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Aims: Patients with atrial fibrillation (AF) may experience other supraventricular tachycardias (SVT) that can trigger AF and cause similar symptoms. The aim of this study was to assess the safety and effectivity of inducing SVT in patients undergoing catheter ablation (CA) for AF., Methods: In 61 patients with paroxysmal AF undergoing CA between January 2022 and March 2023, an electrophysiological study was performed after pulmonary vein isolation (PVI) to induce SVT. Induced arrhythmias were mapped and ablated. All patients were followed up at 3, 6, and 12 months after the procedure; seven-day ECG Holter monitoring was carried out 6 and 12 months after the procedure., Results: In 24 patients (39%) an SVT was induced during the stimulation protocol. There was no significant difference in procedure time (P=0.408) or fluoroscopy dose (P=0.458) between patients with and without inducible arrhythmia. Further, none of the echocardiographic variables such as left atrial volume index (LAVI) (P=0.936), left ventricular ejection fraction (LVEF) (P=0.586), or right atrial (RA) area (P=0.716), differed significantly in these subgroups. Age was a significant factor in patients with arrhythmia inducibility compared with those without (64.5 ± 7.6 and 58.2 ± 10.5, P=0.04)., Conclusion: SVT inducibility after successful PVI was 39%. Ablation of nonclinical arrhythmia is safe and did not prolong the total procedure or fluoroscopy time., Competing Interests: The authors report no conflicts of interest in this work.

Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns., Objectives: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk)., Methods: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6])., Results: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m 2 , 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily., Conclusions: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone [REALIZE-K]; NCT04676646)., Competing Interests: Funding Support and Author Disclosures The REALIZE-K trial was funded by AstraZeneca. Drs Kosiborod, Cherney, Connelly, Desai, Guimarães, Kuthi, Lala, Madrini, Merkely, Villota, Squire, Testani, Vaclavik, Verma, Wranicz, and Petrie have received research funding in the form of grants to institutions from AstraZeneca and/or consulting for AstraZeneca. Mr Dahl, Mr Eudicone, and Ms Friberg are employees of, and hold or may hold stock in, AstraZeneca., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Heart failure is one of the critical and most costly medical challenges of the 21st century. It is a chronic debilitating condition and adherence to medication, a precondition for successful treatment is often poor. There are various interventions for improving the adherence. Depending on the goal of the intervention, these are roughly patient centric, healthcare provider centric and system centric. We provide an overview of these interventions with a focus on effectiveness and appropriateness in different clinical situations. Their use can lead to improved patient outcomes and reduced economic burden of the disease., Competing Interests: The authors report no conflicts of interest in this work.

Background: Acutely ill older patients frequently suffer not only from their acute disease, but also polymorbidity and frailty. Dehydration is another typical symptom, usually occurring in its both forms: low-intake dehydration and volume depletion. POCUS is goal-directed bedside ultrasound examination and several studies refer to its positive impact on hydration assessment. The aim of our study was to determine whether POCUS might influence (de)hydration diagnostics and/or treatments in older patients with acute illness., Methods: We randomized 120 acutely ill patients, aged ≥65 years, into POCUS and non-POCUS groups. All participants underwent routine laboratory tests, including haematocrit, serum and urine osmolality, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, and C-reactive protein (CRP). POCUS was performed twice during the first two days to determine chest and abdominal status, with inferior vena cava (IVC) measurements. Length of hospital stay (HL) and consumption of infused fluids (CIF) was evaluated too. Data were analysed with exploratory methods and appropriate statistics., Results: Among all participants, the serum osmolality significantly correlated with age, BUN, creatinine and CIF. HL correlated with CRP and CIF. No significant correlations between IVC and other followed parameters were found. The POCUS group consumed significantly less infused fluids than the non-POCUS group, what could be influenced by POCUS examination of defined body compartments., Conclusion: Dehydration is a common feature in older individuals and its diagnostics is rather complicated. The role of POCUS in assessing hydration status remains unclear. However, our study showed, that ultrasound assessment provides next important information for comprehensive understanding of clinical status in older patients and can be beneficial for optimizing the treatment strategy, including fluid management decisions., Competing Interests: The authors report no conflicts of interest in this work.

