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Symptomatic aortic stenosis (AS) is a common valvu-lar heart disease that leads to a high rate of death if left

untreated.1,2 Transcatheter aortic valve implantation (TAVI) is a novel approach to treat patients with AS who are at high risk for or cannot tolerate surgical aortic valve replacement.3,4

Several studies reported sex-specific incidence of complications and deaths after TAVI, but their results are inconsistent. Although some studies found no significant differences in 30-day mortality between men and women,5,6 others, however, suggested a higher 30-day and 1-year mortality among the male population.7,8

So, we performed a meta-analysis of published studies that reported sex-specific data on the incidence of post-TAVI com-plications and deaths, aiming at comprehensively and quan-titatively reviewing all the available studies and providing effect estimates.

MethodsData SearchesThe Cochrane library and PubMed online databases (between January 1, 2002, and April 9, 2013) were searched. The following search strategy was used: (transcatheter or percutaneous or transcuta-neous or transarterial or transvascular or transfemoral or transapical or transaxillary or transaortic or transsubclavian) and (aortic valve) and (male or female or men or women or sex or gender). In addition, reference lists of pertinent articles were screened for potentially rel-evant citations missed by electronic searches.

Study SelectionStudies were initially screened at the level of title and abstract, and then full-length reports were retrieved for detailed evaluation. Two au-thors independently selected articles according to prespecified inclu-sion and exclusion criteria. Articles were included if they (1) reported

Background—There were considerable discrepancies with regard to sex-related differences in complications and prognosis after transcatheter aortic valve implantation.

Methods and Results—The Cochrane library and PubMed online databases were searched. Articles reporting sex-specific post–transcatheter aortic valve implantation complications and mortality were identified. Two authors selected studies and extracted data independently. Random- and fixed-effects models were used depending on between-study heterogeneity. There were 27 articles, a total of 9118 patients, enrolled in our systematic review and meta-analysis, including 4176 men and 4942 women. Pooled analyses suggested considerable sex-related differences in complications and early as well as midterm outcomes after transcatheter aortic valve implantation. The difference in the risk for heart block requiring permanent pacemaker implantation was noted to be significant only in the subgroup of the CoreValve-dominating studies (pooled risk ratio [RR, men versus women], 1.29; 95% confidence interval [CI], 1.13–1.47). Although men had significantly lower risks for major/life-threatening bleeding (pooled RR, 0.81; 95% CI, 0.68–0.96) and major vascular complications (pooled RR, 0.49; 95% CI, 0.37–0.66), they had poorer prognosis. In fact, male sex was associated with significantly higher risks for deaths at both 30 days (RR, 1.37; 95% CI, 1.07–1.76) and 1 year (RR, 1.30; 95% CI, 1.14–1.49).

Conclusions—Although men had lower risks for major/life-threatening bleeding and major vascular complications after transcatheter aortic valve implantation, they had less favorable short-term and midterm survival. (Circ Cardiovasc Interv. 2013;6:543-551.)

Key Words: aortic valve implantation ◼ aortic valve stenosis ◼ complication ◼ outcome ◼ sex characteristics ◼ transcatheter

© 2013 American Heart Association, Inc.

Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org DOI: 10.1161/CIRCINTERVENTIONS.113.000529

Received May 14, 2013; accepted August 23, 2013.From the Department of Cardiology, West China Hospital, Sichuan University, Chengdu, PR China.*Drs Zhao and Liao contributed equally to this work.Correspondence to Mao Chen, MD, PhD or Yuan Feng, MD, Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue St,

Chengdu 610041, PR China. E-mail hmaochen@foxmail.com or fynote@hotmail.com

Sex-Related Differences in Outcomes After Transcatheter Aortic Valve Implantation

A Systematic Review and Meta-analysis

Zhen-Gang Zhao, MD*; Yan-Biao Liao, MD*; Yong Peng, MD; Hua Chai, MD; Wei Liu, MD; Qiao Li, MD; Xin Ren, MD; Xue-Qin Wang, MS; Xiao-Lin Luo, MD; Chen Zhang, MD;

