No-reflow is the situation in which the epicardial vessel has been opened and the myocardium is still not perfused. It occurs in something between five and twenty per cent of primary angioplasty cases, it is an independent predictor of infarct size, heart failure and mortality, and the window in which it can be influenced is short.
Definition and grading
Angiographic no-reflow is TIMI flow of 0 to 1 in the absence of mechanical obstruction — no dissection, no residual stenosis, no spasm, no thrombus visible. Slow flow is TIMI 2. Because epicardial flow can look adequate while tissue perfusion is not, the myocardial blush grade is the more informative measure: grade 0 is no blush, grade 3 is normal. A patient with TIMI 3 flow and blush grade 0 has been reperfused in the artery and not in the muscle, and the outcome tracks the blush rather than the TIMI grade.
Mechanisms
Four contribute, usually together. Distal embolisation of thrombus and atheromatous debris liberated during balloon inflation or stent deployment. Ischaemia-reperfusion injury, with oxidative stress, calcium overload and endothelial swelling. Microvascular spasm mediated by vasoactive substances released from activated platelets. Intramyocardial haemorrhage and oedema compressing the microcirculature from outside. The relative contribution differs between patients, which is why no single agent works reliably in everyone.
Who is at risk
Long ischaemic time before presentation; a heavy angiographic thrombus burden; a large vessel with a proximal occlusion; saphenous vein graft intervention; rotational atherectomy; older age; diabetes; and a low blood pressure on arrival. When several of these coincide, plan the case as if no-reflow is likely rather than reacting once it appears.
Prevention
Prevention beats treatment, because established no-reflow responds poorly. Minimise ischaemic time. Avoid over-aggressive pre-dilatation in a thrombus-laden vessel — direct stenting is preferable where the anatomy permits. Consider deferred stenting after flow is restored in a high thrombus burden case. Use adequate anticoagulation and a potent P2Y12 inhibitor loaded early. Distal protection devices have a role in saphenous vein graft intervention specifically; routine manual thrombus aspiration in native vessels is not supported by TASTE or TOTAL and carries a stroke signal, so it should be reserved for selected high-burden cases rather than used by default.
Stepwise treatment
- Exclude a mechanical cause first. Dissection, residual stenosis, spasm and thrombus all mimic no-reflow and all have different treatments. Intravascular imaging settles the question quickly.
- Adenosine, given intracoronary in boluses, ideally distally through a microcatheter or the balloon lumen so the drug reaches the microcirculation rather than washing back.
- Verapamil or nicorandil intracoronary if adenosine is insufficient. Nicardipine is an alternative where available.
- Sodium nitroprusside intracoronary, effective but with a systemic hypotensive effect that must be anticipated.
- Glycoprotein IIb/IIIa inhibitor, intracoronary or intravenous, where thrombus burden is the dominant mechanism.
- Support the haemodynamics. Perfusion pressure is what drives flow through a compromised microcirculation; treat hypotension actively and consider mechanical support in cardiogenic shock.
Distal delivery through a microcatheter is the detail that most often separates a response from no response. A drug given at the guide catheter in a vessel with no forward flow does not reach the bed it is intended for.
Afterwards
Document the final TIMI grade and blush grade — they are the prognostic information the receiving team needs. Anticipate a larger infarct: these patients have a higher rate of arrhythmia and of heart failure, and they should be monitored accordingly rather than treated as routine post-PCI. Arrange early assessment of ventricular function, and start guideline-directed medical therapy without waiting for the deterioration that justifies it.
Related reading: acute stent thrombosis, DAPT duration after PCI, the interventional and acute care reading list, and the Monday interventional case review.