On singular Lagrangians affine in velocities

The properties of Lagrangians affine in velocities are analyzed in a geometric way. These systems are necessarily singular and exhibit, in general, gauge invariance. The analysis of constraint functions and gauge symmetry leads us to a complete classification of such Lagrangians.Comment: AMSTeX, 22 page

Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing

Abstract Aims Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. Methods and results We performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty‐two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR‐210‐3p, miR‐22‐5p, miR‐22‐3p, miR‐21‐3p, miR‐339‐3p, and miR‐125a‐5p) significantly correlated with HF biomarkers, among which N‐terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR‐125a‐5p, miR‐10b‐5p, and miR‐9‐5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio‐HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82). Conclusions This discovery study has characterized, for the first time, the advanced chronic HF‐specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations

The Schroedinger operator as a generalized Laplacian

The Schroedinger operators on the Newtonian space-time are defined in a way which make them independent on the class of inertial observers. In this picture the Schroedinger operators act not on functions on the space-time but on sections of certain one-dimensional complex vector bundle -- the Schroedinger line bundle. This line bundle has trivializations indexed by inertial observers and is associated with an U(1)-principal bundle with an analogous list of trivializations -- the Schroedinger principal bundle. For the Schroedinger principal bundle a natural differential calculus for `wave forms' is developed that leads to a natural generalization of the concept of Laplace-Beltrami operator associated with a pseudo-Riemannian metric. The free Schroedinger operator turns out to be the Laplace-Beltrami operator associated with a naturally distinguished invariant pseudo-Riemannian metric on the Schroedinger principal bundle. The presented framework is proven to be strictly related to the frame-independent formulation of analytical Newtonian mechanics and Hamilton-Jacobi equations, that makes a bridge between the classical and quantum theory.Comment: 19 pages, a remark, an example and references added - the version to appear in J. Phys. A: Math. and Theo

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

P227 DOES NITROPRUSSIDE TEST BEHAVE AD AN INCREMENTAL PROGNOSTIC FACTOR IN SELECTION OF PATIENTS CANDIDATE TO LVAD IMPLANTATION?

Abstract Background Left ventricular assist device in the last two decades has been used to improve survival and quality of life of patients suffering from heart failure, regardless presence of concomitant pulmonary hypertension. Most patients showed improvement in pulmonary pressure. Current clinical practice lacks a reliable method for prediction of reverse remodelling and prognosis. Aim of this study is to investigate the possible role of nitroprusside test as prognostic factor in candidates to LVAD implantation. Methods We conducted a monocentric prospective observational study analysing 31 consecutive patients implanted with LVAD between July 2013 and October 2021 that underwent right heart catheterization and nitroprusside test before implantation. Basal and nitroprusside–obtained hemodynamic parameters were subsequently correlated with the primary outcome, defined as the composite of death and episodes of right ventricular failure. Results Mean age of study population was 58,6 ± 7,97 years, 12,9% were female. Most prevalent INTERMACS class was 3 and mean EF was 18 ± 4,92 %. Mean follow–up was 31,3 ± 20,4 months, during which 11 death and 14 episodes of RVF occurred. At basal hemodynamic assessment, patients with pulmonary vascular resistance above 3 WU had a significant higher rate of events (50% vs 9%, Likelihood ratio 5.7, p = 0.029). No hemodynamic parameter measured after nitroprusside infusion was found to predict survival or episode of RVF. Conclusion In this exploratory study we have shown that nitroprusside infusion does not add further prognostic information when compared with basal hemodynamic parameters. </jats:sec