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Prognosis of No-reflow Phenomenon
Abstract & Commentary
By Michael H. Crawford, MD
Source: Ndrepepa G, et al. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010;55:2383-2389.
Little is known about the long-term prognosis of the no-reflow phenomenon after percutaneous intervention (PCI) for acute ST elevation myocardial infarction (STEMI). Thus, these investigators from Munich, Germany, studied 1,406 patients with STEMI presenting within 24 hours of symptom onset and undergoing PCI by scintigraphic infarct size measurement 7-14 days after PCI. No-reflow was defined as TIMI flow grade ≤ 2 or a TIMI flow grade of 3 but a TIMI perfusion grade of ≤ 1 at 10 minutes after PCI. The primary endpoint was five years mortality.
Results: No-reflow occurred in 410 of the 1,406 patients (29%). No-reflow patients were, in general, older, more often had prior bypass surgery, and had higher-peak troponin, CK-MB, and high-sensitivity CRP levels. Also, no-reflow patients had a longer time from symptom onset to hospital admission and were more likely to have multivessel disease. Scintigraphic MI size was larger in the no-reflow group (15% vs. 8%, p < 0.001). Mortality at five years was higher in the no-reflow group (18.2% vs. 9.5%, p < 0.001). MI size and the incidence of no-reflow were significantly associated. Multivariate predictors of five-year mortality included no-reflow, age, diabetes, killip class, CRP, multivessel disease, and infarct size. After adjusting for these predictors, the hazard ratio for no-reflow confirmed that it is an independent predictor of five-year mortality (HR = 1.7, 95% CI 1.2-2.4, p = 0.004). The authors concluded that no-reflow is a strong predictor of five-year mortality in STEMI patients treated with PCI, and that no-reflow provides independent prognostic information beyond infarct size.
Depending on your definition, no-reflow occurs in 10%-30% of STEMI cases treated by PCI. Evidence suggests that downstream thrombus embolization in resistance arteries is the cause. This study clearly demonstrates that it is associated with higher mortality, larger infarcts, lower ejection fraction, and increased remodeling. The strengths of this study are its large size and long follow-up. The weaknesses are that we do not know the time course of no-reflow. Smaller studies suggest that it can resolve, but it may take three months. Other studies show that it is persistent in 50% of patients. Also, we do not have details about pharmacologic or other therapies for no-reflow in this study and, thus, cannot assess their effectiveness. Clearly we should try to avoid no-reflow and treat it vigorously if it does occur, but how do we do this?
Prevention of no-reflow involves pre-procedure anticoagulation and antiplatelet pharmacologic therapy. During the procedure, there are mechanical adjuncts to PCI, such as thrombectomy or aspiration catheters, and distal protection wires, filters, or balloons. Studies with these devices have shown higher TIMI flow grades and less distal embolization but no change in 30-day mortality. Thus, routine use of these devices is not recommended, but selective application to those with high thrombus burdens is reasonable.
Once no-reflow is recognized in the catheterization laboratory, pharmacologic therapy can be deployed. Several different types of pharmacologic agents have been used: metabolic agents, vasodilators, anticoagulant, and antiplatelet agents. In hopes of maximum effects, these agents are often given intracoronary (IC). Vasodilators that have been used include adenosine, nitroprusside, diltiazem, verapamil, and nicardipine. Anticoagulation or antiplatelet agents given include abciximab and glycoprotein 11b/111a inhibitors. Despite IC delivery, systemic effects can occur; the most worrisome is hypotension. Thus, vasodilators, even IC, are relatively contraindicated in the face of hypotension and shock. Usually, hypotension is transient, and most patients respond to a brief pressor infusion.
Long-term care of no-reflow patients is focused on left-ventricular performance. These patients should receive ACEI/SRBs for at least three months regardless of the discharge ejection fraction. They should be reassessed at three months to plan further therapy.