Coronary No-Reflow after Primary Percutaneous Coronary Intervention-Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy

Abstract

Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.

Keywords: coronary no-reflow; microcirculation steal syndrome; microvascular obstruction; pathophysiology; therapy.

Figure 1

Pathophysiological mechanisms of microvascular obstruction and coronary no-reflow. Pathophysiological events that develop at epicardial coronary artery and microcirculation (capillary) levels are shown. Black arrows denote forces generated outside the capillaries that compress microcirculation, the red arrow points out to increased permeability. Numbers show the following components of microvascular obstruction: 1, atherothrombotic debris; 2, blebs; 3, neutrophil aggregates; 4, fibrin; 5, platelet aggregates; 6, neutrophil extracellular traps (NETs); 7, monocytes; 8; erythrocyte aggregates; 9, inflammasome.