Association of Postangioplasty Femoropopliteal Dissections With Outcomes After Drug-Coated Balloon Angioplasty in the Femoropopliteal Arteries

Abstract

Purpose:

Balloon angioplasty for the treatment of femoropopliteal lesions is often complicated by postangioplasty dissections. While dissections are known to affect patency and reintervention after balloon angioplasty, the association between dissections and major adverse limb event (MALE) after drug-coated balloon (DCB) angioplasty remains uncertain. Thus, the postangioplasty dissection and bailout stenting patterns were investigated.

Materials and Methods:

This was a single-center retrospective study enrolling patients with de novo femoropopliteal lesions treated with DCB with/without stenting. Postangioplasty target vessel dissection was graded based to the coronary artery classification grades A-F, with grade C-F considered “severe.” Cox regression analysis was performed to examine the association of dissection severity with outcomes during 2-year follow up, among nonstented cases.

Results:

In 85.3% of the cases (N=203/238) a postangioplasty dissection was observed. The average dissection length was 55.57 mm (SD 36.71 mm), with 1 dissection present in 91.8% (N=180/196) and 2 or more dissections present in 8.2% (N=16/196). Dissection severity was grade A (19.8%), B (20.6%), C (23.1%), D (10.9%), E (10.1%), and F (0.8%). Bailout stenting was required in 40.4% of the patients, being more prevalent among grade C and grade E cases. Among 142 nonstented cases, dissections were present in 85.2%. A total of 75 (52.8%) of these dissections were grade A and B, while 46 (32.4%) were grade C to F. Among nonstented cases, grade C (hazard ratio [HR] 5.83; 95% CI 1.25 to 27.31; p=0.025) and grade D (HR 6.32; 95% CI 1.39 to 28.86; p=0.017) vs grade A dissections were associated with a higher risk for 2-year MALE. Multivariate analysis adjusting for several lesion characteristics demonstrated a statistically significant higher risk for 2-year MALE among the severe dissection group (HR 2.94; 95% CI 1.27 to 6.79; p = 0.012). Interestingly, the risks of limb loss (HR 1.30; 95% CI 0.22 to 7.79; p=0.774) and repeat revascularization (HR 0.95; 95% CI 0.40 to 2.26; p=0.905) during follow-up were similar between the 2 groups.

Conclusion:

This study indicated that nonstented moderate and severe postangioplasty dissections after DCB angioplasty were associated with higher risk for MALE. Future studies are needed to validate our results and determine other dissection characteristics (eg, total dissection length, lumen area, total number of dissections) that may affect the efficacy of DCB.

Keywords

dissection endovascular therapy drug-coated balloon paclitaxel coated balloon peripheral artery disease

Introduction

Femoropopliteal disease can lead to disabling claudication, rest pain, or tissue loss,^1–3 constituting the most common cause of symptomatic peripheral arterial disease (PAD).^4,5 Endovascular therapy (EVT) has been widely accepted as an effective treatment for symptomatic femoropopliteal disease, utilized in more than 50% of such cases.^6,7 Variable endovascular techniques and devices have been used for more extensive femoropopliteal lesions to achieve limb salvage,^8,9 offering better durability of endovascular interventions despite the increased biomechanical stress of the artery.^10–12

Novel drug-eluting technologies, including drug-coated balloons (DCB) and drug-eluting stents (DES), promise durable artery patency and superior clinical efficacy to that of plain balloon angioplasty with or without bare metal stenting (BMS).^13–15 Although the lower extremity arteries are conduit arteries, the environment is very hostile for stents due to constant movement, bending, twisting, external forces, and the long, slow flow diffusely diseased arteries. Thus, in accordance with the philosophy of minimizing permanent scaffold implantation due to the risk of in-stent restenosis and stent fracture,^16,17 attributed to repetitive femoropopliteal artery deformations during movements,¹⁸ DCBs have been developed. Innovative DCB designs offer minimal drug loss after balloon inflation, providing effective drug transfer to tissues.^19,20

Balloon angioplasty at the femoropopliteal segment is associated with angiographically visible acute target vessel dissections in 47% to 88% of the cases.^21,22 Postangioplasty dissections have been associated with both short- and long-term adverse outcomes,^23–25 with severe dissections correlated with worse outcome.²⁵ However, it has been proposed that high grade dissections (non–flow limiting) treated with a DCB might have acceptable outcome without the need for stent implantation.^23,26 This study aimed to investigate which grade of dissection post-DCB angioplasty is associated with worse clinical efficacy and as such, should be considered for further treatment.

