Lineage-Specific Induced Pluripotent Stem Cell-Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice.

BACKGROUND: The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv blockade as a therapeutic strategy to reduce aneurysm progression in MFS. METHODS: Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms. The pathological role of integrin αv during aneurysm formation was confirmed by blockade of integrin αv with GLPG0187 in Fbn1C1039G/+ MFS mice. RESULTS: iPSC-derived MFS SHF SMCs overexpress integrin αv relative to MFS NC and healthy control SHF cells. Furthermore, integrin αv downstream targets (FAK [focal adhesion kinase]/AktThr308/mTORC1 [mechanistic target of rapamycin complex 1]) were activated, especially in MFS SHF. Treatment of MFS SHF SMCs with GLPG0187 reduced p-FAK/p-AktThr308/mTORC1 activity back to control SHF levels. Functionally, MFS SHF SMCs had increased proliferation and migration compared to MFS NC SMCs and control SMCs, which normalized with GLPG0187 treatment. In the Fbn1C1039G/+ MFS mouse model, integrin αv, p-AktThr308, and downstream targets of mTORC1 proteins were elevated in the aortic root/ascending segment compared to littermate wild-type control. Mice treated with GLPG0187 (age 6-14 weeks) had reduced aneurysm growth, elastin fragmentation, and reduction of the FAK/AktThr308/mTORC1 pathway. GLPG0187 treatment reduced the amount and severity of SMC modulation assessed by single-cell RNA sequencing. CONCLUSIONS: The integrin αv-FAK-AktThr308 signaling pathway is activated in iPSC SMCs from MFS patients, specifically from the SHF lineage. Mechanistically, this signaling pathway promotes SMC proliferation and migration in vitro. As biological proof of concept, GLPG0187 treatment slowed aneurysm growth and p-AktThr308 signaling in Fbn1C1039G/+ mice. Integrin αv blockade via GLPG0187 may be a promising therapeutic approach to inhibit MFS aneurysmal growth.

Safe and promising outcomes of in-hospital preoperative rehabilitation for coronary artery bypass grafting after an acute coronary syndrome.

OBJECTIVE: In patients with stable hemodynamic status after an acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) after preoperative investigations can provide outcomes comparable to those of emergency surgery. However, no established guidelines exist regarding the preparation period before surgery. We report the results of the use of an inpatient cardiac rehabilitation program followed by CABG after an ACS to improve post-operative outcomes and prognosis after discharge. METHODS: From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution, and of those, the 393 who received isolated CABG were included in the analysis. Twenty-seven patients (6.9%) were admitted with ACS and underwent preoperative rehabilitation before undergoing CABG, with a subsequent review of surgical morbidity and mortality rates. Propensity score matching yielded a cohort of 26 patients who underwent preoperative rehabilitation (group A) and 26 controls (group B). Preoperative characteristics were similar between groups. RESULTS: The completion rate of the rehabilitation program was 96.3%. All programs were conducted with inpatients, with an average length of stay of 23 ± 12 days. All patients completed in-bed exercises, and 85% completed out-of-bed exercises. The 30-day postoperative mortality was 0% in both groups A and B, and the rate of postoperative major adverse cardiac or cerebrovascular events at 12 months did not differ significantly between groups (7.7% vs 3.9%, respectively; p = 1.0). The duration of mechanical ventilation (1.3 ± 0.3 vs 1.5 ± 0.3 days, respectively; p = 0.633), length of intensive care unit stay (4.4 ± 2.1 vs 4.8 ± 2.3 days, respectively; p = 0.584) and length of hospital stay (25 ± 13 vs 22 ± 9 days, respectively; p = 0.378) did not differ significantly between groups. CONCLUSIONS: No complications of preoperative rehabilitation were observed, suggesting that it is an acceptable option for patients who experience ACS and undergo CABG. These results are promising in offering more robust designs of future trials.

Salivary metabolites as potential predictive biomarkers for lung surgery complications: a retrospective cross-sectional study.

