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.

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.

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.

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.

Impella support as a bridge to heart surgery in patients with cardiogenic shock.

OBJECTIVES: In patients with cardiogenic shock, delayed surgery after stabilization of haemodynamics and improvement in end-organ function by mechanical circulatory support is known to yield better outcomes than emergency surgery. We aimed to investigate the effectiveness of Impella (Abiomed, Danvers, MA, USA) as a bridge to cardiac surgery in patients with cardiogenic shock. METHODS: We reviewed 7 patients with cardiogenic shock who underwent Impella support as a bridge to cardiac surgery using cardiopulmonary bypass at our institution between April 2018 and August 2021. RESULTS: Cardiogenic shock was caused by ventricular septal rupture in 3 patients, papillary muscle rupture in 1 and acute myocardial infarction in 3. Cardiac surgery was delayed by 1-7 (3.9 ± 2.5) days with Impella support after the diagnosis of cardiogenic shock, during which the hepatic and renal function of the patients improved significantly. Device-related or operation-related adverse events included re-exploration for bleeding in 3 patients, acute limb ischaemia due to thromboembolism in 1 and intraoperative aortic dissection in 1. Thirty-day mortality was 14.3%, and the cumulative survival was 71.4% at 1 year. The survival tended to be better than that in historical control group in which extracorporeal membrane oxygenation was used as a bridge to surgery (P = 0.0992). CONCLUSIONS: Impella is an effective tool for bridging patients with cardiogenic shock to surgery. This strategy may improve surgical outcomes in patients with cardiogenic shock. However, prolonged Impella support may increase significant adverse events, and further investigation is required to determine the optimal duration of support before surgery.

Predictive Biomarker for Progression Into the Sunset Glow Fundus of Vogt-Koyanagi-Harada Disease, Using Adaptive Binarization of Fundus Photographs.

Purpose: The sunset glow fundus (SGF) appearance in Vogt-Koyanagi-Harada (VKH) disease was evaluated by means of adaptive binarization of patients' fundus photographs. Methods: Twenty-nine Japanese patients with acute VKH were enrolled in this study. We evaluated one eye of each patient, and thereby divided the patients into two groups; SGF+ and SGF- at 6 months after treatment. We compared patient age, gender, and spherical equivalent refractive error (SERE) and choroidal thickness measured using optical coherence tomography. We also compared the choroidal vascular appearance index (CVAI), derived by adaptive binarization image processing of fundus photographs, between the two groups. Measurements of choroidal thickness and CVAI were taken at the onset of disease, and 1, 3, and 6 months after treatment. The sunset glow index (SGI), as previously reported, was calculated using color fundus photographs, and compared to the CVAI. Results: Eight patients (27.6%) were categorized into the SGF+ group. At all time points, the mean CVAI in the SGF+ group was significantly greater than that in the SGF- group. No significant difference was observed in choroidal thicknesses at any time point. The SGI was significantly greater in the SGF+ group at 6 months. Conclusions: CVAI could be a new predictive biomarker for the development of SGF in patients with VKH disease. Translational Relevance: Detecting SGF is important for management of patients with VKH, and CVAI may indicate the possibility of developing into SGF, although the color fundus photographs do not yet show SGF at that time.

Attempt at intracytoplasmic sperm injection of in vitro matured oocytes in common minke whales (Balaenoptera acutorostrata) captured during the Kushiro Coast Survey.

The present study was conducted during the Kushiro Coast Survey in an attempt to produce common minke whale embryos. In Experiment 1, we attempted to determine the appropriate culture duration (30 or 40 h) for in vitro maturation (IVM) of immature oocytes using the Well of the Well method. In Experiment 2, and intracytoplasmic sperm injection (ICSI) was applied to matured oocytes from prepubertal and adult common minke whales after IVM culture (40 or 48 h), and then their embryonic development was assessed. In Experiment 1, the maturation rate of oocytes cultured for 40 h (30.4%) was significantly higher than that of oocytes cultured for 30 h (6.8%; P<0.01). In Experiment 2, a total of 35 and 46 immature oocytes derived from adult (n=2) and prepubertal (n=6) minke whales, respectively, were cultured for 40 or 48 h. The maturation rate in the oocytes from the adult whales (34.2%) tended to be higher than that of the oocytes from the prepubertal whales (19.6%), but there was no significant difference. Following ICSI, 3 out of the 10 inseminated and cultured oocytes from the adult whales cleaved (2-, 8-, and 16-cell stages); all of these oocytes had been matured for 40 in culture. However, these oocytes did not develop to further stages. Only one of the 6 oocytes derived from the prepubertal whales, IVM cultured for 40 h and inseminated, developed to the 4-cell stage. The present results indicate that a 40 h IVM culture produces significantly higher rates of in vitro maturation than a 30 h IVM culture for common minke whale oocytes. Following ICSI, some oocytes cleaved to the 16-cell stage, but no further development was observed.