Along with the known kaempferol-3- O -α-l-rhamnopyranosyl-(1 → 2)-[6- O -(3-hydroxy-3-methylglutaryl)]-β-d-galactopyranoside ( 1 ), five new flavonoids, containing the rarely isolated aglycon tamarixetin, were isolated from a methanolic extract of the endemic Balkan species Astragalus thracicus Griseb. Three of the new compounds are substituted with 3-hydroxy-3-methylglutaryl residue (HMG), untypical for the genus Astragalus . The compounds were identified as tamarixetin-3- O -α-l-rhamnopyranosyl-(1 → 2)-[6- O -(3-hydroxy-3-methylglutaryl)]-β-d-galactopyranoside ( 2 ), tamarixetin-3- O -(2,6-di- O -α-l-rhamnopyranosyl)-β-d-galactopyranoside ( 3 ), tamarixetin 3- O -β-d-apiofuranosyl-(1 → 2)-β-d-galactopyranoside ( 4 ), tamarixetin-3- O -β-d-apiofuranosyl-(1 → 2)-[6- O -(3-hydroxy-3-methylglutaryl)]-β-d-galactopyranoside ( 5 ), and tamarixetin-3- O -β-d-apiofuranosyl-(1 → 2)-[α-l-rhamnopyranosyl-(1 → 6)]-β-d-galactopyranoside ( 6 ). Selected compounds from A. thracicus were tested to evaluate their anticollagenase activity. The greatest effect was observed for quercetin-3- O -β-d-apiofuranosyl-(1 → 2)-β-d-galactopyranoside, possibly due to the presence of an ortho -dihydroxy arrangement of flavonoid ring B. The effect on collagenase and elastase was further evaluated also by in silico study, and the test compounds showed some level of in silico interaction., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality, especially in hospitalized high-risk patients. We aimed to evaluate the effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) on hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic., Methods: Initially, 991 patients hospitalized in the period January 1, 2021, to March 31, 2021, with PCR-confirmed SARS-CoV-2 acute respiratory infection in two university and five rural hospitals were included in the study. After exclusion of patients with an unknown outcome, a total of 790 patients entered the final analysis. The effects of different treatments were assessed in this cohort by means of propensity score matching., Results: Of the 790 patients, 282 patients died in the hospital; 37.7% were male and 33.3% were female. Age, sex, state of the disease, pneumonia, therapy, and several comorbidities were matched to simulate a case-control study. For anticoagulation treatment, 233 cases (full-dose) vs. 233 controls (prophylactic dose) were matched. The difference in mortality was significant in 16 of the 50 runs. For the treatment with isoprinosine, ivermectin, and vitamin D, none of the 50 runs led to a significant difference in hospital mortality., Conclusion: Prophylactic-dose anticoagulation treatment in our study was found to be beneficial in comparison with the full dose. Supplementation with vitamin D did not show any meaningful benefit in terms of lowering the hospital mortality. Neither ivermectin nor, isoprinosine was found to significantly decrease hospital mortality., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA)., Methods: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardized comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis., Results: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. Complete biochemical success of surgery was reached 67 patients (77%), 19 patients (22%) had partial biochemical success. Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure-partial clinical success. Thus, in 76 (87%) of all enrolled patients, surgery had an overall positive effect on hypertension control. Multivariable logistic regression showed that complete clinical success was independently associated with female gender and baseline sum of antihypertensive drugs DDD < 4., Conclusion: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. Almost a quarter of patients were cured and able to cease using all antihypertensive drugs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Environmental concentrations of pharmacologically active substances are increasing dramatically throughout the world, to the point where they are now considered a serious threat to the aquatic environment. This high occurrence of pharmaceutical residues in the aquatic environment is due to an increase in i) the prescription and consumption of drugs, and ii) their subsequent discharge into wastewater and its imperfect purification in wastewater treatment plants. Recent surveys have clearly shown that such substances can have serious negative effects on non-target organisms. In the present study, we tested the effects of several commonly used pharmaceuticals, such as antidepressants, analgesics and antibiotics, on the embryonic stages of different fishes. Specifically, we applied concentration ranges of tramadol, enrofloxacin and nortriptylined on a common toxicological model organism, the zebrafish (Danio rerio), and other species native to Central European freshwaters, i.e. common carp (Cyprinus carpio), catfish (Silurus glanis) and tench (Tinca tinca). Our results show that, though malformation and negative impacts on hatching and mortality were only observed at the highest test concentrations, gene expression indicated that even low environmentally relevant concentrations (0.1 μg/L) can cause significant changes in early development of embryo., (Copyright © 2021. Published by Elsevier Ltd.)

The aim of this study was to reveal the effects of foodborne fluoxetine on morphological and condition profile, hematological profile, biochemical and oxidative stress indices on juvenile rainbow trout. The study was performed according to OECD Guideline No. 215. Fluoxetine was incorporated into Biomar 921 pellets at a dose of 0.047 mg/kg (environmental concentration), 0.577 mg/kg and 6.7 mg/kg. There was statistically significant change in hematological profile, including an increasing trend in neutrophil/lymphocyte ratio and a decreasing trend in the number of lymphocytes. Measurements of oxidative stress indicated decreased activity of the detoxifying enzyme glutathione-S-transferase in the liver and kidney. However, the measurement of GR, GPx, CAT, SOD activity, and TBARS showed no changes. Histopathological examination revealed damage to the proximal tubules of caudal kidney in exposed groups. This study confirms that fluoxetine has a significant effect on immune response., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence., Materials and Methods: Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres., Results: Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring., Conclusions: The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits.

The growing consumption of pharmaceuticals in the human population and the insufficient efficiency of their elimination in waste water has a long-term negative impact on the environment of aquatic ecosystems, including the organisms that inhabit them. A significant contributor is the consumption of anti-depressants from the SSRI group, which corresponds to their increasing concentration in the environment. The aim of this work was to determine if antidepressant sertraline is able to be stored in fish organisms and to evaluate the content of residues in various body tissues. Rainbow trout (Oncorhynchuss mykkis) was selected as the test organism and was artificially exposed to the antidepressant for 1 month (concentrations 0; 4.2; 44 and 400 ng.g-1 sertraline in the feed). Liver, kidney, brain and muscle tissue biopsies samples were taken for analysis. Detection was performed using an Accela 1250 LC pump and an Accela autosampler coupled with a high-performance mass analyzer with a heated electrospray ionization source Q-Exactive Orbitrap, operating in positive ionization mode and in PRM mode (m/z 306.08108->275.03888 and 309.009991->275.03888 for sertraline and internal standard, respectively). The limit of quantification of the method was 0.1 ng.g-1 of sertraline and the calibration curve showed a good linearity up to 20 ng.g-1. From the collected data, amount of residues was found in the liver, kidney and brain. In contrast, the incidence of residues in muscle tissue was not detected in all groups, which is favorable from the point of view of fish meat consumption, by humans.