Materials and Methods

Study Design and Patient Population

This was a single center, retrospective study of patients with either superficial femoral artery (SFA) or popliteal artery atherosclerotic disease treated with DCB angioplasty with/without provisional stent implantation at the Rocky Mountain Regional Veterans Affairs Medical Center (Aurora, CO). The study cohort included veterans who underwent peripheral vascular intervention of femoropopliteal lesions between 2014 and 2020. The study’s protocol was approved by the institutional review board and the study was conducted in accordance with the Declaration of Helsinki. Using the electronic medical records of each included subject, experienced data abstractors collected data about baseline, angiographic, procedure characteristics, and outcomes during a 2-year follow up period. Patients were grouped according to the severity of dissection based on the criteria for coronary artery dissection.²⁷ Grade A dissection was defined as dissection with minor radiolucent territories at the postangioplasty angiography, grade B was defined as any linear dissection, grade C was defined as dissection with extraluminal extravasation of contrast, any spiral dissection was defined as grade D, grade E was any dissection with persistent filling defects, and grade F was defined as complete occlusion of antegrade blood flow.

Treatment Methods

The anesthesia type, access site, crossing guidewires, support catheters, the adjuvant use of cutting balloons, stents, and/or atherectomy devices employed, were at the discretion of the operator. Aspirin and clopidogrel were administered pre- and postprocedurally at the discretion of the operator as well. For intraprocedural anticoagulation, heparin was administered, with the goal of activated clotting time (ACT) >250 seconds. The stents and/or balloons utilized were chosen based on availability and operator’s preference. The DCBs were used with inflation to nominal pressures for at least 3 minutes in all cases. Stents were placed in cases of significant residual stenosis (>30%), recoil, and/or flow-limiting dissection at the discretion of the operator. Final angiography was performed in all cases in order to determine procedural success and in cases of dissections to determine the dissection’s severity.

Definitions and Study Endpoints

Analyses of the DCB ± stenting cases were performed in order to determine postangioplasty dissection patterns and identify risk factors for dissection. The degree of dissection was assessed through consensus of 2 experienced interventional cardiologists, who examined all available angiograms. In cases of several dissection grades identified at the same target area, the highest grade was used for analysis purposes. Additionally, patients with grade A to F dissections that did not undergo stenting were grouped to nonsevere (none/A-B; N = 96) vs severe (C-F; N = 46) dissection groups. Comparisons were made between the 2 groups in terms of short- and long-term outcomes. The primary outcome was the 2-year major adverse limb event (MALE) rate (ie, defined as endovascular or surgical target lesion revascularization (TLR) for clinically significant femoropopliteal lesions, all-cause mortality and/or limb loss). Secondary outcomes included periprocedural outcomes [ie, procedural success (<30% residual stenosis and nonlimiting blood flow), myocardial infarction (MI), all-cause mortality, stroke] and 2-year freedom from limb loss, freedom from TLR, and freedom from all-cause mortality. Further sensitivity analyses, adjusted for several clinically significant lesion characteristics (ie, degree of PAD, chronic total occlusion, degree of calcification, lesion length, degree of target lesion stenosis at baseline) were conducted for the primary outcome in order to identify any associations of dissection grade with worse outcome at 2 years of follow-up.

Statistical Analysis

Binary variables, presented as absolute and relative frequencies, were compared using chi-square and Fisher’s exact tests. All continuous variables are presented as means ± standard deviations and were compared with the Wilcoxon rank-sum test. A logistic regression model was used to identify baseline patient and lesion characteristics associated with postangioplasty dissection. A Cox regression hazard model was developed to compare primary and secondary outcomes between the nonsevere vs severe dissection groups and investigate potential association between MALE and the degree of postangioplasty dissection. Hazard ratios (HR) with the corresponding 95% confidence intervals (CI) were used to examine the association of dissection severity and outcomes during 2-year follow-up. Additionally, the 2-year Kaplan-Meier (KM) survival curves for MALE, TLR, limb loss and all-cause mortality were estimated for each group. For all tests, p<0.05 was considered significant. All analyses were performed using STATA 14.1 software (STATA Corporation, College Station, TX, USA).

