- Email: [email protected]
Quantitative angiographic and intravascular ultrasound study >5 years after directional coronary atherectomy
Quantitative Angiographic and Intravascular Ultrasound Study >5 Years After Directional Coronary Atherectomy Kenya Nasu, MD, Etsuo Tsuchikane, MD, Nobuhisa Awata, MD, Hiroaki Matsumoto, MD, Atsushi Shiota, MD, Yoshihiro Takeda, MD, and Tohru Kobayashi, MD Aggressive and optimal directional coronary atherectomy (DCA) using intravascular ultrasound (IVUS) guidance provides favorable outcomes within 1 year. However, no previous data are available on the changes that occur in target lesions for the long term after stand-alone DCA. This study’s aim evaluates, using quantitative angiography and intravascular ultrasonography, the natural history of changes that occur in target lesions between short- (about 6 months) and long-term (>5 years) follow-up angiography after stand-alone DCA. Of 186 patients (221 lesions) with successful stand-alone DCA, 48 patients (53 lesions) underwent revascularization within 6 months, and 14 patients subsequently died, leaving a study population of 124 patients (154 lesions). Complete quantitative coronary angiography (QCA) was obtained in 91 patients (101 lesions) and complete serial IVUS assessment was obtained for 38 lesions before and after intervention and during follow-up.
From short- to long-term follow-up angiography, the minimal luminal diameter significantly increased (from 2.12 to 2.56 mm; p <0.0001); lesion subgroups with >30% diameter stenosis at short-term follow-up angiography showed significant late regression as assessed by QCA. Serial IVUS assessment revealed that the vessel cross-sectional area did not change (from 17.3 to 17.4 mm2; p ⴝ NS); however the lumen cross-sectional area significantly increased (from 7.3 to 9.5 mm2; p <0.0001) due to the reduction of plaque plus media cross-sectional area (from 10.0 to 7.9 mm2; p <0.0001). The change in lumen crosssectional area correlated with the change in plaque plus media cross-sectional area (r ⴝ ⴚ0.686, p <0.0001). Target lesions show late regression due to plaque reduction at >5 years after stand-alone DCA. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:543–548)
irectional coronary atherectomy (DCA) was developed to excise obstructive coronary atheroma. D Recent studies have shown that aggressive and opti-
and restenotic lesions; these patients routinely underwent follow-up angiography 3 and 6 months after the procedure. To evaluate the long-term results after stand-alone DCA, a prospective follow-up protocol was devised. Study eligible patients had successful stand-alone DCA, had short-term follow-up angiography, and were free from death and any target lesion revascularization (percutaneous coronary intervention or coronary bypass surgery) during follow-up. Of 186 patients, 48 patients (53 lesions) underwent revascularization surgery or repeat angioplasty within 6 months and 14 patients (6 cardiac patients, 8 noncardiac patients) subsequently died; therefore,124 patients (154 lesions) were eligible for the study. Complete serial quantitative coronary angiographic (QCA) analysis was performed before and after the procedure, and short- and long-term follow-up was achieved in a study population of 91 patients with 101 lesions (73% of study-eligible patients). Complete serial IVUS assessments were obtained for 38 patients with 38 lesions. The study protocol was approved by our institutional ethics committee. Written informed consent was obtained from all patients. Procedure and medication: All patients were given aspirin for ⱖ1 week before the procedure. During the procedure, heparin was given as a bolus of 150 U/kg with additional boluses to 2,000 U/hour. DCA was performed using a 6Fr, 7Fr, or 7Fr graft Simpson Atherocath (Guidant Corp., Santa Clara, California) and in conjunction with IVUS guidance in 48% of lesions. All baseline, postprocedure, and follow-up angiog-
mal DCA in conjunction with intravascular ultrasound (IVUS) guidance can be performed safely with favorable outcomes lasting up to 6 months or 1 year.1– 4 In contrast, late angiographic studies have shown that late regression occurs in target lesions after standard balloon angioplasty and stent implantation5–12; however, serial IVUS assessments were not performed in these studies and the mechanisms of late regression were not established. This study examines the changes in target lesions without subsequent target lesion revascularization and reveals the mechanisms of late response between short- (about 6 months) and longterm (⬎5 years) follow-up after stand-alone DCA.
METHODS
Study patients: Between December 1992 and July 1997, DCA was performed in 332 consecutive patients (441 lesions) at our hospital, and 186 patients (221 lesions) underwent stand-alone DCA to de novo From the Department of Cardiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. Manuscript received August 26, 2003; revised manuscript received and accepted November 12, 2003. Address for reprints: Kenya Nasu, MD, Department of Cardiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari, Osaka-City, Osaka, 537-0025 Japan. E-mail: [email protected]. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 March 1, 2004
0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.11.015
543
