Acute Dapagliflozin Administration Ameliorates Cardiac Surgery-Associated Acute Kidney Injury in a Rabbit Model.

BACKGROUND: Several studies have shown that sodium-glucose cotransporter-2 inhibitors have a renoprotective effect on acute kidney injury (AKI), but their effect on cardiac surgery-associated AKI is unknown.Methods and Results: AKI was induced in 25 rabbits without diabetes mellitus by cardiopulmonary bypass (CPB) for 2 h and they were divided into 5 groups: sham; dapagliflozin-treated sham; CPB; dapagliflozin-treated CPB; and furosemide-treated CPB (n=5 in each group). Dapagliflozin was administered via the femoral vein before initiating CPB. Kidney tissue and urine and blood samples were collected after the surgical procedure. There were no differences in the hemodynamic variables of each group. Dapagliflozin reduced serum creatinine and blood urea nitrogen concentrations, and increased overall urine output (all P<0.05). Hematoxylin and eosin staining showed that the tubular injury score was improved after dapagliflozin administration (P<0.01). Dapagliflozin administration mitigated reactive oxygen species and kidney injury molecule-1 as assessed by immunohistochemistry (both P<0.0001). Protein expression analysis showed improvement of inflammatory cytokines and apoptosis, and antioxidant enzyme expression was elevated (all P<0.05) through activation of the nuclear factor erythroid 2-related factor 2 pathway (P<0.01) by dapagliflozin. CONCLUSIONS: Acute intravenous administration of dapagliflozin protects against CPB-induced AKI. Dapagliflozin may have direct renoprotective effects in renal tubular cells.

Use of endoscopic hand-suturing to treat refractory bleeding from a gastric ulcer in a patient with a left ventricular assist device.

We herein describe a 49-year-old man with severe heart failure due to fulminant myocarditis who underwent left ventricular assist device implantation and received clopidogrel and warfarin as antithrombotic agents. The patient developed anemia secondary to chronic bleeding gastric hyperplastic polyps, necessitating endoscopic mucosal resection. Despite attempts to manage post-endoscopic mucosal resection bleeding from a gastric ulcer by endoscopic hemostasis using hemostatic forceps, local hemostatic agents, and polyglycolic acid sheets, the bleeding persisted. Hemostasis of the refractory bleeding was finally achieved by endoscopic hand-suturing of the ulcer. One month later, the ulcer was almost completely scarred. This case has important clinical value in that it demonstrates the efficacy of endoscopic hand-suturing even in challenging cases such as refractory bleeding gastric ulcers in patients with left ventricular assist devices.

Cannula to Femoral Artery Diameter Ratio Predicts Potential Lower-Limb Ischemia in Minimally Invasive Cardiac Surgery With Femoral Cannulation.

OBJECTIVE: Lower-limb ischemia is a complication of minimally invasive cardiac surgery with femoral cannulation. Herein, we verified our strategy using distal perfusion cannulation (DPC) against this complication. METHODS: We retrospectively assessed 91 cases of aortic valve replacement with femoral cannulation between January 2019 and March 2023. DPC was applied when lower-limb tissue oxygenation index declined by ≥20%. The cannula to femoral artery diameter ratio (C/FA) was calculated by dividing the cannula size (Fr) divided by 3 by the femoral artery inner diameter (mm). Postoperative maximum creatinine kinase (CKmax), lactate dehydrogenase (LDHmax), and lactate levels were analyzed, and univariable logistic regression and receiver operating characteristic curve analyses were employed to determine DPC predictors and the cutoff C/FA for DPC, respectively. Patients without DPC were divided into 2 subgroups based on the cutoff C/FA for further comparisons. RESULTS: DPC was required in 9 patients. Symptomatic ischemia was not observed. All laboratory data were similar in the DPC and non-DPC groups. C/FA was significantly associated with DPC (odds ratio = 1.27, 95% confidence interval: 1.09 to 1.47, P = 0.002), and the cutoff C/FA was 0.70 (sensitivity = 0.89, specificity = 0.80). In the non-DPC group, CKmax (P = 0.027) and LDHmax (P = 0.041) were significantly higher in patients with C/FA ≥0.7 (n = 16) than in those with C/FA <0.7 (n = 66). CONCLUSIONS: Our strategy for preventing symptomatic ischemia is reasonable and could be almost achieved without DPC when C/FA is <0.7. C/FA also predicts asymptomatic potential ischemia, and proactive DPC is preferable when C/FA is ≥0.7.

