56 Atrial fibrillation and supraventricular arrhythmias

This chapter deals with the acute management of supraventricular tachycardias, ie atrial arrhythmias, including atrial fibrillation, atrioventricular nodal reentry, and atrioventricular reentry due to accessory pathway(s). Epidemiology data, clinical presentation, and 12 lead electrocardiogram (ECG) morphologies that can provide diagnostic clues for differential diagnosis between supraventricular tachycardias and ventricular arrhythmias are discussed, and specific, appropriate therapy is presented.

Traditionally, the term supraventricular tachycardia (SVT) has been used to describe all kinds of tachycardias, apart from ventricular tachycardias (VTs) and atrial fibrillation (AF), and has therefore included tachycardias such as atrioventricular nodal re-entral tachycardia (AVNRT) or atrioventricular re-entrant tachycardia (AVRT) due to accessory connections (see Table 56.1) [1]. AF, although a typical supraventricular arrhythmia, is conventionally considered separately from other supraventricular tachycardias (SVTs) that are usually, but not invariably, regular arrhythmias. In clinical practice, supraventricular arrhythmia and AF may present as narrow or wide QRS tachycardias (see Table 56.2) [1]. Although an electrophysiological study may be necessary for the differential diagnosis between supraventricular arrhythmia and ventricular arrhythmias, consideration of epidemiology data, clinical presentation, and the 12-lead ECG can provide diagnostic clues and guide appropriate acute therapy.

Epidemiology data may provide clues for an appropriate diagnosis of SVT in patients presenting with tachyarrhythmias. It is conventionally accepted that the first episode of SVT tends to appear first in youth, but the actual mean age at presentation is 37–45 years [2, 3], and the incidence and prevalence of SVTs increase with age, with a risk of arrhythmia >5 times greater in persons >65 years than in those <65 years old [2]. AVNRT accounts for approximately 56% of SVT cases, followed by AVRT due to accessory pathway for 27%, and atrial tachycardia (AT) for 17% [3]. The majority of patients with AVNRT and AT are women.

Atrial flutter has an incidence of 0.09%, and 58% of the patients have AF (the MESA study) [4]. It is 2.5 times more common in men than in women. Atrial flutter is usually associated with heart disease, such as heart failure (3.5 times increased risk of flutter), chronic obstructive lung disease (double risk), and myocardial ischaemia, whereas an apparently normal heart is found in <2% of patients [4].

AF is the most common sustained arrhythmia in humans and affects 1–2% of the general population worldwide. The prevalence of AF increases with age, from approximately 2% in the general population [5] to 5–15% at 80 years [6, 7]. Whites are more often affected than blacks, while the overall number of men and women with AF is about equal [8]. In the EU, 8.8 million adults over 55 years were estimated to have AF in 2010, and this number is expected to double by 2060 to 17.9 million [9].

Patients with SVT present due to paroxysms of regular or irregular palpitations, with a characteristically sudden onset and offset, that occur mostly in daylight, may be associated with fatigue, light-headedness, dyspnoea, chest discomfort, and presyncope. Occasionally, certain events, such as physical exercise, emotional upset, indigestion, or alcohol consumption, precipitate attacks. Syncope and cardiac arrest are rare (<15%), usually denote an underlying structural heart disease or advanced age, and may be due to a rapid heart rate or vasomotor factors [10, 11]. Polyuria is due to the release of atrial natriuretic peptide (ANP) in response to increased atrial pressure, and vagal manoeuvres usually interrupt the tachycardia.

AF is characterized by uncoordinated atrial activation that usually results in an irregular ventricular activation pattern [8, 12]. Patients present due to palpitations or a constantly irregular heartbeat. Shortness of breath on exertion may be described. Syncope is rare and may occur either with a very fast ventricular response, especially in the presence of an accessory pathway, or in the case of a concomitant AV block and an inadequate escape rhythm.

VTs are usually associated with syncope, but their clinical presentation depends on the haemodynamic disturbance they produce. When the cardiac output and blood pressure are maintained, and when the episodes are short-lived, the arrhythmia may also present as recurrent palpitations, breathlessness, or chest pain (CP). Occasionally, patients are completely asymptomatic during tachycardia, especially with idiopathic VT. Thus, the haemodynamic status should not be used as the main criterion for distinguishing between SVT/AF and VT. In addition, VT usually occurs in patients with structural heart disease, mainly ischaemic or non-ischaemic cardiomyopathy. However, in the case of idiopathic VT, monomorphic VT may occur in the absence of a clinically apparent structural heart disease [1].

