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a Yvonne Viens, SGM, Research Institute, Saint Vincent Mercy Medical Center, Toledo, Ohio
b Division of Cardiothoracic Surgery, Regional Heart and Vascular Center, Saint Vincent Mercy Medical Center, Toledo, Ohio
c Department of Surgery, University of Toledo, College of Medicine, Toledo, Ohio
Accepted for publication September 19, 2008.
* Address correspondence to Dr Habib, Cardiovascular and Pulmonary Research, Yvonne Viens, SGM, Research Institute, St. Vincent Mercy Medical Center, 2222 Cherry St, MOB2, Suite 1250, Toledo, OH 43608 (Email: robert_habib{at}mhsnr.org).
| Adult cardiac surgery:
The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.
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| Abstract |
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Methods: We compared propensity-adjusted 12-year survival in two contemporaneous multivessel primary CABG cohorts with all patients receiving 2 or more grafts: (1) all-arterial cohort (n = 612; 297 three-vessel disease [49%]); and (2) single internal thoracic artery (ITA) plus saphenous vein (SV) cohort (n = 4,131; 3,187 three-vessel disease [77%]).
Results: Early (30-day) deaths were similar for the all-arterial and ITA/SV cohorts (8 [1.30%] versus 69 [1.67%]) whereas late mortality was substantially greater for the ITA/SV cohort (85 [13.9%] versus 1,216 [29.4%]; p < 0.0001). The risk-adjusted 12-year survival was significantly better for all-arterial (with a risk ratio [RR] = 0.60; 95% confidence interval [CI]: 0.48 to 0.75; p < 0.001), but this benefit was true only for three-vessel disease (RR = 0.58; 95% CI: 0.43 to 0.78; p < 0.001) and not for two-vessel disease (RR = 0.97; 95% CI: 0.66 to 1.43; p = 0.89). The all-arterial survival benefit was also true for varying risk subcohorts: no diabetes mellitus (RR = 0.50; 95% CI: 0.37 to 0.69), diabetes mellitus (RR = 0.77; 95% CI: 0.56 to 1.07), ejection fraction 40% or greater (RR = 0.60; 95% CI: 0.45 to 0.78), and ejection fraction less than 40% (RR = 0.62; 95% CI: 0.40 to 0.98). Lastly, the multivariate analysis indicated a strong long-term effect of completeness of revascularization, particularly for all-arterial patients, so that compared with patients with two grafts, survival was significantly better when three grafts (RR = 0.54; 95% CI: 0.33 to 0.87) or four grafts (RR = 0.40; 95% CI: 0.21 to 0.76) were completed.
Conclusions: All-arterial revascularization is associated with significantly better 12-year survival compared with the standard single ITA with saphenous vein CABG operation, in particular for triple-vessel disease patients. The completeness of revascularization of the underlying coronary disease is critical for maximizing the long-term benefits of arterial-only grafting.
The left internal thoracic artery (LITA) to left anterior descending artery (LAD) graft has become the standard of care in coronary artery bypass graft surgery (CABG) after the long-term survival benefit demonstrated in the mid 1980s [1, 2]. This benefit is believed to be a result of the superior patency of LITA grafts compared with saphenous vein (SV) [1–4]. Consequently, surgeons have extrapolated their LITA results to other arterial conduits and are currently using the right internal thoracic artery (RITA) [5–10], radial artery (RA) [9–13], or gastroepiploic artery conduits with increasing frequency [14].
Over the past decade, several studies have reported an incremental survival benefit by increasing the number of arterial grafts [5, 6, 8, 11], and this has increased interest in avoiding vein grafts altogether in favor of all-arterial CABG for multivessel coronary disease. Such all-arterial revascularization is usually accomplished through varying combinations of multiple arterial conduits and grafting methods (eg, T or Y grafts) [15–17]. Most reports thus far have focused on perioperative results demonstrating that all-arterial CABG is a safe option with excellent early outcomes [18–20]. Yet, the corresponding midterm to long-term survival results for all-arterial CABG in two- and three-vessel disease patients is presently very limited [21, 22]—especially compared with the current standard ITA with vein operation [22].
