www.elsevier.com/locate/ppedcard

Progress in Pediatric Cardio

Tachyarrhythmias in the fetus: State of the art diagnosis and treatment

Zeev Perles, Sagui Gavri, Azaria J.J.T. Rein*

Division of Pediatric Cardiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

Abstract

Sophisticated methods for detection of tachyarrhythmias in the fetus as well as effective treatment strategies exist. In this chapter, we

discuss the current state-of-the art in detection and management of tachyarrhythmias in the fetus, with an update on new diagnostic

methodologies and the most current treatment strategies.

D 2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: Supraventricular tachycardia; Junctional ectopic tachycardia; Anti-arrhythmic medications

1. Introduction

Fetal tachycardia is a relatively common condition

occurring in approximately 0.5% of all pregnancies [1].

About 1 in 200 fetuses with frequent atrial ectopy will

develop supraventricular tachycardia (SVT), either in utero

or in the newborn period [2]. The risk of SVT increases to

about 10% when ectopy is re-entrant or when complex

ectopy (couplets, triplets) is noted [3]. Only a small fraction

of this group have sustained tachyarrhythmias and is

therefore at risk for developing low cardiac output, hydrops

fetalis and ultimately fetal death or significant neurological

morbidity [4–6]. There is a consensus that fetuses which

present with persistent tachyarrhythmia and clinical signs as

hydrops should be treated. The choice of the specific drug

therapy and the chances of success depend largely on the

type of tachyarrhythmia. The determination of the type of

tachycardia is therefore of utmost importance [7]. The

available diagnostic armamentarium is persistently growing.

In addition to the widely used M-mode and flow Doppler

echocardiography, new non-invasive techniques have be-

come available which fundamentally improve our ability to

characterize the type of fetal tachyarrhythmia. Such methods

include myocardial deformation imaging, fetal magneto-

cardiography and electrocardiography. In this chapter, we

will discuss the different methods for diagnosing fetal

1058-9813/$ - see front matter D 2006 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.ppedcard.2006.01.010

* Corresponding author. Tel.: +972 2 6777111; fax: +972 2 6434520.

E-mail address: rein@cc.huji.ac.il (A.J.J.T. Rein).

tachyarrhythmia. The various types of tachyarrhythmia will

be discussed along with their treatment.

2. Historical overview

Fetal tachyarrhythmia was first diagnosed in 1930 using

phonocardiography [8]. Surprisingly, it took 40 years until

its clinical significance became apparent, when Silber et al.

noted the association of fetal supraventricular tachycardia

with mortality from non-immune hydrops fetalis [9]. The

recognition in the late 1970s of groups at risk for malignant

fetal arrhythmias [10] led to the first efforts to treat the fetus

using transplacental drug transfer after maternal administra-

tion of digoxin [11], verapamil [12], or propranolol [13].

More aggressive efforts with umbilical cord adenosine

administration started in the mid-1990s [14,15]. The

diagnosis of fetal tachyarrhythmia paralleled the develop-

ment of echocardiography. The earliest analyses of fetal

arrhythmias were made in the early 1980s [16–19]. They

were based on M-mode echocardiography in which the

cursor would be directed through the atrial wall and the

ventricular wall or the atrioventricular valve. This technique

was not only tedious, but was frequently unsuccessful

because of inability to align the M-mode cursor through

these structures due to the position of the fetus. Dual M-

mode echocardiography has been used to overcome some of

these difficulties [20]. With the introduction of two-

dimensional echocardiography, one was able to provide a

logy 22 (2006) 95 – 107

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–10796

qualitative assessment of the relationship between atrio-

ventricular events as well as to detect atrial or ventricular

ectopic activity. Two-dimensional-guided pulsed wave

Doppler provided rapid information on cardiac rhythm as

it sampled the blood flow from different chambers

throughout cardiac cycle. Simultaneous pulsed Doppler

interrogation of the inflow and outflow of the ventricle

[21] was easier to perform and thus had been advocated in

the mid-1980s to use rather than M-mode echocardiogra-

phy [22]. The simultaneous recordings of superior vena

caval and aortic flow patterns was found later to be even

more accurate in determining atrio-ventricular relationships

[23].

By the end of the 1990s, new techniques have emerged

which changed our understanding and ability to treat fetal

tachyarrhythmias. In the late 1990s , fetal magnetocardio-

gram was developed and fetal arrhythmia could be

diagnosed based on the ECG signal. The fetal magneto-

cardiogram became more accurate with the ability to detect

P and T waves [24–26]. In fact, the first fetal QRS-complex

based on magnetocardiography had already been observed

in 1974 [27], however this signal-averaged method preclud-

ed its use in the diagnosis of fetal arrhythmia. By the

beginning of the millennium, with the introduction of tissue

myocardial imaging, tissue velocity and strain rate imaging

were used in the diagnosis of fetal tachyarrhythmias [28–

30]. The use of fetal tissue velocity imaging in the diagnosis

of various atrial and ventricular arrhythmia was established

in 2002 [31].

