Adenosine in Interventional Cardiology: Physiopathologic and Pharmacologic Effects in Coronary Artery Disease.

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.

Role of Intracoronary Adrenaline in the Treatment of No-Reflow Phenomenon in Patients Undergoing Percutaneous Coronary Intervention.

The no-reflow phenomenon is defined as the failure to restore coronary flow demonstrated by the reduced or missing flow in angiography despite the patent artery. There are pharmacological strategies proposed and studied to manage the no-reflow phenomenon. The medication groups used are purine nucleoside (adenosine), calcium channel blockers (verapamil, nicardipine), beta 2 receptor agonists (adrenaline, nitroprusside), fibrinolytic agents (streptokinase, tissue plasminogen activators), glycoprotein IIb/IIIa inhibitors (abciximab, tirofiban). We present a case of a woman hospitalized in non-ST elevation myocardial infarction (NSTEMI) conditions. The patient underwent coronary angiography, in which a single vessel coronary artery disease (CAD); left anterior descending (LAD) stenosis of 90% was found. In this condition, the patient underwent percutaneous coronary intervention (PCI) of LAD. The no-reflow phenomenon occurred with thrombolysis in myocardial infarction (TIMI) flow grade of 0 during the procedure. As a consequence, the patient presented chest pain and important hypotension (BP of 70/45). Because of the hypotensive state of the patient, we decided to administer intracoronary (IC) adrenaline directly. In our case, we used adrenaline as a first-line treatment for the no-flow phenomenon due to the hypotensive state during the PCI procedure. Generally, we initially use IC nitrate or IC adenosine to resolve the phenomenon, and when the no-reflow persists we use IC adrenaline because of its side effects mentioned above. Anyway, we believe that in specific cases of hypotension and bradycardia, the use of adrenaline as the first line of therapy should be considered.

Impacts of futile reperfusion and reperfusion injury in acute ischemic stroke.

Acute ischemic stroke (AIS) remains to be a challenging cerebrovascular disease. The mainstay of AIS management is endovascular reperfusion therapy, including thrombectomy and thrombolysis. However, ineffective (futile) reperfusion (FR) or reperfusion injury (RI) can be seen in a significant number of patients undergoing reperfusion strategy. In this article, we discuss two clinically relevant concepts known as "time window" and "tissue window" that can impact the clinical outcome of reperfusion therapy. We also explore patient risk factors, leading to FR and RI as well as an emerging concept of "no-reflow phenomenon" seen in ineffective reperfusion. These fundamental concepts provide insight into the clinical management of AIS patients and provide references for future research.

O Valor Preditivo do Índice Prognóstico Inflamatório para Detecção de No-Reflow em Pacientes com Infarto do Miocárdio com Supradesnivelamento do Segmento ST / The Predictive Value of the Inflammatory Prognostic Index for Detecting No-Reflow in ST-Elevation Myocardial Infarction Patients

Resumo Fundamento: O no-reflow (NR) é caracterizado por uma redução aguda no fluxo coronário que não é acompanhada por espasmo coronário, trombose ou dissecção. O índice prognóstico inflamatório (IPI) é um novo marcador que foi relatado como tendo um papel prognóstico em pacientes com câncer e é calculado pela razão neutrófilos/linfócitos (NLR) multiplicada pela razão proteína C reativa/albumina. Objetivo: Nosso objetivo foi investigar a relação entre IPI e NR em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST) submetidos a intervenção coronária percutânea primária (ICPp). Métodos: Um total de 1.541 pacientes foram incluídos neste estudo (178 com NR e 1.363 com refluxo). A regressão penalizada LASSO (Least Absolute Shrinkage and Select Operator) foi usada para seleção de variáveis. Foi criado um nomograma baseado no IPI para detecção do risco de desenvolvimento de NR. A validação interna com reamostragem Bootstrap foi utilizada para reprodutibilidade do modelo. Um valor de p bilateral <0,05 foi aceito como nível de significância para análises estatísticas. Resultados: O IPI foi maior em pacientes com NR do que em pacientes com refluxo. O IPI esteve associado de forma não linear com a NR. O IPI apresentou maior capacidade discriminativa do que o índice de imunoinflamação sistêmica, NLR e relação PCR/albumina. A adição do IPI ao modelo de regressão logística multivariável de base melhorou a discriminação e o efeito do benefício clínico líquido do modelo para detecção de pacientes com NR, e o IPI foi a variável mais proeminente no modelo completo. Foi criado um nomograma baseado no IPI para prever o risco de NR. A validação interna do nomograma Bootstrap mostrou uma boa capacidade de calibração e discriminação. Conclusão: Este é o primeiro estudo que mostra a associação de IPI com NR em pacientes com IAMCSST submetidos a ICPp.

