- Email: [email protected]
Should We Perform Carotid Doppler Screening Before Surgical or Transcatheter Aortic Valve Replacement?
Should We Perform Carotid Doppler Screening Before Surgical or Transcatheter Aortic Valve Replacement? Jose F. Condado, MD, MS, Hanna A. Jensen, MD, PhD, Aneel Maini, Yi-An Ko, PhD, Mohammad H. Rajaei, MD, Lillian L. Tsai, AB, Chandan Devireddy, MD, Bradley Leshnower, MD, Kreton Mavromatis, MD, Eric L. Sarin, MD, James Stewart, MD, Robert A. Guyton, MD, Vasilis Babaliaros, MD, Edward P. Chen, MD, Michael Halkos, MD, Amy Simone, PA, Patricia Keegan, NP, Peter C. Block, MD, and Vinod H. Thourani, MD for The Emory Structural Heart and Valve Center Division of Cardiology, Structural Heart and Valve Center, Atlanta; Cardiothoracic Surgery, Emory University School of Medicine, Atlanta; and Department of Biostatistics and Bioinformatics, for Emory University Rollins School of Public Health, Atlanta, Georgia
Background. Screening for internal carotid artery stenosis (ICAS) with Doppler ultrasound is commonly used before cardiovascular surgery. Nevertheless, the relationship between ICAS and procedure-related stroke in isolated aortic valve replacement is unclear. Methods. We retrospectively reviewed patients with artery stenosis who underwent ICAS screening before surgical (SAVR) or transcatheter aortic valve replacement (TAVR) between January 2007 and August 2014. Logistic regression models were used to determine the relation between post-procedure stroke and total (sum of left and right ICAS) and maximal unilateral ICAS. Age, sex, history of atrial fibrillation, cerebrovascular disease and diabetes, left ventricular ejection fraction, and procedure type were considered as covariates. Two-subgroup analyses were performed in patients who underwent TAVR and SAVR, adjusting for procedure specific details. Results. A total of 996 patients underwent ICAS screening before TAVR (n [ 467) or SAVR (n [ 529).
The prevalence of at least ‡70% ICAS was 5.2% (n [ 52) and incidence of 30-day stroke was 3.4% (n [ 34). Eight patients who underwent carotid intervention before valve replacement and 6 patients with poor Doppler images were excluded from the final analysis. We found no statistically significant association between stroke and either the total or maximal unilateral ICAS for all patients (p [ 0.13 and p [ 0.39, respectively) or those undergoing TAVR (p [ 0.27 and p [ 0.63, respectively) or SAVR (p [ 0.21 and p [ 0.36, respectively). Conclusions. We found no statistically significant association between ICAS severity procedure-related stroke after aortic valve replacement. This suggests that universal carotid Doppler screening before isolated TAVR or SAVR is unnecessary.
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65 years and older, presence of carotid bruit, and prior cerebrovascular disease) [8]. The benefit of universal carotid Doppler screening for stroke prevention before isolated valve replacement remains unclear [9–11]. Studies supporting guidelines have included cohorts of patients undergoing CABG or any cardiac surgery [1, 3, 4, 9–11]; no study has solely focused on patients with aortic stenosis (AS). We aimed to evaluate the relationship between ICAS and procedure-
arotid doppler screening is commonly performed before isolated surgical and transcatheter aortic valve replacements (SAVR and TAVR) because of an observed increased prevalence of greater than or equal to 50% internal carotid artery stenosis (ICAS) in patients undergoing cardiac surgery [1, 2] and a reported association between previous cerebrovascular disease and stroke [3–5]. The benefit of universal carotid Doppler screening before coronary artery bypass graft (CABG) has been recently questioned [6, 7]. Current guidelines recommend ICAS screening before CABG in asymptomatic patients with high-risk characteristics (ie, patients Accepted for publication June 20, 2016. Presented at the Conference of Transcatheter Cardiovascular Therapeutics, San Francisco, CA, Oct 11–15, 2015. Address correspondence to Dr Thourani, Emory Hospital Midtown, 550 Peachtree St NE, Atlanta, GA 30308; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2016;-:-–-) Ó 2016 by The Society of Thoracic Surgeons
Dr Babaliaros discloses a financial relationship with Edwards Lifesciences, Medtronic, St. Jude Medical, Boston Scientific, Abbott Medical, and DirectFlow Medical; Dr Block with Direct Flow, Medtronic, and St. Jude Medical; Dr Thourani with Edwards Lifesciences, Medtronic, St. Jude Medical, Sorin Medical, Boston Scientific, Abbott Medical, and Directflow Medical.
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.06.076
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related stroke in patients with severe AS undergoing isolated TAVR or SAVR.
Material and Methods A retrospective review was performed on 996 consecutive patients with severe AS who underwent carotid Doppler screening before SAVR or TAVR between January 1, 2009, and August 31, 2014, at Emory Healthcare hospitals. To focus the study in a population with AS that underwent aortic valve replacement, we excluded patients who underwent valve replacement for the treatment of aortic regurgitation or concomitant CABG. Patients who underwent preoperative carotid intervention (stenting or endarterectomy) before SAVR or TAVR were excluded from the final statistical analysis. A Consort diagram of the study design is shown in Figure 1. This study was approved by the Emory University institutional review board.
Carotid Doppler At our institution, carotid Doppler screening was encouraged but left to the surgeon’s discretion. On those patients that underwent carotid Doppler screening, reports were reviewed and the severity of both left and right ICAS was classified using measured velocities, spectral Fig 1. Consort diagram of the study design evaluating the role of carotid Doppler screening in patients with severe aortic stenosis (AS) who underwent aortic valve replacement (AVR, transcatheter or surgical).
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analysis, and color flow images as described by the Society of Radiologists in Ultrasound consensus: normal, less than 50% stenosis, 50% to 69% stenosis, 70% stenosis and greater (but less than near occlusion), near total occlusion, and total occlusion [8, 12]. Because of the difficulty in differentiating between normal and less than 50%, and the low prevalence of normal carotids in our population, these two categories were combined.
Patient and Procedure Characteristics Baseline patient characteristics, procedural details, and complications (including stroke) were obtained from the Emory TAVR/SAVR database. New York Heart Association functional class and race were dichotomized into I/II and III/IV and Caucasian and non-Caucasian, respectively. Patients were divided in two groups: those who developed a procedure-related stroke (stroke patients) and those who did (nonstroke patients). Procedural stroke was defined as any image-confirmed (computed tomography or magnetic resonance imaging) cerebrovascular accident that occurred within 30 days after the procedure. The distribution of the stroke (left, right, or bilateral/embolic) was collected. There were no transient ischemic accidents (TIAs) in this study. All TAVRs were performed using a SAPIEN or SAPIEN XT valve (Edwards Lifescience, Irvine, CA). Procedure access was classified as transfemoral (TF) and non-TF
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(transapical, transaortic, transcarotid, and transcaval). TAVR-specific procedural details and complications were classified using the Valve Academic Research Consortium2 criteria [13], and included: need for postdilation or second transcather valve, use of intraaortic balloon pump, procedure time, postprocedure paravalvular leak, heart block requiring permanent pacemaker, and vascular complications. Minimalist TAVR was defined as those TF procedures performed under conscious sedation [14, 15]. Similarly, operative details for SAVR were collected including cardiopulmonary bypass and aortic cross clamp times. The SAVR technique and outcomes for our institution have been previously reported [16].
