Author + information
- Received April 21, 2011
- Revision received July 13, 2011
- Accepted August 9, 2011
- Published online November 29, 2011.
- Gary R. Small, MB, ChB, PhD*,
- Yeung Yam, BSc*,
- Li Chen, MSc*,
- Osman Ahmed, BSc*,
- Mouaz Al-Mallah, MSc, MD†,
- Daniel S. Berman, MD‡,
- Victor Y. Cheng, MD‡,
- Kavitha Chinnaiyan, MD§,
- Gilbert Raff, MD§,
- Todd C. Villines, MD∥,
- Stephan Achenbach, MD¶,
- Matthew J. Budoff, MD#,
- Filippo Cademartiri, PhD, MD††,§§§,
- Tracy Q. Callister, MD††,
- Hyuk-Jae Chang, PhD, MD‡‡,
- Augustin Delago, MD§§,
- Allison Dunning, MS∥∥,
- Martin Hadamitzky, MD¶¶,
- Jorg Hausleiter, MD¶¶,
- Philipp Kaufmann, MD##,***,
- Fay Lin, MD***,†††,
- Erica Maffei, MD**,††,
- James K. Min, MD***,†††,
- Leslee J. Shaw, PhD‡‡‡ and
- Benjamin J.W. Chow, MD*,* ()
- ↵*Reprint requests and correspondence:
Dr. Benjamin J. W. Chow, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada
Objectives We sought to determine the incremental prognostic value of 64 multi-slice coronary computed tomography angiography (CCTA) in coronary artery bypass graft (CABG) patients.
Background Prognostication in CABG patients can be difficult. Anatomical assessment of native coronary artery disease and graft patency might provide useful information, but the utility of CCTA in the assessment of CABG patients is unknown.
Methods Six hundred fifty-seven CABG patients with all-cause mortality follow-up were identified from a multicenter CCTA registry, of 10,628 patients from 5 CCTA centers. Clinical risk was profiled with modified logistic and additive EuroSCOREs (European Systems for Cardiac Operative Risk Evaluations). The CCTA defined coronary anatomy. Patients were classified by unprotected coronary territory (UCT) or a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS).
Results Forty-four deaths occurred during a mean follow-up of 20 months. Left ventricular ejection fraction, creatinine, age, severity of native vessel disease, UCT, CAPS, and EuroSCOREs were univariate predictors of mortality (p &amp;amp;amp;lt; 0.001). In multivariate analysis with additive EuroSCORE, UCT (p = 0.004) and CAPS were predictive of events (p &amp;amp;amp;lt; 0.001). In comparison with additive EuroSCORE, CAPS score was associated with a 27% net reclassification index.
Conclusions Coronary computed tomography angiography provides incremental anatomical data to clinical risk assessment to help determine the prognosis of patients after CABG. The CAPS evaluation with CCTA might help identify those patients at highest risk.
Coronary computed tomography angiography (CCTA) is an emerging technique, with the potential ability to risk-stratify coronary artery bypass (CABG) patients on the basis of native vessel anatomy and graft patency (1–4). The utility of risk stratification of CABG patients on the basis of anatomy has been shown with invasive angiography but has not been well-studied with CCTA (5). A noninvasive anatomical test might be desirable, acknowledging that complications from invasive coronary angiography are higher in the CABG population (6).
There are limited data demonstrating the prognostic utility of CCTA in CABG patients. With a multicenter CCTA registry, we sought to evaluate the incremental prognostic value of CCTA to predict all-cause death in CABG patients.
From February 2004 to June 2010, 10,628 consecutive patients underwent CCTA at 5 centers and were prospectively entered into a multicenter cardiac CCTA registry. The CCTA patients with a history of CABG and coronary and graft CCTA data were selected for study analysis. The study was approved by the Human Research Ethics Board at each participating center, and all patients provided written informed consent.
Modified additive and logistical European Systems for Cardiac Operative Risk Evaluation (EuroSCORE) were used. Acute pre-operative markers of operative and anesthetic risk were not consistently available (such as pre-operative state, acute endocarditis, neurological dysfunction, pulmonary hypertension, ventricular septal rupture, or additional surgery other than CABG) and therefore were omitted. With the additive EuroSCORE, patients were categorized as low (0 to 2), intermediate (&amp;amp;amp;gt;2 to 5), or high risk (&amp;amp;amp;gt;5); and for the logistic EuroSCORE, patients were categorized as low (0 to 3), intermediate (&amp;amp;amp;gt;3 to 10), high (&amp;amp;amp;gt;10 to 20), and very high risk (&amp;amp;amp;gt;20) (7–9).
