Seung-Whan Lee

Stents versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease

BACKGROUND Several studies have compared the treatment effects of coronary stenting and coronary-artery bypass grafting (CABG). However, there are limited data regarding the long-term outcomes of these two interventions for patients with unprotected left main coronary artery disease. METHODS We evaluated 1102 patients with unprotected left main coronary artery disease who underwent stent implantation and 1138 patients who underwent CABG in Korea between January 2000 and June 2006. We compared adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and target-vessel revascularization) with the use of propensity-score matching in the overall cohort and in separate subgroups according to type of stent. RESULTS In the overall matched cohort, there was no significant difference between the stenting and CABG groups in the risk of death (hazard ratio for the stenting group, 1.18; 95% confidence interval [CI], 0.77 to 1.80) or the risk of the composite outcome (hazard ratio for the stenting group, 1.10; 95% CI, 0.75 to 1.62). The rates of target-vessel revascularization were significantly higher in the group that received stents than in the group that underwent CABG (hazard ratio, 4.76; 95% CI, 2.80 to 8.11). Comparisons of the group that received bare-metal stents with the group that underwent CABG and of the group that received drug-eluting stents with the group that underwent CABG produced similar results, although there was a trend toward higher rates of death and the composite end point in the group that received drug-eluting stents. CONCLUSIONS In a cohort of patients with unprotected left main coronary artery disease, we found no significant difference in rates of death or of the composite end point of death, Q-wave myocardial infarction, or stroke between patients receiving stents and those undergoing CABG. However, stenting, even with drug-eluting stents, was associated with higher rates of target-vessel revascularization than was CABG.

Impact of Intravascular Ultrasound Guidance on Long-Term Mortality in Stenting for Unprotected Left Main Coronary Artery Stenosis

Background—Although intravascular ultrasound (IVUS) guidance has been useful in stenting for unprotected left main coronary artery stenosis, its impact on long-term mortality is still unclear. Methods and Results—In the MAIN-COMPARE registry, patients with unprotected left main coronary artery stenosis in a hemodynamically stable condition underwent elective stenting under the guidance of IVUS (756 patients) or conventional angiography (219 patients). Patients with acute myocardial infarction were excluded. The 3-year outcomes between the 2 groups were primarily compared using propensity-score matching in the entire and separate populations according to stent type. In 201 matched pairs of the overall population, there was a tendency of lower risk of 3-year morality with IVUS guidance compared with angiography guidance (6.0% versus 13.6%, log-rank P=0.063; hazard ratio, 0.54; 95% CI, 0.28 to 1.03; Cox-model P=0.061). In particular, in 145 matched pairs of patients receiving drug-eluting stent, the 3-year incidence of mortality was lower with IVUS guidance as compared with angiography guidance (4.7% versus 16.0%, log-rank P=0.048; hazard ratio, 0.39; 95% CI, 0.15 to 1.02; Cox model P=0.055). In contrast, the use of IVUS guidance did not reduce the risk of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6% versus 10.8%, log-rank P=0.35; hazard ratio, 0.59; 95% CI, 0.18 to 1.91; Cox model P=0.38). The risk of myocardial infarction or target vessel revascularization was not associated with the use of IVUS guidance. Conclusions—Elective stenting with IVUS guidance, especially in the placement of drug-eluting stent, may reduce the long-term mortality rate for unprotected left main coronary artery stenosis when compared with conventional angiography guidance.

Comparison of Coronary Plaque Rupture Between Stable Angina and Acute Myocardial Infarction A Three-Vessel Intravascular Ultrasound Study in 235 Patients

