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Inflammation is involved in initiation and progression of aortic stenosis (AS). However, the role of the complement system, a crucial component of innate immunity in AS, is unclear. We hypothesized that circulating levels of complement factor B (FB), an important component of the alternative pathway, are upregulated and could predict outcome in patients with severe symptomatic AS. Therefore, plasma levels of FB, Bb, and terminal complement complex were analyzed in three cohorts of patients with severe symptomatic AS and mild-to-moderate or severe asymptomatic AS (population 1, n = 123; population 2, n = 436; population 3, n = 61) and in healthy controls by enzyme immunoassays. Compared with controls, symptomatic AS patients had significantly elevated levels of FB (2.9- and 2.8-fold increase in population 1 and 2, respectively). FB levels in symptomatic and asymptomatic AS patients were comparable (population 2 and 3), and in asymptomatic patients FB correlated inversely with valve area. FB levels in population 1 and 2 correlated with terminal complement complex levels and measures of systemic inflammation (i.e., CRP), cardiac function (i.e., NT-proBNP), and cardiac necrosis (i.e., Troponin T). High FB levels were significantly associated with mortality also after adjusting for clinical and biochemical covariates (hazard ratio 1.37; p = 0.028, population 2). Plasma levels of the Bb fragment showed a similar pattern in relation to mortality. We concluded that elevated levels of FB and Bb are associated with adverse outcome in patients with symptomatic AS. Increased levels of FB in asymptomatic patients suggest the involvement of FB from the early phase of the disease.

Background: Identification of novel biomarkers could provide prognostic information and improve risk stratification in patients with aortic stenosis (AS). YKL-40 (chitinase-3-like protein 1), a protein involved in atherogenesis, is upregulated in human calcific aortic valves. We hypothesized that circulating YKL-40 would be elevated and associated with the degree of AS severity and outcome in patients with symptomatic AS. Methods: Plasma YKL-40 was analyzed in 2 AS populations, one severe AS (n=572) with outcome measures and one with mixed severity (n=67). YKL-40 expression in calcified valves and in an experimental pressure overload model was assessed. Results: We found (1) patients with AS had upregulated circulating YKL-40 compared with healthy controls (median 109 versus 34 ng/mL, P P Conclusions: YKL-40 levels were elevated in AS and associated with mortality but not with other metrics of disease severity including the degree of AS severity. Despite scientific rationale for its role in AS, the clinical utility of circulating YKL-40 as a biomarker is limited. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01794832.

Objectives Health-related quality of life (HRQoL) is an important outcome after surgical aortic valve replacement (SAVR). To improve interpretation of HRQoL, mean score change and change in terms of minimal important difference (MID) were assessed using validated instruments for measuring patient-reported outcomes in patients with severe aortic stenosis referred for possible SAVR. Methods Of the 442 included patients with severe aortic stenosis evaluated for possible SAVR, 351 were referred to SAVR (operated) and 91 to medical treatment (unoperated). At presurgical evaluation and 1 year postoperatively, HRQoL was assessed using SF-36v2 and EQ-5D. Results were compared with outcomes reported in unoperated patients. We explored the association of clinical factors and improvements corresponding to MID. Results Among the operated patients, statistically significant change was found for EQ-5D scores and SF-36 scale scores for physical functioning, role-physical, bodily pain, general health, vitality and physical summary score. The largest proportion of operated patients achieving change corresponding to at least MID was 61.5% for physical summary score. Change in unoperated patients also related largely to physical scales of the SF-36. However, smaller proportions of unoperated patients reported improvements, and larger proportions reported decline reaching MID. Baseline scores, but no clinical covariates, were consistently associated with improved HRQoL reaching MID across instruments for those referred to SAVR. Conclusions This study found improvement in HRQoL 1 year after SAVR for patients with severe aortic stenosis. Results in unoperated patients suggest that HRQoL deteriorates 1 year after evaluation of possible SAVR. Clinical trial registration www.clinicaltrials.gov (NCT01794832).

ObjectiveThe aim of this study was to evaluate the prevalence and prognostic implication of iron deficiency (ID) and anaemia in patients with severe aortic stenosis (AS).MethodsIn an observational study of consecutive patients referred for aortic valve replacement (AVR), we assessed a wide range of biomarkers of iron status, including the definition of ID commonly applied in patients with chronic heart failure (ferritin Results464 patients were included in this substudy. 91 patients (20%) received conservative treatment and 373 patients (80%) received AVR. ID was detected in 246 patients (53%). 94 patients (20%) had anaemia. Patients with ID had an overall worse clinical profile than patients without ID. During follow-up, 129 patients (28%) died. Neither ID as defined above, soluble transferrin receptor nor hepcidin were associated with short-term or long-term mortality or MACE independent on treatment allocation. Anaemia was associated with one-year mortality in conservatively treated patients.ConclusionsID and anaemia are prevalent in patients with severe AS. In our cohort, ID did not provide independent prognostic information on top of conventional risk factors. More studies are required to determine how to correctly diagnose ID in patients with AS.Trial registration numberNCT01794832.

