Chronic total occlusions (CTOs) are defined as 100% atherosclerotic lesions that have been present for at least 3 months, which result in complete loss of antegrade blood flow.1 It also encompasses lesions that have antegrade TIMI grade 1 flow with an angiographically obscure lumen. The prevalence for CTOs exhibits marked variability in labs across North America, ranging between 18%-59%.2 While these chronically occluded vessels undergo regional neovascularization over time with the development of collaterals, research over the years has shown that these collaterals exhibit endothelial and smooth muscle cell dysfunction, with abnormal responses to metabolic stress and in turn inadequate blood flow at times of higher demand – one reason that patients may present with anginal symptoms.3 However, many patients with CTOs have no symptoms whatsoever with or without medical therapy.
Interestingly, despite the high prevalence of CTOs, only 6%-9% are treated with percutaneous options in North America, while in Japan, 61% of these lesions are managed with percutaneous coronary intervention (PCI).2 The reason for this regional difference is uncertain. The current data available for CTO-based revascularization show mixed outcomes and are mostly observational in nature, with no large, prospective, randomized trials. That being said, there are smaller, mostly observational studies that suggest an improvement in anginal symptoms, left ventricular function, as well as mortality in patients who undergo successful CTO-PCI.4-6 Joyal et al, for example, have shown a significant reduction in angina post revascularization in CTO patients over a 6-year period when compared with patients who were not successfully revascularized.6 Similarly, Kirschbaum et al, in a cohort of 21 patients who were followed over a 3-year period after CTO recanalization, showed an improvement in left ventricular functional indices on cardiac magnetic resonance imaging (ejection fraction, end-diastolic and systolic volume, segmental wall thickening).7 Joyal et al also suggest in their meta-analysis that CTO-PCI does confer a mortality benefit when compared with failed revascularization; however, their results were in contrast to those from the prospective CREDO-Kyoto registry where 1192 successfully treated patients were compared with 332 unsuccessfully treated patients. Here, there was no long-term mortality benefit of one group over the other, although freedom from coronary artery bypass grafting and cardiac-related deaths were definitely lower in the revascularized group.8
With the current mix of observational outcomes data available, it is important to focus on the technical aspect of the procedure. While PCI success rates in non-CTO vessels approach 93% or higher, those for CTO vessels have remained static around 75% (at best – usually in the hands of skilled operators).9,10 Some of the reasons for failure include the extensive plaque burden associated with these lesions, longer lesion lengths, coronary tortuosity, inability to visualize the course of the vessel, the presence of a blunt or flush occlusion, side-branch occlusion, small vessel size, multiple bridging collaterals, and failure to reenter the true lumen, among a host of other factors.11,12 To facilitate CTO-PCI, various hydrophilic and coil wires have been developed along with different techniques to allow successful crossing of the lesion. This includes parallel wiring, subintimal tracking and reentry (STAR), as well as retrograde techniques. While a discussion on these two important aspects of CTO-PCI is beyond the scope of this editorial, the crux really is that success rates still do not approach those of conventional PCIs despite the available options. This is where it is worth mentioning that the most important factors that can lead to failure of CTO-PCI are operator inexperience and poor case selection. These are crucial issues and would be an important aspect of any prospective trial.
In this issue of the Journal of Invasive Cardiology, Nguyen-Trong and colleagues discuss native coronary revascularization of CTO lesions using a retrograde approach through saphenous vein grafts (SVGs),13 a technique that has been used in limited situations so far. The authors extracted data from four centers with expertise in CTO revascularization (Appleton Cardiology in Appleton, Wisconsin; Mid America Heart Institute in Kansas City, Missouri; Piedmont Heart Institute in Atlanta, Georgia; and VA North Texas Health Care System in Dallas, Texas). Out of 572 patients, a total of 144 underwent CTO-PCI, while 21 of these underwent PCI via an SVG conduit. Successful retrograde crossing was achieved in 14 out of 21 patients and the authors divided this group into those who achieved technical and procedural success. Technical success (85.7%) was defined as successful intervention of the occlusive lesion, while procedural success (81.0%) was freedom from major adverse cardiovascular event (MACE). The mean age of their patient population was 70.8 ± 7.3 years and 95.2% of patients were male. Anginal scores per the Canadian Cardiovascular Society (CCS) were available for only 14 patients, with 57.1% being CCS III, while 35.7% were CCS II and 7.2% were CCS I. The vessels targeted via SVG conduits included the right coronary (38%), circumflex (38%), and left anterior descending artery (24%). The median length of the lesions in this study was 38 mm (range, 30-60 mm), while mean J-CTO score was 3.5 ± 1.0.
The authors used a primary retrograde approach in most cases (52%), while failure of the antegrade approach resulted in a retrograde approach in 48% of cases. Furthermore, 20 out of the 21 cases that underwent retrograde CTO required the use of more than one crossing strategy, with the highest being four different crossing strategies.
