Abstract
Background
Thrombus is highly prevalent in patients with recent symptoms (<6 months) of claudication or limb ischemia with occluded culprit lower extremity arterial vessels. Treatment of these thrombotic occlusions is challenging. In this feasibility study, the Vascular ClearWay Irrigating PTFE Balloon Catheter (Atrium, Husdson, NH, USA) has been tested for its safety and ability to dissolve thrombus in patients with recent arterial occlusions.
Methods
Twenty consecutive patients with lower extremity occlusion were prospectively enrolled to test the feasibility of the ClearWay balloon irrigation system. Cohorts of five patients were tested with increasing doses of tPA (five control patients with saline, five patients with 0.25 mg/cm, five patients with 0.4 mg/cm and five patients with 0.6 mg/cm of lesion length). Volumetric intravascular ultrasound core laboratory assessment of the thrombus was performed at baseline and after ClearWay thrombolysis (but prior to definitive treatment of the vessel with other debulking or stenting) to evaluate the effectiveness of ClearWay to remove thrombus.
Results
Twenty consecutive patients were enrolled in this study (11 men; mean age, 68.54±8.15 years), and 14 had volumetric intravascular ultrasound available both before and after Clearway. Based on patients’ symptom onset, 1 patient was acute (<24 h), 4 subacute (>24 h, <30 days) and 15 chronic (between 1 and 6 months). There were no safety events as predefined by the protocol including no major bleeding, death, distal embolization distal to the filter, acute renal failure or vascular complications. Acute procedural success was seen in 100% of cases. There were no statistical difference in plaque–thrombus volume between baseline (pretreatment) and control ClearWay treatment (saline infusion; P =.911, n =4). Also, there was no statistical difference in plaque–thrombus volume between pretreatment baseline and ClearWay tPA treatment ( P =.628, n =14). Following Angiojet rheolytic thrombectomy ( n =8 patients) post-ClearWay lytic treatment, there was a statistical reduction of plaque–thrombus volume versus ClearWay lytic treatment alone ( P =.030) or pretreatment baseline ( P =.029). There were no deaths or amputations. Macrodebris >2 mm were present in 50% of patients captured by embolic filter protection. In-hospital reocclusion of the treated vessel occurred in one patient (5%) and 30-day reocclusion occurred in two patients (10%) on follow-up.
Conclusion
Using the ClearWay to deliver lytic therapy appears safe in this small feasibility study. Although lytic treatment with the ClearWay balloon alone did not demonstrate reduction in plaque–thrombus volume in this small population, the use of Angiojet rheolytic thrombectomy following ClearWay did reduce plaque volume. Further data are needed to address definitive effects of ClearWay balloon alone and utility to facilitate Angiojet thromboreduction.
1
Introduction
The onset of recent severe claudication or limb ischemia along with lower extremity peripheral arterial occlusions is highly associated with intravascular thrombus . Thrombus was identified using intravascular ultrasound (IVUS) in over 95% of patients with recent symptoms (within 6 months of onset) with occluded lower extremity vessels . Angiography severely underestimates the presence of thrombus in these vessels . Acute (within 24 h) thrombus leads to multiple complications including death and amputation and is often treated with surgery, lytic treatment and aspiration embolectomy with and without lysis .
Subacute and chronic thrombotic occlusions are often difficult to treat. Several therapies have been attempted including prolonged lysis or Angiojet rheolytic thrombectomy (RT) with or without power pulse lytic treatment . Partial resolution of thrombus has been noted presumably because of the highly organized nature of the thrombus and the difficulty in administering lytic treatment deep into the thrombus to be effective.
