Jul 4, 2009 - Among developed countries, valvular aortic stenosis (AS) in pregnant ... Choi), and the Division of Maternal and Fetal Medicine, Department of ...
Usefulness of serial brain natriuretic peptide measurements for managing aortic valve stenosis in pregnancy Sneha Patel, MD, Paul A. Grayburn, MD, Shyla T. High, MD, Jon Rosnes, MD, and James W. Choi, MD
Among developed countries, valvular aortic stenosis (AS) in pregnant women is primarily due to a congenitally bicuspid aortic valve, which occurs in ~1% of the general adult population. Most asymptomatic patients and those with mild to moderate AS can be managed conservatively to full-term pregnancy. However, those with more severe AS with symptoms require more aggressive treatment. The medical management of severe symptomatic AS is not ideal; hence, these women are typically treated with percutaneous balloon valvuloplasty or surgical aortic valve replacement. However, both interventions are associated with inherent risks. In addition, symptoms such as dyspnea and decreased exercise tolerance are commonly exhibited in normal pregnant women, making it difficult to distinguish symptoms associated with normal pregnancy from those caused by AS. We report the first case of congenitally bicuspid severe AS in pregnancy that was successfully managed medically to full term by following consecutive brain natriuretic peptide levels.
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alvular aortic stenosis (AS) is typically the result of degenerative changes in an otherwise normally structured aortic valve, rheumatic valve disease, or a congenitally bicuspid aortic valve. Congenitally bicuspid aortic valves are a fairly common abnormality and may be present in up to 1% of the general population (1). Management of a patient with AS is primarily symptom driven. Asymptomatic patients are typically followed closely for the onset of symptoms or worsening of left ventricular parameters, including left ventricular dysfunction and dilatation. Once either occurs, outcomes are poor without treatment, and there is a high risk of heart failure and sudden cardiac death. Consequently, the American College of Cardiology/American Heart Association guidelines recommend that the aortic valve be replaced for severe symptomatic AS, moderate to severe stenosis at the time of other cardiac surgery, severe AS causing left ventricular systolic failure, or symptomatic combined moderate AS and regurgitation (2). These recommendations are dependent on the definition of “symptomatic.” The classic symptoms of AS are angina pectoris, syncope, and heart failure. However, symptoms are often insidious in onset, and it can be difficult to discern their etiology. This difficulty is especially apparent in pregnancy or when there are other comorbid conditions. Serum brain natriuretic peptide 226
(BNP) levels have been shown to correlate with symptomatic AS (3–6). Importantly, serum BNP levels remain within normal range during uncomplicated pregnancies; however, peptide levels have been shown to increase during pathological pregnancy states that increase wall stress (7). Hence, serum BNP levels may aid in the management of pregnant patients with severe AS and thus help to distinguish between symptoms associated with pregnancy and symptoms associated with AS. Once a pregnant patient is found to have truly symptomatic severe AS that is no longer manageable by medical therapy, the options for management are then limited to aortic valve replacement, percutaneous balloon valvuloplasty, or termination of pregnancy (8). Unfortunately, all three of these options come with risks both to the mother and fetus. Case Report A 31-year-old gravida 1, para 1 Caucasian woman at 20 weeks’ gestation was referred for the evaluation and management of a newly diagnosed bicuspid AS. The patient had a lifelong precordial murmur and had had an echocardiogram Table. Serial BNP measurements and echo Doppler measurements
BNP level (pg/mL)
Mean echo gradient (mm Hg)
Peak echo gradient (mm Hg)
Peak velocity (m/s)
Aortic valve area (cm2)
20
24
38
83
4.5
0.8
23
42
45
79
4.5
0.8
26
10
41
85
4.6
0.8
30
17
40
87
4.7
0.8
35
19
40
90
4.8
0.7
Week of gestation
BNP indicates brain natriuretic peptide.
