Prognostic value of three iron deficiency definitions in patients with advanced heart failure.

AIMS: There is uncertainty about the definition of iron deficiency (ID) and the association between ID and prognosis in patients with advanced heart failure. We evaluated three definitions of ID in patients referred for heart transplantation. METHODS AND RESULTS: Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as (1) serum ferritin concentration of <100 ng/ml, or 100-299 ng/ml with transferrin saturation <20% (guideline definition), (2) serum iron concentration ≤13 µmol/L, or (3) transferrin saturation <20%. The primary outcome measure was a composite of all-cause mortality, urgent heart transplantation or need for mechanical circulatory support. Overall, 801 patients were included, and the prevalence of ID was 39-55% depending on the definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure (hazard ratio [HR] 1.532, 95% confidence interval [CI] 1.264-1.944, and HR 1.595, 95% CI 1.323-2.033, respectively), but the same association was not seen with the guideline definition of ID (HR 1.085, 95% CI 0.8827-1.333). These findings were robust in multivariable Cox regression analysis. ID, by all definitions, was associated with lower 6-min walk distance, lower peak oxygen consumption, higher intra-cardiac filling pressures and lower cardiac output. CONCLUSIONS: Iron deficiency, when defined by serum iron concentration or transferrin saturation, was associated with increased frequency of adverse clinical outcomes in patients with advanced heart failure. The same association was not seen with guideline definition of ID.

Feature optimization in high dimensional chemical space: statistical and data mining solutions.

OBJECTIVES: The primary goal of this experiment is to prioritize molecular descriptors that control the activity of active molecules that could reduce the dimensionality produced during the virtual screening process. It also aims to: (1) develop a methodology for sampling large datasets and the statistical verification of the sampling process, (2) apply screening filter to detect molecules with polypharmacological or promiscuous activity. RESULTS: Sampling from large a dataset and its verification were done by applying Z-test. Molecular descriptors were prioritized using principal component analysis (PCA) by eliminating the least influencing ones. The original dimensions were reduced to one-twelfth by the application of PCA. There was a significant improvement in statistical parameter values of virtual screening model which in turn resulted in better screening results. Further improvement of screened results was done by applying Eli Lilly MedChem rules filter that removed molecules with polypharmacological or promiscuous activity. It was also shown that similarities in the activity of compounds were due to the molecular descriptors which were not apparent in prima facie structural studies.

Socioeconomic Deprivation and Survival After Heart Transplantation in England: An Analysis of the United Kingdom Transplant Registry.

BACKGROUND: Socioeconomic deprivation (SED) is associated with shorter survival across a range of cardiovascular and noncardiovascular diseases. The association of SED with survival after heart transplantation in England, where there is universal healthcare provision, is unknown. METHODS AND RESULTS: Long-term follow-up data were obtained for all patients in England who underwent heart transplantation between 1995 and 2014. We used the United Kingdom Index of Multiple Deprivation (UK IMD), a neighborhood level measure of SED, to estimate the relative degree of deprivation for each recipient. Cox proportional hazard models were used to examine the association between SED and overall survival and conditional survival (dependant on survival at 1 year after transplantation) during follow-up. Models were stratified by transplant center and adjusted for donor and recipient age and sex, ethnicity, serum creatinine, diabetes mellitus, and heart failure cause. A total of 2384 patients underwent heart transplantation. There were 1101 deaths during 17 040 patient-year follow-up. Median overall survival was 12.6 years, and conditional survival was 15.6 years. Comparing the most deprived with the least deprived quintile, adjusted hazard ratios for all-cause mortality were 1.27 (1.04-1.55; P=0.021) and 1.59 (1.22-2.09; P=0.001) in the overall and conditional models, respectively. Median overall survival and conditional survival were 3.4 years shorter in the most deprived quintile than in the least deprived. CONCLUSIONS: Higher SED is associated with shorter survival in heart transplant recipients in England and should be considered when comparing outcomes between centers. Future research should seek to identify modifiable mediators of this association.