Li-Hui Lu, MS; Qing-Tao Meng, MD; Chi Chen, MD; Mao Chen, MD, PhD; Yuan Feng, MD; De-Jia Huang, MD

Transcatheter Aortic Valve Replacement

Original Article

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the number or incidence of ≥1 complication and death for men and women separately; (2) used the standardized definition of complica-tions according to the Valve Academic Research Consortium criteria9; and (3) were human studies and published in English. Abstracts, let-ters, editorials, and reviews were excluded.

Data ExtractionTwo authors extracted data independently. A table was designed to record data of eligible studies on the year of publication, first au-thor, outcome definition, follow-up duration, number of men and women, prosthetic valve type, baseline characteristics, and number of complications and deaths. Baseline characteristics included age, body mass index, hypertension, diabetes mellitus, chronic obstruc-tive pulmonary disease, previous coronary artery disease, New York Heart Association class III or IV, previous myocardial infarction, previous percutaneous coronary intervention, previous peripheral vascular disease, previous cerebrovascular disease, atrial fibrillation, logistic European system for cardiac operative risk evaluation, mean aortic gradient, and vascular access. Complications included major/life-threatening bleeding, major vascular complications, permanent pacemaker implantation (PPMI), and stroke. Mortality included 30-day and 1-year death.

Data Synthesis and AnalysesThe risk ratio (RR) of men compared with women, with regard to post-TAVI complications and deaths at 30 days and 1 year, was calculated and synthesized using the Mantel–Haenszel method in the RevMan software version 5.10 (The Nordic Cochrane Centre, Copenhagen, Denmark). Heterogeneity was assessed by calculating the I2 statistic and its P value. A fixed-effects model was selected in the case of an I2 <50% and a corresponding P>0.1; otherwise, a random-effects model was used to obtain the combined effect estimates. Two-sided P<0.05 were considered statistically significant.

Sensitivity and Publication Bias AnalysesSensitivity analyses were performed by excluding 1 study at a time in case that ≥5 studies were included and by discarding smaller studies

(reporting no more than 100 successful TAVI procedures), where ap-plicable, using the STATA software version 12.0 (StataCorp, College Station, TX). Because the CoreValve (Medtronic Inc) is associated with a much higher risk for heart block requiring PPMI than the Edwards valve (Edwards Lifesciences LLC), an additional subgroup analysis was performed for this outcome according to the predomi-nant type of valve (CoreValve or Edwards valve) that was used in each study.

Publication bias was detected by Begg and Egger tests. Two-sided P<0.05 were considered statistically significant. In addition, funnel plots were constructed to inspect the symmetry visually.

Outcome Quality AssessmentGrading of Recommendations Assessment, Development, and Evaluation system evaluation was performed to grade the quality of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation handbook. The GRADEpro software version 3.2 was used. We got the assessment by judging the design of study, risk of bias, inconsistency, and imprecision.

Present systematic review and meta-analysis were conducted and reported according to the recommendations of the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.10

ResultsLiterature Search and Study SelectionThe process of study selection is illustrated in Figure 1. There were 1679 citations after removing duplicates. A total of 27 full-text articles were eligible for our systematic review and meta-analysis.5–8,11–33 These studies included 4176 men and 4942 women for the comparison of sex-related differences in complications and mortality after TAVI. Although the 2 stud-ies overlapped in patient population, they provided different outcomes. One reported 30-day mortality,22 and the other pro-vided 1-year mortality.33

Study and Patient CharacteristicsThe characteristics of the included studies are presented in Table 1. Of the 27 full-length reports, only 5 detailed the base-line data of men and women separately.5–8,26 The pooled sex-specific baseline characteristics based on these studies showed that men were more likely to experience diabetes mellitus, chronic obstructive pulmonary disease, coronary artery dis-ease, previous myocardial infarction, previous percutaneous

WhAT IS KNOWN

•Transcatheter aortic valve implantation has been shown to improve symptoms and survival effectively in surgically high-risk patients with severe aortic ste-nosis but is associated with specific complications.

