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Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) and redo surgical mitral valve replacement (redo-SMVR) are 2 treatment strategies for patients with bioprosthetic mitral valve dysfunction. We conducted a systematic review and meta-analysis to compare the outcomes of ViV-TMVR versus redo-SMVR. We searched PubMed, EMBASE, Cochrane, and Google Scholar for studies comparing outcomes of ViV-TMVR versus redo-SMVR in degenerated bioprosthetic mitral valves. We used a random-effects model to calculate odd ratios (ORs) with 95% confidence intervals (CIs). Outcomes included in-hospital, 30-day, 1-year, and 2-year mortality, stroke, bleeding, acute kidney injury, arrhythmias, permanent pacemaker insertion, and hospital length of stay (LOS). A total of 6 observational studies with 707 subjects were included. The median follow-up was 2.7 years. Despite their older age and greater co-morbidity burden, patients who underwent ViV-TMVR had a similar in-hospital mortality (OR 0.52, 95% CI 0.22 to 1.23, p = 0.14), 30-day mortality (OR 0.65, 95% CI 0.36 to 1.17, p = 0.15), 1-year mortality (OR 0.97, 95% CI 0.63 to 1.49, p = 0.89), and 2-year mortality (OR 1.17, 95% CI 0.65 to 2.13, p = 0.60) compared with redo-SMVR. ViV-TMVR was associated with significantly lower periprocedural complications, including stroke, bleeding, acute kidney injury, arrhythmias, and permanent pacemaker insertion, and shorter hospital LOS than redo-SMVR. In conclusion, ViV-TMVR was associated with better outcomes than redo-SMVR in patients with degenerated bioprosthetic mitral valves, including lower complication rates and shorter hospital LOS, with no significant difference in mortality rates. Large-scale randomized trials are needed to mitigate biases and confirm our findings.
The volume of mitral valve (MV) surgeries in the United States has steadily increased, exceeding 30,000 per year in 2016, with approximately 1/3 of them being MV replacement (MVR).
Bioprosthetic valves have a lower risk of thrombotic complications than mechanical valves and do not require anticoagulation; however, they degenerate over time, requiring reintervention.
The optimal strategy for replacing degenerated bioprosthetic MVs continues to evolve with randomized comparisons of transcatheter and surgical approaches lacking. Although conventional redo surgical MVR (redo-SMVR) has been the gold standard strategy for degenerated bioprotheses, redo-SMVR is associated with significant resource utilization, nonnegligible rates of periprocedural complications, and mortality rates approaching 11%.
Hospital Outcome and Risk Indices of Mortality after redo-mitral valve surgery in Potential Candidates for Transcatheter Procedures: results from a European Registry.
To date, data comparing the safety and efficacy of valve-in-valve transcatheter MVR (ViV-TMVR) versus redo-SMVR remain limited to small retrospective studies.
Therefore, the present study aimed to perform a comprehensive contemporary meta-analysis comparing the outcomes of ViV-TMVR versus redo-SMVR among patients with degenerated bioprosthetic MVs from available studies.
Methods
The systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Meta-Analyses of Observational Studies in Epidemiology guidelines
and were registered with PROSPERO (CRD42022354049). A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane, and Google Scholar databases by 2 independent authors (MI and MAA) for randomized controlled trials (RCTs) and observational studies comparing ViV-TMVR with redo-SMVR in patients with bioprosthetic MV disease from the inception of each database to September 15, 2022. To increase the sensitivity of our search, we combined variants of the words “valve-in-valve,” “transcatheter,” “redo surgical,” “failed prosthesis,” and “mitral valve” as either keywords or Medical Subject Headings terms. No language, sample size, publication date, or publication status restrictions were placed on the search. The search strategy used in each database is summarized in Supplementary Table 1. The references of the retrieved studies were also manually checked for relevant studies.
After removing duplicate publications, all citations were downloaded and screened by 2 authors (MI and MAA) independently based on titles and abstracts. Potentially relevant studies were subjected to full-text review to assess further for eligibility. Discrepancies in study selection were discussed and resolved with another author (AMG). Eligible studies had to satisfy the following inclusion criteria: (1) studies comparing ViV-TMVR versus redo-SMVR for bioprosthetic MV degeneration, and (2) the availability of clinical outcomes data at 1 or more time points. We excluded studies that lacked clinical outcomes data, and abstracts, case reports, review articles, editorials, and letters.
