John O’Connor, MD

ABSTRACT

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to volume expansion and pressure overload. Levels correlate with severity of congestive heart failure (CHF) and prognosis. A rapid assay for B-type natriuretic peptide might help clinicians’ accuracy in distinguishing CHF from other conditions (eg, chronic obstructive pulmonary disease) as the cause of acute dyspnea in an emergency setting.

POPULATION STUDIED: The investigators enrolled 1586 patients from 7 sites (5 in the United States, 1 in France, 1 in Norway). Eligible subjects (at least 18 years old) presented to the emergency department with shortness of breath for which CHF could not be obviously ruled out (such as in trauma or cardiac tamponade). Patients were not included if they had acute myocardial infarction or renal failure; patients were also not included if they had unstable angina, unless their predominant presenting symptom was dyspnea. Forty-four percent of the subjects were women; 49% were white, 45% were black, and 6% were from other races.

STUDY DESIGN AND VALIDITY: This study evaluated the role B-type natriuretic peptide determinations might play in the diagnosis of CHF by comparing B-type natriuretic peptide levels with clinical diagnosis as the gold standard. Blood was drawn from all included patients for measurement of B-type natriuretic peptide. Emergency room physicians, who were not given the laboratory results, assessed the probability that the patient had CHF. Patients with a history of CHF were classified as having either an exacerbation of CHF or dyspnea from another cause with underlying left ventricular dysfunction.

OUTCOMES MEASURED: Whole blood or plasma levels of B-type natriuretic peptide were measured using a fluorescence immunoassay kit (Triage BNP Test; Biosite Inc, San Diego, CA) and the results were compared with clinical diagnoses to determine the sensitivity, specificity, and accuracy of the test in the diagnosis of CHF. Receiver-operating-characteristic curves were constructed to illustrate various cutoff values of B-type natriuretic peptide. Long-term outcomes of patients with CHF were not measured.

RESULTS: Congestive heart failure was diagnosed in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of CHF (5%), and no CHF in 770 (48%). The B-type natriuretic peptide level test performed well for diagnosing CHF; the area under the receiver-operating-characteristic curve was 0.91 (where 1.0 indicates a perfect test). A value of 100 pg/mL or more was the single most accurate predictor of the presence of CHF when compared with clinical predictors such as history, physical examination, or chest x-ray. This B-type natriuretic peptide cutoff value of 100 pg/mL was 90% sensitive, 76% specific, and 83% accurate in differentiating CHF from other causes of dyspnea. As such, this cutoff value outperformed the accuracy of 2 commonly used clinical criteria used for diagnosing CHF, the National Health and Nutrition Examination Survey (NHANES) criteria (67%) and Framingham criteria (73%). At this prevalence of 47%, a level of 50 pg/mL was associated with a negative predictive value of 96%. B-type natriuretic peptide values also correlated with CHF severity as determined by the New York Heart Association functional class.

ABSTRACT

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to volume expansion and pressure overload. Levels correlate with severity of congestive heart failure (CHF) and prognosis. A rapid assay for B-type natriuretic peptide might help clinicians’ accuracy in distinguishing CHF from other conditions (eg, chronic obstructive pulmonary disease) as the cause of acute dyspnea in an emergency setting.

POPULATION STUDIED: The investigators enrolled 1586 patients from 7 sites (5 in the United States, 1 in France, 1 in Norway). Eligible subjects (at least 18 years old) presented to the emergency department with shortness of breath for which CHF could not be obviously ruled out (such as in trauma or cardiac tamponade). Patients were not included if they had acute myocardial infarction or renal failure; patients were also not included if they had unstable angina, unless their predominant presenting symptom was dyspnea. Forty-four percent of the subjects were women; 49% were white, 45% were black, and 6% were from other races.