Changes of fructose concentrations in seminal plasma and glucose and testosterone concentrations in blood plasma in rams over the course of a year.

The present study was performed to examine seasonal changes in the fructose concentrations of seminal plasma and glucose and testosterone concentrations of blood plasma over the course of a year (from November 2004 to November 2005) using 5 Suffolk rams. Osmolality of the seminal plasma was also measured. The fructose concentrations in the seminal plasma increased as the breeding season approached, with the maximum in October (179.8 mg/dl) and the minimum in May (6.9 mg/dl), although there were no significant differences during the year. Osmolality of the seminal plasma in February (304 mOsm) was significantly (P<0.05) lower than in January (325 mOsm), July (327 mOsm), and August (325 mOsm). It was also significantly (P<0.05) lower in November (308 mOsm) than in January and August. The blood plasma glucose concentration in October (79.3 mg/dl) was significantly (P<0.05) higher than in January and February (43.2 and 43.7 mg/dl, respectively). The blood plasma testosterone (T) concentrations were significantly (P<0.05) higher in September (8.5 ng/ml) and October (10.2 ng/ml) than in other months. The fructose concentrations in the seminal plasma appeared to be related to the glucose and T concentrations in the blood plasma. These results show that fructose concentrations in the seminal plasma and blood plasma glucose and T concentrations tended to increase during the breeding season, with the highest concentrations in October.

Effects of bovine serum albumin and trehalose in semen diluents for improvement of frozen-thawed ram spermatozoa.

In this study, two following experiments were performed to improve post-thaw motility and viability of frozen-thawed ram spermatozoa. We examined i) the effects of different concentrations of bovine serum albumin (0, 0.3, 1, 5, 10 and 15% BSA) in semen diluents lacking egg yolk and ii) the effects of four semen diluents, fructose (F: control) and trehalose (T) in semen diluents containing egg yolk, 15% BSA in semen diluents without egg yolk (BSA), and modified phosphate buffered saline (m-PBS). Frozen-thawed spermatozoa were examined for progressive sperm motility, viability, morphological abnormality, sperm tail swelling test, and sperm acrosome integrity. In Experiment 1, the rates of sperm motility immediately after thawing (0 h) were significantly (P<0.05) higher in the 10 and 15% BSA groups (55.0 +/- 2.9 and 58.3 +/- 6.7%, respectively) than in the positive control (F) group (41.7 +/- 4.4%). The rate of sperm viability in the negative control (0% BSA) group (80.2 +/- 3.3%) was significantly (P<0.05) lower than in the positive control (F) group (89.8 +/- 1.5%), but when compared with the F group, no significant differences were found among the 0.3, 1, 5, 10 and 15% BSA groups at 0 h. The rates of sperm morphological abnormality of the 10 and 15% BSA groups (6.5 +/- 1.3 and 6.3 +/- 1.1%, respectively) were significantly (P<0.05) lower at 0 h than that in the 1% BSA group (16.3 +/- 5.2%). In Experiment 2, T addition improved (P<0.05) the post-thaw motility compared with the F and BSA groups. Furthermore, at 3 and 6 h, the post-thaw motility of the T group (36.3 +/- 2.4 and 25.0 +/- 2.0%, respectively) was significantly (P<0.05) higher than in the BSA (26.3 +/- 2.4 and 18.8 +/- 1.3%, respectively) and F (28.8 +/- 3.8 and 18.8 +/- 2.4%, respectively) groups. The post-thaw sperm motility and viability in the m-PBS group were significantly (P<0.05) lower than those of the control (F), T, and BSA groups throughout all observation points. These results indicate that 10 and 15% BSA can be substituted for egg-yolk for ram semen diluent and that the addition of trehalose enhances motility and viability of ram spermatozoa after freezing and thawing.