Abstract
Background
Thrombus is highly prevalent in patients with recent symptoms (< 6 months) of claudication or limb ischemia due to an occluded culprit lower extremity vessels. Treatment of these thrombotic occlusions is challenging. In this feasibility study, the excimer laser (Spectranetics, Colorado Springs, CO) has been tested for its safety and ability to ablate thrombus in patients with recent arterial occlusions.
Methods
Angiographic operator assessment and volumetric core lab quantitation of the thrombus were performed at baseline and after excimer laser but prior to definitive treatment of the vessel to evaluate thrombus resolution. Consecutive patients were prospectively enrolled at a single site. Procedural success was defined as achieving a residual stenosis of < 30% after final treatment with no intraprocedural complications requiring additional treatment.
Results
20 consecutive patients were enrolled in this study (8 males, mean age 69.5 ± 11.1 years). Based on patients symptom onset, 12 patients were subacute (> 24 h, < 30 days), and 8 chronic (between 1 to 6 months). 15/20 (75%) had restenotic occlusions. Due to the long, occlusive nature of these lesions, only 8 patients had complete intravascular ultrasound images at each time point which allowed volumetric analysis by the core lab. There was no statistical difference in plaque/thrombus volume between baseline (pretreatment) and excimer laser ( P = .68). There was however a significant reduction in residual angiographic stenosis post laser alone (100% vs. 66.75% ± 23.9%, P = .001). Procedural success was 100%. There were no deaths or amputations. Bail out stenting was performed in 10/20 (50%) patients. Embolic filters were used in 15/20 (75%) of patients. Macrodebris > 2 mm were seen in 85.7% of filters. There was no in-hospital or 30-day reocclusion of the treated vessel but one patient had a vascular access complication (small AV fistula) conservatively managed. No other serious adverse events were noted.
Conclusion
Using the excimer laser appears safe in this small feasibility study of subacute and chronic thrombotic occlusions. Angiographically, there was a significant reduction in percent stenosis with the laser alone. The limited IVUS data did not show a reduction in plaque/thrombus volume but the number of interpretable ultrasounds was small. Further data are needed to address the effectiveness of the laser in treating these thrombotic occlusions and its advantages over balloon angioplasty.
1
Introduction
Intravascular thrombus is highly prevalent in patients with symptomatic recent occlusions . Using intravascular ultrasound, thrombus was noted in more than 95% of patients with less than 6 months onset of symptoms and occluded culprit vessel on angiography . Thrombus is often missed on an angiogram within an occluded vessel .
Several therapies have been suggested to treat subacute and chronic thrombotic occlusions including prolonged fibrinolysis, power pulse spray technique with AngioJet embolectomy, and direct lytic infusion into the thrombus with an infusion balloon followed by AngioJet embolectomy . These techniques reported partial resolution of thrombus presumably because of the presence of a predominantly highly organized thrombus.
We hypothesize that mechanical ablative treatment of these organized thrombi using the excimer laser is safe and likely effective in reducing thrombus burden. Thrombus favorably absorbs ultraviolet excimer light making it a suitable target for laser ablative treatment . Coronary studies have shown that laser effectively ablates plaque and thrombus in the setting of acute myocardial infarction and improves thrombolysis in myocardial infarction (TIMI) flow in the infarct-related artery . In contrast to balloon angioplasty of thrombotic lesions, excimer laser also suppresses platelet aggregation and therefore potentially reduces the chance of platelet mediated thrombotic reocclusion . Furthermore, in vitro observations have shown that the laser enhances treatment with fibrinolytic therapy . Finally, laser-facilitated thrombus ablation was successfully achieved in deep venous chronic thrombotic occlusions of the lower extremities and acute and subacute thrombotic occlusions of hemodialysis shunts .
This study was conducted to assess the safety of the excimer laser in treating chronic and subacute thrombotic occlusions in femoropopliteal arterial disease as demonstrated by intravascular ultrasound prior to a more definitive efficacy trial.
2
Methods
In this single center prospective registry, 20 consecutive patients with an occluded lower extremity artery and symptomatic claudication or limb ischemia were enrolled. This study was approved by the IRB at our institution and all patients signed an informed consent before enrollment. Patients were included if they are > 18 years of age, able to provide written informed consent, had an occluded vessel on angiogram and had a recent clinical history of < 6 months of onset of symptoms. Patients were excluded if they cannot take aspirin or ADP receptor antagonists.
