from april 2003 to june 2005 , 40 limbs of 36 patients with chronic lower limb ischemia were treated with sa . three patients underwent bilateral subintimal angioplasties at separate times , one of whom underwent a repeated sa on the right lower limb due to re - occlusion of the vessel treated eight months previously . there were 32 men and four women , ranging in age from 57 to 83 years with a mean age of 70.5 years . a majority of patients had significant medical comorbidities , including hypertension ( n = 30 ) , diabetes mellitus ( n = 23 ) , symptomatic ischemic heart disease ( n = 24 ) , smoking ( n = 20 ) , cerebrovascular disease ( n = 10 ) , and chronic renal failure ( n = 6 ) . patient selection occurred at multidisciplinary meetings involving surgeons and interventional radiologists . prior to committing to a specific therapeutic decision at the multidisciplinary meetings , the aortoiliac and lower extremity arteries of each patient were objectively evaluated by magnetic resonance angiography ( n = 1 ) , diagnostic angiography ( n = 4 ) , or computed tomography ( ct ) angiography with generation of three dimensional reconstructions ( n = 35 ) . sa was undertaken as an alternative to surgery or when a patient with chronic lower limb ischemia was thought to be unsuitable for bypass surgery either because of co - morbidity or an unfavorable disease pattern . the indications for treatment were intermittent claudication ( walking distance < 300 m ) ( n = 18 ) , pain at rest ( n = 2 ) , ulceration ( n = 11 ) , gangrene ( n = 5 ) , or a non - healing wound ( n = 4 ) at the site of prior amputation . following sa , subsequent minor amputations , including toe or transmetatarsal procedures , were planned in eight patients presenting with gangrene or a non - healing wound at the site of amputation . below - knee amputation was planned for one patient who presented with a non - healing wound at the site of prior transtarsal amputation . the location of the arterial occlusions treated by sa included the iliac ( n = 2 ) , femoral ( n = 10 ) , femoropopliteal ( n = 4 ) , popliteal ( n = 1 ) , popliteotibial ( n = 2 ) , tibial ( n = 13 ) , and femorotibial arteries ( n = 1 ) . the remaining seven patients had two separate occlusions at femoral and tibial locations ( n = 5 ) , femoral and popliteotibial ones ( n = 1 ) , and popliteal and tibial arteries ( n = 1 ) . the length of the occlusions ranged from 2 to 34 cm , with a mean length of 12.8 cm ( < 5 cm , 12 occlusions ; 5 - 10 cm , 9 occlusions ; > 10 cm , 19 occlusions ) . the length of the occlusions in the seven patients with two separate occlusions in the target extremity were counted as the sum of the two lesions . before all procedures , the potential risks and benefits were explained in detail , and an informed written consent was obtained from each patient . all punctures were made using a micropuncture set ( cook , bloomington , in ) with / without ultrasound guidance . for the two iliac subintimal angioplasties , bilateral retrograde punctures of the common femoral artery ( cfa ) were used . for the 38 infrainguinal subintimal angioplasties , access to 37 was made by an ipsilateral antegrade puncture of the cfa . three of these cases needed an additional contralateral retrograde puncture of the cfa to treat a concomitant severe stenosis at the inflow of the iliac artery . one infrainguinal lesion was accessed by a contralateral retrograde puncture of the cfa to treat a concomitant severe stenosis at the inflow of the common iliac artery . following 6 or 7 fr arterial sheath placement , a diagnostic angiogram of the target lower extremity was obtained and recanalization procedures were attempted . in two cases of iliac occlusion , sa was used because the initial transluminal recanalization was failed . following administration of intravenous heparin ( 3,000 - 5,000 iu , 70 iu / kg ) , and an intraarterial vasodilating agent such as nitroglycerin ( 100 - 200 g ) at the discretion of treating interventional radiologist , sa was performed using a technique similar to that described by reekers and bolia ( 5 ) . an angled 0.035-inch hydrophilic guide wire ( terumo , tokyo , japan ) and a supporting 5 fr catheter ( angled tapered catheter , terumo , tokyo , japan ; davis or van andel catheters , cook , bloomington , in ) were used to create a subintimal dissection plane above the level of the occlusion . the wire then was advanced , and a loop was naturally formed at the tip of the guide wire . the loop and catheter were advanced through the subintimal plane until the occlusion was passed . a loss of resistance was often encountered as the wire reentered the true lumen of the native artery distal to the occlusion . recanalization was confirmed by advancing the catheter over the guide wire beyond the point of reentry and performing an angiogram . in a case of proximal superficial femoral artery ( sfa ) occlusion accessed by a contralateral retrograde puncture of cfa , a subintimal dissection plane was successfully made by a simple combination of a guide wire and a 5 fr angled tapered catheter , without requirement of balloon stabilization recommended in a previous study ( 5 ) . the recanalized segment was then balloon dilated at 8 to 10 atmospheres for 5 to 10 seconds with an appropriately sized angioplasty balloon ( 5- or 6-mm balloon for