RESEARCH ARTICLE Open Access

Application of a new blood flow regulatorin aortic endovascular therapyChang Liu†, Yun-xing Xue†, Dong-jin Wang and Qing Zhou*

Abstract

Background: Endovascular repair involving branches of the aorta is still difficult in clinical treatment. A new type ofblood flow regulator has been used in thoracic endovascular aortic repair/endovascular aortic repair in our centre,and the effects were followed and analysed.

Methods: From March 2014 to January 2015, 14 patients with Stanford type B aortic dissection or penetratingulcers and aortic arch pseudoaneurysms were consecutively enrolled. All patients were evaluated and underwentendovascular repair. The average age of these patients was 59 ± 14 years (34–76 years old, median 62 years), andthere were 12 males and 2 females. The blood flow regulator was a self-expanding membrane-supported artificialblood vessel. The film was made from polyester that was formed into a mesh 1 mm2 in size. The metal stent usedwas made of nickel-titanium alloy.

Results: The success rate for the technique was 100%. All patients underwent postoperative aortic CTA and hadtype III endoleak. There were no deaths and no instances of stroke, transient ischemic attack (TIA), hemiplegia, paraplegia orother central nervous system complications, and there were no left upper limb ischaemia symptoms in the group. Theaverage follow-up time was 14.7 ± 3.6months. One patient died of sudden death 4months after the operation. One patientdied due to abdominal aortic aneurysm rupture, and the other 12 patients survived. The survival rate was 86%. The bloodflow regulator covered a total of 19 branch vessels (the intercostal artery was not counted), of which 18 experienced smoothblood flow. One patient continued to have a type III endoleak after the operation, and the endoleak disappeared afterendovascular repair.

Conclusions: This clinical case series of 14 patients with percutaneous transluminal stents indicates that the blood flowregulator is safe and feasible in TEVAR surgery, providing a promising new technology.

Keywords: Aorta, Stent, Endoleak

BackgroundThe operation involved in aortic branch vessels is difficultand traumatic; it is not appropriate to perform open sur-gery in elderly patients or high-risk patients with multiplecomplications. Recently, with the rapid development ofendovascular repair technology, the restricted area of opensurgery has been expanded, and the mortality rate of opensurgery has been reduced. One of the major challenges ofthoracic endovascular aortic repair (TEVAR) is that it isdifficult to have an appropriate anchoring area when thelesion is located next to a large branch of blood vessels.

To expand the anchoring area, various techniques havebeen introduced, such as the direct closure of branch ves-sels, debranching techniques, fenestration techniques, andchimney techniques.Here, we designed a new type of blood flow regulator

based on the concept of a multilayer bare stent. Thisblood flow regulator can achieve results of a properlanding zone and can preserve the normal flow ofbranches of the aorta. We reported our preliminaryexperiences.

MethodsPatients’ enrolmentThis study was approved by the Ethics Committee ofNanjing Drum Tower Hospital. From March 2014 to

© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

* Correspondence: qingzhou_gl@163.com†Chang Liu and Yun-xing Xue contributed equally to this work.Department of Thoracic and Cardiovascular Surgery, Nanjing Drum TowerHospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing210000, Jiangsu, China

Liu et al. Journal of Cardiothoracic Surgery (2020) 15:47 https://doi.org/10.1186/s13019-020-1081-x

January 2015, 14 patients were enrolled, with an averageage of 59 ± 14 years (34–76 years, median 62 years) andwith 12 males and 2 females. All patients were diagnosedby aortic CTA before surgery, and the type, location,and extent of the lesion were determined. All patientsunderwent routine examinations, including routineblood, coagulation, liver and kidney function, electrocar-diogram, echocardiography, and head CT examinations.Coronary angiography was performed in patients withtypical angina symptoms or electrocardiographic ischae-mic changes.

DeviceWe designed a new type of blood flow regulator (Fig. 1,Yuhengjia Science and Technology Co Ltd., Beijing,China) based on the design concept of a multi-layer barestent and the haemodynamic changes after multi-layerbare stent implantation. The blood flow regulator is aself-expanding membrane-supported artificial blood ves-sel, the film is made of polyester, the polyester radialand the weft are formed into a mesh 1mm2 in size, andthe metal stent is a nickel-titanium alloy.

