Applied Radiology

Drs. Lovelace and Moneta are with the Division of Vascular Surgery, Oregon Health Sciences University and Portland Department of Veteran's Affairs Hospital, Portland, OR.

Recent randomized controlled trials comparing combined carotid endarterectomy (CEA) and medical therapy with medical therapy alone have determined that patients with specific levels of internal carotid artery (ICA) stenosis benefit from endarterectomy. ^1-4 The North American Symptomatic Carotid En-darterectomy Trial (NASCET) determined that patients presenting with transient ischemic attacks, nondisabling stroke, or amaurosis fugax and 50% to 69% or 70% to 99% angiographic internal carotid artery stenosis achieved significant reduction in stroke rates with ipsilateral CEA over medical therapy alone. ^3,4 In patients with high grade stenosis, 70% to 99%, there was an absolute reduction in stroke risk by 17% at 2 years following surgery. ⁴ In patients with moderate stenosis, 50% to 69%, benefit of surgery was less dramatic, with an absolute reduction in stroke risk of 5.5% at 5 years. ³

The European Carotid Surgery Trial (ECST) also found that symptomatic patients with internal carotid artery stenosis benefit from carotid endarterectomy. ² In this multi-center, randomized controlled trial of more than 3000 patients, frequency of major stroke or death in the medically treated group was 26.5% at 3 years, compared with 14.9% for surgically treated patients. Benefit was confined to patients with 80% to 99% angiographic ICA stenosis.

Asymptomatic patients modestly benefit from CEA. ¹ The Asymptomatic Carotid Artery Surgery (ACAS) trial randomized 1662 patients with angiographic ICA stenosis of 60% to 99% to receive surgery and medical therapy or medical therapy only. Aggregate stroke and death rates over a 5-year period were 11% for the medical group and 5.1% for the surgical group. In addition, the study documented a 1.2% stroke rate resulting from angiography. ¹

Severity of internal carotid artery stenosis in the NASCET, ECST, and ACAS studies was determined using angiography. Angiographic measurement of percent ICA stenosis is usually calculated by one of three methods. ⁵ Each method uses the diameter of the ICA lumen at the point of maximal narrowing as the numerator, but the reference value used as the denominator in the equation to calculate percent stenosis varies. In NASCET and ACAS, the presumably disease-free distal cervical ICA diameter is used as the reference value, whereas in ECST the estimated normal diameter of the carotid bulb was chosen. (Use of the common carotid artery [CCA] diameter has also been advocated.)

Each method of measurement (NASCET, ECST, and CCA) leads to a different calculation of percent ICA stenosis. Three different levels of stenosis will be calculated depending on the value chosen as the denominator (figure 1). An evaluation of 1001 angiograms comparing these three methods concluded that calculations using the distal ICA diameter as the denominator (NASCET method) consistently result in a lower value of percent angiographic ICA stenosis than calculations using the estimated normal carotid bulb diameter (ECST method). ⁶

Contrast cerebral angiography is invasive and can be associated with significant neurologic morbidity that will diminish the benefit conferred by CEA. ¹ Nearly half of the perioperative morbidity attributed to the surgical arm of the ACAS trial resulted from cerebral angiography, not from the actual surgical procedure itself. Conversely, duplex ultrasound scanning of the carotid arteries is a safe, noninvasive means of determining severity of ICA stenosis.

Duplex velocity and spectral criteria developed at the University of Washington (UW) have been the most widely employed criteria to noninvasively determine levels of "angiographic" ICA stenosis (Table 1). ⁷ These criteria, however, are not applicable to the threshold levels of ICA stenosis determined to be of benefit in ACAS and NASCET, in that there are no cutoffs for >= 60% and
>= 70% ICA stenosis. In addition, the UW criteria were developed using the estimated normal diameter of the carotid bulb as the denominator in calculations of percent angiographic ICA stenosis.