Data were collected online via an electronic data capture system. The electronic case report form included a wide range of variables including demographic, clinical, and angiographic variables. The Rutherford Becker classification was used to classify symptoms: 0 = no symptoms, I = claudication with high level of activity, II = claudication with moderate level of activity, III = claudication with low level of activity, IV = foot pain at rest, V = presence of foot ulceration, VI = presence of foot ulceration and gangrenous changes.
Patients were pretreated with aspirin 325 mg po and clopidogrel 600 po load the day of the procedure (unless they have been on clopidogrel 75 mg po daily which was continued). Intravascular ultrasound (IVUS) (Volcano, Rancho Cordova, CA) was performed at baseline after crossing the lesion and immediately after laser treatment and before adjunctive therapy. All patients had their initial treatment with the excimer laser (laser Elite (2.3 mm (n = 4); 2.5 mm (n = 6)) and Tandem laser (2.5 mm (n = 10)) (Spectranetics, Colorado Springs, CO). Photoablation using the laser was performed at 0.5 mm per second with saline infusion to clear any contrast in the vessel. A total of 4.9 ± 2.3 runs were performed per lesion. A Fluence of 60 mJ per mm 2 and a repetition rate of 45 Hz were used. Embolic filter protection was not mandated and the Spider Embolic Filter protection device (eV3, Minneapolis, MN) was used when the operator felt it was feasible.
All patients were kept on clopidogrel 75 mg po daily and aspirin 81–324 mg po daily post procedure. Angiographic percent residual stenosis was estimated qualitatively by the operator before and immediately after laser treatment and after final adjunctive therapy with balloon angioplasty or stenting. Stenting was performed only if residual narrowing was more than 30% after adjunctive balloon angioplasty. All patients were followed up in the office at 30 days and had an ankle–brachial index obtained on the treated lower extremity.
2.1
IVUS analysis
The IVUS images were interpreted quantitatively by MedStar core laboratory (NJW) blinded to the patient’s clinical history. Because it is often difficult to differentiate thrombus from soft plaque, the total plaque–thrombus volume was determined within the same section of vessel treated at baseline and post excimer laser. Standard planar measurements of lumen, plaque/thrombus and vessel were performed every millimeter throughout the treatment segment and summated to calculate plaque/thrombus and vessel volume.
2.2
Primary Safety endpoints
The following safety endpoints were used:
- 1.
30-day and in-hospital major bleeding was defined as intracranial bleeding or bleeding severe enough to result in death, surgery, cessation of therapy, prolonged hospitalization or blood transfusion with concomitant drop in baseline hemoglobin > 3 g/dL.
- 2.
Embolization had to be observed during the procedure and require further treatment by embolectomy or further adjunctive pharmacologic treatment (with the exception of intravascular nitroglycerin or nipride).
- 3.
In-hospital and 30-day vascular access complications including AV fistula and pseudoaneurysm.
- 4.
Renal failure was defined as a drop of CrCl by 25% below baseline checked at approximately 72 h post procedure.
2.3
Secondary effectiveness endpoints
The following secondary effectiveness endpoints were used:
- 1.
Procedural success was defined as the ability of the laser after adjunctive final treatment to reduce stenosis to < 30% in the treated vessel as qualitatively assessed by the operator and with no visible angiographic thrombus at the end of treatment.
- 2.
IVUS determined reduction in plaque–thrombus volume, as described above, after excimer laser treatment.
- 3.
In-hospital and 30-day individual and combined rates of procedure-related death, stroke, unplanned amputation, and unplanned urgent revascularization of the treated limb after initial successful revascularization.
2.4
Statistical Analysis
Descriptive analysis was performed on all variables. Two tailed, paired t-test was performed on continuous variables. P < .05 was considered significant.
2
Methods
In this single center prospective registry, 20 consecutive patients with an occluded lower extremity artery and symptomatic claudication or limb ischemia were enrolled. This study was approved by the IRB at our institution and all patients signed an informed consent before enrollment. Patients were included if they are > 18 years of age, able to provide written informed consent, had an occluded vessel on angiogram and had a recent clinical history of < 6 months of onset of symptoms. Patients were excluded if they cannot take aspirin or ADP receptor antagonists.
Data were collected online via an electronic data capture system. The electronic case report form included a wide range of variables including demographic, clinical, and angiographic variables. The Rutherford Becker classification was used to classify symptoms: 0 = no symptoms, I = claudication with high level of activity, II = claudication with moderate level of activity, III = claudication with low level of activity, IV = foot pain at rest, V = presence of foot ulceration, VI = presence of foot ulceration and gangrenous changes.
Patients were pretreated with aspirin 325 mg po and clopidogrel 600 po load the day of the procedure (unless they have been on clopidogrel 75 mg po daily which was continued). Intravascular ultrasound (IVUS) (Volcano, Rancho Cordova, CA) was performed at baseline after crossing the lesion and immediately after laser treatment and before adjunctive therapy. All patients had their initial treatment with the excimer laser (laser Elite (2.3 mm (n = 4); 2.5 mm (n = 6)) and Tandem laser (2.5 mm (n = 10)) (Spectranetics, Colorado Springs, CO). Photoablation using the laser was performed at 0.5 mm per second with saline infusion to clear any contrast in the vessel. A total of 4.9 ± 2.3 runs were performed per lesion. A Fluence of 60 mJ per mm 2 and a repetition rate of 45 Hz were used. Embolic filter protection was not mandated and the Spider Embolic Filter protection device (eV3, Minneapolis, MN) was used when the operator felt it was feasible.
All patients were kept on clopidogrel 75 mg po daily and aspirin 81–324 mg po daily post procedure. Angiographic percent residual stenosis was estimated qualitatively by the operator before and immediately after laser treatment and after final adjunctive therapy with balloon angioplasty or stenting. Stenting was performed only if residual narrowing was more than 30% after adjunctive balloon angioplasty. All patients were followed up in the office at 30 days and had an ankle–brachial index obtained on the treated lower extremity.
2.1
IVUS analysis
The IVUS images were interpreted quantitatively by MedStar core laboratory (NJW) blinded to the patient’s clinical history. Because it is often difficult to differentiate thrombus from soft plaque, the total plaque–thrombus volume was determined within the same section of vessel treated at baseline and post excimer laser. Standard planar measurements of lumen, plaque/thrombus and vessel were performed every millimeter throughout the treatment segment and summated to calculate plaque/thrombus and vessel volume.
2.2
Primary Safety endpoints
The following safety endpoints were used:
- 1.
30-day and in-hospital major bleeding was defined as intracranial bleeding or bleeding severe enough to result in death, surgery, cessation of therapy, prolonged hospitalization or blood transfusion with concomitant drop in baseline hemoglobin > 3 g/dL.
- 2.
Embolization had to be observed during the procedure and require further treatment by embolectomy or further adjunctive pharmacologic treatment (with the exception of intravascular nitroglycerin or nipride).
- 3.
In-hospital and 30-day vascular access complications including AV fistula and pseudoaneurysm.
- 4.
Renal failure was defined as a drop of CrCl by 25% below baseline checked at approximately 72 h post procedure.
2.3
Secondary effectiveness endpoints
The following secondary effectiveness endpoints were used:
- 1.
Procedural success was defined as the ability of the laser after adjunctive final treatment to reduce stenosis to < 30% in the treated vessel as qualitatively assessed by the operator and with no visible angiographic thrombus at the end of treatment.
- 2.
IVUS determined reduction in plaque–thrombus volume, as described above, after excimer laser treatment.
- 3.
In-hospital and 30-day individual and combined rates of procedure-related death, stroke, unplanned amputation, and unplanned urgent revascularization of the treated limb after initial successful revascularization.
2.4
Statistical Analysis
Descriptive analysis was performed on all variables. Two tailed, paired t-test was performed on continuous variables. P < .05 was considered significant.
3
Results
20 consecutive patients were enrolled in this study (8 males, mean age 69.5 ± 11.1 years) between December of 2009 and July of 2011. Based on patients’ symptom onset, 12 patients were subacute (> 24 h, < 30 days), and 8 were chronic (between 1 to 6 months). Demographic and clinical variables are shown in Table 1 . A high prevalence of hyperlipidemia (70%), smoking (85%), diabetes (40%) and prior peripheral interventions (85%) was noted. Limb ischemia was present in 55% of patients (Rutherford class IV and V).
