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Tachyarrhythmias and pregnancy

An article from the e-Journal of Cardiology Practice

With a few exceptions, antiarrhythmic medications appear to be safe for acute treatment of narrow and wide tachycardias when there is hemodynamic compromise during pregnancy. However no drug is absolutely safe, and chronic pharmacologic therapy is best avoided during pregnancy. Radiofrequency ablation can be recommended as an alternative for women with tachyarrythmias prior to pregnancy.

Pregnancy and Cardiovascular Disease


Normal pregnancy is characterised by increased cardiac output, reduced systemic vascular resistance, and a modest decline in mean blood pressure. These changes are associated with a 10–15 bpm increase in HR.
Potential risk factors in pregnancy that can promote arrhythmogenesis include the hyperdynamic state, the altered hormonal milieu, and underlying heart disease. Therapy is justified when there is hemodynamic compromise, which may jeopardise the mother and her fetus due to associated decrease in uterine blood flow.

I - Arrhythmias in context

Supraventricular tachycardias

Paroxysmal SVT refers to intermittent pathologic tachycardia that includes atrial fibrillation and flutter, as well as atrial tachycardia. There are no reliable data on the incidence of paroxysmal SVT in pregnant women (incidence in the general population is 35 per 100,000 person years). The main mechanism for the development of SVT is via re-entry (in 60% of cases). Nevertheless, other mechanisms, such as micro re-entry and focal tachycardias, can be at play.
Episodes of SVT occur with increased frequency during pregnancy, particularly in those with underlying congenital or structural heart disease.

Atrioventricular nodal re-entrant tachycardia

The most common supraventricular tachycardia in pregnant women is atrioventricular nodal re-entrant tachycardia. (1) Atrioventricular nodal re-entrant tachycardia usually does not cause any significant problems in healthy pregnant women or their fetuses. However, rapid nodal re-entrant tachycardia in the presence of heart disease may produce hemodynamic instability. (2)

Atrioventricular re-entrant tachycardia

The second most common form of supraventricular tachycardia is atrioventricular re-entrant tachycardia.
Atrioventricular re-entrant tachycardia has been reported during pregnancy in patients with pre-excitation syndromes. It is caused by accessory pathways sometimes associated with certain forms of congenital heart disease. It can result in serious hemodynamic deterioration in patients with heart failure due to systolic or diastolic dysfunction, congenital heart disease, or a rapidly conducting antegrade accessory pathway. (3)

Atrial fibrillation

 Atrial fibrillation rarely occurs in the absence of congenital or valvular heart disease. When it does happen that atrial fibrillation arises in healthy pregnancies, it is usually well tolerated.
However, atrial fibrillation is frequently encountered in pregnant women with underlying heart disease or thyrotoxicosis. Drugs such as adenosine, digoxin, propranolol, procainamide and flecainide are relatively secure. Direct cardioversion can be used: there has been no evidence of significant complications.

Ventricular tachycardias

Sustained ventricular tachycardia (VT) - duration >30 s - is rare in pregnant women. However, there are reports that VT, when occurring, originates in the patient with a normal heart, mainly from the right ventricular outflow tract. (4) Idiopathic left VT also occurs in pregnant patients with structurally normal hearts, but prognosis is poor when VT is associated with structural heart disease. (5)

II - Diagnosis and treatment considerations

Diagnosis

The pregnant patient with arrhythmias most often seeks medical attention because of palpitations, light-headedness, shortness of breath and/or anxiety. First off, it is important to correctly diagnose the type and mechanism of any underlying arrhythmia and to implement the appropriate therapeutic modality, examining the existence of organic heart disease and discarding causes likely to favor or trigger it. Clues for correct diagnosis and treatment come from findings during physical examination and correct analysis of the electrocardiogram (ECG). Knowing the ECG features of the various types of narrow-QRS or wide-QRS tachycardias are of extreme importance to obtain ECG documentation of the arrhythmia so that the pregnant woman can receive the correct treatment.
In many patients with a narrow-QRS complex tachycardia, the tachycardia rate is very high (180-240 beats/ min.) and, therefore, after onset of the tachycardia, the patient will arrive soon after in an intensive care unit for diagnosis and treatment. If the arrhythmia persists after correction of all factors, treatment should be provided.

Treatment

Certain drugs may cross the placental barrier, such that careful consideration should be given in selecting the antiarrhythmic drug to prevent adverse effects on the fetus. (7,8) Teratogenic risk is higher during the first eight weeks after fertilization, when organogenesis takes place: after this period, risk is substantially reduced. However, certain drugs may interfere with growth and fetal development. Choice of the drug will depend not only on the type of arrhythmia, but also whether a single dose or long-term treatment for prevention of recurrence is considered. The use of multiple antiarrhythmic drugs in the treatment of an episode of tachycardia has been associated with fetal bradycardia, so performing fetal rate monitoring is recommended during acute antiarrhythmic therapy.

