Abstract
Aim: The accuracy of the DISFORM (diameter reduction, spiral shape, flow impairment, or adverse morphology) classification system has not been validated.
Methods: This retrospective multicenter observational study enrolled 288 consecutive patients with lower extremity artery disease who underwent endovascular therapy with drug-coated balloons for femoropopliteal lesions between January 2018 and December 2021. Patients were classified into DISFORM I–IV groups. Primary patency (PP) and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months, and recurrence predictors at 12 months were investigated.
Results: In total, 183, 66, 11, and 28 patients were classified into DISFORM I, II, III, and IV groups, respectively. In the DISFORM I, II, III, and IV groups, the PP rates were 75.3%, 91.1%, 87.5%, and 50.0%, respectively, and freedom from CD-TLR rates were 86.0%, 91.6%, 88.9%, and 76.7%, respectively, at 12 months. In the DISFORM I–III and IV groups, the PP rates were 79.4% and 50.0%, respectively, and freedom from CD-TLR rates were 87.5% and 76.7%, respectively, at 12 months. Multivariate analysis showed that chronic limb-threatening ischemia, DISFORM IV, and Lutonix™ use were independent predictors of PP loss at 12 months.
Conclusion: DISFORM IV had a lower PP rate than DISFORM I–III in midterm phase.
Introduction
Recent advances in drug-eluting technology have been remarkable. With the advent of two types of drug-eluting devices, drug eluting-stents (DES) and drug-coated balloons (DCB), the outcomes of femoropopliteal (FP) lesions have dramatically improved. DES shows better primary patency rates than drug-coated and bare nitinol stents1, 2). Although DES also demonstrates good clinical performance in real-world practice, they carry a risk of thrombotic occlusion3). In contrast, DCB shows better primary patency than plain old balloon angioplasty (POBA), and comparable results have been reported in direct comparisons with DES in real-world clinical settings4, 5). As real-world clinical-based studies have progressed, predictors of recurrence have gradually been identified for both DES and DCB; however, the distinction depending on lesion characteristics is unclear3, 5-10). Moreover, reports regarding whether severe dissection predicts recurrence of DCB are controversial7, 10).
In 2021, the DISFORM (diameter reduction, spiral shape, flow impairment, or adverse morphology) classification system was proposed as an index to determine the necessity of scaffolding based on angiographic dissection11). Dissection in DISFORM was evaluated morphologically and hemodynamically regarding uniaxial width, longitudinal length, spiral shape, flow impairment, and multiplicity. After evaluating each factor, the dissection was classified into four groups (grades I, II, III, and IV). The DISFORM classification system is unique because it comprehensively consists of clinical experience by expert physicians and hemodynamic assessment of the dissection. However, its accuracy has not been validated in real-world clinical settings.
Aim
This study aimed to investigate accuracy of the DISFORM classification system in real-world clinical settings.
Methods
Population & Procedure Protocol
We analyzed the ASIGARU PAD registry database, which included consecutive patients with lower extremity artery disease (LEAD) who underwent endovascular therapy (EVT) between January 2018 and December 2021 at eight institutions in Japan. The ASIGARU PAD registry is an ongoing multi-center observational registry. The inclusion criteria were as follows: aged ≥ 20 years, patients with symptomatic LEAD of Rutherford category 2–6, and de novo stenotic or occlusive FP lesions treated with DCB. Patients who underwent EVT for acute limb ischemia (ALI), traumatic complications, or aortic dissection were excluded. Patients undergoing hybrid therapy with EVT and open surgical procedures, restenotic lesions, or bailout stenting were excluded. In total, 288 consecutive patients were enrolled in this study. At least one antithrombotic agent (Aspirin, Clopidogrel, or Prasugrel) was administered before EVT as the initial antithrombotic therapy. The common femoral, brachial, and radial arteries were used as primary access sites for EVT. After sheath insertion, an intra-arterial or intravenous heparin bolus was administered as an anticoagulant in all cases. The heparin dose was at the investigators’ discretion, and the activated clotting time was controlled between 250 and 300 s. After the wire was passed, balloon dilatation was performed using a plain, high-pressure, or scoring balloon. An angiographic evaluation was performed in all the cases after balloon dilatation. If necessary, additional balloon dilatation was performed at the investigators’ discretion, and angiography was performed again. Subsequently, DCB dilatation and a final angiographic evaluation were performed. IN.PACT™ Admiral™ (Medtronic, Dublin, Ireland), Lutonix™ (BD, Franklin Lakes, U.S.A.), and Ranger™ (Boston Scientific, Marlboro, U.S.A.) were used as DCB.