raphy and IVUS imaging was performed after administration of 200 g of nitroglycerin. Angiography was performed so that each lesion was viewed from over 2 angles. For the IVUS procedure, a CVIS insight ultrasonograph (Boston Scientific Scimed Inc., Maple Grove, Minnesota), incorporating a single-element, 30-MHz beveled transducer within a 3.2Fr short monorail imaging catheter, was used. After placing the IVUS catheter at a point distal to the lesion, the catheter was pulled back to the aortic ostium using the motorized pull-back system at 0.5 cm/s. A successful procedure was defined as a residual diameter stenosis of ⬍20% or a residual percent plaque plus media cross-sectional area of ⬍50% in cases using IVUS guidance without major cardiac complications (death, acute myocardial infarction, or coronary artery bypass surgery) during hospitalization. All patients received intensive anticoagulation using aspirin or cilostazol (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan). Quantitative analysis: Off-line QCA was conducted using the view that revealed the highest degree of stenosis. Severity of coronary stenosis was measured using the Cardiovascular Measurement System (CMSMEDIS Medical Imaging System, Leiden, The Netherlands). Baseline, postprocedure, and follow-up angiography were evaluated in the same view. The lesion length, reference diameter, minimal luminal diameter, and diameter stenosis were calculated by an isolated operator who was blinded to the order of follow-up cine angiograms. Analysis of cine frames was performed in end-diastole. The serial IVUS assessments (postprocedure, shortand long-term follow-up) were obtained at the same point as the smallest lumen before the procedure. Care was taken to assess the vessel at the same point during all subsequent imaging by accurately measuring the distance from the side branches, which were used as landmarks. Calculations were made by an experienced operator who was blinded to the order of follow-up. Vessel cross-sectional area and lumen cross-sectional area were calculated, and the difference between the 2 values was defined as plaque plus media cross-sectional area. Percent plaque plus media cross-sectional area was defined as plaque plus media cross-sectional area divided by vessel cross-sectional area. Patient follow-up: During hospitalization, all clinical outcomes, complications and laboratory data were recorded by a physician and entered into a database. Creatine kinase and creatine kinase-MB were obtained before treatment and at 4 to 6 and 24 hours after the procedure. After discharge, clinical follow-up examinations were performed every month to assess the occurrence of major adverse cardiac events (death, Q-wave myocardial infarction due to the initial angioplasty, or any repeat revascularization procedure). Short-term follow-up angiography was performed between 4 and 10 months after the procedure, and longterm follow-up angiography was performed between 5 and 9 years after the procedure. Statistical analysis: Continuous data are reported as mean ⫾ SD. Categorical data were expressed as fre544 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
TABLE 1 Baseline Clinical and Lesion Characteristics
Variable Age (yrs) Range Men Systemic hypertension Diabetes mellitus Hyperlipidemia Current smoker Prior myocardial infarction Prior coronary bypass Lesions Coronary artery treated Right Left anterior decending Left circumflex Left main AHA/ACC type A/B1 B2/C Ostial De novo lesions Lesion length (mm) Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%)
With Late Follow-up (n ⫽ 91)
Without Late Follow-up (n ⫽ 33)
61 ⫾ 8 34–80 80 (90%) 57 (64%) 32 (36%) 68 (76%) 66 (74%) 59 (66%) 26 (29%) 101
59 ⫾ 9 45–78 28 (82%) 20 (60%) 11 (31%) 23 (68%) 21 (66%) 25 (74%) 5 (15%) 53
37 47 10 7
17 25 8 3
37 64 22 67 11.9 3.29 1.01 69
(37%) (47%) (10%) (7%) (37%) (63%) (22%) (66%) ⫾ 5.6 ⫾ 0.62 ⫾ 0.39 ⫾ 10
23 30 15 32 10.2 3.09 1.00 68
(32%) (47%) (15%) (6%) (44%) (56%) (29%) (60%) ⫾ 5.3 ⫾ 0.55 ⫾ 0.49 ⫾ 14
Data are presented as number (percent) of patients or mean value ⫾ SD. Hyperlipidemia was defined as serum total cholesterol level ⬎250 mg/dl and/or triglyceride level ⬎150 mg/dl ACC ⫽ American College of Cardiology; AHA ⫽ American Heart Association.
quencies of occurrence. Comparisons between specific groups were carried out using Student’s t test or nonparametric analysis by the Mann-Whitney U statistic test. Repeated measures of analysis of variance were used to estimate any significant differences over time in data from serial QCA and IVUS assessments in all lesions and in the 5 subgroups on the basis of diameter stenosis at short-term follow-up angiography. The chi-square test or Fisher’s exact test was used for comparing frequency of occurrence. Linear regression analysis was performed to examine the correlation between paired continuous variables. Statview version 5.0 (Abacus Concepts Inc., Berkeley, California) was used for data analysis. A p value of ⬍0.05 was considered statistically significant.
RESULTS
Patient characteristics: Of the 124 patients (154 lesions), 33 patients (53 lesions) did not undergo longterm follow-up angiography. Of these, 15 patients who were free from angina refused long-term follow-up angiography and the remaining 18 patients were lost to follow-up. The baseline clinical and lesion characteristics of the study population (91 patients) are compared with those of the 33 patients who did not undergo longterm follow-up in Table 1. No significant differences were observed between the 2 groups. Acute results: The results of postprocedural QCA and IVUS are shown in Tables 2 and 3. During hospitalization, there were no major complications associated with the procedure. Non–Q-wave myocardial MARCH 1, 2004
TABLE 2 Angiographic Results for the 101 Lesions of the Study Population of 91 Patients Variable Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%) Restenosis rate (%) Target lesion revascularization (%)
Post
S-Fu
L-Fu
3.34 ⫾ 0.52 2.83 ⫾ 0.46 15.3 ⫾ 9.6
3.09 ⫾ 0.59 2.12 ⫾ 0.50* 31.8 ⫾ 12.7* 8 0 †
3.15 ⫾ 0.6 2.56 ⫾ 0.73 19.4 ⫾ 18.4 2 1
Data are presented as percent or mean value ⫾ SD. *p ⬍0.0001 versus postprocedure and long-term follow-up; †p ⬍0.0001 versus postprocedure. L-Fu ⫽ long-term follow-up angiography (5.7 ⫾ 0.5 years); Post ⫽ postprocedure; S-Fu ⫽ short-term follow-up angiography (6.4 ⫾ 2.5 months).
TABLE 3 Serial Intravascular Ultrasound Measurement in 38 Lesions Variable
Post 2
Vessel CSA (mm ) Lumen CSA (mm2) Plaque plus media CSA (mm2) Percent plaque plus media CSA (%)
17.6 9.4 8.2 45.8
⫾ ⫾ ⫾ ⫾
S-Fu
3.6 2.0 3.0 11.2
17.3 7.3 10.0 57.3
⫾ ⫾ ⫾ ⫾
3.8 2.6* 2.7* 10.0*
L-Fu 17.4 9.5 7.9 45.6
⫾ ⫾ ⫾ ⫾
3.1 2.6 2.4 10.5
Data are presented as percent or mean value ⫾ SD. *p ⬍0.0001 versus postprocedure and long-term follow-up. CSA ⫽ cross sectional area; other abbreviation as in Table 2.
