Increase In N-terminal Pro-brain Natriuretic Peptide Research Articles

Importance of blood biomarker determination in the selection of patients with heart failure for cardioverterdefibrillator implantation

Aim. To conduct a comparative analysis of blood biomarker concentrations, to study their prognostic role in the occurrence of sustained ventricular tachyarrhythmia (VT) or VT episodes requiring electrotherapy in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤35% without prior syncope or sustained ventricular arrhythmias.Material and methods. This single-center prospective clinical study included 319 patients (men, 83%) aged 57 (51-63) years with LVEF of 29 (24-33)% receiving optimal therapy for HF, hospitalized for cardioverterdefibrillator implantation for the purpose of primary prevention of sudden cardiac death. Before the procedure, the concentration of blood biomarkers (blood electrolytes, C-reactive protein, creatinine, Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3) was determined. Based on blood creatinine concentration, glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Patients underwent a two-year prospective follow-up to record the end point of newly occurring clinically significant VT episodes detected by an implantable cardioverter-defibrillator.Results. The studied arrhythmic endpoint occurred in 84 (26,3%) patients. The multivariate analysis revealed three blood biomarkers, the concentration of which was associated with the first manifestation of VT. With sST-2 >35 ng/ml, this risk increased by ~3 times (odds ratio (OR)=2,86; 95% confidence interval (CI): 1,23-6,64 (p=0,013)). Galectin-3 level >12 ng/ml had a comparable prognostic value (OR=2,64; 95% CI: 1,06-6,53 (p=0,032)). In case of an increase in NT-proBNP >2000 pg/ml, the risk of the same outcome was 2,2 times lower (OR=0,46; 95% CI: 0,22-0,95 (p=0,034)).Conclusion. Pre-implantation laboratory screening of NT-proBNP, sST-2 and galectin-3 concentrations can help in personalized assessment of arrhythmic risk in patients with HF and LVEF ≤35% referred for interventional primary prevention of sudden cardiac death.

Oligosaccharides and diet-related dilated cardiomyopathy in beagles.

In 2018 the US Food and Drug Administration reported a potential link between grain-free, legume-containing dog foods and the development of canine dilated cardiomyopathy in atypical breeds. One hypothesis was that high oligosaccharide content in legumes reduced bioavailability of taurine, an amino acid with some previous links to canine dilated cardiomyopathy. To address this hypothesis, in the present study, 8 Beagle dogs consumed four diets: a husbandry commercial dental diet, and three test diets formulated with either 30% rice (control), 30% pea (grain-free) or 30% rice with the addition of 1% raffinose (the predominant oligosaccharide found in peas). The study was conducted in a randomized, crossover design with 5 week feeding periods. Measurement of basic health parameters (weight, body condition score, complete blood cell count, chemistry panel), plasma amino acids, cardiac biomarkers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac-specific troponin I), fecal bile acids and echocardiographic exams were completed pre-study after feeding the husbandry diet as well as after each test feeding period. Echocardiography showed 9-11% reduction in ejection fraction and 17- 20% greater left ventricular end systolic volume with the husbandry diet compared to both grain-containing test diets. Concentrations of plasma NT-proBNP were 1.3-2 times greater after the husbandry diet compared to the grain-based diet, with the oligosaccharide and pea-based diets showing intermediate levels. Plasma taurine levels were unchanged across diets, while plasma methionine levels were highest and cysteine/cystine levels were lowest after dogs ate the husbandry diet. Results indicate that raffinose in the diet is sufficient, but not required to see an increase NT-proBNP, but did not induce any changes in cardiac function after 5 weeks of feeding. Whether this could progress to reduction in cardiac function with longer term feeding is uncertain. A reduced cardiac function along with the greatest increase in NT-proBNP was observed after feeding the husbandry diet that contained the highest amount of insoluble fiber but did not contain legumes or oligosaccharide. Further research into the impact of insoluble fiber in the dental diet is needed to support these novel observations.

Percutaneous closure of ventricular septal rupture after myocardial infarction: A retrospective study of 81 cases.

