregulated miR-142-3p has been implicated in multiple cardiovascular diseases and is significantly downregulated in CME-induced myocardial injury. However, the role of miR-142-3p in CME-induced myocardial injury is unclear. This study herein built a porcine CME model by infusing microembolization spheres into the left anterior descending branch via a microcatheter, and detected the downregulation of miR-142-3p in the myocardial tissues of CME pigs. Echocardiography, hematoxylin basic fuchsin picric acid (HBFP) staining, and western blotting of NF-κB p65, TNF-α, IL-1β, and IL-6 showed that the pharmacological overexpression of miR-142-3p using agomiR has improved cardiac function and attenuated CME-induced myocardiac inflammatory response, while its inhibition using antagomiR demonstrated inverse effects. Moreover, in vitro experiments demonstrated IRAK-1 as a direct target gene of miR-142-3p. Luciferase reporter assays, quantitative real-time polymerase chain reaction and western blotting demonstrated its effects in controlling the inflammation of cardiomyocytes. It is noteworthy that miR-142-3p was found to be decreased in the plasma of STEMI patients undergoing pPCI with no-reflow, indicating a potential clinical relevance of miR-142-3p. The receiver-operator characteristic curve indicated that plasma miR-142-3p might be an independent predictor of no-reflow during pPCI in patients with STEMI. Therefore, overexpression of miR-142-3p acts as a novel therapy for CME-induced myocardial injury. 10.1038/s41419-019-1341-7
    Interleukin-1 gene cluster polymorphisms associated with coronary slow flow phenomenon. Yasri Sora,Wiwanitkit Viroj Anatolian journal of cardiology 10.14744/AnatolJCardiol.2018.26429
    [Relationship between plasma miR-126 and coronary slow flow phenomenon]. Wang L,Wang H N,Zu X L Zhonghua yi xue za zhi To investigate the relationship between miR-126 in plasma and coronary slow flow (CSF) phenomenon. A total of 109 patients without coronary artery disease who underwent coronary angiography at Beijing Anzhen Hospital Affiliated to Capital Medical University from August 2016 to March 2018 were enrolled. The patients were divided into CSF groups (53 cases) and the control group (56 cases) according to CSF existing or not. Clinical data and blood samples of the participants in two groups were collected. Real-time quantitative PCR (RT-qPCR) was used to determine the expression of miR-126 in plasma, and the relationship between miR-126 and CSF and its predictive effect were analyzed. Mean TIMI frame counts (34±4 vs 20±3), left anterior descending TIMI frame counts (35±5 vs 21±3), left gyroscopic TIMI frame counts (36±5 vs 20±3), right coronary TIMI frame counts (34±5 vs 20±35) and expression level of hypersensitive C-reactive protein (hs-CRP, (3.0±1.2) mg/L vs (2.1±0.9) mg/L) and plasma miR-126 (0.25±0.09 vs 0.19±0.10) of the CSF group were significantly higher than those of the control group (0.05). Correlation analysis showed that miR-126 and hs-CRP levels were significantly correlated with mean TIMI frame count (0.367, 0.05), and miR-126 was also significantly associated with the hs-CRP level (0.388, 0.05). Logistic regression analysis showed that miR-126 (2.513) and hs-CRP (1.568) were independent risk factors for coronary slow flow. The area under the ROC curve of miR-126 predicting for CSF was 0.661. When the cutoff value was set at 0.225, the Youden index reached the maximum with a sensitivity of 0.660 and a specificity of 0.714. The expression level of miR-126 in plasma is significantly correlated with CSF, and miR-126 can be used as a predictor of coronary slow flow phenomenon. 10.3760/cma.j.issn.0376-2491.2019.17.010
    Clinical and laboratory predictors of coronary slow flow in coronary angiography. Ghaffari Samad,Tajlil Arezou,Aslanabadi Naser,Separham Ahmad,Sohrabi Bahram,Saeidi Gholamreza,Pourafkari Leili Perfusion BACKGROUND:The coronary slow-flow phenomenon (CSFP) is a multifactorial angiographic finding with no established pathogenesis. OBJECTIVE:To investigate the role of clinical profile and laboratory findings in patients with CSFP. METHODS:We prospectively recruited 69 patients with angiographically diagnosed CSFP and compared them with 88 patients with normal coronary flow. Demographic information, comorbidities and laboratory analysis, including complete blood count with differential, lipid profile and serum biochemical analysis, were documented and compared in univariate and multivariate analyses. RESULTS:Patients with CSFP were more likely to be male and active smokers. Total cholesterol, triglyceride, hemoglobin and hematocrit, platelet count, mean platelet volume, platelet distribution width and red cell distribution width (RDW) were all higher in patients with CSFP. In multivariate regression analysis, including smoking, total cholesterol, hematocrit, fasting blood glucose and red cell distribution width, except fasting blood glucose, all variables were independently associated with CSFP. Receiver operating characteristic curve analysis revealed a cut-off point of 13.05% for RDW with a sensitivity of 74.6% and a specificity of 77.3% (p<0.001, AUC = 0.802) A cut-off value of 11.35% for PDW had a 89.9% sensitivity and 98.9% specificity for the prediction of CSFP (p<0.001, AUC = 0.970) Conclusion: The changes of circulating blood cell components in patients with CSFP may be indicative of underlying inflammation and endothelial dysfunction that should be investigated in experimental studies. 10.1177/0267659116659918
    Feasibility Study of Transthoracic Echocardiography for Coronary Slow Flow Phenomenon Evaluation: Validation by Coronary Angiography. Li Yijia,Fang Fang,Ma Ning,Li Rongjuan,Sun Qiwei,Yang Jiao,Nie Shaoping,Yu Cheuk-Man,Yang Ya Microcirculation (New York, N.Y. : 1994) OBJECTIVE:This study aimed to assess echocardiography parameters in CSFP evaluation. METHODS:This study enrolled 79 consecutive patients with CSFP validated by coronary angiography and control individuals with normal coronary flow. Coronary flow rates were determined by corrected CTFC. Clinical and coronary angiography data and coronary parameters assessed by echocardiography using the CFI were recorded. RESULTS:Baseline characteristics were similar between the two groups. Patients with CSFP were predominantly males, with higher BMI values, weights and triglyceride levels (p < 0.05), but lower platelet counts (p < 0.05). Conventional echocardiography parameters were similar in the two groups. However, echocardiographic measurements of the LAD, including PDV, MDV, PDP, MDP and VTI, in the CSFP group were lower compared with control values (p < 0.05). BMI was positively correlated with CSFP. LAD's CTFC showed strong inverse correlations with PDV, MDV, PDP, and MDP in CSFP groups. ROC curve analysis revealed that coronary artery flow-related parameters occupied more than half of the AUC. CONCLUSIONS:CSFP could be identified with the help of echocardiography. 10.1111/micc.12274
    CHA2DS2-VASc Score as an Independent Predictor of Suboptimal Reperfusion and Short-Term Mortality after Primary PCI in Patients with Acute ST Segment Elevation Myocardial Infarction. Ashoori Ammar,Pourhosseini Hamidreza,Ghodsi Saeed,Salarifar Mojtaba,Nematipour Ebrahim,Alidoosti Mohammad,Haji-Zeinali Ali-Mohammad,Nozari Yones,Amirzadegan Alireza,Aghajani Hassan,Jalali Arash,Hosseini Zahra,Jenab Yaser,Geraiely Babak,Omidi Negar Medicina (Kaunas, Lithuania) We aimed to demonstrate the clinical utility of CHA2DS2-VASc score in risk assessment of patients with STEMI regarding adverse clinical outcomes particularly no-reflow phenomenon. We designed a retrospective cohort study using the data of Tehran Heart Center registry for acute coronary syndrome. The study included 1331 consecutive patients with STEMI who underwent primary angioplasty. Patients were divided into two groups according to low and high CHA2DS2-VASc score. Angiographic results of reperfusion were inspected to evaluate the association of high CHA2DS2-VASc score and the likelihood of suboptimal TIMI flow. The secondary endpoint of the study was short-term in-hospital mortality of all cause. The present study confirmed that CHA2DS2-VASc model enables us to determine the risk of no-reflow and all-cause in-hospital mortality independently. Odds ratios were 1.59 (1.30⁻2.25) and 1.60 (1.17⁻2.19), respectively. Moreover, BMI, high thrombus grade, and cardiogenic shock were predictors of failed reperfusion (odds were 1.07 (1.01⁻1.35), 1.59 (1.28⁻1.76), and 8.65 (3.76⁻24.46), respectively). We showed that using a cut off value of ≥ two in CHA2DS2-VASc model provides a sensitivity of 69.7% and specificity of 64.4% for discrimination of increased mortality hazards. Area under the curve: 0.72 with 95% CI (0.62⁻0.81). Calculation of CHA2DS2-VASc score applied as a simple risk stratification tool before primary PCI affords great predictive power. Furthermore, incremental values are obtained by using both CHA2DS2-VASc and no-reflow regarding mortality risk assessment. 10.3390/medicina55020035
    Long-Term Follow-up of Patients with Coronary Slow Flow Phenomenon. Sadamatsu Kenji,Koga Yasuaki,Tashiro Hideki American journal of cardiovascular drugs : drugs, devices, and other interventions 10.1007/s40256-017-0241-4
    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. Keeble Thomas R,Karamasis Grigoris V,Noc Marco,Sredniawa Beata,Aradi Daniel,Neskovic Aleksandar N,Arheden Håkan,Erlinge David,Holzer Michael Cardiovascular revascularization medicine : including molecular interventions 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 ± 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. 10.1016/j.carrev.2018.09.014
