Mean Pressure Gradient and Fractional Flow Reserve at A Superficial Femoral Artery Dissection after Drug-Coated Balloon Angioplasty

Abstract

Objectives

Residual dissection is a concern in endovascular treatment with a DCB, and there is limited knowledge of hemodynamics at a dissection lesion. Therefore, the objective of this study is to evaluate the mean pressure gradient (MPG) and fractional flow reserve (FFR) at a residual dissection after DCB angioplasty for the superficial femoral artery (SFA).

Methods

A total of 59 cases with residual SFA dissection treated with DCB angioplasty at a single center were analyzed retrospectively. The dissection was classified into 6 types (A-F). The primary endpoints were MPG and FFR at a residual dissection lesion after DCB angioplasty, using evaluation with a pressure wire.

Results

The median lesion length was 70 (40-130) mm with 24% popliteal involvement, and 11 cases (18%) had chronic total occlusion. A completion angiogram revealed dissection of types A (n = 33, 56%), B (n = 18, 31%), C (n = 7, 12%), and D (n = 1, 2%). The median MPGs in type A, B, and C cases were 0 (0-2), 0 (0-4), and 3 (0-6) mmHg, with a significant lower in type C cases than in type A cases (A vs C, P = .021). The median FFRs in type A, B, and C cases of 1.0 (.98-1.00), 1.0 (.96-1.00), and .98 (.95-1.00) did not differ significantly among dissection types (A vs B, P = .86; A vs C, P = .055; B vs C, P = .15).

Conclusions

This is the first report of hemodynamics at a SFA dissection. The results suggest that low-grade dissection (types A or B) does not affect MPG and FFR at a SFA lesion. This indicates that a bailout stent may be unnecessary for patients with dissection of types A or B. A further investigation is needed to determine whether a scaffold is required for a SFA lesion with type C dissection.

Keywords

endovascular treatment drug-coated balloon dissection mean pressure gradient fractional flow reserve

Introduction

Endovascular treatment (EVT) for the superficial femoral artery (SFA) is performed worldwide due to its efficacy and safety. The 2017 European Society of Cardiology (ESC) guidelines recommend an EVT-first strategy for short (<25 cm) femoropopliteal occlusive lesions.¹ Device advances for SFA lesions have been remarkable and a paclitaxel device is now widely used. Many investigators have also reported the effectiveness of a drug-coated balloon (DCB) for femoropopliteal lesions.^2-5 However, residual dissection is a concern in EVT with a DCB, with Soga et al⁶ finding that 66.6% of femoropopliteal lesions had residual dissection after DCB angioplasty in a Japanese multicenter registry of 3165 EVT cases.

Vessel dissection after SFA angioplasty is divided into 6 types (A to F) in the modified version of the coronary artery classification of the National Heart, Lung, and Blood Institute (NHLBI).^7,8 In general, a bailout stent after DCB is not needed for SFA lesions with lower grade dissection. However, there is limited knowledge of hemodynamics at a residual dissection after DCB angioplasty. In coronary intervention, technologies for calculating hemodynamics based on invasive coronary angiography, intravascular ultrasound, and optical coherence tomography have also emerged. Mean pressure gradient (MPG) and fractional flow reserve (FFR) (defined as the distal mean pressure/proximal mean pressure) are often evaluated using a pressure wire, and hemodynamics assessment (MPG and FFR) is now performed worldwide in coronary intervention, with the aim of identifying the flow-limiting coronary artery with intermediate stenotic lesions on angiography. Therefore, the purpose of this study is to evaluate the hemodynamics (MPG and FFR) at a residual dissection after DCB angioplasty.

Methods

A total of 59 cases with residual SFA dissection after DCB angioplasty at a single center between December 2021 and December 2023 were reviewed retrospectively. Symptomatic patients (Rutherford class 2-6) who underwent EVT for de novo SFA lesions were included in the study. Patients treated with EVT for intra-stent restenosis and those with residual stenosis (≥30%) and no residual dissection angiographically at the SFA DCB lesion were excluded. The primary endpoints were MPG and FFR at the residual dissection after DCB angioplasty. The secondary endpoints were primary patency and freedom from clinically driven target lesion revascularization (CD-TLR) of the SFA lesion. Patient backgrounds, procedural details, hospital outcomes, and short-term outcomes were collected from medical records.

