Intraoperative postinfarct ventricular septal rupture during coronary bypass grafting.

We report a case of a ventricular septal rupture (VSR) which occurred during coronary artery bypass grafting (CABG) operation. The procedure took place 5 days after ST-elevation myocardial infarction of the inferior wall. The VSR repair was not performed at the time of the CABG operation. The intention was to wait until scar formation occurs to facilitate the repair. The patient was supported with venoarterial extracorporeal membranous oxygenation (VA-ECMO) and additional intra-aortic balloon pump (IABP) on intensive care unit. Ten days after CABG the patient underwent a successful VSR repair and 5 days later was weaned from VA-ECMO. He was discharged from hospital 6 weeks after the initial CABG. This case report underlines the importance of VA-ECMO and a multidisciplinary approach with frequent examination of haemodynamic state in the treatment of patients with mechanical complications of myocardial infarction who are not suitable for immediate repair.

Implementation of a specific safety check is associated with lower postoperative mortality in cardiac surgery.

INTRODUCTION: In cardiac surgery, a preincision safety checklist may decrease complications and improve survival. Until now, it has not been demonstrated whether the implementation of such a checklist indeed reduces mortality. OBJECTIVE: Introduction of a preincision safety checklist on mortality was studied in a large adult cardiac surgery population. METHODS: This prospective, multicenter cohort study included 5937 consecutive adult patients, undergoing cardiac surgery, between January 2015 and December 2015, in 7 Dutch non-academic cardiac centers. The Isala Safety Check (ISC) is a short checklist addressing specific cardiac surgery safety items, in combination with a concise postinduction transesophageal echocardiography, which was gradually over time introduced in the 7 hospitals during 2015. We compared 120-day mortality and major complications between patients undergoing surgery with or without the use of the ISC. Propensity matching and Cox regression analyses were performed to adjust for potential confounders. RESULTS: The ISC was applied in 2718 patients (46%). Comorbidity and age were comparable in both groups. In the ISC group, 120-day mortality was significantly lower (1.7% vs 3.0%; P < .01). Both after propensity matching (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87) and Cox regression analysis (hazard ratio, 0.56; 95% confidence interval, 0.35-0.90), the use of the ISC was still associated with reduced 120-day mortality. Deep sternal wound infection, surgical re-exploration, and stroke were not significantly different between both groups. CONCLUSIONS: Application of a short preincision safety checklist in a mixed population of adult cardiac surgery patients is associated with significantly reduced 120-day mortality.

Clinical Effects of Perioperative Selective Decontamination of the Digestive Tract (SDD) in Cardiac Surgery: A Propensity Score Matched Cohort Analysis.

OBJECTIVES: To determine the clinical effects of perioperative endotoxin reduction in the gut lumen in patients undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Retrospective cohort analysis with propensity score matching according to treatment group. SETTING: Tertiary center for cardiopulmonary diseases and intensive care medicine. PARTICIPANTS: Included were patients who underwent cardiac surgery with cardiopulmonary bypass between 2008 and 2017. Excluded were readmitted patients. INTERVENTIONS: Endotoxin reduction in the gut lumen by ingestion of oral tobramycin 80 mg and polymyxin B 100 mg 4 times daily (TP) as part of selective digestive tract decontamination, which contains amphotericin B 500 mg as well. MEASUREMENTS AND MAIN RESULTS: A total of 6,394 patients were included, of whom 2,044 patients were in the intervention group. A total of 835 patients received both pre- and postoperative TP (Pre+/Post+), and 1,165 patients received TP only postoperatively (Pre-/Post+). The control group, not treated with TP at any moment, consisted of 4,350 patients (Pre-/Post-). After matching, 652 Pre+/Post+ patients were compared with an equal number of controls (Pre-/Post-). Pre+/Post+ group did not do better for any clinical outcome. A total of 682 Pre+/Post+ patients matched with an equal number of Pre-/Post+ patients. The latter group had a 0.3 points higher mean Sequential Organ Failure Assessment score and in the regression analysis a significantly higher intensive care unit mortality but not hospital mortality. A significant reduction in length of stay and length of mechanical ventilation for the Pre+/Post+ group was shown compared with Pre-/Post+, but these differences can be explained by unbalanced differences in the severity of illness. CONCLUSION: Cardiosurgical patients who receive tobramycin and polymyxin orally preoperatively to reduce the gut endotoxin level do not expose convincing and relevant beneficial effects on clinical outcomes in this retrospective propensity score matching cohort study.

Myocardial adaptation after surgical therapy differs for aortic valve stenosis and hypertrophic obstructive cardiomyopathy.

