Imatinib­ and ponatinib­mediated cardiotoxicity in zebrafish embryos and H9c2 cardiomyoblasts.

Tyrosine kinase inhibitors (TKIs) offer targeted therapy for cancers but can cause severe cardiotoxicities. Determining their dose­dependent impact on cardiac function is required to optimize therapy and minimize adverse effects. The dose­dependent cardiotoxic effects of two TKIs, imatinib and ponatinib, were assessed in vitro using H9c2 cardiomyoblasts and in vivo using zebrafish embryos. In vitro, H9c2 cardiomyocyte viability, apoptosis, size, and surface area were evaluated to assess the impact on cellular health. In vivo, zebrafish embryos were analyzed for heart rate, blood flow velocity, and morphological malformations to determine functional and structural changes. Additionally, reverse transcription­quantitative PCR (RT­qPCR) was employed to measure the gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), established markers of cardiac injury. This comprehensive approach, utilizing both in vitro and in vivo models alongside functional and molecular analyses, provides a robust assessment of the potential cardiotoxic effects. TKI exposure decreased viability and surface area in H9c2 cells in a dose­dependent manner. Similarly, zebrafish embryos exposed to TKIs exhibited dose­dependent heart malformation. Both TKIs upregulated ANP and BNP expression, indicating heart injury. The present study demonstrated dose­dependent cardiotoxic effects of imatinib and ponatinib in H9c2 cells and zebrafish models. These findings emphasize the importance of tailoring TKI dosage to minimize cardiac risks while maintaining therapeutic efficacy. Future research should explore the underlying mechanisms and potential mitigation strategies of TKI­induced cardiotoxicities.

Neutrophil-Lymphocyte Ratio and High Sensitivity C-Reactive Protein as Markers of Heart Failure Severity: A Study at the University of Port-Harcourt Teaching Hospital Heart Failure Clinic.

BACKGROUND: Systemic inflammatory markers, such as the Neutrophil-Lymphocyte Ratio (NLR) and high-sensitivity Creactive protein (hs-CRP), have been linked to cardiovascular diseases, including heart failure (HF), and increased mortality rates. This study aimed to assess NLR and hs-CRP levels in chronic HF patients and determine the relationship between these markers with HF severity. METHODS: A descriptive cross-sectional study was conducted on 136 chronic HF patients at the University of Port-Harcourt Teaching Hospital. Informed consent was obtained, and participants completed a questionnaire. Blood samples were collected for a complete blood count, hs-CRP, and N Terminal-pro-Brain Natriuretic Peptide measurements. Echocardiography was performed for all study participants. RESULTS: The mean age was 59 years and 51.5% were males. Among the participants, 27(19.9%) had an NLR >2, while 91(66.9%) had elevated hs-CRP levels. There was a non-significant positive correlation between NLR and CRP values (r=0.131, p=0.128). Elevated hs-CRP levels were found in 67.1% and 66.7% of patients with left ventricular systolic and diastolic dysfunction, respectively. However, elevated NLR >2 was found in only 21.5% and 17.6% of these patients respectively. Highly sensitive-CRP significantly correlated with NT-Pro-BNP (0.410<0.0001) but not with NYHA classification, Ejection Fraction, and Anemia. CONCLUSION: Highly sensitive CRP was a more reliable inflammation marker in HF patients than NLR. High hs-CRP levels could predict rising NT-Pro-BNP and were associated with left ventricular systolic dysfunction than NLR. The Neutrophil Lymphocyte ratio, while cheap and accessible in the study environment, was unable to predict worsening HF possibly due to typically lower NLR values in blacks.

CONTEXTE: Les marqueurs inflammatoires systémiques, tels que le ratio neutrophiles-lymphocytes (NLR) et la protéine C-réactive ultrasensible (hs-CRP), ont été liés aux maladies cardiovasculaires, y compris l'insuffisance cardiaque (IC), et à des taux de mortalité accrus. Cette étude visait à évaluer les niveaux de NLR et de hs-CRP chez les patients atteints d'IC chronique et à déterminer la relation entre ces marqueurs et la gravité de l'IC. MÉTHODES: Une étude descriptive transversale a été menée sur 136 patients atteints d'IC chronique à l'Hôpital Universitaire de PortHarcourt. Le consentement éclairé a été obtenu et les participants ont rempli un questionnaire. Des échantillons de sang ont été prélevés pour une numération formule sanguine complète, hs-CRP, et des mesures de peptide natriurétique de type B terminal (NT-pro-BNP). Une échocardiographie a été réalisée pour tous les participants à l'étude. RÉSULTATS: L'âge moyen était de 59 ans et 51,5% étaient des hommes. Parmi les participants, 27 (19,9%) avaient un NLR >2, tandis que 91 (66,9%) avaient des niveaux élevés de hs-CRP. Il y avait une corrélation positive non significative entre les valeurs de NLR et de CRP (r=0,131, p=0,128). Des niveaux élevés de hs-CRP ont été trouvés chez 67,1% et 66,7% des patients atteints de dysfonction systolique et diastolique du ventricule gauche, respectivement. Cependant, un NLR élevé >2 n'a été trouvé que chez 21,5% et 17,6% de ces patients respectivement. La hs-CRP a significativement corrélé avec le NT-pro-BNP (0,410<0,0001) mais pas avec la classification NYHA, la fraction d'éjection et l'anémie. CONCLUSION: La hs-CRP était un marqueur inflammatoire plus fiable chez les patients atteints d'IC que le NLR. Des niveaux élevés de hs-CRP pouvaient prédire une augmentation du NT-pro-BNP et étaient associés à une dysfonction systolique du ventricule gauche plutôt que le NLR. Le ratio neutrophiles-lymphocytes, bien que bon marché et accessible dans l'environnement de l'étude, n'a pas pu prédire l'aggravation de l'IC, probablement en raison de valeurs de NLR typiquement plus basses chez les noirs. MOTS-CLÉS: Insuffisance cardiaque, Marqueurs inflammatoires, Ratio neutrophiles-lymphocytes, hs-CRP, chronique.

Prognostic Significance and Biologic Associations of Senescence-Associated Secretory Phenotype Biomarkers in Heart Failure.

BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach. METHODS AND RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or HF hospital admission. We also assessed the relationship of each SASP factor to 4746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Two SASP factors were identified. Both factors were associated with older age, lower estimated glomerular filtration rate, and more advanced New York Heart Association class, among other clinical variables. Both SASP factors exhibited a significant positive association with the risk of death independent of the Meta-Analysis of Global-Group in Chronic HF score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The 2 identified SASP factors were associated with 1201 and 1554 proteins, respectively, belonging to various pathways including the coagulation system, complement system, acute phase response signaling, and retinoid X receptor-related pathways that regulate cell metabolism. CONCLUSIONS: Increased SASP components are independently associated with adverse outcomes in HF. Biologic pathways associated with SASP are predominantly related to coagulation, inflammation, and cell metabolism.

[Clinical analysis of maternal autoantibody-mediated complete left bundle branch block in 9 children].

Objective: To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies. Methods: A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results: Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) µg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions: Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

Role of dietary inflammatory index in the association of NT-proBNP with all-cause and cardiovascular mortality in NHANES 1999-2004.

N-terminal pro-Brain-type natriuretic peptide (NT-proBNP) has a predictive value of cardiovascular disease (CVD). Pro-inflammatory diet has been proven to be related to CVD. Our study investigated whether the association between NT-proBNP and mortality differed among general U.S. adults with different dietary inflammatory index (DII) scores. This study utilized the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2004. Non-pregnant U.S. adults aged ≥ 20 years and without CVD were included. Cox regression model and restricted cubic splines were used to investigate the associations between NT-proBNP, DII, and mortality. A total of 9788 adults were included, and 2386 all-cause deaths with 668 CVD deaths occurred over 17.08 years of follow-up. NT-proBNP was positively associated with DII scores (P < 0.001). Among subjects without CVD, elevated NT-proBNP was positively associated with an increased risk of mortality, with per unit increase in log transformed NT-proBNP, the risk of all-cause and cardiovascular mortality increased by approximately 1.40 times (HR 2.397, 95%CI 1.966-2.922, P < 0.001) and 2.89 times (HR 3.889, 95%CI 2.756-5.490, P < 0.001) after adjusting for cardiovascular risk factors, similar results were observed after adjusting DII scores. Besides, significant interaction was found between lgNT-proBNP and DII on mortality (all P for interaction < 0.05). While as the DII quartiles increased, the association between lgNT-proBNP and mortality partially weakened. Our findings reveal that the association of NT-proBNP with all-cause and cardiovascular mortality differed with different DII scores among U.S. adults without CVD. A pro-inflammatory diet may partially explain the association between NT-proBNP and mortality and warrant further study.

Clinical Significance of B-Type Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Pediatric Patients: Insights into Their Utility in the Presence or Absence of Pre-Existing Heart Conditions.

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions.

S100B Serum Levels in Chronic Heart Failure Patients: A Multifaceted Biomarker Linking Cardiac and Cognitive Dysfunction.

S100 calcium-binding protein B (S100B) is a protein primarily known as a biomarker for central nervous system (CNS) injuries, reflecting blood-brain barrier (BBB) permeability and dysfunction. Recently, S100B has also been implicated in cardiovascular diseases, including heart failure (HF). Thus, we investigated serum levels of S100B in 146 chronic HF patients from the Cognition.Matters-HF study and their association with cardiac and cognitive dysfunction. The median S100B level was 33 pg/mL (IQR: 22-47 pg/mL). Higher S100B levels were linked to longer HF duration (p = 0.014) and increased left atrial volume index (p = 0.041), but also with a higher prevalence of mild cognitive impairment (p = 0.023) and lower visual/verbal memory scores (p = 0.006). In a multivariable model, NT-proBNP levels independently predicted S100B (T-value = 2.27, p = 0.026). S100B did not impact mortality (univariable HR (95% CI) 1.00 (0.99-1.01); p = 0.517; multivariable HR (95% CI) 1.01 (1.00-1.03); p = 0.142), likely due to its reflection of acute injury rather than long-term outcomes and the mild HF phenotype in our cohort. These findings underscore S100B's value in comprehensive disease assessment, reflecting both cardiac dysfunction and potentially related BBB disruption.

Analysis of ultrasound coronary parameters and blood red cell distribution width and N-terminal pro-brain natriuretic peptide concentrations following coronary lesions in children with Kawasaki disease.

Aims/Background Kawasaki disease is an acute inflammatory condition primarily affecting the young children. It can lead to coronary artery abnormalities, which can worsen the prognosis. Early diagnosis of coronary disease is crucial for the effective treatment and the prognosis evaluation. To explore the clinical significance of ultrasound examination characteristics, peripheral blood red cell distribution width, and changes in N-terminal pro-brain natriuretic peptide levels for the early detect coronary artery abnormality in children with Kawasaki disease. Methods The case-control study was conducted. 85 Kawasaki disease patients diagnosed in our hospital from January 2020 to December 2023 were selected as the Kawasaki disease group. 100 healthy children who received physical examination in the Department of Child Healthcare during the same period were selected as control group. The cardiac ultrasound indicators, erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, N-terminal pro-brain natriuretic peptide of two groups were compared. The Kawasaki disease group was further divided into the coronary artery lesion group and the non-coronary artery lesion group based on whether coronary artery lesions occurred in the Kawasaki disease patients. The differences of above indicators were compared. Results The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of the Kawasaki disease group were all higher than those of the control group (p < 0.05). There was no significant difference in left ventricular ejection fraction between Kawasaki disease group and control group (p > 0.05). The erythrocyte sedimentation rate, C-reactive protein, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease group were all higher than those of control group (p < 0.05). The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions (p < 0.05). The left ventricular ejection fraction of Kawasaki disease patients with coronary artery lesions was lower than that of Kawasaki disease patients without coronary artery lesions (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions, and the differences were statistically significant (p < 0.05). After treatment, the left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions significantly decreased (p < 0.05), and the left ventricular ejection fraction significantly increased (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with or without coronary artery lesions significantly decreased after treatment compared with before treatment in the same group (p < 0.05). Conclusion Kawasaki disease patients with coronary artery lesions exhibit significantly increased coronary artery vessel diameter, as well as elevated red cell distribution width and N-terminal pro-brain natriuretic peptide concentration. The combined use of ultrasound combined with red cell distribution width and N-terminal pro-brain natriuretic peptide examination can assist in determining whether Kawasaki disease patients have coronary artery lesions and assessing the clinical treatment effect.

Detecting heart stress using NT-proBNP in patients with type 2 diabetes mellitus and hypertension or high-normal blood pressure: a cross-sectional multicentric study.

BACKGROUND: We evaluated the prevalence of "heart stress" (HS) based on NT-proBNP cut-points proposed by the 2023 Consensus of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in asymptomatic patients with T2DM and hypertension or high-normal blood pressure (BP) eligible for SGLT2 inhibitors (SGLT2i) and/or GLP-1 receptor agonists (GLP1-RA), drugs with proven benefits on reducing the incidence of HF, hospitalizations, cardiovascular events and mortality. METHODS: A cross-sectional multicentric study was conducted on 192 consecutive outpatients, aged ≥ 55 years, with hypertension or high-normal BP, referred to three diabetology units. NT-proBNP was collected before starting new anti-diabetic therapy. Patients with known HF were excluded, and participants were classified based on the age-adjusted NT-proBNP cut-points. RESULTS: Mean age: 70.3 ± 7.8 years (67.5% males). Patients with obesity (BMI ≥ 30 Kg/m2): 63.8%. Median NT-proBNP: 96.0 (38.8-213.0) pg/mL. Prevalence of chronic kidney disease (CKD, eGFR < 60 mL/min/1.73m2): 32.1%. Mean arterial BP: 138.5/77.0 ± 15.8/9.9 mmHg. The NT-proBNP values, according to the proposed age-adjusted cut-points, classified 28.6% of patients as "HS likely" (organize elective echocardiography and specialist evaluation), 43.2% as "HS not likely" (a grey area, repeat NT-proBNP at six months) and 28.2% as "very unlikely HS" (repeat NT-proBNP at one year). The presence of CKD and the number of anti-hypertensive drugs, but not glycemic parameters, were independently associated with HS. CONCLUSIONS: According to NT-proBNP, over a quarter of T2DM patients with hypertension/high-normal BP, among those eligible for SGLT2i and/or GLP1-RA, were already at risk of cardiac damage, even subclinical. Most would receive an indication to echocardiogram and be referred to a specialist, allowing the early implementation of effective strategies to prevent or delay the progression to advanced stages of cardiac disease and overt HF.

A two-stage ensemble learning based prediction and grading model for PD-1/PD-L1 inhibitor-related cardiac adverse events: A multicenter retrospective study.

BACKGROUND: Immune-related cardiac adverse events (ircAEs) caused by programmed cell death protein-1 (PD-1) and programmed death-ligand-1 (PD-L1) inhibitors can lead to fulminant and even fatal consequences. This study aims to develop a prediction and grading model for ircAEs, enabling graded management of patients. METHODS: This study utilized medical record systems from two medical institutions to develop a prediction and grading model for ircAEs using ten machine learning algorithms and two variable screening methods. The model was developed based on a two-stage ensemble learning framework. In the first stage, the ircAEs and non-ircAEs cases were classified. In the second stage, ircAEs cases were grouped into grades 1-2 and 3-5. The experiments were evaluated using five-fold cross-validation. The model's prediction performance was assessed using accuracy, precision, recall, F1 value, Brier score, receiver operating characteristic curve area (AUC), and area under the precision-recall curve (AUPR). RESULTS: 615 patients were included in the study. 147 experienced ircAEs, and 44 experienced grade 3-5 ircAEs. The soft voting classifier trained using the variables screened by feature importance ranking performed better than other classifiers in both stages. The average AUC for the first and second stages is 84.18 % and 85.13 %, respectively. In the first stage, the three most important variables are N-terminal B-type natriuretic peptide (NT-proBNP), interleukin-2 (IL-2), and C-reactive protein (CRP). In the second stage, the patient's age, NT-proBNP, and left ventricular ejection fraction (LVEF) are the three most critical variables. CONCLUSIONS: The prediction and grading model of ircAEs based on two-stage ensemble learning established in this study has good performance and potential clinical application.

Markers of imminent myocardial infarction.

Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case-cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.

Relationship between NT-proBNP levels and existing/de novo QRS fragmentation in patients with myocardial infarction.

Aim: to assess the evolution of fragmented QRS (fQRS) and NT-proBNP levels during myocardial infarction (MI).Methods: Among 511 patients, 205 (40.1%) had fQRS, with 54 (26.3%) developing de novo fragmentation during hospitalization.Results: NT-proBNP levels were significantly higher in the fQRS+ group compared with the fQRS- group (1555 vs. 796 pg/ml, p < 0.001). NT-proBNP levels were higher in patients with de novo fragmentation than in those without (2852 vs. 1370 pg/ml, p = 0.011). The incidence of major adverse cardiovascular events was notably higher in fQRS+ patients compared with fQRS- patients (p = 0.001).Conclusion: In acute MI, there was a significant association between fQRS and NT-proBNP levels, with higher NT-proBNP levels observed in those with de novo fQRS compared with those without.

[Box: see text].

Predictive value of perioperative NT-proBNP levels for acute kidney injury in patients with compromised renal function undergoing cardiac surgery: a case control study.

BACKGROUND: Acute kidney injury (AKI) significantly increases morbidity and mortality following cardiac surgery, especially in patients with pre-existing renal impairments. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and dysfunction, conditions often exacerbated during cardiac surgery and prevalent in chronic kidney disease (CKD) patients. Elevated NT-proBNP levels can indicate underlying cardiac strain, hemodynamic instability and volume overload. This study evaluated the association between perioperative changes in NT-proBNP levels and the incidence of AKI in this particular patient group. METHODS: This retrospective study involved patients with impaired renal function (eGFR 15-60 ml/min/1.73 m²) who underwent cardiac surgery from July to December 2022. It analyzed the association between the ratio of preoperative and ICU admittance post-surgery NT-proBNP levels and the development of AKI and AKI stage 2-3, based on KDIGO criteria, using multivariate logistic regression models. Restricted cubic spline analysis assessed non-linear associations between NT-proBNP and endpoints. Subgroup analysis was performed to assess the heterogeneity of the association between NT-proBNP and endpoints in subgroups. RESULTS: Among the 199 participants, 116 developed postoperative AKI and 16 required renal replacement therapy. Patients with AKI showed significantly higher postoperative NT-proBNP levels compared to those without AKI. Decreased baseline eGFR and increased post/preoperative NT-proBNP ratios were associated with higher AKI risk. Specifically, the highest quantile post/preoperative NT-proBNP ratio indicated an approximately seven-fold increase in AKI risk and a ninefold increase in AKI stage 2-3 risk compared to the lowest quantile. The area under the receiver operating characteristic curve for predicting AKI and AKI stage 2-3 using NT-proBNP were 0.63 and 0.71, respectively, demonstrating moderate accuracy. Subgroup analysis demonstrated that the positive association between endpoints and logarithmic transformed post/preoperative NT-proBNP levels was consistently robust in subgroup analyses stratified by age, sex, surgery, CPB application, hypertension, diabetes status and fluid balance. CONCLUSION: Perioperative NT-proBNP level changes are predictive of postoperative AKI in patients with pre-existing renal deficiencies undergoing cardiac surgery, aiding in risk assessment and patient management.

