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Plasma Levels of B - Type Natriuretic Peptide (BNP) and Non-Invasive Cardiac Index in Diagnosing Congestive Heart Failure in the Emergency Department Radmila Kazanegra, Erin A. Barcarse, Amelia J. Chen, Alan S. Maisel Cardiology, School of Medicine, UCSD, San Diego, CA; Cardiology, SDVAHCS, San Diego, CA Presented at the 6th Scientific Meeting of the Heart Failure Society of America, September 22 - 25, 2002. Abstract Published in Journal of Cardiac Failure, August 2002, Vol.8, No. 4., Suppl. Background B-type natriuretic peptide (BNP) is a cardiac neurohormone secreted primarily from the left ventricle in response to volume expansion and pressure overload and is elevated in both systolic and diastolic dysfunction. While elevated BNP levels in dyspneic patients can help to diagnose congestive heart failure (CHF), BNP levels alone cannot differentiate systolic from diastolic dysfunction. We propose that the combination of a BNP level with various non-invasive cardiodynamic parameters will help physicians more quickly and accurately diagnose CHF. Methods Impedance Cardiography (ICG) is a non-invasive method for measuring various hemodynamic parameters. Changes in electrical impedance (resistance) of the thorax are due primarily to changes in the velocity and volume of the blood in the aorta. Monitoring ICG involves injecting a high frequency (70 kHz), low amplitude (2.5 mA) alternating electrical current through the thorax and detecting the resulting current with sensors. Measuring changes in ICG as a function of time allows cardiac output, systemic vascular resistance, acceleration index, and many other hemodynamic parameters to be calculated non-invasively. 98 patients seen in the the emergency department (ED) of the VA San Diego hospital with acute dyspnea enrolled in the study. Plasma concentration of BNP quantified using the Triage BNP Test (Biosite Diagnostics, Inc). Non-invasive hemodynamic monitoring done using the BioZ ICG monitor (CardioDynamics Corp). Data sheets completed include health history, physical exam findings, lab results, and medications. Final CHF diagnosis made by cardiologist reviewing patient charts. Cardiologist blinded to hemodynamic parameters but not to BNP level. Statistical analyses: Mann-Whitney Test, Logistic Regression, ROC curves. Table 1. Patient Demographics Characteristics Age Gender: male/female Race White African-American Hispanic Asian Height (inches) Weight (lbs) Habits Smoking Ethanol abuse % of Total Patients 64.6 ± 1.2 100 79.6 10.2 6.1 4.1 69.1 ± 0.3 204.1 ± 5.4 72.4 58.2 Characteristics History Congestive heart failure Hypertension Diabetes mellitus COPD Asthma Pulmonary embolism Myocardial infarction CAD / Angina Atrial fibrillation Any cardiac surgery Stroke % of Total Patients 59.2 74.5 41.8 37.8 13.3 3.1 40.8 44.9 13.6 33.7 14.3 Table 2. Signs and Symptoms Characteristics Symptoms Dyspnea Lethargy Ankle/peripheral edema Cough Orthopnea Chest pain Recent weight gain Paroxysmal nocturnal dyspnea % of Total Patients 100 65.3 59.2 54.1 43.9 41.8 35.7 30.6 Characteristics Physical Exam Pulmonary rales JVP > 6 cm Wheezing Abnormal heart sounds S3 Gallop Murmurs Diffuse/lateral PMI Ascites % of Total Patients 48 44.9 36.7 27.6 9.2 19.4 4.1 4.1 ROC curves for CI and BNP: Determining Systolic Dysfunction in Patients with BNP > 100 pg/ml Results Plasma BNP Levels in All Patients Plasma BNP Level (pg/ml) 900 *p<0.001 800 1.0 400 2.6 496 550 0.6 590 0.4 BNP (pg/ml) 670 2.3 725 BNP: AUC = 0.640 (0.487-0.793) p < 0.078 0.2 CI: AUC = 0.735 (0.598-0.871) p < 0.003 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1 - Specificity Table 3. CI in Determining Systolic Dysfunction in Patients with BNP > 100 Positive Negative CI Sensitivity Specificity Accuracy Predictive Predictive 2 (%) (%) (%) (l/min m ) Value (%) Value (%) * 700 3.0 2 CI (L/min m ) 0.8 Sensitivity Regardless of their cardiac index (CI) (N=37), patients with a BNP < 100 pg/ml had no evidence of CHF 97% of the time. In those with a BNP > 100 pg/ml (601 ± 55 pg/ml, N = 61), a CI of 2.6 L/min m2 is 71% sensitive and 69% specific in distinguishing systolic from diastolic heart failure. In patients with a BNP > 100 pg/ml, a multivariate model consisting of thoracic fluid content (TFC), acceleration index (ACI), and left cardiac work index (LCWI) measurements was able to predict cardiac deaths, re-admissions, and ED visits within 90 days with an 80% accuracy. < 2.3 29 92 82 50 56 < 2.6 65 88 87 66 75 < 3.0 84 50 68 71 69 600 500 698 ± 73 630 ± 57 535 ± 88 400 300 200 * Table 4. A Multivariate Model of LCWI, ACI, and TFC for Predicting Endpoints in Patients with BNP >100 pg/ml 44 ± 9 100 0 Non-CHF All CHF 1 Systolic (N=41) (N=57) Diastolic (N=33) (N=24) Hemodynamic Parameters CI Measurements in All Patients * 3 LCWI 31 89 56 74 71 LCWI + ACI 45 88 62 78 74 LCWI + ACI + TFC 59 89 71 83 80 *p<0.003 2.9 2.8 2.7 2.94 ± 0.10 2.88 ± 0.12 Conclusion * 2.6 2.71 ± 0.08 2.5 2.54 ± 0.11 2.4 Plasma BNP level is a sensitive and specific test for identifying patients with CHF in an emergency setting. A CI of 2.6 l/min m2 is 75% accurate in determining the type of LV dysfunction in CHF patients. A multivariate model of LCWI, ACI, and TFC in patients with BNP > 100 pg/ml is 80% accurate in predicting cardiac death, re-admission, and ED visits within 90 days. In patients presenting to the ED with dyspnea, the addition of non-invasive hemodynamic measurements to a BNP level more effectively diagnoses CHF by: 2.3 2.2 Non-CHF All CHF (N=41) 1 (N=57) Systolic Diastolic (N=33) (N=24) ROC curves for CI and BNP: Determining CHF versus Non-CHF in all patients 1.0 110 BNP (pg/ml) 0.8 Sensitivity Cardiac Index (l/min m2) 3.1 Positive Negative Sensitivity Specificity Predictive Predictive Accuracy (% ) (% ) (% ) Value Value (% ) (% ) 170 2 CI (L/min m ) 3.0 300 0.6 2.8 0.4 - Differentiating between systolic and diastolic dysfunction in a rapid and inexpensive manner. 2.6 2.5 2.4 0.2 BNP: AUC = 0.979 (0.956-1.002) p < 0.001 - Determining the severity of illness. CI: AUC = 0.577 (0.460-0.693) p < 0.196 0.0 0.0 0.2 0.4 0.6 1 - Specificity 0.8 1.0 M357 Rev. A