Objectives: The scope of the present study was to specify the therapeutic potential for neurodegenerative diseases through evaluating cholinesterase and tyrosinase (TYR) inhibitory and antioxidant activity of Lysimachia verticillaris (LV), and to isolate the major compounds considering the most active fraction., Materials and Methods: The methanol extract (ME) of LV and the chloroform, ethyl acetate (EtOAC), and aqueous fractions obtained from it were used for biological activity and isolation studies. The ME and all fractions were tested for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and TYR inhibitory and antioxidant potentials using ELISA microtiter assays. Seven major compounds were isolated from the active EtOAC fraction by semi-preparative high performance liquid chromatography. The structures of the compounds were elucidated by several spectroscopic methods., Results: Marked AChE inhibitory activity was observed in the EtOAC fraction (6337±1.74%), BChE inhibitory activity in the ME and EtOAC fraction (85.84±3.01% and 83.82±3.93%), total phenol content in the EtOAC fraction (261.59±3.95 mg equivalent of gallic acid/1 g of extract) and total flavonoid contents in the EtOAC fraction (515.54±2.80 mg equivalent of quercetin/1 g of extract), and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and ferric-reducing antioxidant power values in the aqueous and EtOAC fractions (92.54±0.67%, 92.11±0.30%; 2.318±0.054, 2.224±0.091, respectively). Accordingly, the isolation studies were carried out on the EtOAC fractions. Compounds 1-7 (gallic acid, (+)-catechin, myricetin 3-O-arabinofuranoside, myricetin 3-O-α-rhamnopyranoside, quercetin 3-O-β-glucopyranoside, quercetin 3-O-arabinofuranoside, and quercetin 3-O-α-rhamnopyranoside, respectively) were isolated from the active EtOAC fraction., Conclusion: LV may be a potential herbal source for treatment of neurodegenerative diseases based on its strong antioxidant activity and significant cholinesterase inhibition similar to that of the reference., Competing Interests: Conflicts of interest: No conflict of interest was declared by the authors. The authors alone are responsible for the content and writing of the paper., (©Copyright 2020 Turk J Pharm Sci, Published by Galenos Publishing House.)

Background: Heart rate (HR) at admission in patients with acute heart failure (AHF) has been shown to be an important risk marker of in-hospital mortality. However, its relation with mid and long-term prognosis as well as the impact of Ejection Fraction (EF) is unknown. Our objective was to study the relationship between long-term survival and HR at admission depending on EF in a cohort of patients hospitalized for AHF., Methods: We analyzed the data of 2335 patients in sinus rhythm hospitalized for AHF from AHEAD registry. Patients with cardiogenic shock and AHF from surgical or non-cardiac etiology were excluded., Results: Survival rates at 6 and 12 months were 84.8% and 78% respectively. Increased age, decreased diastolic BP, lack of PCI during hospitalization, increased creatinine level and increased HR (with different cut-offs according to EF categories) were found as predictors whatever the EF at 6 and 12 months. Optimal prognostic cut-offs of heart rate were identified for Heart Failure with reduced EF at 100 bpm, for Heart Failure with mid-range EF at 90 bpm and for Heart Failure with preserved EF at 80 bpm for both 6 and 12 months., Conclusion: Our study suggests that HR at admission appears to be an independent prognostic parameter in AHF patients in sinus rhythm irrespective of EF and can be used to classify patients according to the severity of the disease., Competing Interests: Declaration of conflict of interest The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. BT and FF are employees of Institut de Recherches Internationales Servier (IRIS). All authors declare no potential conflict of interest related to this article., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: Adipose tissue produces a number of adipokines that have metabolic effect. Visfatin is a recently discovered adipokine whose concentration in plasma increases in obesity. It is also a proinflammatory mediator that promotes atherosclerosis and plays a role in plaque destabilization. The aim of this study was to evaluate an assay for the determination of visfatin in human plasma and to investigate its clinical relevance as a marker of acute coronary syndrome (ACS) in a young population (Men under 45 y, Women under 55 y)., Design and Methods: We clinically tested a sandwich ELISA assay in young individuals with acute myocardial infarction (n=36) vs. a control group (n=21). The control sample was a healthy proband without inflammation, hepatic or renal injury and under 55 years of age., Results: Visfatin in plasma was able to differentiate the control group from young patients with acute myocardial infarction (5 vs. 27 ng/L). Visfatin in the plasma of acute myocardial infarction (AMI) probands, correlated in individuals with acute coronary syndrome was related to plasma glucose (r=0.47; P=0.01), type 2 diabetes mellitus (r=0.65; P=0.01), plasma creatinine concentration (r=0.3, P=0.02), hsCRP (r=0.29; P=0.03), BMI values (r=0.18; P=0.04), triglycerides (r=0.5; P=0.01) and NT-proBNP (r=0.21; P=0.04). In healthy subjects, these relations were not found. ROC analysis: visfatin cut-off concentration was 20 ng/L with a sensitivity of 84% and a specificity of 90%. The area under the curve (AUC) of cTNI was 0.96, the AUC of visfatin was 0.96. Thus, there was no difference., Conclusion: We conclude that visfatin in serum may be a new independent potential marker of AMI.

