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Cardiovascular disease in pregnancy
CASE-BASED LEARNING
Cardiovascular disease in pregnancy
interpret cardiovascular signs and symptoms correctly as many of these can occur in normal pregnancy. Hence, the management of women with cardiovascular disease during pregnancy poses a challenge to obstetricians, cardiologists and anaesthetists. This article considers a range of cases where cardiological conditions can complicate pregnancy.
Dipanwita Kapoor Suzanne VF Wallace
Case 1 congenital heart disease: tetralogy of Fallot A 26 year old primiparous woman was seen in the obstetric cardiology clinic at 11 weeks gestation. She initially had modified BlalockeTaussig shunts and then had a repair to tetralogy of Fallot (ToF) at the age of four. Five years ago she needed a pulmonary valve replacement (23 mm bioprosthesis) with augmentation of the main pulmonary artery and distal right ventricular outflow tract using Vascutek patching. Her echocardiogram in early pregnancy showed moderate pulmonary regurgitation with good left and right ventricular function which was similar to the one done a year previously. She complained of increasing shortness of breath in the first trimester compared to pre-pregnancy. However, her shortness of breath was not been progressive and remained about the same as the first trimester. There was no significant change on the echocardiogram repeated in third trimester. Detailed fetal anatomy and fetal cardiac scans showed no evidence of fetal heart defects. Serial fetal growth scans in the third trimester showed a linear growth velocity at 50th centile. Her labour was induced at 39 weeks gestation because of complex social reasons. She delivered vaginally a live male infant weighing 3600 g. She remained haemodynamically stable throughout the intrapartum and immediate postpartum period. Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect, occurring in approximately 0.1% of live births. ‘Classic’ tetralogy includes ventricular septal defect (VSD), over-riding of the aorta, sub-pulmonary stenosis and secondary right ventricular hypertrophy. However, there is a wide range of morphological variation including minimal pulmonary stenosis to pulmonary atresia, small VSD with minimal ‘override’ and double outlet ventricle. Di George Syndrome (chromosome 22q11 deletion) is associated with similar cardiac defects in addition to facial abnormalities and learning difficulties. With the advances in medical science and improved healthcare systems, the majority of those born with ToF have now undergone some form of surgical treatment e either shunt palliation or radical repair. Radical repair is the treatment of choice and involves patch closure of VSD, resection of pulmonary infundibular stenosis and often a transannular patch to increase the size of the pulmonary annulus. Patients with palliative shunts remain cyanotic as the shunt creates a further systemicpulmonary shunt. The prognosis of ToF after primary surgical repair is good, with majority of the women reaching child bearing age. However, pulmonary regurgitation (PR) and progressive right ventricular (RV) remodelling have been documented in adults with repaired ToF and are associated with cardiovascular morbidity and mortality e right ventricular failure secondary to residual right ventricle outflow tract obstruction (RVOT), atrial or ventricular arrhythmias, sudden death. An increasing number of successful pregnancies have been reported in this cohort.
Abstract Cardiac disease continues to be a major cause of maternal mortality and morbidity. It is now the leading cause of overall and indirect maternal deaths in United Kingdom and has accounted for 22.2% of all maternal deaths in the UK from 2010 to 2012. Extensive haemodynamic changes that occur in pregnancy can have a profound effect on pre-existing heart disease. Management can be challenging and often a multidisciplinary approach involving the obstetricians, cardiologists and anaesthetists is necessary to optimise pregnancy outcomes.
Keywords cardiac; heart disease; mitral stenosis; paroxysmal supraventricular tachycardia; peripartum cardiomyopathy; pregnancy; tetralogy of Fallot
Introduction Cardiac diseases remain a major cause of complications in pregnancy worldwide and the number of women developing cardiac problems during pregnancy is rising. In the United Kingdom (UK) the maternal mortality including death from direct causes (e.g. postpartum haemorrhage, sepsis, hypertensive disease in pregnancy) has fallen dramatically over the last three decades. However, there has been a significant increase in deaths from indirect causes such as pre-existing or new onset medical and psychiatric conditions. Cardiac disease remains the largest single cause of overall and indirect maternal death. It accounted for 22.2% of all maternal death in UK between 2010 and 2012 according to the last Confidential Enquiries into Maternal Deaths and Morbidity 2009e12 report, which is significantly higher when compared with the report in 1985e87. The trend of overall maternal death and of deaths from cardiac disease in the last three decades is shown in Figure 1. Addressing this issue remains a challenge to the current health system and will involve a wide range of health services including maternity services, public health, primary and secondary care to improve awareness and patient care. There is also a need to engage and appropriately train physicians in the care of pregnant women. Cardiovascular changes during pregnancy and puerperium are summarised in Table 1 and pregnancy can have profound effects on pre-existing heart disease. In addition, it may be difficult to
Dipanwita Kapoor MBBS MRCOG is a Post CCT fellow in Obstetrics and Gynaecology at Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK. Conflicts of interest: none declared. Suzanne V F Wallace BM BCh MA MRCOG is a Consultant Obstetrician at Nottingham University Hospitals NHS Trust, Queens Medical Centre, Nottingham, UK. Conflicts of interest: none declared.
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CASE-BASED LEARNING
Maternal death from cardiac disease in the UK (1985–2012) Proportion of cardiac disease related death Rate of cardiac disease related death per 100,000 maternities Total maternal deaths per 100,000 maternities 25 20 15 10 5 0 7
–8
85
19
0
–9
88
19
3
–9
91
19
6
–9
94
19
9
–9
97
19
2
–0
00
20
5
–0
03
20
8
–0
06
20
1
–1
09
20
2
–1
10
20
Figure 1
Pregnancy in women with corrected ToF is generally tolerated well. A small proportion of women will develop heart failure and arrhythmias during pregnancy. It can also be associated with fetal growth restriction. The feto-maternal risks increase in the presence of severe PR, significant residual RVOT obstruction, and right ventricular dysfunction. In symptomatic women with marked dilatation of the right ventricle due to severe pulmonary regurgitation, a pulmonary valve replacement (homograft) should be considered before contemplating pregnancy. Recent studies demonstrated that there is acceleration in the rate of right ventricular remodelling, defined as an increase in end-diastolic volume, following pregnancy in women with repaired ToF particular for those women with severely dilated RV at baseline. Pregnancy in women with uncorrected ToF is considered high risk with a maternal mortality rate between 4 and 15% and fetal loss rates are as high as 30%. The main concerns in this group are highlighted in Box 1. The risk is significantly increased (maternal mortality 25e40%) in the presence of pulmonary hypertension (Eisenmenger’s syndrome) and women should be advised against pregnancy or to consider therapeutic termination if pregnancy occurs. Where maternal death occurs, this is usually in the last trimester of pregnancy and in the first months after delivery because of pulmonary hypertensive crises, pulmonary thrombosis, or refractory right heart failure. If a women chooses
Feto-maternal risks associated with uncorrected ToF C
Worsening cyanosis and maternal hypoxaemia because of increased right to left shunt secondary to decrease in peripheral resistance, causes:
C
C C C C C
Worsening breathlessness Polycythaemia and thromboembolism Increased risk of miscarriage Fetal growth restriction Fetal death Preterm delivery (spontaneous or iatrogenic)
Paradoxical embolism through the right to left shunt resulting in cerebrovascular accidents (risk increases in pregnancy because of physiological hypercoagulable state) Heart failure Tachyarrhythmias Infective endocarditis Cerebral abscesses Maternal death (as high as 25e40% in presence of pulmonary hypertension)
Box 1
Cardiovascular changes during pregnancy and puerperium Pregnancy
Intrapartum
Post-partum
Cardiac output
[by 40%
Stroke volume Heart rate Blood pressure
[ [by 10e20 beats Yfirst and second trimester [third trimester Y
[by 15% (1st stage) [by 50% (2nd stage) [ [ [
[by 60e80% in the first hour and then Yover the next 24 weeks Y Returns to pre-pregnancy level over first 2 weeks Falls initially and then increases Day 3e7. Returns to pre-pregnancy level by 6 weeks [by 30% over first 2 weeks above delivery values
Systemic vascular resistance (SVR)
[
Table 1
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CASE-BASED LEARNING
to continue pregnancy, a multidisciplinary approach should be adopted to achieve the best possible pregnancy outcome. These risks can be minimised by bed rest, oxygen therapy to maintain oxygen saturation >85% and thromboprophylaxis. Women with ToF should be offered prepregnancy counselling and assessment including genetic tests for 22q11 deletion. All pregnant women with ToF should be cared for in a specialist tertiary centre with input from obstetricians, cardiologists and anaesthetists to improve maternal and fetal outcomes. Follow up in each trimester is sufficient for the majority of these women. However, monthly or bimonthly cardiac evaluation with echocardiography is indicated in women with severe PR. If RV failure occurs during pregnancy, treatment with diuretics should be started and bed rest advised. All women should be offered fetal echocardiography during pregnancy as it can be familial. Additional fetal growth scans are indicated in third trimester to exclude fetal growth restriction. The preferred mode of delivery is vaginal in majority of the cases. Planned delivery (vaginal delivery with incremental regional anaesthesia or caesarean section) should be reserved for women at higher risk such as those with worsening symptoms or with pulmonary hypertension.
