A single stent crossover technique is the most common approach to treating bifurcation lesions. In 90 bifurcation lesions with side branch (SB) angiographic diameter stenosis <75%, we assessed preintervention intravascular ultrasound (IVUS; of main branch [MB] and SB) predictors for SB compromise (fractional flow reserve [FFR] <0.80) after a single stent crossover. Minimal lumen area (MLA) was measured within each of 4 segments (MB just distal to the carina, polygon of confluence, MB just proximal to polygon of confluence, and SB ostium). All lesions showed Thrombolysis In Myocardial Infarction grade 3 flow in the SB after MB stenting. Although angiographic diameter stenosis at the SB ostium increased from 26 ± 15% before the procedure to 36 ± 21% after stenting (p = 0.001), FFR <0.80 was observed in only 16 patients (18%). Negative remodeling (remodeling index <1) was seen in 83 (92%) lesions but did not correlate with FFR after stenting. Independent predictors for FFR after stenting were maximal balloon pressure (p = 0.002) and MLA of SB ostium before percutaneous coronary intervention (p <0.001), MLA within the MB just distal to the carina (p = 0.025), and plaque burden at the SB ostium before percutaneous coronary intervention (p = 0.005), but not angiographic poststenting diameter stenosis or minimal lumen diameter. For prediction of FFR <0.80 after percutaneous coronary intervention, the best cutoff of MLA within the SB ostium before percutaneous coronary intervention was 2.4 mm 2 (sensitivity 94%, specificity 69%). Also, the cutoff of plaque burden within the SB ostium before percutaneous coronary intervention was ≥51% (sensitivity 75%, specificity 71%). In 67 lesions with an MLA ≥2.4 mm 2 or plaque burden <50% before percutaneous coronary intervention, 63 (94%) showed FFR ≥0.80. However, FFR <0.80 was seen in only 12 (52%) of 23 lesions with an MLA <2.4 mm 2 and plaque burden ≥50%. In conclusion, there do not appear to be reliable IVUS predictors of functional SB compromise after crossover stenting.
Bifurcation stenting remains technically challenging and is a major determinant of lower procedural success rates and adverse outcomes. Fractional flow reserve (FFR) <0.80 identifies ischemia-inducing stenoses with an accuracy of >90%. Recent studies have suggested that FFR-guided percutaneous coronary intervention is associated with decreased major adverse cardiac events in patients with multivessel coronary artery disease, especially by avoiding stent implantation into nonischemia-producing lesions. Furthermore, an FFR-guided provisional side branch (SB) intervention strategy in bifurcating lesions has been found to result sin a low rate of functional restenosis and 9-month cardiac events. In light of these data, the role of intravascular ultrasound (IVUS) has become unclear. Thus, the aims of the present study were to assess anatomic (angiographic and intravascular ultrasound) predictors before percutaneous coronary intervention of an abnormal SB FFR after percutaneous coronary intervention when a bifurcation lesion is treated using a single-stent crossover technique.
Methods
From May 2007 through February 2010, 288 patients with significant stenosis of a coronary artery bifurcation underwent drug-eluting stent implantation with single-stent crossover or provisional stent strategy. Preprocedure IVUS imaging with main branch (MB) and SB pullbacks and SB FFR measurements after MB stenting were performed in 187 lesions with an angiographic diameter stenosis of the SB ostium <75%, distal reference lumen diameter of the SB >2 mm, and lesion length of the SB ostium <10 mm by visual estimation. We then excluded patients with myocardial infarction, regional wall motion abnormality in the MB or SB territories, ejection fraction <40%, bypass graft lesions, presence of left main coronary artery disease, a significant distal lesion within the SB, a significant lesion within the MB proximal to the stented segment, in-stent restenosis, previous percutaneous coronary intervention, thrombus-containing lesions, predilation of SB before IVUS or FFR, inability of the IVUS imaging catheter to cross lesions in the SB because of tight stenosis or tortuosity, and SB balloon inflations at any time before SB FFR measurements. Ninety bifurcation lesions in 90 patients were analyzed in the present study. We obtained written informed consent from all patients, and the ethics committee approved this study.
