Fetal tachyarrhythmias occur in approximately 0.4-0.6% of all fetuses.1-3 Normal fetal heart rates range from 120-160 beats per minute (bpm), with rates greater than 180bpm indicative of tachycardia.4-7 Usually, fetal arrhythmias are isolated findings; however, 5% of fetuses will also have congenital heart disease,8,9 such as Ebstein's anomaly, atrioventricular canal, hypoplastic left heart syndrome, or intracardiac tumors. While most arrhythmias are intermittent, more persistent arrhythmias may lead to fetal heart failure, or non-immune hydrops fetalis;4,10 progression to hydrops may be seen in up to 40% of cases with sustained tachycardia.11 Hydrops is seen with ventricular rates greater than 230bpm lasting for over 12 hours.2,5,12 Early echocardiographic evidence of hemodynamic compromise includes biatrial enlargement and atrioventricular valvar regurgitation; later findings include cardiomegaly and decreased systolic function. The diagnosis of hydrops is made by echocardiographic findings of ascites, pericardial effusion, pleural effusions, and subcutaneous edema. The prognosis for hydrops associated with fetal arrhythmia is poor with mortality as high as 50-98%,4,13 compared with 0-4% in cases without evidence of significant failure.6
The primary goal of fetal therapy is the prevention or resolution of hydrops.14,15 This may be achieved by: conversion to sinus rhythm; or ventricular rate control.8,12,16 The use of fetal echocardiography, M-mode and pulse-wave Doppler has lead to improved diagnosis of fetal arrhythmias, and remains the cornerstone of diagnosis.1,6 Fetal magnetocardiography, a non-invasive method for diagnosing complex fetal arrhythmias, is available at limited centers.1,8
Initial medical therapy is delivered transplacentally by administering medication to the mother orally or intravenously. Since there are reports of serious maternal adverse events, it is recommended that the mother remain hospitalized and monitored during initiation of therapy.4,15,17 If transplacental therapy fails, there are other modalities (i.e. direct fetal therapies) for therapy including intramuscular, intra-amniotic, intra-peritoneal, intra-umbilical, and intra-cardiac fetal injections.14 There is a greater mortality for fetuses who undergo these procedures;16 it is unclear if the increased mortality is due to the procedure or the severity of the underlying condition.14
Successful cardioversion to sinus rhythm occurs from 65-95% usually one week into treatment in the hydropic fetus,13 or within 48 hours in the non-hydropic fetus; long-term prognosis post-cardioversion is good.5 Neurologic complications have been reported postnatally in hydropic fetuses, possibly related to periods of cerebral ischemia associated with hypotension.9,13,18
Supraventricular tachycardia (SVT), the most common fetal tachyarrhythmia, accounts for 70-80% of fetal tachycardia.7 It is often diagnosed around 28-32 weeks gestational age but may be seen earlier.5,7 Typically, the mechanism for SVT is atrioventricular re-entrant tachycardia (AVRT) from an accessory pathway, with left-sided pathways being most common.7 Multiple pathways can seen in pre-natal life,5,7 and 25% of fetuses have been noted to have pre-excitation post-natally.6,7 By echocardiogram, there is 1:1 atrioventricular conduction with a short VA interval.4-7,19 The rate of SVT is typically greater than 250bpm and is regular,5 with little beat-to-beat variability. This rhythm may be intermittent (see Figure 1) or incessant leading to fetal hydrops.5 Overall mortality for sustained fetal SVT is 8.9%,7,11 and higher in hydropic fetuses.5
First-line therapy in a non-hydropic fetus is digoxin;4,8,10,14,17,19,20 however, in hydropic fetuses, it has limited utility.21 Digoxin (pregnancy category C) acts to increase the refractoriness of the AV node8 and its therapeutic effect is due to its negative chronotropic and positive inotropic effects.11,14 Fetuses with poor ventricular function may not respond well to digoxin. Fetal digoxin levels are less than maternal levels; due to variable absorption, large volume of distribution, and rapid clearance of medication.4,7,8 The mother must be treated with high therapeutic doses of digoxin, which may result in maternal side effects, including GI and CNS disturbances, and cardiac arrhythmias (premature beats, AV block).8,14,20 Intramuscular fetal digoxin therapy has also been effective in treating the refractory hydropic fetus.5,7
Propranolol (pregnancy category C), a β-blocker, is used primarily in combination therapy. The mechanism of action is to increase AV node refractoriness.20 As a negative inotrope, ventricular function may be effected.4 Side effects include hypoglycemia and low birth weight.7,20 Amiodarone (pregnancy category D), a class III anti-arrhythmic blocking sodium, potassium, and calcium channels,8 has been used successfully for treating fetal tachycardia with associated hydrops.8,14,16 It has been used alone and in combination with digoxin and/or sotalol.22
