Endoscopic Minimally Invasive Approach Versus Median Sternotomy for Multiple-Valve Surgery: A Propensity-Matched Analysis
 

Minimally invasive techniques in cardiac surgery constitute the state of art in the field of heart surgery offering an alternative to traditional surgery through a total sternotomy and can be applied in a wide spectrum of different procedures including coronary revascularization surgery, valve surgery, aortic surgery, as well as surgery of congenital malformations and anatomical abnormalities . Minimally invasive valve surgery (MIVS) has better postoperative outcomes than the traditional median sternotomy (MS) for single-valve disease in terms of cosmesis, respiratory functions, blood product use, and a lower overall cost . MIVS is now used safely in multiple centers around the world for isolated aortic valve , mitral valve , and tricuspid valve surgeries . Moreover, minimally invasive approaches to multiple-valve surgery (MIMVS) have also been described as feasible and safe . However, limited comparative data assessing the safety and feasibility of the minimally invasive approach to multiple-valve surgeries compared with MS is available through the current literature . There are several techniques for MIVS, including among others right anterior mini-thoracotomy (RAMT), partial upper sternotomy, and robot-assisted surgery . This study aims to present our experience with endoscopic MIMVS via RAMT, evaluate its early outcomes compared with those of the traditional approach, and emphasize its advantages and disadvantages over MS. 

Ethical Approval The study was approved by the respective institutional review boards (Medical Association of North Rhine number 82/2021, local ethics board of the University of Bonn number 169/20). Individual patient consent for the study was waived. Study Design The electronic records of all patients who underwent combined multiple-valve surgeries at two cardiac referral centers in Germany (Siegburg Heart Center and Bonn Heart Center) from March of 2017 to March of 2023 were retrospectively reviewed for this study. Multiple-valve surgery was defined as any surgery involving more than one valve including combined mitral and tricuspid valve procedures. All perioperative data were prospectively collected from the clinic’s internal databases, archived patient files and examination results from referring clinics or practices, and electronically filed and catalogued in the electronic patient record database during the patient’s hospital stay; thus no missing data was encountered. The choice of a minimally invasive access rather than a median sternotomy was based on an individual assessment of the patient’s characteristics, associated comorbidities, and anatomical conditions. The patient’s informed preference and the surgeon’s experience were also considered. Prior to the surgery, computed tomography angiography of the aorta and arterial vascular system was performed, and the possibility of a minimally invasive approach was excluded in cases of severe aortic and pelvic artery calcifications, severe anatomical abnormalities, e.g., pronounced severe sternum excavatum, or strong adhesions of the lungs. Patients with extensive endocarditis were also excluded. All patients undergoing multiple-valve surgery were otherwise selected for a minimally invasive procedure. A total of 317 consecutive patients undergoing surgery for double or triple valve disease were included. Procedures with concomitant coronary artery bypass grafting and ascending aortic surgery were excluded. However, concomitant procedures such as left atrial appendage (LAA) ligature/clipping, atrial septal defect (ASD) or ventricular septal defect (VSD) closure, and cryomaze were included in the study. The patients were divided into MIMVS group, patients who underwent valve surgery via an endoscopic minimally invasive approach, and MS group for the valve surgeries via median sternotomy. Preoperative baseline characteristics of the patients between the two groups were then investigated and analyzed. Operative Techniques All patients were placed on the operating table in the supine position. Intubation was then performed following the induction of general anesthesia, using a single-lumen endotracheal tube. To monitor the heart and valve functions perioperatively, a transesophageal echocardiography (TEE) was used. Endoscopic MIMVS group Early in our experience with minimally invasive surgery, cannulation of the femoral vessels for cardiopulmonary bypass (CPB) in the endoscopic group was done surgically. Since January 2019, however, peripheral cannulation was achieved percutaneously while femoral artery closure was performed with the use of the MANTA vascular closure device (Essential Medical Inc., Malvern, Pennsylvania, PA, USA). Detailed steps of both surgical and percutaneous femoral cannulations were previously published . In the minimally invasive group, a single RAMT was used for surgical access. For surgeries involving the aortic valve, it consists of a small incision 3–4 cm long at the level of the second or third intercostal space, placed 2 cm to the right of the sternal border without dislocating or resecting the ribs or the cartilage junction. RAMT was otherwise achieved using either a small incision at the level of the fourth intercostal space or using a periareolar incision (nipple-cut). The pleural space was accessed laterally following a careful dissection of the intercostal tissue preserving the right internal thoracic vessels. Exposure of the surgical field was then aided with a soft tissue retractor (Valve Gate ® Soft Tissue Protector, Geister, Germany). Pericardiotomy followed above the phrenic nerve while a three-dimensional (3D) camera port (Aesculap Einstein Vision, Tuttlingen, Germany) is placed through a 10-mm incision in the intercostal space above the main incision. A small 5-mm incision for the Chitwood clamp (Scanlan International, Inc, St Paul, MN, USA) was then performed laterally to the camera port incision. CO 2 was then infused through the 3D camera port. A long cardioplegia catheter (Medtronic DLP 9F, Ref 10012) was placed in the ascending aorta and secured with a polypropylene purse string suture. The left ventricular vent was inserted in the right upper pulmonary vein after a polypropylene purse string suture. After aortic clamping and administration of crystalloid cardioplegia (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany), normothermic CPB was achieved. Depending on the procedure required, the concerned valves were then operated on, and in all cases, the aortotomy and/or the atrial incisions were closed in two layers. After the heart was de-aired, ventricular pacing wires were placed prior to declamping the aorta and the patient was then gradually weaned from CPB. Protamine/heparin was administered in a 1:1 ratio, and TEE was used to assess valvular function. Decannulation was then achieved by either slowly removing the arterial and venous cannulas from the groin followed by soft tissue and skin closure with resorbable sutures in case of surgical femoral access, or with the use of the MANTA system in case of a percutaneous approach. A pleural drain was placed through the clamp incision, the ribs were then secured, and the wound was finally closed in layers. MS group In the MS group, a standard median sternotomy was performed. In aortic valve surgery, CPB was initiated after a direct cannulation of the ascending aorta and the right atrium. Double cannulation of the superior and inferior vena cava was used when the mitral and/or tricuspid valves were involved. Antegrade Calafiore cardioplegia was administered using an aortic vent catheter, and then directly into the coronary ostia in case of aortic regurgitation. The remaining surgical steps were performed in standard fashion. Concomitant procedures When a concomitant left atrial cryoablation was performed, the Complete Left-Atrial Cox-Maze III Lesion Set was used with three lesion lines: superior pulmonary vein–inferior pulmonary vein, and superior pulmonary vein–LAA, inferior pulmonary vein–LAA. Atrial septal defect repair was done with either a simple PFO stitch or using a patch implantation. Variables The primary outcome was operation-related mortality, which was defined as inhospital mortality occurring within 30 postoperative days. Secondary endpoints were inhospital mortality of any cause and inhospital morbidity, which was defined as the occurrence of stroke, delirium, acute kidney injury, new-onset atrial fibrillation, atrioventricular block (AVB) requiring a temporary pacemaker (PM), low cardiac output syndrome (LCOS), number of procedure-related wound revision, and respiratory insufficiency requiring invasive management, namely prolonged intubation (≥ 24 h) and tracheostomy. Other outcome variables included were CPB time and aortic cross clamping (AoX) time for the intraoperative parameters, as well as nights spent in the intensive care unit (ICU), total postoperative hospital stay, number of re-exploration for intrathoracic bleeding, number of packed red blood cells (pRBC) transfused per patient, number of patients requiring transfusions, and patient discharge destination, namely whether a patient required rehabilitation (discharged to a rehabilitation center or another clinic) or were discharged home directly. Statistical Analysis Continuous variables were represented as mean ± standard deviation (SD) or as median (interquartile range) depending on the normality of their distribution. The latter was analyzed using inspection of the QQ plot and the Shapiro–Wilk normality test. The interquartile range (IQR) was expressed as an interval. Categorical variables were reported as counts and their respective percentages N . Prior to propensity matching, continuous outcome variables were compared with the non-parametric Mann–Whitney test. Pearson’s χ 2 test and Fisher’s exact test were used for comparing categorical outcomes between the two study groups where appropriate, depending on whether the minimum expected assumption was met. In all cases, a two-tailed p value of less than 0.05 was considered statistically significant. In order to take into account possible treatment bias due to confounding factors, propensity score matching was performed. The propensity score for each patient was calculated by logistic regression with adjustment for 13 key baseline variables: age, female sex, body mass index (BMI), New York Heart Association classification (NYHA) ≥ 3, hypertension, diabetes, endocarditis, nonelective surgery, heart failure, Euroscore II, three concomitant valve operation, previous heart surgery, peripheral artery disease, and coronary artery disease. Patients were matched using a 1 to 1 nearest neighbor propensity score matching without replacement with a caliper of 0.12. Standardized mean difference (SMD) was used instead of p values to assess the balance between the two groups . After matching, all SMD values for the covariates were below 0.1. A love plot of absolute standardized mean differences is shown in Fig. and a jitter plot of the propensity scores in Fig. . Comparisons between the two matched groups were carried out using either a paired t test or the Wilcoxon signed rank sum test for continuous variables, depending on the normality of their distribution, and binary categorical variables were compared using McNemar’s mid- p test while the Bhapkar test was used for categorical variables with more than two outcomes. All statistical analyses were performed using the R statistical software (R Foundation for Statistical Computing, Vienna, Austria). The MatchIt package was used for propensity score matching . 

