Extended Eversion Carotid Endarterectomy: Computation of Hemodynamics

Accepted Manuscript Extended Eversion Carotid Endarterectomy: Computation of Hemodynamics Tomislav Istvanić, Zvonimir Vrselja, Hrvoje Brkić, Radivoje Radić, Igor Lekšan, Goran Curic PII:

S0890-5096(15)00620-2

DOI:

10.1016/j.avsg.2015.05.034

Reference:

AVSG 2504

To appear in:

Annals of Vascular Surgery

Received Date: 13 February 2015 Revised Date:

14 May 2015

Accepted Date: 26 May 2015

Please cite this article as: Istvanić T, Vrselja Z, Brkić H, Radić R, Lekšan I, Curic G, Extended Eversion Carotid Endarterectomy: Computation of Hemodynamics, Annals of Vascular Surgery (2015), doi: 10.1016/j.avsg.2015.05.034. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Extended Eversion Carotid Endarterectomy: Computation of Hemodynamics

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Tomislav Istvanića,* , Zvonimir Vrseljab,c,*, Hrvoje Brkićd, Radivoje Radićc, Igor Lekšanc,

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Goran Curice,**¶

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*These authors equally contributed to the manuscript.

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a

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b

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Croatia

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Department of Vascular Surgery of Clinic for Surgery, University Hospital Osijek, Croatia Department of Radiology, University Hospital Osijek, Croatia

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University of Osijek, Croatia

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Medicine, University of Osijek, Croatia

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Department of Anatomy and Neuroscience, Faculty of Medicine, University of Osijek,

Department of Biophysics, Medical Statistics and Medical Informatics, Faculty of Medicine,

Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of

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**Correspondence to Goran Curic, Faculty of Medicine, University of Osijek, J. Huttlera 4,

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31000 Osijek, Croatia. [email protected]. Phone +385911612584. Fax +38531505615.

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ACCEPTED MANUSCRIPT ABSTRACT

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Background: Stroke prevention includes surgery for significant stenosis of internal carotid

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artery. Consensus on a standard approach lacks and one alternative approach is eversion

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carotid endarterectomy (eCEA). In order to overcome disadvantages of eCEA, we developed

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extended eversion carotid endarterectomy (exeCEA). Aiming to investigate hemodynamics

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after different surgical approaches, we created computational fluid dynamics models of

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exeCEA and eCEA with included progressing lumen narrowing - representation of artery

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restenosis at the incision line.

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Methods: Blood flow velocities, volume flow rates and wall shear stress were established in

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carotid arteries from models of eCEA and exeCEA with included increasing groove (1, 1.5, 2

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and 2.5 mm) at the ‘incision line’, under input pressure of 120 and 150 mmHg.

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Results: For the corresponding restenosis grade, models of exeCEA had a larger orifice

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towards internal carotid artery, lower blood flow velocities and higher volume flow rates in

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internal carotid artery, with lower volume flow rates in external carotid artery. Wall shear

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stress values in internal carotid artery of exeCEA models were lower than in eCEA models,

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later reaching the thrombotic range.

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Conclusions: Computational fluid dynamics showed better hemodynamic properties in

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exeCEA models, indicating presented approach might be better at preserving brain perfusion.

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Keywords: carotid endarterectomy, circulation, blood flow, wall shear stress, computational

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fluid dynamics

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ACCEPTED MANUSCRIPT 1. Introduction

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Stroke is the second most common cause of death and stroke survivors have the highest risk

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for a recurrent stroke [1]. About 30% of all strokes is considered to be associated with

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stenosis of carotid artery (i.e., due to reduction of blood flow, or thrombi developing at

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atherosclerotic plaque) [1]. In order to reduce absolute risk for stroke, prevention strategy

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includes eversion carotid endarterectomy (eCEA): surgery of stenotic internal carotid artery

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(ICA) [2]. Carotid endarterectomy (CEA) is recommended when the lumen of the ICA is

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reduced more than 70%, as documented by noninvasive imaging, i.e. Doppler

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ultrasonography. CEA is performed in both (I) symptomatic (history of ipsilateral minor

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stroke or transient ischemic attack) and (II) asymptomatic patients (evident stenosis at carotid

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bifurcation).

