Angiopoietin-1 enhances skeletal muscle regeneration in mice.

Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang-1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle satellite cell survival; however, its role in skeletal muscle regeneration after injury is unknown. We assessed the effects of Ang-1 on fiber regeneration, myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA) in mice. We also assessed endogenous Ang-1 levels and localization in intact and injured TA muscles. TA fiber injury was triggered by cardiotoxin injection. Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin then increased during the 2 wk. Ang-1 protein was expressed in satellite cells, both in noninjured and recovering TA muscles. Positive Ang-1 staining was present in blood vessels but not in nerve fibers. Four days after the initiation of injury, injection of adenoviral Ang-1 into injured muscles resulted in significant increases in in situ TA muscle contractility, muscle fiber regeneration, and capillary density. In cultured human skeletal myoblasts, recombinant Ang-1 protein increased survival, proliferation, migration, and differentiation into myotubes. The latter effect was associated with significant upregulation of the expression of the myogenic regulatory factors MyoD and Myogenin and certain genes involved in cell cycle regulation. We conclude that Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angiogenesis program in endothelial cells.

Reining in Sternal Wound Infections: The Achilles' Heel of Bilateral Internal Thoracic Artery Grafting.

Background: Although the survival advantage of bilateral internal thoracic artery grafting (BITA) is well known in patients undergoing coronary artery bypass grafting (CABG), this technique has not been widely adopted. This is mainly because of the increased risk of deep sternal wound infections (DSWI) associated with its use. However, in recent years the overall risk of DSWI has decreased. This is mainly because of strategies that have been adopted to decrease the risk of these infections in patients undergoing CABG. Conclusion: In this review we identified DSWI preventive strategies and described them in detail so that their use by surgeons can be increased. This would minimize the risk of DSWI after BITA grafting and maximize the use of this highly effective surgical technique.

Simple versus complex degenerative mitral valve disease.

OBJECTIVES: At a center where surgeons favor mitral valve (MV) repair for all subsets of leaflet prolapse, we compared results of patients undergoing repair for simple versus complex degenerative MV disease. METHODS: From January 1985 to January 2016, 6153 patients underwent primary isolated MV repair for degenerative disease, 3101 patients underwent primary isolated MV repair for simple disease (posterior prolapse), and 3052 patients underwent primary isolated MV repair for complex disease (anterior or bileaflet prolapse), based on preoperative echocardiographic images. Logistic regression analysis was used to generate propensity scores for risk-adjusted comparisons (n = 2065 matched pairs). Durability was assessed by longitudinal recurrence of mitral regurgitation and reoperation. RESULTS: Compared with patients with simple disease, those undergoing repair of complex pathology were more likely to be younger and female (both P values < .0001) but with similar symptoms (P = .3). The most common repair technique was ring/band annuloplasty (3055/99% simple vs 3000/98% complex; P = .5), followed by leaflet resection (2802/90% simple vs 2249/74% complex; P < .0001). Among propensity-matched patients, recurrence of severe mitral regurgitation 10 years after repair was 6.2% for simple pathology versus 11% for complex pathology (P = .007), reoperation at 18 years was 6.3% for simple pathology versus 11% for complex pathology, and 20-year survival was 62% for simple pathology versus 61% for complex pathology (P = .6). CONCLUSIONS: Early surgical intervention has become more common in patients with degenerative MV disease, regardless of valve prolapse complexity or symptom status. Valve repair was associated with similarly low operative risk and time-related survival but less durability in complex disease. Lifelong annual echocardiographic surveillance after MV repair is recommended, particularly in patients with complex disease.

Robotic mitral valve repair for degenerative posterior leaflet prolapse.

