Pathophysiology, Diagnosis, and Management of Coronary No-Reflow Phenomenon

Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but they have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon.

766 Distal embolization protection systems. A rare complication

Aims The no reflow phenomenon is a not rare complication that occurs in up to 30% of patients with acute coronary syndrome undergoing myocardial reperfusion by percutaneous coronary intervention. The use of coronary artery thrombus aspiration or distal embolization protection systems has reduced the risk of distal embolization and no-reflow phenomenon. Methods and results We describe the case of a 77 year old female suffering from hypertension presented at our emergency department for inferior STEMI. An urgent coronary angiography was performed, showing a three-vessel coronary artery disease with right coronary artery sub-occluded in the middle segment (culprit lesion), with a voluminous endoluminal minus image, as intracoronary thrombosis. Before performing the coronary angioplasty, a Spider FX3 filter was placed on the distal segment of the right coronary artery; thrombus aspiration was performed, which was ineffective, then angioplasty and Zotarolimus eluting stent implantation in the mid segment of the right coronary artery. After stent implantation, an image of minus was highlighted inside the basket of the filter, as a migrated and incarcerated thrombotic formation; then, the filter was removed. During the removal of the filter, longitudinal crush of the distal portion of the stent is caused, with limitation of the downstream flow, in the absence of haemodynamic instability. The stent was recrossed with Fielder XT guidewire supported by Turnpike LP Microcatheter. Multiple dilations werenperformed with semi-compliant and non-compliant increasing-caliber balloons and then Zotarolimus eluting stent implantation, in partial overlap with the distal portion of the previously implanted stent, with TIMI flow 3. The echocardiogram showed a normal global systolic function, with alterations in regional kinetics. On the 6th day, angioplasty and Zotarolimus eluting stent implantation was performed on the mid-proximal segment of the left anterior descending artery. During the hospitalization the patient was stable and has been discharged in good condition on the ninth day. Conclusions The interest of this case is the evidence of a rare complication related to the use of distal embolization protection system, probably due to an incomplete closure of the filter before removal, due to the high amount of thrombotic material inside it. The rapid recrossing of the stent after the longitudinal crush, the angioplasty and the second stent implantation, led to a quick flow restoration, without haemodynamic and clinical consequences on the patient's outcome.

D-dimer for risk stratification and antithrombotic treatment management in acute coronary syndrome patients: asystematic review and metanalysis

Background Data on the prognostic role of D-dimer in patients with acute coronary syndrome (ACS) are controversial. Our aim was to summarize current evidence on the association between D-dimer levels and short/long-term poor prognosis of ACS patients. We also investigated the association between D-dimer and no-reflow phenomenon. Methods Systematic review and metanalysis of observational studies including ACS patients and reporting data on D-dimer levels. PubMed and SCOPUS databases were searched. Data were combined with hazard ratio (HR) and metanalysed. The principal endpoint was a composite of cardiovascular events (CVEs) including myocardial infarction, all-cause and cardiovascular mortality. Results Overall, 32 studies included in the systematic review with 28,869 patients. Of them, 6 studies investigated in-hospital and 26 studies long-term outcomes. Overall, 23 studies showed positive association of high D-dimer levels with CVEs. D-dimer levels predicted poor prognosis in all studies reporting in-hospital outcomes. Five studies satisfied inclusion criteria and were included in the metanalysis, with a total of 8616 patients. Median follow-up was 13.2 months with 626 CVEs. The pooled HR for D-dimer levels and CVEs was 1.264 (95% CI 1.134–1.409). Five out of 7 studies (4195 STEMI patients) investigating the association between D-dimer levels and no-reflow showed a positive correlation of D-dimer levels with no-reflow. Conclusions In patients with ACS, D-dimer was associated with higher in-hospital and short/long-term complications. D-dimer was also higher in patients with no-reflow phenomenon. The use of D-dimer may help to identify patients with residual thrombotic risk after ACS. Trial registration The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews: CRD42021267233.

Serum Triglycerides Fasting Glycemic Product Index Predict No-Reflow Phenomenon in Patients with Actue Myocardial Infarction Undergoing Primary Coronary Intervention

Objective: To investigate the value of serum triglyceride and fasting glycemic index in predicting no reflow in patients with acute myocardial infarction after percutaneous coronary intervention. Methods: A total of 1037 patients with acute myocardial infarction who received PCI in the Department of Cardiology of Shanghai General Hospital and Jiading Branch of Shanghai General Hospital from January 2016 to May 2021 were retrospectively selected. According to postoperative TIMI blood flow classification, all patients were divided into no reflow group (TIMI blood flow≤grade 2) (309 cases) and reflow group (TIMI blood flow = grade 3) (728 cases). Clinical data, laboratory indicators and surgical information were collected from the two groups of patients. Logistic univariate and multivariate regression were used to analyze the independent risk factors of no reflow in actue myocardial infarction patients after PCI. ROC curve was used to analyze the best cut-off point for TyG index to predict the occurrence of no reflow. Results: The TyG index of no reflow group was significantly higher than of reflow group (7.16±0.64 vs 6.63±0.38, P=0.001). Multivariate logistic regression analysis showed that TyG index(OR=1.484,95%Cl 1.203-1.831,P< 0.001);WMSI(OR=2.640,95%Cl1.036-4.722,P=0.039);CSI (OR=2.299,95%Cl1.117-4.767,P=0.022) was independent predictors of no reflow phenomenon in patients with acute myocardial infarction after PCI .The area under the ROC curve predicted by TyG index after PCI without reflow was 0.809,95%Cl(0.740-0.879),higher than CSI and WMSI.When the TyG index was 6.995, the sensitivity and specificity of Youden index were 82.4% and 70.3% respectively at the maximum.Conclusion: TyG index can be used as an indicator to predict the occurrence of no-reflow in patients with acute myocardial infarction after PCI, which is helpful for clinicians to select high-risk patients and take interventions timely, so as to reduce the risk of no-reflow in patients after PCI.

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

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

Mechanism and Potential Treatment of the 'No Reflow' Phenomenon After Acute Myocardial Infarction: Role of Pericytes and GPR39

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