Introduction
Stroke has a significant impact on disability, leading to a decline in the overall health and standard of living of individuals aged 50 years and older and impairing their day-to-day activities. It has consistently been a major contributor to ailments in this age group from 1990 to 2019 [
1], with the highest global disease burden persisting to be cardiovascular diseases [
2], reporting approximately 19.9 million deaths in 2021 [
3].
Aortic valve stenosis (AVS) is considered the most prevalent acquired valvular heart disease [
4], carrying a specific risk factor for ischemic stroke [
5]. It is currently widespread in the West [
6] especially affecting those 60 years of age and beyond, with a prevalence of more than 2% [
4]. The etiology of AVS is highly comparable to that of atherosclerosis and is closely linked with cardiac risk factors including age, male gender, smoking, hypertension, high low-density lipoprotein (LDL) cholesterol, and diabetes mellitus [
7]. When manifesting symptoms, severe AVS has an intimidating 50% 2-year mortality rate [
4], however, the advent of transcatheter aortic valve replacement (TAVR) in 2002 has revolutionized the treatment approach [
8].
TAVR offers a good substitute to patients ineligible for surgery while demonstrating comparable, and, in some cases, superior outcomes to SAVR across various risk profiles based on several patient randomized control trials [
8]. A 3-year study predominantly directed toward the primary outcome of all-cause mortality or disabling stroke revealed a substantial difference, with an incidence of 7.4% for the TAVR group compared to 10.4% in the SAVR group [
8]. Another prospective study conducted over 4 years on 196 individuals, aged 65 and older, who underwent SAVR were assessed by MRI scans and neurological examinations pre- and post-operatively. The results revealed clinical stroke in 17%, transient ischemic attack in 2%, and an in-hospital mortality rate of 5% [
9]. This disparity in results led to a discernible increase in the annual performance of TAVR surgeries, indicating its effectiveness and wide acceptance [
8].
There has been a consistently higher incidence of stroke with SAVR at 21 per 1000 cases, compared to TAVR which is 16 per 1000 cases, in multiple clinical trials involving 2818 participants with follow-up periods of up to 30 days [
10]. The cause of neurological complication post-procedure remains a subject of ongoing debate, with a possible assumption of manipulation of atherosclerotic plaque during aortic valve repair [
11]. Additionally, a longer cardiopulmonary bypass time during surgical aortic valve replacement (SAVR) is linked to a higher stroke risk, likely due to hemodynamic changes. A lack of early imaging may contribute to the delayed diagnosis of stroke, in addition to giving time for a thrombus to form on embolized material, leading to a delayed onset of post-procedural clinical presentation [
12]. The prevention of postoperative stroke may be possible with an adequate antithrombotic or anticoagulant regimen, with studies leading the American College of Chest Physicians to recommend the use of aspirin as the preferred antithrombotic therapy after SAVR for ≥ 3 months, and the combination of aspirin and clopidogrel after TAVR [
11]. This further emphasizes the importance of understanding and mitigating these risks in both procedures. Thus, this study aims to scrutinize the incidence of stroke following TAVR and SAVR procedures in AVS patients, hoping to yield valuable insights into the relative safety and efficacy of these interventions.
Methods
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and recommendations of the Cochrane Collaboration [
13].
Search strategy and data sources
A comprehensive electronic search was performed on Medline (PubMed), Google Scholar, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from their inception to December 2023 by two independent investigators (V.K. and M.G). The following search strategy was used: ((ischemic stroke) OR (non-hemorrhagic stroke)) AND ((surgical aortic valve replacement) AND (transcatheter aortic valve replacement)). Duplicate references were identified and removed. We included all qualifying randomized controlled trials (RCT) and observational studies without any time restriction but limited our study to English-language research to focus on relevant literature. The detailed search strategy for each database along with the retrieved number of search results is found in Supplementary Table S1.