PURPOSE: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. METHODS: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien-Dindo grade ≥ III. RESULTS: Postoperative complications of Clavien-Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455-10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694-0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien-Dindo grade ≥ III. CONCLUSION: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery.

[Left Atrial Appendage Closure with Various Types of Surgical Technique and Its Results].

BACKGROUND: Occlusion of the left atrial appendage( LAA) may prevent stroke in patients with atrial fibrillation. In this study, we reviewed various types of LAA occlusion techniques and results of patients underwent surgical LAA closure. METHODS: Between 2004 and 2022, 182 patients who underwent surgical LAA closure were enrolled in this study. RESULTS: The surgical LAA closure consisted of 90 cases of closure device, AtriCure, 63 cases of surgical excision, 13 cases of stapler excision, 3 cases of ligation, and 13 cases of internal suture ligation. During the follow-up period, there were no deaths owing to cardiogenic emboli and no cerebral infarctions. CONCLUSIONS: Regardless of the surgical techniques, LAA closure was effective in preventing cardiogenic stroke. The AtriClip is a safe, simple, and effective and thoracoscopic LAA closure using AtriClip is expected as a less-invasive LAA management.

Unexpected Bare Metal Stent Migration Associated With Aortic Remodeling After PETTICOAT Technique for Aortic Dissection.

PURPOSE: To report a unique case of bare metal stent migration in the overlapping zone and subsequent distal stent graft-induced new entry (SINE) after the Provisional Extension to Induce a Complete Attachment (PETTICOAT) technique for aortic dissection. CASE REPORT: A 67-year-old man underwent thoracic endovascular aortic repair (TEVAR) using the PETTICOAT technique for acute complicated type B aortic dissection. The postoperative course was uneventful, and follow-up computed tomography (CT) showed not only favorable aortic remodeling but also progressive bare metal stent migration in the overlapping zone between the stent graft and the bare metal stent. A 6-month postoperative CT revealed a distal SINE, and the patient underwent re-TEVAR to cover the new entry. Postoperative CT demonstrated successful repair of the distal SINE. The patient is currently in good health 2 years after the reintervention. CONCLUSION: Surgeons should consider the potential risk of device migration due to favorable aortic remodeling after TEVAR for aortic dissection, especially with the use of additional bare metal stents.

[Minimally Invasive Surgery for Mediastinal Diseases in Our Institute:Innovations and Surgical Practice].

Since the early 1990s, minimally invasive surgery has been introduced in many surgical fields. The progress of technology and increased interest in minimally invasive surgery has led to innovation from surgery with a large incision to complete thoracoscopic surgery in many facilities. We started thoracoscopic mediastinal surgery in 1997 and robot-assisted mediastinal surgery in 2021. Considering the approach for anterior mediastinal tumor resection, it is necessary to fully understand tumor size, tumor location, and the existence of the tumor invasion to other organs. Especially in the case of tumors located on the cranial side above the innominate vein or thymectomy with dissection of the superior pole of the thymus, ensuring surgical field visibility is essential. In our institute, from the point of cosmetics, surgical field visibility is ensured using carbon dioxide insufflation and a sternum-lifting method. Although the number of cases is limited, we report our ingenuity and actual implementation of the techniques.

[Surgical Treatment of Extensive Annular Defects by Aortic Valve Infective Endocarditis Using Stentless Bioprosthesis].

BACKGROUND: The optimal surgical technique and valve prosthesis in patients with active aortic valve infective endocarditis with annular abscess is controversial. If extensive annular defects occur after debridement, standard techniques are difficult;more complex aortic root replacement is inevitable. The SOLO SMART stentless bioprosthesis is specially designed for supra-annular implantation without annular stitches. METHODS: Since 2016, 15 patients with active aortic valve infective endocarditis underwent aortic valve surgery. Of these, we performed aortic valve replacement using the SOLO SMART valve in six patients with extensive annular destruction and complex aortic root pathologies requiring reconstruction. RESULTS: Although more than two-thirds of the annular structure was missing after radical debridement of infected tissues, supra-annular aortic valve replacement with the SOLO SMART valve could be performed successfully in all six patients. All patients are doing well without prosthetic valve dysfunction and/or recurrent infection. CONCLUSIONS: The supraannular aortic valve replacement using the SOLO SMART valve is considered to be a useful alternative to standard aortic valve replacement in patients complicated with extensive annular defect. It is a simple and technically less demanding alternative to aortic root replacement.

