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Comparative Evaluation of the Incidence of Postoperative Pulmonary Complications After Minimally Invasive Valve Surgery vs. Full Sternotomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Propensity Score-Matched Studies

Background: Postoperative pulmonary complications remain a leading cause of increased morbidity, mortality, longer hospital stays, and increased costs after cardiac surgery; therefore, our study aims to analyze whether minimally invasive valve surgery (MIVS) for both aortic and mitral valves can improve pulmonary function and reduce the incidence of postoperative pulmonary complications when compared with the full median sternotomy (FS) approach. Methods: A comprehensive systematic literature research was performed for studies comparing MIVS and FS up to February 2021. Randomized controlled trials (RCTs) and propensity score-matching (PSM) studies comparing early respiratory function and pulmonary complications after MIVS and FS were extracted and analyzed. Secondary outcomes included intra- and postoperative outcomes. Results: A total of 10,194 patients from 30 studies (6 RCTs and 24 PSM studies) were analyzed. Early mortality differed significantly between the groups (MIVS 1.2 vs. FS 1.9%; p = 0.005). Compared with FS, MIVS significantly lowered the incidence of postoperative pulmonary complications (odds ratio 0.79, 95% confidence interval [0.67, 0.93]; p = 0.004) and improved early postoperative respiratory function status (mean difference −24.83 [−29.90, −19.76]; p < 0.00001). Blood transfusion amount was significantly lower after MIVS (p < 0.02), whereas cardiopulmonary bypass time and aortic cross-clamp time were significantly longer after MIVS (p < 0.00001). Conclusions: Our study showed that minimally invasive valve surgery decreases the incidence of postoperative pulmonary complications and improves postoperative respiratory function status.


INTRODUCTION
Full median sternotomy (FS) has long been the standard incision for cardiac surgery due to it is excellent exposure of the heart FIGURE 1 | Flowchart for studies included in data search in accordance with PRISMA guidelines. and great vessels. However, to reduce the size of the sternotomy, cardiac surgeons have long pursued less extensive incisions to improve outcomes and thus have used minimally invasive approaches that have undergone rapid development in the last few decades (1)(2)(3). These approaches have multiple benefits over an FS because of a smaller surgical incision, reduced pain, earlier discharge, and quicker postoperative recovery (4,5). On the other hand, some potential technical disadvantages tend to have prolonged cardiopulmonary bypass (CPB) and aortic cross-clamp time (6,7).
Given such developments in surgical management and patients' treatment over the years, postoperative pulmonary complications remain a leading cause of mortality and morbidity following cardiac surgery (8,9). These complications contribute to longer hospital stays and more readmissions into the ICU, significantly affecting health care and increasing healthcare systems' financial burden (8,10). Atelectasis and pleural effusions, pneumonia, pneumothorax, diaphragm paralysis because of phrenic nerve damage, and pulmonary infection are the most common pulmonary complications (11).
Although considerable benefits were associated with the MIVS over FS, there is still ongoing debate about the advantage of MIVS on postoperative pulmonary complications (PPCs), and the associations remain unclear. To our knowledge, there is still limited evidence on PPCs and respiratory system function analysis of patients after MIVS compared with the FS approach has not been analyzed. Therefore, based on the existing clinical literature, we conducted this systematic review and metaanalysis of high-quality randomized controlled trials (RCTs) and propensity score-matched (PSM) studies to analyze the incidence of PPCs and respiratory function of patients who underwent a minimally invasive approach for mitral or aortic valve vs. FS.

Selection Criteria
We included all articles reporting clinical outcomes for MIVS (repair or replacement of the mitral valve, aortic valve, or both valves) via right/lateral mini-thoracotomy or mini-sternotomy, with either a camera or direct visualization, vs. traditional FS. Studies were considered using a PICOS (Population, Intervention, Comparison, Outcome, and Study) strategy if (1) articles were published in English, (2) articles reported RCTs or PSM studies, (3) articles compared the outcomes of MIVS and FS for either mitral or aortic valve disease, and (4) outcomes included postoperative pulmonary complications and early postoperative respiratory function. Articles without a full report available, review studies, studies with previous cardiac surgery and concomitant surgical procedures (coronary artery bypass grafting, and procedure involving ascending aortic) other than isolated mitral and aortic or both valve surgery were excluded and studies with no comparison group were also excluded.

Information Sources
The following databases were used: PubMed, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, and Google Scholar. The reference lists of identified articles were also included in manual searches.

Search Strategy
We searched articles and studies comparing FS vs. MIVS using the following medical subject headings: aortic valve, aortic valve surgery, mitral valve or mitral valve surgery, minimally/partial invasive, full/conventional/partial sternotomy or mini-sternotomy, anterolateral/right mini-thoracotomy, partial upper Hemi-sternotomy or upper mini-sternotomy.

