BNP Concentrations Research Articles

Prognostic Implications of Ambulatory N-Terminal Pro-B-Type Natriuretic Peptide Changes in Patients with Continuous-Flow Left Ventricular Assist Devices.

Data regarding the role of N-terminal Pro-B-type natriuretic peptide (NT-pro BNP) in patients with a continuous-flow left ventricular assist device (CFLVAD) is scarce. To evaluate the prognostic implications of measuring both absolute values and changes in NT-pro BNP concentrations in ambulatory patients with a CFLVAD, we performed a retrospective study of 168 consecutive patients who had an LVAD implantation at our institution and survived beyond their index hospitalization. Of these, 127 patients (56.2 ± 12.5 years, 21.2% female) had NT-pro BNP measured at 1 and 3 months postdischarge in ambulatory settings. Compared to the NT-pro BNP concentration at 1 month, 94 patients (74%) had a decline, and 33 patients (26%) had an increase in concentrations, from their 1 month baseline. After a median follow-up of 17 months, a total of 53 (41.7%) adverse events occurred. Of these, 37 (69.8%) were heart failure (HF) hospitalizations, and 16 (30.2%) were deaths. For each 1,000 unit increase in NT-pro BNP concentration at 3 months, there was a 17% increase in the risk of HF hospitalization or death (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04-1.32, p = 0.007). Conversely, each 1000 unit decline during the same time, was associated with an 11% decrease in the risk of HF hospitalization or death (HR = 0.89, 95% CI = 0.77-0.98, p = 0.04). In conclusion, in patients with a CFLAD, an increase in NT-pro BNP concentration from 1 to 3 months is associated with an increased risk of HF hospitalization and death. In contrast, a decline is associated with a reduction in the risk of HF hospitalization and death.

N-terminal pro-brain natriuretic peptide as a predictor of hemodynamic significance of functioning ductus arteriosus in premature newborns

Objective. To study the possibility of using N-terminal pro-BNP fragment as a screening criterion of hemodynamic significant of the functioning arterial duct in extremely premature newborns. Hemodynamically significant functioning arterial duct (HSFAD) is a reason of the development of various complications in extremely premature newborns. The basic method for HSFAD diagnosis is Echo CG. The limited technical abilities of ultrasound devices can prevent from an early diagnosis and timely treatment of this state. The search of additional markers of hemodynamic significance the functioning arterial duct (FAD) is actual.
 Materials and methods. A continuous prospective observational study included patients aged 1 to 3 days with FAD, gestation period of 2532 weeks and birth weight from 500 to 1500 g. Hemodynamic significance of FAD was determined according to generally accepted Eco CG criteria. The level of NT-pro-BNP was identified with IFA on the third day of life. Mathematical modelling was used to calculate a threshold value of NT-pro-BNP, corresponding to 6500 pg/ml, at which the probability of hemodynamic significance of the functioning arterial duct exceeds 80 %.
 Results. The assessment of NT-pro BNP concentration on the third day of life permitted to establish the following reliable differences: in the main group, the median concentration for NT-pro BNP was 15000 [IQR 2 587; 26 500] pg/ml, in the comparison group 1920 [IQR 1379; 3467] pg/ml, р = 0.001. Mean force direct correlation, r = 0.52, between Echo CG results and NT-pro-BNP values was stated.
 Conclusions. The obtained results make it possible to use NT-pro-BNP as a screening criterion of FAD hemodynamic significance in extremely premature newborns.

Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type-A recapitulated by soluble guanylyl cyclase agonists.

Natriuretic peptides, BNP and ANP increase renal blood flow in experimental animals. The signalling pathway in human kidney vasculature is unknown. It was hypothesized that BNP and ANP cause endothelium-independent relaxation of human intrarenal arteries by vascular natriuretic peptide receptor-A, but not -B and -C, which is mimicked by agonists of soluble guanylyl cyclase sGC. Human (n=54, diameter: 665±29µm 95% CI) and control murine intrarenal arteries (n=83, diameter 300±6µm 95% CI) were dissected and used for force recording by four-channel wire myography. Arterial segments were pre-contracted, then subjected to increasing concentrations of BNP, ANP, phosphodiesterase 5-inhibitor sildenafil, sGC-activator BAY 60-2770 and -stimulator BAY 41-2272. Endothelial nitric oxide synthase (eNOS) dependence was examined by use of L-NAME and eNOS knockout respectively. Molecular targets (NPR A-C, sGC, phosphodiesterase-5 and neprilysin) were mapped by PCR, immunohistochemistry and RNAscope. BNP, ANP, sildenafil, sGC-activation and -stimulation caused concentration-dependent relaxation of human and murine intrarenal arteries. BNP responses were independent of eNOS and were not potentiated by low concentration of phosphodiesterase-5-inhibitor, sGC-stimulator or NPR-C blocker. PCR showed NPR-A and C, phosphodiesterase-5, neprilysin and sGC mRNA in renal arteries. NPR-A mRNA and protein was observed in vascular smooth muscle and endothelial cells in arteries, podocytes, Bowmans capsule and vasa recta. NPR-C was observed in tubules, glomeruli and vasculature. Activation of transmembrane NPR-A and soluble guanylyl cyclase relax human preglomerular arteries similarly to phosphodiestase-5 inhibition. The human renal arterial bed relaxes in response to cGMP pathway.

