Dissections and Elastic Recoil Post Chocolate™ Balloon Catheter Treatment in Femoropopliteal Artery Lesions: Visions from Intravascular Ultrasound and 12- month following-up results

doi:10.21203/rs.3.rs-1749358/v1

Purpose

Situations of vessel wall in IVUS images after Chocolate balloon dilatation remains unknown and 12-month following-up results would be performed.

Materials and Methods

25 patients were enrolled in this observational study. Angiography and intravascular ultrasound were performed before Chocolate balloon inflation and post inflation. Dissections were quantified and classified according to the iDissection classification on intravascular ultrasound (IVUS) and National Heart, Lung, and Blood Institute classification on angiography. The elastic recoil rate, plaque burden and luminal gain were calculated in each patient too. Doppler ultrasound was presented in 30days, 3months, 6months and 12months each patient during follow-up.

Results

The mean lesion length was 168.3 ± 26.6 mm and arc of calcium was 115.1 ± 84.6°. 7 of the 25 patients required stents because of flow-limiting dissections and another 8 patients used stents with residual narrowing > 30%. Post Chocolate balloon angioplasty, the elastic recoil rate was 32.4 ± 13.1% and luminal gain was 6.1 ± 2.8mm². The plaque burden volume reduction was 7.0 ± 4.6%. Diameters on cine were 5.1 ± 0.7mm and 5.9 ± 0.6mm on IVUS. Total number of dissections were 2.9 times (114/40) on IVUS images than cine film, more non-flow-limiting dissections observed on IVUS compared cine (102/31). 2 patients lost follow-up because of death, primary patency in patients was 52.2% (12/23) and secondary patency was 82.6% (19/23) in 12-month.

Conclusion

Vessel injury from Chocolate balloon angioplasty and diameter in femoropopliteal artery lesions were grossly underestimated on angiography. Severe elastic recoil performed in most of patients according to IVUS images after Chocolate. Further randomized controlled trials are needed to support their use.

intravascular ultrasound

dissections

angiography

elastic recoil

iDissection classification

femoropopliteal artery

percutaneous transluminal angioplasty

Percutaneous transluminal angioplasty (PTA) has been the first-choice treatment for arteriosclerosis in femoropopliteal artery¹. Flow-limiting dissections and immediate elastic recoil leading to residual stenosis > 30% post femoropopliteal arterial angioplasty may require bailout stents which affect luminal gain and long-term patency. The theory “Leave Nothing Behind” means reducing the use of implants like stents in lumens to increase the long-term patency rate². Many adjunctive technologies with the purpose of reducing dissections and luminal injures such as atherectomy, scoring balloon, focal-force balloon or flex scoring catheter have been used for vessel preparation.

A “nitinol-constrained” balloon named the Chocolate PTA Balloon Catheter consists of a standard balloon and nitinol scaffold that constrains the inflation of the balloon to avoid injuring the vessel wall. The nitinol scaffold on the surface of balloon makes many uniform grooves like pillows to increase the surface contact area of the Chocolate balloon catheter. The aim of Chocolate balloon catheter is to disperse the force with balloon dilatation and increase the surface contact to minimize overall vessel trauma³. In the Chocolate BAR registry research, the positive reduction of dissections suggests that the Chocolate balloon is effective in reducing vessel trauma⁴.

However, no study has considered that dissections and acute elastic recoil post Chocolate balloon catheter treatment may be underestimated on angiogram compared to intravascular ultrasound (IVUS). Recent data has shown that defined dissections with IVUS are more precise^5–7. This study aimed to present data on the number and characteristics of dissections as seen on IVUS compared to angiogram post Chocolate balloon catheter treatment according to the iDissection⁸ and NHLBI (National Heart, Lung, and Blood Institute) classifications. The quantification of elastic recoil rates, plaque burden and diameters from IVUS scans were discussed. In addition, primary and secondary patency after using Chocolate balloon would present in our study.

Between September 2020 and July 2021, 25 patients with femoropopliteal disease were included in this prospective study by an experienced vascular surgeon at our institution.

