J ENDOVASC THER 2013;20:801–804
^COMMENTARY
801
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^
How Do We Deal With Dissection After Angioplasty? Fabrizio Fanelli, MD, EBIR1; Alessandro Cannavale, MD1; Marianna Gazzetti, MD, PhD2; and Alessandro D’Adamo, MD1 Vascular and Interventional Radiology Unit and 2Department of Vascular and Endovascular Surgery, ‘‘Sapienza’’ University of Rome, Italy.
1
Over the last decades, percutaneous transluminal angioplasty (PTA) has evolved as the first-line approach to peripheral artery disease.1,2 The mechanism consists of abrupt plaque fracture, vessel wall stretching, and subsequent remodeling over time. However, acute vessel damage is quite common, and it may vary from simple plaque rupture with a non-flow-limiting dissection to a more severe flow-limiting dissection or acute vessel thrombosis. It is noteworthy that subintimal tears may initiate a reactive inflammation process leading to restenosis. Thus, the long-term effects of a dissection, according to its severity, could involve the development of intimal hyperplasia and restenosis.3 On the other hand, thanks to arterial remodeling, dissection flaps tend to decrease in number and extent over long-term follow-up4; still, owing to the risk of stenosis, stent deployment (i.e., provisional stenting) is generally performed in cases of dissection secondary to conventional PTA.5 Even though flow-limiting dissections can affect clinical outcome, the question is: do all these dissections require stenting? In this issue of the JEVT, Tepe and colleagues6 analyze the midterm outcomes of vessel injury in the form of non-flow-limiting dissection among a historical cohort from the THUNDER (Local Taxan with Short Exposure for Reduction of Restenosis in Distal Arteries) trial. The randomized, controlled, double-
blinded THUNDER study was designed to evaluate the effect of local paclitaxel administration via a drug-coated balloon (DCB) on the restenosis rate after interventions in the superficial femoral artery (SFA) and the popliteal artery. In comparison with standard balloon angioplasty, short-term exposure of the inner vessel wall to the paclitaxel-coated balloon effectively reduced restenosis up to 1 year.7 The incidence of a flow-limiting dissection after conventional femoropopliteal PTA has been reported by many studies and randomized controlled trials5,7–10 to range from 7.4%8 to 53% of cases.9 The initial rates of flowlimiting dissection using DCB were around 32%9 to 50%.7 However, in most recent studies, lower rates of flow-limiting dissection after angioplasty with DCB have been documented (9.6% in an Italian registry,10 7.4% in the DEBELLUM trial8), so the use of DCB has led to a lower rate of provisional stenting. These positive outcomes have been related to the recent introduction of the ‘‘optimal PTA’’ technique, in which angioplasty is performed as correctly as possible, inflating the balloon very slowly and keeping it inflated for more than 1 minute, thus reducing the incidence of plaque dissection. At present, the correct time to keep a DCB inflated is 2 minutes: the first 30 to 60 seconds are required for drug transfer and the rest of the time is needed to
Invited commentaries published in the Journal of Endovascular Therapy reflect the opinions of the author(s) and do not necessarily represent the views of the Journal or the INTERNATIONAL SOCIETY OF ENDOVASCULAR SPECIALISTS. The authors declare no association with any individual, company, or organization having a vested interest in the subject matter/products mentioned in this article. Corresponding author: Fabrizio Fanelli, MD, EBIR, Vascular and Interventional Radiology Unit, ‘‘Sapienza’’ University of Rome, Italy. E-mail: [email protected] Q 2013 by the INTERNATIONAL SOCIETY
OF
ENDOVASCULAR SPECIALISTS
Available at www.jevt.org
802
COMMENTARY Fanelli et al.