In this investigation, we analyzed a large multivessel coronary revascularization experience with the primary aim of testing the hypothesis that all-arterial CABG will confer a significant long-term survival benefit compared with the current standard-of-care operation of using a single ITA (usually LITA to LAD) with additional SV grafting. A second aim of this study was to determine if the all-arterial CABG survival benefit applies to specific comorbidity subcohorts of the surgical multivessel coronary artery disease population.
| Material and Methods |
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The CABG patients were excluded if they had single-vessel disease only, in case of a single completed graft; if they underwent any concomitant acquired or congenital cardiac or aortic surgery; or if they had emergency salvage, in case of prior sternotomy or in case of preoperative renal failure. The all-arterial study population was derived from the 1992 to 2006 primary isolated two-vessel and three-vessel disease CABG patients revascularized with two or more arterial conduits. This grouping was based on actual constructed grafts, even if a vein graft was originally planned. A corresponding multigraft (two or more), primary and isolated CABG comparison cohort was derived from the contemporaneous single ITA with additional SV multivessel disease CABG population. Patients were excluded from the ITA/SV cohort if they received other arterial grafts. Cardiopulmonary bypass was used in a large majority of patients, with only 148 off-pump cases (3.1%) among the 4,773 overall patients, including 97 of 4,131 ITA/SV patients (2.3%) and 51 of 612 all-arterial patients (8.3%).
Coronary Grafts
The surgical approach and RA harvesting were previously described [11, 13]. Aortocoronary grafting was the method of choice (more than 95%) unless aorta quality was suboptimal or there were other considerations. All ITA/SV patients received a single ITA graft (usually a LITA to LAD unless no LAD disease) with one or more additional vein grafts. All-arterial revascularization (two or more grafts) was done using a combination of ITA and RA (556 of 612; 90.8%), ITA-only grafting (51 of 612; 8.3%), or RA-only grafting (0.8%; Table 1, and Appendix Table 1
*). Bilateral dissections of RA (46%) and ITA (19%) were frequent, and they were commonly used as sequential grafts (178 of 612; 29.1%; Table 1).
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All-Arterial CABG Propensity Score Model
The all-arterial and ITA/SV cohorts exhibited significant demographic and risk factor differences (Table 2, and Appendix Table 2
*). Such differences confound outcome comparisons in observational treatment groups [23, 24]. To minimize such confounding, we used propensity score adjustment where all-arterial grafting was considered as treatment [24]. Briefly, the probability that a patient received only arterial grafts was defined by a propensity score derived from a nonparsimonious logistic multivariate model applied to all patients. A total of 47 preoperative risk factors, demographics, and operative variables were entered into the model irrespective of their significance (Appendix Table 2
*). Coronary artery disease and number of grafts were incorporated into the model through a completeness of revascularization index (CRI) defined as the difference between the number of grafts and vessel disease. Accordingly, patients were grouped as incomplete (CRI < 0), complete (CRI = 0), or complete-plus (CRI > 0). Time of surgery was also entered as a continuous month of series variable (January 1992 = 1, up to December 2006 = 180) to account for the varying frequency of all-arterial CABG over time. Highly redundant variables were avoided. Expectedly, the resulting propensity scores were distinctly different (mean ± SD: 0.296 ± 0.204 all-arterial versus 0.104 ± 0.121 ITA/SV; p = 0.0000). The propensity model C-statistic (area under the receiver operating characteristic curve) was 0.823, indicating excellent discrimination.
