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Clinical results of single-vessel versus multiple-vessel infrapopliteal intervention
From the Society for Clinical Vascular Surgery
Clinical results of single-vessel versus multiple-vessel infrapopliteal intervention Jeremy D. Darling, BA,a John C. McCallum, MD,a Peter A. Soden, MD,a John J. Hon, BS,b Raul J. Guzman, MD,a Mark C. Wyers, MD,a Hence J. Verhagen, MD, PhD,c and Marc L. Schermerhorn, MD,a Boston, Mass; Hanover, NH; and Rotterdam, The Netherlands
ABSTRACT Objective: The effects of concomitant endovascular interventions on multiple infrapopliteal vessels are not well known, and the short-term and long-term sequelae of such procedures have not been reported. Methods: From 2004 to 2014, 673 limbs in 528 patients underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). Outcomes included wound healing, RAS events (reintervention, major amputation, or stenosis [>3.5x step-up by duplex]), and mortality. Patients without an initial indication of critical limb ischemia (CLI) were excluded. Patients were characterized as having undergone either a single-vessel infrapopliteal intervention or a multiple-vessel infrapopliteal intervention. Results: Of the 673 limbs, 558 underwent a successful infrapopliteal endovascular intervention for CLI (86% for tissue loss, 14% for rest pain). During a single procedure, 503 limbs (90%) underwent a single-vessel intervention and 55 (10%) underwent a multiple-vessel intervention. Patients undergoing a single-vessel intervention more commonly underwent a prior ipsilateral endovascular procedure (17% vs 6%; P ¼ .03) or a prior ipsilateral bypass procedure (20% vs 9%; P ¼ .04). Kaplan-Meier analysis revealed that a RAS event #1 year occurred in 229 limbs (49%), with no significant difference in the 1-year rates of reintervention (22% vs 20%; P ¼ .53), major amputation (16% vs 10%; P ¼ .24), or stenosis (29% vs 21%; P ¼ .25). After adjustment for baseline characteristics, multivariable regression illustrated that neither major amputation rates nor RAS events differed between patients undergoing a single-vessel vs a multiple-vessel intervention (P ¼ .26 and P ¼ .61, respectively). Conclusions: Our data suggest that a multiple-vessel intervention does not improve outcomes when compared to a single-vessel intervention following infrapopliteal angioplasty for CLI. (J Vasc Surg 2016;-:1-7.)
Peripheral artery disease can be a severe and complex condition that is still a challenge for both surgical and endovascular therapies.1 Arterial disease is known to be located predominantly in the superficial femoral artery in patients with claudication and in the below-the-knee region in patients with critical limb ischemia (CLI). Especially in patients with diabetesdwhere arterial disease is commonly characterized by long, multilevel disease From the Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Bostona; the Geisel School of Medicine at Dartmouth, Hanoverb; and the Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam.c This work was supported by National Institutes of Health Harvard-Longwood Research Training in Vascular Surgery Grant 2T32-HL-007734-21A. Author conflict of interest: A.H. is on the Data Safety Monitoring Board for Endologix, Inc. M.L.S. is a consultant for Endologix, Inc. Presented at the Forty-third Annual Symposium of the Society for Clinical Vascular Surgery, Miami, Fla, March 29-April 2, 2015, and recipient of Top Honors in the 2015 SCVS Peter B Samuels Award Competition. Correspondence: Marc L. Schermerhorn, MD, 110 Francis St, Ste 5B, Boston, MA 02215 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2016 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2016.05.080
involving all infrapopliteal vesselsdthe risk of peripheral artery disease is significantly higher and tends to be more aggressive than in patients without diabetes.2-4 Multilevel lesion distribution is not infrequent and requires treatment of both the superficial femoral artery and, more challengingly, below-the-knee vessels. In tibial vein bypass planning, the choice of tibial target vessel requires the selection of the best single outflow vessel; however, the endovascular approach offers the possibility of concomitantly treating more than one tibial vessel and may provide similar clinical outcomes with lower rates of restenosis and reinterventions.5-7 Although those performing endovascular revascularization have the ability to treat multiple tibial vessels concomitantly, considering that major amputation and mortality rates of CLI patients are substantial after an unsuccessful revascularization, understanding whether this strategy proves beneficial is important. Studies have shown that at least one patent tibial artery to the foot is often needed to achieve a sufficient amount of blood flow necessary for limb salvage,8-11 but the potential benefit(s) of treating multiple infrapopliteal arteries remains uncertain. Importantly, although many believe that treating multiple infrapopliteal vessels may increase blood flow more so than treating a single infrapopliteal vessel, recent studies 1
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have shown that distal targets can be altered from multiple percutaneous interventions, necessitating a more prudent use of these multiple-vessel procedures.12-14 Several studies have reported results of multilevel endovascular interventions15,16; however, few have considered the short-term and long-term effects of concomitant endovascular interventions on multiple infrapopliteal vessels. Therefore, with this study, we sought to better understand the effects of concomitant endovascular interventions on multiple infrapopliteal vessels.
METHODS We performed a retrospective record review of all Beth Israel Deaconess Medical Center patients undergoing an infrapopliteal angioplasty/stent for CLI between January 2004 and May 2014. The Beth Israel Deaconess Medical Center Institutional Review Board approved this study and waived the need for patient consent due to the retrospective design. Current Procedural Terminology codes (American Medical Association, Chicago, Ill) were used as a means to identify patients undergoing infrapopliteal revascularization (angioplasty and atherectomy, with or without stenting). Throughout our study timeline, 673 limbs in 528 patients underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). For this analysis, only patients with an initial indication of CLI (ie, tissue loss or rest pain) and a successful intervention were included, totaling 558 limbs in 448 patients. The follow-up interval was at the discretion of the primary vascular attending, with common practice being arterial duplex ultrasound imaging and ankle-brachial indices every 4 months for 1 to 2 years and every 6 months thereafter. Indications for intervention included tissue loss or rest pain; patients presenting with more than one indication for intervention were assigned hierarchically, where gangrene was considered most severe, followed by ulcer, and lastly rest pain. Procedures were performed using 5F or 6F sheaths, preferentially by retrograde contralateral access and occasionally by antegrade ipsilateral access. Brachial or other means of upper extremity access were not used for tibial interventions throughout our study period. For obtaining percutaneous access for catheter-based interventions, ultrasound guidance has routinely been used by the vascular surgeons at our institution since September 2007. Stent type varied depending on availability and surgeon preference, and the number of infrapopliteal vessels treated was at the discretion of the treating surgeon. All patients were discharged on aspirin and clopidogrel unless a contraindication was present, selected patients were taking anticoagulants, or a bypass was planned.
