Pregnant pause: Evaluating pregnant women with heart disease

December 24, 2003


In the forum of this summer, doctors discussed the case of a 34-year-old woman who presented at the emergency department with sudden-onset chest pain. She had just had a baby, one week earlier. Following a full examination, diagnostic tests including an ECG and a 12-hour observation period, the patient was discharged. A week later she was brought back by ambulance after suffering a cardiac arrest; unfortunately, she died. Autopsy showed a spontaneous dissection of the left anterior descending coronary artery.

Although extremely rare, this case demonstrates that emergency physicians and cardiologists would not usually consider coronary artery dissection as a possible diagnosis in a patient such as this. In the minds of doctors, pregnant women and heart disease do not go together.

"Cardiologists are scared stiff of pregnant women, because they don't see many of them," says Dr Celia Oakley (Hammersmith Hospital, London, UK), chair of the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology.

But women with heart disease do conceive, and others develop cardiac problems during pregnancy or afterward, as the above story illustrates. And although these scenarios are very rareonly 1% of women seen in obstetric referral centers have cardiac conditions, and the frequency in the unreferred population is much lessit is important that these women are identified because they require special care.

Cardiologists are scared stiff of pregnant women, because they don't see many of them.

The potential problems of women of childbearing age who also have heart disease or who subsequently develop it are numerous. For starters, what kind of contraception should they use if they don't want to become pregnant, given that many methods may be risky for them? If they want to try to conceive, how risky is it, either for them or for the baby, and at what age should they try? Should they have surgery to correct any defects before attempting to conceive? If they become pregnant, do they need to continue treatment for their heart disease, and if so, how will this affect the growing fetus? If they have congenital heart disease or some other inherited disorder with cardiac manifestations, what are the risks of the child being affected? What if they develop further complications during pregnancy, such as preeclampsia? What kind of birth should they opt for? Can they breast-feed?

The subject of pregnancy and heart disease was discussed at a session at the European Society of Cardiology meeting in Vienna in September, at which Oakley was one of the speakers. She is also the lead author of a consensus document on the subject published in the European Heart Journal earlier this year; this is to be made available as a pocket guide before the end of the year[1].

High risk: Women who should not get pregnant

All the experts agree that women with certain high-risk conditions should avoid pregnancy altogether, because of the high risk of maternal death. These include pulmonary hypertension, whether with septal defects (as in Eisenmenger's syndrome) or without, severe left ventricular outflow tract obstruction, cyanotic heart disease, and Marfan syndrome with aortic root involvement. Severe pulmonary hypertension carries the highest risk of maternal mortality (30% to 50%) because of life-threatening rises in pulmonary vascular resistance that develop due to physiological changes occurring during pregnancy.

Dr Helmut Baumgartner

At the ESC session, Dr Helmut Baumgartner (University of Vienna, Austria) criticized cardiologists for failing to broach the subject of contraception [see contraception sidebar]. "Many cardiac patients are not correctly informed about their individual risk with regard to pregnancy and the most appropriate advice. Patients don't ask for advice, and cardiologists don't offer advice. It is our duty, particularly with congenital-heart-disease patients, to bring up the topic of pregnancy and contraception," he stressed.

And another speaker who runs a specialized maternal cardiac clinic, Dr Jack Colman (University of Toronto, ON), said preconception counseling is essential, especially for those women with the above-mentioned high-risk conditions. "Doctors should stress the extreme pregnancy-associated risks," he says.

Dr Jack Colman

In situations where women with high-risk conditions present already pregnant, the cardiologist will usually advise termination, Colman says. "We try to provide them with information on the risks and let them make their own decision." There are many things to think about, he says. A high risk of maternal mortality has implications not just for the mother but also for any potential baby and siblings at home. And even if she survives the pregnancy, the woman may have a reduced life expectancy or suffer from limited physical capacity, both of which have obvious implications for children. There are also risks to the fetus to consider in many cases, and the risk of passing on a congenital defect to the offspring. For example, Marfan syndrome is an autosomal dominant condition, which will confer a 50% risk of recurrence in any offspring.

But despite all of these risks, some of these women do choose to conceive and/or continue their pregnancies, Colman says. "Some patients are risk averse," he explains, "but some will take any risks. You have to remember that some women with congenital heart disease have successfully gone through lots of traumas, and often they want to normalize their lives. They reason that they have endured difficulties before and it's been okay, so they hope they can do it again."