Using a new balloon irrigation system that allows delivery of the lytic therapy deep into the thrombus, we evaluated the safety of the ClearWay (CW) Transcatheter Balloon Irrigation system (Atrium, Hudson, NH, USA) to deliver local thrombolysis into subacute and chronic lesions and prior to RT to facilitate thrombus removal. The CW is a microporous PTFE balloon designed for intraluminal irrigation without mechanical disruption of the vessel wall. CW uses a low-pressure, noncompliant balloon that limits mechanical stress on the vessel wall and is able to deliver drugs straight into the thrombus or vessel wall. We hypothesized that by delivering the thrombolytics deeper into the thrombus, the perfusion balloon will lead to more effective lysis at a lower systemic concentration and therefore lower bleeding complications. However, prior to a definitive study to determine effectiveness, this study was conducted to assess system feasibility with the intent of collecting pilot data on which to base a subsequent efficacy trial.
2
Methods
In this single-center prospective registry, 20 consecutive patients were enrolled. All patients received the CW balloon irrigation system. Cohorts of five patients were used to study differing doses of tPA. Five patients were used as control (saline infusion through CW). The remaining 15 patients were treated with increasing levels of tPA through the CW balloon irrigation system at a dose of 0.25 mg/cm (5 patients), 0.4 mg/cm (5 patients) and 0.6 mg/cm (5 patients) of lesion length. The lowest dose of 0.25 mg tPA per centimeter of lesion treated was previously evaluated in the DETHROMBOSIS protocol and was found to be safe. Maximum lesion length treated with lytic treatment was 16 cm limiting the tPA dose to a maximum of 10 mg. tPA was mixed as 10 mg per 50 cc normal saline and infused via the CW balloon using a 30-cc syringe. Following CW infusion, the final treatment of the lesion was left up to operator’s discretion including the use of rheolytic thrombectomy with the Angiojet system (MEDRAD, Warrendale, PA, USA).
All patients signed an informed consent form before enrollment. The protocol was approved by the institutional board review at our center. All 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). IVUS (Volcano, Rancho Cordova, CA, USA) was performed at three intervals: baseline after crossing the lesion, after CW treatment and after Angiojet RT (MEDRAD) using the Xpeedior or DVX aspiration catheter but before final treatment. All patients were kept on Plavix 75 mg po daily and aspirin 81–324 mg po daily postprocedure.
2.1
IVUS analysis
The IVUS images were interpreted quantitatively by MedStar core laboratory (N.J.W.) 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, post-CW and post-Angiojet RT. Standard planar measurements of lumen, plaque–thrombus and vessel were performed every millimeter throughout the treatment segment.
2.2
Angiographic thrombus grading
Angiographic thrombus was graded based on a modified thrombolysis in myocardial infarction (TIMI) thrombus scale:
Grade 0: no thrombus
Grade 1: thrombus suspected but not definite
Grade 2: thrombus is definite with a hazy filling defect and with linear length less than or equal double the reference vessel diameter
Grade 3: thrombus is definite with a hazy filling defect and with linear length more than double the reference vessel diameter
Grade 4: thrombus causing total occlusion
2.3
Primary safety end points
The following safety end points were used:
- 1.
30-day and in-hospital major bleeding 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 observed during the procedure that requires further treatment by embolectomy or further adjunctive pharmacologic treatment (with the exception of intravascular nitroglycerin or nipride). The Spider Embolic Filter protection device (eV3, MN) was used on patients when the operator felt it was feasible.
- 3.
In-hospital and 30-day vascular access complications including AV fistula and pseudoaneurysm
- 4.
Renal failure defined as a drop of CrCl by 25% below baseline checked at approximately 72 h postprocedure.
2.4
Secondary effectiveness end points
The following secondary effectiveness end points were used:
- 1.
Angiographic outcome: evaluate the angiographic procedural success rate in restoring normal flow (TIMI III) in limbs treated with a residual stenosis of <30% in the treated vessel by the CW system as qualitatively assessed by the operator and with no visible angiographic thrombus at the end of treatment.
- 2.
IVUS outcome: evaluate thrombus resolution after CW thrombolysis and CW+RT in the treated segment using volumetric core laboratory assessment of the plaque–thrombus prior to definitive treatment.
- 3.
Clinical outcome: determine the 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.
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 had a contraindication to pharmacologic thrombolysis, cannot take aspirin or ADP receptor antagonists and had known clotting disorder.