Since the randomized trials were completed, new duplex criteria for determining angiographic ICA stenosis have been developed to provide criteria directly relevant to ACAS and NASCET. In our opinion, these supplemental duplex criteria should not replace existing UW criteria, which very accurately quantify atherosclerosis in the carotid bulb. The new criteria are most useful in properly selecting patients for CEA based on results of the randomized clinical trials that quantify stenosis using the distal cervical ICA diameter as the reference value in calculations of angiographic percent ICA stenosis.

We proposed the first duplex criteria directly applicable to the initial NASCET report. This study used receiver operator characteristic (ROC) curves to compare sensitivities and specificities of different duplex parameters for predicting a 70% to 99% angiographic ICA stenosis using the distal cervical ICA diameter as the denominator in calculations of percent stenosis. ⁸ Data was obtained from 100 patients with 184 angiographically patent ICAs. Doppler-derived peak systolic velocity (PSV) and end diastolic velocity (EDV) in the CCA and ICA, as well as ICA/CCA PSV ratios were correlated with their ability to predict 70% to 99% angiographic ICA stenosis. An ICA/CCAPSV ratio of >= 4.0 was the most accurate overall predictor of 70% to 99% angiographic ICA stenosis with 91% sensitivity, 87% specificity, and overall accuracy of 88%. ⁸ This data was later confirmed in a prospective study utilizing duplex scans and angiographic studies from our institution and from the University of Washington. ⁹ A total of 168 angiograms and duplex scans were compared. An ICA/CCA PSV ratio of >= 4.0 was able to predict 70% to 99% angiographic ICA stenosis with 90% sensitivity, 90% specificity, and 90% overall accuracy. ⁹

Other investigators have since developed additional duplex criteria applicable to the initial and final NASCET reports. In a review of duplex scans and angiograms from 120 patients, Neale et al ¹⁰ found that an ICA PSV > 270 cm/s determined 70% to 99% angiographic ICA stenosis with 96% sensitivity, 86% specificity, and 88% accuracy. An ICA EDV > 110 cm/s resulted in 91% sensitivity, 93% specificity, and 93% accuracy. If both PSV > 270 cm/s and EDV >l10 cm/s were present, 96% sensitivity, 91% specificity, and 93% overall accuracy was achieved. ¹⁰ Faught et al ¹¹ found a combination of PSV >130 cm/s and EDV >100 cm/s had an overall accuracy of 95% for detecting 70% to 99% angiographic ICA stenosis. These variables were subsequently applied in a prospective study evaluating 457 internal carotid arteries in 248 patients. ¹² Overall accuracy of 95% was maintained, with 87% sensitivity and 97% specificity. (The PSV of 130 cm/s is quite low and data from this institution is likely driven by the requirement for an EDV >100 cm/s). In another study by Carpenter et al, ¹³ PSV >210 cm/s, EDV >70 cm/s, and ICA/CCA PSV ratio >= 3.0 each had an 83% accuracy for detecting 70% to 99% angiographic ICA stenosis. Finally, Winkelaar et al ¹⁴ studied 188 carotid arteries with both duplex scanning and angiography to identify duplex criteria for detecting a 50% to 99% angiographic ICA stenosis by NASCET methods. These investigators determined that an ICA/CCA PSV ratio >= 2.0 identified a 50% to 99% ICA stenosis with 93% accuracy, 96% sensitivity, and 89% specificity. ¹⁴

