Median N-terminal Pro-brain Natriuretic Peptide Research Articles

Prognostic value of RDW alone and in combination with NT-proBNP in patients with heart failure.

BackgroundRed blood cell distribution width (RDW) and N‐terminal pro brain natriuretic peptide (NT‐proBNP) may predict the prognosis of heart failure (HF). However, the impact of combined RDW and NT‐proBNP levels as a prognostic marker of HF remains unclear and the significance of this combination at various time‐points has not been sufficiently studied.HypothesisRDW can predict prognosis in HF at various time‐points and combination with NT‐proBNP improves the prognostic value.MethodsPatients admitted to HF care unit of Fuwai Hospital CAMS&PUMC (Beijing, China) with a diagnosis of HF from November 2008 to November 2018 were analyzed retrospectively.ResultsIn total, 3231 patients with available RDW data at admission were evaluated (median age 58 years, 71.9% males, 39.7% coronary heart disease, 68.6% New York Heart Association [NYHA] III or IV). Median RDW and NT‐proBNP at admission were 13.4% (interquartile range [IQR]: 12.7%–14.5%), and 1723.00 pg/ml (IQR: 754.00–4006.25 pg/ml), respectively. During 2.9‐year median follow‐up, all‐cause death occurred in 1075 (33.27%) patients. Kaplan–Meier survival curve and Cox proportional‐hazard models, showed patients in the top quarter RDW had a 32.0% increased mortality compared to the bottom quarter (hazard ratio: 4.39, 95% confidence interval: 3.59–5.38; p <.001). The top quarter RDW retained independent prognostic value across HF with reduced ejection fraction [HFrEF], HF with mid‐range ejection fraction [HFmrEF], and HF with preserved ejection fraction [HFpEF] subgroups. Patients were subsequently divided into four groups by median RDW and NT‐proBNP. Comparison of Kaplan–Meier survival curves for various groups showed good risk stratification (p < .001).ConclusionsRDW is an independent predictor of mortality among patients with HF in the short‐, medium‐, and long‐term. Combination of RDW and NT‐proBNP improves the prognostic value. This is true across all clinical subtypes of heart failure (HFrEF, HFmrEF, HFpEF), and among most subgroups of patients with various comorbidities (infection, diabetes, hypertension).

Performance of the Abbott Architect Immuno-Chemiluminometric NT-proBNP Assay.

Background: We evaluated the performance of the Abbott N-terminal pro-brain natriuretic peptide (NT-proBNP) assay against the Roche NT-proBNP immunoassay across two sites. Methods: Precision, linearity, and sensitivity studies were performed. A combined method of comparison and regression analysis was performed between the Roche and Abbott assays using samples from both sites (n = 494). To verify biotin interference, lyophilised biotin powder was reconstituted and spiked into serum samples at two medical decision levels (final concentration 500/4250 ng/mL) and compared to controls. NT-proBNP was also measured in anonymised leftover sera (n = 388) in a cardio-renal healthy population and stratified into three age bands—<50 (n = 145), 50–75 (n = 183) and >75 (n = 60). Results: Between-run precision (CV%) for NT-proBNP was 4.17/4.50 (139.5/142.0 pg/mL), 3.83/2.17 (521.6/506.3), and 4.60/2.51 (5053/4973), respectively. The assay was linear from 0.7–41,501 pg/mL. The limit of blank/quantitation was 1.2/7.9 pg/mL. The assay showed no interference from biotin up to 4250 ng/mL. Passing–Bablok regression analysis showed excellent agreement between the two assays (r = 0.999, 95% CI 0.999 to 0.999, p < 0.0001). The Roche assay had a slightly persistent, negative bias across different levels of NT-proBNP. ESC age cut-offs for diagnosing acute heart failure are applicable for the Abbott assay, with the median NT-proBNP of subjects < 50 years old at 43.0 pg/mL (range 4.9–456 pg/mL), 50–75 years old at 95.1 pg/mL (range 10.5–1079 pg/mL), and >75 years old at 173.1 pg/mL (range 23.2–1948 pg/mL). Conclusions: The Abbott Architect NT-proBNP assay has good performance that agrees with the manufacturer’s specifications. ESC/AHA recommended NT-proBNP age groups for acute heart failure diagnosis are applicable to this assay.