In past reviews on fetal tachyarrhythmia [32,33], the

diagnosis of the different types was based upon conven-

tional M-mode, two-dimensional and Doppler flow meth-

ods. The diagnosis of ectopic tachycardias such as atrial

ectopic tachycardia, multifocal atrial tachycardia, junctional

ectopic tachycardia or ventricular tachycardia could only be

made by inference and not by direct observation. With the

introduction of the latest myocardial deformation method-

ology, these tachyarrhythmias can now be diagnosed more

accurately. The origin of the ectopic focus, their pathway

and the atrioventricular time relationship can now be more

precisely assessed [29,31]. We therefore elected to include

also atrial ectopic tachycardia and multifocal atrial tachy-

cardia in this review.

Table 1

Fetal tachycardia can be roughly differentiated by the heart rate

Heart rate (bpm)

<165 NSR

Blocked tachyarrhythmia

165–210 Sinus tachycardia

SVT

AET

slow VT/accelerated ventricular rhythm

>210 SVT

AET

JET

VT

A heart rate of 210 bpm or more is always abnormal.

3. Diagnostic workup

3.1. Medical history

Careful family history of arrhythmia is important as

familial congenital predisposition such as LQTS or Wolf-

Parkinson-White syndrome may occur. Also, a family

history of tuberous sclerosis should raise the suspicion of

cardiac neurofibromata in the fetus with tachyarrhythmia.

The mother with a diagnosis of tachyarrhythmia should

be taught to pay attention to diminished fetal movements as

this might be the only maternal sign of tachycardia-induced

heart failure.

3.2. Auscultation

Although tachycardia can be detected by auscultation of

the fetus, its value is merely for screening and referral for

further investigation.

3.3. Cardiotocography

This continuous wave Doppler-based technique is

routinely used in obstetric units. It is the only means for

continuous fetal monitoring during initiation of transpla-

cental therapy and during labor. It can truncate the fetal

heart rate if greater than 220 bpm, and is unreliable for

recording fetal ectopic activity (Table 1).

3.4. Fetal electrocardiography

Despite continuous research aimed to improve signal to

noise ratio, transabdominal fetal electrocardiography is still

clinically limited in arrhythmia analysis. Since this is a

signal average based methodology, beat-to-beat analysis is

not available. Atrial activity is not usually discernible even

in early gestational weeks, and this becomes worse from the

32nd week and on, due to the insulation of the vernix

caseosa [34]. During labor, however, if a fetal scalp

electrode is in place, adequate rhythm strip can frequently

be obtained by attaching the two lead ends to record lead I

and the remaining leads to the upper maternal abdomen. The

utility of this method is limited to the expertise of the staff at

labor.

3.5. M-mode echocardiography

This is the earliest technique which allowed effective

analyses of fetal arrhythmias. The cursor would be directed

through the atrial wall and the ventricular wall or the atrio-

ventricular valve [16–19] to show simultaneous mechanical

atrial and ventricular activity over time. The advantage of

M-mode is that it is available in virtually all ultrasound

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107 97

machines. Also, the sampling rate is the highest among all

the available techniques (in the order of 1000 Hz). However,

this technique is tedious and also frequently unsuccessful

because of the inability to align the M-mode cursor through

these structures due to the position of the fetus. There is also

loss of clear markers of atrial and ventricular contractions in

hydropic fetuses with hypocontractile myocardium and poor

picture resolution related to factors such as maternal obesity,

fetal position, or polyhydramnios.

Physicians have tried to overcome the problem of

alignment by using dual M-mode methodology. Some

echocardiographic systems can produce M-mode data from

any line which would be drawn through previously stored

scan-line raw 2D data (Fig. 1). This last methodology, the

‘‘anatomical M-mode’’, allows analysis in any orientation of

the fetal heart. However its sampling rate being dependent

on the 2D frame rate is lower than conventional M-mode by

one order of magnitude.

3.6. Two-dimensional echocardiography

It only provides qualitative assessment of a tachyar-

rhythmia. A trained ultrasonographist will detect a fast heart

rate and in many cases will be able to ‘‘perceive’’ atrial

flutter.

3.7. Doppler echocardiography

Pulsed Doppler echocardiography has an important role

in the evaluation of fetal arrhythmias [22]. The sample

volume size must be adjusted to relatively small sizes (1–

Fig. 1. Two-dimensional-directed M-mode tracing of a 30-week-old fetus with a

tachycardia was observed and atrial ectopic tachycardia suspected. The M-mode

panel). The eccentric ‘‘anatomical’’ M-mode line was drawn through the right ven

atrial (RA) free wall. There is a one-to-one atrio-ventricular conduction (around 8

