Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

BACKGROUND: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. AIMS: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. METHODS: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. RESULTS: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). CONCLUSIONS: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Clinical Features of 544 Patients With Ruptured Aortic Aneurysm　- A Report From the Tokyo Acute Aortic Super Network Database.

BACKGROUND: Epidemiological data on ruptured aortic aneurysms from large-scale studies are scarce. The aims of this study were to: clarify the clinical course of ruptured aortic aneurysms; identify aneurysm site-specific therapies and outcomes; and determine the clinical course of patients receiving conservative therapy.Methods and Results: Using the Tokyo Acute Aortic Super Network database, we retrospectively analyzed 544 patients (mean [±SD] age 78±10 years; 70% male) with ruptured non-dissecting aortic aneurysms (AAs) after excluding those with impending rupture. Patient characteristics, status on admission, therapeutic strategy, and outcomes were evaluated. Shock or pulselessness on admission were observed in 45% of all patients. Conservative therapy, endovascular therapy (EVT), and open surgery (OS) accounted for 32%, 23%, and 42% of cases, respectively, with corresponding mortality rates of 93%, 30%, and 29%. The overall in-hospital mortality rate was 50%. The prevalence of pulselessness was highest (48%) in the ruptured ascending AA group, and in-hospital mortality was the highest (70%) in the ruptured thoracoabdominal AA group. Multivariable logistic regression analysis indicated in-hospital mortality was positively associated with pulselessness (odds ratio [OR] 10.12; 95% confidence interval [CI] 4.09-25.07), and negatively associated with invasive therapy (EVT and OS; OR 0.11; 95% CI 0.06-0.20). CONCLUSIONS: The outcomes of ruptured AAs remain poor; emergency invasive therapy is essential to save lives, although it remains challenging to reduce the risk of death.

Catenulopyrizomicins, new anti-Hepatitis B virus compounds, from the rare actinomycete Catenuloplanes sp. MM782L-181F7.

Hepatitis B virus (HBV) causes chronic hepatitis in humans, and current antiviral therapies rarely treat viral infections. To improve the treatment efficacy, novel therapeutic agents, especially those with different mechanisms of action, need to be developed for use in combination with the current antivirals. Here, we isolated new anti-HBV compounds, named catenulopyrizomicins A-C, from the fermentation broth of rare actinomycete Catenuloplanes sp. MM782L-181F7. Structural analysis revealed that these compounds contained a structure that is composed of thiazolyl pyridine moiety. The catenulopyrizomicins reduced the amount of intracellular viral DNA in HepG2.2.15 cells with EC50 values ranging from 1.94 to 2.63 µM with small but notable selectivity. Mechanistic studies indicated that catenulopyrizomicin promotes the release of immature virion particles that fail to be enveloped through alterations in membrane permeability.

Development of a novel artificial intelligence algorithm to detect pulmonary nodules on chest radiography.

BACKGROUND: In this study, we aimed to develop a novel artificial intelligence (AI) algorithm to support pulmonary nodule detection, which will enable physicians to efficiently interpret chest radiographs for lung cancer diagnosis. METHODS: We analyzed chest X-ray images obtained from a health examination center in Fukushima and the National Institutes of Health (NIH) Chest X-ray 14 dataset. We categorized these data into two types: type A included both Fukushima and NIH datasets, and type B included only the Fukushima dataset. We also demonstrated pulmonary nodules in the form of a heatmap display on each chest radiograph and calculated the positive probability score as an index value. RESULTS: Our novel AI algorithms had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.74, a sensitivity of 0.75, and a specificity of 0.60 for the type A dataset. For the type B dataset, the respective values were 0.79, 0.72, and 0.74. The algorithms in both the type A and B datasets were superior to the accuracy of radiologists and similar to previous studies. CONCLUSIONS: The proprietary AI algorithms had a similar accuracy for interpreting chest radiographs when compared with previous studies and radiologists. Especially, we could train a high quality AI algorithm, even with our small type B data set. However, further studies are needed to improve and further validate the accuracy of our AI algorithm.

Outcomes of type A acute aortic dissection with cardiopulmonary arrest: Tokyo Acute Aortic Super-network Registry.