To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI). This retrospective study included 81 patients who underwent transcatheter closure for postinfarction VSR. We analyzed clinical data from hospitalization and the 30-day follow-up, compared clinical data from the survival and death groups, and explored the best closure time and the safety and efficacy of occlusion. The risk factors for death at 30 days were analyzed by logistic regression. C-reactive protein (CRP), white blood cell counts, N-terminal pro brain natriuretic peptide (NT-ProBNP), and aspartate aminotransferase were higher in the death group than in the survival group (p < .01), with a higher rate of application of vasoactive drugs, and a shorter time from AMI to operation (p < .05). At 30 days postocclusion, 19 patients (23.5%) had died. The mortality rate was significantly lower for operation performed 3 weeks after AMI than for operation performed within 3 weeks of AMI (12.5% vs. 48%, p < .001). Devices were successfully implanted in 76 patients, with 16 (21.1%) operation-related complications and 12 (15.8%) valve injuries. Cardiac function improved significantly (p < .001) at discharge (N = 66) and 30 days after procedure (N = 62). Qp/Qs and pulmonary artery systolic pressure decreased significantly, while aortic systolic pressure increased significantly (p < .001). Additionally, EF and LVDd improved (p < .05) after occlusion. Increases in CRP and NT-ProBNP were risk factors for death at 30 days after closure (p < .05). Percutaneous VSR closure can be a valuable treatment option for suitable patients with VSR.

1-Year Results from a Phase 2 Study to Determine Safety and Tolerability of Treating Patients with Light-Chain (AL) Amyloidosis with Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia

Background: Light-chain (AL) amyloidosis is a rare, systemic disease caused by plasma cell dyscrasia (PCD). Excess immunoglobulin light chains misfold and form insoluble amyloid fibrils that deposit in organs, primarily the heart. Survival depends largely on the extent of heart involvement. Current therapies target PCD to halt fibril formation but do not treat existing fibril deposited in organs. CAEL-101 is a novel, investigational, potentially first-in-class therapy designed to remove amyloid fibrils from organs. Safety, tolerability, and biomarker data after all patients with AL amyloidosis enrolled in the trial received 1 year of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab, are presented. Methods: Adult patients with AL amyloidosis (European Modification of Mayo Stage I-IIIa) and measurable hematologic disease were eligible for this ongoing, open-label, phase 2 study (NCT04304144). Other forms of amyloidosis and multiple myeloma were excluded. CAEL-101 ≤1000 mg/m2 is administered every other week with anti-PCD therapy as directed by the investigator. In addition to safety assessments, cardiac and renal response were assessed by change over time in N-terminal pro-brain natriuretic peptide (NT-proBNP) and proteinuria, respectively. Results: Patients (n = 25; mean age 65 years; 72% male) with Mayo Stage I (8%), II (76%), and IIIa (16%) AL amyloidosis were treated with CAEL-101 for 1 year at this analysis. Patients presented with cardiac involvement (n = 22), renal involvement (n = 9, reported from one site), and prior anti-PCD therapy (n = 20). All 25 patients experienced treatment-emergent adverse events (TEAEs), and 6 (24%) experienced at least possibly treatment-related TEAEs. Five patients discontinued for non-treatment-related reasons (Table). Fifteen (60%) patients experienced TEAEs of Grade ≥3 severity and 13 (52%) experienced ≥1 serious adverse event (SAE). The most common TEAEs were nausea (n = 10), constipation or fatigue (n = 9 each), anemia, insomnia, or diarrhea (n = 8 each), and dizziness, cough, or rash (n = 7 each). After 1 year of CAEL-101 treatment of the 22 cardiac evaluable patients (baseline NT-proBNP ≥332 pg/mL), 10 (46%) patients experienced ≥30% NT-proBNP decrease from baseline, 4 (18%) were stable (±30% change from baseline), and 3 (14%) showed disease progression (≥30% NT-proBNP increase from baseline); data for 5 patients were missing. Of the 9 renal evaluable patients from a single site as reported by the investigator, 8 showed ≥30% decrease from baseline in proteinuria. Conclusions: The long-term safety evaluation of CAEL-101 continues in this study. All patients currently enrolled have been treated for at least 1 year. At this 1-year time point, CAEL-101 has been generally well tolerated without evidence of organ toxicity. Organ response persisted even after cessation of anti-PCD treatment. Most TEAEs were mild to moderate. A phase 3 program has commenced to elucidate the efficacy and safety of CAEL-101 in cardiac AL amyloidosis European Modification Mayo Stages IIIa and IIIb. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Iron deficiency in Russia heart failure patients. Observational cross-sectional multicenter study