Statistical Analysis The prevalence of the ICAS categories was determined. Statistical analysis was performed using SAS (Cary, NC). Baseline characteristics, procedure details, and complications were compared between groups using c2 or Fisher test for categorical variables and t test or Wilcoxon test for continuous variables when appropriate. Categorical variables were summarized as n (%) and
continuous variables as mean (standard deviation) or median (interquartile range), depending of the distribution. We were unable to analyze the association between ICAS and ipsilateral versus contralateral stroke because only 3 patients (TAVR ¼ 1 and SAVR ¼ 2) had an ipsilateral stroke to an ICAS. Thus, the relationship between procedurerelated stroke and both the total (sum of left and right) and the worst unilateral (maximal left or right) ICAS was determined using separate logistic regression models, adjusting for age, sex, history of atrial fibrillation, cerebrovascular disease and diabetes, procedure type (SAVR or TAVR), or left ventricular ejection fraction. Because of the small number of events, we adjusted for one covariate at a time to avoid model overfitting. The resulting parameter estimates corresponding to stenosis remain fairly stable with variations fewer than 10% compared with the unadjusted one, indicating little confounding effect resulting from the covariates. As such, we report the unadjusted analysis results. Two-subgroup analyses were also performed to evaluate this same relationship in patients who underwent TAVR (further adjusting for the access used,
Table 1. Baseline Characteristics of Patients Who Underwent Aortic Valve Replacement According to the Presence or Absence of Stroke All (n ¼ 982) Age in years, mean (SD) Female, n (%) Caucasian, n (%) STS score in %, mean (SD) Diabetes, n (%) Hypertension, n (%) Atrial fibrillation, n (%) Chronic lung disease None, n (%) Mild, n (%) Moderate, n (%) Severe, n (%) NYHA class III/IV, n (%) CAD, n (%) Prior CABG, n (%) Prior cerebrovascular disease, n (%) ESRD on dialysis, n (%) PAD, n (%) Immunocompromised, n (%) Liver disease, n (%) Prior cardiac surgery, n (%) History of carotid intervention, n (%)a Carotid endarterectomy, n (%) Carotid stent, n (%) LVEF in %, mean (SD) Creatinine in mg/dL, mean (SD) a
Nonstroke (n ¼ 948)
Stroke (n ¼ 34)
76.0 448 845 8.0 402 923 262
(11.0) (45.6) (86.0) (6.0) (40.9) (94.0) (26.7)
76.0 429 815 8.0 387 890 250
(11.0) (45.3) (86.0) (6.0) (40.6) (93.9) (26.4)
77.0 19 30 7.0 15 33 12
(8.0) (55.9) (88.2) (5.0) (44.1) (97.1) (35.3)
592 190 92 108 666 470 264 245 31 225 106 40 332 74 53 14 51.0 1.3
(60.3) (19.3) (9.4) (11.0) (81.8) (47.9) (26.9) (24.9) (3.1) (22.9) (10.8) (4.1) (33.8) (7.5) (5.4%) (1.4) (14.0) (1.05)
571 184 89 104 642 456 256 237 29 216 99 39 321 70 51 11 51.0 1.3
(60.2) (19.4) (9.4) (11.0) (81.8) (48.1) (27.0) (25.0) (3) (22.8) (10.4) (4.1) (33.9) (7.4) (5.4) (1.2) (14) (1.1)
21 6 3 4 24 14 8 8 2 9 7 1 11 4 2 3 55.0 1.4
(61.8) (17.6) (8.8) (11.8) (82.8) (41.2) (23.5) (23.5) (5.9) (26.5) (20.6) (2.9) (32.4) (11.8) (5.9) (8.8) (14.0) (1.2)
p 0.82 0.22 0.71 0.55 0.70 0.44 0.25 0.99
0.89 0.42 0.65 0.85 0.36 0.61 0.06 1.00 0.86 0.32 0.71 0.01 0.14 0.39
History of carotid intervention prior to carotid Doppler screening.
CABG ¼ coronary artery bypass grafting; CAD ¼ coronary artery disease; ESRD ¼ end-stage renal disease; LVEF ¼ left ventricular ejection fraction; NYHA ¼ new york heart association; PAD ¼ peripheral arterial disease; SD ¼ standard deviation; STS ¼ Society of Thoracic Surgeons.
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Table 2. Procedure Details for Patients Who Underwent Transcatheter Aortic Valve Replacement (TAVR) According to the Presence or Absence of Stroke All (n ¼ 463) Valve generation SAPIEN, n (%) SAPIEN XT, n (%) Valve size 23 mm, n (%) 26 mm, n (%) 29 mm, n (%) Access Transfemoral, n (%) Nontransfemoral, n (%) Second valve implanted, n (%) Postdilation, n (%) IABP used, n (%) Postprocedure paravalvular leak None, n (%) Mild, n (%) Moderate, n (%) Procedural time in minutes, mean (SD) ICU time in hours, median (Q1, Q3) Length of stay in days, median (Q1, Q3)a a
Nonstroke (n ¼ 451)
Stroke (n ¼ 12)
p
338 (73.3) 123 (26.7)
327 (72.8) 122 (27.2)
11 (91.7) 1 (8.3)
0.20
240 (52.1) 189 (41.0) 32 (6.9)
230 (51.2) 187 (41.6) 32 (7.1)
10 (83.3) 2 (16.7) 0 (0)
0.08
245 218 37 119 21
238 213 36 115 19
(52.9) (47.1) (8.0) (25.7) (4.5)
318 123 11 124.3 29.4 5.0
(70.4) (27.2) (2.4) (42.8) (23.3, 56.0) (3.0, 7.0)
310 119 11 124.1 29.0 5.0
(52.8) (47.2) (8.0) (25.5) (4.2)
7 5 1 4 2
(70.5) (27.0) (2.5) (42.9) (23.0, 54.4) (3.0, 7.0)
8 4 0 129.8 104.0 13.0
(58.3) (41.7) (8.3) (33.3) (16.7)
0.70
(66.7) (33.3) (0) (39.6) (56.8, 455.7) (7.0, 31.0)
0.78
0.99 0.52 0.10
0.65 <0.001 <0.001
From procedure to discharge.
IABP ¼ intraaortic balloon pump;
ICU ¼ intensive care unit;
Q ¼ interquartile range;
need for postdilation, and procedure time) or SAVR (further adjusting for cardiopulmonary bypass). A p value of 0.05 or less was considered significant.
Results A total of 1,372 patients with severe AS underwent TAVR or SAVR during the study period. Of those, 996 (73%) patients underwent preprocedural carotid Doppler screening. Fourteen patients were further excluded: 6 patients who had missing Doppler data (poor windows) and 8 patients who had a carotid intervention for the treatment of ICAS discovered on carotid Doppler screening prior to valve replacement (TAVR ¼ 2, and SAVR ¼ 6). The final study
SD ¼ standard deviation.
population was composed of 982 patients (TAVR ¼ 463, SAVR ¼ 519). In those patients who did not undergo carotid Doppler screening (TAVR ¼ 186, SAVR ¼ 189), 2 patients had a postprocedural stroke. Both of these patients had undergone SAVR and had imaged confirmed embolic ischemic strokes (carotid disease is unknown). In those patients in which carotid Doppler screening was performed, 34 (3.4%) had a procedure-related stroke. There were no significant differences in baseline characteristics between stroke and nonstroke patients (Table 1). Procedure-specific characteristics for TAVR and SAVR are shown in Tables 2 and 3, respectively. As expected, patients with a stroke after both SAVR and TAVR had a longer intensive care unit stay and overall postoperative length of
Table 3. Procedure Details for Patients Who Underwent Surgical Aortic Valve Replacement (SAVR), According to the Presence or Absence of Stroke All (n ¼ 519) CBP time in minutes, mean (SD) Cross clamp time in minutes, mean (SD) ICU time in hours, median (Q1, Q3) Length of stay in days, median (Q1, Q3)a Operation time in hours, median (Q1, Q3) IABP used, n (%) a
108.0 81.0 48.5 7.0 313.0 47
(33) (24.0) (26.5, 97.6) (5.0, 9.0) (275.0, 364.0) (9.1)
Nonstroke (n ¼ 497) 108.0 80.0 47.8 6.0 311.0 44
(33.0) (24) (26.1, 95.1) (5.0, 9.0) (275.0, 361.0) (8.9)
Stroke (n ¼ 22) 121.0 87.0 139.4 14.0 336.0 3
(39.0) (24.0) (78.7, 496.4) (9.0, 21.0) (295.0, 391.0) (13.6)
p 0.08 0.20 <0.001 <0.001 <0.001 0.44
From procedure to discharge.
