Coronary revascularization may be performed for relief of angina symptoms and, in specific patient subgroups, to reduce the incidence of myocardial infarction (MI) and long-term mortality. Current US and European clinical practice guidelines recommend coronary bypass graft surgery (CABG) over percutaneous coronary intervention (PCI) for the treatment of multivessel coronary artery disease (MVCAD) and confer a class IIb (of uncertain benefit) recommendation to PCI for improvement in survival.^1-3 Prior studies suggest that the magnitude of clinical benefit attributable to coronary revascularization is, at least in part, proportional to the completeness of revascularization achieved by either CABG or PCI.^4-6 Although these studies suggest that incomplete revascularization (IR) is associated with persistent hazard for death, MI, or additional revascularization procedures, they are limited by their observational and retrospective study designs, lack of randomization, and reliance on the ascertainment of revascularization completeness by the treating physician. Furthermore, the lack of a uniform definition for complete revascularization (CR) or accepted metrics to quantify both the presence and magnitude of IR have contributed to conflicting reports on the clinical importance of complete revascularization from observational studies, and no large-scale randomized clinical trial has yet tested the hypothesis for superiority of CR (vs IR). In the context of recent information it is appropriate to review what is currently known regarding completeness of coronary revascularization, its impact on clinical outcomes, and its utility in the therapeutic decision algorithm for choosing an optimal revascularization strategy.

The Challenge of Definition

Numerous definitions have been used to describe the completeness of coronary revascularization and have included anatomic, functional, numerical, score-based, and physiology-based criteria (Table 1). These definitions vary with respect to target vessel size, target stenosis location, and the presence or absence of objectively documented ischemia. Although a recent large-scale meta-analysis⁷ demonstrated a differential, salutary effect of CR (vs IR) on survival (following PCI or CABG), as well as MI and repeat revascularization (following PCI) regardless of the definition (anatomic vs physiologic) for CR employed, much focus has currently been directed toward more accurate descriptive quantification regarding not only the presence, but also the magnitude of revascularization completeness. In this regard, the residual SYNTAX score appears to provide a standardized, graded quantification of IR and has been correlated with adverse clinical events, including mortality following PCI in patients presenting with acute coronary syndrome,⁸ multivessel stable is-chemic heart disease,⁹ and unprotected left main coronary artery disease (CAD).¹⁰ The baseline (pre-PCI) SYNTAX score, which describes angiographic lesion complexity using 12 readily available angiographic variables, has been correlated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in follow-up through 5 years after PCI but not CABG,¹¹ and has been incorporated into clinical practice guideline recommendations for selection of revascularization strategy. The SYNTAX score has been validated and employed in a tertile distribution to describe relative risk for death, MI, stroke, and requirement for repeat revascularization following PCI.^8,12,13 More recently, both the residual SYNTAX score (calculated after PCI) and the ▵ SYNTAX score (difference between pre- and post-PCI scores) have been evaluated for prognostic discriminatory ability following PCI.^8,12 Despite demonstrated colinearity of the baseline and residual SYNTAX scores,^8,10,12 the residual SYNTAX score provides significant incremental predictive accuracy for late adverse clinical outcomes and appears to perform best when applied in a graded (tertile) quantitative fashion. Thus, the residual SYNTAX score appears to be the best currently available and validated descriptor of residual atherosclerotic burden following PCI revascularization. More recently, a universal definition of IR that integrates anatomic (coronary angiography) and physiologic (fractional flow reserve [FFR]) data has been proposed.¹⁴ This definition of IR is based on the inability to treat coronary segments with stenoses ≥ 50% to 70% severity with an FFR ≤ 0.80, or stenoses > 70% without FFR assessment, that supply a significant region of viable myocardium. Although the baseline SYNTAX score has relatively poor prognostic capacity after CABG revascularization, investigations are currently underway to determine the discriminatory predictive capacity of the residual SYNTAX score following CABG.

The Importance of Complete Revascularization

Recent randomized studies and meta-analyses suggest that CR is more often achieved with CABG than PCI (Figure 1).^7,15,16 Furthermore, CR has been associated with significant reductions in long-term mortality, MI, and repeat revascularization procedures. Although the association between CR and reduced risk for cardiovascular events may be causal, through reduction or elimination of ischemia, important covariate imbalances exist between the CR and IR groups that have been compared based on the various determinants of IR, as well as the lack of randomized assignment to CR versus IR. Indeed, IR was more frequent in PCI-treated patients with chronic total coronary occlusion, bifurcation stenoses, and diffuse or small vessel coronary disease.¹⁷ Similarly, unstable angina presentation, diffuse or small vessel disease, and the total number of target coronary stenoses predicted IR following CABG.¹⁷ Thus, IR may be a surrogate marker for a greater baseline ischemic burden and more advanced CAD, which is less amenable to revascularization by either PCI or CABG. Although the baseline SYNTAX score prior to revascularization appears to be proportional to the likelihood of IR (Figure 2) following both PCI or CABG, this relationship is more marked for PCI.¹⁷ Indeed, for patients in the lowest tertile of baseline SYNTAX scores (≤ 22) rates of IR were similar for PCI and CABG (31% vs 27%, respectively). Conversely, patients in the highest tertile of SYNTAX scores (≥ 33) had a disproportionate increase in IR following PCI (57%) versus CABG (44%). Thus, both the incidence of IR and the relative advantage of CABG (vs PCI) for achieving CR are directly proportional to the complexity of CAD as reflected by baseline SYNTAX score tertile.

