Chronic Total Occlusions - The Challenge Continues

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Chronic total occlusions (CTOs) remain one of the greatest challenges facing interventional cardiologists and represent 10-15% of all percutaneous coronary intervention (PCI) procedures performed.1 Not only are procedures more prolonged and involve additional radiation exposure, but audit data from the British Cardiovascular Intervention Society for 2005 reported a procedural success of only 68% compared with 95% for non-CTO lesions.2 Many patients are therefore left untreated or referred for coronary artery bypass graft (CABG) surgery. This short article addresses what progress is being made in improving the success rate of PCI in this difficult subset of patients.


CTOs are defined as a more than three-month-old obstruction of a native coronary artery without any luminal continuity and thrombolysis in myocardial infarction (TIMI) flow 0. Thrombosed segments become densely organised with fibrous tissue and calcified with time and this makes them difficult to cross and treat (see Figure 1). Sometimes, endothelialised micro-channels may traverse the occlusion and increase the chance of a successful guidewire passage.

Rationale for Opening CTOs

The usual reason for performing PCI to a CTO is to relieve angina but perhaps also to improve left ventricular function, reduce the risk of arrhythmias and the need for CABG surgery and to prolong survival. Baks et al., using magnetic resonance imaging (MRI), demonstrated that successful revascularisation of CTOs using drug-eluting stents was associated with improvement in segment wall thickening and left ventricular volumes.3 In a study of 543 patients who underwent PCI for CTO at the Cardiothoracic Centre, technical success for CTO was 69%.4 Over a mean follow-up of 1.7 years, the mortality rate was 2.5% in the CTO success patients and 7.3% in the failure cases (p=0.004). The rates of CABG were 3.2% versus 21.7% (p<0.001), respectively. Similar results with improved survival for CTO-success patients at five and 10 years' follow-up have also been reported.5,6Figure 2 shows a coronary angiogram before and after opening a chronically occluded left anterior descending coronary artery.

Predictors of Success and Failure

Factors that predict a lower procedural success rate still include a longer duration of occlusion (> three months), length of occlusion (>15 mm), blunt-ended stump, side-branch at the occlusion point, presence of lesion calcification, bridging collaterals, extensive vessel and lesion tortuosity, ostial occlusion and absence of a distal visible vessel.7 There is a learning curve for CTO PCI and this affects success rates. The commonest reason for PCI failure in CTOs is inability to pass a guidewire beyond the occlusion.8 Failure to cross a lesion with one of today's low-profile, single-marker balloon catheters is infrequent (2-9%).

Choice of Guidewire

Routine guidewires used to cross non-occlusive lesions do not have the tip stiffness or push required to cross tough CTOs. Moderately stiff Teflon-coated guidewires, such as the 0.014-inch diameter Intermediate™ or Standard™ guidewire (Guidant) may be the initial choice, especially if a 'dimple' is evident. A low-profile balloon catheter may be advanced close to the tip of the guidewire to provide extra support for the wire as it is pushed into the occlusion. Specialised CTO guidewires are manufactured with thick cores that gradually taper towards the tip - increasing tip stiffness and support. With increasing tip stiffness, torque response increases and this may be particularly important in penetrating the fibrous cap of the CTO. To reduce tip resistance and increase the likelihood of selecting micro-channels, specialised tapered tip (0.009-0.010-inch) guidewires can be used. Examples include the hydrophilic-coated Cross-It™ 100-400 series (Guidant) with a tip diameter of 0.010 inches and increasing stiffness from 2-6g. Hydrophilic-coated guidewires have a lubricous coating that reduces friction and aids traversing micro-channels within the occlusion, offer good manoeuvrability down tortuous vessels and advance with minimal resistance. However, the wires do not maintain their tip shape and are more likely to enter side branches, pass down false channels and cause vessel perforation. Commonly used hydrophilic guidewires are the Whisper™ , Cross-It™, Pilot™ (Guidant), PT Graphix™ (Boston Scientific) and Crosswire™-NT (Terumo Medical Co.).

Enhanced-force wires such as the Miracle™ and Conquest Pro™ (Asahi Intecc, Japan) with tip stiffness of 9-12 g are considered specialist devices (see Figure 3). Extreme care is essential when using these stiff wires, which are more likely to create false channels, dissection and perforation. If the distal lumen is reached, a low-profile 1.5 mm over the wire balloon catheter or a Transit™ catheter should be used to exchange the stiff wire for a floppy wire to reduce the risk of distal perforation.

In the event of a failure-to-cross with any guidewire, the Prima™ excimer laser wire (Spectranetics International) may be worth considering.9 If wire crossing is successful but the smallest balloon catheter will not cross, one option may be to ablate a channel using excimer laser atherectomy or rotational atherectomy using the Rotablator™ (Boston Scientific).