Low blood pressure, heart failure, and CS may be present only as signs of haemodynamic distress. Apart from VT, they may be seen in fast AF in the context of a reduced left ventricular function or an accessory pathway, and rarely with SVT in the elderly.

A variable first heart sound may be seen if a retrograde ventriculoatrial block is present. Retrograde conduction may be seen in 20–30% of VTs, thus limiting the diagnostic value of this sign [1].

AV dissociation, apparent by a changeable pulse pressure (or by Doppler assessment of flow in the ascending aorta [13]), and irregular cannon waves in the jugular venous pulse indicate VT. Rarely, however, they may also be seen with non-conducted ATs or very rarely with AVNRT.

Usually, the ECG during SVT is narrow, unless atrial activity is conducted to the ventricles with aberration, and, in most instances, regular. Irregular rhythms can be seen with ATs such as polymorphic AT or flutter with varying block (see Table 56.2). AF is characterized by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in amplitude, shape, and timing (when visible, usually in lead V1, the atrial length is variable and <200 ms, i.e. >300 beats/min), associated with an irregular ventricular response [12]. QRS complexes may also be of variable amplitude. Regular R–R intervals are possible in the presence of a concomitant atrio-ventricular (AV) block or AV junctional or ventricular tachycardia. Most ATs and flutters show longer atrial cycle lengths of ≥200 ms, but patients on antiarrhythmic drugs may have slower atrial cycle lengths during AF. Extremely rapid ventricular rates (>200 beats/min) suggest the presence of an accessory pathway or VT.

If the arrhythmia stops spontaneously, or previous records of the patient are available, the ECG during sinus rhythm may also be of help. If a bundle branch block is present, but with a different morphology or axis to that during tachycardia, the tachycardia is likely to be ventricular in origin. If delta waves are present and they have the same polarity as the QRS complexes of tachycardia, the diagnosis is most probably that of Wolff–Parkinson–White syndrome with antidromic AVRT or AF. Patients with concealed pathways and latent anterogradely conducting pathways, such as Mahaim fibres, have a completely normal resting ECG [1]. Patients with atrial flutter, AVNRT, or AVRT due to a concealed accessory pathway may also have a normal resting ECG.

Apart from SVT or AF, a narrow QRS may also be seen in idiopathic VT (right ventricle (RV)/left ventrical (LV) outflow tract or fascicular), bundle branch re-entrant VT, and septal myocardial VT, due to their origin within, or in close proximity to, the His–Purkinje network. The differential diagnosis, based on ECG during tachycardia, is presented in Figure 56.1 and 56.2. When the ventricular rate is fast, AV nodal blockade during the Valsalva manoeuvre, carotid massage, or IV adenosine administration can help to unmask atrial activity (see Figure 56.3).

In the presence of a regular, narrow QRS tachycardia, AVNRT should be differentiated from AT or orthodromic AVRT due to an accessory pathway. Typically, focal AT is associated with a long and variable R–P relationship. However, focal AT can show a short R–P relationship at higher rates and an increased AV node conduction. Atypical AVNRT and a concealed accessory pathway with a slow retrograde conduction may demonstrate a long R–P interval, but the R–P interval is typically constant. The presence of a pseudo r’ wave in lead V1 or a pseudo S wave in leads II, III, and aVF has been reported to indicate anterior AVNRT with an accuracy of 100%. A difference of R–P intervals in leads V1 and III of >20 ms is indicative of posterior AVNRT, rather than AVRT, due to a posteroseptal pathway [14]. ST elevation in aVR and marked repolarization changes during tachycardia suggest AVRT [15]. The documentation of pre-excited beats, as well as AV dissociation and the induction of bundle branch block, during tachycardia may assist the differential diagnosis. AV block or AV dissociation, although uncommon and short-lasting, may be seen in AVNRT and excludes the presence of an accessory pathway. A significant change in the ventricular–atrial (VA) interval, with the development of a bundle branch block, is diagnostic of orthodromic AVRT and localizes the pathway to the same side as the block. AVRT due to a relatively fast-conducting concealed posteroseptal pathway cannot be differentiated from AVNRT without a detailed electrophysiological study (see Figure 56.4).