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Lesion anatomy was defined according to the modified Trans Atlantic Inter-Society Consensus (TASC) classification described by Dormandy and Rutherford.4 Technical success in single-vessel interventions was defined as a residual stenosis <30%, where success in multiple-vessel interventions was defined as interventions in which at least two intervened vessels achieved technical success. Interventions that did not meet these criteria were deemed a failure and were excluded from the analysis. Primary outcomes included perioperative complications, wound healing, RAS events (reintervention, major amputation, or stenosis [>3.5x step-up by duplex]), and mortality. Perioperative complications were identified by review of operative reports, discharge summaries, and physician progress notes and included access site arterial injury, acute kidney injury or acute renal failure, acute myocardial infarction, congestive heart failure, dysrhythmia, respiratory failure or pneumonia, gastrointestinal bleeding, and cerebrovascular accidents #30 days of the index procedure or during the patient’s hospital stay. Patients were characterized as having undergone either a single-vessel infrapopliteal intervention or a multiple-vessel infrapopliteal intervention. Multiplevessel interventions were defined as interventions on infrapopliteal vessels in parallel rather than in series. Considering the tibial peroneal trunk (TPT) as an extension of the peroneal and posterior tibial (PT) vessels (as opposed to an additional vessel), an intervention was considered multiple-vessel when an anterior tibial (AT) or dorsalis pedis (DP) vessel (or AT and DP) was intervened on in addition to the TPT, peroneal, or PT (or any combination of the three). For example, an angioplasty of the TPT and PT vessels within one procedure would be categorized as a single-vessel intervention (because the TPT and PT are in-line), while an angioplasty of the TPT and the AT would be categorized as multiple-vessel. For multiple-vessel interventions, a restenosis was classified when stenoses developed in all relevant multiple vessels (eg, stenosis of both AT and PT after both were treated) or when proximal in-line flow was impaired (eg, stenosis of the TPT after the peroneal, PT, and TPT were treated). For multilevel index procedures (ie, femoropopliteal and tibial), a reintervention was denoted only when an infrapopliteal vessel was re-treated. Importantly, Fig 1 illustrates the yearly proportion of multiple-vessel procedures performed within our practice throughout our study years. As will be further detailed in the Discussion, the spike of multiple-vessel procedures in 2007 was in response to a 2007 Faglia et al9 study suggesting the effectiveness of multiplevessel PTA on freedom from amputation. To account for this potential bias, we constructed a separate analysis with the same primary outcomes, but limited to the time period of 2007 to 2014. All analyses were performed on a per-limb basis. Pearson c2 and Fisher exact test were used for comparisons
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Fig 1. Yearly proportion of multiple-vessel endovascular infrapopliteal interventions for critical limb ischemia (CLI). *Data through May 2014.
of categoric variables. Means of continuous variables were compared using the Student t-test, assuming equal variances. Time-to-event analyses, by log-rank test and Cox proportional hazards regression modeling, were used to identify predictors of adverse outcomes for end points of interest. Statistical analyses were performed using Stata 12 software (StataCorp LP, College Station, Tex).
RESULTS Successful infrapopliteal endovascular intervention for CLI was performed in 558 limbs in 448 patients (86% for tissue loss, 14% for rest pain). At the index procedure, 503 (90%) were single-vessel and 55 (10%) were multiplevessel interventions. Patient baseline characteristics of both intervention types are provided in Table I. Patients most commonly presented with ulcerations, but no difference was noted between procedure types (53% in singlevessel vs 56% in multiple-vessel; P ¼ .62). Further, 15% of single-vessel and 11% of multiple-vessel patients presented with rest pain, which was also not significantly different (P ¼ .38). Wound, ischemia, and foot infection clinical stage proportions were also similar between groups (P ¼ .63), with both procedure types most commonly presenting with clinical stage 4 (41% vs 47%; P ¼ .45).17 Postoperative aspirin (88% vs 86%; P ¼ .70), clopidogrel (89% vs 88%; P ¼ .83), statin (72% vs 70%; P ¼ .79), and warfarin (24% vs 23%; P ¼ .83) were also seen to have no significant difference when single-vessel and multiple-vessel interventions were compared. Patients undergoing a single-vessel procedure tended to be older (72 vs 68 years), but this difference was also insignificant (P ¼ .05). Overall, there were no significant demographic differences between the two procedure types.
The proportional distribution of multiple-vessel interventions during the 10-year study ranged from w6% in 2005 to w18% in 2007 (Fig 1), after which the rate gradually declined. Technical success was achieved in 503 single-vessel limbs (94%) and in 49 multiple-vessel limbs (89% [94% total]; P ¼ .12). The six multiple-vessel limbs experiencing a failure that were included within this analysis involved a failure within one vessel, and at least two successful intervened-on vessels. Single-vessel interventions were more commonly performed in those with a prior ipsilateral endovascular procedure (16% vs 6%; P ¼ .03) and in those with a prior ipsilateral bypass procedure (20% vs 9%, P ¼ .04; Table I). Tibial TASC1 classification did not differ between groups, with TASC D lesions occurring in 30% of both single-vessel and multiplevessel interventions. In addition, infrapopliteal stenting occurred in 13% of single-vessel procedures and in 6% of multiple-vessel procedures (P ¼ .10; Table II). Of the single-vessel procedures, 54% were multilevel, with 35% performed in conjunction with a popliteal angioplasty. Similarly, 40% of multiple-vessel procedures were multilevel, with 31% performed in conjunction with a popliteal angioplasty. Perioperative complications (ie, in-hospital or 30-day) did not differ between single-vessel and multiple-vessel interventions (10% vs 15%; P ¼ .32). Among the 293 patients with follow-up $6 months, complete wound healing occurred in 37% of single-vessel patients and in 41% of multiple-vessel patients (P ¼ .13; Table III). KaplanMeier analysis revealed that freedom from restenosis #1 year (71% vs 79%, P ¼ .32; Fig 2, a), freedom from major amputation #1 year (84% vs 90%, P ¼ .23; Fig 2, b), and freedom from reintervention #1 year (78% vs 80%,
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Table I. Baseline characteristics of patients undergoing single-vessel and multiple-vessel infrapopliteal endovascular interventions for critical limb ischemia (CLI)
Variable
Single-vessel Multiple-vessel (n ¼ 503), (n ¼ 55), No. (%) No. (%) P value