Efficacy of Sac Coil Embolization in Endovascular Aortic Repair for Sac Shrinkage in Patients at a High Risk of Type II Endoleak from Lumbar Arteries.

BACKGROUND: In endovascular aortic repair (EVAR), preemptive embolization of sac branch vessels is effective in preventing postoperative type II endoleak (T2EL). However, this technique has not been widely adopted especially for lumbar arteries (LAs) because of technical difficulties and time constraints. This study aimed to investigate the efficacy of nonselective sac coil embolization, which is a simpler surgical method, in postoperative sac shrinkage for patients at a high risk of T2EL from LAs. METHODS: We retrospectively assessed 76 patients who underwent elective EVAR for abdominal aortic aneurysm with 4 or more patent LAs or at least 1 patent LA of ≥2 mm at our hospital between January 2014 and December 2022. The patients who underwent sac coil embolization were included in Group Ⅰ (n = 20), and the others were divided into 2 groups: those with an inferior mesenteric artery that was originally occluded or embolized by coils or stent graft bodies (Group Ⅱ, n = 21), and those without that (Group Ⅲ, n = 35). In Group Ⅰ, 0.035-inch coils were inserted into the sac after complete stent graft deployment. The cumulative incidence of sac shrinkage (≥5 mm) was compared between the groups. Further, univariable and multivariable Cox regression analyses were used to determine the predictors of sac shrinkage. RESULTS: Sac shrinkage (≥5 mm) was observed more frequently in Group Ⅰ (50%) than in Group Ⅱ (19%) and Group Ⅲ (17%) (P = 0.052 and 0.043, respectively). The cumulative incidence of sac shrinkage was significantly higher in Group Ⅰ than in Group Ⅱ (log-rank P = 0.039) and Group Ⅲ (log-rank P = 0.024). Multivariable Cox regression analyses revealed that sac embolization was a significant predictor of sac shrinkage (hazard ratio, 4.23; 95% confidence interval, 1.66-10.8; P = 0.003). CONCLUSIONS: Nonselective sac coil embolization in EVAR is potentially effective for sac shrinkage in the early postoperative phase in patients at high risk of T2EL from LAs. This simple procedure may improve prognosis after EVAR.

Prevalence of bleeding events in real-world Japanese registry for Percutaneous Ventricular Assist Device.

PURPOSE: Bleeding complication is a critical risk factor for outcomes of acute heart failure patients requiring mechanical circulatory support (MCS), including percutaneous catheter-type heart pumps (Impella). The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) is an ongoing, large-scale, real-world registry to characterize Japanese patients requiring Impella. Here we analyzed bleeding complication profiles in patients who received Impella. METHODS: All consecutive Japanese patients who received Impella from October 2017 to January 2020 were enrolled. The 30-day survival and bleeding complications were analyzed. RESULTS: A total of 1344 patients were included: 653 patients received Impella alone, 685 patients received a combination of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), and 6 patients had failed Impella delivery. Overall 30-day survival was 67.0%, with Impella alone at 81.9% and ECPELLA at 52.7%. Overall bleeding/hematoma adverse events with a relation or not-excluded relation to Impella was 6.92%. Among them, the rates of hematoma and bleeding from medical device access sites were 1.41% and 4.09%, respectively. There was no difference between etiologies for these events. CONCLUSION: This study represents the first 3-year survival and the safety profile focused on bleeding adverse events from the J-PVAD registry. The results show that the real-world frequency of bleeding adverse events for patients who received Impella was an expected range from previous reports, and future real-world studies should aim to expand this data set to improve outcomes and adverse events.

Outcomes of Veno-Arterial Extracorporeal Membrane Oxygenation With Percutaneous Left Ventricular Unloading in Fulminant Myocarditis.

Fulminant myocarditis requiring peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has a high mortality rate. We investigated clinical outcomes of combined use of VA-ECMO and percutaneous left ventricular assist device (VAD) (Impella) for fulminant myocarditis in 104 consecutive patients enrolled in the Japan Registry for Percutaneous VAD (J-pVAD) between October 2017 and January 2020. Patients were followed until hospital discharge and predictors of survival were analyzed with a Cox proportional hazards model. The median support duration of combined use of VA-ECMO and Impella (ECMO/Impella) was 6 days, and the median left ventricular ejection fraction improved from 15% to 52% during support ( p < 0.0001). Overall, 66 patients (63%) survived to discharge. Multivariate analysis revealed ECMO/Impella support at a transplant center as an independent predictor of survival ( p = 0.0231). Patients treated at transplant centers had better 60 days survival rates when compared to nontransplant centers (83% vs. 55%, p = 0.005). However, baseline characteristics and treatment strategies differed between the two groups. This real-world national registry database suggested the difference in survival after ECMO/Impella support for fulminant myocarditis between transplant and nontransplant centers, which may indicate hospital variations regarding patient management, although further controlled studies are needed.