TABLE 4 Angiographic Results in the 38 Lesions With Serial IVUS Assessment Compared With That in the 63 Lesions Without IVUS Assessment Variable Reference diameter (mm) Post S-Fu L-Fu Minimal luminal diameter (mm) Post S-Fu L-Fu Diameter stenosis (%) Post S-Fu L-Fu
With IVUS (n ⫽ 38)
Without IVUS (n ⫽ 63)
p Value
3.31 ⫾ 0.17 3.09 ⫾ 0.41 3.03 ⫾ 0.56
3.36 ⫾ 0.56 3.09 ⫾ 0.65 3.19 ⫾ 0.61
0.69 0.99 0.37
low-up and decreased from short- to long-term follow-up. The angiographic restenosis rate, which was defined as ⬎50% diameter stenosis, was not significantly different between the 2 periods. Only 1 lesion required target lesion revascularization due to restenosis at long-term follow-up. Lesions were divided into 5 subgroups according to diameter stenosis at short-term follow-up angiography; the change in diameter stenosis was observed from short- to long-term follow-up (Figure 2). In the 2 subgroups with ⬍20% and 20% to 29% diameter stenosis, some lesions increased and some decreased in stenosis severity; however, overall, there were no significant change in diameter stenosis between short- and long-term follow-up. The remaining 3 groups (diameter stenosis ⬎30%) showed a significant reduction in diameter stenosis by long-term follow-up angiography. In the 2 subgroups (diameter stenosis ⬎40%, n ⫽ 36), no lesion showed late progression. The more severe lesions at short-term follow-up showed greater late regression. Serial intravascular ultrasound analysis: A complete serial IVUS
study (baseline, postprocedure, and short- and long-term follow-up angiography) was performed in 38 le2.91 ⫾ 0.35 2.79 ⫾ 0.50 0.23 sions. Table 4 compares the angio2.17 ⫾ 0.51 2.09 ⫾ 0.49 0.44 graphic results in the 38 lesions with 2.60 ⫾ 0.79 2.54 ⫾ 0.71 0.69 complete serial IVUS assessment with those in the 63 lesions without 12.6 ⫾ 8.3 16.5 ⫾ 10.5 0.07 29.7 ⫾ 13.8 32.8 ⫾ 12.1 0.27 IVUS assessment. After the proce15.9 ⫾ 20.3 20.9 ⫾ 17.5 0.21 dure, and the short- and long-term follow-up time points, no significant Data are presented as mean value ⫾ SD. Abbreviations as in Table 2. differences were observed between the 2 groups. The serial IVUS assessments are infarction was observed in 2% of patients due to distal listed in Table 3. Vessel cross-sectional area did not change significantly over both follow-up periods. Luembolism. Angiographic follow-up: Short-term follow-up an- men cross-sectional area was decreased significantgiography was performed at 6.4 ⫾ 2.5 months (range ly from postprocedure to short-term follow-up angi4.0 to 9.2) and long-term follow-up angiography was ography but increased significantly from short- to performed at 5.7 ⫾ 0.5 years (range 5.1 to 8.7) after long-term follow-up. In contrast, plaque plus media the procedure. The QCA data are listed in Table 2 and cross-sectional area increased significantly from postthe change in minimal luminal diameter is shown in procedure to short-term follow-up, but decreased sigFigure 1. The reference diameter was not significantly nificantly from short- to long-term follow-up. Lumen different between short- and long-term follow-up an- cross-sectional area and plaque plus media cross-secgiography; however, the reference diameter at short- tional area were not significantly different between term follow-up was significantly smaller than that postprocedure and long-term follow-up. The mechanism of improvement in the lumen after the procedure. The minimal luminal diameter decreased significantly after the procedure to short- cross-sectional area from short- to long-term folterm follow-up, but increased significantly from short- low-up angiography is illustrated in Figure 3. No to long-term follow-up. In contrast, diameter stenosis significant differences in changes in the vessel crossincreased from after the procedure to short-term fol- sectional area were observed between the 2 periods. CORONARY ARTERY DISEASE/LATE REGRESSION AFTER STAND-ALONE DCA
545
FIGURE 1. Cumulative distribution of minimal luminal diameter at preprocedure (Pre), postprocedure (Post), short-term follow-up (S-Fu), and long-term follow-up (L-Fu) angiography. Minimal luminal diameter decreased significantly from postprocedure to short-term follow-up angiography and significantly increased from short- to long-term follow-up angiography.
FIGURE 2. Changes in diameter stenosis between S-Fu and L-Fu angiography. Lesions were divided into 5 groups according to diameter stenosis at S-Fu. Patient subsets with lesions with 30% to 39%, 40% to 49% and >50% diameter stenosis showed significant late lesion regression. Abbreviations as in Figure 1.
However, the plaque plus media cross-sectional area increased from postprocedure to short-term follow-up angiography and decreased from short- to long-term follow-up, which mainly accounted for the improvement in the lumen cross-sectional area from short- to long-term follow-up. From postprocedure to short-term follow-up angiography, the change in the lumen cross-sectional area was correlated with the change in vessel crosssectional area (r ⫽ 0.723, p ⬍0.0001); however, this change was bidirectional. From short- to long-term follow-up, the change in the lumen cross-sectional area was not correlated with the change in vessel cross-sectional area (Figure 4; r ⫽ ⫺0.259, p ⫽ 0.17) 546 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
but was correlated with the change in plaque plus media cross-sectional area (Figure 4; r ⫽ ⫺0.686, p ⬍0.0001).
DISCUSSION Significant late regression of target lesions was observed from 6 months to ⬎5 years after stand-alone DCA by serial QCA analysis and IVUS assessment. This is the first study to show that target lesions enlarge because of plaque reduction from short-term to long-term follow-up angiography. Recent studies have revealed that use of an “optimal” DCA technique, in particular IVUS, can achieve favorable initial and long-term (⬍1 year) outcomes.1– 4 However, MARCH 1, 2004
FIGURE 3. The mechanisms of the improvement in lumen cross-sectional area (LA) assessed by serial IVUS assessments. The change in vessel cross-sectional area (VA) were not remarkable between the 2 periods (ⴚ0.32 ⴞ 2.5 vs 0.09 ⴞ 1.7 mm2, p ⴝ 0.45). The plaque plus media cross-sectional area (PA) increased from postprocedure (Post) to S-Fu angiography and decreased from S-Fu to L-Fu angiography (1.8 ⴞ 1.1 vs ⴚ2.1 ⴞ 2.0 mm2; p <0.0001), which accounted for the improvement in the lumen crosssectional area (ⴚ2.1 ⴞ 2.1 vs 2.2 ⴞ 1.1 mm2; p <0.0001). Abbreviations as in Figure 1.
few studies have examined the changes in target lesions ⱖ5 years after stand-alone DCA. In our study, a significant decrease in minimal luminal diameter was observed from postprocedure to short-term follow-up angiography; however, significant late lesion regression was observed a mean of 5.7 years after stand-alone DCA. Importantly, all borderline restenotic lesions (diameter stenosis ⬎40%, n ⫽ 36) at short-term follow-up showed significant late regression. In a previous study,13 minimal luminal diameter significantly decreased from 1 to 3 months after balloon angioplasty but did not significantly change from 6 to 12 months. Another study6 that used serial QCA showed that minimal luminal diameter did not significantly change from postprocedure to 6 months and that late regression occurred up to 4.5 years after angioplasty. The time course of change in target lesions after stent implantation appears similar to that after angioplasty, as determined by serial QCA analysis.5,7,8,14 In such studies, the minimal luminal diameter of target lesions significantly decreased from postprocedure to 6 months, but then improved from 6 months to 2.5 to 4 years after coronary stenting. However, ⬎4 years after stenting, late luminal renarrowing was common at the stented site due to chronic inflammation, followed by heavy infiltration of lipid laden macrophages around the stent struts.7,15 When these data are taken together, the target lesion after balloon angioplasty displays a continuum of change that occurs with 3 distinct phases: phase 1; from after the procedure to 6 months, the minimal luminal diameter decreases, phase 2; from 6 to 12 months minimal luminal diameter changes little, and phase 3; at ⬎12 months minimal luminal diameter enlarges. In contrast, these 3 phases are followed by a
long-term progression phase (⬎4 years) in target lesions after stent deployment. The time course of luminal enlargement after stand-alone DCA appears similar to that after balloon angioplasty. This study has several important limitations. Of the 124 study patients, 33 did not undergo long-term follow-up angiography, leading to a potential bias. However, clinical and baseline lesion characteristics did not differ significantly between these 33 patients and the 91 study patients (Table 1). Because all 15 patients who refused late angiography were free from angina, it is unlikely that the target lesions of these patients would have had severe stenosis. This series of patients included our early experiences without IVUS guidance. Aggressive DCA, which cannot be performed without IVUS guidance, may improve the serial angiographic and IVUS findings. In contrast, extending the application of aggressive DCA using a Flexi-Cut atherocatheter (Guidant Corp., Santa Clara, California) to calcificated lesions, small coronary arteries, or both might bring about different clinical, angiographic, and IVUS results. In the present study, serial angiographic findings were not significantly different between the 38 lesions that underwent DCA with IVUS guidance and the 63 lesions without IVUS (Table 4). Intravascular ultrasonography can only measure net changes in the plaque plus media cross-sectional area and cannot evaluate cellular proliferation and apoptosis, matrix deposition, and atherosclerotic changes (progression or regression).16,17 Because changes in vessel cross-sectional area are also evaluated as those of net change, it is difficult to distinguish the effect of active adventitial constriction with a passive response to a decrease in plaque plus media cross-sectional area.
