Systematic review and meta-analysis of the impact of sex on outcomes after aortic valve replacement.

AIMS: In recent years, extensive literature has been produced demonstrating inferior outcomes for women when compared with men undergoing heart valve interventions. Herein, we seek to analyze the literature comparing outcomes between men and women undergoing surgical aortic valve replacement (SAVR). METHODS: A systematic literature search of PubMed, MEDLINE, and Embase was conducted for articles comparing differences in outcomes between adult men and women undergoing SAVR. One thousand nine hundred and ninety titles were screened, of which 75 full texts were reviewed, and a total of 19 manuscripts met the inclusion criteria and were included in this review. RESULTS: Pooled estimates of mortality demonstrated that women tended to have lower rates of survival within the first 30 days post-SAVR, although mid-term and long-term mortality did not differ significantly up to 10 years postoperatively. Pooled estimates of postoperative data indicated no difference in the rates of stroke and postoperative bleeding. Rates of aortic valve reoperation and acute kidney injury favored women. CONCLUSION: Despite the inferior outcomes for women post-SAVR that have been reported in recent years, the results of this meta-analysis demonstrate comparable results between the sexes with comparable mid- to long-term mortality in data pooled from the literature. Although mortality favored men in the short term, rates of aortic valve reoperation and acute kidney injury favored women. Future investigation into this field should focus on identifying discrepancies in diagnosis and initial surgical management in order to address any potential factors contributing to discrepant short-term outcomes. GRAPHICAL ABSTRACT: http://links.lww.com/JCM/A651.

Teaching heart valve surgery techniques using simulators: a systematic review.

The apprentice model has traditionally been the primary method of teaching cardiac surgery trainees. Limitations of this model include insufficient time to learn all necessary skills, minimal exposure to rare cases and to complex repair techniques, small number of patients in small centres, high cost and absence of objective measures of feedback. In recent years, simulation-based training (SBT) has been used in order to address the gaps left by the apprentice model. We performed a systematic review of PubMed and Embase for articles investigating the use of SBT in teaching surgical valve techniques published in 2022 or earlier in order to summarize the current literature regarding the use of SBT for trainees learning surgical valve repair and replacement techniques. We compiled data on the impact of SBT on time to completion of tasks, proportion of trainees who committed technical errors, skills scores and theoretical knowledge. Studies in which outcomes were evaluated showed significant improvement in these measures after participation in SBT. Simulation-based training has been shown to improve the surgical skills of trainees in a rela-tively short period. As hands-on experience in the field of cardiac surgery is invaluable and often difficult to reproduce effectively, it is likely that a combination of hands-on training and SBT will be adopted moving forward to provide optimal exposure for surgical trainees.

Alternative Approaches to Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention, How Do They Compare?: A Systematic Review and Meta-Analysis.

Coronary artery disease (CAD) is a leading cause of mortality worldwide. Severe symptomatic CAD is treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Alternative CABG (ACABG) approaches including thoracotomy, off-pump, total endoscopic, and robotic-assisted CABG are increasing in prevalence to address the increased early risk of CABG. This systematic review and meta-analysis aims to review the contemporary literature comparing outcomes after ACABG and PCI. Pubmed, Medline, and Embase were systematically searched by 2 authors for articles comparing the outcomes after ACABG and PCI. A total of 1154 articles were screened, and 11 were included in this review. The RevMan 5.4 software was used to perform a meta-analysis of the pooled data. Individual studies found rates of long-term survival, major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and repeat revascularization either favored ACABG or did not differ significantly. Pooled estimates of the compiled data identified rates of MACCE, MI, and repeat revascularization favored ACABG. The results of this review demonstrated the favorable rates of long-term mortality, MACCE, MI, and repeat revascularization for ACABG in addition to similar short-term mortality and stroke when compared with PCI. Advancement of both CABG and PCI continues to improve patient outcomes. With the increasing prevalence of ACABG, similar studies will need to be undertaken with further direct comparisons between ACABG and PCI. Finally, hybrid revascularization should continue to be explored for its combined benefits of long-term outcomes, short-term safety, and ability to achieve complete revascularization.

