Exposure to noise and ototoxic chemicals in the Australian workforce.

OBJECTIVE: To determine the current prevalence of exposure to workplace noise and ototoxic chemicals, including co-exposures. METHOD: A cross-sectional telephone survey of nearly 5000 Australian workers was conducted using the web-based application, OccIDEAS. Participants were asked about workplace tasks they performed and predefined algorithms automatically assessed worker's likelihood of exposure to 10 known ototoxic chemicals as well as estimated their full shift noise exposure level (LAeq,8h) of their most recent working day. Results were extrapolated to represent the Australian working population using a raked weighting technique. RESULTS: In the Australian workforce, 19.5% of men and 2.8% of women exceeded the recommended full shift noise limit of 85 dBA during their last working day. Men were more likely to be exposed to noise if they were younger, had trade qualifications and did not live in a major city. Men were more likely exposed to workplace ototoxic chemicals (57.3%) than women (25.3%). Over 80% of workers who exceeded the full shift noise limit were also exposed to at least one ototoxic chemical in their workplace. CONCLUSION: The results demonstrate that exposures to hazardous noise and ototoxic chemicals are widespread in Australian workplaces and co-exposure is common. Occupational exposure occurs predominantly for men and could explain some of the discrepancies in hearing loss prevalence between genders.

Inter-rater Agreement Between Exposure Assessment Using Automatic Algorithms and Using Experts.

Objectives: To estimate the inter-rater agreement between exposure assessment to asthmagens in current jobs by algorithms based on task-based questionnaires (OccIDEAS) and by experts. Methods: Participants in a cross-sectional national survey of exposure to asthmagens (AWES-Asthma) were randomly split into two subcohorts of equal size. Subcohort 1 was used to determine the most common asthmagen groups and occupational groups. From subcohort 2, a random sample of 200 participants was drawn and current occupational exposure (yes/no) was assessed in these by OccIDEAS and by two experts independently and then as a consensus. Inter-rater agreement was estimated using Cohen's Kappa coefficient. The null hypothesis was set at 0.4, because both the experts and the automatic algorithm assessed the exposure using the same task-based questionnaires and therefore an agreement better than by chance would be expected. Results: The Kappa coefficients for the agreement between the experts and the algorithm-based assessments ranged from 0.37 to 1, while the agreement between the two experts ranged from 0.29 to 0.94, depending on the agent being assessed. After discussion by both experts the Kappa coefficients for the consensus decision and OccIDEAS were significantly larger than 0.4 for 7 of the 10 asthmagen groups, while overall the inter-rater agreement was greater than by chance (P < 0.0001). Conclusions: The web-based application OccIDEAS is an appropriate tool for automated assessment of current exposure to asthmagens (yes/no), and requires less time-consuming work by highly-qualified research personnel than the traditional expert-based method. Further, it can learn and reuse expert determinations in future studies.

Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study.

BACKGROUND: While the breast cancer risk associated with increasing adult BMI in postmenopausal women can be explained by increases in concentrations of endogenous estrogens the biologic mechanisms behind the inverse association between adolescent BMI and breast cancer risk are still a subject of controversial debate. METHODS: We investigated the association of breast cancer with body size and changes in body size across life time estimated by age-specific BMI Z scores and changes in BMI Z scores from teenage years to middle age in an age-matched population-based case-control study of 2994 Australian women. Logistic regression adjusted for the matching factor age and further potential confounders was used. RESULTS: Adolescent body leanness in postmenopausal women and excess adult weight gain in all study participants were associated with an increased breast cancer risk with an odds ratio [95% confidence interval] of 1.29 [1.08,1.54] and 1.31 [1.09,1.59], respectively. Interaction analyses restricted to postmenopausal women revealed an increased risk of breast cancer in those who were lean during adolescence and gained excess weight during adulthood (odds ratio [95% confidence interval]: 1.52 [1.19,1.95]) but not in women who were lean during adolescence and did not gain excess weight during adulthood (1.20 [0.97,1.48]) and not in women who were not lean during adolescence and but gained excess weight during adulthood (1.10 [0.95,1.27]) compared to postmenopausal women who were neither lean during adolescence nor gained excess weight. CONCLUSION: In postmenopausal women adolescent leanness was only associated with increased breast cancer risk when excess weight was gained during adulthood.