Sex-based differences in remote monitoring of biometric, psychometric and biomarker indices in stable ischemic heart disease

BackgroundSex-based differences are crucial to consider in the formulation of a personalized treatment plan. We evaluated sex-based differences in adherence and remotely monitored biometric, psychometric, and biomarker data among patients with stable ischemic heart disease (IHD).MethodsThe Prediction, Risk, and Evaluation of Major Adverse Cardiac Events (PRE–MACE) study evaluated patients with stable IHD over a 12-week period. We collected biometric and sleep data using remote patient monitoring via FitBit and psychometric data from Patient-Reported Outcomes Measurement Information System (PROMIS), Kansas City Cardiomyopathy (KCC) and Seattle Angina Questionnaire-7 (SAQ-7) questionnaires. Serum biomarker levels were collected at the baseline visit. We explored sex-based differences in demographics, adherence to study protocols, biometric data, sleep, psychometric data, and biomarker levels.ResultsThere were 198 patients enrolled, with mean age 65.5 ± 11 years (± Standard deviation, SD), and 60% were females. Females were less adherent to weekly collection of PROMIS, KCC and SAQ-7 physical limitations questionnaires (all p < 0.05), compared to males. There was no difference in biometric physical activity. There was a statistically significant (p < 0.05) difference in sleep duration between sexes, with females sleeping 6 min longer. However, females reported higher PROMIS sleep disturbance scores (p < 0.001) and poorer psychometric scores overall (p < 0.05). A higher proportion of males had clinically significant elevations of median N-terminal pro-brain natriuretic peptide (p = 0.005) and high-sensitivity cardiac troponin levels (p < 0.001) compared to females.ConclusionsAmong females and males with stable IHD, there are sex-based differences in remote monitoring behavior and data. Females are less adherent to psychometric data collection and report poorer psychometric and sleep quality scores than males. Elevated levels of biomarkers for MACE are more common in males. These findings may improve sex-specific understanding of IHD using remote patient monitoring.

Effect Of Saxagliptin On LV Structure And Function In Patients With Type 2 Diabetes And Heart Failure: Results Of Measure-HF

Introduction Further investigation was suggested by the SAVOR-TIMI 53 results regarding the risk of hospitalisation for heart failure (HF) and the dipeptidyl-peptidase 4 inhibitor saxagliptin (SAXA), especially for high-risk patients with type 2 diabetes (T2D) and established HF with reduced ejection fraction (HFrEF). The Measure-HF Trial investigated the effect of SAXA on left ventricular (LV) structure, function and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with T2D and established symptomatic heart failure with LV ejection fraction (LVEF) &lt 45% (HFrEF) and NT-proBNP &gt 300 pg/mL. Methods Patients were randomised to SAXA (n=112), sitagliptin (SITA, n=115) or placebo (PBO, n=121) plus usual care for 24 weeks. Primary endpoint was change from baseline in LV end diastolic volume index (LVEDVi) measured by MRI (core laboratory). Secondary endpoints included changes in LV end systolic volume index (LVESVi), LVEF, LV mass, and NT-proBNP levels. Worsening HF events were adjudicated. Exploratory analyses also evaluated the same endpoints for SITA vs PBO. Results Mean age was 65.4 years, 68.9% male, mean LVEF 37.3%, and median NT-proBNP 941 pg/mL. Primary and secondary endpoints demonstrated no difference between SAXA vs PBO (Table). There was no significant difference in the change in NT-proBNP levels between SAXA and PBO groups. The changes in endpoints for SITA were consistent with those of SAXA. Adjudicated HF events were balanced: SAXA (5), SITA (3) and PBO (6). Conclusions In patients with T2D and HFrEF, SAXA compared with PBO produced no unfavorable effects on LV structure, function or natriuretic peptide levels. Further investigation was suggested by the SAVOR-TIMI 53 results regarding the risk of hospitalisation for heart failure (HF) and the dipeptidyl-peptidase 4 inhibitor saxagliptin (SAXA), especially for high-risk patients with type 2 diabetes (T2D) and established HF with reduced ejection fraction (HFrEF). The Measure-HF Trial investigated the effect of SAXA on left ventricular (LV) structure, function and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with T2D and established symptomatic heart failure with LV ejection fraction (LVEF) &lt 45% (HFrEF) and NT-proBNP &gt 300 pg/mL. Patients were randomised to SAXA (n=112), sitagliptin (SITA, n=115) or placebo (PBO, n=121) plus usual care for 24 weeks. Primary endpoint was change from baseline in LV end diastolic volume index (LVEDVi) measured by MRI (core laboratory). Secondary endpoints included changes in LV end systolic volume index (LVESVi), LVEF, LV mass, and NT-proBNP levels. Worsening HF events were adjudicated. Exploratory analyses also evaluated the same endpoints for SITA vs PBO. Mean age was 65.4 years, 68.9% male, mean LVEF 37.3%, and median NT-proBNP 941 pg/mL. Primary and secondary endpoints demonstrated no difference between SAXA vs PBO (Table). There was no significant difference in the change in NT-proBNP levels between SAXA and PBO groups. The changes in endpoints for SITA were consistent with those of SAXA. Adjudicated HF events were balanced: SAXA (5), SITA (3) and PBO (6). In patients with T2D and HFrEF, SAXA compared with PBO produced no unfavorable effects on LV structure, function or natriuretic peptide levels.