CBP ¼ cardiopulmonary bypass; deviation.
ICU ¼ intensive care unit;
IABP ¼ intraaortic balloon pump;
IQ ¼ interquartile range;
SD ¼ standard
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Table 4. Procedure Complications
Acute renal failure, n (%) Pneumonia, n (%) Procedure mortality, n (%) 30-day mortality, n (%) Post-operative atrial fibrillation, n (%) TAVR-specific complications Heart block requiring pacemaker, n (%) Major vascular complication, n (%) Minor vascular complication, n (%)
All (n ¼ 982)
Nonstroke (n ¼ 948)
Stroke (n ¼ 34)
19 39 31 28 262
17 31 28 25 250
2 8 3 3 12
(1.9) (4.0) (3.2) (2.9) (26.7)
22 (4.8) 19 (4.1) 38 (8.2)
(1.8) (3.3) (3.0) (2.6) (26.4)
21 (4.7) 18 (4.0) 35 (7.8)
(5.9) (23.5) (8.8) (8.8) (35.3)
1 (8.3) 1 (8.3) 3 (25.0)
p 0.14 <0.001 0.09 0.07 0.25 0.45 0.46 0.07
TAVR ¼ transcatheter aortic valve replacement.
stay than nonstroke patients. There was a higher frequency of postprocedure pneumonia in stroke than in nonstroke patients (23.5% versus 3.3%, p 0.0001). There were no significant differences in the remaining procedural complications between groups (Table 4), including the rate of postoperative atrial fibrillation. When present, atrial fibrillation was managed by a multidisciplinary team according to American Association for Thoracic Surgery guidelines [17].
Stroke and ICAS The prevalence of the different degrees of ICAS in the whole cohort and in patients with and without postprocedure stroke is depicted in Figure 2. Fifty-two of the 996 patients (5.2%) had at least 70% or greater ICAS.
Thirty-four patients (3.4%) had a procedure-related stroke (TAVR ¼ 12 and SAVR ¼ 22). The location was right-sided in 12 patients (35.3%), left-sided in 8 patients (23.5%) and bilateral/embolic in 14 patients (41.2%). Only 3 patients (TAVR ¼ 1 and SAVR ¼ 2) had an ipsilateral stroke in the region of the ICAS (one had 70% ICAS and two had 50%–59% ICAS). Table 5 shows the characteristics of the 8 patients who underwent a prior carotid intervention. Although all these patients eventually underwent valve replacement without developing a procedural stroke, we did not include those patients who had a carotid intervention but did not undergo valve intervention, as we were unable to identify them all. Though the overall prevalence of ICAS 70% or greater was higher in stroke than in nonstroke patients (8.8%
Fig 2. Prevalence of internal carotid stenosis in patients with severe aortic stenosis scheduled for valve replacement. Classified by (A) procedure type, (surgical or transcatheter aortic valve replacement [SAVR or TAVR]), and by the presence or absence of procedure-related stroke (stroke and non-stroke) in the following groups: (B) whole cohort, (C) SAVR patients; and (D) TAVR patients. (ICAS ¼ internal carotid artery stenosis.)
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Table 5. Characteristics of Patients Who Underwent Preprocedure Carotid Intervention STS Score (%)
Right ICAS
Left ICAS
Symptoms? Intervention
1 2
8.9 7.8
<50% 70%
50%–69% 50%–69%
Yes: TIA No
3 4 5 6 7
4.3 3.8 1.3 6.4 4.5
<50% 70% Total occlusion Near total occlusion <50%
70% <50% 70% <50% 70%
No Yes: TIA Yes: TIA No No
8
5.1
<50%
Near total occlusion No
Complications after Carotid Intervention SAVR or TAVR
Left ICA stent None Right CEA Hematuria and gastrointestinal bleeding. Required blood transfusion. Cardiogenic shock requiring vasopressors and emergent TAVR. Left CEA None Right CEA New onset atrial fibrillation Left ICA stent None Right CEA None Left CEA Delirium and surgical site hematoma that required evacuation. Left ICA stent None
TAVR TAVR
SAVR SAVR SAVR SAVR SAVR
SAVR
CEA ¼ carotid endarterectomy; CVA ¼ cerebrovascular event; ICA ¼ internal carotid artery stenosis; ICAS ¼ internal carotid artery stenosis; SAVR ¼ surgical aortic valve replacement; STS ¼ Society of Thoracic Surgeons; TAVR ¼ transcatheter aortic valve replacement; TIA ¼ transient ischemic attack.
versus 3.6%), we did not find a statistically significant association between procedural stroke and the total (p ¼ 0.13) or maximal unilateral (p ¼ 0.39) ICAS.
Subgroup Analysis Compared with SAVR patients, TAVR patients were older (71 versus 81 years p 0.001), had higher STS scores (5.0% versus 11.0%, p 0.001), and had more history of diabetes (37.4% versus 44.5%, p ¼ 0.02), hypertension (91.9% versus 96.6%, p ¼ 0.002), atrial fibrillation (18.0% versus 36.6%, p 0.001), severe chronic lung disease (4.9% versus. 17.8%, p 0.001), coronary artery disease (35.7% versus 63%, p 0.001), and cerebrovascular disease (20.8% versus 31.3%, p 0.001). More TAVR patients also had history of prior cardiac surgery (47.5% versus 22.3%, p 0.001) and carotid endarterectomy (8.0% versus 3.7%, p ¼ 0.04) than SAVR patients. Specific procedure characteristics for TAVR and SAVR are shown in Tables 2 and 3. Though the number of stroke patients was low in our subgroups, we found that of the 7 patients who had a procedure-related stroke after TF-TAVR, 6 patients had surgery performed using the minimalist approach (stroke rates: minimalist ¼ 6.0% versus standard ¼ 0.9%, p ¼ 0.02). Similar to our main analysis and despite observed increased prevalence of 70% or greater ICAS in stroke patients (Fig 2), there was no statistical association between stroke and total or maximal unilateral ICAS in patients who underwent either TAVR (p ¼ 0.27 and p ¼ 0.63) or SAVR (p ¼ 0.21 and p ¼ 0.36).