Surgical therapies in aortic valve stenosis (AVS) and hypertrophic obstructive cardiomyopathy (HOCM) aim to relief intraventricular pressure overload and improve clinical outcome. It is currently unknown to what extent myocardial adaptation concurs with restoration of intraventricular pressures, and whether this is similar in both patient groups. The aim of this study was to investigate changes in myocardial adaptation after surgical therapies for AVS and HOCM. Ten AVS and ten HOCM patients were enrolled and underwent cardiac magnetic resonance cine imaging and myocardial tagging prior to, and 4 months after aortic valve replacement (AVR) and septal myectomy, respectively. Global left ventricular (LV) analyses were derived from cine images. Circumferential strain was assessed from myocardial tagging images at the septal and lateral wall of the mid ventricle. Pressure gradients significantly decreased in both AVS and HOCM after surgery (p < 0.01), with a concomitant decrease in left atrial volume (p < 0.05) suggesting lower diastolic filling pressures. Also, LV volumes, mass and septal wall thickness decreased in both, but to a larger extent in AVS than in HOCM patients. AVR improved wall thickening (p < 0.05) and did not change systolic strain rate. Myectomy did not affect wall thickening and reduced septal systolic strain rate (p = 0.03). Both AVR and myectomy induced positive structural remodeling in line with a reduction of pressure overload. A concomitant recovery in systolic function however was found in AVR only. The systolic functional deterioration in HOCM patients seems to be inherent to myectomy and the ongoing and irreversible disease.

PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure.

BACKGROUND: Arterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory phospholipase A2 (sPLA2-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA2-IIA herein. METHODS: The effects of PX-18, an inhibitor of both sPLA2-IIA and apoptosis, on residual endothelium and the presence of sPLA2-IIA were studied in human saphenous vein segments (n = 6) perfused at arterial blood pressure with autologous blood for 6 hrs. RESULTS: The presence of PX-18 in the perfusion blood induced a significant 20% reduction in endothelial cell loss compared to veins perfused without PX18, coinciding with significantly reduced sPLA2-IIA levels in the media of the vein graft wall. In addition, PX-18 significantly attenuated caspase-3 activation in human umbilical vein endothelial cells subjected to shear stress via mechanical stretch independent of sPLA2-IIA. CONCLUSIONS: In conclusion, PX-18 protects saphenous vein endothelial cells from arterial blood pressure-induced death, possibly also independent of sPLA2-IIA inhibition.

Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts.

BACKGROUND: Complement is an important mediator in arterial blood pressure-induced vein graft failure. Previously, we noted activation of cell protective mechanisms in human saphenous veins too. Here we have analyzed whether C4b-binding protein (C4bp), an endogenous complement inhibitor, is present in the vein wall. METHODS: Human saphenous vein segments obtained from patients undergoing coronary artery bypass grafting (n = 55) were perfused in vitro at arterial blood pressure with either autologous blood for 1, 2, 4, or 6 hr or with autologous blood supplemented with reactive oxygen species scavenger N-acetylcysteine. The segments were subsequently analyzed quantitatively for presence of C4bp and complement activation product C3d using immunohistochemistry. RESULTS: Perfusion induced deposition of C3d and C4bp within the media of the vessel wall, which increased reproducibly and significantly over a period of 4 hr up to 3.8% for C3d and 81% for C4bp of the total vessel area. Remarkably after 6 hr of perfusion, the C3d-positive area decreased significantly to 1.3% and the C4bp-positive area to 19% of the total area of the vein. The areas positive for both C4bp and C3d were increased in the presence of N-acetylcysteine. CONCLUSIONS: Exposure to arterial blood pressure leads to a transient presence of C4bp in the vein wall. This may be part of a cell-protective mechanism to counteract arterial blood pressure-induced cellular stress and inflammation in grafted veins.

Atrial fibrillation coincides with the advanced glycation end product N(ε)-(carboxymethyl)lysine in the atrium.

Presence of advanced glycation end products (AGEs) in the heart induces a proinflammatory phenotype. However, the presence of AGEs within atrial tissue of atrial fibrillation (AF) patients is unknown and was analyzed here. Left atrial appendage tissue from 33 AF patients and 9 controls was analyzed for the presence of the major AGEs N(ε)-(carboxymethyl)lysine (CML), VCAM-1, neutrophilic granulocytes, lymphocytes, and macrophages in both the fat tissue and myocardium separately. The total amount of fibrosis was also analyzed. Presence of CML was significantly higher in blood vessels of the left atrial appendage in AF patients as compared to controls, independent of diabetes mellitus. In AF patients, VCAM-1 expression in blood vessels and the numbers of infiltrated neutrophilic granulocytes, lymphocytes, and macrophages significantly increased compared to controls, and were highest in the fat tissue; there was no significant difference in fibrosis compared to controls. Interestingly, total amount of CML and fibrosis in AF and control patients correlated positively. Finally, there was no difference between AF patients based on AF type or surgical indication in the presence of CML, VCAM-1 expression, inflammatory cells, and fibrosis. Our results indicate that in AF the intramyocardial blood vessels of the left atrial appendage have an increased CML presence and proinflammatory status coinciding with a local increase in the number of inflammatory cells.

C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

OBJECTIVES: Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. METHODS: Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. RESULTS: Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. CONCLUSION: C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting.

