N-terminal Brain Research Articles

Biomarkers in early and late period after radiofrequency and pulsed field catheter ablation of atrial fibrillation

Abstract Introduction Biomarkers are routinely used parameters for disease diagnosis, treatment control and risk stratification. In connection with atrial fibrillation (AF), the importance of GDF-15 (growth differentiation factor 15), NT-proBNP (N-terminal fragment brain natriuretic factor) and hs-TnT (high sensitivity cardiac troponin T) is discussed. Catheter ablation is an established treatment method in selected population with AF. However, biomarker response to radiofrequency catheter ablation (RFCA) and pulsed field ablation (PFA) of AF has not been precisely described. Purpose Purpose of the study was to describe early and late dynamics of GDF-15, hs-TnT and NT-proBNP in different ablation technologies. Methods We prospectively enrolled 48 patients (median (IQR) age 62 (55; 70) years, 30 males) undergoing RFCA, which we compared with 30 patients (median (IQR) age 64 (56; 71) years, 18 males) undergoing PFA. All patients underwent 6 sequential blood takes: before ablation (baseline), right after ablation (0h), 24 and 48 hours after procedure (24h and 48h), 90 and 180 days after procedure. Levels of GDF-15, hs-TnT and NT-proBNP were analyzed. Results Out of all patients, 19 (40 %) and 20 (67 %) patients had paroxysmal AF in RFCA and PFA group, respectively. Additional ablation lesions over pulmonary vein isolation were done in 26 (54 %) patients in RFCA group and 11 (43 %) patients in PFA group. Median procedural time was significantly longer in RFCA than in PFA group (155 (130; 190) vs. 80 (70; 90) min; p < 0.01). Early dynamics of GDF-15 and cardiac hs-TnT are visualised in Figure 1 and 2. GDF-15 level peak was registered 48 hours after ablation with median (IQR) 1183 (824; 1988) ng/l. Compared to baseline, GDF-15 values sustained elevated up to 90 days after ablation in both groups and decreased to baseline levels after 180 days. No significant differences were found in GDF-15 levels between patients treated with RFCA and PFA. Maximal values of hs-TnT were significantly higher in PFA group than in RFCA group (1001±589 vs. 458±202 ng/l; p < 0.001). We have recognised decrease of NT-proBNP between baseline and 90 days after procedure in both groups: 338 (112; 613) vs. 209 (101; 545) ng/l; p < 0.05. Conclusion Eventhough GDF-15 is considered as a nonspecific biomarker reflecting general condition of patient, the levels are significantly affected by catheter ablation of AF for several months irrespective to ablation technology. PFA is associated with advanced elevation of hs-TnT.Dynamics of GDF-15 (median; IQR)Dynamics of hs-TnT (median; IQR)

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.

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.

Serum concentrations of chromogranin A, serotonin and natriuretic peptide are decreased in patients with neuroendocrine tumors with overweight and obesity compared to healthy donors

