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Clinical and silent stroke following aortic valve surgery and transcatheter aortic valve implantation
Cardiovascular Revascularization Medicine 13 (2012) 133 – 140
Clinical and silent stroke following aortic valve surgery and transcatheter aortic valve implantation☆,☆☆ Camille Hauville, Itsik Ben-Dor, Joseph Lindsay, Augusto D. Pichard, Ron Waksman⁎ Washington Hospital Center, Washington DC Received 10 November 2011; accepted 10 November 2011
Abstract
Transcatheter aortic valve implantation (TAVI) has been introduced as an alternative to conventional surgery for high-risk patients with aortic stenosis. A recently published randomized clinical trial demonstrated reduction of mortality in high-risk or inoperable patients when compared to medical treatment or balloon aortic valvuloplasty. Despite this evidence of superiority, the rate of TAVI complications is high, and perhaps the most devastating of the nonfatal complications is cerebral injury. This review will compare the incidence of stroke and “silent” cerebral injury after surgical aortic valve replacement and after TAVI and will discuss mechanisms that can lead to cerebral injury during these procedures and subsequently how to prevent this with new protection devices. © 2012 Published by Elsevier Inc.
Keywords:
Transcatheter aortic valve implantation; Aortic valve replacement; Silent and clinical strokes
1. Introduction Aortic stenosis (AS) is the most common valvular disease in adults. Its prevalence increases with age, reaching 2%–4% in patients over 85 years [1]. Once patients with severe AS become symptomatic or develop left ventricular dysfunction, life expectancy is significantly reduced [2]. Because of this dire prognosis, surgical aortic valve replacement (AVR) is recommended for such patients and substantially improves outlook. Transcatheter aortic valve implantation (TAVI) has been introduced as a less morbid alternative to conventional surgery for high-risk patients with AS [3–5]. A recently published randomized clinical trial demonstrated improved outcomes in high-risk or inoperable patients when compared to medical treatment or balloon aortic valvuloplasty (BAV) [6]. However, despite this evidence of superiority, the ☆
absolute complication rate of TAVI is high, especially in this high-risk population. Perhaps the most devastating of the nonfatal complications is cerebral injury. Brain injury, an infrequent complication of all cardiac surgeries, may also occur after TAVI. This review will compare the available evidence bearing on the incidence of stroke and “silent” cerebral injury after surgical AVR and after TAVI. It will also discuss mechanisms that can lead to cerebral injury during these procedures. 2. Cerebral injury after surgical AVR 2.1. Clinical stroke The frequency of overt neurological injury varies with the type of cardiac surgery. Retrospective studies
Funding: No external or third-party funding was used for this study. Dr C. Hauville was supported by the French Federation of Cardiology. Conflict of interest statement: The authors have no conflict of interest to report related to this study. ⁎ Corresponding author. Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. Tel.: +1 202 877 2812; fax: +1 202 877 2715. E-mail address: [email protected] (R. Waksman). ☆☆
1553-8389/11/$ – see front matter © 2012 Published by Elsevier Inc. doi:10.1016/j.carrev.2011.11.001
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report an incidence of 0.8%–3.2% after coronary artery bypass grafting (CABG) [7,8], while prospective studies report 1.5%–5.2% [9,10]. A similar incidence (0.7%–5.0%) has been reported in a clinical series of isolated AVR (Table 1). The incidence is higher if the AVR is combined with CABG or mitral valve replacement [11]. Not only can stroke have a devastating effect on quality of life, but its occurrence is also strongly related to mortality. Hospital mortality in patients with stroke can reach 24%, while the mortality rate in similar patients without cerebral complication is 4.6% [12]. Unsurprisingly, median length of hospital stay is also substantially increased in patients with stroke. Clinical risk factors for perioperative stroke in cardiac valve surgery include older age, female gender, previous cerebrovascular disease, previous peripheral vascular disease, diabetes mellitus, hypertension, previous cardiac surgery, and urgent operation. In addition, certain facets of the procedure also affect the incidence of perioperative stroke, e.g., cardiopulmonary bypass time longer than 2 h, use of hemofiltration, and requirement for more than usual blood transfusion [11–14]. The importance of age is especially noteworthy. For example, Brown et al.[15] found a postoperative stroke rate of 0.7% in those younger than 70 years and 2.5% in those older than 80 years. It is therefore surprising that despite the fact that the age of patients undergoing AVR has increased in the past 10 years, the rate of death or stroke has decreased for isolated AVR [15].
2.2. Asymptomatic brain injury A new imaging technology, diffusion-weighted magnetic resonance imaging (DWMRI), has proven to be more sensitive than computed tomography and conventional magnetic resonance imaging (MRI) for the detection of brain lesions [16,17]. This technique is sensitive to changes in the mobility of water molecules; lowered water mobility is an early event in the ischemic tissue change. After cardiac surgery, this modality often demonstrates small, multiple subcortical lesions. Since these lesions appear in patients with no overt signs of brain injury, they can be regarded as “silent brain injury”[18]. The appearance of new DWMRI lesions following surgery has been tentatively associated with the presence and severity of preexisting white matter lesions [16] as well as with age, preexisting T2 lesion volume, and postoperative S100β protein [18]. New, silent DWMRI lesions appear so frequently after a variety of invasive cardiovascular procedures that Bendszus and Stoll [19] have referred to them as “fingerprints of invasive medical procedures.” Several studies (Table 2) performed DWMRI before and up to 4 months after a cardiac surgical procedure. The incidence of new lesions postoperatively was surprisingly high at 38%–71%. 2.3. Neurocognitive decline after AVR Most patients with new lesions have no overt neurological signs, but there has been considerable interest in a possible association between their appearance and postprocedure cognitive dysfunction. Supporters of this propo-
Table 1 Incidence of stroke and cerebral events with cardiac surgery Study
Design of study
Incidence of stroke
Bucerius et al. [11]
Prospective Apr 1996–Aug 2001 1830 AVR 2506 CABG+valve surgery Prospective Jan 1998–Dec 2006 2808 valve surgery±CABG
AVR: 4.8% CABG+valve surgery: 7.4%
Filsoufi et al. [13]
Gulbins et al. [14] Brown et al. [15]
Prospective 1996–2005 1014 stentless AVR Prospective 108,687 patients 928 hospitals 1997–2006
Bakaeen et al. [12]
Retrospective 1991–2007 7142 patients isolated AVR
Wolman et al. [41]
Prospective 273 patients, 24 centers
TIA, transient ischemic attack.
Overall 2.2% (n=63, AVR n=17) 1998: n=3.3% 2002: n=1.3% b50 years: 0.6% 50–79: 1.5% N80: 2.5% Perioperative cerebral event: 1.8% 1997: 1.7% 2006: 1.3% In 2006: b70 years: 0.7% 70–80 years: b2% N80 years: b2.5% Incidence of stroke b80 years: 1.9% N80: 2.4% Cerebral outcomes: 16% 8.5%: 5 cerebral deaths, 16 nonfatal strokes, 2 TIA 7.3%: 17 new intellectual deteriorations, 3 seizures
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Table 2 Incidence of new silent cerebral event with cardiac surgery Study
Study design
Incidence of clinical cerebral event
Incidence of new MRI lesions
Stolz et al. [18]
Prospective 45 patients, 37 pre- and postoperative (AVR) DWMRI Retrospective 14 patients with postoperative (cardiac surgery) DWMRI Prospective 30 patients cardiac valve replacement DWMRI before and after Prospective 34 patients DWMRI Cardiac surgery
3 focal neurological deficits
New postoperative DWMRI lesions in 38%
14 patients with clinical cerebral events
New cerebral lesions in 71%
No focal neurological deficit Impaired cognitive function in 5 of 13 tests (all resolved within 4 months) 2 clinical strokes in the AVR group
New focal brain lesions in 47%
Wityk et al. [32]
Knipp et al. [21]
Floyd et al. [16]
sition point to the apparent connection between DWMRI lesions and cognitive dysfunction in population-based studies of healthy subjects. While DWMRI lesions are detected in up to 20% of putatively normal elderly participants, they are more frequent and larger in size in those with evidence of dementia. By means of careful psychological testing, neurocognitive deficits have been observed in 33%–83% of patients in the first weeks after cardiac surgery [20]. As a rule, these deficits resolve within 4 months [21], but a fear exists among patients, cardiologists, and surgeons that persistent or progressive problems may develop. Evidence points to older age and preoperative vascular disease as major risk factors for postoperative cognitive dysfunction [20]. An association between the postoperative appearance of new small, “silent,” subcortical brain injury and postoperative cognitive dysfunction is intuitively attractive, but confirmation of this relationship has been elusive[16]. Major practical constraints hinder a careful examination of this association. It is expensive and can be awkward to schedule serial DWMRI studies in the setting of pre- and postoperative clinical care. Moreover, expertise in conducting the required neuropsychological testing [22] can also be expensive and difficult to schedule. Thus, surgical AVR is associated with a clinical stroke rate of 0.8%–5%. “Silent” brain injury may be detected by sophisticated imaging in about half of surgical AVR patients. At first glance, such small “silent” lesions result in more concern for physicians and patients than their permanent clinical impact deserves, but their possible association with subtle, permanent cognitive impairment appropriately heightens interest in this phenomenon. 3. Brain injury and TAVI 3.1. Clinical strokes To this point, patients are referred to TAVI specifically because they are at high risk for surgical AVR and are, therefore, typically older and sicker than those who undergo
New infarction in 6 of 15 (40%) in procedures involving aortic valve replacement
surgical AVR. As a consequence, they arguably also have a higher risk for perioperative brain injury. The early experience with TAVI indicates that the incidence of clinically apparent neurological events varies widely. A broad review of all reported series reveals a range of such events of from 0% to 10% (Table 3). It is important to note that these reports describe initial experiences with a variety of approaches to TAVI, including transfemoral and transapical procedures, as well as utilization of both the Edwards valve (Edwards LifeSciences LLC, Irvine, CA, USA) and the CoreValve (Medtronic CoreValve LLC, Minneapolis, MN, USA). The most recent trial to be completed and published is PARTNER US [6]. Cohort B randomized 1058 patients deemed not suitable for surgical AVR to transfemoral TAVI or medical treatment. At 30 days, the overall incidence of stroke was 6.7%; 5% were defined as “major” and 1.7% as “minor.” At 1 year, the overall rate was 10.0% (7.8% major, 2.2% minor). As compared to medically managed patients, the overall stroke rate was greater in the TAVI group (6.7% vs. 1.7%, P=.03). Moreover, the occurrence of a major stroke was associated with significantly greater mortality (Pb.0001). Due to the lack of a consistent definition of neurological events in the PARTNER trial, it is hard to understand the exact timing of these events and their relation to procedures performed (e.g., TAVI procedure or balloon aortic valvuloplasty in the medical therapy group). This issue was address by constructing the Valve Academic Research Consortium definitions for adverse neurological events [23]. Atrial fibrillation was present in a significant proportion of patients with neurologic events in both groups. Of note, there was no standardized protocol for anticoagulation in the TAVI group, so it is impossible to assess the effect of various anticoagulant regimens on the incidence of neurological events. In cohort A of PARTNER US [24], 699 high-risk patients were randomized to TAVI (n=348) or surgical AVR (n=351). The results showed that the incidence of all strokes or transient ischemic events at 30 days was significantly higher in the TAVI group (n=19, 5.5%) compared to the
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Table 3 Incidence of stroke with TAVI Study
Year
Patient population
Incidence of stroke
Thomas et al. [46]
Nov 2007–Jan 2008
Rodes-Cabau et al.[47]
Jan 2005–June 2009
Walther et al.[50]
Feb 2006–Oct 2006
TA: 2.6% (n=16) TF: 2.4% (n=11) Total: 2.5% (n=27) TA: 0.6% (n=1) TF: 0.6% (n=1) Total: 0.6% (n=2) TA: 3%
Grube et al.[51]
Aug 2005–Sept 2006
TA: 575 TF: 463 Edwards TA: 177 TF: 168 Edwards 53 TA Edwards 86 TF and SC Corevalve
Walther et al.[52]
Feb 2006–Sept 2006
Himbert et al.[26]
Oct 2006–Nov 2008
Bleizieffer et al.[27]
June 2007–Feb 2009
Eltchaninoff et al. [48] FRANCE
Feb 2009–Sept 2009
Leon et al. [6] PARTNER Cohort B
King [24] PARTNER Cohort A
30 TA Edwards TA: 24 : 51 Edwards TA: 50 TF: 151 Edwards and Corevalve TA: 71 TF: 161 Edwards and Corevalve Edwards TF: 358
Edwards TAVI
Major stroke: 4% Minor stroke: 7% Total: 10% TA: 0 TA: 0 TF: 6% Total: 4% (all recovered) TA: 0 TF: 7% (n=11) TA: 2.8% TF: Edwards 4.2% Corevalve 4.5% Total: 6.7% (30-day results) Minor stroke: 1.7% Major stroke: 5% Total: 5.5% (30-day results) Major stroke: 3.8% Minor stroke: 0.9%
TA, transapical; TF, transfemoral; SC, subclavian.
surgical group (n=8, 2.4%, P=.04). However, no significant differences were found in the major and minor subgroups. The results at 1 year also demonstrated a significantly higher risk of stroke in the TAVI group (P=.04). Since the transapical approach to TAVI avoids the risk of catheter manipulation in an atherosclerotic aorta, it was anticipated that this approach might avoid some of the stroke risk associated with the femoral approach. The experiences of Kempfert et al. [25], Himbert et al. [26], and Bleiziffer et al. [27] suggest that this hope may be realized, but some new studies [28] have failed to confirm this advantage; no difference in stroke incidence between transapical and transfemoral approaches was found. 3.2. Silent cerebral events As is true of surgical AVR, silent cerebral events are more frequent than clinical stroke with TAVI procedures. There are several reports (Table 4) of DWMRI before and 48 h to 5 days after TAVI (the longer delays were intended to ensure that the effects of anesthetic drugs had dissipated). The intent of each study was to detect new cerebral lesions and to compare those results to clinical events. In some studies, an additional MRI was performed several months after the TAVI to look for long-term changes. Moreover, most of the study protocols included neurological examination and comprehensive neuropsychological assessment.
These reports describe a high incidence (68%–84%) of new lesions at the MRI [28–31]. Most were multiple and had characteristics of ischemic lesions, probably due to emboli. Comparable studies with surgical AVR suggest that such lesions are more frequent with TAVI [18,19]. Kahlert et al. directly compared the incidence of silent lesions in surgical AVR and TAVI [30]. There were no overt neurological events with either approach, but new “silent” lesions were found in 84% in the TAVI group and 48% in the AVR group [19,21,31]. Patients undergoing TAVI were significantly older than those undergoing open cardiac surgery (80.0 versus 67.4 years; Pb.001). In addition, patients in the TAVI group had significantly higher logistic EuroSCOREs and significantly more comorbidities than did patients in the AVR group. Importantly, 80% of the new lesions had disappeared by the 3-month MRI exam. Thus, it appears that “silent” DWMRI lesions are significantly more frequent after TAVI. The majority resolve within a few months. 3.3. Neurocognitive decline after TAVI Although controversial for reasons previously described, many believe that silent brain injury after cardiac surgery is frequently associated with deficits in physical and cognitive function that commonly go unnoticed [32]. Although “silent” lesions are more frequent after TAVI, no relation
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Table 4 Incidence of silent cerebral events with TAVI Study
Year
Patient population
Incidence of new MRI lesions
Ghanem et al. [29]
Nov 2008–June 2009
TF: 30 Corevalve
Kahlert et al. [30]
Sept 2007–Mar 2009
TF: 32 Edwards: 22 Corevalve: 10 AVR: 21
Arnold et al. [31]
Dec 2008–Nov 2009
Rodes-Cabau et al. [28]
Aug 2008–Feb 2010
TA: 25 Edwards TA: 31 TF: 29 Edwards
New silent embolic cerebral lesions (DWMRI): 72.7% 3-month clinical deficit: 3.6% Clinical deficit: 0 New cerebral lesions (DWMRI): TAVI: 84% AVR: 48% 80% of lesions gone at 3 months Clinical syndromes: n=5 New cerebral lesions (DWMRI): 68% Clinical stroke: 3.3% n=2 New cerebral ischemic lesions (DWMRI): 68% TA: 71% TF: 66%
is seen between new cerebral lesions and neurocognitive dysfunction. It is difficult to confidently identify the cognitive abnormalities. An additional confounder is the fact that, currently, there is no validated model to assess neurocognitive status or even quality of life measurements for patients undergoing TAVI. In the available studies, the National Institute of Health Stroke Scale and the Mini Mental State Examination have been employed. A more thorough study may be able to detect more subtle changes. The greatest fear, chronic cognitive dysfunction attributable to procedure-related brain injury, will be difficult to identify conclusively. Development of a control population will be required since, in many TAVI patients, naturally occurring cognitive decline is under way and can be expected to continue. Some investigators have proposed that periprocedural “silent” brain injury may increase the risk of vascular dementia or even Alzheimer's disease [21,33,34]. Conversely, a recent prospective study, which assessed the relationship between clinical and subclinical stroke in a small number of patients (n=31), did not find an association between any stroke event and quality of life as assessed by the SF-12v2 Health Outcomes Questionnaire and SF-36 [35]. The considerations outlined in this review assume even greater urgency as the indications for TAVI are widened to include younger patients. 3.4. Overall comparison of TAVI and surgical AVR This review shows that in the initial TAVI experience, the incidence of overt cerebral events appears to be higher after TAVI than after AVR. The incidence of “silent” DWMRI lesions, while much higher than strokes in both groups, is even higher in the TAVI group. Sometimes, periprocedural strokes are hemorrhagic, but the vast majority are ischemic [13,31,32,36]. Age, diabetes, female gender, a calcified ascending aorta, prior stroke, or preexisting lesions on imaging appear to be risk factors for both overt and silent brain injury after both
AVR and TAVI. A correlation between new “silent” lesions found on MRI and impaired neurocognitive function remains controversial. 4. Mechanisms 4.1. After cardiac surgery The pathogenesis of brain injury after heart surgery is not completely defined. There is a long-held assumption that embolization of atherosclerotic material, thrombus, or other particulate matter is a major mechanism. This assumption is supported by transcranial Doppler studies demonstrating “microemboli” at the time of aortic clamp release [37,38]. Furthermore, postmortem observations on the nature of cerebral lesions after cardiac surgery [39,40] are consistent with the presence of numerous emboli lodged in the small arteries. Insofar as the embolic basis for brain injury is true, the frequency with which it associates with AS surgery becomes understandable. Patients with AS often have more severe aortic arch atheroma than do others and, consequently, a greater risk of stroke after AVR [18,41]. Other mechanisms include compromised cerebral blood flow, cerebral edema, inflammation, and metabolic disturbances [42,43]. The existence of a synergy of sorts between hypoperfusion and embolization can be considered [44]. Low cerebral flow may allow small emboli to lodge at points at which a higher flow might “wash them out.” DWMRI lesions may be as frequent with “on-pump” and “off-pump” procedures. Cognitive dysfunction after CABG has a multifactor physiopathology like cerebral embolism, systemic inflammation, body temperature, and cerebral hemodynamics. Off-pump surgery reduces intraoperative cerebral embolization, systemic inflammatory responses, and the degree of postoperative brain edema. But cardiac output and cerebral perfusion pressure may vary significantly during some periods of off-pump surgery, which may subsequently lead to a reduction in cerebral perfusion
