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J Thorac Cardiovasc Surg 1999;118:618-627
© 1999 Mosby, Inc.

SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE

ANGIOGRAPHIC QUANTIFICATION OF DIFFUSE CORONARY ARTERY DISEASE: RELIABILITY AND PROGNOSTIC VALUE FOR BYPASS OPERATIONS

From the Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Address for reprints: Richard F. Davies, MD, University of Ottawa Heart Institute, 40 Ruskin St, H147, Ottawa, Ontario K1Y 4W7, Canada.

	Abstract

Top Abstract Introduction Method Results Discussion Summary References

 
Objectives: Diffuse distal coronary disease is thought to worsen the outcome of coronary bypass operations, but it is not easily quantified. The present study seeks to show that distal coronary diffuseness can be assessed by a structured reading of the coronary angiogram and that the resulting measure predicts operative mortality.
Methods: Sequential survivors (n = 100) and nonsurvivors (n = 34) of nonemergency bypass operations were studied retrospectively. Angiograms were read as follows: (1) Coronary branches at risk were identified; (2) the amount of myocardium supplied by each branch was estimated in steps of 0.5 such that the entire left ventricle added to 8 segments; (3) distal disease severity in each branch was rated on a 5-point scale; and (4) a distal coronary diffuseness score was determined by summing (severity rating x segments supplied) for all branches. Reliability was assessed by correlating the results of blinded re-readings of the same angiograms by the same and different investigators. The score’s association with mortality was determined by means of logistic regression.
Results: A distal coronary diffuseness score could be determined from all angiograms. Interobserver and intraobserver reliabilities were high, with r values of 0.81 and 0.83, respectively (P < .001). The score was 1 of 3 significant independent predictors of operative mortality, along with nonelective and repeat operations.
Conclusion: Diffuse distal coronary disease can be quantified by a structured reading of the coronary angiogram and is a powerful independent predictor of surgical death. Inclusion of a standardized measure of this risk factor would improve statistical models of operative risk. (J Thorac Cardiovasc Surg 1999;118:618-27)

	Introduction

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Surgeons and hospitals that perform coronary artery bypass grafting (CABG) sometimes consider high mortality figures to be misleading because they believe their patients are in a higher risk category than those operated on by others. To address this, statistical models have been developed to estimate operative risk on the basis of the presence or absence of clinical risk factors. To be applicable to all patients undergoing cardiac operations, such a risk model should include only objective factors that are available on all patients and should leave little room for observer bias. ¹ At the same time, models should take into account all factors that have a strong independent association with operative risk. Several previous studies attempting to quantify the angiographic extent of coronary disease to predict operative risk have concentrated on the amount of myocardium at risk or the severity of proximal coronary lesions. ^2-6 Although the extent of disease in the distal coronary vessels is generally accepted to be associated with a poor surgical outcome, measures of distal coronary disease have not been included in predictive models ^1,7-12 because they were considered subjective and prone to interobserver bias. ¹ To our knowledge, only 2 studies have attempted to include a measure of distal disease status in predictive models. One of these scored diffuse distal coronary disease as present if a coronary endarterectomy was planned as part of the procedure, ¹³ and the other scored it as present if it was mentioned in the patient’s chart. ¹⁴ Neither of these studies used an objective measure based on angiographic findings.

The present study uses a retrospective parallel case-series design with 2 consecutive groups of patients, those who survived CABG and those who did not, to test the following hypotheses: (1) a structured reading of the coronary angiogram can provide a reproducible and reliable semiquantitative measure of the severity of distal coronary disease, and (2) such a measure would contribute additional information regarding surgical outcomes beyond that provided by baseline clinical indicators.

	Method

Top Abstract Introduction Method Results Discussion Summary References

 
Patient population.
Patients were identified retrospectively from a database containing all patients undergoing CABG at the Ottawa Heart Institute. Two sequential case series were identified. The first consisted of 34 consecutive patients who died in the hospital after non-urgent CABG over a period of 1 year. The second consisted of 100 consecutive patients undergoing CABG who were discharged alive during a 2-month period in the same year in which the nonsurvivors were treated. This method was used to limit this pilot study to a manageable number of patients, while at the same time including a sufficient number of end points to evaluate the diffuseness score. Patients who were in hemodynamically unstable condition immediately before the operation were excluded because this subgroup would include patients with premorbid conditions that would contaminate the evaluation of distal coronary anatomy as a risk factor. Patients undergoing repeat CABG were included because distal coronary disease might contribute to their known high operative risk and because this would allow comparison of distal coronary disease with other risk factors known to be important. Patients requiring concomitant procedures such as valve surgery or aneurysmectomy were excluded because these other procedures would contribute significantly to operative mortality.

The medical records of each eligible patient were reviewed for the following variables: age, sex, diabetes mellitus, prior myocardial infarction, and previous or current congestive heart failure. Tu, Jaglal, and Naylor ¹¹ have shown that the inclusion of these variables, in combination with a measure of left ventricular function, accounts for most of the predictive ability of statistical models of surgical risk. A measure of ejection fraction was not included in this study because it was not available on all patients, and we thought it important to include sequential series of survivors and nonsurvivors.

Development of the method to quantify distal coronary disease.
All angiograms were read by 1 of 2 investigators (R.J.C. or R.F.D.). To develop a reproducible and reliable method, these 2 investigators read 30 angiograms together to identify factors that might introduce variability into the method and develop conventions to deal with them. After they had evaluated the 30 angiograms, it was apparent that an angiogram could be scored in between 6 and 10 minutes and that accomplishing this during the usual clinical reading of an angiogram would require only an additional 1 to 3 minutes. The method that was developed allowed for anatomic variations in the distribution and size of different coronary branches by taking into account the area of myocardium supplied by each vascular segment. It was accomplished by means of the following 4 steps.

1. Weighting coronary segments according to the amount of myocardium supplied.
The left ventricle was divided into 8 approximately equal areas by means of a method similar to that developed for the Coronary Artery Surgery Study (CASS). The coronary tree was then divided into anatomically meaningful segments, each of which was given a weight based on the estimated amount of left ventricular myocardium it supplied. To account for patient-to-patient variation in the size of individual coronary branches, the weights assigned to each segment were adjusted in steps of 0.5, such that the summed weight for all coronary segments was 8. For a patient with right dominant circulation in which the left anterior descending coronary artery (LAD) extends to the left ventricular (LV) apex, weights might be distributed as shown in Table I, column 2 (Balanced). If a patient had a large distal LAD segment that extended around the LV apex and a large isolated marginal branch, the weights might be assigned as shown in Table I, column 3 (Large LAD, IM). In the case of a left dominant circulation, more weight was assigned to branches of the circumflex artery and less to branches of the right coronary artery, as shown in Table I, column 4 (Left dominance).

3. Grading of segments.
Segments not at risk were given a rating of 0. Segments at risk were given a grade of 1 to 5 on the basis of vessel caliber and extent of atherosclerosis (Table II). The catheter diameter was used as a reference (8F = 2.63 mm, 6F = 2.00 mm). The rating assigned to each segment took into account all stenoses with the exception of the most proximal stenosis. Segments at risk that were deemed inaccessible to revascularization by CABG were assigned the worst grade (5), regardless of vessel caliber (eg, a large septal branch of the LAD "bracketed" by two stenoses: one proximal and one distal). If a completely occluded artery was well visualized via collateral filling, it was graded in the same way as other segments. A completely occluded artery that was not visualized was also assigned a grade of 5 regardless of whether the other vessels were of good caliber. For convenience, contiguous segments not separated by a significant focal stenosis were weighted and graded as 1 unit.

The evaluation of angiograms with high and low diffuseness scores is illustrated in Figs 1 to 3.

