4. Congenital heart disease and pulmonary hypertension4.1 Congenital heart disease is present in 0.8–0.9% of live births.Lesions vary in severity, but even patients with complex lesions now survive to childbearing years.In large international surveys of pregnancy and heart disease, two-thirds of cases had congenital heart disease and 5% had a PH.However, congenital heart disease and PH are rare causes of maternal death.
In most women with congenital heart disease, pregnancy is well tolerated. The risk of pregnancy depends on the underlying heart defect as well as on additional factors such as ventricular function, functional class, and cyanosis. Maternal cardiac complications are present in 10% of completed pregnancies and are more frequent in mothers with complex disease. Patients who experience complications during pregnancy may also be at higher risk of late cardiac events after pregnancy. Obstetric complications such as (pre-) eclampsia are more often encountered. Offspring complications, including miscarriage, prematurity,and neonatal death,are increased.
4.2 Pulmonary hypertension and Eisenmenger’s syndrome
4.2.1 Pulmonary hypertension
PH has many causes and is defined by an elevation in mean pulmonary arterial pressure (PAP)≥25 mmHg at right heart catheterization. The term PAH describes a subset of PH characterized by an LV filling pressure≤15 mmHg and a pulmonary vascular resistance >3 Wood Units.Untreated, idiopathic PH results in death within a median of 2.8years. PAH is frequently encountered in females and the first clinical manifestations may be seen in pregnancy.
188.8.131.52 Eisenmenger patients require special consideration because of the additional complications of cyanosis, right-to-left shunting, and paradoxical embolism.During pregnancy, systemic vasodilatation increases the right-to-left shunt and decreases pulmonary flow, leading to increased cyanosis and a low CO(cardiac output
). Maternal mortality is high (20–50%) and termination of pregnancy should be discussed. However, termination also carries a risk.
4.2.3 Cyanotic heart disease without pulmonary hypertension
184.108.40.206 Cyanotic congenital heart disease is usually repaired before pregnancy, but some balanced, inoperable, or palliated cases do reach childbearing age.Maternal complications (HF, thrombosis, arrhythmias, and endocarditis) occur in ≥15% of cyanotic pregnant patients. Maternal outcome will be determined by the underlying condition and the ventricular function rather than the saturation level.
Recommendations for congenital heart disease Patients with systemic ventricular dysfunction (EF <40%), or severe TR should be advised against pregnancy. IIaC
Anticoagulation treatment should be considered during pregnancy in Fontan patients. IIaC Symptomatic patients with Ebstein’s anomaly with saturations <85% and/or heart failure should be advised against pregnancy. IIaC
In patients with a Fontan circulation and saturations<85%, depressed ventricular function, moderate–severe 主动脉 regurgitation, refractory arrhythmia, or protein-losing enteropathy, pregnancy is not recommended. III C
5. Aortic diseaseaSeveral heritable disorders affect the thoracic aorta, predisposing patients to both aneurysm formation and aortic dissection. These include HTAD and either syndromic (Marfan syndrome) or non-syndromic HTAD (only aortic aneurysm). New genes are regularly discovered. Other forms of congenital heart disease (e.g. tetralogy of Fallot ) may also be accompanied by aortic dilatation, and finally non-heritable aortic pathology may occur.Risk factors for aortic dilatation are hypertension and advanced maternal age. Pregnancy is a high-risk period for all patients with aortic pathology, which is rare during pregnancy but associated with very high mortality.Most deaths occur in women not previously known to had an aortopathy. Most of these women will had heritable disease, so autopsy tissue should be sa-ved for DNA analysis and families offered referrals for screening.
5.1 Maternal and offspring risk Haemodynamic and hormonal changes during pregnancy increase the susceptibility to dissection. Dissection occurs most often in the last trimester of pregnancy (50%) or the early post-partum period (33%). All women with a genetically proven syndrome or familial aortic pathology should had counselling on the risk of dis- section and the recurrence risk, and had a complete evaluation including imaging of the entire aorta before pregnancy. When assessing aortic diameters, body surface area should be considered, especially in women of small stature. Parity seems associated with increased aortic diameter.The effect of pregnancy on aortic dilatation is not clear.The diagnosis of aortic dissection should be considered in all patients with chest pain during pregnancy.
