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Abstract Background The purpose of this study was to quantify myocardial strain on the subendocardial and epicardial layers of the left ventricle (LV) using tagged cardiovascular magnetic resonance (CMR) and to investigate the transmural degree of contractile impairment in the chronic ischemic myocardium. Methods 3T tagged CMR was performed at rest in 12 patients with severe coronary artery disease who had been scheduled for coronary artery bypass grafting. Circumferential strain (C-strain) at end-systole on subendocardial and epicardial layers was measured using the short-axis tagged images of the LV and available software (Intag; Osirix). The myocardial segment was divided into stenotic and non-stenotic segments by invasive coronary angiography, and ischemic and non-ischemic segments by stress myocardial perfusion scintigraphy. The difference in C-strain between the two groups was analyzed using the Mann-Whitney U-test. The diagnostic capability of C-strain was analyzed using receiver operating characteristics analysis. Results The absolute subendocardial C-strain was significantly lower for stenotic (-7.5 ± 12.6%) than non-stenotic segment (-18.8 ± 10.2%, p < 0.0001). There was no difference in epicardial C-strain between the two groups. Use of cutoff thresholds for subendocardial C-strain differentiated stenotic segments from non-stenotic segments with a sensitivity of 77%, a specificity of 70%, and areas under the curve (AUC) of 0.76. The absolute subendocardial C-strain was significantly lower for ischemic (-6.7 ± 13.1%) than non-ischemic segments (-21.6 ± 7.0%, p < 0.0001). The absolute epicardial C-strain was also significantly lower for ischemic (-5.1 ± 7.8%) than non-ischemic segments (-9.6 ± 9.1%, p < 0.05). Use of cutoff thresholds for subendocardial C-strain differentiated ischemic segments from non-ischemic segments with sensitivities of 86%, specificities of 84%, and AUC of 0.86. Conclusions Analysis of tagged CMR can non-invasively demonstrate predominant impairment of subendocardial strain in the chronic ischemic myocardium at rest.

Abstract A partial lower inverted J sternotomy and an extended transseptal incision provide excellent exposure for minimally invasive mitral valve surgery. However, the extended trasnsseptal incision causes dividing the sinus node artery, which may result in conduction system disturbance and need for permanent pacemaker implantation. Therefore, there is a challenge in the patient who requires concomitant ablation for atrial fibrillation because of possible conduction system disturbance caused by extended transseptal incision. We describe a new strategy for combined ablation of atrial fibrillation with minimally invasive cardiac surgery by a transseptal approach to the mitral valve through a partial lower sternotomy incision. Cryoablation was performed using a T-shaped cryoprobe with a lesion set of pulmonary vein isolation and ablation of the left and right isthmus in performing mitral annuloplasty, tricuspid annuloplasty, and atrial septal defect closure through a limited sternotomy incision. This technique might minimize possible conduction system disturbance and provide good surgical result for the patients who undergo mitral valve surgery and ablation of atrial fibrillation.

Objectives: We introduced the use of an upper partial sternal split for pediatric cardiac surgical procedures in our unit in 2016. We report the outcomes of our experience in 51 patients using this approach., Methods: From February 2016 to September 2022, 51 patients underwent congenital cardiac surgical procedures using an upper partial sternal split including vascular ring repair (n = 20), subaortic membrane (n = 12), ventricular septal defect closure with aortic valve resuspension (n = 9), aortic arch repair (n = 4), pulmonary artery band (n = 2), pulmonary artery sling (n = 1), supravalvular aortic stenosis (n = 1), aortic valve replacement (n = 1), and pulmonary artery plasty (n = 1). The surgical approach involved a midline skin incision, based on the manubrium, followed by an upper manubriotomy. No special surgical instrumentation was required. Median patient age was 2.9 years (IQR 1.3, 6.0); median body weight was 15 kg (IQR 9.8, 20)., Results: There was no mortality and no patient required intraoperative conversion to full sternotomy. One patient required re-exploration for bleeding when the incision was converted to a full sternotomy. There were no wound complications in any patient. Twenty-one patients (41%) were extubated on the table and of the remaining 30 patients, 23 patients (76%) were extubated within 24 h of surgery. Eleven patients did not require intensive care unit (ICU) admission. Median ICU and hospital stay was 1 day (IQR 1, 1.25) and 5 days (IQR 4, 8) ,respectively., Conclusion: An upper partial sternal split approach is straightforward and can be performed safely with a preferable cosmetic result in selected pediatric cardiac operations., (© 2024. The Author(s).)