View larger version (66K): [in this window] [in a new window]   Fig. 1. Example of structured reading of an angiogram with a diffuseness score of 9.5. All 8 left ventricular (LV) segments were "at risk." A small first diagonal branch (D1) of the left anterior descending artery (LAD) was given a weight of 0.5 and a rating of 4 (0.5-1.0 mm, severe disease). The remainder of the LAD and its branches were given a combined weight of 3.5 and a rating of 1 (>2 mm, large normal vessel). A large first marginal branch (M1) of the circumflex coronary artery was given a weight of 2 and a rating of 1. The posterior intraventricular (PIV) and LV branches of the right coronary artery (RCA) were scored together and given a combined weight of 2 and a rating of 1.

View larger version (70K): [in this window] [in a new window]   Fig. 2. Example of structured reading of an angiogram with a diffuseness score of 18. All 8 left ventricular (LV) segments were "at risk." A large first septal perforator (S1) was given a weight of 1. It was deemed not suitable for revascularization because of a proximal lesion and therefore given a rating of 5. Other branches of the left anterior descending artery (LAD) were rated as 3 (1-1.5 mm, moderate disease). A large first marginal branch of the circumflex artery (M1) was given a weight of 2 and a rating of 1 (>2 mm, large normal vessel). The posterior intraventricular branch (PIV) of the right coronary artery (RCA) and LV branches of the RCA were scored separately because of a lesion involving the crux. Each was given a weight of 1 and rating of 1.

View larger version (61K): [in this window] [in a new window]   Fig. 3. Example of structured reading of an angiogram with a diffuseness score of 36. The first diagonal branch (D1) of the left anterior descending artery (LAD) was given a weight of 1 and a rating of 4 (0.5-1.0 mm, severe disease), as was an isolated marginal branch. The first marginal branch (M1) of the circumflex artery was given a weight of 1 and rating of 3 (1.0-1.5 mm, moderate disease). The distal right coronary (RCA) and circumflex arteries filled by collaterals and were given a combined rating of 3 (<0.5 mm, very severe disease or totally occluded and poorly visualized). An RCA frame late in the angiographic cycle is shown to demonstrate the faint, late filling of the distal LAD via collaterals. This vessel was given a weight of 2 and a rating of 5.

Interobserver and intraobserver reliability of distal coronary diffuseness score.
Once the initial 30 angiograms were read, all 134 angiograms were then read by 2 of the investigators (R.F.D., R.J.C.). Interobserver reliability was assessed by giving each of the 2 readers 25 of the same angiograms to read separately and comparing the results. Intraobserver reliability was assessed by presenting 1 reader (R.J.C.) with the same angiogram on 2 occasions (n = 30) and comparing the results.

To preserve blinding, the investigator who was not a reader (M.M.G.) removed identifying information from angiograms and then presented them to the 2 readers for interpretation. During validation of the technique, angiograms presented to the investigator responsible for re-reading were randomly interspersed with other angiograms in such a way that the reader was not aware that it had been previously read. These re-readings were separated by at least 2 days. Subsequently, readers had no knowledge of clinical outcomes at the time angiograms were scored.

Statistical analysis.
Data were analyzed with the use of SPSS version 8.0 (SPSS, Inc, Chicago, Ill). Interobserver and intraobserver reliability of the diffuseness score was assessed by calculating Pearson’s correlation coefficient for paired readings of the same angiogram. Univariate associations with in-hospital mortality were assessed by means of the ² test for categoric variables (sex, prior myocardial infarction, prior heart failure, diabetes, surgical urgency, repeat surgery, and LV function). The Student t test was used for continuous variables (age and distal coronary diffuseness score). The independent associations of all factors with a univariate association with hospital death ( of .10 or less) were determined by logistic regression modeling. LV function, which was not a significant univariate predictor of mortality in those patients who had undergone left ventriculography, was not included as a predictor in logistic models because it was not available in all patients. A 2-tailed of .05 was used as the minimum criterion for statistical significance in logistic models.