The differential diagnosis is between SVT with aberrant (bundle branch block) conduction, AV junctional re-entrant tachycardia with a bystander accessory pathway, antidromic (pre-excited) AVRT, fast AF conducted over an accessory pathway, and electrolyte-induced QRS widening. A history of ischaemic heart disease or congestive heart failure in men older than 35 years suggests that a wide QRS tachycardia is probably ventricular in origin [16].

Several morphologic criteria have been described, and the 12-lead ECG may provide an accurate diagnosis of monomorphic VT in most, but not all, circumstances (see Table 56.3 and Figures 56.5 to 56.7) [17–20]. However, most of the existing morphologic criteria favouring VT have been noted to be present in a substantial number of patients with an intraventricular conduction defect during sinus rhythm [21].

The following features are easily assessed.

AV dissociation may be seen as independent atrial activity, especially in lead II, or as a 2:1 or 3:1 retrograde block with a P wave following every second or third QRS complex. Intermittent capture of the ventricles by conduction from the independent atrial activity will produce fusion beats (slightly premature with a shape intermediate between sinus and tachycardia morphologies), due to a depolarization of the ventricles, partially by the tachycardia beat and partially by the sinus beat, or capture beats (premature beats with a morphology of conducted beats), due to complete depolarization of the ventricles by the sinus beat. However, because VT may show a 1:1 retrograde conduction to the atrium, the presence of an AV association cannot exclude the diagnosis of VT.

Concordant negativity or concordant positivity in all chest leads is also suggestive of VT.

A QRS complex of >0.14 s in an right bundle branch block (RBBB)-like tachycardia or >0.16 s in an left bundle branch block (LBBB)-like morphology, with regular R–R intervals and with a left axis or an axis between –90 and +180, especially in the presence of a narrow normal axis QRS during sinus rhythm, is suggestive of VT.

If an RS complex is present in one or more precordial leads, an RS interval (beginning of the R wave to the deepest part of the S wave) of >100 ms is highly specific for VT (see Figure 56.5) [17].

In lead aVR, the presence of an initial R wave, or a width of an initial r or q wave of >40 ms, or notching on the initial downstroke of a predominantly negative QRS complex, suggest VT. If none of these criteria is present, then a v(i)/v(t) < or = 1 (see Figure 56.6) suggests VT [20].

An R-wave peak time (RWPT) of ≥50 ms in lead II (from the isoelectric line to the point of first change in polarity) suggests VT (see Figure 56.7) [19]. The high accuracy of this criterion, however, was not verified in its first large external application [22].

A triphasic RSR’, with R’ > R and the S wave extending beyond the baseline in lead V1, and an RS complex with R > S in lead V6 in tachycardias with a RBBB morphology favours the diagnosis of SVT.

A monophasic R wave (no q wave) in lead V6 in tachycardias with an LBBB morphology favours the diagnosis of VT.

When the tachycardia has been terminated, further information can be gained from the 12-lead ECG in sinus rhythm. If bundle branch block is present, but with a different morphology or axis to that during tachycardia, the tachycardia is likely to be ventricular in origin. If delta waves are present and they have the same polarity as the QRS complexes of tachycardia, the diagnosis is most probably that of Wolff–Parkinson–White syndrome with antidromic AVRT or atrial fibrillation. An irregular, wide-QRS tachycardia with ventricular rates faster than 200 bpm, especially in the younger patient with no previous history of ischaemic heart disease, should always raise the question of pre-excited atrial fibrillation.

Adenosine, a naturally occurring nucleoside with a short-lived negative dromotropic effect on the AV node, given in rapid IV doses up to 0.25 mg/kg, will terminate or reveal most supraventricular tachycardias. Adenosine does not affect most ventricular tachycardias, with the exception of some forms associated with apparently normal hearts, and can therefore be used as a diagnostic agent. Verapamil should not be used in this way, because of the considerable incidence of life-threatening hypotension which is associated with its administration in ventricular tachycardia.

The acute management depends on the haemodynamic condition of the patient (see Figures 56.8 and 56.9 and Tables 56.4 and 56.5) [26].

In narrow QRS tachycardia, vagal manoeuvres, such as Valsalva, unilateral carotid massage, and facial immersion in cold water, may be tried to terminate the tachycardia. A modified Valsalva manoeuvre with leg elevation and supine positioning at the end of the strain is more effective and safe, and can be taught to patients [23].