Abstract Background: No-reflow (NR) is characterized by an acute reduction in coronary flow that is not accompanied by coronary spasm, thrombosis, or dissection. Inflammatory prognostic index (IPI) is a novel marker that was reported to have a prognostic role in cancer patients and is calculated by neutrophil/lymphocyte ratio (NLR) multiplied by C-reactive protein/albumin ratio. Objective: We aimed to investigate the relationship between IPI and NR in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). Methods: A total of 1541 patients were enrolled in this study (178 with NR and 1363 with reflow). Lasso panelized shrinkage was used for variable selection. A nomogram was created based on IPI for detecting the risk of NR development. Internal validation with Bootstrap resampling was used for model reproducibility. A two-sided p-value <0.05 was accepted as a significance level for statistical analyses. Results: IPI was higher in patients with NR than in patients with reflow. IPI was non-linearly associated with NR. IPI had a higher discriminative ability than the systemic immune-inflammation index, NLR, and CRP/albumin ratio. Adding IPI to the baseline multivariable logistic regression model improved the discrimination and net-clinical benefit effect of the model for detecting NR patients, and IPI was the most prominent variable in the full model. A nomogram was created based on IPI to predict the risk of NR. Bootstrap internal validation of nomogram showed a good calibration and discrimination ability. Conclusion: This is the first study that shows the association of IPI with NR in STEMI patients who undergo pPCI.

Intracoronary Near-Infrared Spectroscopy to Predict No-Reflow Phenomenon During Percutaneous Coronary Intervention in Acute Coronary Syndrome.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) can identify the lipid-rich lesions, described as high lipid-core burden index (LCBI). The aim of this study was to investigate the relation between lipid-core plaque (LCP) in the infarct-related lesion detected using NIRS-IVUS and no-reflow phenomenon during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We investigated 371 patients with ACS who underwent NIRS-IVUS in the infarct-related lesions before PCI. The extent of LCP in the infarct-related lesion was calculated as the maximum LCBI for each of the 4-mm longitudinal segments (maxLCBI4mm) measured by NIRS-IVUS. The patients were divided into 2 groups using a maxLCBI4mm cut-off value of 400. The overall incidence of no-reflow phenomenon was 53 of 371 (14.3%). No-reflow phenomenon more frequently occurred in patients with maxLCBI4mm ≥400 compared with those with maxLCBI4mm<400 (17.5% vs 2.5%, p <0.001). After propensity score matching, multivariable logistic regression analysis demonstrated that maxLCBI4mm (odds ratio: 1.008; 95% confidence interval: 1.005 to 1.012, p <0.001) was independently associated with the no-reflow phenomenon. The maxLCBI4mm of 719 in the infarct-related lesion had the highest combined sensitivity (69.8%) and specificity (72.1%) for the identification of no-reflow phenomenon. In conclusion, in patients with ACS, maxLCBI4mm in the infarct-related lesion assessed by NIRS-IVUS was independently associated with the no-reflow phenomenon during PCI.

Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

No-reflow after stroke reperfusion therapy: An emerging phenomenon to be explored.

In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.

The non-HDL-C/HDL-C ratio is a strong and independent predictor of the no-reflow phenomenon in patients with ST-elevation myocardial infarction.