Results

Target Vessel Dissection Patterns

Over the study period, 238 patients were treated for atherosclerotic femoropopliteal disease with DCB angioplasty with/without stenting. In 85.3% of those patients (N=203/238) a postangioplasty dissection was observed, while in the remaining 14.7% of those patients no dissections occurred. The average dissection length was 55.57 mm (SD 36.71 mm) among stented and non-stented cases. In 91.8% (N=180/196) of those patients, 1 dissection was present, while in 7.6% (N=15/196) and 0.5% (N=1/196) 1 and 2 dissections were present, respectively. Most patients had dissections of grades A (N=47/238; 19.8%; mean dissection length 50.71 mm; SD 30.34), B (N=49/238; 20.6%; mean dissection length: 62.18 mm; SD 50.47), and C (N=55/238; 23.1%; mean dissection length 52.14 mm; SD 31.98), whereas grades D (N=26/238; 10.9%; mean dissection length 62.35 mm; SD 37.17), E (N=24; 10.1%; mean dissection length 61.50 mm; SD 35.62), and F (N=2/238; 0.8%; mean dissection length 75.00 mm; SD 35.36) were less often. Overall bailout stenting was required in 40.3% of the patients (N=96/238), being more prevalent among grade C (N=28/55; 29.2%), grade D (N=12/26; 12.5%), and grade E (N=17/24; 17.7%) cases. The corresponding vessel dissection pattern and bailout stenting rates after DCB angioplasty for femoropopliteal lesions is illustrated in Figure 1. The proportion of patients undergoing bailout stent within each dissection stratum increased with the degree of dissection severity and is presented in Figure 2.

Predictors of Any Grade of Postangioplasty Dissection Among Patients Undergoing DCB Angioplasty With/Without Stenting

The association of any grade of postangioplasty dissection and several baseline patient and lesion characteristics were examined with a multivariate analysis using a logistic regression model. Multivessel revascularization procedures (adjusted OR 5.21; 95% CI 1.06 to 25.75; p=0.043) and utilization of atherectomy devices (adjusted OR 4.52; 95% CI 1.13 to 18.04; p=0.033) were identified to be associated with higher incidence of dissection. Interestingly, univariate analysis showed that dissections were more commonly observed among cases of moderate/severe target lesion calcification (univariate OR 1.94; 95% CI 0.93 to 4.03; p=0.077) and active smokers (univariate OR 2.99; 95% CI 0.83 to 10.78; p=0.093); however, no statistical significance was reached. Additionally, obese patients with greater body mass index (BMI) were more likely to develop postangioplasty dissection in the univariate analysis, although multivariate analysis failed to show any association (adjusted OR 1.10; 95% CI 0.98 to 1.25; p=0.113). Predictive factors for postangioplasty dissection are presented in Table 1.

Table 1.

Predictive Factors for Postangioplasty Dissection.

Outcomes	Unadjusted OR (95% CI) p-Value	Unadjusted OR (95% CI) p-Value
Male	1.17 (0.25 to 5.58) p=0.844	—
Caucasian	0.76 (0.27 to 2.09) p=0.591	—
BMI	1.07 (1.00 to 1.15) p=0.047	1.10 (0.98 to 1.25) p=0.113
Diabetes	0.87 (0.41 to 1.86) p=0.723	—
HTN	0.34 (0.04 to 2.68) p=0.308	—
CAD	1.03 (0.49 to 2.13) p=0.947	—
CHF	0.59 (0.25 to 1.37) p=0.217	—
AAA	0.47 (0.17 to 1.28) p=0.141	—
Pulmonary disease	1.35 (0.44 to 4.11) p=0.595	—
Dyslipidemia	0.57 (0.07 to 4.58) p=0.595	—
Malignancy	2.07 (0.60 to 7.16) p=0.250	—
ESRD	1.04 (0.22 to 4.84) p=0.964	—
Previous smoker	1.33 (0.39 to 4.53) p=0.650	—
Current smoker	2.99 (0.83 to 10.78) p=0.093	—
Statin	0.84 (0.27 to 2.57) p=0.757	—
Multivessel treatment	5.15 (1.10 to 24.09) p=0.037	5.21 (1.06 to 25.75) p=0.043
Lesion length	0.99 (0.99 to 1.01) p=0.632	—
Rutherford classification >3	0.50 (0.24 to 1.05) p=0.069	—
Poor run-off (<3)	0.85 (0.21 to 3.41) p=0.814	—
History of amputation	0.17 (0.01 to 2.76) p=0.212	—
Urgent vs emergent	0.97 (0.30 to 3.08) p=0.957	—
Moderate/severe calcification	1.94 (0.93 to 4.03) p=0.077	—
Thrombus	0.90 (0.10 to 8.27) p=0.924	—
CTO	2.20 (0.64 to 7.61) p=0.213	—
Cutting balloon	1.79 (0.82 to 3.92) p=0.144	—
Atherectomy	2.37 (1.12 to 5.03) p=0.024	4.52 (1.13 to 18.04) p=0.033

Abbreviations: AAA, abdominal aortic aneurysm; BMI, body mass index; CAD, coronary artery disease; CHF, congestive heart failure; CTO, chronic total occlusion; ESRD, end-stage renal disease; HTN, hypertension.