CORONARY ARTERY DISEASE/LATE REGRESSION AFTER STAND-ALONE DCA
547
The study population involved various lesions (de novo and restenotic) in all 3 coronary arteries and in patients with or without diabetes mellitus. Because the number of lesions was relatively small, quantitative analysis was not able to identify lesion-related or patient characteristics related differences in late progression mechanisms. 1. Baim DS, Cutip DE, Sharna SK, Sharma SK, for the BOAT Investigators.
FIGURE 4. Change in lumen cross-sectional area (LA) from shortto long-term follow-up did not correlate with the change in vessel cross-sectional area (VA) (r ⴝ ⴚ0.259, p ⴝ 0.17) (A); however, the change was correlated with the change in plaque plus media cross-sectional area (PA) (r ⴝ ⴚ0.686, p <0.0001) (B).
Differences in vasomotor tone could have contributed to measurements of vessel and lumen dimensions. However, in this study, nitroglycerin was administered before angiography and IVUS analysis, and differences in vasomotor tone should not have affected measurements of quantitative analysis. Serum cholesterol was also unlikely to have an effect on late regression. A previous follow-up study6 after balloon angioplasty showed that there was 14% increase in minimal luminal diameter, although there was 5% reduction in serum cholesterol between 7-month and 4.5-year follow-up angiography. In a lipid-lowering study of patients who underwent percutaneous coronary intervention with high levels of apolipoprotein B, low-density lipoprotein was reduced by 32% but the increase of the mean minimal diameter was only 0.035 mm between baseline and 2.5-year follow-up.18
548 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
Final results of the Balloon vs. Optimal Atherectomy Trial (BOAT). Circulation 1998;97:322–331. 2. Simonton CA, Leon MB, Baim DS, Hinohara T, Kent KM, Bersim RM, Wilson BH, Mintz GS, Fitzgerald PJ, Yock PG, et al. ‘Optimal’ directional coronary athrectomy: final results of the Optimal Atherectomy Restenosis Study (OARS). Circulation 1998;97:332–339. 3. Tsuchikane E, Sumitsuji S, Awata N, Nakamura T, Kobayashi T, Izumi M, Otsuji S, Tateyama H, Sakurai M, Kobayashi T. Final results of the STent versus directional coronary Atherctomy randomized Trial (START). J Am Coll Cardiol 1999;34:1050 –1057. 4. Suzuki T, Hosokawa H, Katoh O, for ABACAS Investigators. Effect of adjunctive balloon angioplasty after intravascular ultrasound-guided optimal directional coronary atherectomy: the result of Adjunctive Balloon Angioplasty After Coronary Atherectomy Study (ABACAS). J Am Coll Cardiol 1998;34: 1028 –1035. 5. Kimura T, Yokoi H, Nakagawa Y, Tamura T, Kaburagi S, Sawada Y, Sato Y, Yokoi H, Hamasaki N, Nosaka H, Nobuyoshi M. Three-year follow-up after implantation of metallic coronary-artery stents. N Engl J Med 1996;334:561–566. 6. Ormiston JA, Stewart FM, Roche AHG, Webber BJ, Whitlock RML, Webster MWI. Late regression of the dilated site after coronary angioplasty: a 5-year quantitative angiographic study. Circulation 1997;96:468 –474. 7. Kimura T, Abe K, Shizuta S, Odashiro K, Yoshida Y, Sakai K, Kaitani K, Katsumi I, Nakagawa Y, Yokoi H, et al. Long-term clinical and angiographic follow-up after coronary stent implantation in native coronary arteries. Circulation 2002;105:2986 –2991. 8. Asakura M, Ueda Y, Nanto S, Hirayama A, Adachi T, Kitakaze M, Hori M, Kodama K. Remodeling of in-stent neointima, which became thinner and transparent over 3 years: serial angiographic and angioscopic follow-up. Circulation 1998;97:2003–2006. 9. Rosing DR, Cannon RO 3rd, Watson RM, Bonow RO, Mincemoyer R, Leon MB, Lakatos E, Epstein SE, Kent KM. Three year anatomic, functional and clinical follow-up after successful percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1987;9:1–7. 10. Sharaf B, Riley RS, Drew TM, Williams DO. Late (five to eight years) clinical and angiographic assessment of patients undergoing successful percutaneous transluminal coronary angioplasty. Am J Cardiol 1992;69:965–967. 11. Mehta VY, Jorgensen MB, Raizner AE, Wolde-Tsadik G, Mahrer PR, Mansukhani P. Spontaneous regression of restenosis: an angiographic study. Am J Coll Cardiol 1995;26:696 –702. 12. Mikuriya Y, Wakayama K, Kadota M, Matsumoto Y, Tamura A, Yano S, Kanzaki K, Kataoka H. Long-term angiographic follow-up results in patients undergoing percutaneous trasluminal coronary angioplasty. Jpn Circ J 1989;53: 728 –734. 13. Nobuyoshi M, Kimura T, Nosaka H, Mioka S, Ueno K, Yokoi H, Hamasaki N, Horiuchi H, Ohishi H. Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients. J Am Coll Cardiol 1988;12:616 –623. 14. Hermiller JB, Fry ET, Peters TF, Orr CM, Tassel JV, Waller B, Pinkerton CA. Late coronary artery stenosis regression within the Gianturco-Roubin intracoronary stent. Am J Cardiol 1996;77:247–251. 15. Inoue K, Ando K, Shirai S, Nakanishi M, Yokoi H, Nakagawa Y, Hamasaki N, Kimura T, Nosaka H, Nobuyoshi M. Comparative pathologic studies of chronic tissue response to successful stent implantation and balloon angioplasty (abstr). J Am Coll Cardiol 2001;37:83A. 16. Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Wong SC, Hong MK, Kowach JA, Leon MB. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation 1996;94:35–43. 17. Lansky AJ, Mintz GS, Pompa JJ, Pichard AD, Kent KM, Satler RE, Baim DS, Kuntz RE, Simonton C, Bersin RM, et al. Remodeling after directional coronary atherectomy (with and without coronary angioplasty): a serial angiographic and intravascular ultrasound analysis from the optimal atherectomy restenosis study. J Am Coll Cardiol 1998;32:329 –337. 18. Brown BG, Albers JJ, Fisher LD, Schaeffer SM, Lin J-T, Kaplan C, Zhao X-Q, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289 –1298.