Study Selection
Search strategies, inclusion with exclusion criteria, statistical analysis, and outcomes were predefined. Thirty publications fulfilled our eligibility criteria (5,6,. Two independent investigators (MA, SZ) reviewed all abstracts that fulfilled the search criteria. When there were differences of opinion between these investigators, other authors were included to resolve disagreements. Figure 1 summarizes the search strategy.

Data Extraction
Two reviewers independently extracted data from each included study and performed the quality assessment. Data extracted included the first author's name, year of publication, country, study interval, study type, the number of subjects who underwent MIVS or FS, and outcomes of interest. The following clinical outcomes of interest from each study were extracted to compare MIVS with FS: postoperative pulmonary complications (overall complications, pneumonia, pleural effusion, pneumothorax, pulmonary infection, and respiratory insufficiency), early postoperative pulmonary function variables after 1 week (forced expiratory volume in 1 second [FEV1], forced total lung capacity (TLC), and forced vital capacity [FVC%]). Secondary outcomes of interest included early mortality, blood transfusion and, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, and operative time.

Risk-of-Bias and Study Quality Assessment
Two independent reviewers (SZAS and NID) assessed the riskof-bias using the Cochrane risk-of-bias (RoB2) tool. The riskof-bias was categorized as low, high, or unclear risk-of-bias. The RoB2 Excel tool was applied to individual studies, and results were entered into Cochrane's Review Manager 5.3 (40). The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of all observational studies. The NOS assesses the following characteristics of a study: selection of the general population, comparability, and adequate assessment of outcomes, to evaluate the methodological quality of studies (41). Based on the NOS, a maximum of 9 points can be given to each study. In this review, the modified NOS scores ≥ 7 were considered to indicate high-quality publications. Furthermore, the methodological quality of RCTs was assessed using the Jadad scale, which evaluates RCT quality using a maximum score of 5. A Jadad score ≥ 3 was considered to indicate high-quality RCTs (42).

Definitions of Outcomes
MIVS was defined as any procedure not performed with an FS. A full sternotomy was performed from the sternal notch to the xiphoid process. The definitions of the postoperative outcomes mainly depend on the descriptions mentioned in the original articles (8,18,39,(43)(44)(45). Besides postoperative pulmonary complications were defined as complications occurring in the postoperative period and producing clinical diseases, such as pneumonia, pleural effusion, pneumothorax, pulmonary infection, and respiratory insufficiency (defined as the need for reintubation or tracheostomy after initial extubation), and prolonged ventilation time, which was defined as mechanical ventilatory support requirement for more than 24 h. Pulmonary function tests, represented by FEV1, TLC, and FVC, were assessed based on a spirometry test 1 week after surgery. The incidence of early mortality was defined as death in the hospital or within 30 days post-surgery.

Statistical Analysis
As per Cochrane Collaboration guidelines, all statistical meta-analyses were performed using Review Manager 5.3 software (Cochrane Collaboration, Copenhagen, Denmark). We calculated pooled odds ratios (ORs) with their 95% confidence intervals (CIs) for dichotomous data, which are presented as numbers and percentages. Weighted mean differences (WMDs) were used to assess continuous data, which are presented as means ± standard deviation or medians with interquartile ranges. We assessed the heterogeneity of studies by means of I 2 and chi-square test. As a sensitivity analysis, FS and MIVS from RCTs and from PSM studies were compared separately. The reported results all are two-sided, and a p < 0.05 was considered to indicate statistical significance.
The RCTs scored at least 3 out of 5 on the Jadad scale, and most of the PSM studies scored at least 7 out of 9, based on a modified version of the NOS scale (Table 1 and Figure 2). Therefore, overall, the studies were considered to be of high quality.

Postoperative Pulmonary Complications Outcomes
We analyzed data on postoperative pulmonary complications from 27 studies (6, 12-14, 16-34, 36-39). The overall complications were less in MIVS patients than in FS patients (OR   Table 2, and forest plots are shown in Figure 3.
In subgroup analysis, postoperative pulmonary complications differed significantly between the two groups (p = 0.0007) in terms of the incidence of postoperative respiratory insufficiency, reported by 12 studies (12 Table 2 and forest plots are shown in

