Femoropopliteal Arterial Dissections Post Flex Vessel Prep and Adjunctive Angioplasty: Results of the Flex iDissection Study

Abstract: Background. Luminal gain post balloon angioplasty (PTA) is in part due to the occurrence of dissections. The depth and extent of dissections, however, can influence the short- and long-term outcomes of a procedure. Focal force and scoring balloons have been used to reduce angiographic dissections post PTA. The role of the Flex Vessel Prep (VP) system (VentureMed Group), a dynamic, microincision, non-balloon based system, prior to PTA in reducing and/or limiting severe dissections has not been fully characterized. Methods. In this prospective pilot study, a total of 15 patients were evaluated by angiography and intravascular ultrasound (IVUS) following treatment of femoropopliteal de novo or no-stent restenosis with the Flex VP system and PTA. Eagle Eye Platinum ST IVUS catheters were used in this study. No atherectomy devices were allowed. Cine and IVUS images were obtained at baseline, after Flex, and following adjunctive PTA. Angiographic and IVUS core labs analyzed the images. Results. Mean patient age was 74.6 ± 11.7 years. Diabetes and claudication were present in 40% and 73.3%, respectively. Median baseline, post-Flex, and postadjunctive PTA stenosis severities were 77.0%, 60.0%, and 34.0%, respectively (P=.07 and P<.001 for baseline vs post Flex and post Flex vs post PTA, respectively). Lesion length was 63.6 ± 32.5 mm. Using PACSS classification for calcium grading, grades 3 and 4 were 6.7% and 40.0%, respectively. Total dissections identified on IVUS post-Flex microincisions were 14 compared with 3 dissections on angiogram (P=.35) (ratio, 4.7 to 1). Post adjunctive angioplasty, there were 49 dissections on IVUS vs 6 on angiogram (P<.01) (ratio, 8.2 to 1). Of these dissections and when compared with baseline, 3 and 37 dissections were new on IVUS post Flex and PTA, respectively. Of these dissections, 2/3 and 7/37 were ≥180° in circumference post Flex and post PTA, respectively. Also, 1/3 and 8/37 dissections involved the media and/or adventitia as seen on IVUS post Flex and PTA, respectively. The majority of dissections post PTA following Flex VP involved mostly the intima (71.4%) and were <180° in circumference (77.6%). Conclusion. Dissections are grossly under-appreciated on angiogram when compared with IVUS. Dissections on IVUS post PTA following the Flex VP system involved mostly the intima, with <180° in width. The clinical significance of these findings needs to be further explored.

J INVASIVE CARDIOL 2019;31(5):121-126.

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

Intentional dissection is a key mechanism for luminal gain post balloon angioplasty (PTA). Controlling the severity of dissections has been the subject of many adjunctive technologies prior to PTA including debulking with atherectomy^1-3 or treatment with scoring or focal-force balloons.^4-6 However, these studies aassessed the presence of dissections with angiography, a suboptimal method to identify and characterize the depth and circumference of dissections. The iDissection classification has been proposed to classify dissections as seen on intravascular ultrasound (IVUS) during infrainguinal interventions.⁷ Using this classification, 39% of dissections post atherectomy (predominantly Jetstream in this study) and adjunctive PTA were noted to involve the media and adventitia and 13% were wider than 180° in circumference; both were grossly under-appreciated on cine angiography.⁸ Despite debulking of plaque, atherectomy was not superior to PTA in achieving better patency and target-lesion revascularization,^9,10 which may partly be explained by the occurrence of deep and wide dissections seen on IVUS. In the drug-coated balloon (DCB) era, the negative impact of dissections on outcomes appears to have been partially mitigated, as seen in the Thunder trial.¹¹ However, recent data from TOBA II suggest that repair of dissections may confer a positive outcome even with the use of DCB.¹²

The Flex VP system (VentureMed Group) (Figure 1) was designed to create multiple longitudinal controlled-depth microincisions across the entire lesion length in infrainguinal arteries with the intention to alter vessel compliance and allow a controlled stretching of the artery with PTA, without causing significant deep or wide dissections. The distal end of the Flex system utilizes a treatment element consisting of three protective skids, each with an atherotome mounted on the proximal end of each skid (Figure 2). The protective skids are designed to follow the contours of the vessel wall, while continuously exerting a maximum pressure of approximately 1 atm and controlling the microincision depth. A retrograde pull-back is performed to engage the Flex VP system’s dynamic microincision technology to prep the lesion for subsequent PTA. We present data on the number and nature of dissections as seen on IVUS following Flex VP and PTA based on the iDissection classification for IVUS⁷ and the National Heart, Lung, and Blood Institute (NHLBI) classification for angiography.¹³

The iDissection classification combines depth and circumference of injury. It exhibits six dissection grades (A1, A2, B1, B2, C1, and C2). Grade A involves the intima, B involves the media, and C involves the external elastic lamina. Dissection circumferences <180° are numbered 1 and ≥180° are numbered 2 (Figure 3). The NHLBI classification is angiography based and also uses six grades of dissection (A-F). Dissections A and B are considered minor, C and D are moderate, and E and F are severe with flow impairment.

Methods

A total of 15 patients undergoing Flex vessel prep followed by PTA (including non-DCB PTA, Shockwave lithoplasty [Shockwave Medical], and/or DCB) of the femoropopliteal arteries for de novo or restenotic disease (non-stent restenosis) were prospectively included in this study by one operator at a single center. The study was approved by the Trinity Health System Institutional Review Board and informed consent was obtained for all patients. Cine angiography and IVUS using the Eagle Eye Platinum ST catheter (Philips) were performed on the treated segments at baseline, post Flex and post adjunctive PTA. Adjunctive PTA was left to the operator’s preference for the choice of the balloon (non-DCB, DCB, Shockwave, or a combination) sized 1:1 to the vessel size. Also, stenting was left to the operator’s discretion.

