- Email: [email protected]
Cardiac diseases complicating pregnancy
OBSTETRIC ANAESTHESIA
Cardiac diseases complicating pregnancy
Learning objectives After reading this article you should: C understand the cardiovascular adaptations that occur during pregnancy and their impact on key cardiac diseases C know about the causes and recognize the symptoms and signs of acquired cardiac disease in pregnancy C understand the general management principles for rheumatic valve disease, pulmonary hypertension, metallic heart valves and cardiac arrhythmias during pregnancy.
Sheba Jarvis Catherine Nelson-Piercy
Abstract Cardiac disease is the commonest cause of maternal mortality in the UK. A clear understanding of the physiological cardiovascular adaptations that occur in pregnancy is important to understand the impact this may have on women with pre-existing cardiac disease. The incidence of acquired cardiac disease in pregnancy is increasing and it is important to be vigilant of new onset cardiac disease in pregnancy. Social changes, with women waiting longer to start families and advances in reproductive technologies, mean that women may become pregnant at an age when some diseases are more prevalent. Newer therapies and improved understanding of cardiac disease in pregnancy have altered the prognosis in part but the management of cardiac disease remains a challenge in pregnancy. Appropriate referral and multidisciplinary planning with the appropriate specialists are mandatory.
Physiological cardiovascular adaptations during pregnancy and delivery Marked physiological adaptations that occur during pregnancy include an overall increase in blood volume of w30e40%. This adaptation begins at 6 weeks of gestation, reaching a peak between weeks 20 and 24 where it remains constant over the remainder of the pregnancy. Cardiac output increases in parallel, initially as a result of increased stroke volume in the early phases and later as a result of increased heart rate (Table 1). Cardiac output is highly sensitive to changes in maternal position, particularly in the later stages of the pregnancy when the gravid uterus exerting pressure upon the inferior vena cava reduces venous return. As a result the supine position may be associated with a 25% decrease in cardiac output. Reductions in peripheral vascular resistance occur in pregnancy and the reduction in afterload is due to the low-pressure uterine circulation, which is partly mediated by vasoactive prostaglandins and enhanced nitric oxide production. In addition, there is reduced response to noradrenaline and angiotensin II during pregnancy. Peripheral vasodilatation leads to reductions in blood pressure in the first and second trimesters and decreased vascular tone sensed by the kidney leads to activation of the renineangiotensin system and vasopressin production which increases plasma volume. Other changes include a reduction in serum colloid pressure by 10e15%, thus making pregnancy a susceptible time to interstitial and pulmonary oedema.
Keywords Cardiac disease; cardiomyopathy; maternal mortality; peripartum; pregnancy
Introduction Cardiac disease in pregnancy is an important cause of maternal morbidity and mortality. In the UK, cardiac disease in pregnancy is the commonest cause of maternal mortality (Confidential Enquiries into Maternal and Child Health, CEMACH, 2007). Although typically more common in developing countries, the number of maternal deaths associated with cardiac disease has been increasing in the Western world. Maternal mortality appears to be significantly rising in women who have no known history of cardiac disease. In addition, there is a rising incidence of women becoming pregnant who have had corrective surgery for congenital heart defects representing the surgical advances which have allowed women to reach childbearing age.
Physiological cardiovascular adaptations during pregnancy Cardiac output Stroke volume Heart rate Blood pressure Central venous pressure PCWP SVR and PVR Serum colloid oncotic pressure
Sheba Jarvis BSc MBBS MRCP is an Academic Specialist Registrar in Endocrinology within the North West Thames sector. She qualified from Guys, Kings and St Thomas’ School of Medicine. Her research interests include cardiac disease in pregnancy and fertility studies. Conflicts of interest: none declared. Catherine Nelson-Piercy MA FRCP FRCOG is a Consultant Obstetric Physician working at Queen Charlotte’s and Chelsea Hospital and at Guy’s and St Thomas’ Hospitals, London. She studied at King’s College Cambridge and St Bartholomew’s Hospital and trained in Obstetric Medicine. Her particular research interests include thromboembolism in pregnancy, hyperemesis gravidarum, SLE and antiphospholipid syndrome and drugs in lactating women. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
Increases by 40% Increases Increases by 10e20 beats/minute Decrease in first/second trimester Unchanged Unchanged Decreases Decreases by 10e15%
PCWP, pulmonary capillary wedge pressure; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance.
Table 1
305
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
During delivery, important haemodynamic changes occur. Pain and anxiety affect the heart rate and both systolic and diastolic blood pressure increase. Uterine contractions lead to tachycardia with a shift of the blood volume from the uterine to systemic circulation. The first and second stages of labour are associated with an increase in cardiac output of 15% and 50% respectively. The third stage of labour is associated with high risk of pulmonary oedema and requires careful monitoring if the patient has a history of cardiac disease. After birth, autotransfusion from the uterus means that there is a further increase in cardiac output; however this declines rapidly within 1 hour of delivery.
valvotomy or mitral valve replacement for haemodynamically significant mitral valve disease or planning the pregnancy before ventricular function deteriorates.
Aetiology of cardiac disease in pregnancy The aetiology of heart disease may be divided into congenital or acquired causes. The commonest congenital heart diseases include ventricular and atrial septal defects and patent ductus arteriosus. These are mostly diagnosed before pregnancy and are either corrected or are of little haemodynamic significance. Acquired causes of cardiac disease include ischaemic heart disease, rheumatic heart disease and dissection of the aorta. Social shifts with women waiting longer to start families as well as advances in reproductive technologies mean that women are achieving pregnancies at an age when some diseases are more prevalent. A higher prevalence of obesity and diabetes are also important contributors to the increasing incidence of ischaemic heart disease in pregnancy.