Aim To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines.Results 83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002-1.011, p=0.0152).Conclusion The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

Relationships between the activity of neurohormonal systems and intracardiac hemodynamics in patients with heart failure: focus on galectin-3

The introduction of novel biomarkers necessitates their detailed study in patients with different heart failure (HF) phenotypes as part of a personalized approach to assessing the disease severity and predicting outcomes.Aim. To assessthe activity of following neurohormonal systems: N-terminal probrain natriuretic peptide (NT-proBNP) and galectin-3 in HF with preserved, mildly reduced and reduced ejection fraction (EF).Material and methods. In 69 patients with NYHA class II-IV HF, along with a general clinical examination, the level of NT-proBNP and serum galectin-3 was determined by enzyme immunoassay.Results. Patients included in the study were divided into 3 groups: preserved EF (HFpEF) — 23 patients, mildly reduced EF (HFmrEF) — 26 patients, and reduced EF (HFrEF) — 20 patients. In patients with HF, the level of galectin-3 did not directly depend on EF, but was associated with NT-proBNP level as follows: there was a tendency to increase the concentration of galectin-3 in the tertile groups of NT-proBNP. Correlation analysis revealed significant feedback (r=-0,41, p&lt;0,05) between galectin-3 and left ventricular EF only in patients with preserved systolic function. In the same group of HFpEF patients, the maximum values of serum galectin-3 indices were noted, reaching 10,5 [6,5; 14,5] ng/ml.Conclusion. Analysis of neurohormonal activity demonstrated a unidirectional increase in NT-proBNP and galectin-3 in patients with HF, regardless of left ventricular EF, while the maximum values of galetin-3 were observed in patients with HFpEF.

Relationships between the activity of neurohormonal systems and intracardiac hemodynamics in patients with heart failure: focus on galectin-3

The introduction of novel biomarkers necessitates their detailed study in patients with different heart failure (HF) phenotypes as part of a personalized approach to assessing the disease severity and predicting outcomes.Aim. To assessthe activity of following neurohormonal systems: N-terminal probrain natriuretic peptide (NT-proBNP) and galectin-3 in HF with preserved, mildly reduced and reduced ejection fraction (EF).Material and methods. In 69 patients with NYHA class II-IV HF, along with a general clinical examination, the level of NT-proBNP and serum galectin-3 was determined by enzyme immunoassay.Results. Patients included in the study were divided into 3 groups: preserved EF (HFpEF) — 23 patients, mildly reduced EF (HFmrEF) — 26 patients, and reduced EF (HFrEF) — 20 patients. In patients with HF, the level of galectin-3 did not directly depend on EF, but was associated with NT-proBNP level as follows: there was a tendency to increase the concentration of galectin-3 in the tertile groups of NT-proBNP. Correlation analysis revealed significant feedback (r=-0,41, p&lt;0,05) between galectin-3 and left ventricular EF only in patients with preserved systolic function. In the same group of HFpEF patients, the maximum values of serum galectin-3 indices were noted, reaching 10,5 [6,5; 14,5] ng/ml.Conclusion. Analysis of neurohormonal activity demonstrated a unidirectional increase in NT-proBNP and galectin-3 in patients with HF, regardless of left ventricular EF, while the maximum values of galetin-3 were observed in patients with HFpEF.

Contribution of inflammation to heart failure development in human immunodeficiency virus-infected patients