The worldwide consumption of antidepressants is raising as well as their concentrations in the aquatic environment. This increases the risk of food chain contamination and bioaccumulation in aquatic biota. The aim of this study was to describe a potential risk of sertraline as a pollutant from water environment, wherein rainbow trout (Oncorhynchus mykiss) has been chosen as the test organism, because predatory fish are on the top of the food chain in the aquatic environment. The effects of foodborne sertraline were tested on rainbow trout during a 28-day toxicity test according to OECD 215 method. Sertraline was incorporated in commercial feed at a dose of 4.4 µg/kg (environmental concentration), 42 µg/kg and 400 µg/kg. The results confirmed that sertraline has a significant effect on fish behaviour, resulting in suppression of the escape reflex and increased resistance to stress. Moreover, increased Fultońs condition factor was found in fish fed with the highest concentration of sertraline. Haematological analysis revealed a statistically significant increase in the number of neutrophilic bands and neutrophil/lymphocyte ratio, and decreased number of lymphocytes. The results of biochemical examination showed a statistically significant decrease in ammonia and lactate concentrations and histological examination revealed changes in gills and caudal kidney. Although sertraline reduces stress in fish, the decline in nonspecific immunity is a risk to fish population stability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: The prognosis of patients with heart failure (HF) is still generally unfavorable. HF with reduced ejection fraction (HFrEF) patients reach target medication doses in very low percentages in daily clinical practice. HF disease management programs (DMP), including nurse and telemedicine support that facilitate achieving target medication doses, may improve the unfavorable prognosis., Methods: We retrospectively analyzed the data of 738 patients with HFrEF who were followed in a single HF center during the years 1975-2011, for 6.4 (median) years. DMP, nurse and telemedicine support is established at this center., Results: The group achieved left ventricle (LV) recovery after the HF treatment. The median LV ejection fraction improved from 25.0% at baseline to 50.0% at the time of the latest data collection. The proportion of NYHA II, III and IV classes decreased from 27.6%, 30.2% and 29.7% to 26.6%, 7.2% and 0.1%, respectively while the proportion of NYHA class I increased from 12.5% to 66.1%. Median NT-proBNP decreased from 975.0 to 324.0 pg/mL. The survival of the patient group was favorable; 79.7% survived 18.1 years after diagnosis of HF. A high percentage of the patients received recommended target or higher than target doses of angiotensin-converting enzyme inhibitors (82.0%) and beta-blockers (78.1%)., Conclusion: The established pharmacotherapy resulted from an effective DMP and this contributed to the favorable prognosis.

Background: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients., Methods: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 μmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers., Results: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group)., Conclusion: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: The length of hospital stay in patients with acute myocardial infarction and ST-segment elevation (STEMI) has been shortened in recent years with corresponding savings in costs, but there is limited available data on its implementation in clinical practice. The aim of this trial was to determine whether early discharge in selected patients after STEMI is feasible and safe., Methods: 151 patients with STEMI successfully treated with primary percutaneous coronary intervention (PCI) who fulfilled the inclusion criteria of low risk were randomly assigned to two groups on a 1:1 ratio: early (within 48-72 h of admission) and standard (after 72 h) discharge. The primary end point was the composite of death, myocardial infarction (MI), unstable angina, stroke, unplanned rehospitalization, repeated target vessel revascularization and stent thrombosis at 90 days after discharge. The study is registered with ClinicalTrials.gov (identifier NCT02023983)., Results: The primary end point occurred in 5 patients in the early group and 6 in the standard group (6.6% vs. 8.0%, P=0.765). There were no significant differences in the incidence of individual components of the primary end point at 90 days. The length of hospital stay was significantly shorter in the intervention group (60.8 ± 8.5 vs. 92.1 ± 12.1 h, P<0.0001)., Conclusion: This study confirms that early discharge within 48-72 h in selected low risk patients after STEMI treated with successful primary PCI is feasible and safe, with outcomes comparable to the later discharge. This strategy applies to more than a quarter of all STEMI patients.

Background: Detection of new oral anticoagulant (NOAC) levels by screening, special and global tests, and liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) is important in clinical situations when the cause of bleeding needs to be determined., Methods: We compared a routine coagulation test, special function test for NOACs, global coagulation test, and an LC-MS/MS method that enables simultaneous determination of apixaban, dabigatran and rivaroxaban in human plasma within one analysis to determine the optimal indication of the comparison methods, including their limitations and interferences., Results: This study was conducted on a set of blood samples from 116 patients treated with NOACs. The results of both specific dilute thrombin time (dTT) tests for dabigatran provided the same results as the activated partial thromboplastin time (aPTT) screening test in comparison with LC-MS/MS as a reference. The dTT assay HemosIL® showed better results for low concentrations when compared to LC-MS/MS than dTT HYPHEN® as HemosIL® uses a non-linear calibration curve. Results of the specific anti-Xa assay yielded better results than the prothrombin time test in comparison with LC-MS/MS as a reference, especially for apixaban, but also for rivaroxaban. Our LC MS/MS method is simply feasible, but only in a specialized laboratory. The method is easy-to-use for the simultaneous determination of all dabigatran, apixaban and rivaroxaban by LC-MS/MS within three minutes with a concentration range of 1 to 500 µg/L without dilution., Conclusions: In the normal practice of the coagulation laboratory, it is advisable to use specific tests for NOAC determination as screening and global assays are not sufficiently specific. The dTT test is the optimal choice for dabigatran determination and for xabans to determine anti-Xa activity. The LC-MS/MS method is suitable as an arbitration method for serious conditions.

