European Heart Journal (1996) 17, 1554-1559 orphological changes after percutaneous transluminal coronary angioplasty of unstable plaques Insights from serial angioscopic follow-up C. Bauters, J.-. Lablanche, N. Renaud, E. P. cfadden,. Hamon and. E. Bertrand Service de Cardiologie B et Hemodynamique, Hopital Cardiologique, Boulevard du Professeur J. Leclercq, 59037 Lille Cedex, France Objective To describe the morphological changes occurring in the months following percutaneous transluminal coronary angioplasty (PTCA) of unstable plaques. Background Coronary angioscopy is a relatively new technique to assess plaque morphology. Previous angioscopic studies have shown that unstable coronary lesions are characterized by complex morphology, evidence of plaque rupture, and intraluminal thrombi. serial angioscopic studies have investigated the effects of PTCA on plaque morphology at such lesions. ethods We studied 15 patients who underwent successful PTCA for an unstable coronary syndrome (unstable angina: n = 5; recent myocardial infarction: n=10). Angioscopy was performed immediately before PTCA in 14 patients, immediately after PTCA in 13 patients, and at follow-up (225 ± 62 days after PTCA) in all patients. Results Pre-PTCA, plaque morphology was defined as complex in 18%, ulcerated in 27%; the vessel was totally Introduction Percutaneous transluminal coronary angioplasty (PTCA) is a widely used technique for myocardial revascularization but its long-term efficacy is still limited by the frequent occurrence of restenosis. Numerous angiographic studies have described the time course, incidence, and risk factors of restenosis''" 31. Angiography is, how- Revision submitted 13 October 1995, and accepted 13 vember 1995 Correspondence:. E. Bertrand. Service de Cardiologie B, Hopital Cardiologique. Boulevard du Professeur J. Leclercq. 59037 Lille Cedex, France. occluded in 18% of cases. Plaque colour was yellow in 75% of patients. A thrombus was identified at the lesion site in 71% of patients. Immediately post-ptca, small surface disruptions and dissections were observed in 62% of patients. Plaque colour was yellow in 85% of cases. Seventy-seven percent of patients had an angioscopically visible thrombus at the PTCA site. At follow-up, however, plaque shape was almost uniformly classified as smooth concentric (93%); plaque colour was white in 93%; no thrombus was observed. Conclusions These results demonstrate the healing of unstable plaques in the months following PTCA. The angioscopic appearance at 6 months is that of a stable plaque (smooth concentric, white, without thrombus). Whether this stable angioscopic appearance predicts longterm clinical stability remains to be determined. (Eur Heart J 1996; 17: 1554-1559) Key Words:, myocardial infarction, restenosis, angioscopy. ever, of limited value for the morphological analysis of coronary stenoses; new techniques such as coronary angioscopy 14 ' or intravascular ultrasound' 51 permit more complete characterization of the plaque either before or after PTCA. Previous angioscopic studies have reported, in a limited number of patients, the morphology of dilated sites several months after PTCA' 61 ; individual comparisons with morphology at the time of PTCA were, however, not possible due to the lack of serial angioscopic analysis. The present study was thus designed to describe the morphological changes occurring in the months following PTCA. Angioscopy was performed in the same 15 patients before PTCA, immediately after PTCA, and at 6 months follow-up. Downloaded from http://eurheartj.oxfordjournals.org/ at Pennsylvania State University on arch 6, 2014 0195-668X/96/101554 + 05 S18.00/0 1996 The European Society of Cardiology
Angioscopic follow-up after PTCA 1555 ethods Patients We identified 15 patients who underwent a successful PTCA procedure for either unstable angina (n = 5) or a recent myocardial infarction (n=10) in our institution between ay 1992 and December 1993 and who fulfilled the following criteria: (1) an adequate angioscopy procedure performed at the time of PTCA; (2) angiographic follow-up performed 4-12 months after PTCA; (3) an adequate angioscopy procedure performed in the same vessel at the time of the angiographic follow-up. During the time period of this study all patients undergoing PTCA in our institution were asked to undergo systematic angiographic follow-up; our average rate of angiographic follow-up is >80% [7 ~ 91. All patients gave informed consent for the angioscopy procedures. Angioscopy procedure Coronary angioscopy was performed with the Image- Cath system (Baxter, Edwards LIS