Clinical findings during pregnancy Common findings during a cardiovascular examination in pregnancy include features associated with a hyperdynamic circulation such as a bounding pulse, a third heart sound, sinus tachycardia and dependent peripheral oedema. On auscultation of the heart, an ejection systolic murmur is audible throughout the precordium in w90% of women. Electrocardiogram changes may include atrial and ventricular extrasystoles and ST segment depression or T wave inversion in the inferolateral electrocardiogram (ECG) leads.
Specific cardiac conditions Pulmonary hypertension Pulmonary hypertension (PHT) may be due to primary pulmonary hypertension, lung diseases such as cystic fibrosis or connective tissue disorders for example systemic sclerosis or secondary to congenital heart diseases leading to Eisenmenger’s Syndrome (large left to right cardiac shunt that becomes reversed from right to left leading to cyanosis and pulmonary hypertension). The danger for women with PHT lies with the fixed pulmonary vascular resistance and inability to increase pulmonary flow to match cardiac output, which leads to refractory hypoxaemia. In Eisenmenger’s Syndrome, the fall in peripheral vascular resistance exacerbates the right to left shunt, which may worsen cyanosis and hypoxaemia. Therefore peripheral vasodilatation should be avoided and hypotension treated with adequate volume replacement. Over the last decade, newer treatment strategies in PHT, improved recognition of the underlying disease with improved multidisciplinary management have contributed to reductions in maternal mortality in PHT of 17e33%.2 Despite these improvements, maternal mortality remains high and pregnancy remains contraindicated in women with PHT who should be actively counselled against pregnancy. Women who become pregnant should be advised to have a termination and if declined, elective admission for bed rest, oxygen and thromboprophylaxis is necessary. Drug therapies using endothelin antagonists (bosentan), sildenafil and prostacyclin are maintained during this time. At delivery, there is no evidence to support caesarean section over vaginal delivery nor are there clear data favouring a mode of anaesthesia. Women should be managed in the intensive care setting with intra-arterial monitoring, large bore venous access and with multidisciplinary team input where there is an important role for the obstetric anaesthetists. Hypovolaemia, acidosis and systemic vasodilatation should be avoided and therefore caution in the administration of regional anaesthesia and oxytocin is advised. Most women with PHT who die in pregnancy will do so after delivery and within 1 week postpartum. Thromboembolic events and haemorrhage are also contributors to these high rates of mortality.
General approach to cardiac disease in pregnancy Pre-pregnancy counselling is imperative in women with cardiac diseases. Such counselling should involve obstetricians with expertise in high-risk pregnancies, obstetric physicians and/or cardiologists with expertise in pregnancy. Women with congenital heart disease are at increased risk of having a fetus with congenital heart disease. They therefore will require referral for a detailed fetal cardiac ultrasound. Ultimately, the outcome and safety of the pregnancy are related to the presence of and degree of pulmonary hypertension, cyanosis, haemodynamic significance of lesions and the New York Heart Association (NYHA) functional class (based on the level of activity that leads to dyspnoea). Maternal risk is a concept that should be discussed at an early stage with the patient. Predictive indicators of cardiovascular complications during pregnancy listed in Table 2 have been reported from the Canadian study of pregnancy outcomes in women with cardiac disease (CARPREG).1 Adequate counselling will provide information as to when the pregnancy may pose less risks of complication to the mother. Reduction in risk may include correcting defects prior to pregnancy, for example percutaneous
Independent predictors of maternal cardiac events in pregnancy C C C C C
C
Prior cardiac events or stroke Prior arrhythmia New York Heart Association functional class of >II Presence of cyanosis during the baseline antenatal visit Left-sided obstruction heart lesions e.g. mitral stenosis and left ventricular outflow tract obstruction Left ventricular dysfunction
Table 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
306
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
Aortic dissection and Marfan’s disease Aortic dissection in pregnancy is a life-threatening event to both mother and baby and accounts for 3.6% of maternal deaths in the UK. Between 2003 and 2005, CEMACH reported that 14% of maternal cardiac deaths were attributed to aortic dissection demonstrating the need for rapid identification and treatment. Certain conditions predispose to aortic dissection, including connective tissue disorders (Marfan’s disease, Ehlers-Danlos syndrome type IV), congenital heart diseases (bicuspid aortic valve, Turner’s syndrome or aortic coarctation) and hypertension. Additionally, an association between pregnancy and aortic dissection has been reported and the incidence in pregnancy is rising. Approximately 50% of aortic dissections in women under the age of 40 occur in association with pregnancy and most cases occur in late pregnancy or in the early postpartum period. Patients presenting with aortic dissection may do so with a wide array of symptoms and the condition may be missed or symptoms mistaken for other diseases in pregnancy. Delays in treatment of this disease can lead to potentially catastrophic consequences, since the mortality rate increases by 1% each hour if left untreated. Autopsy data presented by CEMACH reported obesity in a third of the cases and undiagnosed Marfan’s disease in a third of cases. Marfan’s disease is an autosomal dominant disease characterized by typical skeletal features of tall stature, high arched palate, scoliosis and lens dislocation. Cardiac involvement occurs in 80% of patients with aortic root dilation, aortic dissection and mitral valve prolapse being well recognized. Pregnancy carries a five-fold increase in aortic complications in Marfan’s disease particularly if the aortic root diameter is more than 4e4.5 cm or there has been a steady increase in aortic root dimensions during the preceding visits. Recommendations for management include monthly echocardiograms throughout pregnancy, monitoring of aortic root dimensions alongside beta-blocker treatment to reduce the risk of aortic dilatation. Women with an aortic root diameter >4.5 cm should be advised to delay pregnancy until after aortic root repair. In those women with stable aortic root measurements of <4 cm, vaginal delivery with epidural analgesia is recommended and pregnancy outcome appears to be good. Caesarean section under regional anaesthesia should be undertaken with dilated aortic root >4 cm and in those women with increased aortic root dimensions during pregnancy. In the emergency setting blood pressure should be rapidly controlled, acute Type A dissections require emergency surgery whilst Type B aortic dissection should be managed medically with the same indications for surgical intervention as outside of pregnancy.