Additional duplex criteria have also been developed for asymptomatic patients, incorporating the >= 60% ICA stenosis threshold defined by ACAS. Assuming a duplex scan suggesting 60% to 99% ICA stenosis in an asymptomatic patient may lead to angiography or operation, and noting the modest therapuetic benefit of CEA in asymptomatic patients, we reasoned criteria for asymptomatic patients should have a high positive predictive value (PPV) for defining 60% to 99% angiographic ICA stenosis. Cerebral angiograms and duplex scans of 352 ICAs were compared. ¹⁵ A 95% PPV for >= 60% ICA stenosis was achieved with a combination of ICA PSV >290 cm/s and ICA EDV
>80 cm/s. Carpenter et al ¹⁶ also evaluated parameters for defining 60% to 99% angiographic ICA stenosis. In their study, 210 ICAs were examined with angiography and duplex scanning. Assuming high PPV remains the discriminating factor, an EDV
> 60cm/s then provides a PPV of 96%, and a PSV >230 cm/s a PPV of 94%. ¹⁶ In an additional study comparing magnetic resonance angiography (MRA) to duplex for determining
>= 60% ICA stenosis, a combination of PSV >245 and EDV >65 cm/s resulted in an 89% PPV. ¹⁷

Each of these studies used different duplex scanners and determined slightly different criteria for predicting percentage of ICA stenosis (tables 2 and 3). Differences apparently exist between duplex equipment, vascular laboratories, and vascular technologists in measurement of ICA stenosis.

These potential differences were examined by Fillinger et al ¹⁸ in 1996. The study was carried out at two independent centers with separate duplex scanners and technologists. A total of 360 carotid bifurcations were examined using Quantum (Siemens Medical Systems, Inc., Issaquah, WA); Diasonics (Diasonics Ultrasound, Santa Clara, CA); and ATL (Advanced Technology Laboratories, Bothell, WA) brand duplex machines. Percent ICA stenosis was measured by angiogram with the distal ICA diameter as the denominator. Using ROC curves, PPVs between 90% and 95% were determined while attempting to maintain >90% accuracy and >80% sensitivity. To meet these requirements, depending on the scanner empolyed, ICA/CCA PSV ratios varied from 2.6 to 3.3 and the ICA PSV varied from 190 cm/s to 240 cm/s for prediction of 60% to 99% angiographic ICA stenosis. Threshold values differed between scanners and appeared to be machine specific. Investigators determined that relationships between duplex data and percent angiographic ICA stenosis were statistically different for one of the machines (ATL). It was concluded that different duplex-derived criteria determining 60% to 99% angiographic ICA stenosis are not interchangeable from one machine to another.

In an attempt to standardize supplemental duplex criteria between different observers and different machines, a recent study used an entirely different diagnostic variable to determine percent angiographic ICA stenosis. Ranke et al ¹⁹ used the mean velocity ratio, which is the intrastenotic mean blood flow velocity divided by the distal ICA mean blood flow velocity, to evaluate for the presence of a 70% to 99% angiographic ICA stenosis. In this study, Hewlett-Packard (Andover, MA) and ATL duplex machines were used. The study was small, with only 44 patients undergoing both duplex scanning and angiography, and 21 patients were examined to compare differences between scanners and observers. A mean velocity ratio >= 5.0 correlated with a NASCET 70% to 99% angiographic ICA stenosis with a 97% sensitivity and 98% specificity. ¹⁹ Direct velocity measurements between the two scanners were significantly different (P <0.001), but the mean velocity ratios were not. Due to inherent accuracy problems in calculation of mean velocities, variability and reproducibility studies will be required prior to possible acceptance of mean velocities in the calculation of percent angiographic ICA stenosis. If these findings are repeated by independent observers in a larger set of patients, the use of mean velocity ratios may become important in standardizing duplex determination of ICA stenosis.

Conclusion

Although the University of Washington duplex criteria have had enormous clinical and research impact, the categories of ICA stenosis described are only applicable to quantifying stenosis based on the estimated normal diameter of the carotid bulb in calculations of percent angiographic stenosis. Clinical trials of carotid endarterectomy in North America, such as ACAS and NASCET, have based their results on the distal cervical ICA diameter as the reference value. Supplemental duplex criteria were developed to define percent angiographic ICA stenosis using the >= 60% and >= 70% thresholds determined to be significant in these trials. These criteria are apparently machine specific. Individual vascular laboratories must validate their own criteria with internal quality-control studies. In the future, use of distal ICA mean velocity ratios, or possibly some other combination of variables, may help to standardize duplex quantification of ICA stenosis. AR

References

1. Executive Committee for ACAS: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273:1421-1428, 1995.

2. ECST's Collaborative Group: Randomised trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the MRC European Carotid Surgery Trial (ECST). Lancet 351:1379-1387, 1998.

