a novel approach to maternal cardiac disease - a generic test to evaluate the functional adequacy of...

245 ACUTE PHASE RESPONSE OF INJURED ENDOTHELIUM LEADS TO HIGH LEVELS OFCIRCULATING ACTIVE VON WILLEBRAND FACTOR IN PATIENTS WITH HELLPSYNDROME PIETER VAN RUNNARD HEIMEL1, JANINE HULSTEIN2, ARIE FRANX3,PETER LENTING2, HEIN BRUINSE4, KAREN SILENCE5, PHILIP DE GROOT2, ROBFIJNHEER2, 1University Medical Center Utrecht, Utrecht, Netherlands, 2Uni-versity Medical Center Utrecht, Haematology, Utrecht, Netherlands,3St. Elisabeth Ziekenhuis, Obstetrics and Gynaecology, Tilburg, Netherlands,4University Medical Center Utrecht, Perinatology and Gynecology, Utrecht,Netherlands, 5Ablynx, Ghent, Belgium

OBJECTIVE: The HELLP syndrome is a severe form of preeclampsia thatcompromises pregnancy. The pathophysiology is largely unknown, althoughendothelial cell activation leading to thrombotic microangiopathy is suggested.Von Willebrand Factor (vWF) mediates platelet binding to the vessel wall byconversion of the vWF A1-domain into a platelet glycoprotein Ib (GpIb)-binding conformation. AU/vWFa-11, a llama-derived nanobody, which pref-erentially recognizes this GpIb-binding conformation in vWF, was used toassess activated vWF. We hypothesize that endothelial cells secrete active vWFin the HELLP syndrome. To investigate if activated endothelial cells are thesource, we measured vWF propeptide-antigen ratios in plasma and theamounts of active vWF that are secreted by stimulated human umbilicalvein endothelial cells (HUVEC) in vitro.

STUDY DESIGN: Circulating active vWF and vWF propeptide-antigen ratioswas measured in healthy pregnant women (n=9), patients suffering frompreeclampsia (n=6) and patients with HELLP syndrome (n=14) at similargestational age. Synthesis of active vWF by cultured HUVECs was investigatedwith and without stimulation (n = 4). Active vWF was determined by ELISA.

RESULTS: In patients with the HELLP syndrome, the levels of active vWFwere increased 2.1-fold compared to healthy pregnant women (p!0.01) and1.6-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 comparedto healthy pregnant women (p!0.01) and 1.4-fold as compared to patientswith preeclampsia (p!0.05).

The amount of active vWF was increased up to 1.5-fold in medium of thestimulated endothelial cells, compared to unstimulated cells (p!0.05).

CONCLUSION: Acute activation of the endothelium in HELLP syndromeresults in increased amounts of active vWF. This might well explain thethrombocytopenia and thrombotic microangiopathy associated with theHELLP syndrome. Inhibition of this active vWF is a potential new approachin the treatment of patients with the HELLP syndrome.

246 EVALUATION OF B-TYPE NATRIURETIC PEPTIDE (BNP) LEVELS IN PATIENTS ATELEVATED RISK FOR PREECLAMPSIA EMILY WHITCOMB1, JAMIE RESNIK1, THOMASMOORE1, ROBERT RESNIK2, SALLY AGENT3, JENNIFER BEEDE4, ALAN MAISEL5, 1Uni-versity of California, SanDiego,ReproductiveMedicine, SanDiego, California,2University of California, San Diego, La Jolla, California, 3University ofCalifornia, San Diego, Health Care, San Diego, California, 4University of Cal-ifornia, San Diego, Cardiology, San Diego, California, 5University of Califor-nia, San Diego, Medicine, San Diego, California

OBJECTIVE: B-Type natriuretic peptide is synthesized in the cardiacventricles in response to volume expansion. We have previously reportedstable and normal BNP levels in normotensive pregnant women, as well astheir progressive rise in mild and severe preeclamptics. The objectives of thisstudy were to expand the preeclamptic patient base, and to compare BNPconcentrations in chronic hypertensive women with and without superimposedpreeclampsia.

STUDY DESIGN: A retrospective study of BNP levels was performed in 167women ranging from first trimester to term, including 112 normal controls, 55preeclamptics and 17 chronic hypertensives. Plasma BNP levels were deter-mined 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 BNPlevels 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 equivalentto chronic hypertensives (19.50, p= NS), but significantly less than allpreeclamptics combined (53.70 pg/ml, p!0.01). There was an increased trendtoward higher BNP values in chronic hypertensives with superimposedpreeclampsia as compared to chronic hypertensives alone (43.65 vs. 19.50pg/ml), but statistical significance was not achieved due to the small samplesize. A BNP cutoff of !56.23 pg/ml had a specificity of 95%, positivepredictive value of 78%, negative predictive value of 81%, and accuracy of80% for the diagnosis of preeclampsia.

