AVJ-514 Trial　- Baseline Characteristics and 30-Day Outcomes Following MitraClip® Treatment in a Japanese Cohort.

BACKGROUND: The MitraClip®system is a transcatheter-based therapeutic option for patients with chronic mitral regurgitation (MR) who are at high risk for surgery. A prospective, multicenter, single-arm study was initiated to confirm the transferability of this system to Japan.Methods and Results:Patients with symptomatic chronic moderate-to-severe (3+) or severe (4+) functional or degenerative MR with a Society of Thoracic Surgery (STS) score ≥8%, or the presence of 1 predefined risk factor were enrolled. Patients with left ventricular (LV) ejection fraction (EF) <30% were excluded. MR severity and LV function were assessed by an independent echocardiography core lab. Primary outcome included major adverse events (MAE) at 30 days and acute procedural success (APS). A total of 30 patients (age: 80±7 years; STS score: 10.3%±6.6%) were treated with the MitraClip®. At baseline, all patients had MR 3+/4+ with 53%/47% patients with degenerative/functional etiology with mean LVEF of 50.2±12.8%, and 37% of patients were NYHA class III/IV. APS was achieved in 86.7% with no occurrence of MAE. At 30 days, 86.7% of patients had MR ≤2+ and 96.7% were NYHA class I/II. CONCLUSIONS: The MitraClip®procedure resulted in clinically meaningful improvements in MR severity, function and quality of life measures, and low MAE rates. These early results suggest the transferability of this therapy to appropriately selected Japanese patients. (Trial Registration: clinicaltrials.gov Identifier NCT02520310.).

Preservation of Mobility of the Posterior Mitral Leaflet After Mitral Valve Repair With Neochordae Using Loop Technique.

BACKGROUND: Recently, the loop technique has been standardized for mitral valve repair, with excellent long-term outcomes reported. This study thus analyzed whether the loop technique could preserve mitral leaflet mobility on trans-thoracic echocardiography. METHODS AND RESULTS: Among 367 concomitant patients who underwent mitral valve repair at Keio University Hospital between January 2007 and December 2014, 304 patients had a prolapse of the posterior leaflet. Of these, 84 cases assessed on echocardiography were retrospectively analyzed for this study. These patients were divided into 4 groups based on the procedure used: (1) group L1 (n=28), loop technique alone; (2) group L2 (n=14), loop technique with resection and suture; (3) group L3 (n=33), loop technique with plication of indentation; and (4) group R (n=9), resection and suture alone. The mean postoperative mobile posterior mitral leaflet (PML) angles in groups L1 and L2 (39.3±16.0°, 37.3±16.0°) were significantly larger than those in groups L3 and R (18.8±15.7°, 15.3±15.7°), respectively (P<0.01). Ring size, age, and mobile PML angle had a statistically significant correlation with the postoperative mean mitral valve pressure gradient (P<0.05). CONCLUSIONS: The loop technique preserved PML mobility and enabled implantation of a larger ring, resulting in a reduced mean mitral valve pressure gradient. (Circ J 2016; 80: 663-667).

Induction of human cardiomyocyte-like cells from fibroblasts by defined factors.

Heart disease remains a leading cause of death worldwide. Owing to the limited regenerative capacity of heart tissue, cardiac regenerative therapy has emerged as an attractive approach. Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse cardiac fibroblasts in vitro and vivo by transduction of three transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT. In the present study, we sought to determine whether human fibroblasts also could be converted to iCMs by defined factors. Our initial finding that GMT was not sufficient for cardiac induction in HCFs prompted us to screen for additional factors to promote cardiac reprogramming by analyzing multiple cardiac-specific gene induction with quantitative RT-PCR. The addition of Mesp1 and Myocd to GMT up-regulated a broader spectrum of cardiac genes in HCFs more efficiently compared with GMT alone. The HCFs and human dermal fibroblasts transduced with GMT, Mesp1, and Myocd (GMTMM) changed the cell morphology from a spindle shape to a rod-like or polygonal shape, expressed multiple cardiac-specific proteins, increased a broad range of cardiac genes and concomitantly suppressed fibroblast genes, and exhibited spontaneous Ca(2+) oscillations. Moreover, the cells matured to exhibit action potentials and contract synchronously in coculture with murine cardiomyocytes. A 5-ethynyl-2'-deoxyuridine assay revealed that the iCMs thus generated do not pass through a mitotic cell state. These findings demonstrate that human fibroblasts can be directly converted to iCMs by defined factors, which may facilitate future applications in regenerative medicine.

Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.

The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.

Time to revisit role of transcatheter balloon aortic valvuloplasty: a bridge-therapy to subsequent treatment case report.

Recently there has been a noticeable resurgence in the usage of percutaneous balloon aortic valvuloplasty (BAV) by the development of less invasive endovascular therapies including transcatheter aortic valve implantation (TAVI). We performed BAV in a 91-year-old man with end-stage severe symptomatic aortic stenosis (AS) and an impending abdominal aortic aneurysm (AAA) rupture who had been refused surgical treatment because of the comorbidities with stage V chronic kidney disease (CKD) and severe left ventricular dysfunction. Improvement in hemodynamics and kidney function was observed after BAV. Subsequently, we performed endovascular aneurysm repair (EVAR) successfully for AAA using iodinated contrast. No deterioration of kidney function was confirmed after the procedure. The patient was discharged without any adverse events. At present, the possibilities of TAVI or surgical aortic valve replacement (s-AVR) are under consideration as the definitive therapy for the upcoming aortic valve restenosis. In conclusion, this inoperable patient with multiple comorbidities was successfully treated, at lower risk, by catheter-based two-stage therapy.

Postoperative renal function after juxtarenal aortic aneurysm repair with simple cross-clamping.

BACKGROUND: We report our 11-year experience of juxtarenal aortic aneurysm (JAA) repair with suprarenal aortic cross-clamping. METHODS: We retrospectively reviewed 51 consecutive JAA repairs performed between 2000 and 2010. In all 51 patients, aneurysms were replaced by prosthetic grafts with simple suprarenal aortic cross-clamping. No special renal protective measures (except inter-renal cross-clamping) were performed during interruption of perfusion to kidneys. For inter-renal cross-clamping, the aortic cross-clamp was placed from below one renal artery to above the other renal artery to maintain hemilateral renal perfusion. This technique was applied in 27 patients (54%). Postoperative complications, renal function, and survival were evaluated. RESULTS: There were no deaths. The average renal ischemia time was 28.9 ± 9.7 minutes. Postoperatively, transient renal failure (defined as an estimated glomerular filtration rate of <30 mL/min/1.73 m(2)) occurred in 14% of the patients. The postoperative decrease of estimated glomerular filtration rate compared with the preoperative value was significantly smaller in the inter-renal clamp group (7.4% ± 16%) than in the suprarenal clamp group (17.5% ± 16%) (P < 0.05, unpaired t test). However, renal dysfunction was temporary and recovered to baseline before discharge with conservative therapy in all patients except one. In addition, renal function was generally preserved at 1 year after surgery. CONCLUSION: Surgical repair of JAA can be performed with simple cross-clamping and an acceptable renal ischemic time, achieving excellent results. Inter-renal cross-clamping reduces renal damage compared with suprarenal cross-clamping.

Numerical analysis of blood flow distribution in 4- and 3-branch vascular grafts.

