Bioprosthetic Valve Deterioration: Accumulation of Circulating Proteins and Macrophages in the Valve Interstitium.

Histologic evaluations revealed excessive accumulations of macrophages and absence of fibroblastic interstitial cells in explanted bioprosthetic valves. Comprehensive gene and protein expression analysis and histology unveiled an accumulation of fibrinogen and plasminogen, an activator of infiltrated macrophages, from degenerated valve surfaces in the interstitial spaces. These pathologies were completely reproduced in a goat model replaced with an autologous pericardium-derived aortic valve. Further preclinical animal experiments using goats demonstrated that preventing infiltration of macrophages and circulating proteins by increasing collagen density and leaflet strength is an effective treatment option.

Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft "Biotube" in a Goat Model.

OBJECTIVE: There is a need for small diameter vascular substitutes in the absence of available autologous material. A small diameter, long tissue engineered vascular graft was developed using a completely autologous approach called "in body tissue architecture technology (iBTA)". The aim of this pilot study was to evaluate "Biotubes", iBTA induced autologous collagenous tubes, for their potential use as small diameter vascular bypass conduits. METHODS: Biotubes (internal diameter 4 mm, length 50 cm, wall thickness 0.85 mm) were prepared by subcutaneous embedding of plastic moulds (Biotube Maker) in three goats for approximately two months. Allogenic Biotubes (length 10 cm [n = 2], 15 cm [n = 2], 22 cm [n = 2]) were bypassed to both carotid arteries by end to side anastomosis with their ligation between the anastomoses in another three goats. Residual Biotubes were examined for their mechanical properties. After four weeks, the harvested Biotubes were evaluated histologically. RESULTS: All Biotubes had sufficient pressure resistance, approximately 3000 mmHg. Although wall thickening occurred at two proximal anastomosis sites, all six grafts were patent without luminal thrombus formation, stenosis, or aneurysm deformation throughout the implantation period. Endothelial cells covered both anastomosis sites almost completely, with partial covering in the central portion of the grafts. Furthermore, α smooth muscle actin positive cells infiltrated the middle layer along almost the entire graft length. CONCLUSION: This preliminary study showed that small diameter, long, tissue engineered Biotubes could function properly as arterial bypass conduits in a large animal for one month without any abnormal change in vascular shape. Thus, small diameter, long Biotubes are potentially viable conduits, which are biocompatible and labour non-intensive, and therefore, suitable for clinical practice. Additionally, Biotubes can start the regeneration process in a short period of time.

Extensive Aortic Stent Graft Coverage for Thoracoabdominal Aortic Aneurysm is Associated With Hemorrhagic Complications Induced by Disseminated Intravascular Coagulation.

BACKGROUND: Hybrid endovascular repair for thoracoabdominal aortic aneurysm (TAAA) is a less invasive alternative treatment than conventional open repair. However, disseminated intravascular coagulation (DIC) and hemorrhagic complications can occur postoperatively. We investigated risk factors for hemorrhagic complications after hybrid endovascular TAAA repair. METHODS: Sixty-one patients who underwent elective hybrid endovascular TAAA repair between 2007 and 2020 were included. Laboratory data before and after placing stent graft were collected, and DIC was diagnosed using a scoring system established by the Japanese Association for Acute Medicine. The length of the stent graft used to cover the aorta was defined as the aortic coverage length, which was measured using the first postoperative computed tomography image. Predictors of unexpected hemorrhagic complications were evaluated. RESULTS: Postoperative thrombocytopenia was observed in 57 (93%) patients, and their platelet count decreased significantly after stent graft placement (14.3 [9.5-18.0] vs. 8.2 [5.4-10.9] × 104/µL, P < 0.001). Fifteen (25%) and 45 patients (74%) were diagnosed with DIC before and after stent graft placement, respectively. Hemorrhagic complications were observed in 21 patients (34%). Multivariate logistic regression analysis revealed that aortic coverage length was an independent risk factor for hemorrhagic complications (odds ratio 1.441/50 mm increase; 95% confidence interval, 1.041-1.994, P = 0.027). The cutoff value for aortic coverage length obtained from the receiver operating characteristic curve (area under the curve = 0.72) was 304.4 mm (sensitivity 0.76, specificity 0.70). CONCLUSION: Aortic coverage length is a risk factor for hemorrhagic complications. Patients undergoing extensive aortic coverage greater than 304 mm should be closely monitored.