Definitions

The dissection type was defined as type A, minor radiolucent areas (Figure 1A); type B, linear dissection (Figure 1B); type C, contrast outside the lumen (Figure 1C); type D, spiral dissection; type E, persistent filling defects; and type F, total occlusion without distal antegrade flow.^7,8 The type of dissection was determined by two interventionists in July 2023, independent of the intraoperative judgment. If the assigned types differed, the final type was determined after the two interventionists conferred. Technical success of EVT was defined as ≤30% stenosis remaining, based on the completion angiogram. Primary patency of EVT lesions was defined as freedom from CD-TLR and freedom from restenosis; ie, duplex ultrasonography peak systolic velocity ratio (SVR) > 2.4. The peak SVR was defined as the peak systolic velocity at the lesion/peak systolic velocity proximal to the lesion. CD-TLR was defined as reintervention at the target lesion due to symptoms or a decrease in the ankle-brachial index (ABI) by ≥ .15 from the postprocedural baseline ABI.

EVT Procedure

All patients underwent EVT in hospital. Ipsilateral or contralateral femoral access was preferred. Before placing a 5 or 6 Fr sheath, heparin sodium was administered intravenously at 3000 units, with an additional 1000 units every 1 hour thereafter. After pre-intervention angiography, all femoropopliteal occlusive lesions were treated. The stenotic lesion was crossed with a .014-inch guidewire (Jupiter FC, Boston Scientific, Marlborough, MA, USA; Gladius, Asahi Intecc, Tokyo, Japan) and a high-pressure angioplasty balloon (Shiden HP, Kaneka, Tokyo, Japan; Hyperwalker, Nipro, Osaka, Japan; Jade, OrbusNeich, Hong Kong) was advanced. The balloon size was selected based on the reference diameter of the adjacent vessel (4.0-7.0 mm). After pre-dilatation, angiography was performed to detect dissection and stenosis of the lesion. In a case with high-grade dissection (types D-F), a provisional stent was implanted; in other cases, an optimal size DCB (IN.PACT admiral, Medtronic, Ireland; Ranger, Boston Scientific, USA) was used. Completion angiography was performed after use of the DCB. If high-grade dissection (types D-F) occurred or significant stenoses (≥30%) remained, a bailout stent was implanted. Selection of the pre-dilatation balloon and DCB was determined by each interventionist.

Measurement of Mean Arterial Pressure Gradient

After completion angiography, MPG and FFR was measured using a dedicated wire (OptoWire) and monitor (OptoMonitor) (both Zeon Medical, Japan) under treatment with a vasodilator and stable hemodynamics (systematic systolic blood pressure ≥80 mmHg). MPG was displayed in real time and recorded. FFR was defined as the distal mean pressure/proximal mean pressure.

Medication

Patients who were already taking antiplatelet agents continued to take these drugs. For other patients, aspirin (100 mg daily) or clopidogrel (75 mg daily) was started at least 1 week before the procedure and continued lifelong. The interventionist determined whether aspirin or clopidogrel was used. All patients with dyslipidemia were treated with a statin.

Follow-Up

After EVT, all patients were enrolled in a follow up program of measurement of ABI at 1, 3 and 6 months after the procedure and every 6 months thereafter lifelong. When the ABI dropped ≥0.15 compared with the post-procedural ABI, duplex ultrasound (DUS) was conducted to evaluate patency.

The DUS criteria for further investigation with arteriography were stenosis with a peak SVR >2.4. Arteriography was also performed for patients with symptoms or a decrease in ABI of .15 from the postprocedural baseline ABI.

Ethics

This study was approved by the ethics committee of JA Hiroshima General Hospital (Hiroshima, Japan; approval number: 23-38). The analysis is observational without intervention or invasiveness, and thus, the ethics committee waived the need for informed consent from patients and the opt-out method was alternatively utilized.

Statistical Analysis

Continuous variables are expressed as medians (25th-75th percentile) and categorical variables are presented as absolute values and percentages. Differences in MPG and FFR between dissection types were compared by Mann-Whitney U test. Primary patency and freedom from CD-TLR were assessed by Kaplan-Meier analyses. P < .05 was defined as significant. All statistical analyses were conducted with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).⁹

Results

Patient backgrounds are shown in Table 1. The median age was 79 (73-85) years and most patients were male (n = 32, 54%). Of 59 cases with SFA dissection after DCB angioplasty, 64% had a diagnosis of diabetes and 29% were undergoing hemodialysis. Chronic limb-threatening ischemia was present in 27 cases (46%).