•Previous reports were considerably discrepant in terms of the sex-related differences in complication profiles and prognosis after transcatheter aortic valve implantation.

WhAT ThE STuDy ADDS

•This study systematically reviewed and pooled the currently published sex-specific data on outcomes after transcatheter aortic valve implantation.

•The pooled analyses suggested significant sex- related differences in this regard.

•Men were less likely to experience major/life- threatening bleeding and major vascular complica-tions, but they had significantly higher risks for heart block requiring permanent pacemaker implantation and early as well as late deaths after transcatheter aortic valve implantation.

Potentially relevant citations identifiedusing predefined search strategy

(n=1679)

Citations left after removing duplicates(n=1644)

Studies excluded afterevaluating at the level of title

and abstract (n=1523)

Studies included in present meta-analysis(n=27)

Full-length articles retrieved for detailedeligibility assessment

(n=121)

Studies excluded after full review (n=94)

No full-length article (n=2)No sex-specific data (n=91)Sample size <10 (n=1)

Figure 1. Flow diagram of study selection.

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Zhao et al Sex-Specific Outcomes After TAVI 545

Table 1. Characteristics of Included Studies

First Author Year Country Follow-up Sex n

Valve Approach

EV/MCV (n/N) Ta/TA (n/N)

Buja et al5 2013 Italy 1 y Male 291 0/291 291/0

Female 368 0/368 368/0

Hayashida et al6 2012 France 1 y Male 129 102/27 85/44

Female 131 120/11 92/39

Buchanan et al7 2011 Italy 1 y Male 159 88/71 150/9

Female 146 97/49 133/13

Humphries et al8 2012 Canada 2 y Male 312 622/19 193/119

Female 329 158/171

Ye et al11 2009 Canada 1 y Male 13 13/0 0/13

Female 13 13/0 0/13

Rodes-Cabau et al12 2010 Canada 1 y Male 152 152/0 91/61

Female 187 187/0 71/116

Sinning et al13 2010 Germany 1 y Male 37 0/37 37/0

Female 40 0/40 40/0

Rodes-Cabau et al14 2011 Canada 1 y Male 43 43/0 21/22

Female 58 58/0 17/41

Tamburino et al15 2011 Italy 1 y Male 292 0/292 292/0

Female 371 0/371 371/0

Amabile et al16 2012 France 1 y Male 80 132/39 139/32

Female 91

Bagur et al17 2012 Canada NA Male 176 176/0 223/188

Female 235 235/0

Genereux et al18 2012 America 1 y Male 227 227/0 227/0

Female 192 192/0 192/0

Gotzmann et al19 2012 Germany 1 y Male 91 0/91 91/0

Female 107 0/107 107/0

Houthuizen et al20 2012 The Netherlands 1 y Male 360 292/387 473/206

Female 319

Lange et al21 2012 Germany 6 mo Male 155 127/293 290/130

Female 265

Lauten et al22 2012 Germany 30 d Male 544 249/1053 1179/123

Female 758

Munoz-Garcia et al23 (PPM*)

2012 Spain 30 d Male 65 0/65 65/0

Female 109 0/109 109/0

Munoz-Garcia et al24 2012 Spain 1 y Male 50 0/50 50/0

Female 83 0/83 83/0

Seiffert et al25 2012 Germany 1 y Male 145 116/29 68/77

Female 181 165/16 81/100

Stangl et al26 2012 Germany 3 mo Male 42 9/33 42/0

Female 58 8/50 58/0

Van Mieghem et al27 2012 The Netherlands, France

30 d Male 519 487/499 519/0

Female 467 467/0

Yong et al28 2012 The Netherlands 1 y Male 47 0/47 47/0

Female 72 0/72 72/0

Zhao et al29 2012 France 30 d Male 24 24/0 13/11

Female 24 24/0 15/9

Elhmidi et al30 2013 Germany 1 y Male 139 112/261 NA

Female 234(Continued)

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coronary intervention, and peripheral vascular disease, although there were no significant differences in the mean logistic European system for cardiac operative risk evaluation between the 2 sexes (Table 2).