Comment Our study found no statistically significant association between the severity of ICAS and procedure-related stroke in patients with AS who underwent isolated aortic valve replacement. Though other reports have
shown no correlation between ICAS and outcomes after cardiac surgery [9, 10], ours is the first study to look at a population of AS undergoing either SAVR or TAVR. Because patients with severe AS are usually elderly with multiple risk factors for cerebrovascular disease [18, 19], it has been assumed that these patients, in particular, would benefit from carotid Doppler screening. Despite our observation of rates of 70% or greater ICAS similar to previous reports [2, 20], we found no statistical significant association between the severity of ICAS and stroke. Thus, we raise the question of whether universal carotid Doppler screening in neurologically asymptomatic patients with AS being considered for isolated SAVR or TAVR is indicated. Severe (50% or 70%) ICAS in a general population is related to stroke [8, 21]. But the relationship of ICAS to strokes during aortic valve surgery is controversial. In theory, 50% or greater ICAS can decrease brain perfusion during cardiopulmonary bypass and/or anesthesia, and, in fact, some studies have reported an increased prevalence of 50% or greater ICAS in such patients [1]. Our results also show an increased prevalence of 70% or greater ICAS (but not of 50%) in patients who had a stroke after TAVR/SAVR. After adjustment, however there was no statistical association between ICAS severity and stroke. We suspect that the severity of ICAS is a marker of risk and underlying comorbidities. To support this, note that in our study only 1 of 37 patients (2.7%) with 70% or greater ICAS developed an ipsilateral stroke and that 14 of 34 (41.2%) of all strokes were bilateral/ embolic. Existing evidence suggests that these procedurerelated strokes are a consequence of thromboembolic events originating in the aorta from direct or catheter manipulation during SAVR or TAVR [20, 22, 23]. Though our main analysis adjusted for procedure type, we also performed two subgroup analyses in patients who
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underwent TAVR or SAVR because of the differences between these patient populations and techniques. Interestingly, we found a higher rate of strokes with a minimalist approach in those patients who underwent TF-TAVR. Though this observation should warrant evaluation of the stroke risk with minimalist TF-TAVR in future studies, caution must be used in analyzing these results as our study was not designed to evaluate this approach and previous reports have found similar stroke rates between the minimalist and standard approach [14]. Not surprisingly, our TAVR patients were older and had higher surgical risk than our SAVR patients and thus had a higher overall prevalence of 70% or greater ICAS and also had a higher surgical risk for carotid endarterectomy [24]. Nevertheless, our subgroup analyses showed no statistical association between the ICAS and procedure-related stroke after adjusting for procedure specific risk factors. Clinically, one may not need to weigh a theoretical but unproven benefit of carotid intervention before TAVR/ SAVR, with its associated risk of delaying valve surgery, risk of an endarterectomy, or bleeding risk from dualantiplatelet therapy after carotid stenting. Based on our study results, including the complications observed in some patients that underwent prior carotid intervention, our institution has forgone universal preprocedural carotid Doppler screening on asymptomatic patients before aortic valve replacement as a standard of care, especially in highsurgical risk patients scheduled for TAVR.
Limitations This study has the inherent limitations of any retrospective study. Though a small bias is possible because 8 patients with preprocedural carotid intervention were excluded (none of which had a procedure-relate stroke), only 5 had asymptomatic disease, and carotid intervention was complicated in 3 patients (Table 5). The inclusion of these patients are unlikely to have altered our results. Although we adjusted for important risk factors of perioperative stroke, we acknowledge that our number of cerebrovascular events was small (3.4%). Nonetheless, our stroke rate was similar to those previously reported after SAVR (2.0–4.8%) and TAVR (2.7%–5.0%) [4, 5, 25, 26]. Although we report similar rates of postoperative complications (except for pneumonia) between stroke and nonstroke patients, care must be used in analyzing these results as our study was not designed to compare these two groups of patients. Instead, it was designed to evaluate the association between carotid Doppler screening and procedure-related strokes. Further studies of larger populations are warranted to corroborate our findings.
Conclusions We found no statistically significant association between the total or maximal unilateral severity of ICAS and procedure-related strokes in patients with AS undergoing intervention. We hope our results will prompt a randomized clinical study to evaluate the usefulness in preventing strokes of carotid Doppler screening as a guide to preprocedural carotid intervention before TAVR or SAVR.
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References 1. Ascher E, Hingorani A, Yorkovich W, et al. Routine preoperative carotid duplex scanning in patients undergoing open heart surgery: is it worthwhile? Ann Vasc Surg 2001;15: 669–78. 2. Anselmi A, Gaudino M, Risalvato N, et al. Asymptomatic carotid artery disease in valvular heart surgery: impact of systematic screening on surgical strategy and neurological outcome. Angiology 2012;63:171–7. 3. Hogue CW Jr, Murphy SF, Schechtman KB, et al. Risk factors for early or delayed stroke after cardiac surgery. Circulation 1999;100:642–7. 4. Bucerius J, Gummert JF, Borger MA, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg 2003;75:472–8. 5. Nombela-Franco L, Webb JG, de Jaegere PP, et al. Timing, predictive factors, and prognostic value of cerebrovascular events in a large cohort of patients undergoing transcatheter aortic valve implantation. Circulation 2012;18(126):3041–53. 6. Masabni K, Raza S, Blackstone EH, et al. Does preoperative carotid stenosis screening reduce perioperative stroke in patients undergoing coronary artery bypass grafting? J Thorac Cardiovasc Surg 2015;149:1253–60. 7. Masabni K, Sabik JF 3rd, Raza S, et al. Nonselective carotid artery ultrasound screening in patients undergoing coronary artery bypass grafting: is it necessary? J Thorac Cardiovasc Surg 2016;151:402–8. 8. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/ AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/ SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol 2011;57: e16–94. 9. Adams BC, Clark RM, Paap C, et al. There is no benefit to universal carotid artery duplex screening before a major cardiac surgical procedure. Ann Vasc Surg 2014;28:93–101. 10. Naylor AR, Bown MJ. Stroke after cardiac surgery and its association with asymptomatic carotid disease: an updated systematic review and meta-analysis. Eur J Vasc Endovasc Surg 2011;41:607–24. 11. Chun LJ, Tsai J, Tam M, et al. Screening carotid artery duplex in patients undergoing cardiac surgery. Ann Vasc Surg 2014;28:1178–85. 12. Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis—Society of Radiologists in Ultrasound Consensus Conference. Radiology 2003;229:340–6. 13. Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Eur Heart J 2012;33:2403–18. 14. Babaliaros V, Devireddy C, Lerakis S, et al. Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis. JACC Cardiovasc Interv 2014;7:898–904. 15. Jensen HA, Condado JF, Devireddy C, et al. Minimalist transcatheter aortic valve replacement: The new standard for surgeons and cardiologists using transfemoral access? J Thorac Cardiovasc Surg. 2015;150:833–9.
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16. Thourani VH, Ailawadi G, Szeto WY, et al. Outcomes of surgical aortic valve replacement in high-risk patients: a multiinstitutional study. Ann Thorac Surg 2011 Jan;91:49–55; discussion -6. PubMed PMID: 21172485. 17. Frendl G, Sodickson AC, Chung MK, et al. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg 2014;148:e153–93. 18. Osnabrugge RL, Mylotte D, Head SJ, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol 2013;62:1002–12. 19. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005–11. 20. Steinvil A, Sadeh B, Arbel Y, et al. Prevalence and predictors of concomitant carotid and coronary artery atherosclerotic disease. J Am Coll Cardiol 2011;57:779–83. 21. Norris JW. Outcome of transient ischaemic attacks and stroke. Drugs 1991;42(suppl 5):10–5.