accomplish the mechanical effect of vessel wall dilation.11 The low incidence of provisional stenting is a direct consequence of fewer flow-limiting dissections. In the current article, Tepe and colleagues6 discuss the different outcomes of the THUNDER trial vs. FemPac (Femoral Paclitaxel), another very important study on DCBs that reported a lower 30% rate of dissection vs. 50% in THUNDER. A specific reason for the higher rate in the THUNDER cohort was not found, but a greater incidence of dissections among smokers was recorded. But which type of dissection are we talking about? In these studies, did all the detected dissections really need stenting? The authors observed in both the THUNDER and FemPac studies that operators tended to stent dissections more frequently in lesions treated with standard balloon catheters than with DCB. The reason for this behavior is not completely clear: it may be related to the anticipated poorer outcome with a standard balloon compared to a DCB or to the real need to stent severe dissections that are caused more often by standard balloons than by DCBs. Unfortunately, there has until now been little data on the features and evolution of a dissection after PTA in the femoropopliteal segment. Recognizing this void, Tepe and colleagues hoped that an analysis of non-flow-limiting dissections from the THUNDER trial cohort would provide evidence as to the effect of dissection on angiographic and clinical outcomes after peripheral artery interventions. The result is the first DCB study to have a notable influence on the approach to ballooninduced dissections, and as such, it is a first step toward establishing a standard protocol for post-angioplasty dissection. As suggested by Tepe et al.,6 assessing the ‘‘grade’’ of a dissection and distinguishing the non-severe from severe ones would be the first step toward better management of such complications. To this end, the National Heart, Lung, and Blood Institute classification system for coronary intimal tears12 could be a good starting point for the development of a classification system for dissections in the rest of the peripheral vascular tree. Precise definition and grading of vessel dissection
J ENDOVASC THER 2013;20:801–804
with angiographic examples should be available to improve clinical practice. In addition, outcome data about the different types of dissections should be further investigated to obtain prognosis grading. But what do we know at present until these measures become reality? In the Tepe article,6 angiographic parameters of dissections, such as percent stenosis, reference diameter, and mean lesion diameter did not show a significant difference between DCB and the control group soon after the procedure regardless of the grade of dissection, whereas the situation changed during follow-up. Thus, if no difference can be expected between the two types of balloons immediately after dilation, the long-term results (up to 4 years) become extremely useful in confirming the longlasting effect of a DCB in reducing late restenosis after dissection. According to the THUNDER subanalysis, DCBs seem to be associated with better outcomes in terms of late lumen loss (LLL), target lesion revascularization, and lumen area change in both low and high grade dissections at 6 months to 2 years of followup owing to positive vessel remodeling (increase in lumen width and plaque regression). However, data on other clinical parameters, such as ankle-brachial index and Rutherford class shift, are needed because they can show how a dissection may influence the clinical status of the patient over time. Another main determinant of dissection development and evolution is the presence of calcium within the plaque composition. Fitzgerald et al.3 linked the presence of local calcium deposits to a higher risk of developing a dissection and reported that 87% of the ultrasound studies of dissections showed calcium positioned on the same side of the vessel wall as the origin of the tear. Thus, in the presence of inelastic components such as calcium, balloon expansion will result in a non-uniform energy distribution to the vessel wall, leading to the development of deeper cracks and tears close to the calcium deposits. If a dissection occurs after DCB angioplasty in selected cases and we do not stent the lesion, we are trusting in the long-term positive effects of the drug to satisfy the
J ENDOVASC THER 2013;20:801–804
concept of ‘‘nothing left behind.’’ But can such good outcomes be reached even in highly calcified lesions? Currently, no data are available to answer this question, so further studies are strongly needed to better understand the effect of calcium on DCB angioplasty. ‘‘Nothing left behind’’ is obviously fundamental in relatively young patients because a surgical approach may be subsequently indicated, and limitations related to the treated vascular area (geographical area, e.g., flexion points in the common femoral artery and popliteal artery) can be avoided. Another point is how to repair a dissection. There are two currents of thought: one is to immediately perform primary stenting and then dilate with a non-coated balloon. The second is to dilate first with a non-coated balloon, trying to reduce or totally repair the dissection, and then, in case of an unsatisfactory result, to deploy a stent (provisional spot stenting). As Tepe et al.6 explained, the treatment technique must always be aligned with the type (grade) of dissection and with the type of balloon applied (DCB vs. standard balloon). Their study showed that only high-grade dissections were repaired with provisional stenting in DCB-treated cases, whereas treatment with non-coated balloons required a broader application of provisional stenting. A growing number of studies have shown improved outcomes when using DCB in comparison with stenting and angioplasty performed with a non-coated balloon, not only in the femoropopliteal region,8–10 but also below the knee.13,14 At present, new studies with a longer follow-up and careful evaluation of each different aspect of the disease are strongly needed, and perhaps the encouraging results of this THUNDER subanalysis article will spark further clinical investigations into this topic.
REFERENCES 1. Tendera M, Aboyans V, Bartelink ML, et al.; ESC Guidelines on the diagnosis and treatment of peripheral artery diseases. Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery
COMMENTARY Fanelli et al.
2.
3.
4.
5.
6.
7.
8.
9.
