Hazaim Alwair

Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy

Objective Lipid peroxides and their reactive aldehyde derivatives (LPPs) have been linked to obesity-related pathologies, but whether they have a causal role has remained unclear. Glutathione peroxidase 4 (GPx4) is a selenoenzyme that selectively neutralizes lipid hydroperoxides, and human gpx4 gene variants have been associated with obesity and cardiovascular disease in epidemiological studies. This study tested the hypothesis that LPPs underlie cardio-metabolic derangements in obesity using a high fat, high sucrose (HFHS) diet in gpx4 haploinsufficient mice (GPx4+/−) and in samples of human myocardium. Methods Wild-type (WT) and GPx4+/− mice were fed either a standard chow (CNTL) or HFHS diet for 24 weeks, with metabolic and cardiovascular parameters measured throughout. Biochemical and immuno-histological analysis was performed in heart and liver at termination of study, and mitochondrial function was analyzed in heart. Biochemical analysis was also performed on samples of human atrial myocardium from a cohort of 103 patients undergoing elective heart surgery. Results Following HFHS diet, WT mice displayed moderate increases in 4-hydroxynonenal (HNE)-adducts and carbonyl stress, and a 1.5-fold increase in GPx4 enzyme in both liver and heart, while gpx4 haploinsufficient (GPx4+/−) mice had marked carbonyl stress in these organs accompanied by exacerbated glucose intolerance, dyslipidemia, and liver steatosis. Although normotensive, cardiac hypertrophy was evident with obesity, and cardiac fibrosis more pronounced in obese GPx4+/− mice. Mitochondrial dysfunction manifesting as decreased fat oxidation capacity and increased reactive oxygen species was also present in obese GPx4+/− but not WT hearts, along with up-regulation of pro-inflammatory and pro-fibrotic genes. Patients with diabetes and hyperglycemia exhibited significantly less GPx4 enzyme and greater HNE-adducts in their hearts, compared with age-matched non-diabetic patients. Conclusion These findings suggest LPPs are key factors underlying cardio-metabolic derangements that occur with obesity and that GPx4 serves a critical role as an adaptive countermeasure.

Robotic mitral valve surgery—current status and future directions

Robotic mitral valve surgery is the most common robotic cardiac procedure performed today. Benefits include smaller, less invasive incisions resulting in less pain, shorter length of hospital stay, improved cosmesis, quicker return to preoperative level of functional activity, and decreased blood transfusion requirements. The history and evolution of robotic mitral valve surgery is detailed in this article. Our institution has performed over 800 robotic mitral valve surgeries, and our technique and outcomes are described. Outcomes and operative times are similar to that for sternotomy and minimally invasive approaches to mitral valve surgery. The benefits and limitations of robotic mitral valve surgery are compared with conventional approaches, and future directions are also discussed.

Robotically assisted minimally invasive mitral valve surgery

Increased recognition of advantages, over the last decade, of minimizing surgical trauma by operating through smaller incisions and its direct impact on reduced postoperative pain, quicker recovery, improved cosmesis and earlier return to work has spurred the minimally invasive cardiac surgical revolution. This transition began in the early 1990s with advancements in endoscopic instruments, video & fiberoptic technology and improvements in perfusion systems for establishing cardiopulmonary bypass (CPB) via peripheral cannulation. Society of Thoracic Surgeons data documents that 20% of all mitral valve surgeries are performed using minimally invasive techniques, with half being robotically assisted. This article reviews the current status of robotically assisted mitral valve surgery, its advantages and technical modifications for optimizing clinical outcomes.

Plasma Catecholamine Levels on the Morning of Surgery Predict Post-Operative Atrial Fibrillation

