Chronic Total Occlusion Should Not Routinely be Treated with Coronary Artery Bypass Grafting

Abstract

Chronic total occlusions (CTOs) of the coronary arteries are common. In addition, they are often treated by coronary artery bypass graft (CABG) surgery. The decision to perform CABG for CTOs should be predicated on the demonstration of viability of the subtended myocardium and based on evidence that revascularization will increase the probability of some demonstrably better outcome, whether improved quality of life, prevention of future non-fatal everts or prolongation of life. The literature on surgical revascularization of CTOs is limited, and largely descriptive with only one post-hoc analysis from a randomized trial. There are two small non-randomized studies comparing PCI and to medical therapy. That the outcomes data are so limited affects the ability to justify CABG in this setting. The literature on PCI for CTOs is far more extensive, although there is also limited clinical trial data or comparative effectiveness data concerning choice of therapy for CTOs. Nonetheless, CABG for CTOs can be more easily justified in the setting of multivessel disease where bypass of the CTO is part of an overall strategy of complete revascularization. Thus, CABG for CTOs can be best justified where there is multivessel disease, poorly controlled angina pectoris, and evidence of viability in the subtended zone. While carrying out studies concerning CABG for CTOs will be difficult, a research agenda in this space is clearly needed.

Should chronic total occlusions (CTOs) of coronary arteries be revascularized by coronary artery bypass graft (CABG) surgery? It would seem that this is not a question that is often asked. And yet CTOs are common, and more commonly revascularized by CABG than by percutaneous coronary intervention (PCI). In this paper we review the epidemiology of CTOs, discuss issues and viability of the subtended zone, how viability could be assessed, indications for revascularization of CTOs, the literature on CABG for CTO and conclude with recommendations for future research. The fundamental positions put forward here 1) the literature on CABG for CTOs is not strong enough to justify this common procedure on a routine basis, 2) decisions on care still need to be made, and 3) additional research is needed.

Background on Chronic Total Occlusions

CTOs are common findings on coronary arteriograms.^{1, 2} While there has been an extensive literature on the subject concerning PCI for CTOs, there is less literature on CABG for CTOs.^3–5 This is despite data from the early 2000’s showing that patients with CTO are treated more often with CABG than with PCI.¹ Christofferson et al¹ studied 8,004 consecutive patients undergoing diagnostic catheterization at a single institution between 1990 and 2000. CTOs were defined as 100% coronary occlusion present for at least 3 months. Patients with previous CABG or recent myocardial infarctions (n=1,423) were excluded. Of the remaining 6,581 patients, 3,087 (47%) had significant coronary artery disease (>70% coronary stenosis). Of patients with significant coronary artery disease, a CTO was present in 1,612 (52%) patients, of whom 375 (12%) had more than 1 CTO. Among patients with significant CAD and a CTO, 11% were treated with PCI, 40% CABG and 49% medical therapy. In comparison, among patients with significant CAD but no CTO, 36% were treated with PCI, 28% with CABG and 35% medically (p<0.0001). In a multivariable analysis, the presence of a CTO was associated with reduced odds of undergoing PCI (OR 0.26, 95% CI 0.22 to 0.31, p<0.0001). Multivessel disease, not a CTO, was found on multivariable analysis to be associated with the increased choice of CABG. However, multivessel disease and CTO are co-linear, and it difficult to know which is the main driver in decision making.