The segment to be analyzed for dissections was marked on a radiopaque ruler and images obtained with cine angiography and IVUS were analyzed within identical segment lengths. Cine and IVUS images were analyzed at the MCRF Quantitative Vascular Laboratory (QVL) using CAAS software (Pie Medical) and echoPlaque software (Indec Systems, Inc), respectively. Dissections on cine images were classified based on the NHLBI classification. Dissections on IVUS images were classified using the iDissection classification. 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 cine dissection to IVUS dissection direct comparison was not feasible; therefore, only total and severity of dissections could be quantitated within the same segment using both imaging modalities.

Demographics, clinical, and angiographic variables were collected on all patients and are listed in Tables 1 and 2. Procedural success was defined as obtaining <30% residual narrowing after PTA following Flex.

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 Flex and post adjunctive PTA by IVUS and angiogram for both NHLBI and iDissection classifications. Pearson’s Chi-square, Fisher’s, and Kruskal-Wallis tests were performed as appropriate. Spearman’s Rho correlation was performed to compare associations for lesion and procedure variables of the groups. Median Mood test was used to compare the median baseline vs post-Flex stenosis and post-Flex vs PTA stenosis. The difference between total number of dissections post-Flex IVUS vs post-Flex angiogram and post-PTA IVUS vs post-PTA angiogram was tested with the t-test. Minitab 17 and Cytel Studio software was used.

Results

Table 1 displays the demographics and clinical variables. Mean patient age was 74.6 ± 11.7 years. Diabetes and claudication were present in 40.0% and 73.3% of patients, respectively. The majority of patients had histories of hyperlipidemia, hypertension, and smoking. Critical limb ischemia was present in almost 27% of patients.

Table 2 shows the angiographic and procedural variables. Median baseline, post-Flex, and post-PTA stenosis severities were 77.0%, 60.0%, and 34.0%, respectively. Peripheral artery calcium scoring system (PACSS) grades 3 and 4 were 6.7% and 40.0%, respectively. Lesion length was 63.6 ± 32.5 mm. Procedural success rate was 86.7% and no complications were noted. There were no flow-limiting dissections or bail-out stents required.

After Flex VP, a total of 14 dissections were identified on IVUS vs 3 identified on angiogram (P=.35) (ratio, 4.7 to 1). After adjunctive PTA, a total of 49 dissections were identified on IVUS vs 6 identified on angiogram (P<.01) (ratio, 8.2 to 1). Of these dissections (and when compared with baseline), a total of 3 dissection post Flex and 37 dissections post PTA were new on IVUS, when accounting for baseline dissections pretreatment (likely the result of wire manipulation in severe lesions). Of the dissections, 2/3 and 7/37 were ≥180° in circumference post Flex and PTA, respectively. Also, 1/3 and 8/37 dissections involved the media and/or adventitia as seen on IVUS post Flex and PTA, respectively. The majority of dissections post PTA following Flex VP system involved mostly the intima and were <180° in circumference (Table 3 and Table 4). Following Flex and PTA, minimal luminal area significantly increased compared with baseline, with no change in reference diameter or plaque burden of the vessel (Table 5).

Using binomial analysis for predictors of severe dissections (≥180°) post atherectomy, lesion length, balloon pressure, inflation time, critical limb ischemia, and degree of calcium did not correlate with dissection severity as seen on IVUS.

Discussion

The superiority of IVUS in detecting dissections has been previously confirmed in the iDissection study of atherectomy followed by PTA.⁸ Following Flex VP and using the iDissection classification, the dissections appear predominantly confined to the intima and with a smaller circumference (<180°). There were no flow-limiting dissections or bail-out stents required. Pathologic studies have shown that deeper injuries into the media and adventitia correlate with loss of patency and increase in target-lesion recurrence rate.^14-16 Therefore, pretreatment with the Flex VP System may potentially lead to reduced restenosis, a concept that needs to be validated in registries or randomized trials. The additive value of the Flex VP system prior to a DCB is unknown currently and requires additional study. In the recently presented TOBA II study, repair of dissections in complex lesions treated with DCB had improved patency similar to the outcomes of simple lesions treated with DCB.¹² The interaction of dissections with DCBs is complex and poorly understood at this time. More research is needed in this area.

Study limitations. This study included a single center and needs to be validated in larger studies. However, the use of core lab to analyze cine angiography and IVUS images independently adds more validity to the data. Also, this study focused on dissections in the femoropopliteal segment. The nature of calcium distribution and ring fibrosis in below-the-knee vessels may lead to different results than we have seen in this study. Therefore, our data do not apply to tibial and peroneal vessels. Finally, the clinical value of these findings needs to be explored with larger registries or randomized trials in the era of DCBs.

Conclusion

Dissections are grossly under-appreciated on angiogram when compared with IVUS. Dissections on IVUS post PTA following utilization of the Flex VP system involved mostly the intima with <180° in width. There were no flow-limiting dissections or bail-out stents required. The clinical significance of these findings needs to be further explored in larger trials.

References

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From the Midwest Cardiovascular Research Foundation, Davenport, Iowa.

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, VentureMed Group, and Intact Vascular; speakers’ bureau income from Janssen, Boehringer Inghelheim, and Novartis. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted March 5, 2018, provisional acceptance given March 8, 2018, final version accepted March 14, 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