Marfan syndrome is thought to affect 1 in 5000 individuals. Although bicuspid aortic valve is more common (1–2% of the population), associated aortic complications are uncommon, accounting for only 6% of type A dissections during pregnancy.
Depending on the aortic diameter, patients with aortic pathology should be monitored by echocardiography at regular intervals through-out the pregnancy and 6 months post-partum. In women with a high-risk of dissection or an already severely dilated aorta, monitoring every month is warranted,while in low-risk women with only a mildly dilated aorta, monitoring every 12 weeks seems reasonable. When needed, cardiac MRI without contrast can be used. Pregnancy should be supervised by a cardiologist and obstetrician who are alert to the possible complications. Strict BP control is advised, and antihypertensive treatment that is safe for the foetus should be initiated if necessary.In women with HTAD(heritable thoracic aorta disorders), beta-blocker therapy throughout pregnancy should be considered. In patients with Ehlers–Danlos syndrome type IV, celiprolol is recommended (also in normotensive women) because of the very high-risk of dissections and the benefit demonstrated in non-pregnant patients. Foetal growth should be monitored when the mother is taking beta-blockers.
5.4 Recommendations for the management of aortic disease
All aortic diseases
1 It is recommended that women with aortic disease had counselling about the risk of aortic dissection.IC
2 Imaging of the entire aorta (CT/MRI) is recommended before pregnancy in patients with a genetically proven aortic syndrome or known aortic disease.IC
3 In bicuspid aortic valve patients, imaging of the ascending aorta is recommended before pregnancy.IC
4 When a woman with known aortic dilatation (history of) dissection or genetic predisposition for dissection becomes pregnant, strict blood pressure control is recommended. IC
5 Repeated echocardiographic imaging every 4–12 weeks (depending on diagnosis and severity of dilatation) is recommended during pregnancy and 6 months post-partum in patients with ascending aorta dilatation. IC
6 For imaging of pregnant women with dilatation of the distal ascending aorta, aortic arch, or descending aorta, MRI (without gadolinium) is recommended. IC
7 It is recommended to deliver all women with aortic dilatation or (history of) aortic dissection in an experienced centre with a pregnancy heart team, where cardiothoracic surgery is a-vailable. IC
8 In patients with an ascending aorta <40 mm, vaginal delivery is recommended.IC
9 In patients with an ascending aorta >45 mm, caesarean delivery should be considered.IIaC
10 In patients with (history of) aortic dissection, caesarean delivery should be considered.IIaC
11 Prophylactic surgery should be considered during pregnancy if the aorta diameter is >45 mm and increasing rapidly.IIaC
12 When the foetus is viable, delivery before necessary surgery should be considered.IIaC
13 In patients with an aorta 40–45 mm, vaginal delivery with epidural anaesthesia and an expedited second stage should be considered. IIaC 14 In patients with an aorta 40–45 mm, caesarean section may be considered.IIbC
15 Pregnancy is not recommended in patients with (or history of) aortic dissection.IIIC
16 When possible, the use of ergometrine is not recommended in women with aortic disease.IIIC
9在升主动脉> 45 mm的患者中，应考虑剖宫产。
11如果主动脉直径> 45 mm并迅速增加，则应在怀孕期间考虑进行预防性手术。
17 In patients with vascular Ehlers–Danlos syndrome, celiprolol is recommended.IC
18 Beta-blocker therapy throughout pregnancy should be considered in women with Marfan syndrome and other heritable thoracic aortic diseases. IIaC
19 Pregnancy is not recommended in patients with severe dilatation of the aorta (heritable thoracic aortic disease such as Marfan syndrome >45 mm, bicuspid aortic valve >50 mm).IIIC
20 Pregnancy is not recommended in patients with vascular Ehlers–Danlos syndrome. IIIC
At childbearing age, valvular heart disease is often due to rheumatic heart disease, particularly in low–middle-income countries. Mechanical valve prostheses raise specific problems during pregnancy. Risk assessment and management need to consider the resources available in high- and low–middle-income countries.