Background—We evaluated the incidence and predictors of single and multiple plaque ruptures in acute myocardial infarction (AMI) and stable angina pectoris (SAP). Methods and Results—We performed 3-vessel intravascular ultrasound (IVUS) examination in 235 patients: 122 had AMI, and 113 had SAP. Plaque rupture of infarct-related or target lesions occurred in 80 AMI patients (66%) and in 31 SAP patients (27%) (P<0.001). Non–infarct-related or non–target artery plaque ruptures occurred in 21 AMI patients (17%) and 6 SAP patients (5%) (P=0.008). Multiple plaque ruptures were observed in 24 AMI (20%) and 7 SAP patients (6%) (P=0.004). Therefore, at least 1 plaque rupture in any coronary artery was noted in 84 AMI patients (69%) and 35 SAP patients (31%) (P<0.001). Overall, the only independent clinical predictor of plaque rupture in the infarct-related/target lesion was AMI (P<0.01; OR, 4.867; 95% CI, 2.734 to 8.661). The only independent clinical predictor of plaque rupture in AMI patients was an elevated C-reactive protein (CRP) level (P=0.035; OR, 2.139; 95% CI, 1.053 to 4.343). Conversely, in SAP patients, the only independent clinical predictor of plaque rupture was diabetes mellitus (P=0.034; OR, 2.553; 95% CI, 1.071 to 6.085). The only independent clinical predictor of multiple plaque ruptures was AMI (P=0.003; OR, 3.752; 95% CI, 1.546 to 9.105). Conclusions—Three-vessel IVUS imaging showed that culprit lesion plaque rupture, secondary remote plaque ruptures, and multiple plaque ruptures were all more common in AMI patients than SAP patients. In AMI patients, plaque rupture was associated with a high CRP level, whereas in SAP patients, plaque rupture was more common in those with diabetes.

Optical Coherence Tomographic Analysis of In-Stent Neoatherosclerosis After Drug–Eluting Stent Implantation

Background— We report findings from optical coherence tomography (OCT) of in-stent neoatherosclerosis as a cause of drug-eluting stent (DES) failure. Methods and Results— Optical coherence tomography and grayscale and virtual histology intravascular ultrasound were performed in 50 patients (30 stable, 20 unstable angina) with 50 DES in-stent restenosis lesions and intimal hyperplasia >50% of stent area. Median follow-up time was 32.2 months. Overall, 26 lesions (52%) had at least 1 OCT-defined in-stent thin-cap fibroatheroma (TCFA)–containing neointima and 29 (58%) had at least 1 in-stent neointimal rupture. Patients presenting with unstable angina showed a thinner fibrous cap (55 &mgr;m [interquartile range 42 to 105 &mgr;m] versus 100 &mgr;m [interquartile range 60 to 205 &mgr;m], P=0.006) and higher incidence of OCT-defined TCFA-containing neointima (75% versus 37%, P=0.008), intimal rupture (75% versus 47%, P=0.044), thrombi (80% versus 43%, P=0.010), and red thrombi (30% versus 3%, P=0.012) than stable patients. Fibrous cap thickness negatively correlated with follow-up time (r=−0.318, P=0.024). Compared with DES <20 months after implantation (the best cut-off to predict TCFA-containing neointima), DES ≥20 months after implantation had a higher incidence of TCFA-containing neointima (69% versus 33%, P=0.012) and red thrombi (27% versus 0%, P=0.007). Patients with unstable (versus stable) angina had an increasing number of unstable OCT findings including TCFA-containing neointima, neointima rupture, and thrombus (P=0.027). The rate of agreement between grayscale intravascular ultrasound and OCT for detecting intimal rupture was 50% and for detecting thrombus was 44%. The agreement between virtual histology intravascular ultrasound and OCT for identifying TCFA-containing neointima was 78%. Conclusions— In-stent neoatherosclerosis may be an important mechanism of DES failure, especially late after implantation.

Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry.

OBJECTIVES We performed the long-term follow-up of a large cohort of patients in a multicenter study receiving left main coronary artery (LMCA) revascularization. BACKGROUND Limited information is available on long-term outcomes for patients with unprotected LMCA disease who underwent coronary stent procedure or coronary artery bypass grafting (CABG). METHODS We evaluated 2,240 patients with unprotected LMCA disease who received coronary stents (n = 1,102; 318 with bare-metal stents and 784 with drug-eluting stents) or underwent CABG (n = 1,138) between 2000 and 2006 and for whom complete follow-up data were available for at least 3 to 9 years (median 5.2 years). The 5-year adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction [MI], or stroke; and target vessel revascularization [TVR]) were compared with the use of the inverse probability of treatment weighted method and propensity-score matching. RESULTS After adjustment for differences in baseline risk factors with the inverse probability of treatment weighting, the 5-year risk of death (hazard ratio [HR]: 1.13; 95% confidence interval [CI]: 0.88 to 1.44, p = 0.35) and the combined risk of death, Q-wave MI, or stroke (HR: 1.07; 95% CI: 0.84 to 1.37, p = 0.59) were not significantly different for patients undergoing stenting versus CABG. The risk of TVR was significantly higher in the stenting group than in the CABG group (HR: 5.11; 95% CI: 3.52 to 7.42, p < 0.001). Similar results were obtained in comparisons of bare-metal stent with concurrent CABG and of drug-eluting stent with concurrent CABG. In further analysis with propensity-score matching, overall findings were consistent. CONCLUSIONS During 5-year follow-up, stenting showed similar rates of mortality and of the composite of death, Q-wave MI, or stroke but higher rates of TVR as compared with CABG for patients with unprotected LMCA disease.

Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus: The DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients)

OBJECTIVES We sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM). BACKGROUND Although cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients. METHODS This randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months. RESULTS The 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 +/- 0.53 mm vs. 0.38 +/- 0.54 mm, p = 0.025) and in-segment (0.42 +/- 0.50 mm vs. 0.53 +/- 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR. CONCLUSIONS Triple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients.

Validation of Intravascular Ultrasound–Derived Parameters With Fractional Flow Reserve for Assessment of Coronary Stenosis Severity

Background—We assessed optimal intravascular ultrasound (IVUS) criteria for predicting functional significance of intermediate coronary lesions. Methods and Results—Overall, 201 patients with 236 coronary lesions underwent IVUS and invasive physiological assessment before intervention. Fractional flow reserve (FFR) was measured at maximal hyperemia induced by intravenous adenosine infusion. FFR <0.80 at maximum hyperemia was seen in 49 (21%) of the overall 236 lesions. The independent determinants of FFR were minimal lumen area (MLA; &bgr;=0.020; 95% confidence interval [CI], 0.008 to 0.031; P=0.032), plaque burden (&bgr;=−0.002; 95% CI, −0.003 to 0.001; P=0.001), lesion length with a lumen area <3.0 mm2 (&bgr;=−0.003; 95% CI, −0.005 to −0.001; P=0.005), and left anterior descending artery location (&bgr;=−0.035; 95% CI, −0.055 to −0.016; P=0.001). The best cutoff value (with a maximal accuracy) of the MLA to predict FFR <0.80 was <2.4 mm2, with a diagnostic accuracy of 68% (90% sensitivity, 60% specificity, and area under the curve=0.800; 95% CI, 0.742 to 0.848; P<0.001). The cutoff value of plaque burden to predict FFR <0.80 was ≥79% (69% sensitivity, 72% specificity, and area under the curve=0.756; 95% CI, 0.696 to 0.810; P<0.001). The cutoff value of lesion length with a lumen area <3.0 mm2 was 3.1 mm (84%sensitivity, 63%specificity, and area under the curve=0.765; 95% CI, 0.706 to 0.818; P<0.001). Among 117 lesions with an MLA ≥2.4 mm2, 112 (96%) had an FFR ≥0.80,; and all but 1 showed FFR ≥0.75. Conversely, 44 (37%) lesions with an MLA <2.4 mm2 had an FFR <0.80. Conclusions—IVUS-derived MLA ≥2.4 mm2 may be useful to exclude FFR <0.80, but poor specificity limits its value for physiological assessment of lesions with MLA <2.4 mm2. Thus, FFR or stress tests may be necessary to accurately identify ischemia-inducible intermediate stenoses.

Validation of SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) Score for Prediction of Outcomes After Unprotected Left Main Coronary Revascularization

OBJECTIVES This study aimed to validate the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score representing angiographic complexity after unprotected left main coronary artery (ULMCA) revascularization. BACKGROUND The validity of the SYNTAX score has been adequately evaluated. METHODS The SYNTAX scores were calculated for 1,580 patients in a large multicenter registry who underwent percutaneous coronary intervention (PCI) (n = 819) or coronary artery bypass graft (CABG) (n = 761) for ULMCA stenosis. The outcomes of interests were 3-year incidences of major adverse vascular events (MAVE), including death, Q-wave myocardial infarction, and stroke and major adverse cardiac and cerebrovascular events (MACCE), including MAVE and target vessel revascularization of ULMCA. RESULTS The incidence of 3-year MAVE was 6.2% in the lowest (< or =23), 7.1% in the intermediate (23 to approximately 36), and 17.4% in the highest (>36) SYNTAX score tertile groups after PCI (p = 0.010). However, the incidences of MAVE in the CABG group and MACCE in the PCI and CABG groups did not differ among the SYNTAX tertiles. In subgroups, the MAVE (p = 0.005) and MACCE (p = 0.007) rates according to the SYNTAX score tertiles were significantly different in patients receiving drug-eluting stent, not in those receiving bare-metal stent. When compared with the clinical EuroSCORE (European System for Cardiac Operative Risk Evaluation), the C-indexes of SYNTAX score and EuroSCORE were 0.59 and 0.67, respectively, for discrimination of MAVE and 0.53 and 0.57, respectively, for MACCE. CONCLUSIONS The angiographic SYNTAX score seems to play a partial role in predicting long-term adverse events after PCI for ULMCA stenosis. A complementary consideration of patients clinical risk might improve the predictive ability of risk score.