MARCH 1, 2004
From short- to long-term follow-up angiography, the minimal luminal diameter significantly increased (from 2.12 to 2.56 mm; p <0.0001); lesion subgroups with >30% diameter stenosis at short-term follow-up angiography showed significant late regression as assessed by QCA. Serial IVUS assessment revealed that the vessel cross-sectional area did not change (from 17.3 to 17.4 mm2; p ⴝ NS); however the lumen cross-sectional area significantly increased (from 7.3 to 9.5 mm2; p <0.0001) due to the reduction of plaque plus media cross-sectional area (from 10.0 to 7.9 mm2; p <0.0001). The change in lumen crosssectional area correlated with the change in plaque plus media cross-sectional area (r ⴝ ⴚ0.686, p <0.0001). Target lesions show late regression due to plaque reduction at >5 years after stand-alone DCA. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:543–548)
irectional coronary atherectomy (DCA) was developed to excise obstructive coronary atheroma. D Recent studies have shown that aggressive and opti-
and restenotic lesions; these patients routinely underwent follow-up angiography 3 and 6 months after the procedure. To evaluate the long-term results after stand-alone DCA, a prospective follow-up protocol was devised. Study eligible patients had successful stand-alone DCA, had short-term follow-up angiography, and were free from death and any target lesion revascularization (percutaneous coronary intervention or coronary bypass surgery) during follow-up. Of 186 patients, 48 patients (53 lesions) underwent revascularization surgery or repeat angioplasty within 6 months and 14 patients (6 cardiac patients, 8 noncardiac patients) subsequently died; therefore,124 patients (154 lesions) were eligible for the study. Complete serial quantitative coronary angiographic (QCA) analysis was performed before and after the procedure, and short- and long-term follow-up was achieved in a study population of 91 patients with 101 lesions (73% of study-eligible patients). Complete serial IVUS assessments were obtained for 38 patients with 38 lesions. The study protocol was approved by our institutional ethics committee. Written informed consent was obtained from all patients. Procedure and medication: All patients were given aspirin for ⱖ1 week before the procedure. During the procedure, heparin was given as a bolus of 150 U/kg with additional boluses to 2,000 U/hour. DCA was performed using a 6Fr, 7Fr, or 7Fr graft Simpson Atherocath (Guidant Corp., Santa Clara, California) and in conjunction with IVUS guidance in 48% of lesions. All baseline, postprocedure, and follow-up angiog-
mal DCA in conjunction with intravascular ultrasound (IVUS) guidance can be performed safely with favorable outcomes lasting up to 6 months or 1 year.1– 4 In contrast, late angiographic studies have shown that late regression occurs in target lesions after standard balloon angioplasty and stent implantation5–12; however, serial IVUS assessments were not performed in these studies and the mechanisms of late regression were not established. This study examines the changes in target lesions without subsequent target lesion revascularization and reveals the mechanisms of late response between short- (about 6 months) and longterm (⬎5 years) follow-up after stand-alone DCA.
METHODS
Study patients: Between December 1992 and July 1997, DCA was performed in 332 consecutive patients (441 lesions) at our hospital, and 186 patients (221 lesions) underwent stand-alone DCA to de novo From the Department of Cardiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. Manuscript received August 26, 2003; revised manuscript received and accepted November 12, 2003. Address for reprints: Kenya Nasu, MD, Department of Cardiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari, Osaka-City, Osaka, 537-0025 Japan. E-mail: [email protected]. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 March 1, 2004
0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2003.11.015
543
raphy and IVUS imaging was performed after administration of 200 g of nitroglycerin. Angiography was performed so that each lesion was viewed from over 2 angles. For the IVUS procedure, a CVIS insight ultrasonograph (Boston Scientific Scimed Inc., Maple Grove, Minnesota), incorporating a single-element, 30-MHz beveled transducer within a 3.2Fr short monorail imaging catheter, was used. After placing the IVUS catheter at a point distal to the lesion, the catheter was pulled back to the aortic ostium using the motorized pull-back system at 0.5 cm/s. A successful procedure was defined as a residual diameter stenosis of ⬍20% or a residual percent plaque plus media cross-sectional area of ⬍50% in cases using IVUS guidance without major cardiac complications (death, acute myocardial infarction, or coronary artery bypass surgery) during hospitalization. All patients received intensive anticoagulation using aspirin or cilostazol (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan). Quantitative analysis: Off-line QCA was conducted using the view that revealed the highest degree of stenosis. Severity of coronary stenosis was measured using the Cardiovascular Measurement System (CMSMEDIS Medical Imaging System, Leiden, The Netherlands). Baseline, postprocedure, and follow-up angiography were evaluated in the same view. The lesion length, reference diameter, minimal luminal diameter, and diameter stenosis were calculated by an isolated operator who was blinded to the order of follow-up cine angiograms. Analysis of cine frames was performed in end-diastole. The serial IVUS assessments (postprocedure, shortand long-term follow-up) were obtained at the same point as the smallest lumen before the procedure. Care was taken to assess the vessel at the same point during all subsequent imaging by accurately measuring the distance from the side branches, which were used as landmarks. Calculations were made by an experienced operator who was blinded to the order of follow-up. Vessel cross-sectional area and lumen cross-sectional area were calculated, and the difference between the 2 values was defined as plaque plus media cross-sectional area. Percent plaque plus media cross-sectional area was defined as plaque plus media cross-sectional area divided by vessel cross-sectional area. Patient follow-up: During hospitalization, all clinical outcomes, complications and laboratory data were recorded by a physician and entered into a database. Creatine kinase and creatine kinase-MB were obtained before treatment and at 4 to 6 and 24 hours after the procedure. After discharge, clinical follow-up examinations were performed every month to assess the occurrence of major adverse cardiac events (death, Q-wave myocardial infarction due to the initial angioplasty, or any repeat revascularization procedure). Short-term follow-up angiography was performed between 4 and 10 months after the procedure, and longterm follow-up angiography was performed between 5 and 9 years after the procedure. Statistical analysis: Continuous data are reported as mean ⫾ SD. Categorical data were expressed as fre544 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
TABLE 1 Baseline Clinical and Lesion Characteristics
Variable Age (yrs) Range Men Systemic hypertension Diabetes mellitus Hyperlipidemia Current smoker Prior myocardial infarction Prior coronary bypass Lesions Coronary artery treated Right Left anterior decending Left circumflex Left main AHA/ACC type A/B1 B2/C Ostial De novo lesions Lesion length (mm) Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%)
With Late Follow-up (n ⫽ 91)
Without Late Follow-up (n ⫽ 33)
61 ⫾ 8 34–80 80 (90%) 57 (64%) 32 (36%) 68 (76%) 66 (74%) 59 (66%) 26 (29%) 101
59 ⫾ 9 45–78 28 (82%) 20 (60%) 11 (31%) 23 (68%) 21 (66%) 25 (74%) 5 (15%) 53
37 47 10 7
17 25 8 3
37 64 22 67 11.9 3.29 1.01 69
(37%) (47%) (10%) (7%) (37%) (63%) (22%) (66%) ⫾ 5.6 ⫾ 0.62 ⫾ 0.39 ⫾ 10
23 30 15 32 10.2 3.09 1.00 68
(32%) (47%) (15%) (6%) (44%) (56%) (29%) (60%) ⫾ 5.3 ⫾ 0.55 ⫾ 0.49 ⫾ 14
Data are presented as number (percent) of patients or mean value ⫾ SD. Hyperlipidemia was defined as serum total cholesterol level ⬎250 mg/dl and/or triglyceride level ⬎150 mg/dl ACC ⫽ American College of Cardiology; AHA ⫽ American Heart Association.
