Introduction

Cardiac arrhythmia is defined as a variation from the normal heart rate or rhythm that is not physiologically justified [1]. Fetal arrhythmia can occur in up to 2% of pregnancies and account for 10 to 20% of referrals to fetal cardiologists [2, 3].

Fetal heart rates of 110 to 150-160 beats/min (bpm) are considered normal [4]. The rhythm disturbances might be continuous or sporadic. Sometimes a dangerous arrhythmia occurs on the background of a normal rhythm. These, sometimes hidden, fetal arrhythmias may contribute to some cases of undiagnosed fetal death.

Echocardiography is currently the most useful tool for evaluating the fetal heart, and it will detect most structural and cardiac rhythm abnormalities.

Echocardiography also provides assessment of the haemodynamic consequences of structural and functional abnormalities that may accompany arrhythmias. The two dominant methods for fetal heart rhythm evaluation are M-mode and Doppler method. Additional information can be obtained using tissue Doppler, strain imaging, and other modern ultrasound applications. Detection of normal/abnormal fetal heart rhythm is extremely important for appropriate fetal management and treatment, enabling improvements in perinatal outcome [5, 6].

Arrhythmias can be categorised as abnormalities of rate (tachycardia and bradycardia), of regularity, and of atrioventricular synchrony.

Mechanism of normal cardiac rhythm

Normal cardiac rhythms are the result of spontaneously generated, highly regulated electrical stimuli that are transmitted in a tightly choreographed sequence, rapidly transmitted in some places and pausing in others, which, in turn, cause contraction of the surrounding myocardium in a synchronised, physiologically optimised manner (Figure 1). These electrical stimuli depend upon two structures, the pacemaker(s) and the conducting system.

Arrhythmias in most cases originate from an abnormality of the electrical system; either the pacemakers, the conducting system, or both. Most cases occur in structurally normal hearts. Direct assessment of fetal cardiac electrophysiology is difficult, so evaluation is done by analysing the mechanical events like wall movement, blood flow, etc. resulting from the electrical activity. This is readily studied by M-mode, Doppler, tissue Doppler, etc.

For this primer, it suffices to assume that the heart contains three types of cells: pacemaker cells, conducting cells, and contractile cells. In most cases, functional abnormalities of pacemaker/conducting cells cause arrhythmias. Very infrequently, the pacemaker(s) and conduction system are anatomically displaced, distorted, or damaged, causing dysrhythmias.

The pacemaker cells have the following properties:

• Automaticity: meaning they can spontaneously depolarise and create an electrical impulse. These cells do not need an external nerve stimulus to function, and even a completely denervated but perfused heart will contract normally, at least for several hours.
• Excitability: despite the autonomous impulse creation, these cells can also respond to external nerve stimuli.
• Conductivity: the electrical impulse can be transmitted from one cell to another. Normally, this conductivity is unidirectional.
• Refractory periods: all muscles and the conducting system of the heart have an absolute refractory period, where another impulse will not be transmitted, followed by a shorter relative refractory period, where a strong impulse will be transmitted (Figure 2). These periods vary across cardiac components, but all exhibit absolute and relative refractory periods. The refractory periods are essential for normal cardiac function, allowing cardiac contractions to occur in a tightly organised sequence; for example, the refractory period of the AV node allows complete emptying of the atrial chambers before ventricular contraction.

Conducting system

These are circuits that conduct impulses rapidly from the preceding node to another component of the conducting system, like the Bachmann’s bundle, which conducts impulses from the right atrium (RA) to the left atrium (LA), and the bundle of His – atrioventricular (AV) node to the bundle branches. Internodal pathways conduct impulses from the sinoatrial (SA) node to the AV nodes (internodal pathways are not anatomically discrete, but enable rapid conduction due to the specialised alignment of certain atrial myocytes).

These conducting systems also connect to relevant myocardium, causing contraction.

Contractile cells have the following properties:

• Contractility – the ability to shorten. This is an active process with a high energy requirement.
• Extensibility – the ability to stretch. This is a passive process that depends on the heart filling with returning blood. There is minimal energy requirement. Within physiological limits, the greater the degree of stretch of the myocardial muscles, the stronger the subsequent contraction (Frank-Starling law).
• The myocardial muscles also conduct impulses from cell to cell.