Impact of pregnancy in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension: case series and literature review

ObjectiveThis study aimed to investigate the clinical characteristics and outcomes of pregnancy complicated by SLE-associated pulmonary arterial hypertension (SLE-PAH) in a case series and literature review.MethodsThis single-centre retrospective study included...

Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction

There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. ClinicalTrials.gov Identifier: NCT03066804.

Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction

The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. ClinicalTrials.gov Identifier: NCT02816736.

Prognostic value of NT-proBNP for myocardial recovery in peripartum cardiomyopathy (PPCM)

IntroductionPeripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function.MethodsKnowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF).ResultsThis study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2–1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05–0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04–0.89], p = 0.035) at follow-up.ConclusionsWe have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

NT‐proBNP levels and cardiopulmonary function in children with sickle cell disease

Patients with sickle cell disease (SCD) are living longer and subsequently more apt to develop cardiopulmonary dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels have been used in adults with SCD to assess for pulmonary hypertension and mortality. While the incidence of PH is low in pediatrics, it is reasonable to presume that NT-proBNP levels can be used to assess risk for the development of cardiopulmonary morbidity. We hypothesized that NT-proBNP levels would be increased in patients with SCD compared to age-adjusted healthy children; additionally, these levels would be associated with labs indicative of hemolysis and would demonstrate evidence of obstructive lung disease and cardiac dysfunction. We retrospectively evaluated patients with SCD, 8-18 years old, at a large, tertiary care children's hospital. NT-proBNP levels were assessed in correlation with hemolytic lab work, spirometry, and echocardiographic data. The age group 8-14 years old, 75% of our cohort's population, had a median NT-proBNP of 70 pg/ml, greater than their age-adjusted counterparts (52 pg/ml). NT-proBNP levels were associated with an increased degree of hemolysis when compared with hemoglobin (Hb) (r = -0.43, p < .0001), reticulocyte count (r = .25, p = .01) and lactate dehydrogenase levels (r = .47, p < .0001). An inverse trend was found between NT-proBNP and spirometric data. Finally, a positive correlation was found between NT-proBNP and diastolic left ventricular size (r = .28, p = .047]. The correlations found suggest that NT-proBNP may be used prospectively to identify patients with SCD at increased risk for the development of cardiopulmonary dysfunction.

Reference values for N-terminal Pro-brain natriuretic peptide in premature infants during their first weeks of life

The aim of our study was to observe the temporal distribution of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants of ≤ 31 weeks of gestational age (GA) during the first weeks of life. NT-proBNP values of 118 preterm infants born ≤ 31 weeks GA were determined during the first week of life, after 4 ± 1 weeks of life, and at a corrected GA of 36 ± 2 weeks. Infants were divided into two groups: those without relevant complications and those with complications related to prematurity. NT-proBNP values of infants without complications define our exploratory reference values. The Median NT-proBNP level of these infants was 1896 ng/l (n = 27, interquartile range (IQR): 1277–5200) during the first week of life, 463 ng/l (n = 26, IQR: 364–704) at 4 ± 1 weeks of life, and 824 ng/l (n = 33, IQR: 714–1233) at a corrected GA of 36 ± 2 weeks. Infants born < 28 + 0 weeks GA had significantly higher NT-proBNP values (n = 9, median: 5200, IQR: 1750–8972) than infants born ≥ 28 + 0–31 weeks GA (n = 18, median: 1528, IQR: 838–3052; p = 0.017). Growth restriction or PDA status could not account for the difference in NT-proBNP values between GA groups.Conclusions: The results of our observational and cross-sectional study describe exploratory reference values for NT-proBNP levels in preterm infants of ≤ 31 weeks GA according to postnatal age. NT-proBNP levels during the first week of life are high and widely distributed in preterm infants and decrease subsequently to reach a distinctly lower and stable plateau at around 1 month of life. Our results suggest an influence of GA on NT-proBNP values in the first week of life.What is Known:• Several complications related to prematurity, e.g., hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been associated with a temporary rise in NT-proBNP values in preterm infants during their first weeks of life.What is New:• This observational study provides reference values for NT-proBNP levels of very and extremely preterm infants during their first weeks of life.• In premature infants without complications, NT-proBNP values during their first week of life depend on gestational age at birth.

