Sex-based outcomes following thoracic endovascular aortic repair for acute complicated type B aortic dissection: A meta-analysis

Abstract

BACKGROUND

Sex disparities in clinical outcomes following thoracic endovascular aortic repair (TEVAR) for acute complicated type B aortic dissection (TBAD) are not well understood.

AIM

To evaluates the impact of sex on primary and secondary outcomes by comparing male and female cohorts undergoing TEVAR.

METHODS

A systematic search of PubMed, EMBASE, Cochrane Library, and ScienceDirect identified five studies involving 2572 patients (1153 males and 1419 females). The primary outcome was hospital mortality. Secondary outcomes included reintervention rates, acute kidney injury (AKI), ischemic stroke, limb ischemia, and spinal cord ischemia. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic.

RESULTS

The primary outcome showed no significant difference between males and females for hospital mortality (OR: 1.13, 95%CI: 0.81-1.59, P = 0.47, I² = 0). Among secondary outcomes, males had a significantly higher risk of AKI (OR: 1.55, 95%CI: 1.21-2.00, P = 0.0006, I² = 0). No differences were observed for reintervention rates, ischemic stroke, limb ischemia, or spinal cord ischemia.

CONCLUSION

Male patients undergoing TEVAR for complicated TBAD are at increased risk of AKI but show comparable outcomes to females for mortality, ischemic events, reintervention, and other complications. Future research should explore mechanisms and strategies to optimize outcomes.

Key Words: Thoracic endovascular aortic repair; Type B aortic dissection; Sex; Outcomes; Acute kidney injury

Core Tip: This meta-analysis demonstrates that while most clinical outcomes following thoracic endovascular aortic repair (TEVAR) for acute complicated type B aortic dissection are comparable between sexes, male patients face a higher risk of postoperative acute kidney injury (AKI). By addressing modifiable risk factors and exploring innovative care models, clinicians can reduce the burden of AKI and enhance care for patients undergoing TEVAR.

INTRODUCTION

The life-threatening medical emergency, aortic dissection (AD), which is classified within the family of acute aortic syndromes[1], is believed to impact 3-4 individuals per 100000 annually. Among these, 40% of patients are categorized as having type B AD (TBAD), which originates distal to the left subclavian artery[2].

Depending on initial clinical manifestations of malperfusion and rupture, TBAD can be further subdivided into complicated or uncomplicated TBAD[3]. According to the definition, we must observe the presence of at least one of the following features for acute complicated TBAD (cTBAD): Rapid aortic expansion, aortic rupture, intractable pain, relentless hypertension, and malperfusion of the spinal, visceral, renal, and lower extremities[4]. According to a study, it was found that, when compared to uncomplicated TBAD, cTBAD, had a higher mortality rate (16.1% vs 2.6%, P < 0.0001), and the overall mortality in 5 years was 40%[5,6]. The current routine management of cTBAD, is thoracic endovascular aortic repair (TEVAR)[7], as supported by the Society for Vascular Surgery[8].

However, following the procedure, there are still various outcomes of great significance for patients. Operative mortality is the primary outcome, while secondary outcomes include acute kidney injury (AKI), spinal cord ischemia, stroke, length of hospital stay, and overall survival[9].

Despite the growing body of literature on TEVAR for cTBAD, the impact of sex on outcomes remains poorly understood. While individual studies have reported on TEVAR outcomes, few have systematically examined sex-based differences in this population[10]. As a result, there is a notable lack of clarity on whether sex influences the safety and efficacy of TEVAR for cTBAD, underscoring the need for a comprehensive analysis of sex-specific outcomes in this context.

To address the gaps in the findings of various outcomes, we have carried out this meta-analysis to identify the most frequent complications in the two sexes. We believe that the emphasis we have placed on the variation in clinical manifestations following TEVAR can contribute as a guide for further clinical research aimed at achieving better outcomes for patients following TEVAR.

MATERIALS AND METHODS

Search strategy

A comprehensive literature search was conducted by the PRISMA guidelines and recommended methodologies. The search was conducted across various databases, including PubMed, EMBASE, Cochrane Library, and ScienceDirect, from inception to December 2024. The search strategy included a combination of MeSH terms and keywords, including “Thoracic Endovascular Aortic Repair,” “TEVAR,” “Type B Aortic Dissection,” “Acute Aortic Dissection,” and “Sex Differences.” Through a manual search of the bibliographies of relevant studies, additional references were identified. The study adhered to the PRISMA guidelines[11]. Detailed Search String is given in the Supplementary material.