After relevant articles were identified, 2 authors (MI and MAA) independently extracted data (baseline characteristics, definitions of outcomes, and numbers of events) into a spreadsheet for analysis. From studies including both propensity-matched and unmatched analyses, we preferentially included data from the propensity-matched analyses. The same investigators (MI and MAA) independently and systematically assessed the studies’ methodologic quality using the Newcastle-Ottawa scale for observational studies. Publication bias for each outcome was assessed by visual inspection of funnel plots when data were available from at least 3 studies.
The primary outcomes of interest were in-hospital, 30-day, 1-year, and 2-year all-cause mortality. Secondary outcomes included stroke, myocardial infarction, bleeding, acute kidney injury (AKI), arrhythmias, permanent pacemaker (PPM) insertion (PPMI), hospital length of stay (LOS), and mean MV gradient. Bleeding complications were defined as major or life-threatening bleeding or bleeding requiring blood transfusion. Arrhythmias were defined as new-onset atrial fibrillation or complete heart block. The mean MV gradients were measured at discharge or during follow-up.
For dichotomous outcomes, odd ratios (ORs) with 95% confidence intervals (CIs) were calculated from the available data in the included studies, and the study-specific ORs were combined using the DerSimonian and Laird random-effects model, with the estimate of heterogeneity taken from the Mantel–Haenszel model. For continuous outcomes, standard mean differences with 95% CIs were calculated from the available data in the included studies. A 2-tailed α value of p <0.05 was considered statistically significant. The “test for overall effect” was reported as a z value corroborating the inference from the 95% CI. The Higgins I-squared (I2) statistic was used to quantify heterogeneity among the included studies; a value of 0% indicates no observed heterogeneity, and larger values indicate increasing heterogeneity. I2 values of 25%, 50%, and 75% have been assigned adjectives of low, moderate, and high heterogeneity, respectively. All statistical analyses were performed using the Cochrane Review Manager (RevMan) software version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark, 2014).
Results
The initial database search identified a total of 842 studies, from which 88 duplicates and 719 studies not meeting inclusion criteria were removed by screening titles and abstracts. The remaining 35 studies were subject to full-text review, leading to further exclusion of 29 studies. Finally, 6 studies were selected for quantitative analysis.
Figure 1 displays the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for study search and selection.
Figure 1PRISMA flow diagram showing the selection process of the included studies. PRISMA = Preferred Reporting Items for Systematic reviews and Meta-Analyses.
The studies’ methodologic quality was assessed using the Newcastle-Ottawa scale for observational studies (Supplementary Table 2). With respect to clinical outcomes, there was no heterogeneity for in-hospital mortality (I2 = 0%, p = 0.92), 30-day mortality (I2 = 0%, p = 0.41), 1-year mortality (I2 = 0%, p = 0.95), 2-year mortality (I2 = 0%, p = 0.76), stroke (I2 = 0%, p = 0.95), bleeding complications (I2 = 0%, p = 0.57), AKI (I2 = 0%, p = 0.67), and PPMI (I2 = 0%, p = 0.70). Low heterogeneity was present for hospital LOS (I2 = 27%, p = 0.25) and mean MV gradient (I2 = 5%, p = 0.37), and high heterogeneity was present for arrhythmias (I2 = 71%, p = 0.02). Overall, the heterogeneity was low, and there was no to minimal evidence of publication bias on visual inspection of the funnel plots (Supplementary Figure 1).
A total of 6 observational studies were included in the primary analysis (Table 1).
These studies comprised 707 patients with bioprosthetic MV degeneration, of whom 338 underwent ViV-TMVR and 369 underwent redo-SMVR. The median follow-up duration was approximately 2.7 years. All patients in the ViV-TMVR group underwent valve-in-valve TMVR for failed MV bioprosthesis, except for 11 of 86 patients (12%) in the study of Simard et al,
who underwent valve-in-ring TMVR for failed MV annuloplasty rings. Of the 6 included studies, 2 studies used the transapical (TA) approach exclusively,
Given the retrospective observational nature of these studies, many of the authors performed propensity matching based on demographic and clinical characteristics to reduce selection bias and potential confounding.