STUDY DESIGN AND VALIDITY: This study evaluated the role B-type natriuretic peptide determinations might play in the diagnosis of CHF by comparing B-type natriuretic peptide levels with clinical diagnosis as the gold standard. Blood was drawn from all included patients for measurement of B-type natriuretic peptide. Emergency room physicians, who were not given the laboratory results, assessed the probability that the patient had CHF. Patients with a history of CHF were classified as having either an exacerbation of CHF or dyspnea from another cause with underlying left ventricular dysfunction.

OUTCOMES MEASURED: Whole blood or plasma levels of B-type natriuretic peptide were measured using a fluorescence immunoassay kit (Triage BNP Test; Biosite Inc, San Diego, CA) and the results were compared with clinical diagnoses to determine the sensitivity, specificity, and accuracy of the test in the diagnosis of CHF. Receiver-operating-characteristic curves were constructed to illustrate various cutoff values of B-type natriuretic peptide. Long-term outcomes of patients with CHF were not measured.

RESULTS: Congestive heart failure was diagnosed in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of CHF (5%), and no CHF in 770 (48%). The B-type natriuretic peptide level test performed well for diagnosing CHF; the area under the receiver-operating-characteristic curve was 0.91 (where 1.0 indicates a perfect test). A value of 100 pg/mL or more was the single most accurate predictor of the presence of CHF when compared with clinical predictors such as history, physical examination, or chest x-ray. This B-type natriuretic peptide cutoff value of 100 pg/mL was 90% sensitive, 76% specific, and 83% accurate in differentiating CHF from other causes of dyspnea. As such, this cutoff value outperformed the accuracy of 2 commonly used clinical criteria used for diagnosing CHF, the National Health and Nutrition Examination Survey (NHANES) criteria (67%) and Framingham criteria (73%). At this prevalence of 47%, a level of 50 pg/mL was associated with a negative predictive value of 96%. B-type natriuretic peptide values also correlated with CHF severity as determined by the New York Heart Association functional class.

ABSTRACT

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to volume expansion and pressure overload. Levels correlate with severity of congestive heart failure (CHF) and prognosis. A rapid assay for B-type natriuretic peptide might help clinicians’ accuracy in distinguishing CHF from other conditions (eg, chronic obstructive pulmonary disease) as the cause of acute dyspnea in an emergency setting.

POPULATION STUDIED: The investigators enrolled 1586 patients from 7 sites (5 in the United States, 1 in France, 1 in Norway). Eligible subjects (at least 18 years old) presented to the emergency department with shortness of breath for which CHF could not be obviously ruled out (such as in trauma or cardiac tamponade). Patients were not included if they had acute myocardial infarction or renal failure; patients were also not included if they had unstable angina, unless their predominant presenting symptom was dyspnea. Forty-four percent of the subjects were women; 49% were white, 45% were black, and 6% were from other races.

STUDY DESIGN AND VALIDITY: This study evaluated the role B-type natriuretic peptide determinations might play in the diagnosis of CHF by comparing B-type natriuretic peptide levels with clinical diagnosis as the gold standard. Blood was drawn from all included patients for measurement of B-type natriuretic peptide. Emergency room physicians, who were not given the laboratory results, assessed the probability that the patient had CHF. Patients with a history of CHF were classified as having either an exacerbation of CHF or dyspnea from another cause with underlying left ventricular dysfunction.

OUTCOMES MEASURED: Whole blood or plasma levels of B-type natriuretic peptide were measured using a fluorescence immunoassay kit (Triage BNP Test; Biosite Inc, San Diego, CA) and the results were compared with clinical diagnoses to determine the sensitivity, specificity, and accuracy of the test in the diagnosis of CHF. Receiver-operating-characteristic curves were constructed to illustrate various cutoff values of B-type natriuretic peptide. Long-term outcomes of patients with CHF were not measured.

