Coronary Thrombi Increase PTCA Risk
Angioscopy as a Clinical Tool
Background The presence of angiographically identified intracoronary thrombus has been variably associated with complications after coronary angioplasty. Angiography has been shown to be less sensitive than angioscopy for detecting subtle details of intracoronary morphology, such as intracoronary thrombi. The clinical importance of thrombi detectable by angioscopy but not by angiography is not known.
Methods and Results Percutaneous coronary angioscopy was performed in 122 patients undergoing conventional coronary balloon angioplasty (PTCA) at six medical centers. Unstable angina was present in 95 patients (78%) and stable angina in 27 (22%). Therapy was not guided by angioscopic findings, and no patient received thrombolytic therapy as an adjunct to angioplasty. Coronary thrombi were identified in 74 target lesions (61%) by angioscopy versus only 24 (20%) by angiography. A major in-hospital complication (death, myocardial infarction, or emergency bypass surgery) occurred in 10 of 74 patients (14%) with angioscopic intracoronary thrombus, compared with only 1 of 48 patients (2%) without thrombi (P=.03). In-hospital recurrent ischemia (recurrent angina, repeat PTCA, or abrupt occlusion) occurred in 19 of 74 patients (26%) with angioscopic intracoronary thrombi versus only 5 of 48 (10%) without thrombi (P=.03). Relative risk analysis demonstrated that angioscopic thrombus was strongly associated with adverse outcomes (either a major complication or a recurrent ischemic event) after PTCA (relative risk, 3.11; 95% CI, 1.28 to 7.60; P=.01) and that angiographic thrombi were not associated with these complications (relative risk, 0.85; 95% CI, 0.36 to 2.00; P=.91).
Conclusions The presence of intracoronary thrombus associated with coronary stenoses is significantly underestimated by angiography. Angioscopic intracoronary thrombi, the majority of which were not detected by angiography, are associated with an increased incidence of adverse outcomes after coronary angioplasty.
There are conflicting reports in the literature regarding the significance of intracoronary thrombus as a harbinger of potential complications associated with coronary angioplasty.1 2 3 4 5 6 7 8 9 10 11 12 13 14 The presence of intracoronary thrombi might reasonably be expected to predispose a traumatized endovascular surface to thrombotic occlusion. The inability of angiography to convincingly demonstrate a relationship between intracoronary thrombi and angioplasty complications may be related to the documented insensitivity of angiography to subtle details of lesion morphology.15 16 17 18 Percutaneous coronary angioscopy, the direct visualization of the luminal surface of a native coronary artery or bypass graft, is more sensitive than angiography for detecting surface features of complex lesion morphologies, such as dissection or plaque rupture, and intracoronary thrombus.19 20 21 22 23
The purpose of this prospective study was to determine whether the presence of angioscopically identified intracoronary red thrombus was associated with an increase in complications after percutaneous transluminal coronary angioplasty (PTCA).
The study population consisted of 122 nonconsecutive patients undergoing single-vessel conventional balloon angioplasty at six centers, each with at least one experienced angioscopist. There were 103 men (84%) and 19 women (16%), with an average age of 62.7±10.2 years (range, 38 to 81 years). Twenty-seven patients (22%) had stable angina and 95 (78%) had unstable angina defined as either angina at rest (n=48), crescendo angina pectoris (n=32), or recurrent, in-hospital, angina pectoris after a myocardial infarction (n=15). All patients gave informed consent, and the protocol was approved by the hospital’s Institutional Review Board.
We attempted to enroll all patients undergoing single-vessel angioplasty for angioscopic study if the operator felt that the target stenosis for PTCA was suitable for viewing, with the following exceptions: (1) lesions ≤2.0 cm from the ostia of the coronary arteries were excluded as not amenable to viewing (not enough space for the occlusion balloon to be inflated); (2) lesions in tortuous vessels or angulated segments; (3) patients with acute myocardial infarctions or cardiogenic shock; and (4) patients whose care may have been adversely affected by the additional procedure time required to perform the angioscopic examination (10 to 15 minutes).
