Intravascular Ultrasound-Based Left Main Coronary Artery Assessment: (Full title below)

Intravascular Ultrasound-Based Left Main Coronary Artery Assessment: Comparison between Pullback from Left Anterior Descending and Circumflex Arteries

______________________ ABSTRACT: Objective. We compared continuous pullback from the left anterior descending artery (LAD) with pullback from the circumflex artery (CX) for the assessment of the left main coronary artery (LMCA) by intravascular ultrasound (IVUS). Background. Gray-scale IVUS and virtual histology by IVUS (IVUS-VH) overcome many shortcomings of contrast angiography in diagnostic assessment of the LMCA. IVUS of LCMA can be acquired by continuous pullback from LAD or CX. Equivalence of the two pullback methods has not been investigated. Methods. LMCA morphology was assessed by IVUS in 65 patients referred for elective or rescue coronary angiography. In each patient IVUS was performed once using pullback from the LAD and once using pullback from the CX. Intraclass correlation coefficients (ICC) were calculated to measure the degree of reliability. Results. The mean age of patients was 60.4 ± 9.5 years (range 40–84). The IVUS-determined degree of stenosis in the LMCA was a mean of 30% ± 8% (range 15–52%). The ICC showed excellent reliability (ICC > 0.8) for volume measurements within the plaque (lipid volume, fibrolipidic volume, lipid core volume and calcified volume) and for the measurement of large or averaged diameters (maximal vessel diameter, average vessel diameter, average lumen diameter). The ICC was intermediate (ICC 0.5–0.8) for the measurement of small diameters (minimal vessel diameter, minimal lumen diameter, maximal lumen diameter) and for area calculations (minimal lumen area) based on small diameters. Conclusions. Overall, there was excellent reliability between IVUS-based LMCA morphology assessment using pullback from either the LAD or the CX. J INVASIVE CARDIOL 2009;21:457–460 Key words: virtual histology, IVUS, left main, intraobserver reliability Left main coronary artery (LMCA) disease is clinically important, as it results in a worse prognosis with therapeutic implications.1–3 Angiographic assessment of LMCA disease is difficult due to anatomical factors which impair the angiographic evaluation.4,5 In recent years, intravascular ultrasound (IVUS) has evolved as a valuable adjunct to angiography. Whereas angiography depicts only the luminal silhouette, IVUS depicts the lumen area and plaque size, including virtual histology of plaque composition.6–11 Previous studies have shown that IVUS and virtual histology by IVUS (IVUS-VH) provide important additional diagnostic, therapeutic and prognostic information in assessment of the LMCA.12–16 Technically, IVUS of the LMCA is acquired by continuous pullback from either the left anterior descending artery (LAD) or the circumflex artery (CX). Theoretically, both methods should be equivalent but, to our knowledge, this has never been investigated. This study compared pullback from the LAD with pullback from the CX for IVUS-based examination of the LMCA in patients with no disease-to-moderate LMCA disease. Methods Patients. Consecutive patients referred for elective or rescue coronary angiography to a single center (Luzerner Kantonsspital, Switzerland) were evaluated for this study. The decision to perform immediate (rescue) coronary angiography was taken according to the local guidelines where all patients with acute coronary syndrome are defined to undergo immediate (rescue) angiography. Patients unsuitable for the IVUS procedure due to anatomical criteria were excluded. Anatomical criteria precluding safe IVUS examination included total or subtotal stenosis of the proximal LAD or CX, as well as high-grade LMCA stenosis with potential for hemodynamic instability during examination. Sixty-five patients qualified for inclusion in the study and were willing to participate. Written informed consent was obtained from all participating patients. The study was approved by the local ethics committee. IVUS procedure. In all 65 patients, IVUS of the LMCA was performed twice, once by pullback from the LAD and once by pullback from the CX. The LAD and CX were wired to allow pullback and determination of the segment of the LMCA for the analysis. IVUS was acquired using an Eagle Eye® Gold Catheter and an automatic continuous pullback device (Volcano Corp., Rancho Cordova, California). The pullback velocity was 1 mm/sec. IVUS-VH. The validation of IVUS-VH ex vivo has previously been reported.17 Briefly, IVUS-VH uses spectral analysis of IVUS radiofrequency data to construct tissue maps that classify plaque into 