Aim. To determine the peculiarities of heart failure (HF) development in human immunodeficiency virus (HIV)-infected patients, depending on the blood concentration of C-reactive protein (CRP).Material and methods. This cross-sectional screening clinical trial included 100 patients hospitalized with HIV infection and a history of HF for 28 months. The patients were divided into 2 groups depending on blood CRP concentration. The cut-off point was CRP of 15 mg/l. The first group included 37 HIV-infected patients with HF and blood CRP &lt;15 mg/l, while the second group — 63 HIV-infected patients with HF and CRP concentration ≥15 mg/l. The inclusion criteria were HIV infection and prior HF, stable medical state, taking into account the underlying disease that required hospitalization. The study did not include patients with acute cardiovascular diseases within prior 3 months, acute decompensated and acute heart failure, cancer, infectious diseases, conditions that required surgical intervention. N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined in all patients.Results. Correlation analysis revealed a strong inverse relationship between the blood concentrations of NT-proBNP and CRP (r=-0,639; p&lt;0,005). A ROC curve revealed the most optimal cut-off threshold of 9,8 mg/l (AUC=0,796, p&lt;0,05), which ensures sensitivity of 92,9% (p&lt;0,05) and specificity of 57,6% (p&lt;0,05). The odds ratio (OR) of an increase in NT-proBNP &gt;450 pg/ml, and hence the risk of acute decompensated HF in the presence of a CRP concentration of 1-9,8 mg/l in HIV-infected patients with HF was 44,73 (95% CI=8,62;311,10), while relative risk (RR) — 18,73 (95% CI=4,94;112,94). In the presence of in hospital inflammatory diseases and CRP ≥15 mg/l in HIV-infected patients and prior HF, the RR of acute decompensated HF is reduced by 88% (RR=0,12, 95% CI=0,03-0,33).Conclusion. CRP values from 1 to 9,8 mg/l in HIV-infected patients with HF are predictors of its severity, characterized by a higher incidence of HF with reduced ejection fraction, diastolic dysfunction and left ventricular hypertrophy without significant differences with patients who have CRP &gt;9,8 mg/l. CRP concentration &gt;9,8 mg/l in HIV-infected patients and prior HF indicates the development of an inflammatory process, and not a worsening of the HF course.

Evaluation of Ibrutinib Cardiotoxicity By Comparative Use of Speckle-Tracking Technique and Biomarkers.

Ibrutinib, a relatively new antineoplastic agent, has multiple cardiovascular effects that are still insufficiently known and evaluated, including subclinical myocardial damage. The present study aims to assess the role of the myocardial strain, alone and in combination with cardiac biomarkers, in the early detection of ibrutinib-induced cardiotoxicity. We included 31 outpatients with normal left ventricular ejection fraction (LVEF) on ibrutinib, in a tertiary University Hospital between 2019 and 2020, and evaluated them at inclusion and after 3 months. Data on myocardial strain, cardiac biomarkers [high-sensitive troponin T (hs TnT) and N-terminal probrain natriuretic peptide (NT-proBNP)], and ambulatory electrocardiographic monitoring were collected. Myocardial deformation decreased significantly (P < 0.001) at later evaluation and hs TnT and NT-proBNP increased significantly (P = 0.019 and P = 0.03, respectively). The increase in hs TnT correlated with the increase in the left ventricle global longitudinal strain (LVGLS); in other words, it correlated with the decrease in myocardial deformation. No association was found between LVGLS increase and the increase in NT-proBNP. LVGLS modification was not significantly influenced by age, anemia, or arrhythmia burden quantified by 24-hour Holter monitoring (P = 0.747, P = 0.072, respectively; P = 0.812). LVEF did not change significantly during follow-up. In patients on ibrutinib, evaluation of myocardial strain is useful in identifying early cardiac drug toxicity, surpassing the sensitivity and specificity limits of LVEF. In these patients, concomitant assessment of hs TnT increases the predictive power for subclinical myocardial involvement.

Right heart condition in patients with COVID-19 pneumonia

Aim. To assess right heart condition in patients with coronavirus disease 2019 (COVID-19) pneumonia.Material and methods. One hundred and five patients with COVID-19 pneumonia were divided into 3 groups depending on the involvement of lung parenchyma: group I — 0-25%, II — 25-50%, III — 50-75%. The clinical status of patients was assessed using the NEWS2 and SHOKS-COVID scales. A complete blood count and biochemical blood tests were performed to determine the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I. Echocardiography was performed to assess the right heart structural, hemodynamic and functional parameters.Results. In patients with COVID-19 pneumonia, with an increase in lung parenchyma involvement, the intensity of systemic inflammatory response increased: C-reactive protein, group I — (4 [1,9; 35] mg/l), in III — (70,5 [33; 144] mg/l) (pI-III=0,012); myocardial stress marker level increased: NT-proBNP, group I — 77 [48; 150] ng/l, group III — 165 [100; 287] ng/l (pI-III=0,047). The dependence of NT-proBNP on C-reactive protein level was revealed (r=0,335, p=0,03). Intergroup comparison did not reveal significant differences between the main right heart functional parameters: TAPSE, Tei index (PW and TDI), FAC of the right ventricle (RV) (p&gt;0,05). However, differences in the tricuspid annular peaks were found as follows: group I — 0,14 [0,12; 0,14] m/s, group II — 0,14 [0,12; 0,15] m/s, group III — 0,16 [0,14; 0,17] m/s (pI-II=0,012, pI-III=0,014) and RV global longitudinal strain: group I — 19,63±7,72%, group III — 27,4±5,93% (pI-III=0,014). The relationship between the RV global longitudinal strain and SHOKS-COVID score was confirmed (r=0,381; p=0,024).Conclusion. Patients with COVID-19 pneumonia showed no signs of right heart dysfunction. The development of RV hyperfunction was noted. Most likely, this is a compensatory mechanism in response to acute RV afterload. NT-proBNP increase under conditions of an inflammatory response may indicate myocardial stress. The results obtained allow to expand our understanding of the right heart condition in patients with COVID-19 pneumonia.

Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment.

Background: We assesse the evolution and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (cTnT-HS) in transthyretin amyloid cardiomyopathy (ATTR-CA) before and after tafamidis treatment. Methods and Results: 454 ATTR-CA patients without tafamidis (Cohort A) and 248 ATTR-CA with tafamidis (Cohort B) were enrolled. Event-free survival (EFS) events were death, heart transplant, or acute heart failure. In Cohort A, 27% of patients maintained NT-proBNP < 3000 ng/L and 14% cTnT-HS < 50 ng/L at 12 months relative to baseline levels. In Cohort B, the proportions were 49% and 29%, respectively. In Cohort A, among the 333 patients without an increased NT-proBNP > 50% relative to baseline EFS was extended compared to the 121 patients with an increased NT-proBNP > 50% (HR: 0.75 [0.57; 0.98]; p = 0.032). In Cohort A, baseline NT-proBNP > 3000 ng/L and cTnT-HS > 50 ng/L and a relative increase of NT-proBNP > 50% during follow-up were independent prognostic factors of EFS. The slopes of logs NT-proBNP and cTnT-HS increased with time before and stabilized after tafamidis. Conclusion: ATTR-CA patients with increasing NT-proBNP had an increased risk of EFS. Tafamidis stabilize NT-proBNP and cTnT-HS increasing, even if initial NT-proBNP levels were >3000 ng/L. Thus suggesting that all patients, irrespective of baseline NT-proBNP levels, may benefit from tafamidis.

Risk factors of severe heart failure in HIV-positive patients

Aim . To study the relationship of N-terminal pro-brain natriuretic peptide (NT-proBNP) with clinical symptoms, structural and functional cardiac abnormalities in human immunodeficiency virus (HIV)-positive patients with heart failure (HF), as well as to identify risk factors for severe HF. Material and methods . During the year, 150 HIV-positive patients with typical symptoms and signs of stable HF were examined in the hospital. Among them, HF, confirmed by structural and functional cardiac changes and NT-proBNP increase above 125 pg/ml, was identified in 83 (55,3%) patients. These patients were divided into 3 groups depending on the blood concentration of NT-proBNP: group 1 (n=54) — patients with NT-proBNP of 125-700 pg/ml; group 2 (n=12) — patients with NT-proBNP of 701-1500 pg/ml; group 3 (n=17) — patients with NT-proBNP &gt;1500 pg/ml. Results . As NT-proBNP increased in HIV-positive patients with HF, the left ventricular (LV) ejection fraction (EF) significantly decreased (p=0,005). Also, the increase in the severity of HF symptoms (p&lt;0,001), prevalence of chronic kidney disease (CKD) (p&lt;0,001), chronic hepatitis B and/or C (p=0,011), prior infective endocarditis (p=0,002), thromboembolic events (p=0,007), chronic obstructive pulmonary disease (p=0,016), pneumonia (p=0,002) and inflammatory diseases during hospitalization (p=0,002), severe thrombocytopenia (p=0,032). We revealed significant differences between the groups in the frequency of decreased cluster of differentiation antigen 4 (CD4) &lt;200 cells/pl (p=0,013). Conclusion. In HIV-positive patients with clinical symptoms of HF, the prevalence of its verification in accordance with Russian guidelines (2020) was 55,3%. In 62,7% of HIV-positive patients with HF, preserved EF was detected. Among the comorbidities, 9 risk factors of severe HF in HIV-positive patients with NT-proBNP &gt;1500 pg/ml were identified. With CKD and inflammatory diseases during hospitalization, the relative risk of severe HF in patients with HIV infection is increased by more than 6 times, while with thromboembolic events — 5,3 times, infective endocarditis — 4,4 times, pneumonia during hospitalization and severe thrombocytopenia — more than 3,5 times, chronic obstructive pulmonary disease — 2,1 times, chronic hepatitis B and/or C — 1,7 times. As HIV infection progresses (CD4 &lt;200 cells/pL), the risk of severe HF increases 1,6 times.