More recently, the choice of therapy for patients undergoing coronary angiography and found to have CTOs was studied in The Canadian Multicenter Chronic Total Occlusions Registry.⁶ CTOs were identified in consecutive patients undergoing nonurgent diagnostic coronary angiography at 3 sites in Canada between April 2008 and July 2009. CTOs were identified in 2,630 out of 14,439 (18.4%) patients. There was a previous history of myocardial infarction in 40%, Q waves corresponding to the CTO artery territory in 26%, and left ventricular function was normal in the majority. Half the CTOs were in the right coronary artery. Almost half the patients with CTOs were treated medically, and 25% underwent CABG (CTOs bypassed in 88%). PCI was performed in 30%, although CTO lesions were attempted in only 10%, with 70% success rate. While more patients with CTOs have historically been treated with CABG than PCI, technical advancements in PCI of CTOs may be expected to drive more patients with CTOs towards being treated with PCI.⁴

The Need for Viability in the Subtended Zone

Presumably a pre-requisite for revascularizing CTOs is that the myocardium in the subtended zone be viable. There are data which do show improved survival after revascularization in patients with left ventricular dysfunction and viable myocardium, but not in the absence of viability.⁷ However, randomized trial data have not been shown to support the importance of viability testing.^{8, 9} In addition, this issue has not specifically been addressed in patients with CTOs.² How could the myocardium in the CTO subtended zone be viable? Almost certainly this is due to the presence of epicardial collaterals. There could be either intracoronary collaterals bridging the total occlusion or collaterals from another coronary artery. One might postulate that the myocardium subtended by a CTO is sustained by microvascular connections from adjacent myocardial vascular zones. However, experimental data reveal that there are no microvascular connections across zones in the myocardium, and that each vascular distribution is independent, with the only vascular connections being epicardial, generally macroscopic collaterals.^10–12 Thus, in establishing the viability of the distribution subtended by a CTO, the first evidence can come from collaterals. However, this will be imperfect as the collaterals may not be persistently seen or even seen at all on the angiogram.¹³ In addition, there may be collaterals to a CTO, visualized at the time of diagnostic angiography, where the subtended myocardium is not viable. It must be noted that even in the setting of extensive collateralization with normal wall motion, the subtended zone may well be ischemic at rest or with increased demand.¹⁴

Assessment of Viability

The ability to assess viability is difficult and uncertain. If left ventricular function is absolutely normal, then viability is essentially certain. However, quite often the wall motion will not be normal, in which case the wall motion abnormalities will most likely include the CTO subtended zone. Sometimes a transthoracic echo will show the zone to be akinetic and thin, consistent with a myocardial infarction in this zone.¹⁵ The wall there will most likely be scar tissue. In such a case return of function with revascularization seems unlikely. However, there are patients in whom wall motion is not normal, but where the myocardium has not thinned out. In such cases there may be subendocardial scar with normal tissue above it extending to the epicardium. The subendocardial scar, which cannot contract, may pose a mechanical limitation on the amount of return of function that can be expected.¹⁶ While finite element modeling and other approaches to understanding the burden of non-contractile zones on other zones may offer some mathematical understanding of left ventricular function and potential recovery of function, in practice it is not possible to tell the burden of subendocardial scar on the effects of revascularization in that zone on subsequent function.^{17, 18} Finally, there is the situation in which the myocardium is not thin, and the presupposition is that the myocardium is alive but not functioning, i.e. the myocardium is hibernating.¹⁹ Testing may help to determine viability in this setting. There is a literature on assessing viability with Thallium-201, Technetium-99m sestamibi, positron emission tomography (PET), dobutamine stress echocardiography and myocardial resonance imaging (MRI).^19–23 MRI with late gadolinium enhancement is generally recognized as the gold standard for assessing the presence of scar in the myocardium.²⁴ MRI correlates well with PET for areas of scar, finding scar somewhat more frequently and with higher spacial resolution.²⁵ However, the routine use of MRI to guide revascularization is limited by expense and availability. It is not part of routine clinical decision making to assess viability with either PET or MRI prior to revascularization. In part, this is due to the practicality of obtaining these images, partly due to expense and partly due to limited and uncertain accuracy, with generally uncertain false positive and false negative rates, uncertain prevalence of hibernating myocardium and thus uncertain predictive values.²⁶ While there is difficulty in establishing viability and potential return of function when considering revascularization of CTOs,= assessment of viability should be considered prior to surgical revascularization.