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Common approaches are conventional endarterectomy with patch angioplasty and eCEA;

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conventional CEA is performed more often, although some large studies slightly favor eCEA

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[2-6]. These procedures have similar proportions of postoperative stroke, myocardial

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infarction and recurrent stenosis [4, 6, 7]. Restenosis develops primarily because of intimal

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hyperplasia at the site of vessel injury [8, 9]. (Re)stenosis increases blood velocity that can

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lead to increased turbulence. Altered hemodynamics corresponds with sites of development of

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vascular wall pathology (intimal thickening and atherosclerosis) and it is associated with

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altered properties of blood (hypercoagulability) [10]. CEA alters the endothelial lining and

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changes flow pattern; blood velocity, volume flow rate and wall shear stress (WSS), although

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effects on hemodynamics are partially understood [11].

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The eCEA has several disadvantages; difficulty of intraoperative shunt insertion (if needed),

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possible baroreceptor damage, lack of association of reduced restenosis rates and stroke, and

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inadequate endarterectomy when plaque extends well into CCA [4]. Guided by surgical

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experience, knowledge of anatomy and hemodynamics, we projected that modification of

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incision might overcome some disadvantages of eCEA. ‘Hockey stick’ shaped incision in

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extended eCEA (exeCEA) involves transection of CCA, from bifurcation distally, until

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reaching proximal end of plaque, where incision ends by extending under angle of 45°

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towards ICA (Fig. 1).

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We modeled 3D flow simulations in carotid vessels after exeCEA and eCEA procedure, and

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tested hemodynamics after lumen narrowing (restenosis at site of vessel cut) to assess the

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effects of local geometry changes on volume flow rates. Here, we present results of

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computational fluid dynamics (CFD) models of restenosis at incision line after simulated

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eCEA and exeCEA.

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2. Material and methods

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The 3D carotid arterial tree (physiological, lumen obstruction free) model was created on the

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basis of MR angiography of a healthy middle age female, after obtaining informed consent.

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Local ethical committee approved the study. The 3Dslicer software [12] extracted data from

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MR. Raw model was processed with MeshLab (MeshLab Visual Computing Lab - ISTI -

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CNR http://meshlab.sourceforge.net/) software and further processed with SolidWorks,

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software for building models and managing flow simulations.

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The eCEA and exeCEA were mimicked (Fig. 1) on created 3D carotid model. Models

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included simplified folds that represented intimal hyperplasia or recurrent atherosclerotic

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disease that narrow the vessel diameter. Increasing folds at ‘incision line’ (1, 1.5, 2 and 2.5

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mm) – represented restenosis grade I-IV, respectively (accordingly referred in the text).

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Mathematical approximations of incision cross-sectional areas showed that orifice after

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exeCEA is approximately 1.6 times larger (Calculation shown in Supplemental Figure 1). In

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the simulations, the blood was defined as a non-Newtonian liquid (density of 1 g/cm3), wall

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material was set as rubber (elastic modulus 6.2 N/mm2), temperature was 310.15 K (37°C),

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surrounding pressure of 101325 Pa, and adiabatic wall conditions were assumed.

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Volume flow over time at model inlet lid (beginning of CCA) was adjusted to mimic a

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pulsatile flow (single heart cycle) [13]. To assess the effects of changing local geometry

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(restenosis) during ‘usual’ daily pressure oscillations in operated patients, outlet boundary

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condition was set as a constant pressure, with value of 120 or 150 mmHg [14]. Since the

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volume flow rates between eCEA and exeCEA procedure were of primary interest, flow rate

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partition at carotid bifurcation was not fixed outlet boundary condition. Although, it is

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recommended to avoid the coupling of unsteady flow and multiple outflows with constant

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pressure as outlet boundary condition [15], we chose this setting in order to assess the relative

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volume flow rate distribution (see Limitations for details). Because the relative values

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between eCEA and exeCEA were of interest, we find that used simplifications were mitigated

