Marc P. Buijsrogge

Secretion of adipocytokines by perivascular adipose tissue near stenotic and non-stenotic coronary artery segments in patients undergoing CABG

OBJECTIVE Perivascular adipose tissue (pvAT) may induce a local pro-inflammatory environment, possibly contributing to coronary atherosclerosis. We investigated whether there is a difference in adipocytokine production by pvAT near stenotic and non-stenotic coronary artery segments in patients with coronary artery disease (CAD). METHODS In patients undergoing CABG with or without valve replacement (n = 38) pvAT near stenotic and near non-stenotic coronary segments was harvested. PvAT was incubated ex vivo for 24h. Concentrations of 23 adipocytokines were measured in the supernatants with a Multiplex assay. The number of macrophages (CD68, CD11c, CD206) and lymphocytes (CD45) in pvAT was determined. Differences between stenosis and control pvAT were tested with Wilcoxon signed rank test corrected for multiple comparisons. RESULTS Production of IL-5, IL-1α, IL-17, IL-18 and IL-23 was higher in control than stenosis pvAT samples (p < 0.0021). Macrophages were more abundant in stenosis than in control pvAT (median n/400× field: 2.3 IQR: 0.3-4.5 versus 1.2 IQR: 0.1-2.5). There was a predominance of M2 macrophages in both stenosis and control pvAT (median n/400× field: macrophages stenosis: M1: 0.0; M2: 1.0 p = 0.004; control: M1: 0.0; M2: 0.6 p = 0.013). The relation between adipocytokine production and macrophage infiltration was not different in stenosis and control pvAT. CONCLUSION In patients with CAD, multiple adipocytokines were secreted at higher levels by pvAT near non-stenotic than near stenotic coronary artery segments. Furthermore, pvAT macrophages are associated with stenosis of the adjacent vessel. M2 macrophages were more abundant than M1 macrophages in pvAT.

Coronary end-to-side sleeve anastomosis using adhesive in off-pump bypass grafting in the pig

BACKGROUND In the exploration of facilitated coronary anastomosis strategies, we assessed a new octylcyanoacrylate adhesive in combination with a modified end-to-side sleeve anastomosis in off-pump bypass grafting in the pig. METHODS Sleeve-adhesive anastomoses (n = 20) were evaluated intraoperatively, at 3 days (n = 4), and at 5 weeks (n = 16) in an off-pump, low (< or = 15 mL/min; n = 10) and high flow (approximately 60 mL/min; n = 10) porcine bypass model. All anastomoses were examined by flow measurement, angiography, and histology. RESULTS Anastomosis construction took 8.5 minutes (6.7 to 10.2 minutes; median [15th to 85th percentile]). At 5 weeks, all anastomoses were fully patent (FitzGibbon grade A). The adhesive did not cause impaired vessel wall healing, but was surrounded by a focal acute and limited chronic (foreign body giant cells occasionally seen) inflammatory reaction at the adventitial application site. CONCLUSIONS Octyl-cyanoacrylate tissue adhesive combined with end-to-side internal mammary to coronary artery sleeve anastomosis construction proved to be feasible, even in low bypass graft flow conditions (< or = 15 mL/min; prothrombotic milieu) in the pig and deserves interest in exploration of facilitated anastomosis strategies in coronary artery bypass grafting.

“Frozen” Leaflet A Dreadful Complication of Transcatheter Aortic Valve Implantation

An 89-year-old woman with effort angina and dyspnea, known to have diabetes, mild renal impairment, previous coronary artery bypass surgery (2 times), and several percutaneous coronary interventions, was diagnosed with a severe symptomatic aortic valve stenosis and was scheduled for transcatheter aortic valve implantation according to the decision of the Heart Team of our institution and after a complete assessment by means of transthoracic and transesophageal echocardiography, coronary angiography, and computed tomography of the whole aorta to the femoral arteries. The logistic Euroscore was 30%. The procedure was planned through the transfemoral approach, under sedation and with intracardiac echocardiography (ICE) monitoring. An Edwards Sapien XT (Edwards Lifesciences LLC, Irvine, CA) aortic valve bioprosthesis with a diameter of 23 mm was chosen, as the aortic annulus measured 20 mm by preprocedural transesophageal echocardiography and by periprocedural ICE. The right femoral artery was selected as the entry site for the Novaflex valve delivery system (Edwards Lifesciences LLC) by means of a fully percutaneous approach, using the eSheath expandable introducer sheath (Edwards Lifesciences LLC). A temporary pacemaker was placed through the right femoral vein in the apex of the right ventricle. A pigtail catheter was inserted through the …