Percutaneous coronary angioscopy was performed with a 4.5F rapid-exchange angioscope (Imagecath, Baxter Healthcare), shown in Fig 1⇓. The angioscope system consisted of an imaging catheter, a light source, a color television camera and monitor, and a 3/4-in videotape recorder. The angioscope is composed of two elements (delivery catheter and image bundle), both guided in a “monorail” fashion by a single 0.014-in angioplasty guide wire. The inner element (image bundle) is concentrically located within the outer delivery catheter and consists of 3000 optical fibers with a microlens at the distal tip. This image bundle may be independently advanced ≈6 cm in front of the delivery catheter. A compliant occlusion balloon is located at the distal tip of the delivery catheter, which, when inflated, occludes antegrade flow during imaging.
All patients were pretreated with 325 mg aspirin at least 1 day before the procedure and received heparin, nitrates, and other antianginal medications before and after the procedure at the discretion of their primary physicians. The coronary artery of interest was cannulated with a conventional 8F angioplasty guiding catheter, and 10 000 U heparin was administered. After the target lesion was crossed with a 0.014-in angioplasty guide wire, the angioscope was advanced into the proximal portion of the coronary artery. Warmed saline was infused through the outer catheter (distal to the occlusion balloon) at a rate of 0.5 to 1.0 mL/s, and the occlusion balloon was gradually hand-inflated as the live angioscopic image was viewed on the television monitor. When the field of view was flushed clear of blood, inflation of the occlusion balloon was held constant. The image bundle could then be advanced over the guide wire to examine the luminal surface and target lesion of the vessel. Each image acquisition took from 15 to 45 seconds, after which the occlusion balloon was deflated to allow antegrade blood flow to resume in the artery.
Preparation of the angioscope usually took 3 to 5 minutes and included (1) connecting the image bundle to the television camera and the light source, (2) flushing the distal lumen with saline, and (3) color balancing and focusing the angioscope. Very little time (<1 minute) was needed to insert or exchange the angioscope for a balloon dilation catheter because of its rapid-exchange design. Intravascular images were generally obtained within several minutes of introduction of the scope into the vessel.
Angioscopic and Angiographic Analysis
Angioscopic images were recorded on 3/4-in videotape and evaluated in a blinded fashion without knowledge of the patient’s clinical or angiographic findings. Thrombus was defined as a red collection of solid material within the vascular lumen, adherent to the vessel wall, that persisted despite flushing with crystalloid flush solution (Fig 2⇓).
To determine the variability of interpreting the angioscopic findings, two experienced angioscopists reviewed a subset of 37 consecutive cases from a single center and found that there was excellent agreement between the observers. There was 100% agreement in 22 patients with thrombus present and in 14 patients without thrombus present. They disagreed on only 1 patient.
Coronary angiograms were reviewed with the observers blinded to the patient’s clinical and angioscopic information. Angiographic lesion severity was graded according to the American Heart Association/American College of Cardiology (AHA/ACC) criteria as modified by Ellis et al,24 and quantitative measurements of the minimal lumen diameter at the reference segment and target lesion before and after angioplasty were taken with electronic calipers. Angiographic thrombi were defined as discrete or mobile filling defects surrounded by contrast at the site of the lesion. Abrupt occlusion of the dilated artery was defined as a critical reduction in antegrade blood flow consistent with TIMI grade 0 or 1.
Clinical End Points
The clinical end point of a major complication was defined as the in-hospital occurrence of one or more of the following: death, myocardial infarction (creatine phosphokinase >2 times normal), or emergency coronary bypass surgery after PTCA. In-hospital recurrent ischemia after PTCA was defined as one or more of the following: recurrent angina pectoris with ischemic ECG changes, the need for repeat cardiac catheterization and angioplasty, or angiographic documentation of abrupt occlusion of the dilated vessel. The in-hospital occurrence of either a major complication or recurrent ischemia was considered an adverse outcome after PTCA.
Values are expressed as mean±SD where appropriate. Univariate analysis of categorical variables was performed with the χ2 test and Fisher’s exact test when applicable. Continuous variables were compared by Student’s unpaired t test. The relative risk, with a 95% CI for the outcome variables, was calculated from the independent variables as noted. A value of P≤.05 was defined as statistically significant.
Successful angioscopic imaging of the target lesion was achieved in all the patients entered into the study. No complications related to the angioscopy procedure occurred.