Systolic dysfunction of the subpulmonary left ventricle is associated with the severity of heart failure in patients with a systemic right ventricle

BackgroundThe study aimed to assess the relation between echocardiographic parameters of subpulmonary left ventricular (LV) size and function, and the severity of heart failure in patients with a systemic right ventricle (SRV). Methods and resultsA total of 157 patients (89 post Mustard/Senning operations, 68 with congenitally corrected transposition of great arteries [ccTGA]) were included. The size and function of the SRV and subpulmonary LV were assessed on the most recent echocardiographic exam. Clinical data were collected from the electronic records.The majority (133, 84.7%) were in NYHA functional class 1–2. Median BNP concentration was 79.5[38.3–173.3] ng/l, and 100 (63.7%) patients were receiving heart failure therapy. Both LV and SRV fractional area change (FAC) differed significantly between patients with NYHA class 1–2 vs 3–4 (48[41.5–52.8]% vs 34[28.6–38.6]%, p < 0.0001 and 29.5[23–35]% vs 22[20–27]%, p < 0.0001, respectively), but LV FAC had a higher discriminative power for functional class >2 than SRV FAC (AUC 0.90, p < 0.0001 vs 0.79; p < 0.0001, respectively). A LV FAC cut-off value <39.2% had the highest accuracy in identifying patients with NYHA class 3–4 (sensitivity 83% and specificity 88%). In multivariable logistic regression analysis, LV FAC and SRV FAC independently associated to NYHA class 3–4 (OR 0.80 [95%CI 0.72–0.88], p < 0.0001 and OR 0.85 [95%CI 0.76–0.96], p = 0.007, respectively). ConclusionsSubpulmonary LV systolic dysfunction is associated with NYHA functional class 3–4 in patients with ccTGA or after Mustard or Senning operation. Careful evaluation of the subpulmonary LV should be a part of the routine assessment of patients with a SRV.

L’hypo-albuminémie contribue-t-elle à l’aggravation de l’insuffisance cardiaque ?

BackgroundHypoalbuminemia has now emerged as a powerful prognosticator in heart failure regardless of age, clinical presentation, left ventricular ejection fraction and usual prognostic markers. Growing evidence is that this prognostic value persists after adjusting for causative factors for hypoalbuminemia such as malnutrition, inflammation and liver dysfunction. ObjectiveTo address the prognostic relevance of hypoalbuminemia in frail elderly patients with well-characterized cardiogenic pulmonary edema at high risk for adverse outcome, beyond causative factors for low serum albumin levels. Serum albumin was measured after clinical stabilization to avoid hypervolemia. ResultsIn all, 67 patients with a mean age of 86 years were included. Hospital mortality was 30%. Patients who died and who survived were similar in age, ejection fraction, BNP concentration, serum creatinine, serum hemoglobin, total bilirubin and prealbumin. Patients who died had lower serum albumin levels (P<0.001), higher blood urea nitrogen (P=0.03) and higher C-reactive protein (P=0.02). In multivariate analysis, serum albumin was the sole independent predictor of hospital death (P<0.01), after adjusting for malnutrition (prealbumin P=ns), inflammation (C-reactive protein P=ns) and liver dysfunction (total bilirubin P=ns). ConclusionSerum albumin is a powerful prognosticator in frail elderly patients with acute cardiogenic pulmonary edema even after adjusting for main causative factors. These results suggest that hypoalbuminemia may contribute to the worsening of heart failure given the physiological properties of serum albumin that includes antioxidant activity and plasma colloid osmotic pressure action. Further studies are critically needed to address the relevance of prevention and correction of hypoalbuminemia in heart failure.