The influence of renal disease on outcomes and cardiac remodeling following surgical mitral valve replacement.

OBJECTIVES: Chronic kidney disease (CKD) is increasingly prevalent in patients undergoing mitral valve replacement (MVR). While CKD is known to result in suboptimal outcomes for patients with mitral valve disease, there is limited literature evaluating the long-term outcomes and cardiac remodeling of patients with CKD undergoing MVR. We present the first analysis coupling long-term outcomes of combined morbidity, mortality, and cardiac remodeling post-MVR in patients with CKD. METHODS: Patients with varying degrees of CKD undergoing MVR from 2004 to 2018 were compared. Patients were grouped by estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73m2 (n = 109), 60-89 mL/min/1.73m2 (450), 30-59 mL/min/1.73m2 (449), < 30 mL/min/1.73m2 (60). The primary outcome was mortality. Secondary outcomes included measures of postoperative morbidity and cardiac remodeling. RESULTS: One-year mortality was significantly increased in patients with eGFR < 30 (p = 0.023). Mortality at 7 years was significantly increased in patients with eGFR < 30 mL/min/1.73m2 (p < 0.001). Multivariable regression analysis of 7-year all-cause mortality indicated an eGFR of 15 mL/min/1.73m2 (HR 4.03, 95% CI 2.54-6.40) and 30 mL/min/1.73m2 (HR 2.17 95% CI 1.55-3.05) were predictive of increased mortality. Reduced eGFR predicted the development of postoperative sepsis (p = 0.002), but not other morbidities. Positive cardiac remodeling of the left ventricle, left atrium, and valve gradients were identified postoperatively for patients with eGFR > 30 mL/min/1.73m2 while patients with eGFR < 30 mL/min/1.73m2 did not experience the same changes. CONCLUSIONS: CKD is predictive of inferior clinical and echocardiographic outcomes in patients undergoing MVR and consequently requires careful preoperative consideration and planning. Further investigation into optimizing the postoperative outcomes of this patient population is necessary.

Does sex impact outcomes after mitral valve surgery? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The published literature investigating the impact of sex on outcomes after mitral valve (MV) surgery has demonstrated inferior outcomes for females over males. However, the true relationship between sex and outcomes after MV surgery continues to be poorly understood. MATERIALS: PubMed, Medline, and Embase were systematically searched for articles published from 1 January 2005 to 1 August 2021. This systematic review included retrospective and prospective studies investigating the relationship between sex and outcomes after MV surgery. In all, 2068 articles were initially screened and 12 studies were included in this review. RESULTS: Few studies were adequately powered or structured to investigate this topic. Few studies propensity matched patients or isolated for surgical approach. In individual studies, females experienced increased rates of short-term and long-term mortality and increased 1-year mortality in the pooled data. Males experienced increased rates of required pacemaker insertion. The remaining rates of morbidity and mortality did not differ significantly between males and females. CONCLUSIONS: This review identified increased rates of 1-year mortality in the pooled data for females, while males had increased rates of pacemaker insertion. Despite this, the absence of propensity matching and isolating for surgical approach has introduced confounding variables that impair the ability of the included studies to interpret the results found in the current literature. Studies isolating for surgical approach, propensity matching patients, and examining outcomes with long-term follow-up are required to elucidate the true nature of this relationship.

Recellularized bovine pericardium with autologous mesenchymal stem cells reduces immune activation.

