Case presentation

A 66-year-old man without prior cardiac history developed progressive dyspnea on exertion, culminating in rest chest pain. In the emergency department, the electrocardiogram was normal, but he was found to have an elevated troponin I (5.77 ng/mL), and he was admitted with the diagnosis of a non-ST segment elevation myocardial infarction. He became pain-free on nitrates, beta-blockers, low-molecular-weight heparin, aspirin, and clopidogrel. Past medical history was notable for hypertension, dyslipidemia, prior tobacco abuse, adenomatous colon polyps, benign prostatic hypertrophy, and hypothyroidism. Troponin I subsequently rose to 16.5 ng/mL and he was referred for cardiac catheterization the next day.

Cardiac catheterization

There was a severe stenosis of a small, distal branch of the right coronary artery, which appeared to represent the culprit lesion (Figure 38-1 and Video 38-1). The operator considered this artery too small and the lesion too distal for intervention. Atherosclerotic plaque without significant narrowing was seen in the mid-right coronary artery and the first obtuse marginal artery. A long, moderate stenosis affected the proximal to midsegment of the left anterior descending (LAD) artery at a bifurcation with a large diagonal branch (Figure 38-2 and Video 38-2). The left ventriculogram revealed normal function and no specific wall motion abnormalities. Concerned about the lesion of intermediate severity seen in the left anterior descending artery, the physician decided to assess the lesion’s significance by measuring fractional flow reserve, or FFR. Thus, a guide catheter was engaged in the left coronary artery and, after administering a bolus of 50 U/kg of unfractionated heparin, the operator advanced a pressure wire to the distal LAD. The wire transducer was placed distal to the LAD lesion and simultaneous distal coronary pressure and aortic pressure from the guide catheter tip were sampled after maximum coronary vasodilatation was achieved with 100 mcg of intracoronary adenosine (Figure 38-3). Fractional flow reserve was calculated as the ratio of the mean coronary pressure distal to the stenosis (62 mmHg) to mean pressure of the aorta at the guide catheter (76 mmHg) during maximal hyperemia. This ratio calculated to an FFR of 0.82. Thus, the lesion was determined to be a non–flow-limiting stenosis. Based on the results of the angiogram and the FFR determination, it was decided to treat him medically.

FIGURE 38-1 This is a left anterior oblique projection of the right coronary artery. There is a severe stenosis in a distal branch of the right coronary artery (arrow). Although this likely represents the culprit lesion, the vessel is of very small caliber and the lesion is very distal and would not be ideally suited to percutaneous intervention.

FIGURE 38-2 The left coronary angiogram revealed a long, moderate stenosis in the proximal to midsegment (arrows) near a bifurcation of a large diagonal branch. The significance of this intermediate stenosis is not clear from the angiogram.

FIGURE 38-3 Simultaneous pressure measured from the aorta (AO) and left coronary artery (LCA) distal to the moderate disease in the LAD during maximal hyperemia achieved with 100 mcg of intracoronary adenosine. Fractional flow reserve, or FFR is determined as the ratio of the mean distal pressure in the LCA (62 mmHg) to mean AO pressure (76 mmHg) during maximal hyperemia and calculates to 0.82. An FFR less than 0.75 represents a hemodynamically significant stenosis.

Postprocedural course

The patient had no further symptoms. He was discharged on metoprolol, isosorbide mononitrate, aspirin, clopidogrel, valsartan, and Synthroid. During a stress test performed one month later, he exercised for a total of 12 minutes using the standard Bruce exercise protocol, achieving stage 4 and a maximum of 12.9 METs. Gated SPECT myocardial perfusion revealed normal left ventricular function with a calculated ejection fraction of 66% and a small zone of reduced uptake in the mid- to basal inferolateral segment, which was partly reversible and appeared to represent an infarct with peri-infarct ischemia. This zone corresponded to the distal right coronary disease observed on the angiogram. There was no ischemia in the LAD or diagonal territories. Over 2 years of follow-up, he remains free of symptoms and cardiac events.

Discussion

Coronary angiography forms the basis for revascularization decisions in patients with coronary artery disease. When an artery appears normal or minimally diseased or if there is an obvious, severe stenosis, interpretation is easy and decision-making straightforward. However, angiography has well-known limitations, particularly for lesions of moderate or intermediate severity, arbitrarily defined as a 40% to 70% stenosis.¹ In addition, lesions are often eccentric or may be within segments difficult to visualize clearly, leaving the physician with doubt as to the stenosis severity. In such circumstances, adjunctive testing helps the physician decide the significance of a lesion with greater confidence.

Currently, there are two adjunctive techniques commonly used to assess lesion significance: intravascular ultrasound and fractional flow reserve. Intravascular ultrasound, or IVUS, is an anatomically-based technique to precisely measure the arterial lumen. Fractional flow reserve, or FFR, is physiologically based and takes into consideration the multiple, complex variables impacting coronary flow, including lesion severity and length and collateral flow.

Assessment of an ambiguous lesion with intravascular ultrasound requires the identification of a “worse” segment (minimal luminal diameter) and quantification of the lumen. It is not appropriate to make a decision based on the observation that the IVUS “looks bad,” as it is the degree of anatomic lumen compromise that determines lesion significance, not the atherosclerotic plaque burden. In patients with intermediate stenoses of major epicardial arteries (excluding the left main stem), the following IVUS parameters are associated with “significant” lesions”: 1) minimal luminal cross-sectional area narrowing less than 4.0 mm²; 2) minimal luminal diameter less than 1.8 to 2.0 mm; and 3) percentage of area stenosis greater than 70%.^2,3 Left main stem lesions are deemed significant if the minimal luminal area is less than 6 mm² in one study⁴ and less than 7.5 mm² in another.⁵ There are several important caveats to the use of IVUS for determination of lesion significance. First, IVUS parameters have been validated only in large, proximal arteries (average 3.0 mm). The absolute lumen values noted above do not apply to small or distal arteries. Second, disease involving a long segment or tandem proximal lesions may not narrow the lumen below the threshold diameter at any given slice, yet may still compromise flow. Finally, the IVUS catheter may cause spasm, leading to an artifactually small lumen.

Fractional flow reserve describes the ratio of the maximum achievable flow in the presence of a stenosis to the theoretical maximum flow in the same vessel in the absence of a stenosis. It is simple to perform, requiring the measurement of simultaneous aortic and distal coronary pressures using a special angioplasty guidewire outfitted with a micromanometer during maximal hyperemia. The mathematics, experimental basis, technique, limitations, and validation of FFR have been well-described.^6–11 It can be calculated simply by the formula: