Prognostic value of plasma secretoneurin concentration in patients with heart failure with reduced ejection fraction in one-year follow-up.

BACKGROUND: This is the first study to examine the clinical utility of measuring plasma secretoneurin (SN) levels in patients with heart failure with reduced ejection fraction (HFrEF), as a predictor of unplanned hospitalization, and all-cause mortality independently, and as a composite endpoint at one-year follow-up. METHODS: The study group includes 124 caucasian patients in New York Heart Association (NYHA) classes II to IV. Plasma SN concentrations were statistically analyzed in relation to sex, age, BMI, etiology of HFrEF, pharmacotherapy, clinical, laboratory and echocardiographic parameters. Samples were collected within 24 h of admission to the hospital. KEY RESULTS: In the 12-month follow-up, high SN levels were noted for all three endpoints. CONCLUSIONS: SN positively correlates with HF severity measured by NYHA classes and proves to be a useful prognostic parameter in predicting unplanned hospitalizations and all-cause mortality among patients with HFrEF. Patients with high SN levels may benefit from systematic follow-up and may be candidates for more aggressive treatment.

Therapeutic Drug Monitoring of Direct Oral Anticoagulants in Patients with Extremely Low and High Body Weight-Pilot Study.

Phase III clinical trials for individual direct oral anticoagulants (DOACs) contained a limited representation of subjects with abnormal body weight, which were mostly limited to a BMI > 40 kg/m2, or body weight > 120 kg for obese subjects, and <50 kg for underweight subjects. Although low or high body weight is not a contraindication to DOACs therapy, it can significantly affect the safety and effectiveness of treatment. Due to the limited amount of clinical data on the use of DOACs in extremely abnormal weight ranges, optimal pharmacotherapy in this group of patients is a matter of controversy. The objective of this study was to evaluate the pharmacokinetics of DOAC properties in patients with abnormal body weight beyond the established cut-off points in the phase III studies for rivaroxaban, apixaban, and dabigatran. In total, 38 patients took DOACs for at least 12 months for non-valvular atrial fibrillation in 2019-2021. Blood samples were collected before the planned intake of the drug and 4 h after its administration. The determined concentrations of DOACs were statistically analyzed in relation to body weight, age, and eGFR (estimated Glomerular Filtration Rate). Among subjects taking apixaban, rivaroxaban, and dabigatran, the smallest representation of patients who achieved therapeutic concentrations were those treated with dabigatran. The population of people with abnormal body weight is a potential risk group of patients, in which some of them do not reach the therapeutic range of DOACs.

Implementation of recommendations on the check of risk factors for cardiovascular diseases in patients undergoing coronary re-interventions.

METHOD: The study involved 905 patients after coronary interventions, qualified for invasive diagnosis due to symptomatic coronary disease. AIM: The aim of this study was to check the implementation of recommendations on the control of risk factors for cardiovascular diseases in patients undergoing re-interventions. RESULTS: Compared to elderly persons, younger people more often increased their physical activity (62 vs. 65 years, p = 0.009), stopped smoking (61 vs. 65 years, p < 0.001) and reduced alcohol consumption (62 vs. 65 years, p = 0.001). People with secondary and higher education increased their physical activity more often than those with primary education (51%, 31% vs. 23%, p = 0.006). Men more often than women decided to limit their alcohol consumption (48% vs. 37%, p = 0.007). Patients with a history of acute coronary syndrome were more likely to quit smoking and reduce their alcohol consumption than those without such a history (47% vs. 37%, p = 0.003 and 42% vs. 34%, p = 0.020, respectively). Only 2% of the subjects achieved the recommended LDL cholesterol values. Forty-eight percent were qualified for reinvasive procedures on the coronary arteries. Less than half of the patients undertook health-promoting behaviors that required modification of existing habits. CONCLUSION: Age, gender, and education level influence pro-health behaviors. The majority of patients do not achieve the levels of LDL cholesterol and triglycerides consistent with the ESC guidelines in the secondary prevention of coronary disease. Inadequate check of risk factors may result in faster disease progression and coronary re-interventions.

Alcohol and Cardiovascular Diseases-Do the Consumption Pattern and Dose Make the Difference?

Excessive consumption of alcohol is not only a social problem, but it also significantly increases the morbidity and mortality rates of many societies. A correlation has been demonstrated between alcohol consumption and increased mortality from cancer, accidents and injuries, liver cirrhosis and other causes. Alcohol abuse increases the incidence of hemorrhagic stroke and the risk of ischemic stroke, induces serious arrhythmias, adversely affects blood pressure and damages the heart muscle. The dose and way of drinking alcohol play a crucial role in assessing whether this drink allows people to maintain health or whether it is a great health and social threat. The beneficial effects of low and moderate doses of alcohol on the occurrence of cardiovascular diseases have been shown in many population studies and meta-analyses in which the effect of U-shaped or J-shaped curves relating alcohol intake to cardiovascular mortality was observed, especially in ischemic heart disease. However, due to the fact that alcohol consumption is associated with many health hazards, it is not recommended to consume it as a preventive action of cardiovascular diseases. Moreover, recent studies suggest that association of low-to-moderate alcohol consumption with the reduction in cardiovascular risk is a result of lifestyle changes and that any reduction in alcohol consumption is in fact beneficial in terms of general health.

The importance of pharmacokinetics, pharmacodynamic and repetitive use of levosimendan.

Levosimendan was introduced into routine clinical practice in 2000, obtaining approval for the treatment of decompensation of severe chronic heart failure. Levosimendan increases the calcium sensitivity of contractile proteins by binding to myocardial troponin C (cTnC) in a calcium dependent manner. Apart from the mechanism of action of levosimendan, resulting directly in the improvement of heart function, a number of pleiotropic mechanisms have also been identified, including anti-inflammatory, antioxidant and anti-apoptotic effects. Pharmacokinetics of levosimendan is linear in a therapeutic dose range i.e. from 0.05 to 0.2 µg/kg/min. Therapeutic concentration of levosimendan is reached approximately 1 h after the start of intravenous infusion, and steady state is reached within 5 h after continuous infusion initiation. OR-1855 and OR-1896 are the only significant metabolites detected in the systemic circulation after administration of levosimendan. After a 24-hour infusion of levosimendan, the pharmacodynamic effect of the drug is observed for at least one week. Repetitive levosimendan infusions are safe and multiple infusions of levosimendan show a number of benefits. However, experience with multiple doses of levosimendan is scarce. The protocols of clinical trials conducted so far on repeated and intermittent infusions of levosimendan were developed subjectively and were based on the opinion of experts forming a given research team. There is still a need for more clinical research on the multidirectional effect of levosimendan in the group of patients with heart failure. The aim of this review was to summarize most relevant and up-to-date scientific data on pharmacokinetic and pharmacodynamic basis of levosimendan repetitive use in clinical practice that may assist in bedside decision making.

Therapeutic Drug Monitoring of Carbamazepine: A 20-Year Observational Study.

BACKGROUND: Carbamazepine (CBZ) is a first-generation anticonvulsant drug. Hence, in certain cases, therapeutic drug monitoring (TDM) supports pharmacotherapy. METHODS: The presented research was based on a retrospective analysis including 710 ambulatory and hospitalized patients treated with CBZ between the years 1991 and 2011. The method used for the determination of the CBZ concentration was fluorescence polarization immunoassay (FPIA) performed using an Abbott GmbH TDx automatic analyzer, with the therapeutic range for carbamazepine being 4-12 µg/mL. RESULTS: The therapeutic range was observed more often in patients between 3 and 17 years of age compared with the population ≥18 years of age (73.5% vs. 68.8%). The therapeutic level was exceeded less frequently in the population between 3 and 17 years of age despite them being given a significantly higher dose per kilogram of body weight than in the population ≥18 years of age (13.64 mg/kg vs. 10.43 mg/kg, p < 0.0001). Patients ≥18 years of age were statistically significantly more likely to be in the group with a suspected drug overdose (73.9% vs. 26.1%), and suicide attempts only occurred in elderly patients (100.0% vs. 0.0%, p = 0.003). CONCLUSION: The results of the TDM of CBZ showed that only 71% of all samples were at the therapeutic level. To ensure the maximum efficacy and safety of the therapy, it is necessary to monitor the concentration of CBZ regardless of sex and age.

The Clinical Significance of Drug-Food Interactions of Direct Oral Anticoagulants.

