The following are key points to remember from the 2018 American Heart Association and American College of Cardiology guideline for the management of adults with congenital heart disease (ACHD) with concomitant pulmonary hypertension (PH):¹

1. The 2018 guidelines have developed a new classification system to categorize disease severity in ACHD. Previous guidelines relied solely on anatomic classifications in order to rank severity of ACHD. The new ACHD Anatomic and Physiological classification system was created to incorporate anatomic complexity as well as physiological variables. Anatomic stage is divided into I (simple) to III (complex). Physiological stage is divided into A, B, C, and D, with A correlating to New York Heart Association (NYHA) functional class I symptoms and normal exercise capacity and D correlating to NYHA functional class IV symptoms, severe PH, Eisenmenger syndrome, or refractory end-organ dysfunction.
2. The ACHD guidelines define PH as elevation of mean pulmonary arterial pressure to ≥25 mmHg at rest on right heart catheterization. Pulmonary arterial hypertension (PAH) is defined as mean pulmonary artery pressure by right heart catheterization ≥25 mmHg, pulmonary capillary wedge pressure ≤15 mmHg, and pulmonary vascular resistance (PVR) ≥3 Wood units.
3. PH is a physiological variable in the new ACHD Anatomic and Physiological classification system. ACHD with less-than-severe PH are defined as Physiological Stage C and those with severe PH as Physiological Stage D.
4. Although left-to-right shunting was the initial research model of triggered PAH, PH in patients with congenital heart disease (CHD) can be caused by, or associated with, pulmonary venous hypertension (post-capillary), parenchymal or restrictive lung disease, thromboembolic disease, portal hypertension, or toxin exposure.
5. ACHD with PH, particularly PAH, have a poorer prognosis than ACHD with similar histories and anatomic abnormalities who do not have PH. PH is associated with increased risk of perioperative morbidity and mortality in ACHD who are undergoing non-cardiac surgery.
6. Patients with complex CHD (including those with PAH) have generally better outcomes when cared for in an integrated, collaborative, and multidisciplinary program. Because of the complexity of PAH in the setting of CHD, PH expertise is recommended as one of the key services required for an ACHD program. Patients with CHD and PVR ≥2.5 Wood units should be assessed in collaboration with ACHD cardiologists and PH expert providers to develop a management plan (Class I, Level of Evidence [LOE] B-NR).
7. Adults with septal or great artery shunts should have periodic screening to assess for PH with echocardiogram (Class I, LOE B-NR). In patients with CHD who have or who are at risk of developing right ventricular (RV) enlargement and dysfunction, serial cardiac magnetic resonance imaging is recommended for quantitative assessment of RV size and function (Class I, LOE B-NR).
8. Cardiac catheterization is the gold standard to assess pulmonary vascular hemodynamics and is recommended for adults with septal or great artery shunts and clinical signs, symptoms, or echocardiographic findings suggestive of PH (Class I, LOE B-NR). Cardiac catheterization is also beneficial to assess suitability prior to closure in these patients (Class I, LOE B-NR). For those who continue to have a net left-to-right shunt sufficiently large enough to cause physiological sequela (e.g., pulmonary-systemic blood flow ratio ≥1.5) despite elevated pulmonary artery pressures, closure of the defect may prevent exacerbation of PAH.
9. Severe PAH is a contraindication to atrial septal defect (ASD) closure, and its presence must be accurately excluded prior to considering closure. ASD closure should not be performed in adults with pulmonary artery systolic pressure greater than two-thirds systemic or PVR greater than two-thirds systemic (Class III, LOE C-LD).
10. Predictors for development of PAH after shunt closure include anatomic defects (complete atrioventricular septal defect, sinus venosus defect, large defect (ASD >2 cm, ventricular septal defect [VSD] >1 cm, and patent ductus arteriosus >0.6 cm) and concomitant ACHD Anatomic and Physiological II and III abnormalities, pulmonary-systemic blood flow ratio >3 and/or pulmonary artery systolic pressure >40 mm Hg, Down syndrome, older age at repair, and female sex.
11. Right-to-left shunting through septal defects or connections between the great arteries associated with sub-pulmonary ventricular hypertension may be diagnosed as Eisenmenger syndrome. However, one should be aware that other conditions may cause right-to-left shunting for reasons other than shunt-related PAH and thus may require different treatment options (e.g., streaming or sub-pulmonary chamber outflow obstruction).
12. In symptomatic adults with Eisenmenger syndrome associated with ASD or VSD, bosentan is beneficial (Class I, LOE A). It is reasonable to use phosphodiesterase type 5 inhibitors (sildenafil and tadalafil) to treat symptomatic adults with ASD, VSD, or great artery shunt and Eisenmenger syndrome (Class IIa, LOE B-NR). In symptomatic adults with Eisenmenger syndrome, combination therapy with bosentan and phosphodiesterase type 5 inhibitors is reasonable if symptoms do not improve with either medication alone (Class IIa, LOE B-R).
13. Patients with CHD with PAH are at high risk of thromboembolic events. Estrogen-containing contraceptives are potentially harmful for these women and are given a Class III indication for harm (Class III, LOE B-NR).
14. Women with severe PAH or Eisenmenger syndrome have extremely high risk of maternal morbidity and mortality. In collaboration with an ACHD cardiologist, these women should be counseled against becoming pregnant or, if pregnant, be given the option of terminating the pregnancy (Class I, LOE C-EO).
15. Adverse effects of PH therapies in patients with CHD with PH may differ from those noted in other patients because of concomitant multiorgan and vascular effects from long-standing congenital heart and vascular disease.

