In vivo mitral valve repair for the transplanted donor heart in orthotopic heart transplantation.

A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation. Because of the difficulty in weaning from cardiopulmonary bypass, a second aortic cross-clamp was applied, and we detached the inferior vena cava and the right side of the left atrial anastomosis to approach the mitral valve, obtaining a satisfactory exposure. No abnormalities were observed in the mitral valve leaflets, annulus or subvalvular apparatus. Subsequent in vivo mitral annuloplasty using prosthetic full ring successfully controlled the regurgitation, and the patient was easily weaned from cardiopulmonary bypass. She discharged to home with good mitral valve and cardiac functions. And the patient has been doing well without any recurrence of MR or heart failure for over a year after surgery.

How should cardiac xenotransplantation be initiated in Japan?

The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Impact assessment of mandatory safety device installation for gas stoves.

Numerous fire accidents have occurred in Japan owing to food overheating when cooking on gas stoves because users left the cooking area unattended. In response, authorities enacted a legal revision mandating temperature sensor installation on gas stove burners. Nevertheless, the actual effectiveness of this measure remains uncertain. Furthermore, prior studies have raised concerns about the efficacy of specific safety standards for consumer products owing to insufficient evidence of reduction in accidents. Consequently, this study seeks to assess the impact of the standards revision implemented in 2008, requiring the placement of safety devices on all gas stove burners. Through a comprehensive analysis, it was aimed to ascertain how these measures have precisely influenced safety outcomes in cooking-related incidents. The data in this study were subdivided to mitigate potential bias from user attributes during data collection. The analysis employed the difference-in-differences method, specifically utilizing one-burner gas stoves unaffected by the standards revision. The data used in this study include accidents associated with gas stoves, spanning the period 2007-2019. To estimate the likelihood of overheating accidents, a binomial distribution model that utilized the Markov chain Monte Carlo methods was applied. For gas stoves with two or more burners, which were affected by the standards revision, the estimated probability of overheating accidents decreased by approximately 80%. In contrast, no decreasing trend was observed for one-burner gas stoves. The analysis suggests that the mandatory installation of safety devices on gas stoves has indeed resulted in a significant reduction in overheating accidents.

Regulatory Role of GgaR (YegW) for Glycogen Accumulation in Escherichia coli K-12.

Glycogen, the stored form of glucose, accumulates upon growth arrest in the presence of an excess carbon source in Escherichia coli and other bacteria. Chromatin immunoprecipitation screening for the binding site of a functionally unknown GntR family transcription factor, YegW, revealed that the yegTUV operon was a single target of the E. coli genome. Although none of the genes in the yegTUV operon have a clear function, a previous study suggested their involvement in the production of ADP-glucose (ADPG), a glycogen precursor. Various validation through in vivo and in vitro experiments showed that YegW is a single-target transcription factor that acts as a repressor of yegTUV, with an intracellular concentration of consistently approximately 10 molecules, and senses ADPG as an effector. Further analysis revealed that YegW repressed glycogen accumulation in response to increased glucose concentration, which was not accompanied by changes in the growth phase. In minimal glucose medium, yegW-deficient E. coli promoted glycogen accumulation, at the expense of poor cell proliferation. We concluded that YegW is a single-target transcription factor that senses ADPG and represses glycogen accumulation in response to the amount of glucose available to the cell. We propose renaming YegW to GgaR (repressor of glycogen accumulation).

Simulation to determine the approach of transcatheter aortic valve implantation in patients undergoing hemodialysis.

PURPOSE: The present study investigated potential access vessels in patients receiving hemodialysis who underwent surgical aortic valve replacement and determined which approaches were most suitable for performing transcatheter aortic valve implantation. METHODS: Consecutive patients undergoing hemodialysis with aortic valve stenosis who underwent surgical aortic valve replacement were included. Preoperative computed tomography data were analyzed to assess the vessel diameter and calcification. Simulations were conducted to determine the feasibility of inserting the 14-F eSheath of Sapien 3 via transfemoral, trans-cervical, trans-subclavian, and direct aorta approaches. RESULTS: A total of 72 patients were included in this study. The access route was characterized by severe calcification of the common iliac artery. The transfemoral approach was feasible in 77.8% of the cases, but the rate decreased to 33% when the calculations were based on the maximum sheath extension diameter. The trans-cervical, trans-subclavian, and direct aortic approaches were suitable for many patients. Lower extremity artery disease was identified as a risk factor for the unsuitability of the transfemoral approach. CONCLUSIONS: Common iliac artery calcification in patients undergoing hemodialysis restricts the use of the transfemoral approach. Therefore, some patients require alternative approaches.

