Meta-analysis of impact of renin-angiotensin system inhibitors on survival after transcatheter aortic valve implantation.

INTRODUCTION: To determine whether renin-angiotensin system inhibitor (RASI) prescription is associated with better survival after transcatheter aortic valve implantation (TAVI), we performed the first meta-analysis of currently available studies. EVIDENCE ACQUISITION: To identify all studies reporting impact of RASI prescription on survival after TAVI, we searched PubMed, Web of Science, Google Scholar, etc. through October 2019. We extracted adjusted (if unavailable, unadjusted) hazard ratios (HRs) with their confidence intervals (CIs) of midterm (up to ≥6-month) all-cause mortality for RASI prescription from each study and combined study-specific estimates using inverse variance-weighted averages of logarithmic HRs in the random-effects model. EVIDENCE SYNTHESIS: We identified 13 eligible studies with a total of 26,132 TAVI patients and included them in the present meta-analysis. None was a randomized controlled trial, 5 were observational studies comparing patients with versus without RASI prescription (including 3 propensity score matched studies), and 8 were observational studies investigating RASI prescription as one of covariates. The primary meta-analysis of all studies demonstrated that RASI prescription was associated with significantly lower midterm mortality (HR=0.83; 95% CI: 0.76 to 0.92; P=0.0002). Although we identified significant funnel plot asymmetry (P=0.036 by the rank correlation test) suggesting publication bias, correcting for it using the trim-and-fill method did not substantially alter the result favoring RASI prescription (corrected HR=0.85; 95% CI: 0.76 to 0.95; P=0.004). CONCLUSIONS: RASI prescription may be associated with better midterm survival after TAVI.

Transcatheter versus surgical aortic valve replacement in patients with chronic obstructive pulmonary disease.

Although a number of studies compared mortality after transcatheter aortic valve implantation (TAVI) with that after surgical aortic replacement (SAVR) in patients with chronic obstructive pulmonary disease (COPD), no meta-analysis of them has been conducted to date. To determine whether TAVI or SAVR is associated with better postprocedural survival in patients with COPD, a meta-analysis of all studies currently available was performed. Design. To identify all comparative studies of TAVI with SAVR in patients with COPD, PubMed and Web of Science were searched through January 2020. Studies meeting the following criteria were included in the present meta-analysis: the design was an observational comparative study or a randomized controlled trial; the study population was patients with COPD; patients were assigned to TAVI versus SAVR; and outcomes included all-cause mortality. Adjusted (if unavailable, unadjusted) odds or hazard ratios with their confidence intervals (CIs) of mortality for TAVI versus SAVR were extracted from each study. Study-specific estimates were combined in the random-effects model. Results. Six eligible studies with a total of 4771 patients with COPD were identified and included in the present meta-analysis. The meta-analysis indicated significantly lower early (in-hospital or 30-day) mortality after TAVI than after SAVR (odds ratio, 0.69; 95% CI, 0.53-0.90; p = .006) but no significant difference in midterm (1-year to 5-year) mortality between TAVI and SAVR (hazard ratio, 1.07; 95% CI, 0.79-1.44; p = .68). Conclusions. In patients with COPD, TAVI was associated with reduced early mortality, while midterm mortality appeared similar, as compared with SAVR.

Prognostic impact of baseline C-reactive protein levels on mortality after transcatheter aortic valve implantation.

OBJECTIVES: To determine whether baseline C-reactive protein (CRP) levels can predict mortality after transcatheter aortic valve implantation (TAVI), we performed a meta-analysis of currently available studies. METHODS: All studies investigating the prognostic impact of baseline (preprocedural) CRP levels on all-cause mortality after TAVI were identified by means of searching PubMed and Google Scholar through May 2019. For each study, (preferentially, adjusted rather than unadjusted) odds/hazard ratios (ORs/HRs) with corresponding 95% confidence intervals of mortality per standard-deviation (SD) (or unit) increase in CRP levels or those for high vs low CRP levels. RESULTS: Our search identified 14 eligible studies including a total of 3449 patients undergoing TAVI and reporting early (in-hospital to 3-month) and midterm (1-year to 3-year) all-cause mortality after TAVI. Pooled analyses demonstrated associations of high-baseline CRP levels with a marginal, but statistically nonsignificant increase in early mortality (pooled OR/HR per SD increase in CRP levels, 2.72; P = .09 and pooled OR/HR for high vs low CRP levels, 3.32; P = .07) and a statistically significant increase in midterm mortality after TAVI (pooled OR/HR per SD increase in CRP levels, 1.45; P < .0001 and pooled OR/HR for high vs low CRP levels, 1.78; P < .00001). Excluding HRs for high-sensitivity CRP, combining ORs/HRs of 1-year mortality, pooling HRs of ≥2-year mortality, and combining adjusted HRs did not alter the primary results. CONCLUSION: High-baseline CRP levels may predict increased midterm, but not early, mortality after TAVI.

