Brody Wehman

Hybrid coronary revascularization using robotic totally endoscopic surgery: perioperative outcomes and 5-year results.

BACKGROUND Hybrid coronary revascularization combines minimally invasive coronary artery bypass grafting and catheter-based interventions. This treatment option represents a viable alternative to both open multivessel coronary bypass surgery through sternotomy and multivessel percutaneous coronary intervention. The surgical component of hybrid coronary intervention can be offered in a completely endoscopic fashion using robotic technology. We report on one of the largest series to date. METHODS From 2001 to 2011, 226 patients (age, 61 years [range, 31 to 90 years]; 77.0% male; EuroSCORE, 2 [range, 0 to 13]) underwent hybrid coronary interventions on an intention-to-treat basis. Robotically assisted procedures were performed using the daVinci, daVinci S, and daVinci Si surgical telemanipulation systems (Intuitive Surgical, Inc, Sunnyvale, CA) and included 147 single, 72 double, and 7 triple endoscopic coronary artery bypass grafting procedures. Surgery was carried out first in 160 cases (70.8%), percutaneous coronary intervention was carried out first in 38 cases (16.8%), and 28 patients underwent simultaneous operations in a hybrid operating room (12.4%). Drug-eluting stents were used in 70.0% of the patients. RESULTS Hospital mortality was 3 of 226 patients (1.3%), and hospital stay averaged 6 days (range, 3 to 54 days). Patients walked outside 7 days (range, 3 to 97 days) postoperatively and performed general household work 14 days (range, 7 to 180 days) postoperatively. Full activity was resumed at 42 days (range, 7 to 720 days). Five-year survival was 92.9%, and 5-year freedom from major adverse cardiac and cerebral events was 75.2%. At 5 years, 2.7% of bypass grafts and 14.2% of percutaneous coronary intervention targets needed reintervention. CONCLUSIONS Robotically assisted hybrid coronary intervention enables surgical treatment of multivessel coronary artery disease with minimal trauma. Perioperative results and intermediate-term outcomes meet the standards of open coronary artery bypass grafting. Recovery time is short, and reintervention rates are acceptable.

A Deep Proteome Analysis Identifies the Complete Secretome as the Functional Unit of Human Cardiac Progenitor Cells.

Rationale: Cardiac progenitor cells are an attractive cell type for tissue regeneration, but their mechanism for myocardial remodeling is still unclear. Objective: This investigation determines how chronological age influences the phenotypic characteristics and the secretome of human cardiac progenitor cells (CPCs), and their potential to recover injured myocardium. Methods and Results: Adult (aCPCs) and neonatal (nCPCs) cells were derived from patients aged >40 years or <1 month, respectively, and their functional potential was determined in a rodent myocardial infarction model. A more robust in vitro proliferative capacity of nCPCs, compared with aCPCs, correlated with significantly greater myocardial recovery mediated by nCPCs in vivo. Strikingly, a single injection of nCPC-derived total conditioned media was significantly more effective than nCPCs, aCPC-derived TCM, or nCPC-derived exosomes in recovering cardiac function, stimulating neovascularization, and promoting myocardial remodeling. High-resolution accurate mass spectrometry with reverse phase liquid chromatography fractionation and mass spectrometry was used to identify proteins in the secretome of aCPCs and nCPCs, and the literature-based networking software identified specific pathways affected by the secretome of CPCs in the setting of myocardial infarction. Examining the TCM, we quantified changes in the expression pattern of 804 proteins in nCPC-derived TCM and 513 proteins in aCPC-derived TCM. The literature-based proteomic network analysis identified that 46 and 6 canonical signaling pathways were significantly targeted by nCPC-derived TCM and aCPC-derived TCM, respectively. One leading candidate pathway is heat-shock factor-1, potentially affecting 8 identified pathways for nCPC-derived TCM but none for aCPC-derived TCM. To validate this prediction, we demonstrated that the modulation of heat-shock factor-1 by knockdown in nCPCs or overexpression in aCPCs significantly altered the quality of their secretome. Conclusions: A deep proteomic analysis revealed both detailed and global mechanisms underlying the chronological age-based differences in the ability of CPCs to promote myocardial recovery via the components of their secretome.

Adults with congenital heart disease and heart transplantation: Optimizing outcomes

The growing population of adults with congenital heart disease (ACHD) present a distinct set of challenges in the evaluation, listing, and safe performance of heart transplantation. We review existing literature to (1) describe the complex anatomic and physiologic features that characterize this group of patients, (2) discuss factors contributing to high waiting list times and waiting list morbidity and mortality experienced by this population, and finally, (3) identify risk factors for the elevated post-transplant morbidity and mortality reported in ACHD patients. We conclude with a discussion of critical areas in need of further investigation as well as ways to amend the current listing criteria to better accommodate ACHD patients in need of heart transplantation.

