Annulative coupling of vinylboronic esters: aryne-triggered 1,2-metallate rearrangement.

A stereoselective annulative coupling of a vinylboronic ester ate-complex with arynes producing cyclic borinic esters has been developed. An annulation reaction that proceeded through the formation of two C-C bonds and a C-B bond was realized by exploiting a 1,2-metallate rearrangement of boronate triggered by the addition of a vinyl group to the strained triple bond of an aryne. The generated aryl anion would then cyclize to a boron atom to complete the annulation cascade. The annulated borinic ester could be converted to boronic acids and their derivatives by oxidation, halogenation, and cross-coupling. Particularly, halogenation and Suzuki-Miyaura coupling proceeded in a site-selective fashion and produced highly substituted alkylboronic acid derivatives.

A tissue-engineered, decellularized, connective tissue membrane for allogeneic arterial patch implantation.

BACKGROUND: We have previously applied in vivo tissue-engineered vascular grafts constructed in patients' subcutaneous spaces. However, since the formation of these vascular grafts depends on host health, their application is challenging in patients with suppressed regenerative ability. Therefore, the allogeneic implantation of grafts from healthy donors needs to be evaluated. This study aimed to fabricate allogeneic cardiovascular grafts in animals. MATERIALS AND METHODS: Silicone rod molds were implanted into subcutaneous pouches in dogs; the implants, along with surrounding connective tissues, were harvested after four weeks. Tubular connective tissues were decellularized and stored before they were cut open, trimmed to elliptical sheets, and implanted into the common carotid arteries of another dog as vascular patches (n = 6); these were resected and histologically evaluated at 1, 2, and 4 weeks after implantation. RESULTS: No aneurysmal changes were observed by echocardiography. Histologically, we observed neointima formation on the luminal graft surface and graft wall cell infiltration. At 2 and 4 weeks after implantation, α-SMA-positive cells were observed in the neointima and graft wall. At 4 weeks after implantation, the endothelial lining was observed at the grafts' luminal surfaces. CONCLUSION: Our data suggest that decellularized connective tissue membranes can be prepared and stored for later use as allogeneic cardiovascular grafts.

The Novel Technique of Sternal Closure With Absorbable Mesh for Osteoporotic Patients.

After a median sternotomy, sternal instability can result in sternal infection. The usual sternal closure with stainless steel wires may result in sternal instability, especially in osteoporotic patients. An absorbable mesh (Super-FIXSORB-MX®40, Takiron Co Ltd, Osaka, Japan) for reinforcing the sternum has become commercially available. This paper reports a modified sternal closure procedure using this absorbable mesh in combination with heavy braided Polydiaxanon (PDS cord®, Ethicon, Inc., Somerville, NJ, USA) for osteoporotic patients.

Formal Total Synthesis of Manzacidin B via Sequential Diastereodivergent Henry Reaction.

A formal total synthesis of manzacidin B is described. ß,ß-Disubstituted γ-hydroxy-ß-aminoalcohol, the key structure of manzacidin B, is stereoselectively constructed via sequential Henry reactions. By taking advantage of noncovalent interactions, such as intramolecular hydrogen bonding and chelation, we could diastereodivergently control the stereoselectivity of the Henry reaction.

Impact of right ventricular volume and function evaluated using cardiovascular magnetic resonance imaging on outcomes after surgical ventricular reconstruction.

OBJECTIVES: This study aimed to evaluate whether cardiac magnetic resonance imaging (MRI)-derived right ventricular (RV) assessment can facilitate risk stratification among patients with ischaemic cardiomyopathy who underwent surgical ventricular reconstruction (SVR). METHODS: We retrospectively analysed 53 patients who underwent SVR. The patients were preoperatively evaluated using cardiac MRI. Cine-MRI was acquired for left ventricular (LV) and RV volume. Gadolinium-enhanced MRI was performed to evaluate LV scarring. The mid-term (median, 58 months) risk factors of all-cause mortality and major adverse cardiac events were analysed. RESULTS: A significant reduction in LV end-diastolic and end-systolic volume index and an increase in LV ejection fraction were observed early after SVR. RV end-diastolic volume index (RVEDVI) and RV end-systolic volume index (RVESVI) decreased after SVR (preoperative versus postoperative: RVEDVI, 71 ± 24 vs 62 ± 17 ml/m2, P = 0.006; RVESVI, 44 ± 26 vs 37 ± 16 ml/m2, P = 0.033), but RV ejection fraction did not change (preoperative versus postoperative: RV ejection fraction 40.8±14.6 vs 42.0±11.0%, P = 0.067). At follow-up, 25 deaths and 31 major adverse cardiac events occurred. After adjustment for age, creatinine level and preoperative mitral regurgitation grade, the Cox-hazard model indicated that RVEDVI [P = 0.006, hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05] and RVESVI [P = 0.007, HR 1.02, 95% CI 1.01-1.04] were significant predictors for all-cause mortality. As for major adverse cardiac events, RVEDVI (P = 0.007, HR 1.03, 95% CI 1.01-1.05), RVESVI (P = 0.002, HR 1.03, 95% CI 1.01-1.04) and RV ejection fraction (P = 0.018, HR 0.97, 95% CI 0.94-0.99) were significant. CONCLUSIONS: RV parameters were more sensitive than LV parameters for predicting worse outcomes following SVR. Preoperative assessment of RV volume and function using cardiac MRI may improve the risk stratification of SVR.