Impact of postprocedural thrombocytopenia on mortality after transcatheter aortic valve implantation.

AIMS: We performed a meta-analysis of currently available studies investigating the impact of postprocedural thrombocytopenia on mortality after transcatheter aortic valve implantation (TAVI). METHODS: All studies researching the impact of postprocedural thrombocytopenia on mortality after TAVI were identified after searching PubMed and Web of Science through July 2019. The outcome of interest was early (in-hospital or 30-day) and overall (1- to 2-year) all-cause mortality after TAVI. From each study, the number of deaths in both patients with major (moderate/severe or higher postprocedural drop platelet counts defined in each study) and nonmajor (no/minor or lower drop platelet counts defined in each study) postprocedural thrombocytopenia was extracted. Then, odds ratios (ORs) of mortality for major vs. no/minor thrombocytopenia and their confidence intervals were generated. Alternatively, ORs and hazard ratios of mortality for major vs. no/minor thrombocytopenia (if available, adjusted) were directly extracted. Study-specific estimates were pooled in both the fixed-effect and random-effects models. RESULTS: The principal pooled analysis demonstrated that postprocedural thrombocytopenia was associated with statistically significant increases in early (OR, 3.79; P for effect <0.00001; P for heterogeneity = 0.89) and overall mortality (OR/hazard ratio, 1.22; P for effect = 0.009; P for heterogeneity = 0.17) in the fixed-effect model. All sensitivity analyses did not substantively alter the results of the principal analysis. No funnel plot asymmetry of the principal analysis was detected (P for early mortality = 0.88; P for overall mortality = 0.14), which suggested probably no publication bias. CONCLUSION: Postprocedural thrombocytopenia is associated with increased early and overall mortality after TAVI.

Gait and fate: Baseline gait speed and mortality after transcatheter aortic valve implantation.

BACKGROUND: To determine whether baseline gait speed predicts mortality after transcatheter aortic valve implantation (TAVI), a meta-analysis of currently available studies was performed. METHODS: To identify all studies researching the impact of preprocedural gait speed on mortality after TAVI, PubMed and Web of Science were searched through May 2019. Adjusted (if unavailable, unadjusted) hazard/odds ratios (ORs/HRs) with their confidence interval of mortality for slow (if available, the slowest) versus fast (if available, the fastest) gait speed (with cut-off values defined in each study) and those for unable to walk versus walker (if available, with the fastest gait speed) were extracted from each study, and then separately pooled by means of inverse variance-weighted averages of logarithmic ORs/HRs in the random-effects model. RESULTS: Twelve eligible studies (7 and 5 based on the distance-limited and time-limited walk test, respectively) were identified and integrated in the present meta-analysis. The pooled analysis of all ORs/HRs demonstrated that slow walkers (primary meta-analysis; OR/HR, 2.38; p < 0.00001) and unable to walk (OR/HR, 1.75; p = 0.01) were significantly associated with increased mortality. The subgroup analysis for the primary meta-analysis indicated no significant subgroup difference between studies utilizing the 4-m/5-m/15-foot walk test and those applying the 6-min walk test (p = 0.45). Combining studies with 1-year follow-up did not alter the primary result (p < 0.0001). Pooling studies with adjusted ORs/HRs did not change the principal result (p = 0.0002). No funnel plot asymmetry for the primary meta-analysis was identified. CONCLUSIONS: Slow baseline gait speed (and unable to walk) is associated with increased mortality after TAVI.

Egg Consumption and Coronary Artery Disease: A Nice Knockdown Argument.

To identify prospective cohort studies enrolling adults and investigating an association of egg consumption with incidence and mortality of coronary artery disease (CAD), PubMed and Web of Science were searched through June 2019. Adjusted hazard ratios (HRs) of CAD incidence/mortality for more versus the least frequent egg consumption were extracted from each study. Study-specific estimates were pooled in the random-effects model. Sixteen eligible studies with a total of 1 285 505 participants were identified and included in the present meta-analysis. The primary meta-analysis pooling all HRs for the most versus least frequent egg consumption demonstrated that egg consumption was associated with significantly low CAD incidence/mortality (pooled HR: 0.93; 95% confidence interval: 0.89-0.98; I2 = 9%). In the secondary meta-analyses (separately combining HRs for the third vs first tertile, the fourth vs first quartile, the third vs first quartile, the fifth vs first quintile, the fourth vs first quintile, and the third vs first quintile egg consumption), the fifth (vs first) quintile egg consumption was only associated with significantly low CAD incidence/mortality. In conclusion, egg consumption is independently associated with low incidence/mortality of CAD, which may be derived from the comparisons of the fifth versus first quintile egg consumption.

