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Successful Management and Risk Stratification by Exercise Right Heart Catheterization before Pregnancy in Patient with Pulmonary Arterial Hypertension

Open AccessPublished:January 20, 2023DOI:https://doi.org/10.1016/j.cjco.2023.01.004
      Despite recent advancements in pharmacological treatment, guidelines for patients with pulmonary arterial hypertension (PAH) recommend discussion about maternal risks, and recommend offering pregnancy termination if pregnancy occurs. Preconceptional risk stratification and its association with pregnancy outcomes in women with PAH should be prospectively studied. We present the case of a patient with idiopathic PAH (IPAH) who was risk-stratified using an exercise stress test before pregnancy.

      Case Presentation

      A 40-year-old woman (gravida 3, para 0, two spontaneous miscarriages at 33 years of age) was diagnosed with IPAH at 34 years of age. Right heart catheterization (RHC) at the time of diagnosis revealed pulmonary artery pressure (PAP) of 79/24 mmHg, mean PAP (mPAP) of 50 mmHg, pulmonary vascular resistance (PVR) of 11.7 Wood units, and cardiac output (CO) of 3.9 L/min calculated using the Fick method. We administered PAH-targeted drugs, including tadalafil and ambrisentan. Due to side effects, ambrisentan was replaced with bosentan, which was subsequently replaced with macitentan with the expectation of further hemodynamic improvement (Figure 1). RHC revealed no improvement in hemodynamics by 4 months of treatment (mPAP of 44 mmHg, PVR of 8.2 Wood units, right atrium pressure (RAP) of 8 mmHg, CO of 4.3 L/min; WHO-FC III); therefore, intravenous epoprostenol was initiated and titrated up to 115 ng/kg/min over 12 months, leading to hemodynamic improvement (mPAP of 21 mmHg, PVR of 2.2 Wood units, 4 mmHg RAP of 4 mmHg, CO of 4.8 L/min; WHO-FC I). At the age of 37 years, intravenous epoprostenol was transitioned to subcutaneous treprostinil due to repeated catheter infections. Thereafter, her hemodynamics at rest were stable, and exercise RHC was performed to examine the feasibility of switching from treprostinil to oral selexipag. No exercise pulmonary hypertension was confirmed by exercise stress RHC (mPAP of 28 mmHg during 10.0 L/min of CO at peak exercise, mPAP-CO slope of 2.6, peak Work Rate of 70 Watt, resting heart rate (HR) of 74 bpm and peak HR of 124 bpm), which suggested that switch from treprostinil to oral selexipag was feasible based on the criteria that the parenteral prostacyclin can be safely tapered with the aid of an exercise RHC that was previously reported by our hospital (Supplementary Methods).
      • Takeuchi K.
      • Goda A.
      • Ito J.
      • et al.
      Successful epoprostenol withdrawal and termination with an aid of the exercise stress test in pulmonary arterial hypertension.
      Figure thumbnail gr1
      Figure 1Clinical course from initial treatment to after childbirth
      She reported her decision to become pregnant; therefore, we respected the patient's decision even though we had considered switching from treprostinil to oral selexipag. We informed the patient and her family about the risks of deterioration of PAH at any time during or after pregnancy to aid in making informed decisions. Taking into consideration these clinical courses, alongside exercise stress RHC data, we respected the patient's decision to get pregnant. Macitentan was discontinued due to teratogenicity. Six months later, she became pregnant. Based on the decision of a multidisciplinary team of cardiologists, obstetricians and gynecologists, and anesthesiologists, oral tadalafil and subcutaneous treprostinil were continued during pregnancy. Prophylactic or therapeutic anticoagulation was not used. Regular monthly outpatient clinic visits revealed no abnormalities in symptoms, physical examination, plasma brain natriuretic peptide level (BNP), and electrocardiography. The plasma BNP values remained under 20 pg/mL during pregnancy and delivery. There was no deterioration of the right heart parameters when the echocardiography was performed (e.g., estimated right ventricular systolic pressure 38 mmHg, tricuspid annular plane systolic excursion 30 mm, estimated RAP 0∼5 mmHg). We evaluated RHC in the 32nd week of pregnancy (in the third trimester at age 40) when pregnancy-associated fluid retention became pronounced and the risk of radiation exposure to the fetus was reduced. RHC showed mPAP of 22 mmHg, PVR of 2.9 Wood units, RAP of 3 mmHg, and CO of 5.1 L/min. Four days before delivery, intravenous heparin was administered. We performed an elective cesarean section under spinal anesthesia in the 38th week, according to the schedules of the multidisciplinary team. She delivered a healthy boy weighing 2211 g, with the 1- and 5-min Apgar score of 8 and 9 points, respectively in an operating room with hemodynamic monitoring. After delivery, the patient spent two days in the intensive care unit for close monitoring and volume adjustment. The postpartum period was uneventful. RHC was performed at 9 months after delivery (mPAP of 20 mmHg, PVR of 4.6 Wood units, RAP of 4 mmHg, and CO of 2.9 L/min) without any change of PAH medications. There was no derioration in right heart failure and functional class (i.e., maintenace of WHO-FC I).

