Author + information
- Received September 20, 2016
- Revision received December 6, 2016
- Accepted December 15, 2016
- Published online February 20, 2017.
- Prakash Krishnan, MD∗ (, )
- Arthur Tarricone, MPH,
- K. Raman Purushothaman, MD,
- Meerarani Purushothaman, PhD,
- Miguel Vasquez, MD,
- Jason Kovacic, MD,
- Usman Baber, MD,
- Vishal Kapur, MD,
- Karthik Gujja, MD,
- Annapoorna Kini, MD and
- Samin Sharma, MD
- ↵∗Address for correspondence:
Dr. Prakash Krishnan, Department of Interventional Cardiology, Mount Sinai Medical Center, 1 Gustave Levy Place, Box 1030, New York, New York.
Objectives This study sought to identify an algorithm for the use of distal embolic protection on the basis of angiographic lesion morphology and vascular anatomy for patients undergoing atherectomy for femoropopliteal lesions.
Background Atherectomy has been shown to create more embolic debris than angioplasty alone. Distal embolic protection has been shown to be efficacious in capturing macroemboli; however, no consensus exists for the appropriate lesions to use distal embolic protection during atherectomy.
Methods Patients with symptomatic lower extremity peripheral artery disease treated with atherectomy and distal embolic protection were evaluated to identify potential predictors of DE. Plaque collected from the SilverHawk nose cone subset was sent to pathology for analysis to evaluate the accuracy of angiography in assessing plaque morphology.
Results Significant differences were found in lesion length (142.1 ± 62.98 vs. 56.91 ± 41.04; p = 0.0001), low-density lipoprotein (82.3 ± 40.3 vs. 70.9 ± 23.2; p = 0.0006), vessel runoff (1.18 ± 0.9 vs. 1.8 ± 0.9; p = 0.0001), chronic total occlusion (131 vs. 10; p = 0.001), in-stent restenosis (33 vs. 6; p = 0.0081), and calcified lesions (136 vs. 65; p < 0.001). In simple logistic regression analysis lesion length, reference vessel diameter, chronic total occlusion, runoff vessels, and in-stent restenosis were found to be strongly associated with macroemboli. Angiographic assessment of plaque morphology was accurate. Positive predictive value of 92.31, negative predictive value of 95.35, sensitivity of 92.31, and specificity of 95.35 for calcium; positive predictive value of 95.56, negative predictive value of 100, sensitivity of 100, and specificity of 92.31 for atherosclerotic plaque. Thrombus/in-stent restenosis was correctly predicted.
Conclusions Chronic total occlusion, in-stent restenosis, thrombotic, calcific lesions >40 mm, and atherosclerotic lesions >140 mm identified by peripheral angiography necessitate concomitant filter use during atherectomy to prevent embolic complications.
Atherectomy is a viable option for the endovascular treatment of symptomatic lower extremity peripheral artery disease (1). Established complications of atherectomy include dissection, perforation, thrombosis, and distal embolization (2). Concern over potential embolic events with endovascular intervention was described by Morrissey when he reported that all patients undergoing superficial femoral artery intervention have detectable embolic signals identified by transcutaneous Doppler hits, at the level of the popliteal artery (3). However, the overall incidence of clinically significant distal emboli (DE) has been shown to be rare; but clinical concern remains because DE is associated with adverse outcomes (4). Atherectomy has been shown to create more emboli than angioplasty alone (3), and embolic protection devices have been shown to be effective in capturing macrodebris (5). Angiographic imaging remains the cornerstone of vascular intervention, and has been proven effective at providing accurate determination of luminal diameters and diameter-reducing stenosis measurements (6). Lesion morphologies that are at high risk for DE have been postulated in small sample sizes (5–7). However, it has been shown that angiography is poor in identifying plaque morphology (6), and this is the major challenge for developing a clinically relevant algorithm for the appropriate use of DE protection during atherectomy.
To validate the use of angiography for this purpose, our goal was to identify the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of angiography for identifying the morphology of peripheral stenotic plaque at a high risk for DE with atherectomy. We used pathology specimens from a cohort of patients undergoing SilverHawk (Medtronic, Irvine, California) atherectomy for the purpose of comparing embolic plaque specimens (from the SilverHawk nose cone) analyzed by histopathology as the gold standard to assess the accuracy of angiographic assessment. The goal of this study is to identify an algorithm for the use of distal embolic protection on the basis of angiographic lesion morphology and vascular anatomy for patients undergoing atherectomy for femoropopliteal lesions.