Division, California) which includes an angioscopy catheter, an irrigation system, a light source, and a video system. The angioscopy catheter has an outer diameter of 45 F (15 mm) and includes a mobile fibre bundle that can be moved independently of the catheter over a 5 cm distance. Visualization of the coronary lumen is performed during low pressure inflation of a proximal, distensible, lowpressure occlusion cuff with continuous flushing of normal (09%) saline at 30-45 ml. min ~ ' through the irrigation channel of the angioscope by means of a power injector. All angioscopy sequences were recorded on videotape for subsequent analysis. Angioscopy was performed before PTCA in 14 patients. After administration of 10 000 IU of heparin, the lesion was crossed with a standard 0014 inch guidewire. The angioscopy catheter was then advanced over the guidewire and an initial series of images was obtained while the angioscope was advanced through the lesion; subsequently, another recording was obtained while the angioscope was withdrawn. The guidewire was left in place and the angioscopy catheter was then exchanged for a standard PTCA catheter. Angioplasty was performed as previously described 17 ' 81. In 13 patients, an adequate angioscopy procedure was repeated immediately after PTCA by exchanging the balloon catheter for the angioscope. Angioscopy was performed at follow-up (225 ± 62 days after PTCA) in all patients. After administration of 10 000IU of heparin, the lesion was again crossed with a guidewire and an angioscopy catheter was advanced through the lesion. The vessel segment of interest (i.e. the previously dilated segment) was defined by its distance from recognizable landmarks (i.e. side branches). Angioscopic analysis All videotapes were reviewed by two physicians who were unaware of the angiographic findings. The definitions and classifications used are adapted from the angioscopic classification system that was developed and evaluated by the European Working Group on Coronary Angioscopy 141. Intraobserver and interobserver agreements of angioscopic recordings, evaluated by this working group have been recently published 141. Image quality was defined as either adequate or inadequate for diagnostic purposes. The shape of narrowing was classified as smooth concentric, smooth eccentric, complex, or ulcerated. A lesion was classified as smooth eccentric if a segment of wall of normal appearance was visualized at the site of the lesion. A complex narrowing was defined as an irregular plaque with jagged edges. An ulcerated plaque was defined as an area of lining red clot surrounded by irregular plaque. The predominant colour of the plaque was classified as white or yellow. Angioscopic thrombus was defined as an ihtraluminal, superficial (lining), or protruding mass, adherent to the vessel surface but clearly a separate structure. Thrombi were further classified by colour (white, red, or mixed red and white). A white thrombus was defined as a shaggy, irregular, and cottonwool-like mass. Angioscopic dissection was defined as visible cracks or fissures of either the plaque or of the adjacent normal wall. Dissections were classified as simple (one or two well delineated fissures) or complex (multiple fissures associated with large structures protruding into the lumen or with a thick flap more or less occluding the lumen). Angiographic analysis Quantitative computer-assisted angiographic measurements of the dilated lesion were performed on enddiastolic frames by a single investigator unaware of the angioscopic findings with the CAESAR (Computer Assisted Evaluation of Stenosis And Restenosis) system. A detailed description of this system has previously been reported 1 ' 01. We routinely perform angiography in at least two projections, after intracoronary injection of isosorbide dinitrate (2 mg), just before and immediately after angioplasty. These projections are recorded in our database and the follow-up angiogram is performed, after the intracoronary injection of isosorbide dinitrate, in the same projections. Results Table 1 shows the baseline characteristics of the study population. ost of the patients (87%) were male; mean (±SD) age was 57-4 ± 10-5 years. Ten patients had elective PTCA of an infarct-related lesion performed between 9 and 60 days after the infarct; five had PTCA for unstable angina. Sixty percent of the procedures Eur Heart J, Vol. 17, October 1996 Downloaded from http://eurheartj.oxfordjournals.org/ at Pennsylvania State University on arch 6, 2014