the beginning of pregnancy may still develop exertional dyspnoea, orthopnoea and paroxysmal nocturnal dyspnoea due to pulmonary oedema later in gestation. The risk of pulmonary oedema is greatest immediately after delivery during the third stage of labour because of autotransfusion from the contracted uterus. Management of MS during pregnancy should include close follow-up with echocardiographic monitoring. Symptomatic women in whom there are no contraindications should be prescribed beta-blockers, which reduce the heart rate and allow time for left atrial emptying. If atrial fibrillation occurs it should be converted to sinus rhythm with digoxin, beta-blockers or synchronized direct current cardioversion. At the time of delivery, the supine and lithotomy position should be avoided as should fluid overload. If pulmonary oedema develops it should be treated rapidly, with oxygen, diuretics and diamorphine. In women with severe MS, it may be advisable that they delay pregnancy until correction (balloon, open or closed mitral valvotomy) or replacement of the mitral valve. Women who remain symptomatic despite optimized medical therapy should be considered for balloon valvuloplasty which when compared to surgery has a reduced risk of maternal complications of 1% for valvuloplasty versus 3e5% for surgery and is also associated with markedly reduced rates of foetal compromise. Valvular regurgitant disease Systemic vasodilation and a fall in peripheral vascular resistance diminish afterload. The increased heart rate in pregnancy shortens diastole and improves aortic regurgitation. Overall both mitral and aortic regurgitation are well tolerated in pregnancy provided there is no left ventricular dysfunction. Hypertrophic cardiomyopathy Most cases of hypertrophic cardiomyopathy (HCM) demonstrate autosomal dominant inheritance. Women may be asymptomatic and may be aware of the condition from familial screening whilst other women may experience syncope or anginal symptoms. HCM is relatively well tolerated in pregnancy and large case series report no increase in mortality although postpartum pulmonary oedema is a recognized complication because of diastolic dysfunction. Peripartum cardiomyopathy Peripartum cardiomyopathy (PPCM) is a pregnancy-specific cardiomyopathy of unknown cause occurring in the peripartum period in women without pre-existing heart disease with a reported mortality of w15%.3 It occurs between the last month of pregnancy and 5 months postpartum. Risk factors for PPCM include multiparity, advanced maternal age, multiple pregnancy, pre-eclampsia, gestational and pre-existing hypertension and Afro-Caribbean race. Dilated cardiomyopathy and congestive heart failure with markedly reduced left ventricular dysfunction occur with an increased risk of systemic and pulmonary embolization. Clinical suspicion of PPCM should arise when women present in late pregnancy with dyspnoea and signs of heart failure. The diagnosis of PPCM is confirmed by echocardiographic identification of new left ventricular systolic dysfunction during the peripartum period. Management of this condition is with oxygen, diuretics, vasodilators, angiotensin-converting
Mitral stenosis Mitral stenosis (MS) is the most common rheumatic disease and is increasingly recognized in migrant women who may or may not have had the diagnosis made prior to pregnancy. The normal cardiac changes that ensue in pregnancy may lead to significant haemodynamic compromise and therefore MS is not well tolerated during pregnancy. Tachycardia in MS may be dangerous as left ventricle filling decreases during diastole with subsequent reductions in stroke volume. Raised left atrial pressures may ensue precipitating pulmonary oedema, the commonest complication. Women with severe MS or moderateesevere symptoms are at greatest risk, however women who are asymptomatic at
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
307
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
attention must be given to other aetiological factors which include coronary artery thrombosis and dissection which have been shown to occur in 21% and 15% of AMI cases in pregnancy respectively. Diagnosis comes from clinical history, ECG changes and conventional troponin assays since troponin levels are not altered in pregnancy. Management is the same as that of the nonpregnant patient and coronary angiography must not be withheld due to the pregnancy. Percutaneous coronary intervention is considered the treatment of choice for coronary revascularization as it is associated with less bleeding than thrombolysis and it allows diagnosis and stenting of coronary artery dissection. Secondary prevention with aspirin and beta-blockade is also appropriate and clopidogrel is thought to be safe in pregnancy. Clopidogrel must be stopped for at least 7 days before regional anaesthesia/analgesia; however it should not be stopped without prior consultation with the cardiologist. Statins should be withheld for the duration of the pregnancy as they are associated with foetal central nervous system and limb malformations.
Anticoagulation management for women with metallic heart valves C C
C
Continue warfarin during pregnancy (safest option for mother) Replace warfarin with low-molecular-weight heparin between 6 and 12 weeks’ gestation to avoid warfarin embryopathy and switch back to warfarin Use low-molecular-weight heparin* throughout pregnancy
* Close monitoring required with anti-Xa levels for low-molecular-weight heparin treatment.
Table 3
enzyme blockers (if postpartum) and inotropic support if necessary. Anticoagulation is mandatory in severely impaired left ventricular function (<35%). In severe cases, intra-aortic balloon pumps or left ventricular assist devices may be required acutely. Although women with PPCM are thought to have a better long term prognosis than other forms of cardiomyopathy, the risk of recurrent left ventricular dysfunction in future pregnancies remains.3 Women with PPCM should thus be informed of the likelihood of recurrence in future pregnancies particularly if cardiac function remains impaired.