P0728ASSOCIATIONS BETWEEN LUNG WATER NON-TRADITIONAL PARAMETERS AND FUNCTIONAL TEST IN CKD G4-5 WITH PRESERVED EJECTION FRACTION

Abstract Background and Aims Patients with chronic kidney disease (CKD) are characterized by higher cardiovascular risk resulting amongst others from fluid expansion. Lung water measured by ultrasound (US) technique is increasingly recognised as an effective, quick and objective technique of even subclinical congestion/fluid overload. We aim to search correlates between the amount of artifact b-lines in lungs ultrasound (US-B lines; a metric of lung water), intra- and extracellular water (ICW, ECW), arterial stiffness by pulse wave velocity, result of functional six minute walk tests (6MWT) and global longitudinal strain score (GLS) assessed during heart ultrasound in patients with preserved ejection fraction. Method ICW/ ECW was assessed by bioimpedance (BIA 101 Akern), pulse wave velocity (PWV) by oscillometric method (mobilograph, IEM Germany). GLS was calculated using 2-dimensional speckle tracking. Traditional biochemical cardiac and renal markers and inflammatory markers were also assessed. Results The study included 51 consecutive patients (34 male) with CKD stage 4 and 5 (median eGFR MDRD4 11 ml/min IQR 9; 17) with oligosymptomatic congestion. The median (IQR) EF was 60 (60; 65)%, GLS was -18,7 (-21; -14)%, US-B lines was 10,5 (6; 17). Factors that were associated with US-B lines include BNP (r 0,5), ECW (r 0,4), distance in 6MWT (r –0,48) and hemoglobin (r -0,37). In comparison between groups (below vs above median) with more lung water (&amp;gt;11 US-B lines) and less lung water amount (&amp;lt;11) assessed after 5 min in a supine position we found markedly higher concentration of BNP and more extracellular water (ECW) in the first mentioned group (table). Patients with more B-lines have had lower hemoglobin level and shorter distance walked in 6MWT. Conclusion Lung water assessed by US is an quick and objective measure of congestion in advanced CKD with normal EF showing correlation with BNP concentration, distance walked in 6MWT and with extracellular water in bioimpedance. Its application into daily practice can be recommended.

Screening for asymptomatic heart failure with preserved ejection fraction in mongolian population at high risk.

Objective The goals of the present study were to assess the prevalence of asymptomatic heart failure with preserved ejection fraction (HFpEF) in subjects at high risk of developing HF and to define the diagnostic accuracy of NT-pro BNP assay compared with echocardiography in this setting.Material and methods This cross-sectional study included subjects aged from 35 to 64 years, with high risk of HF, who had no clinical symptoms of HF. Risk factors of HF were detected by clinical examinations. NT-pro BNP determination was performed using immunoassay analyzer (FIA8000, Getein Bio Medical Inc, China),. The cut-off point for NT-pro BNP was 125 pg/ml. Diagnosis of HFpEF was based on criteria recommended by 2016 ESC heart failure guidelines. Diastolic dysfunction was assessed according to the algorithm proposed in the joint recommendations of the ASE/EACVI.Results 602 patients with risk factors of HF were included in the study, of which 256 (42.5 %) were males and 346 (57.5 %) females. The mean age was 51.71±8.07 years. 83 patients (13.8 %) showed elevated NT-pro BNP levels of ≥125 pg / ml. Our study has shown that NT-pro BNP concentration was positively correlating with age, both systolic and diastolic blood pressure, left ventricular mass and E / e' ratio and negatively correlating with waist circumference, body mass index, left ventricular EF and E / A ratio in asymptomatic population. The likelihood of positive NT-pro BNP test was independently (p&lt;0.05) associated with age, hypertension and diabetes. The diagnosis of asymptomatic HFpEF was confirmed in 12.3 % of studied population. A cutoff value of 125 pg / ml for NT-proBNP concentration showed the following diagnostic re-abilities in identifying asymptomatic HFpEF: sensitivity 85.0 %, specificity 88.6 % and area under curve 0.92 (95 % CI 0.86-0.98).Conclusion Subjects with raised NT-pro BNP level (≥125 pg/ml) were more likely to have a confirmed diagnosis of asymptomatic HFpEF after screening. In summary, in at-risk population, natriuretic peptide based screening combined with echocardiography identifies high prevalence of asymptomatic HFpEF.

N-terminal pro brain natriuretic peptide as a marker of myocardial dysfunction in newborns with perinatal asphyxia

Background: Perinatal asphyxia refers to a condition during first and second stage of labour in which impaired gas exchange leads to foetal hypoxemia. Perinatal asphyxia causes cardiac dysfunction in 24 to 60 percent of the cases. The reduced cardiovascular reserve is associated with hypoxic brain damage and has high impact on neonatal mortality and adverse neurological outcomes. It has been challenging to diagnose myocardial dysfunction in resource constraint setting. Aim and objective of this study was to Determine N-Terminal Pro BNP concentrations in perinatal asphyxia and correlate with modified Sarnat stages of hypoxic ischemic encephalopathy.Methods: Among 120 Neonates admitted in neonatal intensive care unit with diagnosis of perinatal asphyxia were considered for the study. 2mL of venous blood drawn within 48hours of life was analyzed for quantitative N-Terminal Pro BNP and was correlated with modified Sarnat stages of hypoxic ischemic encephalopathy.Results: A Total of 120 cases of perinatal asphyxia were considered for the study, among which 44 cases had HIE stage 1, 48 had HIE stage 2 and rest 28 had HIE stage 3. The mean and standard deviation of N-Terminal Pro BNP concentrations in stage 1 was 1,502.86±3,581.170 pg/mL, stage 2 was 4,916.31±8,001.674 pg/mL and stage 3 was 8,912.41±13,927.152 pg/mL with significant p value of 0.003.Conclusions: Early N-Terminal Pro BNP concentrations may provide a useful marker for the anticipated severity of myocardial dysfunction.