Late Patency Rates

Several randomised trials have shown that stenting is superior to balloon angioplasty, with lower restenosis and reocclusion rates.10-15 However, the long-term results with bare metal stents (BMS) in CTOs are still poor compared with non-occlusive lesions. In-stent restenosis rates of >50% in long lesions and reocclusion in up to 12% of patients have been reported16 - and reocclusion is associated with a worse late outcome.10

The Primary Stenting of Totally Occluded Arteries (PRISON II) study randomised 200 patients with coronary occlusions (duration over two weeks) who underwent successful PCI with either Cypher™ sirolimus-eluting stents (SES) (Cordis) or bare metal Bx Velocity™ stents (Cordis).17 At six-month follow-up, the SES group had significantly lower binary in-stent restenosis and target vessel revascularisation rates than the BMS group - 7% versus 36% (p<0.001) and 4% versus 19% (p<0.001), respectively. The reocclusion rate was 4% in the SES group compared with 17% in the BMS group (p=0.04). One weakness of this study was that only 45% of the patients had CTOs with occlusion duration over three months. There are no randomised studies of paclitaxel-eluting stents (PES) in CTOs. Werner et al. reported observational data in 61 patients who underwent PCI for coronary occlusions (over two weeks) with PES.18 The results were compared with a BMS matched group. The PES group had a lower angiographic in-stent restenosis rate (11.7% versus 55%, p<0.001) and less reocclusion (1.7% versus 21.7%, p<0.001).

New Devices

Several new devices are under development and clinical evaluation in the hope of increasing procedural success and reducing complications in CTO PCI.


The Frontrunner™ catheter (LuMend (Cordis/ Johnson&Johnson), Redwood City, CA) uses controlled blunt micro-dissection to create a channel through the CTO, allowing the passage of a guidewire and adjunctive angioplasty. It consists of a 135 cm long central shaft, a proximal control knob and a distal articulating bioptome-like jaw, which can be opened and closed manually to a maximum diameter of 3.75 mm (see Figure 4). The distal catheter tip is blunt and no guidewire lumen is present. There is a proximal port to allow flushing and lubrication of the distal jaws. The control knob is used to advance, rotate and open the catheter jaws. The risk of vessel perforation is thought to be reduced as the dissection planes are limited to the fibrocalcific plaque, which is more rigid and less stretchable than the elastic arterial wall. It can be used through a 6 Fr guide catheter and is supported by a 4 Fr micro guide catheter (MGC). Once across the CTO, the MGC can function as a conduit for wire exchange. Orlic et al. reported the results of using the Frontrunner™ catheter in 50 patients with CTOs (duration over three months) refractory to guidewire crossing or thought to be unsuitable for conventional guidewire attempts.19 Angiographic success was achieved in 50% of patients with a relatively high perforation rate of 18%, and cardiac tamponade developed in 4% of patients. A significant operator learning curve was noted with higher success rates and fewer complications during the final year of the registry.

The Crosser™ System

The Crosser™ system (FlowCardia, CA) uses high-frequency mechanical vibrations to facilitate the crossing of CTOs. It consists of a generator that applies AC current to piezoelectric crystals in the transducer, which amplifies and transmits this energy to the catheter tip. The tip vibrates at 20 MHz, acting like a mechanical jackhammer that facilitates the crossing of CTOs. The catheter tip is olive shaped, hydrophilic and 1.1 mm in diameter (see Figure 5).

It is compatible with a 6 Fr guide catheter, available in both rapid-exchange and over-the-wire versions. The Crosser™ catheter can be mounted on a standard 0.014 inch guidewire. Initial registry data from 28 patients with CTOs resistant to the passage of conventional guidewires has reported a 53% angiographic success rate with coronary perforation in one patient.20 In this study the success rate was 26% in lesions with prior guidewire failure and 73% when the Crosser™ system was used in the same procedure after initial guidewire failure. This data suggests that the overall success rate may have been lower had only lesions that were truly refractory to a prolonged attempt at guidewire passage been included. More recently, Grube et al. reported a 76% success rate in lesions that could not be crossed with conventional guidewires.21


The SafeCross-RF™ radiofrequency guidewire (Intraluminal Therapeutics, CA) consists of an intermediate stiffness 0.014 inch guidewire (Intraluminal™ wire) with a near warning system called optical coherence reflectometry (OCR). A 0.007 inch optical fibre in the tip of the guidewire emits near infra-red light that is reflected from the tissue ahead. Reflections from plaque and vessel wall differ according to the tissue structure. This information is displayed as a continuous waveform on the screen, which warns the operator when the wire tip approaches within 1 mm of the vessel wall (see Figure 6). This allows the operator to withdraw and redirect the wire, reducing the risk of vessel perforation or dissection. When proximity to the wall is not detected, radiofrequency energy can be emitted from the tip of the SafeCross-RF™ wire to enables it to create a channel through the CTO.

The Guided Radio Frequency Energy Ablation of Total Occlusions (GREAT) registry study was a prospective non-randomised multicentre study in 116 patients with CTOs refractory to a 10-minute attempt with conventional guidewires.22 The median occlusion duration was 22 months. Device success with placement of a guidewire in the distal lumen was achieved in 54% of patients. Coronary perforation occurred in three patients (2.6% overall), who all required pericardiocentesis. Ng et al. reported a success rate of 60% in guidewirere-fractory CTOs using the SafeCross-RF™ guidewire.23 Limited steerability within the lesion remains a problem and interchange between conventional guidewires and SafeCross-RF™ was necessary in hard lesions.


Procedural success rates for CTOs have improved with specialised guidewires and better techniques and long-term vessel patency can be achieved in a high proportion of patients using drug-eluting stents. Newer devices are still required to tackle longstanding calcified CTOs with unfavourable anatomy - especially long segments of occlusion. The innovative devices described in this article need more rigorous testing to determine their efficacy and complication rates and newer tools are required by interventionists if success rates are to be increased in this difficult lesion subset.


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