Inclusion and exclusion criteria

Patients eligible for inclusion in this study met the following criteria: (1) age range from 40 to 85 years; (2) a resting ankle-brachial index (ABI) < 0.9; (3) target lesion localized in femoral and popliteal artery with primary occlusion or stenosis (non-stent); (4) Length of target lesion is shorter than 250 mm, estimated by angiography; and (5) reference vessel diameter is from 4 to 7 mm, and runoff vessel remained as at least one vessel. The exclusion criteria were: (1) life expectancy is less than 1 year; (2) allergic to radiocontrast agent; (3) serious cardiovascular disease or renal dysfunction where operations could not be performed safely; (4) coagulation dysfunction; and (5) in-stent stenosis.

All patients were screened according to protocol of our institution with physical examination, ABI measurement, and computed tomography angiography. All patients gave written informed consent before the operation. Studies involving human subjects have approval of the ethics committee, and participants gave informed consent before enrollment.

Procedure details

Angiography was performed before treatment in target lesions and the size of sheath was decided by the operator. The radio-opaque ruler was located on the treatment areas to make sure that the IVUS catheter (OptiCross 40Hz, Boston Scientific, USA) marker was placed in the same segment in each pullback. Pre-dilation with a 2 mm normal balloon was performed when the IVUS catheter was unable to cross the target lesion and before the Chocolate balloon catheter (TriReme Medical LLC, Pleasanton, CA) was used. IVUS and cine angiography were performed on the treated areas at baseline and post Chocolate balloon angioplasty. Adjunctive stent or drug-coated balloon were required when angiogram images showed flow-limiting dissection or residual stenosis > 30%. The starting points of the IVUS catheter pullback was at 10 mm distance from the target lesion with a healthy lumen in the distal vessel and the ending point was at 10 mm distance from the target lesion in the proximal vessel. A motorized pullback device with a dedicated IVUS console at 1 mm/s produced uniformed images.

Measurement

The vessel diameters defined in the IVUS images are the medial external elastic lamina (EEL). The choice of the Chocolate balloon catheter size is 1:1 to the reference diameter which is the average diameter in the distal and proximal medial EEL determined from IVUS images. The need for angioplasty or stent was determined by the surgeon at their absolute discretion. IVUS images was analyzed with the Polar Viewer™ (Boston Scientific, USA) and RadiAnt DICOM Viewer (Medixant, 2020, Poland) within the same segment length. Quantitative vascular analysis was used for cine angiography images and each image were analyzed by two seasoned vascular surgeons. Disagreements on IVUS or cine images estimates were reviewed by a cardiologist experienced in IVUS. Consecutive IVUS images were divided into many slices at every 5-mm axial interval through the entire disease segment to analyzed, and the post-dilatation image slices were reviewed in the same way to calculate immediate elastic recoil rate, plaque burden, diameter and area of external elastic membrane. (Fig. 2D)

Defined of IVUS images

The IVUS images were reviewed according to the iDissection classification (Fig. 2), and dissections on cine angiography images were classified according to the NHLBI classification. The iDissection results combined depth and circumference of dissections as seen on IVUS. This classification includes six dissection grades (A1, A2, B1, B2, C1, and C2) (Fig. 2). Grade A involves the intima, B involves the media, and C involves the EEL. Number 1 indicates the circumference of the dissection is \(<\)180\(^\circ\) and number 2 indicates \(\ge 180^\circ\). The NHLBI classification also includes six dissection grades from A to F as displayed on angiogram. Grade A indicate dissections with minor radiolucent areas, grade B indicate dissections with parallel tracts, grade C indicate dissections that angiographically appear as contrast outside the lumen, grade D indicate spiral dissections with luminal filling defects, grade E indicate persistent filling defects, and grade F indicate dissections without distal antegrade flow. Flow-limiting dissections are considered more serious than grade C (including grade C) in the NHLBI classification. And the Fanelli classification⁹ was used for vascular calcification grades in IVUS.

The Elastic recoil rate = 1- A(final) / A(inflated)

A(final) means: Area of lumine after Chocolate balloon dilatation,

A(inflated) means: Area of standard sized Chocolate balloon dilatation.

External elastic membrane refactor area = post-EEMa – pre-EEMa

Post-EEMa: area of external elastic membrane after Chocolate dilatation.

Pre-EEMa: area of external elastic membrane before Chocolate dilatation.

Volume reduction of plaque = (plaque burden pre-dilatation – plaque burden post-dilatation) / plaque burden pre-dilatation.

Following-up

Patients were followed by the treating physician at 30days, 6months and 12months. Duplex ultrasound, functional test and physical examination were presented. Reinterventions requiring were estimated by computed tomography angiography when patients had apparent limb ischemia and reinterventions were performed according to standard practice using PTA balloons and metal stenting.

The primary patency defined as freedom from clinically- driven target lesion reintervention (CD-TLR) and freedom from restenosis as determined by duplex-derived peak systolic velocity ratio (PSVR) \(\le\) 2.4. CD-TLR was estimated by computed tomography angiography presented restenosis and decrease in ankle-brachial index (ABI) \(\ge\) 20% compared with last ABI post-operation.

The secondary patency was avoiding major adverse events (MAEs) which including death from any cause, major target limb amputation, bypass operation and acute thrombosis.

Statistical analysis

All data was analyzed by GraphPad Prism version 8.0.0 (GraphPad Software, San Diego, California USA, www.graphpad.com.) A descriptive analysis was performed for each patient. Quantitative data was presented as mean ± stander deviation, median and count date as n’ in percent. Multivariate analysis compared the number of dissections post Chocolate balloon treatment by cine angiography and IVUS according to NHLBI and iDissection classifications. T-test compared vessel diameter in IVUS versus angiogram images to test differences for significance. Pearson’s Chi-square, Kruskal-Wallis, and Fisher’s tests were performed when the date is abnormal distribution. Kaplan-Meier was used to descript patients’ primary and secondary patency.

Clinical variables were presented in Table 1. The mean age of the 25 patients is 76.2 ± 6.8 years with 64.0% male and mean body mass index of 22.6 ± 3.2 and the ABI at baseline was 0.4±0.1. A total of 44.0% of patients are smokers and 32.0% had a history of drinking. Medical history included diabetes (48.0%), hypertension (72.0%) and hyperlipidemia (48.0%). Seven patients (28.0%) have coronary heart disease, 2 patients (8.0%) are in renal insufficiency and 8 patients (32.0%) have cerebral vascular disease. Mean following-up time was 14.2±2.9 with 23 patients.

Target lesion length was 168.3±26.6 mm and the mean diameter of Chocolate balloon was 5.1±0.8mm. During Chocolate balloon dilatation, the inflation time was 150.7±23.4s with pressure of 12.0±1.8 atm. 13 patients (52.0%) needed to pre-inflation because of the IVUS catheter cannot pass through target disease. Drug- coated balloons were used in 5 patients (20.0%) and 7 patients (28.0%) required stents because of flow-limiting dissections and other 8 patients (32.0%) using stents with residual stenosis >30% (Table 2). Procedural success rate was 100% but complications happened in 2 patients, one patient caught hematoma in puncture point and another died because of myocardial infarction at the second day after operation.

From optic of IVUS images, mean luminal gain post Chocolate dilatation was 6.1±2.8mm² and external elastic membrane refactor area was 5.4±2.1mm². Plaque burden post-PTA (21.1±4.6mm²) compared to plaque burden before dilatation (22.8±5.2mm²), the volume of plaque just decreased 7.0±4.6%. (Table 3)

Diameter evaluated on IVUS images was significant different with diameter measured on angiography (5.9±0.6mm versus 5.1±0.7mm, p<.05). After Chocolate balloon dilatation, a total of 114 dissections were discovered on IVUS (grade A1 67/114, B1 28/114, C1 7/114, A2 7/114, B2 5/114, C2 0/114) versus 40 dissections on angiogram (grade A 12/40, B 12/40, C 7/40, D 8/40, E 1/40, F 0/40) (Table 4), respectively. All dissections defined in IVUS were 2.9 times more than cine film images. Regarding arc of dissections, 12/114 were more than 180° post Chocolate balloon treatment. IVUS observed more non-limiting-flow dissections compared angiogram (4.1±2.6 versus 1.2±1.0, p<.05) and in detecting the flow-limiting dissections, they were not significant different. Mean elastic recoil after Chocolate dilatation was 32.4±13.1% which was more than 30%.