Clinical Outcomes According to Postangioplasty Dissection Pattern Among Nonstented Cases

Among the 142 nonstented patients, a postangioplasty dissection of any grade occurred in 85.2% of the cases (type A/B: N=96/142; 67.6% vs type C-F: N=46/142; 32.4%). Most patients had dissections of grades A (N=37/142; 26.1%), B (N=38/142; 26.8%), and C (N=27/142; 19.0%), whereas grades D (N=12/142; 8.5%), E (N=7/142; 4.9%), and F (N=0/142; 0%) were less often. Overall, the nonsevere and severe dissection groups were similar in baseline, lesion, and procedural characteristics, with only a few differences detected. Details about important baseline and lesion characteristics are presented in Tables 2 and 3, respectively. No deaths, strokes, and MI occurred periprocedurally. The overall target lesion success was 94.9%, without any differences between the 2 groups (nonsevere 94.5% vs severe 95.6%; p=0.794). Most patients were discharged on dual antiplatelet therapy with aspirin and clopidogrel and were followed up for up to 2 years. Details regarding procedural characteristics, periprocedural, and long-term outcomes are presented in Table 4.

Table 2.

Baseline Characteristics.

Variables	Nonsevere Dissection (n= 96)	Severe Dissection (n=46)	Total (n=142)	p
Male	92.7% (89/96)	95.7% (44/46)	93.7% (133/142)	0.500
Whites	81.1% (77/95)	82.2% (37/45)	81.4% (114/140)	0.868
Age, years	69.8±7.6	63.5±15.2	67.7±11.0	0.007
BMI, kg/m²	28.5±7.1	29.4±6.2	28.8±6.8	0.269
Diabetes	65.9% (58/88)	71.7% (33/46)	67.9% (91/134)	0.492
HbA1c, %	7.4±1.9	8.1±2.3	7.6±2.0	0.055
HTN	95.8% (92/96)	89.1% (41/46)	93.7% (133/142)	0.125
SBP, mm Hg	137.8±22.0	135.7±20.8	137.2±21.5	0.571
Carotid stenosis	24.5% (23/94)	19.6% (9/46)	22.9% (32/140)	0.516
CAD	62.5% (60/96)	58.7% (27/46)	61.3% (87/142)	0.663
CHF	19.0% (18/95)	22.2% (10/45)	20.0% (28/140)	0.651
AAA	12.5% (12/96)	4.4% (2/46)	9.9% (14/142)	0.127
Dyslipidemia	95.8% (92/96)	95.6% (44/46)	95.8% (136/142)	0.960
Total cholesterol, mg/dL	172.6±58.1	164.5±48.8	170.1±55.3	0.751
LDL, mg/dL	99.2±45.4	97.0 ± 36.8	98.5 ± 42.7	0.867
HDL, mg/dL	44.3±28.6	40.3 ± 10.9	43.0 ± 24.4	0.468
TG, mg/dL	242.4±210.2	221.2 ± 129.8	235.6 ± 187.8	0.895
Statin use	90.9% (80/88)	84.4% (8/45)	88.7% (118/133)	0.265
ESRD	5.2% (5/96)	8.7% (4/46)	6.3% (9/142)	0.425
Serum creatinine, mg/dL	1.5±1.4	1.8±2.2	1.6±1.7	0.831
Cancer	10.4% (10/96)	15.2% (7/46)	12.0% (17/142)	0.410
COPD	9.4% (9/96)	17.4% (8/46)	12.0% (17/142)	0.168
Nonsmokers	11.6% (11/95)	2.2% (1/46)	8.5% (12/141)	0.172
Previous smokers (>3 mo abstinence)	45.3% (43/95)	50.0% (23/46)	46.8% (66/141)
Current smokers	43.2% (41/95)	47.8% (22/46)	44.7% (63/141)
CLI	47.9% (46/96)	37.0% (17/46)	44.4% (63/142)	0.219
Rutherford classification
Category 1	0.0% (0/95)	2.2% (1/46)	0.7% (1/141)	0.107
Category 2	6.3% (6/95)	2.2% (1/46)	5.0% (7/141)
Category 3	41.1% (39/95)	52.2% (24/46)	44.7% (63/141)
Category 4	24.2% (23/95)	8.7% (4/46)	19.2% (27/141)
Category 5	24.2% (23/95)	32.6% (15/46)	27.0% (38/141)
Category 6	4.2% (4/95)	2.2% (1/46)	3.6% (5/141)
CVA history	21.9% (21/96)	6.5% (3/46)	16.9% (24/142)	0.022
Preprocedural ABI	0.61±0.27	0.66±0.36	0.63±0.30	0.275
Preprocedural TBI	0.38±0.19	0.42±0.20	0.39±0.19	0.509

