The effect of obesity on the outcome of thoracic endovascular aortic repair: a systematic review and meta-analysis

Introduction

Descending thoracic aortic (DTA) diseases mainly include dissections, aneurysms and traumatic injuries. These diseases can cause a serious risk of bleeding or vital organ malperfusion in acute conditions, leading to fatal outcomes.

Because of the progress of diagnostic imaging and the prolonged life expectancy of the population, the incidence of thoracic aortic aneurysm (TAA) and type B aortic dissection (TBAD) is increasing (Kuzmik, Sang & Elefteriades, 2012; Howard et al., 2013). It is estimated that AD annually affects 3–4 people per 100,000, most of whom are men over 60 years old with a history of abnormal blood vessels and/or hypertension (Jubouri et al., 2022). Aortic aneuryism (AA) which refers to pathological dilatation of the aorta, is considered to be the second most common disease of the aorta, subsequent to atherosclerosis (Badran et al., 2023).

Although significant progress in medical and surgical treatment modalities has been achieved for years, the general mortality associated with aortic diseases is still high. In recent decades, the surgical treatment modality for emergent thoracic aortic conditions has shifted from open surgery to thoracic endovascular aortic repair (TEVAR), a relatively minimally invasive modality (Habib et al., 2023). In particular, TEVAR is recommended as the first-line treatment for DTAA with no elastopathy and a maximal diameter of aneurysm ≥55 mm (Isselbacher et al., 2022). In addition, technological progress in TEVAR has also decreased the mortality rates in acute TBAD patients (Eleshra et al., 2020).

Unfortunately, postoperative complications of TEVAR, such as cerebrovascular diseases, arterial perforation or rupture, and renal insufficiency, may lead to higher early mortality, longer hospital stays, and a poor quality of life (Liu et al., 2021). In addition, reintervention may be required in some TEVAR procedures. However, the risk factors for poor outcome of TEVAR remain unclear and need to be identified.

Obesity is closely associated with adverse postoperative outcomes including wound, cardiopulmonary, and respiratory complications (Choban & Flancbaum, 1997). Physiologic and anatomic factors related to obesity may increase the risk of anaesthetic-related events and perioperative complications (Alshaikh et al., 2018). When undergoing emergent surgery, obesity may increase the risk of death caused by fulminant respiratory failure (Choban & Flancbaum, 1997). The elevated rate of obstructive sleep apnea in patients with obesity who received general anaesthesia may also lead to cardiovascular complications, such as stroke, myocardial infarction or ischemia, and mortality (Choban & Flancbaum, 1997). Surprisingly, in a systematic review, obese patients are found to have lower 30-day mortality in abdominal aortic aneurysm patients undergoing endovascular aortic repair (Naiem et al., 2022). However, the role of obesity in the prognosis of TEVAR has not been fully elucidated. Therefore, we conducted this systematic review and meta-analysis to summarize the roles of obesity in the prognosis of TEVAR.

Materials & Methods

This study was performed according to the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) guidelines (Liberati et al., 2009). Before identifying studies from databases, we registered this study in the International Prospective Register of Systematic Reviews (PROSPERO) on July 3, 2023 (ID: CRD42023438854).

Results

After excluding duplicate articles, three hundred and five articles were obtained in the initial search. Twenty-six articles were chosen for further full-text evaluation according to titles and abstracts. Finally, 10 articles with 7,849 individuals were included (Romijn et al., 2023; Borghese et al., 2023; Niu et al., 2023; Zha et al., 2021; An et al., 2021; Naazie et al., 2022; Lu et al., 2020; Janczak et al., 2019; Zakko et al., 2014; Khoynezhad et al., 2007). The study screening flow diagram is shown in Fig. 1. The basic information and patient baseline characteristics are summarized in Table S1, Fig. S2. Among these studies, three reported the BMI of patients who experienced adverse events after TEVAR or not (Niu et al., 2023; An et al., 2021; Zakko et al., 2014), five reported the ORs or HRs of obesity and the incidence of adverse events (Romijn et al., 2023; Borghese et al., 2023; Naazie et al., 2022; Lu et al., 2020; Khoynezhad et al., 2007), and four reported the incidence of adverse events in patients with or without obesity (Borghese et al., 2023; Zha et al., 2021; Janczak et al., 2019; Khoynezhad et al., 2007). According to the NOS, all enrolled studies were considered high quality (Table S3).

