Failure of Prolonged Dilation to Improve Long-term Patency of Femoropopliteal Artery Angioplasty: Results of a Prospective Trial

Failure of Prolonged Dilation to Improve Long-term Patency of Femoropopliteal Artery Angioplasty: Results of a Prospective Trial Heini K. Söder MD, Hannu I. Manninen, MD, PhD, Heikki T. Räsänen, MD, Erkki Kaukanen, MD, Pekka Jaakkola, MD, PhD, and Pekka J. Matsi, MD, PhD

PURPOSE: To determine long-term patency of femoropopliteal artery percutaneous transluminal angioplasty (PTA) in a prospective trial during which prolonged balloon inflation was used for optimization of initial results. MATERIALS AND METHODS: Femoropopliteal PTA was performed in 112 limbs of 97 patients. The mean total length of the treated segments was 7.2 cm (95% CI: 5.99 – 8.46; median: 5.5 cm). In cases of unsatisfactory primary results after standard dilation for 1–3 minutes, the procedure was continued with prolonged dilation (93 limbs; mean balloon inflation time: 31 min; 95% CI: 24.2–37.7; median: 15 min) with use of the same balloon catheter (77 limbs) or a perfusion balloon catheter (35 limbs). Thirty-four proximal infrapopliteal artery stenoses were treated to improve peripheral runoff and 12 short stents were placed because of flow-limiting dissections. RESULTS: Primary hemodynamic success established by Doppler ultrasound (US) criteria was achieved in 92.9% (104 of 112) of the limbs. Three major complications were encountered; none were related to prolonged balloon inflation. The primary patency rate according to Kaplan-Meier analysis was 42% (ⴞ5% SE) at 1 year and 39% (ⴞ5%) at 2 and 3 years. The corresponding secondary patency rates were 51% (ⴞ5%) and 47% (ⴞ5%). Large numbers of diseased vessels in the treated limb (four to 10 instead of one to three), eccentric lesions (as opposed to concentric morphology), and additional treated segments (instead of only femoropopliteal lesions) were associated with poorer long-term patency. The duration of balloon dilation was not a determinant of long-term patency. CONCLUSION: Although prolonged dilation is safe and feasible in femoropopliteal artery PTA, its routine use is not warranted because it does not result in superior long-term patency rates. Index terms:

Angioplasty

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Arteries, femoral

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Arteries, popliteal

J Vasc Interv Radiol 2002; 13:361–369 Abbreviations:

IVUS ⫽ intravascular ultrasound, PTA ⫽ percutaneous transluminal angioplasty

THE utility of endovascular treatment of athero-occlusive changes in iliac arteries is widely accepted, and especially with stents, the short- and longterm results are comparable with surgical treatments (1,2). The situation in the femoropopliteal region is different; percutaneous transluminal angioplasty (PTA) has a high initial success

From the Departments of Clinical Radiology (H.K.S., H.I.M., H.T.R., E.K., P.K.) and Surgery (P.K.), Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland. Received August 28; revision requested October 13; final revision received and accepted December 12. Address correspondence to H.K.S.; E-mail: [email protected] © SCVIR, 2002

rate but a considerably lower longterm patency rate, which is not markedly improved even by the use of stents (3– 6). However, data from coronary arteries, mainly based on intravascular ultrasound (IVUS) imaging, suggest that an insufficient primary result is a major cause for poor longterm patency; ie, the better the primary result, the better the long-term result (7–9). Studies have shown that prolonged balloon inflation with a perfusion balloon catheter effectively improves poor initial results of coronary angioplasty (10 –13). In a recent study, we found that prolonged balloon inflation after standard 1–3minute dilation improved insufficient

angiographic primary results in 95% of the femoropopliteal artery lesions (14). Further, poor peripheral runoff has been shown to be a predictor of low long-term patency rates in femoropopliteal PTA (3,15). Similarly, the use of short stents placed with a high dilation pressure and the use of ticlopidine has markedly improved the results of coronary stent placement (16,17). The purpose of our study is to test the hypothesis that long-term patency after femoropopliteal angioplasty can be optimized by selective use of prolonged balloon inflations, stent placement for residual disease, and treatment of distal runoff obstructions.