    Effect of Chinese Medicine on No or Slow Reflow after Percutaneous Coronary Intervention in Myocardial Infarction Patients: A Systematic Review and Meta-Analysis. Zhang Xiao-Yu,Sun Yang,Yang Xin-Yu,Hu Jia-Yuan,Zheng Rui,Chen Shi-Qi,Li Min,Li Cheng-Yu,Jiang Yin,Liu Shuo,Zhao Chen,Xing Yan-Wei,Shang Hong-Cai Chinese journal of integrative medicine OBJECTIVE:To systematic review the effect of Chinese medicine (CM) on no or slow reflow after percutaneous coronary intervention (PCI) in myocardial infarction (MI) patients. METHODS:The PubMed, EMBASE databases, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Knowledge Service Platform (Wanfang Database) and Chinese Scientific Journal Database (VIP) were searched up to December 2017. Randomized controlled trials (RCTs) which evaluated the effect of CM therapies on no or slow reflow after PCI in MI patients were included. The primary outcome was the effect of reperfusion. Secondary outcomes were left ventricular ejection fraction, incidence of major adverse cardiovascular events and adverse effect. RESULTS:Ten RCTs covering 814 patients were included. Two studies revealed that the incidence of no or slow reflow was less in Shenmai Injection () group than in the control group measured by thrombolysis in myocardial infarction (TIMI) ⩽ 2 (risk ratio=0.55, 95% confidence interval 0.38 to 0.81, P=0.003, I=37%). Two studies indicated that Salvianolate Injection showed no additional benefit on no or slow reflow measured by corrected TIMI frame count compared with the conventional treatment (mean difference -4.24, 95% confidence interval -13.03 to 4.54, P=0.34, I=86%). In addition, Tongxinluo Capsules (), Danhong Injection () and Xuesaitong Injection () may have the potential to reduce no or slow reflow measured during or after PCI in individual studies. CONCLUSIONS:Current evidence from RCTs are not sufficient to evaluate the effect of CM adjuvant therapies on no or slow reflow after PCI for MI patients. The included studies are limited by small sample size and unclear baseline conditions. Further rigorously designed researches and verification studies with sufficient number of patients are warranted. 10.1007/s11655-019-2703-9
    Relationship between R-wave peak time and no-reflow in ST elevation myocardial infarction treated with a primary percutaneous coronary intervention. Çağdaş Metin,Karakoyun Süleyman,Rencüzoğullari İbrahim,Karabağ Yavuz,Yesin Mahmut,Uluganyan Mahmut,Gürsoy Mustafa O,Artaç İnanç,İliş Doğan,Efe Süleyman Ç,Taşar Onur Coronary artery disease OBJECTIVES:Coronary no-reflow (NR) is observed in nearly half of ST segment elevation myocardial infarction (STEMI) patients who undergo a primary percutaneous coronary intervention (pPCI) despite epicardial coronary vessel patency. Several methods used to define NR include thrombolysis in myocardial infarction grade, corrected thrombolysis in myocardial infarction frame count, myocardial blush grade, ST-segment resolution, contrast echocardiography, and MRI. The aim of our study was to evaluate the relationship between NR and R-wave peak time (RWPT) measured from infarct-related artery leads METHOD: We enrolled 282 consecutive STEMI patients treated with pPCI in Kafkas University Hospital from January 2014 to January 2015. After exclusion, the remaining 233 patients were included in the study population RESULTS: Patients were divided into two groups according to the development of NR. We observed that increased preprocedural (31 (27-37) vs 27 (21-30) p<0,001) and postprocedural RWPT(35±7 vs 22±6 p<0,001) was associated with the development of NR and preprocedural RWPT(OR: 1.254 95% CI: 1.104-1.425 p<0,001) was found to be independent predictor of NR. The association between postprocedural RWPT and angiographic NR was statistically noninferior to that between ST-segment resolution % and NR(difference between area under curves: 0.0232, p= 0.38) CONCLUSION: the present study is the first to report a significant correlation between NR and RWPT in STEMI patients treated with primary pPCI. 10.1097/MCA.0000000000000477
    Intracoronary or intravenous abciximab after aspiration thrombectomy in patients with STEMI undergoing primary percutaneous coronary intervention. Bedjaoui Ali,Allal Karima,Lounes Mohamed Sofiane,Belhadi Chams Eddine,Mekarnia Abdelmoumen,Sediki Saber,Kara Maamar,Azaza Adel,Monsuez Jean-Jacques,Benkhedda Salim Cardiovascular journal of Africa 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. 10.5830/CVJA-2018-063
    Invasive Assessment of the Coronary Microcirculation in Reperfused ST-Segment-Elevation Myocardial Infarction Patients: Where Do We Stand? Bulluck Heerajnarain,Foin Nicolas,Tan Jack W,Low Adrian F,Sezer Murat,Hausenloy Derek J Circulation. Cardiovascular interventions For patients presenting with an acute ST-segment-elevation myocardial infarction, the most effective therapy for reducing myocardial infarct size and preserving left ventricular systolic function is primary percutaneous coronary intervention (PPCI). However, mortality and morbidity remain significant. This is partly attributed to the development of microvascular obstruction, which occurs in around 50% of ST-segment-elevation myocardial infarction patients post-PPCI, and it is associated with adverse left ventricular remodeling and worse clinical outcomes. Although microvascular obstruction can be detected by cardiac imaging techniques several hours post-PPCI, it may be too late to intervene at that time. Therefore, being able to predict the development of microvascular obstruction at the time of PPCI may identify high-risk patients who might benefit from further adjuvant intracoronary therapies, such as thrombolysis, vasodilators, glycoprotein IIb/IIIa inhibitors, and anti-inflammatory agents that may reduce microvascular obstruction. Recent studies have shown that invasive coronary physiology measurements performed during PPCI can be used to assess the coronary microcirculation. In this article, we provide an overview of the various invasive methods currently available to assess the coronary microcirculation in the setting of ST-segment-elevation myocardial infarction, and how they could potentially be used in the future for tailoring therapies to those most at risk. 10.1161/CIRCINTERVENTIONS.116.004373
    Association of Interleukin-1 Gene cluster polymorphisms with coronary slow flow phenomenon. Mutluer Ferit Onur,Ural Dilek,Güngör Barış,Bolca Osman,Aksu Tolga Anatolian journal of cardiology OBJECTIVE:Coronary slow flow phenomenon (CSFP) is characterized by the decreased rate of contrast progression in epicardial coronary arteries in the absence of significant coronary stenosis. Mounting evidence has showed a significant association between inflammation and CSFP severity. This study aimed to evaluate possible associations between interleukin-1 receptor antagonist (IL-1ra) gene variable number tandem repeat (VNTR), IL-1ß -511 single nucleotide (SNP), and IL-1ß+3954 SNP mutations with CSFP. METHODS:Forty-eight patients with CSFP and 62 controls with angiographically normal coronary arteries were prospectively enrolled in the study. Genotypes were assessed using the polymerase chain reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS:Homozygote genotype for allele 2 of+3954 C>T 2/2 genotype was significantly more frequent in patients with CSFP than in the control group, whereas 1/2 genotype was more frequent in the control group (35.4% versus 14.5% for 2/2 genotype and 25% versus 35.5% for 1/2 genotype in CSFP and control groups, respectively, X=6.6; p=0.04). The allelic frequency of allele 2 of this polymorphism was significantly higher in the CSFP group than in the control group (47.9% versus 28.6% in the control group, X=5.6; p=0.02). However, there was no significant difference with regard to genotype or allelic frequencies of IL-1ra VNTR or IL-1ß -511 SNP polymorphisms between patients with CSFP and controls. CONCLUSION:IL-1ß+3954 SNP mutations are significantly more common in patients with CSFP. It may suggest that the tendency for inflammation may contribute to the presence of this phenomenon. 10.14744/AnatolJCardiol.2017.8071
    Usefulness of The C-Reactive Protein/Albumin Ratio for Predicting No-Reflow in ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Karabağ Yavuz,Çağdaş Metin,Rencuzogullari Ibrahim,Karakoyun Süleyman,Artaç İnanç,İliş Doğan,Yesin Mahmut,Çağdaş Öznur Sadioğlu,Altıntaş Bernas,Burak Cengiz,Tanboğa Halil Ibrahim European journal of clinical investigation BACKGROUND:The ratio of serum C-reactive protein (CRP) to albumin has been proven to be a more accurate indicator than albumin and CRP levels alone in determining the prognosis of patients with cancer and critical illness. The aim of this study was to determine whether the CRP/albumin ratio (CAR) can be linked to imperfect reperfusion that can worsen the prognosis of ST-elevation myocardial infarction (STEMI) in patients treated with primary percutaneous coronary intervention (pPCI). MATERIALS AND METHODS:A total of 1217 consecutive STEMI patients who achieved epicardial vessel patency with pPCI were recruited to this study. RESULTS:The study population was divided into 2 groups: reflow (n = 874) and no-reflow (NR) (n = 343) groups. The white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR) and CAR (0.03 [0.01-0.04] vs 0.06 [0.03-0.12] (P < .001) were significantly higher in the NR group than in the reflow group, and these factors were found to be independent predictors of NR development. The best cut-off value of CAR predicting NR was 0.59 with a sensitivity of 54.7% and specificity of 86.7. The predictive power of CAR surpassed that of CRP, albumin, WBC count and NLR in the receiver operator curve (ROC) curve comparison. CONCLUSION:No-reflow can be predicted by systemic inflammation markers including WBC count, NLR and CAR measured from the blood sample obtained on admission. CAR has a higher clinical value than CRP, albumin level, WBC count and NLR in NR prediction. 10.1111/eci.12928