From the Division of Cardiology, Department of Medicine (Patel, Grayburn, High, Choi), and the Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology (Rosnes), Baylor University Medical Center, Dallas, Texas. Corresponding author: James W. Choi, MD, Cardiology Consultants of Texas, 621 North Hall Street, Suite 400, Dallas, Texas 75226 (e-mail: jameswchoi@ yahoo.com). Proc (Bayl Univ Med Cent) 2009;22(3):226–229
She was started on furosemide 20 mg daily and metoprolol 25 mg twice daily. Initially, her symptoms worsened, an effect believed to be due to volume depletion and lowering of the left ventricular preload. Thus, the furosemide was stopped and the patient returned to her baseline symptoms. She was followed clinically once every 4 to 6 weeks and also had a BNP drawn at every visit. In addition, she had echocardiograms performed every 4 to 6 weeks (Figure 2). Towards the end of her pregnancy, the patient did experience an increase in dyspnea and slightly worsening echocardiographic parameters. However, the lack of significant changes in BNP levels suggested that her increased dyspnea was likely not due to worsening AS. She was able to reach full-term pregnancy at 38 weeks and 6 days and delivered a healthy daughter via cesarean section without complications. At 18-month follow-up, the patient had returned to baseline prepregnancy levels of activity. Echocardiography showed a peak velocity of 4.2 m/s across the aortic valve, with a peak gradient of 71 mm Hg, a mean gradient of 32 mm Hg, and a calculated aortic valve area of 0.6 cm2. Figure 1. Short-axis bicuspid aortic valve at 23 weeks’ gestation.
Discussion It is important to correctly identify symptoms in patients with AS. Accurate identification of the cause of symptoms is especially important in maternal AS, given not only the high risk of maternal and fetal complications without treatment, but also the risks inherent in surgical/interventional management in this population of patients. Early observational studies estimated maternal morbidity in pregnant women with severe AS at approximately 17% and fetal mortality at about 32% (9). More contemporary observational studies, however, suggest lower rates of both maternal and fetal mortality. A recent study by Silversides et al prospectively followed 49 pregnancies in 39 women with congenital AS for obstetric and cardiac events. Approximately 92% of pregnancies involved women with moderate to severe AS. There were three (6%) maternal events: one patient had recurrent atrial arrhythmias with angina, while two patients developed pulmonary edema during pregnancy. One had percutaneous balloon valvuloplasty during pregnancy. In addition, the fetal event rate was 12%, including five premature births (two were complicated by respiratory distress syndrome, and one was born small for gestational age) and one full-term neonate who developed respiratory distress. There were no maternal, fetal, or neonatal deaths in this study (10). Hameed et al reported on valvular heart disease in 66 pregnancies and compared them to control subjects. Twelve patients had varying degrees of AS. There was a higher incidence of maternal complications, including heart failure, arrhythmias, hospitalization, and need for additional medications, in those patients with moderate and severe AS compared with the control subjects. There was also a higher incidence Figure 2. Continuous-wave Doppler across the aortic valve at 23 weeks’ gestation showing a mean gradient of 49 mm Hg. of preterm birth (44%), intrauterine growth performed about the age of 21. Prior to pregnancy, the patient could walk without limitation; however, when pregnant, she became winded after a couple of flights of stairs. Her initial echocardiographic findings included a mean aortic valve gradient of 38 mm Hg, with a peak velocity of 4.5 m/s and a peak echo gradient of 83 mm Hg (Table). By transesophageal echocardiogram, she had an aortic valve area of 0.6 cm by planimetry (Figure 1) and a mildly dilated aortic root measuring approximately 4.0 cm. At the time of initial consultation, several management options were discussed: termination of the pregnancy, percutaneous aortic balloon valvuloplasty, and aortic valve replacement, with a recommendation for continued close observation with medical management. If she became more symptomatic, a percutaneous balloon valvuloplasty would then be recommended.
