Effects of Atrial Fibrillation on Heart Failure Outcomes and NT-proBNP Levels in the GUIDE-IT Trial.
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ABSTRACT: Objective
To evaluate effects of atrial fibrillation (AF) on cardiac biomarkers and outcomes in a trial population of patients with heart failure (HF) with reduced ejection fraction treated with optimal guideline-directed medical therapy.Methods
We performed a secondary analysis of 894 patients in the Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial (January 2013-July 2016). Patients were stratified by AF status and compared with regard to guideline-directed medical therapy use, longitudinal levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), and outcomes including HF hospitalization and mortality.Results
After adjustment, AF was associated with a significant increase in the risk of HF hospitalization or cardiovascular death (hazard ratio, 1.28; 95% CI, 1.02 to 1.61; P=0.04) and HF hospitalization (hazard ratio, 1.31; 95% CI, 1.02 to 1.68; P=.03) but with no difference in mortality during a median 15 months of follow-up. There were no significant differences in medication treatment between those with and those without AF. At 90 days, a higher proportion of patients with AF (89.4% vs 81.5%; P=.002) had an NT-proBNP level above 1000 pg/mL (to convert NT-proBNP values to pmol/L, multiply by 0.1182), and AF patients had higher NT-proBNP levels at all time points through 2 years of follow-up.Conclusion
Among patients with HF with reduced ejection fraction, prevalent AF was associated with higher NT-proBNP concentrations through 2 years of follow-up and higher risk for HF hospitalization despite no substantial differences in medical therapy.
SUBMITTER: Chouairi F
PROVIDER: S-EPMC8105522 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR). METHODS:In a post hoc analysis of the index cohort of BIOSTAT-CHF (n = 2516), we studied patients with HF categorized into three groups: (1) AF at baseline (n = 733), (2) SR at baseline with a history of AF (n = 183), and (3) SR at baseline and no history of AF (n = 1025). The findings were validated in the validation cohort of BIOSTAT-CHF (n = 1738). RESULTS:Plasma NT-proBNP levels of patients who had AF at baseline were higher than those of patients in SR (both with and without a history of AF), even after multivariable adjustment (3417 [25th-75th percentile 1897-6486] versus 1788 [682-3870], adjusted p < 0.001, versus 2231 pg/mL [902-5270], adjusted p < 0.001). In contrast, after adjusting for clinical confounders, the levels of GDF-15 were comparable between the three groups (3179 [2062-5253] versus 2545 [1686-4337], adjusted p = 0.36, versus 2294 [1471-3855] pg/mL, adjusted p = 0.08). Similar patterns of both NT-proBNP and GDF-15 were found in the validation cohort. CONCLUSION:These data show that in patients with HF, NT-proBNP is significantly influenced by underlying AF at time of measurement and not by previous episodes of AF, whereas the levels of GDF-15 are not influenced by the presence of AF. Therefore, GDF-15 might have additive value combined with NT-proBNP in the assessment of patients with HF and concomitant AF.
| S-EPMC7042190 | biostudies-literature
Project description:AimsHeart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). It is known that AF impairs the diagnostic accuracy of NT-proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT-proBNP for HF and AF in stable outpatients with cardiovascular risk factors.Methods and resultsData were obtained from the DIAST-CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population-based cohorts using the same inclusion/exclusion criteria: LIFE-Adult (n = 2869), SHIP (n = 2013), and SHIP-TREND (n = 2408). Serum levels of NT-proBNP were taken once at baseline. The DIAST-CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT-proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT-proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P < 0.001) and compared with those with only HF [n = 201; 158 (66;363) pg/mL; P < 0.001]. The highest levels of NT-proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF (n = 58; P < 0.001 vs. control and vs. HF, P = 1.0 vs. AF). In patients with AF, NT-proBNP levels did not differ between those with HF and preserved ejection fraction (EF) > 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver-operating characteristic curves of NT-proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79-0.88]) and for HF with EF < 50% (0.78 [0.72-0.85]; P = 0.18). The AUC for HF with EF > 50% was significantly lower (0.61 [0.56-0.65]) than for AF (P = 0.001). During follow-up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT-proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75-0.83]) than of newly diagnosed HF (0.59 [0.55-0.63]; P < 0.001). Data were validated in three independent population-based cohorts (LIFE-Adult, n = 2869; SHIP, n = 2013; and SHIP-TREND, n = 2408).ConclusionsIn stable outpatients, NT-proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT-proBNP for HF with EF > 50% is very limited.
