Author + information
- Received August 11, 2011
- Revision received January 9, 2012
- Accepted January 20, 2012
- Published online April 1, 2012.
- Jin-Sin Koh, MD⁎,†,
- Bon-Kwon Koo, MD, PhD⁎,⁎ (, )
- Ji-Hyun Kim, MD⁎,
- Han-Mo Yang, MD, PhD⁎,
- Kyung-Woo Park, MD, PhD⁎,
- Hyun-Jae Kang, MD, PhD⁎,
- Hyo-Soo Kim, MD, PhD⁎,
- Byung-Hee Oh, MD, PhD⁎ and
- Young-Bae Park, MD, PhD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Bon-Kwon Koo, Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong Chongno-gu, Seoul 110, 744, Korea
Objectives This study sought to assess the relationship of coronary angiography, intravascular ultrasound (IVUS) and fractional flow reserve (FFR) between major epicardial vessel (MV) and side branch (SB) ostial lesions.
Background Evaluation of ostial lesions is clinically very important. However, anatomical parameters have limitations in the prediction of the functional significance of coronary stenoses.
Methods IVUS and FFR measurement were performed in 93 lesions (MV: 38, SB: 55). Optimal angiographic and IVUS criteria and their diagnostic accuracy for functionally significant stenoses (FFR ≤0.8) were assessed.
Results In MV ostial lesions, FFR had correlation with angiographic percent diameter stenosis (r = –0.68, p < 0.001), minimum lumen area (MLA) by IVUS (r = 0.55, p < 0.001), percent plaque burden (r = –0.42, p = 0.011), and percent area stenosis (r = –0.49, p = 0.003). Meanwhile, FFR had no correlation with angiographic percent diameter stenosis (r = –0.067, p = 0.635) and weak correlation with MLA (r = 0.30, p = 0.026) in SB ostial lesions. In MV ostial lesions, best cutoff value of angiographic percent diameter stenosis, MLA, percent plaque burden, and percent area stenosis to determine the functional significance was 53%, 3.5 mm2, 70%, and 50%. However, a statistically significant cutoff value of percent diameter stenosis and MLA could not be found in SB ostial lesions.
Conclusions The relations between angiographic/IVUS parameters and FFR were different between MV and SB ostial lesions. Angiographic and IVUS parameters had poor diagnostic accuracy in predicting the functional significance of SB ostial lesions. (Main Branch Versus Side Branch Ostial Lesion; NCT01335659)
Although coronary angiography is regarded as the gold standard to evaluate coronary artery disease, it has limitations in predicting the presence of myocardial ischemia in ostial lesions. Accurate angiographic assessment of ostial lesions is difficult due to vessel overlap, angulations, and artifacts (1–3). Intravascular ultrasound (IVUS) can provide accurate anatomical information, and earlier studies showed that there was a good correlation between IVUS parameters and physiological parameters (4–7). However, the relationship between IVUS parameters and fractional flow reserve (FFR) in ostial lesions has not been fully evaluated yet. Moreover, recent reports suggest that IVUS parameters also have limitations in the prediction of the functional significance of coronary stenosis and their diagnostic accuracy varies according to the location of lesions (8,9).
We sought to assess the relations between coronary angiography, IVUS, and FFR in coronary ostial lesions and to investigate the difference of those relations between major epicardial vessel (MV) and side branch (SB) ostial lesions.
From February 2009 to February 2011, patients who had ostial stenosis of intermediate degree (40% to 70% by visual estimation) on elective coronary angiography and who underwent both IVUS and FFR for MV or SB ostial lesions were consecutively enrolled in this study. To be included, the stenosis needed to be located within 3 mm of the ostium. MV ostial lesion was defined as the stenotic lesion located at the ostium of left anterior descending, left circumflex, or right coronary arteries. For SB ostial lesions, SB with reference diameter ≥2.25 mm and vessel length >40 mm by visual estimation were included. Patients were excluded if any of the following was present: left main ostial lesion; acute ST-segment elevation myocardial infarction; regional wall motion abnormalities of a target vessel segment; additional stenosis (>50% by visual estimation) in the target vessel; significant distal left main stenosis; left ventricular ejection fraction <40%; primary myocardial or valvular disease; contraindication to adenosine; presence of collateral vessel; or angiographically visible thrombus at a target lesion. In patients with acute coronary syndrome or previous myocardial infarction, only the nonculprit artery was included. The study protocol was approved by the Institutional Review Board of our institution, and all patients provided written informed consent.
Angiographic images were acquired using a guiding catheter of 5- to 7-F. FFR was measured using a 0.014-inch pressure guidewire (St. Jude Medical, Minneapolis, Minnesota) as previously described (10). Hyperemia was induced with an intracoronary bolus administration (80 μg in left coronary artery, 40 μg in right coronary artery) or intravenous infusion (140 μg/kg/min) of adenosine. In cases of ostial lesions of the right coronary artery, intravenous infusion of adenosine was used to induce maximal hyperemia while the guiding catheter was positioned out of its ostium. The lesion was considered functionally significant when FFR ≤0.8 (11).
IVUS was performed in a standard fashion using an automated motorized pullback system (0.5 mm/s) with commercially available imaging catheters (Boston Scientific/SCIMED, Minneapolis, Minnesota; or Volcano Corporation, Rancho Cordova, California). Intracoronary nitroglycerin (100 to 200 μg) was administered before IVUS or FFR measurement.
Quantitative coronary angiography and IVUS analysis
Both quantitative coronary angiography (QCA) and IVUS analysis were performed by an independent core laboratory at Seoul National University Cardiovascular Center. Using the guiding catheter for calibration and an edge detection system (CAAS 5.7 QCA system, Pie Medical, Maastricht, the Netherlands), the reference diameter, minimum lumen diameter, and lesion length were measured and the percent diameter stenosis was calculated. The reference diameter was determined by the interpolated reference method (12). Quantitative IVUS analyses were performed using computerized planimetry software (echoPlaque, Indec Systems Inc., Santa Clara, California) as previously described (13). Minimum lumen area (MLA) was measured at the narrowest luminal cross section and the reference area at the most normal looking cross section within distal 10 mm of the lesion. Percent plaque burden was calculated as: [100 × (external elastic membrane area – lumen area)/external elastic membrane area] at the MLA site. Percent area stenosis was calculated as: [100 × (reference lumen area – lesion lumen area)/reference lumen area]. The vessel remodeling index was defined as the ratio of the vessel area at the site of MLA and that of reference site. Remodeling was categorized as negative when the remodeling index was <0.95 (14).
Continuous variables were presented as mean ± SD and categorical variables as frequency and percentage. Comparison of continuous variables was performed using the Student t test and of discrete variables using the chi-square-test. Correlations between FFR and angiographic/IVUS parameters were assessed by Pearson or Spearman correlation analysis. Normality of continuous variables was checked using the histogram and Shapiro-Wilk test. For the variables with skewed distribution, such as angiographic lesion length, lesion MLA, and percent plaque burden, nonparametric analyses were performed. Receiver-operator characteristic curve analysis was used to examine the angiographic and IVUS parameters as a predictor of the functional significance of a lesion (FFR ≤0.8). The areas under the receiver-operator characteristic curve between MV and SB were compared (15). The resulting sensitivity and specificity were calculated. The best cutoff value (BCV) was determined by the maximum sum of sensitivity and specificity. All statistical analyses were performed using SAS (version 9.1, SAS Institute Inc., Cary, North California) for Windows (version 16.0, Microsoft, Redmond, Washington), and a p value <0.05 was considered statistically significant.
One hundred and seven lesions were consecutively enrolled and 14 lesions were excluded due to other lesions in the target vessel (n = 8), collateral feeder (n = 1), myocardial infarction territory (n = 1), or poor IVUS images (n = 4). Therefore, 93 ostial lesions (MV 38, SB 55) in 77 patients were finally included in this study. The baseline clinical characteristics are shown in Table 1. There was no difference in clinical characteristics between the patients with MV and SB ostial lesions.
FFR versus angiographic and IVUS parameters
Angiographic and IVUS parameters are summarized in Table 2. Functionally significant lesions were 14 (36.8%) and 15 (27.3%) in MV and SB ostial lesions, respectively. Negative remodeling was more common in SB (72.7%) than in MV (52.6%) ostial lesions (p = 0.046). In MV ostial lesions, functionally significant lesions had smaller minimum lumen diameter and MLA and higher percent diameter stenosis, percent plaque burden, and percent area stenosis. In SB ostial lesions, MLA was smaller and percent plaque burden was larger in functionally significant lesions. However, there was no difference in angiographic percent diameter stenosis and percent area stenosis between functionally significant and insignificant lesions.
The relationships between FFR and angiographic and IVUS parameters were shown in Figure 1. In MV ostial lesions, FFR had good correlation with angiographic percent diameter stenosis (r = –0.68, p < 0.001), MLA (r = 0.55, p < 0.001), percent plaque burden (r = –0.42, p = 0.011), and percent area stenosis (r = –0.49, p = 0.003). In SB ostial lesions, FFR had no correlation with angiographic parameters. There was weak correlation between FFR and MLA (r = 0.30 p = 0.03). When only the vessels with >50% diameter stenosis by QCA (MV: 27 cases, SB: 44 cases) were analyzed, FFR had correlation with angiographic percent diameter stenosis (r = –0.441, p = 0.021) and MLA (r = 0.533, p = 0.006) in MV, but not in SB (percent diameter stenosis: r = –0.048, p = 0.757; MLA: r = 0.253, p = 0.102).
Diagnostic accuracy of angiographic and IVUS parameters
The receiver-operator characteristic curve analysis was performed to assess the diagnostic accuracy of angiographic/IVUS parameters for the prediction of functional significance in both MV and SB ostial lesions (Fig. 2). In MV ostial lesions, BCV of angiographic percent diameter stenosis, MLA, percent plaque burden, and percent area stenosis was 53%, 3.5 mm2, 70%, and 50%, respectively. However, statistically significant BCV could not be found in SB ostial lesions except for that of percent plaque burden (56%, area under the curve: 0.71, p = 0.038). There were no differences in areas under the curve between MV and SB ostial lesions. When the diagnostic accuracy of different angiographic and IVUS parameters were evaluated in MV ostial lesions, all parameters had high negative predictive value (Fig. 3). However, positive predictive value of angiographic percent diameter stenosis (53%) was 58%. Sensitivity, specificity, and positive and negative predictive values of MLA (3.5 mm2) was 83%, 75%, 69%, and 87%, respectively. For SB ostial lesions, the positive predictive value of all angiographic and IVUS parameters were ≤50%.
This study revealed that: 1) the relationship between anatomical parameters and FFR was different between MV and SB ostial lesions; 2) angiographic percent diameter stenosis and MLA by IVUS had poor diagnostic accuracy in predicting the functional significance of SB ostial lesions; and 3) IVUS parameters showed high negative predictive value in predicting the functional significance of a stenosis. However, the low positive predictive value limits the use of these parameters in defining the presence of ischemia.
Evaluation of ostial lesion is clinically important as an MV ostial lesion can cause ischemia in large myocardial territory, and MV and SB ostial lesions usually require complex interventions. However, a previous study showed that the angiographic evaluation is not accurate in the prediction of functional significance in ostial lesions (3). Moreover, recent IVUS studies suggested that IVUS parameters have limitations in predicting the functional significance of a stenosis (8,9). In our study, when ostial lesions were divided into MV and SB ostial lesions, the relations between angiographic/IVUS parameters and FFR were different between MV and SB ostial lesions. This may come from the difference in the variability of the size of vessel and branching pattern of coronary trees.
In MV ostial lesions, the correlations among FFR and angiographic percent diameter stenosis (r = −0.68) and MLA by IVUS (r = 0.55) was good. The BCV of MLA in MV ostial lesions was 3.5 mm2 and this parameter had good diagnostic accuracy (area under the curve: 0.82) in predicting the functional significance of a stenosis. However, the low positive predictive value (69%) limits the use of IVUS in defining the presence of ischemia in these lesions. As the negative predictive value of MLA was more than 80% in both MV and SB ostial lesions, MLA by IVUS seems to be more useful for excluding the presence of ischemia and deferring the revascularization than for defining the presence of ischemia. The other IVUS parameters, such as percent plaque burden and percent area stenosis showed fair diagnostic accuracy. It is interesting to notice that the angiographic percent diameter stenosis correlated well with FFR in our study. However, positive predictive value of angiographic percent diameter stenosis was 58%.
Previous studies that compared angiographic percent of diameter stenosis and FFR in jailed SB lesions revealed that the angiography overestimates the functional significance of jailed SB lesions (16–19). However, the relationship between IVUS and FFR in SB ostial lesions has not been evaluated yet. In this study, there was no correlation between angiographic parameters and FFR in SB ostial lesions. Moreover, appropriate angiographic and IVUS parameters to predict the functional significance of SB ostial lesions were difficult to find. These results seem to be natural considering the high variability of SB in vessel size, branching pattern, and the amount of supplying myocardium. As both the severity of a stenosis and the myocardial mass determine the presence of myocardial ischemia, these anatomical variations limit the value of angiographic and IVUS assessment of SB ostial lesions. In a PHANTOM (Physiologic and Anatomical Evaluation Prior to and After Stent Implantation in Small Coronary Vessels) study, which compared angiographic/IVUS parameters and FFR in small and distal lesions, no anatomical parameters had correlation with FFR (8).
First, the number of cases was relatively small; therefore, the results cannot be completely free from the selection bias. Second, as most of MV ostial lesions were left coronary ostial lesions, the study results may not be applied to right coronary artery ostial lesions. Third, as this study was performed in Korean patients, the absolute numbers may not be applied as they are to different ethnic groups. Fourth, the possible influence of proximal lesions and the limitation of IVUS and QCA (20) in small vessels should be considered. As the absolute blood flow is small in SB, FFR of SB is more vulnerable to the influence of proximal lesion. In a small vessel and angulated lesions such as SB ones, mechanical stretch of lumen and vessel by IVUS catheter could have influenced the results of IVUS measurement.
The relations between angiographic/IVUS parameters and FFR were different between MV and SB ostial lesions. These parameters had poor diagnostic accuracy in predicting the functional significance of SB ostial lesions. IVUS parameters seem to be useful only in excluding the presence of ischemia in ostial lesions.
This study was supported by a grant from the Seoul National University Hospital (A062260), Innovative Research Institute for Cell Therapy, the Korea Healthcare Technology Research & Development Project, Ministry of Health and Welfare, Republic of Korea (A102065), and the Seoul National University Hospital Research Fund (03-2010-0270). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- best cutoff value
- fractional flow reserve
- intravascular ultrasound
- minimum lumen area
- major epicardial vessel
- quantitative coronary angiography
- side branch
- Received August 11, 2011.
- Revision received January 9, 2012.
- Accepted January 20, 2012.
- American College of Cardiology Foundation
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