Original Contribution
Distal Protection during Primary Angioplasty: A Feasibility and Safety Study Utilizing a Novel Filter Technology
October 2006
Signs of suboptimal myocardial reperfusion are frequently encountered following primary angioplasty and this phenomenon is associated with poor left ventricular wall motion recovery and unfavorable clinical outcomes.1–4 Patients with acute myocardial infarction are prone to have complex and highly thrombotic lesions where distal embolization during intervention plays a significant role in limiting effective myocardial reperfusion.5,6 Distal protection by either occlusion or filter devices have been used with heterogeneous results. The purpose of the study was to report on the safety and feasibility of the adjunctive use of a novel embolic protection system in patients undergoing primary angioplasty.
Methods
Patient population. Twenty consecutive patients with acute myocardial infarction were included in the study and subjected to primary percutaneous coronary intervention (PCI) with the Spider device after written consent was obtained. The inclusion criteria were as follows: (1) presentation within 12 hours from symptom onset; (2) chest pain lasting >/= 30 minutes and resistant to intravenous nitrates; (3) >/= 0.2 mV ST-segment elevation in at least 2 contiguous leads on a 12-lead ECG; (4) infarct-related native artery with a reference lumen diameter >/= 2.5 mm.
The exclusion criteria were significant left main coronary disease, cardiogenic shock at admission or thrombolytic therapy. The local Institutional Ethics Committee approved the study protocol.
Primary angioplasty with distal protection. Before intervention, patients received standard medical therapy consisting of 100 IU/kg of unfractionated heparin, 500 mg of aspirin, a 300–600 mg loading dose of clopidogrel and beta-blockers, if not contraindicated. Administration of glycoprotein IIb/IIIa inhibitors was at the discretion of the treating physician. Post-stent implantation therapy consisted of aspirin and clopidogrel at standard dosages. Primary PCI was performed using a 6 or 7 Fr guiding catheter, stent placement without restrictions, and treatment of only the infarct-related artery was recommended. The initial attempt to cross the target lesion was performed with an independent 0.014 inch steerable coronary guidewire according to the operator’s preference. The device was then advanced at least 1.5 cm beyond the target lesion and preferably parked proximally to any important side branch. In patients with persistent TIMI grade 0 flow, the filter was blindly deployed beyond the occlusion and repositioned if necessary after predilatation with a 1.5–2.0 mm balloon. After satisfactory stent deployment, the filter was captured into the sheath and retrieved.
Description of the Spider™ Distal Embolic Protection System. The Spider device (ev3, Inc., Plymouth, Minnesota) has a crossing profile of 3.2 Fr, and consists of 4 components: a capture wire, delivery catheter, stylet and recovery catheter. The capture wire consists of a Teflon-coated 0.014 inch stainless steel wire that is convertible from 320 to 175 cm length for use with rapid-exchange systems (Figure 1). The capture wire has a 1.2 cm atraumatic floppy tip and a heparin-coated nitinol mesh filter varying in diameter size from 3–7 mm. The diameter of the capture wire is selected to be approximately 0.5 mm larger than the vessel diameter at the site of deployment. The delivery catheter is a 3.2 Fr polyethylene catheter that is used with the inner polyethylene stylet that provides a tapered transition from the delivery catheter to the primary 0.014 inch guidewire. Unlike other distal protection devices, the capture wire in the Spider device is not used to cross the target lesion. Instead, the operator may select an independent 0.014 inch guidewire of choice to cross the target lesion and access the distal coronary artery based on anatomic or morphologic considerations and personal preference. Once the guidewire is positioned distal to the target lesion, the delivery catheter and stylet are advanced en bloc, and once in position in the distal coronary artery, the stylet and guidewire are removed and exchanged for the capture wire. Once properly positioned, the delivery catheter is retracted to deploy the nitinol filter and then removed. After angioplasty and stent deployment, the 4.2 Fr (3, 4 and 5 mm) or 4.9 Fr (6 and 7 mm) recovery catheter is used to recapture the filter and remove it from the patient.
Electrocardiographic laboratory data. Standard 12-lead electrocardiography (ECG) was performed prior and 60 minutes postintervention. The total ST-segment deviation was calculated in each ECG from leads exploring the infarct area as described previously.2,7,8 ST-segment deviation was measured in 11 leads (all but aVR) to the nearest 0.025 mV with lens-intensified calipers, 20 msec after the end of QRS complex, with the PR-segment considered as the baseline. All ECGs were analyzed as pairs and graded for ST-segment elevation resolution (STR) by a blinded observer. As previously described, ST-segment deviation was calculated as the sum of ST-segment elevation in leads 1, aVL and V1 to V6 for anterior myocardial infarction, and leads II, III, aVF, V5 and V6 for non-anterior myocardial infarction, plus the sum of ST-segment depression from leads with >/= 0.1 mV depression in leads II, III and aVF for anterior, and in leads V1 to V4 for non-anterior infarction. Complete STR was defined as >/= 50% reduction of the initial sum of ST-segment deviation between the pre- and post-angioplasty ECGs.9Angiographic analysis. The angiograms were read as a single group by 3 experienced observers. Baseline and final angiograms, the object of analysis, were sliced from the rest of the procedure to blind the investigators to the use of the Spider device. Quantitative coronary angiography parameters were measured.
