From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth.
Burden Christy,Bradley Stephanie,Storey Claire,Ellis Alison,Heazell Alexander E P,Downe Soo,Cacciatore Joanne,Siassakos Dimitrios
BMC pregnancy and childbirth
BACKGROUND:Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our study aimed to systematically review, evaluate and summarise the current evidence regarding the psychosocial impact of stillbirth to parents and their families, with the aim of improving guidance in bereavement care worldwide. METHODS:Systematic review and meta-summary (quantitative aggregation of qualitative findings) of quantitative, qualitative, and mixed-methods studies. All languages and countries were included. RESULTS:Two thousand, six hundred and nineteen abstracts were identified; 144 studies were included. Frequency effect sizes (FES %) were calculated for each theme, as a measure of their prevalence in the literature. Themes ranged from negative psychological symptoms post bereavement (77 · 1) and in subsequent pregnancies (27 · 1), to disenfranchised grief (31 · 2), and incongruent grief (28 · 5), There was also impact on siblings (23 · 6) and on the wider family (2 · 8). They included mixed-feelings about decisions made when the baby died (12 · 5), avoidance of memories (13 · 2), anxiety over other children (7 · 6), chronic pain and fatigue (6 · 9), and a different approach to the use of healthcare services (6 · 9). Some themes were particularly prominent in studies of fathers; grief suppression (avoidance)(18 · 1), employment difficulties, financial debt (5 · 6), and increased substance use (4 · 2). Others found in studies specific to mothers included altered body image (3 · 5) and impact on quality of life (2 · 1). Counter-intuitively, Some themes had mixed connotations. These included parental pride in the baby (5 · 6), motivation for engagement in healthcare improvement (4 · 2) and changed approaches to life and death, self-esteem, and own identity (25 · 7). In studies from low/middle income countries, stigmatisation (13 · 2) and pressure to prioritise or delay conception (9) were especially prevalent. CONCLUSION:Experiencing the birth of a stillborn child is a life-changing event. The focus of the consequences may vary with parent gender and country. Stillbirth can have devastating psychological, physical and social costs, with ongoing effects on interpersonal relationships and subsequently born children. However, parents who experience the tragedy of stillbirth can develop resilience and new life-skills and capacities. Future research should focus on developing interventions that may reduce the psychosocial cost of stillbirth.
10.1186/s12884-016-0800-8
Red blood cell distribution width and 1-year mortality in acute heart failure.
van Kimmenade Roland R J,Mohammed Asim A,Uthamalingam Shanmugam,van der Meer Peter,Felker G Michael,Januzzi James L
European journal of heart failure
AIMS:Red blood cell distribution width (RDW) predicts mortality in chronic heart failure (HF) and stable coronary artery disease. The prognostic value of RDW in more acute settings such as acute HF, and its relative prognostic value compared with more established measures such as N-terminal pro-brain natriuretic peptide (NT-proBNP), remains unknown. METHODS AND RESULTS:In a cohort of 205 patients with acute HF, independent predictors of RDW were identified using linear regression analysis. The association between RDW and 1-year survival in the context of other predictors was assessed using Cox's proportional hazards analysis. Red blood cell distribution width was elevated in 67 (32.7%) patients; RDW was independently associated with haematological variables such as haemoglobin (P < 0.001) as well as the use of loop diuretics (P = 0.006) and beta-blockers (P = 0.015) on presentation, but not with nutritional deficiencies, recent transfusion, or inflammatory variables. Log-transformed RDW values independently predicted mortality in multivariable Cox's proportional hazards analysis (hazards ratio, 1.03; 95% confidence interval, 1.00-1.06; P = 0.04); when stratified on the basis of RDW and NT-proBNP status, the combination provided additional prognostic information. CONCLUSION:Red blood cell distribution width is frequently elevated among patients with acute HF and does not appear to be associated with nutritional status, transfusion history, or inflammation. Red blood cell distribution width independently predicts 1-year mortality in acute HF. The value of RDW appears additive to other established prognostic variables such as NT-proBNP.
10.1093/eurjhf/hfp179
Combination of D-dimer and amino-terminal pro-B-type natriuretic Peptide testing for the evaluation of dyspneic patients with and without acute pulmonary embolism.
Melanson Stacy E F,Laposata Michael,Camargo Carlos A,Chen Annabel A,Tung Roderick,Krauser Dan,Anwaruddin Saif,Baggish Aaron,Cameron Renee,Sluss Patrick,Lewandrowski Kent B,Lee-Lewandrowski Elizabeth,Januzzi James L
Archives of pathology & laboratory medicine
CONTEXT:D-dimer concentration can be used to exclude a diagnosis of acute pulmonary embolism. However, clinicians frequently order unnecessary supplemental testing in patients with low concentrations of D-dimer. Elevations in natriuretic peptides have also been described in the setting of pulmonary embolism. OBJECTIVE:We investigated the integrative role of D-dimer with amino-terminal pro-B-type natriuretic peptide for the evaluation of patients with and without acute pulmonary embolism. DESIGN:Patients were selected for analysis from a previous study in which levels of D-dimer and amino-terminal pro-B-type natriuretic peptide were measured. The presence of pulmonary embolism was determined by computed tomographic angiography. RESULTS:The median levels of D-dimer were significantly higher in patients with acute pulmonary embolism. Similarly, the median levels of amino-terminal pro-B-type natriuretic peptide were higher in patients with pulmonary embolism. CONCLUSIONS:The Roche Tina-quant D-Dimer immunoturbidimetric assay provides a high negative predictive value and can be used to exclude acute pulmonary embolism in patients with dyspnea. Measurement of amino-terminal pro-B-type natriuretic peptide in addition to D-dimer improves specificity for acute pulmonary embolism without sacrificing negative predictive value. A combination of both markers may offer reassurance for excluding acute pulmonary embolism, and thus avoid redundant, expensive confirmatory tests.
10.5858/2006-130-1326-CODAAP
Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: a pooled analysis of 3 clinical trials.