Competing Interests: Conflict of Interest Statement The author reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

The evaluation of right ventricular workload is sometimes complicated in patients after right ventricular outflow tract reconstruction (RVOTR) because both stenotic and regurgitation lesions are involved. In this study, we modified the right ventricular stroke work index (RVSWI) and evaluated the relationship between the modified RVSWI (mRVSWI) and patient prognosis after RVOTR.We enrolled 69 patients who underwent RVOTR (the RVOTR group), including those who needed early reoperation (early reoperation subgroup) and those who did not (follow-up subgroup), and 13 age-matched control participants (control group). Based on the catheterization results 1 year after RVOTR, we compared the mRVSWI between these groups. Additionally, we evaluated the influence of the mRVSWI on the reoperation avoidance rate and survival.The mRVSWI in the RVOTR group was significantly greater than that in the control group (17.7 ± 8.6 vs. 11.0 ± 2.7 g·m/m 2 , p = 0.008). The mRVSWI in the early reoperation subgroup was significantly greater than that in the follow-up subgroup (32.5 ± 11.1 vs. 15.8 ± 6.0 g·m/m 2 , p < 0.0001). In the follow-up subgroup, patients with an mRVSWI higher than the upper limit of normal (16.4 g·m/m 2 ) had a greater rate of reoperation than did the other patients (p = 0.0013). One patient died suddenly, and her mRVSWI was consistently high throughout her life.We established the mRVSWI as an index that integrates the pressure and volume load on the right ventricle. Our results indicate the utility of the mRVSWI for predicting patient prognosis after RVOTR., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This single-center retrospective study evaluated early and midterm outcomes of 100 consecutive patients with type A intramural hematoma., Methods: Initial watch-and-wait strategy was indicated if the maximum aortic diameter was < 50 mm, pain score was < 3/10 on the numerical rating scale, and no ulcer-like projection was observed in the ascending aorta. The primary endpoints of this study were all-cause and aorta-related deaths, and the secondary endpoint was aortic events., Results: Initial watch-and-wait strategy was indicated in 52 patients. Emergency aortic repair was indicated in the remaining 48 patients; 2, 31, and 15 patients died before surgery, underwent emergency surgery, and declined emergency surgery, respectively. Among the watch-and-wait group, 11 (21%) patients underwent aortic repair during hospitalization. In-hospital mortality rates, 5-year survival rates, and 5-year freedom from aorta-related death were not significantly different between the initial watch-and-wait strategy and emergency surgery (2% vs. 6%, 92% vs. 82%, and 100% vs. 94%, respectively). In the initial watch-and-wait strategy group, 5-year freedom from aortic events and freedom from aortic events involving the ascending aorta were 60% and 66%, respectively., Conclusions: The early and midterm outcomes with the initial watch-and-wait strategy in patients with type A intramural hematoma with a maximum aortic diameter of ≤ 50 mm, pain score of ≤ 3/10, and no ulcer-like projection in the ascending aorta were favorable with no aorta-related death., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: This study analyzed the safety and performance of the Perceval valve for aortic valve replacement (AVR) in patients at 1 year after undergoing aortic stenosis (AS) treatment, and its effect on significant declines in the platelet count during the immediate postoperative period., Methods and results: Data were collected retrospectively for the initial 121 patients (median age 77 years; 47.1% females) who underwent Perceval sutureless AVR between May 2019 and July 2022. Implantation was successful in all (100%), with median cross-clamp and CPB times of 59 and 100 min, respectively. Postoperative thrombocytopenia (platelet count <50×10 3 /μL) was noted in 80 (66.1%) patients. Multivariate analysis showed advanced age (>80 years), preoperative low platelet count (<200×10 3 /μL), and a sternotomy approach as significant risk factors for postoperative thrombocytopenia. One (0.8%) patient died within 30 days after the procedure. The 2-year site-reported event rate was 14% (n=17) for all-cause mortality, 0.8% (n=1) for cardiac mortality, 4.1% (n=5) for stroke, and 1.7% (n=2) for endocarditis and valve-related reoperation; there were no instances of paravalvular leakage or structural valve deterioration., Conclusions: Thrombocytopenia was common after Perceval sutureless AVR, although its impact was not significant. Although Perceval sutureless AVR was found to be a safe and effective option, preoperative assessment of potential bleeding should be performed and the Perceval valve should not be used for patients with a high bleeding risk.

Acute respiratory distress syndrome (ARDS) is a serious complication following cardiac surgery mainly associated with the use of cardiopulmonary bypass (CPB), which could increase the risk of mortality and morbidity. This study investigated the association of regional oxygen saturation (rSO 2 ) during CPB with postoperative outcomes, including respiratory function. Patients who underwent cardiac surgery with CPB from 2015 to 2019 were included. Near-infrared spectroscopy was used to monitor rSO 2 at the forehead, abdomen, and thighs throughout the surgery. Postoperative markers associated with CPB were assessed for correlations with PaO 2 /FiO 2 (P/F) ratios at intensive care unit (ICU) admission. Postoperative lung injury (LI) was defined as moderate or severe ARDS based on the Berlin criteria, and its incidence was 29.9% (20/67). On multiple regression analysis, the following were associated with P/F ratios at ICU admission: vasoactive-inotropic scores at CPB induction (P = 0.03), thigh rSO 2 values during CPB (P = 0.04), and body surface area (P < 0.001). A thigh rSO 2 of 71% during CPB was significantly predictive of postoperative LI with an area under the curve of 0.71 (P = 0.03), sensitivity of 0.70, and specificity of 0.68. Patients with postoperative LI had longer ventilation time and ICU stays. Thigh rSO 2 values during CPB were a potential predictor of postoperative pulmonary outcomes., (© 2024. The Japanese Society for Artificial Organs.)