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Table 1 Demographic Data of the Present Trial and the Historical Reference Study (3) No. of Patients Parameter Mean age ⫾ SD (y) Total patients Men Women Associated diseases Coronary artery disease Hypertension Cerebrovascular disease Diabetes Dietary or oral medication Insulin dependent Smoking history Current smoker Ex-smoker Never smoked

Present Study

Reference Study

70 ⫾ 9 97 (100) 61 (63) 36 (37)

67 ⫾ 9 106 (100) 71 (67) 35 (33)

.36

37 (38) 47 (48) 21 (23) 32 (33) 14 (14)

61 (58) 49 (46) 22 (21) 29 (27) 20 (19)

.006 .75 .88 .38

18 (19)

9 (8)

22 (23) 39 (40) 36 (37)

34 (32) 42 (39) 30 (28)

P Value

.54

.18

Note.—Numbers in parentheses are percentages. P value denotes statistical difference between the present and reference study group.

MATERIALS AND METHODS Study Population From May 1995 to December 1997, 97 patients who underwent femoropopliteal artery PTA in 112 limbs in a university hospital were taken into the study. Altogether, 93 patients had intermittent claudication (RutherfordBecker categories 1–3) and four patients had chronic critical limb ischemia (Rutherford-Becker categories 4 and 5). Patients with claudication who had the principal lesion in the femoropopliteal artery and no earlier angioplasty performed were included in the trial. Within the first month, four patients with critical limb ischemia were included. Later, critical limb ischemia was made an exclusion criterion because adequate follow-up of these patients was difficult. Angioplasty was selected as the primary invasive treatment whenever it seemed technically feasible. Only very long femoropopliteal lesions (⬎10 cm) were treated surgically unless there were comorbidities that contraindicated surgical treatment. All our patients with claudication had taken part in an exercise program for at least 6 months before the decision to proceed with invasive treatment. None of the patients had undergone surgical opera-

tions in lower limb arteries. An earlier trial from our institution (3) that involved consecutive femoropopliteal PTA procedures was used as a historic reference study for this trial. Tables 1 and 2 indicate that the demographic data and lesion characteristics defined by identical criteria in both studies did not differ significantly in most parameters. The treatment decisions for each patient were made in a meeting of vascular surgeons and interventional radiologists. The study was approved by the Ethical Committee of the hospital and all patients gave their written informed consent before enrollment. Patient Investigations before PTA Procedure The initial evaluation of the patients included their medical history and a physical examination performed by a vascular surgeon, and ankle-brachial indexes were also measured (a treadmill exercise test with ankle pressure measurements). Earlier outpatient-tailored intraarterial digital subtraction angiography of the aorta and runoff vessels was routinely performed. The following clinical chemical values were routinely measured before PTA: plasma hemoglobin, hematocrit, platelet count, plasma fibrinogen, serum antithrombin-III, partial

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thromboplastin time, prothrombin time, serum cholesterol, serum highdensity lipoprotein cholesterol, serum triglycerides, and serum creatinine. Basic clotting parameters and serum creatinine levels were always available before PTA procedures. Just before angioplasty, duplex US evaluation was performed proximal and several centimeters distal to the femoropopliteal stenosis or occlusion. Peak velocity values were registered and the velocity waveform was assessed. PTA Procedure During the study period, all femoropopliteal PTA procedures were performed according to a strict standard protocol by three experienced interventional radiologists. The laboratory was equipped with digital fluoroscopy equipment and “road-mapping” was available (Multistar T.O.P.; Siemens, Erlangen, Germany). Selective angiography was performed routinely with use of an antegrade approach through the ipsilateral common femoral artery. The introducer sheaths ranged from 6 to 7 F. In two cases, PTA was initiated with intraarterial thrombolytic therapy: one patient was given 500,000 U and another 200,000 U of urokinase before recanalization of an occlusion (because the symptoms had worsened within a few weeks before the planned angioplasty). The balloon catheter was chosen to match the diameter of the nondiseased artery adjacent to the lesion and the balloon length was chosen to match the length of lesion. The length of balloons used varied from 2 cm to 10 cm. Because a separate part of this study focused on evaluation of the mechanism of PTA, IVUS imaging was performed before and after balloon dilation of stenotic lesions (not on total occlusions) with a 3.5-F, 30-MHz catheter (Sonos Intravascular; Hewlett Packard, Andover, MA/Sonicath CV; Mansfield/Boston Scientific, Watertown, MA). Whenever possible, the size of the balloon catheter and assessment of the initial result were determined by IVUS. Balloon dilation was performed by gradually increasing the atmospheric pressure by one unit every 15–30 seconds up to 8 atm or higher until no indentation was visible on the balloon (Opta; Cordis Europe, Oosteinde, The