Qualitative and quantitative angiographic analyses were performed according to standard techniques with automated edge-detection algorithms (CASS-5, Pie-Medical, Netherlands) in the angiographic analysis center of the Cardiovascular Research Foundation, Seoul, Korea. The Medina classification was used to describe the location and distribution of lesions at the bifurcation. The angle between the proximal MB and the SB (proximal carina angle) and the angle between the MB and the SB (distal carina angle) were measured before and after stenting. Measurements were performed in the angiographic view with the least foreshortening of the 3 segments.
IVUS imaging was performed after intracoronary administration of nitroglycerin 0.2 mg using motorized transducer pullback (0.5 mm/s) and a commercial scanner (Boston Scientific/SCIMED, Minneapolis, Minnesota) consisting of a rotating 40-MHz transducer within a 3.2Fr imaging sheath. Using computerized planimetry (EchoPlaque 3.0, Indec Systems, Mountain View, California), off-line IVUS analysis was performed in the IVUS core laboratory of Asan Medical Center (Seoul, Korea).
Four segments of the bifurcation before intervention were assessed using MB pullback and SB pullback. From the MB pullback, the following were identified: (1) MB just distal to the carina, (2) polygon of confluence (confluence zone of the MB and SB on longitudinal IVUS image reconstruction in parallel with the quantitative coronary angiogram-based definition suggested by Ramcharitar et al. and modified for IVUS analysis), and (3) MB just proximal to the polygon of confluence. Separately using the SB pullback, the ostium of the SB just distal to the carina was defined. IVUS-measured minimal lumen area (MLA) was the smallest cross-sectional area within each segment. At the MLA site within each of these 4 segments, the lumen, stent, plaque plus media, and external elastic membrane areas were measured by 2-dimensional planimetry. Plaque burden was calculated as plaque plus media/external elastic membrane × 100 (percentage). Remodeling index of the SB ostium before percutaneous coronary intervention was the ratio of external elastic membrane area at the MLA site within the SB ostium to external elastic membrane area of the distal reference segment.
Three segments of the bifurcation were assessed after stenting using MB IVUS pullback: distal MB, polygon of confluence, and proximal MB in parallel with preprocedure IVUS analysis. Minimal stent area within each of these segments was measured.
After drug-eluting stent implantation of the MB was performed using the crossover technique and before any SB balloon inflations, FFR of the SB was measured. “Equalization” of the 2 pressures was performed with the guidewire sensor positioned at the guiding catheter tip. Then, the 0.014-inch pressure guidewire (St. Jude Medical, Minneapolis, Minnesota) was passed through the MB stent struts into the distal SB, and FFR was measured 5 mm distal to the SB ostium at maximal hyperemia induced by intravenous infusion of adenosine 140 μg/kg/min through a central vein. Hyperemic pressure pullback recordings were performed as described previously. SB stenosis was considered functionally significant and compromised when FFR after stenting was <0.80.
All statistical analyses were performed using SPSS 10.0 (SPSS, Inc., Chicago, Illinois). All values are expressed as mean ± 1 SD (continuous variables) or count and percentage (categorical variables). Continuous variables were compared using unpaired t test or nonparametric Mann–Whitney test; categorical variables were compared using chi-square statistics or Fisher’s exact test. Receiver operating curve characteristics were analyzed to assess best cut-off values of IVUS parameters to determine FFR <0.80 using MedCalc (MedCalc Software, Mariakerke, Belgium). Optimal cutoff was calculated using the Youden index. Sensitivity, specificity, positive predictive value, and negative predictive value with 95% confidence intervals (CIs) were obtained. Including preprocedure and procedural variables such as maximal balloon pressure at the MB, remodeling index at the SB ostium, MLA within the distal MB, MLA within the SB ostium, plaque burden of the SB ostium, and MLA within the polygon of confluence, stepwise regression analysis was performed to determine the independent predictors of FFR after MB crossover stenting. A p value <0.05 was considered statistically significant.