Hypoxia stabilizes the H2 O2 -producing oxidase Nox4 in cardiomyocytes via suppressing autophagy-related lysosomal degradation.

The hydrogen peroxide (H2 O2 )-producing NADPH oxidase Nox4, forming a heterodimer with p22phox , is expressed in a variety of cells including those in the heart to mediate adaptive responses to cellular stresses such as hypoxia. Since Nox4 is constitutively active, H2 O2 production is controlled by its protein abundance. Hypoxia-induced Nox4 expression is observed in various types of cells and generally thought to be regulated at the transcriptional level. Here we show that hypoxia upregulates the Nox4 protein level and Nox4-catalyzed H2 O2 production without increasing the Nox4 mRNA in rat H9c2 cardiomyocytes. In these cells, the Nox4 protein is stabilized under hypoxic conditions in a manner dependent on the presence of p22phox . Cell treatment with the proteasome inhibitor MG132 results in a marked decrease of the Nox4 protein under both normoxic and hypoxic conditions, indicating that the proteasome pathway does not play a major role in Nox4 degradation. The decrease is partially restored by the autophagy inhibitor 3-methyladenine. Furthermore, the Nox4 protein level is upregulated by the lysosome inhibitors bafilomycin A1 and chloroquine. Thus, in cardiomyocytes, Nox4 appears to be degraded via an autophagy-related pathway, and its suppression by hypoxia likely stabilizes Nox4, leading to upregulation of Nox4-catalyzed H2 O2 production.

Open Versus Zone 0/1 Endovascular Aortic Repair for Arch Aneurysm: A Propensity Score-Matched Study from the National Clinical Database in Japan.

BACKGROUND: Although open surgical repair (OSR) is the gold standard for treating arch aneurysms, thoracic endovascular aortic repair (TEVAR) may be a less invasive alternative. However, it remains unclear which of the 2 methods yields better outcomes. In this study, we compared the perioperative outcomes of both procedures for arch aneurysms using a nationwide surgical database. METHODS: Data of patients who underwent elective aortic repair for true arch aneurysms were extracted from the National Clinical Database of Japan. Patients who underwent OSR and Zone 0/1 TEVAR were matched in a 1:1 ratio using propensity scores and their mortality and morbidity rates were compared. RESULTS: A total of 2,815 and 1,125 patients underwent OSR and Zone 0/1 TEVAR, respectively. After propensity score matching, 1,058 patients were included in both groups. Compared with OSR, Zone 0/1 TEVAR was associated with a significantly higher incidence of stroke (5.8 vs. 10.0%, P < 0.001) and paraplegia/paraparesis (1.6 vs. 4.4%, P < 0.001). However, there were no significant differences in the 30-day and operative mortality rates between the 2 groups (2.2 vs. 2.7% and 4.5 vs. 5.4%, respectively). In the Zone 0/1 TEVAR group, postoperative computed tomography was performed in 92.4% of patients, and types I and III endoleaks were identified in 6.4% and 1.1% of patients, respectively. CONCLUSIONS: Zone 0/1 TEVAR has higher incidences of stroke and paraplegia/paraparesis than OSR, with a risk of postoperative endoleaks. Resolving these problems is the key for expanding the application of Zone 0/1 TEVAR and in the meantime OSR remains the gold standard for surgically fit patients.

[Cardiovascular Surgery for Patients Under Immunosuppressive Therapy].

Immunosuppressive agents including steroids are generally given to patients with collagen disease or organ transplant recipients. Cardiovascular surgery for these patients can potentially associate with increased rate of postoperative infection or wound healing complications. Here, some key points for perioperative management in patients under immunosuppressive therapy are reviewed. Before an elective surgery, steroids need to be tapered down as much as possible, because even small amount of steroid can lead to adverse postoperative outcomes. Withholding Biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors is recommended for stable collagen disease patients. Current guidelines for perioperative management of antirheumatic medication are summarized in Table 1. Perioperative Glucocorticoid management is also required for patients exposed to steroid therapy. Intra-and postoperative steroid cover regimen is shown in Table 2. On the other hand, immunosuppressive therapy should not be discontinued for those after organ transplant and patients with severely active collagen disease. Our experience of kidney transplant recipients who underwent cardiovascular surgery is shown in Table 3. Close monitoring of blood Tacrolimus level is highly important, because it tends to fluctuate after operation and high Tacrolimus level possibly leads to deterioration in renal function. In conclusion, careful perioperative management in cooperation with transplant surgeons and rheumatologists is vital in this clinical setting.