Meijers Wouter C,Januzzi James L,deFilippi Christopher,Adourian Aram S,Shah Sanjiv J,van Veldhuisen Dirk J,de Boer Rudolf A
American heart journal
BACKGROUND:Rehospitalization is a major cause for heart failure (HF)-related morbidity and is associated with considerable loss of quality of life and costs. The rate of unplanned rehospitalization in patients with HF is unacceptably high; current risk stratification to identify patients at risk for rehospitalization is inadequate. We evaluated whether measurement of galectin-3 would be helpful in identifying patients at such risk. METHODS:We analyzed pooled data from patients (n = 902) enrolled in 3 cohorts (COACH, n = 592; PRIDE, n = 181; and UMD H-23258, n = 129) originally admitted because of HF. Mean patient age was between 61.6 and 72.9 years across the cohorts, with a wide range of left ventricular ejection fraction. Galectin-3 levels were measured during index admission. We used fixed and random-effects models, as well as continuous and categorical reclassification statistics to assess the association of baseline galectin-3 levels with risk of postdischarge rehospitalization at different time points and the composite end point all-cause mortality and rehospitalization. RESULTS:Compared with patients with galectin-3 concentrations less than 17.8 ng/mL, those with results exceeding this value were significantly more likely to be rehospitalized for HF at 30, 60, 90, and 120 days after discharge, with odds ratios (ORs) of 2.80 (95% CI 1.41-5.57), 2.61 (95% CI 1.46-4.65), 3.01 (95% CI 1.79-5.05), and 2.79 (95% CI 1.75-4.45), respectively. After adjustment for age, gender, New York Heart Association class, renal function (estimated glomerular filtration rate), left ventricular ejection fraction, and B-type natriuretic peptide, galectin-3 remained an independent predictor of HF rehospitalization. The addition of galectin-3 to risk models significantly reclassified patient risk of postdischarge rehospitalization and fatal event at each time point (continuous net reclassification improvement at 30 days of +42.6% [95% CI +19.9%-65.4%], P < .001). CONCLUSIONS:Among patients hospitalized for HF, plasma galectin-3 concentration is useful for the prediction of near-term rehospitalization.
10.1016/j.ahj.2014.02.011
Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure.
Shah Ravi V,Chen-Tournoux Annabel A,Picard Michael H,van Kimmenade Roland R J,Januzzi James L
European journal of heart failure
AIMS:To determine the relationship between galectin-3 concentrations and cardiac structure in patients with acute dyspnoea, and to evaluate the impact of galectin-3 independent of echocardiographic measurements on long-term mortality. METHODS AND RESULTS:One hundred and fifteen patients presenting to the emergency department with acute dyspnoea who had galectin-3 levels and detailed echocardiographic studies on admission were studied. Galectin-3 levels were associated with older age (r = 0.26, P = 0.006), lower creatinine clearance (r = -0.42, P < 0.001), and higher levels of N-terminal-proBNP (r = 0.39, P < 0.001). Higher galectin-3 levels were associated with tissue Doppler E/E(a) ratio (r = 0.35, P = 0.01), a lower right ventricular (RV) fractional area change (r = -0.19, P = 0.05), higher RV systolic pressure (r = 0.37, P < 0.001), and more severe mitral (r = 0.30, P = 0.001) or tricuspid regurgitation (r = 0.26, P = 0.005). In patients diagnosed with heart failure (HF), the association between galectin-3 and valvular regurgitation and RV systolic pressure persisted. In a multivariate Cox regression model, galectin-3 remained a significant predictor of 4-year mortality independent of echocardiographic markers of risk. Dyspnoeic patients with HF and galectin-3 levels above the median value had a 63% mortality; patients less than the median value had a 37% mortality (P = 0.003). CONCLUSION:Among dyspnoeic patients with and without ADHF, galectin-3 concentrations are associated with echocardiographic markers of ventricular function. In patients with ADHF, a single admission galectin-3 level predicts mortality to 4 years, independent of echocardiographic markers of disease severity.
10.1093/eurjhf/hfq091
Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure.
van Kimmenade Roland R,Januzzi James L,Ellinor Patrick T,Sharma Umesh C,Bakker Jaap A,Low Adrian F,Martinez Abelardo,Crijns Harry J,MacRae Calum A,Menheere Paul P,Pinto Yigal M
Journal of the American College of Cardiology
OBJECTIVES:This study sought to explore the role of new biomarkers in heart failure (HF). BACKGROUND:We investigated the utility of novel serum markers alone or together with natriuretic peptide testing for diagnosis and short-term prognosis estimation in subjects with acute HF. METHODS:Plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), apelin, and galectin-3 were measured in 599 patients presenting with dyspnea at the emergency department, of which 209 (35%) had acute HF. RESULTS:The NT-proBNP was superior to either apelin or galectin-3 for diagnosis of acute HF, although galectin-3 levels were significantly higher in subjects with HF compared with those without. Receiver operating characteristic analysis for mortality prediction showed that, for 60-day prognosis, galectin-3 had the greatest area under the curve (AUC) at 0.74 (p = 0.0001), whereas NT-proBNP and apelin had an AUC of 0.67 (p = 0.009) and 0.54 (p = 0.33). In a multivariate logistic regression analysis, an elevated level of galectin-3 was the best independent predictor of 60-day mortality (odds ratio 10.3, p < 0.01) or the combination of death/recurrent HF within 60 days (odds ratio 14.3, p < 0.001). The Kaplan-Meier analyses showed that the combination of an elevated galectin-3 with NT-proBNP was a better predictor of mortality than either of the 2 markers alone. CONCLUSIONS:Our data show potential utility of galectin-3 as a useful marker for evaluation of patients with suspected or proven acute HF, whereas apelin measurement was not useful for these indications. Moreover, the combination of galectin-3 with NT-proBNP was the best predictor for prognosis in subjects with acute HF.