Despite some propensity matching, patients in the ViV-TMVR group were older (aged 75 vs 66 years), with more co-morbidities and higher EuroSCORE and Society of Thoracic Surgeons Predicted Risk of Mortality scores than the redo-SMVR group (Table 2).
Table 1Study characteristics of included investigations comparing ViV-TMVR versus. redo-SMVR in patients with degenerative bioprosthetic mitral valve
In patients with bioprosthetic MV degeneration, ViV-TMVR was associated with similar in-hospital mortality (OR 0.52, 95% CI 0.22 to 1.23, p = 0.14; Figure 2), 30-day mortality (OR 0.65, 95% CI 0.36 to 1.17, p = 0.15; Figure 2), 1-year mortality (OR 0.97, 95% CI 0.63 to 1.49, p = 0.89; Figure 2), and 2-year mortality (OR 1.17, 95% CI 0.65 to 2.13, p = 0.60; Figure 2) compared with redo-SMVR. The risks of stroke (OR 0.31, 95% CI 0.11 to 0.88, p = 0.03; Figure 3), bleeding (OR 0.21, 95% CI 0.12 to 0.39, p <0.00001; Figure 3), AKI (OR 0.43, 95% CI 0.22 to 0.84, p = 0.01; Figure 3), arrhythmias (OR 0.17, 95% CI 0.04 to 0.64, p = 0.009; Figure 3), and PPMI (OR 0.18, 95% CI 0.05 to 0.60, p = 0.005; Figure 4) were significantly lower, and the hospital LOS (standard mean difference −0.64; 95% CI −0.91 to −0.36; p <0.00001, Figure 4) was shorter with ViV-TMVR. ViV-TMVR was associated with higher mean MV gradients (standard mean difference 0.25, 95% CI 0.02 to 0.48, p = 0.04; Figure 4).
Figure 2Forest plot for the comparison of ViV-TMVR (left) and redo-SMVR (right) for degenerated bioprosthetic mitral valves. (A) In-hospital mortality; (B) 30-day mortality; (C) 1-year mortality; (D) 2-year mortality. Odd ratios for individual studies are indicated by squares and 95% CIs by horizontal lines. Overall totals and their 95% CIs are represented by diamonds, in which the diamond's center denotes the point estimate, and the width denotes the 95% CI. The size of the squares and the diamonds are proportional to the statistical information conveyed. M-H = Mantel–Haenszel.
Figure 3Forest plot for the comparison of ViV-TMVR (left) and redo-SMVR (right) for degenerated bioprosthetic mitral valves. (A) Stroke; (B) bleeding complications; (C) acute kidney injury; (D) arrhythmias. Odd ratios for individual studies are indicated by squares and 95% CIs by horizontal lines. Overall totals and their 95% CIs are represented by diamonds, in which the diamond's center denotes the point estimate, and the width denotes the 95% CI. The size of the squares and the diamonds are proportional to the statistical information conveyed. M-H = Mantel–Haenszel.
Figure 4Forest plot for the comparison of ViV-TMVR (left) and redo-SMVR (right) for degenerated bioprosthetic MVs. (A) Permanent pacemaker; (B) hospital LOS; (C) mean MV gradient. Odd ratios for individual studies are indicated by squares and 95% CIs by horizontal lines. Overall totals and their 95% CIs are represented by diamonds, in which the diamond's center denotes the point estimate, and the width denotes the 95% CI. The size of the squares and the diamonds are proportional to the statistical information conveyed. M-H = Mantel–Haenszel.
We conducted a systematic review and meta-analysis to compare the outcomes of ViV-TMVR versus redo-SMVR in patients with bioprosthetic MV degeneration. The systematic review captured 6 observational studies.
