Stapled coronary anastomosis with minimal intraluminal artifact: The S2 Anastomotic System in the off-pump porcine model

AbstractObjectiveA reliable, easy-to-use, 1-shot anastomotic device will significantly push the barrier for less invasive coronary bypass surgery. The current study was designed to test the safety, efficacy, and early patency of a novel distal anastomotic device.MethodsThe S2 Anastomotic System (iiTech BV, Amsterdam, The Netherlands) was used in 10 consecutive pigs (73 kg) on a mild antiplatelet regimen. In each animal, the device was used to create an internal thoracic artery to left anterior descending bypass on the beating heart. The anastomoses were evaluated intraoperatively (n = 10), at 2 days (n = 2), and at 5 weeks (n = 8) by functional flow measurements, postmortem angiography, and histomorphologic examination.ResultsIn all pigs, the S2Anastomic System rapidly created successful anastomoses at the first attempt (graft loading and coronary ischemia time: 1.2 ± 0.3 minutes and 3.0 ± 0.6 minutes) on target vessels of 1.6 to 2 mm inner diameter. There were no technical failures or anastomotic leaks requiring additional sutures. Both intraoperatively and at the time of death, ischemically induced peak hyperemic flow responses demonstrated widely patent bypasses, which were confirmed by postmortem angiography (FitzGibbon grade A, n = 10) and macroscopic evaluation (anastomotic orifice: 2 mm). Histomorphologic evaluation showed a normal healing response with negligible neointima covering the connector and limited streamlining repair tissue formation between the staple-like elements of the connector.ConclusionsThe S2 Anastomotic System consistently created automated, fast, and reliable internal thoracic to coronary artery anastomoses on the porcine beating heart with excellent graft patency and healing characteristics at the 5-week follow-up

Surgical Treatment of Acute Thoracic Stent Graft Occlusion

A 24-year-old man presented with acute onset paraplegia related to complete occlusion of a thoracic stent graft placed 2 years prior for repair of traumatic type B aortic dissection. Following emergency surgery comprising reestablishment of aortic flow by stent removal and aortic reconstruction, the paraplegia started to resolve partly, despite an estimated 5-hour interval of preoperative myelum ischemia. Anatomical characteristics of the stent graft placement appear to have played a role in causing this rare complication. Six months later, the patient could walk again with a stick. This case shows that early intervention in cases of full paraplegia may be considered

Functional connectivity and network analysis during hypoactive delirium and recovery from anesthesia

Objective To gain insight in the underlying mechanism of reduced levels of consciousness due to hypoactive delirium versus recovery from anesthesia, we studied functional connectivity and network topology using electroencephalography (EEG). Methods EEG recordings were performed in age and sex-matched patients with hypoactive delirium (n = 18), patients recovering from anesthesia (n = 20), and non-delirious control patients (n = 20), all after cardiac surgery. Functional and directed connectivity were studied with phase lag index and directed phase transfer entropy. Network topology was characterized using the minimum spanning tree (MST). A random forest classifier was calculated based on all measures to obtain discriminative ability between the three groups. Results Non-delirious control subjects showed a back-to-front information flow, which was lost during hypoactive delirium (p = 0.01) and recovery from anesthesia (p < 0.01). The recovery from anesthesia group had more integrated network in the delta band compared to non-delirious controls. In contrast, hypoactive delirium showed a less integrated network in the alpha band. High accuracy for discrimination between hypoactive delirious patients and controls (86%) and recovery from anesthesia and controls (95%) were found. Accuracy for discrimination between hypoactive delirium and recovery from anesthesia was 73%. Conclusion Loss of functional and directed connectivity were observed in both hypoactive delirium and recovery from anesthesia, which might be related to the reduced level of consciousness in both states. These states could be distinguished in topology, which was a less integrated network during hypoactive delirium. Significance Functional and directed connectivity are similarly disturbed during a reduced level of consciousness due to hypoactive delirium and sedatives, however topology was differently affected

One year improvement of exercise capacity in patients with mechanical circulatory support as bridge to transplantation