Indication for Revascularizing CTOs

What are the indications for revascularizing CTOs? The possible reasons are to relieve angina and prolong life and perhaps to relieve or prevent heart failure.⁵ Relief of angina seems relatively straightforward. If the zone subtended by the CTO is viable but ischemic at rest or with exercise, it could cause angina. This might well be relieved with revascularization, consistent with the literature that revascularization does relieve angina.²⁷ Angina relief following PCI for CTOs has been studied.^28–31 However, the literature on angina relief after CABG for CTOs is limited.³² To prolong survival, treatment would have to prevent or lessen the impact of a future myocardial infarction, prevent arrhythmias, improve LV function or prevent the development of heart failure. If the collaterals supplying the CTO are threatened due to upstream vulnerable plaques, then a ruptured plaque in the upstream vessel supplying the CTO could cause a myocardial infarction in the remote zone as well as the one subtended by the CTO. Such a myocardial infarction involving multiple zones could increase the risk of death due to pump failure or arrhythmias. Arrhythmic death could also occur if there is a small amount of residual surviving but ischemic myocardium. In this case revascularization could reduce the probability of such a lethal arrhythmia. The problem with these indications for revascularization is that they are largely conjectural.

The decision to revascularize with CABG instead of PCI is currently being made despite considerable uncertainty. There are limited clinical data comparing CABG with PCI for CTOs. The decision will be driven by the patients overall condition as well as the angiographic findings, particularly the suitability of the occlusion for PCI and the suitability of the downstream vessel for surgery. Patients revascularized by CABG could have CTOs bypassed as part of an overall operation where other non-CTO vessels are bypassed or as a stand-alone operation for one or more CTOs. In the former case, the decision to perform CABG could be driven by the need to relieve ischemia in myocardium subtended by non-CTO vessels or in part of even primarily by CTO vessels. As return of function is uncertain, the surgeon and other decision makers need to be clear about the decision they are making. If CABG will be performed in any case, then the decision to bypass the CTO is a relatively small one as there will most likely be negligible increased risk and there is some potential for improvement. However, if the decision to perform CABG is being driven by the CTO, then the evidence base is limited.

CTOs and Complete Revascularization

CABG for CTOs will often be part of a strategy of offering complete revascularization.³³ While patients who have CABG with complete revascularization have better outcomes than patients without revascularization,³⁴ there are a few limitations that should be noted. First of all, there is no universally accepted definition of complete revascularization.³⁵ Thus, complete revascularization may not require bypassing smaller vessels or vessels where the subtended zone is not viable. There is no randomized trial comparing patients with complete and incomplete CABG. Indeed, there are only observational comparisons. While patients with complete surgical revascularization may have a better outcomes, patients with incomplete revascularization are generally sicker.³³ Nonetheless, in the SYNTAX trial plus registry, complete revascularization was associated with better outcomes for both PCI and CABG and for both patients with and without CTOs.³⁶ Thus, where the decision to perform CABG has been made independently of the presence of the CTOs, it does seem reasonable to bypass the CTOs in the setting where the subtended zone is most likely viable and as part of an overall surgical approach to achieve complete revascularization.

