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Plasma brain natriuretic peptide may not be useful to assess possible cardiac symptoms during pregnancy
SMFM Abstracts S79 245 ACUTE PHASE RESPONSE OF INJURED ENDOTHELIUM LEADS TO HIGH LEVELS OF CIRCULATING ACTIVE VON WILLEBRAND FACTOR IN PATIENTS WITH HELLP SYNDROME PIETER VAN RUNNARD HEIMEL1, JANINE HULSTEIN2, ARIE FRANX3, PETER LENTING2, HEIN BRUINSE4, KAREN SILENCE5, PHILIP DE GROOT2, ROB FIJNHEER2, 1University Medical Center Utrecht, Utrecht, Netherlands, 2University Medical Center Utrecht, Haematology, Utrecht, Netherlands, 3 St. Elisabeth Ziekenhuis, Obstetrics and Gynaecology, Tilburg, Netherlands, 4 University Medical Center Utrecht, Perinatology and Gynecology, Utrecht, Netherlands, 5Ablynx, Ghent, Belgium OBJECTIVE: The HELLP syndrome is a severe form of preeclampsia that compromises pregnancy. The pathophysiology is largely unknown, although endothelial cell activation leading to thrombotic microangiopathy is suggested. Von Willebrand Factor (vWF) mediates platelet binding to the vessel wall by conversion of the vWF A1-domain into a platelet glycoprotein Ib (GpIb)binding conformation. AU/vWFa-11, a llama-derived nanobody, which preferentially recognizes this GpIb-binding conformation in vWF, was used to assess activated vWF. We hypothesize that endothelial cells secrete active vWF in the HELLP syndrome. To investigate if activated endothelial cells are the source, we measured vWF propeptide-antigen ratios in plasma and the amounts of active vWF that are secreted by stimulated human umbilical vein endothelial cells (HUVEC) in vitro. STUDY DESIGN: Circulating active vWF and vWF propeptide-antigen ratios was measured in healthy pregnant women (n=9), patients suffering from preeclampsia (n=6) and patients with HELLP syndrome (n=14) at similar gestational age. Synthesis of active vWF by cultured HUVEC´s was investigated with and without stimulation (n = 4). Active vWF was determined by ELISA. RESULTS: In patients with the HELLP syndrome, the levels of active vWF were increased 2.1-fold compared to healthy pregnant women (p!0.01) and 1.6-fold as compared to the patients suffering from preeclampsia (p!0.05). The vWF propeptide-antigen ratios were increased up to 1.7-fold as compared to healthy pregnant women (p!0.01) and 1.4-fold as compared to patients with preeclampsia (p!0.05). The amount of active vWF was increased up to 1.5-fold in medium of the stimulated endothelial cells, compared to unstimulated cells (p!0.05). CONCLUSION: Acute activation of the endothelium in HELLP syndrome results in increased amounts of active vWF. This might well explain the thrombocytopenia and thrombotic microangiopathy associated with the HELLP syndrome. Inhibition of this active vWF is a potential new approach in the treatment of patients with the HELLP syndrome.
246 EVALUATION OF B-TYPE NATRIURETIC PEPTIDE (BNP) LEVELS IN PATIENTS AT ELEVATED RISK FOR PREECLAMPSIA EMILY WHITCOMB1, JAMIE RESNIK1, THOMAS MOORE1, ROBERT RESNIK2, SALLY AGENT3, JENNIFER BEEDE4, ALAN MAISEL5, 1University of California, San Diego, Reproductive Medicine, San Diego, California, 2 University of California, San Diego, La Jolla, California, 3University of California, San Diego, Health Care, San Diego, California, 4University of California, San Diego, Cardiology, San Diego, California, 5University of California, San Diego, Medicine, San Diego, California OBJECTIVE: B-Type natriuretic peptide is synthesized in the cardiac ventricles in response to volume expansion. We have previously reported stable and normal BNP levels in normotensive pregnant women, as well as their progressive rise in mild and severe preeclamptics. The objectives of this study were to expand the preeclamptic patient base, and to compare BNP concentrations in chronic hypertensive women with and without superimposed preeclampsia. STUDY DESIGN: A retrospective study of BNP levels was performed in 167 women ranging from first trimester to term, including 112 normal controls, 55 preeclamptics and 17 chronic hypertensives. Plasma BNP levels were determined using a standard assay. RESULTS: The mean BNP levels were equivalent across each trimester (20.58, 14.48, and 13.59 pg/ml respectively, p= NS). At delivery, mean BNP levels in normal, mild and severe preeclamptics were 15.14, 27.54 and 85.11 pg/ ml respectively (p!0.05). Mean BNP levels in normal patients were equivalent to chronic hypertensives (19.50, p= NS), but significantly less than all preeclamptics combined (53.70 pg/ml, p!0.01). There was an increased trend toward higher BNP values in chronic hypertensives with superimposed preeclampsia as compared to chronic hypertensives alone (43.65 vs. 19.50 pg/ml), but statistical significance was not achieved due to the small sample size. A BNP cutoff of !56.23 pg/ml had a specificity of 95%, positive predictive value of 78%, negative predictive value of 81%, and accuracy of 80% for the diagnosis of preeclampsia. CONCLUSION: Mean BNP values are stable throughout normal gestation, and elevated in preeclampsia. BNP level is also elevated in preeclamptics compared to chronic hypertensives, but equivalent between normals and chronic hypertensives. Therefore, elevated BNP levels may become diagnostically useful in the presence of superimposed preeclampsia.