Natriuretic peptide as a predictor of adverse renal outcomes in patients with acute kidney injury

Abstract Background Since cardiorenal syndrome has been increasingly recognised as the intense interaction between the heart and the kidneys, we hypothesised that in patients with acute kidney injury (AKI), a biomarker of cardiovascular stress and heart failure (HF), N-terminal pro-brain natriuretic peptide (NT-proBNP), can predict adverse renal outcomes. Purpose The purpose of this study was to investigate the ability of NT-proBNP to predict need for dialysis and dialysis dependence in patients with AKI. Methods We analysed the association between baseline NT-proBNP measured before renal consultation, and need for dialysis and dialysis dependence, using a cohort of 1,052 AKI patients admitted to the Cleveland Clinic between 2011 and 2016. AKI was defined as acute increase in serum creatinine (Cr) of at least 0.3 mg/dL or 50% from baseline. Dialysis dependence was defined as patients still need dialysis within 72 hours of discharge. Results Mean age was 65.8±13.6 years, 57% were male, 45.4% had chronic HF and 28.2% had chronic kidney disease (CKD). There was no significant difference in chronic HF, CKD, or baseline Cr between AKI patients with and without dialysis. Median NT-proBNP was 6,484.50 pg/mL (interquartile range 2,200.75–15,717.50 pg/mL). We observed that 43.1% had dialysis (among them 67.8% became dialysis dependence). After adjustment for age, gender, hypertension, and baseline Cr, higher NT-proBNP levels were associated with greater likelihood of needing dialysis [quartile (Q) 4 vs. 1, Odd ratio (OR) 1.98, 95% confidence interval (CI) 1.38–2.85, P&amp;lt;0.001] and dialysis dependence (Q 4 vs. 1, OR 2.63, 95% CI 1.41–4.9, P=0.002) (Figure 1). Conclusion Elevated NT-proBNP was independently associated with need for dialysis and dialysis dependence in patients with AKI. Figure 1 Funding Acknowledgement Type of funding source: None

The integrated role of NT-pro BNP and STE-GLS for the early detection of chemotherapy-induced cardiotoxicity

Abstract Background Chemotherapeutic agents, used for the treatment of breast cancer, have many side effects, among them is cardiomyopathy. Ejection fraction (EF) is fails to detect the subtle alterations of left ventricular (LV) function. There comes the need for a more sensitive tool for the detection of preclinical chemotherapy-induced cardiomyopathy. Aim Detection of subclinical LV systolic dysfunction in breast cancer patients after 6 weeks of the initiation of their chemotherapeutic treatment, using N-terminal pro brain natriuretic peptide (NT-proBNP) plasma level as well as Speckle tracking echo-global longitudinal strain (STE-GLS). Methods Seventy-four asymptomatic, non-metastasizing breast cancer female patients were included. They were assessed before taking their first chemotherapeutic session and 6 weeks thereafter. Assessment included baseline clinical characteristics, conventional two-dimensional (2D) as well as three-dimensional (3D) echocardiography. Loops of different apical views were recorded for later offline STE-GLS analysis. Blood samples for NT-BNP plasma level were collected before and 6 weeks after the initiation of chemotherapy. Samples were later analyzed using a Sandwich ELISA technique. Results The median NT-proBNP almost doubled after 6 weeks of chemotherapy (73.50 vs 34.4 pg/L, p value &amp;lt;0.001). One patient died before her scheduled follow up visit, and the cause of death is unknown. Fifty patients showed NT-proBNP elevation at their follow up, compared to the baseline visit, 22 (44%) of them had worse (less negative) LV-GLS in their follow up visit. Five patients had an abnormally elevated NT-proBNP plasma level, all of them had a worse follow up LV-GLS. Only two patients showed significant reduction of LVEF &amp;gt;10% to less &amp;lt;53% (chemotherapy-induced cardiotoxicity) but their NT-proBNP did not exceed the cutoff limit. Conclusion The integration of LV-GLS and NT-proBNP is useful in the diagnosis of subclinical, subtle chemotherapy-induced cardiotoxicity. Early detection will prompt early cardioprotective measures and thus helps improving the clinical outcomes. Funding Acknowledgement Type of funding source: None

Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction

Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life. To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019. Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1. The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks. Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was -1.5 (95% CI, -5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was -0.5 (95% CI, -4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively. Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ. ClinicalTrials.gov Identifier: NCT03547583.