Demographics 71.5 (11.8)
68.2 (13.8)
.05
Male sex
259 (52)
34 (62)
.15
243 (49)
Hypertension
421 (84)
48 (87)
.57
Diabetes
395 (79)
48 (87)
.15
Chronic renal insufficiency
126 (25)
15 (27)
.74
Dialysis dependence
92 (18)
12 (22)
.52
History of myocardial infarction
95 (19)
11 (20)
.86
140 (28)
10 (18)
.12
Smoking history
25 (46)
.65
71 (14)
2 (3.6)
.03
175 (35)
17 (31)
.57
161 (32)
14 (26)
.32
Infrapopliteal
65 (13)
3 (5.5)
.10
Femoropopliteal
114 (23)
11 (20)
.65
Table III. Postoperative outcomes of patients undergoing single-vessel and multiple-vessel infrapopliteal endovascular interventions for critical limb ischemia (CLI) Single-vessel Multiple-vessel (n ¼ 503), (n ¼ 55), No. (%) No. (%)
P value
Perioperative (30-day or in-hospital)
.26
227 (55)
27 (59)
.59
Complications
51 (10)
8 (15)
.32
Length of stay, mean (SD), days
4.6 (10.8)
5.7 (6.8)
.51
Mortality
23 (4.6)
4 (7.3)
.38
3 (5.5)
.03
Infrapopliteal PTA
43 (8.6)
1 (1.8)
.08
Bypass
99 (20)
5 (9.1)
.04
75 (15)
9 (16)
.78
77 (15)
6 (11)
.38
Indication Ulcer
266 (53)
31 (56)
.62
Gangrene
163 (33)
18 (33)
.96
WIfI clinical stage17
.63
Clinical stage 1
7 (1.6)
Clinical stage 2
95 (22)
Clinical stage 3
149 (35)
18 (37)
Clinical stage 4
177 (41)
23 (47)
1 (2.0) 7 (14)
Tibial TASC classification A
.06
2 (3.6)
83 (17)
None
22 (40)
39 (7.8)
PTA (any)
Rest pain
Popliteal
Outcomes
Prior intervention
Minor amputation
269 (54)
Proximal vessel
Stent
Coronary artery disease
COPD
Single-vessel Multiple-vessel (n ¼ 503), (n ¼ 55), No. (%) No. (%) P value
Procedural details
Superficial femoral
Comorbidities
Congestive heart failure
Table II. Procedural details between single-vessel and multiple-vessel infrapopliteal endovascular interventions in patients with critical limb ischemia (CLI)
Multilevel intervention
Age, mean (SD) years
.88 11 (2.2)
1 (1.9)
95 (19)
10 (19)
B
95 (19)
13 (25)
C
147 (30)
13 (25)
D
151 (30)
16 (30)
COPD, Chronic obstructive pulmonary disease; PTA, percutaneous transluminal angioplasty; TASC, TransAtlantic Inter-Society Consensus; SD, standard deviation; WIfI, Wound, Ischemia, foot Infection. Data are presented as number (%) unless otherwise indciated.
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Wound healing at 6 months
.13
Complete
87 (37)
12 (41)
Incomplete
177 (63)
16 (59)
1-year Reintervention
84 (22)
9 (20)
.53
PTA/S
51 (14)
6 (14)
.71
Bypass
34 (9)
3 (7)
.49
Restenosis
113 (29)
9 (21)
.25
Major amputation
63 (16)
4 (10)
.24
205 (48)
22 (49)
.38
179 (48)
22 (53)
.42
RAS events 3-year Mortality
PTA/S, Percutaneous transluminal angioplasty with or without stenting; RAS, reintervention, major amputation, or stenosis. Data are presented as number (%) unless otherwise indciated.
P ¼ .53; Fig 2, c) did not differ between single-vessel and multiple-vessel interventions, combining for insignificant differences in freedom from 1-year RAS events (52% vs
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100 12
1 2 Time to Restenosis (Years)
75
3
Number at risk: Single-vessel: Multiple-vessel: 0
c
146 14
211 24
87 8
1 2 Time to Amputation (Years)
3
d
Single-vessel
75
75
Multiple-vessel
P = .17 S.E. does not exceed 10% ≤ 3 years
100
163 22
100
0
Single-vessel
P = .53
P = .43 S.E. does not exceed 10% ≤ 3 years
Number at risk: Single-vessel: Multiple-vessel: 0
191 25
124 14
1 2 Time to Reintervention (Years)
72 9 3
0
25
S.E. does not exceed 10% ≤ 3 years
50
Survival (%)
50
Multiple-vessel
25
Freedom from Reintervention (%)
100
25
Number at risk: Single-vessel: Multiple-vessel:
b
Single-vessel
50
75 50
P = .13 S.E. does not exceed 10% ≤ 3 years
0
;Freedom from Restenosis (%)
Single-vessel
Multiple-vessel
25
a
Multiple-vessel
0
5
-
Freedom from Amputation (%)
Number
0
-,
100
Volume
Number at risk: Single-vessel: Multiple-vessel: 0
268 30 1
186 17
123 12
2
3
Years
Fig 2. Freedom from primary outcomes between single-vessel vs multiple-vessel infrapopliteal interventions for critical limb ischemia (CLI): (a) restenosis, (b) major amputation, (c) reintervention, and (d) survival. S.E., Standard error.
51%; P ¼ .38). Further, similar analyses illustrated that survival at 1 and 3 years did not differ between procedure types (76% vs 75% [P ¼ .78] and 52% vs 47% [P ¼ .42], respectively; Table III; Fig 2, d). Finally, multivariable regression illustrated that amputation rates and RAS events did not differ between patients undergoing a single-vessel vs multiple-vessel intervention; tibial TASC classification and a prior ipsilateral bypass were, however, independently predictive of both major amputation (hazard ratio, 1.4 [95% confidence interval, 1.1-1.7] and 2.6 [1.6-4.3], respectively) and RAS events (1.2 [1.1-1.3] and 1.5 [1.3-2.3], respectively; Table IV). As mentioned, to account for the influence that the 2007 Faglia et al9 study had on the implementation of multiple-vessel procedures in our practice, we constructed a separate analysis with the same primary outcomes limited to 2007 to 2014. Restriction of the analysis to these years did not yield any substantial differences in wound healing, restenosis, reintervention, major amputation, RAS events, or survival between single-vessel and multiple-vessel infrapopliteal interventions.
DISCUSSION Our data suggest that there were no perioperative or 1-year differences in clinical outcomes among patients undergoing a single-vessel vs multiple-vessel infrapopliteal angioplasty for CLI. Although RAS events proved prevalent overall (49% at 1 year), time-to-event analysis revealed no difference in the proportion of patients experiencing any 1-year outcomes (notably, restenosis, reintervention, major amputation, and mortality) between single-vessel and multiple-vessel infrapopliteal interventions. It is also important to note that our definition of restenosis among patients who underwent a multiple infrapopliteal vessel intervention requires impairment of proximal in-line flow or stenosis among all relevant multiple vessels. Interestingly, despite this methodology allowing multiple-vessel interventions greater opportunity to be free from restenosis, we found no difference in restenosis rates. We previously reported that multilevel (ie, concomitant femoropopliteal and infrapopliteal segment intervention) vs infrapopliteal-only endovascular intervention did not influence amputation rates in a subset
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Table IV. Multivariable models for major amputation and RAS events (reintervention, major amputation, or stenosis) in patients undergoing single-vessel and multiple-vessel infrapopliteal endovascular interventions for critical limb ischemia (CLI) Major amputation Variable Multiple-vessel intervention
Hazard ratio
RAS events
95% Confidence interval
Hazard ratio
95% Confidence interval
0.6
0.2-1.5
0.9
0.6-1.4
Age
1.0
0.9-1.0
1.0
0.9-1.0
Male gender
1.1
0.7-1.8
1.4
a
Dialysis dependence
2.5
1.5-4.1
1.2
TASC classification
1.4
1.1-1.7a
1.2
Unsuitability for bypass
2.8
1.8-4.6a
1.1
2.6
a
1.5
Prior ipsilateral bypass
1.6-4.3
1.1-1.8a 0.9-1.7 1.1-1.3a 0.8-1.5 1.3-2.3a
TASC, TransAtlantic Inter-Society Consensus. a P < .05.