The main findings of the meta-analysis include: (1) ViV-TMVR was associated with similar in-hospital, 30-day, 1-year, and 2-year mortality compared with redo-SMVR; (2) the periprocedural complications, including stroke, bleeding, AKI, arrhythmias, and PPMI, were significantly lower, and hospital LOS was significantly shorter with ViV-TMVR; and (3) the mean MV gradient was higher with ViV-TMVR than redo-SMVR.
involving 790 propensity-matched patients identified from the Nationwide Inpatient Sample database (395 ViV-TMVR [50%], 395 redo-SMVR [50%]), patients who underwent ViV-TMVR had significantly lower in-hospital mortality than redo-SMVR (2.5% vs 7.6%, p = 0.001). This could be explained by the safety of TMVR techniques in terms of both planning (valve apps, echocardiography, and multidetector computed tomography) and approach (from TA to TS with rail, then TS alone), leading to a more effective, less invasive procedure with fewer complications.
Transcatheter valve implantation in failed surgically inserted bioprosthesis: review and practical guide to echocardiographic imaging in valve-in-valve procedures.
than the TA approach based on recent data. On the contrary, a relatively high incidence of complications during redo surgery, such as stroke, bleeding, AKI, arrhythmias, and PPMI, result in greater mortality in the redo-SMVR group. Indeed, AKI is well known to contribute to morbidity in patients who underwent MV surgery.
Furthermore, right-sided valve involvement and right ventricular dysfunction are common in patients with MV disease, and the prognostic impact of significant tricuspid regurgitation in patients after redo valve surgery is also well established.
also found a lower 30‐day mortality with ViV-TMVR (2.4% vs 10.2%, p = 0.04), although subsequent survival crossover occurred at 1 to 2 years, leading to higher 5‐year mortality with ViV-TMVR (49.9% vs 34.0%) than redo-SMVR. The lack of persistent favorable outcomes with ViV-TMVR is likely because of 3 factors. First, the ViV-TMVR population were frailer, with significant co-morbidities. Second, the ViV-TMVR group had higher rates of residual MR ≥ moderate,
Third, the low volume of procedures at some institutions, early experience and learning curve issues, and variable approaches for ViV-TMVR may have led to inferior results.
Despite the older age and greater co-morbidity burden among patients who underwent ViV-TMVR, as evidenced by their significantly higher preoperative risk scores, our meta-analysis revealed similar in-hospital, 30-day, 1-year, and 2-year mortality rates between ViV-TMVR and redo-SMVR for degenerated bioprosthetic MVs. Further studies with longer follow-up are needed to better define the mid- and long-term outcomes of ViV-TMVR compared with redo-SMVR.
Previous individual studies found no significant differences between ViV-TMVR and redo-SMVR in the rates of stroke,
However, on pooled analysis of data from 6 studies, these complications were significantly lower in ViV-TMVR than redo-SMVR, despite the older age and greater co-morbidity burden in the ViV-TMVR group. In the study by Murzi et al,
5 of 40 patients (12.5%) who underwent redo-SMVR had postoperative stroke compared with only 1 of 21 patients (4.8%) who underwent ViV-TMVR (p = 0.94).
Potential factors linked to stroke after redo-SMVR include retrograde perfusion through the femoral artery and procedures performed during hypothermic ventricular fibrillation.
Our pooled analysis revealed significantly higher postoperative AKI with redo-SMVR than ViV-TMVR. Data from the multicenter Mitral Valve Academic Research Consortium demonstrate AKI in around 5% of patients who underwent ViV-TMVR,
and with the current fluoroscopic qualities of previous implanted surgical MV prostheses, the amount of contrast dye may be further reduced or completely avoided.
Furthermore, the postoperative low cardiac output state secondary to high bleeding rates and the presence of multiple co-morbidities in the redo-SMVR group are known risk factors for AKI.
In contrast, the risk of complete heart block and PPM implantation is inherently small to nonexistent with ViV-TMVR because the transcatheter heart valve is implanted in a preshaped ‘docking’ station of known size.
found that although not reaching statistical significance, fewer patients in the ViV-TMVR group needed PPMI than redo-SMVR (0 of 41 [0%] vs 3 of 33 [9.1%], p = 0.08). Szlapka et al
Upon pooling of data, we found significantly lower PPMI rates with ViV-TMVR than redo-SMVR. Despite the lower mean age and preoperative risk scores in patients who underwent redo-SMVR, the hospital LOS was significantly higher in the redo-SMVR cohort than in ViV-TMVR, as reported by previous studies,
which ultimately increases the costs in the periprocedural period. This may be related to the higher periprocedural complications in the redo-SMVR group.