10.1016/j.jacc.2006.03.061
Importance of biomarkers for long-term mortality prediction in acutely dyspneic patients.
Januzzi James L,Rehman Shafiq,Mueller Thomas,van Kimmenade Roland R J,Lloyd-Jones Donald M
Clinical chemistry
BACKGROUND:Although numerous biomarkers may be prognostically meaningful in patients with acute dyspnea, few comparative analyses have addressed possible associations between a wide range of candidate biomarkers and clinical variables. METHODS:Vital status was obtained for 517 acutely dyspneic patients at 4 years after emergency department presentation. A wide array of biomarkers was measured in this cohort, including natriuretic peptides, necrosis markers, inflammatory markers, hematologic markers, and renal markers. We performed statistical evaluation by using minimization of the Bayesian information criterion to evaluate predictors of 4-year mortality. Cox proportional hazards analysis was used to confirm results from the Bayesian information criterion. A final risk model was derived, and this model was then validated by applying it to patients from a separate cohort of acutely dyspneic patients. RESULTS:By 4 years, there were 186 deaths (36%). In addition to several clinical variables, several biomarkers were significant predictors of death, including log-transformed concentrations of hemoglobin (hazard ratio=0.77; P < 0.001), soluble ST2 (hazard ratio=1.38; P < 0.001), and amino-terminal pro-B-type natriuretic peptide (hazard ratio=1.19; P < 0.001). Risk models that used these significant variables were accurate in predicting 4-year mortality in both the training and validation sets. CONCLUSIONS:When added to traditional clinical variables, selected biomarkers added significant value for long-term prognostication in acute dyspnea.
10.1373/clinchem.2010.146506
Independent and incremental prognostic value of multimarker testing in acute dyspnea: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.
Rehman Shafiq U,Martinez-Rumayor Abelardo,Mueller Thomas,Januzzi James L
Clinica chimica acta; international journal of clinical chemistry
BACKGROUND:Acute dyspnea is common in the emergency department (ED) and is associated with mortality. Biomarkers may help stratify risk in this setting. METHODS:Among 577 dyspneic subjects we identified 5 candidate biomarkers with prognostic value: amino terminal B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), the interleukin family member ST2, hemoglobin and blood urea nitrogen (BUN); these were assessed using both receiver operating characteristic curve and Cox proportional hazards analyses. Results were validated in a population of dyspneic patients from a distinct cohort. RESULTS:At 1 y follow up, 93 (16.1%) patients had died. Independent predictive ability was established in an age-adjusted Cox model containing all markers: NT-proBNP (HR=1.89); CRP (HR=1.95); ST2 (HR=7.17); hemoglobin (HR=1.68); BUN (HR=2.06) (all P<.05). Following categorical assessment based on number of abnormal markers, the 1-y risk of death increased in a monotonic fashion with mortality rates of 0%, 2.0%, 7.8%, 22.3%, 29.3%, and 57.6% respectively; similar results were seen in the validation set. CONCLUSION:Simultaneous assessment of pathophysiologically diverse markers in acute dyspnea provides powerful, independent and incremental prognostic information.
10.1016/j.cca.2008.03.002
Soluble ST2 plasma concentrations predict 1-year mortality in acutely dyspneic emergency department patients with pulmonary disease.
Martinez-Rumayor Abelardo,Camargo Carlos A,Green Sandy M,Baggish Aaron L,O'Donoghue Michelle,Januzzi James L
American journal of clinical pathology
We evaluated the association between ST2 concentrations and mortality at 1 year in 231 acutely dyspneic patients with pulmonary diseases seen in the emergency department. Blood concentrations of ST2 were ascertained; using 1-year survival as the reference standard, receiver operating characteristic curves with resultant area under the curve (AUC) were measured. Cox proportional hazards models identified independent predictors of 1-year death. Hazard curves compared rates of death as a function of ST2 concentration. Concentrations of ST2 were significantly higher in patients with pulmonary diseases compared with 153 subjects without cardiopulmonary disease (0.23 vs 0.11 ng/mL; P = .01). Among patients with pulmonary diseases, concentrations of ST2 were higher among decedents compared with survivors (1.14 ng/mL vs 0.19 ng/mL; P < .001). ST2 had an AUC of 0.72 as a predictor of death (P < .0001). An ST2 of 0.20 ng/mL had a hazard ratio for death of 6.1 (95% confidence interval, 1.8-21.0; P = .004). Compared with patients with lower ST2 concentrations, mortality rates for patients with an enrollment ST2 of 0.20 ng/mL or more diverged early and rose progressively in 1 year (P < .001). ST2 concentrations are frequently elevated in acute pulmonary diseases and are markedly prognostic for death by 1 year.
10.1309/WMG2BFRC97MKKQKP
Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.
Januzzi James L,Peacock W Frank,Maisel Alan S,Chae Claudia U,Jesse Robert L,Baggish Aaron L,O'Donoghue Michelle,Sakhuja Rahul,Chen Annabel A,van Kimmenade Roland R J,Lewandrowski Kent B,Lloyd-Jones Donald M,Wu Alan H B
Journal of the American College of Cardiology
OBJECTIVES:The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. BACKGROUND:Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). METHODS:Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. RESULTS:Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration > or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. CONCLUSIONS:Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.
10.1016/j.jacc.2007.05.014
Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea.