	Results

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Demographic and clinical characteristics of the 134 study patients are shown in Table III. Survivors and nonsurvivors did not differ significantly in age, sex, prior heart failure, myocardial infarction and diabetes, or in the distribution of LV function. Nonsurvivors were more likely to have had urgent surgery rather than elective surgery and were more likely to have had a second rather than an initial operation.

View larger version (14K): [in this window] [in a new window]   Fig. 4. Influence plot of 2 independent readings of 30 angiograms by the same reader. The scale at the right represents the amount the overall correlation would change with the removal of a data point of the indicated size. The outlier represented by the large data point in the lower right quadrant was due to an inappropriately good rating being given to a totally occluded vessel that was not well visualized. With this outlier, Pearson’s r was 0.76 (P < .001). When the outlier was re-read according to the conventions developed for this method, this improved to 0.81.

View larger version (16K): [in this window] [in a new window]   Fig. 5. Correlation between blinded, independent determinations of the distal coronary diffuseness score by different readers. Pearson’s r was 0.83; P < .001.

	Discussion

Top Abstract Introduction Method Results Discussion Summary References

 
By limiting blood flow, narrow-caliber native vessels predispose to stasis and thrombosis, resulting in both graft failure and vessel occlusion distal to the point of graft insertion. Even when the graft and the native artery remain patent, the ischemia caused by inadequate blood flow may predispose to arrhythmia and depress ventricular function. The present results show that it is possible to objectively quantify this risk factor via a structured reading of the coronary angiogram and that the resulting measure of distal coronary artery disease strongly predicts in-hospital mortality independently of other risk factors. Such a measure therefore has the potential to significantly improve the objective prediction of operative risk by statistical models.

Previous studies.
Several previous studies have attempted to quantify the angiographic extent of coronary disease to predict operative risk. The method developed by Gensini ² considers the amount of myocardium supplied by each coronary segment and scores lesions according to reduction in luminal diameter. Distal segments are rated as graftable or not graftable; however, the extent of distal disease is not quantified. A method developed by Friesinger, O’Neal, and Ross ³ scores the main coronary trunks for reduction in cross-sectional area, but it does not account for major artery variability or significant stenoses in important branches and does not consider distal disease. The method developed by Brandt, Partridge, and Wattie ⁴ considers the amount of myocardium supplied by each arterial segment but scores only the most severe stenosis in an artery and does not quantify distal disease. Similarly, the Coronary Atherosclerosis Score of Jenkins, Harper, and Nestel ⁵ is based only on the extent and severity of proximal coronary stenoses. The Mean Atherosclerotic Score developed by Oysel and associates ⁶ takes into account the size, severity, and number of lesions in each of 15 coronary segments, but not the state of the vessel distal to these lesions. Neither of the 2 previous studies that included diffuseness of distal coronary disease in predictive models ^13,14 used an objective method to quantify this factor.

Limitations.
This was a small pilot study design to show that a structured reading of the coronary angiogram was feasible and that a semiquantitative measure of the severity of distal coronary disease derived from it was reproducible, reliable, and independently associated with surgical outcome. It was conducted at only 1 clinical site. For this measure to be useful in comparing results across centers, it would have to be demonstrated that a scoring system could be implemented in multiple sites and still be reproducible and reliable.

The limited number of patients included in this study necessarily limits the extent to which these findings can be generalized. Patients included were unselected, sequential groups of survivors and nonsurvivors of nonemergency CABG and are likely representative within these groups. However, combining these 2 cohorts produced a study population with a much higher surgical mortality than would occur among sequential patients referred for nonemergency CABG. This approach is valid for demonstrating that a reproducible and reliable semiquantitative measure of distal coronary disease is both achievable and associated with mortality. It cannot be used to develop predictive models, because the odds ratios associated with clinical predictors have extremely wide confidence bounds. Consequently, several factors known to predict surgical outcome from larger studies were not significantly associated with mortality in this study.