The study was approved by the respective institutional review boards (Medical Association of North Rhine number 82/2021, local ethics board of the University of Bonn number 169/20). Individual patient consent for the study was waived. 

The electronic records of all patients who underwent combined multiple-valve surgeries at two cardiac referral centers in Germany (Siegburg Heart Center and Bonn Heart Center) from March of 2017 to March of 2023 were retrospectively reviewed for this study. Multiple-valve surgery was defined as any surgery involving more than one valve including combined mitral and tricuspid valve procedures. All perioperative data were prospectively collected from the clinic’s internal databases, archived patient files and examination results from referring clinics or practices, and electronically filed and catalogued in the electronic patient record database during the patient’s hospital stay; thus no missing data was encountered. The choice of a minimally invasive access rather than a median sternotomy was based on an individual assessment of the patient’s characteristics, associated comorbidities, and anatomical conditions. The patient’s informed preference and the surgeon’s experience were also considered. Prior to the surgery, computed tomography angiography of the aorta and arterial vascular system was performed, and the possibility of a minimally invasive approach was excluded in cases of severe aortic and pelvic artery calcifications, severe anatomical abnormalities, e.g., pronounced severe sternum excavatum, or strong adhesions of the lungs. Patients with extensive endocarditis were also excluded. All patients undergoing multiple-valve surgery were otherwise selected for a minimally invasive procedure. A total of 317 consecutive patients undergoing surgery for double or triple valve disease were included. Procedures with concomitant coronary artery bypass grafting and ascending aortic surgery were excluded. However, concomitant procedures such as left atrial appendage (LAA) ligature/clipping, atrial septal defect (ASD) or ventricular septal defect (VSD) closure, and cryomaze were included in the study. The patients were divided into MIMVS group, patients who underwent valve surgery via an endoscopic minimally invasive approach, and MS group for the valve surgeries via median sternotomy. Preoperative baseline characteristics of the patients between the two groups were then investigated and analyzed. 