It is our duty, particularly with congenital-heart-disease patients, to bring up the topic of pregnancy and contraception.

When women with these conditions present late in pregnancy, meticulous monitoring is required, including early hospitalization and, where appropriate, supplemental oxygen and anticoagulation, he explains. Labor and delivery are often modifiedfor example, by induction of labor. Vaginal delivery is recommended in most cases, the exceptions being aortic dissection and Marfan syndrome with dilated aortic root, as well as women taking anticoagulants who have failed to switch from warfarin to heparin at least two weeks before labor [see sidebar on anticoagulation]. These women are referred for cesarean section.

For the most part, expect a good outcome

For most women with heart disease, however, the outcome will be good, Colman says. Women with congenital heart disease make up the majority of pregnant women seen by cardiologists, a trend set to continue because patients with congenital heart disease are now living longer than they used to. In 2000, 60% of those living with these conditions in North America were over the age of 20, and the proportion of congenital-heart-disease patients who are adults will continue to increase for several more decades before it levels off, Colman told heartwire .

As a result, most pregnant women with heart disease tend to be looked after by cardiologists who specialize in congenital heart disease, he explains. Colman and colleagues see about 100 pregnant women with heart disease every year and, he says, "My role is usually to reassure during pregnancy."

My role is usually to reassure during pregnancy.

Women with rheumatic heart disease form the next largest group, and doctors are also beginning to see more pregnant women with coronary artery disease, due to the trend in delaying pregnancy and childbirth in Western nations.

The physiological changes that occur during pregnancy are what cause many of the problemshormonally mediated alterations in blood volume, red cell mass, and heart rate result in a 50% increase in cardiac output, increased left ventricular mass, and decreased peripheral vascular resistance and blood pressure, peaking early in the third trimester. Following delivery, there is a further transient increase in cardiac output, but most of the physiologic changes resolve by the second week postpartum, although a complete return to normal may not occur for six months.

For those with congenital heart disease, outcome is related to functional NYHA class, the nature of the disease, and previous cardiac surgery. Colman says. Where appropriate, surgical correction of congenital defects is advisable before a patient contemplates pregnancy. Although this does not completely eliminate problemsand can in certain circumstances cause other complicationsit is generally the best approach.

However, this is not always possibleoften women with congenital heart disease will turn up already pregnant. Patients with noncyanotic congenital heart disease tend to have a good prognosis in pregnancy, but cyanotic patients may decompensate as the pregnancy progresses.

Those with small or moderate shunts without pulmonary hypertension or mild or moderate valve regurgitation benefit from the decrease of systemic vascular resistance that occurs during pregnancy, Colman says. Patients with mild or moderate left ventricular outflow tract obstruction also seem to do well, as do most patients who have had cardiac surgery early in life without mechanical valves. However, management of women with mechanical valves is very tricky during pregnancy because these women need to continue taking anticoagulants [see sidebar on anticoagulation during pregnancy].

With congenital heart disease and other conditions, "it is important to clarify the nature of the maternal cardiac problem at the beginning of pregnancy and then assess the individual risk for that woman," Colman stresses. This step is key to a good outcome, he says, and along with colleagues Dr Samuel Siu and Dr Mathew Sermer, also of the University of Toronto, Colman has devised a risk index based on a prospective study they conducted[2].

A risk index to predict complications

Using data from their study[2], the Canadian cardiologists produced a risk index to predict a woman's chance of having cardiac events or neonatal complications. They identified four maternal risk factors, or clusters of maternal characteristics, that could increase a woman's risk for heart complications:
1. A prior cardiac event (including stroke, transient ischemic attack, or arrhythmia).
2. Cyanosis or poor functional class.*
3. Left heart obstruction.
4. Systemic ventricular dysfunction.
One point was assigned for each risk factor present. No pregnancy received more than 3 points. Women with 0 points had an estimated risk of a cardiac event of 5% (low risk), those with 1 point had a risk of 27% (intermediate risk), and those with more than 1 point had a 75% risk of having a cardiac event (high risk). All three deaths in the study of 562 women occurred in pregnancies with more than one point.
*This denotes that either cyanosis or poor functional class or both together will add one point. They are combined because if one is present, the second does not add additional risk, so they cannot be listed as separate factors.