Sex Differences in Complications After TAVI

Major/Life-Threatening BleedingOnly 6 studies were eligible for the pooled analysis of sex dif-ferences in this outcome.5,7,8,16,26,27 These studies enrolled 1403 men and 1459 women, and the overall incidence of major/life-threatening bleeding was 12.8% and 15.3%, respectively. Men had a significantly lower risk for major/life-threatening bleeding (pooled RR, 0.81; 95% confidence interval [CI], 0.68–0.96; Figure 2). The pooled results remained stable after excluding the study, with no more than 100 successful TAVI procedures (pooled RR, 0.80; 95% CI, 0.67–0.96).26 However, pooled RR became insignificant on deletion of the studies by Humphries et al8 (pooled RR, 0.85; 95% CI, 0.69–1.04) and Van Mieghem et al27 (pooled RR, 0.89; 95% CI, 0.73–1.09). The Begg and Egger plot suggested no sig-nificant publication bias (Begg test statistic, P=1.00; Egger test statistic, P=0.81).

Major Vascular ComplicationOnly 5 studies evaluated the outcome of major vascular com-plications by sex.5,7,8,18,26 The occurrence rate of major vas-cular complication in men and women was 6.1% and 11.3% in the 5 eligible studies incorporating 1031 men and 1093 women. Pooled results suggested a significantly lower risk of major vascular complication in men (pooled RR, 0.49; 95% CI, 0.37–0.66; Figure 3). The results remained stable when omitting individual studies or the study with a relatively small sample size (pooled RR, 0.48; 95% CI, 0.36–0.65).26 No sig-nificant publication bias was observed (Begg test statistic, P=0.46; Egger test statistic, P=0.17).

Permanent Pacemaker ImplantationWe identified 9 studies that reported sex-specific incidence of PPMI.5–8,17,23,26,31,32 Data on 1719 men and 2145 women were available for analysis. In studies that predominantly used the CoreValve, heart block requiring PPMI was a com-mon complication after TAVI, with an incidence of 31.3% and 24.7% for men and women, respectively.5,23,26,31,32 How-ever, the rate of PPMI was much lower in studies mainly using Edwards valve, 8.0% in men and 7.4% in women.6–8,17 The pooled results of sex-related differences in this outcome

Table 2. Pooled Characteristics of Men and Women

Baseline Characteristics Men Women P Value

Age 80.6±1.6 (n=933) 82.1±1.2 (n=1032) <0.001

BMI 26±0.4 (n=333) 26.1±0.5 (n=335) 0.78

Hypertension, n/total (%) 564/774 (72.9) 711/886 (80.2) 0.31

Diabetes mellitus, n/total (%) 292/933 (31.3) 274/1032 (26.6) 0.03

COPD, n/total (%) 306/933 (38.6) 250/1032 (24.2) 0.006

NYHA class III or IV, n/total (%) 671/891 (75.3) 778/974 (79.9) 0.01

CAD, n/total (%) 588/774 (76.0) 459/886 (51.8) <0.001

Previous MI, n/total (%) 320/933 (34.3) 201/1032 (19.5) <0.001

Previous PCI, n/total (%) 411/933 (44.1) 282/1032 (27.3) <0.001

PVD, n/total (%) 257/774 (33.2) 189/886 (21.3) 0.02

Previous stroke, n/total (%) 140/933 (15.0) 120/1032 (11.6) 0.06

Atrial fibrillation, n/total (%) 172/645 (26.7) 183/755 (24.2) 0.50

Logistic EuroSCORE 24.0±1.3 (n=621) 22.7±1.4 (n=703) 0.06

Data are presented as number (percentage) or mean±SD. BMI indicates body mass index; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; EuroSCORE, European system for cardiac operative risk evaluation; MI, myocardial infarction; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; and PVD, peripheral vascular disease.

