Robot-Assisted Aortic Valve Replacement　- First Clinical Report in Japan.

BACKGROUND: Robot-assisted valve surgery represents the latest development in the field of minimally invasive approaches. Robotic assistance may provide greater visualization, enhanced dexterity, and greater precision than traditional mini-thoracotomy aortic valve replacement.Methods and Results: Aortic valve replacement operations using the da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) were performed on 2 patients, 1 with severe aortic insufficiency and the other with aortic stenosis. Both patients had an uneventful postoperative course and were discharged without any adverse events. CONCLUSIONS: Robot-assisted assisted aortic valve replacement appears feasible and safe in limited cases.

Novel Scoring System to Risk Stratify Patients Receiving Durable Left Ventricular Assist Device From J-MACS Registry Data.

BACKGROUND: Recently, destination therapy (DT) was approved in Japan, and patients ineligible for heart transplantation may now receive durable left ventricular assist devices (LVADs). Several conventional risk scores are available, but a risk score that is best to select optimal candidates for DT in the Japanese population remains unestablished.Methods and Results: A total of 1,287 patients who underwent durable LVAD implantation and were listed for the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) were eligible for inclusion. Finally, 494 patients were assigned to the derivation cohort and 487 patients were assigned to the validation cohort. According to the time-to-event analyses, J-MACS risk scores were newly constructed to predict 3-year mortality rate, consisting of age, history of cardiac surgery, serum creatinine level, and central venous pressure to pulmonary artery wedge pressure ratio >0.71. The J-MACS risk score had the highest predictability of 3-year death compared with other conventional scores in the validation cohort, including HeartMate II risk score and HeartMate 3 risk score. CONCLUSIONS: We constructed the J-MACS risk score to estimate 3-year mortality rate after durable LVAD implantation using large-scale multicenter Japanese data. The clinical utility of this scoring to guide the indication of DT should be validated in the next study.

Safe launch of a robotically assisted mitral valve repair program in a single center: experience of initial 20 cases under the Center for Minimally Invasive Surgery.

Robotically assisted mitral valve repair was approved by the Japanese government in April 2018. However, understanding robotic surgery involves steep learning curves of surgeons and dedicated cardiac teams. The Center for Minimally Invasive Surgery (CMIS) of Tottori University Hospital is a multidisciplinary organization established in 2011 with seven surgical departments. In this study, we report strategies for improving the safety of robotic surgery in the CMIS and early results of robotic mitral valve repair at our hospital. We reviewed the first 20 patients who underwent robotic primary mitral valve repair, including concomitant procedures, from October 2019 to September 2021 under the supervision of the CMIS. Before starting the program, the CMIS requires setting console time limit to 180 min and implementing risk management strategies through simulation training for various mechanical failures. Mitral valve repair was completed in all patients. There was no in-hospital or 30-day mortality. No conversion to median sternotomy was necessary. The analysis of mitral pathology revealed 1 case of functional mitral regurgitation, 12 cases of posterior lesions, 3 cases of anterior lesions, 3 cases of bileaflet lesions, and 1 case of commissural lesion. The average cross-clamp time was 133 ± 27 min. Sixteen cases had trace mitral regurgitation postoperatively, and 4 cases had mild mitral regurgitation. The median (interquartile range) postoperative hospital stay was 10 (8.5-12.5) days. Robotically assisted mitral valve repair was performed safely with assistance from the multidisciplinary CMIS, and the early results were satisfactory without compromising clinical outcomes.

Impact of frailty on early and mid-term outcomes of hybrid aortic arch repair.

PURPOSE: The purpose of this study was to investigate the impact of frailty on the clinical outcomes of hybrid aortic arch repair with debranching of the supra-aortic arteries. METHODS: Consecutive patients ≥ 75 years old who underwent hybrid aortic arch repair from January 2010 to December 2019 were retrospectively analyzed. Using the Canadian Study of Health and Aging (CSHA) scale, all patients with a CSHA scale score > 4 were defined as frail. The frail patients (FP) group and the non-frail patients (NFP) group were compared regarding the early and mid-term outcomes of hybrid aortic arch repair. RESULTS: A total of 84 patients were included. The early postoperative results were not markedly different between the groups, except that the rate of transfer to a rehabilitation hospital was higher in the FP group than in the NFP group. The survival at 5 years was significantly lower in the FP group at 43.0% than in the NFP group at 67.7% (P = 0.015). However, the freedom from aorta-related death was not significantly different between the two groups. CONCLUSION: Frailty did not affect the short-term outcomes of hybrid aortic arch repair; however, the mid-term outcomes, including the survival, of the frail patients were significantly worse than those of the non-frail patients, mostly because of non-aorta-related causes.