Trifurcated arch grafts (3-branch grafts) are now being used to repair the thoracic aorta in addition to conventional arch grafts (4-branch grafts). The anatomical shape of the 3-branch graft is different from the original vessel, so it is necessary for clinical application to evaluate blood flow distribution in the graft to assess whether there is adequate blood flow to the target organs. To achieve this, we developed a computational fluid dynamics (CFD) method to evaluate blood flow distribution in the grafts. Aortic blood flow was measured by phase-contrast magnetic resonance imaging (PC-MRI), and flow distribution into the branched vessels was obtained. The MRI image was used to create a patient-specific image model that represents the geometry of the aortic arch. The CFD analysis method was employed to determine a boundary condition of the blood flow analysis in the aorta using a patient-specific image model. We also created simplified models of 4-branch and 3-branch grafts and used our CFD analysis method to compare blood flow distribution among simplified models. It was found that blood flow distribution in the descending aorta was 71.3 % for the 4-branch graft and 67.7 % for the 3-branch graft, indicating that a sum of branching flow in the 3-branch graft was almost the same as the one in the 4-branch graft. Therefore, there is no major concern about implanting a new 3-branch graft. Our CFD analysis method may be applied to estimate blood flow distribution of a newly developed vascular graft prior to its clinical use and provide useful information for safe use of the graft.

Surgery for primary intrapericardial tumors in adults.

Primary intrapericardial tumors in adults, whether benign or malignant are rare. Surgical treatment for these tumors are reviewed together with their incidence, classification, clinical features, and diagnosis.

Bilateral banding of malpositioned pulmonary artery branches.

This report presents two rare cases of malpositioned pulmonary artery branches managed by bilateral banding. The left-branch pulmonary artery, originating from and directly superior to the right branch, entered the posterior mediastinum before heading toward the left pulmonary hilum. The ostium of the left branch could not be visualized by midline sternotomy. Therefore, a double-subtraction technique was used to pass the banding tape around the left branch from the right side. The tape location was adjusted and confirmed by intraoperative echocardiography.

Hybrid repair of a Kommerell diverticulum associated with a right aortic arch and a left descending aorta.

This report describes the first successful case of a hybrid endovascular approach for management of aneurysmal Kommerell diverticulum arising from the left descending aorta in a right aortic arch. This patient also had dilatation of the ascending aorta and a small aortic arch aneurysm. This three-step procedure consisted of (1) ascending aorta replacement with total debranching using a handmade quarto-branched composite graft; (2) endovascular exclusion of Kommerell diverticulum and the aortic arch aneurysm by covering the whole aortic arch; and (3) coil embolization against the root of the left subclavian artery. The patient had no complications at 16 months after completion.

Eye-tracking analysis of skilled performance in clinical extracorporeal circulation.

The manipulation of extracorporeal circulation (ECC), which is performed by perfusionists during cardiovascular surgery, is a highly sophisticated cognitive process based on visual information obtained from information sources such as ECC indicators, surgeons, an operating field, a scrub nurse, surgical instruments, displays, patients, among others. An eye-tracking approach is expected to be a powerful means of automatic and rapid analysis. This paper presents the results of a pilot study in which an eye-tracking approach was applied to the analysis of ECC operation tasks conducted during real clinical cardiovascular surgery in the operating room. Eye-tracking data on four perfusionists were recorded while they were manipulating the ECC during a series of cardiovascular surgeries. The experience of the perfusionists ranged from 2 to 26+ years. Based on the data obtained, fixation-by-fixation cataloging of eye-tracking data in which each fixation was transcribed in timeline style was performed for each perfusionist. Gaze allocation tendencies during the surgeries for all four perfusionists were determined through a comparative analysis. It was noted that an expert engineer dispersed his attention more widely than did intermediate and novice perfusionists. Taking the results of the data analysis into consideration, we discuss the implications of well-skilled perfusionists' performance during the manipulation of ECC, as well as the principles that guide how eye-tracking data obtained in real surgery should be processed. This is the first study on the application of an eye-tracking approach to the analysis of ECC operation tasks to be reported in the Japanese literature.

Hybrid treatment of a ruptured aneurysm in the distal aortic arch: report of a case.