Predictors of myocardial fibrosis and loss of epicardial adipose tissue volume in the long-term period after myocardial infarction

Aim. To assess the changes of biochemical markers in hospitalization, the relationship with the severity of myocardial fibrosis and the epicardial adipose tissue (EAT) thickness one year after myocardial infarction (MI).Material and methods. A total of 88 patients (65 men and 23 women) with MI were examined. The percentage of cicatricial changes in the myocardium and the EAT thickness were measured using the magnetic resonance imaging (MRI) one year after MI. In the hospitalization (days 1 and 12) and 1 year after MI, the concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), stimulating growth factor (ST2), interleukin-33 (IL-33) and type I collagen (COL-1). The data were analyzed using descriptive statistics, correlation and ROC analysis, and logistic regression (Statistica 9.0).Results. One year after MI, cicatricial changes were detected in 68 (77%) patients: 27 people had myocardial fibrosis &lt;5%, 22 patients — 5-15%, and 19 patients &gt;15%. We established that myocardial fibrosis after MI is associated with unfavorable medical history, a complicated course during in-hospital period and higher concentrations of ST2, NT-proBNP, COL-1 compared with patients without myocardial fibrosis. High levels of ST2, NT-proBNP increase the risk of myocardial fibrosis by 1,2 and 1,8 times after hospitalization, respectively. In patients with myocardial fibrosis &gt;15%, IL-33 level was significantly lower in the 1st day of MI. It was found that the EAT thickness increases with fibrosis of 5-15%. An increase in the left (LV) and right ventricular (RV) EAT thickness by 1,33 times and 1,34 times, respectively, increases the risk of myocardial fibrosis (LV EAT thickness, mm (OR 1,33; 95% CI (1,08-1,4), AUC 0,75; RV EAT thickness, mm (OR 1,34; 95% CI (1,15-1,43), AUC 0,79). In patients with myocardial fibrosis &gt;15%, EAT thickness decreases and correlates with NT-proBNP increase in the acute period and a one year after MI.Conclusion. The development of myocardial fibrosis one year after MI is associated with an increase in ST2, NT-proBNP, COL-1, both in the hospitalization and 1 year after MI. The decrease in IL-33 concentration during hospitalization with MI is accompanied by the development of fibrosis &gt;15% of the myocardium.

Relation of IGF-I with subclinical cardiovascular markers including intima-media thickness, left ventricular mass index and NT-proBNP.

Several studies revealed relations between low or high insulin-like growth factor I (IGF-I) levels and risk of cardiovascular diseases or mortality, whereas the mechanisms behind these associations are still unknown. The study aimed to explore the relations between IGF-I and changes in surrogate markers of cardiovascular disease including carotid intima-media thickness (IMT), left ventricular mass index (LVMI) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Longitudinal data of the population-based cohort Study of Health in Pomerania (SHIP) were used. IMT was measured by ultrasonography and LVMI was determined based on echocardiography. IGF-I and IGF-binding protein-3 (IGFBP-3) levels were measured by chemiluminescent immunoassays and the IGF-I/IGFBP-3 ratio was calculated. Mixed linear regression models adjusted for known cardiovascular confounders were performed. Statistical analyses demonstrated relations between low baseline IGF-I levels (beta for ΔIMT per s.d. increase -0.044 (s.e. 0.012)) or IGF-I/IGFBP-3 ratio (beta -0.045 (0.012)) and a long-term IMT increase. No associations between IGF-I, IGFBP-3 or IGF-I/IGFBP-3 ratio and changes in LVMI were detected. With respect to NT-proBNP sex-specific associations with IGF-I were found. In women, higher baseline IGF-I levels (beta for ΔNT-proBNP per s.d. increase 5.92 (2.2)) or IGF-I/IGFBP-3 ratio (beta 4.48 (2.2)) were related to an increase in NT-proBNP levels. Among men, U-shaped relations of baseline levels of IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio with an increase in NT-proBNP were found. The study detected significant relations between IGF-I and long-term changes in IMT and NT-proBNP but not LVMI. These findings argue for different effects of the IGF-I axis with respect to various cardiovascular entities.

Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children\u2019s Oncology Group

BackgroundDexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown.MethodsWe evaluated children with osteosarcoma (OS) on two Children’s Oncology Group trials with higher dose doxorubicin (375–600 mg/m2) preceded by dexrazoxane (10:1 dexrazoxane:doxorubicin dosing). They were evaluated after the minimum expected treatment time (METT), defined as 28 weeks. Cardiotoxicity was identified by echocardiography and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Second malignant neoplasm (SMN) data was collected.ResultsAll children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness Z-scores (P < 0.01) and LV mass Z-scores (P < 0.01) were significantly smaller than normal for body-surface area in both sexes. The average LV mass Z-scores were significantly smaller for girls (P < 0.01) and marginally smaller for boys (P = 0.06). Girls had significantly smaller LV end-diastolic dimension Z-scores normalized to BSA (P < 0.01) compared to healthy controls and had significant increases in NT-proBNP. Four children developed SMNs as first events, a rate similar to historical controls.ConclusionsDexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity.Trial registrationsClinicalTrials.gov: NCT00003937 (P9754) registered 1 Nov 1999, and NCT00023998 (AOST0121) registered 13 Sept 2001.

Effects of a Higher Heart Rate on Quality of Life and Functional Capacity in Patients With Left Ventricular Diastolic Dysfunction

There is no evidence-based treatment for heart failure with preserved ejection fraction. Although lower heart rates (HRs) provide an unequivocal benefit for patients with HF with reduced ejection fraction, higher HR might convey important hemodynamic and substrate-modifying benefits in patients with diastolic dysfunction. In a prospective study of 20 stable outpatients with diastolic dysfunction and pacemakers, we evaluated the effects of a 4-week increase in the lower pacemaker rate to 80 beats/min followed by reversal to the previous lower HR setting from weeks 4 to 6. We assessed quality of life (Minnesota Living with Heart Failure Questionnaire), 6-minute walk test and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Pacing at 80 beats/min significantly improved quality of life and the 6-minute walk test (p ≤0.05). There was a strong positive correlation between the pacing-induced changes in NT-proBNP and baseline QRS intervals (r2 = 0.31, p <0.01). Stratification by QRS duration revealed that pacing at 80 beats/min led to -21 ± 26% reduction in NT-proBNP in patients with QRS ≤150 ms, whereas QRS >150 ms was associated with a 26 ± 35% increase in NT-proBNP (p <0.01). Patients physiologically paced from the conduction system had a -46 ± 26% reduction in NT-proBNP at 80 beats/min as compared with 4 ± 26% and 13 ± 26% change with pacing from the right atrial appendage and right ventricular apical septum (pinteraction = 0.04). In conclusion, increasing the lower rate setting of pacemakers to 80 beats/min in patients with diastolic dysfunction improves quality of life, functional capacity, and NT-proBNP for those patients with a baseline QRS ≤150 ms. These findings suggest that higher HRs may provide meaningful benefits to patients with left ventricular diastolic dysfunction and heart failure with preserved ejection fraction.

NT-proBNP in stable COPD and future exacerbation risk: Analysis of the SPIROMICS cohort.

High N-terminal pro-brain natriuretic peptide (NT-proBNP) during COPD exacerbations is associated with worse clinical outcomes. The prognostic value of NT-proBNP measured during clinical stability has not been well characterized. We studied SPIROMICS participants 40-80 years of age with COPD GOLD spirometric stages 1-4. The association between baseline NT-proBNP and incident COPD exacerbations within one year of follow-up was tested using zero-inflated Poisson regression models adjusted for age, gender, race, body mass index, current smoking status, smoking history, FEV1 percent predicted, COPD Assessment Test score, exacerbation history, total lung capacity on chest CT and cardiovascular disease (any of coronary artery disease, myocardial infarction or congestive heart failure). Among 1051 participants (mean age 66.1 years, 41.4% women), mean NT-proBNP was 608.9 pg/ml. Subjects in GOLD stage D had the highest mean NT-proBNP. After one year of follow-up, 268 participants experienced one or more COPD exacerbations. One standard deviation increase in baseline NT-proBNP was associated with a 13% increase in the risk of incident exacerbations (incident risk ratio 1.13; 95% CI 1.06-1.19; p < 0.0001). This association was maintained in participants with and without cardiovascular disease. Baseline NT-proBNP in COPD is an independent predictor of respiratory exacerbations, even in individuals without overt cardiac disease. The impact of detection and treatment of early cardiovascular dysfunction on COPD exacerbation frequency warrants further investigation.

