N-terminal B-type Natriuretic Peptide Research Articles

Функція зовнішнього дихання та дифузійна здатність легень у пацієнтів із різними формами легеневої гіпертензії

The aim – to compare pulmonary function test (PFT) results and diffusion capacity of the lungs for carbon monoxide (DLCO) in patients with various forms of pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH) and healthy individuals; to establish correlations between PFT, DLCO and parameters used to stratify the risk of death in pulmonary hypertension (PH).Materials and methods. 74 patients were included: 18 with idiopathic PAH (IPAH), 15 with PAH associated with congenital heart defects (PAH-CHD), 21 with CTEPH and 20 healthy persons (control group). All participants underwent an assessment of PFT (vital capacity (VC), forced vital capacity (FVC), forced expiratory volume during one second (FEV1), peak expiratory velocity (PEV), maximum expiratory flow (MEF) 75, MEF-50, MEF-25) and measurement of DLCO. For all PH patients the standard examinations were provided, including N-terminal brain natriuretic peptide (NT-proBNP) assessment and right heart catheterization. Results. Patients of all PH groups had significantly lower parameters of PFT and DLCO, compared to the control group. The most pronounced and reliable decrease in PFT was observed among patients with PAH-CHD. The lowest DLCO was observed in CTEPH group. PH patients with DLCO < 64 %, compared with DLCO ≥ 64 %, had significantly lower distance of the 6-minute walk test (6MWT) (p = 0.014), TAPSE (р = 0.015), SpO2 during pulse oximetry and direct measurement (p = 0.023 and 0.032, respectively), hemoglobin level (p = 0.031). They had a significantly higher level of NT-proBNP (p = 0.012) and they were somewhat older (p = 0.053). DLCO < 64 % correlated with hemoglobin level (r = –0.31, p = 0.022), 6MWT distance (r = –0.35, p = 0.012), SpO2 (r = –0.29, p = 0.036), TAPSE (r = –0.34, p = 0.012) and NT-proBNP (r = 0.27, p = 0.048). Independent predictors of reduced DLCO were hemoglobin level (β = 0.95, CI 0.90-0.99), SpO2 (β = 0.75, CI 0.58-0.95) and TAPSE (β = 0.75, CI 0.63-0.91).Conclusions. Parameters of PFT and DLCO were significantly lower in patients of all PH groups compared to the healthy individuals. Patients with PAH-CHD had significantly worse PFT parameters. In the general population of patients with PH, PFT indicators, which characterize inspiratory capabilities, were independently correlated with the area of ​​the right atrium. The reduced DLCO (< 64 %) correlated with the level of hemoglobin, SpO2 and indicators of the patient functional state. However, low levels of hemoglobin, SpO2, and TAPSE were independent predictors of low DLCO.

Preacinar Arterial Dilation Mediates Outcomes of Quantitative Interstitial Abnormalities in the COPDGene Study.

Rationale: Quantitative interstitial abnormalities (QIAs) are a computed tomography (CT) measure of early parenchymal lung disease associated with worse clinical outcomes, including exercise capacity and symptoms. The presence of pulmonary vasculopathy in QIAs and its role in the QIA-outcome relationship is unknown. Objectives: To quantify radiographic pulmonary vasculopathy in QIAs and determine whether this vasculopathy mediates the QIA-outcome relationship. Methods: Ever-smokers with QIAs, outcomes, and pulmonary vascular mediator data were identified from the Genetic Epidemiology of COPD (COPDGene) study cohort. CT-based vascular mediators were right ventricle-to-left ventricle ratio, pulmonary artery-to-aorta ratio, and preacinar intraparenchymal arterial dilation (pulmonary artery volume, 5-20 mm2 in cross-sectional area, normalized to total arterial volume). Outcomes were 6-minute walk distance and a modified Medical Council Research Council Dyspnea Scale score of 2 or higher. Adjusted causal mediation analyses were used to determine whether the pulmonary vasculature mediated the QIA effect on outcomes. Associations of preacinar arterial dilation with select plasma biomarkers of pulmonary vascular dysfunction were examined. Measurements and Main Results: Among 8,200 participants, QIA burden correlated positively with vascular damage measures, including preacinar arterial dilation. Preacinar arterial dilation mediated 79.6% of the detrimental impact of QIA on 6-minute walk distance (56.2-100%; P < 0.001). Pulmonary artery-to-aorta ratio was a weak mediator, and right ventricle-to-left ventricle ratio was a suppressor. Similar results were observed in the relationship between QIA and modified Medical Council Research Council dyspnea score. Preacinar arterial dilation correlated with increased pulmonary vascular dysfunction biomarker levels, including angiopoietin-2 and N-terminal brain natriuretic peptide. Conclusions: Parenchymal QIAs deleteriously impact outcomes primarily through pulmonary vasculopathy. Preacinar arterial dilation may be a novel marker of pulmonary vasculopathy in QIAs.

