Reduction In B-type Natriuretic Peptide Research Articles

Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure

Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Different Renal Function Patterns in Patients With Acute Heart Failure: Relationship With Outcome and Congestion.

BackgroundThe role of worsening renal function during acute heart failure (AHF) hospitalization is still debated. Very few studies have extensively evaluated the renal function (RF) trend during hospitalization by repetitive measurements.ObjectivesTo investigate the prognostic relevance of different RF trajectories together with the congestion status in hospitalized patients.MethodsThis is a post hoc analysis of a multi-center study including 467 patients admitted with AHF who were screened for the Diur-AHF Trial. We recognized five main RF trajectories based on serum creatinine and estimated glomerular filtration rate (eGFR) behavior. According to the RF trajectories our sample was divided into 1-stable (S), 2-transient improvement (TI), 3-permanent improvement (PI), 4-transient worsening (TW), and 5-persistent worsening (PW). The primary outcome was the combined endpoint of 180 days including all causes of mortality and re-hospitalization.ResultsWe recruited 467 subjects with a mean congestion score of 3.5±1.08 and a median creatinine value of 1.28 (1.00–1.70) mg/dl, eGFR 50 (37–65) ml/min/m2 and NTpro B-type natriuretic peptide (BNP) 7,000 (4,200–11,700) pg/ml. A univariate analysis of the RF pattern demonstrated that TI and PW patterns were significantly related to poor prognosis [HR: 2.71 (1.81–4.05); p < 0.001; HR: 1.68 (1.15–2.45); p = 0.007, respectively]. Conversely, the TW pattern showed a significantly protective effect on outcome [HR:0.34 (0.19–0.60); p < 0.001]. Persistence of congestion and BNP reduction ≥ 30% were significantly related to clinical outcome at univariate analysis [HR: 2.41 (1.81–3.21); p < 0.001 and HR:0.47 (0.35–0.67); p < 0.001]. A multivariable analysis confirmed the independently prognostic role of TI, PW patterns, persistence of congestion, and reduced BNP decrease at discharge.ConclusionsVarious RF patterns during AHF hospitalization are associated with different risk(s). PW and TI appear to be the two trajectories related to worse outcome. Current findings confirm the importance of RF evaluation during and after hospitalization.

Abstract 11852: Prognostic Value of B-type Natriuretic Peptide Reduction and Uric Acid Levels as Predictors of 30-day Re-Admission in Patients With Acute Decompensated Heart Failure With Preserved Ejection Fraction

Introduction: There is limited data comparing re-admission outcomes in patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to determine the prognostic value of B-natriuretic peptide (BNP) level reduction and uric acid levels in hospitalized HFpEF patients. Hypothesis: Higher BNP level reduction and uric acid levels are associated with higher 30-day re-admission rates. Methods: This was a multi-center retrospective analysis of 3,398 patients admitted with acute decompensated HFpEF from January 2017 to December 2019. HFpEF was defined as a left ventricular function ≥ 50% and at least stage I diastolic dysfunction. Outcomes were defined by 30-day re-hospitalization rates for the two groups in the inpatient setting. Baseline characteristics, cardiovascular risk factors, admission laboratory data (troponin, sodium, hemoglobin A1c, uric acid), vital signs, length of stay and time to readmission due to heart failure exacerbation were gathered and compared. Results: The median age was 75.5 years and the mean length of stay was 11.1 days. The mean BNP at admission was 910 and the second BNP following standard therapy was 786. The median percent change in BNP was found to be 16.95%. Of the hypothesized clinical predictors of re-admission, we found that none of them; including change in BNP reduction and uric acid, were predictive of re-admission. Those who were re-admitted had lower sodium levels (136.6±5.86 vs 137.0±6.07, p=0.06), while improved creatinine levels (1.94±1.31 vs 2.06±1.66, p=0.02) was associated with re-admission for unclear reasons. For those patients who are white, the odds of experiencing re-admission is 1.54 times more likely compares to those who are of other race. Conclusions: Lower sodium levels and lower creatinine levels were found to be important risk factors for readmission. None of the hypothesized clinical variables including BNP reduction and uric acid predicted re-admission except for white race, which we feel is a surrogate for socioeconomic status. These findings underline the need for further studies and complexity in planning re-admission prevention algorithms in HFpEF patients.