INTRODUCTION: Current bioprosthetic heart valve replacement options are limited by structural valvular deterioration (SVD) due to an immune response to the xenogenic scaffold. Autologous mesenchymal stem cell (MSC) recellularization is a method of concealing xenogenic scaffolds, preventing recipient immune recognition of xenogenic tissue heart valves, and potentially leading to reduction in SVD incidence. The purpose of this study is to examine the effects of autologous MSC recellularized tissue on the immune response of human whole blood to bovine pericardium (BP). We hypothesized that autologous MSC recellularization of BP will result in reduced pro-inflammatory cytokine production equivalent to autologous human pericardium. METHODS: Bone marrow, human pericardium, and whole blood were collected from adult patients undergoing elective cardiac surgery. Decellularized BP underwent recellularization with autologous MSCs, followed by co-incubation with autologous whole blood. Immunohistochemical, microscopic, and quantitative immune analysis approaches were used. RESULTS: We demonstrated that native BP, exposed to human whole blood, results in significant TNF-α and IL1ß production. When decellularized BP is recellularized with autologous MSCs and exposed to whole blood, there is a significant reduction in TNF-α and IL1ß production. Importantly, recellularized BP exposed to whole blood had similar production of TNF-α and IL1ß when compared to autologous human pericardium exposed to human whole blood. CONCLUSION: Our results suggest that preventing initial immune activation with autologous MSC recellularization may be an effective approach to decrease the recipient immune response, preventing recipient immune recognition of xenogeneic tissue engineered heart valves, and potentially leading to reduction in SVD incidence.

Pericardiectomy for Constrictive Pericarditis in a Young Patient With Erdheim-Chester Disease.

Erdheim-Chester Disease (ECD) is an extremely rare non-Langerhans histiocytosis that most often presents in the fifth to seventh decades of life. In this case report, we present a 34-year-old woman who underwent successful pericardiectomy for constrictive pericarditis secondary to ECD, which is the youngest reported patient with ECD to undergo pericardiectomy. (Level of Difficulty: Advanced.).

Mortality and morbidity of surgical and transcatheter mitral valve repair in octogenarians: A systematic review.

BACKGROUND: Valvular heart disease (VHD) is a prominent problem in healthcare today with mitral regurgitation (MR) being the leading cause of VHD in the elderly population. While mitral valve repair (MVr) surgery is one of the only options for the end-stage disease, octogenarians are often denied MVr due to concerns with operative mortality and postoperative morbidity. To provide information on this underrepresented group of surgical patients, a systematic approach was taken to review the mortality and morbidity rates of octogenarians who received MVr. METHODS: Pubmed and Medline were searched for articles containing outcomes of octogenarians receiving surgical mitral valve repair (SMVr) or transcatheter mitral valve repair (TMVr) published after 2000. Ten articles met the inclusion criteria for a total of 7968 patients included in the analysis using Microsoft Excel, Version 2105. RESULTS: Short-term mortality rates for SMVr and TMVr were 2.6% and 1.4% for in-hospital, and 7.8% and 3.3% for 30 days, respectively. The average incidence of stroke, acute kidney injury, infection, and major bleeding for SMVr were 3.2%, 11.2%, 7.7%, and 24%, respectively, and 0.3%, 6.7%, 2.7%, and 7.9% for TMVr, respectively. CONCLUSION: Octogenarians receiving SMVr or TMVr experienced similar rates of short-term mortality and morbidity as younger populations, and when considering life expectancy, midterm mortality was also similar. With these results, denying octogenarians MVr operations based on age alone should be reconsidered. Depending on risk factors and comorbidities, either SMVr or TMVr is a viable and relatively safe option for octogenarians with severe MR.

Coronary Artery Revascularization in Heart Transplant Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the primary cause of late mortality after heart transplantation. We look to provide a comprehensive review of contemporary revascularization strategies in CAV. METHODS: PubMed and Web of Science were systematically searched by 3 authors. 1,870 articles were initially screened and 24 were included in this review. RESULTS: PCI is the main revascularization technique utilized in CAV. The pooled estimates for restenosis significantly favored DES over BMS (OR 4.26; 95% CI: 2.54-7.13; p < 0.00001; I2 = 4%). There were insufficient data to quantitatively compare mortality following DES versus BMS. There was no difference in short-term mortality between CABG and PCI. In-hospital mortality was 0.0% for CABG and ranged from 0.0 to 8.34% for PCI. One-year mortality was 8.0% for CABG and 5.0-25.0% for PCI. CABG had a potential advantage at 5 years. Five-year mortality was 17.0% for CABG and ranged from 14 to 40.4% following PCI. Select measures of postoperative morbidity trended toward superior outcomes for CABG. CONCLUSION: In CAV, PCI is the primary revascularization strategy utilized, with DES exhibiting superiority to BMS regarding postoperative morbidity. Further investigation into outcomes following CABG in CAV is required to conclusively elucidate the superior management strategy in CAV.

