Pre- and Post-stenting Cerebral Blood Flow Velocities in Patients with Carotid Artery Stenosis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.333439
Source of Support: None, Conflict of Interest: None
Keywords: Carotid artery stenosis, cerebral blood flow, middle cerebral artery, stents, transcranial Doppler ultrasonography
Atherosclerosis-induced internal carotid artery (ICA) stenosis is responsible for about 20% of all ischemic strokes. Carotid artery endarterectomy (CEA) can preclude ischemic strokes. The study of hemodynamic changes following CEA, especially on the side of the procedure, has focused on complications, drastic ones in particular, such as hyperperfusion syndrome and intracerebral hemorrhage.
Carotid angioplasty and stenting (CAS) have many advantages as an alternative to CEA because it substantially reduces the risk of cerebral ischemia when performed appropriately., Transcranial Doppler ultrasound (TCD) is a noninvasive technique that evaluates the velocity, direction, and other properties of blood flow in the cerebral arteries, as well as the cerebrovascular reserve, using a pulsed ultrasonic beam. The flow velocities measured with TCD are directly proportional to invasive flow measurements., The established clinical indications for the use of TCD include cerebral ischemia, sickle cell disease, detection of right-to-left shunts, subarachnoid hemorraghe, periprocedural or surgical monitoring, and brain death. Ultrasound targeting of the occluded artery in combination with intravenous (IV) tissue plasminogen activator (tPA) IV tPA (sonothrombolysis) has been shown to increase the rate of recanalization, both through its direct mechanical effect on the thrombus and indirectly by augmenting the effect of tPA on the clot. This study evaluated the hemodynamic effects of CAS on cerebral blood flow velocity (CBFV) in patients with carotid artery stenosis, before, 3 d, and 3 months after the procedure using TCD.
Gazi University, Faculty of Medicine ethics committee approved the protocol, and all subjects provided informed consent. The study included 36 patients with atheromatous carotid artery stenosis. North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria was used to specify the degree of carotid artery stenosis. More than 50% stenosis in symptomatic patients and 70% stenosis in asymptomatic patients were included in the study. 26 patients were symptomatic and 10 patients were asymptomatic. The angiography results were discussed by a multidisciplinary team, which included an interventional radiologist, neurologist, and neurovascular surgeon; the study enrolled patients for whom CAS was selected as the first-choice treatment. Patients with severe disabilities due to a previous stroke, a history of dementia, or with peripheral vascular or aortic arch disease severe enough to prevent adequate vascular access were excluded.
Written informed consent was taken from all individual participants included in the study. Twenty eight patients (77.8%) were male (mean age 66 ± 8 years) and 8 patients (22.2%) were female (mean age 67 ± 3 years). [Table 1] summarizes their clinical characteristics and vascular risk factors, such as hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, and smoking.
Cerebral computed tomography (CT) or magnetic resonance imaging (MRI) was performed in every patient, and carotid stenosis was evaluated using duplex sonography, CT, and MRI angiography before the procedure. To obtain baseline values, the CBFV was evaluated 1 d before CAS. Follow-up TCD evaluations were performed 3 d and 3 months postoperatively. The patients were treated with 100 mg/day aspirin and 75 mg/day clopidogrel for at least 96 h before CAS. The Verify Now® test was performed on every patient before the procedure.
The TCD studies were performed in a quiet room with the subject lying in a comfortable supine position. All Doppler recordings were performed by 1 of 2 physicians who were blinded to the clinical status of the subjects. The intracranial arteries were insonated through the temporal window using a standard protocol. The sample volume was 8–10 and 5 mm in the axial and lateral directions, respectively. Using a 2-MHz probe, the mean (Vm) and peak systolic (Vpeak-VP) velocities of the middle (MCA) and anterior (ACA) cerebral artery flows were recorded at respective depths of 50–60 and 50–65 mm, as described by Aaslid. Vm and Vpeak-VP were determined for the CBFVs (cm/s) and the pulsatility index (PI) was determined. The measurements with the best signal-to-noise ratio were used, and the highest CBFVs were selected for analysis. Gosling's PI was calculated as the difference between Vmax and Vmin divided by the mean velocity. All TCD studies were performed with a SONARA TCD apparatus (Cardinal Health, Madison, WI, USA).