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Table 2 Target Limb- and Lesion-related Parameters Parameter

Present Study

Total number of treated lesions Femoropopliteal lesions Infrapopliteal lesions Iliac lesions Mean number of hemodynamically significantly diseased arteries (95% CI) Type of femoropopliteal PTA Dilation of stenosis Recanalization of occlusion Mean/median total length of treated segments in cm (95% CI) Peripheral runoff before PTA 0–1 patent calf vessel 2–3 patent calf vessels

Reference Study

204 163 34 7 3.1 (2.84–3.38)

208 171 31 6 3.2 (2.94–3.47)

74 38 7.2/5.5 (5.99–8.46)

71 69 8.0/6.0 (6.97–9.00)

76 36

62 78

P Value .83

.10 .01 .10 .0002

Note.—P value denotes statistical difference between the present and reference study groups.

Netherlands). A three-step dilation protocol was performed. First, a standard 1–3-minute dilation was performed if the primary result was considered inadequate (residual diameter stenosis exceeded 30% or a dissection causing compromise of blood flow was detected in angiogram or by IVUS), the procedure was continued with a prolonged dilation (up to 30 min) with use of a conventional balloon catheter. The third step, if the result remained unsatisfactory, was a longer additional dilation performed with a specially designed perfusion balloon catheter (Smash; Schneider Europe, Bulach, Switzerland) (14) of the same diameter as the initial balloon catheter. Severity of the lesion and stenosis versus occlusion was taken into account while considering the duration of dilation: longer dilation procedures were performed in total occlusions. Long inflations were typically performed for extensive, long dissections. Also, the ability of a patient to lie on the angiography table for longer durations of time was taken into account. Exceptions to this strategy were short lesions with good peripheral runoff, in which the result after 5–10 minutes of dilation was not adequate because of flow-limiting dissection or elastic recoil. In these situations, stent placement was regarded as the treatment of choice. Overall, 12 stents (nine Palmaz, one Memotherm, one Jostent, and one Wallstent) were placed in femoropopliteal lesions. Thirty-four infrapopliteal angioplasty

procedures were performed for proximally located short stenoses to improve peripheral runoff with use of peripheral small-vessel or coronary balloon catheters. Seven iliac lesions were treated to improve inflow approximately 1 week earlier in a separate session; four of these required stent placement. Postprocedural care of the patients took place in the department of vascular surgery and the patients were routinely discharged the day after the PTA procedure. Patient Medication Patients routinely received 250 mg of acetylsalicylic acid on the day of the procedure and continued to take the same daily dose. Prophylactic dose of nifedipine (10 mg) by mouth was given 5–10 minutes before angioplasty. At the beginning, 5,000 U of heparin was given intraarterially and additional doses of 2,500 U were administered to maintain activated clotting times (Hemocron; International Technidyne, Edison, NJ) of longer than 220 seconds during the intervention (total dose did not exceed 10,000 U in any patient). Boluses of intraarterial nitroglycerin (250 ␮g) were administered, especially in cases in which infrapopliteal lesions had also been treated. After the procedure, low-molecular-weight heparin injections (dalteparin, 200 U per kg body weight per day) or 24-hour heparin infusions were used in 40 patients be-

cause of multisegemental or long-segment procedures, especially if the PTA result was unsatisfactory. Ticlopidine medication was begun on the day of the procedure when infrainguinal lesions were treated with use of a stent and continued for as long as 1 month (250 mg twice a day for 1 week and then 250 mg daily). Long-term anticoagulant therapy was not used. Patient Follow-up At discharge, duplex US examination was repeated proximal and distal to the angioplasty site and comparison between pre- and post-PTA peak velocity values and waveforms were made to evaluate the immediate hemodynamic success. The groin was checked for possible hematomas and pseudoaneurysms with US. All patients were scheduled for hospital visits at 1, 3, and 6 months, and yearly thereafter. The treadmill exercise test with ankle pressure measurements was performed at every visit. Follow-up investigations also included subjective history and physical examination. Analysis of the Films Analysis of all films, including the measurements, was performed by one interventional radiologist in a session separate from the PTA and the reader was blinded to the clinical result of the intervention. Diameter stenosis on pre- and postinterventional angiogra-