BACKGROUND: No-reflow (NR) is the inability to achieve adequate myocardial perfusion despite successful restoration of attegrade blood flow in the infarct-related artery after primary percutaneous coronary intervention. The non-HDL-C/HDL-C ratio has been shown to be superior to conventional lipid markers in predicting most cardiovascular diseases. In this study, we wanted to reveal the predictive value of the NR by comparing the Non-HDL-C/HDL-C ratio with traditional and non-traditional lipid markers in patients who underwent primary percutaneous coronary intervention (pPCI) due to ST-elevation myocardial infarction (STEMI). METHODS: A total of 1284 consecutive patients who underwent pPCI for STEMI were included in this study. Traditional lipid profiles were detected and non-traditional lipid indices were calculated. Patients were classified as groups with and without NR and compared in terms of lipid profiles. RESULTS: No-reflow was seen in 18.8% of the patients. SYNTAX score, maximal stent length, high thrombus burden, atherogenic index of plasma and non-HDL-C/HDL-C ratio were determined as independent predictors for NR (p < 0.05, for all). The non-HDL-C/HDL-C ratio predicts the development of NR in STEMI patients with 71% sensitivity and 67% specificity at the best cut-off value. In ROC curve analysis, the non-HDL-C/HDL-C ratio was superior to traditional and non-traditional lipid markers in predicting NR (p < 0.05, for all). CONCLUSION: The non-HDL-C/HDL-C ratio can be a strong and independent predictor of NR in STEMI patients and and therefore non-HDL-C/HDL-C ratio may be a useful lipid-based biomarker that can be used in clinical practice to improve the accuracy of risk assessment in patients with STEMI.

The stress hyperglycemic ratio can predict the no-reflow phenomenon following saphenous vein graft intervention in patients with acute coronary syndrome.

AIMS: The no-reflow phenomenon (NRP) is a common complication of saphenous vein graft (SVG) interventions. The aim of this study was to investigate the effect of the stress hyperglycemia ratio (SHR) on the development of NRP in patients with acute coronary syndrome (ACS) undergoing percutaneous SVG intervention. METHODS: The study included 223 patients who presented at our center with ACS, had a history of coronary artery bypass graft and underwent a saphenous graft procedure. The relationship between SHR calculated at the time of presentation from glucose and HbA1c values, and the development of NRP evaluated after the procedure with angiography was determined with univariate and multivariate binary regression analysis. RESULT: The study population was separated into two groups as those who developed and did not develop NRP. Mean age was determined to be significantly higher in the group that did not develop NRP compared to the group with NRP (p: 0.004). Angiographically, the thrombus burden was determined to be significantly higher in the group that developed NRP (p < 0.001). Patients were separated into 3 tertiles according to the SHR level (T1, T2, T3), and the rate of NRP development was determined at a significantly higher rate in the T3 group (p < 0.001). CONCLUSIONS: This study showed that SHR, a parameter that can be easily calculated noninvasively, is an independent predictor of NRP development in ACS patients undergoing saphenous interventions. In addition, high thrombus burden and predilatation before stenting were also found to be factors that increase the likelihood of developing NRP.

Predictor of No-Reflow in Patients With ST-Segment Elevation Myocardial Infarction.

We have carefully read the article titled 'Prognostic Nutritional Index as a Predictor of No-Reflow Occurrence in Patients With ST-Segment Elevation Myocardial Infarction Who Underwent Primary Percutaneous Coronary Intervention' and find it to be of significant interest. The no-reflow phenomenon (NRP) stands as a formidable complication of ST-segment elevation myocardial infarction (STEMI), carrying a high mortality risk. Managing NRP entails pharmacological and mechanical interventions, making its prediction a crucial aspect in the management of STEMI cases. We extend our gratitude to you and the authors for conducting this valuable and thought-provoking study. We anticipate that our insights will serve as a guide for future comprehensive studies in this dynamic area.

Neuroprotective effects of a hemoglobin-based oxygen carrier (stroma-free hemoglobin nanoparticle) on ischemia reperfusion injury.