vasculature pressure can result in pulmonary oedema. The mitral orifice normally has an area of 4e6 cm2 (2 D echocardiography short axis). Patients start to experience valve-related symptoms when the valve area is 2e2.5 cm2 or less, at which point moderate exercise or tachycardia may result in exertional dyspnoea. Severe MS occurs with a valve area of less than 1 cm2. In pregnancy, the risk of cardiac compromise is further aggravated by physiological increases in intravascular volume and maternal tachycardia. In cases of moderate to severe mitral stenosis, approximately 60% of women will experience their first episode of pulmonary oedema at approximately 30 weeks gestation as this is the time when cardiac output reaches its maximal level during pregnancy. This risk continues during the intrapartum and immediate postpartum period. There is also a risk of thrombus formation because of the hypercoagulability associated with pregnancy together with an increase in left atrial pressure. Atrial fibrillation and stroke are also risks. Perinatal outcome depends on symptoms and pulmonary artery pressure (PAP) during pregnancy. The risk is higher in women with more severe symptoms with a mortality rate of up to 12%e31%. Prematurity rates are 20e30%, intrauterine growth restriction 5e20%, and stillbirth 1e3%. Pregnancy must be managed in a specialist tertiary unit with appropriate care from cardiologists, obstetricians and anaesthetists. The aim of management of MS in pregnancy is to avoid cardiac decompensation. The European Society of Cardiology (ESC) guidance on treatment of MS in pregnancy is outlined in Box 2. Pre-emptive diuresis using furosemide may be considered
Case 2 acquired heart disease: mitral stenosis A 28-year-old, otherwise fit and healthy, Asian woman was booked under midwife-led care during her first pregnancy. She presented at 26 weeks’ gestation to the Emergency Department with worsening breathlessness, pleuritic chest pain and productive cough for the last few days. She also gave a history of limited exercise tolerance pre-pregnancy. On examination, she was tachycardic, hypotensive and found to be in respiratory distress. Her heart sounds revealed a diastolic murmur. On lung auscultation, she had bilateral wheeze and crepitations. An electrocardiogram (ECG) showed sinus tachycardia. Arterial blood gas (ABG) measurement was suggestive of Type 1 respiratory failure. An urgent transthoracic echocardiogram (TTE) was undertaken which showed severe mitral stenosis (MS), likely rheumatic in origin. She was intubated and ventilated, started on intravenous diuretics (furosemide) and metoprolol and transferred to the cardiac unit with a view to perform an emergency percutaneous mitral commissurotomy (PTMC) which was uncomplicated. Her breathlessness improved significantly following the above procedure and an echocardiogram repeated at 34 weeks’ gestation showed residual mild MS. She was followed up regularly in Antenatal Clinic with close input from cardiologists. She went into spontaneous labour at 38 weeks’ gestation and delivered vaginally a live male infant weighing 3200 g. She remained haemodynamically stable throughout the intrapartum and immediate postpartum period. Mitral stenosis is the commonest cause of acquired heart disease in pregnancy. It is almost always caused by rheumatic fever with less than 1% of mitral stenosis in pregnancy due to congenital anomalies or endocarditis. Although rheumatic heart disease is rare in the indigenous UK population, it remains a major problem in developing countries and is still seen in western countries, especially within the immigrant population. MS is a state of fixed cardiac output caused by left atrial outflow obstruction; the increase in left atrial and pulmonary
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ESC guidelines on management of pregnant woman with mitral stenosis C
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C
C
C
C
All patients with moderate or severe MS (even when asymptomatic) should avoid pregnancy until they undergo surgery. Clinical and echocardiographic follow-up is indicated monthly or bimonthly depending on haemodynamic tolerance. In mild MS, evaluation is recommended every trimester and prior to delivery. In presence of symptoms or pulmonary hypertension, activity should be restricted and b1-selective blockers commenced. Diuretics are indicated if symptoms persist. Therapeutic anticoagulation is recommended in the case of paroxysmal or permanent AF, left atrial thrombosis, or prior embolism. PTMC should only be considered in women with refractory disease. Closed commissurotomy remains an alternative in developing countries when percutaneous commissurotomy is not available. Open-heart surgery should be reserved for cases in which all other measures fail as this is associated with a 30%e40% of fetal mortality rate and up to 9% maternal mortality rate. Most women are suitable for vaginal delivery. Caesarean section is indicated in women with moderate or severe MS who have worsening symptoms or pulmonary hypertension despite medical therapy, in whom percutaneous mitral commissurotomy cannot be performed or has failed.
Box 2
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CASE-BASED LEARNING
at delivery to avoid fluid overload and pulmonary oedema secondary to ‘autotransfusion’ and the relief of inferior vena caval compression which occurs at birth and in the immediate postpartum period.
(DC) cardioversion can be safely used to terminate the tachycardia in all stages of pregnancy with close monitoring of the fetus. In haemodynamically stable women, the preferred method of termination is IV adenosine e 6 mg initially, and may be followed by a dose of 12 mg if needed. Adenosine does not cross the placenta and no adverse fetal effects have been reported. Other AV nodal agents that may be used safely during pregnancy for acute treatment of PSVT are digoxin and verapramil. Care should be taken to avoid verapramil induced maternal hypotension as it can be associated with fetal distress. There is limited data on use of flecainide to treat maternal arrhythmias and this should be reserved for refractory cases. Beta blockers are the drug of choice in presence of WPW syndrome as the above mentioned AV nodal agents will further increase the ventricular rate by favouring conduction via the accessory pathways. Women with worsening PSVT during pregnancy, and not on any medication, can be started on lowest effective dose of beta blocker (e.g. sotalol, bisoprolol) or a calcium channel blocker (e.g. verapramil) but will require fetal surveillance with growth scans in the third trimester.
