Abstract: Under-expanded and under-deployed stents carry a high risk of restenosis and thrombosis, with inherent serious clinical complications. The management of under-expanded stents is a difficult clinical entity. Method. A retrospective analysis of prospectively collected data on all under-expanded, under-deployed stents that were managed by excimer laser, with and without contrast, performed at the Freeman Hospital, a large tertiary cardiac center, in the northeast of England. Results. Between November 2014 and September 2016, a total of 19 cases were treated with excimer laser with or without contrast, with the initial approach done without contrast. All cases were successful with a stepwise energy-level approach. There were no clinical, procedural, or in-hospital complications, with full expansion of the stents after laser application. Conclusion. The use of excimer laser with or without contrast offers a safe and effective method for managing under-expanded and under-deployed stents and potentially avoiding long-term complications of under-expansion.
J INVASIVE CARDIOL 2017;29(11):364-369.
Key words: percutaneous coronary intervention, stent, laser PCI, coronary artery disease, contrast media, restenosis, calcified coronary arteries, debulking techniques, under-expanded stent, atherectomy
Percutaneous coronary intervention (PCI) is increasingly undertaken in an aging population with complex coronary disease and heavy calcification.1-3
The inability to dilate or cross calcified lesions with a balloon remains a major limitation of PCI and debulking techniques can help overcome this limitation,4 as the luminal dimension post intervention predicts the likelihood of in-stent restenosis (ISR) and is a factor responsible for stent thrombosis.5,6 Calcified lesions limit PCI success by restricting optimal stent dilation,7 and debulking prior to stent implantation is usually achieved using high-speed rotational atherectomy (HSRA), excimer-laser coronary angioplasty (ELCA), or cutting balloons.1-4,8-12
The propensity for incurring non-dilatable lesions has increased with the increased use of direct stent implantation. Placement of a stent prior to recognition that a lesion is non-dilatable usually leaves limited therapeutic options and difficult management, which are associated with failure and complications. In these difficult scenarios of PCI and under-expanded stents, ELCA has been used to modify the lesions and help expand the deployed stents.
We report a case series of ELCA for managing under-expanded stents and advocate this as the treatment of choice for these challenging cases.
Excimer laser fundamentals. Laser is an acronym for Light Amplification by Stimulated Emission of Radiation. It refers to the process of creating a highly directional beam of monochromatic (single-wavelength) light with high energy. The term excimer is an acronym for excited dimer. Excimer lasers release energy in the ultraviolet (UV) range (10 to 400 nm) in very short pulses rather than in a continuous wave form. The advantage of this as compared with lasers that emit in the infrared ranges is that the absorption depth is less (<100 microns), which reduces the risk of collateral tissue damage when ablating plaque. The precise wavelength of emission depends on the exact nature of the gas mixture from which the photons are generated.
Experience in the cardiovascular field has involved the xenon chloride (XeCl) 308 nm laser, which became available in 1983 for research and was approved by the United States Food and Drug Administration for its first clinical indications in 1992. The laser beam is formed as a result of high-voltage electrical discharge across a mixture of the xenon gas and a highly diluted (0.1%) hydrogen chloride solution. An excited state molecule of XeCl (the excited dimer) is produced, which subsequently drops to its ground state of XeCl, a weakly covalent molecule, which liberates a photon with a wavelength of 308 nm.
The photon can then interact with another excited electron and produce two photons of the same wavelength and phase. Mirrors are used to amplify this process by reflecting the photons but also permit emission of the photons, and these will result in the formation of the laser beam.
The laser machine emits laser energy with a catheter output flow range between 30 and 80 mJ/mm2 (fluence), a repetition rate of 25-80 pulses/sec, and a pulse width of 125 to 200 ns (nominal 135 ns). There are multiple laser catheter sizes, ranging from 0.9, 1.4, 1.7, and 2.0 mm diameter, with only the 0.9 mm catheter able to deliver the highest range of fluence and repetition of 80/80. The other catheters deliver a maximum of 60/40.