Evaluation of DISFORM
Angiographic images before DCB dilatation were used to evaluate DISFORM. DISFORM was evaluated independently by two experienced operators. Dissection was assessed in four categories according to morphology and pathophysiology:1) diameter reduction (DX), 2) presence of a spiral shape (SX), 3) flow impairment (FX), and 4) dissection length and number of dissections (MX)11). Finally, all cases were classified into four grades based on the results of the categories11). Representative cases of DISFORM I–IV are shown in Fig.1.
Follow-Up Protocol
Clinical follow-ups were conducted at baseline, one month, three months, six months, and 12 months. Hemodynamic evaluation using the ankle-brachial pressure index (ABI) was performed at each visit. Vascular assessment using duplex ultrasonography (DUS) was done at six months, and 12 months. Cases in which recurrence was noted on DUS were evaluated for recurrence patterns.
Study Outcome
The outcome measures were primary patency at 12 months and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months. Predictors of recurrence at 12 months were also investigated.
Definition
LEAD is defined as an atherosclerotic occlusive disease of the lower extremity artery12). The clinical severity of LEAD was assessed using the Rutherford classification, which consists of seven grades (0–6). Chronic limb-threatening ischemia (CLTI) was defined according to the following criteria:1) ischemic rest pain with confirmatory hemodynamic studies, 2) diabetic foot ulcer or any lower limb ulceration present for at least two weeks, and 3) gangrene involving any portion of the lower limb or foot13). Frailty severity was categorized into three groups based on the Clinical Frailty Scale (CFS):1–3 (good activities), 4–5 (mild frailty), and 6–8 (moderate or severe frailty)14). The severity of the FP lesions was assessed using the Trans-Atlantic Inter-Society Consensus (TASC II) classification. Angiographic lesion calcification was evaluated using the peripheral artery calcification scoring system (PACSS), which consists of five grades (0–4); PACSS grade 4 was defined as severe calcification15). Angiographic dissection was classified into six grades (A–F) according to the dissection criteria16). Technical success was defined as the successful completion of the procedure with ≤ 30% residual stenosis. Primary patency was freedom from the target lesion recurrence defined as a peak systolic velocity ratio (PSVR) ≥ 2.5 by DUS, ＞50% stenosis by angiography, or an ABI decrease ＞0.15 or revascularization. In DISFORM IV, the target lesion recurrence was defined as a newly observed PSVR ≥ 2.5 by DUS or an ABI decrease ＞0.15. CD-TLR was a revascularization procedure involving repeated EVT or surgical bypass of the culprit target lesion with recurrent symptoms of intermittent claudication, rest pain, or ischemic wound.
Statistical Analysis
Continuous data are presented as mean±standard deviation, and categorical data are presented as counts (percentages). The unpaired t-test was used to compare the continuous variables, and the chi-square test was used for categorical data. Primary patency and freedom from CD-TLR were assessed using the Kaplan–Meier method, and differences between groups were assessed using the log-rank test. Cox proportional hazards regression was used to investigate predictors of primary patency loss at 12 months. All p-values were two-tailed, with a p-value ＜0.05 considered statistically significant for all analyses. Factors with p-values ＜0.1, in the univariate analysis, were evaluated in the multivariate analysis. The results of the univariate and multivariate analyses were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). R (version 4.1.1) (R-project for Statistical Computing [http://www.R-project.org/]) was used for all statistical analyses.
Ethical Statement
This study was conducted following the Declaration of Helsinki and approved by the ethics committee of each institution (Approval Number/2022-045). Written informed consent was obtained from each patient or their relatives before the index procedure.