The heart contains several pacemakers; all pacemakers have the property of entering a refractory period after excitation, during which no further depolarisation can occur. This ensures a hierarchy of pacemakers, with higher-intrinsic-rate pacemakers suppressing the slower ones. This is called overdrive suppression [7]. The primary pacemaker of the heart is the SA node, located within the right atrium near the superior vena cava opening. The other pacemakers (latent, secondary, or subsidiary), in the descending order of intrinsic rate of automaticity, are located in the AV node, the bundles of His, and the Purkinje fibres. Finally, the normal atrial and ventricular myocardial cells do not usually possess automaticity; however, under some conditions, these can generate spontaneous stimuli [1].

Normal electrophysiology

Under normal physiology, the SA node fires an impulse that travels through Bachmann’s bundle to the left atrium and via the internodal pathways to the AV node. The AV node is functionally very important in maintaining normal cardiac function, but it can also be a source of arrhythmia. The AV node acts as the only electrical connection between the atria and ventricles. It functions as a gatekeeper and a delay circuit, holding the received impulse of the SA node for a brief time to enable complete atrial emptying and ventricular filling before initiating ventricular systole. It also protects the ventricles by filtering and not allowing many atrial tachyarrhythmic impulses to pass to the ventricles. It conducts the impulse to the ventricles through the bundle of His and Purkinje fibres. The AV node delay can be prolonged under certain conditions, leading to various forms of heart block. It can function as a pacemaker, albeit with slow automaticity; finally, it can itself be a source of tachyarrhythmias by providing re-entrant pathways into the atria.

Common mechanisms of arrhythmias

Fetal arrhythmias can be caused by ischaemia, inflammation, electrolyte disturbance, or stress. Maternal intake of cardiac stimulants can be a cause. Many cardiac structural abnormalities are known to be associated with arrhythmias, and gene mutations have also been implicated [8]. The underlying mechanisms (Figure 3) can be categorised into the following:

Abnormal automaticity

The intrinsic automaticity might be reduced, causing bradycardia, or increased, causing tachycardia (Figure 3, no. 1, 6). Several conditions affect the pacemaker; these include fetal mechanisms like inflammation (myocarditis), autoimmune disease with anti-Sjögren’s-syndrome-related antigen A or anti-Sjögren’s syndrome type B autoantibodies (anti-SSA/Ro or anti-SSB/La antibodies, which damage the AV node), fetal hypo- or hyperthyroidism, maternal medication (digoxin, caffeine, etc.), maternal fever, etc.

There might be activation of a secondary pacemaker (Figures 2, 3), leading to various dysrhythmias depending upon the subsequent pathways the impulse takes. The arrhythmias that thus occur include premature atrial contractions, atrial flutter, atrial fibrillation, and premature ventricular contractions.

Abnormal conduction pathways

Accessory pathways disrupt the organized progression of electrical impulses, causing a loop that continuously and rapidly stimulates the heart, leading to very fast atrial and ventricular rates.

Some of these pathways allow fast retrograde conduction, so the signals proceed to the ventricle through normal pathways and then move in a retrograde manner back to the atria via pathways adjacent to the AV node. This is the most common cause of supraventricular tachycardia (AVRT, atrioventricular nodal re-entrant tachycardia) (Figure 3, no. 5).

Another pathway could be outside the AV node (Figure 3, no. 6) and allow for faster antegrade conduction bypassing the AV node. The afferent antegrade limb is outside the AV node, while the efferent retrograde limb is through the bundle of His and AV node. One example is the bundle of Kent implicated in Wolff-Parkinson-White syndrome.

Other pathways exist, but they are outside the scope of this paper.

A re-entrant circuit might form within the atria (Figure 3, no. 3), leading to flutter when the atrial rhythm is very fast (> 380 /min). The AV node cannot transmit impulses at this frequency and blocks some, so there might be a 2:1 regular block or, rarely, an irregular block, resulting in a ventricular rate of about 200-250 [9].

Rarely, there can be an ectopic focus of excitation in the ventricles. In this condition, the ventricles beat very rapidly (170-400 bpm), and there is dissociation of the atrioventricular contractions with a slower atrial rate [10].

Structural anomalies

Most cases of fetal arrhythmias occur in structurally normal hearts; however, certain fetal cardiac anomalies have an association with arrhythmias. Displacement of the AV node and other conduction systems and degenerative changes have actually been demonstrated by dissection of the hearts with structural abnormalities [11]. The conditions associated with arrhythmias include L-looped ventricles, such as congenitally corrected transposition of the great arteries, left isomerism, foramen ovale aneurysm, atrioventricular septal defect, ventricular septal defect, rhabdomyomas, tetralogy of Fallot, double outlet right ventricle, pulmonary stenosis, total anomalous pulmonary venous connection (TAPVC), tricuspid dysplasia, and Ebstein’s anomaly. Atrial or ventricular dilatation might predispose the fetus to ectopic foci of impulse generation.