Evaluation of TNF? in Patients with Heart Failure According to BNP Concentration

Background: Heart failure (HF) is a condition in which the heart can no longer pump blood as efficientlyas it used to. This is lead to a complex of clinical symptoms like (dyspnea, orthopnea, lower limb swelling).BNP is a neurohormone released from myocardium and increased when failure of heart is occure and usedfor diagnosing heart failure. TNF? is pro inflammatory cytokine, its concentration increasing in patients withheart failure, this caused by inflammation which is present in heart with failure.Objectives: This study was designed for Examining serum concentrations of TNF? in patients with HF,examining whether this cytokines was involved in the pathophysiology of the HF syndrome, and investigatingthe effectiveness of using BNP concentration as an indicator for heart failure.Subjects and Method: The current study is a cross sectional study that was carried out in the center ofDiyala province, Baquba Teaching Hospital, to determine the serum concentration of BNP and TNF-? inpatients with heart failure. The samples were collected in 2 and a half months, from January the 15th toAprilthe 1st 2019.A total of 150 serum samples were collected . 100 patients with diagnosed heart failure, and the restapparently healthy. The age range was 30-89 years, 50 of them were males, and 50 were females. BNP andTNF? concentrations were tested in the serum samples using the BNP and TNF? ELISA kit (from Sun Redcompany - China).Human privacy was respected by taking the parents’ verbal consent. Statistical analysisof data was carried out using the Statistical Packages for Social Sciences (SPSS), Version 25. Statisticalsignificance was considered whenever the P value was equal to or less than 0.05.Results: The results showed that the BNP concentration range in HF group patients (50-1600) was widerthan that in healthy control group (5-160) with a statistically significant difference between HF groupand healthy control group(P = 0.0001).Also there is statistically significant association between TNF?concentration and HF (P = 0.005). Furthermore, there was no statistically significant effect of age andgender on TNF-? concentration in neither the diseased group nor the control group. Also there is statisticallysignificant relationship between TNF? and family history (P = 0.026). There is direct relationship betweenTNF? and HF grade with a P value of 0.0001.Conclusion: The concentration of TNF? is elevated with increasing the severity of heart failure accompaniedby BNP concentration elevation, where Theincrease the HF grade, the elevation the concentration of TNF?.

The effect of hemodialysis on N-terminal pro-brain natriuretic peptide: A systematic review and meta-analysis.

N-terminal pro-brain natriuretic peptide (NT-pro BNP) increases in patients with heart failure and renal failure. Hemodialysis is a useful treatment to these patients. The aim of this study was to conduct a systematic and meta-analysis to evaluate the influence of hemodialysis on NT-pro BNP concentration. Relevant studies were identified by searching in PubMed, Medline, Embase, OVID, Web of Science, China Biology Medicine (CBM) and Google Scholar. Standard errors of mean difference along with its 95% CI were calculated to assess the association of hemodialysis and NT-pro BNP concentration. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. Individual patient data was obtained from 270 participants in seven articles suffered from chronic renal failure with regular hemodialysis, which was standard normal distribution. A fixed effects model suggested a pooled mean difference of 79.265 (95% CI: -331.172-489.702) without heterogeneity (Q=0.70 df=6 p=0.994 I2=0.0%). The adults group estimated a MD of 209.958 (95% CI: -3080.76-3500.67; p=0.900) with no heterogeneity (Q=0.70 df=4 p=0.983 I2=0.0%). In the four articles whose data were not standard normal distribution, hemodiafiltration protocols were similar; three articles reported increasing and one decreasing in NT-proBNP concentration. Finding of this systematic review and meta-analysis demonstrated that NT-pro BNP may not been influenced by hemodialysis, and it could not been used to determine if heart failure is improving in patients with renal failure who are treated with hemodialysis.

Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications.