Serum potassium levels and in-hospital mortality in distinct phenotypes of myocardial infarction patients by machine learning clustering

Abstract Background Abnormal serum potassium levels are associated with an increased risk of mortality in patients with myocardial infarction (MI); however, it is unclear whether the impact of potassium levels on mortality risk varies depending on the characteristics of MI patients. Purpose We aimed to classify MI patients according to their clinical characteristics and explore the relationship between potassium levels and in-hospital mortality in distinct clusters of MI. Methods Using Medical Information Mart for Intensive Care (MIMIC) IV database, we identified 3,159 patients who admitted for the first time to the intensive care unit with a primary diagnosis of acute MI. Machine learning clustering was performed on this population based on available clinical and laboratory data. Results Three distinct clusters of MI patients were identified using clustering analysis: 1,455 (46%) in cluster 1, 587 (19%) in cluster 2, and 1,117 (35%) in cluster 3. Patients in cluster 2 were older, had the highest comorbidity burden, Sequential Organ Failure Assessment (SOFA) score, peak lactate, creatinine, peak troponin, N-terminal B-type natriuretic peptide (NT-proBNP) levels and the lowest hemoglobin levels among the 3 clusters. Patients in cluster 3 were younger, had the lowest comorbidity burden, SOFA score, peak lactate, creatinine, NT-proBNP levels. Patients belonging to cluster 1 had clinical characteristics intermediate to those of cluster 2 and 3, except for the lowest troponin level. In-hospital mortality was highest in cluster 2, followed by cluster 1 and then cluster 3. Patients in cluster 2 had the highest in-hospital mortality risk with hypokalemia (OR 3.71, 95% 1.81­­-7.63) and patients in cluster 3 had highest in-hospital mortality risk with hyperkalemia (OR 2.77, 95% CI 0.84-9.06). Patients in cluster 1 did not exhibit a linearly increasing mortality with hyperkalemia. Conclusions The use of clustering analysis in patients with acute MI could characterize baseline clinical data into clinically distinct clusters with different in-hospital mortality across the dyskalemia continuum. The results suggest that the optimal range of potassium levels in patients with MI may vary depending on patient characteristics.Figure - clusteringTable - K and In-hospital mortality

GenePHIT phase 2 study design: a double blind, placebo-controlled trial to assess efficacy, safety, and tolerability of AB-1002 gene therapy in adults with heart failure