Blocking Store‐Operated Ca2+ Entry to Protect Cardiomyocytes from Epirubicin‐Induced Toxicity

Epirubicin (EPI) is one of widely used anthracycline chemotherapy drugs, yet its cardiotoxicity severely limits its clinical application. Altered intracellular Ca2+ homeostasis has been linked to epirubicin‐induced cell death and hypertrophy. While store‐operated Ca2+ entry (SOCE) recently has been linked with cardiac hypertrophy and heart failure, its role in epirubicin‐induced cardiotoxicity remains unknown.METHODHL‐1, a cardiomyocyte cell line derived from adult mouse atria, was used in this study. Intracellular ROS was measured by dihydroethidium(DHE) fluorescence and intracellular Ca2+ was monitored by ratiometric dye Fura‐2 on a spectrofluorometer (excitation λ = 350/385nm and emission λ = 510nm; Photon Technology International, NJ). Upon depletion of ER Ca2+ stores by 10μM thapsigargin (TG) in 0mM Ca2+ extracellular solution, SOCE was activated when extracellular solution was rapidly exchanged to 2mM Ca2+. Apoptosis assay was conducted by nuclei staining, F‐actin phalloidin staining and Western Blotting of caspase‐3. While cell size was compared in HL‐1 cells with different treatments using Image J, the mRNA of Orai1, Orai3, STIM1 and B‐type natriuretic peptide (BNP) were also compared using real time qPCR.RESULTSIncubation of 1uM EPI for 30min induced significant ROS production in cultured HL‐1 cells compared with vehicle control (10410±1492 vs. 2762±939, p&lt;0.0001). EPI induced an enhanced SOCE (0.1214±0.0104 vs. 0.0682±0.0062, n=32, p=0.0008), likely through increased expression of SOCE components Orai1, Orai3, and STIM1 compared with control cells. Apoptosis was observed upon EPI treatment, indicated by the condensed and fragmented nuclei, degradation of F‐actin and increased cleavage of caspase‐3 protein. EPI treatment also resulted in larger cell size (3894±120 μm2) compared with non‐treated control cells (2452±57 μm2, n=581, p&lt;0.0001). The hypertrophy marker BNP was up‐regulated upon EPI treatment as well. BTP‐2, a known SOCE blocker, could block this EPI‐induced SOCE and rescue HL‐1 cells from EPI‐induced apoptosis. BTP‐2 also prevented HL‐1 cells from EPI‐induced hypertrophy in terms of cell size (see Figure , 2548±69 μm2) and also reduction of BNP expression.CONCLUSIONEpirubicin upregulated SOCE, induced apoptosis and hypertrophy in HL‐1 cardiomyocytes. Blocking SOCE by BTP‐2 could at least partially rescue HL‐1 cells from epirubicin‐induced apoptosis and hypertrophy.Support or Funding Information(1) NIH S10 OD025230 to Dr. Zui Pan(2) University of Texas at Arlington Center for Research and Scholarship Pilot Grant for Trainee to Xian LiuFigure 1

Lung ultrasound for volume status assessment in chronic hemodialysis patients

Backoground/Aim. Assessing volume status in chronic hemodialysis (HD) patients is difficult despite several techniques have been developed. The aim of this study was to demonstrate the adequacy and efficacy of lung ultrasound (LUS) and B line score (BLS) in the assessment of volume status in patients on HD in comparison to other techniques: ultrasonographic determination of inferior vena cava diameter (IVCD), echocardiography (ECHO) and B-type natriuretic peptide (BNP) determination. Methods. LUS, ECHO, ultrasonography of inferior vena cava in inspiration (IVCDi) and expiration (IVCDe), and BNP sampling were performed before and after HD in 83 patients. Results. A significant reduction of BLS, IVCDi, IVCDe, BNP and several ECHO parameters such as left atrium diameter (LA), left ventricular internal dimension in diastole and systole (LVIDd and LVIDs, respectively), and left atrial volume in systole (LAVs), was registered (p &lt; 0.001). There was a significant correlation between BLS and BNP before (p = 0.01) and after HD (p = 0.05), and a weaker but significant correlation between BLS and IVCDi and IVCDe before HD (p = 0.05). Conclusion. All techniques assessed hypervolemia before and after HD successfully. BNP correlated with LUS before and after HD, and IVCDi and IVCDe correlated with LUS only before HD. LUS is cheap and simple to perform, can be performed bedside and can be reliably used for assessing volume status in HD patients.