The most common side-effect, fetal hypothyroidism, is generally transient and treatable with no long-term complications.7,22 Other reported side-effects include thrombocytopenia and rash.8 Often, amiodarone is administered transplacentally, but has been used in direct fetal therapy.There have been no reported deaths with amiodarone monotherapy;7,20 however there are reports of intrauterine demise with amiodarone and flecanide.22 Flecanide (pregnancy category C) acts on accessory pathways, blocking conduction through sodium channels.4,8 It is effective in the hydropic population.10 Some institutions utilize flecanide as first-line therapy, with/without digoxin, for this group.13,17,19 The excellent fetal bioavailability,14 even in the presence of hydrops, makes flecanide attractive for transplacental therapy. There are reports of fetal demise in patients treated with flecanide, but it is unclear whether the cause of death was proarrhythmia or the severity of the heart failure.14 Flecanide should be avoided in fetal atrial flutter and mothers with structural or ischemic heart disease, cardiomyopathy, or bradycardia.8 Major side-effects are maternal proarrhythmia and QRS prolongation.8,20 Procainamide (pregnancy category C) also acts at the level of the accessory pathway; specifically, blocking sodium, and potassium channels. It has also been tried in hydropic fetuses; however, procainamide is a uterine irritant and may lead to premature labor.4,7 There have been reports of intra-chordal adenosine (pregnancy category C). It has been used both diagnostically (to unmask atrial flutter3) and therapeutically. There is concern for dose-dependent contraction of placental vessels with a potential reduction in blood flow.4
Atrial flutter (AFL), the second most common tachyarrhythmia,11 accounts for 25% of fetal tachyarrhythmias.5 Typical time of presentation is around 32 weeks gestational age but may be noted at delivery.5 The electrophysiologic mechanism of tachycardia is intra-atrial macro-re-entry, similar to adult AFL.6 Overall mortality from AFL is 8%,11 but may be as high as 30% in the hydropic fetus.
Diagnosis is made when there is a regular rapid atrial rate of approximately 400bpm with variable AV conduction. In 80% of patients, conduction is 2:111 (see Figure 2), resulting in ventricular rates of 200bpm.4 AFL may progress to 3:1 block, or alternatively may develop intermittent 1:1 conduction.1 The rhythm is irregular and persistent, and is associated with fetal hydrops in 7-43% of cases.1 AFL may be associated with congenital heart disease or chromosomal abnormalities.5
As in the treatment of fetal SVT, digoxin is used as first-line therapy for non-hydropic fetal AFL.11 Studies have shown that sotalol (pregnancy category B; anti-arrhythmic class III) is efficacious in the treatment of fetal AFL,2,6 and less effective for SVT. It does not contribute to intrauterine growth retardation.18 Side-effects include ventricular arrhythmias, particularly Torsades de Pointes.8 Sotalol has less negative inotropic effects than other β-blockers,23 and crosses the placenta easily reflecting fetal blood levels on a 1:1 ratio with maternal levels.2,14
Other 1:1 A:V Tachycardias
Ectopic atrial tachycardia (EAT) is a rare automatic tachycardia caused by an ectopic atrial focus generating impulses faster than the SA node.4,6,8,12 Typical rates range from 210-250bpm.6,12 It has a characteristic 'warm-up' phenomenon with an accelerated rate.7 EAT is more difficult to control than AVRT; combination medical therapy is often utilized. Persistent junctional reciprocating tachycardia (PJRT) is a slow form of AVRT.The accessory pathway has very slow retrograde conduction conduction6 with the usual obligatory 1:1 atrioventricular association seen in faster AVRT.7 This uncommon arrhythmia has rates around 180-220bpm.7,8 Since it is generally incessant, hydrops can be associated with this arrhythmia. Congenital Junctional Ectopic Tachycardia (JET), a rare tachyarrhythmia in fetuses, is a slower yet incessant tachycardia with rates of 180-200bpm.20 This arrhythmia can be 1:1 or have a faster ventricular rate than atrial rate and may have a familial occurrence.24
Ventricular Tachycardia (VT)
Fetal VT is also quite rare,11 with ventricular rates from 170-400bpm. Often, there is more ventricular dysfunction than seen with AVRT.7 There is atrioventricular dissociation with a faster ventricular than atrial rate.4 VT is usually paroxysmal and may be seen during labor;1,4 it may be associated with myocarditis, complete heart block, or congenital long QT syndrome.7 Prognosis depends on the underlying mechanism. Propranolol and amiodarone have been used for treating fetal VT. Intravenous lidocaine (pregnancy category B) has been utilized with some success,4,7 and magnesium (pregnancy category A) has been reported for treatment of fetal torsades.7
Diagnosis of fetal tachycardia depends on accurate ultrasound assessment of fetal heart rate and atrium to ventricle relationships.Therapy is chosen based on the presence or absence of hydrops as well as the presumed mechanism of tachycardia. Long-term prognosis, of fetal tachycardia despite severity of illness at time of presentation, is good, especially if conversion or rate control can be attained in utero21 and hydrops is avoided. Premature delivery of the hydropic fetus is almost universally fatal and should be avoided. The goal of fetal anti-arrhythic therapy is term delivery of a non-hydropic baby.