Utility of growth differentiation factor-15 as a predictor of cardiovascular surgery outcomes: Current research and future directions.

In a world increasingly confronted by cardiovascular diseases (CVDs) and an aging population, accurate risk assessment prior to cardiac surgery is critical. Although effective, traditional risk calculators such as the Japan SCORE, Society of Thoracic Surgeons score, and EuroSCORE II may not completely capture contemporary risks, particularly due to emerging factors such as frailty and sarcopenia. These calculators often focus on regional and ethnic specificity and rely heavily on evaluations based on age and underlying diseases. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that has been identified as a potential biomarker for sarcopenia and a tool for future cardiac risk assessment. Preoperative plasma GDF-15 levels have been associated with preoperative, intraoperative, and postoperative factors and short- and long-term mortality rates in patients undergoing cardiac surgery. Increased plasma GDF-15 levels have prognostic significance, having been correlated with the use of cardiopulmonary bypass during surgery, amount of bleeding, postoperative acute kidney injury, and intensive care unit stay duration. Notably, the inclusion of preoperative levels of GDF-15 in risk stratification models enhances their predictive value, especially when compared with those of the N-terminal prohormone of brain natriuretic peptide, which does not lead to reclassification. Thus, this review examines traditional risk assessments for cardiac surgery and the role of the novel biomarker GDF-15. This study acknowledges that the relationship between patient outcomes and elevated GDF-15 levels is not limited to CVDs or cardiac surgery but can be associated with variable diseases, including diabetes and cancer. Moreover, the normal range of GDF-15 is not well defined. Given its promise for improving patient care and outcomes in cardiovascular surgery, future research should explore the potential of GDF-15 as a biomarker for postoperative outcomes and target therapeutic intervention.

Impella - Current issues and future expectations for the percutaneous, microaxial flow left ventricular assist device.

The importance of temporary mechanical circulatory support for treating acute heart failure with cardiogenic shock is increasingly recognized, and Impella (Abiomed, Danvers, MA, USA) has received particular attention in this regard. Impella is an axial flow left ventricular assist device (LVAD) built into the tip of a catheter. It is inserted via a peripheral artery and implanted into the left ventricle. Although the morphology of Impella is different from a typical LVAD, it has similar actions and effects as an LVAD in terms of left ventricular drainage and aortic blood delivery. Impella increases mean arterial pressure (MAP) and systemic blood flow, thereby improving peripheral organ perfusion and promoting recovery from multiple organ failure. In addition, left ventricular unloading with increased MAP increases coronary perfusion and decreases myocardial oxygen demand, thereby promoting myocardial recovery. Impella is also useful as a mechanical vent of the left ventricle in patients supported with veno-arterial extracorporeal membrane oxygenation. Indications for Impella include emergency use for cardiogenic shock and non-emergent use during high-risk percutaneous coronary intervention and ventricular tachycardia ablation. Its intended uses for cardiogenic shock include bridge to recovery, durable device, heart transplantation, and heart surgery. Prophylactic use of Impella in high-risk patients undergoing open heart surgery to prevent postcardiotomy cardiogenic shock is also gaining attention. While there have been many case reports and retrospective studies on the benefits of Impella, there is little evidence based on sufficiently large randomized controlled trials (RCTs). Currently, several RCTs are now ongoing, which are critical to determine when, for whom, and how these devices should be used. In this review, we summarize the principles, physiology, indications, and complications of the Impella support and discuss current issues and future expectations for the device.

Hemodynamic predictors of negative false lumen remodeling after frozen elephant trunk for acute aortic dissection.

OBJECTIVE: We evaluated the blood flow within the downstream aortic false lumen after frozen elephant trunk repair for acute aortic dissection and identified hemodynamic predictors of false lumen expansion and negative false lumen remodeling using four-dimensional flow magnetic resonance imaging. METHODS: Thirty-one patients (Stanford type A, n = 28; Stanford type B, n = 3) with patent false lumen who underwent frozen elephant trunk procedures for acute aortic dissection were included in this observational study. Each patient underwent computed tomography during the follow-up period and four-dimensional flow magnetic resonance imaging within 3 postoperative months. The false lumen volumetric expansion rate was calculated using computed tomography data. The direction and the rate of flow in the lower descending aortic false lumen were analyzed. Negative false lumen remodeling was defined as a volumetric increase of > 10% from the baseline volume. RESULTS: Negative false lumen remodeling had developed in 6 of the 31 patients during the observation period. Most of the false lumen flows were biphasic during systole. The range between peak and nadir flow rates was associated with the false lumen volumetric expansion rate (ß coefficient = 6.77; p < 0.01, R2 = 0.43). CONCLUSIONS: The range between peak and nadir flow rates may serve as a hemodynamic predictor of negative false lumen remodeling, enabling further treatment for patients at risk of expansion in the downstream aorta.