Results
Of the 288 cases, 183 had DISFORM I, 66 had DISFORM II, 11 had DISFORM III, and 28 had DISFORM IV. Baseline patient and lesion characteristics are shown in Table 1. The mean age of the patients was 75.0 years, and 63.5% were male. Notably, 60.8%, 36.1%, 16.7%, and 26.4% of patients had DM, dialysis, moderate or severe frailty, and CLTI, respectively. There were no significant differences in patient characteristics among the four groups except for pre-ABI. The mean lesion length was 92.3 mm, 167.2 mm, 142.0 mm, and 178.2 mm in the DISFORM I, II, III, and IV groups (p＜0.001). The percentages of CTO were 25.1%, 34.8%, 54.5%, and 53.6% in the DISFORM I, II, III, and IV groups, respectively (p=0.005); severe calcification was 14.2%, 27.3%, 27.3%, and 28.6%, respectively (p=0.036); and popliteal artery lesions were 35.5%, 36.4%, 54.5%, and 35.7%, respectively (p=0.653). The procedural characteristics are shown in Table 2. Total DCB length was 119.3 mm, 193.3 mm, 185.5 mm and 202.1 mm in the DISFORM I, II, III, and IV groups (p＜0.001). Severe dissections before and after DCB dilatation were less likely to be observed in the lower-grade DISFORM group (4.9%, 16.7%, 27.3%, and 25.0% in DISFORM I, II, III, and IV, respectively; p＜0.001; and 3.3%, 13.6%, 36.4%, and 42.9%, respectively; p＜0.001). Moreover, less residual stenosis before and after DCB dilatation was observed in the lower-grade DISFORM group (22.1%, 23.6%, 30.9% and 40.4% in DISFORM grades I, II, III, and IV, respectively; p＜0.001; 18.1%, 21.4%, 23.2%, and 36.1%, respectively; p＜0.001).
Table 1.Patient and lesion characteristics
|
Overall (n = 288)
|
DISFORM I (n = 183)
|
DISFORM II (n = 66)
|
DISFORM III (n = 11)
|
DISFORM IV (n = 28)
|
P value
|
| Patient characteristics
|
|
|
|
|
|
|
| Age, y |
75.0±9.7 |
75.6±9.8 |
74.2±9.0 |
74.4±8.7 |
73.5±11.0 |
0.623 |
| Male gender, n (%)
|
183 (63.5) |
115 (62.8) |
43 (65.2) |
9 (81.8) |
16 (57.1) |
0.533 |
| BMI, kg/m2
|
22.2±3.4 |
22.4±3.3 |
21.8±3.4 |
20.7±2.7 |
22.4±4.2 |
0.276 |
| Diabetes mellitus, n (%)
|
175 (60.8) |
108 (59.0) |
44 (66.7) |
7 (63.6) |
16 (57.1) |
0.708 |
| Hypertension, n (%)
|
238 (82.6) |
153 (83.6) |
53 (80.3) |
10 (90.9) |
22 (78.6) |
0.749 |
| Dyslipidemia, n (%)
|
157 (54.5) |
104 (56.8) |
33 (50.0) |
7 (63.6) |
13 (46.4) |
0.563 |
| Hemodialysis, n (%)
|
104 (36.1) |
68 (37.2) |
23 (34.8) |
5 (45.5) |
8 (28.6) |
0.744 |
| Current smoker, n (%)
|
69 (24.0) |
40 (21.9) |
20 (30.3) |
2 (18.2) |
7 (25.0) |
0.548 |
| CFS, n (%)
|
|
|
|
|
|
0.206 |
| 1-3 |
175 (60.8) |
110 (60.1) |
42 (63.6) |
8 (72.7) |
15 (53.6) |
|
| 4-5 |
65 (22.6) |
48 (26.2) |
11 (16.7) |
0 (0.0) |
6 (21.4) |