Endovascular Repair for Abdominal Aortic Aneurysm Rupture With Neurofibromatosis Type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a rare congenital disorder with an autosomal dominant inheritance. Severe perioperative complications owing to the congenital fragility of the vascular wall in NF1 patients have been reported. The optimal vascular surgical approach remains controversial. We describe endovascular aortic repair of an abdominal aortic aneurysm rupture in a patient with NF1. CASE PRESENTATION: A 78-year-old woman with NF1 was transferred to our institution with a diagnosis of ruptured abdominal aortic aneurysm. The patient showed multiple café-au-lait spots, numerous neurofibromatosis, and severe scoliosis. Emergency endovascular aortic repair was performed, without technical difficulty. Despite an uneventful postoperative course, she developed an idiopathic left cervical hematoma caused by hemorrhage, and required tracheostomy due to severe airway obstruction. In addition, postoperative CT showed a newly developed saccular aneurysm at the proximal end of the stent graft. On postoperative day 40, she was transferred to a rehabilitation hospital, without recurrent bleeding and saccular aneurysm enlargement. CONCLUSION: In patients with NF1 who require a vascular surgical procedure, surgeons should consider the vascular wall fragility in selecting the optimal treatment strategy and the possible complications.

Unexpected migration of a sternal pin: A word of caution.

BACKGROUND: Sternal pins are adjuncts used to enhance sternal stability after sternotomy, but only a few complications associated with them have been previously reported. MATERIAL, METHODS AND RESULTS: A 42-year-old woman underwent pulmonary valve replacement through re-sternotomy for pulmonary valve regurgitation after repaired tetralogy of Fallot. Because of severe sternal deformity, the sternum was refixed using a sternal pin in addition to sternal wires. However, postoperative computed tomography unexpectedly revealed migration of the sternal pin towards the right coronary artery, necessitating emergency surgical removal of the pin. DISCUSSION: Sternal pins may not adequately fit the deformed sternum, resulting in sternal pin-induced sternal injury. CONCLUSION: Sternal pins are considered useful for sternal stabilization after sternotomy, we should take special care in applying sternal pins to patients presented severe sternal deformity.

Ascending aortic graft penetration by fractured sternal wire: A word of caution.

The fractured sternal wire is a relatively common postoperative finding after sternotomy. However, fractured wires have the potential of surrounding organ injury, which can be fatal. Here, we describe the successful surgical treatment of ascending aortic penetration by fractured sternal wire.

Constrictive pericarditis caused by pericardial substitution using expanded polytetrafluoroethylene.

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) is commonly used as a pericardial substitute during cardiac surgery to prevent cardiac injury during re-sternotomy. However, although rare, constrictive pericarditis associated with ePTFE has been reported. MATERIAL, METHODS AND RESULTS: Here, we report a rare case of constrictive pericarditis developed due to severe restriction of cardiac motion associated with the ePTFE membrane used as a pericardial substitute. Hemodynamic improvement has been achieved by surgical removal of the ePTFE membrane and exudates within the overlapped portion of the ePTFE membranes, and dissection of the epicardial fibrous thickening. CONCLUSION: Considering the risk of constrictive pericarditis, we believe that the use of ePTFE membranes as a pericardial substitute should be carefully indicated for only selected patients.

Perfusion Balloon Is Useful for Preventing Obstruction of Left Main Coronary Artery During Transcatheter Aortic Valve Implantation.