Sex-Related Differences in Transcatheter Mitral Valve Repair: A Systematic Review and Meta-Analysis.

OBJECTIVE: Inequalities in postoperative outcomes between males and females are well described with females often experiencing inferior outcomes after heart valve surgery. The recent literature has demonstrated equivalent or improved outcomes for females after transcatheter aortic valve replacement. Transcatheter mitral valve repair (TMVr) and replacement (TMVR) is a relatively newer field with significantly less literature comparing sex differences. This systematic review and meta-analysis looks to provide a comprehensive summary of the published literature comparing outcomes between males and females undergoing transcatheter MV interventions. METHODS: PubMed, MEDLINE, and Scopus were systematically searched for all studies comparing outcomes between males and females undergoing TMVr and TMVR. A total of 2,178 English manuscript titles and abstracts were reviewed. Articles were excluded if data were not provided regarding sex differences, transcatheter MV intervention, full-length text was not accessible, or if insufficient data was provided. A total of 2,170 articles were excluded, and 8 articles were included in this study. RESULTS: Pooled estimates of outcomes demonstrated rates of acute kidney injury (OR 1.28 [95% CI, 1.14-1.44; p < 0.0001]) favored females, while rates of major bleeding favored males (OR 0.85 [95% CI 0.76-0.96; p = 0.01]). Rates of mortality, postoperative MI, and stroke did not differ significantly. CONCLUSION: A trend has emerged in heart valve interventions with males tending to have improved outcomes after surgical intervention and females experiencing equivalent or improved outcomes after transcatheter interventions. This meta-analysis identified increased rates of acute kidney injury for males, increased rates of major bleeding for females, and otherwise comparable morbidity and mortality in males and females undergoing TMVr.

Coronary Revascularization for Patients with Diabetes Mellitus: A Contemporary Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aims to review the contemporary literature comparing CABG and PCI in diabetic patients providing an up-to-date perspective on the differences between the interventions. BACKGROUND: Diabetes is common and diabetic patients are at a 2-to-4-fold increased risk of developing coronary artery disease. Approximately 75% of diabetic patients die of cardiovascular disease. Previous literature has identified CABG as superior to PCI for revascularization in diabetic patients with complex coronary artery diseas. METHODS: PubMed and Medline were systematically searched for articles published from January 1, 2015 to April 15, 2021. This systematic review included all retrospective, prospective, and randomized trial studies comparing CABG and PCI in diabetic patients. 1552 abstracts were reviewed and 25 studies were included in this review. The data was analyzed using the RevMan 5.4 software. RESULTS: Diabetic patients undergoing CABG experienced significantly reduced rates of 5-year mortality, major adverse cardiovascular and cerebrovascular events, myocardial infarction, and required repeat revascularization. Patients who underwent PCI experienced improved rates of stroke that trended toward significance. CONCLUSIONS: Previous literature regarding coronary revascularization in diabetic patients has consistently demonstrated superior outcomes for patients undergoing CABG over PCI. The development of 1st and 2nd generation DES have narrowed the gap between CABG and PCI, but CABG continues to be superior. Continued investigation with large randomized trials and retrospective studies including long term follow-up comparing CABG and 2nd generation DES is necessary to confirm the optimal intervention for diabetic patients.

Heart valve surgery and the obesity paradox: A systematic review.

Obesity has been associated with increased incidence of comorbidities and shorter life expectancy, and it has generally been assumed that patients with obesity should have inferior outcomes after surgery. Previous literature has often demonstrated equivalent or even improved rates of mortality after cardiac surgery when compared to their lower-weight counterparts, coined the obesity paradox. Herein, we aim to review the literature investigating the impact of obesity on surgical valve interventions. PubMed and Embase were systematically searched for articles published from 1 January 2000 to 15 October 2021. A total of 1315 articles comparing differences in outcomes between patients of varying body mass index (BMI) undergoing valve interventions were reviewed and 25 were included in this study. Patients with higher BMI demonstrated equivalent or reduced rates of postoperative myocardial infarction, stroke, reoperation rates, acute kidney injury, dialysis and bleeding. Two studies identified increased rates of deep sternal wound infection in patients with higher BMI, although the majority of studies found no significant difference in deep sternal wound infection rates. The obesity paradox has described counterintuitive outcomes predominantly in coronary artery bypass grafting and transcatheter aortic valve replacement. Recent literature has identified similar trends in other heart valve interventions. While the obesity paradox has been well characterized, its causes are yet to be identified. Further study is essential in order to identify the causes of the obesity paradox so patients of all body sizes can receive optimal care.