Case 3 arrhythmias: paroxysmal supraventricular tachycardia A 36 year old woman was booked under consultant led care in her first pregnancy because she was diagnosed with paroxysmal supraventricular tachycardia (PSVT) six months ago. She has had palpitations since childhood and can usually terminate these with a Valsalva manoeuvre. Her recent echocardiogram was normal. She was admitted at 22 weeks gestation with severe palpitations; the ECG showed regular narrow complex tachycardia upto 200 bpm. She remained haemodynamically stable throughout the whole episode. She tried vagal manoeuvres but unlike her previous episodes, the tachycardia persisted. Adenosine 6 mg iv was given to terminate this episode of PSVT. She was started on verapamil at 29 weeks gestation because of recurrent SVT. Since then she had occasional episodes of palpitations for remainder of the pregnancy. Fetal growth scan at 30 and 35 weeks gestation were normal. She went into preterm labour at 36 weeks gestation and delivered a live female infant weighing 2900 g vaginally. Cardiac arrhythmias commonly complicate pregnancy. Pregnant women who develop worsening palpitations, near syncope or syncope should be investigated to determine the cause. A 12 lead electrocardiogram (ECG), Holters or events monitors and echocardiogram (to diagnose structural and functional heart disease) should be performed. Sinus tachycardia, 15 degree shift in electrical axis to the left, supraventricular and ventricular ectopic beats, small Q wave, non-specific ST changes such as depression and/or an inverted T wave in leads III and aVL are normal findings in an ECG during pregnancy. Hyperthyroidism and serum electrolyte abnormalities should also be ruled out. Paroxysmal supraventricular tachycardia is the most common cardiac arrhythmia in pregnant women and is characterized by rapid, regular narrow complex atrio-ventricular nodal re-entrant tachycardia (AVNRT) with abrupt onset and termination. This may be associated with WolffeParkinsoneWhite (WPW) syndrome, where the type of SVT would be AV re-entrant tachycardia (AVRT) via the accessory pathways. An echocardiogram is usually normal. New onset PSVT are rare, however, in women with a history of PSVT this can recur during pregnancy in up to 50% in women. PSVTs are almost always benign and are well tolerated during pregnancy with minimal effects on maternal and perinatal outcome. However, one recent study demonstrated a marginal higher risk of septal defects, particularly secundum atrial septal defect in the offspring of pregnant women with PSVT; further research is warranted. The principles of management of cardiac arrhythmias are no different in pregnancy to outside of pregnancy and should be managed in conjunction with the cardiologists. PSVT do not always require treatment but this may be needed for acute management if there is a prolonged episode with or without haemodynamic compromise or in women who find palpitations intolerable. All women should be taught vagal manoeuvres as first-line therapy. If haemodynamically unstable, direct current
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Case 4: peripartum cardiomyopathy A 32 year old Afrocaribbean woman with raised BMI presented in her first pregnancy at 32 weeks with headache. On admission, she was also found to be hypertensive with significant proteinuria and a diagnosis of moderate pre-eclampsia was made. She was started on labetolol 200 mg thrice daily which controlled her blood pressure. Steroids were given for fetal lung maturation. Whilst an inpatient, she complained of worsening breathlessness associated with orthopnoea and paroxysmal nocturnal dyspnoea. She became tachycardic and tachypnoeac. There was no associated chest pain. A chest X-ray revealed cardiomegaly and pulmonary oedema. An echocardiogram revealed a moderately dilated left ventricle with severely impaired systolic function (LVEF < 35%); this was consistent with peripartum cardiomyopathy. She was reviewed by the cardiologists and commenced on Furosemide iv. She had a semi elective Caesarean Section at 33 weeks in view of the above diagnosis. She remained haemodynamically stable during delivery and in immediate postpartum period. She was advised against pregnancy in the near future and contraceptive advice was given. She was discharged home on Day 5 on bisoprolol, cardio selective beta-blocker; perindopril, ACE inhibitor (she had decided not to breast feed); furosemide and low molecular heparin with a plan to follow up in cardiology clinic in few weeks’ time. Peripartum Cardiomyopathy (PPCM) is a rare but potentially life-threatening idiopathic cardiomyopathy that presents with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, in the absence of any other cause of heart failure. PPCM is a diagnosis of exclusion. Although the left ventricle may not be dilated, the ejection fraction is nearly always reduced below 45% and/or there is fractional shortening <30% on an echocardiogram. There is a wide geographic variation in the incidence of the disease, ranging from 1 in 500 live births in Haiti to 1 in 4000 live births in the United States; this is thought to be related to socioeconomic and genetic factors. Identified risk factors for PPCM include advanced maternal age, multiparity, AfricaneCaribbean
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race, multiple pregnancy and hypertensive disorders (pre-existing, gestational hypertension or pre-eclampsia). The aetiology of PPCM remains unclear. Several theories have been proposed: myocarditis autoimmunity against fetal antigens fetal Chimerism genetic associations dietary deficiencies of selenium or excessive salt intake vascular and hormonal disease triggered by lategestational secretion of potent anti-angiogenic agents from the placenta and pituitary (the prolactin theory). The prolactin theory suggests that in PPCM inappropriate secretion of cathepsin D from cardiomyocytes cleaves prolactin into a potent antiangiogenic, proapoptotic, and proinflammatory 16 kDa fragment. This in turn, leads to cardiomyocyte dysfunction, apoptosis, metabolic insufficiency and cardiomyopathy. The diagnosis of PPCM relies on a high degree of suspicion as the symptoms can be confused with physiologic changes associated with advanced pregnancy. Diagnosis is made on the basis of a combination of a temporal relationship with pregnancy, echocardiography findings and exclusion of other causes of heart failure. Common clinical features and investigation findings in PPCM are summarised in Box 3. Cardiac magnetic resonance imaging may have a role in more severe form of PPCM as it provides valuable information about myocardial structure and right ventricular function. The differential diagnosis includes dilated cardiomyopathy of different aetiology, myocardial infarction and pulmonary embolism. Woman with PPCM may develop systemic or pulmonary emboli from mural thrombus, fatal arrhythmias, cardiogenic