BACKGROUND: Robotic mitral valve (MV) repair is the least invasive surgical approach to the MV and provides unparalleled access to the valve. We sought to assess technical aspects and clinical outcomes of robotic MV repair for isolated posterior leaflet prolapse by examining the first 623 such cases performed in a tertiary care center. METHODS: We reviewed the first 623 patients (mean age 56±9.7 years) with isolated posterior leaflet prolapse who underwent robotic primary MV repair from 01/2006 to 11/2013. All procedures were performed via right chest access with femoral perfusion for cardiopulmonary bypass. RESULTS: MV repair was attempted in all patients; 622 (99.8%) underwent MV repair and only 1 (0.2%) converted to replacement. After an initial attempt at robotic MV repair, 8 (1.3%) patients were converted to sternotomy as a result of management of residual mitral regurgitation (n=3), bleeding (n=1), difficulties with surgical exposure (n=2), aortic valve injury (n=1), and aortic dissection (n=1). Intraoperative post-repair echocardiography confirmed that all patients left the operating room with MR graded as mild or less, and pre-discharge echocardiography confirmed mild or less MR in 573 (99.1%). There was no hospital death, sternal wound infection, or renal failure. Seven (1.1%) patients suffered a stroke, 11 (1.8%) patients underwent re-exploration for bleeding, and 111 (19%) experienced new-onset atrial fibrillation. The mean intensive care unit length of stay and hospital length of stay were 29±17 hours and 4.6±1.6 days, respectively. CONCLUSIONS: At a large tertiary care referral center, robotic MV repair for posterior prolapse is associated with zero mortality, infrequent operative morbidity, and near 100% successful repair. The combination of a patient selection algorithm and increased experience improved clinical outcomes and procedural efficiency.

Degenerative mitral valve disease-contemporary surgical approaches and repair techniques.

Given the increasing age of the US population and the accompanying rise in cardiovascular disease, we expect to see an increasing number of patients affected by degenerative mitral valve disease in a more complex patient population. Therefore, increasing the overall rate of mitral valve repair will become even more important than it is today, and the capability to provide a universally and uniformly accepted quality of repair will have important medical, economic, and societal implications. This article will describe preoperative and intraoperative considerations and the currently practiced mitral valve repair approaches and techniques. The aim of the article is to present our contemporary approach to mitral valve repair in the hope that it can be adopted at other institutions that may have low repair rates. Adoption of simple and reproducible mitral valve repair techniques is of paramount importance if we as a profession are to accomplish overall higher rates of mitral valve repair with optimal outcomes.

Combined aortic root replacement and mitral valve surgery: The quest to preserve both valves.

OBJECTIVES: Coexisting aortic root and mitral valve pathology is increasingly recognized among patients undergoing surgery. We characterized the pathology and surgical outcomes of patients with combined aortic root and mitral disease. METHODS: From 1987 to 2016, 118 patients (age 52.40 ± 17.71 years) underwent concomitant aortic root and mitral procedures (excluding aortic stenosis, endocarditis, and reoperations). Aortic root pathologies included degenerative aneurysm (94%) and aortic dissection (6%). The aortic valve was bicuspid in 15% of patients and had normally functioning tricuspid leaflets in 23% of patients. Marfan syndrome was present in 34 patients (29%). Degenerative mitral disease predominated (78%). Mitral procedures were repair (86%) and replacement (14%), and root procedures were valve-preserving root reimplantation (36%), Bentall procedure (47%), and homograft root replacement (17%). In the last 10 years, the combination of valve-preserving root reimplantation and mitral repair has increased to 50%. Kaplan-Meier and competing risk analyses were used to estimate survival and reoperation. RESULTS: There were 2 (1.7%) operative deaths with survival of 79% and 71% at 10 and 15 years, respectively, and reoperation rates of 4.7% and 12% after 5 and 10 years, respectively. There were no operative deaths in patients with combined valve-preserving root reimplantation and mitral repair, with survival of 89% and reoperation rate of 7.8% at 10 years. Among patients with Bentall/homograft and mitral operation, survival was 73% and reoperation was 9.8% at 10 years. CONCLUSIONS: In patients with aortic root and mitral pathology, combined surgical risk is low and valve durability is high. When possible, valve-preserving root reimplantation and mitral repair should be considered to avoid prosthesis degeneration, anticoagulation, and lifestyle limitations.