Mechanical valves and anticoagulation The challenge for women with metallic valves is their need for life-long anticoagulation, which should be continued throughout pregnancy. Warfarin is associated with warfarin embryopathy characterized by nasal hypoplasia and bone defects alongside increased rates of miscarriage, stillbirth and fetal intracerebral haemorrhage. The safest option is for women to continue warfarin throughout pregnancy. Risk of embryopathy is dose related, however this risk may be low in women taking <5 mg per day.5 Other strategies may involve replacing warfarin with high-dose low-molecular-weight heparin (LMWH) with appropriate anti-Xa monitoring and dose adjustment (Table 3). LMWH may be given between weeks 6 and 12 weeks of gestation to avoid warfarin embryopathy or may be continued throughout pregnancy. If LMWH is used, meticulous dose adjustments should provide effective anticoagulation provided that anti-Xa
Ischaemic heart disease The incidence of acute myocardial infarction (AMI) in pregnancy and the prevalence of certain cardiovascular risk factors are rising due to increases in maternal age, diabetes and obesity. Although AMI is rare in women of childbearing age, pregnancy increases the risk by three- to fourfold.4 Rates are higher in pregnant women >40 years where the AMI odds ratio is 30-fold higher than in women <20 years. Independent risk factors also include multiparity, hypertension, and cigarette smoking. Although atherosclerosis contributes to a large number of cases,
Treatment of arrhythmias in pregnancy Adenosine Atropine Amiodarone b-blockers Digoxin Diltiazem Disopyramide Flecainide Lignocaine Quinidine Procainamide Propafenone Sotalol Verapamil DC cardioversion Implantable cardioverter-defibrillators
Safe to use in pregnancy, no detectable effect on fetal rhythm Unknown but used in resuscitation Short-term use in emergencies. Prolonged use risks fetal hypo/hyperthyroidism, FGR, preterm delivery Avoid atenolol in first trimester as concerns about FGR Good safety profile Too little experience Too little data to comment on regular use Limited literature for treatment of maternal arrhythmias; flecainide however used to treat fetal SVTs Good Good safety profile in pregnancy, however not used because of concern over safety profile in non-pregnant women Possibly as safe as quinidine short term in pregnancy Unknown Safe Safe first-choice class IV drug Safe, current reaching fetus is small. Small risk of fetal arrhythmia monitor fetus before and after procedure Little evidence. For women with ongoing malignant arrhythmias despite pharmacological treatment, ICD is a safe alternative. After each ICD delivered shock, monitoring the fetus is advised
FGR, fetal growth restriction; ICD, implantable cardioverter-defibrillator; SVT, supraventricular tachycardia; DC, direct current
Table 4
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
308
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
levels are maintained within a tight therapeutic range of 1.0e1.2 IU/ml (0.8e1.2 IU/ml in the first 3 months of pregnancy).6 Compliance with this LMWH regime and adjunctive aspirin is associated with low risk of valve thrombosis and good fetal outcomes in women with mechanical valves.7 Risks of thrombotic events are reduced with newer bileaflet valves (e.g. CarboMedics) and aortic valve replacements and so high-dose heparin may be adequate for women with these valves. Warfarin must be discontinued and substituted with therapeutic LMWH 10 days prior to delivery. During delivery, LMWH is stopped but restarted promptly in the postpartum phase and warfarin recommenced at 5e7 days postpartum.
dose should be used and best available evidence for the drug safety sought (Table 4). A
REFERENCES 1 Siu SC, Sermer M, Colman JM , et al. On behalf of the Cardiac Disease in Pregnancy (CARPREG) Investigators. Prospective multicenter study of pregnancy outcome in women with heart disease. Circulation 2001; 104: 515e21. 2 Bedard E, Dimopulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension. Eur Heart J 2009; 30: 256e65. 3 Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet 2006; 368: 687e93. 4 James AH, Jamison MG, Biswas MS, Brancazio LR, Swamy GK, Myers ER. Acute myocardial infarction in pregnancy. A United States population based study. Circulation 2009; 113: 1564e71. 5 Cotrufo M, DeFeo M, De Santo LS. Risk of warfarin during pregnancy with mechanical valve prostheses. Obstet Gynecol 2002; 99: 35e40. 6 Quinn J, Von Klemperer K, Brooks R, Peebles D, Walker F, Cohen H. Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single center experience. Haematologica 2009; 94: 1608e12. 7 McLintock C, McCowan LME, North RA. Maternal complications and pregnancy outcome in women with mechanical prosthetic heart valves treated with enoxaparin. BJOG 2009; 116: 1585e92.
Endocarditis prophylaxis Current recommendations from the National Institute for Health and Clinical Excellence (2008) state that prophylactic antibiotics for infective endocarditis (IE) are no longer required for childbirth. Both the American Heart Association and The British Society for Antimicrobial Chemotherapy (2006) recommend antibiotic cover for those women deemed to be at high risk of developing IE for example women with previous IE or those with poor outcomes if IE develops for example women with cyanotic congenital heart disease. In these circumstances, antibiotic prophylaxis with intravenous amoxicillin and gentamicin should be considered. Vancomycin or teicoplanin may be suitable alternatives in women who are allergic to penicillin. Cardiac arrhythmias Palpitations are a common symptom in pregnancy and there are a number of key elements required to manage arrhythmias in pregnancy. Firstly, it is important to accurately identify the arrhythmia and ascertain if any associated cardiac disease is present. Systemic causes of arrhythmias for example pulmonary embolism, sepsis and abnormal thyroid function must be ruled out. A thorough history and examination should be undertaken to determine the presence of debilitating symptoms or haemodynamic compromise which would warrant treatment. The decision to treat is based on a balance between arrhythmia termination and potential maternal/fetal side-effects. If the decision is to treat pharmacologically, the smallest recommended
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
FURTHER READING Lewis G. The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer e 2003e2005. The Seventh Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH, 2007. Nelson-Piercy C. Handbook of obstetric medicine. 3rd edn. London: Informa Healthcare, 2006. Oakley C, Warnes C, eds. Heart disease in pregnancy. London: Blackwell, 2007. Steer P, Gatzoulis M, Baker P, eds. Report of study group on heart disease in pregnancy. Cardiac disease in pregnancy. London: Royal College of Obstetricians and Gynaecologists Press, 2006.
309
Ó 2010 Elsevier Ltd. All rights reserved.