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22. Van Mieghem NM, El Faquir N, Rahhab Z, et al. Incidence and predictors of debris embolizing to the brain during transcatheter aortic valve implantation. JACC Cardiovasc Interv 2015;8:718–24. 23. van der Linden J, Hadjinikolaou L, Bergman P, et al. Postoperative stroke in cardiac surgery is related to the location and extent of atherosclerotic disease in the ascending aorta. J Am Coll Cardiol 2001 Jul;38:131–5. 24. Halm EA, Tuhrim S, Wang JJ, et al. Risk factors for perioperative death and stroke after carotid endarterectomy: results of the new york carotid artery surgery study. Stroke 2009;40: 221–9. 25. Leon MB, Smith CR, Mack M, et al. Transcatheter aorticvalve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363: 1597–607. 26. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187–98.
Background. Screening for internal carotid artery stenosis (ICAS) with Doppler ultrasound is commonly used before cardiovascular surgery. Nevertheless, the relationship between ICAS and procedure-related stroke in isolated aortic valve replacement is unclear. Methods. We retrospectively reviewed patients with artery stenosis who underwent ICAS screening before surgical (SAVR) or transcatheter aortic valve replacement (TAVR) between January 2007 and August 2014. Logistic regression models were used to determine the relation between post-procedure stroke and total (sum of left and right ICAS) and maximal unilateral ICAS. Age, sex, history of atrial fibrillation, cerebrovascular disease and diabetes, left ventricular ejection fraction, and procedure type were considered as covariates. Two-subgroup analyses were performed in patients who underwent TAVR and SAVR, adjusting for procedure specific details. Results. A total of 996 patients underwent ICAS screening before TAVR (n [ 467) or SAVR (n [ 529).
The prevalence of at least ‡70% ICAS was 5.2% (n [ 52) and incidence of 30-day stroke was 3.4% (n [ 34). Eight patients who underwent carotid intervention before valve replacement and 6 patients with poor Doppler images were excluded from the final analysis. We found no statistically significant association between stroke and either the total or maximal unilateral ICAS for all patients (p [ 0.13 and p [ 0.39, respectively) or those undergoing TAVR (p [ 0.27 and p [ 0.63, respectively) or SAVR (p [ 0.21 and p [ 0.36, respectively). Conclusions. We found no statistically significant association between ICAS severity procedure-related stroke after aortic valve replacement. This suggests that universal carotid Doppler screening before isolated TAVR or SAVR is unnecessary.
C
65 years and older, presence of carotid bruit, and prior cerebrovascular disease) [8]. The benefit of universal carotid Doppler screening for stroke prevention before isolated valve replacement remains unclear [9–11]. Studies supporting guidelines have included cohorts of patients undergoing CABG or any cardiac surgery [1, 3, 4, 9–11]; no study has solely focused on patients with aortic stenosis (AS). We aimed to evaluate the relationship between ICAS and procedure-
arotid doppler screening is commonly performed before isolated surgical and transcatheter aortic valve replacements (SAVR and TAVR) because of an observed increased prevalence of greater than or equal to 50% internal carotid artery stenosis (ICAS) in patients undergoing cardiac surgery [1, 2] and a reported association between previous cerebrovascular disease and stroke [3–5]. The benefit of universal carotid Doppler screening before coronary artery bypass graft (CABG) has been recently questioned [6, 7]. Current guidelines recommend ICAS screening before CABG in asymptomatic patients with high-risk characteristics (ie, patients Accepted for publication June 20, 2016. Presented at the Conference of Transcatheter Cardiovascular Therapeutics, San Francisco, CA, Oct 11–15, 2015. Address correspondence to Dr Thourani, Emory Hospital Midtown, 550 Peachtree St NE, Atlanta, GA 30308; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2016;-:-–-) Ó 2016 by The Society of Thoracic Surgeons
Dr Babaliaros discloses a financial relationship with Edwards Lifesciences, Medtronic, St. Jude Medical, Boston Scientific, Abbott Medical, and DirectFlow Medical; Dr Block with Direct Flow, Medtronic, and St. Jude Medical; Dr Thourani with Edwards Lifesciences, Medtronic, St. Jude Medical, Sorin Medical, Boston Scientific, Abbott Medical, and Directflow Medical.
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.06.076
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related stroke in patients with severe AS undergoing isolated TAVR or SAVR.
Material and Methods A retrospective review was performed on 996 consecutive patients with severe AS who underwent carotid Doppler screening before SAVR or TAVR between January 1, 2009, and August 31, 2014, at Emory Healthcare hospitals. To focus the study in a population with AS that underwent aortic valve replacement, we excluded patients who underwent valve replacement for the treatment of aortic regurgitation or concomitant CABG. Patients who underwent preoperative carotid intervention (stenting or endarterectomy) before SAVR or TAVR were excluded from the final statistical analysis. A Consort diagram of the study design is shown in Figure 1. This study was approved by the Emory University institutional review board.
Carotid Doppler At our institution, carotid Doppler screening was encouraged but left to the surgeon’s discretion. On those patients that underwent carotid Doppler screening, reports were reviewed and the severity of both left and right ICAS was classified using measured velocities, spectral Fig 1. Consort diagram of the study design evaluating the role of carotid Doppler screening in patients with severe aortic stenosis (AS) who underwent aortic valve replacement (AVR, transcatheter or surgical).
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analysis, and color flow images as described by the Society of Radiologists in Ultrasound consensus: normal, less than 50% stenosis, 50% to 69% stenosis, 70% stenosis and greater (but less than near occlusion), near total occlusion, and total occlusion [8, 12]. Because of the difficulty in differentiating between normal and less than 50%, and the low prevalence of normal carotids in our population, these two categories were combined.
Patient and Procedure Characteristics Baseline patient characteristics, procedural details, and complications (including stroke) were obtained from the Emory TAVR/SAVR database. New York Heart Association functional class and race were dichotomized into I/II and III/IV and Caucasian and non-Caucasian, respectively. Patients were divided in two groups: those who developed a procedure-related stroke (stroke patients) and those who did (nonstroke patients). Procedural stroke was defined as any image-confirmed (computed tomography or magnetic resonance imaging) cerebrovascular accident that occurred within 30 days after the procedure. The distribution of the stroke (left, right, or bilateral/embolic) was collected. There were no transient ischemic accidents (TIAs) in this study. All TAVRs were performed using a SAPIEN or SAPIEN XT valve (Edwards Lifescience, Irvine, CA). Procedure access was classified as transfemoral (TF) and non-TF
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(transapical, transaortic, transcarotid, and transcaval). TAVR-specific procedural details and complications were classified using the Valve Academic Research Consortium2 criteria [13], and included: need for postdilation or second transcather valve, use of intraaortic balloon pump, procedure time, postprocedure paravalvular leak, heart block requiring permanent pacemaker, and vascular complications. Minimalist TAVR was defined as those TF procedures performed under conscious sedation [14, 15]. Similarly, operative details for SAVR were collected including cardiopulmonary bypass and aortic cross clamp times. The SAVR technique and outcomes for our institution have been previously reported [16].