Study selection
All studies were assessed for eligibility and included if they met the following criteria: (a) participants age ≥ 80 years; or age ≥ 70 years with intermediate or high operative risk from conventional aortic valve replacement (AVR), as determined by the multi-disciplinary team; (b) patients with severe aortic valve stenosis defined as an effective orifice area < 1 cm2 or indexed for body surface area < 0.6 cm2/m2 and a mean aortic valve gradient > 40 mmHg or peak systolic velocity > 4 m/s; (c) symptomatic aortic valve stenosis (NYHA Functional Class II or greater); (d) incidence of stroke and/or transient ischemic attack reported at 30 days and 1-year post-procedure comparing TAVR with SAVR; (e) all patients were evaluated by a heart team consisting of at least an imaging cardiologist, an interventional cardiologist, and a cardiac surgeon; and (e) asymptomatic patients included if they had left ventricular posterior wall thickness of 17 mm, decreasing left ventricular ejection fraction, or new onset Atrial fibrillation (AF). Studies with patients having another severe heart valve disease or coronary artery disease (CAD) requiring intervention or those undergoing SAVR with concomitant coronary artery bypass graft or simultaneous mitral repair/replacement were excluded. Non-English articles and articles not reporting stroke and transient ischemic attack as outcomes were also removed. Detailed exclusion criteria are given in the supplementary appendix.
Two authors (A.A and M.H) independently assessed the retrieved reports and only studies fulfilling the pre-defined inclusion criteria were selected. Initially, all studies were screened based on their title and abstract, followed by a comprehensive review of the full-length article to ascertain its relevancy. A third investigator (S.R) was consulted to address any discrepancies. Data including each study’s design, inclusion/exclusion criteria, the sample size of each treatment group (SAVR and TAVR), baseline patients’ characteristics, and their co-morbids (diabetes, hypertension, cerebrovascular disease, coronary artery disease, and peripheral vascular disease) was extracted using an Excel spreadsheet. The primary outcomes of interest were the risk of stroke and transient ischemic attack (TIA) at 30-day and 1-year follow-ups. All-cause mortality and incidence of periprocedural complications including myocardial infarction (MI), acute kidney injury (AKI), and major vascular complications were also assessed as secondary outcomes at 30 days and 1-year follow-ups. Due to the notable variation in defining disabling versus non-disabling stroke or major versus minor stroke and the limited number of studies included, subgroup analyses were not performed.
Risk of bias and quality assessment
The quality assessment of non-randomized cohort and case–control studies was performed using the Newcastle–Ottawa Scale (NOS) (Supplementary Tables S3 and S4) [
14]. To estimate the potential bias in the included trials, we used the modified Cochrane Collaboration’s risk of bias tool for randomized controlled trials, which assesses the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, completeness of outcome data and selective outcome reporting [
15]. Two researchers (A.R and M.Z) examined the studies and judged the potential for bias, categorizing each item as having low, unclear, or high risk (Supplementary Table S2). Ultimately, the overall risk of bias for each trial was determined, considering whether bias within specific domains could significantly affect risk estimates.
Statistical analysis
The risk of stroke, transient ischemic attack (TIA), all-cause mortality, and periprocedural complications between groups was presented as odds ratios (ORs) with 95% confidence intervals (CIs) for each study, pooled using the DerSimonian and Laird random effects model [
16]. Forest plots were created to visually illustrate the results of pooling. The presence and degree of statistical heterogeneity across studies were assessed using the Chi-square test and Higgins and Thompson's I
2 statistic [
17], with p < 0.10 considered statistically significant. I
2 values were interpreted according to the Cochrane Handbook for Systematic Reviews of Interventions, Sect. 10.10 [
18]. All statistical analyses were conducted using Review Manager (RevMan, Version 5.4; The Cochrane Collaboration, Copenhagen, Denmark). Assessment of publication bias was not possible due to the limited number of studies included (< 10) [
27].
Discussion
Amid a major transformation in the treatment of severe aortic stenosis, an emerging option in the form of a transcatheter approach for aortic valve replacement has challenged traditional full sternotomy valve replacement, first in extreme-risk patients and now in high and intermediate-risk groups. Thus, our study aimed to examine the safety and efficacy of TAVR as an emerging option versus conventional SAVR in intermediate and high-risk patients.
Despite diagnostic and treatment advancements, stroke is a common and feared complication for both TAVR and SAVR. It is a major contributor to disability, causing a significant decline in an individual's overall health. Valve placement and implantation during TAVR can elevate the risk of embolic stroke in patients while cross-clamping the aorta during SAVR can increase the likelihood of dislodging loose atheromatous plaque or mural emboli [
28,
29]. Our meta-analysis compared the occurrence of stroke and transient ischemic attack (TIA) among patients undergoing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) to shed light on the effectiveness of these interventions in preventing such events. Our study's findings, which indicate a comparable 30-day and 1-year stroke risk between TAVR and SAVR patients, align with the 5-year outcomes of the PARTNER trial, as reported by Mack et al. [
30]. In this trial, there was no significant difference in stroke rates between the TAVR and SAVR groups at the 5-year follow-up mark.