shock or death. Other complications include preterm delivery (mostly iatrogenic) and in utero fetal death. A multidisciplinary team approach involving the cardiologists, obstetricians and anaesthetists must be adopted in the management of women with PPCM to optimise the pregnancy outcomes. The principles of management are as follows: management of arrhythmia and heart failure and consider delivery if unstable. Heart failure should be managed according to the ESC guidelines on acute and chronic heart failure: oxygen, betablockers, diuretics, angiotensin enzyme (ACE) inhibitors (or angiotensin-receptor blockers, ARBs) and mineralocorticoidreceptor blockers (MRAs). Diuretics should be used with caution in women with pre-eclampsia because of intravascular volume constriction. During pregnancy, ACE inhibitors or ARBs should be avoided as they are associated with fetotoxicity. Hydralazine and nitrates can be used instead of ACE inhibitors/ ARBs for afterload reduction. Captopril or enalapril is the preferred ACE inhibiters in breast feeding. The data on use of MRAs during pregnancy and lactation is limited and these should be avoided if possible. Recent studies suggested that addition of bromocriptine to standard heart failure therapy may improve left ventricular ejection fraction and the clinical outcome in women with acute severe PPCM. Results from larger studies are awaited before this can be used routinely in clinical practice. Low molecular weight heparin (LMWH) is indicated in women with very low LVEF, intracardiac thrombus on echocardiogram, arrhythmias or embolic phenomenon. Anti-arrhythmic medications should be used to treat associated arrhythmias. It has been suggested that wearable cardioverter/defibrillators may have a role in selected patients with highly reduced or persistent poor LV function as PPCM is associated with sudden death but larger studies are needed. If a woman remains hypoxic or hypotensive, she will need intubation, ventilation, inotropic support and immediate delivery by Caesarean Section. If she remains dependent on inotropes despite optimal medical therapy, she should be transferred to a facility where intra-aortic balloon pump counterpulsation, ventricular assist devices, and transplant consult teams are available. Delivery should be expedited if PPCM is diagnosed antenatally. Steroids for fetal lung maturation are recommended if delivery is planned <34e36 weeks gestation. Vaginal delivery with early regional analgesia is preferable if the patient is haemodynamically stable. Caesarean Section should be reserved for women with severe disease with or without haemodynamic compromise and for obstetric indications. Invasive monitoring with arterial and central venous line is recommended during delivery and in the immediate postpartum period. Maternal mortality from PPCM has improved over the years, particularly in developed countries due to increased awareness about the disease, improved rate of diagnosis and peripartum care. The reported long term (47e56 months) mortality varies from 3% in United States to 30% in Haiti and South Africa. Most deaths occur from progressive heart failure, arrhythmias, systemic or pulmonary embolism. Several studies demonstrated that a total recovery of ventricular function can occur in 23e54% subjects particularly if the LVEF>30 at diagnosis. Recovery
Clinical features and investigations findings for PPCM Symptoms Shortness of breath Orthopnoea Paroxysmal nocturnal dyspnoea Cough haemoptysis Chest and abdominal discomfort Palpitations Fatigue, malaise Signs Tachycardia Tachypnoea Gallop rhythm Signs of right ventricular failure: engorgement of the neck veins, pulmonary crepitations, hepatomegaly, pedal oedema Investigations Chest X-ray: cardiomegaly, pulmonary congestion or oedema bilateral pleural effusion Electrocardiogram: tachycardia arrhythmias Transthoracic echocardiogram: left ventricular ejection fraction (LVEF) <0.45 or M-mode fractional shortening <30% (or both) and end-diastolic dimension >2.7 cm/m2 Box 3
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CASE-BASED LEARNING
usually occurs in the first 6e12 months but can take up to 4 years postpartum. Possible predictors for poor outcome are with severely depressed systolic function (LVEF <30%) and a remodelled left ventricle with greater dilatation (LVEDd 60 mm). Subsequent pregnancy is not advised in women with persistent LV function 6 months after initial diagnosis of PPCM as it is associated with 50% risk of worsening heart failure and a 25% maternal mortality rate. In women where the LV function has returned to normal, the risk of heart failure is around 26% in a subsequent pregnancy. Effective contraception should be discussed with all women with PPCM before discharge from the hospital to avoid unplanned pregnancy. Consider termination of pregnancy for unplanned pregnancy if persistent LV dysfunction. Pre-pregnancy counselling is of paramount importance in this cohort of women. A large prospective international registry, the ESC EURO Observational Research Programme is collecting data worldwide on possible risk factors, diagnosis, mode of delivery, standard management and therapeutic interventions offered to patients with diagnosis of PPCM. This will help in better understanding of the prevalence and pathophysiology of the disease.
FURTHER READING Adamson DL, Dhanjal MK, Nelson-Piercy C. Heart disease in pregnancy. NewYork, United States: Oxford University Press Inc., 2011. Balci A, Drenthen W, Mulder BJ, et al. Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events. Am Heart J 2011; 161: 307e13. Bello NA, Arany Z. Molecular mechanisms of peripartum cardiomyopathy: a vascular/hormonal hypothesis. Trends Cardiovasc Med 2015; 25: 499e504. Hilfiker-Kleiner D, Haghikia A, Nonhoff J, Bauersachs J. Peripartum cardiomyopathy: current management and future perspectives. Eur Heart J 2015; 36: 1090e7. Knotts RJ, Garan H. Cardiac arrhythmias in pregnancy. Semin Perinatol 2014; 38: 285e8. on behalf of MBRRACE-UK. In: Knight MKS, Brocklehurst P, Neilson J, Shakespeare J, Kurinczuk JJ, eds. Saving lives, improving mothers’ care e lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009e12. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2014. Pessel C, Bonanno C. Valve disease in pregnancy. Semin Perinatol 2014; 38: 273e84. Rao S, Ginns JN. Adult congenital heart disease and pregnancy. Semin Perinatol 2014; 38: 260e72. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: the task force on the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 3147e97. Sliwa K, Blauwet L, Tibazarwa K, et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proofof-concept pilot study. Circulation 2010; 121: 1465e73.
Use of uterotonic agents at delivery in women with cardiac disease Obstetric haemorrhage is poorly tolerated in most women with cardiac disease due to rapid change in circulatory parameters. Oxytocin can still be given in majority of women with cardiac disease. However, it can cause fall in blood pressure due to peripheral vasodilatation and decrease cardiac contractility and heart rate. Slow infusion should be used rather than bolus doses to minimize these effects. Ergometrine should generally be avoided as it increases SVR and can precipitate coronary vasospasm. Carboprost, a prostaglandin F2a and misoprostol, a prostaglandin E1 can cause myocardial ischaemia/infarction and should be reserved for patients with life threatening haemorrhage due to uterine atony. Early recourse to mechanical manoeuvres such as bimanual compression of uterus, intra-uterine balloon tamponade and compression sutures are recommended.
Practice points C C
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Conclusion Cardiac disease remains the leading cause of maternal death in the UK. Prepregnancy counselling and contraceptive advice is of paramount importance in women with known cardiac disease to avoid unplanned pregnancy. All pregnant women with cardiac diseases should be looked after by a specialist team comprising of an obstetrician with interest in high risk pregnancies, obstetric physician or cardiologist with interest in pregnancy and obstetric anaesthetist, to improve maternal and fetal outcomes. A
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cardiac disease remains a leading cause of maternal death. women with preexisting cardiac disease should receive prepregnancy assessment and counselling to reduce morbidity and mortality. all pregnant women with cardiac diseases should be looked after by specialist combined obstetric and medical and cardiac teams in pregnancy to improve pregnancy outcomes. early signs and symptoms of heart failure can be mistaken for physiological symptoms of advance pregnancy. there should be a low threshold for echocardiography in pregnancy. vaginal delivery is appropriate in majority of women with cardiac disease. void bolus dose of oxytocin and ergometrine to treat PPH due to uterine atony.