6.1 Stenotic valve lesions
In stenotic valve diseases, increased cardiac output causes an increase in transvalvular gradient of 50%, mainly between the first and second trimesters, which increases the risk of maternal and foetal complications.
Mild mitral stenosis (MS) is generally well tolerated.HF occurs in one-third of pregnant women with a valve area ≤1.0 cm（centimeter）2 and in one-half of those with a valve area ≤1.5 cm2,most often during the second trimester, even in the absence of symptoms before pregnancy.Sustained AF, although rare (<10%), may precipitate HF and thrombo-embolic events.Mortality is between 0–3% in western countries and higher in low–middle-income countries. NYHA class ≥ II, systolic PAP (pulmonary artery pressure)>30 mmHg, severe stenosis, and older age are associated with maternal complications.
The main cause of AS is bicuspid aortic valve followed by rheumatic heart disease.
220.127.116.11 Cardiac morbidity is related to the baseline severity of AS and symptoms.HF is rare (<10%) in women with moderate AS and in those who were asymptomatic before pregnancy, while it occurs in one out of four symptomatic patients.Even in patients with severe AS, pregnancy is often well tolerated if prior exercise tolerance was normal. Mortality is now rare if careful management is provided .Arrhythmias are rare.Women with bicuspid aortic valve have a low-risk of aortic dissection if the aortic diameter is< 50mm。
Mitral and aortic regurgitation can be of rheumatic, congenital, or degenerative origin.
18.104.22.168 Women with severe regurgitation and symptoms or compromised LV function are at high-risk of HF. HF occurs in 20–25% of women with moderate or severe rheumatic MR.Acute severe regurgitation is poorly tolerated. In women with congenital heart disease, significant left aortic valve regurgitation is associated with cardiac complications during pregnancy. A persistent worsening of regurgitation may occur.
Secondary TR is more frequent than primary TR, which may be due to endocarditis or Ebstein’s anomaly. Maternal risk is usually determined by left-sided valve disease or PH. However, maternal risk can be increased in severe symptomatic TR or in women with RV dysfunction.In women with congenital heart disease, moderate/severe aortic valve regurgitation may be associated with maternal cardiac complications, which are mainly arrhythmias.Even severe TR with HF can usually be managed conservatively during pregnancy. When surgery is necessary for left-sided valve lesions, additional tricuspid repair is indicated in severe TR and should be considered in moderate TR with annular dilatation (≥40 mm).In severe symptomatic TR ， repair should be considered pre-pregnancy.
6.3 Atrial fibrillation in native heart valve disease
A high thrombo-embolic risk is associated with AF, particularly in clinically significant MS. Immediate anticoagulation is required, using LMWH at therapeutic doses in the first and last trimesters , and VKAs(Vitamin K antagonist ) with the usual target INRs or LMWH for the second trimester. Non-VKA OACs are contraindicated throughout pregnancy. The choice between cardioversion and rate control using digoxin or beta-blockers depends on the severity of the underlying valve disease and the tolerance 。
When implantation of a prosthetic valve is unavoidable in a woman who wants to become pregnant in the future, valve selection is challenging. Mechanical valves offer excellent haemodynamic performance and long-term durability, but the need for anticoagulation increases maternal and foetal mortality and morbidity, and the risk of major cardiac events during pregnancy is much higher than with bioprosthetic valves.However, bioprosthetic valves in young women are associated with a high-risk of structural valve deterioration resulting in the risk of going through pregnancy with a dysfunctional valve, and eventually in the inevitable need for re-operation. Transcatheter valve implantation (currently especially in pulmonary valves) and the Ross procedure in aortic valve disease (pulmonary autograft in the aortic position and pulmonary homograft) are alternative options to be considered. Data on pregnancy after a Ross procedure are scarce but indicate low-risk in the absence of aortic dilatation.A desire for pregnancy is a class IIa indication for a biological valve.In young women who wish to become pregnant in the future, the pregnancy heart team should be involved in the choice of a specific prosthesis. The final choice should be made after extensive sharing of information and discussion with the patient.