Baseline left ventricular diastolic dysfunction affects midterm mortality after transcatheter aortic valve implantation.

OBJECTIVES: To determine whether preprocedural left ventricular (LV) diastolic dysfunction impairs midterm mortality after transcatheter aortic valve implantation (TAVI) for patients with severe aortic stenosis (AS), we performed a meta-analysis of currently available evidence. METHODS: We identified all studies investigating impact of preprocedural severity of LV diastolic dysfunction on midterm (≥1-year) all-cause mortality after TAVI for patients with AS through a search of databases (MEDLINE and EMBASE) until September 2019. From each study, we extracted an adjusted (if unavailable, unadjusted) hazard ratio (HR) of midterm mortality. We pooled study-specific estimates in the random-effects model. RESULTS: Ten eligible studies with a total of 2380 patients with AS undergoing TAVI were identified. In accordance with pooled analyses, higher-grade preprocedural LV diastolic dysfunction was associated with significantly worse midterm all-cause mortality after TAVI compared to lower-grade dysfunction (HR for grade II vs I, 1.15; P = .002; HR for grade III vs I, 1.35; P = .001; HR for grade III vs II; 1.16, P = .002; HR for grade II-III vs I, II-III vs 0-I, or III vs I-II, 1.34; P < .00001 [primary meta-analysis]; HR per grade, 1.16; P = .003). No funnel plot asymmetry for the primary meta-analysis (for grade II-III vs I, II-III vs 0-I, or III vs I-II) was identified, which probably indicated no publication bias (P = .381 by the linear-regression test). CONCLUSION: Higher-grade preprocedural LV diastolic dysfunction was associated with worse midterm all-cause mortality after TAVI for patients with AS compared to lower-grade dysfunction.

Meta-analysis of propensity matched studies of robotic versus conventional mitral valve surgery.

BACKGROUND: To compare early outcomes after robotic versus conventional mitral valve surgery (R-MVS versus C-MVS), we performed a meta-analysis of currently available propensity score matched (PSM) studies. METHODS: To identify all PSM studies of R-MVS versus C-MVS, PubMed and Web of Science were searched thorough November 2018 using the terms of robotic or robot, mitral, and propensity. Inclusion criteria were PSM studies of isolated R-MVS versus C-MVS. Odds ratios of dichotomous data and mean differences for continuous data were generated for each study and combined in a meta-analysis using the random-effects model. RESULTS: We identified 7 PSM studies of R-MVS versus C-MVS enrolling a total of 3764 patients. Pooled analyses demonstrated significantly longer cardiopulmonary bypass (CPB) (p < 0.00001) and cross-clamp time (p = 0.004) in R-MVS than C-MVS. However, intensive care unit (ICU) (p = 0.0005) and hospital stay (p < 0.0001) was significantly shorter; and incidence of red blood cell (RBC) transfusion (p = 0.03), prolonged ventilation (p = 0.048), and atrial fibrillation (AF) (p = 0.01) was significantly less frequent after R-MVS than C-MVS. There was no significant difference in incidence of reoperation for bleeding and valve dysfunction, ≥moderate mitral regurgitation, renal failure, dialysis, pneumonia, stroke, cardiac arrest, and all-cause death (p = 0.27) between R-MVS and C-MVS. CONCLUSIONS: ICU/hospital stay was shorter and RBC transfusion/prolonged ventilation/AF was less frequent after R-MVS than C-MVS despite longer CPB and cross-clamp time in R-MVS than C-MVS. The other early outcomes including all-cause mortality were similarly frequent after R-MVS and C-MVS.

Meta-Analysis and Meta-Regression of Transcatheter Aortic Valve Implantation for Pure Native Aortic Regurgitation.