Additionally, several factors contributing to the difficulty of maintaining therapeutic blood levels during pregnancy are important to keep in mind: (6,9)

  1. The increase in intravascular volume can lead to an increased loading dose necessary to achieve therapeutic blood concentrations;
  2. Reduction of plasma proteins concentration can reduce the fraction of drug bound to them, producing lower total concentration;
  3. Increased renal blood flow increases associated renal clearance of drugs;
  4. Increased hepatic metabolism secondary to the activity progesterone may also increase the clearance of drugs by this route; and
  5. Gastrointestinal absorption can be altered by changes in gastric secretion and intestinal motility, which renders the serum concentration of some drugs unpredictable.

The FDA has issued the following risk categories concerning use of antiarrhythmic drugs during pregnancy:
A: Controlled studies showed no risk in the fetus in any trimester of pregnancy.
B: No evidence of risk in humans: the chance of fetal harm is remote, although it exists.
C: The risk cannot be ruled out because there are no well-controlled clinical studies, and animal studies show risk to the fetus. Fetal damage Is likely if the drug is administered during pregnancy, but the potential benefits could exceed the potential risk.
D: Sure evidence of risk obtained from human studies, information obtained during investigation or from the demonstrated risk of drug marketing material. However, the potential benefits of using the drug may outweigh the potential risk. For example, the indication may be acceptable in life-threatening situations or for serious diseases for which safer drugs cannot be administered or are ineffective.
X: Contraindicated in pregnancy. Studies in animals or humans or reports during investigation or subsequent marketing of the drug showed certain evidence or risk of fetal abnormality, which clearly outweighed any benefit to the patient (Table 1).

Table 1 : Pharmacologic Treatment within Context of Pregnancy (modified from Ghosh et al. 27)

Table summarises the pharmacological treatment (and adverse effects) for the management of SVT in pregnant women.
(-) Drugs not recommended as first election

Adenosine (C)

 Adenosine is the agent most commonly used during pregnancy, with conversion to normal sinus rhythm in over 80% of cases of acute SVT if non-pharmacological manoeuvres have failed, although manoeuvres such as carotid sinus massage and Valsalva maneuver to control SVT are well tolerated during pregnancy.

Beta-blockers (B-C-D)

Beta-blockers have been extensively used during pregnancy in the treatment of hypertension, hypertrophic cardiomyopathy, thyrotoxicosis, mitral stenosis fetal tachycardia, and are generally well tolerated. (10-14) However, beta-blockers cross the placental barrier and are associated with several adverse effects, such as delayed intrauterine growth, respiratory depression, neonatal bradycardia and hypoglycemia, particularly when treatment is started early on in the pregnancy (i.e. at 12–24 weeks).
In pregnancies complicated by hypertension and treated with propranolol, no congenital abnormalities have been observed (15), but decreased fetal growth has been reported. The administration of atenolol no later than in the first quarter is associated with fetal growth retardation. A meta-analysis in patients with hypertension, which studied the risks of beta-blockers during pregnancy, has found an increase in the number of children who are 'small for gestational age'. The concentration in breast milk is approximately five times higher than in plasma. (16)

Calcium channel blockers (C)

There are few data on verapamil and diltiazem. Clinical studies (17,18) report no maternal teratogenicity and no side effects during pregnancy. Verapamil has been used in treatment of SVT fetal and management of preeclampsia without adverse effects. However, maternal hypotension, fetal heart block and depression of contractility during treatment of fetal arrhythmias has been also reported. (19) There is also a risk potential for reduction in uterine blood flow. For these reasons, verapamil should best be avoided in acute treatment, particularly if adenosine can be used. The effect of diltiazem is less known, but similar limitations are assumed.

Flecainide

It seems unsafe to judge from the experience of isolated cases. However, the use of this drug has not been associated with fetal defects or with adverse hemodynamic or electrocardiographic effects in the newborn. Although it was proven to cross the placental barrier, particularly in the third quarter of gestation, plasma concentration is low compared to amniotic fluid excretion.

Amiodarone (D-E)

There is limited experience with this drug during pregnancy, but studies report serious adverse effects on the fetus, including hypothyroidism, and delayed premature growth. Thus, amiodarone should be reserved only for the treatment of arrhythmias that threaten life and those that are refractory to other drugs. (20) Digoxin crosses the placenta freely, and digitalis toxicity in the mother has been associated with fetal death.