"Those at low risk can usually be managed locally, but in consultation with a specialized maternal cardiac clinic and a high-risk obstetrics team to define any issues and make recommendations," Colman says. For those at intermediate or high risk, Colman recommends monitoring in specialized maternal cardiac clinics"one-stop shops" for pregnant women with heart disease.

A full discussion of the management of pregnant women with specific congenital lesions is beyond the scope of this article but is covered in detail in a paper by Colman and Siu published in Progress in Pediatric Cardiology earlier this year[3].

Rheumatic heart disease can easily be missed

Others at risk include those with valvular disease, and Oakley offers a reminder that rheumatic heart disease can easily be missed. "There has been a great change in the case mix of pregnant women with cardiac disease in recent years. We see less and less mitral valve disease in the West, but this is dangerous because it means we often don't think about it." She stresses that clinicians should particularly think about this and other acquired valvular heart diseases when dealing with patients who grew up in developing countries.

We see less and less mitral valve disease in the West, but this is dangerous because it means we often don't think about it.

Wherever possible, doctors should discuss the management of valve disease with the patient before pregnancy, she says, particularly in cases of mitral stenosis <1.5 cm2 suitable for percutaneous mitral valvulotomy or aortic stenosis <1.0 cm2. All patients with valvular heart disease should have an echocardiogram, and close follow-up after the beginning of the second trimester is required. In cases of mitral stenosis with poor functional tolerance, medical treatment can include beta blockers or diuretics, as appropriate. Percutaneous mitral valvulotomy is indicated during pregnancy only if the patient remains symptomatic despite medical therapy, and open-heart surgery should be performed only when the mother's life is at risk; if viable, the fetus should be delivered beforehand.

A full review of the management of valvular disease in pregnancy was published in July in the New England Journal of Medicine[4].

Moving on to discuss patients with established coronary disease, Oakley says these women should be assessed and treated before conceiving. She notes that previous CABG is not a contraindication to pregnancy provided the woman is fit. If beta blockers and calcium antagonists are insufficient to control angina, which can develop in these women during pregnancy, PCI can be performed during the second trimester, with care to minimize the dose of radiation to the fetus.

Hypertension: The most common cardiac complication of pregnancy


In addition to managing specific cardiac problems during pregnancy, doctors need to know that these women are also at increased risk of developing cardiac complications of pregnancy. Obstetricians together with hypertension doctors will easily manage the more common conditions, such as high blood pressure and preeclampsia, but there are many other quite rare cardiac complications that can first arise or manifest themselves during pregnancy.

Hypertension is the most commonly occurring complication of pregnancy and remains one of the leading causes of both maternal and perinatal morbidity and mortality. Management has not changed significantly for many years, because there has been little progress in understanding and there is a lack of an evidence base for the introduction of new therapies, says Oakley.

There are four main classifications.

Chronic or preexisting hypertension. Raised blood pressure (BP) is the main feature of chronic hypertension in a patient diagnosed before, during, or after pregnancy. Such patients are classified as low risk if they have BPs between 140/90 and 160/110; normal physical exam, ECG, and echo; and no proteinuria. Antihypertensive treatment can be continued during pregnancy, but blood pressure does tend to fall in pregnancy, so it may be possible to discontinue drug therapy, says Oakley. High-risk patients have severe hypertension, with evidence of end-organ involvement, a poor obstetric history or comorbidity from renal impairment, diabetes, or collagen vascular disease. These women require frequent assessment of blood and urine chemistry and monitoring of fetal growth. Antihypertensive therapy is indicated for the mother and may also benefit the fetus by securing prolongation of the pregnancy, she explains.

According to Oakley, methyldopa is the first choice for hypertension, at a dose of 750 mg to 4 g per day in three or four divided doses. This is because it has the best safety record, with no evidence of adverse effects in mothers or babies, she says. Beta blockers have also been extensively used in pregnancy, she notes, although there have been reports of fetal growth retardation with atenolol. Some other antihypertensive drugs commonly used in pregnancy are listed in Table 1.