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pressure and neuronal ischemia [45]. Degenerative AS is an inflammatory process, strongly related to atherosclerosis and perhaps to a more diffuse vascular abnormality. Therefore, a higher rate of stroke might be expected in this population because of intracranial small vessel disease. 4.2. After TAVI Reports from the initial TAVI series suggest that new procedurally related brain injury is more frequent after TAVI than after surgical AVR. As noted earlier in this review, 84% of TAVI patients have MRI-identified cerebral lesions as compared to 48% of patients after surgical AVR. These observations must be regarded as tentative. The available data are limited, and TAVI patients are very different with regard to age and the prevalence of comorbid illness from those accepted for surgical AVR. A potential tool for assessment of the timing of embolism during TAVI is the transcranial Doppler; however, no systematic study has used this tool to determine timing of intraprocedural brain embolism. Intuitively, one would expect that as compared to the transfemoral approach, transapical TAVI might be associated with fewer cerebral embolic events. In transfemoral TAVI, repeated manipulation of large catheters in the aortic arch, crossing of the calcified valve, balloon dilatation, and valve deployment all promote embolism. On the other hand, transapical TAVI, an anterograde procedure, limits manipulation within the aorta. As previously noted, the data of Kempfert et al., Himbert et al., and Bleiziffer et al. [25–27] support this idea, but larger studies indicate that the incidence of new brain injury is similar regardless of the approach used [28,46–48]. Although it is intuitively unlikely, embolism attributable to catheter manipulation in the aorta or retrograde crossing of the aortic valve may not be the only, or even the primary, mechanism. Thus, embolism-provoking mechanisms common to both approaches must be considered. One such possibility is that air embolism attendant on the use of very large catheters and the necessity for multiple catheter exchanges may increase the risk of embolization [28]. This possibility reemphasizes the necessity for careful flushing of the catheter before insertion and assiduous checking for air bubbles within the catheter throughout the procedure. It is also plausible that emboli originate from the aortic valve itself. In a German study [36], 22% of patients who underwent retrograde catheterization of the aortic valve had new cerebral lesions on MRI imaging, and three patients (3%) had clinically apparent neurological deficits. No patient in a control group who did not have their aortic valve crossed had such lesions. Importantly, both transapical and transfemoral TAVIs involve two maneuvers during which the aortic valve leaflets are maximally stretched. This happens with preparatory dilatation of the aortic valve and during the valve implantation itself. These
maneuvers could be associated with dislodgment of calcium fragments and cerebral embolism. Embolism is not the only potential reason for the development of new periprocedural lesions. Kahlert et al.[30] point out a number of other possibilities, particularly for the appearance and subsequent disappearance of lesions in the periprocedural period. To explain the high rate of spontaneous resolution of the lesions following TAVI, they suggest that intraprocedural hemodynamic perturbations, for example, those produced by rapid pacing, may be responsible. 5. Protection devices Due to the likelihood that embolic phenomena are instrumental in brain injury associated with TAVI, embolic protection devices have been devised. We will briefly describe two. First is the Claret device from Claret Medical, Inc. (Santa Rosa, CA, USA), which provides cerebral filter protection. The device is placed into the aortic arch via right-radial or brachial entry preferably in the right arm, but may also be placed via the femoral artery or another access point such as the carotid artery. The device is deployed partially in the aortic arch but also in the innominate and carotid arteries. Additionally or alternatively, the device may deploy to protect the left subclavian artery, where the device is opened and pulled back into position to cover the ostia of both the brachiocephalic and left common carotid arteries. A portion of the device protrudes into the vessel(s), with a portion of the device entering into the vessel or artery to trap emboli. A second embolic protection device for TAVI, the Embrella Embolic Deflector System (Embrella Cardiovascular, Inc., Wayne, PA, USA) [49], consists of a porous membrane deployed in the aortic arch to protect the brachiocephalic trunk and the left carotid artery by deflecting emboli. To date, this device has been used in four patients who underwent BAV or transfemoral TAVI. It proved to be feasible and potentially effective. All patients remained free of neurological symptoms, and MRI evidence of brain injury was found in only one. These devices require significant additional testing. 6. Conclusion The incidence of clinical stroke after TAVI is higher than after AVR. DWMRI and evidence of “silent” brain injury seem to be more frequent also. Data, however, are sparse, and there are no available reports of careful risk adjustment for the remarkable differences between the age and prevalence of comorbid conditions in the two populations. New “silent” lesions are multiple, are probably ischemic in origin, and often regress. The relationship of these lesions to cognitive dysfunction remains unclear. The presumed mechanism for both symptomatic and silent DWMRI lesions
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is cerebral embolism. To protect the brain from embolization, novel protection devices are being developed. Reports of initial experiences with a few patients suggest that the use of such devices is feasible and may reduce the risk of new cerebral lesions due to cardiac embolization. Acknowledgments None. References [1] Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997;29:630–4. [2] Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS, 2006 Writing Committee Members; American College of Cardiology/American Heart Association Task Force. Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008;118 2008:e523–61. [3] Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, Leon MB. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation 2002;106:3006–8. [4] Dvir D, Assali A, Sagie A, Porat E, Shapira Y, Vaknin H, Bobovnikov V, Shafir G, Kupershmidt M, Shor N, Battler A, Kornowski R. Severe aortic stenosis patients at high surgical risk: outcomes according to treatment assignment. Cardiovasc Revasc Med 2011;e27:12. [5] Pasic M, Unbehaun A, Buz S, Drews T, Dreysse S, Kukucka M, Mladenow A, Hetzer R. Transapical aortic valve implantation: first 325 patients in a single center. Cardiovasc Revasc Med 2011;12:e26–7. [6] Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S, PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010; 363:1597–607. [7] Martin WR, Hashimoto SA. Stroke in coronary bypass surgery. Can J Neurol Sci 1982;9:21–6. [8] Coffey CE, Massey EW, Roberts KB, Curtis S, Jones RH, Pryor DB. Natural history of cerebral complications of coronary artery bypass graft surgery. Neurology 1983;33:1416–21. [9] Breuer AC, Furlan AJ, Hanson MR, Lederman RJ, Loop FD, Cosgrove DM, Greenstreet RL, Estafanous FG. Central nervous system complications of coronary artery bypass graft surgery: prospective analysis of 421 patients. Stroke 1983;14:682–7. [10] Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, Aggarwal A, Marschall K, Graham SH, Ley C. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857–63. [11] Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Onnasch JF, Metz S, Falk V, Mohr FW. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg 2003; 75:472–8.