Objectives: This study aimed to investigate changes in haematoma thickness during the early period and their association with disease progression in patients who received initial medical treatment for type A intramural haematoma (IMH)., Methods: Medical records and serial computed tomography angiography (CTA) images of patients who did not undergo emergency aortic repair for type A IMH upon presentation were retrospectively reviewed. The haematoma remodelling rate was determined using the following equation: thickness of the haematoma on the first CTA (mm) - thickness of the haematoma on the second CTA (mm)time between the first and second CTAs (h)., Results: Among the 40 patients included in this study, 38 were indicated for initial watch-and-wait strategy, whereas 2 were indicated for emergency aortic repair but declined it. During hospitalization, 10 patients developed disease progression, with 2 in-hospital mortality cases. Analysis of the haematoma remodelling rate in 39 patients revealed that such a rate was significantly associated with the reciprocal of the time from onset. Analysis of all 70 CTA examinations performed within 24 h after the onset of IMH showed that haematoma thickness was significantly associated with the logarithm of the time from onset. Initial regression of the haematoma was not necessarily associated with avoidance of disease progression., Conclusions: In type A IMH, the thickness of the haematoma in the ascending aorta tended to decrease in the very early period; however, prompt regression of the haematoma was not necessarily associated with avoidance of disease progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Since 2018, we have routinely placed an Amplatzer vascular plug (AVP) in the proximal left subclavian artery (LSCA) to prevent embolic events during thoracic endovascular aortic repair with arch vessel debranching (d-TEVAR). Type II endoleaks of LSCA origin were observed in two patients (20%), and the coil-in-plug (CIP) method, i.e., microcatheter insertion through the plug and addition of coil embolization, which has been used since August 2019, was performed. This study aims to evaluate the effectiveness of the CIP method for LSCA embolization. Methods: A total of 26 patients who underwent d-TEVAR for an aortic arch aneurysm between 2018 and 2022 were retrospectively reviewed. Ten patients who underwent d-TEVAR with a simple AVP placement (the control group) and 16 patients who underwent d-TEVAR with the CIP method (the CIP group) were compared. Results : Two patients had type II endoleaks in the control group, whereas none had them in the CIP group. LSCA length was significantly shorter in patients with endoleaks than in those without endoleaks (24.5 vs. 50.3 mm; p<0.01). No perioperative deaths or cerebral infarctions occurred in either group. Conclusions: AVP placement in the LSCA during d-TEVAR effectively prevented perioperative cerebral infarction. d-TEVAR with CIP was especially useful in patients with a short LSCA., Competing Interests: Declaration of Conflict of InterestThe authors declare that there are no conflicts of interest., (© 2023 The Editorial Committee of Annals of Vascular Diseases.)

Objective: To investigate the early and long-term outcomes of the deferred Norwood procedure by bilateral pulmonary artery banding (BPAB) versus the neonatal Norwood procedure., Methods: This retrospective study examined 46 patients with hypoplastic left heart syndrome and its variants undergoing the Norwood procedure for single ventricle physiology between 2004 and 2022 at 3 institutions. The patients were divided into 2 groups: neonatal Norwood procedure (group N; n = 23) and staged Norwood procedure in infants following BPAB (group I; n = 23). Preoperative risk factors, surgical results, survival rates, Fontan candidacy, and long-term complications were compared., Results: Early survival rates after the Norwood procedure were 91.3% (21 of 23) in both groups. Late survival rates after the Norwood procedure were similar at the 10-year follow-up (group N, 76.3%; group I, 68.7%; P  = .63). Fontan completion rates also were comparable in the 2 groups (group N, 77.8%; group I, 85.7%; P  = .67). Group N showed a higher median pulmonary artery (PA) index before bidirectional cavopulmonary connection (group N, 177 [interquartile range (IQR), 147-243] mm 2 /m 2 ; group I, 152 [IQR, 146-163] mm 2 /m 2 ; P  = .03); this trend continued until 5 years after Fontan completion ( P  = .01). Group N also had a lower rate of freedom from protein-losing enteropathy (PLE) at 9.0 years after the Fontan operation (90.0% vs 52.5% for group I; P  = .04), although the incidences of other Fontan-associated events were not significantly different., Conclusions: Fontan candidacy and survival rates were similar regardless of the timing of the Norwood procedure. Early performance of the Norwood procedure may lead to lower rates of late Fontan-associated events, such as PLE., (© 2023 The Author(s).)