Table 1.

Characteristics of the patients at Baseline.

Variables	Number	(%)
Cases	59
Age (years)	79 (73-85)
Male	32	(54)
Coronary artery disease	16	(27)
Cerebrovascular disease	13	(22)
Diabetes	38	(64)
Hemodialysis	17	(29)
Hypertension	44	(75)
Current smoker	8	(14)
Chronic limb-threatening ischemia	27	(46)
Medication
SAPT	49	(83)
DAPT	10	(17)
Anticoagulation	6	(10)
Statin	29	(49)

SAPT, single antiplatelet therapy; DAPT, double antiplatelet therapy.

Data are presented as n (%) or median values (interquartile range).

Procedural details are shown in Table 2. The median lesion length and reference vessel diameter were 70 (40-130)60 and 5 (4.8-5.8) mm, respectively, with 24% popliteal involvement, and 11 cases (18%) had chronic total occlusion. Poor below-the-knee runoff (0 or 1) and severe calcification (peripheral arterial calcium scoring system [PACCS] class 4) were found in 51% and 20% of cases, respectively.¹⁰ Pre-dilatation before DCB use was performed with a high pressure balloon in 78% of cases. No high-grade dissection (types D-F) occurred after pre-dilatation. High-dose (n = 25, 42%) and low-dose (n = 34, 58%) DCBs were used.

Table 2.

Characteristics of Lesions and procedural Details.

Variables	Number	(%)
Cases	59
Lesion length (mm)	70 (40-130)
Reference vessel diameter (mm)	5 (4.8-5.8)
Chronic total occlusion	11	(18)
Popliteal artery involvement	14	(24)
Poor runoff (below the knee runoff vessel 0 or 1)	30	(51)
Severe calcification (PACCS 4)	12	(20)
Pre-dilatation with a high pressure balloon	46	(78)
DCB type
High-dose	25	(42)
Low-dose	34	(58)
Provisional stent	0	(0)
Bail out stent	2	(3)
Type of dissection
A type	33	(56)
B type	18	(31)
C type	7	(12)
D type	1	(2)
Additional iliac EVT	3	(5)
Additional infrapopliteal EVT	11	(19)
Technical success	44	(100)
Procedural time (min)	38 (28-49)

PACCS, peripheral arterial calcium scoring system; DCB, drug-coated balloon; EVT, endovascular treatment.

Data are presented as n (%) or median values (interquartile range).

A completion angiogram revealed dissection of types A (n = 33, 56%), B (n = 18, 31%), C (n = 7, 12%), and D (n = 1, 2%). The median MPGs in type A, B, and C cases were 0 (0-2), 0 (0-4), and 3 (0-6) mmHg, with a significant lower in type C cases than in type A cases (A vs C, P = .021) (Figure 2A). The median FFRs in type A, B, and C cases of 1.0 (.98-1.00), 1.0 (.96-1.00), and .98 (.95-1.00) did not differ significantly among dissection types (A vs B, P = .86; A vs C, P = .055; B vs C, P = .15) (Figure 2B). One patient (1%) with type C dissection (MPG, 10 mmHg; FFR, .90) and the other (1%) with type D dissection (MPG, 20mmHg; FFR, .81) required bailout stenting. The technical success of EVT was 100% and the median procedural time was 38 (28-49) min. No hospital death or major adverse events occurred within 30 days.

The median follow-up period was 8.1 (4.3-15.8) months, with a follow-up rate of 100%. Primary patency in the whole cohort was 92% at 6 months and 86% at 12 months, with no significant differences among dissection types (Figure 3A). Freedom from CD-TLR in the cohort was 94% at 6 months and 88% at 12 months, again with no significant differences among dissection types (Figure 3B).

