Brain Natriuretic Peptide Precursor Research Articles

Clinical Characteristics of Moxifloxacin-Related Arrhythmias and Development of a Predictive Nomogram: A Case Control Study.

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin-related arrhythmias and electrocardiographic alterations in hospitalized patients using real-world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug-induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156-1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568-9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800-7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531-3.690), and abnormally elevated level of amino-terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640-5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220-0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin-related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin-administered population, offering significant clinical applications.

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

Arterial hypertension in the Arctic: the role of stress and autonomic dysfunction, gender differences

Introduction. Psychological stress and autonomic dysfunction are recognized as risk factors for cardiovascular diseases, but they affect cardiovascular risk differently in men and women.Aim: To study gender differences in factors influencing the probability of detecting arterial hypertension (AH) from the perspective of the role of stress, autonomic dysfunction and nonspecific inflammation in rotational shift workers in the Arctic region.Material and Methods. In the medical unit of the gas production company “Gazprom dobycha Yamburg” (polar settlement of Yamburg, 68°21’40”N) we simultaneously examined 99 men and 81 women with AH 1,2 degree of AH and normotensive persons comparable in age (p = 0.450), work experience in the Arctic (p = 0.956), number of years of rotational shift work (p = 0.824), level of office systolic (SBP) (p = 0.251) and diastolic blood pressure (DBP) (p = 0.579). Questionnaires were used to determine the level of general stress (PSM25 scale), occupational stress (Vaisman questionnaire); assessment of autonomic nervous system (ANS) function (Wayne A.M. questionnaire); 24-hour blood pressure monitoring was performed; biochemical blood test for biomarkers of inflammation, cortisol, brain natriuretic peptide precursor, homocysteine, folliclestimulating hormone was carrued out.Results. Vegetative manifestations (asthenization, increased fatigue, meteorological dependence, headaches) were significantly more often observed in women. Among men with AH, individuals with high levels of neuropsychological tension predominated, every fifth M had a high level of occupational stress. The median scores on the Wayne A.M. questionnaire were significantly higher in women, regardless of BP, and moderate ANS disorders were significantly more prevalent. According to logistic regression data, a significant effect on the probability of AH in men was the number of stress scores (OR = 1.050; 1.029–1.171, p = 0.001), indicators of nocturnal DBP variability (OR = 1.295; 1.109–1.511, p = 0.001) and nonspecific inflammation: rise in high-sensitivity C-reactive protein (hs-CRP) increased the probability of AH by 1.5 times (OR = 1.532; 1.212–1.937, p = 0.001), IL-1β – by 7 times (OR = 7.275; 3.235–16.361, p = 0.001). The probability of AH in women increased by the values of the daily variability of SBP (OR = 1.154; 1.019–1.306, p = 0.024), hs-CRP by 1.5 times (OR = 1.479; 1.226–1.783, p = 0.001), tumor necrosis factor-alpha (TNF-α) (OR = 1.111; 1.001–1.244, p = 0.044), level of IL-6 increased the probability of AH by 1.7 times (OR = 1.676; 1.149–2.958, p = 0.035), the number of scores on ANS questionnaire had a significant effect (OR = 1.055; 1.006–1.107, p = 0.026).Conclusion. In the conditions of the rotational shift work in the Arctic, gender differences were revealed in the stress perception and the severity of ANS dysfunction with a clear relationship between stress, inflammation and AH in men. ANS dysfunction in women was a trigger of nonspecific inflammation and AH. The identified gender differences will help to reveal vulnerable groups among men and women and develop targeted interventions for individuals in the Arctic region.

The effectiveness of hardware CPAP therapy in heart failure with preserved left ventricular ejection fraction and obstructive sleep apnea syndrome

Aim. To evaluate the effectiveness of hardware Continuous Positive Airway Pressure therapy (CPAP therapy) and its likely predictors in patients with heart failure with preserved ejection fraction (HFpEF) associated with obstructive sleep apnea syndrome (OSAS).
 Materials and methods. The study involved 207 men with HFpEF and OSAS (apnea/hypopnea index 15 per hour) who did not initially have ischemic disease and other structural heart pathology. At inclusion in the study, polysomnography and echocardiography were performed with an assessment of diastolic function and global longitudinal deformation of the left ventricular myocardium, as well as a 6-minute walk test (6MWT) and the level of the brain natriuretic peptide precursor (NT-proBNP) in the blood was determined. 80 patients received hardware CPAP the rapy, 127 patients made up the control group. After 12 months, 6MWT was repeated, NT-proBNP was determined, and clinical outcomes were assessed retrospectively.
 Results. The CPAP group had 16% fewer hospitalizations (p=0.011 [95% confidence interval – CI 4.29]) and showed a trend towards an increase in the 6MWT distance (p=0.065). To assess the likely predictors of the effectiveness of CPAP therapy, a subgroup of “responders” was identified, characterized by an increase in the distance according to the 6MWT, a decrease in the level of NT-proBNP, and the absence of adverse clinical events during the observation period. There were significant differences between responders and non-responders in apnea/hypopnea index (p=0.01 [95% CI -10.6; -2.5]), global longitudinal deformation of the left ventricular myocardium (p=0.05 [95% CI -4.7; 0]), diastolic function E/A (p=0.02 [95% CI -0.1; 0]).
 Conclusion. CPAP therapy improves clinical outcomes and functional status in patients with OSAS-associated HFpEF. The predictive model built using the identified efficacy predictors can be used to develop a personalized treatment algorithm for this cohort of patients.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

Optimisation of conservative treatment of patients with severe heart failure by using hemosorption

Background. Heart failure (HF) is a complex cardiac pathology that is the main cause of hospitalisation among adults and is characterised by a high mortality. Dilated cardiomyopathy (DCM) is the most common cause of HF, and it can be fatal within a few years after the first symptoms appear. Many patients with HF remain refractory to medical therapy, despite its constant development and improvement. The study aims to compare the effectiveness of conservative treatment of patients with severe HF that occurred on the background of DCM using drug therapy and its combination with a course of hemosorption (HS). Materials and methods. We analysed treatment outcomes in 30 patients with severe HF against DCM (New York Heart Association class III–V, left ventricular ejection fraction (LV EF) < 30 %). Patients in group 1 (n = 13; N-terminal fragment of brain natriuretic peptide precursor (NT-pro BNP) 4,546.23 ± ± 3,265.01 pg/ml; LV EF 16.77 ± 2.92 %; LV end-diastolic volume (EDV) 261.31 ± 60.60 ml, LV end-systolic volume (ESV) 214.85 ± 49.44 ml) received drug therapy according to local protocols. In group 2 (n = 17; NT-pro BNP 3,974.49 ± 3,550.17 pg/ml; LV EF 18.18 ± 4.36 %; LV EDV 261.12 ± 79.96 ml, LV ESV 212.06 ± 71.67 ml), medical treatment was supplemented with a course of 3 HS procedures using granular deligandizing hemosorbent. Results. Patients in both study groups noted an improvement in well-being and a decrease in the severity of symptoms. The level of NT-pro BNP decreased to 2,609.92 ± 1,465.14 pg/ml (p < 0.01) in group 1 and to 975.35 ± 511.55 pg/ml (p < 0.05) in group 2. LV EF increased to 22.77 ± 4.69 % and 26.76 ± 5.02 %, respectively, in the groups (p < 0.01). In patients of group 1, LV EDV and LV ESV changed to 262.22 ± 40.92 ml and 211.33 ± 35.22 ml, respectively. In group 2, there was a significant decrease in LV EDV to 228.94 ± 73.16 ml and LV ESV to 170.88 ± 60.28 ml (p < 0.01). Conclusions. The use of HS in combination with drug therapy for severe HF on the background of DCM improves the clinical status of patients and LV systolic function.

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

Effect of methoxymine on prevention and treatment of myocardial injury and cardiac function in elderly patients with hypotension during intraspinal anesthesia.