Multimodal deep learning models utilizing chest X-ray and electronic health record data for predictive screening of acute heart failure in emergency department.

BACKGROUND AND OBJECTIVES: Ambiguity in diagnosing acute heart failure (AHF) leads to inappropriate treatment and potential side effects of rescue medications. To address this issue, this study aimed to use multimodality deep learning models combining chest X-ray (CXR) and electronic health record (EHR) data to screen patients with abnormal N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in emergency departments. METHODS: Using the open-source dataset MIMIC-IV and MIMICCXR, the study population consisted of 1,432 patients and 1,833 pairs of CXRs and EHRs. We processed the CXRs, extracted relevant features through lung-heart masks, and combined these with the vital signs at triage to predict corresponding NT-proBNP levels. RESULTS: The proposed method achieved a 0.89 area under the receiver operating characteristic curve by fusing predictions from single-modality models of heart size ratio, radiomic features, CXR, and the region of interest in the CXR. The model can accurately predict dyspneic patients with abnormal NT-proBNP concentrations, allowing physicians to reduce the risks associated with inappropriate treatment. CONCLUSION: The study provided new image features related to AHF and offered insights into future research directions. Overall, these models have great potential to improve patient outcomes and reduce risks in emergency departments.

The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial.

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .

Diastolic Strain Parameters are Associated with Short Term Mortality and Rehospitalization in Patients with Advanced Heart Failure. / Parâmetros de Strain Diastólico Estão Associados à Mortalidade em Curto Prazo e à Reinternação em Pacientes com Insuficiência Cardíaca Avançada.

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization and mortality worldwide and places a great economic burden on healthcare systems. Identification of prognostic factors in HF patients is of great importance to establish optimal management strategies and to avoid unnecessary invasive and costly procedures in end-stage patients. OBJECTIVES: In the current study, we aimed to investigate the association between diastolic strain parameters including E/e' SR, and short-term outcomes in advanced HF patients. METHODS: The population study included 116 advanced HF with reduced ejection fraction (HFrEF) patients. Clinical, laboratory, and echocardiographic evaluations of the patients were performed within the first 24 hours of hospital admission. Patients were followed for one month and any re-hospitalization due to worsening of HF symptoms and any mortality was recorded. The level of significance adopted in the statistical analysis was 5%. RESULTS: E/e' SR was significantly higher in the patient group compared to the control group (p=0.001). During one-month follow-up, 13.8% of patients died and 37.1% of patients were rehospitalized. Serum NT-ProBNP (p=0.034) and E/e' SR (p=0.033) were found to be independent predictors of mortality and ACEI use (p=0.027) and apical 3C strain (p=0.011) were found to be independent predictors of rehospitalization in the patient group. CONCLUSION: Findings of the current prospective study demonstrate that E/e' SR measured by speckle tracking echocardiography is an independent and sensitive predictor of short-term mortality in advanced HFrEF patients and may have a role in the identification of end-stage HFrEF patients.

FUNDAMENTO: A insuficiência cardíaca é uma das principais causas de hospitalização e mortalidade em todo o mundo e representa um grande fardo económico para os sistemas de saúde. A identificação de fatores prognósticos em pacientes com IC é de grande importância para estabelecer estratégias de manejo ideais e evitar procedimentos invasivos e dispendiosos desnecessários em pacientes em estágio terminal. OBJETIVOS: No presente estudo, nosso objetivo foi investigar a associação entre parâmetros de strain diastólico, incluindo E/e' SR, e resultados de curto prazo em pacientes com IC avançada. MÉTODOS: O estudo populacional incluiu 116 pacientes com insuficiência cardíaca avançada com fração de ejeção reduzida (ICFEr) avançada. Avaliações clínicas, laboratoriais e ecocardiográficas dos pacientes foram realizadas nas primeiras 24 horas de internação. Os pacientes foram acompanhados por um mês e qualquer reinternação por piora dos sintomas de IC e qualquer mortalidade foi registrada. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: A E/e' SR foi significativamente maior no grupo de pacientes em comparação ao grupo controle (p=0,001). Durante o acompanhamento de um mês, 13,8% dos pacientes morreram e 37,1% dos pacientes foram reinternados. NT-ProBNP sérico (p=0,034) e E/e' SR (p=0,033) foram considerados preditores independentes de mortalidade e o uso de IECA (p=0,027) e strain 3C apical (p=0,011) foram considerados independentes preditores de reinternação no grupo de pacientes. CONCLUSÃO: Os resultados do presente estudo prospectivo demonstram que a E/e' SR medida pela ecocardiografia com speckle tracking é um preditor independente e sensível de mortalidade em curto prazo em pacientes com ICFEr avançada e pode ter um papel na identificação de pacientes com ICFEr em estágio terminal.

An investigation of the umbilical artery N-terminal proBrain natriuretic peptide levels of fetuses due to fetal distress in term pregnancies.

OBJECTIVE: This study aimed to investigate umbilical artery N-terminal proBrain natriuretic peptide (NT-proBNP) in fetuses delivered by cesarean section due to fetal distress in term pregnancies. METHODS: This prospective case-control study was conducted at the Antalya Training and Research Hospital Obstetric Department, Turkiye. A total of 140 pregnant women, 70 underwent elective cesarean sections between weeks 37 and 40 of gestation (Group 1, the control group) and 70 underwent cesarean sections due to fetal distress (Group 2, the study group), were included. The participants' sociodemographic and obstetric data and fetal umbilical blood NT-proBNP levels were recorded in a database. RESULTS: Age, body mass index, gestational age, prenatal diagnostic tests, fetal anatomical scanning, and baby gender ratios were comparable between the groups (p>0.05), while statistically significant differences were observed in terms of gravidity (3.0 vs. 1.0, p≤0.001) and parity numbers (2 vs. 0, p≤0.001), baby height (50.36±0.88 vs. 49.80±0.86, p≤0.001) and weight (3422.43±409.16 vs. 3239.86±293.74, p=0.003), 1-min Apgar (9.0±0.1 vs. 8.5±1.3, p≤0.001) and 5-min Apgar (10.0±0.1 vs. 9.8±0.4, p=0.026) scores, umbilical artery pH (7.32±0.05 vs. 7.25±0.07, p≤0.001), umbilical artery base deficit (-2.48±1.23 vs. -4.36±1.09. p≤0.001), and NT-proBNP levels [8.77 (7.72-9.39) vs. 12.35 (9.69-12.92), p<0.001]. CONCLUSION: This study showed that NT-proBNP can be used as an important marker in the diagnosis of fetal distress. Prospective studies with more participants are now needed to confirm the accuracy of our results.

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical siabetic cardiomyopathy.

INTRODUCTION: Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. METHODS: In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. RESULTS: The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E', or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = - 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = - 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = - 0.28; p < 0.001), peak VO2 (rho = - 0.26; p < 0.001), and ratio of minute ventilation/carbon dioxide production (rho = 0.12; p = 0.002). After adjustment for known confounders, the correlation with Physical Activity Scale in the Elderly and overall Kansas City Cardiomyopathy Questionnaire score was no longer significant. CONCLUSION: Among patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals. TRIAL REGISTRATION: ARISE-HF, NCT04083339 Date Registered August 23, 2019.