International Journal of Cardiology 172 (2014) e87–e88
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Successful pregnancy and delivery in a patient with vasoreactive idiopathic pulmonary arterial hypertension Anne-Sophie Sillesen a, Niels Vejlstrup a, Björn Kornhall b, Lars Willy Andersen c, Heidi Sharif d, Jørn Carlsen a,⁎ a
Department of Cardiology, Pulmonary Vascular Program, Copenhagen University Hospital, Rigshospitalet, Denmark Department of Cardiology, Skane University Hospital, Lund, Sweden Department of Anaesthesiology, Copenhagen University Hospital, Rigshospitalet, Denmark d Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark b c
a r t i c l e
i n f o
Article history: Received 16 September 2013 Accepted 21 December 2013 Available online 28 December 2013 Keywords: Pulmonary arterial hypertension Vasoreactivity Pregnancy
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an increase in pulmonary vascular resistance (PVR) ultimately leading to right ventricular failure and premature death. PAH is confirmed by right heart catheterization (RHC) and defined by a mean pulmonary arterial pressure (mPAP) ≥25 mm Hg and pulmonary arterial wedge pressure (PAWP) ≤15 mm Hg. Although prognosis has improved after introduction of specific PAH therapy, PAH remains a serious diagnosis with a poor prognosis [1]. Ten percent of patients with idiopathic PAH (IPAH) present with vasoreactive IPAH manageable by calcium-channel blockers, at least initially [2]. PAH associated with pregnancy is previously reported with up to 50% risk of maternal mortality, although recently reported as reduced to 30% [3]. This decline in mortality suggests improvement in terms of earlier diagnosis and better therapeutic options. However, the risk is persistently high, and avoidance of pregnancy or early foetal termination is advised [1,3]. We present a case report of successful pregnancy and delivery by a 23-year-old woman with vasoreactive IPAH, admitted to Copenhagen University Hospital, Rigshospitalet, Denmark, in gestation week 12. She had been diagnosed with vasoreactive IPAH at the University of Lund, Sweden, at the age of 9, following several episodes of syncopes and dizziness, with a medium pulmonary arterial pressure (mPAP) of 33 mm Hg and a pulmonary vascular resistance (PVR) of 3 Wood ⁎ Corresponding author at: Department of Cardiology 2141, Copenhagen University Hospital, Rigshospitalet, Copenhagen University, 9-Blegdamsvej, 2100 Copenhagen, Denmark. Tel.: +45 35458060; fax: +45 35452931. E-mail address: [email protected] (J. Carlsen). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.041
units. Commencing specific medical treatment with slow release nifedipine 60 mg b.i.d. and anticoagulation therapy with coumadin, she was maintained in a stable condition, modified NYHA functional class I, with no tendency to peripheral oedema or exercise induced dyspnoea. At the age of 18, echocardiography revealed a dilated right ventricle with normal systolic function and a normal right atrial size. Right heart catheterization (RHC) showed a mPAP of 42 mm Hg, with a reduction to 32 mm Hg during vasoreactivity testing with nitrogen oxide (NO). Pulmonary arterial wedge pressure (PAWP) 12 mm Hg, right atrial pressure (RAP) 8 mm Hg, cardiac output (CO) 4.4 L/min, cardiac index (CI) 2.7 L/min/m2 and PVR 6.8 Wood units. At subsequent evaluations she remained stable hemodynamically. In agreement with her general practitioner she had altered the treatment with coumadin to low molecular weight heparin, and maintained treatment with nifedipine after pregnancy. She was asymptomatic at admission and was determined to proceed with the pregnancy despite strong recommendations of an early termination. She had a hemodynamic assessment at gestation week 12: RHC revealed mPAP 44 mm Hg, with a reduction to 37 mm Hg during vasoreactivity testing with NO. PAWP 14 mm Hg, RAP 7 mm Hg, CO 6.8 L/min, CI 4.1 L/min/m2 and PVR 4.4 Wood units. In the following three months she remained asymptomatic with unchanged echocardiographic findings, a stable right ventricle diastolic diameter and tricuspid regurgitation gradient of 50 mm Hg. In order to have an appropriate hemodynamic management, an elective Caesarean section at 38-week gestation was decided upon, in epidural analgesia. The delivery went uneventful except for a transient drop in systolic blood pressure to 60 mm Hg at the induction of anaesthesia reversed by atropine, metaoxedrin, dopamine and ephedrine. Following delivery, the patient had an uncomplicated and uneventful week at the ward. Although telemetry revealed a transient seconddegree atrio-ventricular blockage Type I, she was discharged 19 days postpartum for follow-up in the outpatient unit. Within the next six month she improved and maintained a stable condition, had no physical symptoms of PAH and was continuously classified as modified NYHA functional class I. PAH associated with pregnancy induces a 30% risk of maternal mortality [3]. Physiological changes during pregnancy include a 40% increase in blood volume and cardiac output, a systemic arterial vasodilatation and 20% higher oxygen consumption [3–6]. Maternal hemodynamic decompensation in PAH patients will usually manifest itself