Surgical techniqueThe femoral artery approach was used in the operation.The type and location of the lesions were confirmed byangiography. The surgical plan was determined accord-ing to the aortic (CT angiography) CTA findings beforethe operation. Sixteen flow modulators (FM) were im-planted during the operation. There were 10 nativebranched vessels (Additional file 1: Table S1). After thebranch was covered, the blood flow regulator was punc-tured at the opening of the branch with a wire 0.018 in.in size, followed by balloon dilation (3–5 atm) at a diam-eter of 4 mm and then balloon dilation (3–5 atm) at adiameter of 10 mm. Angiography was then performed toobserve the development of branches of blood vessels.The blood flow regulators and intraluminal-supportedartificial blood vessels were located accurately, and therewere no serious ischaemic events that occurred, whichwas considered technical success.

Postoperative management and follow-upAll patients were given long-term oral aspirin enteric-coated tablets (100 mg qd). If there was contraindicationof aspirin enteric-coated tablets, clopidogrel was takenorally for more than 12months (75 mg qd). The patientswere followed up by telephone or as an outpatient for 6months and 1 year, and aortic CTA was performed dur-ing the follow-up. During follow-up, patients withaortic-related events were referred to the hospital at anytime, and any aortic-related event was defined any eventthat was clearly or suspected to be associated with atreated or untreated aortic segment.

Statistical methodsContinuous variables are expressed as medians andquartiles, and categorical variables are expressed ascounts and percentages. Long-term survival rates wereanalysed using Kaplan-Meier curves.

ResultsType of aortic lesionOf the 14 patients, 3 patients underwent acute surgery,and 11 patients underwent subacute surgery. The meantime to onset was 18 ± 6 days (6–27 days, median 19days). There were 10 cases of Stanford type B aortic dis-section (TBAD) in 14 patients: 6 primary intimal tearswere located in the descending thoracic aorta and 4 inthe abdominal aorta. There were 3 cases of penetratingulcer and 2 cases of ulcer at the beginning of the de-scending aorta. Multiple ulcers with a distal aortic archand descending aortic dilatation were found in 1 patient(Figs. 2 and 3, see Additional file 1: Table S1 for moredetails).

In-hospital resultsThe technical success rate was 100%. All patients hadpostoperative aortic CTA with a type III endoleak. Therewere no deaths in the group; no central nervous systemcomplications such as stroke, TIA, hemiplegia, and para-plegia; and no left upper limb ischaemia symptoms.Postoperative serum creatinine levels were increased in

Fig. 1 Modeled blood flow regulator

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3 patients, and postoperative liver function damage oc-curred in 1 patient (Additional file 1: Table S1). Onecase of intestinal obstruction was relieved after conserva-tive treatment. One patient had preoperative haemor-rhagic stroke with numbness of the left limbs: left upperlimb and left lower limb fatigue, lameness, and no post-operative CT findings of cerebral infarction. The symp-toms of the patient were associated with cerebralhaemorrhage but were not related to aortic events (Add-itional file 1: Table S1).

Follow-up resultsAll patients were followed up for an average of 14.7 ± 3.6months (10.4–20.8months, median 13.1months). One pa-tient died of unknown causes 4months after surgery. Onepatient died due to abdominal aortic aneurysm rupture.The remaining 12 patients survived, and the survival ratewas 91% during the 14-month follow-up. The blood flowregulator covered a total of 19 branch vessels (the inter-costal artery was not counted), of which 18 demonstratedsmooth blood flow. One patient had a type III endoleakafter surgery and was implanted with Cook®ESBE Φ 32 ×

L 39mm and a Cook®ESBE Φ 30mm× L 58mm (Cook,Bloomington, Ind) endovascular prostheses. The postop-erative CT showed that the leak had disappeared, and thesecond postoperative follow-up occurred at 3months,during which no adverse events occurred. During thefollow-up period of other patients, 1 case of lower limbparalysis occurred, and muscle strength returned to nor-mal after 1 year; 1 patient had lap gait; 2 patient had upperlimb dysfunction; and 1 patient had left hand numbnessthat occurred 1month after the operation and was moreserious than the numbness before the operation, whichmight be related to preoperative cerebral haemorrhage.One case of left subclavian artery occlusion occurred 1year after the operation, and the patient’s upper limb sys-tolic pressure difference was 70mmHg, the right upperlimb systolic pressure was 180mmHg, and the left upperlimb systolic pressure was 110mmHg (Additional file 1:Tables S1 and S2).