The Emergence of Stem Cell Therapy for Patients With Congenital Heart Disease

Stem cell therapy has emerged as one of the most highly investigated new therapies for cardiovascular disease. Given the enormous health care and economic burden imposed by congestive heart failure on the United States and worldwide, the primary objective of the vast majority of preclinical and clinical research in stem cell therapy for heart disease has been aimed at the recovery or regeneration of ischemic myocardium in adult patients. Less well studied, however, is the growing epidemic of pediatric heart failure. The causes of pediatric heart failure are not homogenous as mostly seen in adult heart failure but include multiple causes related to pressure and volume overload, dysrhythmias, and ischemia triggering ventricular dysfunction.1 On the basis of promising early results in adult patients, the application of stem cell therapy to patients with congenital heart disease (CHD) could potentially offer a new treatment paradigm. Research efforts to this end have been limited to a few number of relevant preclinical animal models and scattered clinical case reports. In this issue of Circulation Research , the Transcoronary Infusion of Cardiac Progenitor Cells in Patients with Single Ventricle Physiology (TICAP) trial, published by Ishigami et al2 represents an effort in the budding field of stem cell therapy for patients with CHD. Their preliminary findings are certain to garner optimism for patients with CHD but more extensive clinical and preclinical studies are needed to validate safety, mechanism, and efficacy. Article, see p 653 It is estimated that in the past decade >5000 patients worldwide have received some form of stem cell therapy for a variety of cardiovascular diseases. Among numerous stem cell types and formulations, 3 stem cell therapy candidates have emerged with promising results in early phase human clinical trials. Backed by a decade of preliminary work in large animal models, bone …

Mesenchymal Stem Cells Preserve Neonatal Right Ventricular Function In A Porcine Model Of Pressure Overload

Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P < 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P < 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P < 0.0001), superior recruitment of endogenous c-kit+ cardiac stem cells to the RV (P < 0.0001) and increased proliferation of cardiomyocytes (P = 0.0009) and endothelial cells (P < 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P = 0.008), increased cardiomyocyte cross-sectional area (P = 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, β-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic strategy to preserve RV function and attenuate remodeling in the setting of pressure overload. Mechanistically, transplanted MSCs possibly stimulated GDF15 and its downstream SMAD proteins to antagonize the hypertrophy response of pressure overload. These encouraging results have implications in congenital cardiac pressure overload lesions.

Class III Obesity is Not a Contraindication to Venovenous Extracorporeal Membrane Oxygenation Support

BACKGROUND The use of venovenous extracorporeal membrane oxygenation (ECMO) has increased as a bridge to recovery for acute respiratory distress syndrome (ARDS) refractory to conventional support. Morbid obesity can pose a significant challenge to obtaining indexed flows, and outcomes in this population are not well described. METHODS Patients requiring ECMO for ARDS between January 2009 and November 2012 were retrospectively reviewed. Demographics, ECMO variables, and outcomes were assessed. Morbid obesity and super obesity were defined as a body mass index (BMI) greater than 40 kg/m(2) and greater than 50 kg/m(2), respectively. RESULTS Fifty-five patients with ARDS were placed on ECMO during the study period. Twelve were morbidly obese with a BMI of 49.0 kg/m(2) (interquartile range [IQR]: 45.4-57.3 kg/m(2)). Pre-ECMO mechanical ventilatory support and indices of disease severity were similar between the 2 groups, as were cannulation strategy and duration of ECMO support. Nine (75%) morbidly obese patients and 27 (63%) non-morbidly obese patients were successfully weaned from ECMO support, and patient survival to time of discharge was 67% and 58%, respectively. In the subset of super obese patients (n = 6; BMI, 57.3 kg/m(2) [IQR: 51.3-66.5 kg/m(2)]), recovery and midterm survival was 100%. CONCLUSIONS In this review, class III obesity was not associated with poorer outcomes, and based on these data, ECMO support should not be withheld from this patient population.

Totally Endoscopic Quadruple Coronary Artery Bypass Grafting Is Feasible Using Robotic Technology

Multivessel robotic totally endoscopic coronary artery bypass grafting is currently under development. Quadruple totally endoscopic coronary artery bypass has so far not been reported. A 75-year-old patient with multivessel coronary artery disease underwent daVinci Si-assisted completely endoscopic placement of a left internal mammary artery bypass to the left anterior descending artery and construction of a right internal mammary artery Y-graft off the left internal mammary artery to the posterior descending artery. The left internal mammary artery was also connected to a diagonal branch as a sequential graft. The obtuse marginal branch was revascularized using an endoscopically harvested vein graft originating from the left axillary artery.

Robotic total endoscopic double-vessel coronary artery bypass grafting--state of procedure development.