A protocol-based treatment for ruptured abdominal aortic aneurysm contributed to improving aorta-related mortality: a retrospective cohort study.

BACKGROUND: Recent guidelines state that improving the survival rate of patients with ruptured abdominal aortic aneurysm (rAAA) requires a protocol or algorithm for the emergency management of these patients. We aimed to investigate whether introducing a protocol treatment for rAAA improves clinical outcomes compared with the pre-protocol strategy. METHODS: At our institution, 92 patients treated for rAAA between June 2008 and August 2022 were retrospectively analyzed. In 2014, the protocol-based treatment was introduced comprising a transfer algorithm to shorten the time to proximal control, use of an endovascular occlusion balloon, strict indications for endovascular aortic aneurysm repair (EVAR) or open surgical repair, and perioperative care, including for abdominal compartment syndrome (ACS). Clinical outcomes were compared between the protocol and pre-protocol group, including operative status, all-cause mortality, and rAAA-related death at 30-day, in-hospital, and 1-year postoperative follow-ups. RESULTS: Overall, 52 and 40 patients received the protocol-based and pre-protocol treatments, respectively. EVAR was more frequently performed in the protocol group. The rate of achieving time to proximal control was significantly faster, and the transfusion volume was lower in the protocol group. ACS occurred more frequently in the protocol group with a higher EVAR. No difference was found in all-cause mortality between the two groups. The protocol group exhibited fewer rAAA-related deaths than the pre-protocol group during the following time points: 30 days (9.6% vs. 22.5%), during the hospital stay (11.5% vs. 30.0%), and 1 year (14.5% vs. 31.5%). CONCLUSIONS: The protocol-based treatment improved the survival rate of patients with rAAA.

Detection and Quantification of Calcium Ions in the Endoplasmic Reticulum and Cytoplasm of Cultured Cells Using Fluorescent Reporter Proteins and ImageJ Software.

This protocol describes a method for detecting and quantifying calcium ions in the endoplasmic reticulum (ER) and cytoplasm of cultured cells using fluorescent reporter proteins and ImageJ software. Genetically engineered fluorescent reporter proteins, such as G-CEPIA1er and GCaMP6f, localize to intracellular regions of interest (i.e., ER and cytoplasm) and emit green fluorescence upon binding to calcium ions. In this way, the fluorescence brightness of cells transfected with expression vectors for these reporters reflects the calcium ion concentration in each intracellular region. Here, we describe procedures for observing cultured cells expressing these fluorescent reporters under a fluorescence microscope, analyzing the obtained image using the free image analysis software ImageJ (https://imagej.net/ij/index.html), and determining the average fluorescence brightness of multiple cells present in the image. The current method allows us to quickly and easily quantify calcium ions on an image containing multiple cells and to determine whether there are relative differences in intracellular calcium ion concentration among experiments with different conditions. Key features Detection and quantification of calcium ions in the ER and cytoplasm using fluorescent reporter proteins Quick and easy verification of measurement results using ImageJ Simultaneous comparison between various experimental conditions (drug treatment, mutants, etc.).

Minimally invasive cardiac surgery via bilateral thoracotomy in treatment of left ventricle aneurysm: a case report.

BACKGROUND: Left ventricle aneurysm (LVA) as a sequela to myocardial infarction or iatrogenic injury is required surgical treatment with full median sternotomy. Herein, we report a case of successful surgical treatment of left ventricle aneurysm performed by minimally invasive cardiac surgery (MICS). CASE PRESENTATION: We describe a case of a LVA treated by minimally invasive cardiac surgery in an 82-year-old woman who reported to the hospital with the complaint of chest pains at rest. Computed tomography (CT) coronary angiography revealed a left ventricle apical aneurysm. The aneurysm was suspected to be a pseudoaneurysm caused by a previous myocardial infarction. Surgery was performed under general anesthesia, with the patient in a supine position. A small incision was made in the 3rd intercostal space through which an aortic root vent cannula and aortic clamp were inserted, followed by exposing the aneurysm via incision of the left 6th intercostal space. The aneurysm was resected and pathologically examined, revealing it to be a "true" aneurysm. The left ventricle wall was closed using polypropene mattress sutures. Postoperative CT scan revealed successful resection of the aneurysm. Usually, a surgical treatment with full median sternotomy and left ventriculostomy is indicated for LVA. We decided to treat the LVA with bilateral thoracotomy MICS. We preferred to perform this procedure under cardiac arrest to ensure safe and secure closure of the aneurysm. The right small thoracotomy was necessary for aortic cross-clamping and aortic root venting. CONCLUSIONS: The procedure was safe and simple and yielded excellent postoperative outcomes. Therefore, we speculate that this method can be applied to the management of larger aneurysms.

