Intravascular Ultrasound Assessment and Correlation With Angiographic Findings Demonstrating Femoropopliteal Arterial Dissections Post Atherectomy: Results From the iDissection Study

Abstract: Background. Dissections occur post atherectomy of the infrainguinal arteries. We hypothesized that angiography under-estimates their presence significantly. Methods. In this prospective pilot study, a total of 15 patients were evaluated by intravascular ultrasound (IVUS) following treatment of femoropopliteal de novo or non-stent restenosis using atherectomy. Eagle Eye Platinum ST IVUS catheters (Philips) were used in this study. Thirteen Jetstream XC atherectomy devices (Boston Scientific) and 2 investigational B-laser atherectomy devices (Eximo Medical) were used. Cine and IVUS images were obtained at baseline, after atherectomy, and after adjunctive balloon angioplasty. Angiographic and IVUS core labs analyzed the images. Results. Mean age was 70.6 ± 8.0 years. Diabetes and claudication were present in 60% and 73%, respectively. Mean baseline, post-atherectomy, and post-adjunctive angioplasty stenosis severity was 71.4%, 38.1%, and 19.7%, respectively (P<.001 for both baseline vs post atherectomy and post atherectomy vs adjunctive angioplasty). Lesion length was 108.5 ± 43.1 mm. Forty-six dissections were identified on IVUS post atherectomy vs 8 dissections on angiogram (P<.01) (ratio, 5.75 to 1). Post adjunctive angioplasty, there were 39 dissections on IVUS vs 11 on angiogram (P<.01) (ratio, 3.55 to 1). Of these dissections, 13% and 30.8% were ≥180° in circumference post atherectomy and adjunctive balloon angioplasty, respectively (P=.047). Also, 39.1% and 33.3% involved the media and/or adventitia as seen on IVUS post atherectomy and adjunctive balloon angioplasty, respectively (P=.58). Longer lesions correlated with more dissections post atherectomy on IVUS (P=.03), but not on angiogram (P=.28). Conclusion. Dissections post atherectomy are grossly under-appreciated on angiogram when compared to IVUS. A multicenter registry correlating these findings with clinical outcomes is needed. 

J INVASIVE CARDIOL 2018;30(7):240-244.

Key words: intravascular ultrasound, peripheral arterial interventions, dissection classification, superficial femoral artery, adventitia, media, perforation, intramural hematoma

Cine angiography has been widely utilized as the main tool to evaluate and treat the infrainguinal arteries. However, angiographic images are suboptimal in identifying the severity of calcium,^1,2 presence of intraluminal thrombus,³ plaque morphology,⁴ true vessel diameter,⁵ and residual narrowing post intervention.^6,7 Also, the number and severity of dissections including medial and adventitial injury have long been suspected to be under-estimated on angiography.⁵

Atherectomy has been reported to reduce angiographic dissections and therefore bailout stenting.⁸ The extent and nature of dissections following atherectomy, however, may have been under-appreciated on cine angiography. Atherectomy has not been shown to be superior to angioplasty in reducing target-lesion revascularization (TLR) or restenosis,⁸ which may be partly explained by undetected deeper dissections on an angiogram. 

We present data on the number and severity of dissections as seen on intravascular ultrasound (IVUS) following atherectomy based on the iDissection classification⁹ and the National Heart, Lung and Blood Institute (NHLBI) classification for coronary dissections.¹⁰ The iDissection classification combines depth of injury from intima to adventitia with the circumference of dissection as seen on IVUS. This classification exhibits six dissection grades (A1, A2, B1, B2, C1, and C2). Grade A involves the intima, grade B involves the media, and grade C involves the external elastic lamina. Number 1 indicates the circumference of the dissection is <180°, whereas number 2 indicates ≥180° (Figure 1). The NHLBI classification is angiography based and also uses six dissection grades (A-F). Grade A is a minor radiolucent area, grade B is a linear dissection, grade C indicates contrast outside the lumen, grade D indicates a spiral dissection, grade E indicates persistent filling defects, and grade F indicates a total occlusion. 