Results
Baseline clinical and procedural characteristics are presented in Table 1 . Angiographic data are presented in Table 2 . In all lesions there was Thrombolysis In Myocardial Infarction grade 3 flow in the SB before and after stenting. Angiographic percent diameter stenosis at the SB ostium significantly increased from 26 ± 15% (range 2 to 70) before the procedure to 36 ± 21% (range 2 to 84) immediately after MB stenting (p = 0.001). The distal carina angle was decreased from 52.1 ± 25.9° before the procedure to 45.7 ± 15.1° after stenting (p = 0.043), whereas there was no change in proximal carina angle after MB stenting (156.3 ± 24.9° vs 157.2 ± 13.6°, p = 0.767).
| Variable | |
|---|---|
| Age (years) | 60 ± 9 |
| Men | 66 (73%) |
| Smoker | 23 (26%) |
| Hypertension | 39 (43%) |
| Hypercholesterolemia | 30 (33%) |
| Diabetes mellitus | 15 (17%) |
| Left ventricular ejection fraction (%) | 60 ± 5 |
| Previous myocardial infarction | 0 (0%) |
| Type of side branch | |
| Diagonal | 82 (91%) |
| Obtuse marginal | 7 (8%) |
| Posterior descending | 1 (1%) |
| Clinical presentation | |
| Stable angina pectoris | 71 (79%) |
| Unstable angina pectoris | 19 (21%) |
| Drug-eluting stent type | |
| Cypher | 34 (38%) |
| Taxus | 6 (7%) |
| Xience | 13 (14%) |
| Endeavor Resolute | 28 (31%) |
| Other drug-eluting stents | 9 (10%) |
| Maximal balloon pressure in main branch (atm) | 13.0 ± 4.2 |
| Maximal balloon size in main branch (mm) | 3.5 ± 0.3 |
| Stent number in main branch | 1.3 ± 0.5 |
| Variable | |
|---|---|
| Pre-procedural | |
| Minimal lumen diameter within distal main branch (mm) | 1.5 ± 0.5 |
| Diameter stenosis of distal main branch (%) | 50.9 ± 16.9 |
| Minimal lumen diameter within proximal main branch (mm) | 1.6 ± 0.5 |
| Diameter stenosis of proximal main branch (%) | 51.0 ± 15.5 |
| Minimal lumen diameter within side branch ostium (mm) | 1.8 ± 0.4 |
| Diameter stenosis of side branch ostium (%) | 26.2 ± 15.4 |
| Minimal lumen diameter within the polygon of confluence (mm) | 1.9 ± 0.5 |
| Diameter stenosis of the polygon of confluence (%) | 43.2 ± 14.6 |
| Proximal reference lumen diameter of main branch (mm) | 3.7 ± 0.5 |
| Distal reference lumen diameter of main branch (mm) | 2.6 ± 0.4 |
| Distal reference lumen diameter of side branch (mm) | 2.3 ± 0.2 |
| Proximal carina angle (°) | 156.3 ± 24.9 |
| Distal carina angle (°) | 52.2 ± 25.9 |
| Medina classification | |
| 1,1,1 | 26 (29%) |
| 1,1,0 | 40 (44%) |
| 1,0,1 | 7 (8%) |
| 0,1,1 | 3 (3%) |
| 1,0,0 | 4 (4%) |
| 0,1,0 | 10 (11%) |
| Post-stenting at the main branch | |
| Minimal lumen diameter within distal main branch (mm) | 2.7 ± 0.3 ⁎ |
| Diameter stenosis of distal main branch (%) | 8.3 ± 6.3 ⁎ |
| Minimal lumen diameter within proximal main branch (mm) | 3.0 ± 0.4 ⁎ |
| Diameter stenosis of proximal main branch (%) | 9.2 ± 6.7 ⁎ |
| Minimal lumen diameter within side branch ostium (mm) | 1.6 ± 0.7 ⁎ |
| Diameter stenosis of side branch ostium (%) | 36.2 ± 21.1 ⁎ |
| Minimal lumen diameter within the polygon of confluence (mm) | 3.1 ± 0.4 ⁎ |
| Diameter stenosis of the polygon of confluence (%) | 8.8 ± 6.5 ⁎ |
| Proximal carina angle (°) | 157.1 ± 13.6 |
| Distal carina angle (°) | 45.7 ± 15.2 ⁎ |
Poststenting FFR of the SB was 0.95 ± 0.07 before adenosine and 0.88 ± 0.09 at maximal hyperemia. FFR <0.80 at maximal hyperemia was observed in 16 patients (18%). Neither poststenting angiographic percent diameter stenosis at the SB ostium (r = −0.045, p = 0.670) nor poststenting minimal lumen diameter at the SB ostium (r = 0.134, p = 0.206) correlated with poststenting FFR. In addition, change in distal carina angle was not related to FFR (r = 0.102, p = 0.338).
