The last three years have seen the application of percutaneous excimer laser atherectomy in patients sustaining acute myocardial infarction (AMI) gaining momentum. Current efforts in the US are concentrated toward identification of the best technologies for efficacious restoration of flow in the infarct-related vessel and toward shortening the time lag between the presentation of AMI patients to the emergency department and the subsequent percutaneous coronary intervention at the cardiac catheterization suite for revascularization of the infarct-related vessels.With this in mind, the interest of interventionalists and medical centers alike in excimer laser atherectomy as a reliable and efficient revascularization modality is justified.
In August 2003, the US Food and Drug Administration (FDA) removed a decade-old set of contraindications for excimer laser use, that were originally imposed by the laser industry as a cautionary measure. Thus, the following clinical conditions are no longer considered contraindications and are currently available for the interventionalist discretions: AMI, acute thrombosis, and depressed left ventricular ejection fraction. The FDA decision and the noted growing recognition of the role of excimer laser atherectomy in AMI are based on discoveries from basic research projects that illuminate the special interaction of excimer laser with thrombus and on clinical evidence from numerous multicenter and single center studies that analyzed excimer laser utilization in coronary and peripheral revascularization.
Thrombolytic pharmacologic therapy and/or balloon angioplasty with adjunct stenting continue to be considered standard of care in the management of patients with Q-wave and non-Q-wave AMI alike. The pharmacologic approach is limited by restoration of adequate antegrade flow in only 50% to 60% of patients and by 20% to 30% post-treatment reocclusion of the infarct-related artery. Although balloon angioplasty has commonly and successfully been used in AMI, it carries significant limitations, especially in dealing with vessels and lesions that contain intracoronary thrombus. Since thrombus is highly prevalent in AMI, its presence within the infarct-related vessel is associated with a higher risk for complications during and after standard balloon angioplasty. Notably, thrombus disruption by balloon inflations or by direct stenting can increase local thrombosis, enhances platelet aggregation, and results in distal embolization. Hence, the application of 308nm ultraviolet pulsed-wave excimer laser energy is intriguing.
This laser provides the following advantages:
- The laser system (CVX-300, Spectranetics) is a technically user-friendly device. It is readily available for urgent utilization in the cardiac catheterization suite, especially in AMI patients who are unstable and need rapid intervention.
- A new catheter technology (termed 'optimal spacing') that was introduced in 2001 provides a 30% increase in plaque ablation and thrombus dissolution in comparison with the previous generation of laser catheters.
- The emission of excimer light results in adequate thrombus removal and clearance, thus, contributing to rapid restoration of enhanced antegrade thrombolysis in myocardial infarction (TIMI) flow within the infarct-related vessel.
- The excimer laser energy is uniquely capable of suppression of platelets aggregation, significantly reducing the need for administration of expensive glycoprotein 2b/3a receptor inhibitors.
- The underlying atherosclerotic plaque is vaporized and debulked.
- The effective interaction of the excimer light with the thrombus and plaque eliminates the need to use distal protection devices, even in saphenous vein graft interventions.
- The laser facilitates subsequent stenting of the target lesion.
Initial clinical applications of the excimer laser atherectomy in AMI were first reported from single-center experience. The safety and efficacy of the ultraviolet excimer light in PCI were assessed and documented in these studies. Investigators repeatedly demonstrated that the excimer laser provided adequate debulking and rapid restoration of normal TIMI 3 flow within infarct-related vessels of treated patients. In the spring of 2004, the Cohort of Acute Revascularization in Myocardial Infarction with Excimer Laser (CARMEL) multicenter report was published. The study involved eight participating centers in the US, Canada, and Germany, enrolling 151 patients with evolving AMI within 24 hours of symptoms onset. These patients experienced continuous chest pain and/or ischemia.The percutaneous treatment included excimer laser atherectomy and adjunct stenting. Importantly, the data obtained by the participating centers was submitted to independent core laboratories for quantitative coronary analysis and for statistical analysis. The clinical profile of the enrolled patients serves as testimony to the scope of associated diseases and the challenge they imposed to the interventionalists - 63% had hypertension, 30% had diabetes, 24% underwent prior coronary bypass surgery, 23% sustained a previous myocardial infarction (MI), and 28% had either contraindications or failure of thrombolytic agents in the initial phase of the AMI treatment. Notably, the target vessel for revascularization was an old saphenous vein bypass graft in 31 (21%) of the participants.
Twenty patients (13%) presented to the cardiac catheterization laboratory already in a severely compromised hemodynamic condition of cardiogenic shock. The pre-treatment baseline left ventricular function as measured by angiographic left ventricular ejection fraction was compromised at a mean left ventricular ejection fraction (LVEF) of 44%±13%. A large proportion (74%) of the AMI patients exhibited critical (95% to 100%) stenosis of the target infarct-related vessel. Specifically, total occlusion with an accompanying TIMI 0 flow was present in 56/151 of patients.This level of critical occlusions is attributed to the underlying atherosclerotic plaque and the significant thrombus burden encountered. Indeed, considering the magnitude of thrombus presenting at the target lesion, a large thrombus burden (TIMI thrombus scale three or four) was present in as many as 65% of the cases. Among those who had TIMI 1 to TIMI 3 coronary flow the mean lesion length was 23±16mm. Thus, it is important to recognize that, altogether, this study included patients who would have been excluded from most previously published trials of percutaneous revascularization in AMI because of the prevailing devastating combination of unstable clinical/hemodynamic conditions and complex angiographic morphology of the target lesions.