Methods

A total of 15 patients undergoing atherectomy of the femoropopliteal arteries for de novo or restenotic disease (non-stent restenosis) were prospectively included in this study by one operator at one center. The study was approved by the Trinity Health System Institutional Review Board and informed consent was obtained from all patients. Thirteen of the 15 patients were treated with Jetstream atherectomy (Boston Scientific) and 2 patients were treated with the investigational B-laser device (Eximo Medical) as part of the Eximo X-PAD trial. Cine angiography and IVUS using the Eagle Eye Platinum ST catheter (Philips) were performed on the treated segments at baseline, post atherectomy, and post adjunctive balloon angioplasty. Adjunctive balloon angioplasty was left to the operator’s preference for the choice of the balloon (non drug-coated, drug-coated, lithoplasty balloon, or combination) sized 1:1 to the vessel size. The segment to be analyzed for dissections was marked on a radiopaque ruler and images obtained with cine and IVUS were analyzed within the same segment length. Cine angiograms were obtained on two orthogonal views. Cine images were analyzed at the MCRF Quantitative Vascular Laboratory (QVL) using CAAS software (Pie Medical) and IVUS images were analyzed independently at MCRF QVL and St. John Providence Health System core lab using Echoplaque software (INDEC Systems, Inc). Disagreements on IVUS image interpretations were reviewed by the principal investigator (NWS) and a consensus was obtained. Dissections on cine images were classified based on the NHLBI classification.¹⁰ Dissections on IVUS images were classified using the iDissection classification.⁹ The number and grade of dissections seen on cine angiography were compared with those identified on IVUS findings for the same segments analyzed. Since co-registration is not available for peripheral applications using IVUS, a direct comparison of cine dissection to IVUS dissection was not feasible; therefore, only total and severity of dissections could be quantitated within the same segment using both imaging modalities. 

Demographics, clinical variables, and angiographic variables were collected on all patients. Procedural success was defined as obtaining <30% residual narrowing after adjunctive treatment. Device success was defined as a residual stenosis of <50% after atherectomy alone. Dissection length (mm) was determined based on the number of frames the dissection starts and ends. Given the total number of frames/run, the length of the run as measured by the ruler, and the number of frames/dissection, the dissection length was then calculated as: number of frames per dissection • total lesion length (mm)/total number of frames per total lesion length. 

Statistical analysis. Analysis was performed per patient. Descriptive analysis on all variables was done. Bivariate analysis was done to compare the number of dissections post atherectomy and post adjunctive angioplasty by IVUS and angiogram for both NHLBI and iDissection classifications. Pearson Chi-square and Kruskal-Wallis tests were performed as appropriate. Spearman Rho correlation was performed to compare associations for lesion and procedure variables of the groups. Minitab 17 software was used.

Results

Table 1 displays the demographics and clinical variables. The mean age was 70.6 ± 8.0 years. Diabetes and claudication were present in 60% and 73%, respectively. The majority of patients had history of hyperlipidemia, hypertension, and smoking. Critical limb ischemia was present in almost 27% of patients. 

Table 2 shows the angiographic and procedural variables. Mean baseline, post-atherectomy, and post-adjunctive angioplasty stenosis severity rates were 71.4%, 38.1%, and 19.7%, respectively. The PACCS classifications for calcium grading were 40%, 20%, 26.7%, and 13.3% for grades 4, 3, 1, and 0, respectively. Lesion length was 108.5 ± 43.1 mm. Procedural and device success rates were 86.7% and 66.7%, respectively. 

Post atherectomy, there were 46 dissections identified on IVUS vs 8 dissections identified on angiogram (P<.01) (ratio, 5.75 to 1). Post adjunctive angioplasty, there were 39 dissections identified on IVUS vs 11 identified on angiogram (P<.01) (ratio, 3.55 to 1). Of these dissections, 13% and 30.8% were ≥180° in circumference post atherectomy and adjunctive balloon angioplasty, respectively. Also, 39.1% and 33.3% involved the media and/or adventitia as seen on IVUS post atherectomy and adjunctive balloon angioplasty, respectively. 