An 80-year-old man was transferred to our hospital for surgical treatment of a ruptured aortic arch aneurysm. Based on a history of severe heart failure and coronary artery bypass, we considered him unsuitable for conventional open repair. He underwent a hybrid repair, in the form of supra-aortic vessel debranching followed by endoluminal aortic repair. Although the ostia of the left carotid and left subclavian arteries were occluded by the stent-graft, the left supra-aortic vessels and the left internal thoracic artery attached to the coronary artery were perfused through an extra-anatomic bypass from the right axillary artery to the left carotid artery and the left axillary artery. After additional endovascular repair for recurrent hemosputum, the patient recovered without complications. Although continued follow-up is necessary, acute hybrid arch repair seems feasible for treating ruptured aortic arch aneurysms, even in the setting of severe heart failure and a previous coronary artery bypass.

[Mitral valve repair with artificial chordal creation].

To achieve optimal long-term result of mitral valve repair, artificial chordae creation has got to be an important technique. Artificial chordae creation can preserve leaflet motion of the posterior mitral leaflet and soft coaptation area. Loop technique is suitable technique for creation of multiple artificial chordae, especially in minimally invasive minithoracotomy setting. Loop-in-loop technique is a new technique to realize easy adjusting of the length of the neochordae using slippery Gore-Tex suture. Loop-in-loop technique helps surgeons to afford variety of mitral valve repair techniques and manage complex mitral valve pathologies.

Impact of serum high-mobility group box 1 protein elevation on oxygenation impairment after thoracic aortic aneurysm repair.

High-mobility group box 1 protein (HMGB1) is a late mediator of inflammatory responses that can cause acute lung injury. We examined the significance of serum HMGB1 elevation in the development of systemic inflammatory response syndrome (SIRS) and lung oxygenation impairment (LOI) after thoracic aortic aneurysm (TAA) repair. Serial measurements of the serum HMGB1 level and SIRS score for 7 days after surgery were determined in 20 patients with TAA who underwent surgical repair. Arterial oxygen tension was measured serially for at least 4 days after surgery, and LOI was defined as the lowest PaO(2)/FiO(2) ratio ≤ 200 mmHg. The serum HMGB1 level was markedly increased after surgery, peaking on day 2, and remained significantly elevated on day 7. Peak HMGB1 level positively correlated with SIRS duration and the cumulative SIRS score during postoperative days 1-7 (P = 0.0013 and P = 0.0004, respectively). Peak HMGB1 level and cumulative SIRS score were higher in patients with LOI than in those without (P = 0.01 and P = 0.044, respectively). Peak HMGB1 level was negatively correlated with the lowest PaO(2)/FiO(2) ratio (P = 0.0077) and positively correlated with postoperative length of hospitalization (P = 0.042). A greater serum HMGB1 elevation after TAA repair was associated with more severe SIRS and a higher incidence of LOI. HMGB1 might play a key role in the pathogenesis of SIRS and LOI after surgical TAA repair.

[Efficacy of surgical left ventricular restoration for the patients with ischemic cardiomyopathy; comparison with the surgical treatments for ischemic heart failure (STICH) trial].

The efficacy of surgical left ventricular restoration (LVR) for the patients with ischemic cardiomyopathy was denied by the surgical treatments for ischemic heart failure (STICH) trial. But the conclusion of the STICH trial is wrong and real message of the STICH trial is as follows. LVR is not effective procedure for the patients with poor left ventricular function and small left ventricular dilatation. In the STICH trial, volume reduction rate of the patients with LVR is too little. Based on the low of Laplace, little volume reduction rate do not contribute the improvement of the ventricular function. In our 33 cases of LVR, the survival rates at 5, 7, and 10 years after LVR were 80%, 76% and 76%. On the other hand, the corresponding cardiac event-free rates were 55%. 44%, and 44%. These discrepancies of the value suggest the importance of both the preoperative strategy and the intensive therapy during the postoperative period. We observed some cases that re-enlarged left ventricle after LVR induced heart failure or ventricular arrhythmia. The timing of operation, left ventricular reconstruction of appropriate size and shape considering the function of residual myocardium has significant effect on prognosis. Postoperative ventricular tachycardia (VT) was the major factor influenced the survival rate. After preoperative or intraoperative three-dimensional electrical mapping by CARTO system to detect focus of VT, endocardiectomy combined with cryoablation at the VT focus is performed and postoperative antiarrhythmic medication is added routinely. If LVR will be performed after appreciation of its concept, indication and method, excellent long term prognosis will be expected.