Genetic conditions

Costello syndrome is an HRAS mutation characterised by polyhydramnios, nuchal thickening, hydrops, shortened long bones, abnormal hand posture, ventriculomegaly, large size, macrocephaly, and especially fetal atrial tachycardia [12].

Long QT syndrome [13] comprises ion channelopathies [14]. Multiple other genes and monogenic disorders have been associated with arrhythmias [15, 16].

Introduction to the tools for cardiac rhythm assessment in the fetus

M-mode

This method provides a graphical representation of the movement of cardiac structures and valves along a thin section, represented by a sampling line, positioned on a conventional real-time grey-scale image. The M-mode graph can be used to measure structures, assess ventricular and atrial wall contraction, and evaluate valve movement. For atria and ventricular walls, it can be used to assess if the ventricular walls are contracting normally or paradoxically, or if the movement is reduced or exaggerated. When applied to ventricles, it enables calculations of fractional shortening, ejection fraction, and related parameters. For valves, it allows assessment of valve structure and movement; it can determine whether the valves are normal or thickened, and whether the valve movement is normal or restricted.

The M-mode cursor is positioned so that it samples an atrium or a structure that moves with atrial contraction (AV valves) and a ventricle or a structure that moves with ventricular contraction (semilunar valves) (Figure 4).

The M-mode cursor can be swept parallel to the long axis of the ultrasound beam, orthogonal to the probe surface, much like the sampling line of pulsed-wave Doppler. A recent development is the ability to rotate the sampling line; this is called anatomical M-mode, and it provides greater flexibility in positioning the line in a more optimal location (Figure 5), but it suffers from degraded resolution. Colour Doppler can be added to M-mode to provide information about blood flow across structures during the cardiac cycle; this can also help in improving the visualisation of cardiac walls and movement.

It is usually possible to distinguish atrial from ventricular contraction and assess the temporal relationship between them. M-mode echocardiography answers the following questions: What is the atrial contraction rate? What is the ventricular contraction rate? Is every atrial contraction followed by a ventricular contraction? Is there a 1:1 relationship between atrial contraction and ventricular contraction, or are atria contracting more often than the ventricles (2:1, 3:1, etc.), or rarely, less often? It can be used to measure the chamber size, wall thickness, and interventricular septum (IVS) thickness. M-mode is useful for assessing movement and diagnosing if the ventricular walls and IVS show appropriate and synchronous movement, akinesia, or paradoxical movement.

Relative disadvantages of M-mode include the following: difficulty visualising contraction in the failing heart, especially in identifying the onset of atrial and ventricular contractions; the time intervals cannot be calculated with great accuracy; and M-mode-derived time intervals have greater interobserver variability and tend to be longer than Doppler-derived intervals. This occurs because the M-mode peak incorporates isovolumetric contraction times as well [17].

The M-mode graph displays time on the x-axis and movement on the y-axis (this paper focuses only on M-Mode as it applies to the evaluation of arrhythmia).

M-mode analyses mechanical cardiac events; Doppler gives information about the blood flow that results from the contractions, or even if it happens passively.

Doppler imaging

Colour Doppler provides basic information about normal and abnormal blood flow, but a more detailed assessment requires Doppler spectral analysis. Before any further discussion about the Doppler spectra, it must be remembered that the polarity of any the spectral components in any vessel or the heart depends upon the probe: flow geometry and polarity setting, with waves depicted above the baseline when the flow is towards the probe and below the baseline when the flow is away from the probe. A state of no-flow is represented with no waves below or above the baseline.

At its simplest, the Doppler spectrum from any fetal artery indicates ventricular contraction rate and rhythm. When the Doppler gate is simultaneously placed over a fetal artery, and a vein near the heart, the spectra reflect both ventricular as well as atrial contractions and calculate various time intervals be calculated. Of the many locations where atrial and ventricular flow can be assessed, the most common location and method is to acquire a Doppler trace with a wide gate placed in the left ventricle, adjacent to the septum, so that it captures left ventricular inflow (atrial contraction) and outflow (ventricular contraction) (Figure 6). This gives the left ventricular inflow-outflow Doppler (LVIO), representing both atrial contraction and ventricular contraction.