4 major components (fibrous, fibrolipid, lipid core and calcium). In addition to plaque composition IVUS-VH software provides geometric data of the vessel. According to the American College of Cardiology consensus document on IVUS studies, frames with acoustic shadowing of more than 90° were excluded from analysis.18 Measurements. Offline analysis was performed by a single investigator who was blinded to the clinical and angiographic data. Manual contour detection of both the lumen and the media-adventitia interface was performed through the entire LMCA. For every cross-sectional area, minimal and maximal vessel and lumen diameters, as well as the area for the different plaque components (fibrous, fibrolipid, lipid core and calcified), were calculated using pcVH Software (Volcano Corp.). Average diameters and total volumes for the different plaque components were also calculated for the analyzed segment. Statistical analysis. Data are expressed as percentages and mean ± standard deviation. Continuous variables were compared by use of the paired Student’s t-test assuming normal distributions or by the Wilcoxon rank sum test for variables with non-normal distributions. Dichotomous variables were compared by the chi-square test or Fisher’s exact test when cell counts were Results Patient characteristics are presented in Table 1. The mean age of patients was 60.4 ± 9.5 years (range 40–84). Fifteen patients (23.1%) were female. Fourteen patients (21.5%) were admitted with an acute coronary syndrome and received rescue coronary angiography. Coronary angiography revealed normal vessel morphology in 15 patients (23.1%), 1-vessel disease in 10 patients (15.4%), 2-vessel disease in 18 patients (27.7%) and 3-vessel disease in 22 patients (33.8%). In only 2 patients the LMCA was the target vessel as determined by coronary angiography. The IVUS-determined degree of stenosis in the LMCA was a mean of 30% ± 8% (range 15–52%). Mean values of measurements by IVUS-VH are shown in Table 2. There were no significant differences in the mean values between pullback from the LAD and pullback from the CX. With the exception of the fibrolipidic volume, the measurements tended toward increased values after pullback from the CX, albeit not significantly. The ICCs for the various measurements are shown in Table 3. The ICC showed excellent reliability (ICC > 0.8) between pullback from the LAD and pullback from the CX for volume measurements within the plaque (lipid volume, fibrolipidic volume, lipid core volume and calcified volume). The ICC for diameter measurements was excellent (ICC > 0.8) if the diameter was large (maximal vessel diameter) or averaged (average vessel diameter and average lumen diameter). Only intermediate ICCs (ICC 0.5–0.8) were found for the measurement of small diameters (minimal vessel diameter, minimal lumen diameter and maximal lumen diameter) and for area calculations (minimal lumen area) based on small diameters. Figure 1 depicts a LMCA examination performed once by pullback from the LAD (upper row) and once by pullback from CX (lower row). The figure documents the high reliability between both methods of pullback. Discussion In this single-center study of patients referred for elective or rescue coronary angiography we compared LMCA IVUS analysis from pullback of the LAD and pullback of the CX. Overall differences for the mean values of IVUS and IVUS-VH parameters were minimal, without potential impact on clinical decision making. ICCs were excellent for most of the measured geometric and virtual histology parameters, pointing to good reliability between the two pullback methods. Mean values of measurements were not significantly different between pullback from the LAD and pullback from the CX. However, there appeared to be a tendency, albeit not statistically significant, toward uniformly higher values after pullback from the CX. The overall high ICCs found in this study suggest a systematic error leading to increased diameters when analyzing the LMCA by pullback from the CX. It is well known that transducer obliquity and vessel curvature can result in a non-coaxial picture-acquisition with lower image quality and errors in interpretation especially in large vessels like the LMCA.19 We assume that the generally more curved offset of the CX might lead to a more non-coaxial transducer position thereby leading to overestimation of diameters. But as presented in Table 2, the absolute differences are very small and therefore not relevant for clinical purposes. While ICCs in general were excellent, for small diameters only intermediate correlations were found. This might be explained by the fact that for small