Overview of mechanical circulatory support for the management of post-myocardial infarction ventricular septal rupture.

Post-myocardial infarction ventricular septal rupture (PIVSR) is becoming increasingly rare in the percutaneous coronary intervention era; however, the mortality rates remain high. Surgical repair is the gold standard treatment for PIVSR but is associated with surgical difficulty and high mortality. Therefore, the timing of surgery is controversial (i.e. either undertake emergency surgery or wait for resolution of organ failure and scarring of the infarcted area). Although long-term medical management is usually ineffective, several mechanical circulatory support (MCS) devices have been used to postpone surgery to an optimal timing. Recently, in addition to venous arterial extracorporeal membrane oxygenation (VA-ECMO), new MCS devices, such as Impella (Abiomed Inc., Boston, MA, USA), have been developed. Impella is a pump catheter that pumps blood directly from the left ventricle, in a progressive fashion, into the ascending aorta. VA-ECMO is a temporary MCS system that provides complete and rapid cardiopulmonary support, with concurrent hemodynamic support and gas exchange. When left and right heart failure and/or respiratory failure occur in cardiogenic shock or PIVSR after acute myocardial infarction, ECpella (Impella and VA-ECMO) is often introduced, as it can provide circulatory and respiratory assistance in a shorter period. This review outlines the basic concepts of MCS in PIVSR treatment strategies and its role as a bridge device, and discusses the efficacy and complications of ECpella therapy and the timing of surgery.

A motor neuron disease-associated mutation produces non-glycosylated Seipin that induces ER stress and apoptosis by inactivating SERCA2b.

A causal relationship between endoplasmic reticulum (ER) stress and the development of neurodegenerative diseases remains controversial. Here, we focused on Seipinopathy, a dominant motor neuron disease, based on the finding that its causal gene product, Seipin, is a protein that spans the ER membrane twice. Gain-of-function mutations of Seipin produce non-glycosylated Seipin (ngSeipin), which was previously shown to induce ER stress and apoptosis at both cell and mouse levels albeit with no clarified mechanism. We found that aggregation-prone ngSeipin dominantly inactivated SERCA2b, the major calcium pump in the ER, and decreased the calcium concentration in the ER, leading to ER stress and apoptosis in human colorectal carcinoma-derived cells (HCT116). This inactivation required oligomerization of ngSeipin and direct interaction of the C-terminus of ngSeipin with SERCA2b, and was observed in Seipin-deficient neuroblastoma (SH-SY5Y) cells expressing ngSeipin at an endogenous protein level. Our results thus provide a new direction to the controversy noted above.

Immunoglobulin G4-related inflammatory pseudotumor of the right ventricle with right coronary artery occlusion.

Immunoglobulin G4-related inflammatory pseudotumors are usually benign. Such tumors of cardiac origin are extremely rare, with no primary cardiac tumors reported to date. We report a case of a 77-year-old woman, with a medical history of diabetes, hypertension, and hyperlipidemia, who was diagnosed with a malignant cardiac tumor on preoperative imaging and had a confirmed pathological diagnosis of immunoglobulin G4-related inflammatory pseudotumor. She was examined for atherosclerosis obliterans, and coronary computed tomography revealed obstruction of the right coronary artery and a cardiac tumor in the right atrium. A suspected malignant tumor measuring 40 mm (maximum standardized uptake value: 12.2) bordering the right atrium was detected using 18F-fluorodeoxyglucose positron emission tomography. Her tumor was in contact with the heart, making biopsy impossible. She was diagnosed with malignancy on preoperative imaging and underwent tumor resection, tricuspid valve replacement, right atrial and right ventricular plasty, coronary artery bypass, lung resection, and diaphragmatic repair. However, the final pathological diagnosis was immunoglobulin G4-related inflammatory pseudotumor. Preoperative diagnosis of immunoglobulin G4-related inflammatory pseudotumor is extremely difficult; however, if the condition is diagnosed preoperatively, chemotherapy or steroid therapy should be administered, and patients who do not respond to chemotherapy should be considered for surgical treatment. Learning objective: Immunoglobulin G4-associated inflammatory pseudotumor is extremely rare. Preoperative imaging diagnosis of immunoglobulin G4-associated inflammatory pseudotumor is extremely difficult, and pathology with biopsy is the only definitive diagnosis. However, if we could make an accurate preoperative diagnosis, patients should be treated with chemotherapy or steroids, and surgical treatment should be considered for patients who do not respond to chemotherapy or steroids.