For CAS, baseline angiography and the intervention was performed in the interventional radiology suite. Stenosis rates were measured using the NASCET criteria. Perioperatively continuous ECG and invasive arterial blood pressure monitoring were provided. Angiography and stenting procedures were carried out in cases under local anesthesia (2% lidocaine hydrochloride). In all cases, a percutaneous transfemoral approach was used for CAS employing a 90-cm-long, 6 Fr or 7 Fr introducer sheath (Destination, Terumo, Tokyo, Japan) placed in the distal common carotid artery. An intravenous (IV) heparin bolus (5,000 IU) was administered after inserting the long introducer sheath. All procedures were performed with monorail systems for stent placement, distal protection, and pre and postdilatation. Postdilatation was performed after stent implantation. The stented segment, ICA, and ipsilateral intracranial vasculature were evaluated angiographically following the intervention via the sheath in the common carotid artery. None of the patients had periprocedural neurological complications.
Immediately after CAS, IV heparin (750 IU per h) was started and maintained for 12 h. All patients remained in the intensive care unit for 24 h postprocedure. The patients were discharged on dual antiplatelet therapy for one month and on aspirin indefinitely.
The data were analyzed using SPSS Statistics ver. 17.0 (IBM, Armonk, NY, USA). The Shapiro–Wilk test was used to identify normal distributions of continuous variables, which were expressed as the mean ± standard deviation (SD) or median (range). Categorical data were expressed as the number of cases and percentages. The mean differences between groups were compared using a Student's t-test while the Mann–Whitney U test was used to compare non-normally distributed data. When there were more than two independent groups, the Kruskal–Wallis test was used to determine the differences among groups. The degree of association between continuous variables was evaluated using Spearman's rank correlation analyses. Categorical data were analyzed using Fisher's exact test. The Wilcoxon signed-rank test was used to evaluate the differences in flow velocity and PI measurements between the two follow-up times. P values less than 0.05 were considered statistically significant. For all multiple comparisons, Bonferroni correction was used to control for type I errors.
The study included 36 patients [28 males, 8 females; mean age 66 ± 7 (range 52–84) years]. The median degree of ICA stenosis in the participants was 90% (range 50%–99%). Age (P = 0.698) and the mean degree of stenosis (P = 0.641) did not differ significantly in males and females, and age had no effect on the degree of stenosis (r = 0.016, P = 0.927).
The median CBFV at the ACA was significantly lower on the ipsilateral side than on the contralateral side (41.6 vs. 54.3 cm/s, respectively; P < 0.001) before stenting; however, there were no significant differences in CBFV (52.7 vs. 53.1 cm/s, respectively; P = 0.017) or PI (1.00 vs. 1.12, respectively; P = 0.007) in the ipsi and contralateral MCA. [Table 2] and [Figure 1] show the CBFV and PI in the ipsi and contralateral MCA and ACA before the procedure.
The median CBFV in the ipsilateral MCA increased significantly 3 d after the procedure (52.5 vs. 64.5 cm/s, respectively; P = 0.0011) and remained higher than the basal values after 3 months (52.5 vs. 62.2 cm/s, respectively; P = 0.0016). The PI also increased in the MCA. The increase in the contralateral MCA CBFV at 3 d (53.7 vs. 59.9 cm/s) and 3 months (53.7 vs. 58.5 cm/s) was not significant. No significant difference was seen in the CBFV or PI of the ACA 3 d (40.6 vs. 45.6 cm/s, respectively) or 3 months (40.6 vs. 45.6 cm/s, respectively) before or after the procedure. [Table 3] and [Figure 2] show the median CBFV and PI of the MCA and ACA before, 3 d, and 3 months after stenting.
The median peak systolic velocity (PSV) in the ipsilateral MCA (87 vs 103 cm/s; P = 0.008) and ipsilateral ACA (73.5 vs 79.3 cm/s; P: 0.225) increased 3 d after the procedure though not reaching a statistically significant difference. [Figure 3] shows the median PSV of the MCA and ACA before, 3 d, and 3 months after stenting.
The degree of carotid stenosis did not correlate with the basal median CBFV or PI of the MCA (P > 0.0028 and P > 0.0028, respectively).