The Consequences of Incomplete Revascularization

IR by PCI is a powerful predictor of death or MI in follow-up even in the absence of a chronic total coronary occlusion.^4,12,13,18 Similarly, IR by PCI has been correlated with an increased incidence of MI, repeat revascularization, and MACCE. Although IR has been analyzed using a binary (0 vs > 0) definition for residual SYNTAX score, further quantification as a tertile function appears to provide greater discriminatory accuracy. Using a residual score of 0 as the referent, increasing tertiles of residual SYNTAX score (> 0-4, > 4-8, and > 8) provided incremental predictive accuracy for all-cause death regardless of the baseline SYNTAX score tertile (Figure 3).¹² In addition, a graded and direct relationship of residual SYNTAX score tertile was observed for the occurrence of all-cause revascularization and MACCE through 5-year follow-up after PCI (Figure 4). This relationship must be viewed in context and tempered by the highly significant trends in the complexity of both clinical and angiographic covariates by tertile of residual SYNTAX score (Table 2).

In the SYNTAX trial, MACCE through 5-year follow-up was statistically significantly increased following IR by PCI but not CABG (Figure 5). This observation suggests a differential impact of IR on clinical outcomes for PCI (vs CABG). As noted previously, both the incidence of IR following PCI, as well as the relative advantage of CABG over PCI for achieving CR, is proportional to coronary disease complexity as reflected by baseline SYNTAX score tertile. Those patients in the highest tertile of baseline SYNTAX scores have a disproportionate increase in the incidence of IR following PCI when compared with patients in the lowest tertile of SYNTAX scores. Although the comparable rates of IR following CABG were 44% and 27% (highest and lowest SYNTAX score tertiles, respectively), the incidence of MACCE to 5 years following CABG was similar for patients in both the lowest and highest SYNTAX score tertiles (26.8% and 24.1%, respectively) but was not similar following PCI (33.3% vs 41.9%, respectively). The relative and disproportionate contribution of IR following PCI (vs CABG) to the incremental incidence of MACCE across tertiles of SYNTAX score cannot be determined definitively but is no doubt a major contributor to the differential between PCI and CABG outcomes in patients with the most complex CAD. Thus, this difference in completeness of revascularization achieved by PCI (vs CABG) and the relative disproportionate weight of adverse events attributable to IR following PCI may, at least in part, contribute to the relative survival advantage attributed to CABG (vs PCI) in both randomized clinical trials of revascularization for MVCAD^11,16 as well as observational studies.¹⁹ This disproportionate impact of IR (vs CR) for outcomes following PCI more so than CABG is supported by a recent meta-analysis of 35 studies involving 89,833 revascularized patients (of whom 50.5% achieved CR), which concluded that among patients treated with CABG, CR was not associated with a reduction in either MI (risk ratio [RR] 0.69; 95% confidence interval [CI], 0.44-1.10; P = .12) or repeat revascularization (RR 0.92; 95% CI, 0.67-1.28; P = .64) procedures.⁷ This observation suggests that the degree of revascularization completeness may not be as important in reducing MI or repeat procedures following CABG as long as the three major epicardial vessels are grafted. Conversely, a confounding effect due to the small number of studies which reported these specific outcomes following CABG could not be excluded. Importantly, a reduction in both MI (RR 0.8; 95% CI, 0.71-0.91; P = .001) and the requirement for repeat revascularization (RR 0.74; 95% CI, 0.65-0.83; P < .0001) was observed following CR (vs IR) by PCI.⁷ Most interesting, however, is the finding of a mortality benefit associated with CR (vs IR) through 4.5-year (mean) follow-up of similar magnitude (∼30%) following either PCI or CABG (Figure 6). This observation suggests that the specific revascularization modality (PCI vs CABG) used may not be as important as the objective of achieving complete revascularization.

Conclusions

CR should be the objective of revascularization for MVCAD and the likelihood of achieving CR should inform the choice of revascularization modality (CABG vs PCI). CR (vs IR) following PCI is associated with significant improvement in important clinical outcomes including survival, as well as reductions in the incidence of MI and requirement for repeat revascularization procedures. CR (vs IR) following CABG confers a survival advantage, but is not convincingly associated with reductions in MI or repeat revascularization. As CR appears to confer a survival advantage following either PCI or CABG, objective assessment of the completeness of revascularization should be incorporated into procedural quality and performance metrics, as well as criteria for appropriate utilization. 

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