Re-elevation of D-dimer as a predictor of re-dissection and venous thromboembolism after Stanford type B acute aortic dissection.

D-dimer measurement is a useful complementary initial diagnostic marker in patients with acute aortic dissection (AAD). However, it has not been clarified whether serial measurements of D-dimer are useful during in-hospital management of Stanford type B AAD. We studied 30 patients who were admitted with diagnosis of Stanford type B AAD and treated conservatively. D-dimer was serially measured on admission and then every 5 days during hospitalization. Patients were divided into two groups according to the presence or absence of re-elevation of D-dimer during hospitalization, in which D-dimer transition were biphasic and latter peak >10.0 µg/ml. Re-elevation of D-dimer was observed in 17 patients. There were no differences in atherosclerotic risk factors, blood pressure on admission, D-dimer level on admission, extent of AAD, and false lumen patency. Patients with re-elevation of D-dimer showed higher incidence of re-dissection and/or venous thromboembolism (VTE). Peak D-dimer level in patients with re-dissection and/or VTE was significantly higher than that without these complications (p = 0.005). In conclusion, serial measurements of D-dimer are useful for early detection of re-dissection or VTE in patients with Stanford type B AAD, which may contribute to the prevention of disastrous consequences such as pulmonary embolism and extension of AAD.

Aberrant left subclavian artery sparing in right-sided interrupted aortic arch repair.

A right-sided interrupted aortic arch is rare, and it may have an associated aberrant left subclavian artery (ALSCA). An ALSCA is most often sacrificed at biventricular repair despite the potential danger of poor left upper-extremity growth. We report a case of ALSCA preservation with extensive dissection during aortic arch repair using direct anastomosis.

Reconstruction of an isolated left subclavian artery in a patient with a right aortic arch and tetralogy of Fallot.

An isolated left subclavian artery (ILSA) is very rarely seen in patients with a right aortic arch. This report describes the case of a 2-year-old boy who underwent ILSA reconstruction during repair of the associated tetralogy of Fallot to prevent future subclavian steal syndrome after surgery.

Open anastomosis of extracardiac conduit for total cavopulmonary connection decreases post-operative pleural effusion.

OBJECTIVE: The goal of this study was to see whether the open anastomosis technique using vacuum-assisted venous drainage at the time of the Fontan procedure was associated with decreased post-operative pleural effusion. METHODS: We analysed a subgroup of patients with a functional single ventricle who underwent non-fenestrated total cavopulmonary connection completion with the insertion of an extracardiac conduit as the sole or predominant procedure conducted by a single surgeon at a single institute, using either an open or closed anastomosis technique. RESULTS: Median age and weight were 2.3 years, with a range from 1.3 to 27.6 years and 11.4 kilograms, with a range from 9.7 to 43 kilograms, respectively. The open anastomosis technique was associated with a shorter bypass run (p = 0.015), decreased surgical duration (p = 0.032), fewer pleural effusion days (p = 0.049), and lesser pleural effusion (p = 0.013) than closed anastomosis. Correlation analysis demonstrated a significant relationship between the amount of pleural effusion and surgical duration (correlation efficient, 0.535; p = 0.033). A logistic regression model showed that the open technique was associated with a 20-fold increase in the likelihood of having a total chest tube discharge of less than 300 millilitres (p = 0.027). CONCLUSIONS: The open anastomosis technique shortens operative duration and bypass run, which in turn might contribute to decreased pleural effusion soon after the modified Fontan procedure.