Eligibility criteria

Those Studies were included if they were observational studies comparing male and female patients undergoing TEVAR for acute cTBAD. Studies were eligible if they reported quantitative data on at least one primary or secondary outcome of interest.

Studies were excluded if they did not have a Sex-specific outcomes comparison. Also, Case reports, conference abstracts, editorials, or expert opinions were excluded. Those studies were also excluded that were duplicate studies with overlapping patient data (the most comprehensive or recent study was retained).

Study selection and data extraction

Two independent reviewers performed the search, assessed full-text articles for eligibility, and screened titles and abstracts. By consulting with a third reviewer, Disagreements were resolved through discussion. Data extraction was conducted independently by the same reviewers and included details on study design, population characteristics, surgical approach, and reported outcomes.

Quality assessment

Two independent reviewers used the Newcastle-Ottawa Scale (NOS) to assess the methodological quality of the included studies. While other tools, such as ROBINS-I, also provide more detailed assessments, the NOS was chosen for its efficiency and consistency in evaluating key domains relevant to our study. The NOS evaluates three domains: Selection (4 items), comparability (1 item, up to 2 stars), and outcome assessment (3 items), with a maximum possible score of 9 stars. Discrepancies were resolved through discussion with a third reviewer[12].

Statistical analysis

All statistical analyses were conducted using Review Manager 5.3 (Cochrane Collaboration)[13]. Since all included outcomes were dichotomous variables, effect estimates were calculated using odds ratios (OR) with 95% confidence intervals (CI). A random-effects model was applied throughout the analysis to account for potential heterogeneity among studies. Due to the limited number of included studies (n = 5), Egger’s regression test and other publication bias assessments were not performed, as recommended for meta-analyses with fewer than 10 studies. According to the Cochrane Handbook (chapter 9), heterogeneity was considered significant if the alpha value of the χ² test is below 0. In contrast, the interpretation of the I-square test is as follows: 0% to 40% indicates no significant heterogeneity, 30% to 60% indicates moderate heterogeneity, 50% to 90% suggests substantial heterogeneity, and 75% to 100% indicates considerable heterogeneity[14,15]. For each outcome, a forest plot was constructed to analyze the data visually.

RESULTS

Included studies

The PRISMA statement flowchart (Figure 1) outlines the literature screening process, study selection, and exclusion criteria. The initial search yielded 582 articles, from which 46 full-text articles were retrieved for assessment. Ultimately, five studies[16-20] met the eligibility criteria and were included in both the qualitative and quantitative meta-analyses.

Figure 1  PRISMA flowchart outlining the literature screening process, study selection, and exclusion criteria.

Baseline characteristics

A total of 2572 patients (1153 males, 1419 females) from five retrospective cohort studies were included in the meta-analysis. The mean age for male patients ranged from 53.84 to 64.67 years (mean: 59.9 ± 12.1 years), while female patients had a mean age between 58.8 and 64.67 years (mean: 62.5 ± 12.1 years).

Regarding comorbidities, hypertension was common in both sexes (male: 84.2%-91.96%, female: 78.3%–94.59%), with slightly higher rates in males in most studies. Smoking was consistently more prevalent in males (38.8%-63%) compared to females (2.5%-59.5%), a difference that may contribute to an increased risk of AKI in male patients, given the established association between smoking and endothelial dysfunction, renal vasoconstriction, and oxidative stress. Diabetes mellitus (DM) showed mixed trends, with higher prevalence in males in most studies (5.4%-16.96%), although one study reported a higher rate in females (up to 27.68%). Chronic obstructive pulmonary disease (COPD) was more frequent in females (5.9%-27.03%) compared to males (5.9%-16.96%), potentially impacting postoperative respiratory complications. Data on chronic kidney disease (CKD) were sparse but indicated a slightly higher rate in females in at least one study.

These baseline characteristics illustrate notable Sex-based differences in age, comorbidities, and risk factors. Notably, the higher prevalence of smoking and DM in males may predispose them to higher rates of postoperative complications such as AKI. In contrast, the greater burden of COPD in females could influence respiratory outcomes following TEVAR for acute cTBAD (Table 1).

Table 1 Detailed characteristics of each included study.