Because of its design, this study gives no information regarding operative mortality. The sequential sample of patients who died was accumulated over approximately 1 year, whereas the sample of survivors was accumulated over a much shorter period. Therefore, although 25% (34/134) of patients included in this study died, the operative mortality rate was in fact much lower.

A larger prospective study of unselected patients referred for CABG will be required to estimate the risk associated with each factor with any accuracy. Such a study would make it possible to construct receiver operating curves for predictive models with and without the diffuseness score included and to examine the improvement in the C index. ⁸ Ideally, this should be accomplished by developing a predictive model based on one sequential cohort of patients and testing its predictive accuracy on a second independent cohort.

Relationship of distal disease to other risk factors.
Several clinical risk factors known from larger studies to be associated with operative mortality were not statistically significant predictors in this study. This is likely because the small sample size of the present study limited its statistical power. The observation that distal coronary diffuseness score was strongly predictive in this study, despite its small sample size, suggests that this is an important risk factor. These results raise the possibility that diffuse distal coronary disease may be a common factor that contributes to the risk associated with clinical and demographic predictors such as advanced age, female sex, and diabetes. A much larger sample of patients will be required to determine the extent to which these factors "share variance." If such a finding were obtained, it might then be possible to select low- and high-risk subgroups from these "high-risk" populations based on their distal coronary anatomy.

Implications.
The need for better models of patient-specific surgical risk has been recognized both by the American College of Cardiology/American Heart Association Task Force on Coronary Artery Bypass Graft Surgery ¹⁵ and the Canadian Consensus Conference on Revascularization. ¹⁶ Weightman and associates ¹⁷ compared 4 different scores for predicting operative risk and found all had areas under receiver operating curves of 0.68 to 0.70. Other studies indicate that most of the prognostic information available from readily available clinical and demographic factors is contained in as few as 6 "core" variables. ^8,18 Such models, although useful in comparing results across centers, are imperfect in this regard. ¹⁹ They also lack sufficient sensitivity and specificity to identify individuals at particularly high risk. ²⁰

To be useful in predictive models, it is not sufficient that a risk factor be strongly predictive of risk. The factor must also have an objective measure that is valid, reproducible both within and between centers, and widely available. In the case of distal coronary disease, our results suggest that it would be possible to develop and standardize a scoring method based on an explicitly structured angiogram reading. The learning curve for the method used in the present study was short. Scoring an angiogram was straightforward and unambiguous once rules and conventions were established. These results suggest that such a measure is at least potentially available in all centers that perform coronary angiography and CABG. By contrast, the difficulties that would be associated with methods that require specialized equipment or standardized views, such as quantitative coronary angiography, would likely be insurmountable. However, since these results are limited to 2 angiographers, the broader applicability of this or any similar method would have to be demonstrated.

Wide availability poses a more difficult issue. After a relatively short learning curve, we found that the structured reading of the coronary angiogram took between 6 and 10 minutes, including the time it took to mount the film or CD on the viewer. Although this is quite short, it is unlikely that centers performing CABG have the resources to re-read the angiograms of all eligible patients for this purpose. Therefore, to be widely available, a standardized measure would have to be incorporated into the routine clinical practice. This could be accomplished either during the clinical reading of angiograms or during peer-review rounds in which patients proposed for CABG are reviewed. However, it would require development and acceptance of a standardized method, an adequate incentive for all of the angiographers to do it consistently, and a mechanism to ensure reproducibility and consistency of results.

	Summary

Top Abstract Introduction Method Results Discussion Summary References

 
Our results demonstrate that quantification of the diffuseness of distal coronary disease is possible on the basis of a structured visual analysis of the coronary angiogram and that the resulting score predicts in-hospital postoperative risk. If this result is borne out in larger prospective studies, and the problems involved with standardizing such a measure and making it widely available can be overcome, its inclusion in models of patient-specific risk may improve their accuracy. This would facilitate the comparison of results within and across institutions and improve our ability to objectively assess the risk of CABG in individual patients.

	References

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