Left atrial geometry in an ovine ischemic mitral regurgitation model: implications for transcatheter mitral valve replacement devices with a left atrial anchoring mechanism.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms. METHODS: A group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI). RESULTS: Six animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI. CONCLUSIONS: Systolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms.

Three-month outcomes of aortic valve reconstruction using collagenous membranes (biosheets) produced by in-body tissue architecture in a goat model: a preliminary study.

BACKGROUND: Autologous pericardium is widely used as a plastic material in intracardiac structures, in the pulmonary artery, and in aortic valve leaflets. For aortic valve reconstruction (AVRec) using the Ozaki procedure, it has produced excellent clinical results over a 10-year period. In-body tissue architecture (iBTA), which is based on the phenomenon of tissue encapsulation of foreign materials, can be used to prepare autologous prosthetic tissues. In this preliminary study, we examined whether biosheets can be used as valve leaflet material for glutaraldehyde-free AVRec by subchronic implantation experiments in goats and evaluated its performance compared with glutaraldehyde-treated autologous pericardium for AVRec. METHODS: Biosheets were prepared by embedding molds for two months into the dorsal subcutaneous spaces of goats. Autogenic biosheets (n = 4) cut into the shape of the valve were then implanted to the aortic valve annulus of four goats for three months without glutaraldehyde treatment. Autologous pericardium (n = 4) was used in four goats as a control. Valve function was observed using echocardiography. RESULTS: All goats survived the three-month study period. With biosheets, the leaflet surfaces were very smooth and, on histology, partially covered with a thin neointima (including endothelial cells). Biosheets were more thoroughly assimilated into the aortic root compared with autologous pericardium. CONCLUSIONS: For the first time, biosheets were used for large animal AVRec. Biosheets could function as leaflets in the aortic position and may have the ability to assimilate into native valves.

Femoral artery anatomy is a risk factor for limb ischemia in minimally invasive cardiac surgery.

OBJECTIVE: In minimally invasive cardiac surgery (MICS), femoral artery cannulation during cardiopulmonary bypass (CPB) can cause limb ischemia. This study evaluated the association between femoral artery anatomy and the risk of limb ischemia in MICS. METHODS: Eighty-one patients who underwent MICS with CPB using single femoral artery cannulation between 2010 and 2018 were included. The patients were stratified by their femoral artery diameter and anatomy of ectopic side branch, i.e., medial or lateral femoral circumflex arteries: Type A, deep femoral artery (DFA) ≥ superficial femoral artery (SFA); type B, DFA < SFA with an ectopic side branch of the common femoral artery (CFA); type C, DFA < SFA with an ectopic side branch at the CFA bifurcation; and type D, DFA < SFA without an ectopic side branch. The ratio of the postoperative creatine kinase concentration and the cross-sectional area of the femoral muscles (CK/MA) was used as a surrogate marker of limb ischemia. Predictors of high CK/MA were evaluated. RESULTS: No critical limb ischemia was observed in this study. The median postoperative creatine kinase and CK/MA were 1954 (1305-2872) IU/l and 15.2 (9.2-19.8) IU/l/cm2. Multivariable logistic regression found that anatomical type D (odds ratio 4.19, 95% confidence interval: (1.26-14.0); p = 0.020) and prolonged CPB time (OR 1.01, 95% CI (1.00-1.02); p = 0.045) were independent risk factors of high CK/MA. CONCLUSION: Anatomical type D and prolonged CPB time were associated with risk of limb ischemia in MICS.

Iron imaging in myocardial infarction reperfusion injury.

Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.

[Combined Valvular Disease with Suspected Acquired von Willebrand Syndrome].