Impact of pericardiectomy on exercise capacity and sleep of patients with chronic constrictive pericarditis.

BackgroundHeart failure is associated with exercise intolerance and sleep- disordered breathing; however, studies in patients with chronic constrictive pericarditis are scarce. The purpose of our study was to assess exercise capacity and sleep in patients with chronic constrictive pericarditis (CCP) undergoing a pericardiectomy.MethodsWe studied consecutive patients scheduled for pericardiectomy due to symptomatic CCP. Were performed quality of life (Minnesota Living with Heart Failure Questionnaire—MLHFQ) and sleep questionnaires (Epworth, Pittsburgh Sleep Quality Index—PSQI), serum B-type natriuretic peptide (BNP), serum C-reactive protein, transthoracic echocardiography, cardiopulmonary exercise test and overnight polysomnography immediately before and six months after pericardiectomy.ResultsTwenty-five patients (76% males, age: 45.5±13.8 years, body mass index: 24.9±3.7 kg/m2, left ventricular ejection fraction: 60±6%) with CCP (76% idiopathic, 12% tuberculosis) were studied. As compared to the preoperative period, pericardiectomy resulted in reduction in BNP (143 (83.5–209.5) vs 76 (40–117.5) pg/mL, p = 0.011), improvement in VO2 peak (18.7±5.6 vs. 25.2±6.3 mL/kg/min, p<0.001), quality of life (MLHFQ score 62 (43,5–77,5) vs. 18 (8,5–22), p<0,001) and sleep (PSQI score 7.8±4.1 vs. 4.7±3.7, p<0.001) and no significant change in sleep disordered breathing (apnea hypopnea index—AHI 15.6 (8.3–31.7) vs. 14.6 (5.75–29.9) events/h, p = 0.253).ConclusionPatients with symptomatic CCP showed reduced exercise capacity and sleep-disordered breathing. After pericardiectomy, there was improvement in exercise capacity and neutral effect on sleep-disordered breathing.

The impact of changes in B-type natriuretic peptide levels on prognosis after transcatheter aortic valve implantation.

Higher B-type natriuretic peptide (BNP) levels at discharge predict higher cardiovascular events in transcatheter aortic valve implantation (TAVI) patients. However, it is not known whether the reduction in BNP levels effectively predicts prognosis. The purpose was to examine the predictive power of percentage changes in BNP levels for all-cause death and hospitalization of heart failure (HF) after TAVI in severe aortic stenosis (AS) patients. We analyzed 70 severe AS patients treated with TAVI who had a record of BNP > 200pg/mL. Receiver operating characteristics (ROC) curves analysis for all-cause death and hospitalization for HF after TAVI revealed the cut-off percentage change in BNP, and we divided the study population into the "responder group" and the "non-responder group". The cut-off level for the percentage change in BNP evaluated by ROC analysis was a 40% decrease in BNP (AUC = 0.733, p < 0.001). There were 48 patients (68.6%) in the responder group and 22 patients (31.4%) in the non-responder group. Kaplan-Meier estimates showed that the responder group had lower all-cause death and hospitalization for HF than the non-responder group by a log rank test (all-cause mortality; p = 0.006, hospitalization rate for HF; p < 0.001). The predictor of the non-responder group using multivariate logistic regression analysis was AF (OR 4.2, 95% CI 1.15-16.2, p = 0.03). A reduction of BNP was associated with improved prognosis after TAVI.

Prognostic Value of BNP Reduction During Hospitalization in Patients With Acute Heart Failure

Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF. We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction. The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.

Effects of sauna bath on heart failure: A systematic review and meta-analysis.