Literature on CABG for CTOs

There are several papers in the literature on surgical revascularization of CTOs (Table 1). Banerjee et al.³⁷ studied one-year outcomes in 605 consecutive patients undergoing CABG between June 2005 and December 2008. A CTO was present in 256 patients (42%), predominantly in the right coronary artery (48.3%). The patients with and without a CTO were similar in baseline clinical characteristics. The SYNTAX score was higher in patients with CTOs compared to patients without CTOs (mean 32.9 versus 23.4, p=0.0001). Of patients with a CTO, 73.8% had a single CTO and 26.2% multiple CTOs. The CTO was successfully bypassed in 100% in the left anterior descending (LAD), 92% in the circumflex and right coronary arteries and 85% when in multiple coronary artery distributions. During a mean follow-up of 349 days, the incidence of all-cause death and myocardial infarction were 7.1% and 7.4% in the CTO non-CTO groups respectively (p = 0.97). The incidence of repeat revascularization by PCI was lower in patients with CTO (0.9%) than without a CTO (4.5%, p=0.01). The reasons for this difference are not clear. CTO length of >20 and >40 mm were present in 74.9% and 37.8% of patients respectively. One-year mortality was higher in patients with CTO length >40 mm compared to ≤20 mm (p = 0.04). CTO length >40 mm was an independent predictor of one year mortality controlling for age, number of CTOs, comorbidity, clopidogrel use, severity of coronary artery disease, renal failure, and left ventricular ejection fraction. The authors speculated that the length of the CTO might be a surrogate for disease burden. The authors concluded that CABG achieved high success in bypassing CTOs, and that CTO length >40 mm is an independent predictor of post-CABG mortality. This paper did not address who should undergo CABG for CTOs, the issue of viability in the zone, and the difference in decision making between those patients where the CTO drove the decision for CABG and where the CTO was bypassed but where non-CTO vessels drove the decision making.

Table 1.

Literature Summary on CABG for CTOs

Author	# Patients	Years	Type of Study	Findings
Banerjee et al37	256	2005–2008	Uncontrolled observational	Cardiovascular event rates reported at a mean of 349 days.
Fefer et al38	174	2005–2007	Uncontrolled observational	Five year mortality similar in patients with and without CTOs.
Holzhey et al39	420	1996–2007	Minimally invasive CABG Uncontrolled observational	Minimally invasive bypass of CTOs of the LAD almost always possible. Similar mortality at 5 years in patients with and without CTOs.
Kim et al40	393 Total 169 CABG 130 PCI 94 Medical	2003–2007	Non-randomized comparative effectiveness	At 46.5 months meah followup, CABG had similar mortality to PCI and lower than medical therapy.
Wijeysundera et al32	304 Total 104 CABG 46 PCI 154 Medical	2008–2009	Non-randomized comparative effectiveness	CABG and PCI of CTOs are associated with improvement in QOL.
Farooq et al36	849 Total 543 Randomized 561 Total CABG 288 Total PCI	2005–2007	Randomized trial and registry	CTOs more successfully revascularized with CABG than PCI. Better clinical outcomes in CTO patients with complete compared to incomplete revascularization.

CABG for CTOs was studied by Fefer et al³⁸ in 405 patients undergoing CABG in 2005 and 2007, with 221 CTOs in 174 patients: 132 patients had 1 CTO; 37 had 2 CTOs and 5 had 3 CTOs. Of the 221 CTOs, 191 (86%) were bypassed, including all in the LAD. However, 12% of left circumflex and 22% of right coronary artery CTOs were not bypassed. Incomplete CTO revascularization was associated with older age, more comorbidities, and lower ejection fraction. Incomplete CTO revascularization was not associated with increased long-term mortality. Furthermore, there was no difference in long-term mortality between patients with and without CTOs. There was no assessment of viability or return of function, and no assessment of functional status. This study does show that CABG for CTOs can be done, but offers little guidance for whom it should be done.