Abstract Introduction Heart failure (HF) is associated with substantial morbidity and mortality, highlighting a critical need for novel therapies. AB-1002, an engineered adeno-associated virus (AAV) vector gene therapy candidate, delivers a constitutively active form of protein phosphatase inhibitor (I-1c) to restore cardiomyocyte intracellular calcium homeostasis. Preliminary results from an ongoing Phase (Ph) 1 trial (NCT04179643) of AB-1002 showed favourable safety and tolerability. Here we describe the design of AB-1002 Ph 2 trial (GenePHIT; NCT05598333) to evaluate efficacy, safety, and tolerability. Methods This phase 2 adaptive, double-blind, placebo-controlled, randomised, multi-centre trial (currently United States; European sites planned) includes a 52-week observation and 4-year follow-up period. Eligible patients are ≥18 years of age with non-ischaemic cardiomyopathy and New York Health Association (NYHA) Class III heart failure symptoms (Figure). Patients will be randomised 1:1:1 (n=30–50/treatment arm), including a single dose of AB-1002 administered via antegrade intracoronary infusion at 1 of 2 different doses, or placebo, all in addition to standard of care. The primary endpoint will evaluate efficacy at 52 weeks based on the composite endpoint by modified win ratio, which includes cardiovascular-related death, change in NYHA classification, and for the responders, improvements in left ventricular ejection fraction (LVEF) (≥5%), peak oxygen uptake (pVO2) ≥1.5 mL/kg/min, and 6-min walk test (6MWT) &amp;gt;30 metres. Key secondary efficacy endpoints include functional status and hospitalisations at 24 and 52 weeks, by assessing changes over time in NYHA classification, LVEF, pVO2, 6MWT, biomarkers (N-terminal pro-hormone b-type natriuretic peptide and troponin), quality of life questionnaires (Minnesota Living with Heart Failure, Kansas City Cardiomyopathy), and physiological assessments. Key safety endpoints will be assessed through 52 weeks and include treatment-emergent adverse events (AEs) and serious AEs (SAEs). Exploratory endpoints will evaluate AAV2i8 antibody titres, T-cell response to AAV2i8 capsid and I-1c, and optional right ventricular biopsy testing. Long-term follow-up will assess treatment-emergent AEs and SAEs, and number of HF hospitalisations. Data safety monitoring board assessment will occur every 3 months. Primary efficacy endpoint will compare both active dose groups combined versus placebo using the joint rank test (1). Key secondary endpoints will be analysed using Analysis of Covariance with baseline as a continuous covariate. Multiple imputations will be used to address missing data. Interim efficacy analysis will be performed using a Bayesian adaptive sample size algorithm. Conclusions GenePHIT is currently recruiting and will evaluate the efficacy, safety, and tolerability of intracoronary infusion of AB-1002, an innovative gene therapy targeting ventricular dysfunction in HF.

The relation between atrial arrhythmias and heart failure in adult patients with congenital heart disease

Abstract Background Advances in care have significantly improved survival in patients with adult congenital heart disease (ACHD). This growing population is now confronted with new challenges due to their structural malformations, surgical scars, cyanosis and/or longstanding abnormal pressure and volume load that lead to progressive atrial fibrosis. Atrial arrhythmias (AA) and heart failure (HF) have become the leading causes of hospitalisation in patients with ACHD and pose specific challenges in management. Purpose To assess the relationship between a first AA diagnosis and development of HF in patients with ACHD and investigate the impact of HF on the treatment success of radiofrequency ablation (RFA) for AA. Methods This single-centre, retrospective study included 3995 patients with ACHD. AA was defined as: (I) Atrial fibrillation (AF); (II) Intra-atrial re-entrant tachycardia (IART); (III) Atrial flutter (AFL); or (IV) Focal atrial tachycardia (AT). HF was defined as clinical signs and/or symptoms of HF necessitating medical intervention, along with one of the following: (I) impaired ventricular function with elevated intracardiac pressures; (II) elevated N-terminal B-type natriuretic peptide; (III) peak oxygen consumption in the lowest quartile as per specific ACHD subtype; or (IV) distinctive HF manifestations in patients with a Fontan circulation. Both AA and HF were collected with corresponding dates of first presentation. Details on RFA procedures were collected and acute and long-term success rates were calculated using Kaplan-Meier analysis. Results The mean age of the ACHD cohort at last follow-up was 35.4 ± 13.2 y. As per Bethesda complexity classification, 28.0% of ACHD patients had mild defects, 59.4% moderate and 12.6% severe defects. AA was documented in 348 (8.7%) patients with mean age at first presentation of 37.3 ± 19.6 y (Figure 1). Patients with Fontan circulation (38.5%), cyanotic ACHD (21.0%), and systemic right ventricle (24.2%) were more likely to present with AA. Furthermore, patients with a Fontan circulation (18.8 ± 12.4 y) or a systemic right ventricle (29.7 ± 16.1 y) presented with AA at younger age. The overall prevalence of HF was 6.4%. A total of 130 (3.3%) patients were diagnosed with AA as well as HF. Of these, 103 (79.2%) patients were diagnosed with AA 8.2 ± 7.4 y before HF diagnosis. RFA procedures were performed in 119 patients (34.2%), of which 45 (21.0%) were performed in patients with HF. Overall, 72% of patients undergoing RFA remained free from AA at 2 years after RFA (Figure 2.A). Acute success rates were higher and recurrence rates lower in those without HF (Figure 2.B, p=0.0001). Conclusions In patients with ACHD AA and HF are prevalent, especially in complex ACHD, and a first AA occurs on average 8 years prior to HF diagnosis. The main outcome is driven by HF and not AA. RFA can be an effective treatment for AA with 72% being recurrence free 2 years after RFA, but outcome is affected by coinciding HF.Overview of relation between AA and HFKaplan-meier analysis of AA RFA.