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A.-S. Sillesen et al. / International Journal of Cardiology 172 (2014) e87–e88
in the second trimester as symptoms of chest pain, dyspnoea, syncope and right heart failure [6]. During labour, interaction between hypoxemia, elevated catecholamine levels and intravascular volume shifts will result in increased vasoconstriction of the pulmonary system [3]. The increased demands to the cardiovascular system during pregnancy and labour explain poor pregnancy tolerance in PAH patients [5,6], with most maternal deaths occurring in the immediate days postpartum, usually as a result of right heart failure [3,4,6]. Following delivery, hemodynamic instability is seen due to decreased preload from blood loss, increased pulmonary vascular resistance and reduced ventricular contractility [6]. Spontaneous premature labour is a common complication for PAH patients, why delivery is often scheduled for 32-34th week of gestation [4]. Caesarean section have been considered a potential risk factor, as this type of delivery has a higher mortality rate than vaginal delivery [6]. However, in hemodynamic unstable patients an elective Caesarean section in general anaesthesia is preferred, since it permits more appropriate hemodynamic monitoring and management [4,7]. Jaïs et al. recently described the outcome in 26 pregnant women, diagnosed with PAH, 16 of which had successful deliveries without complications. All 16 patients had well-controlled PAH and half of them were treated with calcium channel blockers. Three women died from right heart failure and one required urgent heart–lung-transplant, all with more severe PAH than those with successful deliveries [8]. Evidence is accumulating regarding successful pregnancies in patients with PAH [4,9]. To increase the possibility of successful delivery and postpartum period, maintaining right ventricular preload, left ventricular afterload, right ventricular contractility and avoidance of increases in PVR during pregnancy is of paramount importance [4]. Furthermore, it is essential to diagnose and treat PAH early under close surveillance, and have a multidisciplinary team approach before,
during and after delivery [3,5,6]. Since less severe hemodynamic impairment and lower BMI seem to characterize the vasoreactive IPAH phenotype [9] it appears that in selected patients with vasoreactive IPAH pregnancy might be an option. No doubt pregnancy carries a risk of progression of PAH, and more knowledge is needed in order to characterize patients that successfully can undergo pregnancy. Informed consent was obtained from the patient. The study protocol conforms to the ethical guidelines of the 1975 declaration of Helsinki.
References [1] Galie N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J Oct 2009;30(20):2493–537. [2] Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation Jun 14 2005;111(23):3105–11. [3] Stewart R, Tuazon D, Olson G, Duarte AG. Pregnancy and primary pulmonary hypertension: successful outcome with epoprostenol therapy. Chest Mar 2001;119(3):973–5. [4] Monnery L, Nanson J, Charlton G. Primary pulmonary hypertension in pregnancy; a role for novel vasodilators. Br J Anaesth Aug 2001;87(2):295–8. [5] Tacoy G, Ekim NN, Cengel A. Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment. J Obstet Gynaecol Res Apr 2010;36(2):414–7. [6] Smith JS, Mueller J, Daniels CJ. Pulmonary arterial hypertension in the setting of pregnancy: a case series and standard treatment approach. Lung Apr 2012;190(2):155–60. [7] Titia PE, Ruys JC, Roos-Hesselink Jolien W. Pregnancy and delivery in cardiac disease. J Cardiol 2013;61:107–12. [8] Jais X, Olsson KM, Barbera JA, et al. Pregnancy outcomes in pulmonary arterial hypertension in the modern management era. Eur Respir J 2012;40(4):881–5. [9] Zimmerman P, Brown L, Schmidt J, et al. Pulmonary arterial hypertension: is there a vasoreactive phenotype? Am J Respir Crit Care Med 2009;179:A2650.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Successful pregnancy and delivery in a patient with vasoreactive idiopathic pulmonary arterial hypertension Anne-Sophie Sillesen a, Niels Vejlstrup a, Björn Kornhall b, Lars Willy Andersen c, Heidi Sharif d, Jørn Carlsen a,⁎ a