A 73-year-old female was referred to our department for surgical treatment of combined rheumatic valvular disease. She had undergone percutaneous transluminal mitral commissurotomy 29 years before. She underwent double valve replacement with bioprosthetic valves and tricuspid annuloplasty combined with left atrial appendectomy for chronic atrial fibrillation. Because of remarkable bleeding following surgery, rapid blood transfusion and re-thoracotomy were immediately performed. However, the bleeding persisted even after re-thoracotomy, and acquired von Willebrand syndrome due to valvular disease was suspected. Von Willebrand factor/factor Ⅷ preparation was administered, and bleeding promptly became under control. Recently, acquired von Willebrand syndrome due to valvular disease has attracted attention. We need to keep it in mind during perioperative management for patients with valvular disease.

In vitro evaluation of the hemostatic effect of method involving the combined use of Hydrofit® and Spongel®.

OBJECTIVE: We developed an effective hemostatic method using Hydrofit® and a hemostatic gelatin sponge (Spongel®). We evaluated the hemostatic effect in comparison to the conventional silicone sheet method. METHODS: A simulated circuit was created using the pump of a Nipro ventricular assist system and a prosthetic graft. A hole was made in the graft by a needle and three hemostatic methods were applied: the silicone sheet method (SS) using Hydrofit® and a silicone sheet, the bread and butter method (BB) using Hydrofit® and a gelatin sponge instead of a silicone sheet, and French toast method (FT) using Hydrofit® and a gelatin sponge over which water was poured before compression. The amount of leakage before and after the application each of the methods was measured according to the compression time. RESULTS: In the 60 s compression, the amount of leakage after SS, BB, and FT was 0.4 ± 0.8, 0.2 ± 0.6, and 0 ± 0.0 ml, respectively, and FT showed no leakage. In the 30 s compression, the amount of leakage after SS, BB, and FT was 14.2 ± 27.9, 1.0 ± 3.2, and 7.8 ± 22.6 ml, respectively, and did not differ to a statistically significant extent. CONCLUSIONS: The method of combining Hydrofit® and Spongel® could obtain reliable hemostasis in 60 s.

Potential utility of new surgical hemostatic film using Hydrofit®: a preliminary study.

We developed a surgical hemostatic film using Hydrofit® (Hydrofit® film). This film is prepared by reacting Hydrofit® with water in advance, and it can be used in the same way as an accessory silicone sheet. In addition, unlike the silicone sheet, there is no need to remove the Hydrofit® film from the body. In the present study, we describe the hemostatic effect of our new method using Hydrofit® film. We created a pulsatile flow circuit model using a ventricular assist device and a vascular graft. The circuit was filled with water, and the systolic pressure was adjusted to ≥ 130 mmHg. The artificial blood vessel was punctured by an 18-G needle. Operations to prevent water from leaking were attempted through either a conventional method using a silicone sheet or our new method using Hydrofit® film. In the 180-s trial, 14 attempts (93.3%) with the Hydrofit® film were successful. In the silicone sheet group, 13 attempts (86.7%) were successful before the silicone sheet was peeled off, and hemostasis was maintained in 10 (66.5%) cases after the silicone sheet was removed. After short-duration hemostasis for 60 s, good waterproofing was obtained in the Hydrofit® film group (success in 17 cases [85%]). In contrast, in the silicone sheet group, 10 attempts (50%) were successful before the silicone sheet was peeled off, and hemostasis was maintained in only 7 (35%) cases after the silicone sheet was removed. Hydrofit® film showed good hemostatic performance in the pulsatile flow circuit model.

Optimized mitral annuloplasty ring design reduces loading in the posterior annulus.