CCTA measures (coronary artery disease severity and left ventricular ejection fraction)
Native coronary and bypass graft CCTA image acquisition and interpretation were performed with single or dual source 64-slice computed tomography scanners. Coronary and graft diameter stenoses were graded with a 4-point score (normal, mild [&amp;amp;amp;lt;50%], moderate [50% to 69%], severe [≥70%]).
Patients were categorized as having 1, 2, or 3 coronary artery disease (CAD) according to the occurrence of severe disease (≥70%) in the right coronary, left anterior descending, and left circumflex territories. Left main disease was classified as 2-vessel disease for patients with a right dominant circulation and 3-vessel disease for those with a left dominant circulation. Branch vessel disease was apportioned to the parent artery. Revascularization was classified in terms of the territories supplied by grafts (right coronary, left anterior descending, or left circumflex). Bypass grafts to branch vessels were assigned to the parent artery. A coronary territory was protected if the native artery supplying the territory did not have severe disease or if the territory was supplied by a nonstenotic graft (5).
Two models of CAD severity were assessed: unprotected coronary territories (UCT), and coronary artery protection score (CAPS) (5,10). The UCT documented the number of vascular territories that were at risk, whereas CAPS combined the severity of both native and graft disease (Table 1).
Patient follow-up was performed by each local institution by telephone and/or a national death registry. Centers in the United States used the Social Security Death Index (11).
The statistical software SAS (version 9.2, SAS Institute, Inc., Cary, North Carolina) and PASW (Statistics version 18, SPSS, Chicago, Illinois) were used for all statistical analyses, and statistical significance was defined as p &amp;amp;amp;lt; 0.05. Continuous variables were expressed as means and SDs, and categorical variables were presented as frequencies with percentages. Wilcoxon rank-sum test was used to compare continuous variables, and Fisher exact test or chi-square test was used for categorical variables. In 29% of patients, left ventricular ejection fraction data were not recorded at CCTA and completed by multiple imputation procedures assuming missing at random in accordance with the registry protocol.
The prognostic value of CAPS was assessed for both univariable and multivariable associations with all-cause mortality. Unadjusted comparisons of all-cause mortality were performed on survival analysis log-rank tests. Annual event rates were calculated by dividing the Kaplan-Meier event rates by mean years of follow-up. Risk adjusted analyses were performed with Cox proportional hazard models to determine the independent prognostic value of CAPS by controlling for clinical predictors (additive EuroSCORE) and creating adjusted survival curves. Model overfitting was considered, and the proportional hazards assumption was met. The incremental value of CAPS was calculated by defining the clinical predictors model followed by the addition of CAPS. The area under receiver-operator characteristic curves (95% confidence intervals [CIs]) was compared to evaluate the discrimination ability of CAPS over clinical predictors (12). The net reclassification improvement (NRI) assessed the improvement of reclassification with CAPS (13). For calculating the NRI, rescaled individual predicted risks from models with and without CAPS were compared with established EuroSCOREs risk thresholds (7,14,15).
From the 10,628 patients undergoing CCTA, diagnostic data were available for 667 patients with previous CABG surgery. Follow-up was complete on 657 patients (98.5%). The mean follow-up period was 20 ± 10 months (Table 2). The majority of patients had moderate- to high-risk EuroSCOREs (Table 3).
Clinical characteristics associated with mortality
At follow-up, all-cause mortality was observed in 44 patients (6.7%) with an annualized mortality rate of 3.8%. Death occurred in 35 of the 322 patients (10.9%) with triple-vessel CAD, compared with 3 (1.9%) of 160 patients with single-vessel CAD (Table 4). Patients with all 3 coronary territories protected had a crude mortality rate of 3.9%. In contrast, patients with 3-vessel CAD and 0 protected coronary territories experienced a crude mortality rate of 17.4%.
In the univariable Cox proportional hazard models, increased hazard ratios for death were associated with advanced age, left ventricular ejection fraction, creatinine, severity of native vessel disease, UCT, and CAPS (Tables 4 and 5⇓). Both the additive and logistic EuroSCOREs were predictive of all-cause mortality (Table 5).
Cox models of risk-adjusted outcomes
The EuroSCORE was used to determine the incremental value of CCTA. In multivariate analyses with the EuroSCORE, UCT (p = 0.004) and CAPS (p &amp;amp;amp;lt; 0.001) were independent predictors of all-cause mortality (Fig. 1, Table 6).
