Relation of body mass index to long-term survival and cardiac remodelling for patients undergoing mitral valve replacement surgery.

BACKGROUND AND AIMS: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR). METHODS AND RESULTS: In this retrospective, single-center study, 1071 adult patients who underwent an MVR between 2004 and 2018 were stratified into five BMI groups (<20, 20-24.9, 25-29.9, 30-34.9, >35). Cox proportional hazard regression models were used to determine the association between BMI and all-cause mortality. Patients who were underweight had significantly higher all-cause mortality rates at the longest follow-up (median 8.2 years) than patients with normal weight (p = 0.01). Patients who were in the obese group had significantly higher readmission rates due to myocardial infarction (MI) at the longest follow-up (p = 0.017). Subgroup analysis revealed a significant increase in long-term all-cause mortality for female patients who were underweight. Significant changes in left atrial size, mitral valve peak and mean gradients were seen in all BMI groups. CONCLUSIONS: For patients undergoing mitral valve replacement, BMI is unrelated to operative outcomes except for patients who are underweight.

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.

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.

Impact of sex on cardiac remodeling and long-term outcomes, following mitral valve replacement.

BACKGROUND: Differences in cardiac remodeling after mitral valve (MV) surgery between the sexes is poorly understood. Inferior outcomes for females undergoing MV surgery compared with males have been suggested in the literature, although causative factors behind this discrepancy have not been identified. MATERIALS AND METHODS: In this propensity-matched, retrospective, single-center study, we sought to identify the impact that sex may have on cardiac remodeling and long-term outcomes to better inform clinical decision-making in MV surgical intervention. Outcomes were compared between males and females undergoing MV replacement (MVR) between 2004 and 2018. The primary outcome was cardiac remodeling 1 year postoperatively. Secondary outcomes included mortality, stroke, myocardial infarction (MI), reoperation of the MV, and rehospitalization. RESULTS: A total of 311 males and 311 females were included after propensity matching. Both groups demonstrated significant improvement in left atrial remodeling, although only males demonstrated a significant degree of improved left ventricular remodeling while their female counterparts did not. Mortality rates were relatively equivalent between the two groups, although males were more likely to develop sepsis and require rehospitalization due to MI. CONCLUSIONS: There has been little research exploring the differences in cardiac remodeling between the sexes after MVR. The results of this study have suggested that MVR is equally safe for both sexes and has demonstrated a difference in the heart's ability to remodel after MVR. The significance of this difference has the potential to result in largely different clinical outcomes for males and females. Further study is necessary to fully elucidate this relationship.

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.

Impact of sex on long-term outcomes following mitral valve repair.

Introduction: Previous studies have identified inferior outcomes for women undergoing mitral valve (MV) surgery compared to men, although the cause of this discrepancy has not been identified. We look to isolate surgical approach to identify any impact that sex has on outcomes in order to better inform clinical decision making. Materials and methods: In this propensity matched, retrospective, single-center study, outcomes were compared between males and females undergoing a MV repair between 2004 and 2018. The primary outcome was defined as mortality at any point in the follow-up period. Secondary outcomes included stroke, myocardial infarction (MI), repeat revascularization, complications arising from the initial procedure, and postoperative cardiac remodeling. Results: A total of 188 males and 188 females were included after propensity matching. At a median follow up time of 7.6 years, there were 25 deaths in the male group (26.8%) and 23 in the female group (28.2%) (p = 0.771). There were no significant differences in MI, stroke, post-operative pacemaker insertion, or rehospitalization following MV repair. Left ventricular (LV) size for males was reduced from an initial 55.6 ± 7.3 mm to 49.9 ± 7.4 mm (p < 0.001), and for females from an initial 51.5 ± 7 mm to 46.9 ± 7.1 mm (p < 0.001). LV ejection fraction (LVEF) was reduced with a preoperative LVEF for males of 57.7% ± 8.9% and 53.7% ± 9.6% postoperatively (p = 0.002), and LVEF for females of 57.8% ± 9.1% preoperatively and 54.8% ± 9.2% postoperatively (p < 0.001). Left atrial (LA) volume was reduced from an initial 51 ± 22 ml/m2 to 43.7 ± 25.2 ml/m2 (p < 0.001), and 50.9 ± 19.2 ml/m2 to 44.2 ± 19.8 ml/m2 (p < 0.001), for males and females respectively. LA diameter was reduced for males from an initial 49.7 ± 9.7 mm to 47.3 ± 9.4 mm (p = 0.043), and from 48 ± 8.7 mm to 44.3 ± 9.1 mm for females postoperatively (p = 0.017). Conclusions: Current literature demonstrates inferior outcomes for females when compared to males undergoing MV surgery with patients undergoing a variety of surgical approaches. The results of this study suggest that surgical intervention for a subset of patients, those undergoing repair of the MV, is safe and offers similar outcomes for males and females.

Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

BACKGROUND: Pharmaceuticals to inhibit mammalian target of rapamycin (mTOR) protein, which plays an integral role in T cell survival and function, have been used to prevent complications associated with organ transplantation. Although studies have individually shown that resveratrol can inhibit mTOR and that inhibiting mTOR leads to attenuated immune function, no studies to date have examined these two functions conjointly under one study. Therefore, we hypothesize that resveratrol will decrease mTOR activation and expression as well as attenuate stimulated T cell activation and proliferation in peripheral blood mononuclear cells (PBMC). METHODS AND MATERIALS: Human PBMC were isolated and cultured. The cells were pre-treated with resveratrol (50 µM) overnight (18 hrs) before stimulation. The cells were collected for subsequent biochemical analysis after 1, 3, and 5 days. Additionally, the cells were stained with proliferation dye and cultured for 24 hours in PMA/Ionomycin with resveratrol for flow cytometry analysis. RESULTS: Resveratrol treated stimulated PBMCs displayed a significant decrease in activated phosphorylation of mTOR at days 1, 3, and 5 (P < 0.0329). Markers of T cell activation, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), were also significantly reduced along with T cell proliferation following stimulated PBMC resveratrol treatment when compared to vehicle-treated controls (P < 0.01). CONCLUSION: Taken together, our data suggest that resveratrol can decrease the immune response of stimulated T-cells and inhibit the expression and activation of mTOR mediated cellular signalling under the same study setting. Therefore, resveratrol proposes a possible adjunctive therapy option for patients undergoing organ transplantation.