Baseline characteristics
Between January 1st 2018 and December 31st 2021, a total of 448 patients underwent TAVI in our institution, of which 56 (12.5%) had CAS. Among those, 41 (9.2%) had unilateral CAS and 15 (3.3%) had bilateral CAS. Likewise, 41 patients (9.2%) had moderate CAS while 15 patients (3.3%) had severe CAS. Patients’ baseline characteristics are presented in Table 1. Patients with CAS were more often men and had a higher prevalence of peripheral artery disease (PAD), coronary artery disease and previous percutaneous coronary intervention. Regarding technical aspects, the transcarotid vascular access was more frequently used in patients with CAS, and there was a trend towards more use of self-expandable transcatheter heart valves (THVs) in patients without CAS (p=0.054). Supplementary Tables 1 and 2 show patient characteristics in the subgroups of CAS : no significant difference was found between patients with unilateral CAS and those with bilateral CAS, while those with severe CAS had significantly more PAD (p=0.040) compared with those with moderate CAS. One patient with bilateral CAS underwent prophylactic carotid revascularization (right carotid artery stenting) prior to TAVI and was considered as having only left CAS.
Table 1. Baseline clinical and perioperative characteristics of patients undergoing TAVI, any CAS versus no CAS. Values are expressed as percentage, n (%), unless specified otherwise.
|
Any CAS (n = 56)
|
No CAS (n = 392)
|
p value
|
Clinical characteristics
|
Age, years, median (IQR)
|
81.5 (75.25, 87.75)
|
83.0 (78.0, 87.0)
|
0.372
|
Male gender
|
35 (62.5)
|
190 (48.5)
|
0.049
|
BMI, kg/m2, median (IQR)
|
24.68 (22.96, 28.73)
|
25.50 (23.23, 29.41)
|
0.681
|
Euroscore II, median (IQR)
|
3.34 (1.80, 5.72)
|
3.08 (1.83 ,5.15)
|
0.616
|
STS score, median (IQR)
|
2.86 (1.84, 4.67)
|
2.61 (1.81, 4.39)
|
0.822
|
Peripheral artery disease
|
12 (21.4)
|
47 (12.0)
|
0.051
|
Previous pacemaker
|
8 (14.3)
|
38 (9.7)
|
0.290
|
Chronic pulmonary disease
|
9 (16.1)
|
47 (12.0)
|
0.388
|
Diabetes mellitus
|
13 (23.2)
|
91 (23.2)
|
1.000
|
Dyslipidemia
|
33 (59.0)
|
205 (52.3)
|
0.594
|
Previous cardiac surgery
|
9 (16.1)
|
45 (11.5)
|
0.327
|
Coronary artery disease
|
33 (58.9)
|
168 (42.9)
|
0.024
|
Previous PCI
|
14 (25.0)
|
52 (13.3)
|
0.020
|
Hypertension
|
44 (78.6)
|
305 (77.8)
|
0.897
|
Previous stroke or TIA
|
8 (14.3)
|
48 (12.2)
|
0.671
|
Moderate to severe CKD
|
21 (37.5)
|
185 (47.2)
|
0.173
|
Aortic aneurysm
|
3 (5.4)
|
11 (2.8)
|
0.305
|
NYHA Functional class
|
27 (48.2)
29 (51.8)
|
173 (44.1)
219 (55.9)
|
0.576
0.538
|
Technical aspects
TC vascular access
|
15 (26.8)
|
48 (12.2)
|
0.003
|
Use of cerebral embolic protection system
|
3 (5.3)
|
29 (7.4)
|
0.579
|
Use of self-expandable THV
|
3 (5.3)
|
58 (14.8)
|
0.054
|
TAVI: transcatheter aortic valve implantation, CAS : carotid artery stenosis, IQR: interquartile range, BMI: body mass index, STS score : Society of Thoracic Surgeons score, CABG: coronary artery bypass graft, PCI: percutaneous coronary intervention, TIA: transient ischemic attack, CKD: chronic kidney disease, NYHA: Hew York Heart Association, TC: transcarotid, THV: transcatheter heart valve
30-day and periprocedural outcomes
Rates of 30-day stroke or TIA, 30-day all-cause mortality, as well as periprocedural outcomes are presented in Table 2. Kaplan-Meier curves for 30-day stroke and mortality are presented in Figure 1. The overall incidence of ischemic neurovascular complications in our cohort was 2.9%. The incidence of stroke or TIA at 30 days was lower in patients with CAS, as compared with those without CAS (7.1% versus 2.3%, p=0.042). In contrast, there was no significant difference with respect to all-cause 30-day mortality. Likewise, no significant difference was found regarding the other secondary endpoints (namely the perioperative complications).
Table 2. Postoperative outcomes of patients undergoing TAVI, any CAS versus no CAS. Values are expressed as percentage, n (%), unless specified otherwise. TAVI: transcatheter aortic valve implantation, CAS : carotid artery stenosis, TIA : transient ischemic attack
|
Any CAS (n = 56)
|
No CAS (n = 392)
|
p value
|
Stroke or TIA at 30 days
|
4 (7.1)
|
9 (2.3)
|
0.042
|
All-cause 30-day mortality
|
1 (1.8)
|
8 (2.0)
|
0.906
|
Perioperative myocardial infarction
|
0 (0)
|
4 (1.0)
|
0.447
|
Permanent pacemaker implantation
|
9 (16.1)
|
58 (14.8)
|
0.802
|
New-onset atrial fibrillation or atrial flutter
|
3 (5.3)
|
16 (4.1)
|
0.658
|
Postoperative acute kidney injury
|
3 (5.4)
|
8 (2.0)
|
0.134
|
Cardiac tamponade
|
1 (1.8)
|
8 (2.0)
|
0.897
|
Life-threatening bleeding
|
1 (1.8)
|
10 (2.6)
|
0.729
|
Major vascular complication
|
2 (3.6)
|
18 (4.6)
|
0.729
|
Valve malpositioning
|
0 (0)
|
8 (2.0)
|
0.281
|
Conversion to sternotomy
|
0 (0)
|
4 (1.0)
|
0.448
|
Adjusted primary endpoint
The univariate analyses of predictors of stroke or TIA at 30 days are shown in Table 3. Variables with a p-value <0.1 were CAS (HR 3.15, 95%CI 0.97-10.23, p=0.056), PAD (HR 2.98, 95%CI 0.92-9.67, p=0.069), postoperative acute kidney injury (HR 7.65, 95%CI 1.69-34.48, p=0.008) and major vascular complications (HR 6.68, 95%CI 1.83-24.22, p=0.004). No significant association was found between the other variables and the risk of neurovascular complications.