The following are key points to remember from the 2018 European Society of Cardiology guidelines for the management of cardiovascular diseases during pregnancy:²

1. All women of childbearing age with cardiovascular disease should undergo disease-specific risk assessment before and after conception using the modified World Health Organization (WHO) classification of maternal risk (Class I, LOE C).
2. PH has many causes and is defined by an elevation in mean pulmonary artery pressure ≥25 mmHg at right heart catheterization. PAH describes a subset of PH characterized by a left ventricular filling pressure ≤15 mmHg and a PVR >3 Woods units.
3. Pregnancy appears safer today than in the past, but mortality remains high in women with PAH (16-30% maternal mortality). There is also increased fetal and neonatal mortality (0-30%), particularly if there is preterm delivery, reduced maternal cardiac output, and/or hypoxemia. Patients with PAH are considered modified WHO IV and exhibit extremely high risk of maternal mortality or severe morbidity. Pregnancy is not recommended in these patients (Class III, LOE B). Fertility treatment is contraindicated in women with modified WHO IV.
4. Echocardiography is key for diagnosis, and other diagnostic steps are planned individually in concordance with the 2015 European Society of Cardiology and European Respiratory Society PH guidelines.³ Right heart catheterization is recommended if there is diagnostic uncertainty and to assist important therapeutic decisions. This can be performed during pregnancy but with strict indications and should be performed in a specialist center (Class I, LOE C).
5. In women with moderate or high risk of pregnancy complications (modified WHO II-III, III, and IV), pre-pregnancy counseling, management during pregnancy, and delivery should be conducted in an expert center by a multidisciplinary pregnancy heart team (with a PH expert included) (Class I, LOE C).
6. Each pregnant patient with PH should have a care plan by a multidisciplinary pregnancy heart team. This individualized plan will require regular follow-up (often weekly in the third trimester). A full assessment, including oxygen saturation and assessment of RV function, should occur at each visit. Bed rest may be required in symptomatic patients and additional risk factors (such as air travel) avoided.
7. Bosentan and other endothelin receptor antagonists are associated with embryopathy and should be discontinued, taking into account the risks of withdrawal unless doing so would greatly increase maternal risk. Sildenafil, calcium channel antagonists (in vasodilator responsive patients), and intravenous therapies can be continued. Thromboembolism is a major risk, and anticoagulation should be considered. Diuretics may be needed in patients with heart failure, and iron deficiency should be treated.
8. A detailed delivery plan, including the optimal mode and timing of delivery, post-partum need for intensive care, and mechanical support should be decided by the pregnancy heart team. Regional anesthesia is usually favored over general anesthesia. Strict fluid balance and optimization of RV function are important determinants of a good outcome. Patients remain at high risk for many months post-delivery, and individualized counseling is needed to discuss the need for ongoing therapies and the avoidance of future pregnancies. Therapies should not be discontinued in the early post-delivery period.