Abbreviations: AAA, abdominal aortic aneurysm; ABI, ankle-brachial index; BMI, body mass index; CAD, coronary artery disease; CHF, congestive heart failure; CLI, critical limb ischemia; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; eGFR, effective glomerular filtration rate; ESRD, end-stage renal disease; HTN, hypertension; MI, myocardial infarction; SBP, systolic blood pressure; TBI, toe-brachial index; TG, triglycerides.

Table 3.

Lesion Characteristics.

Variables	Nonsevere Dissection (n=96)	Severe Dissection (n=46)	Total (n=142)	p
Lesion location
SFA	75.0% (72/96)	78.3% (36/46)	76.1% (108/142)	0.670
Popliteal	25.0% (24/96)	21.7% (10/46)	23.9% (34/142)	0.670
Mean lesion length, mm	122.4±56.5	134.7±59.1	126.8±57.5	0.207
Mean target lesion stenosis, %	91.2±11.1	95.8±9.0	92.5±10.7	0.032
Mean infrapopliteal runoff	2.29±0.79	2.30±0.86	2.29±0.81	0.851
Calcium (moderate or severe)	63.7% (58/91)	77.8% (35/45)	68.4% (93/136)	0.098
Chronic total occlusion	34.4% (33/96)	43.5% (20/46)	37.3% (53/142)	0.294
Thrombus	4.6% (2/44)	0.0% (0/20)	3.1% (2/64)	0.333

Abbreviation: SFA, superficial femoral artery.

Table 4.

Procedural Characteristics and Complications During Follow-up.

Variables	Nonsevere Dissection (n=96)	Severe Dissection (n=46)	Total (n=142)	p
Procedural characteristics
Fluoroscopy time, min	35.9±22.1	48.0±27.4	39.3±24.1	0.052
Contrast, mL	165.6±70.1	211.5±63.1	178.6±70.8	0.019
Atherectomy	58.8% (50/85)	67.5% (27/40)	61.6% (77/125)	0.352
Cutting balloon	77.3% (68/88)	75.6% (31/41)	76.7% (99/129)	0.835
Target lesion success	94.5% (86/91)	95.6% (43/45)	94.9% (129/136)	0.794
After the procedure
Complications at access site	1.0% (1/96)	6.7% (3/45)	2.8% (4/141)	0.061
Death/stroke/MI in lab	0.0% (0/96)	0.0% (0/45)	0.0% (0/141)	—
All-cause mortality during follow-up	25.3% (24/95)	32.6% (15/46)	27.7% (39/141)	0.361
Stroke during follow-up	5.3% (5/94)	6.5% (3/46)	5.7% (8/140)	0.773
MI during follow-up	8.5% (8/94)	8.7% (4/46)	8.6% (12/140)	0.971
Limb loss during follow-up	3.2% (3/93)	9.1% (4/44)	5.1% (7/137)	0.145
TLR during follow-up	31.2% (24/77)	36.8% (13/38)	32.2% (37/115)	0.743
12-month primary patency	87.7% (71/81)	81.6% (31/38)	85.7% (102/119)	0.377
Mean Rutherford class 30 days	1.3±1.8	1.4±1.8	1.3±1.8	0.680
Mean Rutherford class 1 year	1.5±1.7	1.5±1.8	1.5±1.7	0.776
ABI 30 days	0.67±0.43	0.65±0.40	0.67±0.42	0.622
ABI 1 year	0.70±0.38	0.53±0.48	0.65±0.41	0.661
TBI 30 days	0.40±0.52	0.51±0.08	0.43±0.44	0.723
TBI 1 year	0.42±0.28	0.65±0.32	0.51±0.31	0.288

Abbreviations: ABI, ankle-brachial index; MI, myocardial infarction; TBI, toe-brachial index; TLR, target lesion revascularization.