Ref.	Year	Study design	Max. follow up	Total no. of patients		Age (mean SD) years		Smoker (%)		Hypertension (%)		Diabetes mellitus (%)		COPD (%)		Chronic kidney disease (%)
				Male	Female	Male	Female	Male	Female	Male	Female	Male	Female	Male	Female	Male	Female
Bashir et al[17]	2022	Retrospective cohort	NA	41	17	58.2 ± 13.6	58.8 ± 13.3	NA	NA	87.8	88.2	9.7	5.9	NA	NA	NA	NA
Filiberto et al[18]	2022	Retrospective cohort	5 years	121	38	59.6 ± 14.1	62.5 ± 14	38.8	42.1	90.9	84.2	11.6	13.2	7.4	18.4	32.2	39.5
Luo et al[16]	2021	Retrospective cohort (prospectively maintained single center)	4 years	793	120	53.84 ± 11	56.11 ± 10.07	55.2	2.5	85.6	78.3	5.4	13.4	1.3	0	7.9	6.7
Summers et al[19]	2024	Retrospective cohort	5 years	1095	531	58.67 ± 14.10	64.67 ± 15.61	63	58	87	88	11	14.5	9.3	15	NA	NA
Yammine et al[20]	2024	Retrospective cohort	3 years	112	74	60 ± 12.8	64.1 ± 14.5	42.9	59.5	91.96	94.59	16.96	16.22	15.18	27.03	27.68	21.62

COPD: Chronic obstructive pulmonary disease.

Clinical outcomes

The in-hospital outcomes were examined between males and females undergoing TEVAR, including neurological and renal complications, as well as other perioperative parameters.

AKI: For patients undergoing TEVAR for TBAD, the male population was significantly at a higher risk for postoperative AKI than females, i.e., (OR 1.55, 95%CI: 1.21-2.00, P = 0.0006). There was no heterogeneity (I² = 0%) in our pooled analysis. This demonstrated that Sex could influence postoperative complications (Figure 2A).

Figure 2 Forest plot comparing. A: Acute kidney injury; B: Hospital mortality; C: Ischemic stroke; D: Limb ischemia; E: Reintervention; F: Spinal cord ischemia between male and female in thoracic endovascular aortic repair for acute complicated type B aortic dissection.

Hospital mortality: The male population had a higher risk of hospital mortality compared to females, but the findings were statistically insignificant (OR 1.13, 95%CI: 0.81-1.59, P = 0.4747), with no heterogeneity (I² = 0%). This suggests that Sex had no significant impact on hospital mortality (Figure 2B).

Ischemic stroke: There was no statistically significant difference in ischemic stroke between male and female populations, i.e., (OR 1.08, 95%CI: 0.73-1.60, P = 0.70). There was no observed heterogeneity (I² = 0%) in our analysis (Figure 2C).

Limb ischemia: The incidence of limb ischemia was also statistically insignificant between the two sexes undergoing TEVAR for TBAD, i.e., (OR 1.12, 95%CI: 0.55-2.26, P = 0.76). Additionally, heterogeneity was relatively low, i.e., (I² = 24%) (Figure 2D).

Re intervention: There was no statistically significant Sex-based difference in reintervention between the two groups, i.e., (OR 1.04, 95%CI: 0.61-1.77, P = 0.89). There was low heterogeneity in our pooled analysis (I² = 25%) (Figure 2E).

Spina Cordrd ischemia: There was no statistically significant difference in spinal cord ischemia between the male and female populations (OR 1.38, 95%CI: 0.94-2.0, P = 0.10). No heterogeneity (I² = 0%) was observed. This demonstrated that Sex had no significant impact on perioperative spinal cord ischemia (Figure 2F).

Quality assessment

The NOS evaluation showed that all included studies demonstrated moderate to high methodological quality. Luo et al[16] and Filiberto et al[18] achieved the highest scores (9/9), indicating a high level of methodological rigor. Summers et al[19] and Yammine et al[20] scored 8/9, showing minor limitations in comparability. Bashir et al[17] had the lowest score (7/9) due to lower comparability ratings. Overall, the studies were of high quality, ensuring reliability in the findings (Table 2).

Table 2 Quality assessment scores of the included studies, indicating methodological quality and risk of bias.

Ref.	Selection				Comparability	Outcome			Total
	1	2	3	4	1	1	2	3
Bashir et al[17]	★	★	★	★		★	★	★	7/9
Filiberto et al[18]	★	★	★	★	★★	★	★	★	9/9
Luo et al[16]	★	★	★	★	★★	★	★	★	9/9
Summers et al[19]	★	★	★	★	★	★	★	★	8/9
Yammine et al[20]	★	★	★	★	★	★	★	★	8/9

DISCUSSION

This meta-analysis of 2572 patients (1153 males and 1419 females) from five retrospective cohort studies evaluated sex-based differences in clinical outcomes following TEVAR for acute cTBAD. The results suggest that TEVAR is equally effective for men and women in preventing hospital mortality, ischemic stroke, limb ischemia, reintervention, and spinal cord ischemia. However, male patients experienced a significantly higher incidence of postoperative AKI, highlighting a critical sex-specific disparity that necessitates targeted clinical strategies.