Sauna bath has potential as a lifestyle treatment modality for heart failure (HF). It is important to analyze the current evidence to help suggest paths of future study and potential for clinical application. Sauna bath has a positive effect on HF patients. PubMed, Cochrane Library, and CINAHL databases were searched to identify randomized and nonrandomized controlled studies to compare effects of sauna bath with no sauna bath. Studies were searched for both infrared sauna bath and Finnish sauna bath. The strength of evidence was rated using a modified GRADE approach. Out of 1444 studies, nine met the inclusion criteria and were included in this review. Seven of these nine studies were included in the meta-analysis. Only studies with infrared sauna bath met the inclusion criteria. In the meta-analysis, exposure to an infrared sauna bath in 60°C for 15 minutes, followed by a 30-minute rest in warm environment, five times a week for 2 to 4 weeks, was associated with a significant reduction in B-type natriuretic peptide, cardiothoracic ratio, and an improvement in left-ventricular ejection fraction. There was no significant effect on left-ventricular end-diastolic diameter, left atrial diameter, systolic blood pressure, or diastolic blood pressure. The strength of evidence varied from moderate to insufficient. Infrared sauna bath was associated with short-term improvement in cardiac function. More evidence is needed about long-term effects of sauna bath and the effects of a Finnish sauna on cardiovascular health among patients with HF or other cardiovascular diseases.

Cardiac resynchronization therapy guided by cardiac magnetic resonance imaging: A prospective, single-centre randomized study (CMR-CRT)

BackgroundCardiac resynchronization therapy (CRT) improves symptoms of heart failure (HF), morbidity and mortality in selected population. The aim of the study was to investigate the impact of cardiac magnetic resonance (CMR)-guided left ventricular (LV) lead placement on clinical outcomes and LV reverse remodelling in CRT recipients. MethodsPatients with CRT indication were randomized for CMR-guided (CMR group) or electrophysiologically guided (EP group) LV lead placement between 2011 and 2014. The target site in the CMR group was defined as the most delayed, scar-free, in the EP group as the site with the longest interval between the QRS onset and local electrogram. The primary endpoint was a combination of cardiovascular death or HF hospitalization. Secondary endpoints were New York Heart Association (NYHA) Class improvement ≥1, LV endsystolic diameter reduction >10%, B-type natriuretic peptide reduction by ≥30%. ResultsA total of 99 patients (47 in the CMR and 52 in the EP group) were enrolled. During a median follow-up of 47 months, primary composite endpoint occurred in 5 patients in the CMR group and 14 patients in the EP group (HR = 0.46; 95% CI: 0.16–1.32). Patients with left bundle branch block and NYHA Class >2 had better clinical outcome in the CMR group (HR = 0.09; 95% CI: 0.01–0.75). ConclusionsThe use of CMR did not result in significant reduction of combined endpoint of cardiovascular death or HF hospitalization in the total study population. Significant clinical benefit from CMR-guided procedure was observed in a subgroup of optimum CRT candidates with advanced HF.

Treprostinil Improves Persistent Pulmonary Hypertension Associated with Congenital Diaphragmatic Hernia

To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil. We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis. Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia. In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects.

The Histone Demethylase JMJD2A Modulates the Induction of Hypertrophy Markers in iPSC-Derived Cardiomyocytes.

The development of cardiovascular pathologies is partly attributed to epigenetic causes, including histone methylation, which appears to be an important marker in hearts that develop cardiac hypertrophy. Previous studies showed that the histone demethylase JMJD2A can regulate the hypertrophic process in murine cardiomyocytes. However, the influence of JMJD2A on cardiac hypertrophy in a human cardiomyocyte model is still poorly understood. In the present study, cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) were used. Hypertrophy was induced by angiotensin II and endothelin-1 (ET-1), and transfections were performed to overexpress JMJD2A and for small interfering RNA (siRNA)-induced silencing of JMJD2A. Gene expression analyses were determined using RT-PCR and Western blot. The expression levels of B-type natriuretic peptide (BNP), natriuretic peptide A (ANP), and beta myosin heavy chain (β-MHC) were increased by nearly 2–10-fold with ET-1 compared with the control. However, a higher level of JMJD2A and UTX was detected, whereas the level of JMJD2C was lower. When cardiomyocytes were transiently transfected with JMJD2A, an increase close to 150% in BNP was observed, and this increase was greater after treatment with ET-1. To verify the specificity of JMJD2A activity, a knockdown was performed by means of siRNA-JMJD2A, which led to a significant reduction in BNP. The involvement of JMJD2A suggests that histone-specific modifications are associated with genes encoding proteins that are actively transcribed during the hypertrophy process. Since BNP is closely related to JMJD2A expression, we suggest that there could be a direct influence of JMJD2A on the expression of BNP. These results may be studied further to reduce cardiac hypertrophy via the regulation of epigenetic modifiers.

Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: The paradox of functional and echocardiographic response

IntroductionResponse to cardiac resynchronization therapy (CRT) can currently be assessed by clinical or echocardiographic criteria, and there is no strong evidence supporting the use of one rather than the other. Reductions in B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been shown to be associated with CRT response. This study aims to assess variation in BNP and CRP six months after CRT and to correlate this variation with criteria of functional and echocardiographic response. MethodsPatients undergoing CRT were prospectively enrolled between 2011 and 2014. CRT response was defined by echocardiography (15% reduction in left ventricular end-systolic volume) and by cardiopulmonary exercise testing (10% increase in peak oxygen consumption) from baseline to six months after device implantation. ResultsA total of 115 patients were enrolled (68.7% male, mean age 68.6±10.5 years). Echocardiographic response was seen in 51.4% and 59.2% were functional responders. There was no statistical correlation between the two. Functional response was associated with a significantly greater reduction in BNP (-167.6±264.1 vs. -24.9±269.4 pg/ml; p=0.044) and CRP levels (-1.6±4.4 vs. 2.4±9.9 mg/l; p=0.04). Nonetheless, a non-significant reduction in BNP and CRP was observed in echocardiographic responders (BNP -144.7±260.2 vs. -66.1±538.2 pg/ml and CRP -7.1±24.3 vs. 0.8±10.3 mg/l; p>0.05). ConclusionAn increase in exercise capacity after CRT implantation is associated with improvement in myocardial remodeling and inflammatory biomarkers. This finding highlights the importance of improvement in functional capacity after CRT implantation, not commonly considered a criterion of CRT response.

Discharge BNP is a stronger predictor of 6-month mortality in acute heart failure compared with baseline BNP and admission-to-discharge percentage BNP reduction

IntroductionPrior studies found a significant relationship between admission B-type natriuretic peptide (BNP), discharge BNP and admission-to-discharge percentage BNP reduction and post-discharge mortality in acute heart failure (HF). MethodsThe ESCAPE trial data was utilized to identify which of these BNP parameters best predicts 6-month all-cause mortality. Results433 patients (mean age 56years, 74% men) included in our analysis had an admission BNP, discharge BNP and admission-to-discharge percentage BNP reduction of 1009pg/mL, 743pg/mL and −70%, respectively. There were significant differences between survivors and nonsurvivors with regards to admission BNP (P=0.001), discharge BNP (P=0.0001) and admission-to-discharge percentage BNP reduction (P=0.01). Discharge BNP had the highest area under the curve (AUC) for predicting mortality (AUC=0.702, P<0.001) followed by admission BNP (AUC=0.633, P=0.0006) then percentage BNP reduction (AUC=0.620, P=0.008). Comparison of AUC revealed a significant difference between discharge BNP and admission BNP (difference between areas 0.087, P=0.0223) and a trend towards significance when comparing AUC of discharge BNP with percentage BNP reduction (P=0.0637). Kaplan–Meier analysis showed a significant difference in survival according to optimum cutoff values of discharge BNP of 319pg/mL (log-rank P<0.001), admission BNP of 912pg/mL (P<0.001) and percentage BNP reduction of 7.71% (P=0.008). Cox-proportional-hazard-analysis revealed that discharge BNP is an independent predictor of 6-month mortality (hazard ratio=1.063, 95% CI=1.037–1.089, P<0.001). The combination of a discharge BNP ≤319pg/mL and percentage BNP reduction ≥7.71% was associated with significantly lower mortality (4.8% versus 27.2%, relative risk=0.134, 95% CI=0.046–0.387, P<0.001). ConclusionThe absolute BNP value at discharge is a more accurate predictor of 6-month mortality than the magnitude of percentage in-hospital BNP reduction and baseline BNP.

