Coronary chronic total occlusions (CTO) have been termed the “last frontier” of percutaneous coronary intervention (PCI)1, and remain one of the most technically challenging lesion subsets with lower rates of procedural success, higher complication rates, greater radiation exposure, and longer procedure times compared with interventions in non-CTO stenoses. For these reasons, CTO remains a common indication for referral for coronary artery bypass grafting (CABG)2. However grafting of the CTO can also be challenging, as shown in the SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) clinical trial CTO subset, in which successful bypass grafting of the CTO was achieved in only 69%3.
A large body of evidence suggests that successful CTO PCI results in improved clinical outcomes. Global improvements in left ventricular function have been reported by following successful CTO PCI4-6, while un-revascularised CTO has been reported to increase mortality in the setting of incomplete revascularisation with multivessel coronary artery disease7. Numerous single-centre studies have reported reduced mortality for patients undergoing a successful CTO PCI compared with those who undergo an unsuccessful attempt8,9. However, definitive data regarding a survival advantage are lacking due to the absence of a prospective randomised trial.
Despite the growing body of data suggesting improved outcomes with CTO PCI, attempt rates among patients identified with a CTO remain low (about 11%-13%) and seem unchanged over time during recent years10. Indeed, the contemporary Canadian Multicentre CTO Registry showed similar findings, with marked variation between PCI centres (Fefer P et al, personal communication).
A temporal analysis of CTO PCI trends from the Mayo clinic documented improved procedural success for attempted revascularisation following the introduction of coronary stents, but no significant improvement above the 70% mark in the subsequent 15 years11. Similar success rates are demonstrated in the Canadian Multicentre CTO Registry (Fefer P et al, personal communication). However, recently published registries from Japan12-14, Europe15 and the United States16 have reported success rates in the 85-90% range with low rates of periprocedural MACE.
The paper by Galassi et al17 in this issue of EuroIntervention describes the in-hospital PCI outcomes in a 16-centre registry of 1,983 consecutive CTO lesions. Overall procedural success was attained in 82.9% with a relatively low complication rate: periprocedural MI: 1.3%; coronary perforation: 2.6%; tamponade and pericardiocentesis: 0.5%; access site complications: 0.7%; and in-hospital death: 0.3%. Notably, the retrograde approach was undertaken in 11.8% of cases and, compared with the antegrade approach, was associated with lower technical success rate (64.5% vs. 83.2%, p<0.001), more frequent coronary perforation (4.7% vs. 2.1%, p=0.04), extended fluoroscopy time and greater contrast load. Similar to previous series, long (>20mm) and heavily calcified lesions were associated with procedural failure which, in turn, was associated with increased 30-day mortality and non-fatal MI compared with patients successfully revascularised (1.9% vs. 0, p<0.001 and 3.6% vs. 0.8%, p<0.001, respectively).
The authors are to be commended for this important undertaking of recording and following all cases of CTO PCI. Indeed, the results of this registry demonstrate the successful adoption in Europe of specialised techniques learned from our Japanese colleagues with similar success and complication rates as those reported from Japan. Anumber of caveats apply beyond the non-randomised nature inherent to all registries. First, all procedures were carried out in centres with a specific program for CTO treatment accomplished by skilled operators and staff. Thus, it is unlikely that these results will be reproducible in non-CTO specialised centres. Secondly, the current report only refers to patients referred for PCI and does not inform us how many CTO lesions were turned down for PCI or referred for CABG (also, 15% of PCI CTO patients in this registry were asymptomatic). Thus, the registry may be biased toward cases with a priori higher likelihood of success, again arguing against the generalisability of the results to all CTO lesions. Thirdly, angiographic data was not assessed independently by a core lab. This could result in inclusion of sub-total occlusions and overestimation of angiographic success. Indeed in the TOAST-GISE study7 in which an angiographic corelab was used, 8% of angiograms were excluded, being judged subtotal stenoses.
Notwithstanding these weaknesses, this is a very well conducted and important document which underscores the improved acute results of PCI CTO in recent years beginning in Japan and now iterated in widely disparate clinical and cultural environments.
Now that CTO PCI seems to be technically feasible, how should we proceed from here?
1.We should recognise that CTO PCI is a specialty procedure. Dedicated PCI operators working within centres of excellence should likely be the model of CTO delivery of care in the future. Quality assurance data from individual centres should be available to determine quality of care at each site.
2.Various technical issues regarding the treatment of CTOs remain unclear. A case in point is the retrograde technique. While it is clear that this continues to be a challenging yet enabling technique in certain cases, it is associated with significantly lower (though still reasonable) success rates (65%), higher complication rates and much longer procedure times and contrast exposure. These suggest that it should be limited to highly trained individuals who have high procedure volumes with this technique and that patient selection should be very stringent.
3.Are we currently under-treating CTO by PCI based on recent registries reporting success rates consistently >80% with low complication rates. Supporting this notion, data from the Canadian Multicentre CTO registry suggests that a large proportion of CTO patients with significant viability are not being revascularised by PCI or by CABG (Fefer et al, personal communication).
4.Despite the technical expertise and dedicated equipment used by the operators participating in this study, 17.1% of patients were not successfully revascularised. These patients demonstrated markedly worse 30-day outcomes. Novel devices (BridgePoint Medical System catheters/guidewires18) and intra-plaque manipulation with collagenase prior to PCI recently reported at Late Breaking Trials, 2011 EuroPCR, are both past the first-in-man phases of development with encouraging results that may further increase CTO PCI success rates in these challenging cases.
5.Lastly, but maybe most importantly, it is high time for a well planned randomised trial which will prospectively allocate patients with CTO to different treatment strategies. This should be an international effort and should include detailed angiographic and functional data regarding left ventricular contractility and viability in the CTO territory as well as quality of life indicators. While we seem to be very close to conquering the “last frontier”, the onus is on us to prove that what we are doing indeed has clinical benefit and which subsets of patients are most likely to benefit from the procedure.
Conflict of interest statement
B.Strauss holds intellectual property on the use of collagenase in chronic total occlusions, and is founder of Matrizyme Pharma, acompany that is commercialising collagenase for use in chronic total occlusions. P.Fefer has no conflict of interest to declare.
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