Drugs
FDA
Listed complications
Transfer to breast milk
Atenolol
D
Intrauterine growth restriction and premature birth
Yes
Other beta-blockers
C
Low birth weight, hypoglycemia, and bradycardia in the fetus
Yes
Acetylsalicylic acid (ASA)
B
Low-dose aspirin is safe (large database)
Yes, but well-tolerated
Calcium channel antagonists
C
Diltiazem: an increase in major birth defects has been reported
Yes
Clopidogrel
C
The benefits of using clopidogrel in some high-risk pregnancies may outweigh the potential fetal risk
Unknown
Nitrates
B
Careful titration is advised to avoid maternal hypotension
Unknown
Statins
X
Animal studies demonstrated increased skeletal abnormalities, fetal and neonatal mortality.
Unknown
Percutaneous Intervention (PCI) or Coronary Artery Bypass Surgery
There is only limited information available on PCI during pregnancy. However, pregnancy is not a contraindication for PCI and since PCI is the primary treatment for non-pregnant STEMI (ST Elevation Myocardial Infarction) patients, more and more cases of stenting during pregnancy are published. With PCI as a treatment modality during pregnancy, mortality from ACS has dropped. In the first review of Roth and Elkayam in 1996 only 2 % had PCI, whereas in their second review 40 % had a PCI, all with bare metal stenting (Roth and Elkayam 1996, 2008). The preference for bare metal stenting is based on the requirement of dual anti-platelet treatment around the delivery and the lack of experience with this regime in pregnancy.
Since pregnant women are excluded from most clinical trials, no randomised controlled trials have been performed on thrombolytic therapy, PCI or CABG in the pregnancy. However, thrombotic therapy is considered to be relatively contraindicated in patient with ACS because of the risk of bleeding complications. In stroke, pulmonary embolism and mechanical heart valve thrombosis there is some clinical experience with several strategies such as tPA, urokinase and streptokinase. This medication does not cross the utero-placental barrier (Leonhardt et al. 2006). Maternal and fetal outcomes were favourable, but complications, such as maternal haemorrhage, fetal loss, abruptio placentae, preterm delivery and post partum haemorrhage have been reported in up to 10 % of cases with a maternal mortality rate of 1.2 % (Turrentine et al. 1995; Garvey et al. 1998).
Very limited data is available on coronary artery bypass grafting (CABG) during pregnancy and no conclusion concerning the safety of the mother and the unborn child can be made. In normal non-pregnant patients with ischemic heart disease CABG is used when multiple vessels or the left main coronary artery are involved (Nallamothu et al. 2005). In the case study of Roth and Elkayam ten patients were described who underwent CABG, of which seven were due to coronary artery dissection, in these cases one fetal death and one late maternal death were reported (Garvey et al. 1998; Roth and Elkayam 2008). If CABG is necessary for the management of the mother, it is advised to perform the CABG in the second trimester of pregnancy.
Delivery
Planning delivery should be the task of a multidisciplinary team consisting of at least an obstetrician, anaesthesiologist and cardiologist. The delivery should be postponed if possible for at least 2 or 3 weeks after ACS to allow adequate healing (Presbitero et al. 2009). The mode of delivery depends on the maternal hemodynamic situation and obstetric factors. Women with adequate cardiac output may tolerate induction of labour and vaginal delivery. Vaginal delivery can lead to fluctuations in blood pressure, especially if labour is prolonged. Assisted vaginal delivery (by vacuum or forceps extraction) is recommended in high-risk women to avoid excessive maternal efforts and prolonged labour (Roth and Elkayam 2008). Adequate pain relief is very important, but epidural anaesthesia is contraindicated when the patient is on antithrombotic or anticoagulant treatment. As an alternative, narcotic analgesia can be used to reduce anxiety and pain. Vaginal delivery with a shortened second stage of labour and adequate pain relief can be safe and is preferred to caesarean section, especially as blood loss is lower. However, caesarean section is the preferred mode of delivery in patients with cardiac instability. During caesarean delivery, the blood pressure can be controlled, stress and pain relieved and a stable environment created. However, caesarean section has been associated with a higher risk of venous thrombo-embolism, infection and peripartum haemorrhage. In some cases general anaesthesia will be necessary with some risk of complications (Deneux-Tharaux et al. 2006). In addition, blood loss during caesarean section has been shown to be about twice as high as during vaginal delivery.