Longitudinal BNP follow-up as a marker of treatment response in acute heart failure: Relationship with objective markers of decongestion

IntroductionResults of studies that examined the value of B-type natriuretic peptide (BNP) reduction as a marker of decongestion have been inconsistent. We investigated whether longitudinal admission-to-discharge BNP reduction can be used to monitor decongestion during acute heart failure (HF). MethodsWe used the ESCAPE trial data to study the relationship between the magnitude of BNP reduction and various clinical and objective markers of decongestion. ResultsAdmission-to-discharge reduction in BNP was recorded in 245 patients who were divided into tertiles (tertile 1 had BNP reduction<27pg/mL, tertile 2 had BNP reduction 27–334pg/mL and tertile 3 had BNP reduction>334pg/mL). There were significant differences across tertiles with regard to resolution of jugular venous distension (JVD, P=0.014) and orthopnea (P=0.04) on discharge, admission-to-discharge weight loss (P=0.002), and admission-to-discharge reduction in inferior vena cava (IVC) diameter (P=0.0001). Compared with the first tertile, patients in the third tertile had significantly higher frequency of resolution of JVD (univariate OR 2.657, P=0.004) and orthopnea (univariate OR 2.083, P=0.032) on discharge, more weight loss (P=0.001), higher IVC diameter reduction (P<0.0001), and higher reduction in pulmonary capillary wedge pressure (PCWP) from admission to day of PAC removal compared with first tertile (P<0.0001). Using the whole cohort, we found a significant correlation between admission-to-discharge BNP reduction and admission-to-discharge weight loss (n=232, r=0.211, P=0.001), admission-to-discharge reduction in IVC diameter (n=99, r=0.360, P<0.0001) and reduction in PCWP from admission to the day of pulmonary artery catheter removal (n=92, r=0.242, P=0.02). ConclusionAdmission-to-discharge BNP reduction is a reasonable marker of treatment response in HF that correlated with clinical and objective markers of decongestion.

Effectiveness of aquatic exercise on reduction B-type natriuretic peptide values in postmenopausal hypertensive women: a randomized clinical trial

To compare the responses of aquatic exercise with dry land training and control inactive group on B-type natriuretic peptide and plasma renin activity levels in postmenopausal hypertensive women. Forty postmenopausal hypertensive women were randomly assigned to 3 groups: water group, dry land group and a non-intervention control group. The exercises programs consisted of consisted of 50-min sessions, three-times a week and was performed for 12 weeks. Samples of B-type natriuretic peptide and plasma renin activity levels were collected pre- and post-intervention. In the dry land exercise program, heart rate was maintained at around 50–60 % of the heart rate reserve, deducting 17 heart beats for aquatic exercise. There was a statistically significant reduction in B-type natriuretic peptide in the water group (37 ± 11.1 ng/L) to (22 ± 9.4 ng/L), pre and post intervention, respectively. There was no difference in plasma renin activity levels between groups and moments. This study demonstrated the effectiveness of aquatic exercise in reducing B-type natriuretic peptide values in postmenopausal hypertensive women. Plasma renin activity levels values were not influenced by either of the interventions.