Epigenome-wide search for association of serum 25-hydroxyvitamin D concentration with leukocyte DNA methylation in a large cohort of older men.

AIM: We aimed for an epigenome-wide identification of vitamin D-associated CpG sites in leukocyte DNA. MATERIALS & METHODS: Infinium HumanMethylation450BeadChip measurements in 402 Caucasian older men were evaluated for significant association with 25-hydroxy-vitamin (25(OH)D) using Spearman's correlation and median regression to adjust for confounding variables. A cross-validation approach as well as a bootstrapping procedure were implemented to determine the replicability of significant associations. Multiple testing was corrected for by Benjamini-Hochberg or Bonferroni. RESULTS: Although in the screening subcohorts significant associations of DNAm with 25(OH)D were observed in the validation cohorts these associations were not replicated after adjustment for potential confounders. At none of the 361,945 CpGs a significant association of DNAm with 25(OH)D was found in all 100 random bootstrap samples, but in comparison at 462 CpGs for the well-established association with age. CONCLUSION: Leukocyte DNAm was not associated with 25(OH)D levels after validation and consideration of confounders.

Self-reported smoking, serum cotinine, and blood DNA methylation.

BACKGROUND: Epigenome-wide profiling of DNA methylation pattern with respect to tobacco smoking has given rise to a new measure of smoking exposure. We investigated the relationships of methylation markers with both cotinine, an established marker of internal smoking exposure, and self-reported smoking. METHODS: Blood DNA methylation levels across the genome and serum cotinine were measured in 1000 older adults aged 50-75 years. Epigenome-wide scans were performed to identify methylation markers associated with cotinine. The inter-dose-response relationships between the number of cigarettes smoked per day, cotinine concentration, and DNA methylation were modeled by restricted cubic spline regression. RESULTS: Of 61 CpGs that passed the genome-wide significance threshold (p<1.13×10(-7)), 40 CpGs in 25 chromosomal regions were successfully replicated, showing 0.2-3% demethylation per 10ng/ml increases in cotinine. The strongest associations were observed for several loci at AHRR, F2RL3, 2q37.1, 6p21.33, and GFI1 that were previously identified to be related to self-reported smoking. One locus at RAB34 was newly discovered. Both cotinine and methylation markers exhibited non-linear relationships with the number of cigarettes smoked per day, where the highest rates of increase in cotinine and decreases in methylation were observed at low smoking intensity (1-15 cigarettes/day) and plateaued at high smoking intensity (>15-20 cigarettes/day). A clear linear relationship was observed between cotinine concentration and methylation level. Both cotinine and methylation markers showed similar accuracy in distinguishing current from never smoker, but only methylation markers distinguished former from never smoker with high accuracy. CONCLUSIONS: Our study corroborates and expands the list of smoking-associated DNA methylation markers. Methylation levels were linearly related to cotinine concentration and provided accurate measures for both current and past smoking exposure.

Type 2 diabetes and leucocyte DNA methylation: an epigenome-wide association study in over 1,500 older adults.

AIMS/HYPOTHESIS: Development of type 2 diabetes depends on environmental and genetic factors. We investigated the epigenome-wide association of prevalent diabetes with DNA methylation (DNAm) in peripheral blood. METHODS: DNAm was measured in whole blood with the Illumina Infinium HumanMethylation450 BeadChip in two subsamples of participants from the ESTHER cohort study. Cohort 1 included 988 participants, who were consecutively recruited between July and October 2000 and cohort 2 included 527 randomly selected participants. The association of DNAm with prevalent type 2 diabetes at recruitment was estimated using median regression analysis adjusting for sex, age, BMI, smoking behaviour, cell composition and batch at 361,922 CpG sites. RESULTS: Type 2 diabetes was prevalent in 16% of the participants, and diabetes was poorly controlled in 45% of the diabetic patients. In cohort 1 (discovery) DNAm at 39 CpGs was significantly associated with prevalent diabetes after correction for multiple testing. In cohort 2 (replication) at one of these CpGs, DNAm was still significantly associated. Decreasing methylation levels at cg19693031 with increasing fasting glucose and HbA1c concentrations were observed using restricted cubic spline analysis. In diabetic patients with poorly controlled diabetes, the decrease in estimated DNAm levels was approximately 5% in comparison with participants free of diagnosed diabetes. CONCLUSIONS/INTERPRETATION: Cg19693031, which is located within the 3'-untranslated region of TXNIP, might play a role in the pathophysiology of type 2 diabetes. This result appears biologically plausible given that thioredoxin-interacting protein is overexpressed in diabetic animals and humans and 3'-untranslated regions are known to play a regulatory role in gene expression.

Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality.

BACKGROUND: With epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified. OBJECTIVES: We aimed to assess dose-response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality. METHODS: In a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Illumina 450K assay. Deaths were recorded during a median follow-up of 10.3 years. Dose-response relationships of smoking exposure with methylation at nine CpGs were modeled by restricted cubic spline regression. Associations of individual and aggregate methylation patterns with all-cause, cardiovascular, and cancer mortality were assessed by multiple Cox regression. RESULTS: Clear dose-response relationships with respect to current and lifetime smoking intensity were consistently observed for methylation at six of the nine CpGs. Seven of the nine CpGs were also associated with mortality outcomes to various extents. A methylation score based on the top two CpGs (cg05575921 and cg06126421) showed the strongest associations with all-cause, cardiovascular, and cancer mortality, with adjusted hazard ratios (95% CI) of 3.59 (2.10, 6.16), 7.41 (2.81, 19.54), and 2.48 (1.01, 6.08), respectively, for participants with methylation levels in the lowest quartile at both CpGs. Adding methylation at those two CpGs into a model that included the variables of the Systematic Coronary Risk Evaluation chart for fatal cardiovascular risk prediction improved the predictive discrimination. CONCLUSION: The novel methylation biomarkers are highly informative for both smoking exposure and smoking-related mortality outcomes. In particular, these biomarkers may substantially improve cardiovascular risk prediction. Nevertheless, the findings of the present study need to be further validated in additional large longitudinal studies. CITATION: Zhang Y, Schöttker B, Florath I, Stock C, Butterbach K, Holleczek B, Mons U, Brenner H. 2016. Smoking-associated DNA methylation biomarkers and their predictive value for all-cause and cardiovascular mortality. Environ Health Perspect 124:67-74; http://dx.doi.org/10.1289/ehp.1409020.

Age-specific influence of wheezing phenotypes on pre-adolescent and adolescent health-related quality of life.

INTRODUCTION: Asthma is associated with diminished health-related quality of life (HRQoL). Particularly in adolescence, asthma may be under-diagnosed and undertreated or poorly managed. Therefore, we aimed to determine the association between childhood wheezing phenotypes rather than asthma and adolescent HRQoL in children aged 10-17 yr. METHODS: We analyzed the data from two prospective population-based cohort studies (n = 604 and n = 1804) conducted in southern Germany with baseline assessments in 2000 and 2006 and follow-ups at frequent intervals. Parent-reported wheeze was categorized into never, early transient, persistent, and late-onset wheeze. We assessed child-reported HRQoL in seven scales using the validated KINDL-R. Multivariate linear regression models were computed. RESULTS: Participants with late-onset wheeze had significantly lower values in all HRQoL scales, but physical well-being compared to never wheezers. Early transient wheeze was negatively associated with three HRQoL scales only (family, school, and total). These effects were confined to the oldest age group (≥13.5 yr) in one study. Persistent wheeze was not associated with HRQoL. CONCLUSIONS: In teenagers, late-onset wheezers seem to be particularly vulnerable for impairments in psychosocial aspects of health-related quality of life. They may therefore require particular attention with regard to education about asthma management and potentially family-based psychosocial intervention.

Restrained and external-emotional eating patterns in young overweight children-results of the Ulm Birth Cohort Study.

Childhood obesity is one of the greatest public health challenges in Western countries. Abnormal eating behavior is thought to be a developmental trajectory to obesity. The Eating Pattern Inventory for Children (EPI-C) has not been used for children as young as eight years, and possible associations with body weight have not yet been established. Five hundred and twenty-one children of the Ulm Birth Cohort Study (UBCS; age eight) filled out the EPI-C and BMI was assessed. Adequacy of the scales was tested with confirmatory factor analysis and a MANOVA and cluster analysis established associations between eating patterns and BMI. The factor structure of the EPI-C was confirmed (GFI = .968) and abnormal eating behavior was associated with overweight (χ(2)(8) =79.29, p<.001). The EPI-C is a valid assessment tool in this young age group. Overweight children consciously restrain their eating.

Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites.

Understanding the role of epigenetic modifications, e.g. DNA methylation, in the process of aging requires the characterization of methylation patterns in large cohorts. We analysed >480 000 CpG sites using Infinium HumanMethylation450 BeadChip (Illumina) in whole blood DNA of 965 participants of a population-based cohort study aged between 50 and 75 years. In an exploratory analysis in 400 individuals, 200 CpG sites with the highest Spearman correlation coefficients for the association between methylation and age were identified. Of these 200 CpGs, 162 were significantly associated with age, which was verified in an independent cohort of 498 individuals using mixed linear regression models adjusted for gender, smoking behaviour, age-related diseases and random batch effect and corrected for multiple testing by Bonferroni. In another independent cohort of 67 individuals without history of major age-related diseases and with a follow-up of 8 years, we observed a gain in methylation at 96% (52%, significant) of the positively age-associated CpGs and a loss at all (89%, significant) of the negatively age-associated CpGs in each individual while getting 8 years older. A regression model for age prediction based on 17 CpGs as predicting variables explained 71% of the variance in age with an average accuracy of 2.6 years. In comparison with cord blood samples obtained from the Ulm Birth Cohort Study, we observed a more than 2-fold change in mean methylation levels from birth to older age at 86 CpGs. We were able to identify 65 novel CpG sites with significant association of methylation with age.

Infant atopic eczema and subsequent attention-deficit/hyperactivity disorder--a prospective birth cohort study.

BACKGROUND: Comorbidity between childhood atopic eczema (AE) and attention-deficit/hyperactivity disorder (ADHD) has been observed, but temporal relationships remain unclear. METHODS: We analyzed data of a population-based, prospective birth cohort study among 770 children included at baseline in 2000/2001 with follow-up up to age 11. Information on age at diagnosis of AE, rhinoconjunctivitis, and ADHD was obtained by questionnaires administered to parents and for AE also to caring physicians. Adjusted relative risks (aRR) with 95% confidence intervals (95% CI) were modeled with a modified Poisson regression. RESULTS: Early AE up to age 4 yr was reported for 14.8% of the children by the parents and for 26.0% by the physicians with only fair agreement between these reports (kappa = 0.36). Based on parental reports, the association of early AE with early ADHD was strong (aRR: 5.17, 95% CI: 2.18; 12.28), but absent for late ADHD [aRR: 0.50 (0.13; 2.02)]. The association of late AE with late ADHD [aRR: 3.03 (0.75; 12.29)] was not statistically significant. This pattern was independent of the presence of rhinoconjunctivitis. CONCLUSIONS: The observed comorbidity between AE and ADHD may indicate vulnerability to develop ADHD symptoms in response to AE symptoms or through a common underlying mechanism. This vulnerability seems to decrease with time since AE onset and may be greater in early life. These temporal relationships should be considered in future research investigating mechanisms linking both diseases and in clinical efforts to screen for and prevent ADHD symptoms in children with AE.

Process review of a departmental change from conventional coronary artery bypass grafting to totally arterial coronary artery bypass and its effects on the incidence and severity of postoperative stroke.