Abstract P046: Sex Hormone Levels and 10-Year Change in N-Terminal Pro-Brain Natriuretic Peptide Among Men and Post-Menopausal Women: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The risk of cardiovascular disease (CVD) differs between men and women, and sex hormones are thought to play a key role. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of ventricular wall stress and a strong predictor of incident cardiovascular disease (CVD) and heart failure (HF). It can thus be seen as an early marker of CVD. We evaluated whether sex hormones levels were associated with change in NT-proBNP concentrations over 10 years in MESA. Methods: We studied 2348 men and 2041 post-menopausal women. Serum testosterone (T), estradiol, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) were measured at Exam 1 (2000-02); free T and bioavailable T were calculated. NT-proBNP was measured by Roche assay at Exam 1, plus Exam 3 (2004-05) and/or Exam 5 (2010-12). Multivariable-adjusted linear mixed effects models were used to study associations between sex hormone levels and change in NT-proBNP over an approximately 10-year period. Results: Mean (SD) age (years) at baseline was 65 (9) for women and 62 (10) for men. Women had higher NT-proBNP than men (median 76.6 vs 37.1 pg/ml). Among women, after adjusting for demographic, socioeconomic, and CVD risk factors, higher total T, bioavailable T, and free T were independently associated with a greater increase in NT-proBNP over 10 years, whereas estradiol and SHBG were inversely associated with change in NT-proBNP ( Table ). When sex hormones were analyzed together in the same model, total T was positively associated and SHBG was inversely associated with change in NT-proBNP. In men, higher estradiol was associated with greater 10-year increase in NT-proBNP. These associations were preserved after excluding individuals with ejection fraction &lt;50%. Conclusion: A more androgenic sex hormone profile in post-menopausal women and a more estrogenic profile in men were independently associated with 10-year change in NT-proBNP levels. Sex hormone patterns may thus explain in part sex differences in the development of CVD and HF.

Plasma N-terminal pro-brain natriuretic peptide concentrations before and after pericardiocentesis in dogs with cardiac tamponade secondary to spontaneous pericardial effusion

ObjectiveTo determine if concentrations of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) are increased in dogs with cardiac tamponade and if there is a significant increase in plasma NT-proBNP after pericardiocentesis. AnimalsTen client-owned dogs with spontaneous cardiac tamponade. MethodsProspective clinical study. Cardiac tamponade was suspected from physical examination and confirmed with echocardiography. Blood was collected and plasma NT-proBNP concentrations were measured before and 30–60 min following pericardiocentesis and resolution of cardiac tamponade. Within-subject changes in plasma NT-proBNP were compared by the Wilcoxon signed-rank test. ResultsThe plasma NT-proBNP concentrations measured within the reference interval in seven of 10 dogs before pericardiocentesis and in six of 10 dogs following pericardiocentesis. Following pericardiocentesis, there was a statistically significant increase in median NT-proBNP concentration (733 pmol/L, range 250–3,297) compared with the values measured before (643 pmol/L, range 250–3,210, P = 0.004). The NT-proBNP concentration increased in 90% of the dogs following pericardiocentesis. ConclusionsAn upper reference limit of 900 pmol/L for plasma NT-proBNP is insensitive for the diagnosis of pericardial effusion and cardiac tamponade in dogs. Plasma NT-proBNP concentration commonly increases following pericardiocentesis, perhaps related to improved ventricular filling and stretch.

QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall remodeling in excessive alcohol consumers: The SABPA study.

Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption - measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points - and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n=405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT≥19.5U/L and γ-GT≥55U/L indicated excessive alcohol consumption in Caucasians and Africans, respectively. Ambulatory 24-h blood pressure and electrocardiograms (ECG), 10-lead ECG left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP), and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile and mean 24-h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol and presented significant increases in NT-proBNP (p<0.001), QTc prolongation (p=0.008), and ischemic events (p=0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events, and SBP, in the African high γ-GT group exclusively. High alcohol consumers presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness, predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.