The application of hemoglobin (Hb)-based oxygen carriers (HBOCs) to the treatment of cerebral ischemia has been investigated. A cluster of 1 Hb and 3 human serum albumins (Hb-HSA3) was found to exert neuroprotective effects on ischemia/reperfusion injury. Stroma-free hemoglobin nanoparticles (SFHbNP), a subsequently developed HBOC consisting of a spherical polymerized stroma-free Hb core with a HSA shell, contains the natural antioxidant enzyme catalase and, thus, is expected to exert additive effects. We herein investigated whether SFHbNP exerted enhanced neuroprotective effects in a rat transient middle cerebral artery occlusion (tMCAO) model. Rats were subjected to 2-hour tMCAO and divided into the following 3 groups with the intravenous administration of the respective reagents: (1) phosphate-buffered saline (PBS), as a vehicle (2) Hb-HSA3, and (3) SFHbNP. After 24-hour reperfusion, infarct and edema volumes decreased in the order of the PBS, Hb-HSA3, and SFHbNP groups, with a significant difference (p < 0.05) between the PBS and SFHbNP groups. Similar reductions were observed in oxidative stress, leukocyte recruitment, and blood-brain barrier disruption in the order of the PBS, Hb-HSA3, and SFHbNP groups. In the early phase of reperfusion within 6 h, microvascular HBOC perfusion and cerebral blood flow were maintained at high levels during the reperfusion period in the Hb-HSA3 and SFHbNP groups. However, a difference was observed in tissue oxygen partial pressure levels, which significantly decreased after 6-hour reperfusion in the Hb-HSA3 group, but remained high in the SFHbNP group. A superior oxygen transport ability appears to be related to the enhanced neuroprotective effects of SFHbNP.

An unusual no-reflow phenomenon due to neointimal tissue embolization during drug eluting balloon intervention in stent restenosis: A case report.

Acute coronary syndrome is one of the leading causes of death worldwide. Percutaneous coronary intervention (PCI), along with various devices, have been technically developed to dramatically improve mortality risk in patients with acute myocardial infarction. However, no-reflow phenomenon still remains a problematic complication during a PCI, even in the era of drug eluting stents. There are various hypotheses and mechanisms for no-reflow phenomenon, but none have been confirmed. Treatment for no-reflow phenomenon also depends on various underlying conditions, but have not yet shown effective improvement. We presented a case of no-reflow phenomenon caused by an unusual cause.

Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia: The Randomized RAIN-FLOW Study.

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

No-reflow phenomenon in acute ischemic stroke: an angiographic evaluation.

BACKGROUND: Futile recanalization (FR) is de fined as a poor 90-day outcome or lack of neurological improvement at 24 h despite successful recanalization in acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated by mechanical throbectomy (MT). The No-reflow phenomenon (NRP) could be a possible cause of FR, but its evidence in AIS patients is scarce. METHODS: We retrospectively analyzed 185 digital subtraction angiographies (DSA) of AIS patients with anterior circulation LVO after endovascular treatment. To better define NRP, we designed a score called the modified capillary index score (mCIS). The score is obtained by dividing the middle cerebral artery territory in three segments. For each segment, we gave 2 points if the capillary blush was present without any delay, 1 if delayed, and 0 if absent. The primary endpoint was to use mCIS to identify NRP on post-interventional DSA and to test whether this marker may predict FR and failure of early neurological improvement (fENI). The secondary endpoint was to search for a correlation between NRP, lesion volume, and hemorrhagic transformation. We used the ROC curve to define mCIS ≤ 3 as the cut-off and marker of NRP. RESULTS: NRP was present in 35.1% of patients. NRP predicted fENI at 24 h (aOR 2.825, 95% CI 1.265-6.308, P = 0.011) and at 7 days (aOR 2.191, 95% CI 1.008-4.762, P = 0.048), but not 90-day FR. Moreover, NRP predicted hemorrhagic transformation (aOR 2.444, 95% CI 1.266-4.717, P = 0.008). CONCLUSIONS: The modified capillary index score (mCIS) seems useful in identifying NRP in AIS. In addition, mCIS was able to predict NRP that correlated with early clinical outcome and hemorrhagic transformation of the ischemic lesion. An external validation of the score is warranted.