Statistical Analysis The prevalence of the ICAS categories was determined. Statistical analysis was performed using SAS (Cary, NC). Baseline characteristics, procedure details, and complications were compared between groups using c2 or Fisher test for categorical variables and t test or Wilcoxon test for continuous variables when appropriate. Categorical variables were summarized as n (%) and
continuous variables as mean (standard deviation) or median (interquartile range), depending of the distribution. We were unable to analyze the association between ICAS and ipsilateral versus contralateral stroke because only 3 patients (TAVR ¼ 1 and SAVR ¼ 2) had an ipsilateral stroke to an ICAS. Thus, the relationship between procedurerelated stroke and both the total (sum of left and right) and the worst unilateral (maximal left or right) ICAS was determined using separate logistic regression models, adjusting for age, sex, history of atrial fibrillation, cerebrovascular disease and diabetes, procedure type (SAVR or TAVR), or left ventricular ejection fraction. Because of the small number of events, we adjusted for one covariate at a time to avoid model overfitting. The resulting parameter estimates corresponding to stenosis remain fairly stable with variations fewer than 10% compared with the unadjusted one, indicating little confounding effect resulting from the covariates. As such, we report the unadjusted analysis results. Two-subgroup analyses were also performed to evaluate this same relationship in patients who underwent TAVR (further adjusting for the access used,
Table 1. Baseline Characteristics of Patients Who Underwent Aortic Valve Replacement According to the Presence or Absence of Stroke All (n ¼ 982) Age in years, mean (SD) Female, n (%) Caucasian, n (%) STS score in %, mean (SD) Diabetes, n (%) Hypertension, n (%) Atrial fibrillation, n (%) Chronic lung disease None, n (%) Mild, n (%) Moderate, n (%) Severe, n (%) NYHA class III/IV, n (%) CAD, n (%) Prior CABG, n (%) Prior cerebrovascular disease, n (%) ESRD on dialysis, n (%) PAD, n (%) Immunocompromised, n (%) Liver disease, n (%) Prior cardiac surgery, n (%) History of carotid intervention, n (%)a Carotid endarterectomy, n (%) Carotid stent, n (%) LVEF in %, mean (SD) Creatinine in mg/dL, mean (SD) a
Nonstroke (n ¼ 948)
Stroke (n ¼ 34)
76.0 448 845 8.0 402 923 262
(11.0) (45.6) (86.0) (6.0) (40.9) (94.0) (26.7)
76.0 429 815 8.0 387 890 250
(11.0) (45.3) (86.0) (6.0) (40.6) (93.9) (26.4)
77.0 19 30 7.0 15 33 12
(8.0) (55.9) (88.2) (5.0) (44.1) (97.1) (35.3)
592 190 92 108 666 470 264 245 31 225 106 40 332 74 53 14 51.0 1.3
(60.3) (19.3) (9.4) (11.0) (81.8) (47.9) (26.9) (24.9) (3.1) (22.9) (10.8) (4.1) (33.8) (7.5) (5.4%) (1.4) (14.0) (1.05)
571 184 89 104 642 456 256 237 29 216 99 39 321 70 51 11 51.0 1.3
(60.2) (19.4) (9.4) (11.0) (81.8) (48.1) (27.0) (25.0) (3) (22.8) (10.4) (4.1) (33.9) (7.4) (5.4) (1.2) (14) (1.1)
21 6 3 4 24 14 8 8 2 9 7 1 11 4 2 3 55.0 1.4
(61.8) (17.6) (8.8) (11.8) (82.8) (41.2) (23.5) (23.5) (5.9) (26.5) (20.6) (2.9) (32.4) (11.8) (5.9) (8.8) (14.0) (1.2)
p 0.82 0.22 0.71 0.55 0.70 0.44 0.25 0.99
0.89 0.42 0.65 0.85 0.36 0.61 0.06 1.00 0.86 0.32 0.71 0.01 0.14 0.39
History of carotid intervention prior to carotid Doppler screening.
CABG ¼ coronary artery bypass grafting; CAD ¼ coronary artery disease; ESRD ¼ end-stage renal disease; LVEF ¼ left ventricular ejection fraction; NYHA ¼ new york heart association; PAD ¼ peripheral arterial disease; SD ¼ standard deviation; STS ¼ Society of Thoracic Surgeons.
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Table 2. Procedure Details for Patients Who Underwent Transcatheter Aortic Valve Replacement (TAVR) According to the Presence or Absence of Stroke All (n ¼ 463) Valve generation SAPIEN, n (%) SAPIEN XT, n (%) Valve size 23 mm, n (%) 26 mm, n (%) 29 mm, n (%) Access Transfemoral, n (%) Nontransfemoral, n (%) Second valve implanted, n (%) Postdilation, n (%) IABP used, n (%) Postprocedure paravalvular leak None, n (%) Mild, n (%) Moderate, n (%) Procedural time in minutes, mean (SD) ICU time in hours, median (Q1, Q3) Length of stay in days, median (Q1, Q3)a a
Nonstroke (n ¼ 451)
Stroke (n ¼ 12)
p
338 (73.3) 123 (26.7)
327 (72.8) 122 (27.2)
11 (91.7) 1 (8.3)
0.20
240 (52.1) 189 (41.0) 32 (6.9)
230 (51.2) 187 (41.6) 32 (7.1)
10 (83.3) 2 (16.7) 0 (0)
0.08
245 218 37 119 21
238 213 36 115 19
(52.9) (47.1) (8.0) (25.7) (4.5)
318 123 11 124.3 29.4 5.0
(70.4) (27.2) (2.4) (42.8) (23.3, 56.0) (3.0, 7.0)
310 119 11 124.1 29.0 5.0
(52.8) (47.2) (8.0) (25.5) (4.2)
7 5 1 4 2
(70.5) (27.0) (2.5) (42.9) (23.0, 54.4) (3.0, 7.0)
8 4 0 129.8 104.0 13.0
(58.3) (41.7) (8.3) (33.3) (16.7)
0.70
(66.7) (33.3) (0) (39.6) (56.8, 455.7) (7.0, 31.0)
0.78
0.99 0.52 0.10
0.65 <0.001 <0.001
From procedure to discharge.
IABP ¼ intraaortic balloon pump;
ICU ¼ intensive care unit;
Q ¼ interquartile range;
need for postdilation, and procedure time) or SAVR (further adjusting for cardiopulmonary bypass). A p value of 0.05 or less was considered significant.
Results A total of 1,372 patients with severe AS underwent TAVR or SAVR during the study period. Of those, 996 (73%) patients underwent preprocedural carotid Doppler screening. Fourteen patients were further excluded: 6 patients who had missing Doppler data (poor windows) and 8 patients who had a carotid intervention for the treatment of ICAS discovered on carotid Doppler screening prior to valve replacement (TAVR ¼ 2, and SAVR ¼ 6). The final study
SD ¼ standard deviation.
population was composed of 982 patients (TAVR ¼ 463, SAVR ¼ 519). In those patients who did not undergo carotid Doppler screening (TAVR ¼ 186, SAVR ¼ 189), 2 patients had a postprocedural stroke. Both of these patients had undergone SAVR and had imaged confirmed embolic ischemic strokes (carotid disease is unknown). In those patients in which carotid Doppler screening was performed, 34 (3.4%) had a procedure-related stroke. There were no significant differences in baseline characteristics between stroke and nonstroke patients (Table 1). Procedure-specific characteristics for TAVR and SAVR are shown in Tables 2 and 3, respectively. As expected, patients with a stroke after both SAVR and TAVR had a longer intensive care unit stay and overall postoperative length of
Table 3. Procedure Details for Patients Who Underwent Surgical Aortic Valve Replacement (SAVR), According to the Presence or Absence of Stroke All (n ¼ 519) CBP time in minutes, mean (SD) Cross clamp time in minutes, mean (SD) ICU time in hours, median (Q1, Q3) Length of stay in days, median (Q1, Q3)a Operation time in hours, median (Q1, Q3) IABP used, n (%) a
108.0 81.0 48.5 7.0 313.0 47
(33) (24.0) (26.5, 97.6) (5.0, 9.0) (275.0, 364.0) (9.1)
Nonstroke (n ¼ 497) 108.0 80.0 47.8 6.0 311.0 44
(33.0) (24) (26.1, 95.1) (5.0, 9.0) (275.0, 361.0) (8.9)
Stroke (n ¼ 22) 121.0 87.0 139.4 14.0 336.0 3
(39.0) (24.0) (78.7, 496.4) (9.0, 21.0) (295.0, 391.0) (13.6)
p 0.08 0.20 <0.001 <0.001 <0.001 0.44
From procedure to discharge.
