No-reflow phenomenon

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Jennifer Giuseffi, M.D.; David M. Leder, M.D.; Ayokunle Olubaniyi, M.B,B.S [3]

Many definitions have been given to this phenomenon based on individual’s area of specialty, but the definition that unites all fields was by Kloner et al in 1974 who described the condition as the inability to adequately perfuse myocardium after temporary occlusion of an epicardial coronary artery without evidence of persistent mechanical obstruction, thus implying ongoing myocardial ischaemia. When defined angiographically, it is an acute reduction in coronary flow (TIMI grade 0-1) in the absence of dissection, thrombus, spasm, or high-grade residual stenosis at the original target lesion. In other words, it is the failure of blood to reperfuse an ischemic area after the physical obstruction has been removed or bypassed.^[1][2] It has been clearly shown that a complete restoration of epicardial blood flow (TIMI Flow Grade 3) does not correlate with a better myocardial perfusion in achieving better clinical outcomes. Therefore, over the years, attention has shifted towards methods to evaluate myocardial perfusion. A lesser degree of obstruction to coronary blood flow (TIMI grade 2) is sometimes referred to as slow flow. No-reflow is the decline in TIMI flow from TIMI flow 3 or 2 to TIMI flow 1 or 0, which occurs >5 mm distal to the lesion. No-reflow is an important predictor of mortality after PCI ^[3].

This phenomenon was first described by Krug et al ^[4] during induced myocardial infarction in dog subjects in 1966, but the term ‘no-reflow’ was first used by Majno and colleagues in 1967 when they observed that brains of rabbits exposed to prolonged ischemia suffered significant changes in the microvasculature which impeded blood flow to the brain cells.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Jennifer Giuseffi, M.D.; David M. Leder, M.D.; Ayokunle Olubaniyi, M.B,B.S [2]

This phenomenon was first described by Krug et al ^[1] during induced myocardial infarction in dog subjects in 1966, but the term ‘no-reflow’ was first used by Majno and colleagues in 1967 when they observed that brains of rabbits exposed to prolonged ischemia suffered significant changes in the microvasculature which impeded blood flow to the brain cells.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Jennifer Giuseffi, M.D.; David M. Leder, M.D.; Ayokunle Olubaniyi, M.B,B.S [2]

The primary mechanism of no-reflow is likely due to distal embolization of atheromatous and thrombotic debris dislodged by balloon inflation or stent implantation.^[1][2] During PCI, microthrombi and small particles of plaques are thought to be showered downstream, occluding small arteries, arterioles, and collateral microvasculature. Analysis of the aspirate obtained from patients without no-reflow revealed a greater amount of atheromatous plaques and significantly more platelet and fibrin complex, macrophages, and cholesterolcrystals than those who experienced no-reflow. The 30-day mortality was significantly higher (27.5%) in patients with no-reflow phenomenon than in patients with normal coronary blood flow after PCI (5.3%, P < 0.001). Predictors of no-reflow include a higher plaque burden, thrombus, lipid pools by IVUS, higher lesion elastic membrane cross-sectional area, pre-infarction angina, and TIMI flow grade 0 on the initial coronary angiogram, among other factors.

Other pathophysiologic mechanisms include:

• Release of active tissue factor from the dislodged plaque^[3]
• Vasoconstriction secondary to serotonin, adenosine diphosphate, thromboxane A2, released by the embolized platelet-rich atheromatous material^[4]
• Reperfusion injury from the release of oxygen free radicals during inflammation
• Myocardial necrosis and stunning
• Microvascular damage^[5]
• Microvascular plugging with platelets or leukocytes
• Endothelial swelling and tissue edema compressing vasculature

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Jennifer Giuseffi, M.D.; David M. Leder, M.D.; Ayokunle Olubaniyi, M.B,B.S [2]

The reported incidence of no-reflow phenomenon ranges between 0.6-42% depending on the defining criteria and the clinical setting. It has been reported in anywhere from 11-30% of patients following thrombolysis or intervention in acute myocardial infarction. However, in routine, elective coronary intervention, the prevalence has been reported to be as low as 0.6-2%. This phenomenon appears to be more frequent during interventions on saphenous vein grafts (SVG) or thrombus containing lesions as well as during the use of rotational atherectomy. Gender does not appear to play a role in this phenomenon, but it seems to occur more frequently in older patients and in those who did not experience pre-infarct angina. Admission hyperglycemia has also been associated with higher incidence of no-reflow as well as worse outcomes. Lesions at high-risk forno-reflow include: diffuse atherosclerotic involvement, angiographic demonstrable thrombus, irregular or ulcerative lesions, and long lesions with large plaque volume. No-reflow is a common (15%) finding during primary angioplasty for acute MI.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Heart diseases ^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Jennifer Giuseffi, M.D.; David M. Leder, M.D.; Ayokunle Olubaniyi, M.B,B.S [2]

In the cathetarization laboratory, no-reflow may be clinically silent or appear suddenly associated with severe chest pain, ischemic (EKG) changes, conduction abnormalities, and/or hemodynamic deterioration. This needs to be distinguished from slow-flow which can be caused by coronary dissection, macrothrombus formation, coronary vasospasm, or distal macroembolization. The presence of no-reflow is clinically important as its presence has been associated with a five to ten fold increase in mortality,^[1] as well as a high incidence of myocardial infarction (MI), left ventricular dysfunction, ventricular arrhythmias, early congestive heart failure and cardiogenic shock. Predictors of outcome include:

• Duration of coronary occlusion
• Extent of myocardium supplied by the occluded artery
• Patency of infarct-related artery
• Quality of collateral circulation
• Presence of pre-infarction angina which produces a preconditioning-like effect and might correlate with preservation of collateral circulation.

Hyperglycemia in acute myocardial infarction is associated with an increased risk of in-hospital mortality, as well as no-reflow phenomenon.

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