Similar information about atrial and ventricular flows can be obtained when a Doppler gate is placed over an artery and vein near the heart. The arterial spectrum is monophasic, while the venous spectra are triphasic (except the umbilical vein, which shows constant flow). The venous spectra show two positive peaks, “S” and “D” (corresponding to systole and diastole), and one sharp trough, the “A” wave (Figure 7A, C). The “A” wave is normally above the baseline in the ductus venosus (DV) and pulmonary veins (PV), showing continuous antegrade flow, while it is negative in the hepatic veins, and the superior and inferior venae cavae spectra (Figure 7B, D). The “A” wave corresponds to atrial contractions.

There are several other anatomical locations where an artery and vein are close together and can be used for atrioventricular flow; for example, the pulmonary artery and vein [18], and the aorta and superior vena cava. The use of Doppler spectra from renal artery and vein [19], the inferior vena cava and descending aorta [20], and the innominate vein and aortic arch [21] have also been reported but will not be discussed further. If just the atrial heart rate and rhythm need to be studied, ductus venosus waveforms can be used. Advantages and difficulties at each site are as follows:

• Left ventricular inflow-outflow is the easiest to acquire and remains the most popular (Figure 6). It becomes less useful in tachyarrhythmias when the heart rate ≥ 160/min [22].
• The pulmonary vein and artery flow (Figure 8) need optimised machine settings, but once the operator becomes familiar with the technique, he/she can use this method not only for assessing cardiac rhythm, but the pulmonary vein spectra also give valuable information about left heart function [23]. A pulmonary vein is identified near the left atrium, and a Doppler gate is placed over it. Usually, arterial flow is detected along with venous flow; if not, minor probe manipulation and gate-size adjustments will reveal it. The “a” wave usually shows continuous flow and does not reach or cross the baseline in most normal cases. In some normal cases, it can cross the baseline. A negative “a” wave is also a feature of heart failure.
• The aorta and superior vena cava (SVC) flow (Figure 9) is preferred by some for calculating the AVCT (atrioventricular conduction time, corresponding to the PR interval) and for assessing tachyarrhythmias [24, 25]. The starting section for this view is the bicaval section, then the probe is tilted to the fetal left in a semi-coronal section so that both the SVC and ascending aorta are in the same section. The gate is placed just above the aortic valve and overlying the superior vena cava where it joins the right atrium.
• If just the atrial rate is to be assessed, an easy site is the ductus venosus; the “a” wave of the trace is due to atrial contraction (Figure 7A, C). This view needs to accurately identify the ductus venosus, recognised by the area of aliasing. This section might be most familiar to most operators who perform obstetrical ultrasound. Accurate gate placement is important to avoid contamination of the DV spectrum by the nearby hepatic veins and the proximal umbilical vein from which the DV arises. The sweep speed should be increased when the heart rate is > 150/min to allow the E and A waves of the mitral and tricuspid valves to be seen individually.

The left ventricular inflow-outflow location is most useful when the heart rate is near normal. With a fetal heart rate of > 160/minute, there is an overlap of E and A waves, leading to difficulties in measurement [22]. The SVC-aorta site is more useful at rapid heart rates.

In the LVIO section, the venous spectrum shows atrial activity with two peaks. The first peak is the E (early) peak and represents passive atrial filling (due to ventricular relaxation). This is followed by a small positive peak representing atrial contraction [26], which is followed by a sharp positive peak from the aortic flow tract representing ventricular contraction. The spectral components can be analysed to derive synchrony of atrioventricular contraction and various time intervals that form the basis of sophisticated arrhythmia analysis (Figures 10-12).

A disadvantage of cardiac spectral Doppler is that if there is no flow across the valves, there is no Doppler signal.

Cardiac Doppler spectra can also be used to measure and evaluate times and intervals in a cardiac cycle (Table 1) [27, 28].

Arrhythmias

Arrhythmias can be divided as follows: irregular cardiac rhythm, tachycardia, and bradycardia.

In most cases, arrhythmias are benign and transient. Significant arrhythmias include persistent or frequently irregular beats and persistent bradycardia (transient bradycardia is often induced by transducer pressure on the maternal abdomen and is not significant). Repeated heart-rate decelerations in the third trimester should raise suspicion of hypoxaemia. Mild tachycardia (160-180/min) may be seen during fetal breathing, but persistent tachycardia (> 180/min) warrants evaluation.