of this patient cohort.15,18 Although few studies have compared single-vessel vs multiple infrapopliteal vessel interventions, our results corroborate those of Acin et al,19 who found no difference at 24 months in freedom from major adverse limb events (ie, major reintervention or major amputation) (62% vs 71%; P ¼ .33), freedom from RAS events (24% vs 43%; P ¼ .35), or amputation-free survival (62% vs 64%; P ¼ .96) between 92 patients (101 procedures) in whom a single or a multiple infrapopliteal vessel intervention was attempted, respectively. Similarly, among 539 patients, Iida et al20 accounted for the number of infrapopliteal vessels that were patent after endovascular revascularization; however, although results purported no significant difference in 24-month major amputation rates among patients undergoing angiosome-related direct or indirect revascularization (92% vs 86%; P ¼ .12), no outcome analyses were performed on differences in number of treated vessels. Importantly, the requirements for restenosis for multiple-vessel interventions in these studies were unspecified. These insufficient specifications, differences in patient selection, and cohort size variations may account for the discrepancies in our study’s outcomes. In 2007, Faglia et al9 suggested a relationship between the number of occluded infrapopliteal arteries after angioplasty and the risk of amputation, with an odds ratio of 8.2 (95% confidence interval, 1.35-49.6) for each additionally occluded infrapopliteal vessel. However, this 420-patient study may not have answered the question regarding number of vessels treated, because there was a large spectrum of disease before occlusion that such an analysis does not address. The quality and quantity of vessel runoff to the foot likely plays a large role in patient selection for single-vessel vs multiple-vessel intervention, and we, therefore, believe that it is important to evaluate both occluded and nonoccluded vessels. It is critical to consider that the decision to perform a multiple-vessel procedure may have often been
contingent on either suboptimal outcomes with an initially planned single-vessel procedure or on the perceived technical ease of performance of the intervention in the second vessel and the potential for loss of a bypass target. In addition, as Fig 1 illustrates, our practice was influenced by the report of Faglia et al, with an increase in multiple-vessel revascularization in 2007; however, when we limited our analysis to the period 2007 to 2014, there was no change in our findings. This study has some important limitations. First, the retrospective nature of our study leads to incomplete documentation of certain clinical end points and an inability to inspect records outside of our electronic system, leading to a number of patients without followup $6 months and ultimately limiting our ability to certify practice recommendations from this analysis alone. Further, the indications for a single-vessel vs a multiple-vessel infrapopliteal intervention were variable, based on surgeon preference and the factors listed above, and, ultimately, not clear from the present study; since our data represent the experience of one group of surgeons at a single institution, our results are subject to the influence of specific referral patterns, surgeon experience, and patient selection preferences. In addition, although the inclusion of multiple limbs and multiple procedures from a single patient allowed us to use a larger analytic sample, the potential lack of independence of observations may be of concern. Finally, an assumption may be made about patients with multiple interventions having worse disease and, thus, having similar outcomes. Including tibial TASC class into our multivariable regression models should mitigate these concerns. Importantly, in patients with long-term follow-up, tibial angioplasty had a 49% RAS event rate within 1 year, raising critical questions regarding its durability and utility, certainly warranting further research; however, we hesitate to make strong recommendations based on this finding, because those with failure are more likely
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to have follow-up in our system, and thus, the failure rate may be overestimated.
CONCLUSIONS The results of this study suggest that, when compared to single-vessel intervention, multiple-vessel intervention does not improve outcomes after infrapopliteal angioplasty for CLI. Although our study investigated a large and diverse cohort and corroborated information from several related studies, multicenter and national dataset analyses are necessary to fully explore the outcomes of single-vessel vs multiple-vessel infrapopliteal interventions.
AUTHOR CONTRIBUTIONS Conception and design: JD, JM, PS, JH, RG, MW, MS Analysis and interpretation: JD, JM, PS, RG, MW, HV, MS Data collection: JD, JM, JH Writing the article: JD Critical revision of the article: JD, JM, PS, JH, RG, MW, HV, MS Final approval of the article: JD, JM, PS, JH, RG, MW, HV, MS Statistical analysis: JD Obtained funding: MS Overall responsibility: MS
REFERENCES 1. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45(Suppl S):S5-67. 2. Spiliopoulos S, Katsanos K, Karnabatidis D, Diamantopoulos A, Kagadis GC, Christeas N, et al. Cryoplasty versus conventional balloon angioplasty of the femoropopliteal artery in diabetic patients: long-term results from a prospective randomized single-center controlled trial. Cardiovasc Intervent Radiol 2010;33:929-38. 3. Graziani L, Silvestro A, Bertone V, Manara E, Andreini R, Sigala A, et al. Vascular involvement in diabetic subjects with ischemic foot ulcer: a new morphologic categorization of disease severity. Eur J Vasc Endovasc Surg 2007;33: 453-60. 4. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 2000;31: S1-296. 5. Haider SN, Kavanagh EG, Forlee M, Colgan MP, Madhavan P, Moore DJ, et al. Two-year outcome with preferential use of infrainguinal angioplasty for critical ischemia. J Vasc Surg 2006;43:504-12. 6. Romiti M, Albers M, Brochado-Neto FC, Durazzo AE, Pereira CA, De Luccia N. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg 2008;47:975-81. 7. Varela C, Acin F, De Haro J, March J, Florez A, LopezQuintana A. Influence of surgical or endovascular distal