We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function. A retrospective study was conducted by enrolling sixty elderly patients who underwent femoral head replacement (FHR) under IA in our hospital from August 2019 to August 2020. The patients were divided into two groups according to the random number table method. In the control group (CG) (30 patients), 5 mg of ephedrine was administered sedately when patients developed hypotension (20% below basal blood pressure). In the research group (RG) (30 cases), 2 μg/(kg·h) of methoxamine hydrochloride was given as a constant-rate pump before anesthesia, and 1 mg of methoxamine hydrochloride was administered intraoperatively if hypotension occurred. The hemodynamic [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)], myocardial injury indexes [cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), fatty acid binding protein (FABP), plasma amino-terminal brain natriuretic peptide precursor (NT-proBNP)], cardiac function indexes [systemic vascular resistance (SVR), stroke volume (SV), net percentage ejection time (ET)] were observed before anesthesia (T1), at the end of surgery (T2), and 6 h after surgery (T3) in both groups. The Bruggemann Comfort Score (BCS) and Visual Analog Scale (VAS) scores at T3, 12 h postoperatively (T4) and 24 h postoperatively (T5) in both groups were observed, and the incidence of adverse reactions to intralesional anesthesia in both groups was counted. SBP, DBP and HR at T2 were lower than those at T1 in both groups, and SBP, DBP and HR at T3 were higher than those at T2, and SBP, DBP and HR at T2 and T3 in the RG were higher than those in the CG (p<0.05). In both groups, cTnⅠ, CK-MB and FABP were higher at T2 and T3 than at T1, higher at T3 than at T2, and NT-proBNP was higher at T2 than at T1 and T3, and lower in the RG than in the CG (p<0.05). In both groups, SVR and SV at time point T2 were lower than at time point T1 and ET was higher than at time point T1, SVR and SV at time point T3 were higher than at time point T2 and ET was lower than at time point T2, SVR and SV in the RG were higher than in the CG and ET was lower than in the CG (p<0.05). VAS scores were higher in both groups at T4 and T5 than at T3, and lower in the RG than in the CG (p<0.05). Methoxamine can effectively reduce the risk of hypotension in geriatric endotracheal anesthesia, which can reduce myocardial injury and stabilize cardiac function in patients.

RETRACTED ARTICLE: Effects of Dapagliflozin on myocardial remodeling, inflammatory factors, and cardiac events in heart failure with preserved ejection fraction.

To investigate the effects of Dapagliflozin on myocardial remodeling, inflammatory factors, and cardiac events in the treatment of heart failure with preserved ejection fraction (HFpEF). Ninety-two patients with HFpEF treated in our hospital from August 2021 to March 2022 were retrospectively picked as study subjects. These subjects were randomized as the study group and control group following the random number table, with 46 cases in each group. Patients in the control group adopted standard anti-heart failure (HF) treatment, including diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists β receptor blockers, and digitalis. Patients in the study group received Dapagliflozin on the basis of the control group. Changes in myocardial remodeling-related parameters [left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), the ratio of early diastolic blood flow velocity to late diastolic blood flow velocity (E/A), plasma N-terminal B-type brain natriuretic peptide precursor (NT-proBNP), and cardiac troponin I (CTnI)] were assessed by echocardiography before and 12months after the intervention. The content of inflammatory factors [interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] in serum was measured by enzyme-linked immunosorbent assay. The factors affecting the clinical efficacy of Dapagliflozin were analyzed by the multivariate logistic regression. The incidence of cardiac events was compared between the two groups. The effective rate of 95.65% in the study group was much higher than 80.43% in the control group (P < 0.05). After the intervention, the study group had an especially higher content of LVEF and E/A and sharply lower content of LVEDD, NT-proBNP, and CTnI than the control group (P < 0.001). After the intervention, IL-1β, TNF-α, and IL-6 levels were markedly lower in the study group than in the control group (P < 0.001). The incidence of cardiac events, including arrhythmias, recurrent angina, heart failure rehospitalization, cardiogenic death, and all-cause mortality, was 8.70% in the study group and 26.09% in the control group, which was much lower in the study group (P < 0.05). The results of multivariate logistic regression analysis showed that LVEF and E/A were independent protective factors affecting the ineffectiveness of Dapagliflozin (P < 0.05), and LVEDD, NT-proBNP, CTnI, IL-1β, TNF-α, and IL-6 were independent risk factors affecting the ineffectiveness of Dapagliflozin (P < 0.05). In conclusion, Dapagliflozin could effectively improve myocardial remodeling, inhibit inflammatory reaction, and play a more active role in the treatment of patients with HFpEF, providing a certain clinical basis for the treatment of patients.

Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction.

Objective: To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms. Methods: Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (n = 11), Linggui Zhugan Decoction group (n = 12), and captopril group (n = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (n = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction. Results: Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (p < 0.05), reduced MDA production (p < 0.01), increased SOD activity (p < 0.05), reduced ST-2(p < 0.01), and NT-proBNP(p < 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes. Conclusion: Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.

Clinical efficacy of enhanced external counter pulsation plus sacubitril/valsartan in the treatment of patients with chronic heart failure and the effect on ankle-arm index and cardiac function.

The aim of this study was to evaluate the clinical efficacy of enhanced external counter pulsation (EECP) plus sacubitril/valsartan in the treatment of patients with chronic heart failure (CHF) and the effect on ankle-arm index and cardiac function. In this retrospective study, 106 patients with chronic heart failure treated in our hospital from September 2020 to April 2022 were recruited and randomly assigned to receive either sacubitril/valsartan (observation group) or EECP plus sacubitril/valsartan (combination group) alternately at the point of admission, with 53 patients in each group. Outcome measures included clinical efficacy, ankle brachial index (ABI), cardiac function indices [N-terminal brain natriuretic peptide precursor (NT-proBNP), 6 min walking distance (6MWD), left ventricular ejection fraction (LVEF)], and adverse events. EECP plus sacubitril/valsartan resulted in significantly higher treatment efficiency and ABI levels vs. sacubitril/valsartan (p<0.05). Patients receiving combined therapy showed significantly lower NT-proBNP levels than those given monotherapy (p<0.05). EECP plus sacubitril/valsartan resulted in longer 6MWD and higher LVEF than sacubitril/valsartan alone (p<0.05). No significant differences were observed in the adverse events between the two groups (p>0.05). EECP plus sacubitril/valsartan substantially improves the ABI levels, cardiac functions, and exercise tolerance of patients with chronic heart failure, with a high safety profile. EECP improves blood supply to myocardial ischemic tissues by increasing ventricular diastolic blood return and blood perfusion to ischemic myocardium, raises aortic diastolic pressure, restores pumping function, improves LVEF, and reduces NT-proBNP secretion.

Expression and clinical significance of circRNA cSMARCA5 in patients with acute myocardial infarction

Objective: To investigate the expression level and clinical significance of cSMARCA5 in the patients with acute myocardial infarction (AMI). Methods: This study was a case-control study. A total of 100 patients with AMI and 100 patients without coronary heart disease who received treatment in the Department of Cardiology, Peking University Third Hospital from September to December 2021 were included in the study according to the principle of 1∶1 frequency matching. The expression levels of cSMARCA5 in the peripheral blood of AMI patients and control groups were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) curve was used to calculate the diagnostic ability of cSMARCA5 for AMI. Spearman or Pearson correlation analysis was used to explore the correlation between cSMARCA5 and the degree of myocardial necrosis, coronary lesion severity and GRACE risk stratification score. Bioinformatics analysis was used to predict the possible mechanism of cSMARCA5 in pathological changes of AMI. Results: The age [M (Q1,Q3)] of AMI patients and control group was 63.0 (56.0, 71.5) and 63.0 (53.0, 75.5) (P=0.622), and the proportion of males was 75.0% (75 cases) and 46.0% (46 cases) (P<0.001), respectively. The expression level [M (Q1,Q3)] of cSMARCA5 was significantly lower in AMI patients compared with the control group [0.37 (0.22, 0.73) vs 1.03(0.71, 1.75), P<0.001]. ROC analysis showed that the area under the curve of cSMARCA5 in diagnosing AMI was 0.83 (95%CI: 0.77-0.89, P<0.001), with a sensitivity of 89.0% and specificity of 67.7%. cSMARCA5 was negatively correlated with creatine kinase isoenzyme MB (r=-0.203, P=0.041), troponin T (r=-0.230, P=0.023) and N-terminal brain natriuretic peptide precursor (r=-0.250, P=0.012), and positively correlated with left ventricular ejection fraction (r=0.201, P=0.042). In addition, the expression level of cSMARCA5 was negatively correlated with SYNTAX score (r=-0.196, P=0.048) and GRACE risk score (r=-0.321, P=0.001). Bioinformatic analysis suggested that cSMARCA5 might be involved in the process of AMI through regulating the gene expression of tumor necrosis factor. Conclusions: The expression of cSMARCA5 is significantly decreased in peripheral blood of AMI patients compared with control group, and its expression level is negatively correlated with the severity of myocardial infarction. cSMARCA5 is expected to be a potential biomarker of AMI.

Growth Differentiation Factor-15 (GDF-15) is a Biological Marker in Heart Failure

Heart failure is an important medical, social and economic problem around the world. In recent years, a number of diagnostic and prognostic biological markers of blood in cardiovascular diseases have been studied. Identification of new biological markers, analysis of their pathophysiological aspects and changes in concentration under the influence of various treatment options, allow us to understand many pathogenetic features of the development and course of heart failure. In recent decades, natriuretic peptides have been introduced into clinical practice, which are widely used as reliable markers for diagnostic and prognostic assessment. Growth differentiation factor-15 is a cytokine belonging to the family of transforming growth factors, the activity of which is significantly increased under stress and inflammation. In patients with chronic heart failure, the concentration of this marker is associated with an increased risk of overall mortality and adverse cardiovascular events; in patients with heart failure with preserved left ventricular ejection fraction, the use of the marker showed prognostic and diagnostic significance. Data from the Framingham Heart Study showed that growth differentiation factor-15 was the only marker in multivariate analysis that showed a statistically significant association with all adverse cardiovascular events. Eight studies showed that overexpression of growth differentiation factor-15 was associated with an increased risk of mortality in patients with heart failure. It was shown that growth differentiation factor-15 as a prognostic marker in patients with acute heart failure is not inferior to the brain natriuretic peptide precursor. To confirm the value of this marker in blood in patients with heart failure, it is necessary to conduct extensive prospective randomized clinical trials.

Electrocardiographic Time-Intervals Waveforms as Potential Predictors for Severe Acute Kidney Injury in Critically Ill Patients.

Acute kidney injury (AKI) is common in critically ill patients admitted to intensive care units (ICU) and is frequently associated with poorer outcomes. Hence, if an indicator is available for predicting severe AKI within the first few hours of admission, management strategies can be put into place to improve outcomes. This was a prospective, observational study, involving 63 critically ill patients, that aimed to explore the diagnostic accuracy of different Doppler parameters in predicting AKI in critically ill patients from a mixed ICU. Participants were enrolled at ICU admission. All underwent ultrasonographic examinations and hemodynamic assessment. Renal Doppler resistive index (RDRI), venous impedance index (VII), arterial systolic time intervals (a-STI), and venous systolic time intervals (v-STI) were measured within 2 h from ICU admission. Cox proportional hazards models, including a-STI, v-STI, VII, and RDRI as independent variables, returned a-STI as the only putative predictor for the development of AKI or severe AKI. An overall statistically significant difference (p &lt; 0.001) was observed in the Kaplan-Meier plots for cumulative AKI events between patients with a-STI higher or equal than 0.37 and for cumulative severe AKI-3 between patients with a-STI higher or equal than 0.63. As assessed by the area under the receiver operating curves (ROC) curves, a-STI performed best in diagnosing any AKI and/or severe AKI-3. Positive correlations were found between a-STI and the N-terminal brain natriuretic peptide precursor (NT-pro BNP) (ρ = 0.442, p &lt; 0.001), the sequential organ failure assessment (SOFA) score (ρ: 0.361, p = 0.004), and baseline serum creatinine (ρ: 0.529, p &lt; 0.001). Critically ill patients who developed AKI had statistically significant different a-STI (on admission to ICU), v-STI, and VII than those who did not. Moreover, a-STI was associated with the development of AKI at day 5 and provided the best diagnostic accuracy for the diagnosis of any AKI or severe AKI compared with RDRI, VII, and v-STI.

Sudden cardiac death in a patient with complicated peripartum cardiomyopathy, long QT syndrome and mutation in &lt;I&gt;FLNC&lt;/I&gt; gene

Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion in women presenting with heart failure due to left ventricular (LV) systolic dysfunction. PPCM should be considered in case of unknown etiology of heart failure during pregnancy or after childbirth. Long QT syndrome is a primary electrical heart disease associated with a prolonged QT interval on the ECG, recurrent paroxysms of ventricular tachycardia, and a high risk of sudden death. Our aim was to demonstrate a case of cardiomyopathy in combination with long QT syndrome in a patient with a mutation in the FLNC gene. A 38-years-old woman was hospitalized 4,5 months after childbirth after sudden cardiac arrest and successful cardiopulmonary resuscitation. Long QT interval was revealed on the electrocardiogram. Echocardiography registered an akinesis of the apical and middle segments of the anterior wall of the left ventricle and interventricular septum, apex, left ventricular ejection fraction – 32%. Coronary angiography revealed no stenotic lesion of the coronary arteries. N-terminal precursor of brain natriuretic peptide (NTproBNP) was 33300 mg/l. Mass parallel sequencing of 17 genes revealed the nucleotide variant c.1609T&gt;G (chr7:128480661T&gt;G, NM_001488.4; rs760471547) in a heterozygous state in exon 10 of the FLNC gene (OMIM 102565), leading to the amino acid variant p.Y537D.The combination of peripartum cardiomyopathy and long QT syndrome may increase the likelihood of sudden cardiac death, especially in individuals with a genetic mutation of cardiomyopathy. Timely diagnosis of the described conditions is necessary to prevent complications and increase the life expectancy of patients.

The serum free triiodothyronine to free thyroxine ratio as a potential prognostic biomarker of chronic kidney disease in patients with glomerular crescents: A retrospective study.

BackgroundCrescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation.MethodsThis single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio.ResultsThe age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P < 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (>0.284), those with intermediate and low FT3/FT4 ratios (≤0.284) had an increased risk of the long-term composite endpoint (P < 0.05 for various adjustment models).ConclusionsA low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology.

B-Type Natriuretic Peptide (BNP) Revisited—Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?

Simple SummaryActive BNP-32, less active proBNP-108, and inactive N-terminal proBNP-76 all circulate in the blood. The circulating protease neprilysin has lower substrate specificity for BNP than ANP, while proBNP and N-terminal proBNP are not degraded by neprilysin. Currently available BNP immunoassays react with both mature BNP and proBNP; therefore, measured plasma BNP is mature BNP + proBNP. Because ARNI administration increases mature BNP, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI administration reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase of mature BNP due to inhibition of degradation by neprilysin, resulting in lower plasma BNP levels. In the ARNI era, BNP remains a useful biomarker for heart failure, though mild increases early during ARNI administration should be taken into consideration.Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration.

Role of depressive symptoms in the prognosis of heart failure and its potential clinical predictors.

AimsThis study aims to analyse the factors associated with prognosis in hospitalized patients with heart failure, particularly the role of depressive symptoms, and to develop a prediction model for depressive symptoms based on clinical characteristics in hospitalized patients with heart failure.Methods and resultsBaseline information was collected at admission, and patients were followed up after discharge. The endpoint events were being hospitalized for heart failure or all‐cause death. Depressive symptoms were evaluated and defined via the Patient Health Questionnaire (PHQ)‐2 and PHQ‐9. The bidirectional elimination was used to screen independent predictors of heart failure with depression symptoms. The least absolute shrinkage and selection operator (LASSO) optimized the predictor variables, and the prediction model was constructed. The model was internally validated by the bootstrap sampling method (Bootstrap), and its performance was assessed by discrimination and calibration. The mean age of patients with heart failure was 69.43 ± 12.15 years, and the proportion of males was 66.67%. The prevalence of depressive symptoms in hospitalized patients with heart failure was 46.83%, and the prevalence of moderate/severe depressive symptoms was 11.62%. Eighty cases (30.30%) were readmitted for heart failure, and 13 cases (4.92%) were all‐cause deaths. Depressive symptoms (HR = 2.43, 95% CI: 1.55–3.80) and the PHQ‐9 score (HR = 1.11, 95% CI: 1.06–1.16) were both independent risk factors for endpoint events (P < 0.001). For heart failure patients combined with depressive symptoms, obesity (OR = 0.27, 95% CI: 0.09–0.77, P = 0.015), N‐terminal brain natriuretic peptide precursor (NT‐proBNP) level (lnNT‐proBNP: OR = 1.55, 95% CI: 1.20–2.01, P < 0.001) and red blood cell distribution width (RDW) (OR = 1.26, 95% CI: 1.08–1.47, P = 0.004) were the independent factors. Six variables, including cardiovascular disease hospitalization history, obesity, renal insufficiency, NT‐proBNP level, neutrophil ratio and RDW, were included to construct the prediction model. The area under the curve (AUC) was 0.730 in the original data, and the calibration curve was approximately distributed along the reference line in Bootstrap (500 resamplings), indicating the high level of discrimination and calibration of this model.ConclusionsDepressive symptoms and the PHQ‐9 score are both independent risk factors for the prognosis of hospitalized patients with heart failure. In hospitalized patients with heart failure, the risk prediction model developed in this study has good predictive power for depressive symptoms.