Department of Cardiology, Pulmonary Vascular Program, Copenhagen University Hospital, Rigshospitalet, Denmark Department of Cardiology, Skane University Hospital, Lund, Sweden Department of Anaesthesiology, Copenhagen University Hospital, Rigshospitalet, Denmark d Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark b c
a r t i c l e
i n f o
Article history: Received 16 September 2013 Accepted 21 December 2013 Available online 28 December 2013 Keywords: Pulmonary arterial hypertension Vasoreactivity Pregnancy
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an increase in pulmonary vascular resistance (PVR) ultimately leading to right ventricular failure and premature death. PAH is confirmed by right heart catheterization (RHC) and defined by a mean pulmonary arterial pressure (mPAP) ≥25 mm Hg and pulmonary arterial wedge pressure (PAWP) ≤15 mm Hg. Although prognosis has improved after introduction of specific PAH therapy, PAH remains a serious diagnosis with a poor prognosis [1]. Ten percent of patients with idiopathic PAH (IPAH) present with vasoreactive IPAH manageable by calcium-channel blockers, at least initially [2]. PAH associated with pregnancy is previously reported with up to 50% risk of maternal mortality, although recently reported as reduced to 30% [3]. This decline in mortality suggests improvement in terms of earlier diagnosis and better therapeutic options. However, the risk is persistently high, and avoidance of pregnancy or early foetal termination is advised [1,3]. We present a case report of successful pregnancy and delivery by a 23-year-old woman with vasoreactive IPAH, admitted to Copenhagen University Hospital, Rigshospitalet, Denmark, in gestation week 12. She had been diagnosed with vasoreactive IPAH at the University of Lund, Sweden, at the age of 9, following several episodes of syncopes and dizziness, with a medium pulmonary arterial pressure (mPAP) of 33 mm Hg and a pulmonary vascular resistance (PVR) of 3 Wood ⁎ Corresponding author at: Department of Cardiology 2141, Copenhagen University Hospital, Rigshospitalet, Copenhagen University, 9-Blegdamsvej, 2100 Copenhagen, Denmark. Tel.: +45 35458060; fax: +45 35452931. E-mail address: [email protected] (J. Carlsen). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.041
units. Commencing specific medical treatment with slow release nifedipine 60 mg b.i.d. and anticoagulation therapy with coumadin, she was maintained in a stable condition, modified NYHA functional class I, with no tendency to peripheral oedema or exercise induced dyspnoea. At the age of 18, echocardiography revealed a dilated right ventricle with normal systolic function and a normal right atrial size. Right heart catheterization (RHC) showed a mPAP of 42 mm Hg, with a reduction to 32 mm Hg during vasoreactivity testing with nitrogen oxide (NO). Pulmonary arterial wedge pressure (PAWP) 12 mm Hg, right atrial pressure (RAP) 8 mm Hg, cardiac output (CO) 4.4 L/min, cardiac index (CI) 2.7 L/min/m2 and PVR 6.8 Wood units. At subsequent evaluations she remained stable hemodynamically. In agreement with her general practitioner she had altered the treatment with coumadin to low molecular weight heparin, and maintained treatment with nifedipine after pregnancy. She was asymptomatic at admission and was determined to proceed with the pregnancy despite strong recommendations of an early termination. She had a hemodynamic assessment at gestation week 12: RHC revealed mPAP 44 mm Hg, with a reduction to 37 mm Hg during vasoreactivity testing with NO. PAWP 14 mm Hg, RAP 7 mm Hg, CO 6.8 L/min, CI 4.1 L/min/m2 and PVR 4.4 Wood units. In the following three months she remained asymptomatic with unchanged echocardiographic findings, a stable right ventricle diastolic diameter and tricuspid regurgitation gradient of 50 mm Hg. In order to have an appropriate hemodynamic management, an elective Caesarean section at 38-week gestation was decided upon, in epidural analgesia. The delivery went uneventful except for a transient drop in systolic blood pressure to 60 mm Hg at the induction of anaesthesia reversed by atropine, metaoxedrin, dopamine and ephedrine. Following delivery, the patient had an uncomplicated and uneventful week at the ward. Although telemetry revealed a transient seconddegree atrio-ventricular blockage Type I, she was discharged 19 days postpartum for follow-up in the outpatient unit. Within the next six month she improved and maintained a stable condition, had no physical symptoms of PAH and was continuously classified as modified NYHA functional class I. PAH associated with pregnancy induces a 30% risk of maternal mortality [3]. Physiological changes during pregnancy include a 40% increase in blood volume and cardiac output, a systemic arterial vasodilatation and 20% higher oxygen consumption [3–6]. Maternal hemodynamic decompensation in PAH patients will usually manifest itself