The lack of difference in hospital mortality between sexes aligns with prior research. A large international registry study of 9518 patients across 13 countries reported comparable mortality rates for male and female patients undergoing TEVAR[21]. Similarly, a propensity-score matched analysis of over 10000 patients from the Nationwide Readmissions Database found no sex-based differences in in-hospital mortality[22]. These findings suggest that sex does not independently influence short-term survival after TEVAR, despite females being older on average (approximately 26.5% of patients were female). This age disparity may stem from differences in vascular disease pathophysiology, such as delayed disease onset in women, or variations in care-seeking patterns and comorbidities like hypertension and CKD[23,24]. The comparable mortality rates indicate that TEVAR is a robust treatment for both sexes in managing acute cTBAD.

Similarly, outcomes such as ischemic stroke, limb ischemia, reintervention, and spinal cord ischemia showed no significant sex-based differences, suggesting that the procedural risks of TEVAR are consistent across sexes in the early postoperative period. These findings are reassuring, as they indicate that sex alone does not significantly alter the risk profile for these complications, allowing clinicians to focus on other patient-specific factors when planning TEVAR.

The significantly higher incidence of AKI in male patients is a key finding that requires careful consideration. Biologically, sex hormones influence renal function and response to injury. Estrogen has been shown to confer renoprotection in animal models of AKI, particularly in ischemia-reperfusion injury, which is relevant to TEVAR due to potential renal hypoperfusion during the procedure[25]. In contrast, testosterone may exacerbate renal injury through increased inflammation and oxidative stress[26]. These biological differences may be compounded by clinical factors, as males in our study had a higher prevalence of AKI risk factors, including smoking, hypertension, and CKD[22,23,25]. For instance, two studies reported higher smoking rates among males, a known contributor to vascular and renal damage[22,23]. Similarly, hypertension and CKD were more prevalent in males in some studies, further elevating AKI risk[27]. Procedural factors, such as contrast agent exposure and hemodynamic instability during TEVAR, may also interact with these sex-specific characteristics, increasing AKI risk in males[21]. Notably, AKI was defined using standardized criteria (e.g., RIFLE or KDIGO), which adjust for sex-related differences in creatinine production due to higher muscle mass in males, suggesting that the observed disparity reflects actual differences in renal injury rather than diagnostic bias[28].

The higher risk of AKI in males has significant implications for clinical practice. Perioperative strategies to protect renal function should be prioritized, particularly for male patients. These include ensuring adequate hydration, minimizing exposure to contrast agents, and maintaining hemodynamic stability during and after TEVAR. While pharmacological interventions like N-acetylcysteine have shown mixed results in preventing contrast-induced AKI, their use could be considered in high-risk male patients[29]. Additionally, multidisciplinary care models, such as cluster nursing, have demonstrated potential in reducing AKI rates in other surgical contexts by enhancing perioperative monitoring and early intervention, and their application in TEVAR warrants further exploration[30]. Preoperative optimization of modifiable risk factors, such as smoking cessation and aggressive blood pressure control, could further mitigate AKI risk in males, given their higher prevalence of these conditions.

Limitations

This meta-analysis has several limitations. The inclusion of only five retrospective studies may limit statistical power and introduce selection bias. However, most outcomes showed low heterogeneity (I² = 0 for all except AKI, where I² = 25%). Unmeasured confounding factors, such as differences in comorbidity management between sexes, could influence the results. For example, variations in the preoperative control of hypertension, diabetes, or CKD might differ between male and female patients, affecting their susceptibility to AKI. The lack of individual patient data prevented adjustment for these variables. Variations in AKI definitions, despite the use of standardized criteria, may introduce minor inconsistencies. The analysis did not account for differences in procedural techniques or institutional protocols, which could have impacted the outcomes.

Furthermore, the long-term consequences, quality of life, and sex-specific hormonal impacts were not evaluated, which limits the scope of the conclusions. Future research should employ prospective designs, standardized outcome definitions, and long-term follow-up to address these gaps. Studies incorporating biomarker analysis and advanced imaging could further elucidate the pathophysiological mechanisms underlying the increased risk of AKI in males.

CONCLUSION

This meta-analysis demonstrates that while most clinical outcomes following TEVAR for acute cTBAD are comparable between sexes, male patients face a higher risk of postoperative AKI. These findings underscore the need for sex-specific risk stratification and tailored preventive measures to optimize outcomes. By addressing modifiable risk factors and exploring innovative care models, clinicians can reduce the burden of AKI and enhance care for patients undergoing TEVAR.