Preeclampsia. This is a more ominous condition that rarely develops before week 20 of pregnancy. Although understanding of this condition has advanced, there is still no specific therapy for it, other than delivery, which is the only definitive treatment for the mother, Oakley says. For the fetus, the question is whether it is more likely to survive in utero or in the nursery, but on the subject of maternal vs fetal mortality, Oakley underscores the difficulties faced by a babyand any other siblings at homewhose mother has died. Recently, a review of low-dose aspirin for this condition showed a 15% reduction in the incidence of preeclampsia[5], and the use of magnesium sulfate for severe preeclampsia is now well established, Oakley says, "although little is understood about its mode of action."

Preeclampsia superimposed on chronic hypertension. This develops in 20% to 25% of women with chronic hypertension. Maternal and fetal mortality used to be high in severe hypertensives with superimposed toxemia due to preeclampsia, but this has been reduced by anticipation and early recognition, Oakley says. As in high-risk hypertension, antihypertensive therapy is indicated.

Gestational hypertension. This is distinguished from preeclampsia by a lack of proteinuria and is termed transient hypertension if blood pressure has returned to normal by 12 weeks postpartum. This condition nevertheless requires close attention, because about half of patients will go on to develop preeclampsia.

Other cardiac conditions that develop in pregnancy

There are other cardiac conditions that can develop during pregnancy or just afterward.

Aortic dissection. Patients with certain conditions, such as Marfan syndrome, and those who have had previous aortic surgery such as coarctation repair, are more prone to aortic dissection. If acute dissection of the ascending aorta occurs, this is a surgical emergency; repair with a composite graft is the procedure of choice. Acute dissection with origin beyond the left subclavian artery and not involving the proximal aorta should be managed medically.

Peripartum cardiomyopathy (PPCM). This is an unexplained left ventricular systolic dysfunction developing in the last month of pregnancy or within five months of delivery in previously healthy women. PPCM also sometimes affects women with preexisting heart disease and diminished cardiovascular reserve but whose LV function has previously been normal.

In the West, there is an incidence of PPCM of between 1 in 10000 to 15000 pregnancies, but in developing countries it is seen more frequently. Doctors in South Africa have reported an incidence of 1 in 1000 pregnancies, and in Haiti the figure is 1 in 350.

The worst cases of PPCM tend to develop during the first few days postpartum and women present with heart failure with marked fluid retention. "These patients often improve if you can keep them going," Oakley says. For this reason, implantation of a device as a bridge to recovery is much preferable to transplantation, she notes. Less severe cases require standard therapy for heart failure, and their LV function should be monitored carefully. Anticoagulants are also important, as the risk of systemic embolism is high.

Colman points out that women who have suffered from PPCM should think very carefully about becoming pregnant again. There is a high relapse rate among these women in subsequent pregnancies, particularly if they have persisting cardiac enlargement or LV dysfunction, he says. In one series of 60 such pregnancies[6], 44% of women with LV ejection fraction <50% developed symptoms of CHF again, and there was an associated mortality rate of 19%. In contrast, symptoms of CHF developed in only 21% of women with LVEF >50%, and none in this group died.

Hypertrophic cardiomyopathy. Women with hypertrophic cardiomyopathy are sometimes first diagnosed during pregnancy, which can cause considerable distress because of the genetic implications. These patients usually tolerate pregnancy well, although serious complicationssuch as CHF, supraventricular tachycardia (SVT), ventricular tachycardia (VT), and syncopecan occur. Beta blockers can be used, as in the nonpregnant state, and dual chamber pacing therapy may be of value in patients with symptoms refractory to medical therapy.

Ectopic beats and sustained arrhythmias. Both ectopic beats and sustained arrhythmias become more frequent during pregnancy, when they may even develop for the first time. In general, these are treated in the same way as outside pregnancy but as conservatively as possible, reserving the definitive treatment for later if it is safe to do so. Digoxin and beta blockers are the antiarrhythmic drugs of choice during pregnancy, but quinidine, adenosine, sotalol, and lidocaine are also "safe," says Colman, although published data on their use during pregnancy are more limited. Electrical cardioversion is also safe in pregnancy.

Other cardiac conditions. Pregnant women also have an increased risk of thrombosis and emboli, as well as adverse events of anticoagulants, when these are being used [see sidebar on anticoagulation].