1.5 mm) in order to restrict the sampling artifact. Doppler

positions for rhythm interpretation include: the foramen

ovale and hepatic veins for detection of atrial rate; left

ventricular outflow for ventricular rate and simultaneous

inlet/outlet region of either ventricle for atrioventricular

contraction sequence (Fig. 2). Rhythm assessment of the

atrium during long-standing atrial flutter may be more

accurate by Doppler than by M-mode, since the atrial wall

motion often becomes hypokinetic with mechanical alter-

ation of the contraction.The left ventricular Doppler inflow/

outflow method is feasible in more than 90% of the cases

[35] but is somewhat time consuming. Its major limitation

resides in the fact that any atrial event which would occur

during ventricular systole will not be detected by this

method as the atrio-ventricular valve is closed. Thus, any

tachyarrhythmia involving atrioventricular dissociation will

not be diagnosed by this method. Fouron et al. have

introduced a method which overcomes this last problem. By

sampling simultaneously the superior vena cava and the

ascending aorta, they were able to record the retrograde a

wave in the superior vena cava along with the systolic flow

in the aorta. This elegant method which requires alignment

of these two parallel vessels with the Doppler beam is

tedious and feasible in their experienced hands in only 63%

of the cases [36]. Using this same method in 18 fetuses with

fetal tachycardia, they were also able to differentiate long

VA from short VA tachycardia- the mechanical equivalent to

long and short R-P tachycardias. They divided fetuses into 3

groups: the short V-A tachycardia was interpreted as being

caused by fast accessory pathway reentry and was conse-

quently treated with digoxin, the long V-A tachycardia was

trial ectopic tachycardia (180 bpm). Warming up and cooling down of the

tracing (right panel) was obtained off-line from 2D raw scan-line data (left

tricular (RV) free wall, via the tricuspid valve annulus to the posterior right

0 ms).

Fig. 2. Left ventricular inflow/outflow Doppler tracing of a fetus (34th week of gestation) with atrial ectopic tachycardia at about 190 bpm. There is a one-to-

one relationship between LV outflow in systole (S) and the diastolic filling (D). Note that due to the tachycardia with short diastolic filling period, the rapid

filling and the atrial contraction waves are superimposed and cannot be differentiated. This is one of the limitations of this LV inflow/outflow technique.

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–10798

interpreted as atrial ectopic tachycardia (AET) or paroxys-

mal junctional reciprocating tachycardia (PJRT) and treated

with sotalol, and atrial flutter with variable A-V block,

which was treated with digoxin. They have shown good

therapeutic response and good accuracy of their prenatal

diagnoses compared to the postnatal known mechanisms

[37]. Our experience is that the major limitation of this

elegant technique is its feasibility, which is less then 50%,

especially in obese women.

3.8. Magnetocardiography

The fetal magnetocardiogram is based on the measure-

ment of the magnetic fields produced in association with

cardiac electrical activity. Recording fetal magnetocardio-

gram is even more problematic than recording fetal ECG as

it needs to detect a magnetic flux density of the order 1 pT

(10�12 T) in the presence of the much larger Fbackground_magnetic flux densities produced by the Earth (¨10�4 T),

large nearby metallic objects (¨10�7 T) and even jewellery

or metallic clothing fasteners worn by the patient. The only

sensor that is sensitive enough to monitor such weak fields

is a SQUID (Superconducting Quantum Interference De-

vice). The derived system requires considerable technical

skill and significant costs associated with both the employ-

ment of trained personnel and the purchase of liquid helium

which is needed to cool the SQUID. Furthermore, exams

must be performed in a magnetically shielded room. Also,

fetal magnetocardiography can only be performed when the

fetus is perfectly immobile as motion of the fetus itself

changes the magnetic field. From a clinical perspective, this

methodology does not provide a real solution to fetal

arrhythmia analysis. Having said that, fetal magnetocardiog-

raphy is still the best available method to diagnose LQTS,

by acquiring an accurate averaged signal of the PQRST

complex. It has also been shown as an excellent tool to

study fetal tachyarrhythmias including initiation and termi-

nation patterns [38].

3.9. Myocardial deformation analysis

This novel technique uses similar physical principles as

conventional Doppler echocardiography. However, instead

of interrogating blood flow velocity, the filtering of tissue

Doppler echocardiography is set so that objects with high

amplitude and low velocity such as the myocardium are

interrogated, while low-amplitude, high-velocity signals

from blood cells are filtered-out. Doppler tissue echocardi-

ography has been used to diagnose various tachyarrhyth-

mias [29,31]. It has the advantage over the conventional

Doppler left ventricular inflow/outflow that it detects atrial

events even when the atrioventricular valve is closed. It does

not require perfect alignment as for M-mode or the latest

Doppler superior vena cava-aorta method. Both tissue

velocity (TVI) or strain rate (SRI) are used. Its feasibility

is close to 100% and can be recorded as early as the 13th

week of gestation. Atrial and mechanical events can be

measured and plotted simultaneously on a time base at a

high temporal resolution (up to 12 ms). This ‘‘ladder’’

diagram named fetal kinetocardiogram (Fig. 3) allows fast

and accurate diagnosis of complex reentry and ectopic

tachyarrhythmias. Moreover, location of an ectopic focus or

120

60

211

211

235

185

635

578

764

710

746

746

894

840

1000376

322

490

445

481

481

0 200 400 600 800 1000 1200

Time (msec)

RV

LV

A

V

L

A

RA

Mean Intervals (msec)

PP interval (msec) 126 115 141 114 145 129 130 106

RR Interval (msec) 268 270 265

Atrial rate min-1 477

HR (ventricular) min-1 224

Fig. 3. Fetal kinetocardiogram of a 23-week-old fetus with atrial flutter recorded over a period of 1200 ms (3 cardiac cycles). The time intervals and heart rate

are calculated from time events in the right and left atrium (RA and LA) and in the right and left ventricle (RVand LV) recorded simultaneously (upper panel).

