Evaluation Cardiac Function With Echo and BNP in Obstetrical Patients With/Without Cardiac Disease
Evaluation Cardiac Function With Echo and BNP in Obstetrical Patients With/Without Cardiac Disease
Maternal cardiac disease complicates approximately 2 percent of pregnancies and is the
 leading cause of non-obstetrical maternal death. Evaluating cardiac function and dysfunction
 is a complex process requiring skilled clinicians and technology such as ECG, long-term
 monitoring, and echocardiography. A fast, easily obtained blood test for B-type natriuretic
 peptide (BNP) has been developed that can give evidence for heart muscle stretch and
 dysfunction among adults with suspected congestive heart failure. Preliminary experience
 indicates that ventricular dysfunction among OB patients with a history of heart disease can
 be detected with this serum assay. A prospective cohort design consisting of two groups of
 pregnant patients; one with a history of cardiac disease and one without, will be followed
 over the course of the pregnancies and cardiac function will be measured using
 echocardiography and serum BNP. It is hoped that the blood test for BNP will be a reliable
 way to help evaluate OB patients with suspected abnormal heart function.
The incidence of cardiac disease during pregnancy is about 2 percent, and is the leading
 cause of non-obstetrical maternal mortality (1). Women with known cardiac disease and
 suspected cardiac dysfunction have been monitored and evaluated during pregnancy, labor,
 delivery, and post partum with electrocardiogram, long-term rhythm recording, and
 echocardiogram (2). Physiological changes that occur in normal pregnancy include a 43%
 increase in cardiac output, 45 to 50% increase in intravascular volume, 14% decrease in serum
 colloid osmotic pressure, and 28% decrease in the colloid osmotic pressure to pulmonary
 capillary wedge pressure ratio. These hemodynamic changes are believed to maintain adequate
 uteroplacental perfusion, meet the increased oxygen and nutritional demands throughout
 gestation and to protect against sudden hemodynamic changes precipitated by blood loss,
 decreased venous return to the heart, and hypotension (3).

 B-type natriuretic peptide [BNP] is released from ventricular myocardium in response to
 increased ventricular wall tension or stretch. A rapid assay for the measurement of serum BNP
 levels has been developed and is in clinical use for the evaluation of dyspnea related to
 ventricular dysfunction. Serum BNP determination has been described as having a higher level
 of diagnostic accuracy for congestive heart failure as a cause for dyspnea than any other
 single historical, physical, or laboratory finding. When used in conjunction with other
 clinical information, the rapid assay for serum BNP levels is useful in establishing or
 excluding cardiac dysfunction as a cause for acute onset dyspnea (4). During uncomplicated
 pregnancy, serum BNP levels remain the same as levels seen in non-pregnant women. Among
 patients with severe preeclampsia, serum BNP levels have been observed to rise to eight times
 baseline values. Decreased left ventricular ejection fraction and percentage of fractional
 shortening within myocardium was observed in the preeclampsia group compared to the normal
 pregnancy group. The degree of structural and functional change was linearly related to the
 degree of elevation of cardiac natriuretic peptides, including B-type natriuretic peptide
 levels (5).

 Preliminary clinical experience indicates that serum BNP levels obtained by a commercially
 available rapid assay method may be related to the degree of ventricular dysfunction among
 obstetrical patients with acute dyspnea associated with preeclampsia, tocolysis therapy, or
 an underlying history of cardiopulmonary disease (6). The purpose of this protocol is to
 determine prospectively if the measurement of serum BNP levels will correlate with cardiac
 function changes noted on echocardiography and clinically among pregnant women with a history
 of cardiac disease. This group is to be compared to a group of pregnant women with no history
 of cardiac disease.

 Specific Objectives

 The specific objectives of this study include the following:

 1. Establish a cohort of subjects that have a history of heart disease that have a
 diagnosis of cardiac disease, either congenital or acquired, that are pregnant and wish
 to continue their pregnancies through to delivery.

 2. Provide standard obstetrical and cardiac care for these subjects and their fetuses as
 would be indicated by the type, nature, and degree of cardiac disease present from the
 first trimester until after delivery.

 3. Study interventions to include a series of echocardiograms to begin at the time of
 pregnancy diagnosis and proceed until the end of the post partum time frame. These
 studies will take place in the first, second, third trimesters, during labor, two to
 three days after delivery, and six weeks post partum.

 4. With each echocardiogram a serum BNP level will be drawn and measured for correlation
 with the findings noted on echocardiography.

 5. Additional data may be collected if an individual subject were to require additional
 evaluations with echocardiography and/or BNP serum measurements based on clinical
 indications.

 6. Establish a cohort of control subjects with no history of cardiac disease that will have
 echocardiography and serum BNP measurements on the same schedule described for subjects
 with a history of cardiac disease for comparison.

 7. At the completion of the study, a description of physiologic changes in cardiac function
 in the cardiac disease cohort attributable to the subjects' history of cardiac disease
 versus those attributable to the normal physiologic changes of pregnancy will be
 available.

 8. At the completion of the study, a description of changes in the serum levels of BNP will
 reflect cardiac dysfunction.

 Study Design

 This study protocol employs a prospective cohort design. A group of woman with a history of
 cardiac disease and pregnancy will be identified as potential subjects for a study cohort.
 Each potential subject will have an initial assessment of her cardiac history, condition, and
 functional status. A detailed review of her complete medical, surgical, gynecologic, and
 obstetrical history will be obtained as dictated by standard care. Appropriate management for
 each potential subject's medical and obstetrical care will be initiated and undertaken by
 accepted clinical practice. Potential subjects for this cohort will be obstetrical patients
 either cared for directly by or in consultation with the Regional Perinatal Center, Division
 of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, SUNY Upstate Medical
 University.