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Kapoor D, Wallace SVF, Cardiovascular disease in pregnancy, Obstetrics, Gynaecology and Reproductive Medicine (2016), http://dx.doi.org/10.1016/j.ogrm.2016.01.003
Cardiovascular disease in pregnancy
interpret cardiovascular signs and symptoms correctly as many of these can occur in normal pregnancy. Hence, the management of women with cardiovascular disease during pregnancy poses a challenge to obstetricians, cardiologists and anaesthetists. This article considers a range of cases where cardiological conditions can complicate pregnancy.
Dipanwita Kapoor Suzanne VF Wallace
Case 1 congenital heart disease: tetralogy of Fallot A 26 year old primiparous woman was seen in the obstetric cardiology clinic at 11 weeks gestation. She initially had modified BlalockeTaussig shunts and then had a repair to tetralogy of Fallot (ToF) at the age of four. Five years ago she needed a pulmonary valve replacement (23 mm bioprosthesis) with augmentation of the main pulmonary artery and distal right ventricular outflow tract using Vascutek patching. Her echocardiogram in early pregnancy showed moderate pulmonary regurgitation with good left and right ventricular function which was similar to the one done a year previously. She complained of increasing shortness of breath in the first trimester compared to pre-pregnancy. However, her shortness of breath was not been progressive and remained about the same as the first trimester. There was no significant change on the echocardiogram repeated in third trimester. Detailed fetal anatomy and fetal cardiac scans showed no evidence of fetal heart defects. Serial fetal growth scans in the third trimester showed a linear growth velocity at 50th centile. Her labour was induced at 39 weeks gestation because of complex social reasons. She delivered vaginally a live male infant weighing 3600 g. She remained haemodynamically stable throughout the intrapartum and immediate postpartum period. Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect, occurring in approximately 0.1% of live births. ‘Classic’ tetralogy includes ventricular septal defect (VSD), over-riding of the aorta, sub-pulmonary stenosis and secondary right ventricular hypertrophy. However, there is a wide range of morphological variation including minimal pulmonary stenosis to pulmonary atresia, small VSD with minimal ‘override’ and double outlet ventricle. Di George Syndrome (chromosome 22q11 deletion) is associated with similar cardiac defects in addition to facial abnormalities and learning difficulties. With the advances in medical science and improved healthcare systems, the majority of those born with ToF have now undergone some form of surgical treatment e either shunt palliation or radical repair. Radical repair is the treatment of choice and involves patch closure of VSD, resection of pulmonary infundibular stenosis and often a transannular patch to increase the size of the pulmonary annulus. Patients with palliative shunts remain cyanotic as the shunt creates a further systemicpulmonary shunt. The prognosis of ToF after primary surgical repair is good, with majority of the women reaching child bearing age. However, pulmonary regurgitation (PR) and progressive right ventricular (RV) remodelling have been documented in adults with repaired ToF and are associated with cardiovascular morbidity and mortality e right ventricular failure secondary to residual right ventricle outflow tract obstruction (RVOT), atrial or ventricular arrhythmias, sudden death. An increasing number of successful pregnancies have been reported in this cohort.
Abstract Cardiac disease continues to be a major cause of maternal mortality and morbidity. It is now the leading cause of overall and indirect maternal deaths in United Kingdom and has accounted for 22.2% of all maternal deaths in the UK from 2010 to 2012. Extensive haemodynamic changes that occur in pregnancy can have a profound effect on pre-existing heart disease. Management can be challenging and often a multidisciplinary approach involving the obstetricians, cardiologists and anaesthetists is necessary to optimise pregnancy outcomes.
Keywords cardiac; heart disease; mitral stenosis; paroxysmal supraventricular tachycardia; peripartum cardiomyopathy; pregnancy; tetralogy of Fallot
Introduction Cardiac diseases remain a major cause of complications in pregnancy worldwide and the number of women developing cardiac problems during pregnancy is rising. In the United Kingdom (UK) the maternal mortality including death from direct causes (e.g. postpartum haemorrhage, sepsis, hypertensive disease in pregnancy) has fallen dramatically over the last three decades. However, there has been a significant increase in deaths from indirect causes such as pre-existing or new onset medical and psychiatric conditions. Cardiac disease remains the largest single cause of overall and indirect maternal death. It accounted for 22.2% of all maternal death in UK between 2010 and 2012 according to the last Confidential Enquiries into Maternal Deaths and Morbidity 2009e12 report, which is significantly higher when compared with the report in 1985e87. The trend of overall maternal death and of deaths from cardiac disease in the last three decades is shown in Figure 1. Addressing this issue remains a challenge to the current health system and will involve a wide range of health services including maternity services, public health, primary and secondary care to improve awareness and patient care. There is also a need to engage and appropriately train physicians in the care of pregnant women. Cardiovascular changes during pregnancy and puerperium are summarised in Table 1 and pregnancy can have profound effects on pre-existing heart disease. In addition, it may be difficult to
Dipanwita Kapoor MBBS MRCOG is a Post CCT fellow in Obstetrics and Gynaecology at Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK. Conflicts of interest: none declared. Suzanne V F Wallace BM BCh MA MRCOG is a Consultant Obstetrician at Nottingham University Hospitals NHS Trust, Queens Medical Centre, Nottingham, UK. Conflicts of interest: none declared.