Adenosine, a naturally occurring nucleoside with a short-lived negative dromotropic effect on the AV node, given in rapid IV doses of up to 0.25 mg/kg, will terminate or reveal most SVTs (see Figure 56.3). Adenosine does not affect most VTs, with the exception of some forms associated with apparently normal hearts, and can therefore be used as a diagnostic agent [24]. AF may be caused (1–5%) but is usually transient. Adenosine is contraindicated in severe bronchial asthma. Its action is antagonized by theophylline and potentiated by dipyridamole and carbamazepine. Verapamil should not be used in this way, because of the considerable incidence of life-threatening hypotension which is associated with its administration in VT.

Acute management of wide QRS tachycardia depends on the haemodynamic condition of the patient. Patients should be treated for VT, unless there is documentation of non-sustained VT (NSVT). Haemodynamically unstable patients require immediate direct current cardioversion.

Of the sinus tachycardias, only the sinus re-entrant form can present as paroxysmal tachycardia that might require acute therapy; vagal manoeuvres, or intravenous (IV) adenosine, or premature atrial stimulation may be used (see Table 56.6).

Focal AT is characterized by a P wave rate of >250/min, although it can be <200/min, and an isoelectric interval between the P waves (see Figures 56.10 and 56.11). Classically, the P wave for focal AT is described as distinct with an intervening isoelectric interval, in contrast to a continuous undulation typical of macro re-entry tachycardia. However, an isoelectric interval may not be identifiable during accelerated heart rates and/or in the presence of atrial disease resulting in a slowing of conduction. A change in the P wave morphology and a dissociation between the atrial and ventricular response may also be seen.

Acute therapy is seldom required for haemodynamic instability. Acute management is presented in Table 56.7 and Figure 56.12.

Multifocal AT is an irregular tachycardia characterized by three or more different P wave morphologies at different rates. The arrhythmia is most commonly associated with an underlying pulmonary disease but may result from metabolic or electrolyte derangements, or rarely now by digitalis toxicity. Metoprolol or verapamil (ACC/AHA/HRS GL on SVT, IIa-C-LD), and correction of the underlying disorder are the main therapeutic means. There is no role for direct current cardioversion, antiarrhythmic drugs, or ablation.

Counter clockwise atrial flutter (counter clockwise rotation around the tricuspid valve) is characterized electrocardiographically by dominant negative flutter waves in the inferior leads and a positive flutter deflection in lead V1, with a transition to a negative deflection in lead V6, at rates of 250–350 beats/min (see Figure 56.13). Usually, there is a 2:1 AV conduction, with a resultant ventricular rate of approximately 150 beats/min. A varying block produces an irregular rhythm, whereas a 1:1 conduction may lead to haemodynamic instability.

Clockwise isthmus-dependent flutter (10% of atrial flutters) shows the opposite pattern (i.e. positive flutter waves in the inferior leads and wide, negative flutter waves in lead V1, transitioning to positive waves in lead V6). The typical sawtooth ECG patterns described above may or may not be present. Conduction delays within the circuit can prolong the AT cycle length, making it overlap with the classical focal AT range (>400 ms]) or LA ablation for AF. The ECG during tachycardia has atypical futures resembling those of focal ATs.

In emergencies, direct current cardioversion (<50 J) is indicated (see Table 56.8 and Figure 56.14). Otherwise, ibutilde IV or overdrive pacing are used. For acute rate control, diltiazem IV is as effective as verapamil, but with a lower incidence of hypotension [25]. Atrial flutter lasting >48 hours requires anticoagulation.

Typically, AVNRT is a narrow complex tachycardia, i.e. QRS duration of <120 m, unless an aberrant conduction, which is usually of the RBBB type, or a previous conduction defect exists [26]. Tachycardia-related ST depression, as well as R–R interval variation, may be seen (see Figure 56.15). RR alternans may also be seen but are more common in AVRT.

In the typical form of AVNRT (also called slow-fast AVNRT), abnormal (retrograde) P’ waves are constantly related to the QRS and, in the majority of cases, are indiscernible or very close to the QRS complex (RP’/RR <0.5). Thus, P’ waves are either masked by the QRS complex or seen as a small terminal P’ wave that is not present during sinus rhythm. In the atypical form of AVNRT, P’ waves are clearly visible before the QRS, i.e. RP’/P’R >0.75, denoting a ‘long RP tachycardia’, and are negative or shallow in leads II, III, aVF, and V6, but positive in V1 (see Figure 56.16 and Table 56.9).