247 A NOVEL APPROACH TO MATERNAL CARDIAC DISEASE - A GENERIC TEST TO EVALUATE THE FUNCTIONAL ADEQUACY OF INDIVIDUAL DISEASED HEARTS TO COPE WITH PREGNANCY AND LABOR DIANE BARKER1, GERALD MASON2, DOMINIK SCHLOSSHAN1, HILARY MCLOUGHLIN1, LIP-BUN TAN1, 1Leeds General Infirmary, Cardiology, Leeds, Yorkshire, United Kingdom, 2Leeds General Infirmary, Feto-Maternal Medicine, Leeds, Yorkshire, United Kingdom
OBJECTIVE: Pregnancy in women with heart disease is becoming increasingly common. Not all individuals with a known abnormality will be functionally affected to the same degree. We propose that the adequacy of a diseased heart (irrespective of aetiology) to cope with pregnancy and labor can be evaluated by a generic exercise test. STUDY DESIGN: Twenty-four pregnant women with heart disease (mean age 30 years [range 15-41], mean gestation 21 weeks) and 39 healthy pregnant women with no known cardiac disease (mean age 32 years [range 19-41], mean gestation 24 weeks) underwent maximal symptom-limited treadmill cardiopulmonary exercise testing. All participants exercised to their cardiopulmonary limits (respiratory exchange ratio O 1). Cardiac output (CO) was measured at peak exercise using the CO2 re-breathing method. Cardiac power output (CPO) was calculated as the product of CO and mean arterial pressure (MAP). RESULTS: Compared to healthy pregnant women, pregnant cardiac patients had 12% lower peak CPO. Both groups exercised to similar levels (equivalent RER), although exercise duration was not-significantly lower in cardiac patients. Many cardiac patients had normal cardiac function. The results of this test identified those cardiac disease patients with impaired cardiac function, irrespective of the underlying aetiology.
Graph showing individual peak CPO results from healthy pregnant women and pregnant women with heart disease CONCLUSION: Pregnant cardiac patients were found to have a lower exercise cardiac reserve compared to healthy pregnant women. This generic test would enable identification of individual pregnant patients with congenital or acquired cardiac diseases who have limited cardiac reserve to cope with the cardiovascular stresses of pregnancy and labor.