New imaging tools in cardiovascular medicine: computational fluid dynamics and 4D flow MRI.

Blood flow imaging is a novel technology in cardiovascular medicine and surgery. Today, two types of blood flow imaging tools are available: measurement-based flow visualization including 4D flow MRI (or 3D cine phase-contrast magnetic resonance imaging), or echocardiography flow visualization software, and computer flow simulation modeling based on computational fluid dynamics (CFD). MRI and echocardiography flow visualization provide measured blood flow but have limitations in temporal and spatial resolution, whereas CFD flow calculates the flow according to assumptions instead of flow measurement, and it has sufficiently fine resolution up to the computer memory limit, and it enables even virtual surgery when combined with computer graphics. Blood flow imaging provides profound insight into the pathophysiology of cardiovascular diseases, because it quantifies and visualizes mechanical stress on the vessel walls or heart ventricle. Wall shear stress (WSS) is a stress on the endothelial wall caused by the near wall blood flow, and it is thought to be a predictor of atherosclerosis progression in coronary or aortic diseases. Flow energy loss (EL) is the loss of blood flow energy caused by viscous friction of turbulent diseased flow, and it is expected to be a predictor of ventricular workload on various heart diseases including heart valve disease, cardiomyopathy, and congenital heart diseases. Blood flow imaging can provide useful information for developing predictive medicine in cardiovascular diseases, and may lead to breakthroughs in cardiovascular surgery, especially in the decision-making process.

Single-Centre Experience of Off-Pump Multi-Vessel Coronary Artery Bypass Grafting Using Proximal Suture Device.

BACKGROUND: To investigate the results of off-pump coronary artery grafting (OPCAB) with the proximal suture device (PSD) regarding postoperative stroke and graft patency. METHODS: The PSD was used in 376 patients (32.0%), aorta-no-touch OPCAB was performed in 523 patients (45.2%), on-pump beating coronary artery bypass surgery (CABG) (on-beat group) in 125 patients (10.6%) including 51 conversions (conversion rate: 5.4%), and CABG with aortic clamp use (clamp group) in 152 patients. In the PSD group, Enclose II was used in 267 patients (71.0%). RESULTS: The hospital mortality rate was 1.95%. There was no early stroke in the OPCAB group, whereas the early-stroke rate was 0.8% in the on-beat group and 2.6% in the clamp group. The incidences of stroke at one month were: PSD group, 1.6%; no-touch group, 1.1%; on-beat group, 1.6%; and clamp group, 4.6% (p=0.014). The rates of complete revascularisation were higher in the PSD and clamp groups (94.7 and 94.0%, respectively) compared with the no-touch and on-beat groups (81.5 and 84.9%, respectively; p<0.001). The vein graft patency rates were comparable between the PSD and clamp groups. In multiple logistic regression analysis, OPCAB using the PSD did not increase the risk of stroke compared with the no-touch group (adjusted odds ratio [AOR]: 1.40; p=0.594) or on-beat group (AOR: 0.99; p=0.206), but reduced the risk of stroke compared with the clamp group (AOR: 0.19; p=0.005). CONCLUSIONS: Off-pump coronary artery grafting using the PSD was a safe and effective procedure. It led to lower incidences of postoperative stroke and excellent rates of graft patency and complete revascularisation compared with conventional CABG.

Endocardial linear infarct exclusion technique for infarcted lateral wall.

We report a novel method of surgical ventricular restoration for an infarcted lateral wall: the endocardial linear infarct exclusion technique. First, transmural ventriculotomy is performed at the centre of the scar longitudinally along the coronary artery. Second, the inner layer is sutured in a longitudinal direction with 4-0 polypropylene continuous sutures to approximate the border between the normal and infarcted myocardium. Finally, the outer layer is closed with a combination of interrupted buttress and continuous over-and-over sutures with outer felt reinforcement. The advantages of endocardial linear infarct exclusion technique are as follows: the risk of bleeding is low; it is not technically demanding and is reproducible; the coronary artery can be preserved; approximation of the base of the anterior and posterior papillary muscles is possible in the case of ischaemic mitral regurgitation and it can also be applied to the anterior and inferior walls.