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phy was measured with a digital micrometer on a conventional viewbox. The length of the lesion was measured with use of an external radiopaque ruler. The lesion was classified as heavily calcified, moderately calcified, or noncalcified. A lesion was defined as eccentric if it involved one part of the circumference of the vessel wall in a cross section, leaving the remaining part free of disease, and concentric if it was distributed along the entire circumference of the vessel wall in a cross section (18). Criteria for Classifying Procedure Outcome Determination of angiographic success for the basis of data analysis was based on the quantitative measurement. The angiographic result was classified as a success if the measured residual diameter stenosis of the treated lesion was less than 30% of the reference vessel diameter at angiography after angioplasty (technical success). The primary hemodynamic success of PTA was based on the results on duplex US the day after PTA. Doppler velocity waveforms were classified into three categories: normal (diastolic backflow present), no diastolic backflow, and no flow (19). Hemodynamic success was defined as an improvement in the category of the Doppler velocity waveform or at least doubling of the peak velocity in the popliteal artery distal to the site of angioplasty (20), identical to that of the reference study (3). Major complications were defined as those that prolonged hospital stay, affected treatment substantially and adversely, or necessitated surgical intervention. According to Society of Cardiovascular and Interventional Radiology criteria, 30-day mortality, amputation-free survival, and overall survival were registered. Primary patency (final result of the original angioplasty) and secondary patency (including repeat PTA) were determined by means of the original criteria of Rutherford and Becker (21) using the ankle-brachial index (ie, the treated artery segment was patent if the resting ankle-brachial index increased by more than 0.10 initially and did not deteriorate by more than 0.15 from the maximum early postprocedural level) that was used in the his-

toric reference study. The patency rates were also calculated with use of updated criteria of Rutherford (22). Follow-up angiography was performed when new invasive treatment was considered and was based on the patient’s clinical situation. When follow-up angiography was performed, patency was determined based on it. The following variables were evaluated as potential predictors of longterm patency: demographic factors (age, sex), comorbidities (diabetes, coronary artery disease, hypertension, cerebrovascular disease), smoking history, medication, clinical chemical parameters (plasma fibrinogen, serum antithrombin-III, serum cholesterol, serum creatinine, platelet count), clinical state of the treated limb according to Rutherford classification, number of diseased vessels in the treated limb (3), additional treated lesions, peripheral runoff, lesion characteristics (lesion type and length, lesion morphology, calcification, or thrombosis in the lesion), and the dilation time with different cut-off points (3, 5, 10, and 15 min). Statistical Analysis Univariate logistic regression analyses for continuous variables and the Pearson ␹2 test for discrete variables were employed to analyze the determinants of primary hemodynamic success. The Kaplan-Meier method was used to calculate the cumulative patency rate versus time of follow-up for individual variables and subgroups, and the statistical difference between survival curves was determined by means of the log-rank (Mantel-Cox) test. Variables that reached statistical significance (P ⬍ .05) were used as covariates in the stepwise Cox proportional hazards model (Cox multiple regression analysis) or multiple logistic regression analysis. The level of significance for inclusion in multiple regression analyses was less than 0.10, and the level of significance for removal from the model was greater than 0.15.

