Percutaneous coronary intervention (PCI) is the best available reperfusion strategy in patients with acute ST-segment elevation myocardial infarction (STEMI). Its goal is to restore coronary blood flow and provide tissue reperfusion, thus reducing myocardial infarct size. One of the most important limitation of PCI is no-reflow (NR), a phenomenon consisting in a not optimal myocardial reperfusion despite an effective epicardial recanalization of the infarct-related artery. During the “primary PCI age” NR has been shown to have an incidence of up to 30% according to several reports. In humans, pathophysiology of NR consists of the variable combination of four components: 1) distal atherothrombotic embolization; 2) ischemic injury; 3) ischemia/reperfusion injury; and 4) susceptibility of coronary microcirculation to injury. Diagnosis of NR can be made invasively or non-invasively. This phenomenon can be diagnosed with angiography, using Thrombolysis in myocardial infarction (TIMI) flow grade and myocardial blush grade (MBG), or using a Doppler wire. After PCI, NR can be investigated by electrocardiography, myocardial contrast echocardiography (MCE) or cardiac magnetic resonance imaging (CMR), which is the diagnostic gold standard, being able to quantify the phenomenon . Coronary NR has been shown to increase the risk of cardiovascular events and it has been associated with worse short- and long-term outcomes. This prompted interventionalists to try to overcome this phenomenon using various strategies. However, clear guidelines on the management of NR are still not available. In this review, we discuss the pharmacological and non-pharmacological interventions proposed for the prevention and treatment of NR, highlighting the new updates and evidences on efficacy of these approaches. RISK FACTORS AND OUTCOMES OF NO-REFLOW Detection of patients at higher risk for NR before PCI may be beneficial from the perspective of prevention and treatment of this phenomenon. However, most of the conditions that have been associated with NR overlap with well-known cardiovascular risk factors, such as older age, male gender, arterial hypertension, smoking, diabetes mellitus and dyslipidemia. Unsuccessful myocardial reperfusion after primary PCI has also been linked with Killip class ≥ 2, hypotension at admission, high coronary thrombus burden, low TIMI flow grade before PCI and, importantly, with delayed reperfusion, recalling the rule “ time is muscle, time is outcomes”. Indeed, NR has been linked with severe clinical outcomes [8,9]. A study analysing 4329 patients with STEMI treated with PCI from a Korean multicentre registry has shown that NR was associated with poor in-hospital outcome and increased long-term mortality, mainly driven by increased cardiac mortality. Interestingly, a multicentre study comparing 17547 patients with good final coronary flow with 590 patients with transient and 144 patients with persistent NR confirmed these results showing that inhospital, 30-day all-cause and one-year all-cause mortalities were higher in patients with persistent NR and with transient no-reflow compared with patients with a normal flow, with the highest mortality occurring early (<30 days) in the persistent NR group (p<0.0001).
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