A potentially useful surgical intervention would be to perform CABG to a CTO of the LAD with minimally invasive surgery. This was studied in 1800 patients from 1996 to 2007 undergoing left internal mammary artery bypass to the LAD.³⁹ There were 420 patients with and 1380 without a CTO. Prior MI had occurred in just 5.3% of the CTO and 4% of the non-CTO cases. The LAD could be bypassed in all of the stenosed vessels and all but one of the occluded vessels. Periprocedural mortality was 1.1% and 0.7% for the CTO and non-CTO groups respectively (p = 0.36). Survival for the CTO and non-CTO groups were 98.0% (95% CI 96.5% to 99.5%) and 98.0% (95% CI 96.4% to 99.5%) at 1 year (p = 0.87) and 90.5% (95% CI 85.8% to 95.5%) versus 90.4% (95% CI 85.8% to 95.1%) at 5 years respectively (p = 0.98). Angiography at 6 to 12 months postoperatively showed a patency rate of the LIMA bypass of 98% (94 of 96 patients) in the CTO group and 96% (290 of 301 patients) in the non-CTO group (p = 0.45). Freedom from major adverse cardiac and cerebrovascular events and angina with or without CTO at 5 years was 83.2% (95% CI 77.6% to 88.8%) and 85.5% (95% CI 82.6% to 88.1%), respectively (p = 0.64). Recurrence of angina occurred in 1.41% and 1.16% of the CTO and non-CTO patients respectively. The authors concluded that minimally invasive CABG of a totally occluded LAD is almost always possible and that a CTO is not a negative predictor for short or long-term outcome in patients undergoing this operation. As impressive as these results appear, it is not clear that these patients benefited from surgery. The need for benefit from bypassing the CTO is critical as in these patients the CTO would be the only obstruction bypassed. We do not know about the severity of angina before the operation. We also do not know about the extent of the coronary disease or about whether there are threatened collaterals. If there are no threatened collaterals, and if angina was not present or at least not disabling, then it is hard to see the benefit of the surgery. In addition, we do know if there was hibernating myocardium is the distribution of the CTO and then return of function after surgery.

There is a small, preliminary, non-randomized study comparing the outcomes of patients with CTOs treated with medical therapy, PCI or CABG.⁴⁰ From 2003 to 2012, 2024 patients were enrolled in single-center registry, which included 393 with multiple CTOs. With a median 46.5 month followup, 169 patients (43%) were referred to CABG, 130 (33%) to PCI, 94 (24%) to medical therapy. Baseline characteristics and statistical methods were not reported. CABG had the lowest incidence of major adverse cardiac and cerebral events (11.2%) compared with PCI (20.0%, p<0.01) or medical therapy (39.4%, p < 0.01). The CABG and PCI groups had similar mortality (5.9% and 6.9% respectively, p=0.49), while CABG mortality was lower than with medical therapy (5.9% vs 19.1%, p<0.01). We do not know about viability, wall motion or the presence of collaterals in the three groups. While this study would suggest an advantage for CABG, the study is non-randomized, and treatment selection bias would be expected.

There is also a small, non-randomized, multi-center study comparing quality of life in patients with CTOs treated with medical therapy (n=154), PCI (n=46) and CABG (n=104). The study also included patients with CTO undergoing PCI to only non-CTO lesions (n=83).³² Quality of life was assessed with the Seattle Angina Questionnaire. Medically treated patients had no improvement in quality of life. Patients with CTO revascularization had improvements from before to after revascularization in physical limitation (from PCI 60.5 to 76.4; CABG 61.6 to 80.1; p<0.001), angina frequency (from PCI 79.0 to 92.7; CABG 82.1 to 97.9; p<0.001), and disease perception (from PCI 50.5 to 75.0; CABG 50.2 to 80.0; p<0.001). PCI patients without CTO revascularization had improvement in angina frequency (from 82.8 to 93.3; p<0.001), and disease perception (from 53.8 to 71.4; p<0.001). As the study was non-randomized, there remains the likelihood of treatment selection bias.

Some of the most comprehensive data on total occlusions comes from the SYNTAX trial and registry, over 95% of which were present for over 3 months or unknown.³⁶ For simplicity in this paper I am labelling them as CTOs. In the randomized component of the SYNTAX trial there were 543 patients with CTOs, 277 treated with PCI and 266 with CABG. More of the CTOs were successfully revascularized with CABG (68.1%) than with PCI (49.4%). Overall, of 2636 patients in the SYNTAX trial and registry, there were 840 patients with CTOs, 288 of 1095 PCI patients (26.3%) and 561 of 1541 CABG patients (36.4%). Complete compared to incomplete revascularization was associated with lower event rates for both PCI (4 year MACCE 26.6% vs 39.9%, p=0.024) and CABG (4 year MACCE 18.7% vs 27.8%, p=0.015).