quencies of occurrence. Comparisons between specific groups were carried out using Student’s t test or nonparametric analysis by the Mann-Whitney U statistic test. Repeated measures of analysis of variance were used to estimate any significant differences over time in data from serial QCA and IVUS assessments in all lesions and in the 5 subgroups on the basis of diameter stenosis at short-term follow-up angiography. The chi-square test or Fisher’s exact test was used for comparing frequency of occurrence. Linear regression analysis was performed to examine the correlation between paired continuous variables. Statview version 5.0 (Abacus Concepts Inc., Berkeley, California) was used for data analysis. A p value of ⬍0.05 was considered statistically significant.
RESULTS
Patient characteristics: Of the 124 patients (154 lesions), 33 patients (53 lesions) did not undergo longterm follow-up angiography. Of these, 15 patients who were free from angina refused long-term follow-up angiography and the remaining 18 patients were lost to follow-up. The baseline clinical and lesion characteristics of the study population (91 patients) are compared with those of the 33 patients who did not undergo longterm follow-up in Table 1. No significant differences were observed between the 2 groups. Acute results: The results of postprocedural QCA and IVUS are shown in Tables 2 and 3. During hospitalization, there were no major complications associated with the procedure. Non–Q-wave myocardial MARCH 1, 2004
TABLE 2 Angiographic Results for the 101 Lesions of the Study Population of 91 Patients Variable Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%) Restenosis rate (%) Target lesion revascularization (%)
Post
S-Fu
L-Fu
3.34 ⫾ 0.52 2.83 ⫾ 0.46 15.3 ⫾ 9.6
3.09 ⫾ 0.59 2.12 ⫾ 0.50* 31.8 ⫾ 12.7* 8 0 †
3.15 ⫾ 0.6 2.56 ⫾ 0.73 19.4 ⫾ 18.4 2 1
Data are presented as percent or mean value ⫾ SD. *p ⬍0.0001 versus postprocedure and long-term follow-up; †p ⬍0.0001 versus postprocedure. L-Fu ⫽ long-term follow-up angiography (5.7 ⫾ 0.5 years); Post ⫽ postprocedure; S-Fu ⫽ short-term follow-up angiography (6.4 ⫾ 2.5 months).
TABLE 3 Serial Intravascular Ultrasound Measurement in 38 Lesions Variable
Post 2
Vessel CSA (mm ) Lumen CSA (mm2) Plaque plus media CSA (mm2) Percent plaque plus media CSA (%)
17.6 9.4 8.2 45.8
⫾ ⫾ ⫾ ⫾
S-Fu
3.6 2.0 3.0 11.2
17.3 7.3 10.0 57.3
⫾ ⫾ ⫾ ⫾
3.8 2.6* 2.7* 10.0*
L-Fu 17.4 9.5 7.9 45.6
⫾ ⫾ ⫾ ⫾
3.1 2.6 2.4 10.5
Data are presented as percent or mean value ⫾ SD. *p ⬍0.0001 versus postprocedure and long-term follow-up. CSA ⫽ cross sectional area; other abbreviation as in Table 2.
TABLE 4 Angiographic Results in the 38 Lesions With Serial IVUS Assessment Compared With That in the 63 Lesions Without IVUS Assessment Variable Reference diameter (mm) Post S-Fu L-Fu Minimal luminal diameter (mm) Post S-Fu L-Fu Diameter stenosis (%) Post S-Fu L-Fu
With IVUS (n ⫽ 38)
Without IVUS (n ⫽ 63)
p Value
3.31 ⫾ 0.17 3.09 ⫾ 0.41 3.03 ⫾ 0.56
3.36 ⫾ 0.56 3.09 ⫾ 0.65 3.19 ⫾ 0.61
0.69 0.99 0.37
low-up and decreased from short- to long-term follow-up. The angiographic restenosis rate, which was defined as ⬎50% diameter stenosis, was not significantly different between the 2 periods. Only 1 lesion required target lesion revascularization due to restenosis at long-term follow-up. Lesions were divided into 5 subgroups according to diameter stenosis at short-term follow-up angiography; the change in diameter stenosis was observed from short- to long-term follow-up (Figure 2). In the 2 subgroups with ⬍20% and 20% to 29% diameter stenosis, some lesions increased and some decreased in stenosis severity; however, overall, there were no significant change in diameter stenosis between short- and long-term follow-up. The remaining 3 groups (diameter stenosis ⬎30%) showed a significant reduction in diameter stenosis by long-term follow-up angiography. In the 2 subgroups (diameter stenosis ⬎40%, n ⫽ 36), no lesion showed late progression. The more severe lesions at short-term follow-up showed greater late regression. Serial intravascular ultrasound analysis: A complete serial IVUS
study (baseline, postprocedure, and short- and long-term follow-up angiography) was performed in 38 le2.91 ⫾ 0.35 2.79 ⫾ 0.50 0.23 sions. Table 4 compares the angio2.17 ⫾ 0.51 2.09 ⫾ 0.49 0.44 graphic results in the 38 lesions with 2.60 ⫾ 0.79 2.54 ⫾ 0.71 0.69 complete serial IVUS assessment with those in the 63 lesions without 12.6 ⫾ 8.3 16.5 ⫾ 10.5 0.07 29.7 ⫾ 13.8 32.8 ⫾ 12.1 0.27 IVUS assessment. After the proce15.9 ⫾ 20.3 20.9 ⫾ 17.5 0.21 dure, and the short- and long-term follow-up time points, no significant Data are presented as mean value ⫾ SD. Abbreviations as in Table 2. differences were observed between the 2 groups. The serial IVUS assessments are infarction was observed in 2% of patients due to distal listed in Table 3. Vessel cross-sectional area did not change significantly over both follow-up periods. Luembolism. Angiographic follow-up: Short-term follow-up an- men cross-sectional area was decreased significantgiography was performed at 6.4 ⫾ 2.5 months (range ly from postprocedure to short-term follow-up angi4.0 to 9.2) and long-term follow-up angiography was ography but increased significantly from short- to performed at 5.7 ⫾ 0.5 years (range 5.1 to 8.7) after long-term follow-up. In contrast, plaque plus media the procedure. The QCA data are listed in Table 2 and cross-sectional area increased significantly from postthe change in minimal luminal diameter is shown in procedure to short-term follow-up, but decreased sigFigure 1. The reference diameter was not significantly nificantly from short- to long-term follow-up. Lumen different between short- and long-term follow-up an- cross-sectional area and plaque plus media cross-secgiography; however, the reference diameter at short- tional area were not significantly different between term follow-up was significantly smaller than that postprocedure and long-term follow-up. The mechanism of improvement in the lumen after the procedure. The minimal luminal diameter decreased significantly after the procedure to short- cross-sectional area from short- to long-term folterm follow-up, but increased significantly from short- low-up angiography is illustrated in Figure 3. No to long-term follow-up. In contrast, diameter stenosis significant differences in changes in the vessel crossincreased from after the procedure to short-term fol- sectional area were observed between the 2 periods. CORONARY ARTERY DISEASE/LATE REGRESSION AFTER STAND-ALONE DCA
545
FIGURE 1. Cumulative distribution of minimal luminal diameter at preprocedure (Pre), postprocedure (Post), short-term follow-up (S-Fu), and long-term follow-up (L-Fu) angiography. Minimal luminal diameter decreased significantly from postprocedure to short-term follow-up angiography and significantly increased from short- to long-term follow-up angiography.