The lower panel represents the automatically plotted ‘‘ladder’’ diagram of these events. There is a fast and regular atrial flutter of 477bpm with a 2:1 AV

conduction resulting in a 224 bpm ventricular rate.

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107 99

reentry pathway is usually available using tissue velocity or

strain rate imaging. In our experience, fetal kinetocardiog-

raphy is to date the most appropriate method for assessing

fetal tachyarrhythmia. Its major drawback is that it requires

a high-end system equipped with Doppler myocardial

imaging software.

4. Treatment

4.1. Non-specific therapy

It was recently shown in animal models, that glucose-

insulin infusion during fetal tachycardia has a beneficial

effect on myocardial metabolism and cardiac function [39].

Moreover, induced maternal hyperglycemia improved fetal

cardiac function during fetal tachycardia [40].

4.2. Drug therapy

Most of the antiarrhythmic drugs have been used in the

treatment of fetal arrhythmia. Our purpose in this chapter is

to describe and focus on the drugs which have been

specifically studied in the fetus.

4.3. Amiodarone

This is a type III antiarrhythmic agent. Due to its large

iodine content, it is known to cause fetal and maternal

thyroid dysfunction and postnatal TFT are warranted. It may

also cause hepatic and pulmonary toxicity and corneal

deposits. Recently Strasburger et al. [41] have used

transplacental amiodarone for treatment of 26 hydropic

fetuses who have failed first line treatment with digoxin, and

also failed second line treatment with various drugs in 13.

Sixteen of the 26 (61%) have converted to sinus rhythm

with amiodarone addition alone and 3 fetuses converted

with addition of verapamil or flecainide The only significant

neonatal side effect was thyroid dysfunction in 5 with

practically no clinically significant maternal side effects.

Amiodarone was less effective for atrial flutter (3/9). In light

of these findings, Amiodarone may be considered the best

choice for second line therapy of fetal tachyarrhythmia other

then atrial flutter.

4.4. Digoxin

Digoxin does not fit into the Vaughn Williams classifi-

cation of antiarrhythmic drugs. It has positive inotropic and

negative chronotrophic properties, resulting in an increase in

cardiac output and a decrease in heart rate, respectively. In

addition, digoxin prolongs the refractoriness of the AV-

node, thereby delaying atrioventricular conduction and the

ventricular rate in atrial flutter or supraventricular tachycar-

dia. Transplacental digoxin therapy has been the drug of

choice in the treatment of fetal tachyarrhythmias for over

two decades. Its complications are few and well known. Six

large studies and a great number of small studies and case

reports have been published [7] and have shown that

digoxin monotherapy is relatively effective with conversion

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107100

rates ranging from 32% to 71%. Its effectiveness with fetal

tachyarrhythmias complicated by fetal hydrops is much

lower with conversion rates ranging from 10% to 43%,

probably due to the reduced transplacental transfer of this

drug [42]. Maternal intravenous loading may avoid prob-

lems related to poor absorption of digoxin. Strasburger et al.

have overcame this problem by direct fetal intramuscular

injection (88 Ag/kg fetal non-hydropic weight) [33].

4.5. Flecainide

This is a class IC antiarrhythmic agent which prolongs

the refractory period and slows conduction throughout the

whole myocardium. It has been proposed as an effective

drug in the treatment of SVT, especially when associated

with hydrops, either alone or in combination with digoxin

[43]. The transplacental transfer is good. It has been used as

drug of second choice in non-hydropic SVT, and drug of

first choice in hydropic SVT resulting in conversion rates

ranging from 75% to 92% [44,45]. The adverse effects of

flecainide are dizziness, headache, visual disturbances,

paresthesia, tremor, flushing, nausea and vomiting. Flecai-

nide should probably not be used in fetal atrial flutter as it

may increase the ventricular response.

4.6. Propranolol

A non-selective beta adrenergic blocking agent It

increases AV nodal refractoriness. It may adversely reduce

cardiac output and oxygen consumption. Propranolol does

not seem to be effective in the treatment of fetal tachyar-

rhythmia. Ito et al. [46] published a review article in 1994 in

which they describe failure of maternal propranolol therapy

in 14 of 16 patients Moreover, propranolol has been

associated with intrauterine growth retardation [47] and

many other maternal and fetal adverse effects.

4.7. Sotalol

A type III antiarrhythmic agent. As such it prolongs the

action potential duration of myocardial cells, resulting in

lengthening of the effective refractory period. Its properties

of excellent transplacental transfer, relatively short half life,

and weak h blocker effect, make it a good fetal anti-

arrhythmic agent.

New evidence for its safety and efficacy in the treatment

of fetal tachyarrhythmias may shift interest to this drug.