Comprehensive biomarker profiling in patients with obstructive sleep apnea

ObjectivesThe pathophysiological links between obstructive sleep apnea syndrome (OSAS) and cardiovascular mortality are incompletely understood. We aimed to contribute to a better characterization by using comprehensive biomarker profiling quantifying hemodynamic cardiac stress, cardiomyocyte injury, inflammation, endothelial function, matrix turnover and metabolism. Design and methodsIn 65 patients with moderate or severe OSAS [apnea–hypopnea index (AHI) 39±20/h] and 33 patients with no or mild OSAS (AHI 8+4/h), B-type natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and insulin were measured before and after sleep. In a subgroup measurements were repeated in a second night with continuous positive airway pressure (CPAP). ResultsPatients with moderate/severe OSAS had higher insulin before sleep [median (interquartile range), 36.4 (21.9–52.1) vs. 20.8 (10.6–32.8)mU/mL; p=0.006], higher IL-6 after sleep [1.00 (0.73–1.58) vs. 0.72 (0.48–0.94)pg/mL; p=0.005], and larger relative overnight reduction in BNP [−9 (−35–0) vs. −3 (−21–13)%; p=0.04] than those with mild/no OSAS. Insulin before sleep was the only independent predictor of moderate/severe OSAS. Insulin before and IL-6 after sleep were independent predictors of severe OSAS, and when combined provided high diagnostic accuracy for severe OSAS (area under the receiver operator characteristic curve 0.80; 95%-confidence interval 0.69–0.91). In contrast, there were no significant differences in NT-proBNP, hs-cTnI, VEGF, and MMP-9 between moderate/severe and mild/no OSAS. Short-term CPAP had no impact on biomarker concentrations before and after sleep. ConclusionsSignificant OSAS is characterized by a distinct biomarker profile including high insulin before and high IL-6 after sleep.

Does B-type natriuretic peptide-guided therapy improve outcomes in patients with chronic heart failure? A systematic review and meta-analysis of randomized controlled trials.

The role of B-type natriuretic peptide (BNP) in the management of patients with chronic heart failure (CHF) was uncertain. The aim of this meta-analysis was to comprehensively evaluate the effect of BNP-guided therapy in CHF. Relevant randomized controlled trials were identified by searching of Pubmed, Embase and the Cochrane Library databases. Fixed or randomized effect models were applied to combine the data according to the heterogeneity of the included studies. Fourteen studies with 3,004 CHF patients were included. Results of our meta-analyses suggested that compared with clinical group, BNP-guided treatment significantly decreased the risk of heart failure-related hospitalization (RR 0.79, 95 % CI 0.63-0.98, p = 0.03), although did not significantly affect the risk of all-cause mortality (RR 0.94, 95 % CI 0.81-1.08, p = 0.39) or all-cause hospitalization (RR 0.97, 95 % CI 0.89-1.07, p = 0.56). Furthermore, between-group BNP changes seemed to be a significant modifier to the effects of BNP-guided therapy on clinical outcomes, and BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. In addition, BNP-guided therapy was not associated with increased risk for serious adverse events. BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved. BNP-guided therapy seemed to be safe and promising for CHF patients, and future studies with well-designed BNP-guided medication up-titration strategies are needed to confirm these results.

Changes of Natriuretic Peptides Predict Hospital Admissions in Patients With Chronic Heart Failure: A Meta-Analysis

The goal of this study was to explore the association between changes in B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels and risk of hospital admission for heart failure (HF) worsening in patients with chronic HF. The relationship between BNP and NT-proBNP plasma levels and risk of cardiovascular events in patients with chronic HF has been previously demonstrated. However, it is unclear whether changes in BNP and NT-proBNP levels predict morbidity in patients with chronic HF. The MEDLINE, Cochrane, ISI Web of Science, and SCOPUS databases were searched for papers about HF treatment up to August 2013. Randomized trials enrolling patients with systolic HF, assessing BNP and/or NT-proBNP at baseline and at end of follow-up, and reporting hospital stay for HF were included in the analysis. Meta-regression analysis was performed to test the relationship between BNP and NT-proBNP changes and the clinical endpoint. Sensitivity analysis was performed to assess the influence of baseline variables on results. Egger's linear regression was used to assess publication bias. Nineteen trials enrolling 12,891 participants were included. The median follow-up was 9.5 months (interquartile range: 6 to 18 months), and 22% of patients were women. Active treatments significantly reduced the risk of hospital stay for HF worsening. In meta-regression analysis, changes in BNP and NT-proBNP were significantly associated with risk of hospital stay for HF worsening. Results were confirmed by using sensitivity analysis. No publication bias was detected. In patients with HF, reduction of BNP or NT-proBNP levels was associated with reduced risk of hospital stay for HF worsening.

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial.

IntroductionIntravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.MethodsSubjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.ResultsA total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).ConclusionsIn the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months.Trial registrationClinicalTrials.gov NCT01441245. Registered 23 September 2011.