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Background The optimal surgical timing for asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction remains controversial. Methods and Results Two hundred ten consecutive patients (median age 65 years) with asymptomatic or equivocally symptomatic chronic severe aortic regurgitation and left ventricular ejection fraction ≥50% were registered. First, the treatment plans (aortic valve replacement or watchful waiting) after initial diagnosis were investigated. Then, 2 studies were set: Study A (n=144) investigated the prognosis of patients who were managed under the watchful waiting strategy after initial diagnosis; Study B (n=99) investigated the postoperative prognosis in patients who underwent aortic valve replacement at initial diagnosis or after watchful waiting. The primary outcomes were all‐cause death in Study A and postoperative cardiovascular events in Study B. In Study A, 3 died of noncardiovascular causes during a median follow‐up of 3.2 years. In Kaplan–Meier analysis, the survival curve was similar to that of an age‐sex‐matched general population in Japan. In Study B, 9 experienced the primary outcome during a median follow‐up of 5.0 years. In Cox regression analysis, preoperative left ventricular end‐systolic diameter enlargement (hazard ratio, 1.11; P=0.048) and left ventricular end‐systolic diameter >45 mm (hazard ratio, 12.75; P=0.02) were significantly associated with poor postoperative prognosis. In Kaplan–Meier analysis, left ventricular end‐systolic diameter >45 mm predicted a higher risk of the primary outcome (P 45 mm predicted a poor postoperative outcome and may be an optimal cut‐off value for surgical indication.

Abstract Background Transcatheter aortic valve replacement (TAVR) has become widely used in recent years, However, there is also an increasing need for removal of TAVR valves due to prosthetic valve dysfunction (PVD) and the development of infective endocarditis. Surgical aortic valve replacement (AVR) for these patients is risky due to the original patient background and anatomic conditions. Intuity rapid deployment aortic valve (Edwards Lifesciences, Irvine, CA) replacement would be useful for such high risk patients to prevent longer cardiac arrest time and obtain good hemodynamic results. However, there are few reports which present Intuity valve replacement after TAVR explantation. Herein, We report two cases in which we have achieved good hemodynamics with shorter cardiac arrest times by using a rapid deployment valve after TAVR explantation. Case presentation We present 2 cases of successful implantation of the Intuity rapid deployment valve after TAVR explantation. The 84- and 88-year-old female patients had previously received TAVR for severe aortic stenosis with SAPIEN XT (Edwards Lifesciences, Irvine, CA) and developed PVD during follow-up. The TAVR valve was removed carefully, then an Intuity valve was implanted with cardiac arrest times of 69 and 41 min. Both patients had good echocardiographic results with effective orifice area of 2.0 cm2 and 1.2 cm2 and mean trans-aortic plessure gradient of 9 mmHg and 15 mmHg respectively without aortic regurgitation. They were discharged without major complications. Conclusions Surgical AVR using a rapid deployment valve is a useful alternative to sutured AVR after TAVR valve explantation. It allows for shorter cardiac arrest times and better postoperative hemodynamics without major complication.

Abstract Aims Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. Methods and results Fibrosis extent in 70 RV‐EMB specimens of DCM diagnosis was compared with that in the whole cross‐sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13–19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance–late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV‐EMB correlated significantly with that in the short‐axis cut of the LV of excised hearts (r = 0.82, P

Background: This study elucidated the clinical outcomes and serial allograft function of heart transplant (HTx) recipients who received hearts from super-aged donors (SAD) ≥65 years of age. Methods: Adult HTx recipients between 1999 and 2022 were retrospectively reviewed and divided into 2: donor age ≥65 years [SAD group (n = 12)] and donor age

Abstract Background Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. Case presentation This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m− 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. Conclusions In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management.