Irregular cardiac rhythm

An irregular cardiac rhythm is the most common cause for referrals, and premature atrial contractions are the most common cause of such irregularity. In most cases, there are no structural abnormalities, and the rhythm reverts to normal by birth or soon after. It is prudent to perform a formal fetal echocardiography in fetuses with irregular beats that occur more frequently than in 10% of beats or persist for more than 1-2 weeks. Some of these cases progress to tachycardia (> 180/min) or bradycardia (< 110/min) and require referral to a specialised centre.

An irregular beat is often first detected on auscultation of the fetal heart. The first step is to determine if the irregularity is atrial or ventricular. Ventricular extrasystoles are rare and do not conduct back to the atria, so the atrial pacemaker is not reset, and the atrial contraction rate and rhythm remain normal. The ventricle, however, contracts early, and this is followed by a full compensatory pause. The premature ventricular beat does not follow a normal atrial beat. However, a premature ventricular contraction can close the mitral valve prematurely. An atrial contraction then occurs against a closed valve, resulting in an absent “A” wave (Figures 13, 14).

Atrial extrasystoles are more common than ventricular extrasystoles; these can be continuous or intermittent. The processes that occur are as follows:

A focus other than the SA (sino-atrial node) fires an impulse, causing a premature atrial contraction; this also travels retro­gradely to reset the SA node.

This premature signal can do the following:

– be transmitted to the ventricles (conducted) and cause an extra beat

– or not be transmitted (non-conducted), being blocked at the AV node causing a missed beat

After the SA node reset, the next SA impulse occurs at the normal interval after the reset time.

When the premature atrial systole occurs very early, the impulse reaches AV node during its refractory period and is not conducted into the ventricles, so the ventricles do not contract, giving a missed beat. In this case, the atrial contraction often happens against a closed AV valve, and Doppler shows an absent or almost absent EA complex (Figure 15).

When the premature atrial systole is a little late, it reaches the AV node after its refractory period, but the atrial contraction happens while there is still passive filling (E wave); this will cause an early contraction of the atria, causing the “A” wave to occur early and become superimposed on the “E” wave, resulting in a large, fused wave comprising both the E and A waves (Figure 16).

PAC also affects ventricular beats, leading to premature ventricular beats (from conduction of a premature atrial systole) or dropped beats (from non-conduction of a premature atrial contraction).

When the premature atrial beats happen regularly in a 2:1 or 3:1 pattern (called bigeminy or trigeminy), the premature beat can be regularly conducted or blocked, leading to conducted atrial bigeminy (Figure 16) or blocked atrial bigeminy (Figure 17).

This irregularity in the timing of the heartbeats can be detected on ECG, M-mode, and Doppler in postnatal life and on M-mode and Doppler in prenatal life.

The diagnostic feature of this irregularity is called a non-compensatory pause; the time between two atrial beats in the preceding cycle is longer than the time between two atrial beats that include the premature ectopic beat. This is explained in Figures 18 and 19.

It has been proposed that the time differences between two normal beats and two beats containing the premature event can be used to differentiate PAC from PVC. A threshold of 33 ms has been reported, with the PAC time difference exceeding this and the PVC time difference being smaller than 33 ms [29] (Figure 19). Any arterial spectrum can be used for this purpose, but the umbilical artery is most easily used.

Extrasystoles can occur regularly and more frequently; sometimes every alternate beat (bigeminy) or every third beat (trigeminy) is an extrasystole. These are most commonly blocked atrial beats, but they are of ventricular origin in about 10% of cases [30]. Multiple blocked atrial extrasystoles result in a low ventricular rate because they are not conducted through the AV node and do not trigger ventricular contractions. The usual heart rate in blocked atrial bigeminy is 75-90/min [31]. This condition can be mistaken for a second-degree heart block.

Fetuses with blocked atrial bigeminy or trigeminy have a nearly 10% risk of supraventricular tachycardia [32] (vide infra).

Occasionally, a hiccup will cause an abnormal ventricular wave (Figure 20); this abnormality can be seen in almost all arteries, including the umbilical artery, the aorta, and the MCA. This can be confusing to the inexperienced operator. Hiccups can cause three types of abnormal wave forms: sharp decrease not reaching the baseline, sharp decrease reaching the baseline, and reverse flows [33].