In a study approved by the local institutional review board, 508 patients with symptomatic lower extremity peripheral artery disease treated with atherectomy and distal embolic protection at a single center between January 2014 and October 2015 were evaluated to identify potential predictors of DE. Distal embolization was defined as macroemboli present in the filter following atherectomy.
Clinical, demographic, and angiographic data were collected for all patients (Table 1). No patients with critical limb ischemia were included. All lesions were above the P2 segment of the popliteal artery and presented without inflow disease. All Trans Atlantic Inter-Society Classification (TASC) classifications were included in the study. Three board-certified interventional cardiologists independently reviewed all anonymized angiograms to determine angiographic lesion morphology, grouping lesions into the following groups: atherosclerotic, calcified, in-stent restenosis (ISR), or thrombotic. All reviewers were blinded to all patient information and histopathology. Unanimous agreement was required for a “positive” classification for said groupings.
A subset of plaque collected from the SilverHawk nose cone was sent to pathology for analysis in accordance with institutional standard operating procedure (Table 2). Specimens were then fixed in paraffin, and analyzed using hematoxylin and eosin stain. All pathologists were blinded to the patient’s symptoms and other imaging data. Investigator determination of angiographic lesion morphology was then compared against histopathology findings of the atherectomy specimen as the reference gold standard (defined later). This subset was used to calculate the sensitivity, specificity, NPV, and PPV of angiography to estimate plaque morphology.
After informed consent for the procedure was granted, and a diagnostic peripheral angiogram was performed. All patients received the filter at the discretion of the operator. The atherectomy devices used in this study were limited to directional atherectomy (SilverHawk), rotational atherectomy (Jetstream, Boston Scientific, Cork, Ireland), and laser atherectomy (Turbo Elite, Spectranetics, Colorado Springs, Colorado). The atherectomy procedure was performed in accordance with widely accepted techniques and off-label use of directional SilverHawk atherectomy was at the discretion of the operator. Distal embolic protection was placed before the atherectomy procedure and was in place for all patients in the study. Filters (spider Fx, Medtronic, Minneapolis, Minnesota, and Nav6, Abbott Vascular, Temecula, California) used during the atherectomy (on/off label) were chosen at the discretion of the operator. The filters were placed at the level of the popliteal artery for all patients. After the atherectomy procedure was performed, an angiogram of the filter alone was performed to look for macroemboli and filter overflow. The filter was then captured and distal runoff compared with the index angiogram to verify the presence of embolic events and loss of runoff vessel if embolization occurred. DE was determined by macroscopic evaluation of the filter following filter capture and removal.
The definitive calcium study’s definition of calcium was used. Severe calcification was defined as the presence of radiopacities noted on both sides of the arterial wall and extending more than 1 cm of length before contrast injection or digital subtraction angiography. Moderate calcification was defined as the presence of radiopacities on 1 side of the arterial wall or <1 cm of length before contrast injection or digital subtraction angiography (5).
DE was determined by the presence or absence of macroemboli in the filter or presence of embolic debris in runoff vessels, or loss of runoff vessel that was present at index angiogram.
ISR is defined as any lesion >70% located within the stent or <2 cm from either stent edge.
Chronic total occlusion (CTO) is defined as 100% occlusion at any point within the superficial femoral artery or popliteal artery.
Filter overflow is described as macroscopic debris filling the entire filter with no flow through the filter after intervention. Filter-related complications include dissection and perforation.
Atherosclerotic plaque (Figure 1) is defined by the presence of lipid pool and absence of calcium, thrombus, and neointimal hyperplasia. Calcified plaque (Figure 2) is identified by the presence of calcium within the plaque specimen. ISR plaque (Figure 3) is identified by the presence of neointimal hyperplasia admixed with calcification and fibrosis within the plaque. Thrombus is identified by the presence of fibrin platelet clot within the plaque specimen.
All patients were categorized by the presence or absence of DE in the filter basket. Clinical and demographic parameters were compared among groups using Fisher exact test or Student t test for categorical and continuous variables, respectively. The null hypothesis is that there is no difference in lesion/angiographic characteristics, demographics, and clinical parameters across groups. Associations were evaluated using logistic regression. Outcomes are presented as the odds ratio and 95% confidence intervals (CI). The sensitivity, specificity, PPV, and NPV for determination of angiographic plaque morphology was determined using histopathology as the reference gold standard and unanimous agreement (3 of 3) for positive plaque morphology across the 3 groups (calcified, atherosclerotic, and thrombotic). A p value <0.05 was considered significant and all analyses were conducted using SAS version 9.3 (SAS, Cary, North Carolina).