Oudijk et al. have used maternal sotalol in fetuses with

either a flutter or with SVT. They have shown good and fast

conversion to NSR in most fetuses [48]. A few unexplained

intrauterine deaths, more in the SVT group may be due to

the pro-arrhythmic effects of sotalol [49], which was

described rarely in infants to induce torsade de pointes

tachycardia [50]. Sotalol therefore may become the drug of

choice for atrial flutter. A larger scale study focused on

sotalol safety in fetuses is needed.

4.8. Verapamil

Verapamil is a class IV antiarrhythmic calcium antagonist

agent that inhibits the slow influx of calcium ions through

the cell membrane of contractile and conducting cells in the

heart. It decreases contractility and delays sinus and AV-

nodes conduction. A large study reports a conversion rate of

more than 50% in non-hydropic fetuses and in hydropic

fetuses when using the combination of digoxin and

verapamil [32]. Despite these promising results, major

concerns arise as to its potential side effect. In this study,

one hydropic fetus was treated with an intraumbilical

injection of 0.2 mg verapamil which immediately lead to

asystole and fetal death. Animal studies have shown

verapamil to delay fetal growth and development [7].

Reduced uterine blood flow with fetal hypoxia is a potential

risk. Verapamil should not be initiated in combination with

propranolol as this could have severe negative inotropic

effects or may induce high-grade AV block. Verapamil is not

used as a first line drug for fetal tachyarrhythmias.

5. Specific tachyarrhythmias

5.1. Normal fetal heart rate definition

Controversies exist as to the normal range of fetal heart

rate [51]. The upper limit of normal quoted in most pediatric

cardiology and obstetric textbooks is 160 bpm [52,53], or 165

in some articles [51]. A heart rate which is consistently higher

then 165 bpmmay carry clinical significance regardless of its

underlying electrophysiological mechanism. It should be

emphasized that temporary tachycardia is a normal finding in

any fetus. These normal fetal accelerations are characterized

with gradual onset and cessation and are usually below 200

beats per minute (bpm). Abrupt changes, on the other hand,

especially if the rate is over 200 bpm, are more often

associated with pathologic tachycardias [54].

Fetal tachycardia can be roughly differentiated by the heart

rate. A heart rate of 210 bpm or more is always abnormal.

Tachyarrhythmias are conventionally classified accord-

ing to their origin or pathways, into supraventricular or

ventricular tachycardias (Table 2). We will follow this

classification in the discussion of the specific tachycardias

in the fetus.

Following the widely accepted nomenclature, we also

chose the term supra-ventricular tachycardia (SVT) to

describe atrio-ventricular reentry and atrio-ventricular node

reentry tachycardia. Other forms of supra-ventricular

tachyarrhythmias, such as atrial ectopic tachycardia, will

be separately named.

5.2. Sinus tachycardia

Sinus tachycardia in the fetus seldom exceeds 210 beats/

min. Sinus tachycardia by itself has no effect on heart

Table 2

Conventional classification of fetal tachyarrhythmias

Origin

Supra-ventricular sinus tachycardia

‘‘SVT’’-reentry atrio-ventricular

A-V node

atrial flutter

atrial ectopic tachycardia

junctional ectopic tachycardia

Ventricular ventricular tachycardia

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107 101

contractility or cardiac output. A normal fetus maintains

normal cardiac output even when the heart rate is

artificially increased; the reduced stroke volume would

be proportionate to the increased heart rate [55]. Sinus

tachycardia in the fetus is usually due to underlying fetal

abnormality such as hypoxia, acidosis, infection, distress,

myocarditis, maternal drug ingestion, hormone, or cate-

cholamine transfer [33]. The treatment for sinus tachycar-

dia is to eliminate the underlying cause and to limit further

exposure to medications or drugs that could increase heart

rate.

5.3. Atrial flutter

Atrial flutter accounts for a fifth to a third of all fetal

tachyarrhythmias [32,56]. Experimental observations [57]

and the fact that atrial flutter occurs exclusively during the

third trimester corroborates with the hypothesis that the

electrophysiological mechanism in fetal atrial flutter is

Fig. 4. Tissue velocity tracings of a 22-week-old fetus with atrial flutter. The red tra

the left upper panel). The yellow tracings represent the ventricular motion. The

ventricular conduction).

similar to postnatal atrial flutter which is atrial macroreentry

circuit. It has been speculated that the fetal atrium reaches a

critical size for appearance of the circuit at about 27–30

weeks’ gestation [58].

5.3.1. Definition

Fetal atrial flutter is defined as a rapid regular atrial rate

of 300–600 beats/min accompanied by fixed or variable

atrioventricular (AV) conduction block, resulting in slower

ventricular rates. 2:1 conduction seems to be the most

common (Fig. 4). Rarely paroxysmal 1:1 conduction is seen.

Atrial flutter is considered incessant if it persists for more

than 50% of a 45-min study, and intermittent if the

tachycardia lasts less than 50% of this time [56].

5.3.2. Diagnosis

Diagnosis of fetal atrial flutter depends upon the finding

of fast and regular atrial activity and usually slower

ventricular activity, with fixed A-V relationship (2:1, 3:1,

etc.). All modalities are appropriate-scalp ECG [59], M-

mode echo, Doppler inflow, MCG [60] and TVI [61] (Figs.