The risk for 2-year all-cause mortality and 2-year limb loss was similar between nonsevere and severe dissection groups, with no statistical significance detected. Sensitivity analyses stratified by dissection grade (grade A vs B vs C vs D vs E vs F) failed to show any association between dissection patterns and late survival or limb loss. Interestingly, a strong trend for higher 2-year TLR risk was identified among patients with grade B and C vs A postangioplasty dissections (grade B vs A: HR 2.98; 95% CI 0.99 to 8.89; p=0.051; grade C vs A HR 3.13; 95% CI 0.99 to 9.85; p=0.052). However, statistical significance was not reached. The corresponding HRs and KM estimates are presented in Supplementary Table 1.

Association of the 2-Year Primary Outcome (MALE) With Lesion Characteristics and the Postangioplasty Dissection Patterns

Multivariate analysis adjusting for several lesion characteristics [ie, chronic limb-threatening ischemi (CLTI), chronic total occlusion (CTO), moderate/severe calcification, lesion length, target lesion stenosis], demonstrated a statistically significant higher risk for 2-year MALE among patients with severe postangioplasty dissection (HR 2.94; 95% CI 1.27 to 6.79; p=0.012), likely driven from the higher need for reinterventions among severe dissection cases. Sensitivity analysis based on postprocedural dissection patterns showed a correlation of the postangioplasty dissection pattern and the risk for 2-year MALE. Patients with grade C (grade C vs A HR 5.83; 95% CI 1.25 to 27.31; p=0.025) and grade D (grade D vs A HR 6.32; 95% CI 1.39 to 28.86; p=0.017) dissections were at higher risk for MALE during 2-year follow-up. Among nonstented cases, dissection grade A (univariate: HR 0.90; 95% CI 0.28 to 2.85; p=0.858; multivariate: nonestimable; p=1.000), grade B (univariate: HR 1.33; 95% CI 0.46 to 3.84; p=0.596; multivariate: nonestimable; p=1.000) and combined grades A and B (univariate: HR 1.10; 95% CI 0.41 to 2.96; p=0.854; multivariate: nonestimable) compared with no dissection cases were not associated with higher risk for 2-year MALE.

A summary of 2-year MALE analyses is presented in Supplementary Table 2, while the corresponding HRs for MALE are illustrated in Figure 3. No lesion characteristics (ie, CLTI, CTO, moderate/severe calcification, lesion length, target lesion stenosis) were statistically associated with worse outcome, although a strong trend toward high risk for adverse events was observed among patients presented with Rutherford classification greater than 3 (HR 2.15; 95% CI 0.89 to 5.25; p=0.094).

Discussion

The current study included patients with femoropopliteal lesions who underwent DCB angioplasty with/without provisional stenting. In 85.3% of the patients a postangioplasty dissection was observed, while bailout stenting was deemed necessary in 40.3%. Multivessel intervention and atherectomy were independently associated with postangioplasty dissection. Among the nonstented cases, the univariate 2-year risk for all-cause mortality, TLR and limb loss were not statistically different between the nonsevere vs severe dissection groups. However, the multivariate analysis showed clear association between the postangioplasty dissection and 2-year MALE. More severe grades of dissection were correlated with higher risk for adverse events during 2-year follow-up. Interestingly no associations were identified between risk for MALE and several lesion characteristics, likely indicating that dissection patterns rather than specific lesion characteristics have a more crucial role in the disease course, when drug-eluting technology is utilized.

Animal models^28,29 and studies on cadaveric vessels^30–33 have demonstrated that the acute luminal gain after balloon angioplasty is attributed to a combination of cracking/dehiscence of the intima and arterial wall stretching, resulting in permanent deformation.^34,35 Heterogenous vessel wall elastic properties may lead to nonuniformity dilation of the target vessel during balloon angioplasty leading to fissuring of the inner arterial wall and its separation from the outer portions of the vessel (ie, dissection).^33,36,37 As such, there is an equilibrium between forces applied for adequate acute luminal gain and the creation of dissection. EVT, including balloon angioplasty with/without stenting has been established as the main treatment strategy for femoropopliteal lesions.

