Alan S. Maisel

Short-term mortality risk in emergency department acute heart failure

OBJECTIVESnFew tools exist that provide objective accurate prediction of short-term mortality risk in patients presenting with acute heart failure (AHF). The purpose was to describe the accuracy of several biomarkers for predicting short-term death rates in patients diagnosed with AHF in the emergency department (ED).nnnMETHODSnThe Biomarkers in ACute Heart failure (BACH) trial was a prospective, 15-center, international study of patients presenting to the ED with nontraumatic dyspnea. Clinicians were blinded to all investigational markers, except troponin and natriuretic peptides, which used the local hospital reference range. For this secondary analysis, a core lab was used for all markers except troponin. This study evaluated patients diagnosed with AHF by the on-site emergency physician (EP).nnnRESULTSnIn the 1,641 BACH patients, 466 (28.4%) had an ED diagnosis of AHF, of whom 411 (88.2%) had a final diagnosis of AHF. In the ED-diagnosed HF patients, 59% were male, 69% had a HF history, and 19 (4.1%) died within 14 days of their ED visit. The area under the curve (AUC) for the 14-day mortality receiver operating characteristic (ROC) curve was 0.484 for brain natriuretic peptide (BNP), 0.586 for N-terminal pro-B-type natriuretic peptide (NT-proBNP), 0.755 for troponin (I or T), 0.742 for adrenomedullin (MR-proADM), and 0.803 for copeptin. In combination, MR-proADM and copeptin had the best 14-day mortality prediction (AUC = 0.818), versus all other markers.nnnCONCLUSIONSnMR-proADM and copeptin, alone or in combination, may provide superior short-term mortality prediction compared to natriuretic peptides and troponin. Presented results are explorative due to the limited number of events, but validation in larger trials seems promising.

Determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation and preserved left ventricular ejection fraction

ObjectivesThe present study aimed to investigate the clinical and echocardiographic determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation (AF) and preserved left ventricular ejection fraction (LVEF).MethodsNT-pro-BNP levels were measured in 45 patients with paroxysmal AF, 41 patients with permanent AF and 48 controls.ResultsNT-pro-BNP levels were found significantly elevated in patients with paroxysmal (215 ± 815 pg/ml) and permanent AF (1,086xa0±xa0835xa0pg/ml) in relation to control population (86.3xa0±xa077.9xa0pg/ml) (Pxa0<xa00.001). According to the univariate linear regression analysis, age, hypertension, β-blocker use, left atrial diameter (LAD), LVEF and AF status (paroxysmal or permanent or both) were significantly associated with NT-pro-BNP levels (Pxa0<xa00.05). In multiple linear regression analysis, LVEF (B coefficient: −53.030; CI: −95.738 to −10.322; P: 0.015) and LAD (B coefficient: 285.858; CI: 23.731–547.986; P: 0.033) were significant and independent determinants of NT-pro-BNP levels.ConclusionsPlasma NT-pro-BNP levels were significantly higher in patients with paroxysmal and permanent AF compared to those with sinus rhythm in the setting of preserved left ventricular systolic function. LVEF and LAD were independent predictors of NT-pro-BNP levels.

Hypervolemic and optivolemic natriuretic peptides in acute heart failure.

Acute heart failure has emerged as the leading diagnosis among hospitalized patients, and challenges in accurate diagnosis, risk stratification and optimized management still remain. Here, biomarkers--with their low cost, objectivity and widespread availability--can play an indispensible role. Among the biomarkers available, natriuretic peptides (NPs) are the most validated and accepted for risk stratification and treatment guidance. The physiological basis for this lies in the strong correlation between NP levels and pulmonary capillary wedge pressure. The ability to classify individuals on the basis of risk could allow clinicians to tailor therapies to fit individual patient needs, thus reducing morbidity, mortality and costs.

Copeptin to rule out myocardial infarction in Blacks versus Caucasians

Background: Copeptin in combination with troponin has been shown to have incremental value for the early rule-out of myocardial infarction, but its performance in Black patients specifically has never been examined. In light of a potential for wider use, data on copeptin in different relevant cohorts are needed. This is the first study to determine whether copeptin is equally effective at ruling out myocardial infarction in Black and Caucasian races. Methods: This analysis of the CHOPIN trial included 792 Black and 1075 Caucasian patients who presented to the emergency department with chest pain and had troponin-I and copeptin levels drawn. Results: One hundred and forty-nine patients were diagnosed with myocardial infarction (54 Black and 95 Caucasian). The negative predictive value of copeptin at a cut-off of 14 pmol/l (as in the CHOPIN study) for myocardial infarction was higher in Blacks (98.0%, 95% confidence interval (CI) 96.2–99.1%) than Caucasians (94.1%, 95% CI 92.1–95.7%). The sensitivity at 14 pmol/l was higher in Blacks (83.3%, 95% CI 70.7–92.1%) than Caucasians (53.7%, 95% CI 43.2–64.0%). After controlling for age, hypertension, heart failure, chronic kidney disease and body mass index in a logistic regression model, the interaction term had a P value of 0.03. A cut-off of 6 pmol/l showed similar sensitivity in Caucasians as 14 pmol/l in Blacks. Conclusions: This is the first study to identify a difference in the performance of copeptin to rule out myocardial infarction between Blacks and Caucasians, with increased negative predictive value and sensitivity in the Black population at a cut-off of 14 pmol/l. This also holds true for non-ST-segment elevation myocardial infarction and, although numbers were small, similar trends exist in the normal troponin population. This may have significant implications for early rule-out strategies using copeptin.

Natriuretic Peptides and Biomarkers in the Diagnosis of Heart Failure

Heart failure is common and difficult to diagnosis by history and physical exam alone. Natriuretic peptides (NPs) are synthesized and released in the setting of volume overload and ventricular wall stretch. They have an important physiologic role and are elevated in the setting of heart failure. B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are useful in both diagnosis and prognosis of heart failure. NPs should not be used in isolation and there are caveats to their interpretation. In the future, new biomarkers may be used in conjunction with NPs to aid in the treatment, prognosis, and diagnosis of heart failure. This chapter discusses the physiology of NPs, the role of BNP and NT-proBNP in the diagnosis of heart failure, the caveats to NP interpretation, and the emerging biomarkers in heart failure.

Diagnostic and Prognostic Biomarkers in Emergency Department Heart Failure

Heart failure is a growing public health issue worldwide. Significant challenges still remain in the diagnosis and risk stratification of acute heart failure in the emergency department. Biomarkers, with their objectivity, reproducibility, and widespread availability, have an indispensable role in improving heart failure diagnostic accuracy and risk stratification. Natriuretic peptides are perhaps the most well-known and validated biomarkers for the diagnosis of acute heart failure. They have become a routine part of the diagnostic workup of acute heart failure in many clinical settings. Natriuretic peptides along with traditional biomarkers such as troponin, creatinine, blood urea nitrogen, and serum sodium can help to identify high-risk patients who may need closer monitoring and more intensive therapy. In addition, many novel biomarkers have emerged from basic science laboratories worldwide to provide insight into different pathophysiological processes involved in heart failure. These exciting new biomarkers include mid-region proadrenomedullin (MR-proADM), C-terminal pre-pro-vasopressin (copeptin), ST2, high-sensitivity troponin, and neutrophil gelatinase-associated lipocalin (NGAL). With more experience, these new biomarkers can provide an ever clearer picture into the pathophysiology of heart failure, leading to more accurate diagnosis and better risk stratification of heart failure patients.