|
| 6-8 |
48 (16.7) |
25 (13.7) |
13 (19.7) |
3 (27.3) |
7 (25.0) |
|
| CLTI, n (%)
|
76 (26.4) |
51 (27.9) |
14 (21.2) |
2 (18.2) |
9 (32.1) |
0.578 |
| Pre-ABI |
0.59±0.21 |
0.63±0.19 |
0.55±0.22 |
0.53±0.22 |
0.46±0.25 |
＜0.001 |
| DAPT, n (%)
|
114 (39.6) |
70 (38.3) |
24 (36.4) |
5 (45.5) |
15 (53.6) |
0.96 |
| DOAC, n (%)
|
23 (8.0) |
11 (6.0) |
9 (13.6) |
1 (9.1) |
2 (7.1) |
0.274 |
| Lesion characteristics
|
|
|
|
|
|
|
| SFA lesion, n (%)
|
245 (85.1) |
152 (83.1) |
60 (90.9) |
9 (81.8) |
24 (85.7) |
0.484 |
| Popliteal artery lesion, n (%)
|
105 (36.5) |
65 (35.5) |
24 (36.4) |
6 (54.5) |
10 (35.7) |
0.653 |
| Stenosis, % |
89.3±10.7 |
88.1±11.2 |
89.8±10.1 |
95.5±5.2 |
93.5±8.7 |
0.013 |
| Lesion length, mm |
119.7±89.3 |
92.3±76.7 |
167.2±85.8 |
142.0±80.1 |
178.2±103.7 |
＜0.001 |
| CTO, n (%)
|
90 (31.2) |
46 (25.1) |
23 (34.8) |
6 (54.5) |
15 (53.6) |
0.005 |
| Severe calcification, n (%)
|
55 (19.1) |
26 (14.2) |
18 (27.3) |
3 (27.3) |
8 (28.6) |
0.036 |
| Proximal RVD, mm |
5.8±1.0 |
5.9±1.0 |
5.7±0.9 |
5.7±1.0 |
5.5±1.0 |
0.098 |
| Distal RVD, mm |
5.2±0.9 |
5.3±0.9 |
5.1±0.9 |
5.0±0.7 |
4.9±1.1 |
0.08 |
| Poor BK run-off (0/1), n (%)
|
140 (52.2) |
86 (50.6) |
36 (56.2) |
6 (60.0) |
12 (50.0) |
0.828 |
| TASC II grade C/D, n (%)
|
101 (35.1) |
42 (23.0) |
35 (53.0) |
6 (54.5) |
18 (64.3) |
＜0.001 |
BK, below the knee; BMI, body mass index; CFS, Clinical Frailty Scale; CLTI, chronic limb-threatening ischemia; CTO, chronic total occlusion; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulants; RVD, reference vessel diameter; SFA, superficial femoral artery; TASC, Trans- Atlantic Inter-Society Consensus
Continuous data are presented as means±standard deviation. Categorical data are given as counts (percentage).
Table 2.Procedural characteristics
|
Overall (n = 288)
|
DISFORM I (n = 183)
|
DISFORM II (n = 66)
|
DISFORM III (n = 11)
|
DISFORM IV (n = 28)
|
P value
|
| Pre-dilatation, n (%)
|
287 (99.7) |
182 (99.5) |
66 (100.0) |
11 (100.0) |
28 (100.0) |
0.902 |
| Pre-balloon size, mm |
5.2±0.9 |
5.3±0.9 |
5.1±0.9 |
5.1±0.5 |
4.9±0.7 |
0.262 |
| Total DCB length, mm |
146.8±92.4 |
119.3±81.8 |
193.3±87.9 |
185.5±77.9 |
202.1±102.7 |
＜0.001 |
| Minimum DCB size, mm |
5.2±0.7 |
5.3±0.7 |
5.2±0.7 |
5.0±0.6 |
4.8±0.7 |
0.006 |
| IN.PACT, n (%)
|
139 (48.3) |
79 (43.2) |
42 (63.6) |
3 (27.3) |
15 (53.6) |
0.015 |
| Lutonix, n (%)
|
107 (37.2) |
76 (41.5) |
17 (25.8) |
5 (45.5) |
9 (32.1) |
0.122 |
| Ranger, n (%)
|
44 (15.3) |
29 (15.8) |
8 (12.1) |
3 (27.3) |
4 (14.3) |
0.615 |
| Multi-type DCB use, n (%)
|
2 (0.7) |
1 (0.5) |
1 (1.5) |
0 (0.0) |
0 (0.0) |
0.807 |
| IVUS use, n (%)
|