RESULTS: Congestive heart failure was diagnosed in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of CHF (5%), and no CHF in 770 (48%). The B-type natriuretic peptide level test performed well for diagnosing CHF; the area under the receiver-operating-characteristic curve was 0.91 (where 1.0 indicates a perfect test). A value of 100 pg/mL or more was the single most accurate predictor of the presence of CHF when compared with clinical predictors such as history, physical examination, or chest x-ray. This B-type natriuretic peptide cutoff value of 100 pg/mL was 90% sensitive, 76% specific, and 83% accurate in differentiating CHF from other causes of dyspnea. As such, this cutoff value outperformed the accuracy of 2 commonly used clinical criteria used for diagnosing CHF, the National Health and Nutrition Examination Survey (NHANES) criteria (67%) and Framingham criteria (73%). At this prevalence of 47%, a level of 50 pg/mL was associated with a negative predictive value of 96%. B-type natriuretic peptide values also correlated with CHF severity as determined by the New York Heart Association functional class.

BACKGROUND: Syncope is a very common complaint in primary care and is often very difficult to diagnose. Most previous studies have focused only on high-risk patients and on selected diagnostic tests.

POPULATION STUDIED: All patients were eligible for inclusion who were 18 years or older and who presented to the emergency department (ED) of a large primary and tertiary care teaching hospital with a chief complaint of syncope. Syncope was defined as a sudden transient loss of consciousness with an inability to maintain postural tone, with spontaneous recovery. Patients with a seizure disorder, vertigo, dizziness, coma, or shock were excluded. Of 788 eligible patients, 115 did not complete the standardized evaluation, and 23 refused to participate. The remaining 650 patients ranged in age from 18 to 93 years (mean age = 60 years) and represented both men and women equally.

STUDY DESIGN AND VALIDITY: Patients underwent a standard evaluation including a complete history and physical examination, laboratory evaluation (hematocrit, serum creatine kinase and glucose), electrocardiogram (EKG), testing for orthostatic hypotension, and bilateral carotid massage unless contraindicated. If this approach did not lead to a diagnosis, a second series of tests was conducted: 24-hour Holter monitoring, ambulatory loop monitoring or electrophysiologic studies as guided by an abnormal EKG, or a tilt-table test to identify neurocardiogenic or orthostatic syncope. A committee of 2 internists and a cardiologist reviewed the findings of each case, and explicit and reproducible criteria were used to verify the etiology of the syncope. Some of the diagnoses relied on clinical judgment, since no gold standard reference was available.

OUTCOMES MEASURED: The cause of syncope for each patient based on the sequential evaluation. Follow-up information about mortality and recurrent syncope was obtained at 3 6-month intervals from primary physicians, patients, or their families.

RESULTS: A diagnosis was made in 69% of patients following the initial round of examination. In this group, vasovagal disorders accounted for 53% of the diagnoses, along with orthostatic hypotension (35%), arrhythmia (5%), and other causes (5%). Targeted testing was performed in 67 patients, and the suspected diagnosis was confirmed in an additional 49 patients (8%). Extensive cardiovascular testing of 122 of the remaining 155 patients established a diagnosis in 30 of them through the use of Holter or ambulatory loop monitoring, tilt-table, or electrophysiologic testing. No etiology was found in 92 patients (14%). Overall mortality (9% over 18 months) and sudden death were more common among patients with cardiac causes of syncope compared with other causes of syncope.

BACKGROUND: Syncope is a very common complaint in primary care and is often very difficult to diagnose. Most previous studies have focused only on high-risk patients and on selected diagnostic tests.

POPULATION STUDIED: All patients were eligible for inclusion who were 18 years or older and who presented to the emergency department (ED) of a large primary and tertiary care teaching hospital with a chief complaint of syncope. Syncope was defined as a sudden transient loss of consciousness with an inability to maintain postural tone, with spontaneous recovery. Patients with a seizure disorder, vertigo, dizziness, coma, or shock were excluded. Of 788 eligible patients, 115 did not complete the standardized evaluation, and 23 refused to participate. The remaining 650 patients ranged in age from 18 to 93 years (mean age = 60 years) and represented both men and women equally.