Cardiac diseases complicating pregnancy
Learning objectives After reading this article you should: C understand the cardiovascular adaptations that occur during pregnancy and their impact on key cardiac diseases C know about the causes and recognize the symptoms and signs of acquired cardiac disease in pregnancy C understand the general management principles for rheumatic valve disease, pulmonary hypertension, metallic heart valves and cardiac arrhythmias during pregnancy.
Sheba Jarvis Catherine Nelson-Piercy
Abstract Cardiac disease is the commonest cause of maternal mortality in the UK. A clear understanding of the physiological cardiovascular adaptations that occur in pregnancy is important to understand the impact this may have on women with pre-existing cardiac disease. The incidence of acquired cardiac disease in pregnancy is increasing and it is important to be vigilant of new onset cardiac disease in pregnancy. Social changes, with women waiting longer to start families and advances in reproductive technologies, mean that women may become pregnant at an age when some diseases are more prevalent. Newer therapies and improved understanding of cardiac disease in pregnancy have altered the prognosis in part but the management of cardiac disease remains a challenge in pregnancy. Appropriate referral and multidisciplinary planning with the appropriate specialists are mandatory.
Physiological cardiovascular adaptations during pregnancy and delivery Marked physiological adaptations that occur during pregnancy include an overall increase in blood volume of w30e40%. This adaptation begins at 6 weeks of gestation, reaching a peak between weeks 20 and 24 where it remains constant over the remainder of the pregnancy. Cardiac output increases in parallel, initially as a result of increased stroke volume in the early phases and later as a result of increased heart rate (Table 1). Cardiac output is highly sensitive to changes in maternal position, particularly in the later stages of the pregnancy when the gravid uterus exerting pressure upon the inferior vena cava reduces venous return. As a result the supine position may be associated with a 25% decrease in cardiac output. Reductions in peripheral vascular resistance occur in pregnancy and the reduction in afterload is due to the low-pressure uterine circulation, which is partly mediated by vasoactive prostaglandins and enhanced nitric oxide production. In addition, there is reduced response to noradrenaline and angiotensin II during pregnancy. Peripheral vasodilatation leads to reductions in blood pressure in the first and second trimesters and decreased vascular tone sensed by the kidney leads to activation of the renineangiotensin system and vasopressin production which increases plasma volume. Other changes include a reduction in serum colloid pressure by 10e15%, thus making pregnancy a susceptible time to interstitial and pulmonary oedema.
Keywords Cardiac disease; cardiomyopathy; maternal mortality; peripartum; pregnancy
Introduction Cardiac disease in pregnancy is an important cause of maternal morbidity and mortality. In the UK, cardiac disease in pregnancy is the commonest cause of maternal mortality (Confidential Enquiries into Maternal and Child Health, CEMACH, 2007). Although typically more common in developing countries, the number of maternal deaths associated with cardiac disease has been increasing in the Western world. Maternal mortality appears to be significantly rising in women who have no known history of cardiac disease. In addition, there is a rising incidence of women becoming pregnant who have had corrective surgery for congenital heart defects representing the surgical advances which have allowed women to reach childbearing age.
Physiological cardiovascular adaptations during pregnancy Cardiac output Stroke volume Heart rate Blood pressure Central venous pressure PCWP SVR and PVR Serum colloid oncotic pressure
Sheba Jarvis BSc MBBS MRCP is an Academic Specialist Registrar in Endocrinology within the North West Thames sector. She qualified from Guys, Kings and St Thomas’ School of Medicine. Her research interests include cardiac disease in pregnancy and fertility studies. Conflicts of interest: none declared. Catherine Nelson-Piercy MA FRCP FRCOG is a Consultant Obstetric Physician working at Queen Charlotte’s and Chelsea Hospital and at Guy’s and St Thomas’ Hospitals, London. She studied at King’s College Cambridge and St Bartholomew’s Hospital and trained in Obstetric Medicine. Her particular research interests include thromboembolism in pregnancy, hyperemesis gravidarum, SLE and antiphospholipid syndrome and drugs in lactating women. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
Increases by 40% Increases Increases by 10e20 beats/minute Decrease in first/second trimester Unchanged Unchanged Decreases Decreases by 10e15%
PCWP, pulmonary capillary wedge pressure; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance.
Table 1
305
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
During delivery, important haemodynamic changes occur. Pain and anxiety affect the heart rate and both systolic and diastolic blood pressure increase. Uterine contractions lead to tachycardia with a shift of the blood volume from the uterine to systemic circulation. The first and second stages of labour are associated with an increase in cardiac output of 15% and 50% respectively. The third stage of labour is associated with high risk of pulmonary oedema and requires careful monitoring if the patient has a history of cardiac disease. After birth, autotransfusion from the uterus means that there is a further increase in cardiac output; however this declines rapidly within 1 hour of delivery.
valvotomy or mitral valve replacement for haemodynamically significant mitral valve disease or planning the pregnancy before ventricular function deteriorates.
Aetiology of cardiac disease in pregnancy The aetiology of heart disease may be divided into congenital or acquired causes. The commonest congenital heart diseases include ventricular and atrial septal defects and patent ductus arteriosus. These are mostly diagnosed before pregnancy and are either corrected or are of little haemodynamic significance. Acquired causes of cardiac disease include ischaemic heart disease, rheumatic heart disease and dissection of the aorta. Social shifts with women waiting longer to start families as well as advances in reproductive technologies mean that women are achieving pregnancies at an age when some diseases are more prevalent. A higher prevalence of obesity and diabetes are also important contributors to the increasing incidence of ischaemic heart disease in pregnancy.
Clinical findings during pregnancy Common findings during a cardiovascular examination in pregnancy include features associated with a hyperdynamic circulation such as a bounding pulse, a third heart sound, sinus tachycardia and dependent peripheral oedema. On auscultation of the heart, an ejection systolic murmur is audible throughout the precordium in w90% of women. Electrocardiogram changes may include atrial and ventricular extrasystoles and ST segment depression or T wave inversion in the inferolateral electrocardiogram (ECG) leads.