1556 C. Bauters et al. Table 1 Clinical characteristics and quantitative angiography in individual patients Patient Age (years) Gender Clinical status Thrombolysis Vessel Interval PTCA to follow-up (days) Before PTCA Stenosis I After PTCA 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 64 43 71 71 60 47 57 53 55 59 55 67 37 50 72 F F yocardial infarction (17 days) yocardial infarction (12 days) yocardial infarction (11 days) yocardial infarction (60 days) yocardial infarction (11 days) yocardial infarction (25 days) yocardial infarction (10 days) yocardial infarction (11 days) yocardial infarction (9 days) yocardial infarction (60 days) PTCA indicates percutaneous transluminal coronary angioplasty; = male; F = female; LA D = left anterior descending artery, LCx = left circumflex artery; RCA = right coronary artery. were performed on left anterior descending artery lesions. ean stenosis severity was reduced from 74 ±13% before PTCA to 31 ±11% immediately after the procedure. At angiographic follow-up, five patients had stable angina and 10 were asymptomatic; mean stenosis severity increased to 52 ± 22%; eight patients had a >50% diameter stenosis at follow-up while the seven remaining patients had no restenosis. At follow-up, 11 lesions were smooth and concentric by angiography; four lesions were smooth and eccentric. The results of the serial angioscopic follow-up are summarized in Table 2; representative examples are shown in Fig. 1. Plaque shape Plaque shape was assessable in 11 of the 14 patients who had pre-ptca angioscopy. Three patients had an ulcerated plaque; two patients had a complex lesion; in two patients, the vessel was totally occluded before the procedure; in four patients, plaque shape was classified as smooth. Immediately after the procedure, most lesions were defined as complex; small surface disruptions and dissections were observed in eight (62%) of the 13 angioscopy post-ptca procedures. At follow-up, plaque shape was almost uniformly classified as smooth concentric (93%); in one case, a smooth eccentric plaque was observed. Plaque colour Plaque colour was assessable in 12 patients before PTCA and was defined as yellow in nine (75%) of the RCA RCA RCA LCx LCx LCx 271 122 174 205 170 192 238 301 224 222 213 289 218 368 175 69 100 66 58 58 79 82 64 76 100 86 78 75 70 57 12 28 28 38 29 32 33 35 42 18 33 37 29 59 22 56 72 35 49 50 76 15 22 46 89 38 80 31 53 65 cases; the three remaining patients had white plaques. After PTCA, plaque colour was defined as yellow in 11 (85%) patients. In contrast, at follow-up, plaque colour was white in 14 (93%); in one case (patient no. 2, restudied 4 months after PTCA) a yellow plaque was observed. Thrombus Pre-PTCA, thrombus was seen at the lesion site in nine (71%) patients. The thrombus was classified as lining in six patients and as protruding in three; thrombus colour was red in three patients and mixed red-white in six patients. Immediately post-ptca, a lining thrombus was observed in six patients and a protruding thrombus in four patients. At follow-up, thrombus was not seen in any of the 15 patients. Discussion This study, to the best of our knowledge, represents the first report of the effects of angioplasty on the evolution of the unstable plaque. Previous reports have described the angioscopic appearance of restenotic plaques after PTCA. The present study represents the first serial assessment by coronary angioscopy of the immediate and long-term results of balloon angioplasty. Our results clearly demonstrate the healing of unstable plaques in the months following PTCA. While most of our patients had complex yellow plaque and/or thrombus before angioplasty, the appearance at follow-up was almost unvaryingly that of as smooth concentric white plaque without thrombus, whether or not restenosis was present. Downloaded from http://eurheartj.oxfordjournals.org/ at Pennsylvania State University on arch 6, 2014 Eur Heart J, Vol. 17, October 1996
Table 2 Piiticnt i 2 3 4 5 6 7 8 9 10 II 12 13 14 15 Results of coronary angioscopy in individual patients Before PTCA Total occlusion Total occlusion Smooth eccentric Plaque shape After PTCA, small flaps, small flaps, dissection, dissection, dissection, small flaps, dissection Small flaps Smooth eccentric Before PTCA Plaque colour After PTCA white Downloaded from http://eurheartj.oxfordjournals.org/ at Pennsylvania State University on arch 6, 2014 Before PTCA Thrombus After PTCA S 5' PTCA indicates percutaneous transluniinal coronary angioplasty; = not assessable 2 o 9 o