revascularization of the lower limbs on ischemic ulcer healing. J Cardiovasc Surg (Torino) 2011;52:381-9. 8. Berceli SA, Chan AK, Pomposelli FB Jr, Gibbons GW, Campbell DR, Akbari CM, et al. Efficacy of dorsal pedal artery bypass in limb salvage for ischemic heel ulcers. J Vasc Surg 1999;30:499-508. 9. Faglia E, Clerici G, Clerissi J, Mantero M, Caminiti M, Quarantiello A, et al. When is a technically successful peripheral angioplasty effective in preventing above-theankle amputation in diabetic patients with critical limb ischaemia? Diabet Med 2007;24:823-9. 10. Neville RF, Attinger CE, Bulan EJ, Ducic I, Thomassen M, Sidawy AN. Revascularization of a specific angiosome for limb salvage: does the target artery matter? Ann Vasc Surg 2009;23:367-73. 11. Varela C, Acin F, de Haro J, Bleda S, Esparza L, March JR. The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model. Vasc Endovascular Surg 2010;44:654-60. 12. Lipsitz EC, Ohki T, Veith FJ, Rhee SJ, Kurvers H, Timaran C, et al. Fate of collateral vessels following subintimal angioplasty. J Endovasc Ther 2004;11:269-73. 13. Joels CS, York JW, Kalbaugh CA, Cull DL, Langan EM 3rd, Taylor SM. Surgical implications of early failed endovascular intervention of the superficial femoral artery. J Vasc Surg 2008;47:562-5. 14. Darling JD, McCallum JC, Curran T, Buck DB, Guzman R, Wyers M, et al. Consequences of failed tibial endovascular intervention. J Vasc Surg 2014;59:102S-3S. 15. Lo RC, Darling J, Bensley RP, Giles KA, Dahlberg SE, Hamdan AD, et al. Outcomes following infrapopliteal angioplasty for critical limb ischemia. J Vasc Surg 2013;57: 1455-63; discussion: 1463-4. 16. Fanelli F, Cannavale A, Boatta E, Corona M, Lucatelli P, Wlderk A, et al. Lower limb multilevel treatment with drugeluting balloons: 6-month results from the DEBELLUM randomized trial. J Endovasc Ther 2012;19:571-80. 17. Mills JL Sr, Conte MS, Armstrong DG, Pomposelli FB, Schanzer A, Sidawy AN, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg 2014;59:220-34, e1-2. 18. Giles KA, Pomposelli FB, Spence TL, Hamdan AD, Blattman SB, Panossian H, et al. Infrapopliteal angioplasty for critical limb ischemia: relation of TransAtlantic InterSociety Consensus class to outcome in 176 limbs. J Vasc Surg 2008;48:128-36. 19. Acin F, Varela C, Lopez de Maturana I, de Haro J, Bleda S, Rodriguez-Padilla J. Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy. Int J Vasc Med 2014;2014:270539. 20. Iida O, Takahara M, Soga Y, Yamauchi Y, Hirano K, Tazaki J, et al. Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes. J Endovasc Ther 2014;21:607-15.
Submitted Jan 15, 2016; accepted May 4, 2016.
Clinical results of single-vessel versus multiple-vessel infrapopliteal intervention Jeremy D. Darling, BA,a John C. McCallum, MD,a Peter A. Soden, MD,a John J. Hon, BS,b Raul J. Guzman, MD,a Mark C. Wyers, MD,a Hence J. Verhagen, MD, PhD,c and Marc L. Schermerhorn, MD,a Boston, Mass; Hanover, NH; and Rotterdam, The Netherlands
ABSTRACT Objective: The effects of concomitant endovascular interventions on multiple infrapopliteal vessels are not well known, and the short-term and long-term sequelae of such procedures have not been reported. Methods: From 2004 to 2014, 673 limbs in 528 patients underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). Outcomes included wound healing, RAS events (reintervention, major amputation, or stenosis [>3.5x step-up by duplex]), and mortality. Patients without an initial indication of critical limb ischemia (CLI) were excluded. Patients were characterized as having undergone either a single-vessel infrapopliteal intervention or a multiple-vessel infrapopliteal intervention. Results: Of the 673 limbs, 558 underwent a successful infrapopliteal endovascular intervention for CLI (86% for tissue loss, 14% for rest pain). During a single procedure, 503 limbs (90%) underwent a single-vessel intervention and 55 (10%) underwent a multiple-vessel intervention. Patients undergoing a single-vessel intervention more commonly underwent a prior ipsilateral endovascular procedure (17% vs 6%; P ¼ .03) or a prior ipsilateral bypass procedure (20% vs 9%; P ¼ .04). Kaplan-Meier analysis revealed that a RAS event #1 year occurred in 229 limbs (49%), with no significant difference in the 1-year rates of reintervention (22% vs 20%; P ¼ .53), major amputation (16% vs 10%; P ¼ .24), or stenosis (29% vs 21%; P ¼ .25). After adjustment for baseline characteristics, multivariable regression illustrated that neither major amputation rates nor RAS events differed between patients undergoing a single-vessel vs a multiple-vessel intervention (P ¼ .26 and P ¼ .61, respectively). Conclusions: Our data suggest that a multiple-vessel intervention does not improve outcomes when compared to a single-vessel intervention following infrapopliteal angioplasty for CLI. (J Vasc Surg 2016;-:1-7.)
Peripheral artery disease can be a severe and complex condition that is still a challenge for both surgical and endovascular therapies.1 Arterial disease is known to be located predominantly in the superficial femoral artery in patients with claudication and in the below-the-knee region in patients with critical limb ischemia (CLI). Especially in patients with diabetesdwhere arterial disease is commonly characterized by long, multilevel disease From the Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Bostona; the Geisel School of Medicine at Dartmouth, Hanoverb; and the Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam.c This work was supported by National Institutes of Health Harvard-Longwood Research Training in Vascular Surgery Grant 2T32-HL-007734-21A. Author conflict of interest: A.H. is on the Data Safety Monitoring Board for Endologix, Inc. M.L.S. is a consultant for Endologix, Inc. Presented at the Forty-third Annual Symposium of the Society for Clinical Vascular Surgery, Miami, Fla, March 29-April 2, 2015, and recipient of Top Honors in the 2015 SCVS Peter B Samuels Award Competition. Correspondence: Marc L. Schermerhorn, MD, 110 Francis St, Ste 5B, Boston, MA 02215 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2016 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2016.05.080
involving all infrapopliteal vesselsdthe risk of peripheral artery disease is significantly higher and tends to be more aggressive than in patients without diabetes.2-4 Multilevel lesion distribution is not infrequent and requires treatment of both the superficial femoral artery and, more challengingly, below-the-knee vessels. In tibial vein bypass planning, the choice of tibial target vessel requires the selection of the best single outflow vessel; however, the endovascular approach offers the possibility of concomitantly treating more than one tibial vessel and may provide similar clinical outcomes with lower rates of restenosis and reinterventions.5-7 Although those performing endovascular revascularization have the ability to treat multiple tibial vessels concomitantly, considering that major amputation and mortality rates of CLI patients are substantial after an unsuccessful revascularization, understanding whether this strategy proves beneficial is important. Studies have shown that at least one patent tibial artery to the foot is often needed to achieve a sufficient amount of blood flow necessary for limb salvage,8-11 but the potential benefit(s) of treating multiple infrapopliteal arteries remains uncertain. Importantly, although many believe that treating multiple infrapopliteal vessels may increase blood flow more so than treating a single infrapopliteal vessel, recent studies 1
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have shown that distal targets can be altered from multiple percutaneous interventions, necessitating a more prudent use of these multiple-vessel procedures.12-14 Several studies have reported results of multilevel endovascular interventions15,16; however, few have considered the short-term and long-term effects of concomitant endovascular interventions on multiple infrapopliteal vessels. Therefore, with this study, we sought to better understand the effects of concomitant endovascular interventions on multiple infrapopliteal vessels.