128 (44.4) |
75 (41.0) |
30 (45.5) |
4 (36.4) |
19 (67.9) |
0.06 |
| Pre-DCB dissection grade ≥ D, n (%)
|
30 (10.4) |
9 (4.9) |
11 (16.7) |
3 (27.3) |
7 (25.0) |
＜0.001 |
| Pre DCB residual stenosis, % |
24.5±15.2 |
22.1±14.8 |
23.6±11.3 |
30.9±13.8 |
40.4±17.0 |
＜0.001 |
| DISFORM D |
|
|
|
|
|
＜0.001 |
| DISFORM D1, n (%)
|
22 (7.6) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
22 (78.6) |
|
| DISFORM S |
|
|
|
|
|
＜0.001 |
| DISFORM S1, n (%)
|
14 (4.9) |
0 (0.0) |
0 (0.0) |
6 (54.5) |
8 (28.6) |
|
| DISFORM F |
|
|
|
|
|
＜0.001 |
| DISFORM F1, n (%)
|
15 (5.2) |
0 (0.0) |
11 (16.7) |
1 (9.1) |
3 (10.7) |
|
| DISFORM F2, n (%)
|
1 (0.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (3.6) |
|
| DISFORM F3, n (%)
|
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
| DISFORM M |
|
|
|
|
|
＜0.001 |
| DISFORM M1, n (%)
|
67 (23.3) |
0 (0.0) |
55 (83.3) |
1 (9.1) |
11 (39.3) |
|
| DISFORM M2, n (%)
|
10 (3.5) |
0 (0.0) |
0 (0.0) |
4 (36.4) |
6 (21.4) |
|
| Technical success, n (%)
|
284 (98.6) |
183 (100.0) |
66 (100.0) |
10 (90.9) |
25 (89.3) |
＜0.001 |
| Final dissection grade ≥ D, n (%)
|
31 (10.8) |
6 (3.3) |
9 (13.6) |
4 (36.4) |
12 (42.9) |
＜0.001 |
| Final residual stenosis, % |
20.8±13.7 |
18.1±12.7 |
21.4±12.2 |
23.2±10.1 |
36.1±14.5 |
＜0.001 |
| Complication, n (%)
|
15 (5.2) |
5 (2.7) |
6 (9.1) |
1 (9.1) |
3 (10.7) |
0.096 |
DCB, drug coated balloon; DISFORM, diameter reduction, spiral shape, flow impairment, or adverse morphology; IVUS, intravascular ultrasound Continuous data are presented as means±standard deviation. Categorical data are given as counts (percentage).
The Kaplan–Meier estimate showed a primary patency rate of 76.6% in the overall population at 12 months (Fig.2-A). The primary patency rates in the DISFORM I, II, III, and IV groups were 75.3%, 91.1%, 87.5%, and 50.0%, respectively, at 12 months (overall, p＜0.001; DISFORM I vs. II, p=0.046; I vs. III, p=0.424; I vs. IV, p=0.005; II vs. III, p=0.884; II vs. IV, p＜0.001; III vs. IV, p=0.084; Fig.2-B). The DISFORM IV group showed a lower primary patency than the other groups at 12 months.
Freedom from CD-TLR at 12 Months
The rate of freedom from CD-TLR estimated using the Kaplan–Meier method was 86.5% in the overall population at 12 months (Fig.3-A). Freedom from CD-TLR rates of 86.0%, 91.6%, 88.9%, and 76.7% were observed in the DISFORM I, II, III, and IV groups, respectively, at 12 months (overall, p=0.195; DISFORM I vs. II, p=0.466; I vs. III, p=0.81; I vs. IV, p=0.075; II vs. III, p=0.923; II vs. IV, p=0.039; III vs. IV, p=0.324; Fig.3-B). DISFORM IV showed lower freedom from CD-TLR rate than DISFORM II at 12 months.
Predictors of Recurrence at 12 Months
The univariate and multivariate analyses of the Cox proportional hazards regression are presented in Table 3. Dialysis-dependent, CLTI, severe calcification, poor below-the-knee (BK) run-off, DISFORM grade, final residual stenosis, and DCB type were significantly correlated with primary patency loss at 12 months in the univariate analysis. The multivariate analysis showed that CLTI (HR 3.86; 95% CI 2.14-6.96; p＜0.001), DISFORM IV (HR 3.02; 95% CI 1.45-6.31; p=0.003), and Lutonix™ use (HR 2.18; 95% CI 1.16-4.1; p=0.015) were independent predictors of primary patency loss at 12 months.
Table 3.Predictors of recurrence at 12 months
|
Univariate |
Multivariate |
| HR (95% CI) |
P value
|
HR (95% CI) |
P value
|
| Age ＞75 y/o |
0.87 (0.51-1.50) |
0.627 |
NA |
|
| Male gender |
0.78 (0.45-1.36) |
0.380 |
NA |
|
| Diabetes mellitus |
1.18 (0.67-2.07) |
0.564 |
NA |
|
| Hemodialysis |
2.11 (1.23-3.63) |
0.007 |
1.44 (0.76-2.71) |
0.263 |
| CLTI |
4.37 (2.53-7.54) |
＜0.001 |
3.86 (2.14-6.96) |
＜0.001 |
| CTO |
0.79 (0.44-1.44) |
0.447 |
NA |
|
| Lesion length |
1.00 (0.99-1.00) |
0.370 |
NA |
|
| Severe calcification |
1.91 (1.04-3.52) |
0.038 |
1.18 (0.6-2.34) |
0.628 |
| Distal RVD ＜5mm |
1.31 (0.74-2.31) |
0.353 |
NA |
|
| Poor BK run-off |
2.11 (1.17-3.81) |
0.014 |
1.27 (0.64-2.5) |
0.491 |
| Popliteal artery lesion |
1.13 (0.65-1.97) |
0.653 |
NA |
|
| Final Dissection grade ≥ D |
1.05 (0.42-2.64) |
0.915 |
NA |
|
| DISFORM I (Ref.) |
Ref. |
Ref. |
Ref. |
Ref. |
| DISFORM II |
0.40 (0.16-1.01) |
0.053 |
0.37 (0.13-1.06) |
0.064 |
| DISFORM III |
0.46 (0.06-3.35) |
0.443 |
0.36 (0.05-2.68) |
0.321 |
| DISFORM IV |
2.59 (1.32-5.09) |
0.006 |
3.02 (1.45-6.31) |
0.003 |
| Final Residual stenosis ＞30% |
2.03 (1.15-3.59) |
0.015 |
1.61 (0.84-3.08) |
0.148 |
| DCB type |
|
|
|
0.060 |
| IN.PACT (Ref.) |
Ref. |
Ref. |
Ref. |
Ref. |
| Lutonix |
2.67 (1.49-4.79) |
0.001 |
2.18 (1.16-4.10) |
0.015 |
| Ranger |
1.00 (0.37-2.69) |
0.999 |
0.84 (0.31-2.30) |
0.736 |
| IVUS use, n (%)
|
1.52 (0.88-2.63) |
0.133 |
NA |
|
BK, below the knee; CI; confidence interval; CLTI, chronic limb-threatening ischemia; CTO, chronic total occlusion; DCB, drug coated balloon; DISFORM, diameter reduction, spiral shape, flow impairment, or adverse morphology; HR, hazard ratio; IVUS, intravascular ultrasound; RVD, reference vessel diameter
The primary patency rates in the DISFORM I–III and IV groups at 12 months were 79.4% and 50.0%, respectively (p＜0.001; Fig.4-A). Freedom from CD-TLR rates of 87.5% and 76.7% were observed in the DISFORM I–III and IV groups, respectively, at 12 months (p=0.041; Fig.4-B).
Discussion
This study presented the following three findings:1) DISFORM IV had a worse mid-term primary patency rate than DISFORM I–III; 2) there was no significant difference in the rate of midterm freedom from CD-TLR among the four DISFORM grades, whereas DISFORM IV had a worse freedom from CD-TLR rate than the other groups; and 3) CLTI, DISFORM IV, and Lutonix™ use were independent predictors of recurrence at 12 months. This was the first study to validate the usefulness of the DISFORM classification system.