803
Dis eases of t he Eur opean Soci ety of Cardiology (ESC). Eur Heart J. 2011;32:2851– 2906. Rooke TW, Hirsch AT, Misra S, et al.; American College of Cardiology Foundation; American Heart Association; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society for Vascular Medicine; Society for Vascular Surgery. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine, and Society for Vascular Surgery. Catheter Cardiovasc Interv. 2012;79:501–531. Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. Circulation. 1992;86: 64–70 van Lankeren W, Gussenhoven EJ, Honkoop J, et al. Plaque area increase and vascular remodeling contribute to lumen area change after percutaneous transluminal angioplasty of the femoropopliteal artery: an intravascular ultrasound study. J Vasc Surg. 1999;29:430– 441. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther 2012;19:1–9. Tepe G, Zeller T, Schnorr B, et al. High-grade, non-flow-limiting dissections do not negatively impact long-term outcome after paclitaxelcoated balloon angioplasty: an additional analysis from the THUNDER study. J Endovasc Ther. 2013;20:792–800. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358:689– 699. Fanelli F, Cannavale A, Boatta E, et al. Lower limb multilevel treatment with drug-eluting balloons: 6-month results from the DEBELLUM randomized trial. J Endovasc Ther. 2012;19: 571–580. Werk M, Albrecht T, Meyer DR, et al. Paclitaxelcoated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the
804
COMMENTARY Fanelli et al.
randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;5:831–840. 10. Micari A, Cioppa A, Vadala` G, et al. Clinical evaluation of paclitaxel-eluting balloon for treatment of femoropopliteal arterial disease: 12-month results from a multicenter Italian registry. JACC Cardiovasc Interv. 2012;5:331– 338. 11. Wakman R, Pakala R. Drug-eluting balloon: the comeback kid? Circ Cardiovasc Interv. 2009;2: 352–358. 12. Dorros G, Cowley MJ, Simpson J, et al. Percutaneous transluminal coronary angioplasty: report of complications from the Na-
J ENDOVASC THER 2013;20:801–804
tional Heart, Lung, and Blood Institute PTCA Registry. Circulation. 1983;67:723–730. 13. Schmidt A, Piorkowski M, Werner M, et al. First experience with drug-eluting balloons in infrapopliteal arteries: restenosis rate and clinical outcome. J Am Coll Cardiol. 2011;58:1105– 1109. 14. Liistro F, Porto I, Angioli P, et al. Drug-Eluting Balloon in peripherAl inTErvention for Below The Knee angioplasty evaluation (DEBATEBTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation. 2013; 128;615–621.
^COMMENTARY
801
———————————————————————————————
^
How Do We Deal With Dissection After Angioplasty? Fabrizio Fanelli, MD, EBIR1; Alessandro Cannavale, MD1; Marianna Gazzetti, MD, PhD2; and Alessandro D’Adamo, MD1 Vascular and Interventional Radiology Unit and 2Department of Vascular and Endovascular Surgery, ‘‘Sapienza’’ University of Rome, Italy.
1
Over the last decades, percutaneous transluminal angioplasty (PTA) has evolved as the first-line approach to peripheral artery disease.1,2 The mechanism consists of abrupt plaque fracture, vessel wall stretching, and subsequent remodeling over time. However, acute vessel damage is quite common, and it may vary from simple plaque rupture with a non-flow-limiting dissection to a more severe flow-limiting dissection or acute vessel thrombosis. It is noteworthy that subintimal tears may initiate a reactive inflammation process leading to restenosis. Thus, the long-term effects of a dissection, according to its severity, could involve the development of intimal hyperplasia and restenosis.3 On the other hand, thanks to arterial remodeling, dissection flaps tend to decrease in number and extent over long-term follow-up4; still, owing to the risk of stenosis, stent deployment (i.e., provisional stenting) is generally performed in cases of dissection secondary to conventional PTA.5 Even though flow-limiting dissections can affect clinical outcome, the question is: do all these dissections require stenting? In this issue of the JEVT, Tepe and colleagues6 analyze the midterm outcomes of vessel injury in the form of non-flow-limiting dissection among a historical cohort from the THUNDER (Local Taxan with Short Exposure for Reduction of Restenosis in Distal Arteries) trial. The randomized, controlled, double-
blinded THUNDER study was designed to evaluate the effect of local paclitaxel administration via a drug-coated balloon (DCB) on the restenosis rate after interventions in the superficial femoral artery (SFA) and the popliteal artery. In comparison with standard balloon angioplasty, short-term exposure of the inner vessel wall to the paclitaxel-coated balloon effectively reduced restenosis up to 1 year.7 The incidence of a flow-limiting dissection after conventional femoropopliteal PTA has been reported by many studies and randomized controlled trials5,7–10 to range from 7.4%8 to 53% of cases.9 The initial rates of flowlimiting dissection using DCB were around 32%9 to 50%.7 However, in most recent studies, lower rates of flow-limiting dissection after angioplasty with DCB have been documented (9.6% in an Italian registry,10 7.4% in the DEBELLUM trial8), so the use of DCB has led to a lower rate of provisional stenting. These positive outcomes have been related to the recent introduction of the ‘‘optimal PTA’’ technique, in which angioplasty is performed as correctly as possible, inflating the balloon very slowly and keeping it inflated for more than 1 minute, thus reducing the incidence of plaque dissection. At present, the correct time to keep a DCB inflated is 2 minutes: the first 30 to 60 seconds are required for drug transfer and the rest of the time is needed to
Invited commentaries published in the Journal of Endovascular Therapy reflect the opinions of the author(s) and do not necessarily represent the views of the Journal or the INTERNATIONAL SOCIETY OF ENDOVASCULAR SPECIALISTS. The authors declare no association with any individual, company, or organization having a vested interest in the subject matter/products mentioned in this article. Corresponding author: Fabrizio Fanelli, MD, EBIR, Vascular and Interventional Radiology Unit, ‘‘Sapienza’’ University of Rome, Italy. E-mail: [email protected] Q 2013 by the INTERNATIONAL SOCIETY
OF
ENDOVASCULAR SPECIALISTS
Available at www.jevt.org
802
COMMENTARY Fanelli et al.