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2 or Fisher's exact test for categorical variables and the unpaired t test for continuous variables. Because only 12 of 612 all-arterial multivessel CABG patients underwent CABG during 1992 through 1994 (all are currently alive), the survival analysis follow-up was truncated at 12 years so that the 77 deaths occurring after the 12th postoperative year for the ITA/SV cohort do not bias the analysis in favor of all-arterial CABG. Kaplan-Meier survival plots were derived and compared by the log-rank (Mantel-Cox) test. Risk-adjusted late survival comparisons were done using bivariate proportional hazard Cox regression analysis with the continuous logit propensity score and the grafting method (all-arterial versus ITA/SV) as the two covariates. Early deaths occurring within 30 days of CABG were excluded from this analysis to avoid violation of the proportional hazard assumption in the Cox regression model. Midterm (6-year) and long-term (12-year) survival data were also compared using standard Kaplan-Meier analysis based on propensity score quintile groups. Statistical analysis was conducted with SPSS version 15.0 software (SPSS, Chicago, IL). A p value less than 0.05 indicated significance. | Results |
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The number of completed grafts differed substantially for the all-arterial versus ITA/SV groups, with an average of 2.62 ± 0.77 versus 3.26 ± 0.83 total grafts, respectively (p < 0.0001). The lower number of grafts in all-arterial patients was true in case of both two-vessel disease (2.24 ± 0.51 versus 2.58 ± 0.67; p < 0.0001) and three-vessel disease (3.02 ± 0.81 versus 3.46 ± 0.77; p < 0.001). Incomplete revascularization (Table 2) was more frequent in the all-arterial three-vessel disease subcohort compared with the corresponding ITA/SV group (incomplete, 27.3% versus 7.8%; p < 0.001). Note that the greater incidence of incomplete revascularization in the all-arterial three-vessel disease group is a result of two factors: (1) over the second half of the study, a majority of patients routinely receive two arterial grafts (1 ITA, 1 RA); and (2) hence, those with a planned third graft (venous or arterial) that could not be constructed were, by design, considered as incomplete all-arterial patients.
A total of 1,373 known deaths (28.9%) occurred in the 4,743 overall series, classified into 93 all-arterial deaths (15.2%) and 1280 ITA/SV deaths (31.0%). Early (30-day) mortality was similar for the all-arterial group (1.30%; 8 deaths) and the ITA/SV group (1.67%; 69 deaths). There were no deaths among the 12 all-arterial patients with follow-up of more than 12 years. In contrast, there were 77 known deaths among the 843 ITA/SV patients with more than 12 years of follow-up. Thus, heretofore, all survival analysis will be restricted to 12-year outcomes.
Unadjusted 12-year survival was substantially better for all-arterial patients (p < 0.0001; unadjusted risk ratio [RR] = 0.55; 95% confidence interval [CI]: 0.44 to 0.68). That, however, was less pronounced in two-vessel disease patients (p = 0.12; RR = 0.77; 95% CI: 0.55 to 1.08) compared with three-vessel disease patients (p < 0.0001; RR = 0.52; 95% CI: 0.38 to 0.71; Fig 1).
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40%: RR = 0.62; 95% CI: 0.40 to 0.98; p = 0.039) (see Appendix Table 3
*).
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| Comment |
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The practice of using multiple arterial conduits for CABG is supported by reports showing their early operative morbidity and mortality results to be equivalent or better than for CABG with a single arterial graft [5–11]. Also, several authors have shown that bypass grafts constructed using RITA and RA exhibit superior patency compared with those constructed with vein [4, 11], and some have reported significantly better longer term outcomes when two rather than one arterial conduits are used for CABG [5, 7, 8, 11]. Lytle and coworkers [7] and Rankin and colleagues [8] analyzed large retrospective patient series and found a late survival benefit is achieved when two ITA grafts are used rather than one. More recently, comparing propensity-matched patient cohorts, we demonstrated that a significant survival benefit is achieved when RA is used as a second arterial graft versus LITA-LAD with additional vein grafts [11]. Guru and associates [12] reviewed the Ontario, Canada, CABG experience and showed that the use of multiple arterial grafts is associated with better survival and less morbidity. Such accumulating evidence favoring the use of a second arterial graft has increased interest in all-arterial revascularization as a presumed optimal form of CABG.
The objective evidence that all-arterial CABG will result in better long-term outcomes compared with the conventional single ITA plus vein operation is very limited. In a series of small randomized trials, Muneretto and coworkers [19, 20] reported similar perioperative morbidity and mortality for (1) all-arterial CABG—done through composite ITA and RA grafting—and (2) single ITA/SV CABG. However, they found all-arterial CABG to be associated with fewer midterm (less than 2 years) adverse outcomes defined as late death, nonfatal myocardial infarction, angina recurrence, graft occlusion, or percutaneous intervention. To our knowledge, only Légaré and colleagues [22] have reported survival data beyond 2 years comparing all-arterial revascularization achieved through ITA and RA grafting to the conventional single ITA with vein CABG. They, however, report statistically similar risk-adjusted 7-year all-cause mortality and composite mortality/cardiac readmission for the two grafting approaches [22].