Esm1 and Stc1 as Angiogenic Factors Responsible for Protective Actions of Adipose-Derived Stem Cell Sheets on Chronic Heart Failure After Rat Myocardial Infarction.

BACKGROUND: Although adipose-derived stem cell (ADSC) sheets improve the cardiac function after myocardial infarction (MI), underlying mechanisms remain to be elucidated. The aim of this study was to determine the fate of transplanted ADSC sheets and candidate angiogenic factors released from ADSCs for their cardiac protective actions.Methods and Results:MI was induced by ligation of the left anterior descending coronary artery. Sheets of transgenic (Tg)-ADSCs expressing green fluorescence protein (GFP) and luciferase or wild-type (WT)-ADSCs were transplanted 1 week after MI. Both WT- and Tg-ADSC sheets improved cardiac functions evaluated by echocardiography at 3 and 5 weeks after MI. Histological examination at 5 weeks after MI demonstrated that either sheet suppressed fibrosis and increased vasculogenesis. Luciferase signals from Tg-ADSC sheets were detected at 1 and 2 weeks, but not at 4 weeks, after transplantation. RNA sequencing of PKH (yellow-orange fluorescent dye with long aliphatic tails)-labeled Tg-ADSCs identified mRNAs of 4 molecules related to angiogenesis, including those of Esm1 and Stc1 that increased under hypoxia. Administration of Esm1 or Stc1 promoted tube formation by human umbilical vein endothelial cells. CONCLUSIONS: ADSC sheets improved cardiac contractile functions after MI by suppressing cardiac fibrosis and enhancing neovascularization. Transplanted ADSCs existed for >2 weeks on MI hearts and produced the angiogenic factors Esm1 and Stc1, which may improve cardiac functions after MI.

Cost analysis of transcatheter versus surgical aortic valve replacement in octogenarians: analysis from a single Japanese center.

Transcatheter aortic valve replacement (TAVR) has revolutionized the prognosis of intermediate- or high-risk patients with severe aortic stenosis, particularly among older adults. However, in possible candidates for surgical aortic valve replacement (SAVR), the implantation of expensive prostheses may be questionable in an era when healthcare costs are becoming a major concern. In this retrospective analysis of a single Japanese center, we focused on patients aged over 80 years; the objectives of this study were: (1) to compare TAVR and SAVR in terms of total hospitalization costs and (2) to describe the itemized cost of TAVR and SAVR to identify patients aged over 80 years in whom TAVR or SAVR would be cost-effective. A total of 146 patients aged over 80 years who underwent TAVR or SAVR for severe aortic stenosis were included. These patients were divided into a high-risk group (Society of Thoracic Surgeons [STS] mortality score > 8%; 36: TAVR and 12: SAVR) with 48 patients and a non-high-risk group (STS mortality score < 8%; 45: TAVR and 53 SAVR) with 98 patients. No 30-day mortality was observed in either group. In both groups, postoperative intensive care unit stay and hospital stay were longer with SAVR than with TAVR. In the non-high-risk group, the total cost was comparable for TAVR and SAVR; however, in the high-risk group, the total cost was significantly higher with SAVR than that with TAVR. A breakdown analysis of the total cost in the high-risk group showed both pre- and postoperative costs to be significantly higher with SAVR than with TAVR; however, operative costs were higher with TAVR. Up to 3 years, the overall survival in both groups did not significantly differ between TAVR and SAVR. Our findings suggest that from the perspective of total medical costs, TAVR is more suitable than SAVR for high-risk older adults.

Tolvaptan can limit postoperative paroxysmal atrial fibrillation occurrence after open-heart surgery.