Moreover, consistent with previous studies [
28,
31], our findings demonstrated that performing TAVR in intermediate-to-high-surgical risk patients resulted in comparable 30-day and 1-year rates of transient ischemic attack with SAVR. Villablanca et al. [
32] also found no significant difference in the risk of disabling stroke between TAVR and SAVR in intermediate-risk patients. These findings suggest that TAVR, despite its advantages, did not reduce stroke incidence in intermediate-to-high-risk patients over the course of one year.
However, undoubtedly TAVR has shifted the paradigm of management of severe, symptomatic AS over the past two decades, with innovations in transcatheter valve design, imaging, and increasing operator expertise collectively boosting safety and minimizing procedural complications [
28]. Our findings also reflect this, since TAVR resulted in a significantly lower rate of all-cause mortality than surgery at 1 year post-procedure. This is concurrent with the findings of an NIS study conducted by Alqahtani et al. [
33] which concluded that TAVR is linked to reduced hospital mortality, lower resource use, and decreased costs compared to SAVR. In contrast, a 2020 study providing an overview of multiple systematic reviews revealed that out of 11 peer-reviewed systematic reviews, 8 reported no differences in mortality between TAVR and SAVR at short and long-term follow-up times, albeit in low-intermediate-risk patients [
34].
When safety endpoints were compared between the two procedures, our meta-analysis revealed no significant difference in the incidence of MI at 30 days and 1 year after the procedures, however, TAVR was associated with a significantly lower incidence of acute kidney injury (AKI) at the 1-year follow-up compared with surgery. The relationship between AKI and aortic valve replacement is intricate, with multiple risk factors including hypothermia, non-pulsatile blood flow during cardiopulmonary bypass, euvolemic hemodilution during open-heart surgery, and cholesterol embolization during aortic cannulation increasing the likelihood of AKI after SAVR [
35]. A meta-analysis conducted in 2018 also showed that the incidence of AKI was 59% significantly lower with TAVR than with SAVR [
36].
Arora et al.’s study assessing national trends in complications after TAVR and SAVR in the States demonstrated that TAVR typically shows lower rates of complications like stroke, cardiogenic shock, AKI, and the need for blood transfusions, but higher occurrences of permanent pacemaker implantation, cardiac arrest, and vascular complications [
37]. This is concomitant with Mehmet [
38] and Lazkani’s [
36] studies in which the TAVR group had more vascular complications compared to the SAVR group (17.9% vs. none, 8.78% vs. 3.15% respectively). Our findings also complement data from these studies with major vascular complications seen significantly higher in the TAVR group as opposed to the SAVR group at both 30-day and 1-year follow-ups. Earlier device versions had more frequent aortic injuries and iliac avulsions due to the larger size of the first-generation sheaths. Now, complications are primarily localized to the access site, with dissections, hematomas, and thrombosis being the most common, often treatable with endovascular techniques [
36].
The overall results indicating comparable risks of TIA and stroke between TAVR and SAVR patients hold significant implications for clinical decision-making. Clinicians need to carefully consider the risks and benefits of each procedure when determining the most suitable treatment approach for individual patients. Recent research emphasizes the importance of considering patient-specific factors, procedural risks, and long-term outcomes when choosing between TAVR and SAVR. These findings provide valuable insights to clinicians, aiding them in delivering patient-centered care and improving outcomes in the management of aortic valve disease [
39‐
41].
Limitations
While our meta-analysis offers valuable insights, it is important to recognize several limitations. Firstly, there may be variations among the included studies regarding patient characteristics, procedural methodologies, and follow-up procedures, potentially introducing sources of bias. Moreover, the analysis relies on aggregated data from published studies, lacking individual patient data for a thorough examination, which restricts the ability to control for confounding factors or conduct subgroup analyses.
Conclusion
The comparison between TAVR and SAVR patients revealed no notable disparities in outcomes for both TIA and stroke incidence at 30 days and 1 year post-procedure. The degree of heterogeneity differed between the two outcomes, with TIA analyses showing moderate heterogeneity and stroke analyses indicating either minimal or no heterogeneity. For patients with intermediate-high surgical risk, both TAVR and SAVR exhibit varying safety profiles, with TAVR having better long-term rates of all-cause mortality and AKI, but a higher incidence of major vascular complications post-procedure. Medical professionals should consider this when advising patients, weighing the advantages and disadvantages of each approach, and encouraging patients to make informed, personalized decisions regarding their treatment.
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