OBJECTIVE: The study objective was to develop a novel annuloplasty ring with regional flexibility and assess its suture force dynamics in healthy ovine subjects compared with fully rigid or fully flexible rings. METHODS: Materially heterogeneous rings were created with rigid anterior and posterior, and flexible commissural segments. These rings were created to match the geometry of the Profile 3D ring (Medtronic, Minneapolis, Minn). Each ring was instrumented with 10 force transducers to measure cyclic suture forces (FC) and undersized annuloplasty was performed in 6 healthy ovine subjects. Each FC was recorded and examined for cardiac cycles reaching a maximum left ventricular pressure of 100, 125, and 150 mm Hg. FC was compared with previously reported values from fully rigid Profile 3D and fully flexible prototype rings. RESULTS: Relative to the fully rigid ring, the heterogeneous ring exhibited 48% reduction in FC at its commissural (rigid vs heterogeneous: 1.80 ± 0.94 N vs 0.95 ± 0.52 N; P < .001) and 32% reduction in posterior (1.90 ± 0.92 N vs 1.29 ± 0.91 N; P < .001) regions, but not in its anterior region (2.45 ± 1.21 N vs 2.23 ± 1.22 N; P = .279). Relative to the fully flexible ring, the heterogeneous ring exhibited no significant differences in FC in any region. CONCLUSIONS: The reduced FC of the heterogeneous ring relative to the fully rigid ring suggests a promising approach to reduce suture loading while preserving the annular remodeling capability of fully rigid rings. Future studies in diseased subjects are necessary to explore repair effectiveness of this ring.

Metabolite Exchange between Mammalian Organs Quantified in Pigs.

Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotides by the spleen and TCA intermediates by pancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange.

Mitral annuloplasty ring flexibility preferentially reduces posterior suture forces.

Annuloplasty ring repair is a common procedure for the correction of mitral valve regurgitation. Commercially available rings vary in dimensions and material properties. Annuloplasty ring suture dehiscence from the native annulus is a catastrophic yet poorly understood phenomenon that has been reported across ring types. Recognizing that sutures typically dehisce from the structurally weaker posterior annulus, our group is conducting a multi-part study in search of ring design parameters that influence forces acting on posterior annular sutures in the beating heart. Herein, we report the effect of ring rigidity on suture forces. Measurements utilized custom force sensors, attached to annuloplasty rings and implanted in normal ovine subjects via standard surgical procedure. Tested rings included the semi-rigid Physio (Edwards Lifesciences) and rigid and flexible prototypes of matching geometry. While no significant differences due to ring stiffness existed for sutures in the anterior region, posterior forces were significantly reduced with use of the flexible ring (rigid: 1.95 ±â€¯0.96 N, semi-rigid: 1.76 ±â€¯1.19 N, flexible: 1.04 ±â€¯0.63 N; p < 0.001). The ratio of anterior to posterior FC scaled positively with increasing flexibility (p < 0.001), and posterior forces took more time to reach their peak load when a flexible ring was used (p < 0.001). This suggests a more rigid ring enables more rapid/complete force equilibration around the suture network, transferring higher anterior forces to the weaker posterior tissue. For mitral annuloplasties requiring ring rigidity, we propose a ring design concept to potentially disrupt this force transfer and improve suture retention.

[Transaortic Thoracic Endovascular Aortic Repair Via Right Anterior Mini-thoracotomy;Report of a Case].

An 81-year-old man presented with ruptured thoracic aortic aneurysm under stable condition. He had been suffering from chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. We performed hybrid thoracic endovascular aortic repair via right anterior mini-thoracotomy inserting a device through a conduit on the ascending aorta. The patient was discharged without aorta-related complications.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.

Difficult preoperative diagnosis in a case of rapidly progressive carcinomatous pericarditis.

A 54-year-old woman initially diagnosed with stage IIIb squamous cell carcinoma of the uterine cervix was treated with chemotherapy and radiation therapy. After 8 months, she developed dyspnea, leg edema, pleural effusion, pericardial effusion, and liver congestion. Her cardiac ejection fraction was normal and cardiomegaly was not evident. Metastatic carcinomatous pericarditis or pleurisy was suspected, but laboratory findings, including tumor markers, were normal. She was transferred to our hospital for the repair a cardiac injury caused by a pericardial drainage procedure. Emergency surgery was performed for the misplaced drainage catheter in the right atrium and for an abnormal mass in her right and left atria. The clinical diagnosis of carcinomatous pericarditis was made; however, her condition rapidly deteriorated, and she died 6 days postoperatively. At autopsy, metastasis was identified in a large area of the pericardium and myocardium.