3. Barnett HJ, Taylor DW, Eliasziw M, et al: Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med 339:1415-1425, 1998.

4. NASCET Collaborators: Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325:445-453, 1991.

5. Rothwell PM, Gibson RJ, Slattery J, Warlow CP: Prognostic value and reproducibility of measurements of carotid stenosis. A comparison of three methods on 1001 angiograms. Stroke 25:2440-2444, 1994.

6. Rothwell PM, Gibson RJ, Slattery J, et al: Equivalence of measurements of carotid stenosis. A comparison of three methods on 1001 angiograms. Stroke 25:2435-2439, 1994.

7. Strandness DE: Duplex Scanning in Vascular Disorders. New York, Raven Press, 1993.

8. Moneta GL, Edwards JM, Chitwood RW, et al: Correlation of North American Symptomatic Carotid Endarterectomy Trial (NASCET) angiographic definition of 70% to 99% internal carotid artery stenosis with duplex scanning. J Vasc Surg 17:152-157; discussion 157-159, 1993.

9. Edwards JM, Moneta GL, Papanicolaou G, et al: Prospective validation of a new duplex ultrasound criteria for 70-99% internal carotid stenosis. JEMU 16:3-7, 1995.

10. Neale ML, Chambers JL, Kelly AT, et al: Reappraisal of duplex criteria to assess significant carotid stenosis with special reference to reports from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. J Vasc Surg 20:642-649, 1994.

11. Faught WE, Mattos MA, van Bemmelen PS, et al: Color-flow duplex scanning of carotid arteries: New velocity criteria based on receiver operator characteristic analysis for threshold stenoses used in the symptomatic and asymptornatic carotid trials. J Vasc Surg 19:818-827; discussion 827-828, 1994.

12. Hood DB, Mattos MA, Mansour A, et al: Prospective evaluation of new duplex criteria to identify 70% internal carotid artery stenosis. J Vasc Surg 23:254-261; discussion 261-262, 1996.

13. Carpenter JP, Lexa FJ, Davis JT: Determination of duplex Doppler ultrasound criteria appropriate to the North American Symptomatic Carotid Endarterectomy Trial. Stroke 27:695-699, 1996.

14. Winkelaar GB, Chen JC, Salvian AJ, et al: N ew duplex ultrasound scan criteria for managing symptomatic 50% or greater carotid stenosis. J Vasc Surg 29:986-994, 1999.

15. Moneta GL, Edwards JM, Papanicolaou G, et al: Screening for asymptomatic internal carotid artery stenosis: Duplex criteria for discriminating 60% to 99% stenosis. J Vasc Surg 21:989-994, 1995.

16. Carpenter JP, Lexa FJ, Davis JT: Determination of sixty percent or greater carotid artery stenosis by duplex Doppler ultrasonography. J Vasc Surg 22:697-703; discussion 703-705, 1995.

17. Jackson MR, Chang AS, Robles HA, et al: Determination of 60% or greater carotid stenosis: A prospective comparison of magnetic resonance angiography and duplex ultrasound with conventional angiography. Ann Vasc Surg 12:236-243, 1998.

18. Fillinger W, Baker RJ Jr., Zwolak RM, et al: Carotid duplex criteria for a 60% or greater angiographic stenosis: Variation according to equipment. J Vasc Surg 24:856-864, 1996.

19. Ranke C, Creutzig A, Becker H, Trappe HJ: Standardization of carotid ultrasound: A hemodynamic method to normalize for interindividual and interequipment variability. Stroke 30:402-406, 1999.