diameters minimal “errors” arising during manual contour detection have impact on the ICC. These minimal “errors” are occasionally inevitable due to technical issues inherent in IVUS and IVUS-VH. For example, blood speckles can limit the ability to differentiate lumen from tissue, and ring-down artifacts surrounding the catheter obscure the area immediately adjacent to the catheter.18 Again, absolute differences were minimal, with no impact on clinical decision making. Overall, the data from this study indicate that IVUS-VH examination of the LMCA can be performed by pullback from either the LAD or the CX, without clinically relevant differences. Comparisons of angiography with necropsy findings or with gray-scale ultrasound have shown that angiographic evaluation of the LMCA is subject to considerable error, with both under- and overestimation of stenosis degree.4,13,20 Anatomical factors that impair angiographic evaluation of the LMCA include aortic cusp opacification, short vessel length without a normal segment for comparison and possible concealment of the distal LMCA by bifurcation or trifurcation.5 Proper judgment of LMCA angiography, which has important prognostic and therapeutic implications, is a difficult clinical problem.1–3 Here, IVUS and IVUS-VH have emerged as valuable diagnostic tools that improve diagnostic accuracy, extend the angiographic findings with information about plaque composition and add prognostic information.13–16 Technical advances in percutaneous coronary interventions and stent technology have encouraged interventional cardiologists to test the feasibility of LMCA stenting, with considerable success. IVUS and IVUS-VH will increasingly be valuable adjuncts to coronary angiography because, in contrast to coronary artery bypass grafting, the success of LMCA stenting requires optimal consideration of the body or the length of the LMCA, whether the obstructing plaque involves the ostium and whether disease involves the bifurcation with or without extension into the LAD or CX arteries.21,22 In order to standardize and optimize IVUS studies, a clinical expert consensus document of the American College of Cardiology (ACC) was published in 2001.18 However, this document lacks specific recommendations regarding the performance of LMCA examination, and to our knowledge, our study is the first to have addressed this issue. In our study, IVUS analysis of the LMCA using pullback either from the LAD or the CX yielded comparable results with minimal, clinically non-relevant differences in mean values of IVUS data and with high ICCs. The findings herein indicate equivalence of the two pullback techniques, which would give clinicians the option to perform LMCA IVUS analysis according to their preference. Study limitations. There are some limitations inherent in our study. First, ours was a single-center study with a small population, and our findings need to be confirmed in further studies before generalization to other populations. Second, since all IVUS analyses were performed by a single investigator, the issue of interobserver variability could not be addressed. Third, patients with anatomical criteria that precluded safe IVUS examination were excluded, therefore patients with severe LMCA stenosis or subtotal stenosis of other vessels are underrepresented. Conclusions In this single-center study we have demonstrated that pullback either from the LAD or from the CX for IVUS-based studies of the LMCA provide similar results with high reliability between both techniques. Acknowledgments. This study was supported by the Swiss Heart Foundation, Bern, Switzerland, and the Kamillo-Eisner Foundation, Hergiswil, Switzerland. One of the co-authors was supported by a Forschungskolleg Geriatrie Grant from the Robert Bosch Foundation, Stuttgart, Germany. None of the granting institutions had any influence on the study design, data collection, analysis or interpretation. _______________________ From the aDepartment of Cardiology, Luzerner Kantonsspital, Luzern, Switzerland; the bDepartment of Geriatrics and Internal Medicine, University of Bern Hospital Inselspital Bern, Bern, Switzerland; the cDepartment of Cardiology, University Hospital Zürich, Zürich, Switzerland; and the dDepartment of Biomedicine, University Hospital Basel, Basel, Switzerland. The authors disclose no conflicts of interest regarding the content herein. Manuscript submitted March 3, 2009, provisional acceptance given April 27, 2009, final version accepted May 18, 2009. Address for correspondence: Prof. Paul Erne, MD, FESC, Head of Division of Cardiology Luzerner Kantonsspital, CH-6000 Luzern 16, Switzerland. E-mail: Paul.Erne@ksl.ch