OBJECTIVES: Preventing loss of life in patients with type A acute aortic dissection (AAD) who present with cardiopulmonary arrest (CPA) can be extremely difficult. Thus, we investigated the early outcomes in these patients. METHODS: Patients with type A AAD who were transported to hospitals belonging to the Tokyo Acute Aortic Super-network between January 2015 and December 2019 were considered for this study. We assessed the early mortality of these patients presenting with CPA and also investigated the differences in outcomes between patients with out-of-hospital and in-hospital CPA. RESULTS: A total of 3307 patients with type A AAD were transported, 434 (13.1%) of whom presented with CPA. The overall mortality of patients presenting with CPA was 88.2% (383/434), of which 94.5% (240/254) experienced out-of-hospital CPA and 79.4% (143/180) experienced in-hospital CPA (P < 0.001). Multivariable analysis revealed that aortic surgery [odds ratio (OR), 0.022; 95% confidence interval (CI), 0.008-0.060; P < 0.001] and patient age over 80 years (OR, 2.946; 95% CI, 1.012-8.572; P = 0.047) were related with mortality in patients with type A AAD and CPA. Between in-hospital and out-of-hospital CPA, the proportions of DeBakey type 1 (OR, 2.32; 95% CI, 1.065-5.054; P = 0.034), cerebral malperfusion (OR, 0.188; 95% CI, 0.056-0.629; P = 0.007), aortic surgery (OR, 0.111; 95% CI, 0.045-0.271; P = 0.001), age (OR, 0.969; 95% CI, 0.940-0.998; P = 0.039) and the time from symptom onset to hospital admission (OR, 1.122; 95% CI, 1.025-1.228; P = 0.012) were significantly different. CONCLUSIONS: Patients with type A AAD presenting with CPA exhibited extremely high rates of death. Patient outcomes following in-hospital CPA tended to be better than those following out-of-hospital CPA; however, this difference was not significantly different. To prevent deaths, aortic surgery, when possible, should be considered in patients with type A AAD who sustained CPA.

Sex Differences in DeBakey Type I/II Acute Aortic Dissection Outcomes: The Tokyo Acute Aortic Super-network.

Background: Sex differences in the clinical presentation and outcomes of DeBakey type I/II (Stanford type A) acute aortic dissection (AAD) remain unclear. Objectives: The authors aimed to determine the impact of sex on the clinical presentation and in-hospital outcomes of surgically or medically treated patients with type I/II AAD. Methods: We studied 3,089 patients with type I/II AAD enrolled in multicenter Japanese registry between 2013 and 2018. The patients were divided into 2 treatment groups: surgical and medical. Multivariable logistic regression was used to examine the association between sex and in-hospital mortality. Results: In the entire cohort, women were older and more likely to have hyperlipidemia, previous stroke, altered consciousness, and shock/hypotension at presentation than men. Women had higher proportions of intramural hematomas and type II dissections than men. In the surgical group (n = 2,543), men had higher rates of preoperative end-organ malperfusion (P = 0.003) and in-hospital mortality (P = 0.002) than women. Multivariable analysis revealed that male sex was associated with higher in-hospital mortality after surgery (OR: 1.71; 95% CI: 1.24-2.35; P < 0.001). In the medical group (n = 546), women were older and had higher rates of cardiac tamponade (P = 0.004) and in-hospital mortality (P = 0.039) than men; no significant association between sex and in-hospital mortality was found after multivariable adjustment (OR: 0.95; 95% CI: 0.56-1.59; P = 0.832). Conclusions: Male sex was associated with higher in-hospital mortality for type I/II AAD in the surgical group but not in the medical group. Further research is needed to understand the mechanisms responsible for worse surgical outcomes in men.

In-Hospital Mortality of Patients With Acute Type A Aortic Dissection Hospitalized on Weekends Versus Weekdays.

Background: In acute aortic dissection, weekend admissions are reported to be associated with increased mortality compared with weekday admissions. Objective: This study aimed to determine whether patients with acute type A aortic dissection (ATAAD) admitted on weekends had higher in-hospital mortality than those admitted on weekdays in the Tokyo metropolitan area, where we developed a patient-transfer system for aortic dissection. Methods: Data were collected during the first year after our transfer system began (cohort I) and in the subsequent years from 2013 to 2015 (cohort II). Results: We studied 2,339 patients (500 in cohort I; 1,839 in cohort II) with ATAAD. Patients with weekend admissions had higher in-hospital mortality than those with weekday admissions in cohort I. In association with increased interfacility transfer during weekends and reduced mortality at non-high-volume centers, the in-hospital mortality in the weekend group improved from 37.2% in cohort I to 22.2% in cohort II (P < 0.001). After inverse probability weighting adjustment, weekend admission was associated with higher in-hospital mortality in cohort I (odds ratio: 2.28; 95% confidence interval: 1.48 to 3.52; P < 0.001), but not in cohort II (odds ratio: 0.96; 95% confidence interval: 0.75 to 1.22; P = 0.731). On multivariable analyses, weekend admission was associated with higher in-hospital mortality in combined cohort I+II; the associations between weekend admission and mortality were not significant in cohort II. Conclusions: We found a significant reduction in in-hospital mortality in patients with weekend admissions for ATAAD. No mortality difference between weekend and weekday admissions was observed in the later years of the study.

BioGlue cerebral embolism following acute type A aortic dissection repair.