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- as only differing variable was the shape of incision line. Similarly, differing resistances of

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ICA and ECA were not included in the flow simulations since only relative hemodynamic

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ACCEPTED MANUSCRIPT values were of interest (eCEA vs. exeCEA). Data acquisition of hemodynamic parameters

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was performed in the middle third of CCA, and at middle thirds of modeled ICA and ECA,

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distally from narrowing. WSS size area was analyzed using open source ImageJ software

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[16]. According to previous studies, WSS values between 3.5 Pa and 7 Pa were categorized as

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“high WSS” [17, 18], while WSS values above 7 Pa were categorized as “thrombotic WSS”

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[10]. Calculation of areas under curve (AUC), using trapezoidal approximation, was used for

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comparison of hemodynamic data.

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2.1. Statistical analysis

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IBM SPSS Statistics v15.0 was used for statistical analyses. Normality of distribution was

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tested with Shapiro – Wilks test. Time dependent blood velocities and volume flow rates for a

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given locations were compared using repeated measures T-test. A two-sided p<0.05 was

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considered significant.

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3. RESULTS

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3.1. Blood velocities

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Blood velocities in CCA were similar in both models for corresponding restenosis grades.

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Overall, blood velocities in ICA of exeCEA models varied less with progressing restenosis

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and were lower than in corresponding eCEA models (Table 1.). ECA blood velocities

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increased with progressing restenosis in all models and were higher in eCEA models (Table

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2.). In models of restenosis grade IV, blood velocities in ICA continued to fall in the same

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rate, but blood velocities in ECA increased sharply, more prominently in eCEA models

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(Tables 1 and 2).

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3.2. Volume flow rates

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CCA volume flow rates were constant in all models. ICA volume flow rates decreased more

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with progressing restenosis in eCEA models, so exeCEA models had significantly higher flow

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rates in ICA, with the exception of restenosis grade III model for 150 mmHg pressure

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(p=0.373). ICA peak flow rates for restenosis grade II-IV were lower in eCEA models than in

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physiological and exeCEA models (data not shown).

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ACCEPTED MANUSCRIPT ECA volume flow rates increased with increasing systolic pressure and progressing

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restenosis, and increased more prominently in eCEA restenosis models (Table 2). Similarly to

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ICA volume flow rates, ECA volume flow rates did not differ only in grade III restenosis

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models under simulated pressure of 150 mmHg (p=0.131).

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3.3 Wall shear stress

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Under the pressure of 120 mmHg and during maximal volume flow, ICA in eCEA models

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across all restenosis grades, on average, had 43% more vessel’s surface exposed to high WSS,

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out of which, on average, 11% of the vessel surface was exposed to the thrombotic WSS

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(Fig. 2 and 3 A). Similar results were obtained under the pressure of 150 mmHg during

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maximal volume flow, where ICA in eCEA models across all restenosis grades, on average,

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had 50% more vessel’s surface exposed to high WSS, out of which, on average, 40% of

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vessel surface was exposed to thrombotic WSS (Fig. 3 C).

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In both models, WSS in ECA increased with increasing grade of restenosis. In ECA of eCEA

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models, relatively constant proportion of vessel surface was exposed to high WSS, but with

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progressing restenosis, proportion of vessels surface exposed to thrombotic WSS increased

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(Fig. 3 B and D). In ECA of exeCEA models, vessel surface exposed to high WSS increased

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with progressing restenosis (Fig. 3 B and D). Thrombotic WSS (values of 7 Pa or higher)

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were not detected in ICA nor ECA of exeCEA models (Fig. 2).