    The utility of the TIMI risk index on admission for predicting angiographic no-reflow after primary percutaneous coronary intervention in patients with STEMI. Acet Halit,Ertaş Faruk,Akil Mehmet Ata,Bilik Mehmet Zihni,Aydin Mesut,Polat Nihat,Yildiz Abdulkadir Turkish journal of medical sciences BACKGROUND/AIM:The thrombolysis in myocardial infarction (TIMI) risk score (TRS), and the TIMI risk index (TRI) have been reported in coronary artery disease patients. We investigated whether admission TRI is associated with no-reflow (NRF) in patients undergoing primary percutaneous coronary intervention (p-PCI). MATERIALS AND METHODS:ST-segment elevation myocardial infarction (STEMI) patients treated with p-PCI were included in the study. TRI was calculated on admission using specified variables. We defined the angiographic NRF phenomenon as a coronary TIMI flow grade of ≤2 after the vessel was recanalized or a TIMI flow grade of 3 together with a final myocardial blush grade (MBG) of <2 in a manner as described in previous studies. RESULTS:A total of 371 patients (aged 62 ± 14 years; 73/27 men to women ratio) who underwent p-PCI were enrolled in the study. In terms of age, NRF patients were older than reflow patients (P < 0.017 for MBG). Killip class III-IV designations were more common in NRF patients (P = 0.029 for MBG). TRI (P = 0.014 for MBG) values were significantly greater in the NRF group. TRI was an independent predictor of NRF according to MBG flow (P = 0.003, B = -0.035, Exp B = 0966, 95% CI, 0.944-0.988). CONCLUSION:Admission TRI may predict the development of NRF phenomenon after p-PCI in patients with acute STEMI. 10.3906/sag-1411-157
    P wave peak time; a novel electrocardiographic parameter in the assessment of coronary no-reflow. Çağdaş Metin,Karakoyun Süleyman,Rencüzoğulları İbrahim,Karabağ Yavuz,Yesin Mahmut,Gürsoy Mustafa Ozan,Artaç İnanç,İliş Doğan,Efe Süleyman Çağan,Taşar Onur,Karaca Gürkan Journal of electrocardiology OBJECTIVES:Coronary no-reflow (NR) following primary percutaneous coronary intervention (pPCI) is associated with worsened prognosis in patients with ST segment elevation myocardial infarction (STEMI). Despite rapid developments in cardiovascular area; there are limited data regarding prediction of NR before pPCI. P wave duration and dispersion (PWD, PW respectively) have been studied in STEMI patients and found to be associated with reperfusion success; however none of them has been found to predict NR before PCI. In our study we aimed to evaluate whether PWD, PW and a novel parameter P wave peak time (PWPT) could predict NR development in STEMI patients. METHOD:Fifty six patients who were admitted with anterior STEMI constituted study populations. The diagnosis and treatment of STEMI was made on the basis of current guidelines. P wave parameters including PWD, PW and PWPT were calculated from electrocardiograms that were obtained on admission and 60 min after pPCI. RESULTS:Patients were divided into two groups according to the development of NR. We observed that PWPT that were obtained from D2 (PWPT) and V1 (PWPT) leads were longer in NR group than reflow group. There were significant correlations between PWPT and reperfusion parameters regarding percent of ST segment resolution, peak CKMB level and TIMI frame count of infarct related artery. Preprocedural PWPT was found to be an independent predictor of NR development. CONCLUSION:In our study we observed that PWPT could be a useful parameter in the assessment of reperfusion success and prediction of NR development. 10.1016/j.jelectrocard.2017.06.010
    Reduction of No Reflow with a Loading Dose of Atorvastatin before Primary Angioplasty in Patients with Acute ST Myocardial Infarction. García-Méndez Rosalba C,Almeida-Gutierrez Eduardo,Serrano-Cuevas Leonor,Sánchez-Díaz Jesús Salvador,Rosas-Peralta Martín,Ortega-Ramirez Jose Alberto,Palomo-Villada Jose Antonio,Isordia-Salas Irma,Alonso-Bravo Rosa Marisol,Borrayo-Sanchez Gabriela Archives of medical research 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. 10.1016/j.arcmed.2018.10.006
    Prognostic Association of Circulating Neutrophil Count with No-Reflow in Patients with ST-Segment Elevation Myocardial Infarction following Successful Primary Percutaneous Intervention. Tian Jinfan,Liu Yue,Liu Yanfei,Song Xiantao,Zhang Min,Xu Feng,Yuan Fei,Lyu Shuzheng Disease markers Objective:The aim of the present study was to investigate the predictive value of neutrophil count for no-reflow in patients with ST-segment elevation myocardial infarction (STEMI) who underwent successful primary percutaneous intervention (PCI). Methods:We conducted a retrospective study of 361 patients diagnosed with acute STEMI between 2011 and 2015. All patients underwent successful PCI within 12 h from the onset of symptoms. Angiographic no-reflow was diagnosed based on a post-PCI thrombolysis in myocardial infarction flow grade ≤ 2 without mechanical obstruction. According to a neutrophil count cut-off determined by receiver operating characteristic curve analysis, patients were divided into two groups: group A (neutrophil count < 9.14 × 10/L) and group B (neutrophil count ≥ 9.14 × 10/L). Results:Compared to patients in the normal reflow group, patients with no-reflow had higher neutrophil counts ( < 0.05). The incidence rate of no-reflow in group A (18, 9.3%) was significantly lower than that in group B (38). Multivariate logistic regression analysis revealed that a neutrophil count ≥ 9.14 × 10/L was independently predictive for no-reflow (odds ratio = 4.474, 95% confidence interval: 1.610-12.433, = 0.004) after adjusting for potential confounders. Conclusions:A circulating neutrophil count ≥ 9.14 × 10/L is independently associated with no-reflow in patients with acute STEMI following primary PCI. 10.1155/2017/8458492
    Clinical significance of no-reflow in different stages of primary angioplasty among patients with acute myocardial infarctions. Jiecheng Peng,Ai-Ling Wang Perfusion BACKGROUND:The coronary no-reflow (NR) phenomenon, which is associated with poor clinical outcomes, is usually referred to as a post-percutaneous coronary intervention (PCI) state. NR can occur in different stages of the PCI procedure, not only including the post-stenting stage, but from balloon pre-dilation to pre-stenting. The clinical significance of NR in the different stages of the PCI procedure is unclear. The purpose of the current study was to analyze the clinical and angiographic characteristics, the prognosis for NR patients in the aforementioned two stages and to determine the predictors of NR in the early stage. METHODS:Between January 2009 and December 2013, a total of 420 consecutive patients with ST-segment elevation myocardial infarction (STEMI) underwent primary PCI. Sixty-three patients (15%) with NR constituted the study population. The patients were divided into an early NR group and a subsequent NR group. The clinical and angiographic findings were compared between the two groups. Multivariate logistic regression was used to determine the predictors for early NR. The long-term clinical outcomes after PCI were analyzed. RESULTS:Regarding the baseline characteristics, we identified that the early NR group had statistically significant effects on the higher percentage of diabetes mellitus (42.9% vs. 20%), lower admission systolic blood pressure (SBP) (102.2 ± 8.3 mmHg vs. 110.5 ± 7.6 mmHg), higher percentage of Killip classification III (71.4% vs. 45.7%,) and longer reperfusion time (7.1 ± 2.3 h vs. 5.88 ± 2.2 h) compared to the subsequent NR group.There were significant differences between the two groups with respect to the percentage of initial thrombolysis in myocardial infarction (TIMI) flow 0/1 (64.3% vs. 37.1%), target lesion length (31.4 ± 13.6 mm vs. 20.5 ± 17.3 mm) and thrombus score ⩾ 4 (67.9% vs. 42.9%; p < 0.05 for all). Multiple stepwise logistic regression analysis indicated that an admission SBP < 100 mmHg (OR = 4.580; 95% CI = 1.385-15.150; p = 0.0130), reperfusion time ⩾ 6 h (OR = 4.978; 95% CI = 1.468-16.882; p = 0.010) and a thrombus score ⩾ 4 (OR = 2.708; 95% CI = 0.833-8.799; p = 0.008) were the independent determinants of the early NR. During a 1-year follow-up, the all-cause mortality and overall major adverse cardiac events (MACEs) in the early NR group occurred significantly more often than in the subsequent NR group (28.6% vs. 5.7% and 35.7% vs. 14.3%, respectively, p ITALIC! <0.05). The early NR group had a lower left ventricular ejection fraction (LVEF) (42.5 ± 4.7 vs. 47.8 ± 3.5, p ITALIC! < 0.001) and a larger left ventricular end diastolic diameter (LVEDD) (56.0 ± 4.0 vs. 51.5 ± 4.7, p = 0.001) at the end of the follow-up. CONCLUSION:Early NR patients during primary PCI have more severe baseline clinical and angiographic characteristics, as well as a poorer long-term prognosis. 10.1177/0267659115604891