Transcatheter aortic valve replacement: postoperative CT findings of Sapien and CoreValve transcatheter heart valves.

Transcatheter aortic valve replacement represents one of the most exciting medical technical developments in recent years, offering a much-needed therapeutic alternative for patients with severe aortic valve stenosis who, due to comorbidities and advanced age, are considered to be inoperable or at high surgical risk. The efficacy of this procedure compared with standard surgical intervention has been properly validated in multicenter randomized controlled trials (PARTNER A and B trials), leading to widespread clinical implementation, with over 50,000 procedures currently being performed worldwide each year. Although much of the attention has rightly focused on the potential role of computed tomography (CT) in the preprocedural assessment of the aortic root and the establishment of imaging-guided valve-sizing algorithms, less is known regarding the postprocedural CT characteristics of transcatheter heart valves (THVs). However, given the increasing worldwide recognition and clinical implementation of these devices, they will no doubt be encountered with increasing frequency in patients referred for thoracic CT, either for postprocedural evaluation of the aortic root or for unrelated reasons. Familiarity with these devices and their CT characteristics will increase diagnostic confidence and the value of the radiology report. The authors describe the physical and imaging properties of the currently commercially available THVs, their normal postprocedural imaging appearances, and potential complications that can be detected at CT. In addition, they discuss the relative strengths and weaknesses of CT and echocardiography in this setting.

Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models

Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications.

Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling

Activation of cardiac fibroblasts into myofibroblasts is considered to play an essential role in cardiac remodeling and fibrosis. A limiting factor in studying this process is the spontaneous activation of cardiac fibroblasts when cultured on two-dimensional (2D) culture plates. In this study, a simplified three-dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by transforming growth factor-β1 (TGF-β1), is presented to recapitulate a fibrogenic microenvironment. It is hypothesized that the quiescent state of cardiac fibroblasts can be maintained by mimicking the mechanical stiffness of native heart tissue. To test this hypothesis, a 3D cell culture model consisting of cardiomyocytes and cardiac fibroblasts encapsulated within a mechanically engineered gelatin methacryloyl hydrogel, is developed. The study shows that cardiac fibroblasts maintain their quiescent phenotype in mechanically tuned hydrogels. Additionally, treatment with a beta-adrenergic agonist increases beating frequency, demonstrating physiologic-like behavior of the heart constructs. Subsequently, quiescent cardiac fibroblasts within the constructs are activated by the exogenous addition of TGF-β1. The expression of fibrotic protein markers (and the functional changes in mechanical stiffness) in the fibrotic-like tissues are analyzed to validate the model. Overall, this 3D engineered culture model of contractile cardiac tissue enables controlled activation of cardiac fibroblasts, demonstrating the usability of this platform to study fibrotic remodeling.

A new nonocclusive laser-assisted coronary anastomotic connector in a rabbit model