With 12-month following up, 12 patients (52.2%) showed primary patency with test of doppler ultrasound and 18 patients (78.3%) showed secondary patency (Figure 3). Two patients lost following up because of died.

The Chocolate balloon is a new technology aimed to reduce torsional and radial pressure imparted on the vessel wall during inflation. Theoretically, balloon inflation is limited by the nitinol scaffold which helps to disperse the pressure to reduce thermal injury and the chance of flow-limiting dissections. A multi-center study known as The Chocolate BAR registry showed that the Chocolate balloon showed no flow-limiting dissections. However, our results showed some differences. A total of 28% of patients in our study required stents with flow-limiting dissections. This may because the lesion length was longer than in the Chocolate BAR study (168.3 ± 26.6 mm vs 83.5 ± 59.9 mm)⁴, and more occlusion arteries were included in our study.

From optic of IVUS, more dissections evaluated compared with angiography and most of they were non-flow-limiting. It can also determine the depth and arc of dissections. Pathologic studies have indicated that deeper injury in the luminal wall would result in more loss in long-term patency¹⁰. Although angiogram detected the most flow-limiting dissections, missed vessel wall injury through cine films may affect long-term patency. The application of IVUS can guide surgeons to estimate luminal injury more accurately. Though more detected dissections may cause more stent implantations.

Our results show that mean elastic recoil rate was 32.4 ± 13.1%, and 16 patients (64%) showed severe elastic recoil > 30% in study. Severe elastic recoil decreased the luminal gain after balloon dilatation. Whether Chocolate balloon causes more severe elastic recoil we cannot make it sure, more control experiments are needed to improve it.

In our study, volume reduction of plaque was just 7.0 ± 4.6%, and luminal gain after using Chocolate balloon was 5.9 ± 0.6mm² indicated that most gain of luminal area was provided by external elastic membrane expanded and just a little from plaque compression. Chocolate balloon is difficult to reduce the plaque burden in the lumen, it can only condense or squeeze it which leads to inescapable elastic recoil. With high volume plaque burden in femoropopliteal arteries, debulking is a better choice. Debulking technology like directional atherectomy (DA), Turbo-Elite laser system, and rotational atherectomy can reduce plaque volume with little elastic recoil. Many randomized controlled trials have shown that debulking devices can be used safely with less complications and better long-term recovery¹¹. Debulking devices combined with a Drug-Coated balloon may be a better approach to treat femoropopliteal arterial diseases.

Diameters were longer in IVUS and even in some patients, the difference was more than 1 mm. A study including 1967 limbs to measure the difference between angiography- and IVUS- reference diameter in the femoropopliteal arteries shows

IVUS-assessed reference diameter was significantly larger reference diameter (6.0 ± 1.0 mm in IVUS vs 5.0 ± 1.0 mm in angiogram, p < .05) which was similar with our result (5.9 ± 0.6 mm in IVUS versus 5.1 ± 0.7 mm in angiogram, p < .05)¹². Different evaluation of the diameter affect selections of balloon size and inappropriate balloon size may bring more injury to patients. Choosing the suitable size, type, and way to treat different target lesions may lead to better long-term patency.

The following-up results in our study were not good enough. Primary patency only 52.2% and secondary patency was 78.3% which were lower than other studies. Longer length of disease and less use of drug-coated balloon may be the main reasons. Chocolate touch balloon combines Chocolate balloon with anti-stenosis drug on the surface is a new technology which was presented better patency in studies¹³.

There is much attention paid to dissections, but flow-limiting dissections are not the only factors to indicate the need for stents. Acute elastic recoil, character of plaque and calcification are also important factors to help in deciding if stents are required. Different conditions in the lumen affect patency differently. More multicenter studies in this area are needed.

Limitations

This study had a few limitations: (1) this is a single-center study and more larger sample size studies are needed to validate its results; (2) this study focused on the femoropopliteal artery, below-the-knee vessels were not including and their inclusion may lead to different results; (3) We were unable to avoid wire artifacts in IVUS images and this may have caused some dissections or calcification diseases to be missed.

Majorities of dissections after Chocolate balloon treatment are not flow-limiting, and many dissections post Chocolate balloon angioplasty are ignored in angiography can be performed on IVUS. Severe elastic recoil performed after Chocolate dilatation which affected luminal gain. Vessel diameters evaluated by IVUS were different to cine. More quality clinical studies are needed.