Small-size laser atherectomy catheters (0.9mm and 1.4mm) were used in 34% of the lesions whereas larger size catheters (1.7mm and 2.0mm) were used in 66%. Specifically, the final laser catheter tip size was 2.0mm in 23% of the lesions, 1.7mm in 43%, 1.4mm in 25% and 0.9mm in 9%. By visual assessment the angiographic per-cent stenosis was reduced from a baseline of 95%±6% to 48%±23% (p<0.001) by the laser emission. Adjunct balloon dilation and stenting then achieved a 3%±9% final residual angiographic stenosis (p<0.001 versus baseline and post-laser). Angiographic TIMI flow at baseline was 1.2±1.1. It increased significantly by laser treatment up to 2.8±0.5 (p<0.001) and then to 3.0±0.2 post stenting (p<0.001 versus baseline). Laser success was gained in 143 lesions (95%), angiographic success was achieved in 146 lesions (97%) and the overall procedural success rate was 91%. Figure 1 depicts utilization of excimer laser angioplasty for a patient with an acute inferior wall myocardial infarction. The infarct-related vessel was the right coronary artery, which contained a complex thrombotic lesion in its middle portion.
In reference to the quantitative coronary angiography (QCA) analysis of the coronary angiograms, the minimum lumen diameter (MLD) increased with laser emission from a baseline of 0.5±0.5mm (mean ± scientific data (SD)) to 1.6±0.5mm (p<0.001) and then to 2.7±0.6 following adjunct stenting (p<0.001 versus baseline and versus post laser).
The mean percent diameter stenosis was decreased with laser treatment from a baseline of 83%±17% (mean ±SD) to 52%±15% (p<0.001 versus baseline) and was further reduced by stenting to 20%±16% (p<0.001 versus baseline and versus post laser). By QCA a baseline TIMI flow of 1.6±1.3 was increased by laser emission to 2.5±0.8 (p<0.001) reaching a final TIMI flow of 2.9±0.4 (p<0.001 versus baseline). The plaque area dissolution index was reduced from baseline by 34%±35% with application of the laser and altogether it was decreased from pre-treatment to post-treatment by 80%±21%.
A special consideration in the QCA analysis was given to the excimer laser effect on thrombus debulking. Analysis revealed that the maximal acute gain of the laser was achieved in lesions with an extensive thrombus burden (0.76±0.52 for small thrombus versus 1.21±0.72 for extensive thrombus, p<0.03). Overall, six patients died during hospitalization following the index procedure. Each of these individuals presented to the cardiac catheterization suite already in a state of cardiogenic shock.Thus, among the total of 20 patients who presented with AMI accompanied by cardiogenic shock, there was a 30% mortality rate. Notably, low rates of perforation (0.6%), dissection (5% major, 3% minor), acute closure (0.6%), distal embolization (2%), and bleeding (3%) were recorded. Emergency bypass surgery was not required and no procedure-related cerebral vascular injury occurred.
Subgroup analysis for the 31 patients with saphenous vein grafts interventions revealed that a 97% angiographic success, 87% laser success, and 84% procedural success rates were achieved. Importantly, it demonstrated a 0% distal embolization rate and 3% transient 'no reflow' phenomenon, thus raising a practical suggestion that distal protection devices are not a necessary adjunct for laser procedures.
In order to further identify factors predictive of laser and procedural success, a logistic regression analysis model was used. Univariant analysis revealed that preserved left ventricular ejection fraction (odds ratio 18, CI 2.2 to 141; p=0.003) and absence of cardiogenic shock (odds ratio 17, CI 4.2 to 60; p<0.001) were associated with procedural success. The presence of intracoronary thrombus was not a predictor of procedural failure. In a multivariant regression analysis model, only absence of cardiogenic shock remained as a significant factor affecting procedural success. However, as with other mechanical modalities applied for treatment of an AMI, cardiogenic shock remained a predictor of major adverse coronary event. The investigators concluded that application of excimer laser angioplasty in AMI is feasible and safe providing for efficient debulking of thrombus and the underlying plaque. The exceptionally low rates of distal embolization and 'no reflow' phenomenon as encountered in this multicenter study raise the intriguing possibility that, when excimer laser energy is applied, there is, in fact, no need for distal embolization protection devices.
Basic research provides additional evidence regarding the favorable interaction between excimer laser light and thrombus. Thrombus is known to avidly absorb ultraviolet excimer light. As platelets are among the major constituents of thrombus, the effect of excimer laser energy on platelet aggregation was recently investigated. Specifically, the in vitro interaction between the excimer laser light and platelets in whole blood was examined. The basic research experiments provided strong evidence that aggregation kinetics are altered in platelets exposed to the ultraviolet excimer laser energy. This was manifested by decreased aggregation capability (the 'stunned platelet phenomenon') among irradiated platelets and by platelets' reduced ability to produce the necessary physical force for engagement in the process of aggregation. The suppression of platelet aggregation is dose-dependent (i.e. the higher the laser fluence level delivered the more pronounced suppression is achieved). No adverse effects of this laser light on the morphology of the irradiated platelets were detected. Other experiments revealed that laser-induced acoustic shock waves produce effective fibrinolysis by mechanical dissolution of the fibrin fibers that serve as a scaffolding system for the thrombus structure.
As of spring 2004, there are 388 CVX-300 excimer laser systems worldwide. Two hundred and eighty-seven of these units are based in the US. These systems are used for the treatment of a variety of coronary and peripheral atherosclerotic occlusive diseases and for pacemaker lead removal. Conceivably, the current indications for excimer laser revascularization will further expand and the role of excimer laser atherectomy as a unique reperfusion modality for treatment of patients with AMI will continue to evolve.