AIM: To assess outcomes of transcatheter aortic valve implantation (TAVI) for pure native aortic regurgitation (AR) and to evaluate whether 30-day all-cause mortality is modulated by patient characteristics, we performed a meta-analysis and meta-regression of currently available studies. METHOD: Studies enrolling ≥20 patients undergoing TAVI for AR were considered for inclusion. Study-specific estimates (incidence rates of outcomes) were combined using one-group meta-analysis in a random-effects model. Subgroup meta-analysis of studies exclusively using early-generation devices (EGD) and new-generation devices (NGD) and stepwise random-effects multivariate meta-regression were also performed. RESULTS: The search identified 11 eligible studies including a total of 911 patients undergoing TAVI for AR. Pooled analysis demonstrated an incidence of device success of 80.4% (NGD 90.2%, EGD 67.2%; p < 0.001), moderate or higher paravalvular aortic regurgitation (PAR) of 7.4% (NGD 3.4%, EGD 17.3%; p < 0.001), 30-day all-cause mortality of 9.5% (NGD 6.1%, EGD 14.7%; p < 0.001), mid-term (4 mo - 1 yr) all-cause mortality of 18.8% (NGD 11.8%, EGD 32.2%; p < 0.001), life-threatening/major bleeding complications (BC) 5.7% (NGD 3.5%, EGD 12.4%; p = 0.015), and major vascular complications (MVC) of 3.9% (NGD 3.0%, EGD 6.2%; p = 0.041). All coefficients in the multivariate meta-regression adjusting simultaneously for the proportion of diabetes mellitus, chronic obstructive pulmonary disease, peripheral arterial disease, concomitant moderate or higher mitral regurgitation, and mean left ventricular ejection fraction (with significant coefficients in the univariate meta-regression) were not statistically significant. CONCLUSIONS: Thirty (30)-day all-cause mortality after TAVI for AR was high (9.5%) with a high incidence of moderate or higher PAR (7.4%). Compared with EGD, NGD was associated with significantly higher device success rates and significantly lower rates of second-valve deployment, moderate or higher PAR, 30-day/mid-term all-cause mortality, serious BC, and MVC.

Matrix metalloproteinases and acute aortic dissection: Et Tu, Brute?

OBJECTIVES: To summarize the present evidence for the association of matrix metalloproteinases (MMPs) with acute aortic dissection (AAD), we performed the first meta-analysis of all currently available case-control studies comparing circulating MMP levels between AAD patients and control subjects. METHODS: To identify all studies investigating the levels of circulating MMPs in AAD patients, PubMed and Web of Science were searched up to July 2019. The levels of MMPs in AAD patients and control subjects were extracted from each study, and the standardized mean differences (SMDs) in MMP levels were generated. The study-specific estimates were combined in the random-effects model. RESULTS: Twelve studies enrolling a total of 458 AAD patients and 711 control subjects were identified and included. Pooled analyses demonstrated no significant differences in MMP-1 (4 studies; P = 0.21), MMP-2 (5 studies; P = 0.62) and MMP-3 levels (2 studies; P = 0.94) between AAD patients and control subjects; and significantly higher MMP-8 (2 studies; SMD 2.11; P = 0.020), MMP-9 (9 studies; SMD 1.54; P < 0.001) and MMP-12 levels (2 studies; SMD 1.33; P < 0.001) in AAD patients than in control subjects. CONCLUSION: High circulating MMP-9 levels are associated with AAD, and MMP-8 and MMP-12 levels may be related to AAD.

Echocardiographic outcomes from seven randomized trials of transcatheter versus surgical aortic valve replacement.

AIMS: We performed meta-analyses of echocardiographic outcomes, including postprocedural aortic valve area (AVA), aortic valve mean pressure gradient (MPG), and paravalvular aortic regurgitation (PAR), exclusively from all currently available randomized controlled trials (RCTs) of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR). METHODS: To identify all RCTs providing echocardiographic outcomes (AVA, MPG, and PAR) up to 2 years after TAVI versus SAVR, PubMed and ClinicalTrials.gov were searched through June 2019. Mean differences in AVA (and MPG) between the TAVI and SAVR groups and odds (or hazard) ratios of at least moderate PAR for TAVI versus SAVR were pooled using the random-effects meta-analysis. RESULTS: We identified seven eligible RCTs. At 30 days (P = 0.004), 1 year (P = 0.006), and 2 years (P = 0.03), AVA was significantly larger after TAVI than after SAVR. After TAVI than after SAVR, MPG was significantly lower at 30 days (P = 0.03) and 2 years (P = 0.01), and nonsignificantly lower at 1 year (P = 0.06). At 30 days (P < 0.00001), 1 year (P < 0.00001), and 2 years (P < 0.00001), incidence of at least moderate PAR was significantly greater after TAVI than after SAVR. CONCLUSION: On the basis of the present meta-analyses of all the seven currently available RCTs, AVA is larger, MPG is lower, and incidence of at least moderate PAR is greater 30 days, 1 and 2 years after TAVI than after SAVR.