The results of the IN.PACT SFA randomized trial, a pilot study of DCB, were published in 2015, and IN.PACT™ Admiral™ (Medtronic, Dublin, Ireland) showed better primary patency than POBA at 12 months4). Although limited real-world clinical findings were available during the DCB’s launch, Fanelli et al. reported that calcification greater than 270° was a predictor of recurrence9). Subsequently, long lesions, smaller MLA, and larger residual stenosis were also reported as predictors of recurrence6, 8, 17). Fujihara et al. reported that the severity of angiographic dissection was correlated with the recurrence rate after POBA16). Kozuki et al. reported that the recurrence rate worsened as the dissection angle increased after the DCB treatment7). However, arterial dissection presents diverse forms of FP lesions and lacks an angiographic dissection index that comprehensively includes residual stenosis, bilaterality, length, and flow impairment was a major limitation. In 2021, DISFORM was proposed to guide the use of DCB and scaffolds for FP lesions11). Although the DISFORM was unique in that it used the Delphi consensus methodology, in which questionnaires obtained from expert operators were tabulated and a scoring system was created from the top factors, it has not been validated in real-world clinical practice. This study validated DISFORM in real-world settings and found that DISFORM IV had significantly worse midterm primary patency and TLR rates than DISFORM I–III. Kawasaki et al. reported that angiographic dissection of less than grade C did not cause PSVR elevation, which indicated early recurrence in the perioperative acute phase; however, there have been no reports of severe dissection18). Dissections that apply to DISFORM IV may have flow impairment, which includes those without slow angiographic flow, with elevated PSVR immediately after revascularization. As a result, they may easily recur due to intimal growth and thrombus formation from the small lumen area and flow impairment. Early restenosis and symptom recurrence are treatment failures in revascularization, and the results of this study support the DISFORM recommendations for scaffolding in DISFORM IV. Dissection after balloon dilatation may be reduced by appropriate vessel preparation, such as scoring balloon use, long inflation, long balloon use, or super slow inflation19-22). If severe dissection of DISFORM IV is observed after appropriate vessel preparation, scaffolding is considered a better strategy than non-scaffolding, based on the results of this study. However, further studies are needed to confirm this hypothesis.
This study found that CLTI and Lutonix™ use, in addition to DISFORM IV, were independent predictors of recurrence after 12 months of DCB treatment. CLTI has been reported to predict recurrence in other current FP devices3, 23). CLTI is a more advanced form of LEAD, and the results may comprehensively reflect severe patient background and lesion severity. Soga et al. reported that Lutonix™ use is a recurrence predictor of DCB treatment in a large real-world clinical practice population in Japan10). A similar result was observed in the present study. Previous studies have reported that severe calcification and smaller vessel diameter are predictors of recurrence after DCB treatment9, 10). Although not identified as predictors in this study, severe calcification and a smaller vessel diameter may be confounding factors for DISFORM IV or CLTI.
Limitation
This study has several limitations. First, this was a non-randomized, retrospective study. Second, patients who required bailout stenting were excluded from this study, and selection bias may have occurred. Third, using debulking devices, lithotripsy devices, and some DCBs is not permitted in Japan. Fourth, a third-party organization, such as a core laboratory, did not assess the angiographic data and DISFORM grades. Fifth, the number of patients in each DISFORM grade was not well-balanced, and some groups had a small number of patients. Sixth, only Japanese patients were enrolled in this study; studies on populations of other races may have produced different results.
Conclusion
DISFORM IV had worse primary patency than DISFORM I–III in the midterm phase. CLTI, DISFORM IV, and Lutonix™ use were the independent predictors of recurrence at 12 months. Scaffolding should be considered if DISFORM IV is applicable after the vessel preparation. Further research is required to confirm these hypotheses.
Acknowledgements and Notice of Grant Support
The authors specially thank to the catheterization laboratory medical staff and other ASIGARU investigators at each institution for their assistance. We also acknowledge Mikihito Morimoto, Taro Shibahara, Masaru Nagase, Daiju Ono, Keita Suzuki, Makoto Yamaura, Takahisa Ido, Takashi Nakashima and Shigekiyo Takahashi for their technical support.
Conflict of Interest
The authors declare that there is no conflict of interest.
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