According to the VIVID (Valve-In-Valve International Data) Registry, the largest available source of data on this topic, with a total of 1,079 patients from 90 centers, 857 of whom underwent ViV-TMVR, ViV-TMVR was associated with a mean transprosthetic gradient of 5.6 ± 2.7 mm Hg and 3.1% of patients with residual MR ≥ moderate.
Transcatheter mitral valve replacement after surgical repair or replacement: comprehensive midterm evaluation of valve-in-valve and valve-in-ring implantation from the VIVID registry.
Valve size affects these gradients: in patients who underwent ViV-TMVR, the mean MV gradient and 1-year mortality are lower with larger-sized (26 or 29 mm) transcatheter heart valves than smaller-sized (20 and 23 mm) valves.
found the mean MV gradient to be similar at 30 days between ViV-TMVR and redo-SMVR (7.1 vs 6.5 mm Hg, p = 0.42) and only higher at 1-year with ViV-TMVR (7.2 vs 5.5 mm Hg, p = 0.01).
found similar valve gradients in the TS-ViV-TMVR and TA-ViV-TMVR compared with redo-SMVR at 30 days (6.7 vs 6.6 vs 5.7 mm Hg, p = 0.07) and 1 year (7.0 vs 6.8 vs 5.7 mm Hg, p = 0.07). Upon pooling of data, our meta-analysis demonstrated higher mean MV gradients with ViV-TMVR, which is a known contributor to worse long-term outcomes.
Transcatheter mitral valve replacement after surgical repair or replacement: comprehensive midterm evaluation of valve-in-valve and valve-in-ring implantation from the VIVID registry.
Strategies to improve postprocedural hemodynamics in ViV-TMVR should be further investigated.
The present meta-analysis may help guide clinical decision making for managing patients with degenerated bioprosthetic MVs. The favorable outcomes of ViV-TMVR in our study support ViV-TMVR over redo-SMVR as a primary strategy in patients with degenerated bioprosthetic MVs, particularly in those at intermediate-to-high surgical risk. Furthermore, an RCT of ViV-TMVR versus redo-SMVR is unlikely, so this meta-analysis of observational studies provides the most robust evidence to favor ViV-TMVR.
Our meta-analysis has several important limitations. First, all the included studies were observational, with relatively small sample sizes, and the patient selection for each therapy was influenced by several factors, such as age, co-morbidities, surgical risk, and operator experience, which leads to inherent selection bias. In contrast, the included studies of the present meta-analysis might represent real-world data and real-world practice. Second, the small number of events in some of the included studies represents another limitation that must be considered when interpreting the results. Third, the included studies had a median follow-up period ranging from approximately 1 to 4.5 years, and further studies with longer follow-up are needed to better define the long-term outcomes of ViV-TMVR compared with redo-SMVR. Fourth, like all meta-analyses, the quality of our study depends on the quality of the included studies and is constrained by the limitations of the included studies.
In conclusion, in patients with bioprosthetic MV degeneration, ViV-TMVR was associated with better outcomes than redo-SMVR, including lower complication rates and shorter hospital LOS, with no significant difference in mortality rates. Given these findings and the ongoing advances in transcatheter therapeutics, ViV-TMVR may be preferred over redo-SMVR for appropriate patients, particularly in those at intermediate-to-high surgical risk. Large-scale RCTs are needed to mitigate biases and confirm our findings. More data on the durability and long-term outcomes of ViV-TMVR are needed to extend its application to patients at lower surgical risk.
Disclosures
The authors have no conflicts of interest to declare.
Data availability statement
The data underlying this article are included in the article and in its Supplementary Material.
Hospital Outcome and Risk Indices of Mortality after redo-mitral valve surgery in Potential Candidates for Transcatheter Procedures: results from a European Registry.
Transcatheter valve implantation in failed surgically inserted bioprosthesis: review and practical guide to echocardiographic imaging in valve-in-valve procedures.
Transcatheter mitral valve replacement after surgical repair or replacement: comprehensive midterm evaluation of valve-in-valve and valve-in-ring implantation from the VIVID registry.
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