Project description:AimsIn aortic stenosis (AS), there is poor association between symptoms and conventional markers of AS severity or left ventricular (LV) systolic function. This may reflect that symptoms arise from LV diastolic dysfunction or that aortic valve area (AVA) and transvalvular gradient do not reflect afterload. We aimed to study the impact of afterload (end-systolic wall stress [ESWS]) on the presence of symptoms in AS and to test whether symptoms are related to increased ESWS or LV remodelling.Methods and resultsIn a prospective study, ESWS was estimated by measuring LV wall thickness from MRI and estimated LV end systolic pressure from echocardiographic mean gradient and systolic blood pressure in 78 patients with severe AS scheduled for aortic valve replacement and 91 patients with asymptomatic severe AS. Symptomatic patients had lower indexed AVA (0.40±0.11 vs 0.45±0.09 cm2/m2, p=0.009). They had undergone more extensive remodelling (MRI LV mass index [LVMi]: 85±24 vs 69±17 g/m2, p<0.0001), had higher tricuspid regurgitant gradient (24±8 mm Hg vs 19 ± 7 mm Hg, p=0.0001) and poorer global longitudinal strain (-15.6±3.8 vs -19.9±3.2%, p<0.0001). ESWS was higher among symptomatic patients (96±51 vs 76±25 kdynes/cm2, p=0.003). Multivariate logistic regression identified echocardiographic relative wall thickness, tricuspid gradient, mitral deceleration time, early diastolic strain rate, MRI LVMi, MRI LV end-diastolic volume index and ESWS as independently associated with being symptomatic.ConclusionESWS can be estimated from multimodality imaging combining MRI and echocardiography. It is correlated with LV remodelling and neurohormonal activation and is independently associated with symptomatic status in AS.
Project description:All humans have natural, protective antibodies directed against phosphorylcholine (PC) epitopes, a common inflammatory danger signal appearing at sites of cell injury, oxidative stress, and on bacterial capsules. In large human cohorts, low levels of anti-PC IgM were associated with a significantly increased risk of stroke or myocardial infarction. However, it is not known if these antibodies protect against the premature closure of arterial reconstructions.A prospective, observational study of patients undergoing elective, infrainguinal, autogenous vein bypasses for atherosclerotic occlusive disease of the legs was conducted. Clinical data were recorded prospectively, and preoperative levels of anti-PC IgM measured with the CVDefine kit from Athera Biotechnologies (Solna, Sweden). The principal clinical end point was the loss of primary patency (loss of graft flow, or any intervention for stenosis). Patients were followed regularly by duplex ultrasound at 1, 3, 6, 12, 18 months, and yearly thereafter.Fifty-six patients were studied, for an average of 1.3 years. Indications for surgery were claudication (33.9%), ischemic rest pain (17.9%), and ischemia with ulceration or gangrene (48.2%). Seventeen (30.4%) patients experienced loss of primary patency (10 graft occlusions, seven surgical or endovascular revisions of graft stenoses). Kaplan-Meier survival analysis showed that the quartile of patients with the lowest anti-PC IgM levels had significantly worse primary graft patency (log-rank test, P = .0085). Uni- and multivariate Cox proportional hazards analysis revealed that the preoperative anti-PC IgM level was an important predictor of graft failure. Patients with IgM values in the lowest quartile had a 3.6-fold increased risk of graft failure (95% confidence interval: 1.1-12.1), even after accounting for other significant clinical or technical factors such as indication for surgery, site of distal anastomosis, or vein graft diameter.A naturally occurring IgM antibody directed against the proinflammatory epitope PC may be protective against vein graft stenosis and failure, through anti-inflammatory mechanisms. Measurement of this antibody may be a useful prognostic indicator, although larger studies of more diverse populations will be needed to confirm these results. The biological actions of anti-PC IgM suggest it may be useful in developing immunotherapies to improve bypass longevity.
Project description:BACKGROUND:Transcatheter aortic valve implantation (TAVI) is criticized by some as an expensive treatment in super-elder patients with limited life expectancy. However, there is a knowledge gap regarding the magnitude of clinical benefit provided by TAVI in comparison with conservative management in patients with severe aortic stenosis (AS) in real clinical practice, which would be important in the decision making for TAVI. METHODS:We combined two independent registries, namely CURRENT AS and K-TAVI registries. CURRENT AS was a multicenter registry enrolling 3815 consecutive patients with severe AS irrespective to treatment modalities between January 2003 and December 2011. K-TAVI was a multicenter, prospective registry including 449 consecutive patients with severe AS, who underwent TAVI with SAPIEN XT balloon-expandable valves between October 2013 and June 2016. In these 2 registries, 449 patients received TAVI and 894 patients were managed with conservative strategy. We conducted propensity score matching and finally obtained a cohort of 556 patients (278 patients for each group) for the analysis. The primary outcome measures were all-cause death and heart failure (HF) hospitalization at 2-year. RESULTS:The cumulative 2-year incidences of all-cause death and HF hospitalization were significantly lower in the TAVI group than in the conservative group (16.8% versus 36.6%, P<0.001, and 10.7% versus 37.2%, P<0.001). After adjusting the residual confounders, TAVI reduced the risks of all-cause death (HR, 0.46; 95%CI, 0.32-0.69; P = 0.0001) and HF hospitalizations (HR, 0.25; 95%CI, 0.16-0.40; P<0.0001) compared with conservative strategy. There was no difference in the cumulative incidence of non-cardiovascular death between the 2 groups. CONCLUSIONS:TAVI in the early Japanese experience was associated with striking risk reduction for all-cause death as well as HF hospitalization as compared with the historical cohort of patients with severe AS who were managed conservatively just before introduction of TAVI in Japan.
Project description:We compared 15 severely diseased aortic valve sample to 16 control aortic valve samples using microRNA microarrays (Affymetrix GeneChip miRNA 2.0). The diseased samples were taken from areas of severe disease of aortic valves removed at aortic valve replacement for severe aortic stenosis. Control samples were obtained from macroscopically normal post-mortem aortic valves. In addition, we compared areas of mild or moderate disease on valves from participants with severe aortic stenosis to the same participant's severely diseased sample in seven participants.
Project description:We reported the RNAseq analyses of pulmonary vein tissues at the age of postnatal day 21 (P21) on SD rats with or without pulmonary vein stenosis. Pulmonary vein stenosis was induced by performing pulmonary vein banding surgery within 24 hours postnatally. RNAseq analyses of the pulmonary vein tissues was generated at P21 from 3 sham-operated rats and 3 pulmonary vein banding rats. The results revealed that there were 1124 differentially expressed genes between PAB and sham group at P7, among which 714 were upregulated and 410 were downregulated.
Project description:Diosmin is a classic venoactive drug, which has been shown to have a vascular protective effect in the inflammatory response. However, due to the limitations of experimental methods, the mechanism underlying the venous dysfunction has not been explored yet. It is necessary for us to identify the mechanism underlying whether micronized diosmin protects against venous dysfunction in iliac vein stenosis model. In this study, diosmin was administrated to mice 40 mg/kg per day by intraperitoneal injection after surgery. The characteristics of tight junctions between muscle cells around IVS-induced ligation sites have been detected. GO analysis after RNA sequencing indicated that diosmin can significantly improve the muscle system, involving actin filament organization and muscle contraction.