Mesothelial cells and cardiomyocytes have shared embryonic mesodermal origin. Cardiomyocytes release BNP under stretch. We searched whether malignant mesothelioma cells also secrete BNP and if so, this has a meaningful impact. Part I: Prospectively, patients with pleural lesions on CT having malignant mesothelioma effusions (MME, n = 13) were compared to patients with malignant effusions with pleural lesions (MEa, n = 14). Age-matched patients with ME without pleural lesions (MEb, n = 16) and non-malignant effusions (NME, n = 25) were analysed. Part II: Retrospectively, samples from patients with mesothelioma (n = 14), lung cancer (n = 8) or heart failure (n = 9) were used. BNP was measured in pleural fluid and blood/plasma. Part III: BNP was assessed in the culture supernatants of benign (MeT-5A) and malignant mesothelioma cell lines (M14K-epithelioid, MSTO-biphasic and ZL34-sarcomatoid) (n = 10 per cell line in three different biological replicates). In vitro, BNP concentration was significantly higher in the supernatant of all malignant cell lines than benign ones (P < 0.01), denoting BNP's production from the former. The pleural fluid to blood BNP ratio in MME was extremely high in Part I and Part II subjects (28.3 ± 12.1 and 25.9 ± 8.6, respectively) versus 1.1 ± 0.3 and 0.4 ± 0.1 in Part I ME and NME, respectively (P < 0.0001), and 0.8 ± 0.1 and 0.4 ± 0.1 in Part II ME and NME, respectively (P < 0.0001). BNP ratio ≥2.11 in Part I had 92% sensitivity and 94.5% specificity for MME (P < 0.0001). BNP is secreted from malignant mesothelial cells. In clinical practice, the pleural fluid to blood BNP ratio can help in the diagnosis of malignant mesothelioma.

Clinical value of plasma BNP combined with Tei index in evaluating left ventricular function in children with congenital heart disease before interventional therapy

Objective To explore the clinical value of combined detection of plasma BNP and Tei index in evaluating left ventricular function in children with congenital heart disease before interventional therapy. Methods From April 2017 to April 2019, a total of 60 children with congenital heart disease who were going to receive interventional therapy in Dachong Hospital of Zhongshan and Boai Hospital of Zhongshan were selected as observation subjects, and the patients were divided into cardiac function class Ⅰ group and cardiac function class Ⅱ group according to NYHA cardiac function classification, with 30 cases in each group.At the same time, 30 normal children were selected as healthy control group.The differences of plasma BNP concentration, left ventricular ejection fraction(LVEF) and left ventricular Tei index in different group were compared.The correlation between the plasma concentration and the cardiac function was investigated, and the correlation between the plasma BNP concentration and the Tei index was analyzed. Results The concentration of serum BNP[(6.8±1.2)ng/L] and the Tei index of left ventricle (0.63±0.08) in the cardiac function class Ⅱ group were significantly higher than those in the cardiac function class Ⅰ group[(5.4±1.3)ng/L, (0.48±0.11)], and the differences were statistically significant (t=1.92, 3.01, all P<0.05). These two indicators of the two groups were higher than those of the healthy control group[(3.7±1.5)ng/L, (0.33±0.09)], the differences were statistically significant(t=2.14, 2.28, 4.19, 6.14, all P<0.05). In addition, the LVEF of the cardiac function class Ⅱ group was significantly lower than that of the cardiac function class Ⅰ group(t=5.00, P<0.05), and the LVEF of the two groups were significantly lower those that of the healthy control group(t=10.32, 4.51, all P<0.05). With the increase of severity of cardiac insufficiency, the BNP and Tei index gradually increased(F=3.054, 3.491, all P<0.05), and the LVEF value decreased gradually (F=12.50, P<0.05). At the same time, the linear correlation analysis showed that the plasma BNP concentration had a positive correlation with the left ventricular Tei index(r=0.69, P<0.01). Conclusion Plasma BNP combined with Tei index can quickly and accurately assess the left ventricular function in children with congenital heart disease before intervention.As a sensitive index for clinical detection, it has clinical application value. Key words: Heart defects, congenital; Angioplasty, balloon, coronary; Preoperative period; Natriuretic peptide, brain; Ventricular function, left; Child

Synergistic prognostication of left ventricular hypertrophy and three-dimensional mechanical dyssynchrony in heart failure.

