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Temporal reverse flow by proximal femoral artery occlusion during drug-coated balloon dilatation: a technique to minimize downstream particle embolization and systemic adverse effects

Open AccessPublished:October 13, 2021DOI:https://doi.org/10.1016/j.jvscit.2021.10.001

      Abstract

      Downstream paclitaxel particle embolization for nonhealing ischemic ulcers and systemic adverse effects caused by a paclitaxel drug-coated balloon are of concern, and safety measures to prevent these adverse risks are needed. To reduce distal particle embolization and movement of the paclitaxel particles to systemic blood flow during drug-coated balloon inflation, proximal balloon occlusion using a sheathless temporary occlusion balloon-guiding catheter and extraction by manual aspiration of the paclitaxel-containing blood through the catheter are good treatment options to overcome these risks. Here, we introduce this method with tips and tricks, and demonstrate initial experience of this technique.

      Keywords

      Endovascular therapy for femoropopliteal (FP) lesions has rapidly progressed due to introduction of new devices such as drug-coated balloons (DCBs), atherectomy, and drug-coated stents.
      • Gray W.A.
      • Keirse K.
      • Soga Y.
      • Benko A.
      • Babaev A.
      • Yokoi Y.
      • et al.
      A polymer-coated, paclitaxel-eluting stent (Eluvia) versus a polymer-free, paclitaxel-coated stent(Zilver PTX) for endovascular femoropopliteal intervention (IMPERIAL): a randomised, non-inferiority trial.
      ,
      • Stavroulakis K.
      • Bisdas T.
      • Torsello G.
      • Stachmann A.
      • Schwindt A.
      Combined directional atherectomy and drug-eluting balloon angioplasty for isolated popliteal artery lesions in patients with peripheral artery disease.
      The concept of “leave nothing behind” in FP lesions when using a DCB is particularly promising in endovascular treatment.
      • Armstrong E.J.
      • Waldo S.W.
      Drug-coated balloons for long superficial femoral artery disease: leaving nothing behind in the real-world.
      However, downstream paclitaxel particle embolization for nonhealing ischemic ulcers
      • Thomas S.D.
      • McDonald R.R.
      • Varcoe R.L.
      Vasculitis resulting from a superficial femoral artery angioplasty with a paclitaxel-eluting balloon.
      ,
      • Ibrahim T.
      • Dirschinger R.
      • Hein R.
      • Jaitner J.
      Downstream panniculitis secondary to drug-eluting balloon angioplasty.
      and systemic adverse effects caused by a paclitaxel DCB are of concern,
      • Katsanos K.
      • Spiliopoulos S.
      • Kitrou P.
      • Krokidis M.
      • Karnabatidis D.
      Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Rocha-Singh K.J.
      • Duval S.
      • Jaff M.R.
      • Schneider P.A.
      • Ansel G.M.
      • Lyden S.P.
      • et al.
      Mortality and paclitaxel-coated devices: an individual patient data meta-analysis.
      and safety measures to prevent these adverse risks are needed. To reduce distal emboli during DCB inflation, proximal balloon occlusion using a sheathless temporary occlusion balloon-guiding catheter (b-GC) is a good treatment option to overcome these risks.
      • Kimura M.
      • Shiraishi J.
      • Ikemura N.
      • Matsubara Y.
      • Hyogo M.
      • Sawada T.
      Proximal balloon occlusion to prevent downstream embolization and thus reduce systemic adverse effects of drug-coated balloons.
      Here, we introduce this method with tips and tricks for treatment of FP lesions using a DCB.