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Clinical and silent stroke following aortic valve surgery and transcatheter aortic valve implantation☆,☆☆ Camille Hauville, Itsik Ben-Dor, Joseph Lindsay, Augusto D. Pichard, Ron Waksman⁎ Washington Hospital Center, Washington DC Received 10 November 2011; accepted 10 November 2011
Abstract
Transcatheter aortic valve implantation (TAVI) has been introduced as an alternative to conventional surgery for high-risk patients with aortic stenosis. A recently published randomized clinical trial demonstrated reduction of mortality in high-risk or inoperable patients when compared to medical treatment or balloon aortic valvuloplasty. Despite this evidence of superiority, the rate of TAVI complications is high, and perhaps the most devastating of the nonfatal complications is cerebral injury. This review will compare the incidence of stroke and “silent” cerebral injury after surgical aortic valve replacement and after TAVI and will discuss mechanisms that can lead to cerebral injury during these procedures and subsequently how to prevent this with new protection devices. © 2012 Published by Elsevier Inc.
Keywords:
Transcatheter aortic valve implantation; Aortic valve replacement; Silent and clinical strokes
1. Introduction Aortic stenosis (AS) is the most common valvular disease in adults. Its prevalence increases with age, reaching 2%–4% in patients over 85 years [1]. Once patients with severe AS become symptomatic or develop left ventricular dysfunction, life expectancy is significantly reduced [2]. Because of this dire prognosis, surgical aortic valve replacement (AVR) is recommended for such patients and substantially improves outlook. Transcatheter aortic valve implantation (TAVI) has been introduced as a less morbid alternative to conventional surgery for high-risk patients with AS [3–5]. A recently published randomized clinical trial demonstrated improved outcomes in high-risk or inoperable patients when compared to medical treatment or balloon aortic valvuloplasty (BAV) [6]. However, despite this evidence of superiority, the ☆
absolute complication rate of TAVI is high, especially in this high-risk population. Perhaps the most devastating of the nonfatal complications is cerebral injury. Brain injury, an infrequent complication of all cardiac surgeries, may also occur after TAVI. This review will compare the available evidence bearing on the incidence of stroke and “silent” cerebral injury after surgical AVR and after TAVI. It will also discuss mechanisms that can lead to cerebral injury during these procedures. 2. Cerebral injury after surgical AVR 2.1. Clinical stroke The frequency of overt neurological injury varies with the type of cardiac surgery. Retrospective studies
Funding: No external or third-party funding was used for this study. Dr C. Hauville was supported by the French Federation of Cardiology. Conflict of interest statement: The authors have no conflict of interest to report related to this study. ⁎ Corresponding author. Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. Tel.: +1 202 877 2812; fax: +1 202 877 2715. E-mail address: [email protected] (R. Waksman). ☆☆
1553-8389/11/$ – see front matter © 2012 Published by Elsevier Inc. doi:10.1016/j.carrev.2011.11.001
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report an incidence of 0.8%–3.2% after coronary artery bypass grafting (CABG) [7,8], while prospective studies report 1.5%–5.2% [9,10]. A similar incidence (0.7%–5.0%) has been reported in a clinical series of isolated AVR (Table 1). The incidence is higher if the AVR is combined with CABG or mitral valve replacement [11]. Not only can stroke have a devastating effect on quality of life, but its occurrence is also strongly related to mortality. Hospital mortality in patients with stroke can reach 24%, while the mortality rate in similar patients without cerebral complication is 4.6% [12]. Unsurprisingly, median length of hospital stay is also substantially increased in patients with stroke. Clinical risk factors for perioperative stroke in cardiac valve surgery include older age, female gender, previous cerebrovascular disease, previous peripheral vascular disease, diabetes mellitus, hypertension, previous cardiac surgery, and urgent operation. In addition, certain facets of the procedure also affect the incidence of perioperative stroke, e.g., cardiopulmonary bypass time longer than 2 h, use of hemofiltration, and requirement for more than usual blood transfusion [11–14]. The importance of age is especially noteworthy. For example, Brown et al.[15] found a postoperative stroke rate of 0.7% in those younger than 70 years and 2.5% in those older than 80 years. It is therefore surprising that despite the fact that the age of patients undergoing AVR has increased in the past 10 years, the rate of death or stroke has decreased for isolated AVR [15].