Our long-term multivessel CABG results contrast sharply with the findings reported by Légaré and collagues [22]. We found that all-arterial CABG is associated with a significantly better 12-year all cause mortality, primarily owing to a large survival benefit observed among three-vessel coronary disease patients. Importantly, our analysis indicated that this long-term survival benefit is substantially dependent on the number of completed grafts—or completeness of revascularization (Fig 4). The latter underscores the need to address all (or as many as possible) of the coronary lesions during revascularization to maximize the achievable survival benefit of all-arterial CABG. Also noteworthy was that the observed all-arterial survival benefit versus single ITA with vein becomes evident as early as 2 to 3 years after CABG, and that is substantially earlier than the delayed survival benefit (more than 10 years) reported with bilateral ITA versus single ITA grafting [7, 8]. Although it is possible that this difference reflects a benefit of avoiding vein grafting altogether in all-arterial patients, this study is not designed to address this question.
An important characteristic of our all-arterial series is the predominant reliance on RA grafts (92% received RA grafts; Table 1), including the frequent use of both RA conduits and sequential RA grafts. Also, except for the LITA pedicle graft, a very large majority (more than 95%) of all other arterial grafts were aortocoronary grafts. We contend that this RA-heavy approach for secondary arterial conduits is justified by several factors. First, compared with RITA or gastroepiploic artery, RA conduit harvesting is less technically demanding and can be done while the LITA is being dissected, reducing time in the operating room and under anesthesia. Second, RA use is associated with substantially less harvest site morbidity compared with other arterial or SV conduits [25]. The presence of certain risk factors—such as diabetes, advanced age, significant obesity, or chronic lung disease—have historically limited use of bilateral ITA grafts [7]. Unfortunately, these patients represent an increasingly larger fraction of the surgical coronary revascularization population, which partly explains why only 4% to 5% of the population undergoing CABG in the United States received bilateral ITA grafts in 2006 and 2007, according to the STS national database. At our institution, nearly 60% of CABG patients received one or more RA grafts compared with fewer than 5% receiving RITA.
Long-term survival after coronary revascularization is presumed to be in direct correlation with the long-term patency of the constructed grafts. Consequently, the superior survival we observe among all-arterial patients compared with ITA/SV patients may be a reflection of increased vein graft failure. Some have suggested that using RA grafting in attempts to achieve total arterial revascularization may underserve patients [26]. That is contradicted, however, by several prospective and retrospective reports showing superior RA patency compared with vein [11, 27, 28]. The vasoactive response of arterial grafts to different stimuli has been the focus of extensive investigation, since it has been implicated as one of the most important causes of early graft failure [29, 30]. The angiographic vasospastic abnormalities observed in RA and other arterial grafts or "string sign" are predominantly seen in grafts placed to subcritically diseased coronary targets where a native vessel competitive flow is present [27]. This flow-dependent phenomenon is well illustrated and reported in angiographic studies [29, 30].
Limitations of our study include its retrospective and observational nature. Ideally, the question of whether all-arterial CABG will improve long-term outcomes is best addressed in randomized, prospective, and multicenter trials. Yet, the prospect of completing such a large long-term study is both impractical and prohibitively expensive. Second, the possibility of residual confounding factors is possible. However, we believe that the comprehensiveness of the propensity model used in the risk adjustment and the multivariate modeling mitigate this concern. Third, the cause of death among our patient population is unknown, and consequently, the death rate may be independent of cardiac factors. We contend that the likelihood of noncardiac deaths explaining the risk-adjusted differences in late survival is unlikely, especially after age adjustment. To minimize this concern, we excluded from this analysis all patients diagnosed with preoperative renal failure, given their propensity for late noncardiac death. This omission of preoperative renal failure patients also helped avoid potential residual confounding effects, given their greater prevalence among ITA/SV patients. Lastly, our analysis would have been enhanced substantially if long-term graft patency comparisons in these patients were available to explain the differences in survival data.
In conclusion, when compared with patients undergoing single ITA and SV CABG, all-arterial revascularization is associated with significantly better 12-year survival, in particular for triple-vessel disease patients. We present evidence that completeness of revascularization of the underlying coronary vessel disease is critical for maximizing the achievable long-term benefits of total arterial grafting.
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| Acknowledgments |
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| Footnotes |
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The Appendix is available online only. To access it, please visit: http://ats.ctsnetjournals.org and search for the article by Zacharias, Vol. 87, pages 19–26.e1–2. ![]()
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