      Discussion

      A retrospective study with exercise stress RHC was used to help in pregnancy planning for this patient with PAH.

      Exercise stress test for preconceptional risk stratification

      Exercise stress RHC showed no exercise pulmonary hypertension, indicating mild pulmonary vasculopathy. Therefore, we felt the level of risk with pregnancy was acceptable because pulmonary circulation could withstand the increased CO during the perinatal period. No exacerbation of mPAP or PVR was observed during the increase in CO. At the 20th–24th weeks of gestation, CO increases by 30%–50% and is maintained at a similar level throughout pregnancy because of increased blood volume, increased HR, and reduced systemic vascular resistance, which leads to lower afterload. The right ventricle is overloaded during the third trimester of pregnancy because of cardiovascular stress brought on by a volume shift. The risk of cardiac events, such as right heart failure, is higher during the third trimester of pregnancy, delivery, and postpartum. Pregnancy is the life's cardiovascular stress test.
      • Brislane A.
      • Steinback C.D.
      • Davenport M.H.
      The 9-month stress test: pregnancy and exercise-similarities and interactions.
      Preconceptional exercise stress test has been recommended to identify patients with congenital heart disease at elevated risk for cardiac complications 3 4. A reason for this recommendation might be that the exercise stress test can simulate an increase in CO observed during late pregnancy to confirm the pulmonary vascular response. The normal pulmonary vascular bed is a low-pressure, low-resistance, highly distensible system that can adapt to large increases in blood flow, such as that during physical exercise, with minimal elevation of PAP. Exercise pulmonary hypertension may be indicative of an advanced degree of pulmonary vasculopathy and progressive remodeling, which is a decrease in pulmonary vascular reserve
      • Kovacs G.
      • Herve P.
      • Barbera J.A.
      • et al.
      An official European Respiratory Society statement: pulmonary haemodynamics during exercise.
      .
      Pregnancies with PAH continue to have high maternal mortality rates (11%–25%).
      • Jais X.
      • Olsson K.M.
      • Barbera J.A.
      • et al.
      Pregnancy outcomes in pulmonary arterial hypertension in the modern management era.
      Hence, current guidelines continue to discuss maternal risks and offer pregnancy termination if pregnancy occurs in all patients with PAH. However, recent advancements have improved PAH prognosis and control, allowing an increasing number of young women with PAH to lead nearly normal lives. A recent case series investigating pregnancies in such women evidenced that good outcomes are achievable,
      • Lim K.
      • Chang S.A.
      • Oh S.Y.
      • et al.
      Pulmonary arterial hypertension and pregnancy: single center experience in current era of targeted therapy.
      especially in patients with well-controlled disease, when managed by a multidisciplinary team.

      Management of PAH during pregnancy

      ESC/ERS guidelines recommend that if pregnancy is continued, PAH therapy may have to be adjusted for teratogenicity. Furthermore, compared with non-pregnant women, pregnant women with pulmonary hypertension have a risk of venous thromboembolism that is almost 5-fold higher. Therefore, it is important to perform a risk assessment to determine whether anti-thrombotic therapy should be administered to each patient. In our case, the endothelin receptor antagonist was discontinued in consideration of treprostinil and phosphodiesterase-5 inhibitors due to potential teratogenicity. In addition, since the patient was not at high risk for thrombosis, the anti-thrombotic therapy was not administered except shortly before delivery. Furthermore, premature birth, intrauterine fetal growth retardation, and anomalies require attention.
      The apparent key to successful management of PAH in pregnancy is multidisciplinary team approach, including the preconceptional assessment of pulmonary vascular reserve, pharmacologic management, close management of heart failure, and careful timing of delivery. In the recent era of improved treatment, further accumulation and investigation of cases are expected. Furthermore, prospective international validation of the usefulness of exercise stress testing for preconceptional risk assessment is required.

      Novel Teaching Points

      • The apparent key to the successful management of PAH in pregnancy is a multidisciplinary team approach, including the preconceptional assessment of pulmonary vascular reserve, pharmacologic management, close management of heart failure, and careful delivery timing.
      • ・Exercise stress test may be helpful in preconceptional risk assessment in patients with PAH.

      Uncited reference

      • Lui G.K.
      • Silversides C.K.
      • Khairy P.
      • et al.
      Heart rate response during exercise and pregnancy outcome in women with congenital heart disease.
      ,
      • Ohuchi H.
      • Tanabe Y.
      • Kamiya C.
      • et al.
      Cardiopulmonary variables during exercise predict pregnancy outcome in women with congenital heart disease.
      .

      Acknowledgments

      None.
      Funding Sources
      None.
      Declaration of Interest
      None.

      Supplementary material

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