femoral lesions , 4- or 5-mm balloon for popliteal lesions , and 3-mm balloon for tibial lesions ) , depending on the diameter of the adjacent normal artery . primary stent placement ( smart control , cordis , miami , fl ) and subsequent postdilatation using a balloon catheter 1-mm less in diameter were used in two iliac subintimal angioplasties . in both of these , predilatation of the subintimal tract with a balloon catheter was not needed because the stent delivery system easily passed along the tract . other significant stenotic arterial lesions ( two in a contralateral iliac artery , four in an ipsilateral iliac artery , nine in a sfa , two in a popliteal artery , and four in a tibial artery ) that were identified outside the area of subintimal angioplasty were treated concurrently at the time of the procedure , either with adjunctive balloon angioplasty or stent placement . patency , adequacy of flow , and preservation of runoff were confirmed on completion angiography . if flow was impaired , repeat balloon dilatations were performed throughout the segment , using a higher inflation pressures of up to 12 atmospheres and for a longer time , 30 - 60 seconds . two cases of femoral occlusions required self - expandable stent placement ( smart control , cordis , miami , fl ) at the entry site of sa because flow - limiting stenosis was still observed following repeated balloon angioplasties . unless contraindicated , all patients received aspirin ( 100 mg daily ) and clopidogrel ( 75 mg daily ) at the time of the procedure and thereafter . all patients were closely followed for immediate and delayed complications . because ankle brachial index ( abi ) measurement was performed at the discretion of the examining vascular surgeon , the duration of follow - up was one month to 23 months , with a mean of 10 months ( median , eight months ) . follow - up of the patients included clinical examinations and imaging studies of color doppler us and/or ct angiography at three to six month intervals . technical success was defined as recanalization of the occluded arterial segment , with good antegrade flow on the completion angiography . clinical success was defined as resolution or improvement of claudication , relief of pain at rest , healing of ulcers , or healing of minor amputations required for gangrene and non - healing wounds at the site of previous amputation . patency was defined as the absence of occlusion and less than 50% stenosis in the treated arterial segment . institutional review board approval for the required retrospective review of patient medical and imaging records was obtained . in addition , we compared the results during the first year and thereafter to evaluate whether there was a steep learning curve for sa , and this comparison was statistically analyzed using fisher 's exact test . before all procedures , the potential risks and benefits were explained in detail , and an informed written consent was obtained from each patient . all punctures were made using a micropuncture set ( cook , bloomington , in ) with / without ultrasound guidance . for the two iliac subintimal angioplasties , bilateral retrograde punctures of the common femoral artery ( cfa ) were used . for the 38 infrainguinal subintimal angioplasties , access to 37 was made by an ipsilateral antegrade puncture of the cfa . three of these cases needed an additional contralateral retrograde puncture of the cfa to treat a concomitant severe stenosis at the inflow of the iliac artery . one infrainguinal lesion was accessed by a contralateral retrograde puncture of the cfa to treat a concomitant severe stenosis at the inflow of the common iliac artery . following 6 or 7 fr arterial sheath placement , a diagnostic angiogram of the target lower extremity was obtained and recanalization procedures were attempted . in two cases of iliac occlusion , sa was used because the initial transluminal recanalization was failed . following administration of intravenous heparin ( 3,000 - 5,000 iu , 70 iu / kg ) , and an intraarterial vasodilating agent such as nitroglycerin ( 100 - 200 g ) at the discretion of treating interventional radiologist , sa was performed using a technique similar to that described by reekers and bolia ( 5 ) . an angled 0.035-inch hydrophilic guide wire ( terumo , tokyo , japan ) and a supporting 5 fr catheter ( angled tapered catheter , terumo , tokyo , japan ; davis or van andel catheters , cook , bloomington , in ) were used to create a subintimal dissection plane above the level of the occlusion . the wire then was advanced , and a loop was naturally formed at the tip of the guide wire . the loop and catheter were advanced through the subintimal plane until the occlusion was passed . a loss of resistance was often encountered as the wire reentered the true lumen of the native artery distal to the occlusion . recanalization was confirmed by advancing the catheter over the guide wire beyond the point of reentry and performing an angiogram . in a case of proximal superficial femoral artery ( sfa ) occlusion accessed by a contralateral retrograde puncture of cfa , a subintimal dissection plane was successfully made by a simple combination of a guide wire and a 5 fr angled tapered catheter , without requirement of balloon stabilization recommended in a previous study ( 5 ) . the recanalized segment was then balloon