Surgical outcomes of acute Stanford type A aortic dissection (ATAAD) have significantly improved in recent decades due to advances in surgical techniques and adhesives such as BioGlue (Cryolife, Kennesaw, GA, USA). However, this convenient material can sometimes cause complications such as thrombotic embolism and pseudoaneurysm. Herein, we present the case of a 61-year-old man with ATAAD who successfully underwent total arch replacement. Five days after surgery, he collapsed due to right-sided hemiplegia. We immediately performed cerebral thrombectomy to remove thrombotic embolism caused by BioGlue, which was used to obliterate the false lumen of the dissected aorta during ATAAD repair. Learning objective: Thanks to surgical techniques and adhesives such as BioGlue, surgical outcomes of acute Stanford type A aortic dissection have significantly improved recently. However, thromboembolic events due to adhesives such as BioGlue use can happen not only during surgery, but also a few days after it.

Aortic dissection due to primary aldosteronism in a young adult with adrenal adenoma: A case report.

Although acute type A aortic dissection is relatively rare in young adults, patients with connective tissue diseases are at a higher risk for developing this condition. To the best of our knowledge, type A aortic dissection due to endocrine diseases has been rarely reported. Here, we present a case of acute type A aortic dissection due to primary aldosteronism in a young man with adrenal adenoma. Total arch replacement was successfully performed. Postoperative imaging and endocrine evaluation revealed an adrenal adenoma. This study highlights the importance of considering primary aldosteronism as a potential etiology of acute aortic dissection in young adults. Learning objective: Generally, direct or indirect causes of acute type A aortic dissection (ATAAD) are highly diversified. We tend to suspect the familial aortic diseases such as Marfan syndrome when patients with ATAAD are young adults. By contrast, it is useful to know that endocrine diseases such as primary aldosteronism with functional adenoma can be risk factors of ATAAD in young adults.

Sex-Related Differences in Clinical Features and In-Hospital Outcomes of Type B Acute Aortic Dissection: A Registry Study.

Background The association between female sex and poor outcomes following surgery for type A acute aortic dissection has been reported; however, sex-related differences in clinical features and in-hospital outcomes of type B acute aortic dissection, including classic aortic dissection and intramural hematoma, remain to be elucidated. Methods and Results We studied 2372 patients with type B acute aortic dissection who were enrolled in the Tokyo Acute Aortic Super-Network Registry. There were fewer and older women than men (median age [interquartile range]: 76 years [66-84 years], n=695 versus 68 years [57-77 years], n=1677; P<0.001). Women presented to the aortic centers later than men. Women had a higher proportion of intramural hematoma (63.7% versus 53.7%, P<0.001), were medically managed more frequently (90.9% versus 86.3%, P=0.002), and had less end-organ malperfusion (2.4% versus 5.7%, P<0.001) and higher in-hospital mortality (5.3% versus 2.7%, P=0.002) than men. In multivariable analysis, age (per year, odds ratio [OR], 1.06 [95% CI, 1.03-1.08]; P<0.001), hyperlipidemia (OR, 2.09 [95% CI, 1.13-3.88]; P=0.019), painlessness (OR, 2.59 [95% CI, 1.14-5.89]; P=0.023), shock/hypotension (OR, 2.93 [95% CI, 1.21-7.11]; P=0.017), non-intramural hematoma (OR, 2.31 [95% CI, 1.32-4.05]; P=0.004), aortic rupture (OR, 26.6 [95% CI, 14.1-50.0]; P<0.001), and end-organ malperfusion (OR, 4.61 [95% CI, 2.11-10.1]; P<0.001) were associated with higher in-hospital mortality, but was not female sex (OR, 1.67 [95% CI, 0.96-2.91]; P=0.072). Conclusions Women affected with type B acute aortic dissection were older and had more intramural hematoma, a lower incidence of end-organ malperfusion, and higher in-hospital mortality than men. However, female sex was not associated with in-hospital mortality after multivariable adjustment.

Heart Team risk assessment with angiography-derived fractional flow reserve determining the optimal revascularization strategy in patients with multivessel disease: Trial design and rationale for the DECISION QFR randomized trial.

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography-derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR-based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD.

Acetophenone 4-nitrophenylhydrazone inhibits Hepatitis B virus replication by modulating capsid assembly.

Hepatitis B virus (HBV) is the causative agent of chronic liver disease and is correlated with the development of subsequent hepatic cirrhosis and hepatocellular carcinoma. Current antiviral therapy using nucleos(t)ide analogs is effective in suppressing viral replication and interrupting disease progression, but HBV is rarely cured completely. Thus, there remains an unmet need for the development of novel anti-HBV drugs. Here, we report the identification of N-(4-Nitrophenyl)-1-phenylethanone hydrazone (ANPH) as a novel structural class of selective inhibitors targeting the replication of the HBV genome using adenovirus vector-mediated HBV genome transduction. ANPH inhibited viral genome replication in HepG2.2.15 cells by inducing the formation of empty capsids devoid of pregenomic RNA without affecting its transcription and translation. Biochemical assays using a truncated core protein consisting of the assembly domain showed that ANPH accelerates the formation of morphologically intact capsids. Taken together, we propose that ANPH might provide a new structural scaffold to design a new anti-HBV drug in medicinal chemistry as well as chemical probes for HBV core protein functions in the future.