All patients were placed on the operating table in the supine position. Intubation was then performed following the induction of general anesthesia, using a single-lumen endotracheal tube. To monitor the heart and valve functions perioperatively, a transesophageal echocardiography (TEE) was used. Endoscopic MIMVS group Early in our experience with minimally invasive surgery, cannulation of the femoral vessels for cardiopulmonary bypass (CPB) in the endoscopic group was done surgically. Since January 2019, however, peripheral cannulation was achieved percutaneously while femoral artery closure was performed with the use of the MANTA vascular closure device (Essential Medical Inc., Malvern, Pennsylvania, PA, USA). Detailed steps of both surgical and percutaneous femoral cannulations were previously published . In the minimally invasive group, a single RAMT was used for surgical access. For surgeries involving the aortic valve, it consists of a small incision 3–4 cm long at the level of the second or third intercostal space, placed 2 cm to the right of the sternal border without dislocating or resecting the ribs or the cartilage junction. RAMT was otherwise achieved using either a small incision at the level of the fourth intercostal space or using a periareolar incision (nipple-cut). The pleural space was accessed laterally following a careful dissection of the intercostal tissue preserving the right internal thoracic vessels. Exposure of the surgical field was then aided with a soft tissue retractor (Valve Gate ® Soft Tissue Protector, Geister, Germany). Pericardiotomy followed above the phrenic nerve while a three-dimensional (3D) camera port (Aesculap Einstein Vision, Tuttlingen, Germany) is placed through a 10-mm incision in the intercostal space above the main incision. A small 5-mm incision for the Chitwood clamp (Scanlan International, Inc, St Paul, MN, USA) was then performed laterally to the camera port incision. CO 2 was then infused through the 3D camera port. A long cardioplegia catheter (Medtronic DLP 9F, Ref 10012) was placed in the ascending aorta and secured with a polypropylene purse string suture. The left ventricular vent was inserted in the right upper pulmonary vein after a polypropylene purse string suture. After aortic clamping and administration of crystalloid cardioplegia (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany), normothermic CPB was achieved. Depending on the procedure required, the concerned valves were then operated on, and in all cases, the aortotomy and/or the atrial incisions were closed in two layers. After the heart was de-aired, ventricular pacing wires were placed prior to declamping the aorta and the patient was then gradually weaned from CPB. Protamine/heparin was administered in a 1:1 ratio, and TEE was used to assess valvular function. Decannulation was then achieved by either slowly removing the arterial and venous cannulas from the groin followed by soft tissue and skin closure with resorbable sutures in case of surgical femoral access, or with the use of the MANTA system in case of a percutaneous approach. A pleural drain was placed through the clamp incision, the ribs were then secured, and the wound was finally closed in layers. MS group In the MS group, a standard median sternotomy was performed. In aortic valve surgery, CPB was initiated after a direct cannulation of the ascending aorta and the right atrium. Double cannulation of the superior and inferior vena cava was used when the mitral and/or tricuspid valves were involved. Antegrade Calafiore cardioplegia was administered using an aortic vent catheter, and then directly into the coronary ostia in case of aortic regurgitation. The remaining surgical steps were performed in standard fashion. Concomitant procedures When a concomitant left atrial cryoablation was performed, the Complete Left-Atrial Cox-Maze III Lesion Set was used with three lesion lines: superior pulmonary vein–inferior pulmonary vein, and superior pulmonary vein–LAA, inferior pulmonary vein–LAA. Atrial septal defect repair was done with either a simple PFO stitch or using a patch implantation. 

The primary outcome was operation-related mortality, which was defined as inhospital mortality occurring within 30 postoperative days. Secondary endpoints were inhospital mortality of any cause and inhospital morbidity, which was defined as the occurrence of stroke, delirium, acute kidney injury, new-onset atrial fibrillation, atrioventricular block (AVB) requiring a temporary pacemaker (PM), low cardiac output syndrome (LCOS), number of procedure-related wound revision, and respiratory insufficiency requiring invasive management, namely prolonged intubation (≥ 24 h) and tracheostomy. Other outcome variables included were CPB time and aortic cross clamping (AoX) time for the intraoperative parameters, as well as nights spent in the intensive care unit (ICU), total postoperative hospital stay, number of re-exploration for intrathoracic bleeding, number of packed red blood cells (pRBC) transfused per patient, number of patients requiring transfusions, and patient discharge destination, namely whether a patient required rehabilitation (discharged to a rehabilitation center or another clinic) or were discharged home directly. 

Continuous variables were represented as mean ± standard deviation (SD) or as median (interquartile range) depending on the normality of their distribution. The latter was analyzed using inspection of the QQ plot and the Shapiro–Wilk normality test. The interquartile range (IQR) was expressed as an interval. Categorical variables were reported as counts and their respective percentages N . Prior to propensity matching, continuous outcome variables were compared with the non-parametric Mann–Whitney test. Pearson’s χ 2 test and Fisher’s exact test were used for comparing categorical outcomes between the two study groups where appropriate, depending on whether the minimum expected assumption was met. In all cases, a two-tailed p value of less than 0.05 was considered statistically significant. In order to take into account possible treatment bias due to confounding factors, propensity score matching was performed. The propensity score for each patient was calculated by logistic regression with adjustment for 13 key baseline variables: age, female sex, body mass index (BMI), New York Heart Association classification (NYHA) ≥ 3, hypertension, diabetes, endocarditis, nonelective surgery, heart failure, Euroscore II, three concomitant valve operation, previous heart surgery, peripheral artery disease, and coronary artery disease. Patients were matched using a 1 to 1 nearest neighbor propensity score matching without replacement with a caliper of 0.12. Standardized mean difference (SMD) was used instead of p values to assess the balance between the two groups . After matching, all SMD values for the covariates were below 0.1. A love plot of absolute standardized mean differences is shown in Fig. and a jitter plot of the propensity scores in Fig. . Comparisons between the two matched groups were carried out using either a paired t test or the Wilcoxon signed rank sum test for continuous variables, depending on the normality of their distribution, and binary categorical variables were compared using McNemar’s mid- p test while the Bhapkar test was used for categorical variables with more than two outcomes. All statistical analyses were performed using the R statistical software (R Foundation for Statistical Computing, Vienna, Austria). The MatchIt package was used for propensity score matching . 