Breastfeeding
The effects of breast-feeding on maternal cardiovascular function are caused by circulating hormones. High levels of oxytocin circulate through the body. In the study of Mezzacappa cardiac output during breastfeeding was found to be higher than in bottle-feeding mothers. They describe a decrease in heart rate and a slight increase in systolic blood pressure during the first minutes of breast-feeding (Mezzacappa et al. 2001). The fluctuations in blood pressure may be dangerous in severely symptomatic patients and bottle-feeding should be considered (Light et al. 2000).
Arrhythmias
Arrhythmias in pregnancy are common and may cause concern for the wellbeing of both the mother and child. The arrhythmias may be a recurrence of a previously diagnosed arrhythmia or the first presentation in a woman with known structural heart disease. In most cases, however, no previous history of heart disease is known, and the new occurrence of a cardiac problem can give rise to considerable anxiety. The majority of arrhythmias occurring during pregnancy are benign, and simply troublesome. Reassurance and advice about appropriate actions during symptomatic episodes are usually all that is required. In the remaining minority of cases, judicious use of antiarrhythmic drugs will lead to a safe and successful outcome for both mother and baby (Newstead-Angel and Gibson 2009). The major concern regarding the use of antiarrhythmic drugs is their potential adverse effects on the fetus. All antiarrhythmic drugs should be regarded as potentially toxic to the fetus.
Mechanism of Arrhythmia
The cardiovascular system undergoes significant changes in adaptation to pregnancy, including an increase in heart rate and cardiac output, reduced systemic resistance increased plasma catecholamine concentrations and adrenergic receptor sensitivity, atrial stretch and increased end-diastolic volumes due to intravascular volume expansion, as well as hormonal and emotional changes. A combination of these and the heightened visceral awareness experienced in pregnancy may lead a woman to seek advice on symptoms that are within the normal range and may otherwise have been ignored. Being pregnant is unlikely to generate a new arrhythmia, however, premature extra systolic beats are often seen during pregnancy.
Management of Specific Arrhythmias
Table 2 summaries the drug of choice for specific arrhythmias.
Table 2
Drugs for management of specific arrhythmias: to use or to avoid
Arrhythmia | Preferred medication | Avoid | Comments |
|---|---|---|---|
Supraventricular tachycardia | Adenosine | Dispyramide | β-blockade is often effective at suppressing ventricular ectopy and arrhythmias. Lidocaine followed by proacainamide is suggested for sustained ventricular arrhythmias. In refractory cases, amiodarone or placement of an ICD may be considered |
Metoprolol | Propafenone | ||
Digoxine | |||
Verapamil | |||
Sotalol | |||
Procainamide | |||
Atrial fibrillation | Digoxine | Amiodarone | β-blockers, digoxin or verapamil may be used to slow the ventricular rate. Restoration of sinus rhythm is desirable (to avoid need for anticoagulation) and may be attempted with sotalol, procainamide, flecainide or electrical cardioversion. |
Metoprolol | |||
Verapamil | |||
Sotalol | |||
Fleicainide | |||
Ventricular tachycardia | Metoprolol | Amiodarone | β-blockade is often effective at suppressing ventricular ectopy and arrhythmias. Lidocaine followed by proacainamide is suggested for sustained ventricular arrhythmias. |
Procainamide | |||
Lidocaine |
Supraventricular Tachycardia (SVT)
The drug of choice is partly dependent upon the SVT being treated. Atrioventricular nodal re-entry tachycardia (AVNRT) and atrioventricular re-entry tachycardia (AVRT) involving an accessory pathway can be terminated by vagal manoeuvres or if that fails, an intravenous bolus of adenosine can be administered until the desired response is achieved (Elkayam and Goodwin 1995). Intra-venous metoprolol is recommended if adenosine fails to terminate a tachycardia. Prophylactic antiarrhythmic medication should be used only if symptoms are intolerable or the arrhythmia causes haemodynamic instability. Digoxin or a selective beta-blocker (metoprolol) are the first-line drugs, followed by sotalol, or propafenone (Blomstrom-Lundqvist et al. 2003). AV nodal blocking agents should not be used in patients with manifest pre-excitation on resting ECG. Catheter ablation should be considered only in special cases if necessary during pregnancy.