PURPOSE: Tolvaptan administration in the early postoperative period after cardiac surgery rapidly treats fluid retention without affecting the renal function. Tolvaptan also has the benefit of not stimulating the renin-angiotensin and sympathetic nervous systems, which are risk factors for postoperative paroxysmal atrial fibrillation. In this study, we examined the hypothesis that tolvaptan administration reduces postoperative paroxysmal atrial fibrillation and worsening of the renal function incidence in patients who have undergone open-heart surgery. METHODS: From our previous randomized study, we selected 166 open-heart surgery patients, divided them into 2 groups [tolvaptan group, 83 patients; control (non-tolvaptan) group, 83 patients], and compared the incidence of postoperative paroxysmal atrial fibrillation and worsening of the renal function in the postoperative period between the groups. RESULTS: The incidence of worsening of the renal function was significantly lower in the tolvaptan group than in the control group (4.8% vs. 15.7%; P = 0.04). The incidence of postoperative paroxysmal atrial fibrillation within 14 days was also significantly lower in the tolvaptan group than in the control group (26.5% vs. 42.2%; P = 0.011). CONCLUSION: Tolvaptan administration in the early postoperative period after open-heart surgery may reduce the incidence of postoperative paroxysmal atrial fibrillation and worsening of the renal function.

ß-Adrenergic Blocker, Carvedilol, Abolishes Ameliorating Actions of Adipose-Derived Stem Cell Sheets on Cardiac Dysfunction and Remodeling After Myocardial Infarction.

BACKGROUND: Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI.Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a ß-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts. CONCLUSIONS: ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

Glomerular basement membrane duplication is a predictor of the prognosis of diabetic nephropathy in patients with type 2 diabetes.

BACKGROUND: Several clinical parameters and pathological findings are known to be predictors of the deterioration of diabetic nephropathy (DN). Glomerular basement membrane duplication (GBM-DP) is a pathological feature representing endothelial injury, which is commonly observed in DN. In the present study, we investigated the association between GBM-DP and the renal prognosis in DN. METHODS: The study enrolled 80 patients with renal biopsy-proven DN who were managed at Chiba-East Hospital from 2005 to 2012. We confirmed the pathological findings according to the Renal Pathology Society classifications, and we further evaluated the GBM-DP, which was defined as double contours of the GBM that expanded more than 10% of capillary loops in the most affected nonsclerotic glomerulus. We used Cox regression models to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), with adjustment for age, sex, systolic blood pressure, HbA1c, estimated glomerular filtration rate (eGFR), and urinary protein excretion (UP) at baseline. RESULTS: Of the 80 patients, 56 were male (70.0%) and the mean age was 59.1 years. The median eGFR and UP were 42 ml/min/1.73 m2 (IQR 30, 59) and 3.1 g/gCr (IQR 1.2, 5.2). Twenty-seven patients progressed to ESRD and one patient died during the median observational period of 2.9 years (IQR 1.5, 4.3). The multivariable analyses showed that GBM-DP was significantly associated with ESRD (HR 3.18 [95% confidence interval (CI): 1.02-9.87], p = 0.045). CONCLUSION: We newly identified GBM-DP as a strong prognostic predictor in DN patients. Further study is needed to clarify the pathogenic mechanism of GBM-DP in DN.

Can Tolvaptan Protect Renal Function in the Early Postoperative Period of Cardiac Surgery?　- Results of a Single-Center Randomized Controlled Study.

BACKGROUND: Oral administration of tolvaptan, a vasopressin V2receptor antagonist, significantly reduces deterioration of renal function, which has recently been highlighted as an exacerbating factor for adverse events in patients with acute heart failure. In the present study we tested the hypothesis that concomitant administration of tolvaptan with a conventional diuretic is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery.Methods and Results:In all, 280 patients who underwent cardiac surgery were prospectively randomized to concomitant treatment with tolvaptan and a conventional diuretic (tolvaptan group; 147 patients) or treatment with a conventional diuretic alone (control group; 133 patients). Groups were compared in terms of the time required to restore preoperative body weight and the incidence of worsening renal function (WRF), defined as an increase in the serum creatinine level ≥0.3 mg/dL. The time required to restore preoperative body weight was significantly shorter in the tolvaptan than control group (mean [±SD] 3.97±1.95 vs. 5.02±2.83 days, respectively; P<0.001). The incidence of WRF was significantly lower in the tolvaptan than control group (n=11 [7.5%] vs. n=25 [18.8%], respectively; P=0.011). CONCLUSIONS: Administration of tolvaptan with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function and may thus help avoid WRF.