Ledwoch et al31 2013 Germany 30 d Male 468 232/915 1034/113

Female 679

van der Boon et al32 2013 The Netherlands 1 y Male 77 0/77 167/0

Female 90 0/90

Zahn et al33 2013 Germany 1 y Male 547 244/1074 1203/115

Female 771

EV indicates Edwards valve; MCV, Medtronic CoreValve; NA, not available; PPM, permanent pacemaker; Ta, transarterial; and TA, transapical.*Included in the pooled analysis of the outcome of heart block requiring PPM.

Table 1. Continued

First Author Year Country Follow-up Sex n

Valve Approach

EV/MCV (n/N) Ta/TA (n/N)

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also varied substantially between the 2 subgroups as defined by the predominant type of valve used, although the test for subgroup heterogeneity showed no statistical significance (I2=13.7%; P=0.28; Figure 4). Although no significant dif-ferences were observed between sexes in the subgroup of studies mainly using Edwards valve (pooled RR, 1.06; 95% CI, 0.75–1.48; Figure 4), men were suggested to be at sig-nificantly higher risk for heart block requiring PPMI in the pooled analysis of the CoreValve-dominating studies (pooled RR, 1.29; 95% CI, 1.13–1.47; Figure 4), which drove the overall pooled results toward significance (pooled RR, 1.25; 95% CI, 1.10–1.41; Figure 4).

The pooled results were robust to the deletion of indi-vidual studies, either among the whole group or within each subgroup. Also, the findings remained stable after excluding the relative small study26 and performing meta-analysis in the entire group (pooled RR, 1.24; 95% CI, 1.09–1.40) or in the CoreValve-dominating subgroup (pooled RR, 1.28; 95% CI, 1.12–1.46). No significant publication bias was observed (Begg test statistic, P=1.00; Egger test statistic, P=0.91).

StrokeOnly 4 studies reported the number of stroke after TAVI in a total of 804 men and 901 women.5,7,8,26 The incidence of stroke for men and women was 2.2% and 1.7%, respectively. There were no significant sex differences with regard to the risk of stroke after TAVI (pooled RR, 1.39; 95% CI, 0.71–2.74; Figure 5). Because there are only 4 studies, sensitivity and publication bias analyses were not conducted.

Mortality

Thirty-Day MortalityThirteen studies were identified that compared 30-day mortal-ity between sexes.5–8,11,12,20–22,26–29 A total of 2706 men and 3178 women were included in these studies. The 30-day mortality was 9.3% in men and 6.9% in women. Male sex was associ-ated with a significantly higher risk for death at 30 days after TAVI as shown by the pooled results using a random-effects model (pooled RR, 1.37; 95% CI, 1.07–1.76; Figure 6). The direction of the results remained unchanged when removing

Figure 2. Pooled risk ratio of men com-pared with women on major/life-threatening bleeding after transcatheter aortic valve implantation in 6 studies. CI indicates con-fidence interval; fixed, fixed-effects model; and M-H, Mantel–Haenszel method.

Figure 3. Pooled risk ratio of men com-pared with women on major vascular com-plication after transcatheter aortic valve implantation in 5 studies. CI indicates con-fidence interval; fixed, fixed-effects model; and M-H, Mantel–Haenszel method.

Figure 4. Pooled risk ratio of men com-pared with women on permanent pace-maker implantation after transcatheter aortic valve implantation (TAVI) in 9 studies. In the 5 studies of the CoreValve subgroup, 88.9% (1998 of 2247) of the TAVI proce-dures were performed using the CoreValve, whereas in the 4 studies of the Edwards valve subgroup, 89.1% (1440 of 1617) of the procedures were performed with the Edwards valve. CI indicates confidence interval; fixed, fixed-effects model; M-H, Mantel–Haenszel method; and PPM, per-manent pacemaker.