DiscussionThe open operation of aortic disease results in severetrauma and many perioperative complications; thus,

Fig. 2 Demographics and outcome of 14 patients. a) Sex. b) Diagnose. c) Comorbidity. d) Complications. e) False cavity closure. f) Overall survival rate

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open surgery is not appropriate for elderly patients orpatients with multiple complications because they can-not tolerate the trauma of surgery. With the advance-ment of interventional techniques, TEVAR surgery hasbeen widely used due to its advantages of being less in-vasive and having a rapid recovery and a low rate ofmortality and morbidity. However, TEVAR surgery re-quires a sufficient length of normal blood vessels as theanchoring area; the presence of aortic branch vesselsoften results in an insufficient length of the anchoringarea and limits TEVAR surgical use. In response to thisproblem, many solutions have been introduced, such aschimney technology, in situ fenestration technology,custom-made fenestration technology, branched stents,and multilayer bare stents [1].Among these solutions, the most convenient one is a

multilayer bare stent (known as a multilayer flowmodulator, MFM). The haemodynamic changes afterimplantation of the MFM are aneurysms and penetrat-ing ulcers, and turbulent flow in the aortic dissectioncan become laminar, making the blood flow parallel tothe laminar flow of the aneurysm wall, thus eliminatingturbulence, reducing pressure on the aortic wall and

reducing the risk of rupture. The blood flow velocity ofthe aortic aneurysm or penetrating ulcer is sloweddown and prone to thrombosis. The buffering effect ofthe thrombus further reduces the pressure on the aorticwall, and the reduction in aortic wall pressure promotesthe reconstruction of the middle layer of the artery.The MFM metal stent has a mesh hole, laminar flowparallel to the branch blood vessel can be retained inthe branch blood vessel, and endothelialization of thestent mesh can be inhibited. The blood flow of thebranch blood vessel can be effectively preserved, wherethere is no branch blood vessel. It can slow the bloodflow rate, facilitate the adhesion and growth of endo-thelial cells, and promote endothelialization of the stentmesh to isolate the tumour cavity. Haemodynamicchanges after implantation of the MFM promotethrombosis in the aneurysm cavity, reduce the pressureon the aneurysm wall, and preserve branch vascular pa-tency. TBAD can also seal the endometrial intimalopening, enlarge the true cavity, compress the falselumen and promote the thrombosis of the pseudocath-eter; these mechanisms can promote the reconstructionof the aorta [2, 3].

Fig. 3 CT image of patients before and after TEVAR surgery with new blood flow regulators. a) Preoperative image of aortic arch branches showedthe aortic dissection of a patient involving the beginning of the left subclavian artery (left panel). The centre image demonstrates the coverage of thestent graft 3 months after TEVAR, and the 12-month scan shows continuous blood flow in the aortic arch branches. b) The imaging of the aortic archbefore surgery showed aortic dissection involving the anterior aortic arch wall (left panel). CT images 3 and 12months after TEVAR surgery showedthat aortic dissection was resected and corrected. c) The scan for pulmonary artery bifurcation before and after TEVAR

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Our new blood flow regulator produced similarhaemodynamic changes in 14 patients. The technicalsuccess rate was 100%, and there were no serious liverfunction injuries or instances of renal failure, gastro-intestinal ischaemia, or other organ perfusion symptomsin the early postoperative period. There were no acutesubclavian artery ischaemia complications, such as limbpain and dizziness, and there were no central nervoussystem complications, such as paraplegia and apoplexy.There were 2 patients who died after 14 months offollow-up: one patient died due to abdominal aortic rup-ture, and the other cause was unknown (survival ratewas 86% (12/14)). There were 2 cases of type-III endo-leak and 1 case of aortic-related adverse events, 1 case ofrenal dysfunction, 1 case of repeated TIA, and 1 case ofupper limb dysfunction; however, there were no compli-cations such as stroke, paraplegia or visceral ischaemia.During the follow-up period, 90% (9/10) of patients withTBAD were treated with false lumen thromboembolism.The short-term curative effect was satisfactory, and therewere no complications of covered branch embolization.The new blood flow regulator is a commercialized