Objectives: Developments in both technique and technology have enabled surgeons to perform the maze procedure via right minithoracotomy (RMT) to treat atrial fibrillation (AF). This study aimed to clarify the outcomes of the modified cryomaze procedure via the RMT approach compared with the sternotomy approach. Methods: The study cohort comprised 803 consecutive patients who underwent a modified cryomaze procedure (130 via RMT and 673 via sternotomy) for paroxysmal AF and persistent AF from January 2001 to March 2022. The Gray test was applied to compare the incidence of recurrent atrial tachyarrhythmias. Additionally, residual electrical gaps were investigated in the patients who underwent additional catheter ablation for recurrent atrial tachyarrhythmias. Results: The respective 1-, 2-, and 3-year cumulative incidences of recurrent atrial tachyarrhythmias were 13.1%, 19.5%, and 23.1% in the RMT group, and 9.3%, 10.9%, and 12.8% in the sternotomy group (Gray test P = .036). All 31 patients with recurrent atrial tachyarrhythmias underwent additional catheter ablation, comprising 14 (10.8%) in the RMT group and 17 (2.5%) in the sternotomy group. There was a significant intergroup difference in the site of residual electrical gaps; the RMT group more frequently had residual gaps in the tricuspid annulus than the sternotomy group (6.2% vs 0.4%; P

Abstract Background Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. Case presentation We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. Conclusions While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures.

Background and Aims: Assisted reproductive technology (ART), especially frozen–thawed embryo transfer (FET) in a hormone replacement cycle (HRC) is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies conceived after FET in an HRC. Method: We performed a case–control study in two tertiary perinatal centers in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centers between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed in patients 1) with histopathological findings of placenta increta/percreta, 2) those requiring manual evacuation of the placenta after delivery, or 3) those with retained placental tissue. Among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case–control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of cesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos and endometrial thickness at the initiation of progestin administration. Results: PAS was associated with [Formula: see text]2 previous uterine surgeries (adjusted odds ratio [OR], 3.57; 95% confidence interval [CI], 1.60–7.97) and the number of blastocysts transferred (adjusted OR, 2.89; 95% CI, 1.15–7.26). In patients with

Background This study assessed risk factors for mitral regurgitation (MR) recurrence or functional mitral stenosis during long‐term follow‐up in patients undergoing mitral valve repair for isolated posterior mitral leaflet prolapse. Methods and Results We assessed a consecutive series of 511 patients who underwent primary mitral valve repair for isolated posterior leaflet prolapse between 2001 and 2021. Annuloplasty using a partial band was selected in 86.3%. The leaflet resection technique was used in 83.0%, whereas the chordal replacement without resection was used in 14.5%. Risk factors were analyzed for MR recurrence ≥grade 2 or functional mitral stenosis with mean transmitral pressure gradient ≥5 mm Hg using a multivariable Fine–Gray regression model. The 1‐, 5‐, and 10‐year cumulative incidence of MR ≥grade 2 was 7.8%, 22.7%, and 30.1%, respectively, whereas that of mean transmitral pressure gradient ≥5 mm Hg was 8.1%, 20.6%, and 29.3%, respectively. Risk factors for MR ≥grade 2 included chordal replacement without resection (hazard ratio [HR], 2.50, P

