Chronic total occlusions

# Overview
Chronic total occlusions (CTO) are often defined as coronary occlusions that have had TIMI 0 or 1 flow for an estimated duration of at least one month. Collateral flow to the distal territory maintains viability, but may be insufficient at times of increased oxygen demand, resulting in chronic stable angina or reduced exercise capacity. The tissue composition of the CTO is a variable mix of collagen-rich plaque, layered thrombus, calcium, and inflammatory cells with fibro-calcific caps at both ends. Neovascularization channels may form a neo-lumen or connect with adventitial vasa vasorum. The latter type of channels and bridging collaterals reduce the likelihood of successful guidewire advancement. Percutaneous interventions of CTO remain a technical challenge.

# Epidemiology and Demographics
- One-quarter of patients undergoing coronary angiography has CTO.

# Rentrop Grade of Collateral Filling
Rentrop classification is helpful to define the collateral circulation of CTO. Rentrop et al. proposed the system below to grade collateral filling of recipient arteries:

### Rentrop Grade 0
No visible filling of any collateral channels.

### Rentrop Grade 1
Collateral filling of branches of the vessel to be dilated without any dye reaching the epicardial segment of that vessel (ie, right coronary artery injection showing retrograde filling of septal branches to their origin from the left anterior descending artery, without visualization of the latter occluded artery).

### Rentrop Grade 2
Partial collateral filling of the epicardial segment of the vessel being dilated.

### Rentrop Grade 3
Complete collateral filling of the vessel being dilated.

# Treatment

## Goals of Treatment
- Restoration of epicardial and myocardial perfusion in acute total occlusion
- Improvement of functional status
- Improving anginal status: collaterals may maintain viability but collateral insufficiency may lead to angina symptoms during times of increased myocardial demand
- Increasing exercise capacity
- Reduced need for late bypass surgery
- Improved left ventricular remodeling
- Promotion of electrical stability in border/watershed zones
- Possible benefit of PCI on heart failure, ventricular function, and long-term survival

## Treatment Choices
There are three main treatment choices for CTO:
- Medical Therapy
- Percutaneous revascularization
- Surgical revascularization

## Medical Therapy
All patients should receive optimal medical therapies to reduce angina and cardiovascular events. Revascularization attempts may be considered for patients refractory to antianginal agents.

## Percutaneous Revascularization
- Observational studies, including TOAST-GISE, showed an association between successful PCI of CTO and higher freedom from angina, exercise testing performance, and adjusted survival-free rates from adverse cardiovascular events.
- Successful PCI of CTO has resulted in improved left ventricular ejection fraction on serial examinations, though parallel groups of only medically treated patients were not included in these studies. Long-term patency of successful angioplasty alone is poor; it is improved with the use of drug-eluting stents (DES).
- The randomized trial, PRISON II, showed a superiority of a DES over a bare-metal stent for CTO interventions in adverse clinical events, in-stent late loss, and re-occlusion.

## Surgical Revascularization
- Coronary artery bypass surgery (CABG) may be preferable for occluded vessels in patients with higher risk features, such as low LV ejection fraction, diabetes mellitus, or multi-vessel, left main, or high-complexity disease.

## Patient selection
Contraindications to treatment include:
- Small area of myocardial viability
- Techniques to assess viability prior to the procedure include:
- Low dose Dobutamine echocardiography
- Delayed-enhancement cardiac magnetic resonance
- Thalium/Myoview PET scanning
- Absence of ischemia
- Low likelihood of procedural success based on angiographic predictors (failed intervention patients tend to have higher mortality but also higher procedural complication rate such as coronary artery perforations and coronary dissections)
Clinical predictors of success are very poor. Angiographic predictors of failure include:
- Occlusion length > 15 mm (CT may be helpful in defining the length)
- Moderate to severe coronary calcification
- A flush, rounded or blunt (absence of a tapered "beak" at the origin ) occlusion
- Presence of bridging collaterals
- Higher age of the occlusion
- Tortuosity
- Small vessel size
- Non-visualization of the distal vessel bed
- The presence of a side branch at the occlusion site (the wire may selectively want to enter this rather than the total occlusion)
These predictors may also be assessed with CT, especially occlusion length. CT angiography may aid in choosing a retrograde approach via collaterals (CART and reverse CART technique) rather than the traditional antegrade approach.

## PCI Techniques
- EURO CTO, a randomized multicentre trial, demonstrated that PCI of a CTO is more effective to reduce angina frequency than optimal medical therapy. While another larger trial, the DECISION-CTO, showed no significant difference among these two treatment.
- The potential for vessel perforation during the procedure should be kept in mind in selecting antiplatelet agents.
- Pre-treatment with aspirin may be used in preparation for possible stent implantation.
- Some operators wait to administer a thienopyridine until the procedure is completed without vessel perforation.
- Heparin and a short-acting glycoprotein IIb/IIIa inhibitors are favored in case of severe arterial injury requiring anticoagulation reversal. A strategy of heparin with a low target activated clotting time (ACT), followed by supplemental heparin, and glycoprotein IIb/IIIa inhibitor to be administered only after successful guidewire crossing, may be employed.