BACKGROUND: We evaluated the process of changing from conventional coronary artery bypass grafting (CABG) to totally arterial off-pump coronary artery bypass (TOPCAB) at a single heart center in Germany. METHODS: We (1) used multivariate statistical methods to assess real-time monitoring of OPCAB effects, (2) conducted a case review to assess preventable deaths and identify areas of improvement, (3) conducted a team survey, and (4) evaluated benchmarking results. RESULTS: All surgeons and assistants (n = 18) at this center were involved and were guided by the department head and one of the consultants, who was trained in this procedure in 2004 at the Leuven OPCAB school. The frequency of OPCAB operations increased abruptly in 2005 from 5% to 43% and then increased gradually to 67% (n = 546) by 2008 (total, 1781 OPCAB cases and 1563 on-pump cases). The in-hospital and 30-day mortality rates for OPCAB surgeries (n = 10 [0.6%] and 21 [1.2%], respectively) were lower than for on-pump surgeries (n = 27 [1.7%] and 26 [1.7%], respectively). Stroke rates were also lower for OPCAB surgeries (7 cases [0.4%] versus 15 cases [1%]). The lower risk of stroke in the OPCAB group was significant (P < .05) after risk adjustment. Monitoring curves and case reviews demonstrated a preventable death percentage of at least 30%. The attitude of the team was mostly positive because of the promising results (eg, fewer strokes, increasing TOPCAB popularity, and a top national rank). CONCLUSIONS: The change from conventional CABG to TOPCAB was effective in decreasing the incidence and severity of stroke, in developing a team routine and a positive team attitude, and in producing excellent benchmarking results. The presence of a training and communication deficiency at the beginning of the study suggested an area for further improvement. After 6 years TOPCAB had largely replaced conventional CABG.

Midterm outcome after aortic root replacement with stentless porcine bioprostheses.

OBJECTIVE: Midterm clinical outcome was evaluated after aortic root replacement with Freestyle® stentless aortic root bioprostheses. METHODS: Between April 1996 and December 2007, 301 patients underwent aortic valve replacement with stentless Medtronic Freestyle® bioprostheses in full-root technique at a single center. Concomitant coronary artery bypass grafting (CABG) was required in 96 patients (32%). In 94 patients (31%), the ascending aorta was replaced. The mean age was 71.6 ± 9.1 (range: 36-89) years. Follow-up was closed in October 2008, 99% complete and encompassed 916 patient-years. RESULTS: Overall mortality within 30 days was 5%. A total of 62 patients died during the follow-up period. Overall survival at 5 and 9 years was 74 ± 4% and 53 ± 6%, respectively. Re-operations were required in three patients: in one patient due to structural valve deterioration, and in two patients due to prosthetic valve endocarditis. Non-structural dysfunctions were not observed. In eight patients, prosthetic valve endocarditis occurred, in most of them (N = 6) during the first year after surgery. Rate of freedom from re-operation, structural valve deterioration, prosthetic valve endocarditis, thrombo-embolic and major bleeding events at 9 years was 94 ± 6%, 94 ± 6%, 94 ± 3%, 87 ± 5%, and 95 ± 2%, respectively. The linearized rates of late adverse events in percent per patient-year were 0.35, 0.12, 0.83, 1.7, and 0.7, respectively, for re-operation, structural valve deterioration, prosthetic valve endocarditis, thrombo-embolic and major bleeding events. A little less than a quarter (22%) of the patients required anticoagulation therapy. CONCLUSIONS: Aortic root replacement with the stentless Freestyle® bioprosthesis provided a respectable short-term mortality, optimal valve durability and acceptable rates of valve-related complications within 9 years.