CONCLUSION: Mean BNP values are stable throughout normal gestation,and elevated in preeclampsia. BNP level is also elevated in preeclampticscompared to chronic hypertensives, but equivalent between normals andchronic hypertensives. Therefore, elevated BNP levels may become diagnos-tically useful in the presence of superimposed preeclampsia.

247 A NOVEL APPROACH TO MATERNAL CARDIAC DISEASE - A GENERIC TEST TOEVALUATE THE FUNCTIONAL ADEQUACY OF INDIVIDUAL DISEASED HEARTSTO COPE WITH PREGNANCY AND LABOR DIANE BARKER1, GERALD MASON2,DOMINIK SCHLOSSHAN1, HILARY MCLOUGHLIN1, LIP-BUN TAN1, 1Leeds GeneralInfirmary, Cardiology, Leeds, Yorkshire, United Kingdom, 2Leeds GeneralInfirmary, Feto-Maternal Medicine, Leeds, Yorkshire, United Kingdom

OBJECTIVE: Pregnancy in women with heart disease is becoming increas-ingly common. Not all individuals with a known abnormality will befunctionally affected to the same degree. We propose that the adequacy of adiseased heart (irrespective of aetiology) to cope with pregnancy and labor canbe evaluated by a generic exercise test.

STUDY DESIGN: Twenty-four pregnant women with heart disease (mean age30 years [range 15-41],mean gestation 21weeks) and 39 healthy pregnantwomenwith no known cardiac disease (mean age 32 years [range 19-41], mean gestation24 weeks) underwent maximal symptom-limited treadmill cardiopulmonaryexercise testing. All participants exercised to their cardiopulmonary limits(respiratory exchange ratio O 1). Cardiac output (CO) was measured at peakexercise using the CO2 re-breathing method. Cardiac power output (CPO) wascalculated as the product of CO and mean arterial pressure (MAP).

RESULTS: Compared to healthy pregnant women, pregnant cardiac pa-tients had 12% lower peak CPO. Both groups exercised to similar levels(equivalent RER), although exercise duration was not-significantly lower incardiac patients. Many cardiac patients had normal cardiac function. Theresults of this test identified those cardiac disease patients with impairedcardiac function, irrespective of the underlying aetiology.

Graph showing individual peak CPO results from healthy pregnant women andpregnant women with heart disease

CONCLUSION: Pregnant cardiac patients were found to have a lowerexercise cardiac reserve compared to healthy pregnant women. This generictest would enable identification of individual pregnant patients with congenitalor acquired cardiac diseases who have limited cardiac reserve to cope with thecardiovascular stresses of pregnancy and labor.

248 PLASMA BRAIN NATRIURETIC PEPTIDE MAY NOT BE USEFUL TO ASSESS POSSIBLECARDIAC SYMPTOMS DURING PREGNANCY DIANE BARKER1, SIMON WILLIAMS2,GERALD MASON3, HILARY MCLOUGHLIN1, DOMINIK SCHLOSSHAN1, LIP-BUN TAN1,1Leeds General Infirmary, Cardiology, Leeds, UnitedKingdom, 2WythenshaweHospital, Regional Cardiology & Cardiac Transplant Unit, Wythenshawe,Manchester, United Kingdom, 3Leeds General Infirmary, Feto-Maternal Med-icine, Leeds, Yorkshire, United Kingdom

OBJECTIVE: Plasma brain natriuretic peptide (BNP) is a surrogate markerfor cardiac function and is used to screen patients for cardiac disease.Breathlessness is a common symptom during pregnancy, usually secondaryto physiological changes. However, with increasing maternal mortality fromcardiac disease, a pathological basis for any changes in symptoms needs to beconsidered. We assessed the relationship between plasma N-terminal BNP (N-BNP) and hemodynamic indicators of cardiac function during pregnancy.

STUDY DESIGN: Seventy pregnant women (age 31 G 6 years, meangestation 24 weeks) participated in this study. One third of the subjects hadheart disease whilst two thirds were healthy controls. Cardiac function wasmeasured by maximal symptom-limited cardiopulmonary exercise testing withnon-invasive measurement of peak oxygen consumption (VO2 mx), cardiacoutput (CO) and cardiac power output (CPO). N-BNP was assayed prior toexercising. Pearson correlation coefficients were used to assess the relationshipsbetween plasma BNP and indicators of cardiac function.

RESULTS: We found a weak but statistically significant correlation betweenlog BNP and peak CPO (R2 = �0.3, P = 0.01) and between log BNP andpeak CO (R2 = �0.29, P = 0.02). This correlation was much weaker than thecorrelation between log-BNP and CPO in our clinical practice amongstnonpregnant patients (R2 = �0.64, P ! 0.001).

Graph showing correlation between log BNP and CPO in nonpregnant andpregnant subjects

CONCLUSION: Although it is well known that BNP can be used as asurrogate marker for cardiac function in usual clinical practice, our prelim-inary data from this study suggest that BNP may be of much less use inpregnancy. Further studies are required to investigate the usefulness and roleof BNP testing in pregnancy.

SMFM Abstracts S79