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individual studies from the analysis or after discarding the 3 smaller studies (pooled RR, 1.35; 95% CI, 1.03–1.76).11,26,29 There was no evidence of significant publication bias (Begg test statistic, P=1.00; Egger test statistic, P=0.89).

One-Year MortalityA total of 16 studies enrolling 3013 men and 3649 women were eligible for meta-analysis.5–8,12–16,18–20,24,25,30,33 One-year mortality of men and women was 22.0% and 16.9%, respectively. Pooled analysis using a random-effects model showed that men had significantly higher 1-year mortality (pooled RR, 1.30; 95% CI, 1.14–1.49; Figure 7). The robustness of the results was con-firmed by the sensitivity analysis of deleting individual studies or omitting the 2 smaller studies (pooled RR, 1.29; 95% CI, 1.11–1.49).13,14 No significant publication bias was noted (Begg test statistic, P=0.56; Egger test statistic, P=0.98).

Grading of Recommendations Assessment, Development, and Evaluation System Evaluation Because all the 27 studies were observational studies, the evi-dence of quality of the complication and mortality outcomes

was moderate, except that the quality of major vascular com-plication after TAVI was high and quality of stroke was low (Table 3).

DiscussionThe major findings of present meta-analysis were that there were significant sex differences in terms of the risks for major/life-threatening bleeding, major vascular complication, 30-day mortality, and 1-year mortality after TAVI. Sex-related differences in the risk for heart block requiring PPMI were noted to be significant only in the subgroup of the CoreValve-dominating studies (pooled RR [men versus women], 1.29; 95% CI, 1.13–1.47). Although men were less susceptible to major/life-threatening bleeding (pooled RR, 0.81; 95% CI, 0.68–0.96) and major vascular complication (pooled RR, 0.49; 95% CI, 0.37–0.66), they had significantly higher risks for 30-day (pooled RR, 1.37; 95% CI, 1.07–1.76) and 1-year deaths (pooled RR, 1.30; 95% CI, 1.14–1.49).

Our findings were in line with those from the sex-specific analysis of the Placement of AoRTic TraNscathetER Valve

Figure 5. Pooled risk ratio of men com-pared with women on stroke after trans-catheter aortic valve implantation in 4 studies. CI indicates confidence interval; fixed, fixed-effects model; and M-H, Mantel–Haenszel method.

Figure 6. Pooled risk ratio of men com-pared with women on 30-day mortality after transcatheter aortic valve implantation in 13 studies. CI indicates confidence interval; M-H, Mantel–Haenszel method; and ran-dom, random-effects model.

Figure 7. Pooled risk ratio of men com-pared with women on 1-year mortality after transcatheter aortic valve implantation in 16 studies. CI indicates confidence interval; M-H, Mantel–Haenszel method; and ran-dom, random-effects model.

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Trial (PARTNER), which incorporated a total of 1334 men and 1231 women enrolled in either the randomized or non-randomized continued evaluation phase.34 In that study, male sex was also observed to be associated with a significantly higher incidence of comorbidities (coronary artery disease [87.6% versus 67.5%], prior coronary artery bypass graft [59.3% versus 24.4%], peripheral vascular disease [46.4% versus 39.4%], chronic kidney disease [20.6% versus 12.6%; P<0.001 for all]) and less favorable late outcomes (1-year mortality [24.3% versus 17.6%; P=0.0005], 2-year mortality [35.3% versus 29.6%; P=0.002]).