Tachycardia

Fetal tachycardia is defined as fetal heart rate (FHR) > 180 bpm. It is labelled as sustained when the arrhythmia is present for more than 50% of the examination time or intermittent when periods of tachycardia occur less than 50% of the time and alternate with normal HR [34]. The stimuli for tachyarrhythmias usually arise in the atria; for example, sinus tachycardia and supraventricular tachycardias (atrioventricular re-entrant tachycardia, junctional tachycardia, and atrial flutter). Rarely, the impulses for tachycardia may arise in the ventricles (ventricular tachycardia).

In clinical practice, fetal supraventricular tachycardias often cannot be parsed into individual subtypes, and SVT constitutes a broad category encompassing various re-entrant types [35]. Clinical diagnosis of fetal tachyarrhythmias are categorised as sinus tachycardia, supraventricular tachycardia (including various re-entrant tachycardias and atrial flutter) and ventricular tachycardias [36].

Assessment of fetal tachycardia includes the following [37]:

• Ventricular heart rate (> 180/min).
• Tachyarrhythmia exposure; rare (< 10% of time), intermittent (10-50% of time), sustained (> 50% of time).
• Atrioventricular contraction ratio; atria and ventricles contract at the same rate (AV ratio 1:1), atria contract at a faster rate (AV ratio > 1:1), or the ventricular rate is higher than the atrial rate (AV ratio < 1:1).
• AV and VA intervals (Figures 11 and 12). These can be assessed by M-mode or Doppler. The AV and VA intervals represent PR and RP intervals on EKG. The ratio of AV:VA can be > 1 in ectopic atrial tachycardia and atrial flutter. In permanent junctional reciprocating tachycardia, sinus tachycardia (ST), and nodal re-entry tachycardia, the AV:VA ratio is 1.
• Briefly, tachycardias have the following characteristics:
• Sinus tachycardia (Figure 21): The fetal heart rate is between 180 and 200 bpm, the AV conduction is normal, and the AV ratio is 1:1. Its causes include fetal distress, maternal thyrotoxicosis, fever, fetal anaemia and fetal hypoxia, maternal medication (β-agonists, vagolytics, anticholinergic antihistamines), and infections (chorioamnionitis and cytomegalovirus) [38]. No specific treatment is needed, but the underlying cause should be corrected.
• Supraventricular tachycardia: This is the most common type of tachyarrhythmia, accounting for over 70% of the cases [35].
• An accessory conduction pathway (Figures 3, 5) is implicated in blocked premature atrial contractions leading to tachycardia in the following manner:
• A premature atrial impulse reaches the AV node during its refractory period and is blocked, but it “discovers” an accessory (bidirectional) pathway and reaches the ventricle, causing a ventricular contraction.
• Because the accessory pathway is bidirectional, it allows the retrograde transmission of the impulse back up into the atria.
• By this time, the AV node has recovered enough to transmit the impulse back into the ventricle.
• This means that the atria contract very soon after the ventricles; this results in a short VA interval on Doppler and M-mode.

This sets up a re-entry circuit leading to the most common type of supraventricular tachycardia: atrioventricular re-entrant tachycardia (AVRT) [37]. These tend to have a heart rate of about 220-300 bpm with an AV ratio of 1:1 (Figure 22). These can occur and resolve spontaneously, but if sustained, they can lead to fetal hydrops [37].

Atrial flutter is caused by an intra-atrial circuit. This circular movement of impulses is limited to the atria with no involvement of the AV node (Figure 3, no. 3). This is the second most common type of tachyarrhythmia, accounting for about 25-30% of all cases. Atrial flutter is seen only in the late second and third trimester when the atria are large enough to physically accommodate the circuit path. The atrial rate is 350-500. The AV node cannot conduct all atrial impulses, and conduction rates of 2:1, 3:1, or 4:1 are encountered. A fixed ventricular rate of 200-220 bpm is often encountered. There is no spontaneous termination of atrial flutter. This is often associated with structural cardiac defects (Ebstein anomaly), myocarditis, or maternal autoimmune disease (SSA/SSB).

SVT is the most common form of fetal tachycardia (70-75%), whereas VT is the rarest.

The fetal heart has reduced contractile capacity and compliance. The Frank-Starling mechanism is diminished, and the cardiac output is dependent on fetal heart rate rather than the muscle “stretch” that can increase cardiac output in postnatal life. The fetal heart functions best, i.e. it caters to the body’s metabolic demands, between 60 and 200 bpm. Heart failure ensues beyond this range [39, 40]. Sustained fetal tachycardia may lead to hydrops, premature delivery, and perinatal morbidity and mortality in almost 10% of cases [41].