Table 3 displays the grade of dissections as seen on IVUS post atherectomy and adjunctive angioplasty. A1 to C1 dissections were 40/46 (87%) post atherectomy vs 27/39 (69%) post adjunctive angioplasty. There was no statistical difference between the dissection pattern and number of dissections between post atherectomy and post adjunctive balloon angioplasty (P=.64). Table 4 shows the dissections seen on angiography post atherectomy and adjunctive angioplasty. A to C dissections were 7/8 (87%) post atherectomy and 10/11 (91%) post adjunctive angioplasty. Intramural hematoma was also seen in 2/15 patients (13.3%) post atherectomy and adjunctive balloon angioplasty. 

Using binomial analysis for predictors of severe post-atherectomy dissections (≥180°), balloon pressure, inflation time, critical limb ischemia, and degree of calcium did not correlate with dissection severity as seen on IVUS. Longer lesions, however, correlated with more dissections post atherectomy on IVUS (P=.03) but not on cine angiogram (P=.28). Dissection lengths were not different after atherectomy (12.2 ± 11 mm) vs adjunctive balloon angioplasty (11.4 ± 9.0 mm) (P=.99).     

Discussion

In this small series of patients undergoing atherectomy, there were significantly more dissections noted by IVUS when compared to cine angiography. Angiography has been the main modality used for evaluating the peripheral arteries, but it has consistently under-estimated the severity of calcium, the presence of thrombus, the true vessel size, and lesion severity.^1-7 In contrast to the NHLBI classification, the iDissection classification reveals the extent of injury and its depth. Pathologic studies have shown that deeper injuries into the media and adventitia correlate with loss of patency and increase in TLR rate.¹¹ These deeper injuries were also identified on IVUS.¹² The identification of deeper injury that cannot be seen on angiography may offer an explanatory mechanism for the occurrence of restenosis in otherwise successful procedures as seen on angiography following atherectomy. Although data indicate that atherectomy reduces angiographic dissections and stenting compared to balloon angioplasty, this concept may need to be revisited with IVUS-based imaging. Data from the THUNDER trial¹³ and from Japan¹⁴ indicate that type C or higher dissections on angiogram correlate with poorer outcomes with balloon angioplasty. However, the THUNDER trial also indicated that drug-coated balloon (DCB) use seems to partly mitigate this negative outcome. The contribution of these dissections (particularly the deeper and more extensive ones) to restenosis following DCB is unknown. In this study, we also noted that balloon angioplasty does not statistically change the number of dissections or their severity, although there was a non-statistically significant numerical shift to fewer (but more severe) dissections. 

Study limitations. In this study, we could not match dissections seen on cine angiogram with the exact dissections seen on IVUS since co-registration is not yet available for peripheral vascular applications. However, given the larger number of dissections on IVUS compared to angiogram, it is clear that normal-looking segments on angiogram can have under-appreciated significant dissections. This study is also single center and focused predominantly on the use of the Jetstream (13/15 patients). It is unclear how other atherectomy devices behave. Some data suggest that the Turbo-Booster excimer laser yielded intramural hematoma in 55% of frames analyzed and medial dissections in 24%.¹⁵ Also, it would be expected that deeper cuts and likely dissections would occur with directional atherectomy. The clinical impact of these dissections is unclear in the DCB era. Also, it is unclear how repair of these dissections with a traditional stent or the Tack Endovascular System (Intact Vascular) would alter the outcome. A large, multicenter registry is needed to correlate dissection presence and subtypes with outcomes such as patency and freedom from TLR. Finally, this study focused on dissections in the femoropopliteal segment. The nature of calcium distribution in the vessel wall and the small vessel size in the infrapopliteal arteries are different than the femoropopliteal vessels. Therefore, our data do not apply to tibial and peroneal vessels. 

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From the ¹Midwest Cardiovascular Research Foundation, Davenport, Iowa; and ²St. John Providence Health System, Detroit, Michigan.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Shammas reports educational and research grants from Boston Scientific, Bard, and Intact Vascular; speaker’s bureau income from Janssen, Boehringer Inghelheim, and Novartis. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted May 10, 2018, provisional acceptance given May 13, 2018, final version accepted May 15, 2018.

Address for correspondence: Nicolas W. Shammas, MD, MS, EJD, FACC, FSCAI, Research Director, Midwest Cardiovascular Research Foundation, 1622 E. Lombard Street, Davenport, IA 52803. Email: shammas@mchsi.com