Receiver-operator characteristic curves were created for the additive EuroSCORE, UCT, and CAPS. Area under the curve was 0.64 (95% CI: 0.56 to 0.71) for additive EuroSCORE; 0.68 (95% CI: 0.60 to 0.76) for UCT + additive EuroSCORE (p = 0.08); and 0.75 (95% CI: 0.68 to 0.81) for CAPS + additive EuroSCORE (p &amp;amp;amp;lt; 0.001) (Fig. 2, Table 6). For this reason, CAPS was used in the NRI calculation. The NRI was performed and demonstrated that, after clinical risk stratification with additive EuroSCORE, CAPS was able to reclassify 27.2% (p = 0.003) of patients (Table 7).
Our analysis demonstrates the usefulness of CCTA to determine prognosis in the CABG population. The CAPS, as assessed by CCTA, is incremental to clinical predictors. The study extends our current understanding of the role of CCTA and highlights the utility of this technique in the CABG population.
We also assessed the prognostic utility of UCT and determined that it did have incremental value over the EuroSCORE in predicting all-cause mortality (p = 0.004) (10). The UCT, however, appeared less predictive than CAPS. It should be noted, however, that in earlier descriptions of UCT different outcomes (all-cause mortality vs. nonfatal MI and cardiac death) were used (10).
To understand the value of CAPS, the NRI was calculated. The NRI demonstrated that, after clinical evaluation, CAPS was able to appropriately reclassify 27.2% of patients.
Overall, the annualized mortality in the study cohort was 3.8%. Higher levels of annualized mortality rates were seen with accumulating severity of native vessel disease and CAPS score (Fig. 1). The use of CAPS as a measure of native CAD and graft patency highlights important differences in prognosis between different anatomical subgroups and emphasizes that prognosis in CABG patients does vary. Such results suggest that certain populations of CABG patients might require closer clinical surveillance.
Because cardiac death was not available at all sites, all-cause mortality was used as the outcome variable. Although the authors recognize that noncardiac deaths might have been included in the analysis, 87% of all CABG patient deaths are cardiac (16). The time interval between CABG surgery and CCTA was not available and therefore could not be factored into the analysis. Many of the pre-operative findings and markers of anesthetic risk were absent; therefore, our modified EuroSCORE calculation might have under-estimated its true prognostic value. The registry could not distinguish between the various grafts used; therefore, we were unable to examine the influence of different arterial and venous grafts on prognosis. Not all CCTA studies will be diagnostic in CABG patients. Because the database did not identify nonevaluable CCTA studies, the results of this study should only apply to diagnostic CCTA studies. The mean radiation exposure was nearly 20 mSv; however, recent technological advances have reduced radiation exposure significantly, and therefore it is unlikely this value represents current CCTA practice.
This study suggests that CCTA has independent and incremental prognostic value in CABG patients in predicting all-cause mortality. Patients with a low CAPS have much better outcomes than those with a high CAPS score. Incremental to the clinical predictors, CCTA-derived CAPS appropriately reclassified 27.2% of patients. Further studies are required to understand the role of CCTA in managing patients after CABG (8,9).
The authors extend their gratitude to the investigators at each participating center.
Dr. Small is supported by the University of Ottawa Cardiology Research Endowment Fund Fellowship. Dr. Achenbach has received research grants from Siemens and Bayer and speaker honoraria from Siemens. Dr. Raff has received research grants from Siemens. Dr. Cademartiri has served on the Speaker's Bureau for Bracco, has served as a consultant for Servier, and has received grant support from GE Healthcare. Dr. Hausleiter has served on the Speaker's Bureau for Siemens. Dr. Kaufmann is supported by the Swiss National Science Foundation. Dr. Min has received modest support from GE Healthcare. Dr. Chow has received support from GE Healthcare, TeraRecon, Pfizer, and AstraZeneca; and is supported by Canadian Institutes of Health Research New Investigator Award #MSH-83718.
- Abbreviations and Acronyms
- coronary artery bypass graft
- coronary artery protection score
- coronary computed tomography angiography
- confidence interval
- European Systems for Cardiac Operative Risk Evaluation
- net reclassification improvement
- unprotected coronary territory
- Received April 21, 2011.
- Revision received July 13, 2011.
- Accepted August 9, 2011.
- American College of Cardiology Foundation
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