Background: Neuroendocrine tumors (NETs) are a group of neoplasms, in which circulating biomarkers chromogranin A (CgA), serotonin, and N-terminal brain natriuretic pro-peptide (NT-proBNP), used as a marker of carcinoid heart disease, are especially important in the diagnosis and monitoring. A number of pre-analytical factors, including patients' body mass index (BMI), have an impact on NETs biomarker concentrations. Aim: To perform a comparative analysis of serum concentrations of CgA, serotonin and NT-proBNP in patients with NETs of various locations with normal body weight and with overweight or obesity. Methods: This cross-sectional study included 94 patients with NETs of various locations and 78 provisionally healthy individuals without cancer and cardiovascular disorders, matched by gender and age to the patients. Serum biochemical markers were measured before a course of chemotherapy/biotherapy or surgery with the use of standardized enzyme-linked immunosorbent assays Chromogranin A NEOELISA (Eurodiagnostica), Serotonin ELISA (IBL), and the electrochemiluminescent assay (Cobas e601 analyzer, Roche). All NETs patients were divided into 2 subgroups: 46 patients with normal bodyweight (BMI 18 to 24.9) and 48 patients with overweight/obesity (BMI ≥ 25). Results: The median BMI in the NET patients did not vary depending on their tumor extension, functional activity and malignancy grade. The median concentrations of CgA (150 ng/ml), serotonin (188 ng/ml) and NT-proBNP (117 pg/ml) in the NET patients with obesity and overweight were significantly lower (p = 0.008, p = 0.005 and p = 0.012, respectively) than in the NET patients with normal body weight (769 ng/ml, 704 ng/ml and 197 pg/ml, respectively). In the control group, significantly (p = 0.0001) lower levels in the subgroup with BMI ≥ 25 were obtained only for serotonin. The ROC analysis showed a decrease of the diagnostic efficiency of NET biomarkers in obesity: in the normal BMI group AUC (CgA) was 0.87 and AUC (serotonin) 0.78, whereas in those with BMI ≥ 25, the AUC (CgA) and AUC (serotonin) were 0.81 and 0.62, respectively. Conclusion: Obesity may make it difficult to identify biochemical markers of NETs – CgA, serotonin and NT-proBNP.

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.

Trajectory of Irisin as a Predictor of Kidney-Related Outcomes in Patients with Asymptomatic Heart Failure.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < -16%, LV hypertrophy, left atrial volume index > 34 mL/m2, abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF.

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.

99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients.

Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality. This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied. ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality. Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Chemiluminescence immunoassay amplified by functional acridinium ester for the detection of NT-proBNP in clinical samples

High sensitivity and accuracy of heart failure biomarker, N-terminal prohormone brain natriuretic peptide (NT-proBNP), is critical for the early detection of heart failure. However, traditional chemiluminescent (CL) probe still face the challenges of poor solubility, in particular, significant disappointing bioavailability, which profoundly limit its clinical applications. In this paper, we demonstrate functional CL probe acridinium ester (AE-2) for the detection of NT-proBNP, through introducing a hydrophilic unit for ensuring high water dispersity and reactive group for promoting better bioavaiability with antibody. Compared to the traditional CL probe, the functional CL probe AE-2 exhibits extraordinary features, such as better biocompatibility, higher label rate with antibody, as well as significant chemiluminescence signal. In addition, this CL probe exhibits excellent linearity with the test data of Longhua Hospital, suggesting that AE-2 could be used as a clinical examination assay to detect NT-proBNP in real clinical samples. Thus, this functional CL probe AE-2 can be a powerful tool for elucidating the roles of NT-proBNP in clinical samples.

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.

Development and validation of a machine learning predictive model for perioperative myocardial injury in cardiac surgery with cardiopulmonary bypass