Prosthetic Valve Function after Aortic Valve Replacement for Severe Aortic Stenosis by Transcatheter Procedure versus Surgery.

Background This study compared the clinical outcomes of transcatheter (TAVR) and surgical (SAVR) aortic valve replacements, focusing on postoperative valvular performance assessed by echocardiography. Method and Results A total of 425 patients who underwent TAVR (230 patients) or SAVR (195 patients) were included. Postoperative effective orifice area index (EOAI) was higher in the TAVR group (1.27 ± 0.35 cm2/m2) than in the SAVR group (1.06 ± 0.27 cm2/m2, p < 0.001), and patient−prosthesis mismatch (PPM) was more frequent in the SAVR group (22.6%) than in the TAVR group (8.7%, p < 0.001). Mild or greater paravalvular leakage (PVL) was more frequent in the TAVR group (21.3%) than in the SAVR group (0%, p < 0.001). Moreover, there was no difference in freedom from all-cause death, stroke, or rehospitalization between the groups. Patients with moderate or greater PPM (EOAI < 0.85 cm2/m2) had lower freedom from composite events than those without this PPM criterion (p = 0.008). Patients with mild or greater PVL also had lower freedom from composite events than those without this PVL criterion (p = 0.017). Conclusions Postoperative valvular performance of TAVR was superior to that of SAVR in terms of EOAI. This merit was counterbalanced by the significantly lower rates of PVL in patients who underwent SAVR. The overall clinical outcomes were similar between the study groups.

Infective Endocarditis Revealed after Resolution of COVID-19 Infection.

A 34-year-old previously healthy Japanese woman was diagnosed with COVID-19 and treated with remdesivir and dexamethasone. She was discharge but returned the next day due to acute myocardial infarction. Conservative treatment was selected because of an embolic occlusion in the distal portion. Contrast-enhanced computed tomography and brain magnetic resonance imaging revealed a right renal infarction and multiple cerebral embolisms, respectively; she had a fever of 38.9°C that night. Blood culture was positive for methicillin-susceptible Staphylococcus aureus. Transthoracic echocardiography revealed an 11-mm vegetation on the posterior mitral valve leaflet. Native mitral valve infective endocarditis causing multiple embolizations was diagnosed. She underwent surgical mitral valve replacement.

Hemolytic anemia caused by an excessively kinked prosthetic graft after total arch replacement detected by 4-dimensional flow magnetic resonance imaging: A case report.

RATIONALE: Hemolytic anemia is a rare postoperative complication of aortic surgery, which may be caused by an excessively kinked graft that causes abnormal blood flow. It has been reported that 4-dimensional flow magnetic resonance imaging (4D flow MRI) can identify abnormal flow. Herein, we report the guidance of 4D flow MRI in performing the revision procedure for a patient with hemolytic anemia by evaluating abnormal blood flow based on this method. PATIENT CONCERNS: A 70-year-old woman presented with dizziness and fatigue. She had undergone total arch replacement with a frozen elephant trunk 5 years prior. We diagnosed hemolytic anemia caused by a kinked graft after total arch replacement. DIAGNOSIS: Although computed tomography findings revealed 3 lesions of the kinked graft at the ascending portion and cervical branches, 4D flow MRI findings showed that only the kinked graft at the ascending portion caused hemolytic anemia due to an elevated viscous energy loss around it. INTERVENTION: We performed surgery to remove the kinked section instead of revision surgery consisting of total arch replacement. OUTCOMES: The patient's postoperative course was uneventful and there were no complications. Postoperative enhanced computed tomography findings showed that the repaired graft had an adequate length and smoothly curved shape. The 4D flow MRI findings revealed smooth flow in the ascending portion and decreased viscous energy loss. LESSONS: Based on the 4D flow MRI findings, we adopted a less invasive approach, repairing only the ascending portion of the graft, instead of performing revision surgery comprising total arch replacement.