Conflict of Interest Disclosure:

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This research received no specific grant from any funding agency in the public, commercial, or non-for-profit sectors.

Acknowledgments:

All authors approved final version of the manuscript. Thanks are due to Zexing Song for assistance with the experiments and to La Zhang for valuable artwork and discussion.

Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763-816.
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Table 1. Clinical Variables.

n=25	Mean	Median
Age(years)	76.2±6.8	77.0
Body mass index(kg/m2)	22.6±3.2	21.8
Ankle-brachial index Mean follow-up time(month)	0.4±0.1 14.2±2.9	0.4 14.0
n=25	n’	%
Male（%） Type of disease De novo Occlusion Mixture Rutherford 3 4 5 TASC B C D Run-off 1 2 3 Calcium 0-90° 90-180° 180-270° 270-360°	16 12 5 8 10 14 1 10 11 4 11 11 3 12 8 4 1	64.0 48.0 20.0 32.0 40.0 56.0 4.0 40.0 44.0 16.0 44.0 44.0 12.0 48.0 32.0 16.0 4.0
Smoker	11	44.0
Alcohol	8	32.0
Hypertension	18	72.0
Diabetes mellitus	12	48.0
Hyperlipidemia	12	48.0
Coronary disease	7	28.0
Chronic kidney disease	2	8.0
Cerebral vascular disease	8	32.0

n=total number of patients; n’=numbers of events.

Table 2. Angiographic and IVUS Variables.

n=25	Mean	Median
Lesion length (mm)	168.3±26.6	177.0
Chocolate balloon inflation time(s)	150.7±23.4	140.0
Chocolate balloon diameter (mm)	5.1±0.8	5.0
Maximum Chocolate inflation pressure(atm)	12.0±1.8	12.0
n=25	n’	%
Pre-inflation	13	52.0
Drug-coated balloons used	5	20.0
Stent used	15	60.0
Flow-limiting dissections Residual stenosis>30% Others	7 8 0	28.0 32.0 0
Complications
Contrast-induced nephropathy	0	0
Embolization	0	0
Pseudoaneurysm	0	0
Hematoma	1	4.0
Others	1	4.0

n=total number of patients; n’=numbers of events. A patient died because of myocardial infarction at the second day after operation which including the “Others” of complications.

Table3 Intravascular ultrasoud detected

n=25	Mean	Median
Luminal diameter (mm)	5.9±0.6	5.8
Plaque burden (mm2)
Pre-PTA	22.8±5.2	21.9
Post-PTA	21.1±4.6	19.9
Luminal gain (mm2)	6.1±2.8	5.7
External elastic membrane refactor area	5.4±2.1	5.4
Arc of calcium (°)	115.1±84.6	94.2
Elastic recoil (%)	32.4±13.1	32.0
Volume reduction of plaque (%)	7.0±4.6	5.1

PTA: Percutaneous Transluminal Angioplasty.

Table4 Difference between Angio and IVUS

	Angio	IVUS			p value
Diameter	5.1±0.7	5.9±0.6			<.05
Non-limiting-flow dissections	1.2±1.0	4.1±2.6			<.05
Flow-limiting-dissections	0.4±0.6	0.5±1.0			.40
Total dissections	1.6±1.0	4.6±2.7			<.05
Dissection classification	NHLBI	n	iDissections	n’	Proportion (n’/n)
	A	12	A1	67	5.6
	B	12	B1	28	2.3
	C	7	C1	7	1
	D	8	A2	7	0.9
	E	1	B2	5	5
	F	0	C2	0	1
Total numbers		40		114	2.9

NHLBI: National Heart, Lung, and Blood Institute classification.

No competing interests reported.

Dissections and Elastic Recoil Post Chocolate™ Balloon Catheter Treatment in Femoropopliteal Artery Lesions: Visions from Intravascular Ultrasound and 12- month following-up results

Status:

Version 1

Abstract

Purpose

Materials and Methods

Results

Conclusion

Figures

Introduction

Materials And Methods

Inclusion and exclusion criteria

Procedure details

Measurement

Defined of IVUS images

Following-up

Statistical analysis

Results

Discussion

Limitations

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Version 1