Pharmacological treatment is recommended for sustained tachycardia. Antiarrhythmic medications may be used both in transplacental or fetal therapies. During antiarrhythmic therapy, the fetus should be closely monitored. More than that, mothers should also be under close monitoring during antiarrhythmic therapy because of possible side effects [6-8]. As pharmacological treatment is highly effective, every fetal tachyarrhythmia should be evaluated by a fetal cardiologist as soon as possible to avoid premature delivery.

The main types of fetal tachyarrhythmias are presented in Table 2.

Bradycardia

Fetal bradycardia is defined as a sustained FHR lower than 110 bpm over at least a 10-minute period [42]. A more nuanced definition is an FHR < 2 SD for age [43]. In up to 2% of fetuses, transient bradycardia, caused by increased probe pressure, may be noted during ultrasonography in the second and third trimesters [44]. This is presumably due to increased vagal tone and is of no consequence, and the heart rate rapidly returns to normal within a few seconds to minutes [45]. A persistently slow FHR that does not resolve during the examination is concerning. The most common causes of sustained bradycardia are sinus bradycardia, multiple blocked atrial ectopic beats, and atrioventricular blocks [46]. Bradycardias may occur in fetal hypoxia, congenital structural disorders, maternal connective tissue disorders, and maternal SSA/Ro and/or SSB/La antibodies, or be idiopathic [47]. The most common structural heart defects associated with bradycardia are corrected transposition of the great arteries, AV septal defect, critical pulmonary stenosis, or left isomerism [48, 49].

The features of sinus bradycardia are an FHR < 110/min and a 1:1 conduction.

The cause may be an acquired damage of the SA node, a displaced focus of atrial activation – when the SA node is blocked or damaged, other foci in the atria take over with a slow intrinsic automaticity, these foci can be located anywhere in the atria or even the vessels communicating with the heart, like vena cava and pulmonary veins [50]. Other causes included channelopathies and secondary suppression of SA node. SA node can be suppressed in inflammation and fibrosis in a previously normal node, viral myocarditis, or collagen vascular disorders (SSA/Ro and/or SSB/La antibodies).

It can be physiological and self-resolving or due to structural cardiac anomalies such as heterotaxy. A relatively common cause is long QT syndrome [51]. Many noncardiac conditions of both fetal or maternal origin can lead to sinus bradycardia, such as fetal acidaemia, cord prolapse, fetal haemorrhage, placental abruption, uterine rupture, and fetal hypotension. Maternal causes include hypothyroidism, hypothermia, and autoimmune disease. Maternal treatment with beta blockers etc. can also lead to fetal bradycardias [44].

Long QT syndrome is a channelopathy affecting the sodium and potassium ion channels. It is a genetic condition that may be inherited in an autosomal dominant pattern or arise de novo in the fetus. Most fetuses with this condition present with mild sinus bradycardia with heart rates of 100-110/min. More advanced cases might develop a 2:1 AV block. These fetuses are also at risk of developing ventricular tachycardia [52]. Fetuses who have intermittent bradycardia as well as tachycardia and AV dissociation have a poor prognosis.

Postnatal diagnosis is made by measuring the QT interval on an electrocardiogram; there is no easy way to make the diagnosis antenatally without magnetography. Unfortunately, magnetography is available in only very few international centres (Figures 23, 24).

Atrial bigeminy with blocked premature beats – this is the cause of about 30% of fetal bradycardias [36]. On M-mode, this typically shows sets of two closely timed ventricular contractions followed by a pause (Figure 25). The first of the two atrial beats is conducted, resulting in a ventricular contraction. The second beat occurs while the AV node is in its refractory period and is not conducted, resulting in a missed ventricular contraction and a low heart rate.

These can occur in a structurally normal heart, in which case these are likely to resolve spontaneously, but in about 10% cases they progress to supraventricular tachycardia [51, 53].

There can also be blocked atrial trigeminy, where an ectopic atrial contraction occurs after two normal beats and is blocked.

