Neuregulin-1β, Biomarkers of Inflammation and Myocardial Fibrosis in Heart Failure Patients

Heart failure with preserved ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Little progress has been in the treatment of this condition since its introduction some 30 years ago. It's accepted that HFpEF is heterogeneous in many ways, ethologically and phenotypically. The underlying mechanisms of the syndrome are not clear. Recently, it has been shown that the diagnostic criteria for HFpEF lacks sensitivity and specificity. Novel treatment approaches, which were developed based on current HFpEF pathophysiological concepts, did not show either clinical or prognostic benefit for patients. Therefore, there is an urgent need to revise current diagnostic approaches and to further investigate the underlying mechanisms. Recently, two novel diagnostic score systems were proposed: H2PEF and HFA-PEFF. Recently, a number of phase II and III randomized control trials have been completed. Here, the authors discuss the potential novel diagnostic approaches to HFpEF and treatment perspectives.

Aim. To determine the median levels of neuregulin-1 (NRG-1; endothelium-derived growth factor and the natural agonist of the ERBB3 and ERBB4 receptors) NRG-1 in healthy volunteers and to study the associations of NRG-1 levels with gender and age.Material and Methods. Ninety seven healthy participants were enrolled (median age of 44 [32-54], men 45 men [46.4%]). The following age groups were identified: 20-29 y.о. (n=20, men – 50.0%), 30-39 y.о. (n=21, men – 52.4%), 40-49 y.о. (n=22, men – 45.5%), 50-59 y.о. (n=22, men – 36.4%); 60-69 y.о. (n=12, men – 50.0%). Peripheral blood samples were collected at the time of enrolment, standard laboratory tests were performed, and NRG-1 levels were determined in the plasma samples by ELISA.Results. In the cohort of 97 healthy participants the median value of NRG-1 was 0.3 [0.121-2.24] ng/ml. NRG-1 levels did not differ significantly between men and women (p=0.145), indicating that NRG-1 levels are not influenced by gender. The levels of NRG-1 were similar in the different age groups: age 20-29 years=0.26 [0.17-0.37] ng/ml; age 30-39=0.24 [0.1-0.39] ng/ml; age 40-49=0.31 [0.19-1.15] ng/ml; age 50-59=0.37 [0.19-1.0] ng/ml; age 60-69=0.4 [0.13-0.81] ng/ml. Correlation analysis between NRG-1 levels and route blood measurements (haemoglobin, lipids, glucose, creatinine, and uretic acid) did not show significant associations.Conclusions. In this study, the median value of NRG-1 plasma levels were determined. The results of the study show that age and gender had no influence on NRG-1 values.

Aim      To determine the neuregulin-1β concentration in patients with chronic heart failure with preserved ejection fraction (HFpEF) and the association of this biomarker with the functional status of patients, echocardiographic parameters of the structural and functional condition of the heart, and the risk of unfavorable outcome. Material and methods  This observational, prospective study included 47 patients with HFpEF; 32 (68%) of them were females. Mean age was 70 [66–77] years, EF was 57 [56; 58] %. The group of healthy volunteers consisted of 40 people; 32 (55 %) of them were females; mean age was 56 [53–61] years. For all patients, the functional status was evaluated (6-min walk test, 6MWT); standard echocardiography (EchoCG) was performed; and concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and neuregulin-1β were measured. The follow-up period was two years. Cases of cardiovascular (CV) death and hospitalizations for decompensated chronic heart failure (CHF) were recorded. Results Median concentration of neuregulin-1β was 0.969 [0.348; 1.932] ng/ml in the HFpEF group, which was significantly higher than 0.379 [0.195; 0.861] ng/ml in the group of healthy volunteers (р=0.003). Significant correlations between the neuregulin-1β concentration and the distance walked in 6MWT or with EchoCG parameters of left ventricular diastolic function were not found. Mean observation time was 456 [244; 730] days. 21 outcomes were observed, including 2 CV deaths and 19 hospitalizations for CHF. Patients with high concentrations of neuregulin-1β (≥Me) had a greater frequency of hospitalizations for CHF (Log-rank, p=0.046) and a higher risk of this outcome (risk ratio, 1.30; 95 % confidence interval, 1.01–1.66; p=0.037). Conclusion      Patients with HFpEF had increased concentrations of neuregulin-1β. High levels of neuregulin-1β were associated with a higher risk of hospitalization for decompensated CHF.  

As a result of advances in screening, diagnosis and treatment methods in modern oncology, survival rates of patients with malignant neoplasms have considerably improved. Among the most promising therapeutic trends, emphasis is on the new immunotherapy method with T-cells expressing chimeric antigen receptors (CAR-T). CAR-T cell therapy is most commonly used in oncohematology. However, despite the efficacy of new therapeutic methods, also CAR-T cell therapy, more and more evidence on side effects becomes available. One of the most common complications (in about 1/3 of all cases) is cardiovascular toxicity (CVT) with high mortality. This accounts for an actively developing new interdisciplinary field of research called cardio-oncology that studies cardiovascular complications of chemotherapy and the methods of their monitoring and prevention. This review covers currently known pathophysiologic mechanisms of CVT on CAR-T cell therapy. Additionally, it discusses clinical manifestations, prevention strategy, and programs for monitoring cardiovascular adverse events reported by hematologists.

Aim. To assess the structure and performance of left atrium (LA) before and after 3 cycles of anticancer treatment in lymphoma patients, as well as the incidences of supraventricular arrhythmia (SVA) and the levels of biomarkers of inflammation.Material and Methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma [n=23; 57% men; median age 52 (34;64) years], who had no prior polychemotherapy. The comparison group included persons without lymphoma [n=18; 50% men; median age 43 (37; 54) years] comparable with the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography at baseline and after 3 cycles (within 3 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared with the data of the comparison group.Results. In lymphoma patients, LA reservoir, conduit, and booster function were found to be impaired at baseline but were comparable with these in matched controls. After 3 cycles of anticancer treatment, a trend to reduction of LA booster and conduit strain was found. The proportion of those with SVA was significantly higher in lymphoma patients before chemotherapy compared to those after anti-cancer treatment or controls: 57% vs 10% and 33% respectively (p<0.05). Lymphoma patients had a higher number of premature ventricular beats at baseline than after treatment or in control [183 (14;841) vs 38 (14;94) and 9 (4;38) respectively]. There were no associations found between the parameters of LA structure and function and SVA. Moderate positive correlation between ESR and supraventricular premature complexes was found (r_S=0.44; p<0.05). A positive correlation between LA contractile function and inflammatory biomarkers were revealed: LA active ejection fraction (LA EF_act) and ESR (r_S=0.42, p<0.05); LA volume index and β-globulin (r_S=0.43, p<0.05); LA EF_act and neuregulin-1β (r_S=0.42, p<0.05); LA expansion index and neuregulin-1β (r_S=0.55, p<0.05).Conclusions. In lymphoma patients, LA phasic strain parameters were impaired regardless of anticancer treatment. The associations between inflammatory biomarkers with SVA and parameters of LA performance were found.