Relationship between Hemoglobin Concentration at Admission with the Incidence of No-Reflow Phenomenon and In-Hospital Mortality in Acute Myocardial Infarction with Elevation of ST Segments in Patients who underwent Primary Percutaneous Coronary Intervention.

Anemia in acute ST-segment elevation myocardial infarction (STEMI) is associated with a pro-coagulant state, contributing to the incidence of no-reflow phenomenon and increased mortality following primary percutaneous coronary intervention (PPCI). However, clinical data remain contradictory. The objective of our study was to evaluate the association of admission hemoglobin (Hb) concentration and in-hospital mortality of STEMI patients' post-PPCI, as well as final thrombolysis in myocardial infarction (TIMI) flow. A cross-sectional study was performed from the database of Jakarta Acute Coronary Syndrome Registry, consisting of 3,071 STEMI patients who underwent PPCI between January 2014 and December 2019. No-reflow phenomenon was defined as final TIMI flow <3 of the infarct-related artery. Outcome measures were the occurrence of no-reflow and in-hospital mortality. Anemia criteria were based on the World Health Organization. Anemia was found in 550 patients (17.9%). Patients with anemia were older (60 ± 10 years, p < 0.001), predominantly women (20.7 vs. 11.2%, p < 0.001), TIMI risk score >4 (45.8 vs. 30.4%, p < 0.00), and Killip classification >1 (25.8 vs. 20.8%, p < 0.009). Anemia at admission was not associated with no-reflow phenomenon (odds ratio [OR] = 0.889; 95% confidence interval [CI] = 0.654-1.209, p = 0.455). Multivariate regression models showed that anemia was not associated with in-hospital mortality (OR = 0.963; 95% CI = 0.635-1.459, p = 0.857) and with no-reflow phenomenon (OR = 0.939; 95% CI = 0.361-2.437, p = 0.896). Anemia upon admission was not related to the no-reflow phenomena or in-hospital mortality in STEMI patients undergoing PPCI.

Measurement of Uncertainty in Prediction of No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention Using Systemic Immune Inflammation Index: The Gray Zone Approach.

Systemic immune-inflammation index (SII), which is a good predictive marker for coronary artery disease, can be calculated by using platelet, neutrophil, and lymphocyte counts. The no-reflow occurrence can also be predicted using the SII. The aim of this study is to reveal the uncertainty of SII for diagnosing ST-elevation myocardial infarction (STEMI) patients who were admitted for primary percutaneous coronary intervention (PCI) for the no-reflow phenomenon. A total of 510 consecutive acute (STEMI) patients with primary PCI were reviewed and included retrospectively. For diagnostic tests which are not a gold standard, there is always an overlap between the results of patients with and without a certain disease. In the literature, for quantitative diagnostic tests where the diagnosis is not certain, two approaches have been proposed, named "grey zone" and "uncertain interval". The uncertain area of the SII, which is given the general term "gray zone" in this article, was constructed and its results were compared with the "grey zone" and "uncertain interval" approaches. The lower and upper limits of the gray zone were found to be 611.504-1790.827 and 1186.576-1565.088 for the grey zone and uncertain interval approaches, respectively. A higher number of patients inside the gray zone and higher performance outside the gray zone were found for the grey zone approach. One should be aware of the differences between the two approaches when making a decision. The patients who were in this gray zone should be observed carefully for detection of the no-reflow phenomenon.