FIGURE 2. Changes in diameter stenosis between S-Fu and L-Fu angiography. Lesions were divided into 5 groups according to diameter stenosis at S-Fu. Patient subsets with lesions with 30% to 39%, 40% to 49% and >50% diameter stenosis showed significant late lesion regression. Abbreviations as in Figure 1.
However, the plaque plus media cross-sectional area increased from postprocedure to short-term follow-up angiography and decreased from short- to long-term follow-up, which mainly accounted for the improvement in the lumen cross-sectional area from short- to long-term follow-up. From postprocedure to short-term follow-up angiography, the change in the lumen cross-sectional area was correlated with the change in vessel crosssectional area (r ⫽ 0.723, p ⬍0.0001); however, this change was bidirectional. From short- to long-term follow-up, the change in the lumen cross-sectional area was not correlated with the change in vessel cross-sectional area (Figure 4; r ⫽ ⫺0.259, p ⫽ 0.17) 546 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
but was correlated with the change in plaque plus media cross-sectional area (Figure 4; r ⫽ ⫺0.686, p ⬍0.0001).
DISCUSSION Significant late regression of target lesions was observed from 6 months to ⬎5 years after stand-alone DCA by serial QCA analysis and IVUS assessment. This is the first study to show that target lesions enlarge because of plaque reduction from short-term to long-term follow-up angiography. Recent studies have revealed that use of an “optimal” DCA technique, in particular IVUS, can achieve favorable initial and long-term (⬍1 year) outcomes.1– 4 However, MARCH 1, 2004
FIGURE 3. The mechanisms of the improvement in lumen cross-sectional area (LA) assessed by serial IVUS assessments. The change in vessel cross-sectional area (VA) were not remarkable between the 2 periods (ⴚ0.32 ⴞ 2.5 vs 0.09 ⴞ 1.7 mm2, p ⴝ 0.45). The plaque plus media cross-sectional area (PA) increased from postprocedure (Post) to S-Fu angiography and decreased from S-Fu to L-Fu angiography (1.8 ⴞ 1.1 vs ⴚ2.1 ⴞ 2.0 mm2; p <0.0001), which accounted for the improvement in the lumen crosssectional area (ⴚ2.1 ⴞ 2.1 vs 2.2 ⴞ 1.1 mm2; p <0.0001). Abbreviations as in Figure 1.
few studies have examined the changes in target lesions ⱖ5 years after stand-alone DCA. In our study, a significant decrease in minimal luminal diameter was observed from postprocedure to short-term follow-up angiography; however, significant late lesion regression was observed a mean of 5.7 years after stand-alone DCA. Importantly, all borderline restenotic lesions (diameter stenosis ⬎40%, n ⫽ 36) at short-term follow-up showed significant late regression. In a previous study,13 minimal luminal diameter significantly decreased from 1 to 3 months after balloon angioplasty but did not significantly change from 6 to 12 months. Another study6 that used serial QCA showed that minimal luminal diameter did not significantly change from postprocedure to 6 months and that late regression occurred up to 4.5 years after angioplasty. The time course of change in target lesions after stent implantation appears similar to that after angioplasty, as determined by serial QCA analysis.5,7,8,14 In such studies, the minimal luminal diameter of target lesions significantly decreased from postprocedure to 6 months, but then improved from 6 months to 2.5 to 4 years after coronary stenting. However, ⬎4 years after stenting, late luminal renarrowing was common at the stented site due to chronic inflammation, followed by heavy infiltration of lipid laden macrophages around the stent struts.7,15 When these data are taken together, the target lesion after balloon angioplasty displays a continuum of change that occurs with 3 distinct phases: phase 1; from after the procedure to 6 months, the minimal luminal diameter decreases, phase 2; from 6 to 12 months minimal luminal diameter changes little, and phase 3; at ⬎12 months minimal luminal diameter enlarges. In contrast, these 3 phases are followed by a
long-term progression phase (⬎4 years) in target lesions after stent deployment. The time course of luminal enlargement after stand-alone DCA appears similar to that after balloon angioplasty. This study has several important limitations. Of the 124 study patients, 33 did not undergo long-term follow-up angiography, leading to a potential bias. However, clinical and baseline lesion characteristics did not differ significantly between these 33 patients and the 91 study patients (Table 1). Because all 15 patients who refused late angiography were free from angina, it is unlikely that the target lesions of these patients would have had severe stenosis. This series of patients included our early experiences without IVUS guidance. Aggressive DCA, which cannot be performed without IVUS guidance, may improve the serial angiographic and IVUS findings. In contrast, extending the application of aggressive DCA using a Flexi-Cut atherocatheter (Guidant Corp., Santa Clara, California) to calcificated lesions, small coronary arteries, or both might bring about different clinical, angiographic, and IVUS results. In the present study, serial angiographic findings were not significantly different between the 38 lesions that underwent DCA with IVUS guidance and the 63 lesions without IVUS (Table 4). Intravascular ultrasonography can only measure net changes in the plaque plus media cross-sectional area and cannot evaluate cellular proliferation and apoptosis, matrix deposition, and atherosclerotic changes (progression or regression).16,17 Because changes in vessel cross-sectional area are also evaluated as those of net change, it is difficult to distinguish the effect of active adventitial constriction with a passive response to a decrease in plaque plus media cross-sectional area.