Excimer laser mechanism of action. Excimer laser ablates vascular tissue by three mechanisms:
1. Photochemical (fracture of molecular bonds): the UV light pulse hits the plaque and is highly absorbed with each photon generated carrying sufficient energy to break molecular bonds. The duration of the laser pulse is 125 billionths of a second (125 ns), ie, the time that UV light pulse hits the tissue/plaque.
2. Photothermal (tissue vaporization): the molecular bonds are also vibrated during the absorption process, resulting in heat. Intracellular water is vaporized, leading to cell rupture and the creation of a vapor bubble. This lasts 100 millionths of a second (100 µs).
3. Photokinetic (clearance of by-products): the rapid expansion and collapse of the vapor bubble further breaks down plaque but also assists in clearing by-products of ablation (water, gases, and small particles). The entire process is completed in 400 µs. The vast majority of these particles are minute enough to be cleared by the reticuloendothelial system, minimizing the risk of distal microembolization.
The activation of the laser catheter is performed in a saline medium with continuous flush as the activation in contrast can lead to the formation of large bubbles and increase the risk of vessel damage with dissection or perforation. However, in highly resistant lesions, the use of contrast medium while activating the laser has been reported with great success.12-14
Study design. This is a retrospective analysis of prospectively collected data. The primary source of data was our local coronary artery disease (CAD) database (Dendrite), which holds information on each PCI procedure performed at our hospital. Baseline demographics, clinical presentation, procedure details, and procedural complications were prospectively collected at the end of each procedure by the performing cardiologist. Postprocedural complications, clinical data, and discharge medications are updated on discharge. Our tertiary center performs close to 3000 PCIs/year.
The technique was introduced to the center by the senior author, who is a proctor and uses laser regularly. The cases with laser used were identified from the catheterization laboratory records and the angiograms were reviewed to identify the under-expanded stent cases. The PCI procedures were performed from the radial approach in the normal fashion and under-expansion and full expansion of the stents were identified on angiography. Intravascular imaging with ultrasound or optical coherence tomography was used in only a few cases at the discretion of the operator. All identified under-expanded stents were treated with high-pressure non-compliant balloon dilation originally, with laser used when the stents remained under-expanded. Laser with contrast was mainly used by the senior author when normal use in saline did not produce the desired effect of full stent expansion. Postdilation after laser was done by non-compliant balloons to high pressure (16-20 atm) to ensure full expansion.
Between November 2014 and September 2016, ELCA was used in 19 cases for managing under-expanded stents. The age range of the patients was 47-84 years. Indication for PCI was ST-elevation myocardial infarction (STEMI) in 2 cases, non-ST elevation myocardial infarction (NSTEMI) as urgent procedure in 6 cases, and in an elective setting for stable angina in the remaining 11 cases (Table 1).
ELCA was used for ISR due to previously implanted, under-expanded, old stents in 6 cases and for freshly implanted, under-expanded stents in de novo lesions in 13 cases where laser was used in the same setting. The cases were performed by four experienced operators (operator #1: 9 cases; operator #2: 6 cases; operator #3: 3 cases; and operator #4: 1 case) (Table 2).
The procedure set-up and performance was done in the normal fashion through the radial approach in 13 cases and femoral approach in 6 cases, with all patients receiving antiplatelet loading and intravenous heparin 100 U/kg.
In the cases of old implanted and under-expanded stents, the lesion was wired with a workhorse PCI wire and then the ELCA catheter used. In the other de novo cases, the lesions were wired and predilated, and stents were inserted and postdilated to high pressure (16-24 atm) with non-compliant balloons of appropriate size as per normal practice. None of the cases were performed by direct stenting.