Recellularization of xenograft heart valves reduces the xenoreactive immune response in an in vivo rat model.

OBJECTIVES: Our aim was to address the role of autologous mesenchymal stem cell recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in vivo rat model. METHODS: Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with autologous Sprague-Dawley rat mesenchymal stem cells. Aortic valve xenografts were then implanted into the infrarenal aorta of recipient rats. Grafts were implanted as either autologous grafts, non-decellularized (NGP), decellularized and recellularized xenografts (RGP). Rats were euthanized after 7 and 21 days and exsanguinated and the grafts were explanted. RESULTS: The NGP grafts demonstrated significant burden of granulocytes (14.3 cells/HPF) and CD3+ T cells (3.9 cells/HPF) compared to the autologous grafts (2.1 granulocytes/HPF and 0.72 CD3+ T cells/HPF) after 7 days. A lower absolute number of infiltrating granulocytes (NGP vs autologous, 6.4 vs 2.4 cells/HPF) and CD3+ T cells (NGP vs autologous, 2.8 vs 0.8 cells/HPF) was seen after 21 days. Equivalent granulocyte cell infiltration in the RGP grafts (2.4 cells/HPF) compared to the autologous grafts (2.1 cells/HPF) after 7 and 21 days (2.8 vs 2.4 cells/HPF) was observed. Equivalent CD3+ T-cell infiltration in the RGP grafts (0.63 cells/HPF) compared to the autologous grafts (0.72 cells/HPF) after 7 and 21 days (0.7 vs 0.8 cells/HPF) was observed. Immunoglobulin production was significantly greater in the NGP grafts compared to the autologous grafts at 7 (123.3 vs 52.7 mg/mL) and 21 days (93.3 vs 71.6 mg/mL), with a similar decreasing trend in absolute production. Equivalent immunoglobulin production was observed in the RGP grafts compared to the autologous grafts at 7 (40.8 vs 52.7 mg/mL) and 21 days (29.5 vs 71.6 mg/mL). CONCLUSIONS: Autologous mesenchymal stem cell recellularization of xenogenic valves reduces the xenoreactive immune response in an in vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.

The effects of body mass index on long-term outcomes and cardiac remodeling following mitral valve repair surgery.

BACKGROUND: Previous literature has demonstrated equivalent or improved survival post mitral valve (MV) surgery amongst patients with obesity when compared to their normal-weight counterparts. This relationship is poorly understood and the impact of body mass index (BMI) on cardiac remodeling has not been established. METHODS: In this retrospective, single-center study, we sought to identify the impact that BMI may have on long-term outcomes and cardiac remodeling post-MV repair. Outcomes were compared between patients of varying BMI undergoing MV repair between 2004 and 2018. The primary outcome was mortality and secondary outcomes included stroke, myocardial infarction, reoperation of the MV, rehospitalization, and cardiac remodeling. RESULTS: A total of 32 underweight, 249 normal weight, 249 overweight, 121 obese, and 50 morbidly obese patients were included in this study. Underweight patients had increased mortality at longest follow-up. Patients with morbid obesity were found to have higher rates of readmission for heart failure. Only underweight patients did not demonstrate a significant reduction in LVEF. Patients with normal weight and overweight had a significant reduction in left atrial size, and patients with obesity had a significant reduction in MV area. CONCLUSIONS: An obesity paradox has been identified in cardiac surgery. While patients with obesity have higher rates of comorbidities preoperatively, their rates of mortality are equivalent or even superior to those with lower BMI. The results of our study confirm this finding with patients of high BMI undergoing MV repair demonstrating equivalent rates of morbidity to their normal BMI counterparts. While the obesity paradox has been relatively consistent in the literature, the understanding of its cause and long-term impacts are not well understood. Further focused investigation is necessary to elucidate the cause of this relationship.