The distinction between ‘fast-slow’ and ‘slow-slow’ forms is probably of no practical significance [27].

In acute episodes of AVNRT that do not respond to Valsalva manoeuvres, IV adenosine is the treatment of choice (see Figure 56.17 and Table 56.10). Alternatively, a single dose of oral diltiazem (120 mg) and a β-blocker (i.e. propranolol 80 mg) may be tried [28].

Non-paroxysmal junctional tachycardia was frequently diagnosed in the past as a junctional rhythm of gradual onset and termination, with a rate between 70 and 130 beats/min, and was considered a typical example of digitalis-induced delayed after-depolarizations and triggered activity in the AV node. Myocardial ischaemia, hypokalaemia, chronic obstructive pulmonary disease (COPD), and myocarditis are also associated, and acute therapy should address these conditions. Focal junctional tachycardia occurs as a congenital arrhythmia or early after an infant open heart surgery, but it can also be seen in adult patients with a structurally normal heart [29, 30]. The usual ECG finding is a narrow QRS tachycardia with AV dissociation. Occasionally, the tachycardia might be irregular, thus resembling AF. IV beta blockers, procainamide, or verapamil are used for acute therapy (ACC/AHA/HRS 2015 GL on SVT, IIa-C-LD). Non-re-entrant AV nodal tachycardia, caused by a simultaneous multiple nodal pathway conduction, is an uncommon mechanism of AV nodal tachycardia and has been associated with repetitive retrograde concealment or ‘linking’ phenomena [26]. These are expressed in the form of ventricular pauses, with a consistent AV relationship after the pause. Acute therapy is the same as with AVNRT.

Tachycardias may be orthodromic, i.e. a narrow QRS, due to an antegrade conduction through the AV node and a retrograde conduction through the pathway, or antidromic (<10%), i.e. a wide QRS, due to an antegrade conduction via the pathway (see Figure 56.18). During AF, an antegrade conduction over the accessory pathway also results in an irregular wide QRS complex tachyarrhythmia which may be mistaken for VT.

In acute episodes of narrow QRS tachycardia that do not respond to Valsalva manoeuvres, IV adenosine is the treatment of choice (see Table 56.11). Alternatively, a single dose of oral diltiazem (120 mg) and a β-blocker (i.e. propranolol 80 mg) may be tried [28]. In wide QRS tachycardia, adenosine may also be given, but with caution because it may produce AF with a rapid ventricular rate though a fast pathway. IV ibutilide, flecainide, or procainamide may be given (see Figure 56.19).

Direct current cardioversion is indicated in haemodynamic instability (see Table 56.12 and Figure 56.20) or when pharmacological cardioversion has failed. Biphasic, R wave-synchronized shock (at least 150–200 J to avoid repeated shocks and the occurrence of shock-induced VF), with anteroposterior electrode placement (at least 8 cm from a pacemaker battery, if present), is recommended [31]. A pacing catheter or external pacing pads may be needed in patients with sick sinus syndrome or in elderly patients with structural heart disease. Ventricular arrhythmias (in digitalis intoxication or hypokalaemia) are rare. Pre-treatment with drugs, such as amiodarone, ibutilide, sotalol, flecainide, and propafenone, increase the success rates Vernakalant is also a useful agent for facilitated electrical cardioversion in cardioversion-resistant AF [32].

Pharmacological cardioversion is less effective than direct current cardioversion. The same precautions as for anticoagulation and thromboembolic risk prevention apply as in direct current cardioversion. Drugs used are (see Table 56.13 and 56.14).

Flecainide (1.5–3 mg/kg IV over 10–20 min) or propafenone (2 mg/kg IV over 10 min) achieve sinus rhythm in 67–92% and 41–91% of patients, respectively, within the next 6 hours. They are both contraindicated in patients with coronary artery disease (CAD) or an impaired LV function and are not effective in atrial flutter or persistent AF. They may prolong the QRS duration, with resultant VT (and, with flecainide, also the QT), and inadvertently increase the ventricular rate, due to conversion to atrial flutter and a 1:1 conduction to the ventricles.