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., Competing Interests: This work was supported by Grants-in-Aid for Scientific Research (18K16396 to Dr Namiguchi, 16K10631, and 19H03740 to Dr Izutani, 19K17603 to Dr Hamaguchi, and 19K08585 and 16K109503 to Dr Aono) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Takeda Science Foundation (grants 2016 and 2020 to Dr Sakaue); the Public Trust Cardiovascular Research Foundation (grant 2017 to Dr Sakaue); the SENSHIN Medical Research Foundation (grant 2016 to Drs Aono and 2020 to Dr Sakaue); and the MSD Life Science Foundation, Public Interest Incorporated Foundation (grant 2016 to Dr Aono). Dr Nakayama is an employee of Biotube. There are no financial relationships between Dr Nakayama and the other coauthors, and experimental materials and funding used in this study were not provided by industry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Cardiopulmonary bypass-associated acute kidney injury (CPB-AKI) is a pediatric cardiac surgery postoperative complication that is associated with a longer duration of mechanical ventilation and length of hospital stay. Identifying an early predictor of CPB-AKI is critical. Near infrared spectroscopy (NIRS), which can provide real-time monitoring of regional tissue oxygen saturation (rSO 2 ) during CPB, may predict CPB-AKI in an early phase of surgical treatment. This study analyzed clinical data from 87 children who underwent an elective surgical repair of ventricular septal defect (VSD) from January 2013 to March 2019. NIRS sensors were placed on the patients' forehead, abdomen, and thighs. The pediatric modified risk, injury, failure, loss, and end-stage (p-RIFLE) score was determined for each patient postoperatively. The incidence of AKI based on the p-RIFLE classification was 11.5% at the end of surgery, 23.0% at 24 h after surgery, and 5.7% at 48 h after surgery. The AKI incidence rate was highest at 24 h after surgery. Multiple regression analysis revealed that femoral oxygenation (rSO 2 ) during CPB, CPB time, oxygen delivery index (DO 2 i), and lactate at the end of CPB were independent risk factors for AKI. Receiver-operating characteristic curve analysis indicated that femoral oxygenation of 74% or less predicted AKI development within 24 h after surgery. In conclusion, rSO 2 measured at the thigh during CPB is highly predictive of CPB-AKI.

Objectives: We applied high-flow regional cerebral perfusion (HFRCP) for aortic arch reconstruction in neonates and infants by monitoring regional oxygen saturation of the thigh (rSO2T) using near-infrared spectroscopy to maintain peripheral perfusion. This study was designed to investigate the optimal perfusion flow of HFRCP for renal protection., Methods: From 2009 to 2021, 28 consecutive neonates and infants who underwent aortic arch reconstruction with HFRCP were enrolled. The median age of the patients was 27 days; the median body weight was 3.0 kg. In HFRCP, perfusion flow was targeted at approximately 80-100 mL/kg/min and then lowered corresponding to brain rSO2 levels and blood gas data. Isosorbide dinitrate and chlorpromazine were administered to enhance peripheral perfusion flow. Regional oxygen saturation of the forehead and thighs were monitored. The stage of acute kidney injury (AKI) was classified based on the Kidney Disease Improving Global Outcomes criteria., Results: No patients had neurological events and peritoneal dialysis after surgery. The incidence of AKI was 39.3% with only three patients having greater than stage 2 AKI. The maximum postoperative serum creatinine concentration was negatively associated with the lowest rSO2T during HFRCP. The rSO2T during HFRCP was a predictive factor for postoperative creatinine increase of ≧0.3 mg/dL. The area under receiver operating characteristic curve was 0.78 with the cutoff value of 48% for rSO2T., Conclusions: The rSO2T during HFRCP is a potential predictor of postoperative renal function. To prevent AKI, the rSO2T should be preserved more than 48% by increasing HFRCP flow., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Regression of thrombus in response to treatment with direct oral anticoagulants (DOACs) in patients with extensive deep vein thrombosis (DVT) has not been fully evaluated. This study aimed to determine the therapeutic efficacy of rivaroxaban in the treatment of extensive DVT., Methods: We retrospectively evaluated 76 patients treated with rivaroxaban among 728 new DVT patients, at our hospital from January 2018 to March 2021. Extensive DVT was defined as thrombus connecting to 2 or more segments of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. Localized DVT was defined as a thrombus confined to 1 segment of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. We compared the changes in thrombus between the extensive DVT group (36 patients) and the localized DVT group (40 patients)., Results: In the localized DVT group, 14 (37%) had total recanalization within 3 weeks after DOAC initiation, and 30 (79%) had total recanalization within 3 months. In the extensive DVT group, only 3 (9%) had total recanalization within 3 weeks after starting DOAC, and even after 3 months, only 5 (15%) had total recanalization. Symptoms (P = 0.01) and extensive DVT (P < 0.01) were significantly associated with the risk for failure of total recanalization., Conclusions: Rivaroxaban was highly effective for total recanalization of localized DVT but not for symptomatic or extensive DVT. In patients with symptomatic extensive DVT, catheter-based thrombolysis may be considered in selected cases., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the mid-term outcomes after the repair of aortic arch using a standard patch augmentation technique., Methods: The study included all patients who underwent repair of a hypoplastic/interrupted aortic arch (IAA) in a single institute from June 2012 to December 2019 by a standardized patch augmentation (irrespective of concomitant intra-cardiac lesions). End points evaluated were reintervention for arch obstruction and persistent/new-onset hypertension., Results: The study included 149 patients [hypoplastic aortic arch, n = 92 (62%), IAA, n = 9 (6%), Norwood procedure, n = 48 (32%)]. The patch material used for augmentation of the aortic arch included pulmonary homograft (n = 120, 81%), homograft pericardium (n = 18, 12%), CardioCel® (n = 9, 6%) and glutaraldehyde-treated autologous pericardium (n = 2, 1%). The median age and weight at surgery were 7 days [interquartile range (IQR) 5-17 days] and 3.5 kg (IQR 3-3.9 kg), respectively. The median follow-up was 3.27 years (IQR 1.28, 5.08), range (0.02, 8.76). Freedom from reintervention at 1, 3 and 5 years was 95% [95% confidence interval (CI) = 89%, 98%], 93% (95% CI = 86%, 96%) and 93% (95% CI = 86%, 96%) respectively. One patient (0.6%) had persistent hypertension 8 years after correction for interrupted arch with truncus arteriosus., Conclusions: Repair of hypoplastic/IAA by transection and excision of all ductal tissue and standardized patch augmentation provide good mid-term durability. The freedom from reintervention at 5 years is >90%. The incidence of persistent systemic hypertension following arch reconstruction is low. The technique is reproducible and applicable irrespective of underlying arch anatomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