Intracoronary thrombus was identified in 74 of 122 patients (61%) by angioscopy versus 24 of 122 (20%) by angiography (P<.001) (Fig 3⇓). Of the 74 lesions with angioscopic thrombus visualized, only 20 (25%) had angiographic thrombus identified (Table 1⇓). There was no association of angioscopic intracoronary thrombi with patient age or sex or minimal lumen diameter measurements of the reference segment or the lesion before or after angioplasty (Table 2⇓). Angioscopic thrombus was visualized in 70 (74%) of the 95 unstable angina patients compared with 4 (15%) of the 27 stable angina patients (P<.001) (Fig 4⇓). There was also an increased frequency of angioscopically detected intracoronary thrombi in the angiographically more complex type B (B1 and B2) and C lesions compared with type A lesions (P<.02) (Fig 5⇓).
Univariate analysis of clinical (age, sex, unstable angina, or stable angina), angiographic (intracoronary thrombus or AHA/ACC lesion criteria), and angioscopic (intracoronary thrombus) variables for in-hospital ischemic complications after angioplasty was performed (Table 3⇓ and Fig 6⇓). Among these variables, only the presence of angioscopic intracoronary thrombi was significantly related to the occurrence of a major complication (10 of 74 [14%] versus 1 of 48 [2%], P=.03), a recurrent ischemic event (19 of 74 [26%] versus 5 of 48 [10%], P=.03), or an adverse outcome (24 of 74 [32%], versus 5 of 48 [10%], P=.01) compared with those without thrombus (Fig 7⇓). There was a trend for type C lesions to be associated with a major complication (3 of 13 [23%], P=.06), a recurrent ischemic event (5 of 13 [39%], P=.08), or an adverse outcome (5 of 13 [39%], P=.18), although the absolute number of these lesions was small. The relative risk of an adverse outcome among the selected variables is shown in Fig 8⇓. Only the presence of angioscopic thrombi was significantly related to the occurrence of an in-hospital adverse outcome after PTCA.
Our results are consistent with prior data demonstrating the superior sensitivity of coronary angioscopy for detecting intracoronary red thrombi compared with the sensitivity of contrast angiography.19 20 21 22 The relative insensitivity of angiography to thrombi may be explained by the inherent limitations of a contrast “luminogram” of a tortuous, three-dimensional structure viewed in two dimensions.12 13
Detection of intracoronary thrombus by angiography requires that the thrombus be large enough to displace contrast material and appear as a “filling defect” or a contrast stain in the vessel. Angioscopic detection of a red thrombus is based on color and texture discrimination and does not rely on a “mass effect.” Small quantities of red thrombus are easily seen against the white or yellow background of the vessel wall.
The angioscopic identification of intracoronary thrombus is subjective and requires that the operator have some experience to reliably distinguish red thrombi from other intravascular features manifesting a red color. Thrombi may occur as red intraluminal masses fixed to the vessel wall and distinguished from stagnant blood in the lumen by their globular, gelatinous texture and their inability to be detached from the vessel wall with a flush solution. Mural thrombi appear as patches of red material fixed to the surface of the vessel wall, analogous to a red carpet on a white or yellow floor. The surface texture of a mural thrombus commonly has a “woven” appearance that is not glistening or shiny. It is possible that an inexperienced observer could confuse mural thrombi with either an intramural hematoma or a vessel wall abrasion. However, intramural hematomas have the distinctive appearance of a deep bruise, with a dull, dusky, red color below the smooth glistening surface of the vessel intima; abrasions of the vessel wall, on the other hand, appear as linear scratches or red streaks on the surface of the artery, in contrast to the confluent patches of red thrombus.
The specificity of angiography for detecting intracoronary thrombi is also weakened when one realizes that not all angiographic filling defects are thrombi. Angioscopy, by depicting both color and texture, can readily distinguish white or yellow plaque fragments protruding into the vessel lumen from red thrombus. However, one limitation of angioscopic images is that “white” thrombus and white tissue elements very often appear identical and are difficult to differentiate. The angioscopic distinguishing feature of these white intraluminal masses is their shape and texture. Tissue fragments or dissection flaps usually demonstrate sharp, angular margins analogous to “tattered white bedsheets on a clothesline blowing in the wind,” whereas white thrombi (platelet aggregates and fibrin strands) are globular masses with fuzzy, indistinct borders.