1. Takaro T, Pifarre R, Fish R. Veterans Administration Cooperative Study of medical versus surgical treatment for stable angina — Progress report. Section 3. Left main coronary artery disease. Prog Cardiovasc Dis 1985;28:229–234.

2. Ricciardi MJ, Meyers S, Choi K, et al. Angiographically silent left main disease detected by intravascular ultrasound: A marker for future adverse cardiac events. Am Heart J 2003;146:507–512.

3. Conley MJ, Ely RL, Kisslo J, et al. The prognostic spectrum of left main stenosis. Circulation 1978;57:947–952.

4. Isner JM, Kishel J, Kent KM, et al. Accuracy of angiographic determination of left main coronary arterial narrowing. Angiographic-histologic correlative analysis in 28 patients. Circulation 1981;63:1056–1064.

5. Nissen SE, Yock P. Intravascular ultrasound: Novel pathophysiological insights and current clinical applications. Circulation 2001;103:604–616.

6. Yock PG, Linker DT, Angelsen BA. Two-dimensional intravascular ultrasound: Technical development and initial clinical experience. J Am Soc Echocardiogr 1989;2:296–304.

7. Hodgson JM, Graham SP, Savakus AD, et al. Clinical percutaneous imaging of coronary anatomy using an over-the-wire ultrasound catheter system. Int J Card Imaging 1989;4:187–193.

8. Nissen SE, Grines CL, Gurley JC, et al. Application of a new phased-array ultrasound imaging catheter in the assessment of vascular dimensions. In vivo comparison to cineangiography. Circulation 1990;81:660–666.

9. Tobis JM, Mallery J, Mahon D, et al. Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens. Circulation 1991;83:913–926.

10. Nissen SE, Gurley JC, Grines CL, et al. Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease. Circulation 1991;84:1087–1099.

11. Potkin BN, Bartorelli AL, Gessert JM, et al. Coronary artery imaging with intravascular high-frequency ultrasound. Circulation 1990;81:1575–1585.

12. Okabe T, Mintz GS, Lee SY, et al. Five-year outcomes of moderate or ambiguous left main coronary artery disease and the intravascular ultrasound predictors of events. J Invasive Cardiol 2008;20:635–639.

13. Hermiller JB, Buller CE, Tenaglia AN, et al. Unrecognized left main coronary artery disease in patients undergoing interventional procedures. Am J Cardiol 1993;71:173–176.

14. Sano K, Mintz GS, Carlier SG, et al. Assessing intermediate left main coronary lesions using intravascular ultrasound. Am Heart J 2007;154:983–988.

15. Fassa AA, Wagatsuma K, Higano ST, et al. Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: A long-term follow-up study. J Am Coll Cardiol 2005;45:204–211.

16. Abizaid AS, Mintz GS, Abizaid A, et al. One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms. J Am Coll Cardiol 1999;34:707–715.

17. Nair A, Kuban BD, Tuzcu EM, et al. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation 2002;106:2200–2206.

18. Mintz GS, Nissen SE, Anderson WD, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001;37:1478–1492.

19. Di Mario C, Madretsma S, Linker D, et al. The angle of incidence of the ultrasonic beam: A critical factor for the image quality in intravascular ultrasonography. Am Heart J 1993;125:442–448.

20. Fisher LD, Judkins MP, Lesperance J, et al. Reproducibility of coronary arteriographic reading in the coronary artery surgery study (CASS). Cathet Cardiovasc Diagn 1982;8:565–575.

21. Eeckhout E, Berger A, Lyon X, et al. Elective ostial left main stenting: A tailored approach. J Invasive Cardiol 2005;17:125–128.

22. Shemin RJ. Coronary artery bypass grafting versus stenting for unprotected left main coronary artery disease: where lies the body of proof? Circulation 2008;118:2326–2329.