Baseline demographics and clinical features were similar between the 2 groups defined as macroemboli and absence of macroemboli (Table 1). Macroembolus was identified in 317 of 508 (62.4%). No significant differences were found across atherectomy types (directional atherectomy, p = 0.26; laser atherectomy, p = 0.36; jetstream atherectomy, p = 0.69). All patients who had thrombosis were positive for macroemboli (n = 5). Significant differences were found in lesion length (142.1 ± 62.98 vs. 56.91 ± 41.04; p = 0.0001) (Table 3), low-density lipoprotein (LDL) (82.3 ± 40.3 vs. 70.9 ± 23.2; p = 0.0006), vessel runoff (1.18 ± 0.9 vs. 1.8 ± 0.9; p = 0.0001), chronic total occlusion (131 vs. 10; p = 0.001), ISR (33 vs. 6; p = 0.0081), and calcified lesions (136 vs. 65; p < 0.001) (Table 4). In simple logistic regression analysis lesion length, reference vessel diameter, LDL, CTO, runoff vessels, and ISR were found to be strongly associated with macroemboli. The final model included long lesion (lesion length ≥140 mm), CTO, ISR, calcium, and runoff vessels.
Although there were higher levels of LDL in the patients whose lesions embolized during atherectomy we did not include LDL in our model for the following reasons: both groups fell beneath the Nation Cholesterol Education Program—Adult Treatment Panel III optimal range (LDL <100 mg/dl)7, and LDL levels for the patient being treated may not be readily available to the operator at the time of angiographic assessment of the lesion. Reference vessel diameter was also left out of the model because the difference between the 2 groups (macroemboli and no macroemboli) is likely challenging to assess angiographically (Δ >±0.5 mm). This model produced odds ratio of 20.4 (95% CI: 6.12 to 68.443; p < 0.0001) for long lesion (defined as ≥140 mm), 18.8 (95% CI: 5.38 to 66.024; p < 0.0001) for CTO, 3.009 (95% CI: 0.492 to 18.422) for ISR, 5.550 (95% CI: 2.51 to 12.267) for calcium, and 0.425 (95% CI: 0.29 to 0.6; p < 0.001) for runoff vessels. The C statistic for this model was 0.97.
Fifteen percent (n = 47) experienced filter overflow in the macroemboli group, which resolved with aspiration of the filter. The only complication was 1 perforation caused by migration of the wire in the Nav6. This complication was treated with prolonged balloon inflation without sequelae.
An analysis of patients positive for angiographic calcification was conducted and significant differences in lesion length were detected between the 2 groups (154.4 ± 81.8 mm vs. 42.4 ± 20.2 mm; p < 0.0001). Lesion length ≤40 mm was chosen for our algorithm on the basis of this value.
The subset of 69 patient’s plaque, which was collected from the SilverHawk atherectomy specimens, was analyzed and revealed the following: 68.1% (n = 47) patients had macroemboli, calcified plaque was confirmed in 43 of 69 (62.32%), thrombus in 4 of 69 (5.8%), ISR in 15 of 69 (21.7%), and atherosclerotic plaque (no calcium) in 26 of 69 (37.7%) (Table 2). Similar results were found in this subset; of interest, calcium confirmed by pathology was found to be strongly related with macroemboli (p < 0.001), as was lesion length (p < 0.0001), and all patients with thrombus (n = 4) and ISR (n = 15) were positive for macroemboli.
Pathologic findings were used as the reference gold standard and used to calculate the PPV, NPV, sensitivity, and specificity of operator assessment of angiographic characterization of plaque morphology as calcified, atherosclerotic, thrombotic, and restenotic plaque. PPV of 92.31, NPV of 95.35, sensitivity of 92.31, and specificity of 95.35 for calcium; PPV of 95.56, NPV of 100, sensitivity of 100, and specificity of 92.31 for atherosclerotic plaque. Thrombus was correctly predicted in all cases (n = 4) as was ISR (n = 15).
DE is a dreaded complication of atherectomy. The clinical impact of DE results in longer procedure, increased contrast, radiation exposure, and cost. The acute outcomes are less symptom relief, worsening of symptoms, and increased emergent surgical bypass. Long-term outcomes are also adversely affected with decreased symptom relief at 2 years, and increased above knee, below knee, and below the ankle amputations (3–5). Currently, there is no consensus for the use of distal embolic protection during atherectomy, and the only Food and Drug Administration–approved device with an indication in the femoropopliteal segment is the spider Fx for use in conjunction with directional atherectomy in heavily calcified lesions (8). Recommendations do exist for filter use during mechanical thrombectomy, and limited runoff cases (9). However, no recommendations exist for directional, laser, or Jetstream atherectomy; no significant negatives have been associated with the use of embolic protection save the added cost (10). The decision to use embolic protection in these cases remains subjective, and on the basis of operator preference (9); this is likely because of a lack of evidence demonstrating the ability to predict embolic events on the basis of angiographic lesion morphology and characteristics.