Atrioventricular blocks

Atrioventricular blocks are abnormal conduction of electrical impulses due to functional or structural abnormalities of the AV node. Structural anomalies include congenital displacement or absence of the AV node or acquired inflammatory damage of the atrioventricular node. The most common aetiology is immune-mediated injury to the conduction system due to transplacental passage of maternal anti-SSA/Ro and anti-SSB/La antibodies [54]. An autoimmune cause is postulated in 56-90% of cases [55]. This is followed by structural anomalies in 14-42% of cases, including transposition of the great arteries, left atrial isomerism, tetralogy of Fallot, and defects of the atrioventricular septum [56]. Several genes have recently been identified to be implicated in atrioventricular blocks, e.g. SCN5A, which is involved in progressive cardiac conduction disorders [54]. Many other genes have also been postulated [57].

It is important to make an accurate diagnosis because without treatment a mortality rate of 7-34% is reported [58, 59]. The basic presentation is bradycardia, but this needs to be differentiated from sinus bradycardia, blocked atrial bigeminy, partial AVB, and complete AVB.

AV block is divided into three types:

• Type I (first-degree) heart block: the heart rate remains normal, but the AV time (correlated with the PR interval, Figures 11 and 12) is increased to > 150 ms (normal atrioventricular conduction time is 111 ±17 ms or 120 ±11 ms). The technique of using AV interval has a negative predictive value of almost 100%; the positive predictive value, however, is around 45% [60]. There is 1:1 conduction. A very high index of suspicion is needed to make this diagnosis. The usual context is investigating the fetal heart, specifically the AV interval, in a mother who is positive for anti-SSA/Ro and anti-SSB/LA antibodies [61]. The first report of an antenatal diagnosis of a first-degree heart block was in 2002 [62]. The clues are subtle, but the diagnosis is important because some of these cases can progress to a higher degree of heart block with adverse outcomes.
• Type II (second-degree) heart block presents in two forms:

– Second-degree type 1 (Wenckebach). The AV interval progressively increases until one impulse is blocked. The heart rate is irregular.

– Second-degree type 2 (Mobitz). There is a normal AV interval with blocked impulses, commonly 2:1 conduction (Figure 26), but other rhythms like 3:2 might also be met with.

• Type III (third degree). There is a complete block of impulses from the atria to the ventricles. This results in dissociation of atrial rhythm from the ventricular rhythm. The atria contract at normal rate of automaticity of the SA node (~120-160/min), and the ventricles contract at the rate of their intrinsic automaticity, which is very low (40-50/min) (Figure 27). The third-degree block, also known as complete AV block, is often associated with congenital heart defects, predominantly left isomerism, and corrected transposition of the great arteries.

In cases of bradyarrhythmia, it is important to differentiate second-degree heart block from blocked atrial bigeminies or 3:2 rhythm [63-65]. While blocked atrial bigeminies tend to have a benign outcome, some will progress to supraventricular tachycardia; lower-grade heart blocks can progress to complete heart block with adverse outcomes.

Table 3 highlights some of the differences.

When considering prenatal therapy, it is important to consider the risks and benefits for both the mother and the developing fetus. A single dose of steroids is commonly administered to promote lung maturation in preterm infants with threatened preterm labour. β-sympathomimetics (terbutaline, salbutamol, isoprenaline) have been used to increase low fetal ventricular rates (< 55-60 bpm), but no studies have demonstrated improved long-term survival [17, 18]. Terbutaline is normally well tolerated. Immune-mediated AV block may benefit from in utero treatment with fluorinated steroids, intravenous immunoglobulin, or both. Dexamethasone is believed to reduce inflammation. That is why many clinicians use it to treat first-degree and second-degree AV blocks. A window of time may exist during which incomplete AV blocks can be reversed; therefore, prompt referral is suggested for patients with fetal bradycardia when FHR is < 80 bpm [19, 20]. Nowadays, hydroxychloroquine is usually used as a first-line therapy in the prevention of AVB development.

Conclusions

To conclude, this review explains the basic concepts of the electrophysiology of normal cardiac rhythm. This work outlines how electrical impulses are generated, conducted, and coordinated within the heart under physiological conditions, and how disturbances in impulse formation or conduction can lead to rhythm abnormalities.

This work also describes the key features of M-mode and Doppler spectra used to diagnose common arrhythmias in a sequential, simplified manner, focusing on the physiological basis. While, understandably, this is not a comprehensive or exhaustive work; this emphasises basic concepts that are often presupposed and not explained in other available works.

Acknowledgements

The authors gratefully acknowledge Dr. Dennis Wood’s contribution of Supplementary Figures S1-S3, that appear at the end of this work.

Disclosures

Ethical considerations: none.

This research received no external funding.

The authors declare no conflict of interest.

References