| S-EPMC8788004 | biostudies-literature
Project description:N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a versatile biomarker, that has been extensively studied in large cohorts of individuals in the general population, in subjects at risk for developing left ventricular dysfunction and cardiovascular events, and in patients with chronic or acutely decompensated heart failure (HF). In this paper, the pros and cons of using natriuretic peptide testing to manage patients with HF are presented and discussed over 3 broad areas: (1) dyspnea triage in the emergency room, (2) natriuretic peptide-guided treatment of chronic HF, and (3) management of patients with HF in primary care and nursing homes.
| S-EPMC4975180 | biostudies-literature
Project description:Background Obese patients have lower NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The prognostic implications of achieving NT-proBNP levels ≤1000 pg/mL in obese patients with heart failure (HF) receiving biomarker-guided therapy are not completely known. We evaluated the prognostic implications of obesity and having NT-proBNP levels (≤1000 pg/mL) in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial participants. Methods and Results The risk of adverse cardiovascular events (HF hospitalization or cardiovascular mortality) was assessed using multivariable-adjusted Cox proportional hazard models based on having NT-proBNP ≤1000 pg/mL (taken as a time-varying covariate), stratified by obesity status. The study outcome was also assessed on the basis of the body mass index at baseline. The predictive ability of NT-proBNP for adverse cardiovascular events was assessed using the likelihood ratio test. Compared with nonobese patients, obese patients were mostly younger, Black race, and more likely to be women. NT-proBNP levels were 59.0% (95% CI, 39.5%-83.5%) lower among obese individuals. The risk of adverse cardiovascular events was lower in obese (hazard ratio [HR], 0.48; 95% CI, 0.29-0.59) and nonobese (HR, 0.32; 95% CI, 0.19-0.57) patients with HF who had NT-proBNP levels ≤1000 pg/mL, compared with those who did not. There was no interaction between obesity and having NT-proBNP ≤1000 pg/mL on the study outcome (P>0.10). Obese patients had a greater risk of developing adverse cardiovascular events (HR, 1.39; 95% CI, 1.01-1.90) compared with nonobese patients. NT-proBNP was the strongest predictor of adverse cardiovascular event risk in both obese and nonobese patients. Conclusions On-treatment NT-proBNP level ≤1000 pg/mL has favorable prognostic implications, irrespective of obesity status. NT-proBNP levels were the strongest predictor of cardiovascular events in both obese and nonobese individuals in this trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.
| S-EPMC8174357 | biostudies-literature
Project description:Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02358-y.
| S-EPMC8603582 | biostudies-literature
Project description:The prevalence and prognostic value of chronic heart failure (CHF) in the setting of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has seldom been studied. The aim of this study was to analyze the prevalence and prognosis of CHF in this setting. This single-center study included 829 consecutive patients with SARS-CoV-2 infection from February to April 2020. Patients with a previous history of CHF were matched 1:2 for age and sex. We analyze the prognostic value of pre-existing CHF. Prognostic implications of N terminal pro brain natriuretic peptide (NT-proBNP) levels on admission in the CHF cohort were explored. A total of 129 patients (43 CHF and 86 non-CHF) where finally included. All-cause mortality was higher in CHF patients compared to non-CHF patients (51.2% vs. 29.1%, p = 0.014). CHF was independently associated with 30-day mortality (hazard ratio (HR) 2.3, confidence interval (CI) 95%: 1.26-2.4). Patients with CHF and high-sensitivity troponin T < 14 ng/L showed excellent prognosis. An NT-proBNP level > 2598 pg/mL on admission was associated with higher 30-day mortality in patients with CHF. All-cause mortality in CHF patients hospitalized due to SARS-CoV-2 infection was 51.2%. CHF was independently associated with all-cause mortality (HR 2.3, CI 95% 1.26-4.2). NT-proBNP levels could be used for stratification risk purposes to guide medical decisions if larger studies confirm this finding.