Specific cardiac conditions Pulmonary hypertension Pulmonary hypertension (PHT) may be due to primary pulmonary hypertension, lung diseases such as cystic fibrosis or connective tissue disorders for example systemic sclerosis or secondary to congenital heart diseases leading to Eisenmenger’s Syndrome (large left to right cardiac shunt that becomes reversed from right to left leading to cyanosis and pulmonary hypertension). The danger for women with PHT lies with the fixed pulmonary vascular resistance and inability to increase pulmonary flow to match cardiac output, which leads to refractory hypoxaemia. In Eisenmenger’s Syndrome, the fall in peripheral vascular resistance exacerbates the right to left shunt, which may worsen cyanosis and hypoxaemia. Therefore peripheral vasodilatation should be avoided and hypotension treated with adequate volume replacement. Over the last decade, newer treatment strategies in PHT, improved recognition of the underlying disease with improved multidisciplinary management have contributed to reductions in maternal mortality in PHT of 17e33%.2 Despite these improvements, maternal mortality remains high and pregnancy remains contraindicated in women with PHT who should be actively counselled against pregnancy. Women who become pregnant should be advised to have a termination and if declined, elective admission for bed rest, oxygen and thromboprophylaxis is necessary. Drug therapies using endothelin antagonists (bosentan), sildenafil and prostacyclin are maintained during this time. At delivery, there is no evidence to support caesarean section over vaginal delivery nor are there clear data favouring a mode of anaesthesia. Women should be managed in the intensive care setting with intra-arterial monitoring, large bore venous access and with multidisciplinary team input where there is an important role for the obstetric anaesthetists. Hypovolaemia, acidosis and systemic vasodilatation should be avoided and therefore caution in the administration of regional anaesthesia and oxytocin is advised. Most women with PHT who die in pregnancy will do so after delivery and within 1 week postpartum. Thromboembolic events and haemorrhage are also contributors to these high rates of mortality.
General approach to cardiac disease in pregnancy Pre-pregnancy counselling is imperative in women with cardiac diseases. Such counselling should involve obstetricians with expertise in high-risk pregnancies, obstetric physicians and/or cardiologists with expertise in pregnancy. Women with congenital heart disease are at increased risk of having a fetus with congenital heart disease. They therefore will require referral for a detailed fetal cardiac ultrasound. Ultimately, the outcome and safety of the pregnancy are related to the presence of and degree of pulmonary hypertension, cyanosis, haemodynamic significance of lesions and the New York Heart Association (NYHA) functional class (based on the level of activity that leads to dyspnoea). Maternal risk is a concept that should be discussed at an early stage with the patient. Predictive indicators of cardiovascular complications during pregnancy listed in Table 2 have been reported from the Canadian study of pregnancy outcomes in women with cardiac disease (CARPREG).1 Adequate counselling will provide information as to when the pregnancy may pose less risks of complication to the mother. Reduction in risk may include correcting defects prior to pregnancy, for example percutaneous
Independent predictors of maternal cardiac events in pregnancy C C C C C
C
Prior cardiac events or stroke Prior arrhythmia New York Heart Association functional class of >II Presence of cyanosis during the baseline antenatal visit Left-sided obstruction heart lesions e.g. mitral stenosis and left ventricular outflow tract obstruction Left ventricular dysfunction
Table 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
306
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
Aortic dissection and Marfan’s disease Aortic dissection in pregnancy is a life-threatening event to both mother and baby and accounts for 3.6% of maternal deaths in the UK. Between 2003 and 2005, CEMACH reported that 14% of maternal cardiac deaths were attributed to aortic dissection demonstrating the need for rapid identification and treatment. Certain conditions predispose to aortic dissection, including connective tissue disorders (Marfan’s disease, Ehlers-Danlos syndrome type IV), congenital heart diseases (bicuspid aortic valve, Turner’s syndrome or aortic coarctation) and hypertension. Additionally, an association between pregnancy and aortic dissection has been reported and the incidence in pregnancy is rising. Approximately 50% of aortic dissections in women under the age of 40 occur in association with pregnancy and most cases occur in late pregnancy or in the early postpartum period. Patients presenting with aortic dissection may do so with a wide array of symptoms and the condition may be missed or symptoms mistaken for other diseases in pregnancy. Delays in treatment of this disease can lead to potentially catastrophic consequences, since the mortality rate increases by 1% each hour if left untreated. Autopsy data presented by CEMACH reported obesity in a third of the cases and undiagnosed Marfan’s disease in a third of cases. Marfan’s disease is an autosomal dominant disease characterized by typical skeletal features of tall stature, high arched palate, scoliosis and lens dislocation. Cardiac involvement occurs in 80% of patients with aortic root dilation, aortic dissection and mitral valve prolapse being well recognized. Pregnancy carries a five-fold increase in aortic complications in Marfan’s disease particularly if the aortic root diameter is more than 4e4.5 cm or there has been a steady increase in aortic root dimensions during the preceding visits. Recommendations for management include monthly echocardiograms throughout pregnancy, monitoring of aortic root dimensions alongside beta-blocker treatment to reduce the risk of aortic dilatation. Women with an aortic root diameter >4.5 cm should be advised to delay pregnancy until after aortic root repair. In those women with stable aortic root measurements of <4 cm, vaginal delivery with epidural analgesia is recommended and pregnancy outcome appears to be good. Caesarean section under regional anaesthesia should be undertaken with dilated aortic root >4 cm and in those women with increased aortic root dimensions during pregnancy. In the emergency setting blood pressure should be rapidly controlled, acute Type A dissections require emergency surgery whilst Type B aortic dissection should be managed medically with the same indications for surgical intervention as outside of pregnancy.