OBJECTIVE Robotic total endoscopic coronary artery bypass grafting (TECAB) has been under development for 10 years. With increasing experience and technological improvement, double-vessel TECAB has become feasible. The aim of the present study was to compare the current outcomes of single- and double-vessel TECAB. METHODS Between 2001 and 2011, 484 patients underwent TECAB by 4 surgeons at 2 institutions. The median patient age was 60 years (range, 31-90), and the median European System for Cardiac Operative Risk Evaluation was 2 (range, 0-13). Single-vessel (n = 334) and double-vessel (n = 150) procedures were performed using the da Vinci, da Vinci S, and da Vinci Si robotic systems. RESULTS Compared with the single-vessel procedure, double-vessel TECAB required a longer operative time (median, 375 minutes; range, 168-795; vs median, 240; range, 112-605; P < .001) and had an increased conversion rate to a larger thoracic incision (31/150 [20.7%] vs 31/334 [9.3%]; P < .001). The median ventilation time was 10 hours (range, 0-288) for double-vessel versus 8 hours (range, 0-278) for single-vessel procedures (P = .006). The hospital stay was comparable, with 6 days (range, 2-27) for double-vessel TECAB and 6 days (range, 2-33) for single-vessel TECAB (P = .794). Perioperative mortality was 0.3% (1/334) with single-vessel TECAB and 2.0% (3/150) with double-vessel TECAB (P = .090). Freedom from major adverse cardiac and cerebral events at 5 years was similar after double- and single-vessel TECAB (73.5% vs 83.1%, P = .150). The 5-year survival was 95.8% and 93.9% (P = .708). CONCLUSIONS Double-vessel TECAB appears feasible and reproducible. The operative times were longer and the conversion rates to a larger thoracic incision were greater than with single-vessel TECAB. Also, the postoperative ventilation time was longer. Other perioperative morbidity and mortality and the recovery time and long-term clinical outcomes, however, were comparable.

Engineering Patient-Specific Valves Using Stem Cells Generated From Skin Biopsy Specimens

BACKGROUND Pediatric patients requiring valve replacement will likely require reoperations due to a progressive deterioration of valve durability and limited repair and growth potential. To address these concerns, we sought to generate a biologically active pulmonary valve using patient-specific valvular cells and decellularized human pulmonary valves. METHODS We generated induced pluripotent stem cells (iPSCs) by reprogramming skin fibroblast cells. We then differentiated iPSCs to mesenchymal stem cells (iPCSs-MSCs) using culture conditions that favored an epithelial-to-mesenchymal transition. Next, decellularized human pulmonary heart valves were seeded with iPCS-MSCs using a combination of static and dynamic culture conditions and cultured up to 30 days. RESULTS The iPSCs-MSCs displayed cluster of differentiation CD105 and CD90 expression exceeding 90% after four passages and could differentiate into osteocytes, chondrocytes, and adipocytes (n = 4). Consistent with an MSC phenotype, iPSCs-MSCs lacked expression of CD45 and CD34. Compared with bone marrow MSCs, iPSCs-MSC proliferated more readily by twofold but maintained a gene expression profile exceeding 80% identical to bone marrow MSCs. In repopulated pulmonary valves compared with decellularized pulmonary valves, immunohistochemistry demonstrated increased cellularity, α-smooth muscle actin expression, and increased presence of extracellular matrix components, such as proteoglycans and glycosaminoglycans, suggesting sustained cell function and maturation. CONCLUSIONS Our results demonstrate the feasibility of constructing a biologically active human pulmonary valve using a sustainable and proliferative cell source. The bioactive pulmonary valve is expected to have advantages over existing valvular replacements, which will require further validation.

Long-Term Venovenous Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome

BACKGROUND Given substantial advances in venovenous extracorporeal membrane oxygenation (ECMO) technology, long-term support is increasingly feasible. Although the benefits of short-term ECMO as a bridge to recovery in acute respiratory distress syndrome (ARDS) are well described, the utility and outcomes of long-term support remain unclear. METHODS Patients requiring ECMO for ARDS between January 2009 and November 2012 were retrospectively reviewed and analyzed separately for those requiring ECMO support for less than 3 weeks or for 3 weeks or longer. Demographic factors, ECMO variables, and outcomes were assessed. RESULTS Fifty-five patients with ARDS received ECMO during the study period, with 11 patients requiring long-term ECMO support and a median duration of 36 (interquartile range: 24 to 68) days. Recovery was the initial goal in all patients. Pre-ECMO mechanical ventilatory support, indices of disease severity, and the ECMO cannulation strategy were similar between the two groups. Eight (73%) patients receiving long-term support were bridged to recovery, and 1 patient was bridged to transplantation after a refractory course. Eight (73%) patients receiving long-term support and 25 (57%) patients receiving short-term support survived to 30 days and hospital discharge. CONCLUSIONS Previously, long-term ECMO support was thought to be associated with unfavorable outcomes. This study, however, may provide support for the efficacy of ECMO support even for 3 weeks or more as a bridge to recovery or transplantation.