Between March of 2017 and March of 2023, a total of 317 patients underwent multiple-valve surgeries, 123 (38.8%) were endoscopic MIMVS and 194 (61.2%) were performed via MS. Patient and Procedure Characteristics Prior to Propensity Score Matching Across both groups before matching, 167 (52.7%) patients were female, median age was 69 [61–75] years, and the median BMI was 26.12 [23.77–29.32] kg/m 2 . Fifty-three (16.7%) patients had undergone previous cardiac surgery and 86.1% of patients had a NYHA classification III or IV. The baseline characteristics of both groups prior to matching are summarized in Table . Within the endoscopic MIMVS group, 18 (14.6%) cases were non-elective, which was defined as cases that were not urgent or emergent. The most prevalent procedure was concomitant mitral valve and tricuspid valve repair, followed by mitral valve replacement associated with a tricuspid valve repair, with totals of 47 (38.2%) and 34 (27.6%), respectively. Associated LAA closure, cryoablation, ASD repair, and VSD repair were represented in 9 (7.3%), 18 (14.6%), 8 (6.5%), and 2 (1.6%) cases, respectively. One ASD repair was done using a patch. In the MS group, 49 (25.3%) patients received a non-elective surgery. Mitral valve and aortic valve replacement accounted for the most carried out operation, followed by concomitant aortic valve replacement and mitral valve repair, with totals of 75 (38.7%) and 33 (17%), respectively. Concomitant LAA closure, cryoablation, ASD repair, and VSD repair occurred with 8 (4.1%), 8 (4.1%), 10 (5.2%), and 4 (2.1%) patients, respectively. One ASD repair was done using a patch. Other procedural details as well as grafted valve types for both groups are detailed in Tables and . Patient and Procedure Characteristics of Matched Groups Balance between the two groups after propensity matching was assessed using absolute mean standardized differences. Patient characteristics of the overall matched population as well as both groups, MIMVS and MS, are summarized in Table . There was no significant imbalance between both groups except for the prevalence of atrial fibrillation and renal failure, which were present in 64.3% and 4.5% of patients in the MIMVS group, respectively, in contrast with 46.4% and 8% of patients of the MS group, respectively (SMD = 0.365 and 0.148 for atrial fibrillation and renal failure, respectively). Procedural details as well as grafted valve types for both groups are detailed in Tables and . Outcomes Prior to Propensity Score Matching Intraoperative and postoperative outcomes prior to propensity score matching are summarized in Table . Primary Endpoint: 30-Day Mortality Within the endoscopic MIMVS group, operation-related mortality, defined as inhospital mortality within 30 days postoperatively, occurred in 9 (7.3%) cases, which was non-significantly lower than in the median sternotomy group with 28 (14.4%) cases ( p = 0.055). Secondary Endpoints Inhospital mortality of any cause and at any time within the duration of hospitalization was also less prevalent in the endoscopic minimally invasive group than in the sternotomy group, with 11 (8.9%) versus 31 (16%) occurrences, respectively. This difference was, however, also statistically non-significant ( p = 0.07). Median CPB time and AoX time in the minimally invasive group were 106 [79–124.5] mins and 70 [53–80.5] mins, respectively, both longer than in the MS group but without statistical significance, where the respective durations were 100 [73–147] mins and 65 [48.25–95] mins ( p = 0.97 for CPB time and p = 0.81 for AoX time). Regarding postoperative inhospital morbidity, there were no statistically significant differences between the endoscopic MIMVS group and the MS group in the occurrences of stroke (2.4% vs 3.1%, respectively), delirium (4.9% vs 10.3%, respectively), acute kidney injury (5.7% vs 10.8%, respectively), new-onset atrial fibrillation (4.1% vs 4.6%, respectively), AVB requiring a temporary PM (0.8% vs 3.1%, respectively), LCOS (8.9% vs 7.2%, respectively), respiratory insufficiency (14.6% vs 12.4%, respectively), and wound revisions (3.3%). Median number of transfusions of pRBCs within the group of patients undergoing a mini-thoracotomy was 0 [0–3] transfusion, significantly lower than in the median sternotomy group, where the median was 1 [0–4], p = 0.014. The number of patients requiring transfusion of at least 1 unit of pRBCs was also statistically higher in the MS group, where 59.3% of patients received transfusions of pRBCs, versus 47.2% in the MIMVS group, with a p value of 0.035. Re-exploration for intrathoracic bleeding was only necessary in 1 (0.5%) patient from the MS group. ICU stay following the procedure was similar across both groups ( p = 0.75). Additionally, total hospital stay was also similar between the two groups, with a median stay of 12 [8–17.5] days in the MIMVS group, versus 13 [8.25–21] days for the MS group ( p = 0.36). Following hospitalization, patient discharge directly to their home was successful in more patients from the endoscopic minimally invasive group, with 53 (43.1%) patients versus 60 (30.9%). This difference was, however, not statistically significant ( p = 0.062). There was no incidence of repeat valve operations, paravalvular leak, or moderate to severe valve regurgitation across both groups. There was also no need for a conversion to sternotomy in all patients in the endoscopic MIMVS group. ECMO was required in 8.9% for the MIMVS group and 8.8% for the MS group, p = 0.56. All patients who required ECMO in both groups had an age above the average of the population of the study, as well as CPB times above the 75th percentile. Outcomes of Matched Groups Primary Endpoint: 30-Day Mortality Except for the median number of transfused pRBCs per patients (0 [0–3] units for MIMVS vs 1 [0–4.25] units for MS, p = 0.002), there were no statistically significant differences between the two groups after propensity score matching. Median CPB time in the MIMVS group was 105.5 [79.75–124] mins versus 98 [68.75–130.25] mins in the MS group ( p = 0.92). Similar results were also seen for aortic cross-clamping times (70 [53–80.25] mins vs 63.5 [46–90.25] mins in the MIMVS and MS groups, respectively, p = 0.76). Postoperative mortality within 30 days was still lower in the MIMVS group, albeit non-significantly, as was the overall inhospital mortality. All intraoperative and postoperative outcomes for the matched groups are summarized in Table . 