      Method

       Technique

      This technique is performed for patients with FP lesions treated by DCBs. First, a 6F 11 cm sheath is inserted through the ipsilateral common femoral artery to perform a diagnostic angiogram, which is useful for insertion of a sheathless guiding catheter (Fig 1, A). Immediately after recording this angiogram, a b-GC (Optimo PPI; Tokai Medical Products, Aichi, Japan) with an outer diameter equal to a 6.5F sheath is placed from the 6F sheath and advanced to just proximal of the target lesion (Fig 1, B). After successful guidewire crossing with intraluminal wire passage, predilatation is performed with an over-the-wire (OTW) balloon catheter that is compatible with a 0.035-inch guidewire (Fig 1, C and D). Just before retrieving the balloon catheter, the b-GC balloon lumen is inflated to interrupt the antegrade flow of the superficial femoral artery (SFA) (Fig 1, E). Subsequently, the popliteal artery is compressed from the body surface below the popliteal joint using a blood pressure cuff or tourniquet at a pressure of 20 mm Hg plus systolic pressure. Angiography is then performed through the OTW lumen of the predilatation balloon catheter, concomitant with simultaneous manual aspiration through the guiding catheter lumen of the b-GC. This is performed to confirm reverse flow from the popliteal artery to the proximal superficial artery (Fig 1, F). After confirming reverse flow in the target lesion, DCBs are dilated in the lesion (Fig 1, G). When deflating the DCBs, simultaneous blood aspiration through the guiding catheter lumen of the b-GC avoids distal embolization (Fig 1, H). The amount of blood obtained using this extraction was always 20 mL through the guiding lumen of the b-GC. After deflating the temporary occlusion balloon of the b-GC, a final angiogram is performed (Fig 1, I). All patients provided written informed consent for the intervention. The study was approved by the institutional review board.
      Figure thumbnail gr1
      Fig 1Proximal balloon occlusion procedure. A, Scheme of the common femoral artery (CFA), superficial femoral artery (SFA), and target lesion. B, Insertion of a balloon-assisted guiding catheter (Optimo PPI) through the common femoral artery to just proximal of the target lesion. C, Guidewire crossing. D, Predilatation with a 0.035-inch guidewire compatible with the over-the-wire (OTW) balloon catheter. E, Just before retrieving the balloon catheter, the balloon-guiding catheter (b-GC) balloon lumen is inflated to interrupt the antegrade flow of the SFA. Subsequently, the popliteal artery is compressed from the body surface above or below the popliteal joint using a blood pressure cuff or tourniquet. The combination of proximal balloon occlusion and popliteal artery external compression produces reverse flow from the popliteal artery to the proximal superficial artery. F, Angiography is then performed through the OTW lumen of the predilatation balloon catheter, concomitant with simultaneous manual aspiration through the b-GC lumen to confirm reverse flow from the popliteal artery to the proximal superficial artery. G, After confirming reverse flow in the target lesion, drug-coated balloons (DCBs) are dilated in the lesion. H, When deflating the DCBs, simultaneous blood aspiration through the temporary occlusion b-GC avoids distal embolization. I, After deflating the temporary occlusion balloon of the b-GC, the final angiogram is performed.