Discussion

The main finding in this study was that low-grade dissection (types A-C) at a SFA lesion after DCB angioplasty does not affect hemodynamics, based on our evaluation of FFR. EVT with a DCB for a SFA occlusive lesion is widely performed due to its efficacy and safety, but residual dissection is a concern in a case with scaffold avoidance and the acceptable degree of dissection is controversial. The effect on FFR has been well analyzed in coronary intervention and additional treatment is needed for a lesion with FFR ≤0.80, but there is a limited knowledge in peripheral intervention.^11-15

To our knowledge, this is the first report on hemodynamics (MPG and FFR) at a SFA dissection after EVT with a DCB. In a series of 193 SFA lesions treated with EVT with balloon angioplasty, Fujihara et al found that cases with severe dissection (types C-F) had a significantly lower patency rate (P < .001) and a higher clinically-driven TLR rate (P < .001) compared with those with no dissection or dissection of types A and B.⁸ Similarly, in the current study, type A or B dissection at a SFA lesion after EVT with a DCB did not affect hemodynamics (median MPG: type A, 0, type B, 0; median FFR, type A, 1.00, type B, 1.00). Thus, in patients with type A or B dissection after use of a DCB, an additional scaffold is not needed. Type C dissection also did not affect FFR or 12-month primary patency in our patients, which differed from previous outcomes. The reason is unclear, but the previous studies did not include cases treated with a DCB and the current cohort was relatively small, which might have influenced the results. A further investigation is needed to determine whether a scaffold is required for a SFA lesion with type C dissection.

In a randomized series of 414 cases treated with EVT with a DCB, Steiner et al¹⁶ found that stenting was performed in every fourth intervention. In contrast, in this study, a bailout stent was used in only two case (2%), which may be because bailout stenting is not reimbursed in Japan. In a large Japanese cohort study (3165 cases of EVT with a DCB),⁶ the rate of bailout stenting was 3.5%, which is similar to our report. In this large cohort,⁶ the rate of no or low-grade (types A-C) dissection was 95.4%, and freedom from restenosis and freedom from TLR were 84.5% and 91.5%, respectively, at 12 months, despite the low use of a bailout stent. These results are favorable and comparable to our 12-month rates of primary patency and freedom from CD-TLR, which were 86 and 88%.

Scaffolds such as a bare-nitinol stent, stent graft, and drug-eluting stent are permanent metallic implants that have future risks of stent fractures and acute thrombosis.^17-19 In a meta-analysis with coronary intervention, FFR-guided revascularization was associated with a fewer number of stents.²⁰ Given these disadvantages of scaffold devices and the good hemodynamics in lesions with low-grade dissection (types A or B), we suggest that a bailout stent may be unnecessary for patients with dissection of types A or B.

Limitations

This study has several limitations. First, it is retrospective single-arm observational study. The cohort was relatively small, and having a larger patient subset would give more power for creation of a classification scale based on dissections of types A-D. Second, bailout stents and atherectomy devices are not approved in Japan, which may have affected the outcomes. Third, simultaneous use of intravascular ultrasound (IVUS) and a pressure wire is difficult under the Japanese insurance system, and we were unable to evaluate SFA dissection by IVUS. Thus, comparison was not made between hemodynamic assessment (MPG and FFR) and IVUS assessment. Further investigation is needed before this can be incorporated into practice. Fourth, residual dissection after DCB is unstable, which can result in extension of dissection during follow-up. Also, the follow-up period was relatively short, which might have influenced the outcomes. Longer term follow-up may be needed to assess clinical outcomes in patients with a residual dissection after SFA DCB angioplasty. Fifth, it is unclear how the measurements and interpretation differ in patients with peripheral arterial disease compared with coronary artery disease. Additionally, in a case with distal embolism or a slow flow phenomenon, FFR cannot be evaluated with certainty. Finally, the study was performed in Japanese patients only and the results require confirmation in other ethnic groups.

Conclusion

This is the first report of hemodynamics at SFA dissection lesions after DCB angioplasty. Low grade dissection (types A or B) did not affect MPG and FFR at SFA lesions, which suggests that a bailout stent may be unnecessary for patients with these types of dissection. A further investigation is needed to determine whether a scaffold is required for a SFA lesion with type C dissection.

Footnotes

Acknowledgements

We gratefully acknowledge the work of past and present members of the vascular team (ie, physical therapists, wound nurses, certified diabetes educators, pharmacists, nutritionists, clinical engineers, ultrasound technicians, medical technologists, radiological technologists, medical secretaries, and prosthetists).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

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

ORCID iD

Taira Kobayashi

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