AimsIn this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured three‐dimensionally by gated myocardial perfusion imaging (MPI), in patients with chronic systolic heart failure (HF).Methods and resultsIn 829 consecutive HF patients with reduced left ventricular ejection fraction less than 50%, LVMD was evaluated as a standard deviation (phase SD) of regional onset of mechanical contraction phase angles. A phase histogram was created by Fourier phase analysis applied to regional time‐activity curves obtained by gated MPI. Left ventricular mass index (LVMI) was measured by Corridor 4DM version 6.0. Patients were followed up with a primary endpoint of lethal cardiac events (CE) for a mean interval of 34 months. CE were documented in 223 (27%) of the HF patients. The CE group had a greater phase SD and a greater LVMI than those in the non‐CE group. Patients in the CE group had a more advanced age, greater New York Heart Association (NYHA) functional class, left ventricular cavity size, and left atrial diameter or septal E/e' and lower kidney or cardiac function than did patients in the non‐CE group. Phase SD > 37 and LVMI > 122.7 g/m2 were identified as optimal cut‐off values by receiver operating characteristic analyses for discrimination of the most increased risk HF subgroup from others (P < 0.0001). When classified into four patient subgroups using both cut‐off values, HF patients with phase SD > 37 (LVMD) and LVMI > 122.7g/m2 had the highest CE rate among the subgroups (P < 0.0001). Univariate analysis and subsequent multivariate analysis with a Cox proportional hazards model showed that phase SD and LVMI were significant independent predictors of CE with hazard ratios of 1.038 (confidence interval [CI], 1.024–1.051, P < 0.0001) and 1.005 (CI, 1.001–1.008, P = 0.0073), respectively, as well as conventional clinical parameters such as age, NYHA class, estimated glomerular filtration rate (eGFR), and BNP concentration. Patients with increased phase SD and LVMI had incrementally improved prognostic values of clinical parameters including age, NYHA functional class, eGFR, and BNP with increases in the global χ2 value: 5.9 for age; 139.5 for age and NYHA; 157.9 for age, NYHA, and eGFR; 163.9 for age, NYHA, eGFR, and BNP; 183.4 for age, NYHA, eGFR, BNP, and phase SD; and 192.5 for age, NYHA, eGFR, BNP, phase SD, and LVMI.ConclusionsThree‐dimensionally assessed LVMD has independent prognostic values and can improve the risk stratification of chronic HF patients synergistically in combination with conventional clinical parameters.

Predictors of adverse cardiovascular event in patients with a systemic RV: A prospective cohort study

In complete transposition of the great arteries (TGA) palliated by atrial switch operation, systemic right ventricle (sRV) failure and rhythm disturbances compromise survival. We aimed to determine predictive factors of severe cardiovascular events in this population. Forty-eight adult patients with TGA palliated (36 males, median age = 32 years, IQR [23–35]) were prospectively enrolled from 2011 to 2012. At baseline, all subjects underwent a clinical examination with ECG and exercise test, an echocardiography, a cardiac magnetic resonance imaging (cMRI) assessment and biomarkers measurements. Main adverse cardiac events (MACE) were defined by hospitalization for heart failure, arrhythmia, heart transplantation and death. At baseline, most of patients were asymptomatic (85% NYHA1, median predictive VO2 = 66% IQR [58–73]), with a relatively good sRV function (cMRI sRVEF = 52% IQR [44-58]), and tricuspid regurgitation grade was mild in 87%. Baseline concentration of BNP was 34 pg/ml (IQR [14-54]) but higher than in controls ( P < 0.01), as well as myocardial collagen biomarkers concentrations (pro-MMP1 and P3NP, P < 0.05). After a mean follow-up period of 7 ± 0.3 years, 9 MACE occurred (2.7% patient-years) 4 patients experienced HF, 4 atrial arrhythmia and 1 ventricular tachycardia. 2 patients were transplanted and none death was observed. Among baseline characteristics, NYHA functional class ≥ 2 (HR = 5.17 95%CI [1.37–19.59], P = 0.04), end-diastolic and end–systolic sRV volumes ( P ≤ 0.02) and BNP (HR = 1.02 95%CI [1.00–1.03], P = 0.01), were significantly predictive of MACE. Cumulative incidence of MACE in patients with NYHA functional class ≥ 2 or BNP≥150 pg/mL was 43% to 2 years compared to 5% in patients without ( Fig. 1 ). Patients with a TGA palliated by atrial switch are at high risk of severe cardiovascular events. Increase in NYHA functional class and BNP concentration must be regularly controlled to detect patients at risk.

A porcine model of heart failure with preserved ejection fraction: magnetic resonance imaging and metabolic energetics.