BMS and DES utilized for the treatment of femoropopliteal lesions, have shown a higher primary patency rate compared to plain balloon angioplasty^14,38; however, stenting has been challenged by the burden of scaffold implantation, stent fracture and stent thrombosis.^39,40 Therefore, several stentless approaches have been progressively developed, including atherosclerotic plaque modification with specialty balloons and/or atherectomy devices followed by DCB angioplasty.^20,41,42 Plaque modification promises increased vessel compliance and as such lower risk for post-angioplasty dissection. However, dissection after balloon angioplasty remains a concern. Its prevalence has been estimated between 47% and 88% of cases overall,^21,22 while in our analysis postangioplasty dissection was observed in 85.3% of the cases. In general, post-angioplasty dissections have been associated with poor short- and long-term outcomes, however it still remains unclear in what extent paclitaxel eluting technology may alter the course of postangioplasty dissections.^23–25

Tepe et al²³ investigated the impact of paclitaxel on outcomes after DCB angioplasty resulting in dissection. Overall, data about 86 subjects with femoropopliteal disease were retrieved from the Thunder trial (ClinicalTrials.gov Identifier: NCT00156624) and were analyzed.²³ The study demonstrated less late lumen loss and restenosis among DCB cases, with cases of postangioplasty dissection grades C to E to benefit more from DCB utilization.²³ As such the authors suggested that patients with non–flow limiting dissection after DCB angioplasty might have acceptable outcomes without the need for provisional stenting.²³ Therefore, based on the lower restenosis rate of DCB angioplasty and the antiproliferative properties of paclitaxel, it could be hypothesized that the threshold for stenting should be higher for the treatment of post-DCB dissections.⁴³

Recently the Tack Endovascular System has been introduced, which is an implantable dissection repair device that leaves behind approximately 70% less metal than a comparable stent.⁴⁴ The Tack Optimized Balloon Angioplasty (TOBA) study enrolled 130 patients with postangioplasty dissections, treated with the Tack device and showed favorable technical success (98.5%) and promising 12-month primary patency (76.4%) with no fractures noted.⁴⁴ Similarly, the TOBA II study including 213 patients with dissection types A through F after DCB and standard balloon angioplasty showed excellent procedural success (100%), with 86.5% 12-month freedom from TLR and no device fractures occurred.⁴⁵ Additional data regarding safety and efficacy of Tack implant specifically for post-DCB dissections treatment were provided by TOBA III.⁴⁶ This was a prospective, multicenter, single-arm study of 201 undergoing DCB angioplasty for standard- (≥20 to 150 mm) and long-length femoropopliteal lesions (>150 to 250 mm).⁴⁶ The study demonstrated favorable device success in both cohorts (standard length 95.8%; long length 97.7%), with only 1 bailout stent placed among the entire population and durable patency over time, with low need for secondary interventions.⁴⁶ Thus, due to its unique features, the Tack device could be a safe and effective alternative to balloon inflation and/or stenting for resolution of post-DCB angioplasties, avoiding the metallic burden of stents. However, it is still unknown in what extent post-DCB dissections affect long-term outcomes and whether paclitaxel has an impact on the prognosis of these cases.

A retrospective multicenter study by Fujihara et al²⁶ studying 193 patients, who underwent balloon angioplasty only (ie, without provisional stenting), demonstrated a higher risk for restenosis, TLR, and loss of patency during 2-year follow up among cases with severe dissections (C-F). The study also provided evidence that the risk for adverse events increased with the severity of dissections from grades C to F.²⁶ Thus, the authors suggested that in cases of severe postangioplasty dissections, balloon angioplasty without bailout stenting is of limited efficacy, in terms of patency.²⁶ Similarly, in our study, including only DCB cases, severe grades of dissections were correlated with higher risk for 2-year MALE. Additionally, separate analyses provided evidence that there could be an association between the grade of dissection and adverse outcomes. Thus, this study indicated that DCB angioplasty and as such paclitaxel application, might not be as effective during a 2-year follow up in cases of severe vs nonsevere dissections. Nonetheless, the individual rates of all-cause mortality, TLR and limb loss were acceptable in both the severe and the nonsevere dissections group and as such the actual impact of dissections on DCB efficacy remained unclear.