2.2. Asymptomatic brain injury A new imaging technology, diffusion-weighted magnetic resonance imaging (DWMRI), has proven to be more sensitive than computed tomography and conventional magnetic resonance imaging (MRI) for the detection of brain lesions [16,17]. This technique is sensitive to changes in the mobility of water molecules; lowered water mobility is an early event in the ischemic tissue change. After cardiac surgery, this modality often demonstrates small, multiple subcortical lesions. Since these lesions appear in patients with no overt signs of brain injury, they can be regarded as “silent brain injury”[18]. The appearance of new DWMRI lesions following surgery has been tentatively associated with the presence and severity of preexisting white matter lesions [16] as well as with age, preexisting T2 lesion volume, and postoperative S100β protein [18]. New, silent DWMRI lesions appear so frequently after a variety of invasive cardiovascular procedures that Bendszus and Stoll [19] have referred to them as “fingerprints of invasive medical procedures.” Several studies (Table 2) performed DWMRI before and up to 4 months after a cardiac surgical procedure. The incidence of new lesions postoperatively was surprisingly high at 38%–71%. 2.3. Neurocognitive decline after AVR Most patients with new lesions have no overt neurological signs, but there has been considerable interest in a possible association between their appearance and postprocedure cognitive dysfunction. Supporters of this propo-
Table 1 Incidence of stroke and cerebral events with cardiac surgery Study
Design of study
Incidence of stroke
Bucerius et al. [11]
Prospective Apr 1996–Aug 2001 1830 AVR 2506 CABG+valve surgery Prospective Jan 1998–Dec 2006 2808 valve surgery±CABG
AVR: 4.8% CABG+valve surgery: 7.4%
Filsoufi et al. [13]
Gulbins et al. [14] Brown et al. [15]
Prospective 1996–2005 1014 stentless AVR Prospective 108,687 patients 928 hospitals 1997–2006
Bakaeen et al. [12]
Retrospective 1991–2007 7142 patients isolated AVR
Wolman et al. [41]
Prospective 273 patients, 24 centers
TIA, transient ischemic attack.
Overall 2.2% (n=63, AVR n=17) 1998: n=3.3% 2002: n=1.3% b50 years: 0.6% 50–79: 1.5% N80: 2.5% Perioperative cerebral event: 1.8% 1997: 1.7% 2006: 1.3% In 2006: b70 years: 0.7% 70–80 years: b2% N80 years: b2.5% Incidence of stroke b80 years: 1.9% N80: 2.4% Cerebral outcomes: 16% 8.5%: 5 cerebral deaths, 16 nonfatal strokes, 2 TIA 7.3%: 17 new intellectual deteriorations, 3 seizures
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Table 2 Incidence of new silent cerebral event with cardiac surgery Study
Study design
Incidence of clinical cerebral event
Incidence of new MRI lesions
Stolz et al. [18]
Prospective 45 patients, 37 pre- and postoperative (AVR) DWMRI Retrospective 14 patients with postoperative (cardiac surgery) DWMRI Prospective 30 patients cardiac valve replacement DWMRI before and after Prospective 34 patients DWMRI Cardiac surgery
3 focal neurological deficits
New postoperative DWMRI lesions in 38%
14 patients with clinical cerebral events
New cerebral lesions in 71%
No focal neurological deficit Impaired cognitive function in 5 of 13 tests (all resolved within 4 months) 2 clinical strokes in the AVR group
New focal brain lesions in 47%
Wityk et al. [32]
Knipp et al. [21]
Floyd et al. [16]
sition point to the apparent connection between DWMRI lesions and cognitive dysfunction in population-based studies of healthy subjects. While DWMRI lesions are detected in up to 20% of putatively normal elderly participants, they are more frequent and larger in size in those with evidence of dementia. By means of careful psychological testing, neurocognitive deficits have been observed in 33%–83% of patients in the first weeks after cardiac surgery [20]. As a rule, these deficits resolve within 4 months [21], but a fear exists among patients, cardiologists, and surgeons that persistent or progressive problems may develop. Evidence points to older age and preoperative vascular disease as major risk factors for postoperative cognitive dysfunction [20]. An association between the postoperative appearance of new small, “silent,” subcortical brain injury and postoperative cognitive dysfunction is intuitively attractive, but confirmation of this relationship has been elusive[16]. Major practical constraints hinder a careful examination of this association. It is expensive and can be awkward to schedule serial DWMRI studies in the setting of pre- and postoperative clinical care. Moreover, expertise in conducting the required neuropsychological testing [22] can also be expensive and difficult to schedule. Thus, surgical AVR is associated with a clinical stroke rate of 0.8%–5%. “Silent” brain injury may be detected by sophisticated imaging in about half of surgical AVR patients. At first glance, such small “silent” lesions result in more concern for physicians and patients than their permanent clinical impact deserves, but their possible association with subtle, permanent cognitive impairment appropriately heightens interest in this phenomenon. 3. Brain injury and TAVI 3.1. Clinical strokes To this point, patients are referred to TAVI specifically because they are at high risk for surgical AVR and are, therefore, typically older and sicker than those who undergo
New infarction in 6 of 15 (40%) in procedures involving aortic valve replacement
surgical AVR. As a consequence, they arguably also have a higher risk for perioperative brain injury. The early experience with TAVI indicates that the incidence of clinically apparent neurological events varies widely. A broad review of all reported series reveals a range of such events of from 0% to 10% (Table 3). It is important to note that these reports describe initial experiences with a variety of approaches to TAVI, including transfemoral and transapical procedures, as well as utilization of both the Edwards valve (Edwards LifeSciences LLC, Irvine, CA, USA) and the CoreValve (Medtronic CoreValve LLC, Minneapolis, MN, USA). The most recent trial to be completed and published is PARTNER US [6]. Cohort B randomized 1058 patients deemed not suitable for surgical AVR to transfemoral TAVI or medical treatment. At 30 days, the overall incidence of stroke was 6.7%; 5% were defined as “major” and 1.7% as “minor.” At 1 year, the overall rate was 10.0% (7.8% major, 2.2% minor). As compared to medically managed patients, the overall stroke rate was greater in the TAVI group (6.7% vs. 1.7%, P=.03). Moreover, the occurrence of a major stroke was associated with significantly greater mortality (Pb.0001). Due to the lack of a consistent definition of neurological events in the PARTNER trial, it is hard to understand the exact timing of these events and their relation to procedures performed (e.g., TAVI procedure or balloon aortic valvuloplasty in the medical therapy group). This issue was address by constructing the Valve Academic Research Consortium definitions for adverse neurological events [23]. Atrial fibrillation was present in a significant proportion of patients with neurologic events in both groups. Of note, there was no standardized protocol for anticoagulation in the TAVI group, so it is impossible to assess the effect of various anticoagulant regimens on the incidence of neurological events. In cohort A of PARTNER US [24], 699 high-risk patients were randomized to TAVI (n=348) or surgical AVR (n=351). The results showed that the incidence of all strokes or transient ischemic events at 30 days was significantly higher in the TAVI group (n=19, 5.5%) compared to the
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Table 3 Incidence of stroke with TAVI Study
Year
Patient population
Incidence of stroke
Thomas et al. [46]
Nov 2007–Jan 2008
Rodes-Cabau et al.[47]
Jan 2005–June 2009
Walther et al.[50]
Feb 2006–Oct 2006
TA: 2.6% (n=16) TF: 2.4% (n=11) Total: 2.5% (n=27) TA: 0.6% (n=1) TF: 0.6% (n=1) Total: 0.6% (n=2) TA: 3%
Grube et al.[51]
Aug 2005–Sept 2006
TA: 575 TF: 463 Edwards TA: 177 TF: 168 Edwards 53 TA Edwards 86 TF and SC Corevalve
Walther et al.[52]
Feb 2006–Sept 2006
Himbert et al.[26]
Oct 2006–Nov 2008
Bleizieffer et al.[27]
June 2007–Feb 2009
Eltchaninoff et al. [48] FRANCE
Feb 2009–Sept 2009
Leon et al. [6] PARTNER Cohort B
King [24] PARTNER Cohort A
30 TA Edwards TA: 24 : 51 Edwards TA: 50 TF: 151 Edwards and Corevalve TA: 71 TF: 161 Edwards and Corevalve Edwards TF: 358
Edwards TAVI
Major stroke: 4% Minor stroke: 7% Total: 10% TA: 0 TA: 0 TF: 6% Total: 4% (all recovered) TA: 0 TF: 7% (n=11) TA: 2.8% TF: Edwards 4.2% Corevalve 4.5% Total: 6.7% (30-day results) Minor stroke: 1.7% Major stroke: 5% Total: 5.5% (30-day results) Major stroke: 3.8% Minor stroke: 0.9%
TA, transapical; TF, transfemoral; SC, subclavian.