The late impact of surgical skills and training on the subcoronary implantation of the Freestyle stentless bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: Recent data have demonstrated an impact of higher postoperative mean pressure gradient (MPG) across the subcoronary Freestyle stentless bioprosthesis on the mid-term quality of life, but not on that of survival. Thus, the question remains that, with a prolonged follow up, would an effect on duration of survival also evolve? METHODS: Between 1996 and 2006, a total of 939 patients underwent aortic valve replacement (AVR) for aortic stenosis with the Freestyle stentless bioprosthesis, using the subcoronary technique. A follow up was conducted by mailed questionnaires, and completed by telephone interviews in September 2008. The follow up was 99% complete and totaled 3,468 patient-years (pt-yr); the mean follow up time was 7.7 years (range: 7.3-8.1 years). The maximum follow up was 11.9 years. RESULTS: Actuarial survival rates at five and 10 years were 73 +/- 2% and 35 +/- 4%, respectively. The cut-off gradient was identified at a postoperative MPG of 20 mmHg, where a gradient >20 mmHg had a negative impact on survival rate (p = 0.008), as indicated by the greatest fall of deviance in the Akaike information criterion. Risk factors also affecting survival rate included atrial fibrillation, diabetes, higher serum creatinine levels, greater age, left ventricular ejection fraction < or = 40%, liver insufficiency, lower body mass index, chronic obstructive pulmonary disease, and peripheral arterial disease. Risk factors for MPG >20 mmHg were a smaller valve size, a higher preoperative gradient, individual surgeons and lesser cumulative experience, and early adopters (surgeons) of the subcoronary stentless valve implantation technique. CONCLUSION: A higher MPG impedes long-term survival, with the cut-off being at 20 mmHg. A higher MPG was largely influenced by the individual surgeons and their cumulative experience of using the subcoronary technique. Late adopters of the technique profited from the observations of early adopters. The standardization of a surgical technique and the identification of common pitfalls were key to optimizing the surgical outcome after stentless valve implantation.

Aortic valve replacement in octogenarians: identification of high-risk patients.

OBJECTIVE: This study identifies high-risk octogenarians for surgical aortic valve replacement (AVR) because with the current advances in transcatheter valve therapy, a definition of patient selection criteria is essential. METHODS: Between 1996 and 2006, 493 consecutive octogenarians with symptomatic aortic stenosis underwent AVR with and without (51%) concomitant coronary artery bypass grafting (CABG). To identify high-risk patient groups, risk factors of 6-month mortality were determined using multivariable logistic regression. RESULTS: The 30-day mortality rate was 8.4% and it increased up to 15.2% until 6 months after AVR. Independent risk factors of 6-month mortality were patients older than 84 years (odds ratio (OR): 2.2 (1.29-3.61)), left ventricular ejection fraction <60% (OR: 2.5 (1.35-4.61)), body mass index (BMI) <24 (OR: 2.0 (1.22-3.36)), creatinine (OR: 1.6 (1.04-2.53)) and blood glucose (OR: 1.01 (1.001-1.009)). High-risk groups were patients older than 84 years with an ejection fraction <60% (6-month mortality 28%) and patients younger than 84 years with an ejection fraction <60% and a BMI <24 (6-month mortality 23.2%). These high-risk groups comprised 37% of the patient population. After isolated AVR, the 30-day mortality and survival at 1 and 5 years was 11.6%, 69% and 35% in this high-risk group, respectively. In octogenarians with an STS score >10 and an EuroScore >20, the 30-day mortality and survival at 1 year was 10.5% and 80%, 11.6% and 77%, respectively. CONCLUSIONS: In most octogenarians, AVR is a safe and beneficial procedure. In high-risk octogenarians, identified by STS score >10, EuroScore >20 and by simple three risk factors (age >84 years, ejection fraction <60% and BMI <24), the mortality after surgical AVR was no different from the currently reported outcome after transcatheter AVI.

Impact of gender on outcome after coronary artery bypass surgery.

Following recent studies concerning the increased risk of coronary artery bypass surgery for women, the impact of sex is still a controversial issue. Between 1996 and 2006, 9,527 men and 3,079 women underwent isolated coronary artery bypass in our institute. To adjust for dissimilarities in preoperative risk profiles, propensity score-based matching was applied. Before adjustment, clinical outcomes in terms of operative mortality, arrhythmias, intensive care unit stay, and maximum creatine kinase-MB levels were significantly different for men and women. After balancing the preoperative characteristics, including height, no significant differences in clinical outcomes were observed. However, there was decreased use of internal mammary artery, less total arterial revascularization, and increasing creatine kinase-MB levels with decreasing height. This study supports the theory that female sex per se does not increase operative risk, but shorter height, which is more common in women, affects the outcome, probably due to technical difficulties in shorter patients with smaller internal mammary arteries and coronary vessels. Thus women may especially benefit from sequential arterial grafting.

The Freestyle stentless bioprosthesis in more than 1000 patients: a single-center experience over 10 years.