### Arterial Access and Guide Catheter Selection
Contralateral/ double coronary injection from a second catheter, and arterial access to fill the distal vessel bed via collaterals, may be useful for angiographic guidance of the distal wire.
Greater support is often required for CTO interventions, and good guiding catheter support may facilitate both wire and balloon passage. For the right coronary artery, a left or right Amplatz guiding catheter can provide excellent coaxial support. A guide with side holes is often helpful in dilating the right coronary artery. Extra backup (EBU or XB) guides are useful for the left coronary system. Consideration should be given to the use of 7-8 Fr guide sizes to accommodate extra equipment that may be needed. Further backup support could be provided by a larger caliber guide catheters (7 or 8 French).

### Crossing The Lesion With The Wire
There are several potential choices for crossing a total occlusion. One standard progression in technique might include the following:
- Begin with a conventional softer tipped, less traumatic guidewire as a first step, before progressing to stiffer wires for occlusions with tougher caps. A conventional guidewire crosses > 90% of acute (< 3 month old) total occlusions.
- Several dedicated wires of graded stiffness were developed for CTO crossing, and a successful crossing frequently require trials of multiple different wires.
- Non-hydrophilic or hydrophobic wires with an intermediate stiffness are a good first choice as they have a better tactile response, are less likely to lead to a subintimal position than a hydrophilic wire, and may have an additional advantage in their ability to cross the proximal cap of the occlusion. Choices in this class include the Miracle Bros 3 and the Asahi intermediate wires.
- Hydrophilic wires may track better after the proximal cap of the occlusion has been crossed. Hydrophilic/coated wires have better maneuverability in tortuous or calcified vessels. Intermediate stiffness hydrophilic wire choices include the Choice PT XS (Extra Support), the Pilot 50, the Pilot 100 or the PT Graphix.
- Shaping the wire tip using a modest angulation is better for blunted stump occlusions.
- A low-profile balloon or exchange catheter adds backup support for wire penetration of fibro-calcific caps and may also be used cautiously for balloon-assisted progression within the occlusion.
- Intra-luminal position of the wire distal to the occlusion is suggested by a freely rotating wire tip or angiography in different views by distal catheter or contralateral injections.
- Stiffer wire tips will allow for a greater chance of crossing the proximal cap of the occlusion at the cost of an increased risk of the vessel dissection or perforation.
- Stiff non-hydrophilic wires: The Miracle Bros 6, 9, and 12, Cross-IT, Confienza, Persuader
- Stiff and hydrophilic (most aggressive): Pilot 200 and Shinobi

### Crossing Lesions That Cannot Be Crossed With A Conventional Wire
Tapered-tip wires are occasionally better at navigating into a smaller channel than on 0.014 wire. Lasers, vibrational energy, blunt dissection (e.g. Lumend Frontrunner), and ultrasound catheters have been used with variable success to recanalize chronic total occlusions resistant to standard wires. Fixed wire-balloon systems do not offer the ability to switch out wires and perform distal injection.

### Crossing The Lesion With A Balloon
Once the wire crossed the lesion, the next step is to perform angiography to confirm that you are intraluminal (i.e. that no dissection is present) and that wire perforation is not present. If dissection and wire perforation are not present, then an attempt is made to cross the lesion with a balloon. Fixed wire-balloon systems lack trackability and steer ability therefore over-the-wire systems are usually favored. Fixed wire systems may, however, occasionally be useful because of their very low profile which may allow passage in some cases in which a conventional over-the-wire system will not cross. Monorail systems are inferior to over-the-wire systems in this setting, because of their inferior balloon tracking characteristics, the inability to exchange guidewires and the inability to make a distal injection through the central lumen of the balloon to confirm your position. Often a low profile short over the wire balloon is a good first choice. An example would be a 1.5 mm X 6 mm balloon. Many investigators will remove the wire from the central lumen of the balloon and perform a distal injection at this point to confirm an intraluminal location of the balloon. If intraluminal guidewire position cannot be confirmed, balloon inflation should not be performed. If the balloon cannot be inserted all the way across lesion, inflation in proximal part of lesion can be performed to favorably alter anatomy and potentially facilitate eventual crossing. Consider aborting the procedure if, despite multiple attempts with various guidewires, the lesion cannot be crossed or successfully dilated; the risk of dissection or perforation may outweigh the benefit.

### Special Techniques
- If a wire enters a dissection plane, then a second wire may be used (parallel wire technique) to find a different pathway with the first wire serving as a reference or blocking repeat entry into the false lumen. Also, if a wire favors entering a side branch near the site of occlusion, then a balloon may be inflated in that side branch effecting a block to further wire entry.
- After failed attempts of recanalizing the true lumen, a subintimal tracking and re-entry (STAR) technique may be considered. This is more safely performed in the RCA where major side branches are absent. Retrograde approaches through robust collaterals from the contralateral vessel have been employed with variable success rates.