    Association between SYNTAX II score and electrocardiographic evidence of no-reflow in patients with ST-segment elevation myocardial infarction. Aşkın Lütfü,Aktürk Erdal Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir OBJECTIVE:This study was performed to examine the association between the SYNTAX II score (SS-II) and no-reflow observed on electrocardiography and examine their use in the evaluation of risk of an in-hospital major adverse cardiovascular event (MACE) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS:A total of 126 consecutive STEMI patients who underwent primary percutaneous coronary intervention (pPCI) were recruited. The SS-II was derived using angiographic and basic patient clinical features. The difference in the sum of Stsegment elevations measured between before the pPCI and the assessment determined approximately 60 minutes after the pPCI was interpreted as the sum of ST-segment resolution (ΣSTR). MACE is a composite endpoint frequently used in cardiovascular research and usually includes endpoints reflecting safety and effectiveness. ΣSTR <50% was defined as incomplete ΣSTR (no-reflow group; n=44), while ΣSTR <50% was defined as complete ΣSTR (normal-flow group, n=82). RESULTS:The SS-II was significantly higher in the no-reflow group (p<0.001). SS-II and no-reflow findings were associated with MACE. Logistic regression analysis demonstrated significant predictive values of SS-II (Odds ratio [OR]: 1.169; 95% confidence interval [CI]: 1.084-1.260; p<0.001) and ΣSTR (OR: 0.764; 95% CI: 0.632-0.924; p=0.006) for in-hospital MACE. CONCLUSION:SS-II was significantly associated with no-reflow as assessed by electrocardiography. In patients with STEMI, SS-II and no-reflow (incomplete ΣSTR) may be important predictive factors for in-hospital MACE. 10.5543/tkda.2018.86132
    Effect of Elevated Reperfusion Pressure on "No Reflow" Area and Infarct Size in a Porcine Model of Ischemia-Reperfusion. Pantsios Chris,Kapelios Chris,Vakrou Styliani,Diakos Nikolaos,Pozios Iraklis,Kontogiannis Chris,Nanas John,Malliaras Konstantinos Journal of cardiovascular pharmacology and therapeutics BACKGROUND:The "no reflow" phenomenon (microvascular obstruction despite restoration of epicardial blood flow) develops postreperfusion in acute myocardial infarction and is associated with poor prognosis. We hypothesized that increased reperfusion pressure may attenuate the no reflow phenomenon, as it could provide adequate flow to overcome the high resistance of the microvasculature within the no reflow zone. Thus, we investigated the effect of modestly elevated blood pressure during reperfusion on the extent of no reflow area and infarct size in a porcine model of ischemia-reperfusion. METHODS:Eighteen farm pigs underwent acute myocardial infarction by occlusion of the anterior descending coronary artery for 1 hour, followed by 2 hours of reperfusion. Just prior to reperfusion, animals were randomized into 2 groups: in group 1 (control group, n = 9), no intervention was performed. In group 2 (n = 9), aortic pressure was increased by ∼20% (compared to ischemia) by partial clamping of the ascending aorta during reperfusion. Following 2 hours of reperfusion, animals were euthanized to measure area at risk, infarct size, and area of no reflow. RESULTS:Partial clamping of the ascending aorta resulted in modest elevation of blood pressure during reperfusion. The area at risk did not differ between the 2 groups. The no reflow area was significantly increased in group 2 compared to control animals (50% ± 13% vs 37% ± 9% of the area at risk; P = .04). The infarcted area was significantly increased in group 2 compared to control animals (75% ± 17% vs 52% ± 23% of the area at risk; P = .03). Significant positive correlations were observed between systolic aortic pressure and no reflow area, between systolic aortic pressure and infarcted area and between infarcted area and no reflow area during reperfusion. CONCLUSIONS:Modestly elevated blood pressure during reperfusion is associated with an increase in no reflow area and in infarct size in a clinically relevant porcine model of ischemia-reperfusion. 10.1177/1074248415617850
    Correlates of the "No-Reflow" or "Slow-Flow" Phenomenon in Patients Undergoing Primary Percutaneous Coronary Intervention. Alidoosti Mohammad,Lotfi Reza,Lotfi-Tokaldany Masoumeh,Nematipour Ebrahim,Salarifar Mojtaba,Poorhosseini Hamidreza,Jalali Arash The journal of Tehran Heart Center Despite recent advances in interventional equipment and techniques, the angiographic no-reflow phenomenon occurs in a considerable number of patients undergoing primary percutaneous coronary intervention (PCI). We investigated the clinical, angiographic, preprocedural, and procedural characteristics associated with the no-reflow phenomenon among patients undergoing primary PCI. Between March 2008 and April 2013, 530 patients (78.5% male, mean age=58.11±12.39 y) with ST-segment-elevation myocardial-infarction who underwent primary PCI were categorized in 2 groups according to their postprocedural thrombolysis-in-myocardial infarction (TIMI) flow grades: those with a maximum score of 2 (the no-reflow or slow-flow group) and the ones with a score of 3 (the reflow group). A multivariable logistic regression model was used to find the multiple correlates of the no-reflow phenomenon after PCI. There were 166 (31.3%) patients in the no-reflow group and 364 (68.7%) in the reflow group. The no-reflow patients were older and had significantly longer target lesion lengths, higher SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) scores, higher infarct-related artery SYNTAX scores, more thrombus burden, and a higher frequency of initial TIMI flow grades of 2 or lower. Our multivariable logistic regression analysis demonstrated that older age, higher numbers of Q waves, not using statin, longer target lesion lengths, higher thrombus grades, and higher infarct-related artery SYNTAX scores remained the independent correlates of increased no-reflow rates after primary PCI (area under the ROC curve=0.784, 95% CI: 0.742-0.826; P<0.001). Clinical, angiographic, and procedural features of patients undergoing primary PCI may be correlated with the occurrence of the no-reflow phenomenon. The thrombus grade and the infarct-related artery SYNTAX score could be among these factors.
    Different inflammatory profile in young and elderly STEMI patients undergoing primary percutaneous coronary intervention (PPCI): Its influence on no-reflow and mortality. Del Turco Serena,Basta Giuseppina,De Caterina Alberto Ranieri,Sbrana Silverio,Paradossi Umberto,Taddei Alessandro,Trianni Giuseppe,Ravani Marcello,Palmieri Cataldo,Berti Sergio,Mazzone Annamaria International journal of cardiology BACKGROUND:Coronary no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI) is associated with a poor clinical prognosis. Although its pathophysiology is not fully elucidated, a deregulated systemic inflammatory response plays an important role. Specifically, the relationship between age-associated differences in inflammatory markers and either no-reflow or mortality in STEMI patients undergoing primary percutaneous coronary intervention (pPCI) has never been investigated. METHODS AND RESULTS:We retrospectively enrolled 625 consecutive STEMI patients undergoing pPCI for whom a complete laboratory inflammatory pattern was available. Routinely blood measured laboratory parameters were collected at the moment of admission. No reflow was defined as Thrombolysis in Myocardial Infarction (TIMI) flow-grade lower than 3. The population was divided into two groups using a cut-off centered at 65 years. Compared to younger patients, elderly patients had higher mean values of fibrinogen, brain natriuretic peptide (BNP), leukocytes, neutrophil-to-lymphocyte ratio (NLR), C reactive protein/albumin ratio (CAR). Conversely, lymphocyte count and albumin levels were higher in young patients. In elderly patients, the values of NLR, CAR as well as leukocytes, fibrinogen and neutrophils were associated with no-reflow, while in young patients only BNP value was associated. At multivariate Cox regression analysis, only BNP and NLR resulted as independent predictors of all-cause mortality in the whole population and in elderly patients. CONCLUSIONS:Elderly STEMI patients on admission had a higher acute pro-inflammatory profile than young patients, associated to coronary no-reflow and mortality outcome. These results suggest that a different therapeutic approach between elderly and young STEMI patients should be agreed. 10.1016/j.ijcard.2019.05.002
    CHA2DS2-VASc Score Predict No-Reflow Phenomenon in Primary Percutaneous Coronary Intervention in Primary Percutaneous Coronary Intervention. Mirbolouk Fardin,Gholipour Mahboobeh,Salari Arsalan,Shakiba Maryam,Kheyrkhah Jalal,Nikseresht Vahid,Sotoudeh Nozar,Moghadam Negar,Mirbolouk Mohammad Jaafar,Moayeri Far Mani Journal of cardiovascular and thoracic research No-reflow is one of the major complications of primary PCI in patients with acute ST elevation myocardial infarction. This phenomenon is associated with adverse outcomes in these patients. In the current study, we evaluated the effectiveness of CHA2DS2-VASc score in predicting no-reflow phenomenon. CHA2DS2-VASc score is a risk stratification method to estimate the risk of thromboembolism in patients with atrial fibrillation. In total, 396 patients with ST elevation myocardial infarction who had undergone primary PCI were evaluated in our study. Based on post interventional TIMI flow rate results, the patients were divided into two groups: control group (294 patients) and no-reflow group (102 patients). The CHA2DS2-VASc score was calculated for each participant. Multivariate regression analysis was performed to determine the predictive value of this score. Our findings showed that CHA2DS2-VASc score can predict no-reflow independently (odds ratio: 3.06, 95%, confidence interval: 2.23-4.21, P <0 .001). Moreover, lower systolic blood pressure, higher diastolic blood pressure, grade 0 initial TIMI flow rate and smaller stent size were other independent predictors of the no-reflow in our study. We also defined a cut off value of ≥ 2 for the CHA2DS2-VASc score in predicting the no-reflow with a sensitivity of 88% and specificity of 67%, area under curve: 0.83 with 95% CI (0.79-0.88). The CHA2DS2-VASc score could be used as a simple applicable tool in the prediction of no-reflow before primary PCI in the acute ST elevation myocardial infarction patients. 10.15171/jcvtr.2018.08