4 and 5).

5.3.3. Clinical significance

There appears to be some controversy whether fetal atrial

flutter carries a worse prognosis than fetal supraventricular

tachycardia. Krapp et al. have recently shown in a

retrospective review that the outcome is quite similar, with

hydrops fetalis reported in about 40% and mortality of about

8% in both groups [62].

cings were obtained from the posterior free wall of the left atrium (red dot on

atrial rate is 480 bpm with a fixed ventricular rate of 240 bpm (2:1 atrio-

Fig. 5. Curved anatomical M-mode of a 23-week-old fetus with atrial flutter. This methodology allows assessment of the pathway of the tachyarrhythmia. The

numbers on the vertical axis on the right panel correspond to area of sampling on the curved anatomical M-mode (number dots in the left panel). The atrial rate

is 480 bpm. The color encoded M-mode indicates fast progression of 60 ms from sample #6 to sample #1 (left atrium—LA) to the right atrial (RA) free wall.

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107102

5.3.4. Treatment

Due to its safety and long experience, digoxin continues

to be the first line of treatment, despite a success rate of only

50% in conversion to normal sinus rhythm. The conversion

rate in hydropic fetuses is significantly lower. Other first line

protocols (digoxin+verapamil and flecainide) have been

successfully used in some hydropic fetuses [32,63]. Oudijk

et al. have shown good and rapid conversion to normal sinus

rhythm in most fetuses with either a flutter or with

supraventricular tachycardia [48]. Although sotalol may

eventually become the drug of choice for atrial flutter, a few

unexplained intrauterine deaths, especially in the supraven-

tricular tachycardia group, might have been related to the

pro-arrhythmic effects of sotalol [49]. In infants, Sotalol has

been reported to rarely induce torsade de pointes tachycardia

[50].

5.4. Supraventricular tachycardia

Supraventricular tachycardias account for the majority

of fetal tachyarrhythmias (60–80%). There is indirect

evidence that the most common mechanism for fetal SVT

is orthodromic atrioventricular reentry. This was hypothe-

sized by observing spontaneous recurrences of supraven-

tricular tachycardia in postnatal survivors and by postnatal

transesophageal electrophysiology studies [58,64]. Direct

assessment of fetal SVT is rare. Wakai et al., using

magnetocardiography, have recently shown that, as in

neonates, most fetal supraventricular tachycardia show

evidence of accessory AV connections as opposed to AV

node reentry [38]. Kannankeril et al., using postnatal

transesophageal electrophysiology studies, have found that

left-sided pathways were present in 72% and were

associated with a more grave hemodynamic state and

hydrops fetalis [65]. Jaeggi et al. analyzed the timing of

the ventriculo-atrial relationship using M-mode echocar-

diography. They found that 83% of the cases had a short

ventriculo-atrial time, characteristic of atrioventricular

reentry with the common type of accessory pathway. In

17% of cases there was a long ventriculo-atrial time

typical of permanent junctional reentry tachycardia or

atrial ectopic tachycardia (see below). In the latter group,

three of four babies were born alive and the diagnosis

was confirmed as permanent junctional reentry tachycar-

dia in two cases and atrial ectopic tachycardia in one

[66].

5.4.1. Definition

It is defined by a 1:1 atrio-ventricular activity. Heart rates

in SVT most commonly range from 200 to 300 bpm.

Supraventricular tachycardia is either paroxysmal or inces-

sant in nature, always regular and its initiation and

termination are always abrupt (with no Fwarming up_ or

Fcooling down_ phenomena).

5.4.2. Diagnosis

Diagnosis of fetal SVT relies on the finding of fast and

regular 1:1 atrioventricular activity with abrupt initiation

and termination. All techniques are appropriate although

myocardial deformation methods (TVI/SRI), fetal electro-

cardiogram and Magnetocardiogram can separate SVT from

other ectopic tachyarrhythmias.

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107 103

5.4.3. Clinical significance

SVT is associated with fetal hydrops in about 40% of the

cases and is not different in that sense from atrial flutter

[62]. Supraventricular tachycardia leads rapidly to the

development of hydrops fetalis when it is persistent for

more than 12 h. Controversy exists regarding the relation-

ship between heart rate and the risk to develop hydrops.

This risk relates primarily to the age of the fetus (the

younger fetus being more susceptible) and to the duration of

the supraventricular tachycardia. According to Naheed and

colleagues, the risk is not correlated to the specific rate of

the SVT or to its ventriculo-atrial interval [64].

