Faculty Bibliography

AIMS/OBJECTIVE: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/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/CONCLUSIONS: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.

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/CONCLUSIONS: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.

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/OBJECTIVE: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.

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/CONCLUSIONS: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.

Neurologic toxicity is an infrequently reported and under-recognized consequence of amiodarone, symptoms of which may include tremor, peripheral sensorimotor neuropathy, proximal weakness, and ataxia. The investigators report the rapid and complete remission of 4 months of progressively debilitating ataxia with the discontinuation of small-dose amiodarone in an elderly woman with hypertrophic obstructive cardiomyopathy and paroxysmal atrial fibrillation. Despite the long half-life of amiodarone, her symptoms began to reduce after several days, and she was walking without assistance within 1 week. Wider recognition of this syndrome may avoid unnecessary and lengthy diagnostic evaluation and promote earlier neurologic recovery.

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/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/CONCLUSIONS: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.

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.

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.

Dyspnea is a primary clinical manifestation of acute congestive heart failure (CHF) among patients presenting to the emergency department (ED). Unfortunately, other critical illnesses, including acute coronary syndromes, pulmonary embolism, chronic obstructive pulmonary disease, and pneumonia, may present with clinical symptoms and signs similar to acute CHF. N-terminal pro-brain natriuretic peptide (NT-proBNP) has proven to be a powerful tool in the diagnostic assessment of dyspnea as a result of its ability to confirm or exclude the presence of acute CHF. However, many of the disorders that mimic acute CHF may result in elevated NT-proBNP levels as well. Results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study recently demonstrated that a strategy integrating NT-proBNP testing into routine clinical assessment demonstrated a better diagnostic yield than each strategy used in isolation. We present a diagnostic algorithm integrating NT-proBNP testing with clinical assessment for use in routine clinical practice.