Neither sex nor the presence of diabetes, hypertension, hyperlipidemia, and coronary artery disease had an effect on changes in the MCA and ACA CBFVs or PI following the procedure.
Atherosclerotic carotid stenosis is potentially fatal. Carotid angioplasty and stenting are therapeutic options for patients with severe ICA stenosis. CAS is usually performed as an alternative to CEA, especially in patients at high surgical risk, such as those facing technically demanding surgery or with severe comorbidities, stenosis due to radiation, or restenosis following CEA.,
We found a significant increase in the median CBFV and PI in the MCA bilaterally, particularly on the stented side, measured 3 d and 3 months after stenting in patients with severe unilateral ICA stenosis. Several studies have reported improved hemodynamics in the cerebral circulation in both the ipsi and contralateral MCA following CAS.,,,, Similar results have been published for patients treated with CEA.,,,Contralateral increases in MCA blood flow velocities (BFV) can be explained by the active contribution of the contalateral carotid system in collateral supply through an increase in its flow volume. These findings points to a hemodynamic stress on the contralateral side also that is corrected following revascularization as well as the arrest of cross-flow or improved blood flow through the anterior communicating artery following CAS.,,,, Soon after CAS, the median CBFV and PI are increased in most patients, suggesting an increase in perfusion and sufficient arteriolar vasoconstrictor responses.
Sfyroeras et al. and Kablak-Ziembicka et al. reported improved CBFVs in the ipsilateral MCA and improved cerebrovascular reactivity following CAS., This improvement was seen as early as 6 h after CAS,, and lasted for 2–4 months after CAS., Hsu et al. reported that the increase in the median CBFV 1 year after stenting was minor, with an increased PI. This finding has been interpreted as the progressive improvement of ipsilateral cerebral hyperemia and persistent amelioration in the cerebral perfusion.
The hemodynamic changes that were seen early after CAS in our study agreed with the reported increases in the median CBFV and PI of the ipsilateral MCA, as shown by TCD 3 d and 3 months after the procedure. The early increase in the median CBFV seen in the ipsilateral hemisphere was preserved 3 months after CAS, although it was reduced, implying ongoing normalization of the ipsilateral hemisphere hyperemia. The value still exceeded the basal median CBFV, which implies the recovery of cerebral perfusion. These changes have been explained based on the increased perfusion pressure in the cerebral arteries due to the restoration of the normal diameter and flow in ICA following CAS.
The PI also increased in the ipsilateral MCA following the procedure. This change has been interpreted as the ability of arterioles to constrict to retain the substantial augmentation of flow that takes place in the ICA territory following CAS., A lower PI following CAS suggests ongoing vasodilatation and reduced cerebral reserve, which could cause hyperperfusion syndrome. The PI increase should be considered a more sensitive marker of hemodynamic change than the median CBFV and may be interpreted as a hemodynamic enhancement.,
We have not encountered any clinical or sonographic features of cerebral hyperperfusion. Cerebral hyperperfusion syndrome (CHS) is an uncommon condition after CEA or CAS but is believed to be preventable in some cases. Moulakakis and colleagues in a retrospective study of 4446 patients undergoing CAS reported the incidence of CHS as 1.16%. CHS is most common in patients with CBF increases of more than 100% compared with baseline values after carotid vascularisation and is rare in patients with increases in perfusion less than 100% compared with baseline values. In series of Ogasawara, Suga, and Fukuda 16.7% to 28.6% of the patients with an increase of CBF more than 100% had CHS.,,It is stated that appropriate control of blood pressure is a critical component for the prevention of CHS in the first two weeks following the procedure and blood pressure should be kept below 130/85 mmHg. We followed these guidelines. None of our patients developed hyperperfusion syndrome because the increase in flow velocity did not exceed 50% of the basal values.
Carotid angioplasty and stenting substantially enhance the cerebral hemodynamics in patients presenting with severe carotid artery stenosis. We observed significant increases in the median CBFV and PI in the MCA bilaterally, especially on the stented side, measured 3 d and 3 months after carotid artery stenting in patients with severe ICA stenosis. The reason that we have not seen CHS may be due to cautious blood pressure management in pre and post procedure period, patient characteristics, and the small amount of patients we have evaluated. We believe the amount of patients with clinical or sonographic features of CHS would have been higher if we had evaluated a larger patient population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]