Atrial Fibrillation and Flutter
Atrial fibrillation and flutter are uncommon in pregnancy and are most commonly associated with congenital or valvular heart disease as well as metabolic disturbances such as thyrotoxicosis or electrolyte imbalance. A rapid ventricular response to these arrhythmias can lead to serious haemodynamic consequences for both mother and fetus. Diagnosis and treatment of the underlying condition is therefore the first priority. Electrical cardioversion should be performed in the case of haemodynamic instability. In haemodynamically stable patients, pharmacological termination of the atrial or AF can be considered. Intravenous ibutilide or flecainide are usually effective, but experience during pregnancy is very limited (Kockova et al. 2007).
When rate control is recommended, the ventricular rate can be controlled with AV nodal blocking drugs including digoxin, beta-blockers and non-dihydropyridine calcium channel antagonist (verapamil, diltiazem) (Fuster et al. 2006). Prophylactic antiarrhythmic drugs (sotalol, flecainide or propafenone) may be considered in the cases of severe symptoms despite rate-controlling drugs. Flecainide and propafenone should be combined with AV nodal blocking agents. Mexiletine and amiodarone are contra-indicated in pregnancy with the exception of an acute setting or as last resort (European Society of Gynecology et al. 2011).
The recommendation in respect of anticoagulation in atrial fibrillation and flutter will be discussed in another chapter.
Ventricular Tachycardia (VT)
Life-threatening ventricular arrhythmias are uncommon during pregnancy. Rapid VT causes hypotension, reduced myocardial coronary perfusion and subendocardial ischaemia, an unstable situation that may degenerate into ventricular fibrillation. In healthy patients, idiopathic right ventricular tachycardia (VT) originating from the right ventricular outflow tract is the most frequent type in pregnancy and should be treated using either verapamil or beta-blocking agents. The drugs should be used as prophylaxis only if the VT is associated with severe symptoms or haemodynamic compromise (Nakagawa et al. 2004).
Ventricular tachycardia in the presence of structural heart disease is associated with a significant risk of sudden death and requires emergency treatment. For acute treatment of VT with haemodynamic instability, immediate cardioversion, which seems safe in all phases of pregnancy, is recommended. Prophylactic therapy with a cardioselective beta-blocker, such as metoprolol, may be effective (European Society of Gynecology et al. 2011). Sotalol or Class Ic antiarrhythmic drugs may be considered in the absence of structural heart disease.
Antiarrhythmic Drugs in Pregnancy
The decision to treat a woman depends upon the type of arrhythmia, frequency, duration and tolerability of the arrhythmia. It is a balance between the benefit of arrhythmia reduction or termination and the maternal and fetal side effects of any drug treatment. The greatest risk to the fetus is during organogenesis and this is complete by the end of the first trimester. The smallest recommended dose should be used initially and be accompanied by regular monitoring of the maternal and fetal condition. An overview of medications used in the treatment of arrhythmia, including their pharmacokinetics, mechanism of action, indications, safety and effectiveness in pregnancy is set out in Table 3.
Table 3
Drugs for arrhythmias in pregnancy
Drugs | FDA | Listed complications | Transfer to breast milk |
|---|---|---|---|
Adenosine | C | Pregnant women may respond to lower doses due to a reduction in adenosine deaminase | No |
Atropine | C | Insufficient data | Yes, small amount |
Amiodarone (Class III) | D | If prolonged use; fetal hypo‐ and hyperthyroidism, goitre, IUGR, prematurity | Yes, avoid during breast feeding |
Beta‐blockers | C | IUGR, bradycardia, apnoea, hypoglycaemia, hyperbilirubinaemia | Yes |
Digoxin | C | Miscarriage and fetal death in toxicity | Yes, small amount |
Calcium channel antagonists | C | Skeletal abnormalities, IUGR, fetal death < div class='tao-gold-member'>
Only gold members can continue reading. Log In or Register to continue
 Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|