Ventricular volume and myocardial viability, evaluated using cardiac magnetic resonance imaging, affect long-term results after surgical ventricular reconstruction.

OBJECTIVES: We aimed to investigate the outcomes of surgical ventricular reconstruction (SVR) for ischaemic cardiomyopathy and to identify ideal candidates for this procedure using cardiac magnetic resonance imaging (MRI) studies. METHODS: We retrospectively examined 50 patients who underwent SVR and were preoperatively evaluated using cardiac MRI from 2004 to 2014. Cine MRI and gadolinium-enhanced MRI were performed to evaluate left ventricular (LV) volume and scarring. The midterm (median, 2.5 years) risk factors of cardiac death or major adverse cardiac events (MACEs) were analysed. Patients were divided into three groups-those with preoperative indexed LV end-systolic volume (LVESVI) of ≤100 ml/m2 (Group 1), those with LVESVI of >100 and ≤130 ml/m2 (Group 2) and those with LVESVI of >130 ml/m2 (Group 3)-and examined. RESULTS: In total, 17 patients exhibited MACEs at follow-up. Kaplan-Meier analysis showed that the 5-year rate of freedom from MACEs was 66%. The Cox hazard model indicated that preoperative LVESVI was the only significant predictor for MACEs (P = 0.006; hazard ratio, 1.02; 95% confidence interval, 1.01-1.04). Moreover, a significant reduction in LVESVI and an increase in LV ejection fraction (LVEF) were observed early after SVR (preoperative versus postoperative: LVESVI, 110 ± 44 vs 68 ± 28 ml/m2, P < 0.001; LVEF, 24.3 ± 10.3 vs 32.0 ± 10.4%, P < 0.001) and at follow-up (LVESVI, 61 ± 28 ml/m2, P < 0.001; LVEF, 36.5 ± 11.5%, P < 0.001). Although no difference was observed between the groups at follow-up, LVEF and LVESVI primarily improved in Group 2. LVEF improvement was significantly greater in Group 2 than in Group 1 (%increase in LVEF: Group 1, 6%; Group 2, 18%; P = 0.008). In patients with a preoperative LVESVI of >130 ml/m2, the number of non-viable segments was a significant risk factor for MACEs. CONCLUSIONS: Patients with preoperative LVESVI ranging from 100 to 130 ml/m2 had fairly better outcomes, and the percentage improvement in LVEF and the percentage reduction in LVESVI were more pronounced in these patients. Hence, accurate preoperative assessments of LV volume and viability testing using cardiac MRI studies are essential for better stratification of the SVR procedure.

Blood flow analysis of the aortic arch using computational fluid dynamics.

OBJECTIVES: To obtain predictive information regarding aortic disease, we evaluated how blood flow inside the aortic arch was influenced by thoracic aortic aneurysms. In addition, to reveal the optimal intraoperative management in these cases, we examined blood flow during right subclavian arterial (rSCA) perfusion using computational fluid dynamics (CFD). METHODS: Patient-specific models of the aortic arch were made with six different patterns based on the computed tomographic images. CFD models with finite volume methods were created to simulate the physiological pulsatile flow including the peripheral reflection wave, characteristic impedance and autonomous regulation system. Flow stream patterns, wall shear stress (WSS) and the oscillatory shear index (OSI) were calculated during one cardiac cycle. Furthermore, flow streamlines during rSCA perfusion were simulated under different perfusion flows. RESULTS: Aortic dilatation caused vortical disturbed flow in a dilated space, resulting in turbulent flow not only inside the aneurysm but also in the proximal and/or distal normal aortic portion. In patients with a dilated thoracic aorta, there was a helical spiral flow with a circumferential vortex in systole. In patients with an arch aneurysm, turbulent flow inside the aneurysm caused a high OSI at the tip of the aneurysm. A high OSI was detected at the orifice of the supra-aortic branches, sinotubular junction, posterior lateral side of the ascending aorta and lesser curvature of the proximal descending aorta. rSCA perfusion revealed that the right common carotid artery was perfused by blood flow from rSCA throughout the cardiac cycle. With 75% of the flow from the rSCA, blood flow from the heart reached the left common carotid and subclavian artery only during a short period during the peak of systole. CONCLUSIONS: A dilated aorta causes a turbulent flow pattern in the aortic arch. The high OSI site was similar to the favourite entry site for acute aortic dissection, indicating the causal relationship between mechanical stress and acute aortic dissection. rSCA cannulation might be cerebroprotective from ascending aortic plaque.