    Paving the way for improving no-reflow phenomenon. Senior Roxy International journal of cardiology 10.1016/j.ijcard.2018.08.073
    Morphological predictors for no reflow phenomenon after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction caused by plaque rupture. Soeda Tsunenari,Higuma Takumi,Abe Naoki,Yamada Masahiro,Yokoyama Hiroaki,Shibutani Shuji,Ong Daniel S,Vergallo Rocco,Minami Yoshiyasu,Lee Hang,Okumura Ken,Jang Ik-Kyung European heart journal cardiovascular Imaging AIMS:Myocardial no reflow after percutaneous coronary intervention (PCI) is associated with poor outcome. Patients with ST-segment elevation myocardial infarction (STEMI) caused by plaque rupture are at high risk for no reflow. However, specific morphologic characteristics associated with no reflow are unknown in this population. The aim of this study is to identify the morphological characteristics of culprit plaques associated with no reflow in patients with STEMI caused by plaque rupture using both optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS:We enrolled 145 patients with STEMI who underwent both OCT and IVUS within 12 h of symptom onset. Among these patients, we excluded those with plaque erosion and calcified nodule and included 72 patients who had plaque rupture as an underlying mechanism for STEMI. Myocardial no reflow, defined as Thrombolysis in Myocardial Infarction flow grade 0-2 and/or myocardial blush grade 0-1 after PCI, was observed in 28 patients (38.9%). Onset to recanalization time was similar between the groups with and without no reflow. Receiver-operating curve analysis revealed OCT-derived lipid index > 3500 [area under curve (AUC) 0.77, P < 0.001] and IVUS-derived plaque burden > 81.5% (AUC 0.70, P = 0.002) were the best discriminators for myocardial no reflow. CONCLUSION:No reflow occurred in nearly 40% of patients with STEMI caused by plaque rupture. Large lipid index and plaque burden were critical morphological discriminators between no reflow and normal flow. 10.1093/ehjci/jev341
    Predictors of No-Reflow Phenomenon in Young Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Celik Turgay,Balta Sevket,Ozturk Cengiz,Kaya Mehmet Gungor,Aparci Mustafa,Yildirim Osman A,Demir Mustafa,Unlu Murat,Demirkol Sait,Kilic Selim,Iyisoy Atila Angiology No-reflow is of prognostic value in ST-segment elevation myocardial infarction (STEMI) but has not been extensively investigated in young patients. Young patients with STEMI admitted within 12 hours from symptom onset and treated by primary percutaneous coronary intervention (pPCI) were recruited. Patients were classified into 2 groups based on postintervention thrombolysis in myocardial infarction (TIMI) flow grade; no-reflow: TIMI flow grade 0, 1 or 2 (group 1; n = 27; 21 men, mean age: 42 ± 4 years); and angiographic success: TIMI flow grade 3 (group 2; n = 118; 110 men, mean age: 43 ± 4 years). Adjusted odds ratios were 13.79 for female gender (P < .001; confidence interval [CI] = 1.88-101.26), 2.09 for pain to balloon time (P < .017; CI = 1.14-3.812), 12.29 for high TIMI thrombus grade (P = .012; CI = 1.74-86.94), 0.04 for tirofiban use (P < .001; CI = 0.01-0.22), 5.19 for mean platelet volume (MPV; P < .001; CI = 2.44-11.01), and 1.008 for platelet-lymphocyte ratio (PLR; P = .034; CI = 1.001-1.016). In conclusion, female gender, pain to balloon time, high TIMI thrombus grade, tirofiban, MPV, and PLR were independent predictors of no-reflow in young patients with STEMI after pPCI. 10.1177/0003319715605977
    Plaque Composition and No-Reflow Phenomenon During Percutaneous Coronary Intervention of Low-Echoic Structures in Grayscale Intravascular Ultrasound. Amano Hideo,Ikeda Takanori,Toda Mikihito,Okubo Ryo,Yabe Takayuki,Watanabe Ippei,Saito Daiga International heart journal It has been reported that coronary vasa vasorum is associated with plaque vulnerability, and low-echoic structures in grayscale intravascular ultrasound (IVUS) are consistent pathologically with vasa vasorum. However, the association of low-echoic structures with plaque composition and no-reflow phenomenon during percutaneous coronary intervention (PCI) is unclear. We investigated plaque composition in virtual histology IVUS (VH-IVUS) and no-reflow phenomenon during PCI of low-echoic structures.A total of 106 lesions being treated by VH-IVUS before PCI were included in this study. Low-echoic structure was defined as a small tubular structure exterior to media without a connection to the vessel lumen in ≥ 3 consecutive crosssectional IVUS images. Lesions with low-echoic structures were found in 42% (45/106).Lesions with low-echoic structures were more prevalent in acute coronary syndrome (ACS) patients (53% [24/45] versus 20% [12/61], P < 0.001), had more positive remodeling (49% [22/45] versus 21% [13/61], P = 0.003), a larger number of VH-IVUS derived thin-cap fibroatheromas (VH-TCFAs) (0.64 ± 0.53 versus 0.05 ± 0.22, P < 0.001), more VH-TCFAs with a baseline plaque burden of 70% or more and minimal luminal area of 4.0 mm(2) or less (29% [13/45] versus 2% [1/61], P < 0.001), and more frequent no-reflow phenomenon after stent implantation and more final TIMI flow grade 0/1/2 (38% [17/45] versus 5% [3/61], P < 0.001; 9% [4/45] versus 0% [0/61], P = 0.03) than lesions without low-echo structures.Lesions with low-echoic structures in grayscale IVUS had high plaque vulnerability and were more prevalent in ACS patients, positive remolding, and VH-TCFAs, and they had more frequent no-reflow phenomenon during PCI than lesions without low-echoic structures. 10.1536/ihj.15-373
    Evaluation of related factors, prediction and treatment drugs of no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction after direct PCI. Li Hui,Fu Du-Guan,Liu Fu-Yuan,Zhou Heng,Li Xiao-Mei Experimental and therapeutic medicine This study determined the related factors of no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) after direct percutaneous coronary intervention (PCI), and evaluated related factor scores in predicting the occurrence of no-reflow phenomenon and drug treatments. A total of 203 patients with acute STEMI receiving PCI who were admitted to the Department of Cardiovascularology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine (Xiangyang, China) from January 2015 to December 2016 were selected. The clinical and image data were analyzed to determine the related factors of no-reflow phenomenon after operation, and related factor scores were quantified to predict the occurrence of no-reflow phenomenon. Three drugs (diltiazem, nitroglycerin and tirofiban needles) were continuously injected in coronary arteries of patients with no-reflow phenomenon, and the effects of these drugs were analyzed. There were 38 patients (18.7%) with no-reflow phenomenon. The correlation analysis showed that 10 factors were associated with no-reflow phenomenon, in which five factors were identified as risk factors, including IRA open-up time ≥8 h, SBP <100 mmHg, Hs-CRP >18 mg/l, thrombus loads, length of the culprit vessel ≥20 mm. The score analysis of related factors of 38 patients with no-reflow phenomenon was conducted. Three points were set for five risk factors each, and 1 point was set for the other five factors each. It was found that the score was approximately normally distributed. The average was 11.5±1.57 points and the lower limit of 95% confidence interval was >8.93 points. The effective rates of three drugs were different (P<0.05), and the pairwise comparison showed their effective rates were not fully identical (P<0.05). The results showed that: i) Τhere are 10 related factors, including five risk factors; ii) related factors with the score ≥9 points can be used for clinical prediction of STEMI after direct PCI; and iii) it is obviously effective to use diltiazem needle and tirofiban needle to treat no-reflow phenomenon, but this conclusion lacks statistical support. 10.3892/etm.2018.5900
    Efficacy and Safety of Local Intracoronary Drug Delivery in Treatment of No-Reflow Phenomenon: A Pilot Study. Abu Arab Tamer,Rafik Ramy,El Etriby Adel Journal of interventional cardiology BACKGROUND:Successful reopening of epicardial coronary artery does not always mean optimal myocardial reperfusion in a sizable portion of patients, mostly because of no-reflow phenomenon. OBJECTIVES:We investigated whether local injection of adrenaline ± verapamil in the distal coronary bed is more effective than their intracoronary (IC) injection through the guiding catheter in the treatment of no-reflow phenomenon following percutaneous coronary intervention (PCI). METHODS:A total of 40 patients with no-reflow following PCI were randomized into two groups. Group 1 received IC adrenaline ± verapamil through a well-cannulated guiding catheter while Group 2 received the above-mentioned drugs in the distal coronary bed through a perfusion balloon or selective microcatheter. The primary end points were the achievement of TIMI III flow with MBG II or III. Secondary end points were the occurrence of hypotension, arrhythmias, and major adverse cardiac events (MACEs) during hospital stay. RESULTS:After drug injection, the percentage of patients achieving Thrombolysis in Myocardial Infarction (TIMI) III flow in Group 1 was 40% versus 80% in Group 2, P = 0.032. MBG II and III was significantly lower in Group 1; 10% and 25% versus 15% and 65% in Group 2, respectively, P = 0.033. Primary end points were achieved in only 35% of patients in Group 1 and in 80% of patients in Group 2 (odds ratio, 7.43, 95% confidence interval 1.78-31.04, P < 0.01). Secondary end points were not different between both groups. CONCLUSION:Local intra-coronary delivery of adrenaline ± verapamil is a safe and effective method for the treatment of no-reflow phenomenon complicating PCI. 10.1111/joic.12318