CBP ¼ cardiopulmonary bypass; deviation.
ICU ¼ intensive care unit;
IABP ¼ intraaortic balloon pump;
IQ ¼ interquartile range;
SD ¼ standard
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Table 4. Procedure Complications
Acute renal failure, n (%) Pneumonia, n (%) Procedure mortality, n (%) 30-day mortality, n (%) Post-operative atrial fibrillation, n (%) TAVR-specific complications Heart block requiring pacemaker, n (%) Major vascular complication, n (%) Minor vascular complication, n (%)
All (n ¼ 982)
Nonstroke (n ¼ 948)
Stroke (n ¼ 34)
19 39 31 28 262
17 31 28 25 250
2 8 3 3 12
(1.9) (4.0) (3.2) (2.9) (26.7)
22 (4.8) 19 (4.1) 38 (8.2)
(1.8) (3.3) (3.0) (2.6) (26.4)
21 (4.7) 18 (4.0) 35 (7.8)
(5.9) (23.5) (8.8) (8.8) (35.3)
1 (8.3) 1 (8.3) 3 (25.0)
p 0.14 <0.001 0.09 0.07 0.25 0.45 0.46 0.07
TAVR ¼ transcatheter aortic valve replacement.
stay than nonstroke patients. There was a higher frequency of postprocedure pneumonia in stroke than in nonstroke patients (23.5% versus 3.3%, p 0.0001). There were no significant differences in the remaining procedural complications between groups (Table 4), including the rate of postoperative atrial fibrillation. When present, atrial fibrillation was managed by a multidisciplinary team according to American Association for Thoracic Surgery guidelines [17].
Stroke and ICAS The prevalence of the different degrees of ICAS in the whole cohort and in patients with and without postprocedure stroke is depicted in Figure 2. Fifty-two of the 996 patients (5.2%) had at least 70% or greater ICAS.
Thirty-four patients (3.4%) had a procedure-related stroke (TAVR ¼ 12 and SAVR ¼ 22). The location was right-sided in 12 patients (35.3%), left-sided in 8 patients (23.5%) and bilateral/embolic in 14 patients (41.2%). Only 3 patients (TAVR ¼ 1 and SAVR ¼ 2) had an ipsilateral stroke in the region of the ICAS (one had 70% ICAS and two had 50%–59% ICAS). Table 5 shows the characteristics of the 8 patients who underwent a prior carotid intervention. Although all these patients eventually underwent valve replacement without developing a procedural stroke, we did not include those patients who had a carotid intervention but did not undergo valve intervention, as we were unable to identify them all. Though the overall prevalence of ICAS 70% or greater was higher in stroke than in nonstroke patients (8.8%
Fig 2. Prevalence of internal carotid stenosis in patients with severe aortic stenosis scheduled for valve replacement. Classified by (A) procedure type, (surgical or transcatheter aortic valve replacement [SAVR or TAVR]), and by the presence or absence of procedure-related stroke (stroke and non-stroke) in the following groups: (B) whole cohort, (C) SAVR patients; and (D) TAVR patients. (ICAS ¼ internal carotid artery stenosis.)
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Table 5. Characteristics of Patients Who Underwent Preprocedure Carotid Intervention STS Score (%)
Right ICAS
Left ICAS
Symptoms? Intervention
1 2
8.9 7.8
<50% 70%
50%–69% 50%–69%
Yes: TIA No
3 4 5 6 7
4.3 3.8 1.3 6.4 4.5
<50% 70% Total occlusion Near total occlusion <50%
70% <50% 70% <50% 70%
No Yes: TIA Yes: TIA No No
8
5.1
<50%
Near total occlusion No
Complications after Carotid Intervention SAVR or TAVR
Left ICA stent None Right CEA Hematuria and gastrointestinal bleeding. Required blood transfusion. Cardiogenic shock requiring vasopressors and emergent TAVR. Left CEA None Right CEA New onset atrial fibrillation Left ICA stent None Right CEA None Left CEA Delirium and surgical site hematoma that required evacuation. Left ICA stent None
TAVR TAVR
SAVR SAVR SAVR SAVR SAVR
SAVR
CEA ¼ carotid endarterectomy; CVA ¼ cerebrovascular event; ICA ¼ internal carotid artery stenosis; ICAS ¼ internal carotid artery stenosis; SAVR ¼ surgical aortic valve replacement; STS ¼ Society of Thoracic Surgeons; TAVR ¼ transcatheter aortic valve replacement; TIA ¼ transient ischemic attack.
versus 3.6%), we did not find a statistically significant association between procedural stroke and the total (p ¼ 0.13) or maximal unilateral (p ¼ 0.39) ICAS.
Subgroup Analysis Compared with SAVR patients, TAVR patients were older (71 versus 81 years p 0.001), had higher STS scores (5.0% versus 11.0%, p 0.001), and had more history of diabetes (37.4% versus 44.5%, p ¼ 0.02), hypertension (91.9% versus 96.6%, p ¼ 0.002), atrial fibrillation (18.0% versus 36.6%, p 0.001), severe chronic lung disease (4.9% versus. 17.8%, p 0.001), coronary artery disease (35.7% versus 63%, p 0.001), and cerebrovascular disease (20.8% versus 31.3%, p 0.001). More TAVR patients also had history of prior cardiac surgery (47.5% versus 22.3%, p 0.001) and carotid endarterectomy (8.0% versus 3.7%, p ¼ 0.04) than SAVR patients. Specific procedure characteristics for TAVR and SAVR are shown in Tables 2 and 3. Though the number of stroke patients was low in our subgroups, we found that of the 7 patients who had a procedure-related stroke after TF-TAVR, 6 patients had surgery performed using the minimalist approach (stroke rates: minimalist ¼ 6.0% versus standard ¼ 0.9%, p ¼ 0.02). Similar to our main analysis and despite observed increased prevalence of 70% or greater ICAS in stroke patients (Fig 2), there was no statistical association between stroke and total or maximal unilateral ICAS in patients who underwent either TAVR (p ¼ 0.27 and p ¼ 0.63) or SAVR (p ¼ 0.21 and p ¼ 0.36).