BACKGROUND AND AIM: Early and mid-term clinical outcomes after aortic valve replacement (AVR) with stentless bioprostheses in a large cohort of patients are presented. METHODS: Between April 1996 and November 2005, 1014 patients underwent AVR with the stentless Medtronic Freestyle bioprosthesis, with 168 using the full-root technique. The mean age was 73+/-3 (range: 20 to 90) years. Follow-up included 2953 patient-years and was 95% complete for adverse events. RESULTS: Operative mortality was 3.4% (N=34). Overall survival was 46+/-9% at nine years and similar to age- and gender-matched German general population. Freedom from prosthetic valve endocarditis, major bleeding, neurological events, and reoperation after nine years was 97+/-6%, 92+/-7%, 70+/-16%, and 92+/-9%, respectively. Freedom from structural valve deterioration was 97+/-5% at 9 years. During the learning phase, mean transprosthetic gradients of 23.5+/-3.0 mmHg and 24.8+/-3.1 mmHg were observed for valve sizes 21 and 23 mm, respectively, 10 days after subcoronary implantation in 1997, which could be lowered to 16+/-2.1 mmHg and 14.9+/-0.9 mmHg in 2005, respectively, with increasing experience of the surgeons. During the follow-up period, mean gradients dropped on average by 15 mmHg in patients presenting higher gradients at discharge. CONCLUSIONS: The Freestyle stentless bioprosthesis showed encouraging midterm durability with low rates of valve-related morbidity, and can be safely implanted without increased operative risk even during the learning phase. Special training of the surgeons is recommended to achieve optimal hemodynamic performance.

Cerebrovascular events after stentless aortic valve replacement during a 9-year follow-up period.

BACKGROUND: One major advantage of biologic aortic valve prostheses is their low thrombogenicity compared with mechanical prostheses. The purpose of this study was to evaluate the incidence of cerebrovascular events during long-term follow-up after stentless aortic valve replacement. METHODS: Between 1996 and 2005, 1,014 patients (mean age, 73 years; range, 20 to 90 years) received stentless aortic valve replacement (Freestyle; Medtronic, Minneapolis, MN) and were included into the systematic follow-up that was closed in 2006 with a completeness of 94.7% and a mean follow-up interval of 3 years (range, 0.5 to 9.8 years). Predictors for freedom from cerebrovascular events were identified by Cox regression. RESULTS: Overall survival was 53% +/- 5% after 8 years (mean, 6.8 +/- 0.2 years). Permanent atrial fibrillation at time of surgery was a strong predictor of impaired survival during follow-up. Freedom from cerebrovascular events during follow-up was 68% +/- 5% at 9 years of follow-up. Multivariate regression analysis revealed previous stroke, age at implant, diabetes mellitus, and carotid lesions as significant risk factors. Especially age older than 75 years was a strong risk factor for cerebrovascular events during follow-up (p = 0.004). Atrial fibrillation was not an independent risk factor for cerebrovascular events (p = 0.26) but was a strong predictor of poor survival (p < 0.001) during follow-up. There was no influence of technique of implantation (subcoronary versus full root; p = 0.41), sex (p = 0.35), additional bypass grafting (p = 0.65), and the size of the implanted prosthesis (p = 0.47). CONCLUSIONS: The risk of cerebrovascular events during follow-up after stentless aortic valve replacement is related to the individual risk factors of the patients rather than to the valve prosthesis itself. Without additional risk factors, patients with these aortic valve prostheses showed an incidence of cerebrovascular events similar to those reported for a healthy population adjusted for age.

Impact of valve prosthesis-patient mismatch estimated by echocardiographic-determined effective orifice area on long-term outcome after aortic valve replacement.

BACKGROUND: The impact of valve prosthesis-patient mismatch on long-term outcome after aortic valve replacement estimated by various variables such as projected indexed effective orifice area and internal geometric orifice area obtained from in vivo or in vitro published data is still controversial. METHODS: The effective orifice area was measured by echocardiography in 533 patients. The mean age of the patients was 71 +/- 9 years; mean follow-up time was 4.7 +/- 2.2 years. The impact of severe (indexed effective orifice area