    Risk Factors for No-Reflow Phenomenon after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome. Liang Tian,Liu Min,Wu Chengyu,Zhang Qing,Lu Lei,Wang Zhongliang Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion BACKGROUND:To explore risk factors for no-reflow phenomenon after percutaneous coronary intervention in patients with acute coronary syndrome. METHODS:A total of 733 acute myocardial infarction patients with persistent ischemic chest pain within 12 or 12-24 hours after onset received emergency percutaneous coronary intervention. Patients were divided into a normal reflow group and a no-reflow group, according to TIMI grading and myocardial blush grading after percutaneous coronary intervention. Related risk factors were analyzed. RESULTS:The incidence of no-reflow phenomenon after percutaneous coronary intervention was 16.1%. Univariate analysis showed that, compared with the normal reflow group, the no-reflow group was older, reperfusion time was significantly longer, preoperative systolic pressure was lower, troponin peak was higher, and creatine kinase enzyme peak was higher (p < 0.05). The proportions of preoperative cardiac function Killip grade ≥ 2 and number of patients using preoperative intra-aortic balloon pump were significantly different (p < 0.05). Multivariate logistic regression analysis showed that age > 65 years (OR: 1.471; 95% CI: 1.462-1.492; p = 0.007), reperfusion time > 6 hours (OR: 1.274; 95% CI: 1.164-1.405; p = 0.001), low systolic pressure at admission (< 100 mmHg) (OR: 1.918; 95% CI: 1.017-3.897; p = 0.004), intra-aortic balloon pump use before percutaneous coronary intervention (OR: 1.949; 95% CI: 1.168-3.253; p = 0.011), low TIMI grade (≤ 1) before percutaneous coronary intervention (OR: 1.100; 95% CI: 1.086-1.257; p < 0.01), high thrombus load (OR: 1.274; 95% CI: 1.423-2.761; p = 0.030), and long target lesion (OR: 1.948; 95% CI: 1.908-1.990; p = 0.019) were independent risk factors. CONCLUSIONS:No-reflow phenomenon after percutaneous coronary intervention in patients with acute coronary syndrome was affected by complicated pathological factors. 10.24875/ric.17002190
    Management of No-Reflow Phenomenon in the Catheterization Laboratory. Rezkalla Shereif H,Stankowski Rachel V,Hanna Jennifer,Kloner Robert A JACC. Cardiovascular interventions At the conclusion of a primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, and after the cardiologist makes certain that there is no residual stenosis following stenting, assessment of coronary flow becomes the top priority. The presence of no-reflow is a serious prognostic sign. No-reflow can result in poor healing of the infarct and adverse left ventricular remodeling, increasing the risk for major adverse cardiac events, including congestive heart failure and death. To achieve normal flow, features associated with a high incidence of no-reflow must be anticipated, and measures must be undertaken to prevent its occurrence. In this review, the authors discuss various preventive strategies for no-reflow as well as pharmacological and nonpharmacological interventions that improve coronary blood flow, such as intracoronary adenosine and nitroprusside. Nonpharmacological therapies, such as induced hypothermia, were successful in animal studies, but their effectiveness in reducing no-reflow in humans remains to be determined. 10.1016/j.jcin.2016.11.059
    Delayed therapeutic hypothermia protects against the myocardial no-reflow phenomenon independently of myocardial infarct size in a rat ischemia/reperfusion model. Dai Wangde,Hale Sharon,Kloner Robert A International journal of cardiology BACKGROUND:Adjunctive therapies, given in addition to reperfusion to reduce myocardial infarct size, have been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. The no-reflow phenomenon occurs commonly after the infarct-related coronary artery is opened and predicts poor clinical outcome. We investigated the effects of a single application of delayed (post-reperfusion) therapeutic hypothermia (TH) in a rat model of coronary artery occlusion/reperfusion. METHODS:Rats were subjected to 60min of coronary artery occlusion followed by 3h of reperfusion. Rats were divided into normothermic (n=5) and TH (n=5) groups. In the TH, hypothermia was initiated at 1min after coronary artery reperfusion by pumping room-temperature (22°C) saline into and out of the thoracic cavity for 1h. This decreased intrathoracic temperature to around 26°C within 12min. At 3h after reperfusion, hearts were excised for infarct size and no-reflow zone measurement. RESULTS:Ischemic risk area and infarct size were similar between the 2 groups. No-reflow area (expressed as % of risk area) was significantly reduced in TH group (18.0±4.4%) compared with normothermic group (39.5±2.9%,P=0.005). When expressed as % of necrotic area, no-reflow area was reduced by more than half in TH group (25.5±6.4%) versus innormothermic group (54.4±5.3%,P=0.01). CONCLUSIONS:In this preliminary study, hypothermia initiated after reperfusion following 60min of coronary artery occlusion had no effect on infarct size yet substantially reduced the extent of no-reflow. 10.1016/j.ijcard.2017.01.079
    A simple and rapid method for identification of lesions at high risk for the no-reflow phenomenon immediately before elective coronary stent implantation. Suda Akira,Namiuchi Shigeto,Kawaguchi Tomohiro,Nihei Taro,Takii Toru,Saji Kenya,Sugie Tadashi,Kato Atsushi,Shimokawa Hiroaki Heart and vessels We aimed to design a rapid and reliable method to identify coronary lesions at high risk for the no-reflow phenomenon before elective coronary stent implantation using integrated backscatter intravascular ultrasound (IB-IVUS). The no-reflow phenomenon occurring during elective percutaneous coronary intervention (PCI) worsens patient prognosis, regardless of whether the phenomenon is transient or persistent. We retrospectively studied 353 coronary lesions to identify factors potentially promoting the no-reflow phenomenon, including lesion location and severity. We also performed component analysis by two- and three-dimensional IB-IVUS before elective stent implantation. The cutoff values of the true lipid volume and estimated lipid volume (lipid area at the minimal lumen diameter site × total stent length) for the no-reflow phenomenon were determined by receiver operating curve analysis. Type C lesions, regardless of location and a thrombolysis in myocardial flow grade of 0, were risk factors for the no-reflow phenomenon during PCI. The estimated lipid volume was significantly correlated with the true lipid volume (R  = 0.778, p < 0.0001). The cutoff value of the estimated lipid volume for the no-reflow phenomenon was 132.6 mm (area under the curve = 0.719), and the predictive value was equivalent to that of the true lipid volume. Lesions with an estimated lipid volume of ≥132.6 mm had a significantly higher risk of the no-reflow phenomenon during elective stent implantation (odds ratio, 4.35; 95 % confidence interval, 1.67-12.7; p = 0.0024). The simple and rapid measurement of the estimated lipid volume immediately before stenting during PCI constitutes a reliable predictor of lesions at high risk for the no-reflow phenomenon. 10.1007/s00380-016-0825-y
    Coronary Microcirculation and the No-reflow Phenomenon. Oikonomou Evangelos,Mourouzis Konstantinos,Vogiatzi Georgia,Siasos Gerasimos,Deftereos Spyridon,Papaioannou Spyridon,Latsios George,Tsalamandris Sotiris,Tousoulis Dimitris Current pharmaceutical design The no-reflow phenomenon refers to the post-percutaneous coronary intervention condition in which, despite re-establishing epicardial coronary vessel patency, the flow to the previously ischemic myocardium is markedly reduced. When it does occur, it attenuates the beneficial effect of reperfusion therapy and substantial regions of the myocardium fail to receive adequate perfusion. The pathophysiology of this phenomenon is not completely understood. The possible mechanisms could be related to alterations in the microvascular circulation. Various mechanisms such as activation of inflammatory pathways, vascular damage and hemorrhage, leukocyte infiltration, and cellular edema may be responsible. As the no-reflow phenomenon is associated with adverse clinical consequences, it is of great importance to identify exact responsible mechanisms and apply effective preventive and therapeutic strategies. In this review, we describe an updated overview of the pathophysiological mechanisms and the current preventive tools for no-reflow as well as therapeutic interventions in order to improve coronary blood flow and consequently the prognosis for these patients. 10.2174/1381612824666180911122230