product that can be used in emergency surgery withoutcustomization. It can address branch vessels via balloondilation without implanting stent(s) into branch vessels,which avoids the bracket damage caused by the frictionbetween pluralities of brackets in chimney technology.The blood flow regulator does not block the blood flowof the branch vessels, avoiding the ischaemic time beforethe fenestration of the branch vessels in the in situ fen-estration technique and effectively reducing ischaemia-related complications. The blood flow regulator has theadvantages of simple implantation, a low accuracy oflocalization, low technical difficulty, a small learningcurve, a short operation time, a small dose of radiationto patients and physicians, and a small dosage of con-trast agent.The new blood flow regulator is a stent graft with a

small mesh and demonstrates changes similar to thehaemodynamic changes observed in aortic aneurysmswith multilayer bare stents. Compared with multilayerbare stents, the new blood flow regulator has many ad-vantages in terms of practical applications. (1) Multilayerbare stents promote thrombosis by slowing down theblood flow in the lumen of the isolated aneurysm. Thethrombus of the aneurysm into the branch vessel cancause branch vessel embolization; the new type of bloodflow regulator can dilate the reticular capping of branchvessels and avoid the risk of endovascular thrombo-embolism in isolated aneurysms after the implantationof the stent in the branch vessels. (2) The multilayerbare metal stent is not suitable for implantation in thearea with thrombus because it may cause the thrombusto break off, whereas the new blood flow regulator is a

mesh-shaped stent that does not cut the thrombus andisolates the thrombus from the lumen of the vessel toavoid thrombus loss. (3) The length of the multilayerbare stent is related to the diameter. Furthermore, thedifficulty of accurately locating the distal end of the stentmay lead to the difficulty of incomplete release, whilethe length of the new type of blood flow regulator isfixed after release, and the location of the distal end isaccurate [4].Blood flow through the stent will produce shear force

on the stent, which requires balanced friction betweenthe stent and the vascular wall to ensure that the stentdoes not shift. The friction between the stent and thevascular wall is proportional to the radial support of thestent, and the pressure generated by the radial supportof the stent is inversely proportional to the length of thetumour neck. Therefore, a shorter neck must be sub-jected to high pressure to ensure that it is not displacedfrom the covered stent, and a higher pressure on theneck may lead to long-term neck dilation or even to iat-rogenic aortic rupture or reverse avulsion aortic dissec-tion. The new blood flow regulator reduces the pressureon the anchoring area by extending the proximal an-choring area, avoiding further dilation of the neck of thetumour and reducing iatrogenic aortic injury [5].There was no paraplegia in this group of patients and

no paraplegia or other spinal cord ischaemia after cover-ing the intercostal artery, as permanent paraplegia afterTEVAR is associated with the length of the thoracicaorta covered. Feezor et al. [6] found that spinal cordischaemia after TEVAR occurred when the distance be-tween the stent graft and the proximal end of theabdominal cavity was 17.3 ± 21.8 mm, whereas no is-chaemia was observed when the distance was 63.1 ±62.9 mm (p = 0.0006). The coverage length threshold was205 mm, and the sensitivity and specificity of predictingspinal cord ischaemia after TEVAR were 80 and 92.5%,respectively. The effect of the new blood flow regulatoron preventing spinal cord ischaemia was significantlybetter than that of the stent graft. This was a chronic oc-clusion of the spinal cord artery after the blood flowregulator covered the intercostal artery, and the chronicocclusion provided sufficient time for the establishmentof the spinal artery collateral circulation [7]. Some stud-ies have also suggested that planned, temporary endo-leak after TEVAR can maintain spinal cord blood supplyto reduce the incidence of paraplegia [8].The new blood flow regulator can also be used in

combination with stent grafts in some special cases. (1)When the length of the anchoring area is insufficient,the blood flow regulator is first placed into the normalvessel wall, the anchoring area is expanded, and then thestent graft is implanted in the flow regulator. (2) Whenthe large tumour cavity or endometrial rupture is

