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Patients with congenital heart disease and pulmonary arterial hypertension (PAH) are at risk for severe deterioration during pregnancy and delivery. We discuss the case of a 38-year-old woman who presented to the emergency department complaining of dyspnea 6 days after giving birth to her first child via cesare- an section. When PAH is untreated, maternal mortality may exceed 50%, but aggressive PAH treatment offers improved outcomes. Moreover, initial improvement in functional status made with parenteral prostanoids can be maintained with combination oral therapy.
A 38-year-old woman presented to the emergency department (ED) complaining of dyspnea 6 days after giving birth to her first child via cesarean section. Her medical history was unremarkable, and she had no history of cardiopulmonary symptoms, stimulant or diet pill use, or HIV risk factors. Her pregnancy was uncomplicated with the exception of premature rupture of membranes at 24 weeks.
In the ED, the patient was in moderate distress. Her temperature was 36.9°C (98.5°F), pulse was 94 beats per minute, blood pressure was 141/88 mm Hg, respiration rate was 30 breaths per minute, and oxygen saturation was 88% on room air. Her neck veins were markedly elevated, and 3+ lower extremity edema was present. Crackles were heard in the right lung base, and a grade 4/6 holosystolic murmur at the left lower sternal border was detected on auscultation.
A chest radiograph revealed no infiltrates or pulmonary edema but was remarkable for an enlarged cardiac silhouette and prominent pulmonary vasculature. A CT angiogram showed no evidence of pulmonary embolism or parenchymal lung disease, but it did show dilated pulmonary arteries and a dilated right ventricle.
An ECG showed a right bundle-branch block, right ventricular hypertrophy, and right ventricular strain. An urgent echocardiogram showed severely elevated pulmonary artery pressures (PAPs) and a severely dilated right ventricle with severe tricuspid regurgitation. A color flow Doppler echocardiogram showed a large atrial septal defect with bi-directional shunting (Figure 1). Left ventricular function was normal.
The patient was subsequently transferred to the cardiac ICU and was treated with dobutamine at 2 µg/kg/min, and furosemide, 100 mg intravenously every 8 hours. After stabilization, right heart catheterization revealed PAPs that were 90% of systemic normal. Hemodynamic findings are shown in the Table.
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevation of mean PAP, pulmonary vascular resistance (PVR), and reductions in cardiac output. Without treatment, right heart failure and death result.1,2 Prostanoids, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors have been shown to improve hemodynamics, 6-minute walk distance (6MWD), and quality of life in patients with PAH associated with congenital heart disease.3,4 The 6MWD has long been accepted as the most meaningful clinical measure of disease severity and patient response to treatment.
Pregnancy and the peripartum period involve specific risks for patients with PAH because of the associated volume changes. The expanded blood volume in pregnancy results in increased right ventricular dilatation. During labor, excessive pushing can result in abrupt increases in right-to-left shunting, hypoxemia, and paradoxical embolization. Immediately postpartum, autotransfusion of blood from the placenta and slower mobilization of normal third-space fluid of pregnancy can cause dramatic right heart failure.
On a molecular level, endothelin levels are elevated in gravid females and can remain elevated for as long as 3 months postpartum.5 Congenital heart diseases typically cause symptoms in the third trimester; however, the patient described here became symptomatic postpartum, possibly because of markedly diminished activity during her third trimester (as a result of premature rupture of membranes at 24 weeks).
Our patient was in severe right heart failure at presentation. The combination of third-space fluid mobilization and dramatic left-to-right shunting resulted in rapidly progressive right heart failure. Right ventricular inotropic support and pulmonary vasodilatation were achieved with the administration of low-dose dobutamine. Diuresis was accomplished with high-dose intravenous diuretics.
After stabilization with dobutamine and diuresis, marked dyspnea with minimal activity continued and treatment with intravenous treprostinil was initiated. The dosage of treprostinil was rapidly increased to 8 ng/kg/min over several days. The patient's dyspnea improved dramatically, and she was discharged. One month later, the patient had a 6MWD of 340 meters and a Borg dyspnea score of 5, and she was classified as World Health Organization (WHO) functional class III.
About 8 months after the initiation of treatment with treprostinil, the patient was given sitaxsentan, 100 mg orally qd, as adjunct therapy. At this time, her 6MWD was 440 meters, Borg dyspnea score was 0, and WHO functional class was II. After 2 months of combination therapy with intravenous treprostinil and oral sitaxsentan, another right heart catheterization was performed.
Stabilization with treprostinil and diuretics allowed her severely volume-overloaded right ventricle to recover somewhat. The reduction in PVR resulted in further increased left-to-right shunt with falling systemic blood flow. Thus, we considered transition to oral therapy and then closure of the atrial septal defect. Her hemodynamics improved, and she was successfully weaned off prostanoid infusion over about 3 weeks, without deterioration in her status. She then was maintained on sitaxsentan monotherapy for about 4 weeks.
Sildenafil, 20 mg tid, was added in an attempt to optimize her preoperative status. She then underwent successful surgical closure of her atrial septal defect. Postoperatively, her PAH regimen consists of sitaxsentan, 100 mg orally qd, and sildenafil, 20 mg orally tid. Her recent 6MWD was 489 meters with no perceived exertion by Borg dyspnea scale. She is currently classified as WHO functional class I (Figure 2). Follow-up echocardiography 6 months postoperatively indicated an estimated PAP of 68 mm Hg.
Despite continued excellent 6MWD and reassuring WHO functional class, this patient continues to have a very dilated right ventricle and will require close monitoring.
Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107:216-223.
Rich S. Executive summary from the World Symposium on Primary Pulmonary Hypertension; September 6-10, 1998; Evian, France.
Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation. 1999;99:1858-1865.
Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001; 358:1119-1123.
Ken-Dror S, Weintraub Z, Yechiely H, Kahana L. Atrial natriuretic peptide and endothelin concentrations in human milk during postpartum lactation. Acta Paediatr. 1997;86:793-795.