METHODS We performed a retrospective record review of all Beth Israel Deaconess Medical Center patients undergoing an infrapopliteal angioplasty/stent for CLI between January 2004 and May 2014. The Beth Israel Deaconess Medical Center Institutional Review Board approved this study and waived the need for patient consent due to the retrospective design. Current Procedural Terminology codes (American Medical Association, Chicago, Ill) were used as a means to identify patients undergoing infrapopliteal revascularization (angioplasty and atherectomy, with or without stenting). Throughout our study timeline, 673 limbs in 528 patients underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). For this analysis, only patients with an initial indication of CLI (ie, tissue loss or rest pain) and a successful intervention were included, totaling 558 limbs in 448 patients. The follow-up interval was at the discretion of the primary vascular attending, with common practice being arterial duplex ultrasound imaging and ankle-brachial indices every 4 months for 1 to 2 years and every 6 months thereafter. Indications for intervention included tissue loss or rest pain; patients presenting with more than one indication for intervention were assigned hierarchically, where gangrene was considered most severe, followed by ulcer, and lastly rest pain. Procedures were performed using 5F or 6F sheaths, preferentially by retrograde contralateral access and occasionally by antegrade ipsilateral access. Brachial or other means of upper extremity access were not used for tibial interventions throughout our study period. For obtaining percutaneous access for catheter-based interventions, ultrasound guidance has routinely been used by the vascular surgeons at our institution since September 2007. Stent type varied depending on availability and surgeon preference, and the number of infrapopliteal vessels treated was at the discretion of the treating surgeon. All patients were discharged on aspirin and clopidogrel unless a contraindication was present, selected patients were taking anticoagulants, or a bypass was planned.
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Lesion anatomy was defined according to the modified Trans Atlantic Inter-Society Consensus (TASC) classification described by Dormandy and Rutherford.4 Technical success in single-vessel interventions was defined as a residual stenosis <30%, where success in multiple-vessel interventions was defined as interventions in which at least two intervened vessels achieved technical success. Interventions that did not meet these criteria were deemed a failure and were excluded from the analysis. Primary outcomes included perioperative complications, wound healing, RAS events (reintervention, major amputation, or stenosis [>3.5x step-up by duplex]), and mortality. Perioperative complications were identified by review of operative reports, discharge summaries, and physician progress notes and included access site arterial injury, acute kidney injury or acute renal failure, acute myocardial infarction, congestive heart failure, dysrhythmia, respiratory failure or pneumonia, gastrointestinal bleeding, and cerebrovascular accidents #30 days of the index procedure or during the patient’s hospital stay. Patients were characterized as having undergone either a single-vessel infrapopliteal intervention or a multiple-vessel infrapopliteal intervention. Multiplevessel interventions were defined as interventions on infrapopliteal vessels in parallel rather than in series. Considering the tibial peroneal trunk (TPT) as an extension of the peroneal and posterior tibial (PT) vessels (as opposed to an additional vessel), an intervention was considered multiple-vessel when an anterior tibial (AT) or dorsalis pedis (DP) vessel (or AT and DP) was intervened on in addition to the TPT, peroneal, or PT (or any combination of the three). For example, an angioplasty of the TPT and PT vessels within one procedure would be categorized as a single-vessel intervention (because the TPT and PT are in-line), while an angioplasty of the TPT and the AT would be categorized as multiple-vessel. For multiple-vessel interventions, a restenosis was classified when stenoses developed in all relevant multiple vessels (eg, stenosis of both AT and PT after both were treated) or when proximal in-line flow was impaired (eg, stenosis of the TPT after the peroneal, PT, and TPT were treated). For multilevel index procedures (ie, femoropopliteal and tibial), a reintervention was denoted only when an infrapopliteal vessel was re-treated. Importantly, Fig 1 illustrates the yearly proportion of multiple-vessel procedures performed within our practice throughout our study years. As will be further detailed in the Discussion, the spike of multiple-vessel procedures in 2007 was in response to a 2007 Faglia et al9 study suggesting the effectiveness of multiplevessel PTA on freedom from amputation. To account for this potential bias, we constructed a separate analysis with the same primary outcomes, but limited to the time period of 2007 to 2014. All analyses were performed on a per-limb basis. Pearson c2 and Fisher exact test were used for comparisons
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Fig 1. Yearly proportion of multiple-vessel endovascular infrapopliteal interventions for critical limb ischemia (CLI). *Data through May 2014.
of categoric variables. Means of continuous variables were compared using the Student t-test, assuming equal variances. Time-to-event analyses, by log-rank test and Cox proportional hazards regression modeling, were used to identify predictors of adverse outcomes for end points of interest. Statistical analyses were performed using Stata 12 software (StataCorp LP, College Station, Tex).
RESULTS Successful infrapopliteal endovascular intervention for CLI was performed in 558 limbs in 448 patients (86% for tissue loss, 14% for rest pain). At the index procedure, 503 (90%) were single-vessel and 55 (10%) were multiplevessel interventions. Patient baseline characteristics of both intervention types are provided in Table I. Patients most commonly presented with ulcerations, but no difference was noted between procedure types (53% in singlevessel vs 56% in multiple-vessel; P ¼ .62). Further, 15% of single-vessel and 11% of multiple-vessel patients presented with rest pain, which was also not significantly different (P ¼ .38). Wound, ischemia, and foot infection clinical stage proportions were also similar between groups (P ¼ .63), with both procedure types most commonly presenting with clinical stage 4 (41% vs 47%; P ¼ .45).17 Postoperative aspirin (88% vs 86%; P ¼ .70), clopidogrel (89% vs 88%; P ¼ .83), statin (72% vs 70%; P ¼ .79), and warfarin (24% vs 23%; P ¼ .83) were also seen to have no significant difference when single-vessel and multiple-vessel interventions were compared. Patients undergoing a single-vessel procedure tended to be older (72 vs 68 years), but this difference was also insignificant (P ¼ .05). Overall, there were no significant demographic differences between the two procedure types.