| S-EPMC7829899 | biostudies-literature
Project description:AimsWe examined the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients admitted for coronavirus disease 2019 (COVID-19) without prior history of heart failure (HF) or cardiomyopathy.Methods and resultsRetrospective cohort of consecutive adults (N = 679; median age 59 years; 38.7% women; 87.5% White; 7.1% Black; 5.4% Asian; 34.3% Hispanic) admitted with documented COVID-19 in an academic centre in Long Island, NY. Admission NT-proBNP was categorized using the European Society of Cardiology Heart Failure Association age-specific criteria for acute presentations. We examined (i) mortality and the composite of death or mechanical ventilation and (ii) out-of-hospital, intensive care unit (ICU)-free, and ventilator-free days at 28 days. Estimates were adjusted for confounders using a lasso selection process. Using age-specific criteria, 417 patients (61.4%) had low, 141 (20.8%) borderline, and 121 (17.8%) high NT-proBNP. Mortality was 5.8%, 20.6%, and 36.4% for patients with low, borderline, and high NT-proBNP, respectively. In lasso-adjusted models, high NT-proBNP was associated with higher mortality [hazard ratio (HR) 2.15; 95% confidence interval (CI) 1.06-4.39; P = 0.034] and composite endpoint rates (HR 1.66; 95%CI 1.04-2.66; P = 0.035). Patients with high NT-proBNP had 32%, 33%, and 33% fewer out-of-hospital, ICU-free, and ventilator-free days compared with low NT-proBNP counterparts. Results were consistent across age, sex, and race, and regardless of coronary artery disease or hypertension, except for stronger mortality signal with high NT-proBNP in women.ConclusionsIn patients with COVID-19 and no HF history, high admission NT-proBNP is associated with higher mortality and healthcare resources utilization. Preventive strategies may be required for these patients.
| S-EPMC8426942 | biostudies-literature
Project description:This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin-3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)-21, -29a, -133a, -146b and -328. Comprehensive transthoracic echocardiography was performed in all participants. Biomarkers were significantly altered in patients with AF. The echocardiographic parameter septal PA-TDI, indicating left atrial (LA) remodelling, correlated with concentrations of sST2 (r = 0.249, p = 0.048), miR-21 (r = -0.277, p = 0.012), miR-29a (r = -0.269, p = 0.015), miR-146b (r = -0.319, p = 0.004) and miR-328 (r = -0.296, p = 0.008). In particular, NT-proBNP showed a strong correlation with echocardiographic markers of LA remodelling and dysfunction (septal PA-TDI: r = 0.444, p < 0.001, LAVI/a': r = 0.457, p = 0.001, SRa: r = 0.581, p < 0.001). Multivariate Cox regressions analysis highlighted miR-21 and NT-proBNP as predictive markers for AF (miR-21: hazard ratio (HR) 0.16; 95% confidence interval (CI) 0.04-0.7, p = 0.009; NT-proBNP: HR 1.002 95%CI 1.001-1.004, p = 0.006). Combination of NT-proBNP and miR-21 had the best accuracy to discriminate patients with AF from those without AF (area under the curve (AUC)= 0.843). Our findings indicate that miR-21 and NT-proBNP correlate with echocardiographic parameters of atrial remodeling and predict AF, in particular if combined.
| S-EPMC7230176 | biostudies-literature
Project description:BackgroundThis study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide).MethodsPatients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as </≥ 600 pg/ml in patients with sinus rhythm and </≥ 900 pg/ml in patients with AF. The primary composite endpoint was a 7-year risk of cardiovascular death or HF admission.ResultsIn the HFrEF cohort, 704 patients had high NT-proBNP (median age, 73; mean left ventricular ejection fraction (LVEF), 33%). 416 patients had low NT-proBNP (median age, 65; LVEF, 30%). Patients from both groups were in NYHA class I-III. The primary endpoint occurred in 531 patients (75.4%) with HFrEF and elevated NT-proBNP, and 748 controls (21.3%) (risk difference, 54.2%; 95% confidence interval (CI) 50.7-57.6%). In comparison, it occurred in 199 patients (47.9%) with HFrEF and without elevated NT-proBNP, and 185 controls (8,9%) (risk difference, 38.9%; 95% CI 34.0-43.9%). Risk differences for all secondary endpoints were significant, except for overall mortality in the low NT-proBNP group (risk difference, 3.8%; 95% CI, -0.4-8.0%).ConclusionThis study identified a significant excess risk in patients with HFrEF across various endpoints, which persisted after stratification into high and low levels of NT-proBNP.
| S-EPMC11368590 | biostudies-literature
Project description:BACKGROUND: Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). METHODS: We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. RESULTS: In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. CONCLUSIONS: FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.
| S-EPMC3653725 | biostudies-literature