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procedures with a mean inflation time of 1.8 minutes (95% CI: 1.10 –2.90) and prolonged dilation in 93 procedures with a mean inflation time of 31 minutes (95% CI: 24.2–37.7; median, 15 min). Among the 93 procedures, the perfusion balloon catheter was used in 35 procedures with a mean inflation time of 75 minutes (95% CI: 57.8 –91.3; median, 60 min). The percent diameter stenosis was 84% before angioplasty (95% CI: 81– 87) and 31% after angioplasty (95% CI: 27–35) (P ⬍ .0001). Peripheral runoff after angioplasty was poor in 65 limbs (58%) and good in 47 limbs (42%). The mean length of the 12 femoropopliteal stents was 2.8 cm (95% CI: 2.08 –3.36). The mean anklebrachial indexes were 0.67 (95% CI: 0.63– 0.70) before angioplasty and 0.89 (95% CI: 0.86 – 0.93) after angioplasty (P ⬍ .0001). With use of the criterion of less than 30% residual diameter stenosis as measured during the independent film analysis, the technical success rate was 73.2% (82 of 112). However, the residual diameter stenosis exceeded 50% in only nine limbs. Primary Hemodynamic Success One day after angioplasty, 92.9% of the interventions (104 of 112) were hemodynamically successful. On the basis of univariate analysis, hemodynamic success was significantly associated with the length of treated femoropopliteal segment and the type of lesion treated (Table 3). In cases in which the treated femoropopliteal segment was shorter than 3 cm, the primary hemodynamic success rate was higher than in cases in which the treated lesion was longer than 3 cm. When the lesion was stenosis, the primary hemodynamic success rate was higher than when it was occlusion. In stepwise multiple logistic regression analysis, only the type of lesion proved to be an independent determinant of primary hemodynamic success (Table 3). Long-term Patency

RESULTS Characteristics of the lesions in the treated limbs are shown in Table 2. Among the 112 interventions, standard dilation (1–3 min) was used in 19

The cumulative primary and secondary patency rates versus time of follow-up calculated with the KaplanMeier method for all the 112 treated limbs are shown in Figure 1. The pri-

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Table 3 Result of Univariate and Multiple Logistic Regression Analyses of the Factors Affecting Primary Hemodynamic Success Univariate Analysis Variable Length of treated femoropoliteal lesions ⱕ3 cm ⬎3 cm Type of lesion Stenosis Occlusion

P Value

Primary Hemodynamic Success (%)

.01

Multiple Logistic Regression Analysis P Value

Odds Ratio*

⬎.15

...

100 (48/48) 87.5 (56/64) .002

.01 99 (73/74) 82 (31/38)

16.47 (1.93–139.2)

* Numbers in parentheses are 95% CIs.

mary patency rate was 42% ⫾ 5% (⫾ SE of the estimate) at 1 year, 39% ⫾ 5% at 2 years, and 39% ⫾ 5% at 3 years. The secondary patency rate was 51% ⫾ 5% at 1 year and 47% ⫾ 5% at 2 and 3 years. When evaluated by means of Kaplan-Meier analysis, the following factors proved to be determinants of primary patency after successful angioplasty: the number of diseased vessels in the treated limb, the morphology of the treated femoropopliteal lesion, and other treated lesions in the limb (Table 4). Limbs with one to three diseased vessels showed a significantly better prognosis than limbs with four or more diseased vessels. The prognosis was poorer in the case of eccentric stenoses than in the case of concentric lesions (P ⫽ .05; Fig 2). If lesions in the infrapopliteal or iliac artery of the limb were also treated, the long-term patency was worse than when only femoropopliteal segments were treated. The statistical significance was preserved also after stratification according to diabetes, peripheral runoff, and type of procedure (dilation of stenosis vs recanalization). To determine the strongest predictors among the individual factors that were significant in the Kaplan-Meier analysis and to determine the simultaneous influence of the factors, stepwise Cox multiple regression analysis was performed. Only the presence of other treated lesions in the limb remained in the model (Table 4). Clinical Events during Follow-up The patients were followed for a mean of 22 months (95% CI: 19.7–24.8).

Figure 1. Results of survival analysis (Kaplan-Meier method) for the primary and secondary patency rates for all 112 treated limbs. Numbers indicate number of cases remaining as a function of time since angioplasty. Initial failures are included.