Objective: Paroxysmal hypertension or pseudopheochromocytoma is quite a common problem in clinical practice. The optimal treatment for this condition has not been established. This study sought to investigate whether sertraline (a selective serotonin reuptake inhibitor) reduces the symptoms., Methods: We enrolled 64 patients referred to our department between April 2008 and October 2014 for symptomatic paroxysmal hypertension. Patients received sertraline, 50 mg once daily, in addition to their current medication. The effect of the treatment was assessed during their next clinical visit at least 3 months later., Results: Of the 64 patients, 57 (89%) also had sustained arterial hypertension. Mean office baseline blood pressure (BP) was 147.6/83.8 mmHg and patients used a mean of 3.1 antihypertensive drugs. Five patients did not start using sertraline and three were lost to follow-up. Of the 56 patients who started using sertraline and who came for check up, clinical improvement was observed in 42 (75%) patients - symptoms of paroxysmal hypertension fully subsided in 28 (50%) and were partially reduced in 14 (25%) . Side effects or intolerance leading to discontinuation of treatment occurred in 7 patients (12.5%). Mean office BP in patients using sertraline decreased by 12.8/7.4 mmHg (P<0.001 for both)., Conclusions: Sertraline effectively removed or reduced symptoms of paroxysmal hypertension in the majority of patients who used this treatment.

Sleep apnoea (SA) is common in patients with hypertension. Nowadays, limited data on the prevalence of SA in nocturnal hypertension (NH) exist. Therefore, we studied the occurrence of SA in Czech patients and its association with 24-h ambulatory blood pressure monitoring (ABPM), breathing disturbances in sleep, anthropometric data, Mallampati score and Epworth sleepiness scale (ESS) using the Apnea Link device. Undiagnosed SA was found in 72.9 % patients (29.3 % mild, 26.6 % moderate, 17.0 % severe) of 188 patients with NH measured by ABPM. The median of the apnoea-hypopnoea index (AHI) was 12.0 (25th-75th percentile 5.0-23.8). Moderate/severe SA (AHI>/=15) was associated with BMI, waist circumference, mean night saturation (SpO(2)), t90, oxygen desaturation index (ODI), ESS (daytime BP only) (p0.09). A likelihood of moderate/severe SA was enhanced by ODI>14.5 events/h (odds ratio=57.49, 95 % CI=22.79-145.01), t90>6.5 % (8.07, 4.09-15.92), mean night SpO(2)<93.5 % (3.55, 1.92-6.59), BMI>29.05 kg/m(2) (6.22, 3.10-12.49), circum waist>105.5 cm (3.73, 1.57-8.83), but not by any ABPM parameter. In conclusion, a high incidence of SA (72.9 %) was observed in Czech patients with NH. SA severity was associated with body characteristics and oxygenation parameters, but not with ABMP parameters and Mallampati score.

Adipokines are peptides that signal the functional status of adipose tissue to the brain and other target organs. In adipose tissue dysfunction, adipokine secretion is altered, and this can contribute to a spectrum of obesity-associated conditions including cardiovascular disease. Some adipokines have anti-inflammatory and cardioprotective effects (omentin, apelin, adiponectin). Others are pro-inflammatory with negative impact on cardiovascular function (leptin, visfatin, resistin, adipocyte fatty-acid-binding protein). In the first part, this article reviews the endocrine functions of adipose tissue in general, effects of the distribution and composition of fat tissue, and the roles of cortisol and the renin-angiotensin-aldosterone system in the development of the inflammatory state of addipose tissue. In the second part, the known cardiovascular effects of different adipokines and their clinical potential are discussed in detail.

Aims: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial., Methods and Results: A total of 5856 patients from the AHEAD registry (Czech registry of AHF) were divided into two groups according to RELAX-AHF criteria: relax-comparable ( n  = 1361) and relax-non-comparable ( n  = 4495). As compared with the relax-non-comparable group, patients in the relax-comparable group were older, had higher levels of systolic and diastolic blood pressure, lower creatinine clearance, and a higher number of comorbidities. Relax-comparable patients also had significantly lower short-term as well as long-term mortality rates in comparison to relax-non-comparable patients, but a significantly higher mortality rate in comparison to the placebo group of patients from the RELAX-AHF trial. Using AHEAD score, we have identified higher-risk patients from relax-comparable group who might potentially benefit from new therapeutic approaches in the future., Conclusions: Only about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin. AHF patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial.

Aim: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals., Methods: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed., Results: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files., Conclusions: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use., (© The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Objectives: Omentin-1 is an adipokine which could have a protective role against the manifestation of atherosclerosis. Only limited data are available on omentin-1 serum values in patients with premature clinical manifestations of atherosclerosis., Design and Methods: We tested omentin-1 in human serum by ELISA method in 61 individuals with a premature manifestation of coronary artery disease (CAD), 40 patients with metabolic syndrome and 40 healthy control subjects., Results: Omentin-1 serum levels were significantly lower in patients with CAD (103.1±62.7 mg/L) compared to metabolic syndrome (668.2±339.6 mg/L) and healthy subjects (623.0±373.5 mg/L) (P < 0.01). In CAD patients, omentin-1 serum levels did not differ between patients sampled in the acute phase of myocardial infarction (n = 28; 110.3±82.4 mg/L) and in the chronic phase several months or years after myocardial infarction (n = 33; 97.0±39.3 mg/L) (P = 0.41). We found a weak positive correlation between omentin-1 and body mass index (r = 0.21, P = 0.014). No significant correlation was found between peak cardiac troponin T and omentin-1 (correlation coefficient r = 0.118, P = 0.406)., Conclusion: Serum omentin-1 seems to be a useful biomarker of coronary artery disease across the whole age spectrum.

Background: The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 μmol/l), D--diabetes mellitus) scoring system., Methods: AHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315)., Results: Main outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001)., Conclusion: The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking., Methods: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters., Results: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure., Conclusion: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Introduction: Primary hyperaldosteronism is a common cause of secondary hypertension. In patients with proven unilateral overproduction of aldosterone adrenalectomy can cure hyperaldosteronism with high probability and a positive effect on hypertension. The aim of the study was to determine the effects of unilateral adrenalectomy on blood pressure and laboratory parameters. The secondary objective was to identify parameters that would allow the prediction of hypertension cure., Methods: We performed a cross-sectional analysis of the data of patients who underwent unilateral adrenalectomy for primary aldosteronism at the Department of Urology of University Hospital Olomouc in the years 2000-2011. We assesed the preoperative clinical conditions of patients, the results of biochemical and radiological examinations, course of the surgery and post-operative course including laboratory and clinical parameters during the 12 months postoperatively., Results: 62 patients underwent adrenalectomy for primary aldosteronism in this period. Four patients were excluded from the study due to surprising histology (myelolipoma in 2, carcinoma in 2), seven patients had incomplete postoperative data. The statistical analysis therefore included 51 patients, of which 57% were females. CT or MRI was performed in all patients; 63% patients underwent superselective catheterization of adrenal veins (AVS). Adrenalectomy was performed in all cases laparoscopically. Histology most often showed adrenal hyperplasia (59%), adenoma was detected in 37% and adenoma on the basis of micronodular hyperplasia in 4%. Twelve months after surgery the antihypertensive drugs were discontinued in 17/51 (33%) and the number or dose of antihypertensive drugs was reduced in 25/51 (49%). Normokalemia and normalisation of the aldosterone-renin ratio (ARR) was detected in 92% and 84% of the patients. Performing AVS did not statistically significantly influence the rate of blood pressure control or normalization of ARR, which is probably due to small study size. This study demonstrated a better effect of surgery on blood pressure in younger patients., Conclusions: Unilateral adrenalectomy had a positive effect in 82% of the patients operated for primary aldosteronism and lead to either blood pressure normalization or reduction of the antihypertensive medication.

Aims: To assess the acute side-effects of right ventricular (RV) stimulation applied in apex and mid-septum, in order to establish the optimal lead location in clinical practice., Methods: During pacemaker implantation, the ventricular lead was temporarily fixed in the apex and then moved to mid-septum. In both positions, surface and endocardial electrograms and transvalvular impedance (32 cases), left ventricular (LV) pressure (23), and transthoracic echocardiography (10) were acquired with intrinsic activity and VDD pacing., Results: A larger increase in QRS duration was noticed with apical than septal pacing (65±25 vs. 45±29 ms; P<10(-4)). The proportion of cases where RV stimulation affected the transvalvular impedance waveform was higher with apical lead location (56% vs. 20%; P<0.02). VDD pacing at either site reduced the maximum dP/dt by 6% with respect to intrinsic AV conduction (IAVC; P<0.005). The maximum pressure drop taking place in 100 ms was reduced by 6 and 8%, respectively, with apical and septal pacing (P<0.01 vs. IAVC). Apical VDD decreased mitral annulus velocity in early diastole (E') from 7.5±1.4 to 5.9±0.9 cm/s (P<0.02) and prolonged the E-wave deceleration time (DT) from 156±33 to 199±54 ms (P<0.02), while septal pacing induced non-significant modifications in E' and DT., Conclusion: Ventricular stimulation acutely impairs LV systolic and diastolic performance, independent of the pacing site. Septal lead location preserves RV contraction mechanics and reduces the electrical interventricular delay.

Methods: The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930), COX-1 (-842A>G; rs10306114), GPVI (13254T>C; rs1613662), and GPIbA (5T>C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics)., Results: The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05., Conclusion: The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1&#95;A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T>C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T>C), or GP6 (T13254C) and response to antiplatelet therapy with 75 mg of clopidogrel.