Can CABG for CTOs be justified?

The literature reveals that CTOs are more often treated with CABG than with PCI.² This has been recently confirmed in the SYNTAX registry and trial.³⁶ However, the literature on surgical outcome of CTO’s is quite limited, with just 1684 patients treated by CABG in the studies reviewed here. There have been 6 important studies, with data on clinical event rates and health status. These studies clearly reveal that CTOs can be treated with CABG surgery. CABG is a treatment for angina, and while limited, the published data do suggest that CABG for CTOs reduces angina. However, the only randomized trial data is from a small subgroup in SYNTAX finding more successful CTO revascularization with CABG than PCI. Non-randomized data from SYNTAX also show that CTO patients with complete revascularization have fewer events than patients with incomplete revascularization. There are little data on the role of viability in determining outcome. There are little data on the role of collaterals and whether non-threatened collaterals reduce the incidence of future events and thus the role of revascularization. Data on the how important the CTO was in driving decision making can largely be derived from the several series showing that patients with CTOs are more like to be treated with CABG than with PCI. However, we do not know whether the CTO was the primary driver or contributing. While this may be difficult to sort out, it is critical as the data on ischemic non-CTO lesions could be argued to be more compelling as a justification for CABG. Thus, it would seem that the patients with multivessel disease in whom CTOs are bypassed as part of CABG seeking complete revascularization would be the most appropriate. Where the CTO is the primary driver in multivessel disease, CABG is not as well justified. Despite excellent outcomes for minimally invasive surgery, isolated CABG for an isolated CTO of the LAD disease cannot be justified on the basis of preventing future events compared either medical therapy or PCI.

Appropriate Use and Therapeutic Alternatives

While the literature on CABG for CTOs may be limited, it is still necessary to treat patients with CTOs and to make the best therapeutic decisions possible. The appropriate use criteria for revascularization of CTOs have been considered (Table 2).⁴¹ These recommendations only cover isolated single vessel CTOs and make no recommendation between PCI and CABG. As with other non-ACS patients, those with more severe symptoms on anti-anginal therapy and with greater evidence on ischemia on non-invasive testing are considered more appropriate for revascularization. Revascularization for CTOs as part of multivessel disease was not considered in the appropriate use criteria. CABG for CTOs is barely mentioned in the ACCF/ACC CABG guidelines, noting briefly that it may be considered as part of hybrid procedures.⁴² The literature on PCI, which is beyond the scope of this article, is far more extensive.^{2, 31, 43} However, there are no randomized trials comparing PCI to medical therapy for CTOs. Technical advances in interventional cardiology would limit what could be learned from a CTO subgroup in COURAGE (which compared PCI to medical therapy, as enrollment ended in 2004.⁴⁴ Indeed, the ability to revascularize CTOs with PCI have improved dramatically in recent years.^{4, 45, 46} While the ISCHEMIA trial is randomizing patients prior to the angiogram, most patients will have coronary CT angiograms, which will permit assessment of CTOs, and then comparison of treatment strategies.

Table 2.

Appropriate Use Criteria for CTO Revascularization in Patients Without Prior CABG