Patients with unstable angina had a significantly increased incidence of angioscopic intracoronary thrombi compared with stable angina patients, which is in agreement with prior angioscopic studies.16 17 20 Intracoronary thrombus was also more commonly associated with the more complex AHA/ACC type B and C lesions compared with the less complex type A lesions.
Prior studies have demonstrated an increased incidence of angioplasty complications associated with unstable angina and complex coronary lesion morphology.1 3 4 7 10 11 24 25 Univariate analysis of our data for angina classification and angiographic AHA/ACC lesion criteria did not demonstrate a significant association with in-hospital complications after PTCA (major complications, recurrent ischemia, or adverse events), although there was a trend toward significance in the small number of type C lesions.
Some investigators have reported angiographic intracoronary thrombi to be associated with angioplasty complications,3 4 5 6 while others have not been able to confirm angiographic intracoronary thrombi as a predictor of adverse outcome.1 2 7 12 13 In this study, thrombi detected by angioscopy, but not those identified by angiography, were strongly related to adverse outcomes after angioplasty. Relative risk analysis demonstrated that compared with clinical variables (age, sex, unstable angina, and stable angina) or angiographic morphology (thrombus or AHA/ACC lesion criteria), angioscopic intracoronary thrombus was most strongly associated with in-hospital adverse events after PTCA.
Our inability to demonstrate an association of angiographic thrombus with adverse outcomes after angioplasty is probably due to the high number of false-positive (4 of 24, 16.6%) and false-negative (54 of 98, 55%) results associated with angiography. The limitations of angiography may also explain the variable association of angiographic thrombus with angioplasty complications reported in the literature because of an underestimation of the presence of thrombus and an overestimation of the incidence of intracoronary thrombus in vessels with complex lesion morphology such as plaque fractures, dissections, or ruptured fibrous caps, which may mimic the angiographic appearance of an intracoronary thrombus as filling defects or contrast staining.
Our findings illustrate the clinical importance of angiographically “silent” intracoronary thrombi detected by angioscopy. This is the first study to demonstrate that subtle features of intracoronary morphology, visualized with the angioscope but not detectable by angiography, are relevant to the clinical practice of interventional cardiology.
Limitations of the Study
We did not include postdilation angiographic dissection in our analysis because dissection is a well-established postprocedural predictor of PTCA complications and angioscopic dissections are universally present after dilation of the lesion with an angioplasty balloon. We may have underestimated the incidence of intracoronary thrombi by angioscopy, because thrombi occurring distal to the target lesion would not have been viewed during the pre-PTCA imaging.
Another limitation of this study is that our study population does not represent a consecutive series of patients undergoing angioplasty. Some patients are not candidates for angioscopic imaging, and such patients were excluded on the basis of the location of the target lesion in a very proximal segment or in a tortuous artery that the investigator thought would be unsuitable for imaging. Finally, the assessment of both the angiographic and angioscopic lesion morphology is subjective.
We have demonstrated that angioscopy is a more sensitive and specific tool for identifying intracoronary thrombus than is angiography. We have also shown that angioscopic intracoronary thrombus is strongly associated with in-hospital PTCA complications, even though the majority of angioscopic thrombi were not detected by angiography. What is not demonstrated in this study is a cause-and-effect relationship between the intracoronary thrombi visualized by angioscopy and the occurrence of an angioplasty complication. Thrombus may occur in association with lesions more likely to fail angioplasty rather than directly contributing to that failure. Alternatively, a small amount of red thrombus may serve as a nidus for subsequent growth of a thrombus that directly contributes to vessel closure or recurrent ischemia after angioplasty. Resolution of this question will require a controlled study demonstrating that angioscopically directed therapy to resolve the thrombus can reduce the incidence of in-hospital adverse events.
The authors would like to express their appreciation to Ahmed A. Abdoh, PhD, MSPH, for his assistance with statististical analysis, James O’Meara for technical and computer assistance in preparing the images, and Angela Lorio for her editorial assistance during the preparation of the manuscript.
Reprint requests to Christopher J. White, MD, Director of Invasive Cardiology, HCI International Medical Center, Beardmore St, Clydebank, Scotland, UK, G81 4HX.
The guest editor for this article was Robert A. O’Rourke, MD, UT Health Science Center, San Antonio, Tex.
- Received February 21, 1995.
- Revision received July 18, 1995.
- Accepted September 11, 1995.
- Copyright © 1996 by American Heart Association
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