1558 C. Bauters et al. PTCA site is completely re-endothelialized at follow-up cannot be determined using angioscopy. Differences between restenotic and non-restenotic sites The healing process after vascular injury The response of the vascular wall to injury in animal models has been extensively studied. An experimental balloon angioplasty induces complete deendothelialization and various degrees of injury to the vessel wall such as rupture to the internal elastic membrane and/or dissections. Platelet aggregation and thrombus formation occur very early as a consequence of the exposure of the subendothelial space to blood flow1"1. In the weeks following injury, smooth muscle cell proliferation and migration from the media to the intima, and synthesis of extracellular matrix lead to the development of neointimal thickening1'21. Reendothelialization of the denuded surface also occurs within a few weeks but may be incomplete in case of long denuded segments without collateral branches'131. In comparison to animal models, few data are available regarding the changes in plaque morphology after arterial injury in humans. Necropsy studies have shown evidence of neointimal hyperplasia following PTCA'14', the presence of endothelial cells has also been documented a few months after arterial injury in humans'151. et a/.'61 have recently reported the white and fibrotic angioscopic appearance of five restenotic lesions; angioscopy was, however not performed at the time of PTCA. Our study that included repeated angioscopy procedures in the same patients clearly demonstrates the healing process occurring in the months following PTCA. The typical angioscopic appearance at follow-up (smooth concentric white plaque without thrombus) was in sharp contrast with angioscopic data obtained immediately before and immediately after PTCA. These differences reflect the magnitude of the changes occurring at the lesion site. In addition to disappearance of dissection and thrombi, the smooth concentric white aspect of the plaque is likely to be a consequence of neointimal hyperplasia leading to a remodelling of the inner part of the vessel. Whether the Eur Heart J, Vol. 17. October 1996 Stabilization of unstable plaques Acute coronary syndromes are characterized by plaque rupture and thrombus formation'18191. In the present study, all patients had either had a myocardial infarction (n= 10) or an episode of unstable angina (n = 5). To the best of our knowledge, this is the first serial angioscopic follow-up of unstable plaques. Of course, all these lesions were electively and successfully treated by PTCA and the healing of unstable plaque not subjected to PTCA might be substantially different from that observed in the present study. Four to 12 months after the initial angioscopy, the angioscopic appearance of the previously unstable plaque was that of a smooth fibrotic plaque without thrombus. Whether this angioscopic stabilization will translate into clinical stabilization is unknown. References [1] Leimgruber PP, Roubin GS, Hollman J et al. Restenosis after successful coronary angioplasty in patients with single-vessel disease. Circulation 1986: 73-710-7. [2] Ellis SG, Roubin GS, King SB, Douglas JS, Cox WR. Importance of stenosis morphology in the estimation of restenosis risk after elective percutaneous transluminal coronary angioplasty. Am J Cardiol 1989; 63: 304 [3] Rensing BJ, Hermans WR, Vos J et al. Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factor related to long-term angiographic outcome. Circulation 1993: 88: 975-85 [4] den Heijer P, Foley DP, Hillege HL et al. The 'Ermenonville' classification of observations at coronary angioscopy. Evaluation of intra- and inter-observer agreement. Eur Heart J 1994; 15-815-22. Downloaded from http://eurheartj.oxfordjournals.org/ at Pennsylvania State University on arch 6, 2014 Figure I Angioscopic findings 12 months after PTCA in patient no. 14. The angioscopic appearance is that of a smooth concentric white plaque without thrombus. In the present study, angioscopic follow-up was not limited to patients with angiographic restenosis; half of the patients had less than 50% diameter stenosis by quantitative angiography at follow-up. Individual data presented in Tables 1 and 2 show that, 412 months after PTCA, the angioscopic appearance of nonrestenotic lesions was similar to that of restenotic lesions. These results are consistent with intravascular ultrasound studies that have demonstrated a significant amount of neointimal thickening in patients without angiographic restenosis at follow-up'161. Whether restenosis is predominantly the consequence of excessive neointimal response or of constriction of the vessel wall as recently suggested'171 cannot be determined by angioscopy.
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