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retardation (22%), and lower birth weight in this group (11). There was one death in a woman with associated coarctation of the aorta. She died 10 days after a normal cesarean section delivery. In a retrospective study by Yap et al, 35 pregnant women with congenital AS (mean aortic velocity ~3.3 ± 0.9 m/s prior to pregnancy) had 58 pregnancies. They evaluated the frequency of cardiac, obstetric, and perinatal complications. There were a total of 53 completed pregnancies, 3 spontaneous miscarriages, and 2 elective abortions. Important cardiovascular events including heart failure, transient ischemic attack, and arrhythmias occurred in 5 of 53 pregnancies (9.4%). Heart failure requiring treatment occurred in two patients, one of whom required aortic valve replacement. Twelve patients had obstetric complications, including hypertension-related disorders, which were slightly higher in frequency than in the general population. Other obstetric complications were not any more prevalent than in the general population. There was a total of 13 perinatal events in the 53 live births: seven children were premature, and seven were small for gestational age. There were no fetal or maternal deaths in this study (12). Overall, these studies suggest that mortality rates for both mother and infant have improved; however, there remains a high rate of maternal, fetal, and perinatal morbidity in patients with AS who are treated in contemporary settings. Aortic valve replacement is typically indicated for patients with severe symptomatic AS. The classical symptoms are angina, syncope, and heart failure. However, many patients develop more subtle symptoms, such as decreased exercise tolerance or dyspnea on exertion. When these less specific symptoms are present, it is important to further evaluate the potential causes, especially when there are coexisting medical states (4). This is especially the case in pregnant women with AS, who often experience some decrease in exercise tolerance and dyspnea on exertion due to increased blood volume, cardiac output, anemia, and weight gain. Inaccurate diagnosis or management in these patients can lead to significant morbidity and mortality for both the mother and the fetus. Until now, the most commonly used measures of AS severity have been peak aortic velocity and aortic valve area by continuity equation. Studies have shown these measurements to be strongly associated with the presence of symptoms. However, there remains a large area of overlap between symptomatic and asymptomatic patients. Serum BNP levels, which are elevated in states that increase wall stress, have been proposed and studied as additional noninvasive measurements to further assess the severity of AS and aid in the differentiation of symptomatic and asymptomatic AS. Qi et al evaluated the relation of atrial natriuretic peptide (ANP), N-terminal-pro-atrial natriuretic peptide (NT-proANP), BNP, and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) with various hemodynamic measurements in patients with AS. They noted an association of BNP and NTpro-BNP with left ventricular mass index and mean aortic valve gradient in patients with normal left ventricular systolic function and normal left atrial pressure (4). In 2003, Gerber et al noted a strong association between New York Heart Association 228
symptom class and plasma N-BNP, BNP, and ANP levels (5). Specifically, natriuretic peptide levels were significantly higher in patients with class II symptoms (symptoms with ordinary activity) than in patients with class I symptoms (symptoms with greater than ordinary activity). There was also less overlap of natriuretic peptide levels between symptomatic and asymptomatic patients. This finding was further confirmed in a study by Lim, where 70 consecutive patients with severe AS and preserved left ventricular systolic function had BNP evaluations. A BNP >66 detected symptomatic patients with a sensitivity, specificity, and accuracy of 84%, 82%, and 84%, respectively (6). Hence, it has been shown in numerous studies that the severity of AS in patients with normal left ventricular function correlates with plasma BNP levels, which in turn correlate with the presence of symptoms (4–6). This suggests that natriuretic peptide levels may complement current clinical and echocardiographic evaluation to help discriminate between symptoms associated