9. In pregnant patients with Eisenmenger syndrome, systemic vasodilation increases the right-to-left shunt and decreases pulmonary flow, leading to increased cyanosis and low cardiac output. Maternal mortality is high (20-50%), and termination of pregnancy should be discussed; termination also carries risks. Maternal hypoxemia is the most important predictor of fetal outcome.
10. In addition to the management principles of patients with PAH discussed above, patients with Eisenmenger syndrome are at increased risk of thrombocytopenia, deficiencies in vitamin K-dependent clotting factors, and bleeding. Caution is needed if prescribing antiplatelet therapy or low molecular weight heparin.
11. In patients with Eisenmenger syndrome, care should be exercised when prescribing drugs that could lead to sudden systemic vasodilation or a risk of paradoxical air embolism, such as intravenous therapies.
12. Caesarean delivery should be considered for patients with severe PAH as well as patients with Eisenmenger syndrome (Class IIa, LOE C). Labor should be induced at 40 weeks gestation in all women with cardiac disease (Class IIa, LOE C).
13. Genetic counseling and parental testing should be considered in cases of known carrier status of hereditary PAH (Class IIa, LOE C).
14. Low molecular weight heparin in therapeutic dose is recommended for pregnant patients with chronic thromboembolic PH (Class I, LOE C).
15. In treatment-naive patients with PAH who are pregnant, initiating treatment should be considered (Class IIa, LOE C). Food and Drug Administration pregnancy categories A to X for medications are no longer used; decision-making should be based on clinical safety data in guidelines as well as referencing www.safefetus.com prior to starting any medication.

References

1. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiolo-gy/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Car-diol 2018;Aug 10:[Epub ahead of print].
2. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018;39:3165-241.
3. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treat-ment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the Eu-ropean Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 2016;37:67-119.

Keywords: Calcium Channel Blockers, Cardiac Catheterization, Contraceptive Agents, Cesarean Section, Critical Care, Ductus Arteriosus, Patent, Cyanosis, Diuretics, Endothelin Receptor Antagonists, Cardiac Output, Cardiac Output, Low, Down Syndrome, Follow-Up Studies, Follow-Up Studies, Estrogens, Eisenmenger Complex, Blood Coagulation Factors, Blood Pressure, Anesthesia, General, Embolism, Air, Hypertension, Infant Mortality, Hypertension, Portal, Hypertension, Pulmonary, Heart Septal Defects, Heart Septal Defects, Ventricular, Heart Septal Defects, Atrial, Heart Failure, Heparin, Low-Molecular-Weight, Levonorgestrel, Oxygen, Maternal Mortality, Magnetic Resonance Imaging, Phosphodiesterase 5 Inhibitors, Pulmonary Wedge Pressure, Pregnancy Trimester, Third, Pulmonary Artery, Risk Assessment, Pregnancy Complications, Risk Factors, Sulfonamides, United States Food and Drug Administration, United States Food and Drug Administration, Prognosis, Vascular Resistance, World Health Organization, Thrombocytopenia, Vasodilation, Thromboembolism, Echocardiography, Arterial Pressure, American Heart Association, Pregnancy, Water-Electrolyte Balance, Vasodilator Agents, Vitamin K, Bed Rest, Anesthesia, Conduction, Genetic Counseling

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