surgical group (n=8, 2.4%, P=.04). However, no significant differences were found in the major and minor subgroups. The results at 1 year also demonstrated a significantly higher risk of stroke in the TAVI group (P=.04). Since the transapical approach to TAVI avoids the risk of catheter manipulation in an atherosclerotic aorta, it was anticipated that this approach might avoid some of the stroke risk associated with the femoral approach. The experiences of Kempfert et al. [25], Himbert et al. [26], and Bleiziffer et al. [27] suggest that this hope may be realized, but some new studies [28] have failed to confirm this advantage; no difference in stroke incidence between transapical and transfemoral approaches was found. 3.2. Silent cerebral events As is true of surgical AVR, silent cerebral events are more frequent than clinical stroke with TAVI procedures. There are several reports (Table 4) of DWMRI before and 48 h to 5 days after TAVI (the longer delays were intended to ensure that the effects of anesthetic drugs had dissipated). The intent of each study was to detect new cerebral lesions and to compare those results to clinical events. In some studies, an additional MRI was performed several months after the TAVI to look for long-term changes. Moreover, most of the study protocols included neurological examination and comprehensive neuropsychological assessment.
These reports describe a high incidence (68%–84%) of new lesions at the MRI [28–31]. Most were multiple and had characteristics of ischemic lesions, probably due to emboli. Comparable studies with surgical AVR suggest that such lesions are more frequent with TAVI [18,19]. Kahlert et al. directly compared the incidence of silent lesions in surgical AVR and TAVI [30]. There were no overt neurological events with either approach, but new “silent” lesions were found in 84% in the TAVI group and 48% in the AVR group [19,21,31]. Patients undergoing TAVI were significantly older than those undergoing open cardiac surgery (80.0 versus 67.4 years; Pb.001). In addition, patients in the TAVI group had significantly higher logistic EuroSCOREs and significantly more comorbidities than did patients in the AVR group. Importantly, 80% of the new lesions had disappeared by the 3-month MRI exam. Thus, it appears that “silent” DWMRI lesions are significantly more frequent after TAVI. The majority resolve within a few months. 3.3. Neurocognitive decline after TAVI Although controversial for reasons previously described, many believe that silent brain injury after cardiac surgery is frequently associated with deficits in physical and cognitive function that commonly go unnoticed [32]. Although “silent” lesions are more frequent after TAVI, no relation
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Table 4 Incidence of silent cerebral events with TAVI Study
Year
Patient population
Incidence of new MRI lesions
Ghanem et al. [29]
Nov 2008–June 2009
TF: 30 Corevalve
Kahlert et al. [30]
Sept 2007–Mar 2009
TF: 32 Edwards: 22 Corevalve: 10 AVR: 21
Arnold et al. [31]
Dec 2008–Nov 2009
Rodes-Cabau et al. [28]
Aug 2008–Feb 2010
TA: 25 Edwards TA: 31 TF: 29 Edwards
New silent embolic cerebral lesions (DWMRI): 72.7% 3-month clinical deficit: 3.6% Clinical deficit: 0 New cerebral lesions (DWMRI): TAVI: 84% AVR: 48% 80% of lesions gone at 3 months Clinical syndromes: n=5 New cerebral lesions (DWMRI): 68% Clinical stroke: 3.3% n=2 New cerebral ischemic lesions (DWMRI): 68% TA: 71% TF: 66%
is seen between new cerebral lesions and neurocognitive dysfunction. It is difficult to confidently identify the cognitive abnormalities. An additional confounder is the fact that, currently, there is no validated model to assess neurocognitive status or even quality of life measurements for patients undergoing TAVI. In the available studies, the National Institute of Health Stroke Scale and the Mini Mental State Examination have been employed. A more thorough study may be able to detect more subtle changes. The greatest fear, chronic cognitive dysfunction attributable to procedure-related brain injury, will be difficult to identify conclusively. Development of a control population will be required since, in many TAVI patients, naturally occurring cognitive decline is under way and can be expected to continue. Some investigators have proposed that periprocedural “silent” brain injury may increase the risk of vascular dementia or even Alzheimer's disease [21,33,34]. Conversely, a recent prospective study, which assessed the relationship between clinical and subclinical stroke in a small number of patients (n=31), did not find an association between any stroke event and quality of life as assessed by the SF-12v2 Health Outcomes Questionnaire and SF-36 [35]. The considerations outlined in this review assume even greater urgency as the indications for TAVI are widened to include younger patients. 3.4. Overall comparison of TAVI and surgical AVR This review shows that in the initial TAVI experience, the incidence of overt cerebral events appears to be higher after TAVI than after AVR. The incidence of “silent” DWMRI lesions, while much higher than strokes in both groups, is even higher in the TAVI group. Sometimes, periprocedural strokes are hemorrhagic, but the vast majority are ischemic [13,31,32,36]. Age, diabetes, female gender, a calcified ascending aorta, prior stroke, or preexisting lesions on imaging appear to be risk factors for both overt and silent brain injury after both
AVR and TAVI. A correlation between new “silent” lesions found on MRI and impaired neurocognitive function remains controversial. 4. Mechanisms 4.1. After cardiac surgery The pathogenesis of brain injury after heart surgery is not completely defined. There is a long-held assumption that embolization of atherosclerotic material, thrombus, or other particulate matter is a major mechanism. This assumption is supported by transcranial Doppler studies demonstrating “microemboli” at the time of aortic clamp release [37,38]. Furthermore, postmortem observations on the nature of cerebral lesions after cardiac surgery [39,40] are consistent with the presence of numerous emboli lodged in the small arteries. Insofar as the embolic basis for brain injury is true, the frequency with which it associates with AS surgery becomes understandable. Patients with AS often have more severe aortic arch atheroma than do others and, consequently, a greater risk of stroke after AVR [18,41]. Other mechanisms include compromised cerebral blood flow, cerebral edema, inflammation, and metabolic disturbances [42,43]. The existence of a synergy of sorts between hypoperfusion and embolization can be considered [44]. Low cerebral flow may allow small emboli to lodge at points at which a higher flow might “wash them out.” DWMRI lesions may be as frequent with “on-pump” and “off-pump” procedures. Cognitive dysfunction after CABG has a multifactor physiopathology like cerebral embolism, systemic inflammation, body temperature, and cerebral hemodynamics. Off-pump surgery reduces intraoperative cerebral embolization, systemic inflammatory responses, and the degree of postoperative brain edema. But cardiac output and cerebral perfusion pressure may vary significantly during some periods of off-pump surgery, which may subsequently lead to a reduction in cerebral perfusion