Background: There are currently limited data on whether the effect of spironolactone in patients with resistant arterial hypertension depends on age and sex., Methods: Patients with an office systolic blood pressure (BP)>140 mmHg or diastolic BP>90 mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic, were randomly assigned to receive spironolactone or a placebo for 8 weeks in a double-blind, placebo-controlled, multicentre trial (ASPIRANT)., Results: Analyses were done on 55 patients treated with spironolactone and 56 patients treated with placebo. Significant reductions of office systolic BP (-8.9±6.7 mmHg, P=0.012), 24-h ABPM systolic BP (-7.9±7.2 mmHg, P=0.032) and ABPM day-time systolic BP (-7.5±7.1 mmHg) after 8 weeks of spironolactone treatment, compared to placebo, were only observed in patients with a median age>62 years. The office and ABPM systolic BP reductions in patients aged ≤62 years and diastolic BP reductions by spironolactone in both age groups were not significant compared to placebo. Women tended to have a nonsignificantly higher reduction in systolic BP with spironolactone treatment, and there was no difference in diastolic BP reduction between women and men., Conclusions: Spironolactone only leads to a reduction of systolic BP in older patients with resistant arterial hypertension aged >62 years, and is effective to a similar extent in men and women.

Purpose: The purposes of this study are to identify the strongest clinical parameters in relation to in-hospital mortality, which are available in the earliest phase of the hospitalization of patients, and to create an easy tool for the early identification of patients at risk., Materials and Methods: The classification and regression tree analysis was applied to data from the Acute Heart Failure Database-Main registry comprising patients admitted to specialized cardiology centers with all syndromes of acute heart failure. The classification model was built on derivation cohort (n = 2543) and evaluated on validation cohort (n = 1387)., Results: The classification tree stratifies patients according to the presence of cardiogenic shock (CS), the level of creatinine, and the systolic blood pressure (SBP) at admission into the 5 risk groups with in-hospital mortality ranging from 2.8% to 66.2%. Patients without CS and creatinine level of 155 μmol/L or less were classified into very-low-risk group; patients without CS, creatinine level greater than 155 μmol/L, and SBP greater than 103 mm Hg, into low-risk group, whereas patients without CS, creatinine level greater than 155 μmol/L, and SBP of 103 mm Hg or lower, into intermediate-risk group. The high-risk group patients had CS and creatinine of 140 μmol/L or less; patients with CS and creatinine level greater than 140 μmol/L belong to very-high-risk group. The area under receiver operating characteristic curve was 0.823 and 0.832, and the value of Brier's score was estimated on level 0.091 and 0.084, for the derivation and the validation cohort, respectively., Conclusions: The presented classification model effectively stratified patients with all syndromes of acute heart failure into in-hospital mortality risk groups and might be of advantage for clinical practice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The in-hospital mortality of patients with acute heart failure (AHF) is reported to be 12.7% and mortality on day 30 after admission 17.2%. Less information is known about the long-term prognosis of those patients discharged after hospitalization. As such, the aim of this study was to investigate long-term survival in a cohort of patients who had been hospitalized for AHF and then discharged., Methods: The AHEAD Main registry includes 4153 patients hospitalized for AHF in 7 different medical centers, each with its own cathlab, in the Czech Republic. Patient survival rates were evaluated in 3438 patients who had survived to day 30 after admission, and were used as a measurement of long-term survival., Results: The most common etiologies were acute coronary syndrome (32.3%) and chronic ischemic heart disease (20.1%). The survival rate after day 30 following admission was 79.7% after 1 year and 64.5% after 3 years. No statistically significant difference in syndromes was found in survival after day 30. Independent predictors of a worse prognosis were defined as follows: age>70 years, comorbidities, severe left ventricular systolic dysfunction, valvular disease or ACS as an etiology of AHF. A better prognosis was defined for de-novo AHF patients, and those who were taking ACE inhibitors at the time of discharge. In a sub-analysis, high levels of natriuretic peptides were the most powerful predictors of high-risk, long-term mortality., Conclusion: The AHEAD Main registry provides up-to-date information on the long-term prognosis of patients hospitalized with AHF. The 3-year survival of patients following day 30 of admission was 64.5%. Higher age, LV dysfunction, comorbidities and high levels of natriuretic peptides were the most powerful predictors of worse prognosis in long-term survival., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: There are currently limited data about whether the effect of spironolactone in patients with resistant arterial hypertension depends on baseline blood pressure and the presence of a secondary cause of hypertension., Methods: Patients with office systolic blood pressure (BP) >140 mmHg or diastolic BP >90 mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic, were randomly assigned to receive spironolactone or a placebo for 8 weeks in a double-blind, placebo-controlled, multicentre trial (ASPIRANT)., Results: Analyses were done with 55 patients treated with spironolactone. The degree of BP reduction after 8 weeks of spironolactone treatment did not differ significantly between the three tertiles of baseline systolic BP and patients with and without a secondary cause of hypertension. The reduction of office systolic, office diastolic BP and office pulse pressure was significantly lower in the highest tertile with baseline diastolic BP > 97 mmHg., Conclusions: Spironolactone treatment is effective to a similar extent both in patients with and without a secondary cause of hypertension and regardless of the baseline value of systolic BP. Less effect of spironolactone was found in patients with the highest baseline diastolic BP.

An adaptive system for the suppression of vibration transmission using a single piezoelectric actuator shunted by a negative capacitance circuit is presented. It is known that by using a negative-capacitance shunt, the spring constant of a piezoelectric actuator can be controlled to extreme values of zero or infinity. Because the value of spring constant controls a force transmitted through an elastic element, it is possible to achieve a reduction of transmissibility of vibrations through the use of a piezoelectric actuator by reducing its effective spring constant. Narrow frequency range and broad frequency range vibration isolation systems are analyzed, modeled, and experimentally investigated. The problem of high sensitivity of the vibration control system to varying operational conditions is resolved by applying an adaptive control to the circuit parameters of the negative capacitor. A control law that is based on the estimation of the value of the effective spring constant of a shunted piezoelectric actuator is presented. An adaptive system which achieves a self-adjustment of the negative capacitor parameters is presented. It is shown that such an arrangement allows the design of a simple electronic system which offers a great vibration isolation efficiency under variable vibration conditions.