with AS and symptoms associated with comorbid factors. It may also aid in identifying the transition from compensated to decompensated left ventricular function, when not yet apparent by echocardiogram. In an attempt to help differentiate between dyspnea associated with normal changes of pregnancy and that due to AS, we measured serum BNP levels in our patient, in addition to following her clinical symptoms and performing serial echocardiograms. Valvular repair, either surgically or percutaneously, is the optimal manner of management for a young, nonpregnant patient with severe, symptomatic AS. Ideally, women with severe AS should undergo either valvuloplasty or valve replacement prior to becoming pregnant. However, in those women with severe symptomatic AS who become pregnant prior to a definitive surgical procedure, balloon valvuloplasty is the preferred method of nonmedical treatment (12). It can be performed only if the valve is pliable, noncalcified, and without significant associated aortic regurgitation. This procedure is best performed during the second trimester, when complications to the fetus from radiation and contrast agents are reduced. Aortic valve surgery, which poses little risk in the general population, is associated with a high risk of fetal loss (10%–19%) in pregnant patients (13, 14). Hence, it is reserved for those patients in whom percutaneous balloon valvuloplasty is not amenable. If surgery is required, one option is to confirm fetal maturity and delivery, then perform valve repair or replacement afterwards (15). 1. Stout KK, Otto CM. Indications for aortic valve replacement in aortic stenosis. J Intensive Care Med 2007;22(1):14–25. 2. Bonow RO, Carabello B, de Leon AC Jr., Edmunds LH Jr., Fedderly BJ, Freed MD, Gaasch WH, McKay CR, Nishimura RA, O’Gara PT, O’Rourke RA, Rahimtoola SH. ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association. Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). J Am Coll Cardiol 1998;32(5):1486–1588. 3. Otto CM. Valvular aortic stenosis: disease severity and timing of intervention. J Am Coll Cardiol 2006;47(11):2141–2151.
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4. Qi W, Mathisen P, Kjekshus J, Simonsen S, Bjørnerheim R, Endresen K, Hall C. Natriuretic peptides in patients with aortic stenosis. Am Heart J 2001;142(4):725–732. 5. Gerber IL, Stewart RA, Legget ME, West TM, French RL, Sutton TM, Yandle TG, French JK, Richards AM, White HD. Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis. Circulation 2003;107(14):1884–1890. 6. Lim P, Monin JL, Monchi M, Garot J, Pasquet A, Hittinger L, Vanoverschelde JL, Carayon A, Gueret P. Predictors of outcome in patients with severe aortic stenosis and normal left ventricular function: role of B-type natriuretic peptide. Eur Heart J 2004;25(22):2048–2053. 7. Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A. Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women. Am J Obstet Gynecol 2005;193(2):450–454. 8. Oakley C, Child A, Jung B, Presbitero P, Tornos P; Task Force on the Management of Cardiovascular Diseases During Pregnancy of the European Society of Cardiology. Expert consensus document on management of cardiovascular diseases during pregnancy. Eur Heart J 2003;24(8):761– 781.
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9. Arias F, Pineda J. Aortic stenosis and pregnancy. J Reprod Med 1978;20(4):229–232. 10. Silversides CK, Colman JM, Sermer M, Farine D, Siu SC. Early and intermediate-term outcomes of pregnancy with congenital aortic stenosis. Am J Cardiol 2003;91(11):1386–1389. 11. Hameed A, Karaalp IS, Tummala PP, Wani OR, Canetti M, Akhter MW, Goodwin I, Zapadinsky N, Elkayam U. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol 2001;37(3):893–899. 12. Yap SC, Drenthen W, Pieper PG, Moons P, Mulder BJ, Mostert B, Vliegen HW, van Dijk AP, Meijboom FJ, Steegers EA, Roos-Hesselink JW; ZAHARA investigators. Risk of complications during pregnancy in women with congenital aortic stenosis. Int J Cardiol 2008;126(2):240–246. 13. Bernal JM, Miralles PJ. Cardiac surgery with cardiopulmonary bypass during pregnancy. Obstet Gynecol Surv 1986;41(1):1–6. 14. Parry AJ, Westaby S. Cardiopulmonary bypass during pregnancy. Ann Thorac Surg 1996;61(6):1865–1869. 15. Elkayam U, Bitar F. Valvular heart disease and pregnancy part I: native valves. J Am Coll Cardiol 2005;46(2):223–230.
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