AimsA significant proportion of heart failure (HF) patients have HF preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF remains a critical unmet need. A key obstacle to therapeutic innovation in HFpEF is the paucity of pre‐clinical models. Although several large animal models have been reported, few demonstrate progression to decompensated HF. We have established a model of HFpEF by enhancing a porcine model of progressive left ventricular (LV) pressure overload and characterized HF in this model including advanced cardiometabolic imaging using cardiac magnetic resonance imaging and hyperpolarized carbon‐13 magnetic resonance spectroscopy.Methods and resultsPigs underwent progressive LV pressure overload by means of an inflatable aortic cuff. Pigs developed LV hypertrophy (50% increase in wall thickness, P < 0.001, and two‐fold increase in mass compared to sham control, P < 0.001) with no evidence of LV dilatation but a significant increase in left atrial volume (P = 0.013). Cardiac magnetic resonance imaging demonstrated T1 modified Look‐Locker inversion recovery values increased in 16/17 segments compared to sham pigs (P < 0.05–P < 0.001) indicating global ventricular fibrosis. Mean LV end‐diastolic (P = 0.047) and pulmonary capillary wedge pressures (P = 0.008) were elevated compared with sham control. One‐third of the pigs demonstrated clinical signs of frank decompensated HF, and mean plasma BNP concentrations were raised compared with sham control (P = 0.008). Cardiometabolic imaging with hyperpolarized carbon‐13 magnetic resonance spectroscopy agreed with known metabolic changes in the failing heart with a switch from fatty acid towards glucose substrate utilization.ConclusionsProgressive aortic constriction in growing pigs induces significant LV hypertrophy with cardiac fibrosis associated with left atrial dilation, raised filling pressures, and an ability to transition to overt HF with raised BNP without reduction in LVEF. This model replicates many aspects of clinical HFpEF with a predominant background of hypertension and can be used to advance understanding of underlying pathology and for necessary pre‐clinical testing of novel candidate therapies.

P3793Spironolactone in patients with permanent atrial fibrillation, possible heart failure protective potential

Abstract Background Atrial fibrillation (AF) promotes electrical, neurohormonal and structural remodeling of atria and ventricles. Long lasting AF leads to atrial interstitial fibrosis, apoptosis, loss of myofibrils and finally to heart failure (HF). Purpose The aim of the study was impact of aldosterone antagonist, spironolactone, on exercise tolerance and neurohormonal activity in patients with permanent AF without symptoms of HF. Methods In prospective, randomized study patients with permanent AF at least for 1 year, no signs and symptoms of HF and stable clinical condition were included. Patients were randomized to: beta-blocker plus spironolactone (dose: 25 mg) treatment and rate-control treatment with only beta-blocker. Propranolol, metoprolol and bisoprolol were used, doses were adjusted to achieve resting heart rate 60–80/min. Ergospirometry (CPX) and 6-minute walk (6-MWT) tests were performed during separate days. Results Study group consisted of 49 patients, 69% men, mean age 62.1±9.6 without structural and chronic active diseases, mean time of arrhythmia was 5.5 years, Q1: 2, Q3: 8 years. Follow-up was 11.2 months. All patients were treated with beta-blockers, 27 patients were treated with 25 mg spironolactone. Surprisingly physical capacity in 6-minute walk test (6-MWT) in studied patients was not significantly reduced in comparison with values ranges for healthy volunteers. After 11.2 months follow-up significantly longer exercise time (433±113 vs. 367±162 sec, p&lt;0.05) and lower maximal HR (159±25 vs. 165±22 beats/min, p&lt;0.0550) were observed in spironolactone treated group. Other CPX variables did not differ significantly between groups after 11,2 months: VO2: 20.7±5.1 vs. 20.1±4.8 [ml/kg/min]; VO2 as % of normal value: 78.4±15.2 vs. 76.8±15.2; O2 pulse: 12±2.8 vs. 12.7±3.6 [ml/beat]; AT: 1.4±0.3, 1.6±0.5 [L/min]; VE: 74.9±20.0, 72.6±17.9 [L/min]. All spirometric variables worsened after 11.2 months: VC: 4.3±1.1 vs. 3.8±0.8 [L], p&lt;0.0005, FVC: 4.2±1.1 vs. 3.8±1.0 p&lt;0.005 [L], FEV1: 3.1±0.8 vs. 2.8±0.7 [L], p&lt;0.01. In spironolactone treated group after 11.2 months BNP concentrations were significantly lower: Q1: 54, Q2: 83, Q3: 100 vs. Q1: 42, Q2: 93; Q3: 184 ng/L (p=0.025) and aldosterone levels were markedly increased: Q1: 216, Q2: 266; Q3:443 vs. Q1: 169; Q2: 228; Q3:294 ng/dL (p=0.0007). Conclusions In patients with permanent atrial fibrillation cardiopulmonary exercise responses were markedly abnormal, but exercise capacity was increased after spironolactone treatment. Deterioration of spirometry results might be due to beta-blocker treatment. In spironolactone treated group BNP levels were significantly lower what may correspond to its heart failure protective activity.