The incidence of acute coronary obstruction during transcatheter aortic valve implantation (TAVI) is low (< 1.0%); however, it is associated with high mortality. An 83-year-old female with a history of chest pain and syncope was diagnosed with severe aortic stenosis. Computed tomography showed severely calcified aortic leaflets with a low left coronary ostial height of 7.8 mm, which indicates a high risk of coronary obstruction. TAVI was performed using the right femoral artery approach under general anesthesia. To prevent coronary obstruction and minimize coronary flow obstruction, coronary protection of the left main tract (LMT) via the left radial artery was established with a perfusion balloon. We crossed a 23 mm Sapien 3 transcatheter heart valve and settled it at an appropriate position on the aortic valve. After inflation of the perfusion balloon at the LMT, we started rapid ventricular pacing, and deployed the Sapien 3 using the KBI technique. Hemodynamics were stable and aortography showed excellent coronary flow with no stenosis of the LMT ostium. This strategy may serve as a useful method to prevent coronary obstruction and minimize coronary ischemia.

[Successful Surgical Repair for Adult Ebstein Disease Using Cone Reconstruction Combined with One and a Half Ventricle Repair].

A 67-year-old woman presented with dyspnea on effort and cyanosis due to massive tricuspid regurgitation and an atrial septal defect with right to left shunt. She was diagnosed with Ebstein disease at the age of 53 when she underwent surgery for varicose veins. Echocardiography showed the severe apical displacement of the septal and posterior leaflet. The anterior leaflet also partially displaced to the apex and demonstrated tethering caused by a dilated right ventricle. Cardiac magnetic resonance imaging showed a dilated right atrium and an enlarged atrialized right ventricle, in addition to marked low cardiac output in the dilated right ventricle. The surgical findings corresponded to Carpentier classification type C. Cone reconstruction was performed. Bidirectional Glenn anastomosis was reguired because of low cardiac output in the remaining functional right ventricle after Cone reconstruction. The patient's postoperative course was uneventful, and tricuspid regurgitation and stenosis remained mild. The patients had no occurrence of right heart failure or arrhythmia for two years after surgery.

[Successful Surgical Repair of Left Coronary Ostial Aneurysm after Modified Bentall Procedure Using the Carrel Patch Technique].

A 38-year-old woman underwent aortic root surgery using the Carrel patch technique at the age of 14 years for annuloaortic ectasia of 59 mm. Although there were no clinical findings of Marfan syndrome or bicuspid aortic valve, the pathological findings of the aortic aneurysmal wall showed degeneration of the media. After 24 years, contrast-enhanced computed tomography (CT) showed an enlargement of the left coronary ostial aneurysm of 17 mm with saccular formation. Re-coronary reconstruction with the Piehler technique using an 8 mm Dacron graft was performed. The post-operative course was uneventful, and post-operative CT showed no pseudoaneurysm or stenosis at the anastomosis sites. The Carrel patch coronary ostial reconstruction has been shown to reduce coronary anastomotic pseudoaneurysms and to improve aortic root surgical outcomes. However, coronary ostial aneurysm is a true aneurysm and one of the later complications after the modified Bentall procedure using the Carrel patch technique. Although it is common in Marfan syndrome, the consensus on diagnosis, operative indication, and surgical procedure have not yet been established. Not only in Marfan syndrome, but also after coronary artery reconstruction using the Carrel patch technique, longer-term follow-up is necessary to take care for aneurysmal formation at coronary ostium.

[Aortic Root Replacement with Patch Closure of Membranous Ventricular Septal Aneurysm].

Membranous ventricular septal aneurysm (MSA) complicated with annuloaortic ectasia (AAE) is rare in adults. Herein, we reported two successful surgical cases of this setting. One case is 50-year-old man with extensive infective endocarditis with underwent aortic coarctation repair in childhood. MSA was incidentally diagnosed at preoperative examination. The other patient is 53-year-old man who had severe aortic regurgitation complicated with AAE and membranous type ventricular septal defect with MSA. Simultaneous surgery comprising patch closure of MSA and aortic root replacement was performed in both patients. As for patch closure of MSA, the technical modification should be necessitated according to the fragility of the upper margin of the MSA.

[Stanford Type B Acute Aortic Dissection Associated with Transcatheter Aortic Valve Implantation:Report of a Case].