Safety and Performance of the Micra VR Leadless Pacemaker in a Japanese Cohort　- Comparison With Global Studies.

BACKGROUND: The Micra leadless pacemaker has demonstrated favorable outcomes in global trials, but its real-world performance and safety in a Japan-specific population is unknown.Methods and Results: Micra Acute Performance (MAP) Japan enrolled 300 patients undergoing Micra VR leadless pacemaker implantation in 15 centers. The primary endpoint was the acute (30-day) major complication rate. The 30-day and 6-month major complication rates were compared to global Micra studies. All patients underwent successful implantation with an average follow-up of 7.23±2.83 months. Compared with previous Micra studies, Japanese patients were older, smaller, more frequently female, and had a higher pericardial effusion risk score. 11 acute major complications were reported in 10 patients for an acute complication rate of 3.33% (95% confidence interval: 1.61-6.04%), which was in line with global Micra trials. Pericardial effusion occurred in 4 patients (1.33%; 3 major, 1 minor). No procedure or device-related deaths occurred. Frailty significantly improved from baseline to follow-up as assessed by Japan Cardiovascular Health Study criteria. CONCLUSIONS: In a Japanese cohort, implantation of the Micra leadless pacemaker had a high success rate and low major complication rate. Despite the Japan cohort being older, smaller, and at higher risk, the safety and performance was in line with global Micra trials.

A rare case of cardiac myxoma with light bulb-like cystic morphology: a case report.

Background: Cystic myxomas are quite rare. Moreover, few reports have evaluated the causes that constituted them. Case summary: A 73-year-old Asian man presented for pre-operative examination of osteoarthritis, and transthoracic echocardiography (TTE) revealed an incidental intracardiac mass. Therefore, he was referred to our department for further evaluation. He had no specific symptoms or family history related to tumours and heart failure. The TTE showed a 32 × 24 mm spherical mass adherent to the left atrial septum. The upper part of the mass was cystic in formation and hypoechoic inside and resembled a light bulb. Transoesophageal echocardiography showed the feeding arteries flowing from the bottom into the cystic part. In addition, two jet strips drained from the cystic part in the direction of the mitral valve. Coronary angiography revealed the feeding arteries, which consisted mainly of the right coronary artery conus branch and the left circumflex branch, and the blood flowed into the saccular area from the feeding arteries and excreted towards the mitral valve. Surgical resection was performed due to the mobility, and the histopathology confirmed a cystic myxoma. Discussion: We described the unique anatomical formation of a cystic myxoma, which consisted of an exquisite balance between the tumour-feeding arteries and the draining outlet vessels.

Biventricular repair using subvalvular techniques for unbalanced atrioventricular septal defect.

We report the case of a 19-month-old girl with a right-dominant unbalanced atrioventricular septal defect and severe right-sided atrioventricular valve regurgitation who underwent biventricular repair using basal chordae resection, artificial chordae reconstruction and a left-sided atrioventricular valvuloplasty. At 14-month postoperative follow-up, the patient had minimal heart failure, gained weight and adapted to biventricular circulation.

Histological and immunohistochemical prognostic factors of primary angiosarcoma.

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5 cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

Veno-venous extracorporeal membrane oxygenation support of pulmonary insufficiency using Avalon Elite® cannula in pediatric patients.

The "Avalon Elite®" cannula is a double-lumen cannula used to establish veno-venous extracorporeal membrane oxygenation support. The reported advantages are that extracorporeal circulation can be established by cannulating through the right internal jugular vein only, and there is less re-circulation than with a two-cannula technique. It is available in a wide range of cannula sizes and can be used in a variety of patients, from children to adults. We herein report three pediatric cases in which an Avalon Elite® cannula was useful. The first was a case of acute mitral regurgitation due to idiopathic chordal rupture for postoperative severe lung injury and atelectasis due to cardiogenic pulmonary edema. The second was a case of end-stage radiation pneumonitis for safe transfer to facility of lung transplantation. The third was a convalescent case of fulminant myocarditis with severe atelectasis due to cardiogenic pulmonary edema. In each case, veno-venous extracorporeal membrane oxygenation using an Avalon Elite® cannula was established, the expected sufficient support was secured, and a good clinical course was obtained without major complications associated with an Avalon Elite® cannula.

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.