Association between obesity and incidence of overall mortality and complications for TEVAR

Three studies (Romijn et al., 2023; Borghese et al., 2023; Naazie et al., 2022) reported the ORs of obesity and mortality (Fig. 2). The results indicated that the risk of overall mortality was increased in obese patients (OR = 1.49, 95% CI [1.02–2.17], p = 0.04). Although the heterogeneity was insignificant (I² = 47%, p = 0.15) among studies, only one study showed significant association between obesity with 30-day mortality.

Three studies (Naazie et al., 2022; Lu et al., 2020; Khoynezhad et al., 2007) reported the ORs of obesity and overall complications (Fig. 3). The results indicated that the risk of overall mortality was increased in obese patients, though without statistical significance (OR = 2.41, 95% CI [0.84–6.93], p = 0.10). Significant heterogeneity was found among studies (I² = 88%, p < 0.001).

Association between obesity and incidence of specific complications for TEVAR

Interestingly, the associations between obesity and specific complications were all insignificant (Fig. 4 and Table S4), including stroke (OR = 1.39, 95% CI [0.56–3.45], p = 0.48, heterogeneity: I² = 67%, p = 0.05), spinal ischemia (OR = 0.97, 95% CI [0.64–1.47], p = 0.89, heterogeneity: I² = 0%, p = 0.96), neurological complications (OR = 0.13, 95% CI [0.01–2.37], p = 0.17), endoleaks (OR = 1.02, 95% CI [0.46–2.29], p = 0.96), wound complications (OR = 0.91, 95% CI [0.28–2.96], p = 0.88), renal failure (OR = 2.98, 95% CI [0.92–9.69], p = 0.07) and reintervention (30-day: OR = 1.80, 95% CI [0.56–5.76], p = 0.33; 90-day: OR = 0.77, 95% CI [0.24–2.45], p = 0.66; long-term: OR = 0.44, 95% CI [0.16–1.20], p = 0.11). Only one study reported significant association between obesity with stroke (Khoynezhad et al., 2007).

Differences in BMI between patients who experienced adverse events after TEVAR and those who did not

The patients who suffered from overall postoperative complications (p < 0.001) and postoperative AKI (p = 0.006) were found to have a higher BMI (Fig. 5). However, for patients receiving percutaneous TEVAR, BMI was not significantly associated with the success of the operation, which was defined as achieving hemostasis and maintaining limb perfusion for 30 days postoperatively without the need for exposing the common femoral artery and/or surgical repair of vessels.

Discussion

Obesity is a well-recognized predictor for metabolic and cardiovascular diseases, which is also associated with elevated risks of postoperative general complications or even death (Ogden et al., 2015). First, obesity is associated with some comorbidities, including metabolic disorders (dyslipidemia, diabetes or hypertension), coronary heart diseases and respiratory disorders (sleep apnea syndrome) (Csige et al., 2018). In addition, obese patients also have elevated risk of pulmonary and cardiovascular adverse events as obesity is associated with increased oxygen requirement and consumption, leading to decreased oxygenation index during general anaesthesia with impaired pulmonary compliance, and functional residual capacity (Pelosi et al., 1998; Cullen & Ferguson, 2012). In our meta-analysis, we found obesity significantly associates to high risk of postoperative overall mortality for patients receiving TEVAR.