The ‘pill in the pocket’ approach refers to oral flecainide (200–300 mg PO) or propafenone (450–600 mg PO) that may achieve sinus rhythm in up to 45% of patients who present with a <7 days of AF [33]. Before an antiarrhythmic medication is initiated, a β-blocker or non-dihydropyridine calcium channel antagonist should be given to prevent a rapid AV conduction, in the event atrial flutter occurs (<0.2%).

Ibutilide is a class III agent, blocking the rapid component of the rectifier K⁺ channel (IKr) and also activating the slow inward Na⁺ current [34]. It is a moderately potent drug for the acute conversion of AF (45–75%). It is given IV, 1 mg over 10 min, in one or two doses, and achieves conversion within 90 min in 50% of patients. It prolongs the QTc by approximately 60 ms, and there is a 3.6–8.3% risk of torsades de pointes (watch for abnormal T–U waves or a prominent QT prolongation). Co-administration of β-blockade may increase efficacy and diminish the proarrhythmic risk [35].

Amiodarone (5 mg/kg IV over 1 hour, followed by 50 mg/hour for up to 24 hours) achieves cardioversion in 40–60% of patients (80–90% with pre-treatment), but later than the other drugs [32]. Hypotension and a slow ventricular rate may be seen.

Dofetilide is also a pure class III agent (selective Ikr-blocking agent), that is moderately effective in cardioverting AF to sinus rhythm (30%) and significantly effective in maintaining sinus rhythm for 1 year (60%) [36]. It is given orally 500 mg bd, and 250 or 125 mg bd with a creatinine clearance of <60 mL/min or 20–40 mL/min, respectively, is also effective, even in AF of >7 days’ duration, but the response may be delayed. QTc prolongation also occurs, and there is a small, but not negligible, risk of torsades de pointes that may translate into increased mortality [37]. Inpatient monitoring is recommended (FDA) when initiating dofetilide therapy to avoid torsades de pointes ventricular tachycardia, especially in patients with heart failure, hypertrophy, bradycardia, and those of female gender.

Vernakalant blocks early activating K⁺ channels (Ikur) and frequency-dependent Na⁺ channels. It is relatively atrial-selective, because the density of the Ikur channels is higher in the atria, and the effects on the Na⁺ channels are rate-dependent. At a dose of 3 mg/kg IV over 10 min, with a second infusion of 2 mg/kg IV over 10 min after 15 min of rest, converts AF (of ≤7 days’ duration or ≤3 days after surgery) in up to 51% of patients within 90 min [38]. Vernakalant is contraindicated in patients with a systolic blood pressure of <100 mmHg, severe AS, heart failure (NYHA classes III and IV), ACS within the previous 30 days, or QT interval prolongation (uncorrected QT >440 ms). Before its use, patients should be adequately hydrated.

In patients with AF<48 h from a definite onset a bolus of UFH (5000 U IV) or LMWH (1 mg/kg IV) should be given, especially if the patient is >65 years old or the CHA2DS2VASC score is ≥2. If AF occurred for more than 48 h a trans-oesophageal echocardiography (TOE) is necessary to exclude left atrial thrombus. Patients who have been on oral anticoagulation for at least 4 weeks before cardioversion with warfarin (and INR>2) or a non-vitamin K oral anticoagulant (NOAC) may be subjected to cardioversion without previous TOE. However, these patients may still have left atrial thrombus, and ideally a TOE should be performed [39]. Following cardioversion, further anticoagulation depends on underlying risk factors for thromboembolism. In the absence of such risk factors (CHA₂DS₂-VASc score 0 for males or 1 for females), no oral anticoagulation is needed after cardioversion. In patients with AF >48 h or risk factors for thromboembolism, heparin is continued together with warfarin until the INR becomes 2–3 (for dosing see CAD), or a NOAC is administered immediately after cardioversion. Thereafter, anticoagulation is continued for 4 weeks, and then further anticoagulation depends on the presence of risk factors (see Table 56.15). Recommendations for cardioversion of patients treated with non-vitamin K-dependent anticoagulants are presented in Figure 56.21.