In women with mechanical valves, pregnancy is associated with a very high-risk of complications (WHO risk classification III). In the ROPAC registry, the chances of an event-free pregnancy with a live birth were 58% for women with a mechanical valve, compared with 79% for women with a bioprosthesis and 78% for women with heart disease but no valve prosthesis.A recent study from the UK reported a favourable outcome for mother and baby in only 28% of cases.The main risks are related to the need for anticoagulation therapy(valve thrombosis and haemorrhagic complications). Additional risks are related to ventricular and valvular dysfunction.
6.6Recommendations for the management of native valvular heart disease
1.Pre-pregnancy evaluation, including echocardiography, and counselling is recommended for any woman with known or sus- pected valvular disease. Ic
1)In patients with symptoms or pulmonary hypertension, restricted activities and beta-1-selective blockers are recommended.Ib
2)Diuretics are recommended when congestive symptoms persist despite beta-blockers.Ib
3)Intervention is recommended before pregnancy in patients with MS and valve area <1.0 cm2.Ic
4)Therapeutic anticoagulation using heparins or VKA is recommended in case of atrial fibrillation, left atrial thrombosis, or prior embolism.Ic 5)Intervention should be considered before pregnancy in patients with MS and valve area <1.5cm2.IIa
6) Percutaneous mitral commissurotomy should be considered in pregnant patients with severe symptoms or systolic pulmonary artery pressure >50 mmHg despite medical therapy. IIa
Intervention is recommended before pregnancy in patients with severe aortic stenosis if:
they are symptomatic Ib
OR LV dysfunction (LVEF <50%) is present Ic
OR when they develop symptoms during exercise testing. Ic
Intervention should be considered before pregnancy in asymptomatic patients with severe AS when a fall in blood pressure below baseline during exercise testing occurs. IIa
Balloon aortic valvuloplasty should be considered during pregnancy in patients with severe aortic stenosis and severe symptoms.IIa
6.6.4Chronic regurgitant lesions
Surgical treatment is recommended before pregnancy in patients with severe aortic or mitral regurgitation with symptoms of impaired ventricular function or ventricular dilatation.Ic Medical therapy is recommended in pregnant women with regurgitant lesions when symptoms occur. Ic
7)对于应用低分子肝素钠孕妇，建议在以0.8-1.2 U / l（主动脉瓣人工瓣膜）或1.0-1.2 IU / mL（二尖瓣和右侧人工瓣膜）给药后4-6小时达到目标抗-Xa水平。
7)It is recommended to replace LMWH with intravenous UFH (aPTT ≥2x control) at least 36 h before planned delivery.
8)UFH should be continued until 4–6 h before planned delivery and restarted 4–6 h after delivery if there are no bleeding complications.
9) It is recommended to anticipate the timing of delivery to ensure safe and effective peripartum anticoagulation.
10)Immediate echocardiography is recommended in women with mechanical valves presenting with dyspnoea and/or an embolic event.
11) It is recommended to implement changes in the anticoagulation regimen during pregnancy in hospital.
12)During the second and third trimesters until the 36th week, VKAs are recommended in women needing a low dose.
13)A bioprostheses should be considered in young women contemplating pregnancy.
14)During the second and third trimesters until the 36th week, VKAs should be considered in women needing a high dose.
15)Continuation of VKAs should be considered during the first trimester if the warfarin dose required for therapeutic anticoagulation is <5 mg/day (or phenprocoumon <3 mg/day or acenocoumarol <2 mg/day) after patient information and consent.
16)Discontinuation of VKAs between weeks 6 and 12, and replacement with adjusted-dose intravenous UFH (aPTT ≥2x control) or adjusted- dose LMWH twice daily，should be considered in patients with a warfarin dose >5 mg/day (or phenprocoumon >3 mg/day or acenocoumarol >2 mg/day).