The proportional distribution of multiple-vessel interventions during the 10-year study ranged from w6% in 2005 to w18% in 2007 (Fig 1), after which the rate gradually declined. Technical success was achieved in 503 single-vessel limbs (94%) and in 49 multiple-vessel limbs (89% [94% total]; P ¼ .12). The six multiple-vessel limbs experiencing a failure that were included within this analysis involved a failure within one vessel, and at least two successful intervened-on vessels. Single-vessel interventions were more commonly performed in those with a prior ipsilateral endovascular procedure (16% vs 6%; P ¼ .03) and in those with a prior ipsilateral bypass procedure (20% vs 9%, P ¼ .04; Table I). Tibial TASC1 classification did not differ between groups, with TASC D lesions occurring in 30% of both single-vessel and multiplevessel interventions. In addition, infrapopliteal stenting occurred in 13% of single-vessel procedures and in 6% of multiple-vessel procedures (P ¼ .10; Table II). Of the single-vessel procedures, 54% were multilevel, with 35% performed in conjunction with a popliteal angioplasty. Similarly, 40% of multiple-vessel procedures were multilevel, with 31% performed in conjunction with a popliteal angioplasty. Perioperative complications (ie, in-hospital or 30-day) did not differ between single-vessel and multiple-vessel interventions (10% vs 15%; P ¼ .32). Among the 293 patients with follow-up $6 months, complete wound healing occurred in 37% of single-vessel patients and in 41% of multiple-vessel patients (P ¼ .13; Table III). KaplanMeier analysis revealed that freedom from restenosis #1 year (71% vs 79%, P ¼ .32; Fig 2, a), freedom from major amputation #1 year (84% vs 90%, P ¼ .23; Fig 2, b), and freedom from reintervention #1 year (78% vs 80%,
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Table I. Baseline characteristics of patients undergoing single-vessel and multiple-vessel infrapopliteal endovascular interventions for critical limb ischemia (CLI)
Variable
Single-vessel Multiple-vessel (n ¼ 503), (n ¼ 55), No. (%) No. (%) P value
Demographics 71.5 (11.8)
68.2 (13.8)
.05
Male sex
259 (52)
34 (62)
.15
243 (49)
Hypertension
421 (84)
48 (87)
.57
Diabetes
395 (79)
48 (87)
.15
Chronic renal insufficiency
126 (25)
15 (27)
.74
Dialysis dependence
92 (18)
12 (22)
.52
History of myocardial infarction
95 (19)
11 (20)
.86
140 (28)
10 (18)
.12
Smoking history
25 (46)
.65
71 (14)
2 (3.6)
.03
175 (35)
17 (31)
.57
161 (32)
14 (26)
.32
Infrapopliteal
65 (13)
3 (5.5)
.10
Femoropopliteal
114 (23)
11 (20)
.65
Table III. Postoperative outcomes of patients undergoing single-vessel and multiple-vessel infrapopliteal endovascular interventions for critical limb ischemia (CLI) Single-vessel Multiple-vessel (n ¼ 503), (n ¼ 55), No. (%) No. (%)
P value
Perioperative (30-day or in-hospital)
.26
227 (55)
27 (59)
.59
Complications
51 (10)
8 (15)
.32
Length of stay, mean (SD), days
4.6 (10.8)
5.7 (6.8)
.51
Mortality
23 (4.6)
4 (7.3)
.38
3 (5.5)
.03
Infrapopliteal PTA
43 (8.6)
1 (1.8)
.08
Bypass
99 (20)
5 (9.1)
.04
75 (15)
9 (16)
.78
77 (15)
6 (11)
.38
Indication Ulcer
266 (53)
31 (56)
.62
Gangrene
163 (33)
18 (33)
.96
WIfI clinical stage17
.63
Clinical stage 1
7 (1.6)
Clinical stage 2
95 (22)
Clinical stage 3
149 (35)
18 (37)
Clinical stage 4
177 (41)
23 (47)
1 (2.0) 7 (14)
Tibial TASC classification A
.06
2 (3.6)
83 (17)
None
22 (40)
39 (7.8)
PTA (any)
Rest pain
Popliteal
Outcomes
Prior intervention
Minor amputation
269 (54)
Proximal vessel
Stent
Coronary artery disease
COPD
Single-vessel Multiple-vessel (n ¼ 503), (n ¼ 55), No. (%) No. (%) P value
Procedural details
Superficial femoral
Comorbidities
Congestive heart failure
Table II. Procedural details between single-vessel and multiple-vessel infrapopliteal endovascular interventions in patients with critical limb ischemia (CLI)
Multilevel intervention
Age, mean (SD) years
.88 11 (2.2)
1 (1.9)
95 (19)
10 (19)
B
95 (19)
13 (25)
C
147 (30)
13 (25)
D
151 (30)
16 (30)
COPD, Chronic obstructive pulmonary disease; PTA, percutaneous transluminal angioplasty; TASC, TransAtlantic Inter-Society Consensus; SD, standard deviation; WIfI, Wound, Ischemia, foot Infection. Data are presented as number (%) unless otherwise indciated.
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Wound healing at 6 months
.13
Complete
87 (37)
12 (41)
Incomplete
177 (63)
16 (59)
1-year Reintervention
84 (22)
9 (20)
.53
PTA/S
51 (14)
6 (14)
.71
Bypass
34 (9)
3 (7)
.49
Restenosis
113 (29)
9 (21)
.25
Major amputation
63 (16)
4 (10)
.24
205 (48)
22 (49)
.38
179 (48)
22 (53)
.42
RAS events 3-year Mortality
PTA/S, Percutaneous transluminal angioplasty with or without stenting; RAS, reintervention, major amputation, or stenosis. Data are presented as number (%) unless otherwise indciated.
P ¼ .53; Fig 2, c) did not differ between single-vessel and multiple-vessel interventions, combining for insignificant differences in freedom from 1-year RAS events (52% vs
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59 7
100 12
1 2 Time to Restenosis (Years)
75
3
Number at risk: Single-vessel: Multiple-vessel: 0
c
146 14
211 24
87 8
1 2 Time to Amputation (Years)
3
d
Single-vessel
75
75
Multiple-vessel
P = .17 S.E. does not exceed 10% ≤ 3 years
100
163 22
100
0
Single-vessel
P = .53
P = .43 S.E. does not exceed 10% ≤ 3 years
Number at risk: Single-vessel: Multiple-vessel: 0
191 25
124 14
1 2 Time to Reintervention (Years)
72 9 3
0
25
S.E. does not exceed 10% ≤ 3 years
50
Survival (%)
50
Multiple-vessel
25
Freedom from Reintervention (%)
100
25
Number at risk: Single-vessel: Multiple-vessel:
b
Single-vessel
50
75 50
P = .13 S.E. does not exceed 10% ≤ 3 years
0
;Freedom from Restenosis (%)
Single-vessel
Multiple-vessel
25
a
Multiple-vessel
0
5
-
Freedom from Amputation (%)
Number
0
-,
100
Volume
Number at risk: Single-vessel: Multiple-vessel: 0
268 30 1
186 17
123 12
2
3
Years
Fig 2. Freedom from primary outcomes between single-vessel vs multiple-vessel infrapopliteal interventions for critical limb ischemia (CLI): (a) restenosis, (b) major amputation, (c) reintervention, and (d) survival. S.E., Standard error.