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.
2.5
Statistical analysis
Descriptive analysis was performed on all variables. χ 2 Test and Fisher’s Exact Test were performed on dichotomous variables. Analysis of variance and t test were performed on continuous variables. P <.05 was considered significant.
2
Methods
In this single-center prospective registry, 20 consecutive patients were enrolled. All patients received the CW balloon irrigation system. Cohorts of five patients were used to study differing doses of tPA. Five patients were used as control (saline infusion through CW). The remaining 15 patients were treated with increasing levels of tPA through the CW balloon irrigation system at a dose of 0.25 mg/cm (5 patients), 0.4 mg/cm (5 patients) and 0.6 mg/cm (5 patients) of lesion length. The lowest dose of 0.25 mg tPA per centimeter of lesion treated was previously evaluated in the DETHROMBOSIS protocol and was found to be safe. Maximum lesion length treated with lytic treatment was 16 cm limiting the tPA dose to a maximum of 10 mg. tPA was mixed as 10 mg per 50 cc normal saline and infused via the CW balloon using a 30-cc syringe. Following CW infusion, the final treatment of the lesion was left up to operator’s discretion including the use of rheolytic thrombectomy with the Angiojet system (MEDRAD, Warrendale, PA, USA).
All patients signed an informed consent form before enrollment. The protocol was approved by the institutional board review at our center. All 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). IVUS (Volcano, Rancho Cordova, CA, USA) was performed at three intervals: baseline after crossing the lesion, after CW treatment and after Angiojet RT (MEDRAD) using the Xpeedior or DVX aspiration catheter but before final treatment. All patients were kept on Plavix 75 mg po daily and aspirin 81–324 mg po daily postprocedure.
2.1
IVUS analysis
The IVUS images were interpreted quantitatively by MedStar core laboratory (N.J.W.) 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, post-CW and post-Angiojet RT. Standard planar measurements of lumen, plaque–thrombus and vessel were performed every millimeter throughout the treatment segment.
2.2
Angiographic thrombus grading
Angiographic thrombus was graded based on a modified thrombolysis in myocardial infarction (TIMI) thrombus scale:
Grade 0: no thrombus
Grade 1: thrombus suspected but not definite
Grade 2: thrombus is definite with a hazy filling defect and with linear length less than or equal double the reference vessel diameter
Grade 3: thrombus is definite with a hazy filling defect and with linear length more than double the reference vessel diameter
Grade 4: thrombus causing total occlusion
2.3
Primary safety end points
The following safety end points were used:
- 1.
30-day and in-hospital major bleeding 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 observed during the procedure that requires further treatment by embolectomy or further adjunctive pharmacologic treatment (with the exception of intravascular nitroglycerin or nipride). The Spider Embolic Filter protection device (eV3, MN) was used on patients when the operator felt it was feasible.
- 3.
In-hospital and 30-day vascular access complications including AV fistula and pseudoaneurysm
- 4.
Renal failure defined as a drop of CrCl by 25% below baseline checked at approximately 72 h postprocedure.
2.4
Secondary effectiveness end points
The following secondary effectiveness end points were used:
- 1.
Angiographic outcome: evaluate the angiographic procedural success rate in restoring normal flow (TIMI III) in limbs treated with a residual stenosis of <30% in the treated vessel by the CW system as qualitatively assessed by the operator and with no visible angiographic thrombus at the end of treatment.
- 2.
IVUS outcome: evaluate thrombus resolution after CW thrombolysis and CW+RT in the treated segment using volumetric core laboratory assessment of the plaque–thrombus prior to definitive treatment.
- 3.
Clinical outcome: determine the 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.
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 had a contraindication to pharmacologic thrombolysis, cannot take aspirin or ADP receptor antagonists and had known clotting disorder.
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.
2.5
Statistical analysis
Descriptive analysis was performed on all variables. χ 2 Test and Fisher’s Exact Test were performed on dichotomous variables. Analysis of variance and t test were performed on continuous variables. P <.05 was considered significant.
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