Background: There is currently limited data on which drug should be used to improve blood pressure control in patients with resistant hypertension. Recent observational trials reported spironolactone as having good effects. This study is designed to assess the effect of the addition of 25 mg of spironolactone on blood pressure (BP) in patients with resistant arterial hypertension., Methods: Patients with office systolic BP > 140 mmHg or diastolic BP > 90 mmHg despite treatment with at least 3 antihypertensive drugs including a diuretic, are enrolled in this double-blind, placebo-controlled, multicentre trial. Patients are randomly assigned to receive spironolactone or a placebo at a ratio of 1:1 by the method of simple randomisation. Our primary endpoints are to show a statistically significant difference in the fall of mean day-time systolic and diastolic BP by ambulatory blood pressure monitoring (ABPM), between the spironolactone and placebo groups, after 8 weeks of treatment. Secondary outcomes are changes of serum potassium, natrium, creatinine, body weight, casual blood pressure in office, difference in the fall of mean night-time and 24-hour ABPM BP and treatment response depending on different baseline levels of aldosterone and aldosterone/PRA ratio., Discussion: If spironolactone proves effective, it might become the standard of treatment in patients with resistant arterial hypertension.

Patients with ischemic heart disease and depressed left ventricular (LV) ejection fraction (LVEF) develop varying degrees of LV remodeling after cardiac surgical revascularization. Fifty-three patients with stable ischemic heart disease and impaired LV function (LVEF 34.9 ± 4%) were prospectively followed up for 24 months. Thirty-seven patients underwent coronary artery bypass grafting (CABG), 16 patients were treated conservatively. Cardiac magnetic resonance imaging (MRI) and SPECT were performed at baseline and after 12 and 24 months of follow-up. The patients were divided into responders and non-responders depending on the degree of LVEF improvement at 24 months follow-up (>5%-responders). MRI with ≤5 segments with DE/wall thickness ratio (DEWTR) ≥50% predicted LV reverse remodeling with a sensitivity of 86% and a specificity of 75% (AUC 0.81). An MRI finding of ≤2 segments with the DEWTR ≥75% had a corresponding sensitivity of 71% and specificity of 67% (AUC 0.75) while fixed perfusion defect on SPECT <16.5% of LV predicted reverse remodeling with a sensitivity of 64% and a specificity of 69% (AUC 0.64). A preoperative number of segments with the DE/wall thickness ratio of ≥50 and ≥75% obtained by MRI, was found to be a better predictor of left ventricular reverse remodeling than fixed perfusion defect by SPECT. No other MRI or SPECT parameter predicted LVEF improvement at 24 months after CABG., (© Springer Science+Business Media, B.V. 2010)

The aim of our work was to develop an assay for the determination of proguanylin in human blood, and investigate its levels in healthy volunteers and donors suffer from hypertension often accompanied by body sodium accumulation and plasma volume expansion. We developed and evaluated the sandwich ELISA method for the quantitative determination of human proguanylin in serum samples. We conducted also the pilot study on individuals with hypertension and oh healthy probands and measured proguanylin serum levels, serum and urine sodium and creatinine levels. In the study on 256 healthy volunteers we demonstrated that women have significantly higher values of proguanylin than men (medians 12.7 vs. 9.6 ng/ml, p < 0.01) and proguanylin values increased with age of individuals (p < 0.01). Futhermore, we tested 17 individuals with hypertension and found that probands with anamnesi of hypertension had higher proguanylin values than healthy individuals from the first study (medians 16.2 vs. 11.3 ng/ml, p < 0.01). Both of groups did not differ in sex or age. Proguanylin values correlated with the systolic blood pressure (r = 0.41, p < 0.01), sodium fraction excretion (r = 0.72, p < 0.01) and serum sodium (r = -0.39, p < 0.01). No significant correlation we found with serum proguanylin and creatinine. In the group of 9 healthy probands we demonstrated the existence of a diurnal rhythm of proguanylin with its maximum in the evening hours (between 6-10 p.m.). The pilot study supports the hypothesis about the role of proguanylin in sodium metabolism and its possible importance for hypertension disorder. Further research is necessary to confirm our findings in individuals with hypertension with different medication in order to assess proguanylin value as a risk predictor of accelerated hypertension, and to classify individuals with hypertension for variuos types of diuretic therapy.

Tokamaks with large pressure gradients (alpha(max)) formed in regions of weak magnetic shear are shown to be susceptible to novel, low-n, global, kinetic, electromagnetic modes with a toroidal mode number n in the range 21 on the magnetic axis and alpha(max) near q(min), new, global kinetic infernal modes with a strong mode rotation omega(r) and a finite growth rate gamma<|omega(r)| are found. For equilibria with reverse shear where q(min) is off axis and alpha(max) near q(min), the existence of an unstable low-n global branch of Alfve n ion temperature gradient modes is revealed with an oscillatory gamma as a function of n. The addition of trapped electron dynamics is shown to be further destabilizing.