III - Special consideration: wide-QRS tachycardias

Acute treatment 

Differentiation of VT –hemodynamically unstable or stable – is essential. If at any time VT becomes unstable or if there is evidence of fetal compromise, DC countershock (50–100 J) should be delivered immediately. If a DC shock of 50-100 J is unsuccessful, higher energy is mandatory (100–360 J) and without any risk for mother and children.
Acute therapy should start with intravenous procainamide or with ajmaline (50–100 mg iv over five minutes). Procainamide appears to be equally safe. Procainamide is well tolerated and has not been associated with teratotoxicity, whereas the potential risk of ajmaline during pregnancy is unclear and administration should be limited to emergency situations. (5)
Another potential antiarrhythmic drug is lidocaine, which is not known to be teratogenic. Although several studies have shown some adverse effects (increase in myometrial tone, decrease in placental blood flow, fetal bradycardia), its use during the early months of pregnancy is not associated with a significant increase in the incidence of fetal defects. (21)
Class III antiarrhythmic agents (such as sotalol, amiodarone) are very effective drugs in patients with ventricular tachyarrhythmias. During pregnancy, both drugs are of limited value: sotalol appears to be relatively safe, although there is a 3–5% risk of developing polymorphic or torsade de pointes tachycardia. In addition, the ß- adrenergic properties of sotalol must be considered.
Magnesium is another drug with antiarrhythmic properties, particularly in patients with torsade de pointes tachycardia due to QT prolongation. It has been known for a long time that in emergency circumstances, magnesium sulfate (dosage 1 to 2 g iv) is effective to treat and suppress life-threatening ventricular tachyarrhythmias and should be administered over one to two minutes. Although this drug is associated with few side effects, maternal hypothermia and fetal bradyarrhythmias have been observed. In a few cases, verapamil is effective in pregnant women with right/left ventricular outflow.

IV - Non-pharmacological treatment

Electrical cardioversion

Electrical cardioversion (up to 400 joules) 80 has been performed without complications in all stages of pregnancy (22) to treat both supraventricular and ventricular arrhythmias.
To avoid the risk of fetus arrhythmogenesis from the electrical discharge, some authors have suggested that maternal cardioversion should be performed with fetal monitoring. (23) However, no significant effects are expected on the fetus because the fetuses of mammals have high fibrillation thresholds, and the amounts of current that reach the uteri are usually very small. Despite all these reasons and because of the limited information, cardioversion should be performed only when absolutely indicated.

Radiofrequency ablation

Under certain conditions, in which the episodes of tachycardia are frequent or difficult to control with antiarrhythmic drugs, it is possible to perform a radiofrequency ablation procedure. At present we have the technological means to accomplish this with minimal intervention (24) and even in the absence of X-rays. (25) (see Fig. 1)

Anticoagulation

Vitamins K antagonists (VKA) may be teratogenic and in many cases should be replaced by unfractionated heparin or low molecular weight heparin during first trimester. (26) In a systematic review, administration of warfarin during the entire gestation period produced fetal malformations in 6.4% of cases, but no adverse effects were noted when treatment was changed to heparin between weeks six and 12. Warfarin crosses the placenta barrier, and the fetus may receive an overdose even when the mother is in the therapeutic range. Low molecular weight heparin does not cross the placental barrier and has been widely used for treatment and prophylaxis of thromboembolism vein during pregnancy without adverse fetal effects. During the third trimester, frequent laboratory testing is recommended to check that anticoagulation is appropriate (e.g. every 10-14 days) and the corresponding dose is adjusted, taking into account that some women may require high doses of VKA and heparin to maintain appropriate anticoagulation. Pregnant women with AF and mechanical valves should discontinue VKA between six and 12 weeks gestation and should then receive subcutaneously a continuous  IV infusion of unfractionated heparin with an adjusted dose or low molecular weight. They can start VKA treatment in the second quarter with a only slightly higher teratogenic risk.

Fig. 1: 3-D electroanatomic reconstruction with Ensite NavX navigation system of the left ventricle and aortic root (photo taken in our lab).

Image shows radiofrequency ablation of left lateral accessory pathway in a pregnant patient. The electrophysiological study and ablation were performed in absence of X-rays.

Conclusion:

Prognosis will depend on 1) the type of underlying heart disease and 2) the type of tachycardia, and 3) the degree of hemodynamic compromise of the patient. In cases of absence of structural heart disease, prognosis usually points to a benign condition, responding favorably to antiarrhythmic drugs. Treatment remains a challenge though, as clinical decision must be tackled with appropriate consideration of both maternal and fetal factors. Monitoring both mother and fetus should be continued during acute treatment, and in a stable patient, non-invasive manoeuvres should first be attempted. In all cases, evaluation of the underlying etiology and the degree of left ventricular function (dysfunction) is essential. Correct treatment of arrhythmias in the intensive care patient should be based on understanding the causal mechanism. In pregnant women with maternal and/or fetal arrhythmias, therapeutic strategies should be based on interdisciplinary cooperation (obstetrics, cardiology and neonatology).

In general, acute therapy of arrhythmias during pregnancy is similar to that in the non-pregnant patient. However, special consideration should be given to potential teratogenic and hemodynamic adverse effects on the fetus.
With this in mind, a successful pregnancy, for both mother and the fetus, can usually be the result. However, optimal, evidence-based management of maternal SVT in pregnancy, particularly in the first trimester, is limited by the paucity of reported cases.

References


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Volume Number:

Vol. 9, N° 31

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.