    Coronary No-Reflow Phenomenon in Clinical Practice. Scarpone Marialuisa,Cenko Edina,Manfrini Olivia Current pharmaceutical design Timely delivered coronary revascularization with no residual anatomical stenosis does not always lead to prompt restoration of anterograde coronary flow and complete myocardial reperfusion. This condition is known as coronary no-reflow and is associated with major clinical adverse events and poor prognosis. The pathophysiology of no-reflow phenomenon is still poorly understood. Proposed mechanisms include distal microembolization of thrombus and plaque debris, ischemic injury, endothelial dysfunction and individual susceptibility to microvascular dysfunction/obstruction. Older age, diabetes, hypercholesterolemia, prolonged ischemic time, hemodynamic instability, high thrombus burden, complex angiographic lesions and multivessel disease are frequently reported to be associated with the no-reflow phenomenon. There is no general consensus on the correct prevention and management of no-reflow. Non-pharmacological measures such as distal embolic protection devices and manual thrombus aspiration did not result in improved flow or reduction of infarct size. Current preventive measures include reduction of time from symptoms onset to reperfusion therapy, and intracoronary administration of vasodilators such as adenosine, verapamil or nitroprusside. 10.2174/1381612824666180702112536
    Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis. Niu Xiaowei,Zhang Jingjing,Bai Ming,Peng Yu,Sun Shaobo,Zhang Zheng BMC cardiovascular disorders BACKGROUND:Despite the restoration of epicardial flow after primary percutaneous coronary intervention (PPCI), myocardial reperfusion remains impaired in a significant proportion of patients. We performed a network meta-analysis to assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem, nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI. METHODS:Database searches were conducted to identify randomized controlled trials (RCTs) comparing the 7 agents with each other or with standard PPCI. Outcome measures included thrombolysis in myocardial infarction flow grade (TFG), ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACEs), and adverse events. RESULTS:Forty-one RCTs involving 4069 patients were analyzed. The addition of anisodamine to standard PPCI for STEMI was associated with improved post-procedural TFG, more occurrences of STR, and improvement of LVEF. The cardioprotective effect of anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside was regarded as efficient in improving coronary flow and clinical outcomes. Compared with standard care, adenosine, nicorandil, and verapamil improved coronary flow but had no corresponding benefits regarding cardiac function and clinical outcomes. The ranking probability for the 7 treatment drugs showed that anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR, LVEF, and MACEs). No severe adverse events, such as hypotension and malignant arrhythmia, were observed in patients treated with anisodamine. Network meta-regression analysis showed that age, the time to reperfusion, and study follow-up did not affect the treatment effects. CONCLUSIONS:The intracoronary administration of anisodamine appears to improve myocardial reperfusion, cardiac function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the limited quality and quantity of the included studies, more rigorous RCTs are needed to verify the role of this inexpensive and well-tolerated regimen. 10.1186/s12872-017-0722-z
    Predictors and outcomes of no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Tasar Onur,Karabay Arzu K,Oduncu Vecih,Kirma Cevat Coronary artery disease AIM:The aim of this study is to identify the predictors of angiographic no-reflow development in patients who underwent primary percutaneous coronary intervention and to investigate the long-term (median follow-up time=59 months) clinical endpoints. PATIENTS AND METHODS:We retrospectively evaluated 3205 patients (824 females, mean age: 58.6 years) with acute myocardial infarction (ST-segment elevation myocardial infarction) admitted within the first 12 h of chest pain and treated with primary percutaneous coronary intervention between January 2006 and January 2010. The patients were divided into angiographic no-reflow [final Thrombolysis In Myocardial Infarction (TIMI)<3 flow] (n=324) and reflow (final TIMI 3) (n=2881) groups. RESULTS:On multivariate logistic regression analysis age [odds ratio (OR)=1.02, 95% confidence interval (CI): 1.00-1.04, P=0.003], Killip class≥2 (OR=1.99, 95% CI: 1.30-3.04, P=0.002), pain-to-balloon time more than 4 h (OR=3.98, 95% CI: 2.50-6.32, P<0.001), baseline TIMI≤1 flow (OR=2.55, 95% CI: 1.05-6.22, P=0.038), lesion length of at least 15 mm (OR=4.31, 95% CI: 2.89-6.41, P<0.001), reference vessel diameter of at least 3.5 mm (OR=2.83, 95% CI: 1.87-4.27, P<0.001), cutoff occlusion pattern (OR=1.93, 95% CI: 1.03-3.62, P=0.04), and SYNTAX score of at least 19 (OR=1.76, 95% CI: 1.1.23-3.07, P<0.001)] were found as significant predictors for the development of no-reflow phenomenon. In no-reflow patients, in-hospital mortality (10.8 vs. 2.9%), heart failure (32.1 vs. 8.7%), and severe arrhythmias (23.1 vs. 9.3%) were significantly more common (P<0.001), for all. In the long-term follow-up, death (33.3 vs. 13.4%, P<0.001), advanced heart failure (12.5 vs. 5.4%, P<0.001), and stroke (3.5 vs. 1.7%, P=0.035) rates were significantly higher in the no-reflow group. CONCLUSION:The no-reflow predictors that were identified in this study might be useful in the determination of the patients who could benefit from aggressive pharmaco-invasive therapy. Development of no-reflow is associated with both in-hospital and long-term very high morbidity and mortality rates. 10.1097/MCA.0000000000000726
    Is Atherothromboaspiration a Possible Solution for the Prevention of No-Reflow Phenomenon in Acute Coronary Syndromes? Single Centre Experience and Review of the Literature. Manolis Antonis S Current vascular pharmacology 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. 10.2174/1570161116666180101150956
    Serum cystatin C levels relate to no-reflow phenomenon in percutaneous coronary interventions in ST-segment elevation myocardial infarction. Cheng Chao,Liu Xiao-Bo,Bi Shao-Jie,Lu Qing-Hua,Zhang Juan PloS one BACKGROUND/AIM:No-reflow is a serious and frequent event during primary percutaneous coronary intervention (PPCI) for acute ST segment elevation myocardial infarction (STEMI). The aim of this study was to identify possible predictors for no-reflow. PATIENTS AND METHODS:We investigated 218 patients with acute anterior STEMI who underwent PPCI from December 2016 to December 2018. No-reflow was defined as a coronary TIMI flow grade of ≤ 2. TIMI flow grade 3 was defined as normal reflow. RESULTS:In our study, the no-reflow phenomenon was observed in 39 patients (18%) during angiography. The patients of no-reflow group were found to be more older, diabetics, longer pain-to-balloon time, lower blood pressure, higher platelet counts and higher levels of D-Dimer and Cystatin C (Cys-C). In multivariate logistic regression analysis, only diabetes (OR = 0.371, 95% CI: 0.157-0.872, P = 0.023), longer pain-to-balloon time (OR = 1.147, 95% CI: 1.015-1.297, P = 0.028) and higher Cys-C level (OR = 10.07, 95% CI: 2.340-43.377, P = 0.002) were predictors for no-reflow. CONCLUSION:Cys-C might be a useful predictor for the no-reflow phenomenon after PPCI in STEMI patients. It might help to screen STEMI patients with high risk of no-reflow on admission. 10.1371/journal.pone.0220654
    Association between the No-Reflow Phenomenon and Soluble CD40 Ligand Level in Patients with Acute ST-Segment Elevation Myocardial Infarction. Tascanov Mustafa Begenc,Tanriverdi Zulkif,Gungoren Fatih,Besli Feyzullah,Erkus Muslihittin Emre,Gonel Ataman,Koyuncu Ismail,Demirbag Recep Medicina (Kaunas, Lithuania) : No-reflow (NR) phenomenon is defined as insufficient myocardial perfusion in coronary circulation in the absence of angiographic evidence of mechanical obstruction. The primary mechanisms of the NR occurrence are thought to be high platelet activity and thrombus burden. Soluble CD40 ligand (sCD40L), which is released into the plasma following platelet activation, accelerates the inflammatory process and causes further platelet activation. The aim of our study is to investigate the relationship between the NR phenomenon and sCD40L level in patients with ST-elevation myocardial infarction (STEMI). A total of 81 acute STEMI patients undergoing primary percutaneous coronary intervention and 40 healthy participants were included in this study. Acute STEMI patients were classified into two groups: 41 patients with the NR phenomenon (NR group) and 40 patients without the NR phenomenon (non-NR group). The serum sCD40L level was measured for all groups. The serum sCD40L level was significantly higher in the NR group than in non-NR and control groups (379 ± 20 pg/mL, 200 ± 15 pg/mL and 108 ± 6.53 pg/mL, respectively; < 0.001). Univariate regression analysis demonstrated that male sex, age, Gensini score and sCD40L level were the possible factors affecting the occurrence of the NR phenomenon. In multivariate regression analysis, age (odds ratio [OR], 1.091; 95% confidence interval [CI], 1.023-1.163; < 0.008) and serum sCD40L (OR, 1.016; 95% CI, 1.008-1.024; < 0.001) remained the independent predictor of the presence of NR. Our study showed that serum sCD40L level was an independent predictor of the NR phenomenon occurrence. 10.3390/medicina55070376