Transcatheter aortic valve implantation (TAVI)-related Stanford type B aortic dissection is an extremely rare but potentially fatal complication. Here, we present a case of 82-year-old man who developed acute type B aortic dissection during transfemoral TAVI. During successful TAVI procedure, dissection in the descending aorta was demonstrated by transesophageal echocardiography. Computed tomography( CT) clearly showed Stanford type B aortic dissection and an intimal tear in severely tortuous part of the descending aorta. Cause of aortic dissection was supposed to be related to the guidewire or the device that passed across affected position. The patient showed no complication associated with aortic dissection, such as rupture or malperfusion. Therefore, he was treated conservatively, and follow-up CT confirmed progressive clotting of the false lumen. Although the indication for TAVI has got broaden recently, physicians should be always aware of possible aortic dissection.

Step-by-step aortic clamping technique for safe retrieval of the elephant trunk.

Staged repair of the aortic arch and downstream aorta using the elephant trunk technique is widely accepted for extensive aortic disease. However, elephant trunk retrieval is challenging in patients with unclampable descending aorta caused by extreme aneurysmal dilation or surrounding tissue adhesion. Here, we introduce a new elephant trunk retrieval technique using the step-by-step aortic clamping in descending aortic replacement of dissecting aortic aneurysm. This technique is a safe and feasible method of elephant trunk retrieval that consists of staged clamping and intraoperative ultrasound assessment of blood flow in the aorta.

Simple Retrieval Technique of the Elephant Trunk by Partial Aortic Clamping.

The frozen elephant trunk technique for various thoracic aortic diseases is widely accepted to facilitate future downstream aortic surgery. However, in some cases, the descending aorta is unsuitable for cross-clamping due to progressive aneurysmal changes or dense adhesions to surrounding structures, and frozen elephant trunk retrieval becomes challenging. This paper presents a case of successful frozen elephant trunk retrieval by partial clamping of the descending aortic aneurysm without dissection of peri-aneurysmal adhesions, and subsequent encircling.

[Total Arch Replacement with Brain Isolation Technique for Arch Aneurysm with Shaggy Aorta].

A shaggy aorta with a mobile atheromatous plaque in a thoracic lesion is considered a risk factor for cerebral infarction during aortic arch surgery. The brain isolation technique was introduced to prevent embolic stroke either by manipulating the severely atheromatous aorta, or by producing a sandblasting effect using the arterial jet in cardiopulmonary bypass. We performed total arch replacement with the aid of a brain isolation technique in four patients with aortic arch aneurysm complicated with a shaggy aorta between 2016 and 2020. Antegrade selective cerebral perfusion was established prior to systemic perfusion of the cardiopulmonary bypass. Total arch replacement using the frozen elephant technique was performed in all patients. There was no operative mortality, and all patients were discharged without major neurological complications. Therefore, the brain isolation technique could be a useful adjunctive method to prevent embolic stroke in patients who undergo total arch replacement for aortic arch aneurysm with a shaggy aorta.

[Surgical Strategy for Aortic Arch Aneurysms in Octogenarians].

BACKGROUNDS: The purpose of this study was to evaluate the short- and mid-term outcomes of open aortic arch surgery and debranching thoracic endovascular aortic repair( TEVAR) in octogenarians. METHODS: Between 2011 and 2019, 26 patients with atherosclerotic aortic arch aneurysms underwent surgery at our institution [open aortic arch surgery( group O):10 patients, debranching TEVAR(group D):16 patients]. RESULTS: There was no operative death in either group. The mean length of hospitalization and intensive care unit stay were 49 and 13 days in group O and 12 and 2 days in group O, respectively. Kaplan-Meier analyses of overall survival (1/6/12/24/36/48 months) showed mortality rates of 100/100/88/88/70/70% in group O and 100/100/87/61/43/26% in group D, respectively. CONCLUSIONS: The acceptable outcomes was demonstrated in octogenarians underwent both open aortic arch surgery and debranching TEVAR. Because of early postoperative recovery, debranching TEVER is considered to be a feasible alternative to conventional open aortic arch surgery in octogenarians.