N-terminal pro-brain natriuretic peptide serum levels reflect attrition of the Fontan circulation.

N-terminal pro-brain natriuretic peptide has an established role in the diagnosis and prognosis of heart failure. In Fontan patients, this peptide is often increased, but its diagnostic value in this particular non-physiologic, univentricular circulation is unclear. We investigated whether N-terminal pro-brain natriuretic peptide represents ventricular function or other key variables in Fontan patients. Ninety-five consecutive Fontan patients ≥10 years old who attended the outpatient clinic of the Center for Congenital Heart Diseases in 2012-2013 were included. Time since Fontan completion was 16 ± 9 years. Median N-terminal pro-brain natriuretic peptide was 114 (61-264) ng/l and was higher than gender-and age-dependent normal values in 54% of the patients. Peptide Z-scores were higher in patients in NYHA class III/IV compared to those in class I/II, but did not correlate with ventricular function assessed by MRI and echocardiography, nor with peak exercise capacity. Instead, peptide Z-scores significantly correlated with follow-up duration after Fontan completion (p < 0.001), right ventricular morphology (p = 0.004), indexed ventricular mass (p = 0.001), and inferior caval vein diameter (p < 0.001) (adjusted R2 = 0.615). N-terminal pro-brain natriuretic peptide levels in Fontan patients correlate with functional class, but do not necessarily indicate ventricular dysfunction. Increased peptide levels were associated with a longer existence of the Fontan circulation, morphologic ventricular characteristics, and signs of increased systemic venous congestion. Since the latter are known to be key determinants of the performance of the Fontan circulation, these findings suggest increase in N-terminal pro-brain natriuretic peptide levels to indicate attrition of the Fontan circulation, independent of ventricular function.

Significance of NT-proBNP and High-sensitivity Troponin in Friedreich Ataxia.

Background: Friedreich’s ataxia (FA) is a rare autosomal recessive mitochondrial disease resulting of a triplet repeat expansion guanine-adenine-adenine (GAA) in the frataxin (FXN) gene, exhibiting progressive cerebellar ataxia, diabetes and cardiomyopathy. We aimed to determine the relationship between cardiac biomarkers, serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and serum cardiac high-sensitivity troponin (hsTnT) concentrations, and the extent of genetic abnormality and cardiac parameters. Methods: Between 2013 and 2015, 85 consecutive genetically confirmed FA adult patients were prospectively evaluated by measuring plasma hsTnT and NT-proBNP concentrations, electrocardiogram, and echocardiography. Results: The 85 FA patients (49% women) with a mean age of 39 ± 12 years, a mean disease onset of 17 ± 11 years had a mean SARA (Scale for the Assessment and Rating of Ataxia) score of 26 ± 10. The median hsTnT concentration was 10 ng/L (3 to 85 ng/L) and 34% had a significant elevated hsTnT ≥ 14 ng/L. Increased septal wall thickness was associated with increased hsTnT plasma levels (p < 0.001). The median NT-proBNP concentration was 31 ng/L (5 to 775 ng/L) and 14% had significant elevated NT-proBNP ≥ 125 ng/L. Markers of increased left ventricular filling pressure (trans mitral E/A and lateral E/E’ ratio) were associated with increased NT-proBNP plasma levels (p = 0.01 and p = 0.01). Length of GAA or the SARA score were not associated with hsTnT or NT-proBNP plasma levels. Conclusion: hsTnT was increased in 1/3 of the adult FA and associated with increased septal wall thickness. Increased NT-proBNP remained a marker of increased left ventricular filling pressure. This could be used to identify patients that should undergo a closer cardiac surveillance.