Altogether, 56 angiograms were obtained during follow-up because of the worsening clinical signs of treated or another limb. The mean time after initial angioplasty of the 22 repeated angioplasty procedures, 16 of which were femoropopliteal PTA, was 18 months (range, 3–39 mo; median, 16 mo). Nine percent (n ⫽ 10) of the 112 limbs primarily treated with PTA underwent surgical bypass operation (eight of which were femoropopliteal

and two were femorodistal). Two adjunctive surgical procedures were performed: one endarterectomy of the common femoral artery to improve inflow and one femorofemoral crossover bypass operation because of an occluded iliac stent. The mean time for surgical operation was 13 months (range, 1–32 mo; median, 10 mo) after primary PTA. No major or minor amputations were performed. The overall death rate in the patient population

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Table 4 Results of Kaplan-Meier and Cox Multiple Regression Analyses Kaplan-Meier, Primary Patency Rate (%)* Variable

P Value

No of diseased vessels One to three (n ⫽ 60) Four to ten (n ⫽ 44) Additional treated lesions Yes (n ⫽ 38) No (n ⫽ 66)

.049

1y

2y

3y

54% (0.07) 34% (0.08)

50% (0.07) 34% (0.08)

50% (0.07) 34% (0.08)

28% (0.07) 55% (0.06)

23% (0.08) 54% (0.06)

23% (0.08) 54% (0.06)

.003

Cox Multiple Regression P Value

Odds Ratio†

⬎.15

...

.008

1.94 (1.18–3.18)

* Numbers in parentheses are SE. † Numbers in parentheses are 95% CIs.

was 16% (15 of 97) during the follow-up period. The 30-day mortality rate was zero. Complications During the 134 endovascular interventions (repeat PTA included) in the 112 limbs, there were three major specific local vascular complications that required treatment. One infrapopliteal embolization without tissue loss after angioplasty of a stenosis (dilation time: 2 minutes) required intraarterial thrombolytic therapy (500,000 U urokinase). One growing hematoma of the groin required surgical operation immediately after angioplasty, and one access site pseudoaneurysm was successfully treated with US-guided compression. The rate of major specific local vascular complications was 2.2% (three of 134). Three minor specific local vascular complications occurred: all were puncture site hematomas that did not require any treatment. Hence, the overall complication rate was 4.5% (six of 134). Impact of Prolonged Balloon Inflation To facilitate a detailed analysis of the influence of dilation time on the primary hemodynamic success and long-term patency, a subgroup analysis of the 59 interventions composed of only femoropopliteal balloon angioplasty (12 stents excluded) was performed. In this subgroup, the primary hemodynamic success rate was 98% (58 of 59). The dilation time did not correlate with primary hemodynamic success. Long-term patency, calcu-

Figure 2. Primary patency rates according to morphology of the treated lesions. Initial failures are included.

lated by Kaplan-Meier method, was tested with different cut-off points according to dilation time: 3 minutes, 5 minutes, 10 minutes, and 15 minutes. No significant differences were found between the groups. The primary patency rate was 58% ⫾ 10% in the subgroup of procedures with less than 10 minutes of dilation time (n ⫽ 28) and 56% ⫾ 9% in the subgroup with longer

than 10 minutes of dilation (n ⫽ 31) at 1, 2, and 3 years (P ⫽ .98). These subgroups did not differ significantly in terms of the tested demographic variables (sex, diabetes, coronary disease), peripheral runoff, primary angiographic result, lesion morphology, number of diseased vessels in the treated limb, or mean length of treated lesion.

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DISCUSSION Determinants of Long-term Patency of Femoropopliteal Angioplasty The long-term results of endovascular interventions of the femoropopliteal arteries are fairly poor. The published primary patency rates after conventional balloon angioplasty vary from 46% to 81% at 1 year (3,5,9,15,23) and from 36% to 61% at 3 years (3,9,15,24,25). Even stents do not offer significant advantage over balloon angioplasty alone in terms of long-term results (5,26,27). A large number of factors predicting poorer long-term patency of femoropopliteal angioplasty have been reported, such as the increased length of the treated lesion (3), presence of occlusions (15), multifocal stenoses (28), and diabetes (9). The importance of outflow on success has been stressed by some investigators. In an analysis of femoropopliteal balloon angioplasty, Johnston et al (29) reported peripheral runoff to be a predictor of long-term results; they showed that the success rate at 5 years for stenoses/occlusions with good peripheral runoff was 53%/36%, compared with 31%/16% in cases of poor runoff (29). In another study (3), a 59% primary patency rate at 3 years in cases with good peripheral runoff and 36% in those with poor runoff was reported. Poor tibial runoff was also noticed to be most predictive of lower long-term patency rates in a prospective multicenter study (30). However, in the present study, peripheral runoff proved not to be a significant determinant, and there are congruent results about the importance of peripheral runoff in the literature (24,31). Conversely, an increased number of diseased vessels in the treated limb, which reflects the extent of the atherosclerotic changes, significantly decreased long-term patency (Table 4). Moreover, if lesions additional to the femoropopliteal obstructions were treated, the long-term patency was poorer. This result remained unchanged after stratification according to preinterventional peripheral runoff. However, it is notable that the peripheral runoff improved remarkably because of the 34 adjunctive infrapopliteal PTA procedures. Before PTA, 32% of the limbs (36 of 112) had no patent