BackgroundPerioperative myocardial injury (PMI) with different cut-off values has showed to be associated with different prognostic effect after cardiac surgery. Machine learning (ML) method has been widely used in perioperative risk predictions during cardiac surgery. However, the utilization of ML in PMI has not been studied yet. Therefore, we sought to develop and validate the performances of ML for PMI with different cut-off values in cardiac surgery with cardiopulmonary bypass (CPB).MethodsThis was a second analysis of a multicenter clinical trial (OPTIMAL) and requirement for written informed consent was waived due to the retrospective design. Patients aged 18–70 undergoing elective cardiac surgery with CPB from December 2018 to April 2021 were enrolled in China. The models were developed using the data from Fuwai Hospital and externally validated by the other three cardiac centres. Traditional logistic regression (LR) and eleven ML models were constructed. The primary outcome was PMI, defined as the postoperative maximum cardiac Troponin I beyond different times of upper reference limit (40x, 70x, 100x, 130x) We measured the model performance by examining the area under the receiver operating characteristic curve (AUROC), precision-recall curve (AUPRC), and calibration brier score.ResultsA total of 2983 eligible patients eventually participated in both the model development (n = 2420) and external validation (n = 563). The CatboostClassifier and RandomForestClassifier emerged as potential alternatives to the LR model for predicting PMI. The AUROC demonstrated an increase with each of the four cutoffs, peaking at 100x URL in the testing dataset and at 70x URL in the external validation dataset. However, it’s worth noting that the AUPRC decreased with each cutoff increment. Additionally, the Brier loss score decreased as the cutoffs increased, reaching its lowest point at 0.16 with a 130x URL cutoff. Moreover, extended CPB time, aortic duration, elevated preoperative N-terminal brain sodium peptide, reduced preoperative neutrophil count, higher body mass index, and increased high-sensitivity C-reactive protein levels were identified as risk factors for PMI across all four cutoff values.ConclusionsThe CatboostClassifier and RandomForestClassifer algorithms could be an alternative for LR in prediction of PMI. Furthermore, preoperative higher N-terminal brain sodium peptide and lower high-sensitivity C-reactive protein were strong risk factor for PMI, the underlying mechanism require further investigation.

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.

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.

Rapid Homogeneous Fluorescent Enzyme-Linked Immunosorbent Assay (ELISA) for N-Terminal Brain Natriuretic Peptide (NT-proBNP) Combining Magnetic Probes and Ampliflu Red

Heart failure (HF) is the leading cause of death from cardiovascular disease, and early diagnosis using serum markers holds extraordinary significance for the treatment of patients. N-terminal brain natriuretic peptide (NT-proBNP) is the gold standard for HF diagnosis. Herein, a novel, rapid, sensitive, and immune-sensing strategy for NT-proBNP is reported employing an enzyme-linked immunosorbent assay (ELISA) that combines the use of magnetic biological probes and the fluorogenic substrate Ampliflu Red. Functionalized immunomagnetic nanoparticles with large surface areas provide an abundant reaction platform and reduce the analysis time due to their superparamagnetic properties. Ampliflu Red is catalyzed by horseradish peroxidase (HRP) using hydrogen peroxide (H2O2) to produce strong fluorescence and a low background. The reported method achieved a good detection limit of 2.73 ng mL−1 and a wide linear range from 3.13 to 100 ng mL−1. The analysis time was less than 1 h, which is superior to that of traditional ELISA (3–4 h). In addition, the recoveries of spiked human serum were satisfactory, indicating that the proposed strategy has potential applications for the rapid determination of NT-proBNP and other biomarkers in clinical settings.

Simple models vs. deep learning in detecting low ejection fraction from the electrocardiogram.

Deep learning methods have recently gained success in detecting left ventricular systolic dysfunction (LVSD) from electrocardiogram (ECG) waveforms. Despite their high level of accuracy, they are difficult to interpret and deploy broadly in the clinical setting. In this study, we set out to determine whether simpler models based on standard ECG measurements could detect LVSD with similar accuracy to that of deep learning models. Using an observational data set of 40 994 matched 12-lead ECGs and transthoracic echocardiograms, we trained a range of models with increasing complexity to detect LVSD based on ECG waveforms and derived measurements. The training data were acquired from the Stanford University Medical Center. External validation data were acquired from the Columbia Medical Center and the UK Biobank. The Stanford data set consisted of 40 994 matched ECGs and echocardiograms, of which 9.72% had LVSD. A random forest model using 555 discrete, automated measurements achieved an area under the receiver operator characteristic curve (AUC) of 0.92 (0.91-0.93), similar to a deep learning waveform model with an AUC of 0.94 (0.93-0.94). A logistic regression model based on five measurements achieved high performance [AUC of 0.86 (0.85-0.87)], close to a deep learning model and better than N-terminal prohormone brain natriuretic peptide (NT-proBNP). Finally, we found that simpler models were more portable across sites, with experiments at two independent, external sites. Our study demonstrates the value of simple electrocardiographic models that perform nearly as well as deep learning models, while being much easier to implement and interpret.