Particulate analysis. The distal portion of the filter was cut and immersed in 10% buffered formaldehyde, and after 2–48 hours of fixation, the mesh of the filters was carefully cut from its frame and processed for histological study. Digitized black and white images were used for measurements. The Optimas Analysis Program, version 5.0 (Meyer Instruments, Inc., Houston, Texas), was used. Each of the particles was selected and the longitudinal and transversal diameters were measured, as well as the total area.
Statistical analysis. Data are expressed as mean ± SD for continuous variables and as absolute and relative frequencies for categorical variables. The Student’s paired t-test was used to assess changes from baseline to 30 days (SPSS version 12.0 software, SPSS, Inc., Chicago, Illinois).
Results
A total of 20 patients underwent successful primary angioplasty with the Spider embolic protection device. The patient and lesion characteristics are shown in Table 1. The technical success rate was 95%. In 1 patient, delivery of the Spider device, initially unsuccessful, was finally achieved after predilatation with a 2 mm balloon. The filter was blindly positioned due to persistent TIMI grade 0 flow in 9 patients (45%). The Spider device was successfully retrieved in all cases. Coronary spasm or dissections attributable to the distal protection system were not observed. The final angiographic result is shown in Table 2. Ninety-percent of the patients achieved >/= 50% STR (mean STR was 85.6 ± 16.5%). In-hospital clinical outcome is shown in Table 3. There were no major adverse cardiac events related to the device itself. The rate of in-hospital major adverse cardiac events (death, reinfarction, urgent target vessel revascularization) was 10%.
Particulate analysis. Histopathological analysis was performed in 5 cases. Particles were recovered in all filters. The number of particles analyzed per patient ranged from 8–48 per filter. Particles ranged from 101–1,299 mm in maximum diameter, and from 212–1,487 mm2 in area. The majority of particles were composed of platelets, clumps, red cells and fibrin, which led to the diagnosis of fresh thrombus (Figures 2 A, B, C and D). Cellularity was widely variable, often including monocytes, polymorphonuclear cells and lymphocyte clusters. Amorphous areas were observed within the fibrin network, which suggested the presence of ongoing thrombus organization and/or plaque remnants. Particles with mucopolysaccharidic amorphous extracellular matrix, which stained positive with Alcian blue, were observed, which also supports the presence of plaque components within the detached material. Lipid vacuoles, foam cells, smooth muscle cells, cholesterol clefts and calcified areas were not observed.
Discussion
The main findings of the present study are as follows: (a) the Spider device appears to be safe and feasible as an adjunctive tool during primary angioplasty; (b) the Spider device is associated with a highly successful delivery rate; (c) this success rate translates to elevated rates of post-procedural complete STR.
Effective myocardial reperfusion after primary PCI may be limited by several factors such as distal embolization, microvascular damage, vasoactive cytokines, platelet aggregation and reperfusion injury. Several studies describing the use of distal protection devices or mechanical removal of the thrombus during primary angioplasty have shown heterogeneous results.5,10,11 Population subsets, variety of surrogate endpoints and differences in protection device technology are some potential explanations.12–18
The present study reports the initial experience with an innovatively designed filter protection device in native coronary arteries. The present high degree of delivery success is mostly due to the fact that an independent guidewire is use to cross the target lesion, rather than primary crossing with the filter-wire system. The Spider filter has a very low profile with excellent trackability guaranteeing its passage to virtually all lesions.
We utilized STR, a validated surrogate to assess myocardial reperfusion at the tissue level,2,3 showing an impressive improvement in myocardial reperfusion in spite of the presence of documented angiographic thrombus in all patients. In line with our results, a recent report describing the use of the FilterWire EX (Boston Scientific Corp., Natick, Massachusetts) in STEMI also showed an improvement in STR.15 The recently published EMERALD trial12 failed to demonstrate a benefit from distal protection. However, it is possible that a delay reported with the utilization of the balloon-occlusion device may have hampered its results and attenuated the potential benefit of distal protection.
Conclusions and Clinical Implications
Distal embolization during primary angioplasty is a frequent and deleterious phenomenon. The adjunctive use of the Spider embolic protection device is safe and feasible in the setting of acute myocardial infarction. An international, multicenter, randomized clinical trial is prospectively testing this challenging hypothesis.
References
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