Therefore, larger studies with standardized treatment protocols are warranted to validate our results and further investigate paclitaxel effect on outcomes of EVT complicated with postangioplasty dissection. Furthermore, due to the absence of an objective definition of severe postangioplasty dissection for femoropopliteal interventions, future studies are needed to determine which factors of the dissection patterns (eg, total dissection length, true lumen area, total number of dissections, maximum width of the dissection) affect the efficacy of balloon angioplasty, in an effort to identify which grades of dissections should be treated. However, as dissection cases have been associated with worse outcomes, identification of risk factors for postangioplasty dissection, including lesion and procedural characteristics, would be of great clinical significance as well. This could help minimize iatrogenic post-EVT dissections.

Hereby, vessel calcification has been associated with an additional increased risk for postprocedural flow-limiting dissections.^47,48 Additionally, the iDissection pilot study provided significant evidence that several types of atherectomy were associated with intramural hematoma, detected by intravascular ultrasound, challenging the widely held belief that atherectomy utilization reduces the incidence of postangioplasty dissections.⁴⁹ Therefore, the identification of postangioplasty risk factors would allow an estimation of the outcome, providing important information for an optimal treatment approach minimizing the complications associated with unnecessary stent implantations.

Limitations

This was a retrospective analysis, utilizing data from a Veteran Affairs hospital, which might limit the generalizability of the study results. Second, given the observational design of this study, case selection and operator’s bias might have affected the outcomes. Third, no core laboratory adjudicated the angiographic images. Additionally, the sample size of the study was relatively small and as such the sensitivity analysis about lesion characteristics associated with worse outcomes might be underpowered to show any statistical significance. Moreover, it should be noted that the sensitivity analysis investigating the risk for 2-year MALE among the several dissection grades, failed to show an association between grade E and MALE, likely attributed to small sample size. Last, there were some discrepancies on the results between our study and previous reports. However, we believe that differences in baseline characteristics and overall small sample sizes might have limited the power to determine statistical significance.

Conclusion

EVT of femoropopliteal lesions is often complicated with postangioplasty dissections, which have been associated with worse short- and long-term outcomes. However, it is still unclear what impact drug eluting technology could have on the course of postangioplasty dissections. Similar to previous reports, our study indicated that severe grades of postangioplasty dissections are associated with higher risk for MALE. Additionally, sensitivity analysis showed that this risk for adverse events might increase with greater grades of postangioplasty dissections (from C to F). Future studies are needed to determine characteristics of dissection patterns (eg, total dissection length, true lumen area, total number of dissections, maximum width of the dissection) that may affect efficacy of DCB angioplasty, with the optimal goal to develop specific treatment protocols for the several degrees of postangioplasty dissections at the femoropopliteal segment.

Supplemental Material

sj-pdf-1-jet-10.1177_15266028211016441 – Supplemental material for Association of Postangioplasty Femoropopliteal Dissections With Outcomes After Drug-Coated Balloon Angioplasty in the Femoropopliteal Arteries

Supplemental material, sj-pdf-1-jet-10.1177_15266028211016441 for Association of Postangioplasty Femoropopliteal Dissections With Outcomes After Drug-Coated Balloon Angioplasty in the Femoropopliteal Arteries by Stefanos Giannopoulos, Aaron Strobel, Eric Rudofker, Christopher Kovach, Peter A. Schneider and Ehrin J. Armstrong in Journal of Endovascular Therapy

Supplemental Material

sj-pdf-2-jet-10.1177_15266028211016441 – Supplemental material for Association of Postangioplasty Femoropopliteal Dissections With Outcomes After Drug-Coated Balloon Angioplasty in the Femoropopliteal Arteries

Supplemental material, sj-pdf-2-jet-10.1177_15266028211016441 for Association of Postangioplasty Femoropopliteal Dissections With Outcomes After Drug-Coated Balloon Angioplasty in the Femoropopliteal Arteries by Stefanos Giannopoulos, Aaron Strobel, Eric Rudofker, Christopher Kovach, Peter A. Schneider and Ehrin J. Armstrong in Journal of Endovascular Therapy

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Schneider is a board member of VIVA Physicians Inc; a compensated consultant to Medtronic, Boston Scientific, Cardiovascular Systems Incorporated (CSI); a cofounder of Intact Vascular and Cagent. Dr Armstrong is a consultant to Abbott Vascular, Boston Scientific, Cardiovascular Systems Incorporated (CSI), Gore, Intact Vascular, Medtronic, Philips, and PQ Bypass. All other authors have no relationships to disclose.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Stefanos Giannopoulos

Christopher Kovach

Peter A. Schneider

Supplemental Material

Supplemental material for this article is available online.

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