e88
A.-S. Sillesen et al. / International Journal of Cardiology 172 (2014) e87–e88
in the second trimester as symptoms of chest pain, dyspnoea, syncope and right heart failure [6]. During labour, interaction between hypoxemia, elevated catecholamine levels and intravascular volume shifts will result in increased vasoconstriction of the pulmonary system [3]. The increased demands to the cardiovascular system during pregnancy and labour explain poor pregnancy tolerance in PAH patients [5,6], with most maternal deaths occurring in the immediate days postpartum, usually as a result of right heart failure [3,4,6]. Following delivery, hemodynamic instability is seen due to decreased preload from blood loss, increased pulmonary vascular resistance and reduced ventricular contractility [6]. Spontaneous premature labour is a common complication for PAH patients, why delivery is often scheduled for 32-34th week of gestation [4]. Caesarean section have been considered a potential risk factor, as this type of delivery has a higher mortality rate than vaginal delivery [6]. However, in hemodynamic unstable patients an elective Caesarean section in general anaesthesia is preferred, since it permits more appropriate hemodynamic monitoring and management [4,7]. Jaïs et al. recently described the outcome in 26 pregnant women, diagnosed with PAH, 16 of which had successful deliveries without complications. All 16 patients had well-controlled PAH and half of them were treated with calcium channel blockers. Three women died from right heart failure and one required urgent heart–lung-transplant, all with more severe PAH than those with successful deliveries [8]. Evidence is accumulating regarding successful pregnancies in patients with PAH [4,9]. To increase the possibility of successful delivery and postpartum period, maintaining right ventricular preload, left ventricular afterload, right ventricular contractility and avoidance of increases in PVR during pregnancy is of paramount importance [4]. Furthermore, it is essential to diagnose and treat PAH early under close surveillance, and have a multidisciplinary team approach before,
during and after delivery [3,5,6]. Since less severe hemodynamic impairment and lower BMI seem to characterize the vasoreactive IPAH phenotype [9] it appears that in selected patients with vasoreactive IPAH pregnancy might be an option. No doubt pregnancy carries a risk of progression of PAH, and more knowledge is needed in order to characterize patients that successfully can undergo pregnancy. Informed consent was obtained from the patient. The study protocol conforms to the ethical guidelines of the 1975 declaration of Helsinki.
References [1] Galie N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J Oct 2009;30(20):2493–537. [2] Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation Jun 14 2005;111(23):3105–11. [3] Stewart R, Tuazon D, Olson G, Duarte AG. Pregnancy and primary pulmonary hypertension: successful outcome with epoprostenol therapy. Chest Mar 2001;119(3):973–5. [4] Monnery L, Nanson J, Charlton G. Primary pulmonary hypertension in pregnancy; a role for novel vasodilators. Br J Anaesth Aug 2001;87(2):295–8. [5] Tacoy G, Ekim NN, Cengel A. Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment. J Obstet Gynaecol Res Apr 2010;36(2):414–7. [6] Smith JS, Mueller J, Daniels CJ. Pulmonary arterial hypertension in the setting of pregnancy: a case series and standard treatment approach. Lung Apr 2012;190(2):155–60. [7] Titia PE, Ruys JC, Roos-Hesselink Jolien W. Pregnancy and delivery in cardiac disease. J Cardiol 2013;61:107–12. [8] Jais X, Olsson KM, Barbera JA, et al. Pregnancy outcomes in pulmonary arterial hypertension in the modern management era. Eur Respir J 2012;40(4):881–5. [9] Zimmerman P, Brown L, Schmidt J, et al. Pulmonary arterial hypertension: is there a vasoreactive phenotype? Am J Respir Crit Care Med 2009;179:A2650.