The pathways for biventricular repair of hypoplastic aortic arch with ventricular septal defect, small aortic valve, and normal-sized left ventricle vary depending on the disease spectrum. We report a case of an infant who underwent a staged Norwood-Rastelli procedure for aortic stenosis (bicuspid aortic valve), hypoplastic aortic arch, and coarctation of the aorta with ventricular septal defect and normal-sized left ventricle. Ten years after the initial surgery, normal circulatory physiology was achieved with a takedown of the aortopulmonary amalgamation and VSD closure. This became possible as a result of the growth of the aortic valve and annulus. We suggest that this may have been related to progressive narrowing of the surgically created pathway by which some of the left ventricular outflow had been routed through the ventricular septal defect to the native pulmonary valve.

Objectives: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis., Methods and Results: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity., Conclusions: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Namiguchi, Sakaue, Okazaki, Kanno, Komoda, Shikata, Kurata, Ota, Kubota, Kurobe, Nishimura, Masumoto, Higashiyama and Izutani.)

Introduction: The criteria for placement of distal perfusion cannulas vary among reports. This cohort study aimed to establish a reproducible method to monitor critical leg ischemia during minimally invasive cardiac surgery., Methods: We included 121 patients who underwent minimally invasive cardiac surgery via right thoracotomy with right femoral arterial cannulation from 2015 to 2018. The change rate of regional oxygen saturation (ΔrSO 2 ) was calculated as follows: rSO 2 (baseline) - rSO 2 (actual number)/rSO 2 (baseline). Patients were divided into Group N (ΔrSO 2  < 40%): 100/121 (83%) and Group H (ΔrSO 2  > 40%, <10 minutes if >40%): 21/121 (17%). A distal perfusion cannula was placed when ΔrSO 2 was >40% over 10 minutes., Results: No patients experienced significant leg ischemia. Significantly longer cardiopulmonary bypass and aortic cross-clamp times were observed in Group H than in Group N (cardiopulmonary bypass time, 129 ± 36 minutes (Group N) vs. 151 ± 34 minutes (Group H), p = 0.01). ΔrSO 2 correlated positively with plasma creatine phosphokinase elevation (R = 0.40, p < 0.001) on postoperative day 1. Serum lactate on intensive care unit admission showed a significant positive correlation (R = 0.40, p < 0.001) with ΔrSO 2 ., Conclusion: ΔrSO 2 measurement by near-infrared spectroscopy can facilitate distal leg perfusion monitoring and assist surgeons in preventing critical leg ischemia during minimally invasive cardiac surgery.