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infrapopliteal vessels, whereas after PTA, this proportion was only 15% (17 of 112). Overall, our results do not give support to our original hypothesis that active treatment of stenotic lesions of the outflow tract would be beneficial in terms of the long-term result. Actually, only a few studies have advocated distal PTA in patients with claudication to increase the effectiveness and durability of femoropopliteal PTA (32,33). One limitation of the study protocol was that follow-up angiography was performed only if reocclusion was suspected clinically. So, it remains unknown in how many cases the longterm failure was caused by the infrapopliteal lesion and not the recurrence of femoropopliteal disease. A recent study with angiographic follow-up reported a restenosis rate of 32% for infrapopliteal stenoses and 52% for occlusions (34). Prolonged Balloon Inflation versus Conventional Inflation Strategy Postprocedural residual stenosis has been found to be predictive of restenosis in coronary angioplasty studies (7,8,35). In one study, the presence of residual stenosis worsened the prognosis in femoropopliteal angioplasty (9). One option to improve the initial angiographic result is to use prolonged balloon inflation (14). We used primarily standard dilation, but if the result was considered to be unsatisfactory on angiography and/or IVUS imaging as assessed by the operating interventional radiologist, the procedure was continued with prolonged dilation. Although prolonged balloon inflation was performed in more than 80% of the procedures and the final angiographic result assessed visually by the performing radiologist was acceptable, independent quantitative measurement revealed residual diameter stenosis exceeding 30% in as many as 27% of the limbs. Such underestimation in visual analysis of the residual stenosis has also been reported by others (36,37). However, our strategy resulted in excellent hemodynamic success; only five of the 112 interventions were hemodynamic failures according to Doppler US criteria. The effect of prolonged dilation on improving the primary technical result assessed by angiography was not sep-

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arately analyzed in the present trial because a previous subgroup analysis revealed that the initial angiographic result was improved in a vast majority of the lesions after prolonged dilation (14). The long-term results of the present trial are very similar to those of the reference study from our institution that involved standard dilation strategy in femoropopliteal angioplasty. In the reference study that used the same definitions and classifications of study variables as the present study, primary patency rates of 47% at 1 year and 42% at 2 and 3 years were achieved (3), compared with the corresponding values 42% and 39% of the present trial. Many parameters between the present and reference study were congruent (Tables 1 and 2); mean total length of the treated segments were comparable, as were the total number of treated lesions and hemodynamically significantly diseased arteries in the treated limb, as well as the majority of the demographic parameters. However, there were some differences that complicate the comparison between these two trials. The proportion of limbs with poor peripheral runoff was somewhat larger in the present study, 68% compared to 44%, a fact that might have a worsening effect on the long-term results (30). Conversely, in the present study, the type of lesion was less frequently an occlusion (34% compared to 49%), which might have a beneficial effect on long-term results of the present study; the long-term success was found to be better when the treated lesion was a stenosis rather than an occlusion (15). Overall, our strategy did not result in superior long-term results, contrary to what was expected. A study of coronary angioplasty indicated that the initial improvement in angiographic appearance with prolonged dilation did not lead to a significant reduction in restenosis (12). Two other studies of coronary angioplasty also implied that, although prolonged dilation resulted in high procedural success, the restenosis rate is similar to that reported in large studies of patients treated with standard angioplasty (11,38). However, it is to be noted that these coronary angioplasty studies used maximum dilation times of only 15 minutes, whereas we used considerably longer balloon

