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

Abstract

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.

Keywords: acute ischemic stroke; endovascular thrombectomy; microvascular disturbance; no-reflow phenomenon; reperfusion therapy.

FIGURE 1

Illustration of the no‐reflow phenomenon pathogenesis (Created with BioRender.com) The no‐reflow phenomenon, which refers to the post‐recanalization reperfusion failure, is the clinical manifestation of microcirculation disturbance. The latter is primarily attributed to mechanical obstruction by blood components or clog fragmentation, and compression due to functional or structural change in the vessel wall or the surrounding cells.

FIGURE 2

The potential influence, evaluation strategies, and management of the no‐reflow phenomenon in clinical settings (Created with BioRender.com). (A) The potential influence of the NRP. The NRP is involved in clinically ineffective reperfusion after endovascular therapy. The diagram shows favorable recanalization rates (TICI/mTICI ≥2b) and favorable 90‐day clinical outcome proportions (mRS ≤2) in major studies concerning the efficacy of endovascular thrombectomy. It is of note that nearly half of the patients failed to achieve favorable outcomes despite successful recanalization. (B) Evaluation strategies for the NRP. There are currently no available techniques in clinical settings for the monitoring of microcirculation disturbance. After successful recanalization of the proximal large artery based on imaging assessment (b1), strategies for evaluation of cerebral blood flow status or microcirculatory resistance (b2) are applied for detection of the NRP. (C) Potential management for the NRP. Management of the NRP should be emphasized to further improve the functional outcomes following recanalization therapy. Strategies including first‐aid workflow refinement, distal embolization prevention, antiplatelet and antithrombotic therapy, vasodilator, ischemic conditioning, and therapeutic hypothermia, are promising for NRP management.