Table 1. Common cardiac drugs and pregnancy*


Suitability for use in pregnancy

Digoxin Relatively safe
Methyldopa Safe. Recommended for first-line use in hypertension.
Diuretics Use controversial as concern that they might promote preeclampsia. Use only if volume excess; reduces placental blood flow; hyponatremia.
ACE inhibitors Contraindicated. High risk of fetal defects, spontaneous abortion.
Hydralazine Safe. Useful in heart failure during pregnancy.
Beta blockers Relatively safe. No evidence of teratogenicity. Can cause growth retardation, fetal bradycardia, hypoglycemia at birth.
Ca2+ channel blockers IV or short-acting versions can cause maternal hypotension. Fetal abnormalities rare. High levels excreted in breast milk.
Amiodarone Avoid if possible. Causes growth retardation, neonatal hypothyroidism, premature birth.
Adenosine Safe. For immediate conversion of SVTs.
Procainamide Safe. Occasionally used for conversion of atrial or ventricular arrhythmias.

*Adapted from Grubb NR and Newby DE.[7] Also contains information from Reimold SC and Rutherford JD.[4]

And what about the risk to the baby?


As well as the myriad of potential problems in women with heart disease who become pregnant, doctors also need to consider the risks to the fetus. Colman and his colleagues have looked at independent predictors of fetal or neonatal problems and found that several risk factors in pregnant mothers increase the likelihood of such complications[8].

"We found an important interaction between maternal cardiac disease, additional risk factors, and obstetric complications," Colman explains. "Cardiologists may not be aware that the likelihood of fetal and neonatal complications in pregnant women with heart disease is amplified by concomitant obstetric risk factors," he notes. Conventional obstetric risk factors include the age of the mother (risk is high in women aged below 20 or over 35), and a history of premature dilation, ruptured membranes, incompetent cervix, multiple gestation, or cesarean section.

Maternal cardiac factors that increase the risk of fetal/neonatal problems include: NYHA class >2 or cyanosis, left heart obstruction, and anticoagulation during pregnancy. Noncardiac risk factors include smoking.

Cardiologists may not be aware that the likelihood of fetal and neonatal complications in pregnant women with heart disease is amplified by concomitant obstetric risk factors.

Thus, it is vital that cardiologists and their obstetric colleagues work together to manage cardiac patients who become pregnant and those who develop cardiac complications during pregnancy. Specialized maternal cardiac clinics allow high-risk obstetricians to develop an expertise in cardiac problems and enable cardiologists dealing with these patients to gather knowledge about obstetric risk factors, Colman says. However, these are few and far between and are mainly found in urban areas where the population is large enough to warrant their existence. Nevertheless, the many ways in which people can now communicate from remote regions means that no pregnant woman with heart disease should ever be very far from expert advice, provided doctors pick up on her condition in the first place and are able to adequately assess her risks.

For those with existing heart disease, it is vital that they receive preconception counseling and advice on contraception to avoid the pain of unnecessary terminations. Fortunately, for most women, the outcome will be good.

Anticoagulation during pregnancy

At the ESC symposium in Vienna, Dr Pilar Tornos (Hospital General Universitari Vall d'Hebron, Barcelona, Spain) discussed the specific problems of anticoagulation during pregnancy, when hemostatic changes lead to an increased risk of thromboembolic events. "The need to maintain anticoagulation for the mother's safety must be balanced against the risk to the fetus," she says. Anticoagulation must be continued during pregnancy for certain patients, including those with mechanical heart valves, atrial fibrillation, prior VT or pulmonary embolism (PE), and other hypercoagulability states.

The need to maintain anticoagulation for the mother's safety must be balanced against the risk to the fetus.

Vitamin K antagonists, such as warfarin, are safe for the mother and are especially suitable for those with mechanical heart valves, Tornos says. "But they cross the placenta and can be teratogenicdwarfism and nasal hypoplasia have been reportedand they also carry the possibility of causing fetal bleeding. In addition, the warfarin label states that it is contraindicated in pregnancy, which carries with it medicolegal implications." However, there is growing evidence that if a patient can be adequately controlled on a low dose of warfarinless than 5 mg a daythese risks to the fetus are less, Tornos says.

Unfractionated heparin (UFH) does not cross the placenta, but it can cause retroplacental bleeding and premature birth and stillbirth, she notes. Most important, it can cause major maternal bleeding, and "there can be serious maternal consequences in patients with mechanical valves, particularly if adequate anticoagulation is not achieved."

