Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.

There are no studies to date on the early changes in the hemostasis profile of patients with paroxysmal atrial fibrillation (PAF).Given the key role of the fibrinolytic system in maintaining blood fluidity, our aim was to examine its activity in patients with clinical manifestation of the disease <24 hours.We studied 51 nonanticoagulated patients with a first episode of the disease (26 men, 25 women; mean age 59.84 ± 1.60 years) and 52 controls (26 men, 26 women; mean age 59.50 ± 1.46 years) who matched the patients in terms of gender, age, comorbidities, and conducted treatment. Using enzyme-linked immunoassays and colorimetric assays we assessed the plasminogen activity, tissue plasminogen activator level (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), α2-antiplasmin activity (α2-AP), D-dimer level, and vitronectin level. Blood samples were collected immediately after hospitalization.Patients were hospitalized between the second and twenty fourth hours (mean 8.14 ± 0.76 hours) after the onset of PAF. Compared to controls, plasminogen (159.40 ± 4.81 vs 100.2 ± 2.88%, P < 0.001) and t-PA levels (11.25 ± 0.35 vs 6.05 ± 0.31 ng/mL, P < 0.001) were significantly higher in the patient group. PAI-1 activity (7.33 ± 0.37 vs 15.15 ± 0.52 AU/mL, P < 0.001) and α2-AP (112.9 ± 2.80 vs 125.60 ± 3.74%, P < 0.05) as well as vitronectin plasma levels (134.7 ± 5.83 vs 287.3 ± 10.44 mcg/mL, P < 0.001) were lower in the PAF group. Conversely, the levels of D-dimer in patients were significantly higher (0.53 ± 0.07 vs 0.33 ± 0.02 ng/mL, P < 0.05).Early changes in the fibrinolytic system occur in PAF, suggesting their close relationship with the manifestation of the disease. There is high plasma fibrinolytic activity, during the very first 24 hours of the disease, which is most likely a pathophysiological response to the intensified procoagulation process.

IntroductionMatrix metalloproteinase-9 (MMP-9) plays an important role in extracellular and vascular remodelling. We aimed therefore to assess the role of blood pressure (BP) control on plasma MMP-9 in relation to the presence of diabetes mellitus (DM) type II.Material and methodsPlasma MMP-9 was measured in 61 patients who were divided into two groups depending on their BP control as follows: 49 patients with uncontrolled arterial hypertension (AH) defined as BP values > 130/80 mm Hg and 12 patients with optimal blood pressure values. Plasma MMP-9 levels were measured with immunoassay at discharge. Group comparisons were made with the independent t-test, Mann-Whitney U-test and χ2 test where appropriate. The associations of the variables with MMP-9 were investigated with linear regression analyses.ResultsThe diabetics made up 34.4% of the investigated patients. Frequency of DM did not differ between the two BP groups (30.0% vs. 36.6%, p > 0.05). Plasma MMP-9 concentrations differed significantly between the diabetics vs. non-diabetics (median: 1.9 ng/ml, range: 1.0–7.3 vs. 1.4 ng/ml, range: 0.5–4.7, p < 0.05). Stratification across the categories of BP control showed a significant correlation between plasma MMP-9 and DM type II only in the uncontrolled BP group. The significance of that relationship disappeared in the group of patients with optimal BP control.ConclusionsPlasma values of MMP-9 are raised in patients with DM type II. The results revealed the impact of the combination of uncontrolled AH and DM type II on vascular remodelling processes.

Introduction Paroxysmal atrial fibrillation (PAF) is a well-documented prothrombotic state that carries significant embolic risk. However, precise hemostatic changes in the very early stage of the disease are not completely studied. The aim of the study was to study von Willebrand factor (vWF) and coagulation factor VIII (FVIII) plasma levels and activity in the first hours (up to 24 h) of PAF clinical manifestation. Material and methods We selected consecutively 51 non-anticoagulated patients (26 men, 25 women, mean age: 59.84 ±1.60) with PAF and 52 controls (26 men, 26 women, mean age: 59.50 ±1.46 years) corresponding in gender, accompanying diseases and conducted treatment. The indicators were examined using enzyme-linked immunoassays and photometric tests. Results All patients were hospitalized between the 2 nd and 24 th h after the onset of arrhythmia (mean: 8.14 ±0.74 h). Higher FVIII levels (107.52 ±3.48% vs. 93.85 ±2.93%, p < 0.05) and activity (200.03 ±11.11% vs. 109.73 ±4.90%, p < 0.001) were found in the PAF group. vWF levels (178.40 ±12.95% vs. 119.53 ±6.12%, p < 0.001) and activity (200.92 ±12.45% vs. 110.80 ±5.14%, p < 0.001) were also higher. These changes did not depend on age, sex, body mass index or CHA 2 DS 2 -VASc score in the PAF group ( p > 0.05). PAF duration was a significant predictor of increased FVIII levels and activity. Increased PAF duration was followed by increased values of the factors ( r = 0.85, p < 0.001; r = 0.83, p < 0.001). Conclusions The results presented an activated coagulation cascade and endothelial injury, suggesting hypercoagulability still in the early hours of PAF. These changes in PAF did not correlate with CHA 2 DS 2 -VASc score risk factors, outlining PAF as a possible independent embolic risk factor.