TR3 nuclear orphan receptor prevents cyclic stretch-induced proliferation of venous smooth muscle cells.

In coronary artery bypass surgery, the patency of arterial grafts is higher than that of venous grafts because of vein-graft disease, which involves excessive proliferation of venous smooth muscle cells (SMCs) and subsequent accelerated atherosclerosis. We studied the function of TR3 nuclear orphan receptor (TR3) in the early response of SMCs to mechanical strain, a major initiator of vein-graft disease. We demonstrate that TR3 expression is induced in human saphenous vein segments exposed ex vivo to whole-blood perfusion under arterial pressure. Cultured venous SMCs challenged by cyclic stretch displayed TR3 induction and enhanced DNA synthesis, whereas SMCs derived from the internal mammary artery remained quiescent. Small-interfering RNA-mediated knockdown of TR3 and adenovirus-mediated overexpression of TR3 in venous SMCs enhanced and abolished stretch-induced DNA synthesis, respectively. Accordingly, in organ cultures of wild-type murine vessel segments exposed to cyclic stretch, p27(Kip1) was down-regulated, whereas expression of this cell cycle inhibitor was unaffected by cyclic stretch in TR3-transgenic vessels, concordant with a lower proliferative response. Finally, stretch-mediated proliferation was inhibited by 6-mercaptopurine, an agonist of TR3. In conclusion, TR3 represents inhibitory mechanisms to restrict venous SMC proliferation and may contribute to prevention of vein-graft disease.

N(omega)-(carboxymethyl)lysine depositions in human aortic heart valves: similarities with atherosclerotic blood vessels.

Recent studies indicate a role of atherosclerosis-like changes involved in the pathogenesis of aortic valve stenosis. Interestingly, one of the major advanced glycation end products (AGEs), N(omega)-(carboxymethyl)lysine (CML) has been related to the process of atherosclerosis in blood vessels. In the present study, we have analyzed the presence of CML in degenerative altered aortic valves with atherosclerosis-like changes, and in degenerated mitral valves without atherosclerosis-like changes, derived from patients suffering from acute rheumatism during childhood. Degenerated and non-degenerated valves were derived from autopsy or obtained during cardiac surgery. The presence of CML was examined by immunohistochemistry. CML was found on the endothelium and fibroblasts in control aortic and mitral valves. Minor differences in CML staining were observed between control and degeneratively affected mitral valves. In contrast, in degenerated aortic valves, CML accumulation was found in macrophages and on calcification sites, comparable to that in atherosclerotic arteries, while the presence of CML staining on the endothelium and fibroblasts was significantly less as compared with control aortic valves. Our data support the hypothesis that the process of degeneration of aortic valves resembles that of atherosclerosis in blood vessels. They suggest that CML also plays a role in the process of atherosclerosis in aortic valves.

Pressure-diameter relationship in the human greater saphenous vein.

BACKGROUND: Compliance of artificial and autologous vascular grafts is related to future patency. We investigated whether differences in compliance exist between saphenous vein grafts derived from the upper or lower leg, which might indicate upper or lower leg saphenous vein preference in coronary artery bypass surgery. Furthermore, the effect of perivenous application of fibrin glue on mechanical vein wall properties was studied to evaluate its possible use as perivenous graft support. METHODS: Vein segments (N = 10) from upper or lower leg saphenous vein grafts were collected for histopathologic examination and smooth muscle cell/extracellular matrix (SMC/ECM) ratio was calculated. This ratio is suggested to be related with vascular elastic compliance. In a second group vein graft segments (N = 6) from upper and lower leg were placed in an in vitro model generating stepwise increasing static pressure up to 150 cm H(2)O. Outer diameter was measured continuously with a video micrometer system. Distensibility was calculated from the pressure-diameter curves. A third group of vein graft segments (N = 7) was pressurized after fibrin glue application to prevent overdistension, and studied in the same setup. RESULTS: Vein segments from the lower leg demonstrated a consistent higher relative response compared with the upper leg saphenous vein graft (0.9176 +/- 0.03993 vs 0.5245 +/- 0.02512). Both reach a plateau in the high-pressure range (> 100 cm H(2)O). A significant difference in in vitro distensibility between upper and lower leg saphenous vein was only found at a pressure of 50 cm H(2)O (p < 0.05). With fibrin glue, support overdistension is prevented as revealed by the maximum relative response between fibrin glue supported upper and lower leg saphenous vein segments (0.4080 +/- 0.02464 vs 0.582 +/- 0.051), and no plateau is reached in the pressure range up to 150 cm H(2)O. CONCLUSIONS: No upper or lower leg saphenous vein preference could be deduced from the differences in pressure-diameter response due to loss of distensibility (and thus of compliance) in the high-pressure range. Fibrin glue effectively prevents overdistension and preserves some distensibility in the high-pressure range in both the upper and lower leg saphenous vein. This might provide a basis for clinical application of perivenous support.