Indication	Appropriate Use Score 1–9
Canadian Cardiovascular Society Angina Class	Asymptomatic	Class I or II	Class III or IV
● Chronic total occlusion of 1 major epicardial coronary artery, without other coronary stenoses ● Low-risk findings on noninvasive testing ● Receiving no or minimal anti-ischemic medical therapy	I(1)	I(2)	I(3)
● Chronic total occlusion of 1 major epicardial coronary artery, without other coronary stenoses ● Low-risk findings on noninvasive testing ● Receiving a course of maximal anti-ischemic medical therapy	I(1)	U(4)	U(6)
● Chronic total occlusion of 1 major epicardial coronary artery, without other coronary stenoses ● Intermediate-risk findings on noninvasive testing ● Receiving no or minimal anti-ischemic medical therapy	I(3)	U(4)	U(6)
● Chronic total occlusion of 1 major epicardial coronary artery, without other coronary stenoses ● Intermediate-risk criteria on noninvasive testing ● Receiving a course of maximal anti-ischemic medical therapy	U(4)	U(5)	A(7)
● Chronic total occlusion of 1 major epicardial coronary artery, without other coronary stenoses ● High-risk findings on noninvasive testing ● Receiving no or minimal anti-ischemic medical therapy	U(4)	U(5)	A(7)
● Chronic total occlusion of 1 major epicardial coronary artery, without other coronary stenoses ● High-risk criteria on noninvasive testing ● Receiving a course of maximal anti-ischemic medical therapy	U(5)	A(7)	A(8)

A=appropriate, I=inappropriate, U=uncertain

Conclusions and Need for Additional Studies

At present, in the absence of adequate clinical trial data, anginal symptoms, evidence of ischemia in viable myocardium in the subtended zone, angiographic appropriateness and an overall strategy for complete revascularization must be used to consider which patients should be treated with CABG for CTOs. Patients not suitable for PCI on angiographic grounds, with both CTO and non-CTO lesions in multiple vessels, presence of intolerable angina and evidence of viability in the zone subtended by the CTO would be most suitable for surgical revascularization. Angina would be best evaluated with a validated tool such as the Seattle Angina Questionnaire.^{47, 48} The suitability of patients with a mix of these three characteristics is offered in Table 3, scaled from one to four stars, corresponding to lowest to highest suitability for CABG. This simple set of recommendations can only be considered preliminary pending better outcomes data.

Table 3.

Suitability for Revascularization by CABG in patients with CTOs

	Multivessel Coronary Artery Disease	Angina Pectoris	Myocardial Viability in the CTO Subtended Zone	Suitable for Surgical CTO Revascularization
Patient 1	√	√	√	****
Patient 2	√	√		**
Patient 3		√	√	**
Patient 4	√		√	**
Patient 5	√			*
Patient 6		√		*
Patient 7			√	*

It would appear that we need a research agenda to study CABG for CTOs. Outcomes to be evaluated include surrogates such as left ventricular function, events such as mortality and heart failure exacerbations, and objective measures of angina before and after the procedure.^{48, 49} It may be possible to further mine existing databases such at the Canadian CTO registry to consider several of the questions poised above. Another database which may have critical information is the Society of Thoracic Surgeons CABG database. To gain the anatomic data needed, the database could be linked with the American College of Cardiology CathPCI database, and for outcomes to the Medicare database. There is excellent precedent for combining these databases to consider long term outcome.^{50, 51} There will also be a role for prospective data collection where the issues particularly relevant to CTO, including viability and details of the collaterals, are carefully considered. However, non-randomized comparisons will have treatment selection bias which cannot be entirely accounted for by statistical methods.^{50, 52} Indeed, to truly answer questions concerning therapeutic choices, randomized trials remain the gold standard, and certainly there should be consideration of randomized trials of revascularization of CTOs. If CABG is the intervention to be considered, the alternatives of PCI or medical therapy would constitute the control groups. In principal, a trial could be constructed in which CABG patients with a CTO as part of multivessel disease, underwent bypass of all significant non-CTO lesions, and were randomized to get or not get the CTO bypassed as part of the overall operation. Such a trial would be a difficult, perhaps even unrealistic, to conduct, especially where the subtended zone is considered to be viable. In the absence of randomized trials, careful observational comparative effectiveness studies are needed. What should not be acceptable is to indefinitely continue performing CABG for CTOs routinely in the absence of data suggesting that such procedures lead to better outcomes, economic as well as clinical, compared to other therapeutic options.