Background and Aim: There is no report on silent brain infarction (SBI) after minimally invasive cardiac surgery (MICS) with retrograde perfusion. Thus, the current study aimed to investigate the incidence of SBI after MICS using magnetic resonance imaging (MRI)., Methods: This study included 174 patients who underwent MICS with retrograde perfusion between July 2014 and July 2018. Preoperative computed tomography (CT) angiography was routinely performed and vascular pathology was evaluated for patient selection. Postoperative MRI was performed to investigate the occurrence of SBI., Results: Out of the total 174 patients, 26 (14.9%) presented with SBI. A total of 61 SBI lesions were found in the 26 patients; of these, 34 (56%) SBI lesions were in the right hemisphere and 27 (44%) in the left hemisphere. SBIs were primarily observed in the posterior cerebral artery territory. Multivariate analysis revealed aortic stenosis to be the only risk factor of SBI., Conclusions: Retrograde perfusion via femoral cannulation may not increase the incidence of SBI in selected MICS patients based on preoperative CT findings., (© 2020 Wiley Periodicals LLC.)

Background: The molecular mechanisms underlying aortic valve calcification are poorly understood. Here, we aimed to identify the master regulators of calcification by comparison of genes in valve interstitial cells (VICs) with calcified and noncalcified aortic valves., Methods: Calcified aortic valves were surgically excised from patients with aortic valve stenosis who required aortic valve replacements. Noncalcified and calcified sections were obtained from aortic valve leaflets. Collagenase-digested tissues were seeded into dishes, and VICs adhering to the dishes were cultured for 3 weeks, followed by comprehensive gene expression analysis. Functional analyses of identified proteins were performed by in vitro calcification assays. Tissue localization was determined by immunohistochemical staining for normal (n = 11) and stenotic valves (n = 30)., Results: We found 87 genes showing greater than a twofold change in calcified tissues. Among these genes, 68 were downregulated and 19 were upregulated. Cyclooxygenase-1 (COX1) messenger RNA and protein levels were upregulated in VICs from calcified tissues. The COX1 messenger RNA and protein levels in VICs were also strongly increased by stimulation with osteoblast differentiation medium. These were VIC-specific phenotypes and were not observed in other cell types. Immunohistochemical staining revealed that COX1-positive VICs were specifically localized in the calcified area of aortic valve tissues., Conclusions: The VIC-specific COX1 overexpression played a crucial role in calcification by promoting osteoblast differentiation in aortic valve tissues., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative pericardial adhesions are considered a risk factor for redo cardiac surgery. Several large- and medium-size animal models of pericardial adhesions have been reported, but small animal models for investigating the development of anti-adhesion materials and molecular mechanisms of this condition are lacking. In this study, we aimed to establish a simple mouse model of pericardial adhesions to address this gap., Methods: We administered blood, minocycline, picibanil, and talc into the murine pericardial cavity via one-shot injection. Micro-computed tomography analyses of contrast agent-injected mice were carried out for methodological evaluation. We investigated various dosages and treatment durations for molecules identified to be inducers of pericardial adhesion. The adhesive grade was quantified by scoring the strength and volume of adhesion tissues at sacrificed time points. Histological staining with hematoxylin and eosin and Masson's trichrome, and immunostaining for F4/80 or αSMA was performed to investigate the structural features of pericardial adhesions, and pathological features of the pericardial adhesion tissue were compared with human clinical specimens., Results: Administration of talc resulted in the most extensive pericardial adhesions. Micro-computed tomography imaging data confirmed that accurate injection into the pericardial cavity was achieved. We found the optimal condition for the formation of strong pericardial adhesions to be injection of 2.5 mg/g talc for 2 weeks. Furthermore, histological analysis showed that talc administration led to an invasion of myofibroblasts and macrophages in the pericardial cavity and epicardium, consistent with pathological findings in patients with left ventricular assistive devices., Conclusions: We successfully established a simple mouse model of talc-induced pericardial adhesions, which mimics human pathology and could contribute to solving the clinical issues related to pericardial adhesions.

Gut microbiota modulates metabolic and immunoregulatory axes and contributes to the pathophysiology of diseases with inflammatory components, such as atherosclerosis, diabetes mellitus, and ischemic stroke. Inflammation is emerging as a critical player in the pathophysiology of an intracranial aneurysm. Therefore, we hypothesized that the gut microbiota affects aneurysm formation by modulating inflammation. We induced intracranial aneurysms in mice by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Depletion of the gut microbiota was achieved via an oral antibiotic cocktail of vancomycin, metronidazole, ampicillin, and neomycin. Antibiotics were given 3 weeks before aneurysm induction and either continued until the end of the experiment or stopped 1 day before aneurysm induction. We also assessed the effects of the gut microbiota depletion on macrophage infiltration and mRNA levels of inflammatory cytokines. Gut microbiota depletion by antibiotics reduced the incidence when antibiotics were started 3 weeks before aneurysm induction and continued until the end of the experiment (83% versus 6%, P<0.001). Even when antibiotics were stopped 1 day before aneurysm induction, the gut microbiota depletion significantly reduced the incidence of aneurysms (86% versus 28%, P<0.05). Both macrophage infiltration and mRNA levels of inflammatory cytokines were reduced with gut microbiota depletion. These findings suggest that the gut microbiota contributes to the pathophysiology of aneurysms by modulating inflammation. Human studies are needed to determine the exact contribution of the gut microbiota to the pathophysiology of aneurysm formation and disease course in humans.