CORONARY ARTERY DISEASE/LATE REGRESSION AFTER STAND-ALONE DCA
547
The study population involved various lesions (de novo and restenotic) in all 3 coronary arteries and in patients with or without diabetes mellitus. Because the number of lesions was relatively small, quantitative analysis was not able to identify lesion-related or patient characteristics related differences in late progression mechanisms. 1. Baim DS, Cutip DE, Sharna SK, Sharma SK, for the BOAT Investigators.
FIGURE 4. Change in lumen cross-sectional area (LA) from shortto long-term follow-up did not correlate with the change in vessel cross-sectional area (VA) (r ⴝ ⴚ0.259, p ⴝ 0.17) (A); however, the change was correlated with the change in plaque plus media cross-sectional area (PA) (r ⴝ ⴚ0.686, p <0.0001) (B).
Differences in vasomotor tone could have contributed to measurements of vessel and lumen dimensions. However, in this study, nitroglycerin was administered before angiography and IVUS analysis, and differences in vasomotor tone should not have affected measurements of quantitative analysis. Serum cholesterol was also unlikely to have an effect on late regression. A previous follow-up study6 after balloon angioplasty showed that there was 14% increase in minimal luminal diameter, although there was 5% reduction in serum cholesterol between 7-month and 4.5-year follow-up angiography. In a lipid-lowering study of patients who underwent percutaneous coronary intervention with high levels of apolipoprotein B, low-density lipoprotein was reduced by 32% but the increase of the mean minimal diameter was only 0.035 mm between baseline and 2.5-year follow-up.18
548 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
Final results of the Balloon vs. Optimal Atherectomy Trial (BOAT). Circulation 1998;97:322–331. 2. Simonton CA, Leon MB, Baim DS, Hinohara T, Kent KM, Bersim RM, Wilson BH, Mintz GS, Fitzgerald PJ, Yock PG, et al. ‘Optimal’ directional coronary athrectomy: final results of the Optimal Atherectomy Restenosis Study (OARS). Circulation 1998;97:332–339. 3. Tsuchikane E, Sumitsuji S, Awata N, Nakamura T, Kobayashi T, Izumi M, Otsuji S, Tateyama H, Sakurai M, Kobayashi T. Final results of the STent versus directional coronary Atherctomy randomized Trial (START). J Am Coll Cardiol 1999;34:1050 –1057. 4. Suzuki T, Hosokawa H, Katoh O, for ABACAS Investigators. Effect of adjunctive balloon angioplasty after intravascular ultrasound-guided optimal directional coronary atherectomy: the result of Adjunctive Balloon Angioplasty After Coronary Atherectomy Study (ABACAS). J Am Coll Cardiol 1998;34: 1028 –1035. 5. Kimura T, Yokoi H, Nakagawa Y, Tamura T, Kaburagi S, Sawada Y, Sato Y, Yokoi H, Hamasaki N, Nosaka H, Nobuyoshi M. Three-year follow-up after implantation of metallic coronary-artery stents. N Engl J Med 1996;334:561–566. 6. Ormiston JA, Stewart FM, Roche AHG, Webber BJ, Whitlock RML, Webster MWI. Late regression of the dilated site after coronary angioplasty: a 5-year quantitative angiographic study. Circulation 1997;96:468 –474. 7. Kimura T, Abe K, Shizuta S, Odashiro K, Yoshida Y, Sakai K, Kaitani K, Katsumi I, Nakagawa Y, Yokoi H, et al. Long-term clinical and angiographic follow-up after coronary stent implantation in native coronary arteries. Circulation 2002;105:2986 –2991. 8. Asakura M, Ueda Y, Nanto S, Hirayama A, Adachi T, Kitakaze M, Hori M, Kodama K. Remodeling of in-stent neointima, which became thinner and transparent over 3 years: serial angiographic and angioscopic follow-up. Circulation 1998;97:2003–2006. 9. Rosing DR, Cannon RO 3rd, Watson RM, Bonow RO, Mincemoyer R, Leon MB, Lakatos E, Epstein SE, Kent KM. Three year anatomic, functional and clinical follow-up after successful percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1987;9:1–7. 10. Sharaf B, Riley RS, Drew TM, Williams DO. Late (five to eight years) clinical and angiographic assessment of patients undergoing successful percutaneous transluminal coronary angioplasty. Am J Cardiol 1992;69:965–967. 11. Mehta VY, Jorgensen MB, Raizner AE, Wolde-Tsadik G, Mahrer PR, Mansukhani P. Spontaneous regression of restenosis: an angiographic study. Am J Coll Cardiol 1995;26:696 –702. 12. Mikuriya Y, Wakayama K, Kadota M, Matsumoto Y, Tamura A, Yano S, Kanzaki K, Kataoka H. Long-term angiographic follow-up results in patients undergoing percutaneous trasluminal coronary angioplasty. Jpn Circ J 1989;53: 728 –734. 13. Nobuyoshi M, Kimura T, Nosaka H, Mioka S, Ueno K, Yokoi H, Hamasaki N, Horiuchi H, Ohishi H. Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients. J Am Coll Cardiol 1988;12:616 –623. 14. Hermiller JB, Fry ET, Peters TF, Orr CM, Tassel JV, Waller B, Pinkerton CA. Late coronary artery stenosis regression within the Gianturco-Roubin intracoronary stent. Am J Cardiol 1996;77:247–251. 15. Inoue K, Ando K, Shirai S, Nakanishi M, Yokoi H, Nakagawa Y, Hamasaki N, Kimura T, Nosaka H, Nobuyoshi M. Comparative pathologic studies of chronic tissue response to successful stent implantation and balloon angioplasty (abstr). J Am Coll Cardiol 2001;37:83A. 16. Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Wong SC, Hong MK, Kowach JA, Leon MB. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation 1996;94:35–43. 17. Lansky AJ, Mintz GS, Pompa JJ, Pichard AD, Kent KM, Satler RE, Baim DS, Kuntz RE, Simonton C, Bersin RM, et al. Remodeling after directional coronary atherectomy (with and without coronary angioplasty): a serial angiographic and intravascular ultrasound analysis from the optimal atherectomy restenosis study. J Am Coll Cardiol 1998;32:329 –337. 18. Brown BG, Albers JJ, Fisher LD, Schaeffer SM, Lin J-T, Kaplan C, Zhao X-Q, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289 –1298.
MARCH 1, 2004