Cardiovascular diseases are the most common cause of death in the world. For almost 60 years, vitamin K antagonists (VKAs) were the mainstay of anticoagulation therapy, but in recent years direct oral anticoagulants (DOACs) have become the anticoagulant treatment of choice. DOACs were initially considered drugs with no significant food interactions; however, clinical observations from daily practice have proved otherwise as interactions with food ingredients have been reported. Food, dietary supplements or herbs may contain substances that, when administered concomitantly with DOACs, can potentially affect the plasma concentration of the drugs. The aim of this paper was to evaluate the clinical significance of drug-food interactions of DOACs, such as dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban. Patients treated with anticoagulants should avoid products containing St. John's wort and take special care with other food ingredients. As the interest in dietary supplements is on the rise, healthcare providers can contribute to the development of well-designed clinical trials on interactions between DOACs and food, and distribute sufficient knowledge about the proper use of these supplements among patients.

Treatment of Hypertension Because of Immunosuppressive Therapy After Solid Organ Transplantation-Pharmacological Approach.

ABSTRACT: Solid organs transplantation procedures have been performed for more than half a century. Growing knowledge of immune response and development of new immunosuppressive regimens guarantee more and more successful outcomes. However, many of the applied drugs lead to cardiovascular complications, the most frequent of which is hypertension. This article describes epidemiology, pathogenetic mechanisms, and treatment of hypertension induced by immunosuppressive medication. The main impact is focused on drugs belonging to the following groups: calcineurin inhibitors, the inhibitors of the mammalian target of rapamycin, and glucocorticosteroids. We analyze the mechanism of action of the main hypertensive drugs and their influence on the reversing hypertonic action of the immunosuppressive agents. In the absence of current guidelines addressing this problem, this article is an attempt to fill the gap, helping clinicians to choose proper medication.

Resveratrol and cardiovascular system-the unfulfilled hopes.

INTRODUCTION: Resveratrol is a natural polyphenolic compound with a stilbene structure endowed with multiple health-promoting effects. Among phenolic compounds, resveratrol is assigned a leading role in the health-promoting effects of red wine. METHODS: The aim of the study was to assess the effect of resveratrol on the cardiovascular system in the experimental and clinical studies conducted so far. Moreover, the paper discusses the results of the most recent meta-analyses assessing resveratrol's therapeutic effect on the cardiovascular system in humans. RESULTS: In animal and preclinical studies, resveratrol has demonstrated a wide physiological and biochemical spectrum of activity, including antioxidant, anti-inflammatory, antiplatelet, and anticoagulant activities, which translated into its health-promoting effects on the cardiovascular system. The performed meta-analyses allow to confirm such an impact, however, after the assessment with the use of the SYRCLE's tool, these studies are burdened with a high risk of bias, and the results are not clearly presented. CONCLUSION: Despite numerous articles and clinical studies, the convincing beneficial mechanisms of resveratrol as well as its health-promoting effects in cardiovascular diseases have not been clearly confirmed in humans. Therefore, there is a need for further clinical studies, especially randomized, double-blind, placebo-controlled trials to objectively confirm the possible health-promoting effects of this substance and to determine both the efficacy and safety, and possible therapeutic potential.

Catestatin as a New Prognostic Marker in Stable Patients with Heart Failure with Reduced Ejection Fraction in Two-Year Follow-Up.

Background and Purpose. The main goal of the study was to assess the usefulness of plasma concentrations of catestatin as a predictor of a composite endpoint (CE): unplanned hospitalization and death for all causes in patients with HFrEF in the midterm follow-up. Experimental Approach. The study group consisted of 52 Caucasian patients in NYHA classes II and III. The control group consisted of 24 healthy volunteers. The biomarkers, whose concentration was assessed before and after physical exertion as well as the variability of their concentration under the influence of the physical exertion, were NT-proBNP, troponin T, and catestatin. Key Results. During the 24-month follow-up period, 11 endpoints were recorded. The univariate analysis of the Cox proportional hazard model showed a statistically significant effect of all assessed CST concentrations on the occurrence of CE. In the 24-month follow-up, where the starting concentration of catestatin was compared with other recognized prognostic factors in HF, the initial concentration of catestatin showed statistical significance in CE prognosis as the only parameter tested. Conclusions. Plasma concentration of catestatin before and after physical exertion is a valuable prognostic parameter in predicting death from all causes and unplanned hospitalization in the group of patients with HFrEF in the 2-year follow-up.

The Interactions of Nintedanib and Oral Anticoagulants-Molecular Mechanisms and Clinical Implications.

Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families. The drug also affects other kinases, including Src, Flt-3, LCK, LYN. Nintedanib is used in the treatment of idiopathic pulmonary fibrosis, chronic fibrosing interstitial lung diseases and lung cancer. The mechanism of action suggests that nintedanib should be considered one of the potential agents for inhibiting and revising the fibrosis process related to COVID-19 infections. Due to the known induction of coagulation pathways during COVID-19 infections, possible interaction between nintedanib and anticoagulant seems to be an extremely important issue. In theory, nintedanib could increase the bleeding risk, thrombosis and lead to thrombocytopenia. The data from clinical trials on the concomitant use of nintedanib and antithrombotic agents is very limited as this patient group was within the standard exclusion criteria. Nintedanib is an important therapeutic option, despite its interaction with anticoagulants. If anticoagulant therapy is necessary, the more effective and safer option is the concomitant administration of DOACs and nintedanib, especially when drug-monitored therapy will be used in patients at high risk of bleeding complications.

Bone morphogenetic protein 6-a possible new player in pathophysiology of heart failure.

Derangement of bone morphogenetic protein (BMP) signalling was observed in cardiovascular disorders. The present study assesses the diagnostic and prognostic value of BMP6 plasma concentration in chronic heart failure (CHF). 130 CHF patients and 32 controls participated in the study. BMP6 plasma level was measured at baseline. During 12-month follow-up death and hospitalisation with CHF exacerbation were recorded. BMP6 was significantly increased in CHF patients with highest concentration in most advanced disease. Individuals with pulmonary congestion or peripheral oedema had higher levels of BMP6 than isovolemic patients. BMP6 was not a predictor of all-cause mortality or CHF hospitalisation. BMP6 may be involved in pathophysiology of systolic CHF. BMP6 plasma level is related to the disease severity and signs of exacerbation.

Prognostic significance of red cell distribution width and other red cell parameters in patients with chronic heart failure during two years of follow-up.

BACKGROUND: Studies published during the last decade seem to indicate red blood cell parameters as inexpensive, rapidly available, and simple tools for the assessment of prognosis in patients with chronic heart failure (CHF). AIM: To evaluate the prognostic value of red cell parameters determined in a routine blood count in patients with CHF. METHODS: The study group included 165 patients with the New York Heart Association (NYHA) class II-IV CHF hospitalised in the 2nd Department of Cardiology in Bydgoszcz. On the first day of hospitalisation, all patients in the study group underwent a complete blood count with an assessment of haemoglobin (Hb) level, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red blood cell distribution width (RDW). Follow-up was carried over 24 months by phone calls every 3 months. RESULTS: MCV, MCH and MCHC were not shown to be significant predictors of mortality in CHF patients at 1 and 2 years of follow-up. In univariate analysis at 1-year follow-up, the following variables were significantly associated with the occurrence of the study endpoint: Hb level (p = 0.022; HR = 0.80), RDW (p = 0.004; HR = 1.257), and N-terminal pro-B-type na-triuretic peptide (NT-proBNP) level (p = 0.0001; HR = 1). At 2 years of follow-up, the following variables were significantly associated with the occurrence of the study endpoint: left ventricular ejection fraction (p = 0.018; HR = 0.956), NYHA class (p = 0.007; HR = 0.378), RDW (p = 0.044; HR = 1.175), and NT-proBNP level (p < 0.001; HR = 1). Multivariate analysis for 1-year follow-up showed that RDW and NT-proBNP level were independent significant predictors of mortality, while NT-proBNP level (p = 0.006; HR = 1) and NYHA class (p = 0.024; HR = 0.439) were significant predictors of mortality at 2 years of follow-up. Based on receiver operating characteristic curve analysis, the cut-off RDW was 15.00% (AUC = 0.63; 0.523-0.737), at 12 months of follow-up and 14.00% (AUC = 0.6; 0.504-0.697), at 24 months of follow-up. The cut-off for Hb level was 13.9 g/dL (AUC = 0.662; 0.553-0.77), at 12 months of follow-up and 12.2 g/dL (AUC = 0.581; 0.482-0.681), at 24 months of follow-up. CONCLUSIONS: Baseline RDW and Hb level in patients hospitalised with the diagnosis of NYHA class II-IV CHF seem to be important predictors of mortality in this population. Among the red blood cell parameters, only RDW was shown to be an independent prognostic factor at 1 year of follow-up but it appeared to lose its significance during longer-term follow-up.