Objectives: The aim of the study is to compare a technique of pump-controlled retrograde trial off (PCRTO) to insertion of an arterio-venous (AV) bridge to conduct a trial from venoarterial extracorporeal membrane oxygenation (VA ECMO)., Methods: We studied all patients who were weaned from VA ECMO using either PCRTO or AV bridging from November 2014 to April 2018. Demographic data, indications for ECMO, duration of ECMO, duration of trial period off ECMO and survival were compared between the 2 groups., Results: Seventy-nine patients were placed on VA ECMO from November 2014 to April 2018, of whom, 51 (65%) patients met the study inclusion criteria: 31 (61%) patients who had a trial period from VA ECMO using PCRTO and 20 (39%) patients who were weaned using an AV bridge. The indications for ECMO included cardiac (n = 16 and 11, respectively) and non-cardiac aetiologies (n = 15 and 9, respectively). There was 1 death in each group. The duration of the trial off VA ECMO was significantly shorter in the PCRTO group (median = 88.0 vs 196.6 min, P < 0.001). There were 2 conversions from PCRTO to AV bridging during the trial period off ECMO (2.9-kg neonate following a Norwood procedure and 2.2-kg patient following repair of ectopia cordis)., Conclusions: PCRTO is a safe, simple and reproducible approach for enabling a trial period while preserving the circuit during weaning from VA ECMO. In our study, the duration of the trial period off VA ECMO was significantly shorter in the PCRTO group. PCRTO avoids manipulation of the ECMO circuit, provides a 'stress test' to evaluate cardiorespiratory reserve during the trial period off ECMO, is applicable for a wide variety of cardiac and non-cardiac indications and facilitates multiple attempts at weaning from ECMO.

Objective: To investigate whether radial artery pressure is a reliable surrogate measure of central arterial pressure as approximated by femoral artery pressure in minimally invasive cardiac surgery with retrograde perfusion via femoral cannulation., Method: Fifty-two consecutive patients undergoing minimally invasive cardiac surgery were prospectively included in this study. Cardiopulmonary bypass was established via a femoral artery cannulation and femoral vein. Radial and femoral arterial pressures were recorded continuously, and the pressure differential between them was calculated for both systolic and mean arterial pressures. The agreement between measurements from the two arteries was compared using Bland-Altman plots. An interval of 95% limits of agreement of less than 20 mm Hg was set as satisfactory agreement., Results: Average age was 65 ± 14 years. With respect to systolic arterial pressure, 28 patients (54%) had a peak pressure differential between radial and femoral arteries ⩾20 mm Hg. With respect to mean arterial pressure, only five patients (9%) had a peak pressure differential ⩾20 mm Hg. The pressure differential changed with time. Pressure differential in systolic arterial pressure was 5 ± 8 mm Hg until aortic declamping, then increased to a peak of 23 ± 16 mm Hg when cardiopulmonary bypass was turned off. The femoral systolic arterial pressures were significantly greater than radial systolic arterial pressures from time of aortic declamping to 20 min after cardiopulmonary bypass. The Bland-Altman plots revealed large biases and poor agreement in this period., Conclusion: Radial and femoral systolic artery pressure readings can differ significantly in minimally invasive cardiac surgery with retrograde perfusion. Intraoperative arterial pressure management based solely on radial systolic arterial pressure readings should be avoided.

Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)-specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Masson's Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMA-positive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Background and Purpose: Inflammatory cells play a significant role in secondary injury after ischemic stroke. Recent studies have suggested that a lack of autophagy in myeloid cells causes augmented proinflammatory cytokine release and prolonged inflammation after tissue injury. In this study, we investigated the roles of myeloid cell autophagy in ischemic brain injury., Methods: Focal cerebral ischemia was induced via transient middle cerebral artery occlusion in mice with autophagy-deficient myeloid lineage cells (Atg5flox/flox LysMCre+) and in their littermate controls (Atg5flox/flox). Infarct volume, neurological function, inflammatory cell infiltration, and proinflammatory cytokine expression levels were evaluated., Results: Mice lacking autophagy in myeloid lineage cells had a lower survival rate for 14 days than control mice (20% versus 70%; P <0.05). Although there was no difference in infarct volume at 12 hours between the 2 groups, mice lacking autophagy in myeloid lineage cells had larger infarct volumes at later time points (3 and 7 days after reperfusion) with worse neurological deficit scores and lower grip test scores. There were a higher number of ionized calcium binding adaptor molecule 1-positive cells and cells expressing M1 marker CD16/32 in mice lacking autophagy in myeloid cells at the later time points. Moreover, these mice had higher expression levels of proinflammatory cytokines at later time points; however, there was no difference in ionized calcium binding adaptor molecule 1-positive cells or mRNA levels of proinflammatory cytokines at the earlier time point (12 hours after reperfusion)., Conclusions: These data suggest that the lack of myeloid cell autophagy aggravates secondary injury by augmenting and prolonging inflammation after ischemic stroke without affecting the initial injury., (© 2018 American Heart Association, Inc.)