Shah Ravi V,Truong Quynh A,Gaggin Hanna K,Pfannkuche Jens,Hartmann Oliver,Januzzi James L
European heart journal
AIMS:The aim of this study was to assess diagnostic and prognostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP) and adrenomedullin (MR-proADM) for the evaluation of patients presenting to the emergency department with acute dyspnoea. METHODS AND RESULTS:A total of 560 patients from the pro-B type natriuretic peptide Investigation of Dyspnoea in the Emergency Department were evaluated; 180 had acutely decompensated heart failure (ADHF). Concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), MR-proADM, and MR-proANP were measured, and patients were followed to 4 years for survival. Logistic regression evaluated utility of MR-proANP in ADHF diagnosis. Area under the curve (AUC), multivariate Cox regression, net reclassification improvement, and Kaplan-Meier survival analyses were used for mortality analyses. Mid-regional pro-atrial natriuretic peptide was higher in patients with ADHF (median 329 vs. 58 pmol/L; P < 0.001), and remained an independent predictor of HF diagnosis even when NT-proBNP was included as a covariate (odds ratio = 4.34, 95% CI = 2.11-8.92; P < 0.001). In time-dependent analyses, MR-proADM had the highest AUC for death during the first year; after 1 year, MR-proANP and NT-proBNP had a higher AUC. Both mid-regional peptides were independently prognostic and reclassified risk at 1 year [MR-proANP, hazard ratio (HR) = 2.99, MR-proADM, HR = 2.70; both P < 0.001] and at 4 years (MR-proANP, HR = 3.12, P < 0.001; MR-proADM, HR = 1.51, P = 0.03) and in Kaplan-Meier curves both mid-regional peptides were associated with death out to 4 years, individually or in a multimarker strategy. CONCLUSION:Among patients with acute dyspnoea, MR-proANP is accurate for diagnosis of ADHF, while both MR-proANP and MR-proADM are independently prognostic to 4 years of the follow-up.
10.1093/eurheartj/ehs136
A clinical and biochemical score for mortality prediction in patients with acute dyspnoea: derivation, validation and incorporation into a bedside programme.
Baggish A L,Lloyd-Jones D M,Blatt J,Richards A M,Lainchbury J,O'Donoghue M,Sakhuja R,Chen A A,Januzzi J L
Heart (British Cardiac Society)
BACKGROUND:Risk stratification for patients with acute dyspnoea is a challenging task. No quantitative tool for mortality prediction among patients with acute dyspnoea is available. METHODS:595 dyspnoeic subjects were enrolled in an emergency department. Clinical and biochemical factors independently predictive of death by 1 year were used to develop a mortality risk prediction tool. RESULTS:Seven factors comprised the final tool: age (x0.3), heart rate (x0.2), blood urea nitrogen (x0.3), New York Heart Association class (x5), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) >or=986 pg/ml (18 points), systolic blood pressure <100 mm Hg (11 points) and presence of a murmur (11 points). A continuous rise in mortality was seen from 1.7% in the lowest score quintile (n = 118; score <or=48.5) to 43.1% in the highest quintile (n = 116, score >or=85.5; p<0.001 for trend). Receiver operating characteristic curve analysis of the score's accuracy produced an area under the curve (AUC) of 0.82 (95% CI 0.78 to 0.85) with similar AUCs in subjects with acutely destabilised heart failure (AUC = 0.73, 95% CI 0.67 to 0.79) and those without (AUC = 0.83, 95% CI 0.77 to 0.85, p for the comparison = NS). The score was validated in a separate population of dyspnoeic patients (AUC = 0.73, 95% CI 0.64 to 0.82; p<0.001) and was incorporated into a computer program suitable for near-patient calculation. CONCLUSION:A new risk stratification tool for acutely dyspnoeic patients has been derived and validated.
10.1136/hrt.2007.128132
A validated clinical and biochemical score for the diagnosis of acute heart failure: the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Acute Heart Failure Score.
Baggish Aaron L,Siebert Uwe,Lainchbury John G,Cameron Renee,Anwaruddin Saif,Chen Annabel,Krauser Daniel G,Tung Roderick,Brown David F,Richards A Mark,Januzzi James L
American heart journal
BACKGROUND:No method integrating amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with clinical assessment for the evaluation of patients with suspected acute heart failure (HF) has been described. METHODS:Amino-terminal pro-brain natriuretic peptide results and clinical factors from 599 patients with dyspnea were analyzed. The beta coefficients of the 8 independent predictors of HF were used to assign a weighted integeric score for predictor. The sum of these integers provided a diagnostic HF "score" for each patient. Receiver operating characteristic curve analysis determined the optimal cut point for the diagnosis of acute HF. The performance of the score was evaluated in the development cohort and subsequently in a patient population from a separate clinical trial of patients with dyspnea conducted in Christchurch, New Zealand. RESULTS:Eight factors comprised the score: elevated NT-proBNP (4 points), interstitial edema on chest x-ray (2 points), orthopnea (2 points), absence of fever (2 points), loop diuretic use, age > 75 years, rales, and absence of cough (all 1 point). Median scores in patients with acute HF were higher than those without acute HF (9 vs 3 points, P < .001). At a cut point of > or = 6 points, the score had a sensitivity of 96% and a specificity of 84% for the diagnosis of acute HF (P < .001). The score improved diagnostic accuracy over NT-proBNP testing alone and retained discriminative capacity in patients in whom clinical uncertainty was present. Lastly, the accuracy of the score was validated in the external data set of patients with suspected acute HF. CONCLUSION:We report a simple and accurate scoring system combining NT-proBNP testing and clinical assessment for the diagnosis or exclusion of acute HF in patients with dyspnea.
10.1016/j.ahj.2005.02.031
Cost-effectiveness of using N-terminal pro-brain natriuretic peptide to guide the diagnostic assessment and management of dyspneic patients in the emergency department.