dilated at 8 to 10 atmospheres for 5 to 10 seconds with an appropriately sized angioplasty balloon ( 5- or 6-mm balloon for femoral lesions , 4- or 5-mm balloon for popliteal lesions , and 3-mm balloon for tibial lesions ) , depending on the diameter of the adjacent normal artery . primary stent placement ( smart control , cordis , miami , fl ) and subsequent postdilatation using a balloon catheter 1-mm less in diameter were used in two iliac subintimal angioplasties . in both of these , predilatation of the subintimal tract with a balloon catheter was not needed because the stent delivery system easily passed along the tract . other significant stenotic arterial lesions ( two in a contralateral iliac artery , four in an ipsilateral iliac artery , nine in a sfa , two in a popliteal artery , and four in a tibial artery ) that were identified outside the area of subintimal angioplasty were treated concurrently at the time of the procedure , either with adjunctive balloon angioplasty or stent placement . patency , adequacy of flow , and preservation of runoff were confirmed on completion angiography . if flow was impaired , repeat balloon dilatations were performed throughout the segment , using a higher inflation pressures of up to 12 atmospheres and for a longer time , 30 - 60 seconds . two cases of femoral occlusions required self - expandable stent placement ( smart control , cordis , miami , fl ) at the entry site of sa because flow - limiting stenosis was still observed following repeated balloon angioplasties . unless contraindicated , all patients received aspirin ( 100 mg daily ) and clopidogrel ( 75 mg daily ) at the time of the procedure and thereafter . all patients were closely followed for immediate and delayed complications . because ankle brachial index ( abi ) measurement was performed at the discretion of the examining vascular surgeon , the duration of follow - up was one month to 23 months , with a mean of 10 months ( median , eight months ) . follow - up of the patients included clinical examinations and imaging studies of color doppler us and/or ct angiography at three to six month intervals . technical success was defined as recanalization of the occluded arterial segment , with good antegrade flow on the completion angiography . clinical success was defined as resolution or improvement of claudication , relief of pain at rest , healing of ulcers , or healing of minor amputations required for gangrene and non - healing wounds at the site of previous amputation . patency was defined as the absence of occlusion and less than 50% stenosis in the treated arterial segment . institutional review board approval for the required retrospective review of patient medical and imaging records was obtained . in addition , we compared the results during the first year and thereafter to evaluate whether there was a steep learning curve for sa , and this comparison was statistically analyzed using fisher 's exact test . technical success for sa was achieved in 32 ( 80% ) of 40 limbs in 28 ( 78% ) of 36 patients ( fig . , seven resulted from an inability to reenter the true lumen distal to the occlusion , and one resulted from failure to pass the wire into the subintimal plane . two of these eight patients who failed sa were treated conservatively , due to refusal of below - knee amputation in one and an unfavorable disease pattern for surgery in the other . one patient died of acute respiratory distress syndrome unrelated to the procedure one month later . two patients underwent a below - knee amputation , and two patients required minor amputation ( great toe amputation in one and transmetatarsal amputation in the other ) for healing of gangrene or of the wound at the amputation site . clinical success was achieved in 31 ( 78% ) of 40 limbs in 27 ( 75% ) of 36 patients . despite technical success , one patient underwent a below - knee amputation because his wound did not heal following sa and subsequent transmetatarsal amputation . one patient who presented with a non - healing wound at the site of prior transtarsal amputation had a successful sa and subsequent below - knee amputation . there were four complications ( 10% ) in 40 procedures : two arterial perforations , one pseudoaneurysm at the puncture site , and one hematoma at the sa site . one arterial perforation occurred at a collateral branch vessel during the guide wire manipulation for subintimal cannulation of the occluded peroneal artery . the other arterial perforation occurred at a subintimally dissected distal sfa in a patient with a long segmental sfa occlusion . this was treated by ultrasound guided compression , because we failed to reenter the distal true lumen . a small pseudoaneurysm with surrounding hematoma at the puncture site , which was identified on us examination the day after the procedure , spontaneously occluded during follow - up . a hematoma occurred two days after the procedure at the sa site of the posterior tibial artery . arterial re - occlusion or stenosis > 50% occurred in 13 limbs of 12 patients , with the time of onset ranging from two to 19 months ( mean , 7.2 months ; median , six months ) . one patient in whom re - occlusion of the treated arteries occurred six months after sa underwent a repeat sa with clinical success . however , the arteries occluded again eight month later and the patient