STUDY DESIGN AND VALIDITY: Patients underwent a standard evaluation including a complete history and physical examination, laboratory evaluation (hematocrit, serum creatine kinase and glucose), electrocardiogram (EKG), testing for orthostatic hypotension, and bilateral carotid massage unless contraindicated. If this approach did not lead to a diagnosis, a second series of tests was conducted: 24-hour Holter monitoring, ambulatory loop monitoring or electrophysiologic studies as guided by an abnormal EKG, or a tilt-table test to identify neurocardiogenic or orthostatic syncope. A committee of 2 internists and a cardiologist reviewed the findings of each case, and explicit and reproducible criteria were used to verify the etiology of the syncope. Some of the diagnoses relied on clinical judgment, since no gold standard reference was available.

OUTCOMES MEASURED: The cause of syncope for each patient based on the sequential evaluation. Follow-up information about mortality and recurrent syncope was obtained at 3 6-month intervals from primary physicians, patients, or their families.

RESULTS: A diagnosis was made in 69% of patients following the initial round of examination. In this group, vasovagal disorders accounted for 53% of the diagnoses, along with orthostatic hypotension (35%), arrhythmia (5%), and other causes (5%). Targeted testing was performed in 67 patients, and the suspected diagnosis was confirmed in an additional 49 patients (8%). Extensive cardiovascular testing of 122 of the remaining 155 patients established a diagnosis in 30 of them through the use of Holter or ambulatory loop monitoring, tilt-table, or electrophysiologic testing. No etiology was found in 92 patients (14%). Overall mortality (9% over 18 months) and sudden death were more common among patients with cardiac causes of syncope compared with other causes of syncope.

BACKGROUND: Syncope is a very common complaint in primary care and is often very difficult to diagnose. Most previous studies have focused only on high-risk patients and on selected diagnostic tests.

POPULATION STUDIED: All patients were eligible for inclusion who were 18 years or older and who presented to the emergency department (ED) of a large primary and tertiary care teaching hospital with a chief complaint of syncope. Syncope was defined as a sudden transient loss of consciousness with an inability to maintain postural tone, with spontaneous recovery. Patients with a seizure disorder, vertigo, dizziness, coma, or shock were excluded. Of 788 eligible patients, 115 did not complete the standardized evaluation, and 23 refused to participate. The remaining 650 patients ranged in age from 18 to 93 years (mean age = 60 years) and represented both men and women equally.

STUDY DESIGN AND VALIDITY: Patients underwent a standard evaluation including a complete history and physical examination, laboratory evaluation (hematocrit, serum creatine kinase and glucose), electrocardiogram (EKG), testing for orthostatic hypotension, and bilateral carotid massage unless contraindicated. If this approach did not lead to a diagnosis, a second series of tests was conducted: 24-hour Holter monitoring, ambulatory loop monitoring or electrophysiologic studies as guided by an abnormal EKG, or a tilt-table test to identify neurocardiogenic or orthostatic syncope. A committee of 2 internists and a cardiologist reviewed the findings of each case, and explicit and reproducible criteria were used to verify the etiology of the syncope. Some of the diagnoses relied on clinical judgment, since no gold standard reference was available.

OUTCOMES MEASURED: The cause of syncope for each patient based on the sequential evaluation. Follow-up information about mortality and recurrent syncope was obtained at 3 6-month intervals from primary physicians, patients, or their families.

RESULTS: A diagnosis was made in 69% of patients following the initial round of examination. In this group, vasovagal disorders accounted for 53% of the diagnoses, along with orthostatic hypotension (35%), arrhythmia (5%), and other causes (5%). Targeted testing was performed in 67 patients, and the suspected diagnosis was confirmed in an additional 49 patients (8%). Extensive cardiovascular testing of 122 of the remaining 155 patients established a diagnosis in 30 of them through the use of Holter or ambulatory loop monitoring, tilt-table, or electrophysiologic testing. No etiology was found in 92 patients (14%). Overall mortality (9% over 18 months) and sudden death were more common among patients with cardiac causes of syncope compared with other causes of syncope.