Scoring balloon (Angiosculpt; Spectranetics) was used for de novo lesion preparation in 2 cases, cutting balloon was used in another 2 cases, and rotational atherectomy was used in another 2 cases (1.5 mm burr Rotablator; Boston Scientific). Intravascular imaging was used in 8 cases (intravascular ultrasound in 5 cases and optical coherence tomography in 3 cases).
ELCA (Spectranetics) was used with the 0.9 mm laser catheter in 16 cases and 1.4 mm catheter in 3 cases. Laser energy was delivered within the stent at the under-expanded segment in saline medium as a start in all cases. Operator #1 performed laser in contrast medium in 8 out of the 9 cases while operator #2 used contrast in 1 case only. Operator #3 and #4 did not use contrast. The fluence (mJ/mm2)/repetition rate (Hz) varied according to the operator to achieve optimum result in pulses of 40/40, 60/60, and 80/80 with 0.9 mm catheter and 60/40 in the 1.4 mm catheters (Figures 1-4).
After laser use, the under-expanded stent segment was further postdilated to high pressure (16 atm or more) with appropriately sized non-compliant balloon to achieve full expansion. All cases were successful and full expansion was achieved in all but 3 cases where a minor (<10%) under-expansion, identified angiographically, remained despite laser and high-pressure non-compliant balloon inflation. In these 3 cases, laser was performed in saline only and no contrast was used.
There were no major procedural or in-hospital complications associated with any of the cases. The under-expanded stent was a drug eluting stent (DES) in 17 cases and a bioresorbable vascular scaffold (BVS) in 2 cases where the poor preparation of the lesions was unrecognized. One patient with BVS presented within a week with STEMI and thrombosis distal to the BVS, 2 days after he prematurely stopped his antiplatelet therapy. He had a successful PCI and outcome. No other major complications were noted in the 30 days post PCI. One patient returned with ISR within 4 months. There have been no documented clinical events in the rest of the patients, who remain well.
Laser PCI with or without contrast medium offers a safe and innovative approach to managing difficult cases of undilatable and under-expanded stents, with successful outcomes.1,2,12-14 Complications were low in the previously reported cases, with moderate coronary dissection reported in 5%-7% with the use of saline medium while activating the laser, and perforation in 0%-1.4%. Goldberg et al were the first to report the use of contrast injection during laser activation to amplify the energy and shock waves to successfully treat under-expanded stents resistant to balloon dilation.13 Another report was published a decade later on using a blood medium to modify and treat under-expanded stent. There were also subsequent case reports and a registry.1,3,12,14,15
The presence of heavily calcified lesions, which are resistant and difficult to treat, can lead to under-expansion of deployed stents; under-expanded stents have a higher rate of future complications, such as restenosis or thrombosis, and it is imperative that steps are taken to achieve full expansion of the stent, as managing these under-expanded stents can be challenging.
Although rotational atherectomy is an option, it is not an ideal one because it is associated with increased complications due to the presence of stent struts coming in contact with the burr,15 particularly in freshly deployed stents.16 Furthermore, the stent struts can be a barrier between the burr and the calcified plaque of inadequately expanded stent in a non-dilatable calcified lesion. In addition, there is a potential for damaging the exposed stent struts.17 Likewise, cutting balloons offer similar constraints to success and given their bulky size, may not be deliverable in such under-expanded stents. In our experience, however, both HSRA and cutting balloons have been used on occasion with successful outcomes.