The newer low-molecular-weight heparins (LMWHs) do not cross the placenta and "are likely to become the anticoagulation of choice," although there is as yet a lack of data regarding their use in pregnant women with heart valve prostheses, Tornos says. And she warned there can still be serious maternal consequences in patients with mechanical valves, especially if there is inadequate anticoagulationlast year, for example, the FDA strengthened the label for enoxaparin because some pregnant women with mechanical heart valves who had received enoxaparin for thromboprophylaxis suffered thrombosis leading to maternal and fetal deaths.

But Colman told heartwire that the FDA warning was based on only a few cases and that many cardiologists treating such women will continue to use LMWHs: "There is no good treatment, there are choices, and there are upsides and downsides for each choice This warning has scared people, but the alternatives are not better."

In conclusion, Tornos said, at the present time the best option for those with mechanical heart valves is to use UFH during the first trimester, to reduce the risk of teratogenicity, then move onto warfarin (as long as the dose can be kept at <5 mg), until the ninth month, when heparin must be resumed. For delivery, heparin should be stopped four to six hours beforehand and then resumed six to 12 hours afterward. Breast-feeding is safe, because heparin is not secreted into breast milk and the amount of warfarin secreted is low.

Table 2. Anticoagulation therapy and outcomes during pregnancy

Anticoagulation regime Embryopathy (%) Spontaneous abortion (%) Thromboembolic complications (%) Maternal death (%)
Warfarin throughout pregnancy 6.4 25 3.9 1.8
UFH throughout pregnancy 0 24 33 15
 Low dose 0 20 60 40
 Adjusted dose 0 25 25 6.7
UFH during first trimester, then warfarin 3.4 25 9.2 4.2


Contraception in women with heart disease

Dr Helmut Baumgartner (University of Vienna, Austria) told the ESC session that, in women with heart disease, "the risks of contraception always need to be weighed against the risks of pregnancy and the risks to the fetus." Whether this risk/benefit equation is temporary or permanent is also important, he says. For example, would treatment of cardiac disease in a specific woman alter this balance?

Baumgartner stressed that individual counseling is key, involving cardiologists, obstetricians, psychologists, and geneticists. There are very few women who should be positively discouraged from becoming pregnant, with the exception of those already mentioned. Running through the various forms of birth control, he explained their relative suitability for women with cardiac disease.

Barrier and "traditional" methods. From a cardiovascular point of view, these are safe, but there is a high failure rate in single women under 35, and for these patients this method is not considered a reliable option, he says.

Combined oral contraceptive pill. This is very reliable but causes concern among cardiologists for those with cyanosis, hypertension, atrial dysrhythmias, or thromboembolic disorders (eg, factor V Leiden mutation), he says. It should be avoided in those with documented cardiovascular or coronary artery disease, especially where additional risk factors, such as smoking or diabetes, are involved.

The failure to give adequate family planning advice to women with heart disease can . . . have devastating consequences, such as the requirement for a termination.

Progesterone-only methods. The "mini," or progesterone-only, pill has less thromboembolic risk, but patients must be highly motivated because it must be taken within the same three-hour window every day. The mini pill can also precipitate deterioration in left ventricular function because of fluid overload, Baumgartner notes. A depot injection of progesterone avoids the problems of compliance associated with the mini pill but otherwise has the same risks.

Intrauterine contraceptive devices (IUDs). IUDs are "fairly effective" but can increase the risk of pelvic inflammatory disease and therefore may fuel fears of endocarditis, Baumgartner says. "They are also not recommended for nulliparous women [those who have not had a baby before]." There is also a levonorgestrel-releasing IUD, which is "highly effective" and carries less risk of endocarditis.

Sterilization. Sterilization is the final option. This should be considered only for patients for whom pregnancy is highly dangerous, such as those with Eisenmenger's syndrome. "Also, in some cardiac patients the operation required for sterilization is dangerous in itself," Baumgartner cautioned. Another option is for the patient's partner to undergo vasectomy.

In conclusion, he said: "The majority of patients will tolerate pregnancy and contraception well." But "the failure to give adequate family planning advice to women with heart disease can cause them an unnecessary burden that can have devastating consequences, such as the requirement for a termination."


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