Across both groups before matching, 167 (52.7%) patients were female, median age was 69 [61–75] years, and the median BMI was 26.12 [23.77–29.32] kg/m 2 . Fifty-three (16.7%) patients had undergone previous cardiac surgery and 86.1% of patients had a NYHA classification III or IV. The baseline characteristics of both groups prior to matching are summarized in Table . Within the endoscopic MIMVS group, 18 (14.6%) cases were non-elective, which was defined as cases that were not urgent or emergent. The most prevalent procedure was concomitant mitral valve and tricuspid valve repair, followed by mitral valve replacement associated with a tricuspid valve repair, with totals of 47 (38.2%) and 34 (27.6%), respectively. Associated LAA closure, cryoablation, ASD repair, and VSD repair were represented in 9 (7.3%), 18 (14.6%), 8 (6.5%), and 2 (1.6%) cases, respectively. One ASD repair was done using a patch. In the MS group, 49 (25.3%) patients received a non-elective surgery. Mitral valve and aortic valve replacement accounted for the most carried out operation, followed by concomitant aortic valve replacement and mitral valve repair, with totals of 75 (38.7%) and 33 (17%), respectively. Concomitant LAA closure, cryoablation, ASD repair, and VSD repair occurred with 8 (4.1%), 8 (4.1%), 10 (5.2%), and 4 (2.1%) patients, respectively. One ASD repair was done using a patch. Other procedural details as well as grafted valve types for both groups are detailed in Tables and . 

Balance between the two groups after propensity matching was assessed using absolute mean standardized differences. Patient characteristics of the overall matched population as well as both groups, MIMVS and MS, are summarized in Table . There was no significant imbalance between both groups except for the prevalence of atrial fibrillation and renal failure, which were present in 64.3% and 4.5% of patients in the MIMVS group, respectively, in contrast with 46.4% and 8% of patients of the MS group, respectively (SMD = 0.365 and 0.148 for atrial fibrillation and renal failure, respectively). Procedural details as well as grafted valve types for both groups are detailed in Tables and . 

Intraoperative and postoperative outcomes prior to propensity score matching are summarized in Table . Primary Endpoint: 30-Day Mortality Within the endoscopic MIMVS group, operation-related mortality, defined as inhospital mortality within 30 days postoperatively, occurred in 9 (7.3%) cases, which was non-significantly lower than in the median sternotomy group with 28 (14.4%) cases ( p = 0.055). Secondary Endpoints Inhospital mortality of any cause and at any time within the duration of hospitalization was also less prevalent in the endoscopic minimally invasive group than in the sternotomy group, with 11 (8.9%) versus 31 (16%) occurrences, respectively. This difference was, however, also statistically non-significant ( p = 0.07). Median CPB time and AoX time in the minimally invasive group were 106 [79–124.5] mins and 70 [53–80.5] mins, respectively, both longer than in the MS group but without statistical significance, where the respective durations were 100 [73–147] mins and 65 [48.25–95] mins ( p = 0.97 for CPB time and p = 0.81 for AoX time). Regarding postoperative inhospital morbidity, there were no statistically significant differences between the endoscopic MIMVS group and the MS group in the occurrences of stroke (2.4% vs 3.1%, respectively), delirium (4.9% vs 10.3%, respectively), acute kidney injury (5.7% vs 10.8%, respectively), new-onset atrial fibrillation (4.1% vs 4.6%, respectively), AVB requiring a temporary PM (0.8% vs 3.1%, respectively), LCOS (8.9% vs 7.2%, respectively), respiratory insufficiency (14.6% vs 12.4%, respectively), and wound revisions (3.3%). Median number of transfusions of pRBCs within the group of patients undergoing a mini-thoracotomy was 0 [0–3] transfusion, significantly lower than in the median sternotomy group, where the median was 1 [0–4], p = 0.014. The number of patients requiring transfusion of at least 1 unit of pRBCs was also statistically higher in the MS group, where 59.3% of patients received transfusions of pRBCs, versus 47.2% in the MIMVS group, with a p value of 0.035. Re-exploration for intrathoracic bleeding was only necessary in 1 (0.5%) patient from the MS group. ICU stay following the procedure was similar across both groups ( p = 0.75). Additionally, total hospital stay was also similar between the two groups, with a median stay of 12 [8–17.5] days in the MIMVS group, versus 13 [8.25–21] days for the MS group ( p = 0.36). Following hospitalization, patient discharge directly to their home was successful in more patients from the endoscopic minimally invasive group, with 53 (43.1%) patients versus 60 (30.9%). This difference was, however, not statistically significant ( p = 0.062). There was no incidence of repeat valve operations, paravalvular leak, or moderate to severe valve regurgitation across both groups. There was also no need for a conversion to sternotomy in all patients in the endoscopic MIMVS group. ECMO was required in 8.9% for the MIMVS group and 8.8% for the MS group, p = 0.56. All patients who required ECMO in both groups had an age above the average of the population of the study, as well as CPB times above the 75th percentile. 

Within the endoscopic MIMVS group, operation-related mortality, defined as inhospital mortality within 30 days postoperatively, occurred in 9 (7.3%) cases, which was non-significantly lower than in the median sternotomy group with 28 (14.4%) cases ( p = 0.055). 

Inhospital mortality of any cause and at any time within the duration of hospitalization was also less prevalent in the endoscopic minimally invasive group than in the sternotomy group, with 11 (8.9%) versus 31 (16%) occurrences, respectively. This difference was, however, also statistically non-significant ( p = 0.07). Median CPB time and AoX time in the minimally invasive group were 106 [79–124.5] mins and 70 [53–80.5] mins, respectively, both longer than in the MS group but without statistical significance, where the respective durations were 100 [73–147] mins and 65 [48.25–95] mins ( p = 0.97 for CPB time and p = 0.81 for AoX time). Regarding postoperative inhospital morbidity, there were no statistically significant differences between the endoscopic MIMVS group and the MS group in the occurrences of stroke (2.4% vs 3.1%, respectively), delirium (4.9% vs 10.3%, respectively), acute kidney injury (5.7% vs 10.8%, respectively), new-onset atrial fibrillation (4.1% vs 4.6%, respectively), AVB requiring a temporary PM (0.8% vs 3.1%, respectively), LCOS (8.9% vs 7.2%, respectively), respiratory insufficiency (14.6% vs 12.4%, respectively), and wound revisions (3.3%). Median number of transfusions of pRBCs within the group of patients undergoing a mini-thoracotomy was 0 [0–3] transfusion, significantly lower than in the median sternotomy group, where the median was 1 [0–4], p = 0.014. The number of patients requiring transfusion of at least 1 unit of pRBCs was also statistically higher in the MS group, where 59.3% of patients received transfusions of pRBCs, versus 47.2% in the MIMVS group, with a p value of 0.035. Re-exploration for intrathoracic bleeding was only necessary in 1 (0.5%) patient from the MS group. ICU stay following the procedure was similar across both groups ( p = 0.75). Additionally, total hospital stay was also similar between the two groups, with a median stay of 12 [8–17.5] days in the MIMVS group, versus 13 [8.25–21] days for the MS group ( p = 0.36). Following hospitalization, patient discharge directly to their home was successful in more patients from the endoscopic minimally invasive group, with 53 (43.1%) patients versus 60 (30.9%). This difference was, however, not statistically significant ( p = 0.062). There was no incidence of repeat valve operations, paravalvular leak, or moderate to severe valve regurgitation across both groups. There was also no need for a conversion to sternotomy in all patients in the endoscopic MIMVS group. ECMO was required in 8.9% for the MIMVS group and 8.8% for the MS group, p = 0.56. All patients who required ECMO in both groups had an age above the average of the population of the study, as well as CPB times above the 75th percentile. 

Primary Endpoint: 30-Day Mortality Except for the median number of transfused pRBCs per patients (0 [0–3] units for MIMVS vs 1 [0–4.25] units for MS, p = 0.002), there were no statistically significant differences between the two groups after propensity score matching. Median CPB time in the MIMVS group was 105.5 [79.75–124] mins versus 98 [68.75–130.25] mins in the MS group ( p = 0.92). Similar results were also seen for aortic cross-clamping times (70 [53–80.25] mins vs 63.5 [46–90.25] mins in the MIMVS and MS groups, respectively, p = 0.76). Postoperative mortality within 30 days was still lower in the MIMVS group, albeit non-significantly, as was the overall inhospital mortality. All intraoperative and postoperative outcomes for the matched groups are summarized in Table . 

Except for the median number of transfused pRBCs per patients (0 [0–3] units for MIMVS vs 1 [0–4.25] units for MS, p = 0.002), there were no statistically significant differences between the two groups after propensity score matching. Median CPB time in the MIMVS group was 105.5 [79.75–124] mins versus 98 [68.75–130.25] mins in the MS group ( p = 0.92). Similar results were also seen for aortic cross-clamping times (70 [53–80.25] mins vs 63.5 [46–90.25] mins in the MIMVS and MS groups, respectively, p = 0.76). Postoperative mortality within 30 days was still lower in the MIMVS group, albeit non-significantly, as was the overall inhospital mortality. All intraoperative and postoperative outcomes for the matched groups are summarized in Table . 

Video-assisted RAMT has been shown to be a safe and feasible minimally invasive approach for multiple-valve surgeries . However, the current literature lacks comparative data assessing the feasibility and safety of a totally endoscopic access versus the more conventional median sternotomy  RAMT is achieved through a small 3–5-cm incision, and the minimal invasiveness of this technique compared with a full sternotomy offers the advantage of a smaller operational scar and minimal postoperative pain, leading to a more favorable patient satisfaction . Re-exploration for Bleeding and Transfusion Requirements Aside from the better cosmesis, the smaller incision should also have a favorable effect on postoperative bleeding and blood product requirements , although these reports are mainly based on results from studies concerning single-valve minimally invasive surgeries. Blood transfusions have previously been linked to an increased risk of postoperative morbidity and mortality in patients undergoing heart surgeries, including a longer hospital stay and increased costs . When compared with full sternotomy, our study showed that endoscopic MIMVS was associated with a lower need for pRBC transfusions, and no difference in the need for a re-exploration surgery for bleeding. According to similar, albeit limited in number, comparative studies in the current literature, the favorable effect of MIMVS on transfusion requirements and re-exploration for bleeding is somewhat controversial. Atik et al. found similar transfusion rates and returns to the operation room for bleeding between the minimally invasive group and the median sternotomy group . In a study comparing the outcomes RAMT to re-sternotomy in mitral and tricuspid valve surgeries with previous sternotomies, Miura et al. also reported no difference in the number of transfusions between the two groups, as well as similar incidences of postoperative major complications, which included reoperation for bleeding . Indeed, another study comparing the outcomes of video-assisted RAMT for double valve surgeries to those of MS done by Qiao et al. showed a statistically significant lower amount of thoracic drainage in their study group comprising patients who underwent MIMVS, as well as no reoperation for bleeding across both groups, which would agree with the findings of our current study, although they did not report the number of required transfusions . Additionally, our findings concur with those of a propensity matched comparative study done by Zhao et al. . ICU and Hospital Lengths of Stay, and Rehabilitation Requirements Minimally invasive cardiac valve operations were previously shown to be associated with similar lengths of ICU stay and hospitalization, if not more favorable, compared with median sternotomy, as well as a decreased need for rehabilitation services following patient discharge . It has been proposed that this has the effect of lowering the overall costs of cardiac valve operations in association with a less traumatic surgical access and more cosmetic incisions . Our current series showed that patients who underwent endoscopic MIMVS had a comparable postoperative ICU stay as those in the MS group, as well as similar hospitalization duration. Within the current literature, similar comparative studies report comparable results regarding ICU length of stay and hospitalization duration . Atik et al. reported shorter ICU and hospital stay within the MIMVS group compared with the MS group overall, but there was no significant difference within the propensity matched patients, which would align with our findings. The same results were reported in a recent propensity matched retrospective study done by Paparella et al., which evaluated the outcomes of MIMVS compared with MS in concomitant mitral and tricuspid valve surgeries . In a retrospective study by Gumus et al. comparing RAMT and MS for multiple-valve surgery, both ICU and hospital stays were reported to be not significantly shorter in the MIMVS group . Similar results were also reported by Miura et al. . Data regarding rehabilitation requirements and cost-effectiveness of a minimally invasive approach has previously been reported for single-valve surgeries ; however, data is still lacking with regards to multiple-valve surgeries in comparison with median sternotomy. Respiratory Insufficiency and Invasive Respiratory Support Concerns for respiratory insufficiency following minimally invasive valve operations arise because they have been associated with longer operative times, as well as the risks associated with general anesthesia and mechanical ventilation . However, minimally invasive valve surgeries have an improved respiratory outcome for single valves . This can be in part be attributed to the preserved stability of the sternum and the improved pain score associated with the smaller surgical access . Our results show, however, that MIMVS was not associated with higher rates of respiratory insufficiency postoperatively, requiring invasive interventions or otherwise when compared with MS for multiple concomitant valve surgeries, both prior to and following propensity matching. These results are in line with other similar studies in the literature, which report similar rates of prolonged ventilation or respiratory insufficiency across both groups . Cardiopulmonary Bypass and Aortic Cross Clamping Time Prolonged AoX and CPB times are independent risk factors for postoperative morbidity, including acute kidney injury, as well as mortality in low- and high-risk patients undergoing minimally invasive heart surgeries . Furthermore, retrograde CPB presents an increased risk for stroke, delirium, and aortic dissection in contrast to anterograde CPB . Nonetheless, this current study showed similar rates of cerebrovascular events, delirium, and AKI across both groups, all of which resolved with either supportive treatment or spontaneously. This can be attributed to the fact that, even though the CPB and AoX times were slightly prolonged in the endoscopic MIMVS group without being statistically significant, median cross clamping time and IQR were still under 90 min. Reports by Al-Sarraf et al. indeed showed increased morbidity and mortality rates for AoX times of more than 90 min. While similar studies in the current literature have found an increase in CPB and AoX times for the minimally invasive groups, our findings did not show a statistically significant difference between MIMVS and MS for multiple-valve surgery . However, Atik et al. showed a decreased CPB time in the minimally invasive group. This can be explained by the different surgical techniques employed for the MIMVS, which consists of a right paramedian incision at the early stages of their study and later a partial upper sternotomy, instead of an endoscopic approach through right mini-thoracotomy . Mortality and Morbidity Mortality rates associated with minimally invasive valve surgeries are similar to those of conventional sternotomy . Furthermore, current studies comparing MIMVS specifically with MS also show similar mortality rates . Our findings are in agreement with these reports. Both early mortality, defined as mortality occurring within 30 days postoperatively, and overall mortality prior to patient discharge, were lower in the endoscopic MIMVS group than in the MS group in our study. However, the lower rate of 30-day mortality in the MIMVS group was not statistically significant for our sample, both before and after matching. This could be explained by the fact that the patients included in our study were operated on by a team that is skilled and experienced in the minimally invasive technique, while minimally invasive valve surgery has a notoriously steep learning curve. Additionally, our study was retrospective, and thus non-randomized, inherently subject to selection bias. Regarding other postoperative outcomes that could contribute to operative morbidity, our study showed similar incidences of LCOS, new onset atrial fibrillation, AVB requiring a PM, wound revisions, postoperative ECMO requirements, and coagulopathy, as well as pleural effusion and pneumothorax. These findings concur with the results of similar studies in the literature . However, Gumus et al. reported an increased incidence of delirium in the MIMVS group compared with the MS group , and Zhao et al. found an increased incidence of new-onset atrial fibrillation within patients in the MIMVS . 

Aside from the better cosmesis, the smaller incision should also have a favorable effect on postoperative bleeding and blood product requirements , although these reports are mainly based on results from studies concerning single-valve minimally invasive surgeries. Blood transfusions have previously been linked to an increased risk of postoperative morbidity and mortality in patients undergoing heart surgeries, including a longer hospital stay and increased costs . When compared with full sternotomy, our study showed that endoscopic MIMVS was associated with a lower need for pRBC transfusions, and no difference in the need for a re-exploration surgery for bleeding. According to similar, albeit limited in number, comparative studies in the current literature, the favorable effect of MIMVS on transfusion requirements and re-exploration for bleeding is somewhat controversial. Atik et al. found similar transfusion rates and returns to the operation room for bleeding between the minimally invasive group and the median sternotomy group . In a study comparing the outcomes RAMT to re-sternotomy in mitral and tricuspid valve surgeries with previous sternotomies, Miura et al. also reported no difference in the number of transfusions between the two groups, as well as similar incidences of postoperative major complications, which included reoperation for bleeding . Indeed, another study comparing the outcomes of video-assisted RAMT for double valve surgeries to those of MS done by Qiao et al. showed a statistically significant lower amount of thoracic drainage in their study group comprising patients who underwent MIMVS, as well as no reoperation for bleeding across both groups, which would agree with the findings of our current study, although they did not report the number of required transfusions . Additionally, our findings concur with those of a propensity matched comparative study done by Zhao et al. . 