Abstract Aims The outcomes of patients with hypertrophic cardiomyopathy with left ventricular systolic dysfunction (HCM‐LVSD) undergoing left ventricular assist device (LVAD) implantation remain unclear. We retrospectively evaluated the clinical impact of LVAD implantation on clinical outcomes, including haemodynamics and brain natriuretic peptide (BNP) levels, in patients with HCM‐LVSD, in comparison with those with dilated cardiomyopathy (DCM). Methods and results In this retrospective, single‐centre, observational study conducted in Japan, the medical records of patients who underwent LVAD implantation in the National Cerebral and Cardiovascular Center between 2011 and 2020 were reviewed. We enrolled 96 patients with DCM (average age: 43.5 years; 73 men) and 24 patients with HCM‐LVSD (average age: 48.3 years; 16 men). The HCM‐LVSD group had smaller left ventricles with thicker ventricular walls than the DCM group, which became more prominent after LVAD implantation. Preoperatively, BNP values were comparable between both groups; however, 3 months post‐implantation, they were significantly higher in the HCM‐LVSD group. Pulmonary artery pulsatility index, right ventricular stroke work index, and cardiac index were lower, and right atrial pressure was higher, in the HCM‐LVSD group, suggesting subclinical impairment of right ventricular function. The HCM‐LVSD group demonstrated equivalent outcomes, including overall survival, cerebrovascular accidents, right ventricular failure, LVAD‐related infections, arrhythmia, and aortic insufficiency, post‐implantation. Conclusions Despite a decreased right ventricular function with higher BNP values, patients with HCM‐LVSD and DCM showed comparable outcomes post‐LVAD implantation.

Abstract Aims Percutaneous veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) is utilized for patients with cardiogenic shock or cardiac arrest. However, the procedure protocol for weaning from VA‐ECMO has not been well established. The present study aimed to determine the usefulness of echocardiographic and pulmonary artery catheter parameters for predicting successful weaning from VA‐ECMO in patients with refractory cardiogenic shock. Methods and results We retrospectively studied 50 patients who were hospitalized and supported by VA‐ECMO for >48 h between January 2013 and March 2017. Patients successfully weaned from VA‐ECMO without reintroduction of VA‐ECMO or left ventricular assist device implantation were defined as 30 day survivors. Echocardiographic and pulmonary artery catheter parameters were evaluated when ECMO flow was limited to a maximum of 1.5–2.0 L/min. Twenty‐four patients were successfully weaned from VA‐ECMO, whereas 26 were not. Fractional shortening, corrected left ventricular ejection time (LVETc, defined as LVET divided by the square root of heart rate), left ventricular outflow tract velocity time integral, and LVETc divided by pulmonary artery wedge pressure (PAWP) were significantly larger in the 30 day survivor groups. Multivariable analysis revealed LVETc∕PAWP as a significant independent predictor of successful weaning (LVETc∕PAWP, odds ratio 0.82, 95% confidence interval 0.71–0.94, P = 0.005). Receiver operating characteristic curve analysis revealed 15.9 as the optimal LVETc∕PAWP for predicting successful weaning (area under the curve 0.82). Conclusions The present findings indicate that LVETc∕PAWP is a potential predictor of successful weaning from VA‐ECMO.

We describe an extracardiac mass in a 72-year-old man with a history of pericardiectomy for constrictive pericarditis. Imaging studies revealed that progressive shrinkage of the residual pericardium compressed mitral valve anteriority, and fat replacement of the secondarily enlarged posterior space of the atrioventricular groove appeared as a space-occupying lesion. (Level of Difficulty: Intermediate.)

This report describes a successful transcatheter aortic valve replacement in an older patient with severe aortic stenosis, mitral paravalvular leak, and associated hemolytic anemia. Transcatheter aortic valve replacement is worth considering as a first-line procedure in this high-risk patient because of its beneficial impact on reducing shear forces at the mitral valve. (Level of Difficulty: Intermediate.)