Given that female sex was a risk factor for major vascular complication and major/life-threatening bleeding, why did women have a better prognosis? This phenomenon could be explained from 3 aspects. (1) Although female sex was a risk factor of some complications (such as major vascular com-plication), these complications were not the major causes of deaths. Besides, another study found no significant differ-ences in prognosis between patients with and without major vascular complication.16 (2) The sex differences in the patho-physiological characteristics might serve as a possible under-lying mechanism. Several studies have demonstrated cardiac remodeling and fibrosis to be less prevalent and less severe in women with AS than those in men with AS, which might be related to the lower expression of collagen I, collagen III, metal matrix proteinase-2, and metal matrix proteinase-9 in women.35–37 Furthermore, AS has recently been demonstrated to share some common pathogenic bases with atherosclero-sis.38,39 As female sex is a protective factor for atherosclerosis, this may also affect AS. (3) The unbalanced baseline risk pro-files may be an important explanation. As shown in Table 2, diabetes mellitus, chronic obstructive pulmonary disease, and

atherosclerotic diseases were much more prevalent among the male patient population. The higher burden of these morbidi-ties in men may adversely affect their survival after TAVI.

Our meta-analysis has several limitations. (1) Although great care was taken in selecting studies, the possibility of duplicated data synthesis as a result of their overlap in the patients enrolled cannot be completely ruled out. (2) The sex differences in long-term prognosis after TAVI could not be assessed because of the lack of studies. (3) The power of the Egger and Begg tests for funnel plot asymmetry is too low to distinguish chance from real asymmetry when there are no more than 10 studies eligible for the pooled analysis. Thus, the possibility of potential publication bias could not be ruled out, particularly from the meta-analyses of the bleeding, vascular complication, and pacemaker outcomes. (4) Because only 5 studies reported sex-specific baseline characteristics and the patient-level data were not available, the effects of potential mediators (comorbidities) could not be assessed. However, the unadjusted summary RRs presented in current meta-analyses can be interpreted as the total causal effects of sex, which might be more clinically relevant. (5) The sex-related differ-ences in post-TAVI outcomes, as observed in present meta-analyses, are not large enough to be used alone in treatment directing or patient counseling. Nevertheless, sex may be a useful part of the risk stratification model of TAVI, at least for major vascular complication and possibly for early as well as midterm mortality.

In conclusion, there were significant sex differences in complications and prognosis after TAVI. Although men had lower risks for major/life-threatening bleeding and major vas-cular complication after TAVI, they had less favorable short-term and midterm survival.

Table 3. Summary of GRADE Evidence Profile

Quality Assessment

Quality*No. of Studies Design Serious Risk of Bias Serious Inconsistency Serious Indirectness Serious Imprecision

Major/life-threatening bleeding after TAVI

6 Observational studies Possible† No No No Moderate

Major vascular complication after TAVI

5 Observational studies Unlikely‡ No No No High

New pacemaker implantation after TAVI

6 Observational studies Possible† No No No Moderate

Stroke after TAVI

4 Observational studies Possible† No No Yes§ Low

30-d mortality after TAVI

14 Observational studies Possible† No No No Moderate

1-y mortality after TAVI

17 Observational studies Possible† No No No Moderate

CI indicates confidence interval; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RR, risk ratio; and TAVI, transcatheter aortic valve implantation.

*High quality indicates that further research is unlikely to change our confidence in the estimate of effect; moderate quality indicates that further research is likely to have an important effect on our confidence in the estimate of effect and may change the estimate; low quality indicates that further research is likely to have an important effect on our confidence in the estimate of effect and is likely to change the estimate.

†Although the unadjusted RRs represented the total causal effects of sex and thus cannot be confounded by the differences in comorbidity profiles, which were also driven by sex, the potential effects of exogenous factors that were independent of sex cannot be ruled out.

‡A value of RR <0.5 with statistical significance indicates that it is unlikely to be seriously biased.§The 95% CI for the pooled RR showed a wide variety.

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DisclosuresNone.

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Feng and De-Jia HuangWang, Xiao-Lin Luo, Chen Zhang, Li-Hui Lu, Qing-Tao Meng, Chi Chen, Mao Chen, Yuan

Zhen-Gang Zhao, Yan-Biao Liao, Yong Peng, Hua Chai, Wei Liu, Qiao Li, Xin Ren, Xue-QinSystematic Review and Meta-analysis

Sex-Related Differences in Outcomes After Transcatheter Aortic Valve Implantation: A

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