### Special Crossing Devices
- Blunt micro-dissection catheters
- Optical coherence reflectometry guidance of the wire
- Radiofrequency ablation, ultrasonic energy, or microscopic oscillations delivered by special catheter/wire systems to penetrate fibro-calcific caps

### Dilation of the Totally Occluded Lesion
Following initial conventional balloon angioplasty of the lesion, stent placement reduces restenosis, revascularization, and reocclusion rates. Placement of a drug eluting stent is a rational choice given the high risk of restenosis with this lesion type. Given that the lesion was totally occluded, the occurrence of stent thrombosis and complete reocclusion, while unfavorable, may not be as dangerous as it would be in an artery that was patent prior to placement of the stent. Other dilation techniques include rotational atherectomy and laser debulking.
- Determine duration of occlusion:
If duration of occlusion <3 months, standard PTCA wires are usually sufficient.
- If duration of occlusion <3 months, standard PTCA wires are usually sufficient.
- Laserwires are rarely used because they are limited to short lesions where distal vessel can be visualized via collaterals.
- Ball-tipped guidewires have not demonstrated clear superiority over conventional wires in observational and randomized trials.
- Blunt dissection may be considered if conventional wires fail to cross the occlusion.
- Debulking calcified or rigid lesions with rotational atherectomy can facilitate distal delivery of stents or PTCA balloons.
- If there is good collateral flow to the vessel distal to the stenosis, the use of two catheters for dual injections may be considered.
- Anchor balloon technique Mother-child catheter (5 Fr within an 8 Fr guide)
- Parallel wire and seesaw wiring
- IVUS guidance to look for the true lumen
- Retrograde approach (especially in previous antegrade failures)
- Controlled antegrade and retrograde technique (CART)

### Outcomes
- The thrity day mortality rate after PCI of a CTO is 1.3%.
- Success rates of 50-80% have been reported but may be affected by selection or publication biases.
- If the occlusion is less than 3 months old, the angiographic success rate is >90%, while patients with occlusions greater than 3 months old have a success rate of 70% and higher acute closure rates.
- The most common reason for failure is the inability to cross the occlusion with a guidewire (80-90%). Other common reasons for failure are the inability for the balloon to cross the lesion (15%), and lesions cannot be dilated adequately (5%) (>30% residual stenosis). Calcifications are often a major obstacle to crossing the lesion.
- Restenosis and reocclusion rates following successful PCI are higher in CTO compared to non-occlusive stenoses. These rates are improved with the use of DES.
- Successful PCI of a CTO is associated with a 50-70% rate reduction of future CABG.
- The salient complication of CTO PCI is perforation, which occurs in 4.8% of cases.
- If perforation occurs, it requires a rapid response: proximal balloon inflation, protamine administration for heparin reversal, consideration of a covered stent placement, and pericardiocentesis, if indicated.
- Integration of several angiographic factors helps determine the likelihood of success (see above). No single factor should preclude a revascularization attempt.
- Most patients (70%) are angina-free 1-4 years after successful PTCA.
- Revascularization may prevent ventricular dilation, and some studies suggest improvement in global ventricular function.
- Successful PTCA reduces the need for CABG by 50-75% but does not reduce total mortality or late MI.
- Restenosis rates are high (40-75%); stents reduce restenosis rates.
- Difficult guidewire rotation, difficulty advancing wire or balloon, or guidewire buckling may signify an extraluminal position of the wire.
- Intraluminal positioning of the crossing wire may be verified by distal injection through the central lumen of PTCA balloon or distal injection (Ultrafuse) catheter.

### Other Concerns
The decision to terminate the procedure if guidewires fail to cross the occlusion is based on the severity of symptoms (i.e. angina) weighed against the risk of more aggressive techniques/devices, fluoroscopy time, and contrast load).

# 2017 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention
- Up to 2011, only observational data had indicated the success of PCI over OMT (Optimal Medical therapy) in improving cardiovascular outcomes in patients with CTO.
- However, three major randomized control trials were conducted between 2011-17. They were called EURO-CTO, DECISION-CTO and EXPLORE.
- These trials concluded that PCI was non-superior to OMT in patients with at least 1 CTO.
- In 2017, the updated ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria (AUC) for Coronary Revascularization in Patients With Stable Ischemic Heart Disease (SIHD) was characterized by:
- Elimination of separate criteria for CTO or anatomy specific criteria for revascularization
- Criteria for revascularization include:
Symptoms of the patient
Risk of ischemia
Use of antianginal medications
- Symptoms of the patient
- Risk of ischemia
- Use of antianginal medications

# 2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)

## Chronic Total Occlusions
- In 2011, The AHA assigned a Class IIa recommendation for CTO-PCI.

# 2021 ACA Revascularization Guideline
- Despite appreciable retrospective and registry data proposing some benefits, there is no clear benefit demonstration from prospective randomized trials.