Minimally invasive cardiac valve operations were previously shown to be associated with similar lengths of ICU stay and hospitalization, if not more favorable, compared with median sternotomy, as well as a decreased need for rehabilitation services following patient discharge . It has been proposed that this has the effect of lowering the overall costs of cardiac valve operations in association with a less traumatic surgical access and more cosmetic incisions . Our current series showed that patients who underwent endoscopic MIMVS had a comparable postoperative ICU stay as those in the MS group, as well as similar hospitalization duration. Within the current literature, similar comparative studies report comparable results regarding ICU length of stay and hospitalization duration . Atik et al. reported shorter ICU and hospital stay within the MIMVS group compared with the MS group overall, but there was no significant difference within the propensity matched patients, which would align with our findings. The same results were reported in a recent propensity matched retrospective study done by Paparella et al., which evaluated the outcomes of MIMVS compared with MS in concomitant mitral and tricuspid valve surgeries . In a retrospective study by Gumus et al. comparing RAMT and MS for multiple-valve surgery, both ICU and hospital stays were reported to be not significantly shorter in the MIMVS group . Similar results were also reported by Miura et al. . Data regarding rehabilitation requirements and cost-effectiveness of a minimally invasive approach has previously been reported for single-valve surgeries ; however, data is still lacking with regards to multiple-valve surgeries in comparison with median sternotomy. 

Concerns for respiratory insufficiency following minimally invasive valve operations arise because they have been associated with longer operative times, as well as the risks associated with general anesthesia and mechanical ventilation . However, minimally invasive valve surgeries have an improved respiratory outcome for single valves . This can be in part be attributed to the preserved stability of the sternum and the improved pain score associated with the smaller surgical access . Our results show, however, that MIMVS was not associated with higher rates of respiratory insufficiency postoperatively, requiring invasive interventions or otherwise when compared with MS for multiple concomitant valve surgeries, both prior to and following propensity matching. These results are in line with other similar studies in the literature, which report similar rates of prolonged ventilation or respiratory insufficiency across both groups . 

Prolonged AoX and CPB times are independent risk factors for postoperative morbidity, including acute kidney injury, as well as mortality in low- and high-risk patients undergoing minimally invasive heart surgeries . Furthermore, retrograde CPB presents an increased risk for stroke, delirium, and aortic dissection in contrast to anterograde CPB . Nonetheless, this current study showed similar rates of cerebrovascular events, delirium, and AKI across both groups, all of which resolved with either supportive treatment or spontaneously. This can be attributed to the fact that, even though the CPB and AoX times were slightly prolonged in the endoscopic MIMVS group without being statistically significant, median cross clamping time and IQR were still under 90 min. Reports by Al-Sarraf et al. indeed showed increased morbidity and mortality rates for AoX times of more than 90 min. While similar studies in the current literature have found an increase in CPB and AoX times for the minimally invasive groups, our findings did not show a statistically significant difference between MIMVS and MS for multiple-valve surgery . However, Atik et al. showed a decreased CPB time in the minimally invasive group. This can be explained by the different surgical techniques employed for the MIMVS, which consists of a right paramedian incision at the early stages of their study and later a partial upper sternotomy, instead of an endoscopic approach through right mini-thoracotomy . 

Mortality rates associated with minimally invasive valve surgeries are similar to those of conventional sternotomy . Furthermore, current studies comparing MIMVS specifically with MS also show similar mortality rates . Our findings are in agreement with these reports. Both early mortality, defined as mortality occurring within 30 days postoperatively, and overall mortality prior to patient discharge, were lower in the endoscopic MIMVS group than in the MS group in our study. However, the lower rate of 30-day mortality in the MIMVS group was not statistically significant for our sample, both before and after matching. This could be explained by the fact that the patients included in our study were operated on by a team that is skilled and experienced in the minimally invasive technique, while minimally invasive valve surgery has a notoriously steep learning curve. Additionally, our study was retrospective, and thus non-randomized, inherently subject to selection bias. Regarding other postoperative outcomes that could contribute to operative morbidity, our study showed similar incidences of LCOS, new onset atrial fibrillation, AVB requiring a PM, wound revisions, postoperative ECMO requirements, and coagulopathy, as well as pleural effusion and pneumothorax. These findings concur with the results of similar studies in the literature . However, Gumus et al. reported an increased incidence of delirium in the MIMVS group compared with the MS group , and Zhao et al. found an increased incidence of new-onset atrial fibrillation within patients in the MIMVS . 

This study has, however, several limitations, some of which are inherent to being a retrospective study, and thus non-randomized. Although propensity score matching was done to mitigate some of the treatment selection bias, the relatively small sample size limits the statistical power of our analyses. A larger multicenter prospective randomized trial is needed in the future. Furthermore, regarding the patients in the minimally invasive group, the MANTA vascular closure device was introduced mid-study in favor of an open surgical approach to femoral cannulation for cardiopulmonary bypass. The use of this percutaneous device at our institution was shown to have favorable outcomes with regards to morbidity and the length of stay in the ICU , when compared with the open surgical femoral access, and the inclusion of the patients who underwent a surgical femoral access for CPB in this study might have masked more favorable outcomes for the patients in the endoscopic MIMVS group, especially that within the patients who underwent a vascular closure through MANTA, there was no incidence of vascular closure device-related morbidity, including pseudoaneurysms, bleeding, or otherwise. Additionally, there was no follow-up as part of the study design. Finally, minimally invasive multiple-valve surgery is known to have a steep learning curve; however, the surgeons operating on the patients of this study are experienced in the totally endoscopic RAMT technique, which impacts further on the selection bias of our study, where patients selected for a median sternotomy were excluded from a minimally invasive approach as a result of contraindications and limitations that could not be taken into account when doing propensity matching. As a result of these inherent biases of our study, we cannot generalize the conclusions of our comparisons therein to a more general population. Although our present results reflect our experience with minimally invasive valve surgery at our institutions, performed by surgeons experienced in its techniques, the results of the comparisons with median sternotomy should be carefully considered. 

Endoscopic concomitant multiple-valve surgery through RAMT is a feasible, safe, and effective approach. This study shows that this approach for MIMVS is associated with low transfusion requirements, short hospital stay, and a low overall inhospital mortality and morbidity in selected patients. It was also associated with comparable CPB time and aortic cross clamping duration with MS, without increase in associated morbidities such as acute kidney injury or neurological events. 