Hybrid Repair of Proximal Subclavian Artery Aneurysm.

OBJECTIVE: Conventional open repair for proximal subclavian artery aneurysms (SCAAs) requires cardiopulmonary bypass. However, patients with proximal SCAA can be treated with hybrid repair. METHODS: Between 2007 and 2012, we performed hybrid repair to treat six consecutive patients with proximal SCAA (three left SCAAs, one right aberrant SCAA, two right SCAAs). Their median age was 73.5 [70-87] years, and the size of their aneurysm was 33.5 [30-45] mm. Thoracic endovascular aneurysm repair (TEVAR) only was used for one patient with left SCAA, TEVAR and supra-aortic bypass for two with left SCAA and one with right aberrant SCAA, and endovascular repair with reconstruction of the vertebral artery using the saphenous vein graft (SVG) for two with right SCAA. RESULTS: The follow-up duration was 3.7 [0.2-6.8] years. There was no 30-day mortality and only one early complication consisting of a minor stroke after TEVAR for shaggy aorta. Two late deaths occurred, one caused by cerebral infarction due to occlusion of SVG to the dominant vertebral artery 2 months after the operation and the other by aortic dissection 5 years postoperatively. CONCLUSIONS: Hybrid repair can be a less-invasive alternative for proximal SCAA. Revascularization of neck vessels and TEVAR should be performed very carefully to prevent neurologic complications.

Impact of Ross Operation on Outcome in Young Female Adult Patients Wanting to Have Children.

BACKGROUND: The most appropriate valve substitute at aortic valve replacement (AVR) for young female adult patients wanting to have children is unclear. METHODS AND RESULTS: Between 1992 and 2013, 12 consecutive female patients aged >18 (median, 22.5 years; range, 18-34 years) underwent Ross operation (Ross group). Between 1984 and 2013, 9 consecutive female patients aged >18 (median, 30 years; range, 22-39 years) underwent AVR with bioprosthesis (bioprosthesis group). There was 1 late mortality in the bioprosthesis group, due to prosthetic valve endocarditis (PVE). Freedom from reoperation for aortic valve at 15 years was 90.0% in the Ross group, and 57.1% in the bioprosthesis group (log-rank, P=0.098). One in the Ross group underwent reoperation for aortic regurgitation (AR), whereas 4 in the bioprosthesis group did so for aortic stenosis (AS) in 2, combined AS and AR in 1, and PVE in 1. Five patients in the Ross group and 3 in the bioprosthesis group had 7 and 4 uneventful pregnancies, respectively. AR progressed during the perinatal period in a total of 7 of 11 pregnancies. No AS was seen at discharge, after 5 years, or during pregnancy in the Ross group. CONCLUSIONS: The long-term outcome of Ross operation for female patients wanting to have children is excellent. Although subclinical pulmonary autograft valve regurgitation during pregnancy was often observed, pulmonary autograft stenosis did not occur, therefore it would be an ideal option for patients wanting to have children.

Post-operative left atrioventricular valve function after the staged repair of complete atrioventricular septal defect with tetralogy of Fallot.

OBJECTIVE: This study reviewed surgical outcomes of staged repair for complete atrioventricular septal defect with tetralogy of Fallot, especially with focusing on the post-operative left-sided atrioventricular valve function. METHODS: Between 1992 and 2013, 10 patients with complete atrioventricular septal defect with tetralogy of Fallot underwent total correction by the following surgical strategy. Systemic-to-pulmonary shunt was placed at first at the mean age of 1.5 ± 1.3 months. Then confirming sufficient development of the left heart structures, the total correction was performed at the mean age of 1.4 ± 0.6 years. Second shunt was required in 4 (40 %) patients to develop the left heart structures. RESULTS: The left ventricular end-diastolic volume before total correction was 127 ± 30 % of normal size. The two-patch repair was applied in 8 (80 %) patients. There was no mortality, and 1 reoperation case for left-sided atrioventricular valve regurgitation. The follow-up was completed on all patients and the mean follow-up period was 7.4 ± 7.0 years. The post-operative left-sided atrioventricular valve regurgitation kept less than moderate for 10-year follow-up in all patients except one patient who required the repair of left-sided atrioventricular valve 1 year after the total correction. CONCLUSIONS: The post-operative left-sided atrioventricular valve function after the repair of complete atrioventricular septal defect with tetralogy of Fallot maintained with the application of the two-patch repair, early and repeated palliative systemic-to-pulmonary shunt, and the early definitive surgery.