We developed a method for the optimization of dissolution properties of solid oral dosage forms manufacturing using high shear wet granulation (HSWG) by using near-infrared spectroscopy (NIRS) with chemometrics in small-scale experiments. The changes in rheology and NIR spectra of the granules were monitored to verify the granulation mechanism and determine the suitable water amount for model formulation during the HSWG. Tablets were manufactured by altering the added water amount to investigate the impact of the granulation mechanism on drug product qualities. Model formulation granules were prepared with 10-20% w/w water in a funicular state, corresponding to the plateau region in score plots obtained by principal component analysis (PCA). The dissolution rate of model formulation tablets manufactured with more than 20% w/w of water was significantly delayed while tablets manufactured with 15% w/w water showed 100% dissolution at 15 min. NIRS and PCA are applicable to the optimization of dissolution properties via the process understanding of HSWG at the early formulation development stage and could facilitate drug development.

Background: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history., Case Presentation: A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8., Conclusions: This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

Background: Lung injury is a life-threatening complication in patients with liver dysfunction. We recently provided an experimental lung injury model in mouse with common bile duct ligation. In this study, we aimed to characterize the pathologic and biochemical features of lung tissues in common bile duct ligation mice using a proteomic approach., Methods: Common bile ducts of BALB/c mice, 8 weeks of age, were ligated operatively. CD31-expressing pulmonary cells were sorted with immunomagnetic microbeads, and protein profiles were examined by 2-dimensional gel electrophoresis. Based on the results of protein identification, immunohistochemistry and quantitative reverse transcription polymerase chain reaction were carried out in pulmonary and hepatic tissues., Results: Two-dimensional gel electrophoresis revealed 3 major inflammation-associated proteins exhibiting considerable increases in the number of CD31-positive pulmonary cells after common bile duct ligation. Mass spectrometry analysis identified these proteins as SerpinB1a (48 kDa), ANXA1 (46 kDa), and S100A9 (16 kDa). Furthermore, the 3 proteins were more highly expressed in dilated pulmonary blood vessels of common bile duct ligation mice, in which neutrophils and monocytes were prominent, as shown by immunohistochemistry. More importantly, SerpinB1a mRNA and protein were significantly upregulated in the liver, whereas S100A9 and ANXA1 mRNA and protein were upregulated in the lungs, as shown by quantitative reverse transcription polymerase chain reaction and Western blotting., Conclusion: We identified 3 proteins that were highly expressed in the lung after common bile duct ligation using a proteomics-based approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aortic coarctation rarely occurs after an arterial switch operation for D-transposition of the great arteries with intact ventricular septum. We report the case of a neonate patient in whom aortic coarctation developed 28 days after an uncomplicated arterial switch operation. Preoperatively, the aorta was noted to have an irregular shape, but there was no pressure gradient across the lesion. The patient underwent successful reoperation to correct the coarctation. We hope that our report raises awareness of a rare early complication after arterial switch operation with intact ventricular septum, and the need to carefully monitor the aortic isthmus in patients who have aortic irregularities, even in the absence of a pressure gradient.

Collateral vascular arteries from the descending aorta to the pulmonary arteries are uncommon after arterial switch operation. Here, we report the case of a baby girl treated with coil embolization for abnormal blood flow from the descending aorta to the pulmonary arteries after arterial switch operation. A baby girl weighing 1324 g was delivered at 32 weeks 4 days of gestation, and she had D-transposition of the great arteries and a ventricular septal defect. She underwent nitrogen inhalation to reduce pulmonary blood flow before arterial switch operation. After the operation, she presented with left heart failure due to the presence of abnormal blood flow from the descending aorta to the pulmonary arteries, and she was successfully treated with coil embolization. After the treatment, her condition improved dramatically, and she was discharged without any complications.

Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling, which are processes that have important roles in the pathophysiology of intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in the development of intracranial aneurysm rupture using a mouse model of intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10 mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks. Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. The protective effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7) was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and aneurysms, Mas receptor mRNA expression was very scarce in these tissues. Angiotensin-(1-7) reduced the expression of tumor necrosis factor-α and interleukin-1β in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner.