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Dr. Vassilis I. Barberis
Managing cardiovascular disease in pregnancy is a growing challenge for the individual physician to whom the number of such presenting patients is nevertheless, usually small. This article reviews the practical recommendations from a general and disease-specific standpoint.
Interesting linkESC Clinical Practice Guidelines on Management of Cardiovascular Diseases during PregnancyCardiovascular morbidity and mortality associated with pregnancy is low (1) however cases of cardiovascular diseases (CVD) during pregnancy are increasing due to the 1) rise in prevalence of hypertension, diabetes and obesity, and 2) older maternal age. Advances in treatment of congenital heart disease (CHD) leading to more CHD patients reaching childbearing age also have added to the number of cases (2). In the western world, congenital heart disease is the most frequent CVD present during pregnancy - they are shunt lesions mostly, whereas rheumatic heart disease dominates in the non-western countries. Hypertensive disorders are the most frequent cardiovascular event during pregnancy (6-8%)(3).To help prevent, prepare for and address the needs of these situations, here are the practical recommendations to look over, from a general and a disease-specific approach.
Physiological alterations during pregnancy are 1) haemodynamic: increases in blood volume, cardiac output (30-50%), and heart rate (20-32 weeks), while there is a decrease in blood pressure and systemic vascular resistance (second trimester) and 2) hemostatic: a classic hypercoagulable state increases the risk of thrombo-embolic events, further enhanced by venous stasis. and 3) metabolic: disturbed glucose homeostasis, hypercholesterolemia, altered drug pharmacokinetics requiring dose adjustments and monitoring.Prepregnancy risk assessment and counselling is indicated in women with 1) known or suspected congenital or acquired cardiovascular and aortic disease - a review of any medications is needed to stop or substitute these which are contraindicated during pregnancy and 2) significant heart disease - they should be managed jointly by an obstetrician and a cardiologist with relevant experience, and those at high risk should be managed by a multidisciplinary team in a specialised center, with a clear plan of follow-up during pregnancy and hospital delivery.Predictors in the CARPREG risk score are poor functional status (NYHA class > cyanosis,systemic (left) ventricular systolic dysfunction, left heart obstruction, and history of prior cardiac events. Each predictor is assigned one point. Patients with 0 predictors were at low risk (5%), patients with 1 predictor were at intermediate risk (25%) and those with >1 predictor was at high risk (75%) of adverse cardiac events during pregnancy risk estimation scores. CARPREG and ZAHARA (4,5). Look here for a look at biomarkers and risk stratification of pregnancy. Find here treatment of the hypertensive pregnant or lactating patient, and here treatment of the high-risk pregnant patient.The 2011 ESC Guidelines (6) recommend the use of the modified World Health Organization (WHO) classification for the assessment of maternal risk (Table 1) (7).
Table 1. Modified WHO classification of maternal conditions
Risk of pregnancy by medical condition, Risk class
WHO : World Health Organization> Modified from Thorne S, MacGregor A, Nelson-Piercy C. Risks of contraception and pregnancy in heart disease. Heart 2006;92:1520 – 1525.
Women in conditions of the WHO IV category should be advised against pregnancy, and in case they become pregnant and termination is not considered, should be closely followed-up in an experienced tertiary center. These conditions are: pulmonary arterial hypertension (maternal mortality 17-50%), severe symptomatic LV dysfunction (LVEF<30%, NYHA III-IV), previous peripartum cardiomyopathy with any residual impairment of LV function, severe mitral stenosis, severe symptomatic aortic stenosis, Marfan syndrome with aortic dilatation > 45mm, aortic dilatation > 50mm associated with bicuspid aortic valve and native severe aortic coarctation.Equally important is the WHO III category in which pregnancy is not directly contraindicated but confers a high risk of maternal complications and should be the object of close follow-up in an experienced tertiary center. This includes the following conditions: presence of mechanical valve, systemic right ventricle, Fontan circulation, unrepaired cyanotic heart disease, other complex congenital heart disease, aortic dilatation 40-45mm in Marfan syndrome and aortic dilatation 45-50mm associated with bicuspid aortic valve.Pregnant patients with unoperated atrio-septal defect (ASD) or ventricular septal defect (VSD), repaired Tetralogy of Fallot and most arrhyhmias comprise the WHO II category and will generally go fairly well if otherwise in good condition and uncomplicated (moderate morbidity risk but small mortality risk), whereas the intermediate WHO II-III category includes patients who could end up to the higher or lower risk category depending on their individual characteristics. The corresponding conditions for these patients are: mild left ventricular impairment, hypertrophic cardiomyopathy, native or tissue valvular heart disease but not considered class I or IV, Marfan syndrome without aortic dilatation, aortic dilatation < 45mm associated with bicuspid aortic valve, and repaired aortic coarctation.Neonatal complications occur in 20-28% of patients with heart disease (8,9), with neonatal mortality between 1% and 4%. Maternal and neonatal events are highly correlated. Maternal predictors of neonatal adverse events in women with heart disease are: baseline NYHA class > II or cyanosis, maternal left heart obstruction, smoking during pregnancy, multiple gestation, use of oral anticoagulants during pregnancy and mechanical valve prosthesis.
The risk of inheritance of cardiac abnormalities to the descendants is significantly higher in women with CVD (between 3% and 50% depending on type of disease) compared to parents without CVD (10).Genetic testing may be useful in some cases (in cardiomyoapathies and channelopathies, when other family members are affected and when other genetic malformations associated with CVD are present).All women with congenital heart disease should be offered fetal echocardiography in the 19th to 22nd week of pregnancy.Detailed personal and family history is mandatory. Thorough clinical examination for new or changing murmurs and signs of heart failure is needed. If such findings, echocardiography should be performed. Blood pressure, proteinuria especially in pregnant women at risk for preeclampsia, pulse oximetry in congenital heart disease need to be taken. Echocardiography for the evaluation of chest pain, 24-hour Holter monitoring in cases of known history of paroxysmal or persistent arrhythmia or palpitations are required.Echocardiography is the preferred diagnostic tool during pregnancy due to absence of radiation exposure, ease of use, bedside availability and ability to evaluate a multitude of CVD (congenital heart disease, cardiomyopathy, aortic disease, etc). Trans-esophageal electrocardiography on the other hand is fairly safe but rarely needed.Submaximal stress testing (80% of max.) could be performed in asymptomatic patients with suspected CVD.Cardiac MRI (without gadolinium) only for congenital heart disease or aortic disease if echo inconclusive is indicated. Chest X-ray, CT, cardiac cath, electrophysiological study generally not recommended, may be considered with shielding of the fetus under very strict and vital indications if no alternative.(You may follow the link for a special look at congenital heart disease, pharmacotherapy and in utero diagnostics in pregnancy)
In families with heart disease, screening for congenital heart disease can start as early as in the 13th week. Screening stands a good chance of accurately detecting major congenital abnormalities (85% sensitivity, 99% specificity) and allow parents to consider all options including termination in case of major malformations. Optimal screening time for normal pregnancies is 18-22 weeks, and studies should be performed by experienced specialists.In general, the preferred mode of delivery is vaginal. In high risk cases, delivery should take place in a tertiary centre under specialist multidisciplinary care. No routine endocarditis prophylaxis is necessary. There is no clear consensus regarding absolute contraindications to vaginal delivery.Cardiovascular conditions that should prompt elective caesarean section consideration are: cases of oral anticoagulation in pre-term labour, Marfan syndrome with aortic diameter > 45mm (class IIaC), or 40-45mm (IIbC) (11), acute or chronic aortic dissection, severe intractable heart failure, Eisenmenger syndrome and aortic stenosis (in some centers) (12).
The risk of pregnancy depends on the underlying heart disease.All patients with these conditions should receive pre-pregnancy assessment.
During the peripartum period (last trimester and first weeks after delivery), there is an increased susceptibility of the aorta to dissection. A larger aorta confers higher risk, but there is no completely ‘safe’ diameter.In Marfan patients with aortic diameter >= 45mm prophylactic surgery is indicated (15).In patients with bicuspid valve, pre-pregnancy surgery should be considered at diameters > 50mm.When progressive dilatation occurs, aortic repair during pregnancy or directly after delivery (depending on viability of the fetus) is indicated.A Cesarean section is indicated when aortic diameter > 45mm.
Moderate-severe mitral stenosis is poorly tolerated during pregnancy, and is associated with heart failure in second and third trimester (16) and implies elevated offspring morbidity.Intervention should preferably be percutaneous pre-pregnancy or after 20 weeks if intractable heart failure.Patients with aortic stenosis should be evaluated before pregnancy to define clinical status.An increase of cardiac output can produce marked increase of transaortic gradient during pregnancy.Pre-pregnancy aortic valve intervention is indicated for severe symptomatic aortic stenosis.Left-sided regurgitant lesions are usually well tolerated during pregnancy due to decreased systemic vascular resistance.Pre-pregnancy surgery (preferably repair) when symptomatic or with compromised LV function.Regarding medical therapy for heart failure symptoms, always have in mind that the significant category of RAS inhibitors (ACE-I, ARBs, renin inhibitors) are absolutely contraindicated during pregnancy due to fetotoxicity.Presence of mechanical prosthetic valve means a high risk pregnancy due to need for anticoagulation and an increased risk of valve thrombosis during pregnancy.Oral anticoagulation (OAC) should be used until pregnancy is achieved. The continuation of OAC throughout pregnancy is the safest strategy for the mother (17) (valid also for first trimester if the daily dose needed is low (warfarin < 5mg).For a look at how to anticoagulate in the pregnant on the pregnant or lactating mother, see previous article here or slides here.Substitution with UFH or LMWH (with dose adjustment according to APTT or anti-Xa activity correspondingly) between 6 and 12 weeks when higher warfarin dose would be needed or anyway when the mother does not accept the low risk of embryopathy associated with warfarin.At the 36th week OAC is to be replaced by dose-adjusted UFH or LMWH. In the event of obstructive valve thrombosis, critically ill patients will need emergency surgery or fibrinolysis.Cesarean delivery is recommended when the patient is still on OAC to avoid fetal cerebral bleeding.
Although generally low, the rate of acute coronary syndromes during pregnancy is expected to increase due to increasing maternal age and prevalence of risk factors.Coronary artery dissection is more prevalent than in non-pregnant women, - to have in mind when ACS occurs around delivery or postpartum (18).Coronary angiography with the possibility of PCI preferred over thrombolysis (it can diagnose coronary artery dissection too).
Peripartum cardiomyopathy is idiopathic cardiomyopathy presenting with heart failure and LV dysfunction towards the end of pregnancy or during the first months following delivery.Exact aetiology is still uncertain, however several pathophysiological mechanisms have been proposed (19).A multitude of predisposing factors (proposed, probable, emerging or novel) exist, they are summarised in Figure 1 (20).These factors can develop very rapidly, and guidelines for the management of acute heart failure apply.Patients not responding to medical therapy and inotropic support should be transferred to centers capable of offering IABP, ventricular assist devices or even heart transplantation. There is a high rate of spontaneous recovery (approx. 50%).Medical treatment should be according to heart failure guidelines except that ACE inhibitors, ARBs and direct renin inhibitors are contraindicated during pregnancy.Urgent delivery in advanced heart failure or hemodynamic instability should be processed by an experienced multidisciplinary team. There is 30-50% risk of recurrence in subsequent pregnancies. Given the high morbidity, pregnancy should be discouraged when EF not normalised, and counselling delivered even if EF normal. (See here the latest congress report on peripartum cardiomyopathy).
In dilated cardiomyopathy, consider pregnancy termination if EF < 20%. In hypertrophic cardiomyopathy, frequently first time diagnosis in pregnancy. Usually tolerated well, high risk if symptomatic high LVOT gradient. B-blockers preferred medical treatment.
Extrasystoles and sustained tachyarrhtyhmias are more frequent or manifest for the first time during pregnancy.Symptomatic exacerbation of SVT in 20-44% of cases (21).Antiarrhythmic drugs potentially toxic for the fetus.Adenosine i.v. treatment of choice for termination of SVT.When new onset ventricular tachycardia at the last weeks of pregnancy or first months after delivery, peripartum cardiomyopathy should be excluded. Most frequent cause of VT in healthy pregnant women is idiopathic RVOT tachycardia.Catheter ablation may be necessary for drug-refractory, poorly tolerated tachycardias (second trimester).For a more in depth-look at this topic see previous article here.
Hypertension is the most common medical problem in pregnancy (up to 15% of total) (22). Hypertension is a major cause of maternal, fetal and neonatal morbidity and mortality.Blood pressure measurements are necessary at least on two occasions and urinalysis is also needed to detect proteinuria.There are four categories:
The drug of choice and safest for hypertension in pregnancy is α-Methyldopa (for mild-moderate cases).In more severe hypertension and pre-eclampsia, will use labetalol, metoprolol and/or nifedipine. ACE-I, ARB’s, and renin inhibitors are contraindicated during pregnancy (fetotoxicity).For severe hypertension (SBP>=170mmHg and/or DBP>=110mmHg, hospitalisation is indicated. Breastfeeding does not increase BP in the nursing mother and can be encouraged, however antihypertensive medication is excreted in the milk. Hypertensive disorders in pregnancy are important risk factors for CVD in later life.
There is an increased risk for venous thromboembolism (VTE) during pregnancy and puerperium, significant cause for morbidity and mortality. Caesarean sections increases this risk.D-dimers and vein ultrasonography are used to exclude pulmonary embolism in pregnant women with acute onset or worsening dyspnoea. Low-molecular weight heparin is the drug of choice for prophylaxis and treatment of VTE in pregnant patients.(See see here a disorder-specific review of the 2011 ESC pregnancy guidelines divided according to the stages of motherhood - pre-pregnancy, pregnancy, delivery and lactation).
Knowledge of the principles of management of cardiovascular disease associated with pregnancy is important in order to allow clinicians to offer reliable pre-pregnancy counseling and optimize maternal and fetal outcome when pregnancy occurs. This often represents a challenge, as long as certain therapies may have diverse effects on the mother and fetus. We hope that this review offered the cardiologist with tools for an up-to-date approach.Nevertheless most of the recommendations included in relevant guidelines have a level C evidence due to the lack of prospective or randomized trials. Therefore, large databases of pregnancy complications (such as the ROPAC and peripartum cardiomyopathy ESC registries), genetic testing and risk assessment are needed in order to fill the gaps in evidence, enhance our knowledge and improve our clinical practice in the management of these patients.
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Vassilis I. Barberis MD, FESCDepartment of CardiologyAmerican Heart Institute/American Medical CenterP.O. Box 25610, 1311 NicosiaTel. +357 22476777 Author's disclosures: None declared.