Comment Our study found no statistically significant association between the severity of ICAS and procedure-related stroke in patients with AS who underwent isolated aortic valve replacement. Though other reports have
shown no correlation between ICAS and outcomes after cardiac surgery [9, 10], ours is the first study to look at a population of AS undergoing either SAVR or TAVR. Because patients with severe AS are usually elderly with multiple risk factors for cerebrovascular disease [18, 19], it has been assumed that these patients, in particular, would benefit from carotid Doppler screening. Despite our observation of rates of 70% or greater ICAS similar to previous reports [2, 20], we found no statistical significant association between the severity of ICAS and stroke. Thus, we raise the question of whether universal carotid Doppler screening in neurologically asymptomatic patients with AS being considered for isolated SAVR or TAVR is indicated. Severe (50% or 70%) ICAS in a general population is related to stroke [8, 21]. But the relationship of ICAS to strokes during aortic valve surgery is controversial. In theory, 50% or greater ICAS can decrease brain perfusion during cardiopulmonary bypass and/or anesthesia, and, in fact, some studies have reported an increased prevalence of 50% or greater ICAS in such patients [1]. Our results also show an increased prevalence of 70% or greater ICAS (but not of 50%) in patients who had a stroke after TAVR/SAVR. After adjustment, however there was no statistical association between ICAS severity and stroke. We suspect that the severity of ICAS is a marker of risk and underlying comorbidities. To support this, note that in our study only 1 of 37 patients (2.7%) with 70% or greater ICAS developed an ipsilateral stroke and that 14 of 34 (41.2%) of all strokes were bilateral/ embolic. Existing evidence suggests that these procedurerelated strokes are a consequence of thromboembolic events originating in the aorta from direct or catheter manipulation during SAVR or TAVR [20, 22, 23]. Though our main analysis adjusted for procedure type, we also performed two subgroup analyses in patients who
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underwent TAVR or SAVR because of the differences between these patient populations and techniques. Interestingly, we found a higher rate of strokes with a minimalist approach in those patients who underwent TF-TAVR. Though this observation should warrant evaluation of the stroke risk with minimalist TF-TAVR in future studies, caution must be used in analyzing these results as our study was not designed to evaluate this approach and previous reports have found similar stroke rates between the minimalist and standard approach [14]. Not surprisingly, our TAVR patients were older and had higher surgical risk than our SAVR patients and thus had a higher overall prevalence of 70% or greater ICAS and also had a higher surgical risk for carotid endarterectomy [24]. Nevertheless, our subgroup analyses showed no statistical association between the ICAS and procedure-related stroke after adjusting for procedure specific risk factors. Clinically, one may not need to weigh a theoretical but unproven benefit of carotid intervention before TAVR/ SAVR, with its associated risk of delaying valve surgery, risk of an endarterectomy, or bleeding risk from dualantiplatelet therapy after carotid stenting. Based on our study results, including the complications observed in some patients that underwent prior carotid intervention, our institution has forgone universal preprocedural carotid Doppler screening on asymptomatic patients before aortic valve replacement as a standard of care, especially in highsurgical risk patients scheduled for TAVR.
Limitations This study has the inherent limitations of any retrospective study. Though a small bias is possible because 8 patients with preprocedural carotid intervention were excluded (none of which had a procedure-relate stroke), only 5 had asymptomatic disease, and carotid intervention was complicated in 3 patients (Table 5). The inclusion of these patients are unlikely to have altered our results. Although we adjusted for important risk factors of perioperative stroke, we acknowledge that our number of cerebrovascular events was small (3.4%). Nonetheless, our stroke rate was similar to those previously reported after SAVR (2.0–4.8%) and TAVR (2.7%–5.0%) [4, 5, 25, 26]. Although we report similar rates of postoperative complications (except for pneumonia) between stroke and nonstroke patients, care must be used in analyzing these results as our study was not designed to compare these two groups of patients. Instead, it was designed to evaluate the association between carotid Doppler screening and procedure-related strokes. Further studies of larger populations are warranted to corroborate our findings.
Conclusions We found no statistically significant association between the total or maximal unilateral severity of ICAS and procedure-related strokes in patients with AS undergoing intervention. We hope our results will prompt a randomized clinical study to evaluate the usefulness in preventing strokes of carotid Doppler screening as a guide to preprocedural carotid intervention before TAVR or SAVR.
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References 1. Ascher E, Hingorani A, Yorkovich W, et al. Routine preoperative carotid duplex scanning in patients undergoing open heart surgery: is it worthwhile? Ann Vasc Surg 2001;15: 669–78. 2. Anselmi A, Gaudino M, Risalvato N, et al. Asymptomatic carotid artery disease in valvular heart surgery: impact of systematic screening on surgical strategy and neurological outcome. Angiology 2012;63:171–7. 3. Hogue CW Jr, Murphy SF, Schechtman KB, et al. Risk factors for early or delayed stroke after cardiac surgery. Circulation 1999;100:642–7. 4. Bucerius J, Gummert JF, Borger MA, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg 2003;75:472–8. 5. Nombela-Franco L, Webb JG, de Jaegere PP, et al. Timing, predictive factors, and prognostic value of cerebrovascular events in a large cohort of patients undergoing transcatheter aortic valve implantation. Circulation 2012;18(126):3041–53. 6. Masabni K, Raza S, Blackstone EH, et al. Does preoperative carotid stenosis screening reduce perioperative stroke in patients undergoing coronary artery bypass grafting? J Thorac Cardiovasc Surg 2015;149:1253–60. 7. Masabni K, Sabik JF 3rd, Raza S, et al. Nonselective carotid artery ultrasound screening in patients undergoing coronary artery bypass grafting: is it necessary? J Thorac Cardiovasc Surg 2016;151:402–8. 8. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/ AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/ SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol 2011;57: e16–94. 9. Adams BC, Clark RM, Paap C, et al. There is no benefit to universal carotid artery duplex screening before a major cardiac surgical procedure. Ann Vasc Surg 2014;28:93–101. 10. Naylor AR, Bown MJ. Stroke after cardiac surgery and its association with asymptomatic carotid disease: an updated systematic review and meta-analysis. Eur J Vasc Endovasc Surg 2011;41:607–24. 11. Chun LJ, Tsai J, Tam M, et al. Screening carotid artery duplex in patients undergoing cardiac surgery. Ann Vasc Surg 2014;28:1178–85. 12. Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis—Society of Radiologists in Ultrasound Consensus Conference. Radiology 2003;229:340–6. 13. Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Eur Heart J 2012;33:2403–18. 14. Babaliaros V, Devireddy C, Lerakis S, et al. Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis. JACC Cardiovasc Interv 2014;7:898–904. 15. Jensen HA, Condado JF, Devireddy C, et al. Minimalist transcatheter aortic valve replacement: The new standard for surgeons and cardiologists using transfemoral access? J Thorac Cardiovasc Surg. 2015;150:833–9.
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CONDADO ET AL CAROTID DOPPLER BEFORE SAVR OR TAVR
16. Thourani VH, Ailawadi G, Szeto WY, et al. Outcomes of surgical aortic valve replacement in high-risk patients: a multiinstitutional study. Ann Thorac Surg 2011 Jan;91:49–55; discussion -6. PubMed PMID: 21172485. 17. Frendl G, Sodickson AC, Chung MK, et al. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg 2014;148:e153–93. 18. Osnabrugge RL, Mylotte D, Head SJ, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol 2013;62:1002–12. 19. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005–11. 20. Steinvil A, Sadeh B, Arbel Y, et al. Prevalence and predictors of concomitant carotid and coronary artery atherosclerotic disease. J Am Coll Cardiol 2011;57:779–83. 21. Norris JW. Outcome of transient ischaemic attacks and stroke. Drugs 1991;42(suppl 5):10–5.
Ann Thorac Surg 2016;-:-–-
22. Van Mieghem NM, El Faquir N, Rahhab Z, et al. Incidence and predictors of debris embolizing to the brain during transcatheter aortic valve implantation. JACC Cardiovasc Interv 2015;8:718–24. 23. van der Linden J, Hadjinikolaou L, Bergman P, et al. Postoperative stroke in cardiac surgery is related to the location and extent of atherosclerotic disease in the ascending aorta. J Am Coll Cardiol 2001 Jul;38:131–5. 24. Halm EA, Tuhrim S, Wang JJ, et al. Risk factors for perioperative death and stroke after carotid endarterectomy: results of the new york carotid artery surgery study. Stroke 2009;40: 221–9. 25. Leon MB, Smith CR, Mack M, et al. Transcatheter aorticvalve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363: 1597–607. 26. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187–98.