5.4.4. Treatment

Digoxin is still the first line therapy in non-complicated

fetal supraventricular tachycardia with conversion rate of

about 50% [7]. This success rate significantly decreases

when hydrops fetalis or ventricular dysfunction are present,

probably due to the reduced transplacental transfer of this

drug [42]. Maternal intravenous loading may avoid prob-

lems related to poor absorption of digoxin. Strasburger et al

have overcame this problem by direct fetal intramuscular

injection (88 Ag/kg fetal non-hydropic weight) [33]. The

second line drug is probably amiodarone. Recently it was

shown that the majority of fetal supraventricular tachycardia

which failed to convert with digoxin or other drugs did

convert to normal sinus rhythm with transplacental amio-

darone therapy [41]. Sotalol may be another option for

second line therapy. See the paragraph on atrial flutter for

limitation and concern of the use of sotalol in the fetus. Price

et al. have shown in very young infants (median age<1

month) that in failures of single drug therapy, a 100%

success rate was achieved using the combination of

flecainide and sotalol [67].

Direct fetal treatment with adenosine (100–400 Ag) is

mostly anecdotal. There are reports of injection into the

umbilical vein [14,15,32,68] or into the right ventricle [32]

with at least temporary conversion to sinus rhythm. No

adverse reaction was reported.

5.5. Atrial tachycardia

Atrial tachycardias are induced by an automatic focus-

single in atrial ectopic tachycardia (AET) and multiple in

multifocal atrial tachycardia (MAT). Atrial ectopic tachy-

cardia is the common form of atrial ectopic tachycardia. The

rarer form, MAT, also known as chaotic atrial tachycardia,

accounts for less than 1% of the SVT. It usually appears in

the last weeks of pregnancy.

5.5.1. Definition

AET: (1) A single focus of initiation of atrial activity;

(2) regular and normal to minimally prolonged A-V

mechanical intervals; (3) warm-up phenomenon seen at

initiation of tachycardia and cool-down seen on termina-

tion of tachycardia.

MAT: (1) Multiple (at least three) focuses of initiation of

atrial activity; (2) irregular A-V mechanical intervals; (3)

ventricular rate >100 bpm [69].

5.5.2. Diagnosis

Methods: Atrial tachycardia may be diagnosed by M-

mode echo [66], Doppler inflow/outflow (Fig. 2) or SVC/

Aorta techniques [37], by magnetocardiogram [38] and

myocardial deformation [31] (Fig. 6).

AET: 1:1 atrio-ventricular activity with warm-up and

cool-down phenomena, at rates of 170–240 bpm, with short

A-V/long V-A intervals.

MAT: Irregularly irregular atrial activity or Doppler flow

patterns with irregular ventricular rate >100 bpm (usually

fast atrial activity up to 400/min and variable ventricular

response of 150–250 bpm). TVI may in theory show

multiple atrial origins of mechanical activity (right and left).

However, we did not encounter MAT in our laboratory.

5.5.3. Clinical significance

AET: In children, antiarrhythmic therapy response and

spontaneous resolution is inversely related to the age ,

with 80% complete resolution in young children [70].

Only 23% of the young patients were symptomatic at

diagnosis. Extrapolation of this data suggests that fetal

response to therapy and spontaneous resolution is favo-

rable. Lower heart rate AET may not necessitate medical

therapy.

MAT: Unlike what is used to think in the past, it is

usually a relatively benign condition. Mild ventricular

dysfunction may be observed in the presence of MAT, but

fetal cardiac decompensation is unlikely and resolution is

generally complete [33,69].

5.5.4. Treatment

MAT: There is no standard, proven therapeutic approach

to patients with MAT. Response to antiarrhythmic agents is

variable [33].

AET: Availability of fetal treatment is limited. Fouron et

al. have recently reported their experience. They diagnosed

5 fetuses with AET. Their drug of choice was sotalol

(maternal administration, 80 mg bid for 24–48 h, then

doubling the dose), and they added digoxin if fluid

accumulation was present [71].

5.6. Junctional ectopic tachycardia

An extremely rare, often familial [72] form of supraven-

tricular tachycardia. Due to its automatic focus etiology, it

tends to be incessant in nature (as seen postpartum) and

therefore carries high associated fetal mortality.

5.6.1. Definition

Tachycardia with complete atrio-ventricular dissociation

or with short V-A interval where the ventricular rate is

equal or higher than the atrial rate. In the fetus, junctional

Fig. 6. Tissue velocity tracing of a fetus (34th week of gestation) with atrial ectopic tachycardia. The right ventricular myocardium is sampled close to the

tricuspid valve annulus. The tachycardia seems to be fixed at about 190 bpm. However, the RR interval showed a slow cooling–down from 290 ms to 340 ms

during the 12 s of recording.

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107104

ectopic tachycardia cannot be differentiated from ventri-

cular tachycardia.

5.6.2. Diagnosis

All methods which record simultaneous atrial and ven-

tricular activity are appropriate. However, left ventricular

inflow/outflow method is not useful as in all cases of AV dis-

sociation. Ventricular rate usually does not exceed 200 bpm.

5.6.3. Clinical significance

As mentioned above, prenatal JET carries the same grave

prognosis as neonatal JET, and treatment is always

warranted despite the relatively low ventricular rate.

5.6.4. Treatment

There seems to be an agreement in the relevant literature

that amiodarone is the drug of choice for JET [41,71,73].