Reinitiation of anticoagulation following a non-fibrinolysed ischaemic stroke should be within 14 days after the onset of symptoms (AHA/ASA 2014 GL for prevention of stroke, IIa-B), since the risk of early recurrence is as high as 8% [40]. In patients with a TIA, anticoagulation can be initiated 1 day after the onset of neurological symptoms, whereas 3–6 days are required for small, non-disabling, and large infarcts [41]. However, in the presence of high risk for haemorrhagic conversion (i.e. large infarct, haemorrhagic transformation on initial imaging, uncontrolled hypertension, or haemorrhage tendency), it is reasonable to delay initiation of oral anticoagulation beyond 14 days (AHA/ASA 2014 GL for prevention of stroke, IIa-B) [40]. The EHRA recommendations for the initiation or reinitiation of anticoagulation after TIA/stroke or intracerebral haemorrhage are presented in Figure 56.22.

When AF cannot be cardioverted, or cardioversion is contraindicated (i.e. in the presence of an LA thrombus), acute rate control (80–100 beats/min) can be accomplished by IV β-blockers (i.e. esmolol 0.5 mg/kg IV over 1 min, followed by 60–200 micrograms/kg/min, or metoprolol 2.5–5 mg bolus with up to three doses) or non-dihydropyridine calcium antagonists (diltiazem 0.25 mg/kg over 2 min, followed by 5–15 mg/hour, or verapamil 0.075–0.15 mg/kg over 2 min) (see Table 56.16) [1]. Diltiazem appears to be more effective than metoprolol in achieving acute rate control in patients with atrial fibrillation or flutter in the emergency department[42].

In the setting of heart failure or hypotension, digitalis (0.25–1.5 mg IV) or amiodarone (150 mg IV over 10 min, or 5 mg/kg IV over 1 hour, and then followed by 50 mg/hour) may be used. In pre-excitation, only class I drugs or amiodarone are safe. AF with slow ventricular rates may respond to atropine (0.5–2 mg IV), but temporary pacing may be required.

Premature atrial beats are observed in up to 50% of pregnant women and are benign (see Chapter 63). Exacerbations of SVT occur in 20–40% of them [43]. Adenosine and electrical cardioversion are not contraindicated (see Table 56.17). Digoxin is safe, but of limited value. AF is rare during pregnancy in women without previously detected AF and without a pre-existing heart disease [8, 12]. In patients with previously diagnosed AF, 52% experience new episodes during pregnancy. AF during pregnancy is well tolerated in most patients without a congenital or valvular disease, but more fetal complications occur in those women who develop arrhythmias during pregnancy.

Several case reports have demonstrated successful cardioversion of maternal AF, without harm to the fetus (see Table 56.18). Prior anticoagulation or TOE exclusion of an LA thrombus is mandatory when AF is of >48 hours, and anticoagulation is maintained for 4 weeks. In AF of <48 hours, one IV UH or LMWH is given pericardioversion. Energy requirements in pregnant and non-pregnant women are similar.

β-blockers cross the placenta and are associated with various adverse effects, including intrauterine growth retardation, neonatal respiratory depression, bradycardia, and hypoglycaemia, especially if the treatment is initiated early in pregnancy (i.e. 12–24 weeks). A meta-analysis in patients with hypertension, assessing the risks of β-receptor blockers, in pregnancy found a borderline increase in ‘small for gestational age’ infants [44]. No association with low weight for gestational age has been found for labetalol (started after the 6th week of gestation), as opposed to atenolol. Digoxin crosses the placenta freely, and digitalis intoxication in the mother has been associated with fetal death. Oral verapamil and diltiazem are most probably safe (see Table 56.18). Sotalol, flecainide, or propafenone are second-choice drugs.

IV ibutilide or flecainide are usually effective and may be considered, although the experience during pregnancy is limited [43, 45]. Amiodarone may cause neonatal hypothyroidism (9% of newborns), hyperthyroidism, goitre, and growth retardation. All drugs should, if possible, be avoided during the period of organogenesis in the first trimester of pregnancy.

Anticoagulation is recommended in patients with ≥2 risk points of the CHADS₂ score or 2 risk points of the CHA₂DS₂-VASc score [43]. VKAs can be teratogenic in up to 7% of fetuses and, in many cases, should be substituted with UFH or LMWH for the first trimester [43]. Warfarin may be used in the second trimester, with an only slightly elevated teratogenic risk. Warfarin crosses the placenta freely, and the fetus may be overdosed, even when the mother is in the therapeutic INR range. LMWH does not cross the placenta barrier and has been used for the treatment and prophylaxis of venous thromboembolism (VTE) during pregnancy, without adverse fetal effects. The new oral thrombin antagonists, such as dabigatran, have shown fetotoxicity with high doses and should not be used.