Emergency aortic valve replacement complicated by unmanaged pheochromocytoma.

A 53-year-old male undergoing emergency aortic valve replacement for infective endocarditis developed a hypertensive crisis early during the operation. Suspecting a pheochromocytoma, intravenous phentolamine was immediately administered, after which the procedure was completed as scheduled. Although quite rare, a pheochromocytoma can be encountered during emergency open heart surgery; thus, early recognition of abnormal blood pressure change and appropriate management are important. Here, we present details of blood pressure control mainly by use of phentolamine, in this case, to demonstrate effective management of a hypertensive crisis during emergency cardiac surgery because of a pheochromocytoma.

Giant biatrial myxoma in an atrial septal defect.

Myxomas account for a majority of the reported primary cardiac tumors that are relatively rare, and biatrial myxomas in an atrial septal defect are extremely rare. Here, we present the case of a healthy 79-year-old woman who was referred to our hospital after a giant mass in the left atrium was incidentally detected by transthoracic echocardiography. Although she was asymptomatic, we surgically resected the mass soon after admission, considering the risk of embolism. During the surgery, we observed the giant bilateral tumor in an atrial septal defect, which was, on pathological evaluation, found to be a myxoma. .

Risk analysis for early mortality in emergency acute type A aortic dissection surgery: experience of Tokyo Acute Aortic Super-network.

OBJECTIVES: We investigated the various pre- and postoperative complications related to early (30-day) mortality after open surgery for acute type A aortic dissection. METHODS: Data from the Tokyo Acute Aortic Super-network database spanning January 2015 to December 2017 were retrospectively reviewed. Pre- and postoperative factors related to early postoperative mortality were assessed in 1504 of 2058 (73.0%) consecutive patients [age: 66.6 (SD: 13.5) years, male: 52.9%] who underwent acute type A aortic dissection repair. RESULTS: The early mortality rate following surgical repair was 8.9%. According to multivariable analysis, male sex [odds ratio (OR) 1.670, 95% confidence interval (CI) 1.063-2.624, P = 0.026], use of percutaneous circulatory assist devices (n = 116, 7.7%) including extracorporeal membrane oxygenators or intra-aortic balloon pumps (OR 4.857, 95% CI 2.867-8.228, P < 0.001), shock (n = 162, 10.8%) (OR 3.06, 95% CI 1.741-5.387, P < 0.001), cardiopulmonary arrest (n = 41, 2.7%) (OR 7.534, 95% CI 3.407-16.661, P < 0.001), coronary ischaemia (n = 36, 2.3%) (OR 2.583, 95% CI 1.042-6.404, P = 0.041) and cerebral ischaemia (n = 59, 3.9%) (OR 2.904, 95% CI 1.347-6.261, P = 0.007) were independent preoperative risk factors for early mortality, while cardiac tamponade (n = 34, 2.3%) (OR 10.282, 95% CI 4.640-22.785, P < 0.001), cerebral ischaemia (n = 80, 5.3%) (OR 2.409, 95% CI 1.179-4.923, P = 0.016) and mesenteric ischaemia (n = 15, 1.0%) (OR 44.763, 95% CI 13.027-153.808, P < 0.001) were independent postoperative risk factors. CONCLUSIONS: Not only critical preoperative conditions but also postoperative cardiac tamponade and vital organ ischaemia are risk factors for early mortality after acute type A aortic dissection repair.

Infected aortic aneurysm caused by Helicobacter cinaedi: case series and systematic review of the literature.

BACKGROUND: Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi. CASE PRESENTATION: We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks. CONCLUSIONS: These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.

A Novel Technique of Endoscopic Vein Harvesting With Preserved Perivascular Tissue.

The no-touch saphenous vein harvesting technique is considered to be the ideal procedure to achieve the best quality of vein, whereas the endoscopic vein harvesting (EVH) technique is considered to be ideal for decreasing wound complications. We developed a new technique of EVH with perivascular tissue preservation. This procedure was performed by dissecting the immediate anterior and posterior perivascular connective tissues of the saphenous vein followed by cutting approximately 1 cm laterally from the saphenous vein with the use of a harvester (MAQUET Getinge Group, Getinge AB, Göteborg, Sweden). Histopathological examination revealed preserved perivascular tissue and intimal folding.