finally underwent femoral - popliteal bypass . of the remaining 11 patients with arterial re - occlusion or stenosis > 50% , five were asymptomatic ( n = 4 ) or had improved symptoms ( n = 1 ) , and they were followed up without further treatment ( fig . six patients with tolerable symptoms ( n = 3 ) or an unfavorable disease pattern for bypass surgery ( n = 3 ) were treated conservatively . two patients were lost to follow - up at three and six months , and two patients were referred to secondary hospitals at one month and three months after sa . one patient died of pneumonia at 14 months . using a basis of intention to treat , the primary patency rates at six months and 12 months were 55% and 44% , respectively , and the secondary patency rates at six months and 12 months were 58% and 47% , respectively ( fig . 3 ) . excluding initial technical failures , the primary patency rates at six months and 12 months were 68% and 55% , respectively , and the secondary patency rates at six months and 12 months were 73% and 59% , respectively . when we compared the results of the 24 procedures performed during the first year with those of the 16 procedures that followed , the technical success rates were 75% ( 18 of 24 procedures ) and 88% ( 14 of 16 procedures ) , respectively , and the complication rates were 8.3% ( 2 of 24 procedures ) and 12.5% ( 2 of 16 procedures ) , respectively . there was no statistically significant difference in technical success between the two groups ( p = .439 ) . first , the new lumen between the tunica intima and media is presumably free from atheroma and more likely to remain patent . second , since the wire moves freely in the newly created plane , the procedure enables treatment of long segments of disease with minimal additional morbidity . third , there is a minimal risk of embolization , because plaque is not ruptured . finally , failure to create a reentry site or to secure successful wire passage is unlikely to further jeopardize distal perfusion , because the procedure is limited to an already chronically occluded segment . the assessment of technical success has been based on the findings of completion angiography in most studies , but , in some ( 7 , 13 , 21 ) , a duplex scan , abi , clinical improvement , or their combinations have been used to determine technical success . the assessment of technical success in the present study is based on completion angiography , with a technical success rate of 80% ( 32 of 40 procedures ) , which is comparable to that ( 74%-90% ) of previous studies ( 2 , 4 , 6 , 8 - 14 , 16 , 18 - 21 ) . reported technical failures have been attributable to an inability to enter the subintimal space , failure to advance the wire in a calcified vessel , an inability to reenter the true lumen distal to the occlusion , an inability to maintain patency of the recanalized lumen despite successful wire and catheter passage , and abandonment of the procedure so as to avoid damage to a major distal collateral ( 2 , 6 , 7 , 11 , 18 , 20 ) . technical failures of the present study are attributed mostly to an inability to reenter the distal true lumen ( 7 of 8 technical failures ) . some authors have tried alternative approaches for sa , including retrograde popliteal artery puncture using ultrasound guidance ( 22 ) , and simultaneous antegrade cfa and retrograde popliteal artery punctures ( 23 ) . balas et al have described open sa in cases of complete sfa occlusion where initiation of the subintimal dissection may be difficult ( 24 ) . recently , new catheter systems ( outback catheter , perclose , redwood city , ca ) have been developed to facilitate reentry into the true lumen ( 25 ) . it is hoped that variations of these methods may help overcome the technical failures of sa . clinical and hemodynamic patencies have been used to assess the durability of sa in the previous studies ( 2 , 4 - 6 , 8 - 11 , 13 , 14 , 16 , 18 - 21 ) . the assessment of clinical patency has been based on clinical symptoms alone , or on both clinical symptoms and abi , and that of hemodynamic patency has been based on duplex us with or without abi measurement . based on the results of this and previous studies that present cases of arterial re - occlusion with no or unchanged symptoms ( 9 , 13 , 18 ) , an absence of clinical events does not necessarily indicate the anatomic patency of sa . conversely , the presence of additional ipsilateral proximal or distal arterial lesions in some cases makes it difficult to determine the clinical patency for each repaired occlusion ( 6 ) . therefore , hemodynamic patency is believed to be better and more objective than the presence or absence of symptoms for assessing the efficacy of sa . although it is clear that invasive arterial angiography is the best method for assessing vessel patency , almost all studies have used duplex ultrasound with or without abi measurement for routine follow - up . angiography has generally been reserved for confirmation of stenosis or occlusion , because it is hard to justify its use for routine follow - up . we used ct angiography , instead of diagnostic angiography , to confirm vessel patency and to check for concurrent arterial lesions which can cause recurrent symptoms . a recent study prospectively compared the accuracy of 16-detector row ct angiography with conventional digital subtraction