accomplish the mechanical effect of vessel wall dilation.11 The low incidence of provisional stenting is a direct consequence of fewer flow-limiting dissections. In the current article, Tepe and colleagues6 discuss the different outcomes of the THUNDER trial vs. FemPac (Femoral Paclitaxel), another very important study on DCBs that reported a lower 30% rate of dissection vs. 50% in THUNDER. A specific reason for the higher rate in the THUNDER cohort was not found, but a greater incidence of dissections among smokers was recorded. But which type of dissection are we talking about? In these studies, did all the detected dissections really need stenting? The authors observed in both the THUNDER and FemPac studies that operators tended to stent dissections more frequently in lesions treated with standard balloon catheters than with DCB. The reason for this behavior is not completely clear: it may be related to the anticipated poorer outcome with a standard balloon compared to a DCB or to the real need to stent severe dissections that are caused more often by standard balloons than by DCBs. Unfortunately, there has until now been little data on the features and evolution of a dissection after PTA in the femoropopliteal segment. Recognizing this void, Tepe and colleagues hoped that an analysis of non-flow-limiting dissections from the THUNDER trial cohort would provide evidence as to the effect of dissection on angiographic and clinical outcomes after peripheral artery interventions. The result is the first DCB study to have a notable influence on the approach to ballooninduced dissections, and as such, it is a first step toward establishing a standard protocol for post-angioplasty dissection. As suggested by Tepe et al.,6 assessing the ‘‘grade’’ of a dissection and distinguishing the non-severe from severe ones would be the first step toward better management of such complications. To this end, the National Heart, Lung, and Blood Institute classification system for coronary intimal tears12 could be a good starting point for the development of a classification system for dissections in the rest of the peripheral vascular tree. Precise definition and grading of vessel dissection
J ENDOVASC THER 2013;20:801–804
with angiographic examples should be available to improve clinical practice. In addition, outcome data about the different types of dissections should be further investigated to obtain prognosis grading. But what do we know at present until these measures become reality? In the Tepe article,6 angiographic parameters of dissections, such as percent stenosis, reference diameter, and mean lesion diameter did not show a significant difference between DCB and the control group soon after the procedure regardless of the grade of dissection, whereas the situation changed during follow-up. Thus, if no difference can be expected between the two types of balloons immediately after dilation, the long-term results (up to 4 years) become extremely useful in confirming the longlasting effect of a DCB in reducing late restenosis after dissection. According to the THUNDER subanalysis, DCBs seem to be associated with better outcomes in terms of late lumen loss (LLL), target lesion revascularization, and lumen area change in both low and high grade dissections at 6 months to 2 years of followup owing to positive vessel remodeling (increase in lumen width and plaque regression). However, data on other clinical parameters, such as ankle-brachial index and Rutherford class shift, are needed because they can show how a dissection may influence the clinical status of the patient over time. Another main determinant of dissection development and evolution is the presence of calcium within the plaque composition. Fitzgerald et al.3 linked the presence of local calcium deposits to a higher risk of developing a dissection and reported that 87% of the ultrasound studies of dissections showed calcium positioned on the same side of the vessel wall as the origin of the tear. Thus, in the presence of inelastic components such as calcium, balloon expansion will result in a non-uniform energy distribution to the vessel wall, leading to the development of deeper cracks and tears close to the calcium deposits. If a dissection occurs after DCB angioplasty in selected cases and we do not stent the lesion, we are trusting in the long-term positive effects of the drug to satisfy the
J ENDOVASC THER 2013;20:801–804