Incidence, mechanism, predictors, and long-term prognosis of late stent malapposition after bare-metal stent implantation.

Background—Predictors and long-term prognosis of late stent malapposition (LSM) after bare-metal stent (BMS) implantation are unknown. Methods and Results—We evaluated the incidence, mechanisms, predictors, and long-term prognosis of LSM after BMS implantation in 881 patients (992 native lesions) in whom intravascular ultrasound was performed at index and 6-month follow-up. LSM was defined as a separation of stent struts from the intimal surface of the arterial wall that was not presented at stent implantation. LSM occurred in 54 patients with 54 lesions (5.4% overall); the incidence was 10.3% (9 of 87) after directional coronary atherectomy (DCA) before stenting and 11.5% (11 of 96) after primary stenting in acute myocardial infarction (P =0.031 and P =0.007, respectively, versus elective stenting with conventional balloon pre-dilation, 4.3% [30 of 692]). There was an increase of external elastic membrane area (18.9±3.9 to 24.5±5.1 mm2, P <0.001) that was greater than the increase in plaque area (9.6±3.0 to 11.4±2.9 mm2, P <0.001). Independent predictors of LSM were primary stenting in acute myocardial infarction (P =0.023, OR=2.55, 95% CI=1.14 to 5.69) and DCA before stenting (P =0.025, OR=3.02, 95% CI=1.15 to 7.96). There were no significant differences in major adverse cardiac events between LSM and non-LSM groups during mean 3-year follow-up (1.9% versus 1.8%, respectively, P =NS). Conclusions—LSM occurs in ≈5% after BMS implantation. The predictors of LSM are primary stenting in acute myocardial infarction and DCA before stenting. Compared with complete stent apposition at follow-up, LSM after BMS implantation is not associated with any major adverse cardiac events during a mean 3-year follow-up after detection of LSM.

Sirolimus-eluting stent versus paclitaxel-eluting stent for patients with long coronary artery disease.

Background— Outcomes remain relatively unfavorable for stent-based coronary intervention of lesions with long diseased segments. This study compared sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) for long coronary lesions. Methods and Results— The present randomized, multicenter, prospective study compared the use of long (≥32 mm) SES with PES in 500 patients with long (≥25 mm) native coronary lesions. The primary end point of the trial was the rate of binary in-segment restenosis according to follow-up angiography at 6 months. The SES and PES groups had similar baseline characteristics. Lesion length was 33.9±11.6 mm in the SES group and 34.5±12.6 mm in the PES group (P=0.527). The in-segment binary restenosis rate was significantly lower in the SES group than in the PES group (3.3% versus 14.6%; relative risk 0.23; P<0.001). In-stent late loss of lumen diameter was 0.09±0.37 mm in the SES group and 0.45±0.55 mm in the PES group (P<0.001). In patients with restenoses, a pattern of focal restenosis was more common in the SES group than in the PES group (100% versus 53.3%, P=0.031). Consequently, SES patients had a lower rate of target-lesion revascularization at 9 months (2.4% versus 7.2%, P=0.012). The incidence of death (0.8% in SES versus 0% in PES, P=0.499) or myocardial infarction (8.8% in SES versus 10.8% in PES, P=0.452) at 9 months of follow-up was not statistically different between the 2 groups. Conclusions— For patients with long native coronary artery disease, SES implantation was associated with a reduced incidence of angiographic restenosis and a reduced need for target-lesion revascularization compared with PES implantation.