Relationship between NT-pro Brain Natriuretic Peptide and Filling Pressures in Ambulatory Patients with Left Ventricular Assist Devices and Accuracy to Detect Need for Optimization

We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP) can serve as a noninvasive marker of filling pressures in ambulatory patients with continuous flow left ventricular assist devices. We retrospectively identified patients who had an outpatient right heart catheterization and NT-proBNP performed the same day between 01/01/2012 and 12/18/2018 at our institution. We evaluated the correlations between NT- proBNP and right atrial pressure (RA), pulmonary artery pressure (PA) and pulmonary capillary wedge pressure (PCWP). The best cut off for NT-proBNP to predict patients that were hemodynamically optimized (CVP<15 and PCWP<18) was derived as the value that minimized the square of the difference between sensitivity and specificity RESULTS: A total of 40 patients were included in the study, Patients characteristics are shown in Table 1. The median NT-proBNP was 1114 pg/mL(IQR 553-2056). The correlations between NT-proBNP and RA (r = 0.58;p<0.001; Coefficient of variation (CV) = 37%); PA(r = 0.34;p=0.03; CV = 26%) and PCWP (r = 0.45;p=0.004; CV = 32%) are shown in figure 1 panels A, B and C respectively. NT-proBNP ≥1168 pg/mL had a 60 %sensitivity and 61% specificity in identifying non-optimum hemodynamics.(Figure 1 panel D). NT-proBNP level is elevated in ambulatory patients with continuous flow left ventricular assist devices and has a moderate correlation with filling pressures. The best cutoff value identified to predict need of hemodynamic optimization had low sensitivity and specificity.

Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF).

Inhibition of sodium-glucose co-transporter 2 (SGLT2) reduces the risk of death and heart failure (HF) admissions in patients with chronic HF. However, safety and clinical efficacy of SGLT2 inhibitors in patients with acute decompensated HF are unknown. In this randomized, placebo-controlled, double-blind, parallel group, multicentre pilot study, we randomized 80 acute HF patients with and without diabetes to either empagliflozin 10mg/day or placebo for 30 days. The primary outcomes were change in visual analogue scale (VAS) dyspnoea score, diuretic response (weight change per 40 mg furosemide), change in N-terminal pro brain natriuretic peptide (NT-proBNP), and length of stay. Secondary outcomes included safety and clinical endpoints. Mean age was 76 years, 33% were female, 47% had de novo HF and median NT-proBNP was 5236 pg/mL. No difference was observed in VAS dyspnoea score, diuretic response, length of stay, or change in NT-proBNP between empagliflozin and placebo. Empagliflozin reduced a combined endpoint of in-hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); P=0.014]. Urinary output up until day 4 was significantly greater with empagliflozin vs. placebo [difference 3449 (95% confidence interval 578-6321) mL; P < 0.01]. Empagliflozin was safe, well tolerated, and had no adverse effects on blood pressure or renal function. In patients with acute HF, treatment with empagliflozin had no effect on change in VAS dyspnoea, diuretic response, NT-proBNP, and length of hospital stay, but was safe, increased urinary output and reduced a combined endpoint of worsening HF, rehospitalization for HF or death at 60 days.

N-Terminal Pro-Brain Natriuretic Peptide Levels in Patients Presenting with Acute Breathlessness in Emergency Department

Introduction: Breathlessness is one of the most common symptoms in patients presenting to the emergency department. Differentiating Congestive Heart Failure (CHF) from other causes of dyspnea is of extreme importance. N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels may be valuable for the diagnosis of Heart Failure (HF) in patients with acute breathlessness when used in combination with other clinical information. Aim: To find the utility of NT-proBNP levels in patients presenting with acute breathlessness. Materials and Methods: This cross-sectional study was conducted on 255 patients presenting with acute breathlessness. Details of clinical history, clinical examination, laboratory tests, Electrocardiogram (ECG), X-ray chest, and 2D echocardiogram were collected from each patient. A 5 mL sample of peripheral venous blood was taken from the patients for the quantitative determination of NT-proBNP levels. Mann-Whitney U test was used to compare medians of continuous variables. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and accuracy were determined for NT-proBNP levels. Results: The mean age of the patients was 58.9 years. The median NT-proBNP level was significantly higher in patients who had HF compared to respiratory failure and Hyperventilation Syndrome (HVS). The sensitivity and specificity of NT-proBNP level &gt;450 pg/mL was 76.9% and 90.0%, respectively for patients &lt;50 years of age. The sensitivity and specificity of NT-proBNP level &gt;900 pg/mL was 82.9% and 92.3%, respectively for patients 50-75 years of age. The sensitivity and specificity of NT-proBNP level &gt;1800 pg/mL was 61.5% and 100.0%, respectively for patients &gt;75 years of age. Conclusion: NT-proBNP measurement is a useful biochemical tool for the emergency room physician in the rapid and reliable diagnosis of HF in patients with acute breathlessness.