angiography in the assessment of aortoiliac and lower extremity arteries in patients with peripheral arterial disease . the sensitivity and specificity of ct angiography with regard to detection of hemodynamically significant stenosis ( > 50% luminal narrowing ) were 96% and 97% , respectively ( 26 ) . however , further study will be required to establish the role of ct angiography in sa . on an intention to treat basis , primary and secondary patency rates in our study are 55% and 58% at six months , and 44% and 47% at 12 months , respectively . these are somewhat disappointing , but quite comparable to those of previous studies ( 4 , 6 , 8 , 10 , 11 , 14 , 27 ) . primary patency rates at six months and 12 months were 68% and 55% , respectively , and secondary patency rates at six months and 12 months were 73% and 59% , respectively . in view of clinical symptoms , five of the 12 patients who had arterial re - occlusion or stenosis > 50% during the follow - up period were asymptomatic or had unchanged symptoms , and three patients were treated conservatively due to tolerable symptoms . furthermore , in 2 of the 8 technical failures , gangrene or wound infection at the amputation site healed following minor amputation . some previous studies have also reported cases of no or unchanged symptoms , despite technical failure or late arterial re - occlusion ( 9 , 13 , 18 ) . the overall complication rates of sa are 5% to 20% , and a majority of them can be treated conservatively or by endovascular techniques ( 2 , 6 - 14 , 18 , 19 ) . the complications reported are those inherent in endovascular procedures , including groin hematomas , pseudoaneurysm at the puncture site , distal embolism , arterial injury , renal insufficiency , and retroperitoneal hemorrhage . there are also those associated with the underlying health of the patient population , such as myocardial infarction . endovascular treatment was required in one arterial perforation , and the other complications ( one arterial perforation , one pseudoaneurysm at the puncture site , and one delayed hematoma at the sa site ) were treated conservatively . we could not find the cause of the delayed hematoma that occurred at the site two days after sa . there have been two case reports of late arterial rupture associated with sa ( 28 , 29 ) , which could be a possible cause of this . ( 10 ) reported a technical success rate of 92% in their last 23 cases versus 64% in the first 25 , suggesting that sa is associated with a short learning curve . with further experience and improved patient selection for sa , our technical success rate has also improved , with technical success rates of 75% ( 18 of 24 ) during the first year and 88% ( 14 of 16 ) thereafter . however , this did not reach statistical significance ( p = .439 ) . recently , bolia has suggested that a steep learning curve is present for the first 100 to 200 procedures , and results during this time may vary ( 30 ) . this suggestion might explain the above discrepancy in the steepness of the learning curve for performing sa . furthermore , data were confined to the last known follow - up , so patency data could have been underestimated . thus , we believe that a larger , prospective study with a longer follow - up period is necessary . in conclusion , subintimal angioplasty is feasible with a high initial technical success rate , and our primary patency rate is comparable to that of other previous studies . thus , we feel that sa should be attempted in patients with chronic lower limb ischemia , either as an alternative to surgery , or when surgical treatment is not feasible because of comorbidity or an unfavorable disease pattern .
objectiveto present our experience with subintimal angioplasty ( sa ) for treatment of chronic lower limb ischemia ( clli ) and to assess its effectiveness and durability.materials and methodsfrom april 2003 through june 2005 , we treated 40 limbs in 36 patients with clli by sa . 
 balloons with or without secondary stent placement appropriate in size to the occluded arteries were used for sa of all lesions , except for iliac lesions where primary stent placement was done . 
 the patients were followed for 1 - 23 months by clinical examination and color doppler ultrasound and/or ct angiography . 
 technical results and outcomes were retrospectively evaluated . 
 the presence of a steep learning curve for performance of sa was also evaluated . 
 primary and secondary patencies were determined using kaplan - meier analysis.resultstechnical success was achieved in 32 ( 80% ) of 40 limbs . 
 there was no statistical difference between technical success rates of 75% ( 18/24 ) during the first year and 88% ( 14/16 ) thereafter . 
 there were four complications ( 10% ) in 40 procedures ; two arterial perforations , one pseudoaneurysm at the puncture site , and one delayed hematoma at the sa site . excluding initial technical failures , 
 the primary patency rates at six and 12 months were 68% and 55% , respectively . 
 secondary patency rates at six and 12 months were 73% and 59% , respectively.conclusionsubintimal angioplasty can be accomplished with a high technical success rate . 
 it should be attempted in patients with clli as an alternative to more extended surgery , or when surgical treatment is not recommended due to comorbidity or an unfavorable disease pattern .