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4. DISCUSSION

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4.1. Surgical techniques and restenosis

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Leading invasive stroke prevention strategy includes surgical intervention, recommended in

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asymptomatic and symptomatic patients and in later ‘should be performed sooner rather than

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later […] within two weeks’ [19]. CEA is a standard surgical approach for carotid

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revascularization, but alternative to CEA for symptomatic patients is carotid artery stenting,

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which has advantages for some patients [11, 20]. Conventional CEA includes longitudinal

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incision from CCA into ICA, while the incision in eCEA is made from carotid bifurcation

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obliquely, parallel to ECA, downward to CCA lateral border. The later is performed more

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often and commonly includes larger, oblique transection of CCA. Both techniques have

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advantages and disadvantages [1-5]. Advantages of eCEA include omitting incision of ICA

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ACCEPTED MANUSCRIPT (minimizing risk of restenosis of ICA), while disadvantage is restenosis and need for an

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additional incision of CCA, where atheroma spreads deep in CCA (Fig. 1) [21].

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Several modifications of eCEA has been described previously; including longitudinal

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arteriotomy that begins on CCA and skews towards ECA [22], and anterior incision of carotid

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bulbus [23]. In presented exeCEA approach, the cut is limited to CCA, enables better

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visualization of proximal end of endarterectomy and length of incision can be adjusted to

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remove atheroma from proximal parts of CCA. At carotid bifurcation, a typical location of

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carotid atheroma, the vessel incision line in exeCEA is 1.6 times larger (Supplemental Figure

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1). As the larger incision means technical ease, vessel injury is also larger - where intimal

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hyperplasia (considered as the most common cause of restenosis) is expected to develop [9].

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Although incision is larger in exeCEA, the intimal ridge occupies relatively smaller

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proportion of the orifice of a crucial vessel, the ICA (Fig. 1). Oblique tansection of CCA is

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often extended during eCEA, in order to create a larger orifice towards ICA, but the orifice is

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still smaller than in exeCEA (calculation not shown), implying that a larger volume flow

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towards ICA should be present after exeCEA. Other contributing factors for development of a

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restenosis is an intimal flap in suture line, continuing atherosclerosis, increased turbulence

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[24] and change in vessel wall properties [25].

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4.2. Hemodynamics after carotid endarterectomy

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As intimal hyperplasia at the site of vessel injury is expected to develop after every CEA, we

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modeled lumen narrowing at the suture line after original and extended eCEA. Although

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carotid revascularization is performed on stenotic arteries (arterial lining with irregular

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atherosclerotic plaques), our simplified model is based on ‘clean’ vessels, since one would

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expect that after the procedure the arteries would be ‘clean’. As restenosis at suture develops,

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the lumen of ICA narrows, causing the reduction of volume flow in ICA and shunt of blood

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into ECA (increase in volume flow in ECA). Beside reduced blood delivery into the brain,

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altered hemodynamics in narrowed vessel further jeopardizes the brain perfusion, as thrombi

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that might build-up on the atherosclerotic plaque can cause ipsilateral thromboembolic stroke.

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Recanalization of ICA leads to the reduction of a peak blood flow velocity and pressure

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gradients, but effects on WSS and vascular wall properties are less understood [26-28].

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Intraluminal vascular wall is subjected to physical forces that affect its physiological

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response, development of atherosclerosis and other wall pathologies [29]. Hemodynamic

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forces that act on arteries can be perpendicular (i.e., blood pressure) or parallel to the wall

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ACCEPTED MANUSCRIPT (i.e., WSS) [30]. Both low and high WSS are considered pathological [10, 30, 31]. A low

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WSS and its high oscillations are linked to the development of local atherosclerosis, through

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remodeling of the vessel wall [10]. WSS in large arteries ranges from 1 to 10 Pa, reaching

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peak values during increased cardiac output or hypertension [10, 30]. High WSS leads to

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development of vortices that entrap non-activated platelets and cause platelet activation and

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aggregation [31]. Therefore, progressing stenosis, through increased WSS leads to platelet

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activation and thrombus formation [32]. Lumen narrowing in eCEA models resulted in higher

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blood velocities causing higher WSS (reaching the thrombotic range; above 7 Pa) (Fig. 2) [10,

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33]. Accumulated WSS over time is other possible biomechanical parameter of thrombus

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formation [34] and CFD indicate that exeCEA should have less chance of thrombus

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formation. As stated previously, due to the selected CFD parameters absolute values of WSS

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might not be similar to experimentally observed values but their relative (eCEA vs. exeCEA)

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values can be taken into account. Our results show that eCEA models had higher WSS than

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exeCEA models, indicating that after exeCEA approach thrombotic events might be less

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frequent, but recurrent atherosclerotic process might be more progressive (as in vessels of

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exeCEA models part of surface had low WSS). These assumptions remain to be tested in

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comparative clinical study.