Predischarge Peak Atrial Longitudinal Strain and Plasma N-terminal Pro-hormone Brain Natriuretic Peptide as a Predictor of Short-term Rehospitalization and Cardiovascular Mortality in Patients with Acute Heart Failure.

The postacute heart failure (AHF) rehospitalization rate is attributed to persistent hemodynamic congestion despite clinical improvement. Peak atrial longitudinal strain (PALS), utilizing speckle tracking echocardiography technology, shows potential in post-AHF prognosis. Meanwhile, N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) remains a known biomarker of intracardiac congestion. This study aimed to determine the relationship between predischarge PALS and NT-proBNP as predictors of major adverse cardiac event (MACE) in patients after AHF hospitalization. This study is a prospective cohort study, conducted in Prof. Dr. I G.N.G Ngoerah Hospital, Bali, Indonesia. The study included hospitalized AHF patients, collecting demographic data, comorbidities, therapies, and echocardiographic measures before discharge. Predischarge PALS and NT-proBNP were taken within 24 h before discharge. The main outcome was MACE, defined as rehospitalization and cardiovascular mortality within 90 days. Comparative statistical analyses was done using independent t-test for continuous variables (Mann-Whitney U test for variables with abnormal distribution) and Chi-squared tests. Receiver operating characteristic (ROC) used in determining optimal threshold values of predischarge PALS and NT-proBNP as a predictor of MACE. Kaplan-Meier curves were employed to gauge event-free survival differences between these cohorts. Then, independent Cox regression was used to identify the predictors of MACE. The study enrolled 67 patients with varying ejection fraction (EF) (16 - heart failure with preserved ejection fraction, 10 - heart failure with mildly reduced ejection fraction, and 41 - heart failure with reduced ejection fraction; mean age: 56.88 ± 14.57 years). Over the 90-day follow-up, 21 patients (31.3%) encountered MACE. Both PALS (area under the curve [AUC] 0.816) and NT-proBNP (AUC 0.856) before discharge served as predictors of MACE. There was no significant AUC difference between ROC curves (area difference: 0.039, P = 0.553). The regression model highlighted that PALS and NT-proBNP level before discharge acted as independent predictors of MACE, irrespective of EF, average E/e', or estimated predischarge pulmonary capillary wedge pressure. Predischarge PALS is comparable to NT-proBNP levels as independent predictors of short-term MACE after AHF hospitalization.

Association between basal metabolic rate and cardio-metabolic risk factors: Evidence from a Mendelian Randomization study

BackgroundCardio-metabolic risk factors play a crucial role in the development of cardiovascular and metabolic diseases. Basal metabolic rate (BMR) is a fundamental physiological parameter that affects energy expenditure and might contribute to variations in these risk factors. However, the exact relationship between BMR and cardio-metabolic risk factors has remained unclear. MethodsWe employed Mendelian Randomization (MR) analysis to explore the association between BMR (N: 534,045) and various cardio-metabolic risk factors, including body mass index (BMI, N: 681,275), fasting glucose (N: 200,622), high-density lipoprotein (HDL) cholesterol (N = 403,943), low-density lipoprotein (LDL) cholesterol (N = 431,167), total cholesterol (N: 344,278), and triglycerides (N: 441,016), C-reactive protein (N: 436,939), waist circumference (N: 232,101), systolic blood pressure (N: 810,865), diastolic blood pressure (N: 810,865), glycated haemoglobin (N: 389,889), and N-terminal prohormone brain natriuretic peptide (N: 21,758). We leveraged genetic variants strongly associated with BMR as instrumental variables to investigate potential causal relationships, with the primary analysis using the Inverse Variance Weighted (IVW) method. ResultsOur MR analysis revealed compelling evidence of a causal link between BMR and specific cardio-metabolic risk factors. Specifically, genetically determined higher BMR was associated with an increased BMI (β = 0.7538, 95% confidence interval [CI]: 0.6418 to 0.8659, p < 0.001), lower levels of HDL cholesterol (β = −0.3293, 95% CI: 0.4474 to −0.2111, p < 0.001), higher levels of triglycerides (β = 0.1472, 95% CI: 0.0370 to 0.2574, p = 0.0088), waist circumference (β = 0.4416, 95% CI: 0.2949 to 0.5883, p < 0.001), and glycated haemoglobin (β = 0.1037, 95% CI: 0.0080 to 0.1995, p = 0.0377). However, we did not observe any significant association between BMR and fasting glucose, LDL cholesterol, total cholesterol, C-reactive protein, systolic blood pressure, diastolic blood pressure, or N-terminal prohormone brain natriuretic peptide (all p-values>0.05). ConclusionThis MR study provides valuable insights into the relationship between BMR and cardio-metabolic risk factors. Understanding the causal links between BMR and these factors could have important implications for the development of targeted interventions and therapies.