Novel temporary left ventricular assist system with hydrodynamically levitated bearing pump for bridge to decision: initial preclinical assessment in a goat model.

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

Advanced stage of chronic kidney disease is risk of poor treatment outcome for smear-positive pulmonary tuberculosis.

Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but few studies have analyzed the treatment outcome of pulmonary tuberculosis among CKD patients. A retrospective cohort study was conducted at Chiba-East Hospital in Chiba, Japan. Our study estimated the treatment outcomes in smear-positive pulmonary tuberculosis in relation to CKD and its stages. Total subjects were 759 patients (12-99 years) hospitalized between 2007 and 2012. Patients suffering from multi-drug-resistant tuberculosis were excluded. Patients with CKD were 19.3% aged <65 years (n = 384), and 49.6% aged ≥ 65 years, respectively (P < 0.001). Successful treatment was 52.7% in CKD (n = 260) and 67.3% in non-CKD (n = 499) (P < 0.001). Death was 25.4% in CKD and 12.4% in non-CKD (P < 0.001). Treatment outcome was especially poor in patients with low estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m(2), as successful treatment was 20.0%, and death was 50.0%, significantly lower than in other CKD and non-CKD patients. After multivariate logistic regression analysis, eGFR<30 ml/min/1.73 m(2) was an independent factor affecting successful treatment and death, and its adjusted odds ratios (aOR) were 0.20 (95% confidence interval (CI) 0.07-0.50) and 2.99 (95%CI 1.20-7.51), respectively. Other factors affecting successful treatment were serum albumin <3.0 mg/dl, steroid therapy for underlying disease and cardiovascular disease, with aOR (95%CI) of 0.28 (0.20-0.39), 0.32 (0.16-0.63) and 0.49 (0.28-0.86), respectively. Several factors were associated with poor treatment outcome of smear-positive pulmonary tuberculosis. Advanced stage of CKD with eGFR of <30 ml/min/1.73 m(2) was a risk factor for poor treatment outcome.

Sutureless aortic valve replacement using a novel autologous tissue heart valve with stent (stent biovalve): proof of concept.

We developed an autologous, trileaflet tissue valve ("biovalve") using in-body tissue architecture technology to overcome the disadvantages of current bioprosthetic valves. We designed a novel biovalve with a balloon-expandable stent: the stent biovalve (SBV). This study evaluated the technical feasibility of sutureless aortic valve replacement using the SBV in an orthotopic position, as well as the functionality of the SBV under systemic circulation, in an acute experimental goat model. Three adult goats (54.5-56.1 kg) underwent sutureless AVR under cardiopulmonary bypass (CPB). The technical feasibility and functionality of the SBVs were assessed using angiography, pressure catheterization, and two-dimensional echocardiography. The sutureless AVR was successful in all goats, and all animals could be weaned off CPB. The mean aortic cross-clamp time was 45 min. Angiogram, after weaning the animals off CPB, showed less than mild paravalvular leakage and central leakage was not detected in any of the goats. The mean peak-to-peak pressure gradient was 6.3 ± 5.0 mmHg. Epicardial two-dimensional echocardiograms showed smooth leaflet movement, including adequate closed positions with good coaptation; the open position demonstrated a large orifice area (average aortic valve area 2.4 ± 0.1 cm2). Sutureless AVR, using SBVs, was feasible in a goat model. The early valvular functionalities of the SBV were sufficient; future long-term experiments are needed to evaluate its durability and histological regeneration potential.

Influence of a novel electrocardiogram-synchronized rotational-speed-change system of an implantable continuous-flow left ventricular assist device (EVAHEART) on hemolytic performance.