the beginning of pregnancy may still develop exertional dyspnoea, orthopnoea and paroxysmal nocturnal dyspnoea due to pulmonary oedema later in gestation. The risk of pulmonary oedema is greatest immediately after delivery during the third stage of labour because of autotransfusion from the contracted uterus. Management of MS during pregnancy should include close follow-up with echocardiographic monitoring. Symptomatic women in whom there are no contraindications should be prescribed beta-blockers, which reduce the heart rate and allow time for left atrial emptying. If atrial fibrillation occurs it should be converted to sinus rhythm with digoxin, beta-blockers or synchronized direct current cardioversion. At the time of delivery, the supine and lithotomy position should be avoided as should fluid overload. If pulmonary oedema develops it should be treated rapidly, with oxygen, diuretics and diamorphine. In women with severe MS, it may be advisable that they delay pregnancy until correction (balloon, open or closed mitral valvotomy) or replacement of the mitral valve. Women who remain symptomatic despite optimized medical therapy should be considered for balloon valvuloplasty which when compared to surgery has a reduced risk of maternal complications of 1% for valvuloplasty versus 3e5% for surgery and is also associated with markedly reduced rates of foetal compromise. Valvular regurgitant disease Systemic vasodilation and a fall in peripheral vascular resistance diminish afterload. The increased heart rate in pregnancy shortens diastole and improves aortic regurgitation. Overall both mitral and aortic regurgitation are well tolerated in pregnancy provided there is no left ventricular dysfunction. Hypertrophic cardiomyopathy Most cases of hypertrophic cardiomyopathy (HCM) demonstrate autosomal dominant inheritance. Women may be asymptomatic and may be aware of the condition from familial screening whilst other women may experience syncope or anginal symptoms. HCM is relatively well tolerated in pregnancy and large case series report no increase in mortality although postpartum pulmonary oedema is a recognized complication because of diastolic dysfunction. Peripartum cardiomyopathy Peripartum cardiomyopathy (PPCM) is a pregnancy-specific cardiomyopathy of unknown cause occurring in the peripartum period in women without pre-existing heart disease with a reported mortality of w15%.3 It occurs between the last month of pregnancy and 5 months postpartum. Risk factors for PPCM include multiparity, advanced maternal age, multiple pregnancy, pre-eclampsia, gestational and pre-existing hypertension and Afro-Caribbean race. Dilated cardiomyopathy and congestive heart failure with markedly reduced left ventricular dysfunction occur with an increased risk of systemic and pulmonary embolization. Clinical suspicion of PPCM should arise when women present in late pregnancy with dyspnoea and signs of heart failure. The diagnosis of PPCM is confirmed by echocardiographic identification of new left ventricular systolic dysfunction during the peripartum period. Management of this condition is with oxygen, diuretics, vasodilators, angiotensin-converting
Mitral stenosis Mitral stenosis (MS) is the most common rheumatic disease and is increasingly recognized in migrant women who may or may not have had the diagnosis made prior to pregnancy. The normal cardiac changes that ensue in pregnancy may lead to significant haemodynamic compromise and therefore MS is not well tolerated during pregnancy. Tachycardia in MS may be dangerous as left ventricle filling decreases during diastole with subsequent reductions in stroke volume. Raised left atrial pressures may ensue precipitating pulmonary oedema, the commonest complication. Women with severe MS or moderateesevere symptoms are at greatest risk, however women who are asymptomatic at
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
307
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
attention must be given to other aetiological factors which include coronary artery thrombosis and dissection which have been shown to occur in 21% and 15% of AMI cases in pregnancy respectively. Diagnosis comes from clinical history, ECG changes and conventional troponin assays since troponin levels are not altered in pregnancy. Management is the same as that of the nonpregnant patient and coronary angiography must not be withheld due to the pregnancy. Percutaneous coronary intervention is considered the treatment of choice for coronary revascularization as it is associated with less bleeding than thrombolysis and it allows diagnosis and stenting of coronary artery dissection. Secondary prevention with aspirin and beta-blockade is also appropriate and clopidogrel is thought to be safe in pregnancy. Clopidogrel must be stopped for at least 7 days before regional anaesthesia/analgesia; however it should not be stopped without prior consultation with the cardiologist. Statins should be withheld for the duration of the pregnancy as they are associated with foetal central nervous system and limb malformations.
Anticoagulation management for women with metallic heart valves C C
C
Continue warfarin during pregnancy (safest option for mother) Replace warfarin with low-molecular-weight heparin between 6 and 12 weeks’ gestation to avoid warfarin embryopathy and switch back to warfarin Use low-molecular-weight heparin* throughout pregnancy
* Close monitoring required with anti-Xa levels for low-molecular-weight heparin treatment.
Table 3
enzyme blockers (if postpartum) and inotropic support if necessary. Anticoagulation is mandatory in severely impaired left ventricular function (<35%). In severe cases, intra-aortic balloon pumps or left ventricular assist devices may be required acutely. Although women with PPCM are thought to have a better long term prognosis than other forms of cardiomyopathy, the risk of recurrent left ventricular dysfunction in future pregnancies remains.3 Women with PPCM should thus be informed of the likelihood of recurrence in future pregnancies particularly if cardiac function remains impaired.
Mechanical valves and anticoagulation The challenge for women with metallic valves is their need for life-long anticoagulation, which should be continued throughout pregnancy. Warfarin is associated with warfarin embryopathy characterized by nasal hypoplasia and bone defects alongside increased rates of miscarriage, stillbirth and fetal intracerebral haemorrhage. The safest option is for women to continue warfarin throughout pregnancy. Risk of embryopathy is dose related, however this risk may be low in women taking <5 mg per day.5 Other strategies may involve replacing warfarin with high-dose low-molecular-weight heparin (LMWH) with appropriate anti-Xa monitoring and dose adjustment (Table 3). LMWH may be given between weeks 6 and 12 weeks of gestation to avoid warfarin embryopathy or may be continued throughout pregnancy. If LMWH is used, meticulous dose adjustments should provide effective anticoagulation provided that anti-Xa
Ischaemic heart disease The incidence of acute myocardial infarction (AMI) in pregnancy and the prevalence of certain cardiovascular risk factors are rising due to increases in maternal age, diabetes and obesity. Although AMI is rare in women of childbearing age, pregnancy increases the risk by three- to fourfold.4 Rates are higher in pregnant women >40 years where the AMI odds ratio is 30-fold higher than in women <20 years. Independent risk factors also include multiparity, hypertension, and cigarette smoking. Although atherosclerosis contributes to a large number of cases,
Treatment of arrhythmias in pregnancy Adenosine Atropine Amiodarone b-blockers Digoxin Diltiazem Disopyramide Flecainide Lignocaine Quinidine Procainamide Propafenone Sotalol Verapamil DC cardioversion Implantable cardioverter-defibrillators
Safe to use in pregnancy, no detectable effect on fetal rhythm Unknown but used in resuscitation Short-term use in emergencies. Prolonged use risks fetal hypo/hyperthyroidism, FGR, preterm delivery Avoid atenolol in first trimester as concerns about FGR Good safety profile Too little experience Too little data to comment on regular use Limited literature for treatment of maternal arrhythmias; flecainide however used to treat fetal SVTs Good Good safety profile in pregnancy, however not used because of concern over safety profile in non-pregnant women Possibly as safe as quinidine short term in pregnancy Unknown Safe Safe first-choice class IV drug Safe, current reaching fetus is small. Small risk of fetal arrhythmia monitor fetus before and after procedure Little evidence. For women with ongoing malignant arrhythmias despite pharmacological treatment, ICD is a safe alternative. After each ICD delivered shock, monitoring the fetus is advised
FGR, fetal growth restriction; ICD, implantable cardioverter-defibrillator; SVT, supraventricular tachycardia; DC, direct current
Table 4
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
308
Ó 2010 Elsevier Ltd. All rights reserved.
OBSTETRIC ANAESTHESIA
levels are maintained within a tight therapeutic range of 1.0e1.2 IU/ml (0.8e1.2 IU/ml in the first 3 months of pregnancy).6 Compliance with this LMWH regime and adjunctive aspirin is associated with low risk of valve thrombosis and good fetal outcomes in women with mechanical valves.7 Risks of thrombotic events are reduced with newer bileaflet valves (e.g. CarboMedics) and aortic valve replacements and so high-dose heparin may be adequate for women with these valves. Warfarin must be discontinued and substituted with therapeutic LMWH 10 days prior to delivery. During delivery, LMWH is stopped but restarted promptly in the postpartum phase and warfarin recommenced at 5e7 days postpartum.
dose should be used and best available evidence for the drug safety sought (Table 4). A
REFERENCES 1 Siu SC, Sermer M, Colman JM , et al. On behalf of the Cardiac Disease in Pregnancy (CARPREG) Investigators. Prospective multicenter study of pregnancy outcome in women with heart disease. Circulation 2001; 104: 515e21. 2 Bedard E, Dimopulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension. Eur Heart J 2009; 30: 256e65. 3 Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet 2006; 368: 687e93. 4 James AH, Jamison MG, Biswas MS, Brancazio LR, Swamy GK, Myers ER. Acute myocardial infarction in pregnancy. A United States population based study. Circulation 2009; 113: 1564e71. 5 Cotrufo M, DeFeo M, De Santo LS. Risk of warfarin during pregnancy with mechanical valve prostheses. Obstet Gynecol 2002; 99: 35e40. 6 Quinn J, Von Klemperer K, Brooks R, Peebles D, Walker F, Cohen H. Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single center experience. Haematologica 2009; 94: 1608e12. 7 McLintock C, McCowan LME, North RA. Maternal complications and pregnancy outcome in women with mechanical prosthetic heart valves treated with enoxaparin. BJOG 2009; 116: 1585e92.
Endocarditis prophylaxis Current recommendations from the National Institute for Health and Clinical Excellence (2008) state that prophylactic antibiotics for infective endocarditis (IE) are no longer required for childbirth. Both the American Heart Association and The British Society for Antimicrobial Chemotherapy (2006) recommend antibiotic cover for those women deemed to be at high risk of developing IE for example women with previous IE or those with poor outcomes if IE develops for example women with cyanotic congenital heart disease. In these circumstances, antibiotic prophylaxis with intravenous amoxicillin and gentamicin should be considered. Vancomycin or teicoplanin may be suitable alternatives in women who are allergic to penicillin. Cardiac arrhythmias Palpitations are a common symptom in pregnancy and there are a number of key elements required to manage arrhythmias in pregnancy. Firstly, it is important to accurately identify the arrhythmia and ascertain if any associated cardiac disease is present. Systemic causes of arrhythmias for example pulmonary embolism, sepsis and abnormal thyroid function must be ruled out. A thorough history and examination should be undertaken to determine the presence of debilitating symptoms or haemodynamic compromise which would warrant treatment. The decision to treat is based on a balance between arrhythmia termination and potential maternal/fetal side-effects. If the decision is to treat pharmacologically, the smallest recommended
ANAESTHESIA AND INTENSIVE CARE MEDICINE 11:8
FURTHER READING Lewis G. The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer e 2003e2005. The Seventh Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH, 2007. Nelson-Piercy C. Handbook of obstetric medicine. 3rd edn. London: Informa Healthcare, 2006. Oakley C, Warnes C, eds. Heart disease in pregnancy. London: Blackwell, 2007. Steer P, Gatzoulis M, Baker P, eds. Report of study group on heart disease in pregnancy. Cardiac disease in pregnancy. London: Royal College of Obstetricians and Gynaecologists Press, 2006.
309
Ó 2010 Elsevier Ltd. All rights reserved.