Median contrast volume, procedure time, and fluoroscopy time were 250 mL (range, 200-400 mL), 214 min (range, 177-254 min), and 91.6 min (range, 58.9-106 min), respectively. Complications were noted in 2 patients out of their cohort, and included conduit perforation resulting in tamponade, cardiogenic shock and death, as well as periprocedural myocardial infarction from loss of a native coronary.
The first series on retrograde CTO balloon angioplasty via SVG conduits dates back to a cohort of patients evaluated between 1985-1989 by Kahn et al.14 They evaluated a total of 16 patients, out of which 12 underwent successful coronary balloon angioplasty (71%). The reasons cited for failure to cross lesions in this study were most often an inability to steer the guidewire and balloon through very acute vein graft to coronary anastomoses angles. Fast forward almost 26 years later, and there has been a marked improvement in the efficacy of general catheter-based interventions with the availability of newer crossing techniques and newer wires; however, the technical and procedural success involved in these procedures has not shown a significant improvement. For instance, in a study by Rathore et al from a high-volume CTO-PCI center in Japan, 12 patients (7.6%) underwent retrograde PCI through an SVG graft, with 83.3% of such PCI cases being successful.15 The current authors also exhibited similar success rates; however, an important point to keep in mind is that the registry data examined here are from four centers where the authors have had extensive experience with CTOs. Similarly, conventional CTO-PCI techniques have frequently shown success rates around 71%-75%, with rates in some cases falling as low as 58% in those centers where CTO experience is lacking.16 More advanced techniques, which have not been adopted in all centers due to the technical complexity they are associated with, can improve success rates to >80%; however, these are not as widely practiced because of the learning curve associated with them.
While CTO-PCI through venous conduits would seem to be a natural extension of this technique, it also adds a whole new level of complexity since it requires skillful maneuverability across graft-conduits into the native coronary circulation. The different inherent biology of SVGs adds the potential for distal embolization, in addition to the possibility of a differential likelihood of known complications usually encountered during the retrograde procedure including acute or subacute loss of the vein graft conduit itself.
Important detractors from this study are both the lack of preintervention and postintervention clinical data (anginal class) for all the patients involved in the study and an assessment of long-term outcomes. Certainly it would be very important to know whether the tradeoff between the benefit associated with CTO-PCI through SVG conduits is worth the risks, keeping in mind the complication rates associated with this technically challenging procedure. The authors had 2 deaths in their cohort of 21 patients, yielding a mortality rate of nearly 10%. This would appear to not only be much higher than traditional PCI complication rates, but also apparently much higher than those encountered during traditional CTO-PCIs, as has been shown in a meta-analysis of 65 studies published by Patel et al (coronary artery bypass graft rate, 0.17%; tamponade rate, 1.2%) as well as those from an experienced CTO center in Japan (death rate, 0.5%; myocardial infarction rate, 3.0%; tamponade rate, 0.6%).17 Both changes in functional class as well as medium and long-term outcomes here will dictate the approach taken in patients with bypass conduits. In future investigations, it will be helpful to know how these patients do with respect to left ventricular function, and freedom from angina and MACE.
Actually, MACE is probably the incorrect term – and in these retrograde CTO procedures, the term MACER should be employed. The “R” is for radiation effects on the skin. In procedures where the average radiation exposure goes up dramatically, the incidence of skin effects would be expected to go up dramatically as well. Just as the complication of death is not a worthwhile tradeoff in a minimally symptomatic individual, many patients might hesitate to consent to a procedure potentially complicated by a moderate-sized full-thickness burn requiring months of meticulous care and eventual skin grafting.18
Currently, the issue plaguing CTOs is the lack of randomized clinical trials. Most of the data currently available are observational in nature and there are no clear-cut guidelines on when to intervene on these lesions. Despite how cumbersome these procedures are and the limited success associated with them, these procedures make intuitive sense and there is a small but growing body of literature suggesting the possibility of long-term benefits with this type of revascularization. However, more robust data are required in the form of randomized trials before CTO-PCI becomes commonplace. An important clinical implication of this study is that we are currently not just limited to the traditional approach to CTOs, which was mostly through epicardial vessels/septal perforators. The authors have demonstrated that PCI through vein grafts into the native coronaries is feasible. This can help set the foundation for future studies where, if properly done and successful, this form of PCI can set a new precedent and potentially make patients feel better, live longer, and avoid the pitfalls associated with re-do coronary artery bypass graft surgery. As with every new procedure or technique, we must ensure, however, that the Price is Right.
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From the Krannert Institute of Cardiology, Indiana University School of Medicine and Indiana University Health, Indianapolis, Indiana.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Breall reports consultant fees from FujiFilm (CPACS product line) and Siemens Medical (interventional cardiology line). The remaining authors report no conflicts of interest regarding the content herein.
Address for correspondence: Jeffrey A. Breall, MD, PhD, Professor of Clinical Medicine, Krannert Institute of Cardiology, 1800 N. Capitol Ave, #E-490, Indianapolis, IN 46202. Email: firstname.lastname@example.org