51%; P ¼ .38). Further, similar analyses illustrated that survival at 1 and 3 years did not differ between procedure types (76% vs 75% [P ¼ .78] and 52% vs 47% [P ¼ .42], respectively; Table III; Fig 2, d). Finally, multivariable regression illustrated that amputation rates and RAS events did not differ between patients undergoing a single-vessel vs multiple-vessel intervention; tibial TASC classification and a prior ipsilateral bypass were, however, independently predictive of both major amputation (hazard ratio, 1.4 [95% confidence interval, 1.1-1.7] and 2.6 [1.6-4.3], respectively) and RAS events (1.2 [1.1-1.3] and 1.5 [1.3-2.3], respectively; Table IV). As mentioned, to account for the influence that the 2007 Faglia et al9 study had on the implementation of multiple-vessel procedures in our practice, we constructed a separate analysis with the same primary outcomes limited to 2007 to 2014. Restriction of the analysis to these years did not yield any substantial differences in wound healing, restenosis, reintervention, major amputation, RAS events, or survival between single-vessel and multiple-vessel infrapopliteal interventions.
DISCUSSION Our data suggest that there were no perioperative or 1-year differences in clinical outcomes among patients undergoing a single-vessel vs multiple-vessel infrapopliteal angioplasty for CLI. Although RAS events proved prevalent overall (49% at 1 year), time-to-event analysis revealed no difference in the proportion of patients experiencing any 1-year outcomes (notably, restenosis, reintervention, major amputation, and mortality) between single-vessel and multiple-vessel infrapopliteal interventions. It is also important to note that our definition of restenosis among patients who underwent a multiple infrapopliteal vessel intervention requires impairment of proximal in-line flow or stenosis among all relevant multiple vessels. Interestingly, despite this methodology allowing multiple-vessel interventions greater opportunity to be free from restenosis, we found no difference in restenosis rates. We previously reported that multilevel (ie, concomitant femoropopliteal and infrapopliteal segment intervention) vs infrapopliteal-only endovascular intervention did not influence amputation rates in a subset
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Table IV. Multivariable models for major amputation and RAS events (reintervention, major amputation, or stenosis) in patients undergoing single-vessel and multiple-vessel infrapopliteal endovascular interventions for critical limb ischemia (CLI) Major amputation Variable Multiple-vessel intervention
Hazard ratio
RAS events
95% Confidence interval
Hazard ratio
95% Confidence interval
0.6
0.2-1.5
0.9
0.6-1.4
Age
1.0
0.9-1.0
1.0
0.9-1.0
Male gender
1.1
0.7-1.8
1.4
a
Dialysis dependence
2.5
1.5-4.1
1.2
TASC classification
1.4
1.1-1.7a
1.2
Unsuitability for bypass
2.8
1.8-4.6a
1.1
2.6
a
1.5
Prior ipsilateral bypass
1.6-4.3
1.1-1.8a 0.9-1.7 1.1-1.3a 0.8-1.5 1.3-2.3a
TASC, TransAtlantic Inter-Society Consensus. a P < .05.
of this patient cohort.15,18 Although few studies have compared single-vessel vs multiple infrapopliteal vessel interventions, our results corroborate those of Acin et al,19 who found no difference at 24 months in freedom from major adverse limb events (ie, major reintervention or major amputation) (62% vs 71%; P ¼ .33), freedom from RAS events (24% vs 43%; P ¼ .35), or amputation-free survival (62% vs 64%; P ¼ .96) between 92 patients (101 procedures) in whom a single or a multiple infrapopliteal vessel intervention was attempted, respectively. Similarly, among 539 patients, Iida et al20 accounted for the number of infrapopliteal vessels that were patent after endovascular revascularization; however, although results purported no significant difference in 24-month major amputation rates among patients undergoing angiosome-related direct or indirect revascularization (92% vs 86%; P ¼ .12), no outcome analyses were performed on differences in number of treated vessels. Importantly, the requirements for restenosis for multiple-vessel interventions in these studies were unspecified. These insufficient specifications, differences in patient selection, and cohort size variations may account for the discrepancies in our study’s outcomes. In 2007, Faglia et al9 suggested a relationship between the number of occluded infrapopliteal arteries after angioplasty and the risk of amputation, with an odds ratio of 8.2 (95% confidence interval, 1.35-49.6) for each additionally occluded infrapopliteal vessel. However, this 420-patient study may not have answered the question regarding number of vessels treated, because there was a large spectrum of disease before occlusion that such an analysis does not address. The quality and quantity of vessel runoff to the foot likely plays a large role in patient selection for single-vessel vs multiple-vessel intervention, and we, therefore, believe that it is important to evaluate both occluded and nonoccluded vessels. It is critical to consider that the decision to perform a multiple-vessel procedure may have often been
contingent on either suboptimal outcomes with an initially planned single-vessel procedure or on the perceived technical ease of performance of the intervention in the second vessel and the potential for loss of a bypass target. In addition, as Fig 1 illustrates, our practice was influenced by the report of Faglia et al, with an increase in multiple-vessel revascularization in 2007; however, when we limited our analysis to the period 2007 to 2014, there was no change in our findings. This study has some important limitations. First, the retrospective nature of our study leads to incomplete documentation of certain clinical end points and an inability to inspect records outside of our electronic system, leading to a number of patients without followup $6 months and ultimately limiting our ability to certify practice recommendations from this analysis alone. Further, the indications for a single-vessel vs a multiple-vessel infrapopliteal intervention were variable, based on surgeon preference and the factors listed above, and, ultimately, not clear from the present study; since our data represent the experience of one group of surgeons at a single institution, our results are subject to the influence of specific referral patterns, surgeon experience, and patient selection preferences. In addition, although the inclusion of multiple limbs and multiple procedures from a single patient allowed us to use a larger analytic sample, the potential lack of independence of observations may be of concern. Finally, an assumption may be made about patients with multiple interventions having worse disease and, thus, having similar outcomes. Including tibial TASC class into our multivariable regression models should mitigate these concerns. Importantly, in patients with long-term follow-up, tibial angioplasty had a 49% RAS event rate within 1 year, raising critical questions regarding its durability and utility, certainly warranting further research; however, we hesitate to make strong recommendations based on this finding, because those with failure are more likely
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to have follow-up in our system, and thus, the failure rate may be overestimated.
CONCLUSIONS The results of this study suggest that, when compared to single-vessel intervention, multiple-vessel intervention does not improve outcomes after infrapopliteal angioplasty for CLI. Although our study investigated a large and diverse cohort and corroborated information from several related studies, multicenter and national dataset analyses are necessary to fully explore the outcomes of single-vessel vs multiple-vessel infrapopliteal interventions.
AUTHOR CONTRIBUTIONS Conception and design: JD, JM, PS, JH, RG, MW, MS Analysis and interpretation: JD, JM, PS, RG, MW, HV, MS Data collection: JD, JM, JH Writing the article: JD Critical revision of the article: JD, JM, PS, JH, RG, MW, HV, MS Final approval of the article: JD, JM, PS, JH, RG, MW, HV, MS Statistical analysis: JD Obtained funding: MS Overall responsibility: MS
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Submitted Jan 15, 2016; accepted May 4, 2016.