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Prolonged Balloon Dilation of the Femoropopliteal Arteries

inflation times, a mean of 31 minutes and as long as 180 minutes. One reason for unfavorable longterm results is elastic recoil, which occurs after the completion of angiography even though the initial result is acceptable (39). Eighty-one percent of the patients who showed loss in minimal luminal diameter 24 hours after coronary angioplasty also showed early loss in minimal luminal diameter within 1 hour at angiography. The early loss was not related to thrombus but usually to dissection or recoil (40). Other investigators have noticed elastic recoil in approximately 40% of their patients at angiography 15 minutes after apparently successful coronary angioplasty (41). There are data suggesting that, in humans, “recoil” and/or vascular contraction with healing response to balloon injury is a major contributor to restenosis after balloon angioplasty (42). Because we performed angiography within minutes of balloon dilation, it remains unresolved whether prolonged dilation has any effect on these subacute phenomena that may be related to the development of restenosis. As newer technologies have become clinically available, it is increasingly evident that in-stent restenosis seems to be caused primarily by smooth muscle cell proliferation (43). However, in the process of restenosis after balloon angioplasty, other factors are clearly important: thrombus, intimal and medial dissections, and especially arterial remodeling (44). Techniques such as stent placement and catheter atherectomy that cause more severe vascular wall damage induce more pronounced myointimal hyperplasia than balloon angioplasty (45,46). Tissue proliferation inside and surrounding the stents may be related to the aggressiveness of the stent implantation technique (47). One might argue that prolonged balloon inflation may cause more severe vessel wall damage than standard dilation, and theoretically stimulate the restenotic process. In this case, the benefit from the better acute gain is lost as a result of more pronounced myointimal hyperplasia. Unfortunately, our study does not give an answer as to the optimal balloon inflation strategy. Because prolonged dilation effectively improves the acute angiographic findings in

cases of unacceptable results after 1–3 minutes of dilation, an additional dilation with the conventional angioplasty balloon of as long as 30 minutes seems warranted, especially in lesions that are poor candidates for stent placement. The usefulness of longer dilation times with the perfusion balloon catheter seems questionable because of practical reasons: the patient gets tired and it requires excessive time in a busy daily practice. Overall, we conclude that although prolonged balloon inflation is a feasible and safe method for improving unacceptable initial results of femoropopliteal angioplasty. However, the routine use of prolonged dilation is not warranted because this strategy does not result in superior long-term patency rates. Acknowledgments: This work was supported by the Kuopio University Hospital (grant number 5063501), the Koskelo Foundation, and the Foundation of Aarne and Aili Turunen. The authors wish to thank research secretary Tuula Bruun. References 1. Vorwerk D, Gunther RW, Schurmann K, Wendt G. Aortic and iliac stenoses: follow-up results of stent placement after insufficient balloon angioplasty in 118 cases. Radiology 1996; 198:45– 48. 2. Bosch JL, Hunink MG. Meta-analysis of the results of percutaneous transluminal angioplasty and stent placement for aortoiliac occlusive disease. Radiology 1997; 204:87–96. [published erratum appears in Radiology 1997 Nov; 205(2):584] 3. Matsi PJ, Manninen HI, Vanninen RL, et al. Femoropopliteal angioplasty in patients with claudication: primary and secondary patency in 140 limbs with 1–3-year follow-up. Radiology 1994; 191:727–733. 4. Murray JG, Apthorp LA, Wilkins RA. Long-segment (⬎ or ⫽ 10 cm) femoropopliteal angioplasty: improved technical success and long-term patency. Radiology 1995; 195:158 –162. 5. Cejna M, Thurnher S, Illiasch H, et al. PTA versus Palmaz stent placement in femoropopliteal artery obstructions: a multicenter prospective randomized study. J Vasc Interv Radiol 2001; 12:23– 31. 6. Grimm J, Muller-Hulsbeck S, Jahnke T, Hilbert C, Brossmann J, Heller M. Randomized study to compare PTA alone versus PTA with Palmaz stent placement for femoropopliteal lesions. J Vasc Interv Radiol 2001; 12:935–942. 7. Renkin J, Melin J, Robert A, et al. De-

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