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The year prior to the description of syndrome X, Tambe and associates described a curious angiographic finding of slow contrast flow in six patients with angina and angio-graphically smooth epicardial coronary arteries. They speculated that this angiographic observation was attributable to an increased coronary microvascular resistance. Today, the coronary slow flow phenomenon (CSFP) is characterized as a delayed passage of contrast media during adequate selective coronary arteriography in the absence of obstructive epicardial coronary artery disease. It is referred to as a "phenomenon" because it is defined on the basis of an angiographic observation rather than a clinical syndrome.

What constitutes slow contrast flow has not been uniformly defined. Most published studies have utilized the subjective impression of an experienced angiographer. However, an objective definition is required if clinicians and researchers are to ensure they are referring to the same condition. Two approaches to this problem have evolved. These both utilize conventional indices developed by the Throm-bolytics in Myocardial Infarction (TIMI) investigators.

The TIMI flow grade is a qualitative index of angio-graphic coronary flow where TIMI-3 flow is considered as normal flow. In TIMI-2 flow, distal vessel opacification is delayed and often arbitrarily defined as requiring three or more cardiac cycles to opacify the distal vasculature. Thus a simple quantifiable definition of the CSFP is the presence of TIMI-2 flow in the absence of obstructive epicardial coronary disease. The advantage of this definition is its simplicity, which allows prompt identification of the phenomenon during angiography. Furthermore, angiographic flow is normalized for heart rate, thus reducing artifacts. Its disadvantage is that it incorporates angiographic flows that are six or more standard deviations from the mean and thus may be too restrictive.

The TIMI frame count (TFC) is a quantitative angio-graphic flow index that assesses the number of angiographic frames required to opacify a coronary vessel. Published average TFC for the left anterior descending (LAD), circumflex (Cx), and right coronary arteries (RCA) are 36.2 ±

2.6, 22.2 ± 4.1, and 20.4 ± 3.0 frames, respectively [1]. Some investigators have defined the CSFP on the basis of TFC just above these threshold values, whereas others have required counts at least two standard deviations above these values, and yet others have utilized their own control values. Although this approach is more quantitative than those described earlier, its limitations include (a) frequent necessity for offline analysis; (b) TFC variations with heart rate, nitrate therapy, and dye injection relative to cardiac phase; (c) literature references that require adjustment for angiographic acquisition rate; and (d) clinical characteristics of the control data that are often ill-defined.

Irrespective whether the CSFP is defined by subjective impression, TIMI flow grade, or TFC, the criterion for what constitutes slow contrast flow remains an arbitrary definition. Despite this, there is clearly a group of patients with curious delayed vessel opacification in the absence of obstructive epicardial coronary disease and thus attributable to an increased microvascular resistance. The purpose of this chapter is to summarize the angiographic, pathophy-siologic, and clinical characteristics associated with this angiographic phenomenon as well as describing potential therapies for the associated angina.

Primary and Secondary Coronary Slow Flow Phenomenon

The initial description of the CSFP was reported in patients undergoing angiography for the evaluation of chest pain. This same angiographic appearance has also been observed in patients immediately following technically successful coronary angioplasty. As the delayed opacification occurs in the absence of significant large vessel coronary disease in both scenarios, it is plausible that both have a similar underlying pathophysiology and therefore warrant concurrent consideration. Accordingly, CSFP occurring de novo (usually in patients undergoing angiography for evaluation of chest pain) with angiographically normal or near-normal coronary arteries should be considered as primary CSFP. When the phenomenon occurs following successful dilatation of a coronary stenosis (by angioplasty, Atherectomy, or stent deployment) resulting in a widely patent residual lesion and no evidence of vessel dissection, then it is referred to as secondary CSFP. This chapter will exclusively focus on primary CSFP, as discussion of the secondary form (often referred to as the "no reflow phenomenon") warrants a chapter of its own.

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