Excimer laser contains a mixture of xenon and chloride gases.18 An understanding of the excimer-laser mechanism is essential to know why laser in a contrast medium is effective at treating cases of under-expanded stents. Absorption of laser by the tissue leads to photochemical, photomechanical, and photothermal effects, as mentioned earlier. However, the main effect is the thermomechanical one leading to a rapid expansion and imploding of vapor bubbles.14,19,20 The rapid conversion of intracellular water into vapor leads to an increase in volume, which generates acoustic pressure shock waves at and distal to the area of laser activation.19,20
These mechanisms are responsible for the beneficial as well as the detrimental effects and complications of laser angioplasty. The recommendation for activating laser in saline medium (the “flush and bathe” technique) stemmed from the understanding of these effects, as no pressure waves are generated when laser is activated in saline, while significant pulse pressure is generated in a 25% vol/vol blood in saline or in as low as 1% vol/vol contrast.21 Thus, the use of saline flush during laser activation reduces the incidence of dissection and complications.18
The activation of laser in contrast medium leads to the generation of a significant pulse pressure >100 atm, which explains the success of this technique in treating under-expanded stents because these pulse-pressure waves modify the resistant plaques underneath the deployed stents. Furthermore, understanding this effect highlights the importance of using this technique only within the stented area to minimize any potential vessel injury. However, in operator #1’s experience, and in selected cases of undilatable and heavily calcified lesions, laser was used in contrast medium in the absence of a stent, with successful outcome and with no complications. This approach should only be undertaken by highly experienced laser operators and the recommendation should continue to be contrast use only within the stent.
Although laser in saline is effective for under-expanded stents, as we demonstrated, 3 cases out of the 10 where contrast was not used had a residual 10% stenosis, and full expansion may have been achieved in these cases if laser had been used in contrast medium.
When considering the size of the laser catheter, we recommend the smallest 0.9 mm catheter for multiple reasons. First, the deliverability of the smaller size is better in complex lesions. Second, the maximum energy level of the smaller catheter is 80 mJ/mm2 (fluence), with a maximum repetition rate of 80 pulses/sec, in comparison with 60/40 maximum energy and repetition rate for the larger-size catheters. Third, the size of the generated vapor bubbles is estimated to be three times the diameter of the laser catheter.12,19 Thus, larger-size catheters activated in contrast can lead to macrobubbles, with increased risk of complications.12
Except for the ELLEMENT registry,12 all other instances of successful use of laser for under-expanded stents have been case reports.14,18,21-24 This may be due to the uncommon occurrence of under-expanded stents, or possibly due to the limited availability of excimer laser and the lack of guidelines for the management of under-expanded stents.
In this series, we successfully managed 13 cases of freshly implanted and under-expanded stents in de novo lesions, which is the largest number that has been reported to date, and included 7 cases at the time of stent implantation as well as 6 cases of ISR.
We believe we are the first to report laser use for under-expanded BVS, which was successful immediately. One of these cases was the only case that had a complication. The patient presented 1 week later with subacute stent thrombosis, having stopped his antiplatelet therapy 2 days after scaffold implantation. He was successfully treated with PCI and has been well since. The mechanism behind the scaffold thrombosis is more than likely the early cessation of antiplatelet therapy; however, it is not clear if any disruption of the scaffold by laser energy had occurred because no intravascular imaging was performed by the treating physician.
We demonstrated that the use of excimer laser with and without contrast medium was successful in managing complex and difficult cases of under-expanded stents, which if not treated and dilated fully, can lead to significant clinical events with high morbidity and possible mortality.
Laser angioplasty with or without contrast medium is a novel and safe technique for dealing with under-expanded stents. Our series demonstrates that this technique is effective in modifying the underlying lesions and helps to improve stent expansion to the optimal level. Adequate lesion preparation prior to stent deployment remains the most important step to prevent stent under-expansion and subsequent difficulties. Guidelines need to incorporate laser for this group of cases to widen the use by more operators and PCI centers.
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From the 1Cardiac Department, Freeman Hospital, Newcastle upon Tyne, United Kingdom; and 2Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Egred is a proctor for Laser and has received honoraria from Spectranetics. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted March 6, 2017, final version accepted March 24, 2017.
Address for correspondence: Dr Mohaned Egred BSc (Hons), MBChB, FRCP, FESC, MD, Consultant Interventional Cardiologist & Honorary Senior Lecturer, Freeman Hospital, Newcastle University, Newcastle upon Tyne, NE7 7DN, United Kingdom. Email: firstname.lastname@example.org