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The major advantage of exeCEA should be a wider lumen (cross-section area) at the site of

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restenosis, allowing better flow and pressure pulsation transmission [35]. Due to surgical

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procedure and subsequent restenosis, altered arterial geometry results with altered flow

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pulsations [36]. In physiological conditions, 70% of blood from CCA goes into ICA, but as

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ICA narrows, more blood is shunted towards ECA. ECA blood flow is usually overlooked

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and considered clinically irrelevant, although increased volume blood flow through ECA

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means less blood volume in ICA. Volume flow rate in ECA increased with increasing

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restenosis in both models, but ‘shunt’ was more pronounced in eCEA models (Table 2). WSS

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in ECA also increased with increasing restenosis, more in eCEA models, where increasingly

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larger ECA vessel surface was exposed to thrombotic WSS (B and D in Fig. 3). In the light of

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previous research [37], hemodynamics of ECA indicate that its occlusion after exeCEA might

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be less frequent. Overall, the hemodynamics of ICA and ECA changed less with progression

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of restenosis in exeCEA models. Therefore, presented modification of surgical approach

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might have advantages over the original eCEA.

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4.3. Study limitations

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ACCEPTED MANUSCRIPT In order to assess the relative difference in volume flow distribution, velocity and WSS after

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eCEA and exeCEA, constant pressure was selected as boundary condition (therefore not

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taking in count peripheral resistance). Such simplification can deviate the results when model

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includes pulsatile flow and multiple outlets, but in a model of a relatively simple geometry

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(like the one with single inlet and two outlets), the used boundary condition might be

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applicable for CFD analysis [15]. We aimed to compare two approaches and, thus, selected

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CFD parameters were uniformly applied across eCEA and exeCEA models. In this way, the

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only differing variable was the shape and position of the incision line with its restenosis fold.

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Therefore, we find that such ‘relative’ experimental setting mitigated our study’s major

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limitation. CFD studies have become valuable tool in hemodynamic analyses, allowing

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interpretation of clinical observations and experimental planning based on CFD.

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4.4. Conclusions

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Presented CFD models of modification of standard eversive carotid endarterectomy approach

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showed better hemodynamic parameters with progressing restenosis (lower wall shear stress,

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higher volume flow rate and lower blood velocities in ICA). These results indicate that, when

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compared to eCEA, exeCEA might be less thrombotic prone and better at long-term

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preservation of brain perfusion.

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Acknowledgements

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None.

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Disclosure

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The authors report no proprietary or commercial interest in any product mentioned or concept

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discussed in this article.

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157-175.

36) Farrar, D.J., H.D. Green, and D.W. Peterson, Noninvasively and invasively measured

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pulsatile haemodynamics with graded arterial stenosis. Cardiovasc Res. 1979. 13(1):

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p. 45-57.

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artery following carotid endarterectomy? BMC Surg. 2008. 8(1): p. 20.

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37) Abbas, S.M., D. Adams, and P. Vanniasingham, What happens to the external carotid

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ACCEPTED MANUSCRIPT Table 1. Internal carotid artery blood velocities and volume flow rates in eCEA and exeCEA models. BLOOD VELOCITY Restenosis

VOLUME FLOW RATE p

eCEA [AUC]

exeCEA [AUC]

p

Grade I

0.332

0.304

<0.001

5.28

5.43

<0.001

Grade II

0.327

0.303

<0.001

5.13

5.37

<0.001

Grade III

0.281

0.282

0.734

4.71

5.05

<0.001

Grade IV

0.220

0.234

0.003

3.61

3.93

0.005

Grade I

0.415

0.385

<0.001

6.59

6.72

<0.001

Grade II

0.404

0.385

<0.001

6.29

6.66

<0.001

Grade III

0.343

0.331

0.034

5.93

6.01

0.373

Grade IV

0.267

0.287

0.001

4.49

4.86

0.003

120 mmHg

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150 mmHg

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eCEA [AUC]

exeCEA [AUC]

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Input pressure

AUC - area under curve.