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CASE-BASED LEARNING
Maternal death from cardiac disease in the UK (1985–2012) Proportion of cardiac disease related death Rate of cardiac disease related death per 100,000 maternities Total maternal deaths per 100,000 maternities 25 20 15 10 5 0 7
–8
85
19
0
–9
88
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3
–9
91
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–9
94
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9
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97
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–0
00
20
5
–0
03
20
8
–0
06
20
1
–1
09
20
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–1
10
20
Figure 1
Pregnancy in women with corrected ToF is generally tolerated well. A small proportion of women will develop heart failure and arrhythmias during pregnancy. It can also be associated with fetal growth restriction. The feto-maternal risks increase in the presence of severe PR, significant residual RVOT obstruction, and right ventricular dysfunction. In symptomatic women with marked dilatation of the right ventricle due to severe pulmonary regurgitation, a pulmonary valve replacement (homograft) should be considered before contemplating pregnancy. Recent studies demonstrated that there is acceleration in the rate of right ventricular remodelling, defined as an increase in end-diastolic volume, following pregnancy in women with repaired ToF particular for those women with severely dilated RV at baseline. Pregnancy in women with uncorrected ToF is considered high risk with a maternal mortality rate between 4 and 15% and fetal loss rates are as high as 30%. The main concerns in this group are highlighted in Box 1. The risk is significantly increased (maternal mortality 25e40%) in the presence of pulmonary hypertension (Eisenmenger’s syndrome) and women should be advised against pregnancy or to consider therapeutic termination if pregnancy occurs. Where maternal death occurs, this is usually in the last trimester of pregnancy and in the first months after delivery because of pulmonary hypertensive crises, pulmonary thrombosis, or refractory right heart failure. If a women chooses
Feto-maternal risks associated with uncorrected ToF C
Worsening cyanosis and maternal hypoxaemia because of increased right to left shunt secondary to decrease in peripheral resistance, causes:
C
C C C C C
Worsening breathlessness Polycythaemia and thromboembolism Increased risk of miscarriage Fetal growth restriction Fetal death Preterm delivery (spontaneous or iatrogenic)
Paradoxical embolism through the right to left shunt resulting in cerebrovascular accidents (risk increases in pregnancy because of physiological hypercoagulable state) Heart failure Tachyarrhythmias Infective endocarditis Cerebral abscesses Maternal death (as high as 25e40% in presence of pulmonary hypertension)
Box 1
Cardiovascular changes during pregnancy and puerperium Pregnancy
Intrapartum
Post-partum
Cardiac output
[by 40%
Stroke volume Heart rate Blood pressure
[ [by 10e20 beats Yfirst and second trimester [third trimester Y
[by 15% (1st stage) [by 50% (2nd stage) [ [ [
[by 60e80% in the first hour and then Yover the next 24 weeks Y Returns to pre-pregnancy level over first 2 weeks Falls initially and then increases Day 3e7. Returns to pre-pregnancy level by 6 weeks [by 30% over first 2 weeks above delivery values
Systemic vascular resistance (SVR)
[
Table 1
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to continue pregnancy, a multidisciplinary approach should be adopted to achieve the best possible pregnancy outcome. These risks can be minimised by bed rest, oxygen therapy to maintain oxygen saturation >85% and thromboprophylaxis. Women with ToF should be offered prepregnancy counselling and assessment including genetic tests for 22q11 deletion. All pregnant women with ToF should be cared for in a specialist tertiary centre with input from obstetricians, cardiologists and anaesthetists to improve maternal and fetal outcomes. Follow up in each trimester is sufficient for the majority of these women. However, monthly or bimonthly cardiac evaluation with echocardiography is indicated in women with severe PR. If RV failure occurs during pregnancy, treatment with diuretics should be started and bed rest advised. All women should be offered fetal echocardiography during pregnancy as it can be familial. Additional fetal growth scans are indicated in third trimester to exclude fetal growth restriction. The preferred mode of delivery is vaginal in majority of the cases. Planned delivery (vaginal delivery with incremental regional anaesthesia or caesarean section) should be reserved for women at higher risk such as those with worsening symptoms or with pulmonary hypertension.
vasculature pressure can result in pulmonary oedema. The mitral orifice normally has an area of 4e6 cm2 (2 D echocardiography short axis). Patients start to experience valve-related symptoms when the valve area is 2e2.5 cm2 or less, at which point moderate exercise or tachycardia may result in exertional dyspnoea. Severe MS occurs with a valve area of less than 1 cm2. In pregnancy, the risk of cardiac compromise is further aggravated by physiological increases in intravascular volume and maternal tachycardia. In cases of moderate to severe mitral stenosis, approximately 60% of women will experience their first episode of pulmonary oedema at approximately 30 weeks gestation as this is the time when cardiac output reaches its maximal level during pregnancy. This risk continues during the intrapartum and immediate postpartum period. There is also a risk of thrombus formation because of the hypercoagulability associated with pregnancy together with an increase in left atrial pressure. Atrial fibrillation and stroke are also risks. Perinatal outcome depends on symptoms and pulmonary artery pressure (PAP) during pregnancy. The risk is higher in women with more severe symptoms with a mortality rate of up to 12%e31%. Prematurity rates are 20e30%, intrauterine growth restriction 5e20%, and stillbirth 1e3%. Pregnancy must be managed in a specialist tertiary unit with appropriate care from cardiologists, obstetricians and anaesthetists. The aim of management of MS in pregnancy is to avoid cardiac decompensation. The European Society of Cardiology (ESC) guidance on treatment of MS in pregnancy is outlined in Box 2. Pre-emptive diuresis using furosemide may be considered
Case 2 acquired heart disease: mitral stenosis A 28-year-old, otherwise fit and healthy, Asian woman was booked under midwife-led care during her first pregnancy. She presented at 26 weeks’ gestation to the Emergency Department with worsening breathlessness, pleuritic chest pain and productive cough for the last few days. She also gave a history of limited exercise tolerance pre-pregnancy. On examination, she was tachycardic, hypotensive and found to be in respiratory distress. Her heart sounds revealed a diastolic murmur. On lung auscultation, she had bilateral wheeze and crepitations. An electrocardiogram (ECG) showed sinus tachycardia. Arterial blood gas (ABG) measurement was suggestive of Type 1 respiratory failure. An urgent transthoracic echocardiogram (TTE) was undertaken which showed severe mitral stenosis (MS), likely rheumatic in origin. She was intubated and ventilated, started on intravenous diuretics (furosemide) and metoprolol and transferred to the cardiac unit with a view to perform an emergency percutaneous mitral commissurotomy (PTMC) which was uncomplicated. Her breathlessness improved significantly following the above procedure and an echocardiogram repeated at 34 weeks’ gestation showed residual mild MS. She was followed up regularly in Antenatal Clinic with close input from cardiologists. She went into spontaneous labour at 38 weeks’ gestation and delivered vaginally a live male infant weighing 3200 g. She remained haemodynamically stable throughout the intrapartum and immediate postpartum period. Mitral stenosis is the commonest cause of acquired heart disease in pregnancy. It is almost always caused by rheumatic fever with less than 1% of mitral stenosis in pregnancy due to congenital anomalies or endocarditis. Although rheumatic heart disease is rare in the indigenous UK population, it remains a major problem in developing countries and is still seen in western countries, especially within the immigrant population. MS is a state of fixed cardiac output caused by left atrial outflow obstruction; the increase in left atrial and pulmonary
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ESC guidelines on management of pregnant woman with mitral stenosis C
C
C
C
C
C
C
All patients with moderate or severe MS (even when asymptomatic) should avoid pregnancy until they undergo surgery. Clinical and echocardiographic follow-up is indicated monthly or bimonthly depending on haemodynamic tolerance. In mild MS, evaluation is recommended every trimester and prior to delivery. In presence of symptoms or pulmonary hypertension, activity should be restricted and b1-selective blockers commenced. Diuretics are indicated if symptoms persist. Therapeutic anticoagulation is recommended in the case of paroxysmal or permanent AF, left atrial thrombosis, or prior embolism. PTMC should only be considered in women with refractory disease. Closed commissurotomy remains an alternative in developing countries when percutaneous commissurotomy is not available. Open-heart surgery should be reserved for cases in which all other measures fail as this is associated with a 30%e40% of fetal mortality rate and up to 9% maternal mortality rate. Most women are suitable for vaginal delivery. Caesarean section is indicated in women with moderate or severe MS who have worsening symptoms or pulmonary hypertension despite medical therapy, in whom percutaneous mitral commissurotomy cannot be performed or has failed.
Box 2
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at delivery to avoid fluid overload and pulmonary oedema secondary to ‘autotransfusion’ and the relief of inferior vena caval compression which occurs at birth and in the immediate postpartum period.