Siebert Uwe,Januzzi James L,Beinfeld Molly T,Cameron Renee,Gazelle G Scott
The American journal of cardiology
The cost-effectiveness of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in dyspneic patients in emergency departments (EDs) is unknown. The objective of this study was to assess the cost-effectiveness of NT-pro-BNP testing for the evaluation and initial management of patients with dyspnea in the ED setting. A decision model was developed to evaluate the cost-effectiveness of diagnostic assessment and patient management guided by NT-pro-BNP, compared with standard clinical assessment. The model includes the diagnostic accuracy of the 2 strategies for congestive heart failure and resulting events at 60-day follow-up. Clinical data were obtained from a prospective blinded study of 599 patients presenting to the ED with dyspnea. Costs were based on the Massachusetts General Hospital cost accounting database. The model predicted serious adverse events during follow-up (i.e., urgent care visits, repeat ED presentations, rehospitalizations) and direct medical costs for echocardiograms and hospitalizations. NT-pro-BNP-guided assessment was associated with a 1.6% relative reduction of serious adverse event risk and a 9.4% reduction in costs, translating into savings of $474 per patient, compared with standard clinical assessment. In a sensitivity analysis considering mortality, NT-pro-BNP testing was associated with a 1.0% relative reduction in post-discharge mortality. The optimal use of NT-pro-BNP guidance could reduce the use of echocardiography by up to 58%, prevent 13% of initial hospitalizations, and reduce hospital days by 12%. In conclusion, on the basis of this model, the use of NT-pro-BNP in the diagnostic assessment and subsequent management of patients with dyspnea in the ED setting could lead to improved patient care while providing substantial cost savings to the health care system.
10.1016/j.amjcard.2006.06.005
Inflammatory markers, amino-terminal pro-brain natriuretic peptide, and mortality risk in dyspneic patients.
Rehman Shafiq,Lloyd-Jones Donald M,Martinez-Rumayor Abelardo,Januzzi James L
American journal of clinical pathology
Dyspnea is a common emergency department (ED) complaint, and it may be associated with significant mortality risk. We studied 599 dyspneic subjects enrolled in an ED. At 1 year, the role of inflammatory markers (including C-reactive protein [CRP]) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) as independent predictors of mortality was assessed. By 1 year, 91 subjects (15.2%) had died. Among patients who died, the median CRP concentration at admission was significantly higher than in survivors: 47.2 mg/L (449.5 nmol/L; interquartile range [IQR], 10.2-101.9 mg/L [97.1-970.5 nmol/L]) vs 7.25 mg/L (69.5 nmol/L; IQR, 2.2-29.6 mg/L [21.0-281.9 nmol/L]; P < .001). For 1-year mortality, CRP had an area under the receiver operating characteristic curve of 0.76 (95% confidence interval [CI], 0.69-0.80; P < .001). In multivariable analysis, a CRP concentration greater than 14 mg/L was a strong predictor of mortality at 1 year (hazard ratio, 2.47; 95% CI, 1.51-4.02; P < .001). In multivariable models, CRP and NT-proBNP demonstrated independent and additive prognostic value. Among dyspneic patients, CRP levels are significantly associated with mortality at 1 year and show additive value to natriuretic peptide testing for prognosis.
10.1309/L7BP57F7UF7YNYKX
Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department.
Januzzi James L,Sakhuja Rahul,O'donoghue Michelle,Baggish Aaron L,Anwaruddin Saif,Chae Claudia U,Cameron Renee,Krauser Daniel G,Tung Roderick,Camargo Carlos A,Lloyd-Jones Donald M
Archives of internal medicine
BACKGROUND:Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for diagnosis and triage of patients with dyspnea, but its role for predicting outcomes in such patients remains undefined. METHODS:A total of 599 breathless patients treated in the emergency department were prospectively enrolled, and a sample of blood was obtained for NT-proBNP measurements. After 1 year, the vital status of each patient was ascertained, and the association between NT-proBNP values at presentation and mortality was assessed. RESULTS:At 1 year, 91 patients (15.2%) had died. Median NT-proBNP concentrations at presentation among decedents were significantly higher than those of survivors (3277 vs 299 pg/mL; P<.001). The optimal NT-proBNP cut point for predicting 1-year mortality was 986 pg/mL. In a multivariable model, an NT-proBNP concentration greater than 986 pg/mL at presentation was the single strongest predictor of death at 1 year (hazard ratio [HR], 2.88; 95% confidence interval, 1.64-5.06; P<.001), independent of a diagnosis of heart failure. Other factors associated with death included age (by decade; HR, 1.20), heart rate (by decile; HR, 1.13), urea nitrogen level (by decile; HR, 1.20), systolic blood pressure less than 100 mm Hg (HR, 1.94), heart murmur (HR, 1.92), and New York Heart Association classification (HR, 1.38 for each increase in class). The NT-proBNP concentration alone had an area under the receiver operating characteristic curve (AUC) of 0.76 for predicting mortality; the other significant covariates combined had an AUC of 0.80. The final model for predicting death, combining NT-proBNP with other covariates associated with mortality, had a superior AUC of 0.82. CONCLUSION:In addition to assisting in emergency department diagnosis and triage, NT-proBNP concentrations at presentation are strongly predictive of 1-year mortality in dyspneic patients.
10.1001/archinte.166.3.315
Clinical uncertainty, diagnostic accuracy, and outcomes in emergency department patients presenting with dyspnea.
Green Sandy M,Martinez-Rumayor Abelardo,Gregory Shawn A,Baggish Aaron L,O'Donoghue Michelle L,Green Jamie A,Lewandrowski Kent B,Januzzi James L
Archives of internal medicine
BACKGROUND:Dyspnea is a common complaint in the emergency department (ED) and may be a diagnostic challenge. We hypothesized that diagnostic uncertainty in this setting is associated with adverse outcomes, and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing would improve diagnostic accuracy and reduce diagnostic uncertainty. METHODS:A total of 592 dyspneic patients were evaluated from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Managing physicians were asked to provide estimates from 0% to 100%of the likelihood of acutely destabilized heart failure (ADHF). A certainty estimate of either 20% or lower or 80% or higher was classified as clinical certainty, while estimates between 21% and 79% were defined as clinical uncertainty. Associations between clinical uncertainty,hospital length of stay, morbidity, and mortality were examined. The diagnostic value of clinical judgment vs NT-proBNP measurement was compared across categories of clinical certainty. RESULTS:Clinical uncertainty was present in 185 patients (31%), 103 (56%) of whom had ADHF. Patients judged with clinical uncertainty had longer hospital length of stay and increased morbidity and mortality,especially those with ADHF. Receiver operating characteristic analysis of clinical judgment yielded an area under the curve (AUC) of 0.88 in the clinical certainty group and 0.76 in the uncertainty group (P<.001); NT-proBNP testing alone in these same groups had AUCs of 0.96 and 0.91, respectively. The combination of clinical judgment with NT-proBNP testing yielded improvements in AUC. CONCLUSIONS:Among dyspneic patients in the ED, clinical uncertainty is associated with increased morbidity and mortality, especially in those with ADHF.The addition of NT-proBNP testing to clinical judgment may reduce diagnostic uncertainty in this setting.