We developed a novel controller for a continuous-flow left ventricular assist device (EVAHEART) that can change the pump's rotational speed (RS) in synchronization with a patient's myocardial electrocardiogram (ECG) with the aim of facilitating cardiac recovery. We previously presented various applications of this system in animal models, but there remained a concern that the repeated acceleration and deceleration of the impeller may induce additional hemolysis. In this study, we evaluated the blood trauma and motor power consumption induced by our system in a mock circulation. We evaluated our system with a 60-bpm pulse frequency and a variance between the high and low RSs of 500 rpm (EVA-P; n = 4). The continuous modes of EVAHEART (EVA-C; n = 4) and ROTAFLOW (n = 4) were used as controls. The pumps were examined at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mmHg for a 4-h period. As a result, the normalized indexes of the hemolysis levels of EVA-P and EVA-C were 0.0023 ± 0.0019 and 0.0023 ± 0.0025, respectively, and their difference was not significant. The estimated mean motor power consumptions of EVA-C and EVA-P were 6.24 ± 0.33 and 7.19 ± 0.93 W, respectively. When a novel ECG-synchronized RS-change system was applied to EVAHEART, the periodic RS change with a 500-rpm RS variance did not affect the hemolysis at a 60-bpm pulse frequency.

Optimal timing of aortic valve replacement in elderly patients with severe aortic stenosis.

PURPOSE: The elderly population with severe aortic stenosis (AS) requiring aortic valve replacement (AVR) is increasing. The optimal timing of AVR in these patients has been under discussion. METHODS: We retrospectively reviewed the data from severe AS patients (n = 84) who underwent AVR with/without concomitant procedures from 2005 to 2010. The symptom status, preoperative data, operative outcome, late survival and freedom from cardiac events were compared between elderly patients (age ≥80 years [n = 31]) and younger patients (age <80 years [n = 53]). RESULTS: The operative mortality in elderly patients (3.2 %) and younger patients (3.8 %) was comparable. The symptoms in elderly patients were more severe and hospitalized heart failure (HF) was more frequently noted as the primary symptom (p = 0.017). Patients with and without hospitalized HF differed significantly in late survival and freedom from cardiac events (p = 0.001), but advanced age had no significant effect. The results of a Cox proportional hazards analysis revealed that hospitalized HF was a significant predictor for cardiac events after AVR, irrespective of age (hazard ratio 6.93, 95 % confidence interval 1.83-26.26, p < 0.004). CONCLUSIONS: In elderly patients with severe AS, surgery should be recommended even in the presence of minimal symptoms and should be performed before the onset of life-threatening HF.

Missing leaflet: a rare cause of structural deterioration of a bovine pericardial aortic bioprosthesis-report of a case.

We experienced a rare cause of aortic bioprosthesis deterioration in which one of the leaflets disappeared 8.7 years after primary aortic valve replacement (AVR) in a male octogenarian. Successful redo AVR with a 23-mm Magna EASE (Carpentier-Edwards, Irvine, CA) was performed. No embolic complications occurred. We were unable to identify the cause of this devastating complication. When heart failure symptoms develop in patients with bioprostheses, clinicians should therefore consider a diagnosis of acute progression of structural valve deterioration and follow the patient carefully with echocardiography.

7501 T > A mitochondrial DNA variant in a patient with glomerulosclerosis.

The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported to be a specific change associated with mitochondrial cytopathy. However, at present, GSEC is not routinely evaluated. We, in this study, present a case of glomerulosclerosis, in which the presence of GSECs should provide us one clue to understand the pathogenesis of its progressive decline of renal function. A 54-year-old Japanese female, who had been diagnosed with Graves' disease, was referred for the examination and treatment of her proteinuria (5.4 g/gCre at the first visit to our hospital). A kidney biopsy showed 28.6% of the glomeruli to be globally sclerosed and 10.7% of the glomeruli to have completely collapsed. However, according to a light microscopic analysis, all other glomeruli showed an almost normal appearance, except for some slight enlargement. Almost 30% of the interstitium was damaged by fibrosis. Characteristically, GSECs were observed in the medulla collecting ducts. Although she had no symptoms of either myopathy or encephalopathy, no history of stroke-like episodes or difficulty in hearing, her serum concentrations of lactate and pyruvate were both elevated. Therefore, mitochondrial DNA sequencing was performed to assess the etiopathogenesis of her nephropathy. Consequently, a homoplasmic 7501 T > A replacement, which has not been previously reported in patients with renal diseases, was detected. This case suggests that the routine evaluation of GSECs can provide important clues to assess the etiopathogenesis of cryptogenic glomerulosclerosis.