Utility of urinary NT-proBNP in congenital diaphragmatic hernia: a prospective pilot study.

Echocardiography is the reference standard for diagnosing pulmonary hypertension (PH) and cardiac dysfunction (CD) in congenital diaphragmatic hernia (CDH). The use of an adjunct non-invasive biomarker would be invaluable. Plasma N-terminal brain Natriuretic Peptide (NT-proBNP) has been evaluated as a biomarker in CDH. Our objective was to investigate the utility of urinary NT-proBNP as an adjunct biomarker in CDH. Prospective observational study of neonates with CDH. Urinary NT-proBNP and its ratio to urinary creatinine (UNBCR) were analyzed at 24 h of life (HOL). Spearman's correlation was used to quantify the association between the urinary NT-proBNP with corresponding plasma concentrations. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine urinary NT-proBNP and UNBCR's association with need for ECMO. The Kruskal-Wallis test was used to compare urinary NT-proBNP concentrations with echocardiography parameters of PH and CD. Urinary NT-proBNP and UNBCR positively correlated with plasma concentrations. Patients with high right ventricular (RV) pressures had higher urinary NT-proBNP concentrations. Both urinary NT-proBNP and UNBCR concentrations increased with worsening left and right ventricular dysfunction on first postnatal echocardiogram. We report the feasibility of urinary NT-proBNP as a non-invasive biomarker to assess PH and CD in CDH. Non-invasive biomarkers are an important area of research in neonates as they have the potential to decrease the need for blood sampling, which may cause pain, stress, and induce iatrogenic anemia. Use of non-invasive biomarkers could be especially useful in congenital diaphragmatic hernia (CDH) who may need Extra-Corporeal Life Support (ECLS) for their management. We evaluated the potential utility of the urinary NT-proBNP in CDH. Plasma NT-proBNP has been studied in neonates with CDH; however, urinary NT-proBNP has not been explored, making this the first study to examine its potential as a biomarker.

Artificial intelligence machine learning based evaluation of elevated left ventricular end-diastolic pressure: a Cleveland Clinic cohort study.

Left ventricular end-diastolic pressure (LVEDP) is a key indicator of cardiac health. The gold-standard method of measuring LVEDP is invasive intra-cardiac catheterization. Echocardiography is used for non-invasive estimation of left ventricular (LV) filling pressures; however, correlation with invasive LVEDP is variable. We sought to use machine learning (ML) algorithms to predict elevated LVEDP (>20 mmHg) using clinical, echocardiographic, and biomarker parameters. We identified a cohort of 460 consecutive patients from the Cleveland Clinic, without atrial fibrillation or significant mitral valve disease who underwent transthoracic echocardiography within 24 hours of elective heart catheterization between January 2008 and October 2010. We included patients' clinical (e.g., heart rate), echocardiographic (e.g., E/e'), and biomarker [e.g., N-terminal brain natriuretic peptide (NT-proBNP)] profiles. We fit logistic regression (LR), random forest (RF), gradient boosting (GB), support vector machine (SVM), and K-nearest neighbors (KNN) algorithms in a 20-iteration train-validate-test workflow and measured performance using average area under the receiver operating characteristic curve (AUROC). We also predicted elevated tau (>45 ms), the gold-standard parameter for LV diastolic dysfunction, and performed multi-class classification of the patients' cardiac conditions. For each outcome, LR weights were used to identify clinically relevant variables. ML algorithms predicted elevated LVEDP (>20 mmHg) with good performance [AUROC =0.761, 95% confidence interval (CI): 0.725-0.796]. ML models showed excellent performance predicting elevated tau (>45 ms) (AUROC =0.832, 95% CI: 0.700-0.964) and classifying cardiac conditions (AUROC =0.757-0.975). We identified several clinical variables [e.g., diastolic blood pressure, body mass index (BMI), heart rate, left atrial volume, mitral valve deceleration time, and NT-proBNP] relevant for LVEDP prediction. Our study shows ML approaches can robustly predict elevated LVEDP and tau. ML may assist in the clinical interpretation of echocardiographic data.

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects in patients with hypertrophic cardiomyopathy

AimWe sought the cardiopulmonary exercise testing (CPET) parameter that most accurately reflected therapeutic efficacy in patients with hypertrophic cardiomyopathy (HCM). MethodsWell-being questionnaire, N-terminal brain natriuretic peptide measurements, echocardiography, and CPET were performed in patients with symptomatic non-obstructive HCM during phase II, randomized, open-label multicentre study, before and after 16 weeks of traditional or sacubitril/valsartan treatment. Patients were followed 36 months after the initial CPET. Primary endpoints were changes in: 1) peak oxygen consumption (VO2); 2) VO2 at anaerobic threshold (AT); 3) oxygen pulse; 4) minute ventilation (VE)/carbon-dioxide (CO2) production slope; 5) VE/VCO2 at AT (VE/VCO2_AT); 6) VE/VCO2 nadir; 7) VE/VCO2 intercept; and 8) partial end-tidal pressure of carbon-dioxide (PETCO2) change during CPET. ResultsOf 115 screened patients, 61 (52 ± 14 years, 43 % women) were included. Within subject therapy effects were detected only by the VE/VCO2 intercept and PETCO2 change, whereas the differences between medical regimens were detected by differences in VE/VCO2 nadir and VE/VCO2_AT changes after the treatment. The best predictors of the change in well-being were left ventricular outflow tract maximal gradient and VE/VCO2 intercept (B = 0.41,0.36; SE = 0.16,0.30; CI = 0.14–0.79, 0.15–1.14; p = 0.006,0.016, respectively). Adverse cardiac events were best predicted by the initial VE/VCO2 nadir. ConclusionVentilatory efficiency parameters outperform peak VO2 in gauging therapy effects in patients with HCM.

Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures

Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55–71) years. Median LVEDP was 13.5 (8–19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20–0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22–0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11–0.46]), sST2 (p < 0.0001, r = 0.47 [0.30–0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e’, sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable model.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

Efficacy and Safety of Canagliflozin in STEMI Patients with Type 2 Diabetes after PCI: A Retrospective Study

Objective: To assess the effectiveness and safety of canagliflozin in the management of ST segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (T2DM) post-percutaneous coronary intervention (PCI). Methods: A retrospective analysis on data of patients diagnosed with STEMI and T2DM who underwent PCI treatment at our hospital was performed from June 2020 to September 2023. The patients were divided into two groups based on the exposure factor: the canagliflozin and conventional treatment groups and the canagliflozin and routine treatment groups. Various parameters, such as demographic characteristics, cardiac function indicators, and insulin-related factors, were collected and compared postprocedure. In addition, evaluation of the insulin sensitivity index (ISI), lipid profile parameters, and safety outcomes was conducted. A balanced baseline characteristics of patients was achieved via propensity score matching (PSM) at a 1:1 ratio. Statistical analyses were performed through t-tests, nonparametric tests, and chi-square tests. Results: This work included data on 156 patients, including 63 and 93 patients in the canagliflozin and routine treatment groups, respectively. Later, each group comprised 63 patients after 1:1 matching by PSM. After treatment, the canagliflozin treatment group exhibited notably reduced levels of N-terminal B-type natriuretic peptide, cardiac troponin T (cTnT), and creatine kinase-MB and a significantly higher level of left ventricular ejection fraction in comparison with the routine treatment group (p &lt; 0.05). In addition, following treatment, the canagliflozin treatment group exhibited a significant decrease in homeostatic model assessment (HOMA)-insulin resistance levels and a significant increase in HOMA-β levels (p &lt; 0.05). Conversely, the groups manifested no significant variances in terms of major adverse cardiovascular events, hypoglycemia, diabetic ketoacidosis, acute kidney injury, and urinary tract infection (p &gt; 0.05). Conclusion: The concurrent administration of canagliflozin following PCI improves cardiac function, insulin sensitivity, and lipid profile in patients with STEMI and T2DM, which ultimately lowers the likelihood of cardiovascular incidents. Canagliflozin demonstrates favorable clinical safety profiles in such individuals and displays promising prospects for clinical utility.

Adropin Predicts Asymptomatic Heart Failure in Patients with Type 2 Diabetes Mellitus Independent of the Levels of Natriuretic Peptides.

In patients with type 2 diabetes mellitus (T2DM), asymptomatic adverse cardiac remodeling plays a pivotal role in the development of heart failure (HF). Patients with T2DM often have low or near-normal levels of natriuretic peptides, including N-terminal brain natriuretic peptide (NT-proBNP), which have been inconclusive in predicting the transition from asymptomatic adverse cardiac remodeling to HF with preserved ejection fraction (HFpEF). The aim of this study was to elucidate the predictive ability of adropin for HFpEF depending on the circulating levels of NT-proBNP. We prospectively enrolled 561 T2DM patients (glycated hemoglobin < 6.9%) with echocardiographic evidence of structural cardiac abnormalities and left ventricular ejection fractions >50%. All patients underwent B-mode transthoracic echocardiographic and Doppler examinations. Circulating biomarkers, i.e., NT-proBNP and adropin, were assessed at baseline. All individuals were divided into two groups according to the presence of low levels (<125 pmol/mL; n = 162) or elevated levels (≥125 pmol/mL; n = 399) of NT-proBNP. Patients with known asymptomatic adverse cardiac remodeling and elevated NT-proBNP were classified as having asymptomatic HFpEF. A multivariate logistic regression showed that low serum levels of adropin (<3.5 ng/mL), its combination with any level of NT-proBNP, and use of SGLT2 inhibitors were independent predictors of HFpEF. However, low levels of adropin significantly increased the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM, even though the concentrations of NT-proBNP were low, while adropin added discriminatory value to all concentrations of NT-proBNP. In conclusion, low levels of adropin significantly increase the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM.

Study on novel inflammatory indicators in marathon exercise monitoring

To analyze the changes in lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammatory indices (neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammation index) before and after competitions in amateur marathon runners, and to assess the effects of myocardial injury due to acute exercise and the value of novel inflammatory indices in marathon exercise monitoring. This paper is an analytical study. Amateur athletes recruited by Beijing Hospital to participate in the 2022 Beijing Marathon and the 2023 Tianjin Marathon, and those who underwent health checkups at the Beijing Hospital Medical Checkup Center from January to June 2023 were selected as the study subjects, and 65 amateur marathon runners (41 males and 24 females) and 130 healthy controls (82 males and 48 females) were enrolled in the study according to the inclusion criteria. Peripheral blood was collected one week before, immediately after, and one week after running, and routine blood tests, cardiac enzymes, infarction markers, N-terminal B-type natriuretic peptide precursor, and homocysteine were performed to calculate the values of novel inflammatory indexes. Wilcoxon signed-rank test and Spearman's rank correlation analysis were used to compare the differences in the levels of each index between the amateur marathon population and the health checkup population, and to compare the changes and correlations of each index at the three time points in the amateur marathoners.The results showed that the neutrophil-lymphocyte ratios of the healthy physical examination population and 65 amateur marathoners 1 week before running were 1.73 (1.33, 2.16) and 1.67 (1.21, 2.16), the platelet-lymphocyte ratios were 122.75 (96.69, 155.89) and 120.86 (100.74, 154.63), and the systemic immune inflammation index was 398.62 (274.50, 538.69) and 338.41 (258.62, 485.38), etc.; on 1 week before running, immediately after running and 1 week after running, lactate dehydrogenase of 65 amateur marathon runners was 173.00(159.00, 196.50)U/L,284.00(237.50, 310.50)U/L, 183.00(165.50, 206.50)U/L, creatine kinase was 131.00(94.30, 188.20)U/L,318.00(212.00, 573.15)U/L,139.00(90.55, 202.40)U/L, creatine kinase isoenzyme was 2.50(1.76, 3.43)μg/L,6.24(4.87, 10.30)μg/L,2.73(1.57, 4.40)μg/L.In 65 amateur marathon runners, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammation markers were significantly elevated in the immediate post-run period compared with 1 week before the run, and the differences were statistically significant (Z=-7.009, Z=-6.813, Z=-6.885, Z=-7.009, Z=-7.009, Z=-6.656; P<0.05 for the above indicators).Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammatory index all showed significant positive correlation with the pre-and post-run rates of change of high-sensitivity troponin T (ρ=0.28, P=0.03;ρ=0.31, P=0.01;ρ=0.27, P=0.03); these 3 markers were also significantly and positively correlated with the pre-and post-run rates of change in a collection of myocardial-related markers such as lactate dehydrogenase, creatine kinase, creatine kinase isozymes, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, and homocysteine, respectively(r=0.446, P=0.039; r=0.452, P=0.033; r=0.449, P=0.036).In addition, the platelet-lymphocyte ratio was positively correlated with the pre-and post-run rates of change in creatine kinase and creatine kinase isoenzymes(ρ=0.27, P=0.03;ρ=0.28, P=0.02).In conclusion, acute myocardial injury may be triggered during marathon exercise. Changes in novel inflammatory markers were significantly associated with changes in myocardial enzymes, infarction markers, N-terminal B-type natriuretic peptide precursors, and homocysteine, which may be of value for the prediction of myocardial injury during exercise.

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

BackgroundImmune-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. MethodsThis 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). Results615 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. ConclusionsThe prediction and grading model of ircAEs based on two-stage ensemble learning established in this study has good performance and potential clinical application.

Elevated plasma protein carbonylation increases the risk of ischemic cerebrovascular events in patients with atrial fibrillation: association with a prothrombotic state.

Plasma protein carbonylation that reflects oxidative stress has been demonstrated to be associated with the prothrombotic fibrin clot phenotype. However, the role of protein carbonyls (PC) in predicting ischemic stroke in atrial fibrillation (AF) is largely unknown. This study aimed to investigate whether PC increase the risk of stroke in anticoagulated AF patients during follow-up. In 243 AF patients on anticoagulation (median age 69years; median CHA2DS2-VASc of 4), we measured plasma PC using the assay by Becatti, along with plasma clot permeability (Ks), clot lysis time (CLT), thrombin generation, and fibrinolytic proteins, including plasminogen activator inhibitor type 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). Ischemic stroke, major bleeding, and mortality were recorded during a median follow-up of 53months. Plasma PC levels (median, 3.16 [2.54-3.99] nM/mg protein) at baseline showed positive associations with age (P < 0.001), CHA2DS2-VASc (P = 0.003), and N-terminal B-type natriuretic peptide (P = 0.001), but not with type of AF or comorbidities except for heart failure (P = 0.007). PC levels were correlated with CLT (r = 0.342, P < 0.001), endogenous thrombin potential (r = 0.217, P = 0.001) and weakly with Ks (r = -0.145, P = 0.024), but not with fibrinogen, PAI-1, or TAFI levels. Stroke was recorded in 20 patients (1.9%/year), who had at baseline 36% higher PC levels (P < 0.001). Elevated PC (P = 0.003) at baseline were independently associated with stroke risk. Our findings suggest that in patients with AF enhanced protein carbonylation is associated with increased "residual" risk of stroke despite anticoagulation, which is at least in part due to unfavorably altered fibrin clot phenotype.

Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval

Aims Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. Methods and results Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p = .008). Conclusions The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous.

The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality.

The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden. 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study. Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals. Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.