NATRIURETIC PEPTIDE: DIAGNOSTIC, PROGNOSTIC, AND CLINICAL RELEVANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS, ARTERIAL HYPERTENSION AND OBESITY

Natriuretic peptides are one of the main biomarkers of chronic heart failure (CHF). The level of NT-proBNP makes it possible to evaluate the negative prognosis in patients with CHF, as well as to monitor the sensitivity of patients with left ventricular dysfunction to the appointment of treatment. The purpose of the study: to study the NT-proBNP biomarker in comorbid patients with hypertension, obesity, type 2 diabetes and determine the relationship with a number of hormonal and biochemical indicators. Materials and methods: all patients were divided into 4 groups depending on the presence of comorbid pathology in them: patients with hypertension – 1 group – 22 people; patients with hypertension combined with obesity – group 2 – 30 people; Hypertension in combination with type 2 diabetes – group 3 – 31 people; patients with hypertension, type 2 diabetes and obesity – group 4 – 28 people. Determination of the content of N-terminal brain natriuretic peptide (NT-proBNP) in the blood serum of patients was carried out by the immunoenzymatic method on the analyzer "Labline-90" (Austria) using a commercial test system manufactured by the company "Elabscience" (ELISA, China) according to the instructions, which was part of the set. Conclusions. It was established that in patients with hypertension, hypertension in combination with obesity, hypertension in combination with type 2 diabetes, as well as hypertension in combination with type 2 diabetes and obesity, there is a significant increase in NT-proBNP compared to the indicator of the control group (p&lt;0.05). It has been proven that NT-proBNP has a direct correlation with creatinine (p=0.045), urea (p=0.038), triglyceride level (p=0.027) and cholesterol (p=0.031); direct correlation with the level of HbA1c (r=0.202; p=0.0038). The level of NT-proBNP has a significant predictive value for the risk of developing cardiovascular complications in patients with hypertension.

Evaluation of all-cause mortality and cardiovascular safety in patients receiving chimeric antigen receptor T cell therapy: a prospective cohort study

Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM). In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint. Overall, 137 patients (median age 60, range 20-83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02-4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03-2.38 years, IQR 0.79). A septal wall thickness above 11mm (HR 2.48, 95%-CI=1.10-5.67, p=0.029) was associated with an increased risk of ACM, with a trend seen for reduced left ventricular ejection fraction prior to therapy (LVEF <40%; HR 9.17, 95%-CI=1.30-183.11, p=0.051). Secondary endpoint was reached by 93 patients while no baseline parameter was able to predict an elevated risk. However, hs-cTnT change from baseline of 50% or more during the first 14 days after CAR infusion predicted ACM (HR 3.81, 95%-CI=1.58-9.45; p=0.003). None of the baseline characteristics was able to predict the incidence of cardiac events. Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance. The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research.

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.