248 PLASMA BRAIN NATRIURETIC PEPTIDE MAY NOT BE USEFUL TO ASSESS POSSIBLE CARDIAC SYMPTOMS DURING PREGNANCY DIANE BARKER1, SIMON WILLIAMS2, GERALD MASON3, HILARY MCLOUGHLIN1, DOMINIK SCHLOSSHAN1, LIP-BUN TAN1, 1 Leeds General Infirmary, Cardiology, Leeds, United Kingdom, 2Wythenshawe Hospital, Regional Cardiology & Cardiac Transplant Unit, Wythenshawe, Manchester, United Kingdom, 3Leeds General Infirmary, Feto-Maternal Medicine, Leeds, Yorkshire, United Kingdom OBJECTIVE: Plasma brain natriuretic peptide (BNP) is a surrogate marker for cardiac function and is used to screen patients for cardiac disease. Breathlessness is a common symptom during pregnancy, usually secondary to physiological changes. However, with increasing maternal mortality from cardiac disease, a pathological basis for any changes in symptoms needs to be considered. We assessed the relationship between plasma N-terminal BNP (NBNP) and hemodynamic indicators of cardiac function during pregnancy. STUDY DESIGN: Seventy pregnant women (age 31 G 6 years, mean gestation 24 weeks) participated in this study. One third of the subjects had heart disease whilst two thirds were healthy controls. Cardiac function was measured by maximal symptom-limited cardiopulmonary exercise testing with non-invasive measurement of peak oxygen consumption (VO2 mx), cardiac output (CO) and cardiac power output (CPO). N-BNP was assayed prior to exercising. Pearson correlation coefficients were used to assess the relationships between plasma BNP and indicators of cardiac function. RESULTS: We found a weak but statistically significant correlation between log BNP and peak CPO (R2 = ÿ0.3, P = 0.01) and between log BNP and peak CO (R2 = ÿ0.29, P = 0.02). This correlation was much weaker than the correlation between log-BNP and CPO in our clinical practice amongst nonpregnant patients (R2 = ÿ0.64, P ! 0.001).
Graph showing correlation between log BNP and CPO in nonpregnant and pregnant subjects CONCLUSION: Although it is well known that BNP can be used as a surrogate marker for cardiac function in usual clinical practice, our preliminary data from this study suggest that BNP may be of much less use in pregnancy. Further studies are required to investigate the usefulness and role of BNP testing in pregnancy.
246 EVALUATION OF B-TYPE NATRIURETIC PEPTIDE (BNP) LEVELS IN PATIENTS AT ELEVATED RISK FOR PREECLAMPSIA EMILY WHITCOMB1, JAMIE RESNIK1, THOMAS MOORE1, ROBERT RESNIK2, SALLY AGENT3, JENNIFER BEEDE4, ALAN MAISEL5, 1University of California, San Diego, Reproductive Medicine, San Diego, California, 2 University of California, San Diego, La Jolla, California, 3University of California, San Diego, Health Care, San Diego, California, 4University of California, San Diego, Cardiology, San Diego, California, 5University of California, San Diego, Medicine, San Diego, California OBJECTIVE: B-Type natriuretic peptide is synthesized in the cardiac ventricles in response to volume expansion. We have previously reported stable and normal BNP levels in normotensive pregnant women, as well as their progressive rise in mild and severe preeclamptics. The objectives of this study were to expand the preeclamptic patient base, and to compare BNP concentrations in chronic hypertensive women with and without superimposed preeclampsia. STUDY DESIGN: A retrospective study of BNP levels was performed in 167 women ranging from first trimester to term, including 112 normal controls, 55 preeclamptics and 17 chronic hypertensives. Plasma BNP levels were determined using a standard assay. RESULTS: The mean BNP levels were equivalent across each trimester (20.58, 14.48, and 13.59 pg/ml respectively, p= NS). At delivery, mean BNP levels in normal, mild and severe preeclamptics were 15.14, 27.54 and 85.11 pg/ ml respectively (p!0.05). Mean BNP levels in normal patients were equivalent to chronic hypertensives (19.50, p= NS), but significantly less than all preeclamptics combined (53.70 pg/ml, p!0.01). There was an increased trend toward higher BNP values in chronic hypertensives with superimposed preeclampsia as compared to chronic hypertensives alone (43.65 vs. 19.50 pg/ml), but statistical significance was not achieved due to the small sample size. A BNP cutoff of !56.23 pg/ml had a specificity of 95%, positive predictive value of 78%, negative predictive value of 81%, and accuracy of 80% for the diagnosis of preeclampsia. CONCLUSION: Mean BNP values are stable throughout normal gestation, and elevated in preeclampsia. BNP level is also elevated in preeclamptics compared to chronic hypertensives, but equivalent between normals and chronic hypertensives. Therefore, elevated BNP levels may become diagnostically useful in the presence of superimposed preeclampsia.