Table 3. Univariate predictors for stroke or TIA at 30 days. TIA : transient ischemic attack, CAS : carotid artery stenosis, STS score : Society of Thoracic Surgeons score, PCI: percutaneous coronary intervention, NYHA: Hew York Heart Association, TC: transcarotid, THV: transcatheter heart valve
Variables
|
hazard ratio (95% CI)
|
p value
|
Any CAS
|
3.151 (0.970, 10.233)
|
0.056
|
Male gender
|
0.866 (0.291, 2.577)
|
0.796
|
Euroscore II
|
0.897 (0.714, 1.127)
|
0.353
|
STS score
|
1.020 (0.882, 1.179)
|
0.789
|
Peripheral artery disease
|
2.977 (0.917, 9.669)
|
0.069
|
Diabetes mellitus
|
0.599 (0.133, 2.704)
|
0.505
|
Dyslipidemia
|
0.388 (0.120, 1.256)
|
0.114
|
Previous cardiac surgery
|
0.041 (0, 55.379)
|
0.384
|
Coronary artery disease
|
1.431 (0.481, 4.259)
|
0.519
|
Previous PCI
|
1.058 (0.235, 4.773)
|
0.942
|
Hypertension
|
0.632 (0.195, 2.052)
|
0.445
|
Chronic kidney disease
|
0.729 (0.239, 2.229)
|
0.580
|
NYHA Functional class III-IV
|
1.808 (0.557, 5.872)
|
0.324
|
TC vascular access
|
0.507 (0.066, 3.900)
|
0.514
|
Use of cerebral embolic protection system
|
2.396 (0.531, 10.809)
|
0.256
|
Use of self-expandable THV
|
1.147 (0.254, 5.176)
|
0.858
|
Postoperative acute kidney injury
|
7.647 (1.692, 34.479)
|
0.008
|
New-onset atrial fibrillation or atrial flutter
|
1.872 (0.243, 14.396)
|
0.547
|
Major vascular complications
|
6.683 (1.833, 24.217)
|
0.004
|
Permanent pacemaker implantation
|
1.710 (0.471, 6.214)
|
0.415
|
Life-threatening bleeding
|
3.393 (0.441, 26.095)
|
0.241
|
After adjustment for PAD, postoperative acute kidney injury and major vascular complications, CAS was no longer independently associated with the primary outcome (adjusted HR 2.55, 95%CI 0.73-8.91, p=0.142). However, a significant association was found with bilateral CAS and the primary outcome (adjusted HR 8.40, 95%CI 1.60-44.00, p=0.012) (Table 4). An independent subgroup analysis did not find severe CAS to be a predictor of stroke or TIA at 30 days (adjusted HR 2.30, 95%CI 0.25-21.39, p=0.464).
Table 4. Multivariable predictors for stroke or TIA at 30 days. TIA : transient ischemic attack, CAS : carotid artery stenosis
Variables
|
hazard ratio (95% CI)
|
p value
|
Any CAS
Unilateral CAS
Bilateral CAS
|
2.551 (0.731, 8.906)
1.401 (0.271, 7.239)
8.399 (1.603, 44.000)
|
0.142
0.688
0.012
|
Peripheral artery disease
|
1.881 (0.538, 6.576)
|
0.322
|
Postoperative acute kidney injury
|
6.743 (1.311, 34.676)
|
0.022
|
Major vascular complications
|
7.816 (2.035, 30.012)
|
0.003
|
Causality between CAS and stroke lesions
The medical records of the four patients with CAS who had stroke or TIA after TAVI were reviewed. The side of CAS and the location of the ischemic neurovascular lesions are described in Table 5. In only one case was the stroke lesions attributable to CAS (in that case, severe bilateral CAS), in the three other cases, an embolic cause was considered the most likely, due to the number and the distribution of the lesions.
Table 5. Description of stroke lesion locations in relation to the side of CAS
|
Side and degree of CAS
|
Day of onset of first neurological symptoms*
|
Stroke lesion location
|
Causality
|
1st patient
2nd patient
3rd patient
4th patient
|
Left (50% stenosis)
Bilateral (both 50% stenosis)
Bilateral (80% right stenosis, 70% left stenosis)
Left (50% stenosis)
|
Day 3
Day 1
Day 0 (immediately after TAVI)
Day 0 (immediately after TAVI)
|
2 acute ischemic lesions found in the left cerebellum (territory of the superior cerebellum artery)
1 acute ischemic lesion found in the right parietal lobe, 1 acute ischemic lesion found in the right temporal lobe
Acute ischemic left sylvian lesion
Multiple acute ischemic lesions found in the left cerebellum and thalamus
|
Unlikely
Unlikely
Likely
Unlikely
|
* Day 0 is defined as the day of TAVI intervention