Abstract Background Delirium after cardiac surgery affects mortality, but the mechanism remains unclear. Previous studies have reported gut microbiota are associated with brain activity. Systemic inflammation and antibiotics can damage the gut microbiota after cardiac surgery. We aimed to investigate changes in the gut microbiota and the association between the gut microbiota and delirium after cardiac surgery. Methods Twenty-one patients who underwent cardiac surgery were enrolled. Microbiota counts and fecal organic acid concentrations were measured in fecal samples harvested before surgery, just after surgery, and before discharge. To quantify the microbiota, we extracted total RNA fractions and examined gut microbiota composition using 16S and 23S rRNA-targeted quantitative-reverse Transcription-PCR. Postoperative delirium, insomnia, and pseudopsia were assessed for 1 week. Postoperative total bacterial counts changed significantly from 10.2 ± 0.2 log10 cells/g of feces to 9.8 ± 0.5 in the first postoperative samples (p = 0.003) and 10.0 ± 0.4 in the samples before discharge (p = 0.039). Fecal pH was 6.9 ± 0.6 before surgery and 7.4 ± 0.7 in the first postoperative samples (p = 0.001). Postoperative Staphylococcus and Pseudomonas counts were significantly higher in patients with postoperative pseudopsia than in patients without pseudopsia (3.2 ± 1.3 vs. 5.4 ± 0.9; p = 0.012 and 1.7 ± 0.8 vs. 4.6 ± 2.7; p = 0.001). Conclusions Total bacterial counts were significantly lower after surgery and until discharge. Fecal pH was significantly higher than preoperative levels. Staphylococcus and Pseudomonas counts were significantly higher in patients with postoperative pseudopsia.

Abstract Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p

Abstract Surgical treatment is an effective therapy and the gold standard for patients with left ventricular outflow tract obstruction (LVOTO) and drug‐refractory symptoms. However, it is difficult to arrange a concrete surgical plan due to the heterogenous and complex cardiac anatomy. Three‐dimensional (3D) printing is an emerging technology that is able to reproduce complex cardiac anatomy. Here, we present two patients with LVOTO in whom we created 3D printed models. In these two patients, we compared the 3D printed model and the intraoperative findings and confirmed that the 3D printed model we created could reproduce the complex cardiac anatomy including the interventricular septum, papillary muscles, and abnormally thickened chordae. By using 3D printed models, cardiologists and surgeons can comprehend the complex 3D cardiac structure and spatial positional relationship preoperatively and perform surgical rehearsal. 3D printing could be a valuable tool for the management of patients with LVOTO.

Objective Although there are regional reports that the COVID-19 pandemic is associated with a reduction in acute myocardial infarction presentations and primary percutaneous coronary intervention (PCI) procedures, little is known about the impact of the COVID-19 pandemic on mechanical complications resulting from ST-segment elevation myocardial infarction (STEMI) and mortality.Methods This single-centre retrospective cohort study analysed presentations, incidence of mechanical complications, and mortality in patients with STEMI before and after a state of emergency was declared due to the COVID-19 pandemic by the Japanese government on 7 April 2020.Results We analysed 359 patients with STEMI hospitalised before the declaration and 63 patients hospitalised after the declaration. The proportion of patients with late presentation was significantly higher after the declaration than before (25.4% vs 14.2%, p=0.03). The incidence of late presentation was significantly higher during the COVID-19 pandemic than before (incidence rate ratio (IRR), 2.41; 95% CI, 1.37 to 4.05; p=0.001, even after adjusting for month (IRR, 2.61; 95% CI, 1.33 to 5.13; p

Objective Atrial functional mitral regurgitation (A-FMR) has been suggested as a new aetiology of functional MR (MR); however, its prognosis and prognostic predictors are not fully elucidated. Aim of this study was to investigate the prognosis and prognostic predictors of A-FMR in comparison with ventricular functional MR (V-FMR).Methods Three hundred and seventy-eight consecutive patients with moderate-to-severe or severe functional MR were studied. Functional MR was classified into V-FMR (N=288) and A-FMR (N=90) depending on the alterations of left ventricle (LV) or left atrium (LA) along with clinical context and diagnosis of ischaemic heart disease or cardiomyopathy.Results During a median follow-up of 4.1 (2.0–6.7) years, all-cause mortality, cardiovascular mortality and heart failure (HF) hospitalisation occurred in 98 (26%), 81 (21%) and 177 (47%) patients, respectively, and rates of these events and the composite end point of all-cause mortality and HF hospitalisation were consistently higher in V-FMR than A-FMR (unadjusted HR 1.762 (95% CI 1.250 to 2.438), p