5.7. Ventricular tachycardia

Ventricular tachycardia in the fetus is extremely rare and

has scarcely been reported [29,74,75]. It is usually

paroxysmal in nature. The most important predisposing

factor to fetal ventricular tachycardia is the long QT

syndrome (LQTS). It is characterized by prolongation of

the QT interval and the occurrence of polymorphic

ventricular arrhythmia (such as torsade de pointes). LQTS

should thus be considered in fetuses presenting with

(baseline) bradycardia or intermittent ventricular tachycar-

dia of the torsade de pointes type.

Fetal ventricular tachycardia may accompany cardiac

tumor in the fetus or may be related to cardiomyopathies [76].

5.7.1. Definition

The hallmark of ventricular tachycardia is electrical (or

mechanical) atrio-ventricular dissociation with ventricular

rates higher than atrial rates. Rarely, slow ventricular rates or

Faccelerated ventricular rhythm_ with AV dissociation,

competing with sinus rhythm have been observed [33].

The absence of atrio-ventricular dissociation probably does

not totally exclude ventricular tachycardia as some of the

infants [77] and fetuses [73] with ventricular tachycardia

have 1:1 A-V activity probably due to retrograde capture of

the atria. Atrio-ventricular dissociation with fast ventricular

contractions will also appear in junctional ectopic tachycar-

dia, a rare but described fetal arrhythmia [37,72].

5.7.2. Diagnosis

Since the most common condition leading to fetal

ventricular tachycardia is LQTS, its prenatal diagnosis is

essential. Until recently, the prenatal diagnosis of LQTS was

possible only in fetuses of mothers with prolonged QT

syndrome and was made indirectly by presence of fetal

ventricular tachycardia in this group and confirmed by

postnatal ECG and molecular studies. Recently it has

become possible to directly detect fetal QTc prolongation

and torsade de pointes by magnetocardiography [78].

Ventricular tachycardia can be easily diagnosed by tissue

velocity imaging (Fig. 7). Its focus of initiation and its

pathways could be demonstrated using color-encoded tissue

velocity imaging [29].

5.7.3. Clinical significance

Fetal ventricular tachycardia is ominous because of the

hemodynamic burden caused by this type of arrhythmia. It

Fig. 7. Tissue velocity color-encoded M-mode. The M-mode line passed via the left ventricular (LV) and the right atrial (RA) free wall. Note the fast and

regular LV free wall contraction (240 bpm) with a low and ‘‘dissociated’’ right atrial contraction (106 bpm) establishing the diagnosis of ventricular tachycardia.

Z. Perles et al. / Progress in Pediatric Cardiology 22 (2006) 95–107 105

almost always causes cardiac decompensation and if not

promptly treated may lead to fetal death. Ventricular

tachycardia may also result in fatal ventricular fibrillation.

5.7.4. Treatment

Accelerated ventricular rhythm does not require treat-

ment in utero. Due to its rarity, treatment of fetal ventricular

tachycardia is mostly anecdotal. Intracordal lidocaine has

been used in critically ill fetuses with rapid ventricular

tachycardia [33]. Continuous maternal intravenous lido-

caine has also been used. Maternal mexiletine hydrochlo-

ride (200 mg 3 times a day) has also been used with partial

success [29]. Maternal intravenous infusion of magnesium

has been used in cases of LQTS accompanied by fast

torsade de pointes ventricular tachycardia [78]. Amiodarone

or sotalol, may successfully treat some forms of ventricular

tachycardia [79], keeping in mind that these drugs have

their own pro-arrhythmic effects as they prolong repolar-

ization. They may exacerbate torsade de pointes and result

in fetal death.

5.8. Association with other cardiac/non cardiac anomalies

Fetal tachyarrhythmias are usually detected in hearts with

normal structure although the association between various

types of fetal tachyarrhythmia and anatomic lesions has

been reported. Atrial flutter has been associated with atrial

dilation—the right atrium in cases of Ebstein’s malforma-

tion of the tricuspid valve, the left atrium in a case of critical

aortic stenosis and mitral regurgitation, and both atria in a

case of left atrial isomerism and atrioventricular valve

regurgitation [80].

Sustained AET has been described in 4 families in which

other family members suffered from left sided obstructive

lesions [81].

SVT has been reported in a 26-week-old fetus which

developed sub and valvar pulmonic stenosis 2 months after

birth [82].

Fetal tachycardia has been associated with intracardiac

masses such as a pericardial cystic mass [83] or multiple

intracardiac rhabdomyomas [84]. AET associated with a RA

mass has been lately described in a fetus with tuberous

sclerosis [71].

5.9. Future trends in diagnosis and therapy

High intensity focused ultrasound (HIFU) has been

introduced and extensively studied by Ludomirsky et al.

HIFU utilizes frequencies of 500 kHz to 10 MHz, and

causes controlled and localized tissue damage without

damaging intervening or adjacent tissues [85]. This

technique carries a great potential for fetal therapy

including ablation of ectopic focuses or reentry causing

accessory pathways. Fetal mechanical mapping using

myocardial deformation techniques (fetal kinetocardio-

gram) as the diagnostic tool followed by HIFU ablation

may become the treatment of choice in complicated fetal

tachyarrhythmia.

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