      Result and clinical experience

      From December 2018 to December 2019, 26 patients (36 lesions) with lower extremity peripheral artery disease underwent DCB (IN.PACT Admiral; Medtronic Inc, Dublin, Ireland) angioplasty using the above technique. The patients were aged 76 ± 7.9 years, and included 6 males (46.1%) and 8 critical limbs (61.5%). Comorbidities included diabetes (61.5%), hemodialysis (69.2%), and hypertension (69.2%). All lesions were de novo, and the mean diameter and length were 5.6 ± 0.6 mm and 112 ± 58.4 mm, respectively. All procedures were successfully performed with optimal DCB dilatation and without complications such as slow flow, no-reflow, and thrombosis. The details of the patients and preprocedure and procedure characteristics are shown in the Table.
      TableThe details of the patients and preprocedure and procedure characteristics
      Background of the patientsPreprocedure characteristics of the patientsDetails of the procedures characteristics
      ItemValueItemValueItemValue
      Age, years78 ± 6.8Lesion type, % (n/N)Number of treatment DCBs per lesion, mean (N)1.3
      Male gender, % (n/N)69.2 (18/26) De novo83.3 (30/36)
      Body mass index, kg/m221.0 ± 3.6 Restenotic (nonstented)16.7 (6/36)Number of treatment DCBs per leg, mean (N)1.8
      Diabetes mellitus, % (n/N)53.8 (14/26) In-stent restenosis0 (0/36)
      Hypertension, % (n/N)69.2 (18/26)Target lesion, % (n/N)Predilatation, % (n/N)100 (36/36)
      Hyperlipidemia, % (n/N)38.7 (10/26) Superficial femoral artery80.6 (29/36)Postdilatation, % (n/N)0 (0/36)
      Current smoker, % (n/N)15.4 (4/26) Popliteal artery19.4 (7/36)Provisional stenting, % (n/N)0 (0/36)
      Renal insufficiency, % (n/N)84.6 (22/26)Lesion lengthSize of DCBs
      Hemodialysis57.7 (15/26) Mean mm ± SD112.2 ± 58.4 Diameter per balloons, mm5.6 ± 0.7
      Rutherford clinical category, % (n/N) Min, Max40/200 Length per balloons, mm99.8 ± 42.7
      Occluded, % (n/N)13.9 (5/36)Paclitaxel dose, per leg μg12627.9 ± 5333.2
       334.6 (9/26)With calcification, % (n/N)75 (27/36)Procedural success, % (n/N)100 (26/26)
       426.9 (7/26)With severe calcification, % (n/N)38.9 (14/36)Access site complication, % (n/N)0 (0/26)
       526.9 (7/26)Reference vessel diameter, mean mm ± SD5.7 ± 0.6Dissection, % (n/N)
       611.5 (3/26) 03.9 (1/26)
      ABI, per target limb0.67 ± 0.35TASC lesion type, % (n/N) Grade A-C96.1 (25/26)
       A23.1 (6/26) Grade D-F0 (0/26)
       B26.9 (7/26) Slow flow0 (0/26)
       C46.2 (12/26) No flow0 (0/26)
       D3.8 (1/26) Popliteal artery injury by external compression0 (0/26)
      Below-the-knee runoff vessel2 ± 0.9
      ABI, Ankle brachial index; DCB, drug-coated balloon; SD, standard deviation.
      Procedural success was defined as successful drug-coated balloon angioplasty with a residual stenosis <20% without the occurrence of any major in-hospital adverse cardiovascular events. Access site complication was defined as major bleeding requiring transfusion and access site vascular injury. Dissection was classified according to previous report.
      • Fujihara M.
      • Takahara M.
      • Sasaki S.
      • Nanto K.
      • Utsunomiya M.
      • Iida O.
      • et al.
      Angiographic dissection patterns and patency outcomes after balloon angioplasty for superficial femoral artery disease.
      In histologic findings, paclitaxel particles were seen in blood that was aspirated and extracted from the b-GC guiding lumen under proximal balloon occlusion just after deflating the DCB (Fig 2). A representative case of DCB angioplasty using proximal balloon occlusion is illustrated in Fig 3 and Supplementary Video, online only.
      Figure thumbnail gr2
      Fig 2Introduction of the balloon-guiding catheter (b-GC). A, Photograph of the b-GC (Optimo PPI). The arrow shows the occlusion balloon attached to the tip of the sheathless guiding catheter. B, Manual aspiration through the guiding lumen of the b-GC. C-D, A paclitaxel particle (arrow) from the drug-coated balloon (IN.PACT Admiral) in blood extracted using proximal balloon occlusion. C, Hematoxylin-eosin stain. D, Polarized light microscopy.
      Figure thumbnail gr3
      Fig 3A representative case of superficial femoral artery (SFA) intervention using the new technique. An 82-year-old man was referred to our hospital for treatment of peripheral artery disease with nonhealing ulcers on his left foot. The target lesion was a TASC C SFA lesion. A, First, a 6F 11 cm sheath was inserted through the left common femoral artery. Angiography revealed severe stenosis in the left middle to distal SFA and tibial arteries. B, Just after this angiogram, a balloon-guiding catheter (b-CG) was placed from the 6F sheath and advanced to just proximal of the target lesion. After successful guidewire crossing, predilatation was performed with an over-the-wire (OTW) balloon catheter, which was compatible with a 0.035-inch guidewire (DORADO 6.0/100 mm at 26 atm). C, Just before retrieving the balloon catheter, the b-GC balloon lumen (arrow) was inflated to interrupt the antegrade flow of the SFA. In addition, the popliteal artery was compressed from the body surface below the popliteal joint using a blood pressure cuff at 200 mm Hg. Angiography is then performed through the OTW lumen of the predilatation balloon catheter (white arrow), concomitant with simultaneous manual aspiration through the guiding catheter lumen of the b-GC. This is performed to confirm reverse flow from the popliteal artery to the proximal superficial artery (arrows). D, After confirming reverse flow in the target lesion, drug-coated balloons (DCBs) were dilated in the lesion. When deflating the DCBs, simultaneous blood aspiration through the temporary occlusion b-GC was used to avoid distal embolization. E, After deflating the temporary occlusion balloon of the b-GC, the final angiogram revealed optimal dilatation without any slow flow.