OBJECTIVE The Excimer laser-assisted nonocclusive anastomotic technique is a nonocclusive, facilitated bypass technique that is currently Conformité Européenne and Food and Drug Administration approved for clinical application in neurosurgery. In the present study, we assessed the safety and feasibility of a newly developed Excimer laser-assisted nonocclusive anastomosis-based prototype coronary anastomotic connector in an acute rabbit abdominal aortic bypass model before application in experimental coronary bypass surgery. In addition, 2 sealants were tested to facilitate anastomotic hemostasis in the current device prototype. METHODS A total of 40 anastomoses were constructed on the abdominal aorta (3.5 mm outer diameter) of 10 rabbits. The anastomotic circumference was sealed by a surgical sealant to obtain complete hemostasis (BioGlue vs TachoSil). The anastomoses were evaluated by flow measurements construction time, hemostasis, histologic analysis, and burst pressure testing. RESULTS The connector enabled a nonocclusive and fast (6.0 ± 1.7 minutes, mean ± SD [including sealing]) anastomosis construction and complete hemostasis in 95% (35/37). Sealing with BioGlue was faster than with TachoSil (19% vs 53% of construction time). Despite technical imperfections (7/40 failures to completely retrieve the flap by the laser), all 40 anastomoses were patent, showed reproducible construction with intima-adventitia apposition, streamlining thrombus coverage of the intraluminal laser rim, and no vessel wall damage. All anastomoses resisted ex vivo supraphysiologic pressures (> 300 mm Hg). CONCLUSIONS The results of the present study have demonstrated that the Excimer laser-assisted nonocclusive anastomotic connector is safe and reliable and can be efficiently applied in an acute rabbit abdominal aortic bypass model. Provided the limitations can be addressed, this easy-to-use and nonocclusive technique has the potential to facilitate minimally invasive coronary bypass surgery.

Permanent wall stretching in porcine coronary and internal mammary arteries

BACKGROUND Anastomotic connectors may induce substantial arterial wall deformation and, hence, wall injury. We studied arterial wall damage and repair after sustained large longitudinal elongation in the porcine coronary and internal mammary arteries in vivo. METHODS A stretch device that elongates a part of the artery by 80% was implanted in 8 pigs. Elongated coronary arteries (n = 14) and internal mammary arteries (n = 15) were examined histologically at either 2 days (4 pigs) or 5 weeks of follow-up (4 pigs). RESULTS No mural thrombus was observed at the elongated site. In the coronary artery at 2 days, few and only minor histologic changes were found. At 5 weeks, in two of seven coronary segments, a thin rim of intimal hyperplasia was found, in one case with a maximum thickness of 76 micro m. The internal mammary artery hardly showed any changes. CONCLUSIONS Permanent longitudinal elongation by 80% caused little structural changes in the porcine coronary and internal mammary artery wall. Anastomotic connectors that impose relatively large deformations can be safely evaluated in the pig.

Extracorporeal life support in cardiogenic shock : Indications and management in current practice

Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.

S2 Connector Versus Suture Distal Coronary Anastomosis Remodeling, Patency, and Function in the Pig

Background— Anastomotic connectors could be the key to less invasive bypass surgery, including endoscopic procedures, but equivalence to conventional suturing needs to be established. A novel distal coronary connector was tested pre-clinically for safety and efficacy in comparison to conventional suturing. Methods and Results— Left internal thoracic to left anterior descending coronary artery bypasses were constructed off-pump in 35 pigs (73±8 kg). An intraluminal metal connector (S2AS) was used in 21 and conventional suturing in 14 animals. S2AS anastomosis construction was easier achieved in one-fourth of the conventional construction time (3.7±0.7 versus 16.5±2.6 minutes; P<0.001). Acute patency tended to be better (P=0.15). All anastomoses were evaluated intraoperatively, and subgroups at 90 and at 180 days. Patency was 100%. An effective remodeling response was observed in all groups, resulting in unobstructed anastomoses with excellent hemodynamic performance (fractional flow reserve ≥0.93 at 180 days). At 6 months, the noncompliant connector was covered with stabilized neointima that was thinner than found on the suture line (0.10±0.04 versus 0.31±0.13 mm; P=0.01). The connector induced less lumen loss (−0.6±6.5 versus 21.6±19%; P=0.03). The initial side-to-side configuration had remodeled to an end-to-side shape as intended. Conclusions— In the porcine model, the connector rapidly and consistently produced high-quality anastomoses that fully met current standards on patency and function. Unconventional aspects like a noncompliant intraluminal ring and a side-to-side to end-to-side converted configuration did not interfere with favorable anastomosis remodeling. These findings shed a new light on the anatomical prerequisites for anastomosis patency.