Pre- and poststenting IVUS data are listed in Table 3 . Preprocedure MLA and plaque burden at the SB ostium measured 2.9 ± 1.2 mm 2 and 45 ± 15%, respectively. IVUS-measured MLA within the SB ostium correlated with angiographic percent diameter stenosis of the SB ostium (r = −0.382, p <0.001) before percutaneous coronary intervention.
| Intravascular ultrasound before stenting | |
| At distal main branch | |
| Minimal lumen area (mm 2 ) | 3.0 ± 1.5 |
| External elastic membrane area at minimal lumen area site (mm 2 ) | 9.1 ± 3.2 |
| Plaque burden at minimal lumen area site (%) | 65.5 ± 14.3 |
| Minimal lumen area within polygon of confluence (mm 2 ) | 4.4 ± 2.3 |
| At proximal main branch | |
| Minimal lumen area (mm 2 ) | 4.6 ± 2.8 |
| External elastic membrane area at minimal lumen area site (mm 2 ) | 13.2 ± 4.0 |
| Plaque burden at minimal lumen area site (%) | 64.7 ± 17.1 |
| At side branch ostium | |
| Minimal lumen area (mm 2 ) | 2.9 ± 1.2 |
| External elastic membrane area at minimal lumen area site (mm 2 ) | 5.3 ± 1.8 |
| Plaque burden at minimal lumen area site (%) | 45.0 ± 15.7 |
| At distal reference segment | |
| External elastic membrane area (mm 2 ) | 6.7 ± 1.9 |
| Mean external elastic membrane diameter (mm) | 2.9 ± 0.4 |
| Intravascular ultrasound after stenting | |
| Minimal stent area within distal main branch (mm 2 ) | 6.9 ± 1.4 |
| Minimal stent area within polygon of confluence (mm 2 ) | 7.7 ± 1.6 |
| Minimal stent area within distal main branch (mm 2 ) | 8.2 ± 1.5 |
MLA before percutaneous coronary intervention within the polygon of confluence correlated with MLA within the SB ostium (r = 0.482, p <0.001), MLA within the MB proximal to the carina (r = 0.237, p = 0.025), and MLA within the MB distal to the carina (r = 0.670, p <0.001). Also, the polygon of confluence was related to plaque burden at the MLA site of the SB (r = −0.245, p = 0.020) and plaque burden at the MLA site of the proximal MB (r = −0.492, p <0.001).
Remodeling index at the SB ostium was 0.79 ± 0.12. When negative remodeling was defined as a remodeling index <1, negative remodeling was observed in 83 (92%) lesions. Although the remodeling index was positively correlated with preprocedure MLA within the SB ostium (r = 0.345, p = 0.001), it was not related to preprocedure plaque burden at the SB ostium (r = 0.092, p = 0.389), and there was no direct relation between the remodeling index and poststenting SB FFR (r = 0.200, p = 0.060). There was no significant difference in remodeling index between lesions with FFR <0.80 and those with FFR ≥0.80 (0.78 ± 0.15 vs 0.80 ± 0.12, p = 0.597).