      Discussion

      DCBs have improved the patency rate, but two major concerns about negative aspects of DCBs have also been raised recently. One is the potential risk of an embolic effect caused by the downstream release of paclitaxel. Downstream vascular damage has been observed with a DCB,
      • Thomas S.D.
      • McDonald R.R.
      • Varcoe R.L.
      Vasculitis resulting from a superficial femoral artery angioplasty with a paclitaxel-eluting balloon.
      and a clinical case of painful rash after DCB treatment has been reported.
      • Ibrahim T.
      • Dirschinger R.
      • Hein R.
      • Jaitner J.
      Downstream panniculitis secondary to drug-eluting balloon angioplasty.
      Thus, use of a DCB carries a risk of delayed wound healing in patients with critical limb ischemia. The second concern is the increased risk of mortality after the use of a paclitaxel-coated balloon. Since a systematic review and meta-analysis in November 2018, there has been a major debate about these concerns.
      • Rocha-Singh K.J.
      • Duval S.
      • Jaff M.R.
      • Schneider P.A.
      • Ansel G.M.
      • Lyden S.P.
      • et al.
      Mortality and paclitaxel-coated devices: an individual patient data meta-analysis.
      ,
      • Kimura M.
      • Shiraishi J.
      • Ikemura N.
      • Matsubara Y.
      • Hyogo M.
      • Sawada T.
      Proximal balloon occlusion to prevent downstream embolization and thus reduce systemic adverse effects of drug-coated balloons.
      The RADISH study concluded that DCB therapy did not lead to delayed wound healing; even a slow flow phenomenon after DCB was experienced.
      • Hata Y.
      • Iida O.
      • Ito N.
      • Soga Y.
      • Fukunaga M.
      • Kawasaki D.
      • et al.
      Roles of angioplasty with drug-coated balloon for chronic ischemia in wound healing.
      However, it would be better to avoid these negative aspects if it did not take excess invasion and cost. To perform this technique, it takes only an additional few minutes and approximately $300 patient charges in Japan.
      The key device in our technique is the b-GC. In Japan, the Optimo PPI is available. This catheter is often used to perform carotid artery stenting. Proximal artery occlusion using a temporal balloon occlusion catheter can produce temporary reverse flow during DCB angioplasty in FP lesions. The consensus among vascular surgeons is that blood flow in the superficial artery is reversed during arteriotomy in the common femoral artery. This reverse flow and extraction of blood from the b-GC can minimize distal particle embolization during DCB inflation and thus reduce the systemic adverse effects of paclitaxel-coated balloons. Crystals of paclitaxel were detected in blood extracted from the b-GC.
      In our initial approach, only proximal balloon occlusion using a b-GC was performed, without popliteal external compression.
      • Kimura M.
      • Shiraishi J.
      • Ikemura N.
      • Matsubara Y.
      • Hyogo M.
      • Sawada T.
      Proximal balloon occlusion to prevent downstream embolization and thus reduce systemic adverse effects of drug-coated balloons.
      However, there are many small arteries in the distal SFA and popliteal arteries in many cases, and proximal balloon occlusion is not sufficient to produce reverse flow in the distal SFA and popliteal arteries. In such cases, there are two important tips to create reverse flow in target lesions. One is to advance the b-GC to just proximal to the target lesion, and the other is external compression on the popliteal artery just distal to the target lesion. Such external compression can increase the resistance of blood flow to the popliteal artery, which suppresses the small artery antegrade flow. With external compression at the popliteal artery only, the risk of a paclitaxel particle downstream effect on skin around the popliteal artery is greatly increased.
      • Ibrahim T.
      • Dirschinger R.
      • Hein R.
      • Jaitner J.
      Downstream panniculitis secondary to drug-eluting balloon angioplasty.
      Therefore, additional angiography through the OTW lumen is important to confirm reverse flow at the target lesion.
      To perform this technique, it takes only an additional few minutes and approximately $300 patient charges in Japan.
      This study was influenced by two characteristics of the Japanese health insurance system. First, the DCB used in the study (IN.PACT Admiral) was the only one available in our institution as of October 2019. Second, provisional stenting after DCB dilatation is not permitted by the health insurance system in Japan. Thus, we have to manage the dissection and vessel rupture carefully.

       Limitation

      This study has several limitations. One is this study is a single-center observational study including selected patients. Therefore, some specific lesions such as proximal SFA involving the common femoral artery were not analyzed. The other is that we could not measure the concentration of paclitaxel in the extracted blood and serum, which might strongly support the efficacy of this technique.

      Conclusions

      Our proximal balloon occlusion technique using a b-GC, simultaneous manual aspiration, and external compression at the distal popliteal artery may be an important treatment option for DCB angioplasty to potentially minimize risks of distal particle embolization and systemic adverse effects.

      Appendix (online only)

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