Clinical Characteristics of Cryoglobulinemia With Cardiac Involvement in a Single Center.

Background: Cryoglobulinemia is a syndrome characterized by the presence of cryoglobulins (CGs) in serum, and cardiac involvement is a rare occurrence that can affect treatment and prognosis. This study aimed to explore the clinical characteristics of cryoglobulinemia with cardiac involvement.Methods: 108 patients diagnosed with cryoglobulinemia who were admitted and treated in Peking Union Medical College Hospital (PUMCH) between June 1985 and June 2019 were enrolled in the present study. Clinical characteristics, therapy, and prognosis of patients with cardiac involvement were retrospectively analyzed.Results: The cryoglobulinemia with cardiac involvement was found in 7 patients, thus reaching the incidence of 6.5%. Heart failure was the main cardiac manifestation found in these patients, all with the involvement of external cardiac organs. Laboratory examinations showed significant elevation of N-terminal brain natriuretic peptide precursor (NT-proBNP) and brain natriuretic peptide (BNP) with negative troponin (cTnI). Electrocardiogram (ECG) was generally normal or only showed low-flat and biphasic multi-lead T waves. Echocardiography was performed in 6 patients, all of whom showed enlargement of heart cavity. Five patients had reduced left ventricular myocardial contractible motion with decreased ejection fraction, 3 patients had pericardial effusion, and 1 patient had left ventricular hypertrophy or severe aortic insufficiency. Cardiac magnetic resonance imaging showed delayed myocardial enhancement in 2 patients. One patient underwent a myocardial biopsy, which showed perivasculitis. Condition in 6 patients who received active treatment targeting improved in the early stage. Three patients (3/7, 42.9%) died due to disease progression during follow-up period.Conclusions: Cryoglobulinemia with cardiac involvement is a rare but serious condition that has relatively high risk of death. When patients with cryoglobulinemia without underlying heart disease experience heart failure, chest pain, or elevation of asymptomatic NT-proBNP and BNP, there is a high possibility of cardiac involvement, even if the electrocardiogram and troponin are negative. Further examinations such as echocardiography, cardiac magnetic resonance imaging, and myocardial biopsy examination could contribute to the diagnosis. Cardiac manifestations could be timely reversed after active targeted treatment. NT-proBNP and echocardiography could be used for the monitoring of disease efficacy.

Nanomaterials in diagnosis and treatment of cardiovascular diseases

This paper prepared a nucleic acid aptamer functionalised magnetic ball/gold nanorod composite material. This multifunctional composite material can realise the reversible regulation of thrombin activity and assist in the diagnosis and treatment of cardiovascular diseases. Thrombin and its pair of nucleic acid aptamers can be built into a closed-loop structure based on the hybridisation technology of adjacent surfaces. The measurement of human serum coagulation time proves that this inhibition and recovery method has very good clinical application prospects. In the application of multi-functional nanomaterials to assist sports rehabilitation training, the paper analyses the level of serum N-terminal brain natriuretic peptide precursor (NT-pro BNP), high-sensitivity myocardial troponin T (hscTnT) and heart function indexes in patients with chronic heart failure influences. The results show that the use of multifunctional nanomaterials combined with exercise rehabilitation therapy in patients with chronic heart failure can significantly reduce serum NT-pro BNP and hscTnT levels and improve cardiovascular function.