concept of ‘‘nothing left behind.’’ But can such good outcomes be reached even in highly calcified lesions? Currently, no data are available to answer this question, so further studies are strongly needed to better understand the effect of calcium on DCB angioplasty. ‘‘Nothing left behind’’ is obviously fundamental in relatively young patients because a surgical approach may be subsequently indicated, and limitations related to the treated vascular area (geographical area, e.g., flexion points in the common femoral artery and popliteal artery) can be avoided. Another point is how to repair a dissection. There are two currents of thought: one is to immediately perform primary stenting and then dilate with a non-coated balloon. The second is to dilate first with a non-coated balloon, trying to reduce or totally repair the dissection, and then, in case of an unsatisfactory result, to deploy a stent (provisional spot stenting). As Tepe et al.6 explained, the treatment technique must always be aligned with the type (grade) of dissection and with the type of balloon applied (DCB vs. standard balloon). Their study showed that only high-grade dissections were repaired with provisional stenting in DCB-treated cases, whereas treatment with non-coated balloons required a broader application of provisional stenting. A growing number of studies have shown improved outcomes when using DCB in comparison with stenting and angioplasty performed with a non-coated balloon, not only in the femoropopliteal region,8–10 but also below the knee.13,14 At present, new studies with a longer follow-up and careful evaluation of each different aspect of the disease are strongly needed, and perhaps the encouraging results of this THUNDER subanalysis article will spark further clinical investigations into this topic.
REFERENCES 1. Tendera M, Aboyans V, Bartelink ML, et al.; ESC Guidelines on the diagnosis and treatment of peripheral artery diseases. Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery
COMMENTARY Fanelli et al.
2.
3.
4.
5.
6.
7.
8.
9.
803
Dis eases of t he Eur opean Soci ety of Cardiology (ESC). Eur Heart J. 2011;32:2851– 2906. Rooke TW, Hirsch AT, Misra S, et al.; American College of Cardiology Foundation; American Heart Association; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society for Vascular Medicine; Society for Vascular Surgery. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine, and Society for Vascular Surgery. Catheter Cardiovasc Interv. 2012;79:501–531. Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. Circulation. 1992;86: 64–70 van Lankeren W, Gussenhoven EJ, Honkoop J, et al. Plaque area increase and vascular remodeling contribute to lumen area change after percutaneous transluminal angioplasty of the femoropopliteal artery: an intravascular ultrasound study. J Vasc Surg. 1999;29:430– 441. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther 2012;19:1–9. Tepe G, Zeller T, Schnorr B, et al. High-grade, non-flow-limiting dissections do not negatively impact long-term outcome after paclitaxelcoated balloon angioplasty: an additional analysis from the THUNDER study. J Endovasc Ther. 2013;20:792–800. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358:689– 699. Fanelli F, Cannavale A, Boatta E, et al. Lower limb multilevel treatment with drug-eluting balloons: 6-month results from the DEBELLUM randomized trial. J Endovasc Ther. 2012;19: 571–580. Werk M, Albrecht T, Meyer DR, et al. Paclitaxelcoated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the
804
COMMENTARY Fanelli et al.
randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;5:831–840. 10. Micari A, Cioppa A, Vadala` G, et al. Clinical evaluation of paclitaxel-eluting balloon for treatment of femoropopliteal arterial disease: 12-month results from a multicenter Italian registry. JACC Cardiovasc Interv. 2012;5:331– 338. 11. Wakman R, Pakala R. Drug-eluting balloon: the comeback kid? Circ Cardiovasc Interv. 2009;2: 352–358. 12. Dorros G, Cowley MJ, Simpson J, et al. Percutaneous transluminal coronary angioplasty: report of complications from the Na-
J ENDOVASC THER 2013;20:801–804
tional Heart, Lung, and Blood Institute PTCA Registry. Circulation. 1983;67:723–730. 13. Schmidt A, Piorkowski M, Werner M, et al. First experience with drug-eluting balloons in infrapopliteal arteries: restenosis rate and clinical outcome. J Am Coll Cardiol. 2011;58:1105– 1109. 14. Liistro F, Porto I, Angioli P, et al. Drug-Eluting Balloon in peripherAl inTErvention for Below The Knee angioplasty evaluation (DEBATEBTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation. 2013; 128;615–621.