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adjacent to the branch vessel, the blood flow regulatorcan be implanted first, and then the stent graft is im-planted in the vicinity of the branch vessel opening,which can partially close the tumour cavity or break andcan reduce the permeation stent. The amount of internalleakage promotes thrombosis in the tumour cavity orpseudocavity and promotes vascular remodelling. Therewere 5 patients in this group. First, a blood flow regula-tor was placed in the aortic arch, and then a stent graftwas placed in the blood flow regulator. During thefollow-up, the tumour cavity was thrombotic, and thebranch vessels were patent. The combination of bloodflow regulators and stent grafts can expand the surgicalindications of TEVAR and achieve good results.However, there are some defects of this new blood flow

regulator, such as type III endoleak and thromboembol-ism. The occurrence of endoleak is mainly related to themesh-like lamella, the size of the aortic aneurysm and thesize of the aortic dissection. After the operation, the typeIII endoleak can be directly closed by implanting sentgrafts. Otherwise, another blood flow regulator can besuperimposed to reduce the mesh size. To reduce type IIIendoleaks, permeation stents with different mesh sizes canbe applied according to the size of different tumour cav-ities. The mesh-like mulch covering the opening of thebranch vessel may result in thrombosis in the early stage.To solve this problem, aspirin was used orally (100mg qd)to prevent thrombosis. After the transmembrane stentwas covered with endothelial cells, the probability ofthrombosis was significantly reduced. Antiplatelet therapyis thought to affect the thrombosis of the tumour cavity orpseudocavity and aortic remodelling, but it can also in-crease the patency of branch collateral vessels. Our resultsshowed that thromboembolism occurred when the bloodflow regulator was applied to the arcuate vessels. There-fore, anticoagulation is necessary after the blood flowregulator is implanted.The limitation of this study is the small number of

patients and the short follow-up time. The effect ofthe regulator is good according to recent results, butfurther studies are needed to assess the long-term ef-fect. Major long-term observations include the timeof thrombosis of the pseudocavity or tumour cavity,the reconstruction of the aorta, the patency of branchvessels, and changes in the neck pressure. Most pa-tients in recent studies were treated in the subacutephase. At this time, the inflammation of the aorta islower than that in the acute phase, and the toughnessof the endometrium is increased but not rigid. AfterTEVAR, the true cavity is fully enlarged, and thepseudocavity is compressed. The middle layer isclosely adhered to the outer membrane to achieve abetter therapeutic effect. The treatment of chronic in-terlayers remains to be addressed.

ConclusionIn the current study, we demonstrate that the blood flowregulator, when used to treat TBAD, works by achievingresults of a proper landing zone and preserving the nor-mal flow of branches of the aorta. The blood flow regu-lator is a safe and feasible choice for TEVAR surgery inChina. Its application will provide a promising new tech-nology currently used for TEVAR surgery in this region.

Supplementary informationSupplementary information accompanies this paper at https://doi.org/10.1186/s13019-020-1081-x.

Additional file 1: Table S1. Summary of case data and outcome.Table S2. Case data.

Abbreviations2-DM: Type 2 diabetes; AKI: Acute renal failure; BAD: Stanford B aortic dissection;CAD: Coronary artery disease; COPD: Chronic obstructive pulmonary disease;CT: Computed tomography; CTA: CT angiography; FM: Flow modulators;HYT: Hypertension; ICH: Intracranial haemorrhage; MFM: Multilayer flowmodulator; PAU: Penetrating ulcer; PVD: Peripheral artery disease; SLE: Systemiclupus erythematosus; TBAD: Type B aortic dissection; TEVAR: Thoracicendovascular aortic repair; TIA: Transient ischemic attack

AcknowledgementsNone.

Authors’ contributionsCL and YXX contributed to the data collection of the manuscript. CL, YXXand QZ contributed to the study idea and conceptualization of themanuscript. CL, DJW and QZ performed the surgeries.All authors contributed to revisions of the manuscript. All authors read andapproved the final manuscript.

FundingNone.

Availability of data and materialsThe datasets used are available from the corresponding author on reasonablerequest.

Ethics approval and consent to participateThis study was approved by the Ethics Committee of Nanjing Drum TowerHospital.

Consent for publicationObtained from the participants.

Competing interestsThe authors declare that they have no competing interests.

Received: 16 October 2019 Accepted: 17 February 2020

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