 A second group of women with no history of cardiac disease and pregnancy will also be
 identified as potential subjects for a control cohort. Each potential subject will also have
 an initial assessment of her medical, surgical, gynecologic, and obstetrical history as
 dictated by standard care. Appropriate management for each potential subject's medical and
 obstetrical care will be initiated and undertaken by accepted clinical practice. Potential
 subjects for this cohort will be obstetrical patients either cared for directly by or in
 consultation with the Regional Perinatal Center, Division of Maternal Fetal Medicine,
 Department of Obstetrics & Gynecology, SUNY Upstate Medical University.

 In addition to the management given as part of standard medical and obstetrical care, each
 subject from both cohorts will have a series of serum BNP measurements and echocardiograms. A
 serum BNP measurement and echocardiogram will be obtained during the first, second, and third
 trimesters, during the course of labor or delivery, 48 to 72 hours post-delivery, and 6 to 8
 weeks post-delivery. Additional studies will be obtained as indicated by standard clinical
 indications. Serum BNP measurements will be made through laboratory services available at
 SUNY Upstate Medical University or Crouse Hospital. Echocardiogram studies will be performed
 at Cardiology P.C. or Pediatric Cardiology at SUNY Upstate Medical University.

 A standard form will be used for each subject to record the results of the serum BNP
 measurements, results of the maternal echocardiograms, and details of the clinical course
 experienced by each subject during the course of her pregnancy, labor, delivery, and
 post-delivery care. Complications related to cardiac function as well as other medical and
 obstetrical complications will also be recorded. Please see the attached standard data
 collection form for details.

 At the conclusion of the study, a comparison will be made between the cohort of women with
 cardiac disease and the cohort of woman without cardiac disease. Specific comparison will be
 made in regard to serum BNP levels, cardiac function as measured on echocardiography, and
 clinical course.

 Statistical Methods, Data Analysis, Interpretation

 There are no prior published reports regarding the use of a rapid serum BNP assay to evaluate
 cardiac function during pregnancy for women with known cardiac disease. From June 1, 2003 to
 May 31, 2004, the Regional Perinatal Center at SUNY Upstate Medical University provided
 obstetrical care and consultation for 55 patients with ICD-9 Code 648.63, cardiac disease in
 pregnancy. Since this is a pilot study, it is anticipated that 20 subjects for the cardiac
 disease cohort can be followed over the course of 1 to 2 years, along with a control cohort.

 Specific measurements that will be obtained by echocardiography and recorded as measures of
 cardiac function will include:

 -  Estimated left ventricular ejection fraction

 -  Estimated left ventricular wall thickness

 -  Estimated cardiac output

 -  Right and left atrial chamber volumes

 -  Right and left ventricular chamber volumes

 -  Estimated pulmonary artery pressure

 Serum BNP measurements will be obtained and recorded as units of picograms/milliliter.
 Approximately 3-4 milliliters of blood is obtained per assay in a standard lavender-top tube
 by standard blood sampling methods. The rapid quantitative assay for BNP will be run on the
 Triage® BNP Test (International) of Biosite Diagnostics, Incorporated, San Diego, California.

 Measurements of serum BNP will be correlated with clinical course and objective measures of
 cardiac function as determined by echocardiography. A linear relationship between the
 elevation of serum BNP measurement and degree of cardiac dysfunction is expected. Elevated
 serum BNP and cardiac dysfunction demonstrated on echocardiogram should also correlate with
 the clinical estimate of NYHA functional status and the degree of congestive failure.
Inclusion Criteria:

 Potential subjects for the cardiac disease in pregnancy cohort:

 1. At least 18 years of age

 2. Cardiac disease as per Clark's Maternal Mortality Associated with Pregnancy: Group 1
 (mortality less than 1%) atrial septal defect, ventricular septal defect, patent
 ductus arteriosus, pulmonic or tricuspid valve disease, corrected tetrology of Fallot,
 bioprosthetic valve, mitral stenosis with NYHA class I and II functional status Group
 2 (mortality 5-15%) mitral stenosis with NYHA class III and IV functional status,
 aortic stenosis, coarctation of aorta without valvular involvement, uncorrected
 tetrology of Fallot, previous myocardial infarction, Marfan syndrome with normal
 aorta, mitral stenosis with atrial fibrillation, artificial valve Group 3 (mortality
 25-50%) pulmonary hypertension, coarctation of aorta with valvular involvement, Marfan
 syndrome with aortic involvement (7)

 3. Other significant cardiac disease not listed above

 4. Other medical disorders, such as diabetes mellitus, chronic hypertension, asthma,
 other endocrine disorders, et cetera, will be acceptable

 5. Diagnosis of a least a single intrauterine pregnancy, multiple gestation acceptable

 Potential subjects for pregnancy without cardiac disease cohort:

 1. At least 18 years of age

 2. Absence of significant cardiac disease, minor cardiac disorders such as mitral valve
 prolapse without arrythmia

 3. Other medical disorders, not directly related to cardiac disease, such as diabetes
 mellitus, chronic hypertension, asthma, other endocrine disorders et cetera, will be
 acceptable

 4. Diagnosis of at least a single intrauterine pregnancy, multiple gestation acceptable

 Exclusion Criteria:

 1. Less than 18 years of age

 2. Non-viable pregnancy such as a threatened spontaneous miscarriage, or ectopic
 pregnancy

 3. Planned termination of pregnancy, either elective or medically indicated based on
 history

 4. Inability to complete informed consent process or participate in the study protocol