Echocardiographic Features of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

BackgroundThe PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial tested the efficacy of sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF). Existing data on cardiac structure and function in patients with HFpEF suggest significant heterogeneity. ObjectivesThe aim of this study was to characterize cardiac structure and function, quantify their associations with clinical outcomes, and contextualize these findings with other HFpEF studies. MethodsEchocardiography was performed in 1,097 of 4,822 PARAGON-HF patients within 6 months of enrollment. Associations with incident first heart failure hospitalization or cardiovascular death were assessed using Cox proportional hazards models adjusted for age, sex, region of enrollment, randomized treatment, N-terminal pro–brain natriuretic peptide, and clinical risk factors. ResultsAverage age was 74 ± 8 years, 53% of patients were women, median N-terminal pro–brain natriuretic peptide level was 918 pg/ml (interquartile range: 485 to 1,578 pg/ml), 94% had hypertension, and 35% had atrial fibrillation. The mean left ventricular (LV) ejection fraction was 58.6 ± 9.8%, prevalence of LV hypertrophy was 21%, prevalence of left atrial enlargement was 83%, prevalence of elevated E/e′ ratio was 53%, and prevalence of pulmonary hypertension was 31%. Heart failure hospitalization or cardiovascular death occurred in 288 patients at 2.8-year median follow-up. In fully adjusted models, higher LV mass index (hazard ratio [HR]: 1.05 per 10 g/m2; 95% confidence interval [CI]: 1.00 to 1.10; p = 0.03), E/e′ ratio (HR: 1.04 per unit; 95% CI: 1.02 to 1.06; p < 0.001), pulmonary artery systolic pressure (HR: 1.51 per 10 mm Hg; 95% CI: 1.29 to 1.76; p < 0.001), and right ventricular end-diastolic area (HR: 1.04 per cm2; 95% CI: 1.01 to 1.07; p = 0.003) were each associated with this composite, while LV ejection fraction and left atrial size were not (p > 0.05 for all). Appreciable differences were observed in cardiac structure compared with other HFpEF clinical trials, despite similar E/e′ ratio, pulmonary artery systolic pressure, and event rates. ConclusionsDiastolic dysfunction, left atrial enlargement, and pulmonary hypertension were common in PARAGON-HF. LV hypertrophy, elevated left- and right-sided pressures, and right ventricular enlargement were independently predictive of incident heart failure hospitalization or cardiovascular death. Echocardiographic differences among HFpEF trials despite similar clinical event rates highlight the heterogeneity of this syndrome. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Role of N-Terminal Pro-brain Natriuretic Peptide in the Early Diagnosis of Neonatal Sepsis

Objective Sepsis is one of the most significant contributors to mortality and morbidity in the neonatal population. The need to find specific biomarkers that provide meaningful information about the diagnosis of sepsis is still ongoing. This study aimed to investigate the utility of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a diagnostic biomarker in newborn infants with late-onset sepsis. Methods A prospective, observational study was conducted in the neonatal intensive care unit between July 2016 and January 2017. The patients suspected of having late-onset sepsis and meeting the selection criteria were included in the study, and serial measurements of white blood cell count, serum C-reactive protein (CRP), plasma interleukin (IL) 6, and whole blood NT-proBNP levels were performed. Results The study included 87 patients diagnosed with sepsis and 35 control patients. The median NT-proBNP levels were higher in septic patients (58 [22–169] vs. 14 [7–21]; p &lt; 0.001), showing a significant correlation with CRP and IL-6 levels (r = 0.327, p &lt; 0.01 and r = 0.216, p &lt; 0.05, respectively). The optimal diagnostic cutoff value for differentiating sepsis was 27.5 pg/mL. Predictive parameters of NT-proBNP, such as sensitivity (72%) and specificity (86%), were comparable to those of CRP and IL-6 for the early diagnosis of sepsis in neonates. Conclusion Plasma NT-proBNP levels were higher in septic neonates, and the predictive values were comparable to those of CRP and IL-6. However, these values were not high enough to make it a reliable diagnostic biomarker for identifying neonates in the early stages of sepsis.