10.1001/archinte.168.7.741
Amino-terminal pro-brain natriuretic peptide for the diagnosis of acute heart failure in patients with previous obstructive airway disease.
Tung Roderick H,Camargo Carlos A,Krauser Dan,Anwaruddin Saif,Baggish Aaron,Chen Annabel,Januzzi James L
Annals of emergency medicine
STUDY OBJECTIVE:We evaluate results from amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with or without those of clinical judgment for the evaluation of dyspneic patients with previous chronic obstructive pulmonary disease or asthma. METHODS:As a secondary analysis of previously collected observational data from a convenience sample of 599 breathless patients, 216 patients with previous chronic obstructive pulmonary disease or asthma who presented to the emergency department were analyzed according to results of NT-proBNP, clinical impression, and their final diagnosis. Test performance of NT-proBNP in these patients with chronic obstructive pulmonary disease or asthma was examined for the group as a whole, as well as in patients with and without previous heart failure. NT-proBNP results were compared to clinician-estimated likelihood for heart failure using receiver operating curves and as a function of NT-proBNP plus clinical evaluation. The final diagnosis was determined by 2 independent cardiologists blinded to NT-proBNP using all available data from the 60-day follow-up period. RESULTS:Overall, 55 patients (25%) had acute heart failure; the median value of NT-proBNP was higher in these patients compared with those without acute heart failure (2,238 vs 178 pg/mL); use of cut points of 450 pg/mL for patients younger than 50 years and 900 pg/mL for patients 50 years or older yielded a sensitivity of 87% (95% confidence interval [CI] 72% to 93%) and a specificity of 84% (95% CI 76% to 88%). In patients without previous heart failure (n=164), median NT-proBNP levels were also higher in patients with heart failure of new onset compared with those with chronic obstructive pulmonary disease or asthma exacerbation (1561 versus 168 pg/mL). High clinical suspicion for acute heart failure (probability >80%) detected only 23% of patients with new-onset heart failure, whereas 82% of these patients had elevated NT-proBNP levels. In patients who had both previous acute heart failure and chronic obstructive pulmonary disease or asthma (n=52), median NT-proBNP levels were significantly higher in those with acute heart failure (4,435 pg/mL) than patients with chronic obstructive pulmonary disease or asthma exacerbation (536 pg/mL). In patients with acute-on-chronic heart failure, NT-proBNP levels were elevated in 91%, whereas clinical impression considered only 39% of cases as high likelihood for acute heart failure. CONCLUSION:NT-proBNP may be a useful adjunct to standard clinical evaluation of dyspneic patients with previous obstructive airway disease.
10.1016/j.annemergmed.2005.12.022
Relative value of amino-terminal pro-B-type natriuretic peptide testing and radiographic standards for the diagnostic evaluation of heart failure in acutely dyspneic subjects.
Martinez-Rumayor Abelardo A,Vazquez Josue,Rehman Shafiq U,Januzzi James L
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
To define more clearly the relationship between the information provided by the chest radiograph (CXR) and the natriuretic peptide (NT-proBNP) test as part of the evaluation of dyspneic patients presenting to the emergency department with suspected acute heart failure (HF), we evaluated the PRIDE cohort of 599 patients with and without HF, focusing on blinded NT-proBNP and unblinded CXR information. Clinical characteristics and diagnostic performance for each test were compared. We found that NT-proBNP measurement is superior to routine CXR interpretation for diagnosis or exclusion of acute HF and that normal CXR results should not be used to exclude HF in this population.
10.3109/13547500903411087
NT-proBNP levels, echocardiographic findings, and outcomes in breathless patients: results from the ProBNP Investigation of Dyspnoea in the Emergency Department (PRIDE) echocardiographic substudy.
Chen Annabel A,Wood Malissa J,Krauser Daniel G,Baggish Aaron L,Tung Roderick,Anwaruddin Saif,Picard Michael H,Januzzi James L
European heart journal
AIMS:The objective of this study was to determine the integrative utility of measuring plasma NT-proBNP levels with echocardiography in the evaluation of dyspnoeic patients. METHODS AND RESULTS:Of 599 emergency department patients enrolled in a clinical study of NT-proBNP at a tertiary-care hospital, 134 (22%) had echocardiographic results available for analysis. Echocardiographic parameters correlating with NT-proBNP levels were determined using multivariable linear-regression analysis. Independent predictors of 1-year mortality were determined using Cox-proportional hazard analysis. Independent relationships were found between NT-proBNP levels and ejection fraction (P = 0.012), tissue Doppler early and late mitral annular diastolic velocities (P = 0.007 and 0.018), right ventricular (RV) hypokinesis (P = 0.006), and tricuspid regurgitation severity (P < 0.001) and velocity (P = 0.007). An NT-proBNP level <300 pg/mL had a negative predictive value of 91% for significant left ventricular systolic and diastolic dysfunction. Overall 1-year mortality was 20.1% and was independently predicted by NT-proBNP level [HR 8.65, 95% confidence interval (CI) 2.7-27.8, P = 0.0003], ejection fraction (HR 0.95, 95% CI 0.91-0.99, P = 0.009), RV dilation (HR 2.98, 95% CI 1.05-12.8, P = 0.04), and systolic blood pressure (HR 0.97, 95% CI 0.96-0.99, P = 0.01). CONCLUSION:NT-proBNP levels correlate with, and provide important prognostic information beyond, echocardiographic parameters of cardiac structure and function. Routine NT-proBNP testing may thus be useful to triage patients to more timely or deferred echocardiographic evaluation.