(DC) cardioversion can be safely used to terminate the tachycardia in all stages of pregnancy with close monitoring of the fetus. In haemodynamically stable women, the preferred method of termination is IV adenosine e 6 mg initially, and may be followed by a dose of 12 mg if needed. Adenosine does not cross the placenta and no adverse fetal effects have been reported. Other AV nodal agents that may be used safely during pregnancy for acute treatment of PSVT are digoxin and verapramil. Care should be taken to avoid verapramil induced maternal hypotension as it can be associated with fetal distress. There is limited data on use of flecainide to treat maternal arrhythmias and this should be reserved for refractory cases. Beta blockers are the drug of choice in presence of WPW syndrome as the above mentioned AV nodal agents will further increase the ventricular rate by favouring conduction via the accessory pathways. Women with worsening PSVT during pregnancy, and not on any medication, can be started on lowest effective dose of beta blocker (e.g. sotalol, bisoprolol) or a calcium channel blocker (e.g. verapramil) but will require fetal surveillance with growth scans in the third trimester.
Case 3 arrhythmias: paroxysmal supraventricular tachycardia A 36 year old woman was booked under consultant led care in her first pregnancy because she was diagnosed with paroxysmal supraventricular tachycardia (PSVT) six months ago. She has had palpitations since childhood and can usually terminate these with a Valsalva manoeuvre. Her recent echocardiogram was normal. She was admitted at 22 weeks gestation with severe palpitations; the ECG showed regular narrow complex tachycardia upto 200 bpm. She remained haemodynamically stable throughout the whole episode. She tried vagal manoeuvres but unlike her previous episodes, the tachycardia persisted. Adenosine 6 mg iv was given to terminate this episode of PSVT. She was started on verapamil at 29 weeks gestation because of recurrent SVT. Since then she had occasional episodes of palpitations for remainder of the pregnancy. Fetal growth scan at 30 and 35 weeks gestation were normal. She went into preterm labour at 36 weeks gestation and delivered a live female infant weighing 2900 g vaginally. Cardiac arrhythmias commonly complicate pregnancy. Pregnant women who develop worsening palpitations, near syncope or syncope should be investigated to determine the cause. A 12 lead electrocardiogram (ECG), Holters or events monitors and echocardiogram (to diagnose structural and functional heart disease) should be performed. Sinus tachycardia, 15 degree shift in electrical axis to the left, supraventricular and ventricular ectopic beats, small Q wave, non-specific ST changes such as depression and/or an inverted T wave in leads III and aVL are normal findings in an ECG during pregnancy. Hyperthyroidism and serum electrolyte abnormalities should also be ruled out. Paroxysmal supraventricular tachycardia is the most common cardiac arrhythmia in pregnant women and is characterized by rapid, regular narrow complex atrio-ventricular nodal re-entrant tachycardia (AVNRT) with abrupt onset and termination. This may be associated with WolffeParkinsoneWhite (WPW) syndrome, where the type of SVT would be AV re-entrant tachycardia (AVRT) via the accessory pathways. An echocardiogram is usually normal. New onset PSVT are rare, however, in women with a history of PSVT this can recur during pregnancy in up to 50% in women. PSVTs are almost always benign and are well tolerated during pregnancy with minimal effects on maternal and perinatal outcome. However, one recent study demonstrated a marginal higher risk of septal defects, particularly secundum atrial septal defect in the offspring of pregnant women with PSVT; further research is warranted. The principles of management of cardiac arrhythmias are no different in pregnancy to outside of pregnancy and should be managed in conjunction with the cardiologists. PSVT do not always require treatment but this may be needed for acute management if there is a prolonged episode with or without haemodynamic compromise or in women who find palpitations intolerable. All women should be taught vagal manoeuvres as first-line therapy. If haemodynamically unstable, direct current
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Case 4: peripartum cardiomyopathy A 32 year old Afrocaribbean woman with raised BMI presented in her first pregnancy at 32 weeks with headache. On admission, she was also found to be hypertensive with significant proteinuria and a diagnosis of moderate pre-eclampsia was made. She was started on labetolol 200 mg thrice daily which controlled her blood pressure. Steroids were given for fetal lung maturation. Whilst an inpatient, she complained of worsening breathlessness associated with orthopnoea and paroxysmal nocturnal dyspnoea. She became tachycardic and tachypnoeac. There was no associated chest pain. A chest X-ray revealed cardiomegaly and pulmonary oedema. An echocardiogram revealed a moderately dilated left ventricle with severely impaired systolic function (LVEF < 35%); this was consistent with peripartum cardiomyopathy. She was reviewed by the cardiologists and commenced on Furosemide iv. She had a semi elective Caesarean Section at 33 weeks in view of the above diagnosis. She remained haemodynamically stable during delivery and in immediate postpartum period. She was advised against pregnancy in the near future and contraceptive advice was given. She was discharged home on Day 5 on bisoprolol, cardio selective beta-blocker; perindopril, ACE inhibitor (she had decided not to breast feed); furosemide and low molecular heparin with a plan to follow up in cardiology clinic in few weeks’ time. Peripartum Cardiomyopathy (PPCM) is a rare but potentially life-threatening idiopathic cardiomyopathy that presents with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, in the absence of any other cause of heart failure. PPCM is a diagnosis of exclusion. Although the left ventricle may not be dilated, the ejection fraction is nearly always reduced below 45% and/or there is fractional shortening <30% on an echocardiogram. There is a wide geographic variation in the incidence of the disease, ranging from 1 in 500 live births in Haiti to 1 in 4000 live births in the United States; this is thought to be related to socioeconomic and genetic factors. Identified risk factors for PPCM include advanced maternal age, multiparity, AfricaneCaribbean
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race, multiple pregnancy and hypertensive disorders (pre-existing, gestational hypertension or pre-eclampsia). The aetiology of PPCM remains unclear. Several theories have been proposed: myocarditis autoimmunity against fetal antigens fetal Chimerism genetic associations dietary deficiencies of selenium or excessive salt intake vascular and hormonal disease triggered by lategestational secretion of potent anti-angiogenic agents from the placenta and pituitary (the prolactin theory). The prolactin theory suggests that in PPCM inappropriate secretion of cathepsin D from cardiomyocytes cleaves prolactin into a potent antiangiogenic, proapoptotic, and proinflammatory 16 kDa fragment. This in turn, leads to cardiomyocyte dysfunction, apoptosis, metabolic insufficiency and cardiomyopathy. The diagnosis of PPCM relies on a high degree of suspicion as the symptoms can be confused with physiologic changes associated with advanced pregnancy. Diagnosis is made on the basis of a combination of a temporal relationship with pregnancy, echocardiography findings and exclusion of other causes of heart failure. Common clinical features and investigation findings in PPCM are summarised in Box 3. Cardiac magnetic resonance imaging may have a role in more severe form of PPCM as it provides valuable information about myocardial structure and right ventricular function. The differential diagnosis includes dilated cardiomyopathy of different aetiology, myocardial infarction and pulmonary embolism. Woman with PPCM may develop systemic or pulmonary emboli from mural thrombus, fatal arrhythmias, cardiogenic