A Retrospective Study of Whether Sacubitril–Valsartan Improves Cardiac Function in Patients with Acute Coronary Syndrome and Hypertension after Percutaneous Coronary Intervention

Objectives: This study aimed to explore the effect of sacubitril–valsartan on cardiac function in patients with acute coronary syndrome (ACS) and hypertension after percutaneous coronary intervention (PCI). Methods: The study was conducted on 166 patients with ACS and hypertension who underwent PCI at our hospital from July 2022 to June 2023. The patients were divided into two groups: an observation group and a control group, with 83 cases in each group. The observation group was given sacubitril–valsartan, and the control group was given enalapril. The treatment period was 3 months. The cardiac function indexes, biochemical indexes, adverse reactions, and the occurrence of new cardiovascular and cerebrovascular events were compared between the two groups before and after medication. Results: We found no statistically dramatic differences between the two groups in gender, age, body mass index, diabetes, hyperlipidemia, family history of ACS, family history of hypertension, smoking history, drinking history, regular exercise history, low-salt and low-fat diet, New York Heart Association cardiac function classification, number of vessels involved in coronary artery disease, stent length, stent inner diameter, number of stent implants, duration of hypertension, medication time, use of antihypertensive drugs, systolic blood pressure (SBP), and diastolic blood pressure (DBP). The observation group had lower left ventricular end-diastolic internal diameter (LVEDD) levels, higher left ventricular ejection fraction (LVEF) levels, and lower left ventricular end-systolic internal diameter (LVESD) levels compared with the control group. The levels of N-terminal pro-brain B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), and creatine kinase isoenzyme MB (CK-MB) in the observation group decreased compared with those in the control group. Compared with the pre-medication period, LVEDD levels decreased, LVEF levels increased, and LVESD levels decreased in the observation and control groups, whereas NT-proBNP, cTnI, and CK-MB levels decreased in the observation and control groups. The total incidence rates of adverse reactions and new cardiovascular and cerebrovascular events in the observation group were found to be lower than those in the control group. Conclusion: The application of sacubitril–valsartan in patients with ACS complicated with hypertension after PCI can effectively improve patients' cardiac function, reduce biochemical indexes related to myocardial injury, and lower the incidence of adverse cardiovascular events. It features good safety, providing a new treatment strategy and method for patients with ACS complicated with hypertension.

Association of suPAR, ST2, and galectin-3 with eGFR decline and mortality in patients with advanced heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m2, 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (β coefficient = -0.36 √(ml/min/1.73 m2), 95% confidence interval (-0.48 to -0.24), p < 0.001), standardized galectin-3 (-0.14 √(ml/min/1.73 m2) (-0.27 to -0.02), p = 0.02), and log NT-proBNP (-0.23 √(ml/min/1.73 m2) (-0.31 to -0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.

Accuracy of brain natriuretic peptide and N-terminal brain natriuretic peptide for detecting paediatric pulmonary hypertension: a systematic review and meta-analysis

Objective Pulmonary hypertension (PH) is a life-threatening disease, especially in paediatric population. Symptoms of paediatric PH are non-specific. Accurate detection of paediatric PH is helpful for early treatment and mortality reduction. Therefore, we assessed the overall performance of brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) for diagnosing PH in paediatric population. Methods PubMed, Web of Science, Cochrane Library and Embase databases were screened since their respective inceptions until August 2023. A bivariate random model and a hierarchical summary receiver operating characteristic model were used together to evaluate and summarize the overall performance of BNP and NT-proBNP for diagnosing paediatric PH. Results Eighteen studies using BNP/NT-proBNP were assessed, comprising 1127 samples. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUROC) of BNP/NT-proBNP were separately as 0.81, 0.87, 6.33, 0.21, 29.50 and 0.91, suggesting a good diagnostic performance of BNP/NT-proBNP for detecting PH in paediatric population. For BNP, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.83, 0.89, 7.76, 0.19, 40.90 and 0.93, indicating the diagnostic accuracy of BNP for paediatric PH patients was good. For NT-proBNP, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.81, 0.86, 5.59, 0.22, 24.96 and 0.90, showing that NT-proBNP could provide a good value for detecting paediatric PH. Conclusions Both BNP and NT-proBNP are good markers for differentiating paediatric PH patients from non-PH individuals.