Increased Complement Factor B and Bb Levels Are Associated with Mortality in Patients with Severe Aortic Stenosis.

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.

Determinants and Outcome of Decision Making Among Patients with Severe Aortic Stenosis.

BACKGROUND AND AIM OF THE STUDY: 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. METHODS: A prospective observational study of consenting patients aged >18 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. RESULTS: 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 (p <0.001). 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; p <0.001), but not among patients with diabetes. CONCLUSIONS: Supplemental and better parameters to improve patient selection are warranted. Surgical AVR shows a greater prognostic effect in patients without diabetes.

Validity of standard gamble utilities in patients referred for aortic valve replacement.

PURPOSE: Standard gamble (SG) is the preferred method of assessing preferences in situations with uncertainty and risk, which makes it relevant to patients considered for aortic valve replacement (AVR). The present study assesses SG preferences in patients with severe aortic stenosis (AS). METHODS: All patients >18 years old with severe AS referred for AVR to our institution were invited to enroll in the study. The SG was administered by a clinical research nurse. The SF-36, EQ-5D 3L, Hospital Anxiety and Depression Scale (HADS), and AS symptoms were administered by self-completed questionnaire. We hypothesized that SG utilities would have low-to-moderate correlations with physical and mental aspects of health based on our pathophysiological understanding of severe AS. No correlations were expected with echocardiographic measures of the aortic valve. RESULTS: The response rate for SG was 98 %. SG moderately correlated with physical aspects of SF-36 (PCS, role-physical, vitality), health transition, AS symptoms, and EQ-VAS (ρ S = 0.31-0.39, p < 0.001) and had low correlation with mental aspects of SF-36 and EQ-5D (ρ S = 0.17-0.28, p < 0.001). No correlation was found between SG and HADS, echocardiographic measures, age, gender, or education level (ρ S = 0.01-0.06). CONCLUSIONS: SG is an acceptable and feasible method of assessing preferences in patients with severe AS that has evidence for validity. The inclusion of uncertainty lends the SG face validity in this population as a direct approach to assessing preferences and basis for QALY calculations.

Patient-reported outcomes after referral for possible valve replacement in patients with severe aortic stenosis.

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).

Age-dependent morbidity and mortality outcomes after surgical aortic valve replacement.

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 <70 years, 70-79 years and ≥80 years, respectively. Patients aged 70-79 years and ≥80 years had a hazard ratio of 1.88 [95% confidence interval (95% CI) 0.92-3.83, P = 0.08] and 2.90 [95% CI 1.42-5.92, P = 0.003] for mortality, respectively, when compared with patients aged <70 years. The length of stay and rehospitalization rate during the following year were similar between the groups. Patients ≥80 years of age experienced more delirium and infections, whereas the risks of new pacemaker, transient ischaemic attack (TIA) or stroke, myocardial infarction and heart failure were comparable between the age groups. All groups exhibited reduced New York Heart Association class, improved physical quality of life and unchanged mental scores without any clinically significant Mini Mental Status reduction. CONCLUSIONS: Elderly patients (≥80 years of age) have important gains in health measures and satisfactory 5-year survival with an acceptable complications rate during the year following surgery. Active respiratory mobilization and the removal of an indwelling urethra catheter can prevent adverse effects, and measures should be taken to prevent delirium and confusion in elderly patients. Clinical trial registration: clinicaltrials.gov (NCT 01794832).

Eliciting Patient Risk Willingness in Clinical Consultations as a Means of Improving Decision-Making of Aortic Valve Replacement.

BACKGROUND: Treatment decisions for aortic valve replacement (AVR) should be sensitive to patient preferences. However, we lack knowledge of patient preferences and how to obtain them. METHODS AND RESULTS: We assessed the mortality risk patients were willing to accept when undergoing AVR by using the Standard Gamble method and aimed to show how this risk willingness was affected by level of disease burden. We report findings from 439 patients, aged >18 years with severe aortic stenosis who were referred for evaluation of AVR to our institution. The vast majority of patients accepted a mortality risk regarded as high or prohibitive according to current guidelines. Of the 439 patients, 51% patients were willing to forego surgery with high mortality risk (8-50%) and 19% were willing accept a prohibitive mortality risk (>50%) as defined in current guidelines. However, the risk willingness varied considerably. Acceptance of prohibitive risk willingness (>50%) was associated with reporting of 3 to 5 different restricting symptoms, with an odds ratio of 4.07 (95% CI 1.56-10.59) opposed by increasing score on EuroQol-Visual Analog Scale, with an odds ratio of 0.99 (95% CI 0.97-1.00). The poor ability to predict risk willingness based on available clinical variables and health status suggests that other factors may be important advocating the need for tools for soliciting patient's preferences individually. CONCLUSION: When undergoing AVR, patients were willing to accept considerably higher perioperative risk than what is considered acceptable in current guidelines and practice. Patient preferences varied considerably, and they should be directly assessed and taken into account in decision-making and guidelines. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/. Unique identifier: NCT01794832.