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.

Comparison of Intracoronary Epinephrine and Adenosine for No-Reflow in Normotensive Patients With Acute Coronary Syndrome (COAR Trial)

Background: Intracoronary epinephrine has been effectively used in treating refractory no-reflow, but there is a dearth of data on its use as a first-line drug in normotensive patients in comparison to the widely used adenosine. Methods: In this open-labeled randomized clinical trial, 201 patients with no-reflow were randomized 1:1 into intracoronary epinephrine as the treatment group and intracoronary adenosine as the control group and followed for 1 month. The primary end points were improvement in coronary flow, as assessed by TIMI (Thrombolysis in Myocardial Infarction) flow, frame counts, and myocardial blush. Secondary end points were in-hospital and short-term mortality and major adverse cardiac events. Results: In all, 101 patients received intracoronary epinephrine and 100 patients received adenosine. Epinephrine was generally well tolerated with no immediate table death or ventricular fibrillation. No-reflow was more effectively improved with epinephrine with final TIMI III flow (90.1% versus 78%, P =0.019) and final corrected TIMI frame count (24±8.43 versus 26.63±9.22, P =0.036). However, no significant difference was observed in final grade III myocardial blush (55.4% versus 45%, P =0.139), mean reduction of corrected TIMI frame count (−25.71±11.79 versus −26.08±11.71, P =0.825), in-hospital and short-term mortality, and major adverse cardiac events. Conclusions: Epinephrine is relatively safe to use in no-reflow in normotensive patients. A significantly higher frequency of post-treatment TIMI III flow grade and lower final corrected TIMI frame count with relatively better achievement of myocardial blush grade III translate into it displaying relatively better efficacy than adenosine. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04699110.

Применение статинов при ишемическом и реперфузионном повреждении сердца

Статины способствуют повышению толерантности сердца к действию ишемии/реперфузии. Статины вызывают уменьшение размера инфаркта, оказывают антиаритмический эффект, обеспечивают восстановление сократимости сердца во время реперфузии, предупреждают возникновение феномена no-reflow. Статины препятствуют постинфарктному ремоделированию сердца. Установлено, что кардиопротекторный эффект статинов не зависит от уровня холестерина в крови. В инфаркт-лимитирующем эффекте статинов участвует NO-синтаза, PI3-киназа, Akt-киназа, протеинкиназа С и митоКАТФ-каналы. Применение статинов в больших дозах не оказывает кардиопротекторного эффекта у пациентов с коронарным шунтированием или острым инфарктом миокарда. Приём сатинов улучшает отдалённый прогноз у пациентов, перенесших острый инфаркт миокарда.

Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)

BackgroundThe relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiological features of this phenomenon, and its associations with outcomes in three international randomized controlled thrombectomy trials with pre-specified follow-up perfusion imaging.MethodsIn a pooled analysis of the EXTEND-IA (ClinicalTrials.gov number NCT01492725), EXTEND-IA TNK (NCT02388061) and EXTEND-IA TNK Part-two (NCT03340493) trials, patients undergoing thrombectomy with final angiographic extended Thrombolysis In Cerebral Ischemia 2c-3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative Cerebral Blood Volume or Flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homologue in the absence of carotid stenosis or re-occlusion.ResultsRegions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (Interquartile range 47.8-70.7%) of the infarct volume, and involved both subcortical (n=26/33,78.8%) and cortical (n=10/33,30.3%) regions. Patients with no-reflow had a median 25.2% ([Interquartile range 16.4-32.2%],p<0.00001) relative Cerebral Blood Volume interside reduction and 19.1% (Interquartile range 3.9-28.3%,p=0.00011) relative Cerebral Blood Flow reduction but similar mean-transit-time (median -3.3%, Interquartile range -11.9-24.4%,p=0.24) within the infarcted region. Baseline characteristics were similar between patients with and without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (aOR=1.79,95%CI2.32-15.57,p=0.0002), greater infarct growth (ß=11.00,95%CI5.22-16.78,p=0.00027), reduced National Institutes of Health Stroke Score improvement at 24-hours (ß=-4.06,95%CI-6.78--1.34,p=0.004) and being dependent or dead at 90-day as assessed on the modified Rankin Scale (aOR=3.72,95%CI1.35-10.20,p=0.011) in multivariable analysis.ConclusionCerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with post-treatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted.Classification of evidenceThis study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24-hours is associated with post-treatment complications and poor 3-month functional outcome.