RDW as A Predictor for No-Reflow Phenomenon in DM Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: No-reflow phenomenon (NRP) in ST-segment elevation myocardial infarction (STEMI) patients is not infrequent. The predictive value of red blood-cell distribution width (RDW) on NRP has not been explored. METHODS: STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were enrolled. Plasma samples were obtained at admission. Participants were divided into two groups according to RDW. Logistic regression and receiver operating characteristic (ROC) curve were performed to evaluate the relationship between RDW and NRP. Subgroup analysis was made between the diabetes mellitus (DM) group and the No-DM group. RESULTS: The high RDW group had a higher NRP compared to the low group. In multivariate logistic regression analysis, DM (adjusted odds ratio [AOR]:1.847; 95% confidence interval [CI]: 1.209-2.822; p = 0.005) and hemoglobin (AOR: 0.986; 95% CI: 0.973-0.999; p < 0.05), other than RDW, were independent predictors of NRP. RDW (AOR: 2.679; 95% CI: 1.542-4.655; p < 0.001) was an independent predictor of NRP in the DM group, but not in the No-DM group. In the DM group, area under the ROC curve value for RDW predicting NRP was 0.707 (77.3% sensitivity, 56.3% specificity (p < 0.001)). CONCLUSIONS: RDW is a predictor of NRP in DM patients with STEMI, which provides further assistance in clinicians' decision making.

No reflow phenomenon in CAD patients after percutaneous coronary intervention: A prospective hospital based observational study.

The present study assessed incidence, risk factors, in-hospital and short-term outcomes associated with no-reflow in patients undergoing percutaneous coronary intervention (PCI) in STEMI, NSTEMI, unstable angina and stable angina. Out of 449 patients, 42 (9.3%) developed no-reflow. Hypertension, dyslipidemia, obesity and smoking were significant risk factors. There was significant association of no-reflow with left main disease, multiple stents, target lesion length≥ 20 mm and higher thrombus grade. Interestingly, 93 patients (23.4%) of normal flow had myocardial perfusion grade (MPG) of 0/1 with mortality in 9 (10%) patients. No-reflow is associated with poor in-hospital and short-term outcomes with higher incidence of death, cardiogenic shock, heart failure and MACE. Knowledge of risk factors of no-reflow portends a more meticulous approach to improve final outcomes. MPG could be better predictor of outcomes in these patients.

Efficacy and safety of intracoronary epinephrine for the management of the no-reflow phenomenon following percutaneous coronary interventions: a systematic-review study.

BACKGROUND: Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon. OBJECTIVES: To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents. DESIGN: Systematic review. DATA SOURCES AND METHODS: PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review. RESULTS: Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% versus 52.7%, respectively; p value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% versus 26.7%, respectively; p value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine. CONCLUSION: Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.

Effects of Electronic Cigarette Exposure on Myocardial Infarction and No-Reflow, and Cardiac Function in a Rat Model.

PURPOSE: We investigated the effects of exposure to electronic cigarettes (E-cig) vapor on the sizes of the no-reflow and myocardial infarction regions, and cardiovascular function compared to exposure to purified air and standard cigarette smoke. METHODS AND RESULTS: Sprague Dawley rats (both male and female, 6 weeks old) were successfully exposed to filtered air (n = 32), E-cig with nicotine (E-cig Nic+, n = 26), E-cig without nicotine (E-cig Nic-, n = 26), or standard cigarette smoke (1R6F reference, n = 31). All rats were exposed to inhalation exposure for 8 weeks, prior to being subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Exposure to E-cig vapor with or without nicotine or exposure to standard cigarettes did not increase myocardial infarct size or worsen the no-reflow phenomenon. Exposure to E-cig Nic+ reduced the body weight gain, and increased the LV weight normalized to body weight and LV wall thickness and enhanced the collagen deposition within the LV wall. E-cig exposure led to cardiovascular dysfunction, such as reductions in cardiac output, LV positive and negative dp/dt, suggesting a reduction in contractility and relaxation, and increased systemic arterial resistance after coronary artery occlusion and reperfusion in rats compared to air or cigarette exposure. CONCLUSIONS: E-cig exposure did not increase myocardial infarct size or worsen the no-reflow phenomenon, but induced deleterious changes in LV structure leading to cardiovascular dysfunction and increased systemic arterial resistance after coronary artery occlusion followed by reperfusion.