Abstract Aims Mechanical circulatory support (MCS) results in substantial improvement of prognosis and functional capacity. Currently, duration of MCS as a bridge to transplantation (BTT) is often prolonged due to shortage of donor hearts. Because long‐term results of exercise capacity after MCS are largely unknown, we studied serial cardiopulmonary exercise tests (CPETs) during the first year after MCS implantation. Methods and results Cardiopulmonary exercise tests at 6 and 12 months after MCS implantation in BTT patients were retrospectively analysed, including clinical factors related to exercise capacity. A total of 105 MCS patients (67% male, 50 ± 12 years) underwent serial CPET at 6 and 12 months after implantation. Power (105 ± 35 to 114 ± 40 W; P ≤ 0.001) and peak VO2 per kilogram (pVO2/kg) improved significantly (16.5 ± 5.0 to 17.2 ± 5.5 mL/kg/min (P = 0.008)). Improvement in pVO2 between 6 and 12 months after LVAD implantation was not related to heart failure aetiology or haemodynamic severity prior to MCS. We identified maximal heart rate at exercise as an important factor for pVO2. Younger age and lower BMI were related to further improvement. At 12 months, 25 (24%) patients had a normal exercise capacity (Weber classification A, pVO2 > 20 mL/kg/min). Conclusions Exercise capacity (power and pVO2) increased significantly between 6 and 12 months after MCS independent of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile or heart failure aetiology. Heart rate at exercise importantly relates to exercise capacity. This long‐term improvement in exercise capacity is important information for the growing group of long‐term MCS patients as this is critical for the quality of life of patients

Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis

A fundamental process in the development and progression of heart failure is fibrotic remodeling, characterized by excessive deposition of extracellular matrix proteins in response to injury. Currently, therapies that effectively target and reverse cardiac fibrosis are lacking, warranting novel therapeutic strategies and reliable methods to study their effect. Using a gelatin methacryloyl hydrogel, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and human fetal cardiac fibroblasts (hfCF), we developed a multi-cellular mechanically tunable 3D in vitro model of human cardiac fibrosis. This model was used to evaluate the effects of a promising anti-fibrotic drug-pirfenidone-and yields proof-of-concept of the drug testing potential of this platform. Our study demonstrates that pirfenidone has anti-fibrotic effects but does not reverse all TGF-β1 induced pro-fibrotic changes, which provides new insights into its mechanism of action

Cyclic strain has antifibrotic effects on the human cardiac fibroblast transcriptome in a human cardiac fibrosis-on-a-chip platform

In cardiac fibrosis, in response to stress or injury, cardiac fibroblasts deposit excessive amounts of collagens which contribute to the development of heart failure. The biochemical stimuli in this process have been extensively studied, but the influence of cyclic deformation on the fibrogenic behavior of cardiac fibroblasts in the ever-beating heart is not fully understood. In fact, most investigated mechanotransduction pathways in cardiac fibroblasts seem to ultimately have profibrotic effects, which leaves an important question in cardiac fibrosis research unanswered: how do cardiac fibroblasts stay quiescent in the ever-beating human heart? In this study, we developed a human cardiac fibrosis-on-a-chip platform and utilized it to investigate if and how cyclic strain affects fibrogenic signaling. The pneumatically actuated platform can expose engineered tissues to controlled strain magnitudes of 0–25% – which covers the entire physiological and pathological strain range in the human heart – and to biochemical stimuli and enables high-throughput screening of multiple samples. Microtissues of human fetal cardiac fibroblasts (hfCF) embedded in gelatin methacryloyl (GelMA) were 3D-cultured on this platform and exposed to strain conditions which mimic the healthy human heart. The results provide evidence of an antifibrotic effect of the applied strain conditions on cardiac fibroblast behavior, emphasizing the influence of biomechanical stimuli on the fibrogenic process and giving a detailed overview of the mechanosensitive pathways and genes involved, which can be used in the development of novel therapies against cardiac fibrosis.</p