Prognostic markers of heart failure in patients undergoing peritoneal dialysis

BackgroundHeart failure is a significant cause of death and hospitalization in dialysis patients. Controlling the volume status in PD, especially, is difficult, and transferring the PD patients to hemodialysis results mainly from ultrafiltration failure. Thus, the control of heart failure and markers as its predictors in PD patients are of the utmost importance. In this study, we aim to confirm the utility of BNP and NT-proBNP as predictive markers of heart failure and to identify new markers in PD patients.MethodsOur study involved 29 patients who had been undergoing PD. The following were determined: body mass index, primary disease, PD vintage, D/P ratio, D/D ratio, left ventricle ejection fraction, left atrial dimension, left ventricular mass index, cardiac index, change in body weight, CTR, BNP, NT-proBNP, BUN, creatinine, TP, Alb, Na, K, Cl, Ca, P, iPTH, Hb, Ht, sβ2MG, T-SAT, and weekly Kt/V urea and CCr. Furthermore, we categorized the patients’ disease using the NYHA classification and evaluated these indicators.ResultsThe BNP concentration was positively correlated with that of NT-proBNP. In addition, the CTR was positively correlated with BNP and NT-proBNP concentrations. By one-way analysis of variance, the NYHA classification was statistically associated with BNP, NT-proBNP, CTR, Alb, Hb, Ht, sβ2MG, ferritin, and weekly Kt/V urea and CCr, of which Hb and Ht were the most significant. According to the logistic regression analysis of the heart failure risk using the NYHA classification, the CTR, Hb, Ht, and weekly CCr were statistically significant in the univariate analysis. However, none remained statistically significant, and among them, weekly CCr has the highest specificity in the multivariate analysis. Furthermore, the following measurements were associated with a high risk of heart failure: CTR > 51.9%, Hb < 9.4 g/dL, Ht < 29.2%, and weekly CCr < 80.9 L/week/1.73 m2.ConclusionCompared with the classical examinations, BNP and NT-proBNP are less useful as markers of heart failure in PD patients. Consequently, anemia and weekly CCr are the risks of heart failure.Trial registrationThis study was retrospectively registered to the University Hospital Medical Information Network (UMIN no. 000041762).

Clinical Usefulness of N-terminal Prohormone of Brain Natriuretic Peptide and High Sensitivity Troponin T in Patients with Heart Failure Undergoing Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a valuable intracardiac device--based treatment option for a subgroup of patients with advanced heart failure (HF) and QRS prolongation. However, still a significant proportion of patients do not benefit from CRT implantation, labeled as non-responders. The aim of the present study was to evaluate the N-terminal prohormone of brain natriuretic peptide (NT-pro BNP) and high sensitivity troponin T (cTnThs) value as predictors of CRT response in a 12-month observation. The study included 46 patients with HF and implanted CRT-D. Levels of NT-pro BNP and cTnThs were assessed during a 12 month follow up. 46 consecutive patients (76% men) with a mean age of 64±8 were observed for 12 months. The CRT response criteria was met by 26 patients (56,5%). A significant decline in the NT-pro BNP concentrations was documented in responders (p=0.001). Moreover, ΔNT-pro BNP by at least 579 pg/ml had high sensitivity and specificity for identifying the CRT responders. There were no statistically significant differences in the results of cTnThs between the two study groups. The relative change in the level of NT-pro BNP by at least 43,5% allows to identify the responders to CRT after 12 months of follow-up. Serial measurements of NT-pro BNP can be a valuable tool for monitoring the effectiveness of CRT.

Biomarkers for the prediction of early pulmonary embolism related mortality in spontaneous and provoked thrombotic disease

Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882–1.000, p = .001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745–0.902, p < .001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group.

Can the development of atrial fibrillation in patients with ischemic heart failure with low ejection fraction be predicted?

OBJECTIVE:Our aim is to determine the triggering factors of paroxysmal atrial fibrillation (PAF) in ischemic heart failure (HF) patients with low ejection fraction (EF).METHODS:Sixty patients were included in this study. Echocardiography and 24-hours Holter monitoring were performed after measurement of serum NT-pro BNP concentration. The patients were classified into two groups concerning the occurrence of PAF on Holter recordings. Biochemical and echocardiographic parameters of patients with and without PAF were compared.RESULTS:PAF was detected in 28 (46%) patients. Patients with PAF demonstrated higher NT-pro BNP levels, mitral and aortic regurgitation velocities, E/A, E/E’, pulmonary capillary wedge pressure, pulmonary artery systolic pressure, left atrial volume and volume indices. NT-pro BNP was established as the predictor of PAF (OR=1.23, 95% CI: 1.08–1.42; p=0.001). ROC analysis showed an NT-pro BNP value of 2188 pg/mL as cut-off value with 68% sensitivity and 84% specificity [Area under the ROC curve (AUC)=0.826, CI 95%: 0.724–0.927; p<0.001].CONCLUSION:The triggering factors for AF are increased intracardiac pressures, left atrial dilatation and increased wall tension. As an indicator of increased wall tension, elevated levels of NT-pro BNP predict the development of PAF.