10.1093/eurheartj/ehi811
Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy.
Krauser Daniel G,Chen Annabel A,Tung Roderick,Anwaruddin Saif,Baggish Aaron L,Januzzi James L
Journal of cardiac failure
BACKGROUND:Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for the diagnosis and exclusion of congestive heart failure (HF). Little is known about the effect of race on NT-proBNP concentrations. Also, NT-proBNP levels may be higher in apparently well women, but the effect of gender on NT-proBNP concentrations in dyspneic patients is not known. METHODS AND RESULTS:NT-proBNP (Elecsys proBNP, Roche, Indianapolis, IN) was measured in 599 dyspneic patients in a prospective study. Of these, 44 were African American; 295 were female. NT-proBNP levels were examined according to race and gender in patients with and without acute HF using analysis of covariance. Receiver operating characteristic (ROC) curves assessed NT-proBNP by race and gender. Cutpoints for diagnosis (450, 900, and 1800 pg/mL for ages < 50, 50 to 75, and > 75 years) and exclusion (300 pg/mL) were examined in African-American and female subjects. There was no difference in the rates of acute HF between African-American and non-African-American (30% versus 35%, P = .44) or male and female (35% versus 35%, P = .86) subjects. In subjects with HF, there was no difference in median NT-proBNP concentrations between African American and non-African American (6196 versus 3597 pg/mL, P = .37). In subjects without HF, unadjusted NT-proBNP levels were lower in African-American subjects than in non-African-American subjects (68 versus 148 pg/mL, P < .03); however, when adjusted for factors known to influence NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial fibrillation, and body mass index), race no longer significantly affected NT-proBNP concentrations. There was no statistical difference in median NT-proBNP concentrations between male and female subjects with (4686 versus 3622 pg/mL, P = .53) or without HF (116 pg/mL versus 150 pg/mL, P = .62). Among African Americans, NT-proBNP had an area under the ROC for acute HF of 0.96 (P < .0001), and at optimal cutpoints, had a sensitivity of 100% and a specificity of 90%. Among females, NT-proBNP had an area under the ROC for acute HF of 0.95 (P < .0001), and had a sensitivity of 89% and a specificity of 88%; 300 pg/mL had negative predictive value of 100% in African Americans and females. CONCLUSION:NT-proBNP is useful for the diagnosis and exclusion of acute HF in dyspneic subjects, irrespective of race or gender.
10.1016/j.cardfail.2006.04.005
Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.
Anwaruddin Saif,Lloyd-Jones Donald M,Baggish Aaron,Chen Annabel,Krauser Daniel,Tung Roderick,Chae Claudia,Januzzi James L
Journal of the American College of Cardiology
UNLABELLED:The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of renal insufficiency, NT-proBNP remained a valuable tool for the diagnosis of acute congestive heart failure and it provides important prognostic information. OBJECTIVES:We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels. BACKGROUND:The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis. METHODS:A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration. RESULTS:Glomerular filtration rates ranged from 15 ml/min/1.73 m2 to 252 ml/min/1.73 m2. Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of > 450 pg/ml for patients ages <50 years and >900 pg/ml for patients > or =50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR > or =60 ml/min/1.73 m2. Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73 m2, we found sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006). CONCLUSIONS:The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function.
10.1016/j.jacc.2005.08.051
The effects of ejection fraction on N-terminal ProBNP and BNP levels in patients with acute CHF: analysis from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.
O'Donoghue Michelle,Chen Annabel,Baggish Aaron L,Anwaruddin Saif,Krauser Daniel G,Tung Roderick,Januzzi James L
Journal of cardiac failure
BACKGROUND:Limited data exist regarding the impact of left ventricular ejection fraction (LVEF) on N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) levels in patients with acute congestive heart failure (CHF). METHODS AND RESULTS:LVEF data were analyzed for 153 subjects with acute CHF. LVEF > or =50% was defined as non-systolic CHF (NS-CHF); LVEF >50% was defined as systolic CHF (S-CHF). 76 subjects (49.7%) had NS-CHF. Median NT-proBNP and BNP levels were significantly higher among patients with S-CHF (6196 pg/mL, 592 pg/mL, respectively) compared with those patients with NS-CHF (2849 pg/mL, 259 pg/mL, respectively). With optimal cut-points, a false-negative rate of 7% was observed for both assays among patients with S-CHF. Among patients with NS-CHF, BNP had a significantly higher false-negative rate (20%) than did NT-proBNP (9%; P < .001 for difference). NT-proBNP, but not BNP, significantly correlated with CHF symptom severity among patients with NS-CHF. CONCLUSION:Levels of both NT-proBNP and BNP are significantly lower in patients with NS-CHF; however, in contrast to NT-proBNP, BNP may be falsely negative in up to 20% of patients with NS-CHF and does not correlate with symptom severity in NS-CHF. NT-proBNP appears superior to BNP for the evaluation of suspected acute CHF in patients with preserved LVEF.
10.1016/j.cardfail.2005.04.011
Association of atrial fibrillation and amino-terminal pro-brain natriuretic peptide concentrations in dyspneic subjects with and without acute heart failure: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.