Table 2. External carotid artery blood velocities and volume flow rates in eCEA and exeCEA models. BLOOD VELOCITY

Restenosis

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Systolic pressure

VOLUME FLOW RATE

eCEA [AUC]

exeCEA [AUC]

p

eCEA [AUC]

exeCEA [AUC]

p

Grade I

0.318

0.271

<0.001

3.21

3.13

0.002

Grade II

0.328

0.275

<0.001

3.33

3.20

<0.001

Grade III

0.364

0.307

<0.001

3.71

3.59

<0.001

Grade IV

0.455

0.377

<0.001

4.82

4.54

0.014

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120 mmHg

Grade I

0.388

0.336

<0.001

4.02

3.98

0.048

Grade II

0.406

0.340

<0.001

4.19

4.05

<0.001

Grade III

0.448

0.403

<0.001

4.63

4.75

0.131

Grade IV

0.562

0.472

<0.001

6.11

5.79

0.018

150 mmHg

AUC - area under curve.

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ACCEPTED MANUSCRIPT FIGURE TITLES AND CAPTIONS

Figure 1. Incision line in eversion and modified eversion carotid endarterectomy and

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their cross–sectional areas. Scheme of carotid vessels with incision line after eversion (eCEA) and modified eversion carotid endarterectomy (exeCEA). exeCEA involves transection of CCA, from bifurcation

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distally, until reaching proximal end of plaque, where incision ends by extending under angle

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of 45° towards ICA.

Figure 2. Wall shear stress in modified and eversion carotid endarterectomy. Results of computation of wall shear stress in carotid arteries after eversion (eCEA) and modified eversion carotid endarterectomy (exeCEA) during single heart cycle under pressure

restenosis grade I-IV.

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of 120 and 150 mmHg. Simulation included increasing groove at ‘incision line’ - representing

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Figure 3. Relative WSS in ICA and ECA after eCEA and exeCEA procedure. Since the relative values were of interest, WSS values in each chart are normalized to eCEA

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grade I. Line representing WSS higher than 7 Pa in exeCEA is not present since thrombotic range with this procedure is never reached. Supplemental Figure 1. Representation of incision line in eversion and modified eversion carotid endarterectomy and calculation of their cross–sectional areas.

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ACCEPTED MANUSCRIPT SUPPLEMENT METHODS Approximation of cross-sectional areas in eCEA and exeCEA Several assumptions were made in order to simplify calculation of cross-sectional areas. A

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shape composed of rectangle and half of the ellipse.

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cross-sectional incision areas; eCEA has a elliptical shape, while the exeCEA has a complex

dCCA=1 2beCEA=2.05xdCCA 2aeCEA=dCCA

ACCEPTED MANUSCRIPT The cross-sectional area of ellipse in eCEA is: PeCEA=axbxπ PeCEA= (1.02xdCCA)x(0.5xdCCA)xπ

The cross-sectional area of ellipse in exeCEA is:

PexeCEA=Prectangle+Phalf-ellipse

l1=2.02xdCCA

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l2= dCCA

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P=(a x b)+(a x b x π)/2

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PeCEA=1.61xdCCA2

Prectangle= l1 x l2

Prectangle = 2.02dCCA2

2bexeCEA = dCCA/cos 45°

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2bexeCEA= 1.42x dCCA bexeCEA= 0.71 x dCCA

PexeCEA=Prectangle+Phalf-ellipse

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PexeCEA=(a x b)+ (a x b x π)/2

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PexeCEA=2.02dCCA2+(0.5xdCCAx0.71xdCCAx π)/2 PexeCEA=2.57xdCCA2

Ratio of exeCEA to eCEA cross-sectional areas:

PexeCEA:PeCEA=2.57x dCCA2 : 1.61xdCCA2 PexeCEA:PeCEA=1.6