Aims/Introduction: Chronic kidney disease (CKD)-mineral and bone disorders (CKD-MBD) are an adverse outcome derived from decreases in kidney function, where abnormality of serum concentrations of calcium (Ca), phosphorus, parathyroid hormone (PTH), and vitamin D can be seen simultaneously. To identify individuals at risk for CKD-MBD or secondary hyperparathyroidism, the relationships between estimated glomerular filtration rate (eGFR) and serum PTH concentration were evaluated, allowing for confounding factors, in particular vitamin D status, in a general Japanese population.Materials and Methods: Nine-hundred-and-thirty participants in the population-based Iwaki study conducted in 2016 who were not on drugs affecting mineral metabolism nor hemodialysis, were included in the study (326 men and 604 women; age: 55.4 ± 15.9 years).Results: Regression analysis showed a significant correlation between eGFR and serum intact PTH concentration, after adjustment for possible confounding factors (β = −0.122, p < 0.001). The smoothed spline curve applied for the correlation analysis revealed a biphasic correlation, with a division at an eGFR of ~60 mL/min/1.73 m2, below which the correlation coefficient was higher (β = −0.405, p < 0.001). Stratification on the basis of vitamin D status showed that the correlation was present only in participants with vitamin D deficiency (25-dihydroxyvitamin D3:

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.

Inhibition of fructose absorption may suppress adiposity and adiposity-related diseases caused by fructose ingestion. Eucalyptus leaf extract (ELE) inhibits intestinal fructose absorption (but not glucose absorption); however, its active compound has not yet been identified. Therefore, we evaluated the inhibitory activity of ELE obtained from Eucalyptus globulus using an intestinal fructose permeation assay with the human intestinal epithelial cell line Caco-2. The luminal sides of a cell monolayer model cultured on membrane filters were exposed to fructose with or without the ELE. Cellular fructose permeation was evaluated by measuring the fructose concentration in the medium on the basolateral side. ELE inhibited 65% of fructose absorption at a final concentration of 1 mg/mL. Oenothein B isolated from the ELE strongly inhibited fructose absorption; the inhibition rate was 63% at a final concentration of 5 μg/mL. Oenothein B did not affect glucose absorption. In contrast, the other major constituents (i.e., gallic acid and ellagic acid) showed little fructose-inhibitory activity. To our knowledge, this is the first report that oenothein B in ELE strongly inhibits fructose absorption in vitro. ELE containing oenothein B can prevent and ameliorate obesity and other diseases caused by dietary fructose consumption.

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p

Many epidemiological studies have suggested that the recent increase in prevalence and severity of allergic diseases such as asthma is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination. However, the underlying mechanisms by which mycobacterial components suppress allergic diseases are not yet fully understood. Here we showed the inhibitory mechanisms for development of allergic airway inflammation by using highly purified recombinant Ag85B (rAg85B), which is one of the major protein antigens secreted from M. tuberculosis. Ag85B is thought to be a single immunogenic protein that can elicit a strong Th1-type immune response in hosts infected with mycobacteria, including individuals vaccinated with BCG. Administration of rAg85B showed a strong inhibitory effect on the development of allergic airway inflammation with induction of Th1-response and IL-17and IL-22 production. Both cytokines induced by rAg85B were involved in the induction of Th17-related cytokine-production innate immune cells in the lung. Administration of neutralizing antibodies to IL-17 or IL-22 in rAg85B-treated mice revealed that IL-17 induced the infiltration of neutrophils in BAL fluid and that allergen-induced bronchial eosinophilia was inhibited by IL-22. Furthermore, enhancement of the expression of genes associated with tissue homeostasis and wound healing was observed in bronchial tissues after rAg85B administration in a Th17-related cytokine dependent manner. The results of this study provide evidence for the potential usefulness of rAg85B as a novel approach for anti-allergic effect and tissue repair other than the role as a conventional TB vaccine.