shock or death. Other complications include preterm delivery (mostly iatrogenic) and in utero fetal death. A multidisciplinary team approach involving the cardiologists, obstetricians and anaesthetists must be adopted in the management of women with PPCM to optimise the pregnancy outcomes. The principles of management are as follows: management of arrhythmia and heart failure and consider delivery if unstable. Heart failure should be managed according to the ESC guidelines on acute and chronic heart failure: oxygen, betablockers, diuretics, angiotensin enzyme (ACE) inhibitors (or angiotensin-receptor blockers, ARBs) and mineralocorticoidreceptor blockers (MRAs). Diuretics should be used with caution in women with pre-eclampsia because of intravascular volume constriction. During pregnancy, ACE inhibitors or ARBs should be avoided as they are associated with fetotoxicity. Hydralazine and nitrates can be used instead of ACE inhibitors/ ARBs for afterload reduction. Captopril or enalapril is the preferred ACE inhibiters in breast feeding. The data on use of MRAs during pregnancy and lactation is limited and these should be avoided if possible. Recent studies suggested that addition of bromocriptine to standard heart failure therapy may improve left ventricular ejection fraction and the clinical outcome in women with acute severe PPCM. Results from larger studies are awaited before this can be used routinely in clinical practice. Low molecular weight heparin (LMWH) is indicated in women with very low LVEF, intracardiac thrombus on echocardiogram, arrhythmias or embolic phenomenon. Anti-arrhythmic medications should be used to treat associated arrhythmias. It has been suggested that wearable cardioverter/defibrillators may have a role in selected patients with highly reduced or persistent poor LV function as PPCM is associated with sudden death but larger studies are needed. If a woman remains hypoxic or hypotensive, she will need intubation, ventilation, inotropic support and immediate delivery by Caesarean Section. If she remains dependent on inotropes despite optimal medical therapy, she should be transferred to a facility where intra-aortic balloon pump counterpulsation, ventricular assist devices, and transplant consult teams are available. Delivery should be expedited if PPCM is diagnosed antenatally. Steroids for fetal lung maturation are recommended if delivery is planned <34e36 weeks gestation. Vaginal delivery with early regional analgesia is preferable if the patient is haemodynamically stable. Caesarean Section should be reserved for women with severe disease with or without haemodynamic compromise and for obstetric indications. Invasive monitoring with arterial and central venous line is recommended during delivery and in the immediate postpartum period. Maternal mortality from PPCM has improved over the years, particularly in developed countries due to increased awareness about the disease, improved rate of diagnosis and peripartum care. The reported long term (47e56 months) mortality varies from 3% in United States to 30% in Haiti and South Africa. Most deaths occur from progressive heart failure, arrhythmias, systemic or pulmonary embolism. Several studies demonstrated that a total recovery of ventricular function can occur in 23e54% subjects particularly if the LVEF>30 at diagnosis. Recovery
Clinical features and investigations findings for PPCM Symptoms Shortness of breath Orthopnoea Paroxysmal nocturnal dyspnoea Cough haemoptysis Chest and abdominal discomfort Palpitations Fatigue, malaise Signs Tachycardia Tachypnoea Gallop rhythm Signs of right ventricular failure: engorgement of the neck veins, pulmonary crepitations, hepatomegaly, pedal oedema Investigations Chest X-ray: cardiomegaly, pulmonary congestion or oedema bilateral pleural effusion Electrocardiogram: tachycardia arrhythmias Transthoracic echocardiogram: left ventricular ejection fraction (LVEF) <0.45 or M-mode fractional shortening <30% (or both) and end-diastolic dimension >2.7 cm/m2 Box 3
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usually occurs in the first 6e12 months but can take up to 4 years postpartum. Possible predictors for poor outcome are with severely depressed systolic function (LVEF <30%) and a remodelled left ventricle with greater dilatation (LVEDd 60 mm). Subsequent pregnancy is not advised in women with persistent LV function 6 months after initial diagnosis of PPCM as it is associated with 50% risk of worsening heart failure and a 25% maternal mortality rate. In women where the LV function has returned to normal, the risk of heart failure is around 26% in a subsequent pregnancy. Effective contraception should be discussed with all women with PPCM before discharge from the hospital to avoid unplanned pregnancy. Consider termination of pregnancy for unplanned pregnancy if persistent LV dysfunction. Pre-pregnancy counselling is of paramount importance in this cohort of women. A large prospective international registry, the ESC EURO Observational Research Programme is collecting data worldwide on possible risk factors, diagnosis, mode of delivery, standard management and therapeutic interventions offered to patients with diagnosis of PPCM. This will help in better understanding of the prevalence and pathophysiology of the disease.
FURTHER READING Adamson DL, Dhanjal MK, Nelson-Piercy C. Heart disease in pregnancy. NewYork, United States: Oxford University Press Inc., 2011. Balci A, Drenthen W, Mulder BJ, et al. Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events. Am Heart J 2011; 161: 307e13. Bello NA, Arany Z. Molecular mechanisms of peripartum cardiomyopathy: a vascular/hormonal hypothesis. Trends Cardiovasc Med 2015; 25: 499e504. Hilfiker-Kleiner D, Haghikia A, Nonhoff J, Bauersachs J. Peripartum cardiomyopathy: current management and future perspectives. Eur Heart J 2015; 36: 1090e7. Knotts RJ, Garan H. Cardiac arrhythmias in pregnancy. Semin Perinatol 2014; 38: 285e8. on behalf of MBRRACE-UK. In: Knight MKS, Brocklehurst P, Neilson J, Shakespeare J, Kurinczuk JJ, eds. Saving lives, improving mothers’ care e lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009e12. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2014. Pessel C, Bonanno C. Valve disease in pregnancy. Semin Perinatol 2014; 38: 273e84. Rao S, Ginns JN. Adult congenital heart disease and pregnancy. Semin Perinatol 2014; 38: 260e72. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: the task force on the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 3147e97. Sliwa K, Blauwet L, Tibazarwa K, et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proofof-concept pilot study. Circulation 2010; 121: 1465e73.
Use of uterotonic agents at delivery in women with cardiac disease Obstetric haemorrhage is poorly tolerated in most women with cardiac disease due to rapid change in circulatory parameters. Oxytocin can still be given in majority of women with cardiac disease. However, it can cause fall in blood pressure due to peripheral vasodilatation and decrease cardiac contractility and heart rate. Slow infusion should be used rather than bolus doses to minimize these effects. Ergometrine should generally be avoided as it increases SVR and can precipitate coronary vasospasm. Carboprost, a prostaglandin F2a and misoprostol, a prostaglandin E1 can cause myocardial ischaemia/infarction and should be reserved for patients with life threatening haemorrhage due to uterine atony. Early recourse to mechanical manoeuvres such as bimanual compression of uterus, intra-uterine balloon tamponade and compression sutures are recommended.
Practice points C C
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Conclusion Cardiac disease remains the leading cause of maternal death in the UK. Prepregnancy counselling and contraceptive advice is of paramount importance in women with known cardiac disease to avoid unplanned pregnancy. All pregnant women with cardiac diseases should be looked after by a specialist team comprising of an obstetrician with interest in high risk pregnancies, obstetric physician or cardiologist with interest in pregnancy and obstetric anaesthetist, to improve maternal and fetal outcomes. A
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cardiac disease remains a leading cause of maternal death. women with preexisting cardiac disease should receive prepregnancy assessment and counselling to reduce morbidity and mortality. all pregnant women with cardiac diseases should be looked after by specialist combined obstetric and medical and cardiac teams in pregnancy to improve pregnancy outcomes. early signs and symptoms of heart failure can be mistaken for physiological symptoms of advance pregnancy. there should be a low threshold for echocardiography in pregnancy. vaginal delivery is appropriate in majority of women with cardiac disease. void bolus dose of oxytocin and ergometrine to treat PPH due to uterine atony.
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