Morello Angela,Lloyd-Jones Donald M,Chae Claudia U,van Kimmenade Roland R J,Chen Annabel C,Baggish Aaron L,O'Donoghue Michelle,Lee-Lewandrowski Elizabeth,Januzzi James L
American heart journal
BACKGROUND:Amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnosis or exclusion of heart failure (HF) in dyspneic patients. Atrial fibrillation (AF) may cause dyspnea in the absence of acute HF and may also affect plasma levels of NT-proBNP. METHODS:We prospectively enrolled 599 patients presenting with dyspnea to the emergency department and obtained a blood sample for NT-proBNP measurement. The diagnosis of AF was identified via presentation electrocardiogram. A final diagnosis of HF was determined by blinded study physicians using all available hospital records for each subject through 60 days of follow-up. We assessed the association between the presence of AF and level of NT-proBNP in subsets of patients with and without HF. RESULTS:Of 599 dyspneic patients, 75 (13%) were in AF at presentation; these patients had significantly higher median NT-proBNP levels when compared with those without AF (2934 vs 294 pg/mL, P < .0001). Among patients with acute HF, AF was present in 28%; NT-proBNP levels were lower in those with AF versus those without (3488 vs 4492 pg/mL, P < .001), but AF was not independently associated with NT-proBNP after multivariable adjustment. In patients without acute HF, median NT-proBNP concentrations were significantly higher in those with AF than in those without (932 vs 121 pg/mL, P = .02); in these subjects, AF was the strongest predictor of an NT-proBNP concentration in a range consistent with acute HF (odds ratio 9.94, 95% CI 2.97-33.3, P < .001). CONCLUSION:Atrial fibrillation is associated with higher NT-proBNP concentrations in dyspneic patients, particularly in those without acute HF.
10.1016/j.ahj.2006.10.005
Usefulness of aminoterminal pro-brain natriuretic peptide testing for the diagnostic and prognostic evaluation of dyspneic patients with diabetes mellitus seen in the emergency department (from the PRIDE Study).
O'Donoghue Michelle,Kenney Patrick,Oestreicher Eveline,Anwaruddin Saif,Baggish Aaron L,Krauser Daniel G,Chen Annabel,Tung Roderick,Cameron Renee,Januzzi James L
The American journal of cardiology
Despite widespread testing, the utility of aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) for diagnosis or risk assessment in patients with diabetes mellitus (DM) in the emergency department (ED) remains unclear. NT-pro-BNP was measured in subjects with dyspnea in the ED. A final diagnosis of acute heart failure (HF) was determined by blinded study physicians using all available hospital records. Vital status was assessed at 1 year; independent predictors of death were identified using Cox analysis. Of 599 subjects, 157 (26.2%) had DM, which was an independent predictor of a final diagnosis of acute HF. In patients diagnosed with acute HF, median concentrations of NT-pro-BNP were similar in patients with and without DM (4,784 vs 3,382 pg/ml, respectively, p = 0.93). In dyspneic subjects without acute HF, median concentrations of NT-pro-BNP were significantly higher in patients with DM (242 vs 115 pg/ml, p = 0.01), but this difference was no longer significant after adjusting for relevant covariates. The area under the curve for NT-pro-BNP to diagnose acute HF in subjects with DM was 0.94 (p <0.001). Using age-adjusted cutpoints, NT-pro-BNP was 92% sensitive and 90% specific for the diagnosis of HF in diabetic subjects. In diabetic patients, a NT-pro-BNP level > or =986 pg/ml was independently associated with an increased risk of death at 1 year (hazard ratio 3.42, 95% confidence interval 1.09 to 10.7, p <0.001). In conclusion, NT-pro-BNP testing offers valuable diagnostic and prognostic information in the evaluation of dyspneic patients with DM in the ED, using identical cutpoints as the population as whole.
10.1016/j.amjcard.2007.06.020
Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy.
Krauser Daniel G,Lloyd-Jones Donald M,Chae Claudia U,Cameron Renee,Anwaruddin Saif,Baggish Aaron L,Chen Annabel,Tung Roderick,Januzzi James L
American heart journal
BACKGROUND:Obesity is associated with lower B-type natriuretic peptide (BNP) levels in healthy individuals and patients with chronic congestive heart failure (CHF). Neither the mechanism of natriuretic peptide suppression in the obese patient nor whether obesity affects natriuretic peptide levels among patients with acute CHF is known. METHODS:The associations of amino-terminal pro-BNP (NT-proBNP), BNP, and body mass index (BMI) were examined in 204 subjects with acute CHF. Multivariable regression analyses were performed to identify factors independently related to NT-proBNP and BNP levels. RESULTS:Across clinical strata of normal (<25 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2) patients, median NT-proBNP and BNP levels decreased with increasing BMI (both P values < .001). In multivariable analyses adjusting for covariates known to affect BNP levels, the inverse relationship between BMI and both NT-proBNP and BNP remained ( P < .05 for both). Using a cut point of 900 pg/mL, NT-proBNP was falsely negative in up to 10% of CHF cases in overweight patients (25-29.9 kg/m2) and 15% in obese patients (> or =30 kg/m2). Using the standard cut point of 100 pg/mL, BNP testing was falsely negative in 20% of CHF cases in both overweight and obese patients. The assays for NT-proBNP and BNP exhibited similar overall sensitivity for the diagnosis of CHF. CONCLUSIONS:When adjusted for relevant covariates, compared with normal counterparts, overweight and obese patients with acute CHF have lower circulating NT-proBNP and BNP levels, suggesting a BMI-related defect in natriuretic peptide secretion. NT-proBNP fell below the diagnostic cutoff for CHF less often than BNP in overweight and obese individuals; however, when used as a diagnostic tool to identify CHF in such patients, both markers may have reduced sensitivity.
10.1016/j.ahj.2004.07.010
The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.
Januzzi James L,Camargo Carlos A,Anwaruddin Saif,Baggish Aaron L,Chen Annabel A,Krauser Daniel G,Tung Roderick,Cameron Renee,Nagurney J Tobias,Chae Claudia U,Lloyd-Jones Donald M,Brown David F,Foran-Melanson Stacy,Sluss Patrick M,Lee-Lewandrowski Elizabeth,Lewandrowski Kent B
The American journal of cardiology
The utility of aminoterminal pro-brain natriuretic peptide (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p <0.001). NT-proBNP at cutpoints of >450 pg/ml for patients <50 years of age and >900 pg/ml for patients >or=50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p <0.001). An NT-proBNP level <300 pg/ml was optimal for ruling out acute CHF, with a negative predictive value of 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting.
10.1016/j.amjcard.2004.12.032