DISCUSSION
Over the past decades, a steady evolution has taken place in the practice of MIVS, with excellent postoperative outcomes, according to the literature. The minimally invasive approach used for the aorta or mitral valve has advantages over the FS method in terms of decreased surgical trauma, postoperative blood loss, and length of ICU and hospital stay (4,47). Nevertheless, postoperative pulmonary complications remain a common cause of postcardiac surgical morbidity, poor outcomes, increased cost, and hospital stays (48). Therefore, in the context of postoperative pulmonary complications and recovery of early respiratory system function, we considered it necessary to compare MIVS with FS.
In this meta-analysis, we analyzed data of 10,194 patients (5,097 [50%] vs. 5,097 [50%] patients in MIVS vs. FS groups, respectively), from 30 studies (6 RCTs and 24 PSM studies) to evaluate postoperative pulmonary functions status and pulmonary complications after MIVS vs. FS. We also assessed early mortality, CPB time, aortic cross-clamp time, procedure time, and need for blood transfusion between the MIVS and FS. Using the best available level of evidence based on RCTs and PSM studies, our meta-analysis added to the literature that the MIVS is safe and had a significantly reduced overall incidence of postoperative pulmonary complications and respiratory insufficiency and decreased mechanical ventilation time compared with FS.
Moreover, the overall findings for the secondary outcomes suggested that MIVS, both aortic and mitral, significantly reduced early mortality and blood transfusion requirements. To the best of our knowledge, no previous meta-analyses have indicated whether the incidence of pulmonary complications is lower after MIVS compared with FS. Most studies that describe the effect of cardiac surgery on pulmonary complications were related to patients who underwent a coronary bypass operation through full median sternotomy (49).
It has been reported that the MIVS showed better preserved early postoperative respiratory function status and reduced the time needed to make a full recovery of pulmonary status compared with FS (50). However, there has not been explained this improved respiratory function in the MIVS group so far. This study found that patients undergoing MIVS had a reduced incidence of postoperative pulmonary complications and better postoperative respiratory function outcomes than patients undergoing valve surgery via full median sternotomy. Therefore, we believe that our finding of a reduced incidence of pulmonary complications after the MIVS group may explain the improved lung function than patients with a full median sternotomy. As a result, we believe these phenomena are more likely caused by preserving the chest wall's integrity and reduced surgical trauma. Because of their improved respiratory condition, patients could begin mobilization quicker and perform pulmonary bronchial tree ventilation and cleaning more adequately.
Several risk factors may influence the impairment of spirometry and change in pulmonary gas exchange after cardiac surgery performed via a sternotomy; these include surgical trauma, prolonged operative and CPB time (6,12,14,51). CPB causes an inflammatory cascade of compounds associated with the systemic inflammatory syndrome due to blood interaction with the CPB circuit and decreased pulmonary regeneration, mostly because of insufficient surfactant release triggered by poor perfusion of the alveolar epithelium during CPB (49). Because of the more technical problem, patients in the MIVS group had a longer mean CPB duration than those in the FS group. However, we believe that this variation has no influence impact on postoperative pulmonary complications.
However, if CPB duration were the underlying cause, we would predict the MIVS group to have more significant postoperative pulmonary complications. This study found that patients who underwent MIVS had significantly longer cardiopulmonary bypass time, which may have contributed to the lower number of pulmonary complications observed in this group. A randomized clinical trial would be the only approach to analyze the influence of these independent factors on the incidence of postoperative pulmonary problems. MIVS did not result in an adverse postoperative pulmonary complication.
It is likely that patients in whom the MIVS approach was used tended to have better early recovery and more favorable improvement of postoperative pulmonary function because of the shorter mechanical ventilation time, preservation of the chest wall integrity, and reduced postoperative pain, as compared with FS (50,52,53). Previous studies drew a similar conclusion to ours: there is less impaired respiratory function among patients who underwent surgery using the MIVS approach (11).
However, other investigators found no significant differences between the MIVS and FS regarding postoperative respiratory function system improvement (14,15,36,54).
Moreover, we found that patients who underwent MIVS had a significant reduction in the incidence of early mortality (1.2%) compared with FS (1.9%). This finding was in line with that of previously published studies. A study by Mark et al. (30), who analyzed 477 PSM patients who underwent MIVS or FS, showed   (26,34) reported on 2,103 and 2,689 patients, respectively, in PSM analyses that compared minimally invasive to conventional aortic valve surgery. They reported a significantly lower incidence of the need for blood transfusion, as well as respiratory insufficiency in MIVS patients. Similarly, we found that the number of patients who required blood transfusion and the number of units of RBC required for transfusion were significantly reduced in MIVS than in FS.
Our observations provide evidence for the value of MIVS as an acceptable alternative option to traditional FS for patients at higher risk of developing pulmonary complications and for patients with chronic lung  disease and chronic obstructive pulmonary disease undergoing mitral or/and aortic valve operations (12,56).
Nevertheless, our study has certain limitations. Most studies did not report similar outcomes, and there was limited information about the pulmonary effects of MIVS. Follow-up for most studies was limited; hence, we were unable to compare long-term results.

CONCLUSIONS
Based on the above findings in our meta-analysis, MIVS, both mitral and aortic, seem to provide better clinical and surgical outcomes than FS, particularly the benefits of early recovery of postoperative respiratory system functions and reduced incidence of postoperative pulmonary complications. Moreover, MIVS was not associated with an increased incidence of early mortality or a greater need for blood transfusion than FS. We believe that our findings might help surgeons in patient selection, particularly when dealing with patients with a high risk of pulmonary disease undergoing cardiac valve surgical repair or replacement. Finally, further studies comparing MIVS and FS are recommended to validate our findings.

DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.