Aortic valve replacement (AVR) improves survival and quality of life in patients with severe aortic stenosis (AS), but despite clear indications for surgical treatment a significant proportion of patients do not undergo AVR. The study aim was to identify clinical variables associated with the decision to perform AVR, and to assess the prognostic effect of surgery versus medical treatment in patients with severe AS adjusted for significant confounders and effect modifiers.A prospective observational study of consenting patients aged18 years who were under consideration for AVR at the authors' tertiary teaching hospital was conducted. The main outcomes of the study were treatment decisions and survival.Among 480 patients with severe AS who were evaluated, 351 had surgical AVR, 38 had transcatheter AVR, and 91 were declined operative treatment. Typically, non-operated patients were older, were in a lower NYHA class, had fewer symptoms, a lower peak aortic jet velocity, a higher NT-proBNP level, and a lower physical summary score (SF-36). Higher age showed the strongest correlation against AVR (OR 0.91; 95% CI 0.87-0.94). One-, three-, and five-year cumulative survival rates, respectively, were 95%, 87%, and 73% among operated patients, and 82%, 47%, and 27% among non-operated patients. The median survival time was 1,604 days (95% CI 1,554-1,655) in operated patients versus 1,090 days (95% CI 954-1,226) in non-operated patients (p0.001). The effect of operation on mortality was shown to depend on the interaction with diabetes, when adjusted for significant confounders (i.e., age, atrial fibrillation, NT-proBNP, hs-Troponin T, and NYHA class). An effect of AVR on mortality was found in patients without diabetes (HR 0.29; 95% CI 0.19-0.468; p0.001), but not among patients with diabetes.Supplemental and better parameters to improve patient selection are warranted. Surgical AVR shows a greater prognostic effect in patients without diabetes.

OBJECTIVES This study addressed the assumption of increased morbidity and mortality after surgical aortic valve replacement in patients older than 80 years with severe aortic stenosis. METHODS This prospective study was performed in consecutive patients referred for aortic valve replacement. The age-dependent change in cognitive and physical function, quality of life and rehospitalization and complication rates during the following year and 5-year all-cause mortality were documented. RESULTS A total of 351 patients underwent surgical aortic valve replacement. The death risk at 5 years was 10%, 20% and 34% in patients aged

Introduction: Symptoms and echocardiographic assessment of the heart and the aortic valve are key factors in the pre-operative decision-making process in patients with severe aortic stenosis (AS). Improved survival and HRQoL are primary goals after surgical aortic valve replacement (SAVR). In this study, we report changes in HRQoL one year after SAVR and study the association between symptoms, echocardiographic measures, and change in HRQoL. Methods: In a prospective cohort study of 480 patients with severe AS, 327 patients have been to follow-up at one year, and of these 276 patients have had SAVR. Mean age was 74 years, and 40 % (111) were female. HRQoL was measured using Short-Form 36 (SF-36). Response rate was > 90%. Patients` answers on type (fatigue, dyspnea, chest pain or dizziness) - and frequency (last week) of cardinal AS-symptoms were used to create three patient groups based on estimated total symptom load. We used valve area, mean pressure gradient, cardiac output, ejection fraction, and estimated systolic pulmonary artery pressure as echocardiographic measures of heart function and AS characteristics. Results: Mean valve area was 0.7 cm2, mean pressure gradient was 53 mmHg, mean maximum valve velocity 4.5 m/s, mean estimated systolic pulmonary artery pressure 36 mmHg, cardiac output 5,2 m/s, and 89 % had normal ejection fraction. There was a statistically significant improvement in HRQoL one year after SAVR in six of the eight SF-36 scales. Physical Functioning: (mean pre-operative - mean post-operative score) 61 - 72 p < 0.001, Role-physical Functioning: 52 - 62 p < 0.001, Bodily Pain: 65 - 74 p < 0.001, General Health: 58 - 71 p < 0.001, Vitality: 48 - 56 p < 0.001, Social Functioning: 78 - 81 p = 0.2, Role-emotional Functioning: 77 - 80 p = 0.2, Mental Health: 77 - 80 p = 0.02. There was no association between the echocardiographic parameters and change in HRQoL. Conclusions: There was a substantial gain in HRQoL after SAVR. Despite their importance in the pre-operative assessment, echocardiographic measures did not predict change in HRQoL. After SAVR, patients with more symptoms experience the greatest yield in HRQoL, and amount of AS-symptoms is a strong predictor of intermediate HRQoL.