Sternal Bone Marrow Harvesting and Culturing Techniques from Patients Undergoing Cardiac Surgery.

BACKGROUND: Mesenchymal stromal cells (MSCs) are the most prominent cell type used in clinical regenerative medicine and stem cell research. MSCs are commonly harvested from bone marrow that has been aspirated from patients' iliac crest. However, the ethical challenges of finding consenting patients and obtaining fresh autologous cells via invasive extraction methods remain to be barriers to MSC research. METHODS: Techniques of harvesting sternal bone marrow, isolating and culturing MSCs, MSC surface phenotyping, and MSC differentiation are described. Samples from 50 patients undergoing a sternotomy were collected, and the time taken to reach 80% confluency and cell count at the second splitting of MSC were measured. RESULTS: MSC isolated from the sternal bone marrow of patients undergoing cardiac surgery demonstrated successful MSC surface phenotyping and MSC differentiation. The mean cell count at the time of the second split was 1,628,025, and the mean time taken to reach the second split was 24.8 days. CONCLUSION: Herein, we describe the first reported technique of harvesting sternal bone marrow from patients already undergoing open-chest cardiac surgery to reduce the invasiveness of bone marrow harvesting, as well as the methods of isolating, culturing, and identifying MSCs for the clinical application of constructing autologous MSC-derived biomaterials.

Review of the differences in outcomes between males and females after revascularization.

PURPOSE OF REVIEW: This review aims to compare outcomes of males and females undergoing coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), off-pump CABG (OPCAB), minimally invasive direct CABG (MIDCAB), and robotic total endoscopic CABG (TECAB). RECENT FINDINGS: Females demonstrated increased rates of morbidity and mortality post PCI and CABG. In studies that performed risk adjustments, these differences were reduced. Although inferior outcomes were observed for females in some measures, generally outcomes between males and females were comparable post OPCAB, MIDCAB, and TECAB. SUMMARY: Previous literature has demonstrated that females undergoing coronary revascularization experience inferior postoperative outcomes when compared to their male counterparts. The discrepancies between males and females narrow, but do not disappear when preoperative risks are accounted for and when considering minimally invasive approaches such as MIDCAB, OPCAB, and TECAB. Minimally invasive cardiac surgery has demonstrated numerous benefits with reduced morbidity, mortality, and shorter recovery times. In patients with increased comorbidities, minimally invasive approaches confer a greater advantage. As females often fall within this category, it is paramount that the diagnosis and referral process be optimized to account for preoperative differences to provide the most beneficial approach if the disparity between the sexes is to be addressed.

Review of the use of simulators in learning revascularization techniques.

PURPOSE OF REVIEW: The apprentice model has been traditionally used to train cardiac surgery and cardiology learners the techniques for revascularization with the use of simulators recently becoming more prevalent in these training programs. This review aims to summarize research conducted on the use of simulation-based teaching (SBT) for trainees learning percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and off-pump CABG (OPCAB). RECENT FINDINGS: Prior literature evaluating the utility of SBT has demonstrated remarkable results including reduced procedural times, use of fluoroscopy, incidence of mistakes, improved stent placement, and confidence with PCI simulators. Similarly, the use of CABG and OPCAB simulators demonstrated improvement in forceps use, needle angles, Objective Structured Assessment of Technical Skill, and reduced completion times. The apprentice model has undoubtedly been successful as the most successful cardiac surgeons and cardiologists have been produced through this training model. Even so, many shortcomings have been identified including insufficient time to teach all relevant technical skills, inadequate exposure to rare adverse events, high-cost, and often unstructured format while being time-consuming and resource-intensive with little objective assessment of proficiency. SBT has been pursued as a potential adjunct to fill the gaps left by the traditional apprentice model. While simulations have been demonstrated to be successful in teaching both experienced and inexperienced learners complex techniques, it is unlikely that training will ever solely rely on simulations. The most efficient method of training learners for revascularization in the future will likely involve a combination of hands-on learning and SBT.