The correlation between FFR in the SB after percutaneous coronary intervention versus preprocedure angiographic and IVUS parameters and procedural variables are presented in Figure 1 and Table 4 . Independent predictors for FFR within the SB after percutaneous coronary intervention as a continuous variable were maximal balloon pressure at the MB (beta = −0.265, 95% CI −0.010 to −0.002, p = 0.003), MLA of the SB ostium before percutaneous coronary intervention (beta = 0.216, 95% CI 0.001 to 0.035, p = 0.040), plaque burden at the SB ostium (beta = −0.296, 95% CI −0.003 to −0.001, p = 0.005), and MLA within the MB just distal to the carina before percutaneous coronary intervention (beta = 0.250, 95% CI 0.005 to 0.027, p = 0.025). When the model excluded MLA and plaque burden of the SB ostium obtained by SB pullback before percutaneous coronary intervention, independent predictors for FFR within the SB after percutaneous coronary intervention as a continuous variable were maximal balloon pressure (beta = −0.352, 95% CI −0.012 to −0.004, p <0.001), MLA within the polygon of confluence before percutaneous coronary intervention (beta = 0.267, 95% CI 0.003 to 0.019, p = 0.007), and MLA within the MB just distal to the carina before percutaneous coronary intervention (beta = 0.226, 95% CI 0.002 to 0.025, p = 0.026).
| Variable | r | p Value | FFR at SB After Stenting | ||
|---|---|---|---|---|---|
| <0.8 | ≥0.8 | p Value ⁎ | |||
| Maximal balloon pressure of main branch stenting | −0.333 | 0.001 | |||
| Preprocedure angiography | |||||
| Minimal lumen diameter within distal main branch (mm) | 0.189 | 0.074 | 1.26 (1.00–0.71) | 1.45 (1.10–1.82) | 0.156 |
| Diameter stenosis of distal main branch (%) | −0.172 | 0.104 | 58.9 (45.9–63.6) | 51.1 (37.0–62.5) | 0.151 |
| Minimal lumen diameter within proximal main branch (mm) | 0.167 | 0.115 | 1.36 (1.04–2.09) | 1.61 (1.38–2.01) | 0.270 |
| Diameter stenosis of proximal main branch (%) | −0.186 | 0.079 | 59.2 (39.3–69.9) | 50.6 (39.7–60.5) | 0.324 |
| Minimal lumen diameter within polygon of confluence (mm) | 0.244 | 0.020 | 1.75 (1.24–2.11) | 1.89 (1.59–2.29) | 0.133 |
| Diameter stenosis of polygon of confluence (%) | −0.255 | 0.015 | 48.2 (38.5–61.2) | 41.9 (30.5–50.6) | 0.123 |
| Minimal lumen diameter within side branch ostium (mm) | 0.470 | <0.001 | 1.37 (1.18–1.68) | 1.93 (1.70–2.17) | 0.001 |
| Diameter stenosis of side branch ostium (%) | −0.433 | <0.001 | 36.7 (25.1–49.6) | 20.9 (14.7–30.5) | 0.001 |
| Proximal carina angle (°) | 0.062 | 0.560 | 156.0 (143.6–168.7) | 159.1 (147.5–168.5) | 0.496 |
| Distal carina angle (°) | −0.051 | 0.634 | 50.6 (40.4–69.3) | 45.1 (31.9–64.1) | 0.387 |
| Preprocedure intravascular ultrasound | |||||
| At distal main branch | |||||
| Minimal lumen area (mm 2 ) | 0.280 | 0.008 | 2.16 (1.28–3.24) | 2.84 (1.87–3.91) | 0.050 |
| Plaque burden (%) | −0.132 | 0.217 | 69.4 (52.8–80.4) | 64.4 (54.3–77.5) | 0.483 |
| Minimal lumen area within polygon of confluence (mm 2 ) | 0.313 | 0.003 | 2.34 (1.55–4.67) | 4.14 (2.73–5.96) | 0.005 |
| At proximal main branch | |||||
| Minimal lumen area (mm 2 ) | 0.209 | 0.049 | 4.19 (2.39–5.10) | 4.26 (2.35–6.66) | 0.279 |
| Plaque burden (%) | −0.071 | 0.508 | 62.5 (51.8–77.6) | 66.2 (51.7–77.9) | 0.808 |
| At side branch ostium | |||||
| Minimal lumen area (mm 2 ) | 0.454 | <0.001 | 1.91 (1.21–2.15) | 3.00 (2.23–3.76) | <0.001 |
| Plaque burden (%) | −0.431 | <0.001 | 60.0 (49.9–68.7) | 41.6 (31.8–53.8) | <0.001 |
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