    Advances in Coronary No-Reflow Phenomenon-a Contemporary Review. Karimianpour Ahmadreza,Maran Anbukarasi Current atherosclerosis reports PURPOSE OF REVIEW:Coronary artery no-reflow phenomenon is an incidental outcome of percutaneous coronary intervention in patients presenting with acute myocardial infarction. Despite advances in pharmacologic and non-pharmacologic therapies, coronary no-reflow phenomenon occurs more commonly than desired. It often results in poor clinical outcomes and remains as a relevant consideration in the cardiac catheterization laboratory. In this systematic review, we have sought to discuss the topic in detail, and to relay the most recent discoveries and data on management of this condition. RECENT FINDINGS:We discuss several pharmacologic and non-pharmacologic treatments used in the prevention and management of coronary no-reflow and microvascular obstruction. Covered topics include the understanding of pharmacologic mechanisms of current and future agents, and recent discoveries that may result in the development of future treatment options. We conclude that the pathophysiology of coronary no-reflow phenomenon and microvascular obstruction still remains incompletely understood, although several plausible theories have led to the current standard of care for its management. We also conclude that coronary no-reflow phenomenon and microvascular obstruction must be recognized as a multifactorial condition that has certain predispositions and characteristics, therefore its prevention and treatment must begin pre-procedurally and be multi-faceted including certain medications and operator techniques in the cardiac catheterization laboratory. 10.1007/s11883-018-0747-5
    Pathophysiology, Diagnosis, and Management of the No-Reflow Phenomenon. Allencherril Joseph,Jneid Hani,Atar Dan,Alam Mahboob,Levine Glenn,Kloner Robert A,Birnbaum Yochai Cardiovascular drugs and therapy 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. 10.1007/s10557-019-06901-0
    Predictive performance of dual modality of computed tomography angiography and intravascular ultrasound for no-reflow phenomenon after percutaneous coronary stenting in stable coronary artery disease. Okutsu Masaaki,Horio Takeshi,Tanaka Hisataka,Akiyama Maki,Okimoto Niro,Tsubouchi Toshiyuki,Kawajiri Kenji,Ohashi Yasuhiro,Sumitsuji Satoru,Ikari Yuji Heart and vessels Attenuated plaque on intravascular ultrasound (IVUS) and low attenuation plaque on computed tomography angiography (CTA) are associated with no-reflow phenomenon during percutaneous coronary intervention (PCI). However, evaluation by a single modality has been unable to satisfactorily predict this phenomenon. We investigated whether the combination of IVUS and CTA findings can ameliorate the predictive potential for no-reflow phenomenon after stent implantation during PCI in stable coronary artery disease (CAD). A total of 988 lesions of 707 stable CAD patients who underwent coronary CTA before PCI were enrolled. PCI was performed with preprocedural IVUS and stent implantation. As for plaque characters, very low attenuation plaque (CTA v-LAP) whose minimum density was < 0 Hounsfield units on CTA and attenuated plaque (IVUS AP) on IVUS were evaluated. No-reflow phenomenon was observed in 22 lesions (2.2%) of 19 patients (2.7%). Both CTA v-LAP and IVUS AP were much more frequently observed in patients with no-reflow phenomenon. Positive (PPV) and negative predictive values (NPV) and accuracy for prediction of no-reflow were almost equivalent between CTA v-LAP (13.2, 99.6, and 87.0%) and IVUS AP (15.7, 99.8, and 89.0%). The combination of CTA v-LAP and IVUS AP markedly ameliorated PPV (31.7%) without deterioration of NPV (99.7%) and increased the diagnostic accuracy (95.5%). These findings showed that the combination of CTA v-LAP and IVUS AP improved the predictive power for no-reflow phenomenon after coronary stenting in stable CAD patients, suggesting the usefulness of combined estimation by using CTA and IVUS for predicting no-reflow phenomenon during PCI in clinical practice. 10.1007/s00380-018-1160-2
    Lower plasma protein C activity is associated with early myocardial necrosis and no-reflow phenomenon in patients with ST elevation myocardial infarction. Stankovic Suncica,Obradovic Slobodan,Dzudovic Boris,Djenic Nemanja,Romanovic Radoslav,Jovic Zoran,Spasic Marijan,Djuric Obrad,Malovic Dragana,Stavric Milena,Subota Vesna Acta cardiologica Activity of protein C has important role in the development of early necrosis and no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (pPCI). We examined association between plasma activity of protein C, antithrombin, coagulation factors II, VII, VIII and fibrinogen to early formation of new Q-waves (myocardial necrosis) before pPCI and early ST-segment resolution (microcirculatory reperfusion) after pPCI in patients with acute STEMI. According to ischaemic time, patients were considered as early or late presenters. 12-lead ECG was analysed for the presence of new Q-wave at admission and for significant ST-segment resolution 60 minutes after primary PCI. In early presenters' group, protein C activity was significantly lower in patients who did not achieve significant ST-segment resolution after pPCI compared to patients who did (1.11 IU/L vs. 0.99 IU/L,  = .006) and in patients who had new Q-waves compared to group who had not (1.04 UI/l vs. 1.11 IU/L,  = .038). There was significant negative correlation between protein C activity and maximal CK-MB levels ( = 0.06,  = .009) and BNP levels ( = 0.109,  = .003) and significant positive correlation between protein C activity with LVEF ( = 0.065, constant = 33.940,  = 11.968,  = .007) in early STEMI presenters. There were no differences between the activity of other examined haemostasis factors. Therefore we concluded that STEMI patients with early myocardial necrosis and no-reflow phenomenon after pPCI have lower activity of plasma protein C levels. 10.1080/00015385.2018.1494116
    The relationship between serum rheumatoid factor level and no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Quisi Alaa,Alıcı Gökhan Journal of clinical laboratory analysis OBJECTIVE:This study aimed to evaluate the relationship between serum rheumatoid factor (RF) levels and no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS:This single-center, cross-sectional study included a total of 318 consecutive patients who were diagnosed with STEMI and underwent primary PCI within 12 hours of the onset of symptoms. Baseline serum RF levels of all patients were measured. The diagnosis of no-reflow phenomenon was defined as a flow of TIMI II or less without the presence of dissection, mechanical obstruction, significant residual stenosis, or other plausible causes. The patients were divided into reflow group (n = 283) and no-reflow group (n = 46) regarding the angiographic features of thrombolysis in myocardial infarction (TIMI) flow of the infarct-related artery. RESULTS:No-reflow phenomenon was observed in 13.8% of the patients. Median RF level was significantly higher in no-reflow group than in reflow group (18.5 (7.0-27.6) vs 8.0 (4.6-50.8), P < .001). Forward conditional logistic regression analysis demonstrated that body mass index (OR = 0.845, 95% CI: 0.765 to 0.933, P = .001), diabetes mellitus (OR = 5.257, 95% CI: 1.124 to 24.587, P = .035), baseline RF level (OR = 1.198, 95% CI: 1.108 to 1.295, P < .001), and SYNTAX score I (OR = 1.065, 95% CI: 1.025 to 1.107, P = .001) were the independent predictors of no-reflow phenomenon. CONCLUSION:Baseline serum RF concentrations are independently associated with the no-reflow phenomenon in patients undergoing primary PCI for acute STEMI. 10.1002/jcla.22598
    Clinical and procedural predictors and short-term survival of the patients with no reflow phenomenon after primary percutaneous coronary intervention. Ashraf Tariq,Khan Muhammad Nauman,Afaque Syed Muhammad,Aamir Kanwal Fatima,Kumar Mukesh,Saghir Tahir,Rasool Syed Ishtiaq,Rizvi Syed Nadeem Hassan,Sial Jawaid Akbar,Nadeem Asif,Khan Abid Amin,Karim Musa International journal of cardiology OBJECTIVES:In the present study, we analysed the incidence of no-reflow phenomenon, its clinical and procedural predictors, and associated in-hospital outcomes for the patients undergoing primary percutaneous coronary intervention (PCI). BACKGROUND:No-reflow phenomenon after primary PCI is a procedural complication associated with adverse post-procedure outcomes. METHODS:Data for this study were extracted from global registry, NCDR®, the site of National Institute of Cardiovascular Disease (NICVD), Karachi from July 2017 to March 2018. The demographic, clinical, and procedural characteristics, and in-hospital outcomes were analysed for the patients with and without no-reflow after primary PCI. RESULTS:Of total of 3255 patients, no-reflow phenomenon was found in 132 (4.1%) patients and it was associated with significantly higher in-hospitality mortality (6.8% vs. 2.9%; p = 0.01), cerebrovascular accident (1.5% vs. 0%; p < 0.001), post procedure bleeding (2.3% vs. 0.5%; p = 0.009), and cardiogenic shock (3.8% vs. 1.2%; p = 0.011). The multivariate analysis showed advanced age [odds ratio = 1.63, 95% confidence interval 1.09-2.44, p = 0.018], diabetes [1.66, 1.14-2.42, p = 0.009], prior history of CABG [8.70, 1.45-52.04, p = 0.018], low pre-procedure TIMI flow grade [2.04, 1.3-3.21, p = 0.002], longer length of target lesion [1.51, 1.06-2.16, p = 0.023], and 10 fold raised troponin I [1.55, 1.08-2.23, p = 0.018] were the independent predictors of no-reflow. CONCLUSIONS:In this selected group of patients, the no-reflow phenomenon after primary percutaneous coronary intervention is not that uncommon. It is associated with an increased risk of adverse post-procedure hospital course including mortality. Pathophysiology of the no-reflow phenomenon is complex and opaque, however, it can be predicted based on certain clinical and procedural characteristics. 10.1016/j.ijcard.2019.07.067