The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is not appropriate for withholding surgery in high-risk patients with aortic stenosis: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a widely used risk assessment tool in patients with severe aortic stenosis to determine operability and to select patients for alternative therapies such as transcatheter aortic valve implantation. The objective of this study was to determine the accuracy of the EuroSCORE in predicting mortality following aortic valve replacement (AVR).</p> <p>Methods</p> <p>The logistic EuroSCORE was determined for all consecutive patients that underwent conventional AVR between 1995 and 2005 at our institution. Provincial Vital Statistics were used to determine all-cause mortality. The accuracy of the prognostic risk prediction provided by logistic EuroSCORE was assessed by comparing observed and expected operative mortality.</p> <p>Results</p> <p>During the study period, a total of 1,421 patients underwent AVR including 237 patients (16.7%) that had a logistic EuroSCORE > 20. Among these patients, the mean predicted operative mortality was 38.7% (SD = 18.1). The actual mortality of these patients was significantly lower than that predicted by EuroSCORE (11.4% vs. 38.7%, observed/expected ratio 0.29, 95% CI 0.15–0.52, P < 0.05). The EuroSCORE overestimated mortality within all strata of predicted risk. Although medium-term mortality is significantly higher among patients with EuroSCORE > 20 (log rank P = 0.0001), approximately 60% are alive at five years.</p> <p>Conclusion</p> <p>Actual operative mortality in patients undergoing AVR is significantly lower than that predicted by the logistic EuroSCORE. Additionally, medium-term survival following AVR is acceptable in high-risk patients with EuroSCORE > 20. More accurate risk prediction models are needed for risk-stratifying patients with severe aortic stenosis.</p

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

Effect of surgeon on transprosthetic gradients after aortic valve replacement with Freestyle^®stentless bioprosthesis and its consequences: A follow-up study in 587 patients

<p>Abstract</p> <p>Background</p> <p>The implantation of stentless valves is technically demanding and the outcome may depend on the performance of surgeons. We studied systematically the role of surgeons and other possible determinants for mid-term survival, postoperative gradients and Quality of Life (QoL) after aortic valve replacement (AVR) with Freestyle^®stentless bioprostheses.</p> <p>Methods</p> <p>Between 1996 and 2003, 587 patients (mean 75 years) underwent AVR with stentless Medtronic Freestyle^®bioprostheses. Follow-up was 99% complete. Determinants of morbidity, mortality, survival time and QoL were evaluated by multiple, time-related, regression analysis. Risk models were built for all sections of the Nottingham Health Profile (NHP): energy, pain, emotional reaction, sleep, social isolation and physical mobility</p> <p>Results</p> <p>Actuarial freedom from aortic valve re-operation, structural valve deterioration, non-structural valve dysfunction, prosthetic valve endocarditis and thromboembolic events at 6 years were 95.9 ± 2.1%, 100%, 98.7 ± 0.5%, 97.0 ± 1.5%, 79.6 ± 4.3%, respectively. The actuarial freedom from bleeding events at 6 years was 93.1 ± 1.9%. Estimated survival at 6 years was similar to the age-matched German population (61.4 ± 3.8 %). Predictors of survival time were: diabetes mellitus, atrial fibrillation, peripheral vascular disease, renal dysfunction, female gender > 80 years and patients < 165 cm with BMI < 24. Predictive models showed characteristic profiles and good discriminative powers (c-indexes > 0.7) for each of the 6 QoL sections. Early transvalvular gradients were identified as independent risk factors for impaired physical mobility (c-index 0.77, p < 0.002). A saturated propensity score identified besides patient related factors (e.g. preoperative gradients, ejection fraction, haematological factors) indexed geometric orifice area, subcoronary implantation technique and individual surgeons as predictors of high gradients.</p> <p>Conclusion</p> <p>In addition to the valve size (in relation to body size), subcoronary technique (versus total root) and various patient-related factors the risk of elevated gradients after stentless valve implantation depends, considerably on the individual surgeon.</p> <p>Although there was no effect on survival time and most aspects of QoL, higher postoperative transvalvular gradients affect physical mobility after AVR.</p