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pressure and neuronal ischemia [45]. Degenerative AS is an inflammatory process, strongly related to atherosclerosis and perhaps to a more diffuse vascular abnormality. Therefore, a higher rate of stroke might be expected in this population because of intracranial small vessel disease. 4.2. After TAVI Reports from the initial TAVI series suggest that new procedurally related brain injury is more frequent after TAVI than after surgical AVR. As noted earlier in this review, 84% of TAVI patients have MRI-identified cerebral lesions as compared to 48% of patients after surgical AVR. These observations must be regarded as tentative. The available data are limited, and TAVI patients are very different with regard to age and the prevalence of comorbid illness from those accepted for surgical AVR. A potential tool for assessment of the timing of embolism during TAVI is the transcranial Doppler; however, no systematic study has used this tool to determine timing of intraprocedural brain embolism. Intuitively, one would expect that as compared to the transfemoral approach, transapical TAVI might be associated with fewer cerebral embolic events. In transfemoral TAVI, repeated manipulation of large catheters in the aortic arch, crossing of the calcified valve, balloon dilatation, and valve deployment all promote embolism. On the other hand, transapical TAVI, an anterograde procedure, limits manipulation within the aorta. As previously noted, the data of Kempfert et al., Himbert et al., and Bleiziffer et al. [25–27] support this idea, but larger studies indicate that the incidence of new brain injury is similar regardless of the approach used [28,46–48]. Although it is intuitively unlikely, embolism attributable to catheter manipulation in the aorta or retrograde crossing of the aortic valve may not be the only, or even the primary, mechanism. Thus, embolism-provoking mechanisms common to both approaches must be considered. One such possibility is that air embolism attendant on the use of very large catheters and the necessity for multiple catheter exchanges may increase the risk of embolization [28]. This possibility reemphasizes the necessity for careful flushing of the catheter before insertion and assiduous checking for air bubbles within the catheter throughout the procedure. It is also plausible that emboli originate from the aortic valve itself. In a German study [36], 22% of patients who underwent retrograde catheterization of the aortic valve had new cerebral lesions on MRI imaging, and three patients (3%) had clinically apparent neurological deficits. No patient in a control group who did not have their aortic valve crossed had such lesions. Importantly, both transapical and transfemoral TAVIs involve two maneuvers during which the aortic valve leaflets are maximally stretched. This happens with preparatory dilatation of the aortic valve and during the valve implantation itself. These
maneuvers could be associated with dislodgment of calcium fragments and cerebral embolism. Embolism is not the only potential reason for the development of new periprocedural lesions. Kahlert et al.[30] point out a number of other possibilities, particularly for the appearance and subsequent disappearance of lesions in the periprocedural period. To explain the high rate of spontaneous resolution of the lesions following TAVI, they suggest that intraprocedural hemodynamic perturbations, for example, those produced by rapid pacing, may be responsible. 5. Protection devices Due to the likelihood that embolic phenomena are instrumental in brain injury associated with TAVI, embolic protection devices have been devised. We will briefly describe two. First is the Claret device from Claret Medical, Inc. (Santa Rosa, CA, USA), which provides cerebral filter protection. The device is placed into the aortic arch via right-radial or brachial entry preferably in the right arm, but may also be placed via the femoral artery or another access point such as the carotid artery. The device is deployed partially in the aortic arch but also in the innominate and carotid arteries. Additionally or alternatively, the device may deploy to protect the left subclavian artery, where the device is opened and pulled back into position to cover the ostia of both the brachiocephalic and left common carotid arteries. A portion of the device protrudes into the vessel(s), with a portion of the device entering into the vessel or artery to trap emboli. A second embolic protection device for TAVI, the Embrella Embolic Deflector System (Embrella Cardiovascular, Inc., Wayne, PA, USA) [49], consists of a porous membrane deployed in the aortic arch to protect the brachiocephalic trunk and the left carotid artery by deflecting emboli. To date, this device has been used in four patients who underwent BAV or transfemoral TAVI. It proved to be feasible and potentially effective. All patients remained free of neurological symptoms, and MRI evidence of brain injury was found in only one. These devices require significant additional testing. 6. Conclusion The incidence of clinical stroke after TAVI is higher than after AVR. DWMRI and evidence of “silent” brain injury seem to be more frequent also. Data, however, are sparse, and there are no available reports of careful risk adjustment for the remarkable differences between the age and prevalence of comorbid conditions in the two populations. New “silent” lesions are multiple, are probably ischemic in origin, and often regress. The relationship of these lesions to cognitive dysfunction remains unclear. The presumed mechanism for both symptomatic and silent DWMRI lesions
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