Lesion predictors have been established in the carotid and coronary vascular beds (11–16). In the peripheral vascular bed predictors of distal embolic events have been suggested in small cohorts of patients; however, no algorithm exists. This is the largest cohort of patients that establishes the relationship between high-risk plaque morphology (calcific, ISR, CTO, lesion length, and thrombotic) and distal embolic events. The findings of this study establish that angiographic assessment of vascular anatomy and lesion morphology is enough to predict distal embolic events during atherectomy in the femoropopliteal region. The PPV, NPV, sensitivity, and specificity relationship between the angiographic morphology, the embolic event and the pathologic makeup of the plaque specimen has not been previously demonstrated. With the plaque cohort we were able to confirm that the angiographic assessment of the lesion morphology was accurate with sensitivity, specificity NPV, and PPV >90% using histopathology as the gold standard. This in turn allows the operator to analyze the angiographic findings and use lesion morphology, and physical characteristics of the lesion (lesion length/runoff vessels) to predict embolic events and appropriately use embolic protection.
We propose a clinically relevant algorithm (Figure 4) on the basis of our findings for the appropriate use of distal embolic protection during atherectomy for the femoropopliteal segment. The clinical use of this algorithm is effective because it allows the operator to identify key factors in the angiographic morphology of the lesion that predict embolic events. The results of our study establish that operator assessment of the lesion morphology by angiography accurately predicts the pathology of the lesion when the lesion is calcified (not), thrombotic, or restenotic. Other significant independent predictors of embolization are easily identified via angiography including moderate/long lesions >140 mm, 1-vessel runoff, ISR, and CTO.
The algorithm simplifies the clinical decision to use a filter when performing atherectomy for the treatment of peripheral artery disease. Once the diagnostic angiogram is performed, the operator assesses the following morphology and anatomic characteristics: thrombotic, calcific, restenotic, CTO, lesion length, and runoff. It is safe to generalize that all CTO, ISR, and thrombotic lesions treated with atherectomy merit the use of embolic protection devices because of high risk of embolization. The decision for the use of embolic protection device in calcific lesions and atherosclerotic lesions is dependent on lesion length. Lesions >140 mm when atherosclerotic and >40 mm when calcific warrant the use of an embolic protection device to prevent complications. In all other lesions embolic protection device use during atherectomy is unnecessary.
This study establishes the ability of angiograms to accurately assess the high-risk plaque morphology that results in DE. This allows for creation of a clinically relevant and simple algorithm using the angiogram as the central tool for appropriate use of embolic protection during atherectomy of the femoropopliteal segment.
It is important to note the limitations of our study. This study is single center, and plaque samples were not collected for all subjects. In addition, patients treated without embolic protection during the same time period were not included in our analysis. Certain procedural characteristics including post-stenting and post-dilation were not included in the study and may affect the rate of macroemboli. It also should be noted that patients with critical limb ischemia were not included in this study; however, these patients may benefit from distal protection because the clinical consequences associated with significant embolization may be catastrophic in this population. We suggest prudent filter use during atherectomy for patients with critical limb ischemia taking into consideration adequate filter landing zones and appropriate filter sizes. Other limitations that should be noted are the plaque analyzed for this study was collected in the nose cone of the SilverHawk device, and within each cut it is possible to excise a variety of tissue especially in longer lesions. Atherectomy technique may also contribute to the risk of macroembolis, and care should be taken to avoid fast cuts and advancement of the atherectomy device quickly.
Embolic protection devices are safe and effective during atherectomy for femoropopliteal lesions. The following lesion morphologies are high-risk lesions for distal embolization during atherectomy: CTO, ISR, thrombotic, calcific lesions >40 mm, and atherosclerotic lesions >140 mm. Angiographic assessment of the lesion morphology is effective and these lesions merit the use of distal embolic protection to prevent the embolic complications during atherectomy.
WHAT IS KNOWN? Distal embolization during peripheral atherectomy is associated with adverse outcomes.
WHAT IS NEW? There is no current algorithm that allows the operator to use angiographic assessment of the lesion and vascular anatomy to predict embolic events and use filters appropriately to avoid complications.
WHAT IS NEXT? Filter use in critical limb ischemia.
All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- chronic total occlusion
- distal emboli
- in-stent restenosis
- low-density lipoprotein
- negative predictive value
- positive predictive value
- Received September 20, 2016.
- Revision received December 6, 2016.
- Accepted December 15, 2016.
- American College of Cardiology Foundation
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