247 A NOVEL APPROACH TO MATERNAL CARDIAC DISEASE - A GENERIC TEST TO EVALUATE THE FUNCTIONAL ADEQUACY OF INDIVIDUAL DISEASED HEARTS TO COPE WITH PREGNANCY AND LABOR DIANE BARKER1, GERALD MASON2, DOMINIK SCHLOSSHAN1, HILARY MCLOUGHLIN1, LIP-BUN TAN1, 1Leeds General Infirmary, Cardiology, Leeds, Yorkshire, United Kingdom, 2Leeds General Infirmary, Feto-Maternal Medicine, Leeds, Yorkshire, United Kingdom
OBJECTIVE: Pregnancy in women with heart disease is becoming increasingly common. Not all individuals with a known abnormality will be functionally affected to the same degree. We propose that the adequacy of a diseased heart (irrespective of aetiology) to cope with pregnancy and labor can be evaluated by a generic exercise test. STUDY DESIGN: Twenty-four pregnant women with heart disease (mean age 30 years [range 15-41], mean gestation 21 weeks) and 39 healthy pregnant women with no known cardiac disease (mean age 32 years [range 19-41], mean gestation 24 weeks) underwent maximal symptom-limited treadmill cardiopulmonary exercise testing. All participants exercised to their cardiopulmonary limits (respiratory exchange ratio O 1). Cardiac output (CO) was measured at peak exercise using the CO2 re-breathing method. Cardiac power output (CPO) was calculated as the product of CO and mean arterial pressure (MAP). RESULTS: Compared to healthy pregnant women, pregnant cardiac patients had 12% lower peak CPO. Both groups exercised to similar levels (equivalent RER), although exercise duration was not-significantly lower in cardiac patients. Many cardiac patients had normal cardiac function. The results of this test identified those cardiac disease patients with impaired cardiac function, irrespective of the underlying aetiology.
Graph showing individual peak CPO results from healthy pregnant women and pregnant women with heart disease CONCLUSION: Pregnant cardiac patients were found to have a lower exercise cardiac reserve compared to healthy pregnant women. This generic test would enable identification of individual pregnant patients with congenital or acquired cardiac diseases who have limited cardiac reserve to cope with the cardiovascular stresses of pregnancy and labor.
248 PLASMA BRAIN NATRIURETIC PEPTIDE MAY NOT BE USEFUL TO ASSESS POSSIBLE CARDIAC SYMPTOMS DURING PREGNANCY DIANE BARKER1, SIMON WILLIAMS2, GERALD MASON3, HILARY MCLOUGHLIN1, DOMINIK SCHLOSSHAN1, LIP-BUN TAN1, 1 Leeds General Infirmary, Cardiology, Leeds, United Kingdom, 2Wythenshawe Hospital, Regional Cardiology & Cardiac Transplant Unit, Wythenshawe, Manchester, United Kingdom, 3Leeds General Infirmary, Feto-Maternal Medicine, Leeds, Yorkshire, United Kingdom OBJECTIVE: Plasma brain natriuretic peptide (BNP) is a surrogate marker for cardiac function and is used to screen patients for cardiac disease. Breathlessness is a common symptom during pregnancy, usually secondary to physiological changes. However, with increasing maternal mortality from cardiac disease, a pathological basis for any changes in symptoms needs to be considered. We assessed the relationship between plasma N-terminal BNP (NBNP) and hemodynamic indicators of cardiac function during pregnancy. STUDY DESIGN: Seventy pregnant women (age 31 G 6 years, mean gestation 24 weeks) participated in this study. One third of the subjects had heart disease whilst two thirds were healthy controls. Cardiac function was measured by maximal symptom-limited cardiopulmonary exercise testing with non-invasive measurement of peak oxygen consumption (VO2 mx), cardiac output (CO) and cardiac power output (CPO). N-BNP was assayed prior to exercising. Pearson correlation coefficients were used to assess the relationships between plasma BNP and indicators of cardiac function. RESULTS: We found a weak but statistically significant correlation between log BNP and peak CPO (R2 = ÿ0.3, P = 0.01) and between log BNP and peak CO (R2 = ÿ0.29, P = 0.02). This correlation was much weaker than the correlation between log-BNP and CPO in our clinical practice amongst nonpregnant patients (R2 = ÿ0.64, P ! 0.001).
Graph showing correlation between log BNP and CPO in nonpregnant and pregnant subjects CONCLUSION: Although it is well known that BNP can be used as a surrogate marker for cardiac function in usual clinical practice, our preliminary data from this study suggest that BNP may be of much less use in pregnancy. Further studies are required to investigate the usefulness and role of BNP testing in pregnancy.