For Stanford A dissection, obesity is also reported to be a potential risk factor for poor postoperative outcomes, which may be because of acute respiratory distress syndrome (Aizawa et al., 2013). Oxidative stress and chronic inflammation may be increased with obesity, as well as the levels of IL-1β, IL-6 and TNF-α, which contribute to the development of lung injury (Wu et al., 2020). In our meta-analysis, obesity was significantly associated with a high risk of mortality after TEVAR, especially for 30-day mortality. It should be noted that when patients with a BMI less than 18.5 kg/m2 (underweight) were included in the control group, the associations with mortality were not significant. A meta-analysis even found that obese patients have lower 30-day mortality in endovascular aortic repair compared with nonobese patients (Naiem et al., 2022). The obesity paradox may provide a potential explanation. Underweight status is also reported to associate to elevated risk of morbidity and mortality for several causes, such as smoking, malnutrition, malignancy, or some wasting conditions (Saedon et al., 2015; Galyfos et al., 2017). Underweight is also associated with elevated risk of frailty or sarcopenia, which are also associated with a decline in physiologic function and a high risk of mortality in the general population and in patients receiving TEVAR (Newton et al., 2018; Kim et al., 2021; Harris et al., 2020). Frailty and sarcopenia, which are yet to be well-studied may also confound the result that obesity is associated with decreased risk of mortality in abdominal aortic aneurysm patients receiving EVAR (Naiem et al., 2022). Therefore, studies analyzing outcomes for obese, normal weight or underweight patients should be conducted in the future. More confounding factors associated with variance of weight should be adjusted. Interestingly, a study found that the operative outcomes for patients with obesity who received TEVAR vary according to presenting pathology, including DTAA and TBD (Naazie et al., 2022). The significant association between obesity and 30-day mortality was observed only in TBD patients. This result indicates that physicians should pay more attention to obese TBD patients receiving TEVAR in terms of perioperative management.

For postoperative complications, significant associations were not observed for overall complications nor any specific complications, including stroke, spinal ischemia, neurological complications, endoleaks, and wound complications. However, because of impaired immunity and low oxygen tension in fat tissue, obesity is also associated with a high risk of surgical site infection (Dindo et al., 2003; Tanaka et al., 1993). Nevertheless, patients who experienced overall in-hospital complications, including all-cause death and implant-related, deployment-related and systemic complications, or AKI also had higher BMI. In addition, the obesity paradox may conceal the associations between obesity and specific postoperative complications. In the study by Naazie et al. (2022), underweight patients were older with elevated rates of smoking and chronic obstructive pulmonary disease, and they also have larger maximum aortic diameters, which are also reported to be associated with adverse events after TEVAR (Gallo et al., 2023; Zhao et al., 2023; Tang et al., 2023; Romeiro et al., 2021).

The characteristics of thoracic aortic diseases and the detailed process of surgery may play more important roles in the occurrence of these specific complications than obesity. For example, the proximal landing zone location and left subclavian artery revascularization are reported to associate to elevated risk of stroke, spinal ischemia, endoleak and mortality (Ma et al., 2023; Zhu, Li & Lu, 2023; Karaolanis et al., 2022; Chen et al., 2019; Hajibandeh et al., 2016). Besides, the utilization of distinct anesthesia techniques can result in varied clinical outcomes among patients undergoing TEVAR. Specifically, the application of locoregional anesthesia has been significantly associated with a reduced postoperative hospital length of stay, without exhibiting any noteworthy increase in additional postoperative morbidities, compared to the administration of general anesthesia (Panossian et al., 2023). The clinical strategy to avoid worsening AKI in the perioperative obesity patient population is avoidance of hypotension (Citerio et al., 2014). However, to ensure the successful conduct of TEVAR surgery, antihypertensive medications are administered during the procedure, in a hypotensive environment, renal perfusion may be insufficient, ultimately leading to the occurrence of AKI (Suneja & Kumar, 2014). Therefore, the optimization of intraoperative management is paramount in the obese patient population. The precise evaluation of intravascular volume status and adequacy of fluid resuscitation poses significant challenges in obese patients undergoing TEVAR. The limited information with physical examination, and considerable variations in the accuracy of noninvasive blood pressure monitoring contribute to the complexity of these assessments. Consequently, obese patients should utilize, to the extent possible, dynamic indices of intravascular volume responsiveness to guide fluid therapy (Balderi et al., 2008). Additionally, the employment of goal-directed hemodynamic optimization during surgery is essential to mitigate postoperative complications (Prowle, Kirwan & Bellomo, 2014).

In our meta-analysis, studies that investigated the associations with overall complications or specific complications did not exclude underweight patients in the control group. Therefore, the aforementioned confounding factors should be adjusted in subsequent studies to further clearly demonstrate the role of obesity in TEVAR.

Conclusions

Obesity is closely associated with higher risk of mortality after TEVAR. However, TEVAR may still be suitable for obese patients. Physicians should pay more attention to the perioperative management of obese patients.

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