OBJECTIVES This study sought to determine whether plasma catecholamines and monoamine oxidase-B (MOA-B) are associated with post-operative atrial fibrillation (POAF) in patients undergoing elective cardiac surgery. BACKGROUND Although intra- and post-operative adrenergic tone has been demonstrated to be an causative factor for POAF, the role and association of pre-operative plasma catecholamines remains unclear. METHODS Prior to administration of anesthesia on the morning of surgery, blood samples were obtained from 324 patients undergoing nonemergent coronary artery bypass graft and/or aortic valve surgery with cardiopulmonary bypass at East Carolina Heart Institute. The concentrations of norepinephrine (NE), dopamine (DA), epinephrine (EPI), and enzyme MAO-B were assessed in platelet-rich plasma. A log-binomial regression model was used to determine the association between quartiles of these variables and POAF. RESULTS Levels of NE (p = 0.0006) and EPI (p = 0.047) in the 4th quartile [Formula: see text] were positively associated with POAF, whereas DA (p = 0.0034) levels in the 4th quartile [Formula: see text] were inversely associated with POAF. Adjusting for age, heart failure (HF), and history of atrial fibrillation, the composite pre-operative (adrenergic) plasma marker [Formula: see text] was associated with a 4-fold increased occurrence of POAF (adjusted p = 0.0001). No association between plasma MAO-B and POAF was observed. CONCLUSIONS Our results suggest that pre-operative adrenergic tone is an important factor underlying POAF. This information provides evidence that assessment of plasma catecholamines may be a low-cost method that is easy to implement for predicting which patients are likely to develop POAF. More investigation in a multicentric setting is needed to validate our results.

Video-atlas on robotically assisted mitral valve surgery

Mitral valve surgery is the most commonly performed robotically-assisted cardiac surgical procedure. The robotic approach evolved from minimally invasive mitral valve surgery, which was performed via right mini-anterolateral thoracotomy either under direct vision or with endoscopic visualization. The da VinciTM Surgical System (Intuitive Surgical Inc., Sunnydale, CA) has been used in several robotic cardiac surgical centers to successfully perform mitral valve surgery. This system uses high-definition three-dimensional camera imaging and EndowristTM (Intuitive Surgical, Sunnydale, CA) instruments, which allow for motion in six degrees of freedom. When compared with minimally invasive mitral valve surgery, the robotic-assisted approach enables unparalleled visualization of the mitral valve apparatus, tremor-free movements, ambidexterity, and avoidance of the fulcrum effect of using long-shafted endoscopic instruments. The 2 to 3 cm lateral working port incision allows for less pain, quicker recovery, and reduced length of stay when compared with sternotomy. This video article provides a detailed description of our current approach to performing complex mitral valve surgery using the da VinciTM system.

Corrigendum to "Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy" [Mol Metab 4 (6) (2015) 493-506].

[This corrects the article DOI: 10.1016/j.molmet.2015.04.001.].

Minimally invasive mitral valve surgery: still possible when aortic clamping is judged unsafe

We read with great interest the recent article by Vollroth et al. [1], describing their experience with conversion to sternotomy during minimally invasive mitral surgery. The authors are to be congratulated on the low incidence of conversion (1%) that they have reported. The high early mortality (23.5%) associated with conversion in their series remains a reminder of the gravity of such an occurrence, even in experienced hands. Given the fact that 14 of the 34 conversions described were related to the application of the Chitwood clamp, the authors recommend that, with any difficulty encountered during its placement, the option of elective conversion should be considered [1]. In our experience, elective conversion was seldom a consequence of difficulty clamping the aorta. Whenever clamping the aorta is judged unsafe, our alternative strategy is opting for hypothermic fibrillation (HF) as a means of myocardial protection. Over the past few years, our threshold for shifting towards HF has been increasing. We recently reported on our experience with the minimally invasive approach in patients who had a previous sternotomy, where aortic clamping is commonly judged to be unsafe due to dense adhesions. HF was used in 77% of these patients without a single incidence of conversion to sternotomy. Contrary to a common notion, there was no relationship between HF and cerebrovascular accidents [2]. Similarly, previous reports from the authors’ own institution reported exactly the same pattern of adoption of HF (77%) in redo cases [3]. Other authors also reported an increasing trend towards the use of HF in minimally invasive surgery with satisfactory results [4]. Given the demonstrated safety of HF in redo cases, it seems reasonable to extend its use to other clinical situations where aortic clamping is judged unsafe because of a diseased or a dilated aorta. As minimally invasive mitral surgery gains more ground, surgeons are likely to become increasingly exposed to similar situations. And mastering alternative means of myocardial management, rather than opting to convert to a full sternotomy, is a more practical approach. Finally, we would like to commend the authors for a fine article and look forward to their response.

Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective

BACKGROUND Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). METHODS Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. RESULTS Non-smoking men (≤65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. CONCLUSIONS In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures.