Accelerated automaticity (Fig. 14.37a)

The normal mechanism of spontaneous cardiac rhythmicity is slow depolarization of the transmembrane voltage during diastole until the threshold potential is reached and the action potential of the pacemaker cells takes off. This mechanism may be accelerated by increasing the rate of diastolic depolarization or changing the threshold potential. For example, sympathetic stimulation releases epinephrine (adrenaline), which enhances automaticity. Such changes are thought to produce sinus tachycardia, escape rhythms and accelerated AV nodal (junctional) rhythms.

Triggered activity (Fig. 14.37b)

Myocardial damage can result in oscillations of the transmembrane potential at the end of the action potential. These oscillations, which are called ‘after depolarizations’, may reach threshold potential and produce an arrhythmia. If they occur before the transmembrane potential reaches its threshold (at the end of phase 3 of the action potential), they are called ‘early after depolarizations’ (E in Fig. 14.37b). When they develop after the transmembrane potential is completed, they are called ‘delayed after depolarizations’ (D in Fig. 14.37b).

The abnormal oscillations can be exaggerated by pacing, catecholamines, electrolyte disturbances, hypoxia, acidosis and some medications, which may then trigger arrhythmia. The atrial tachycardias produced by digoxin toxicity are due to triggered activity. The initiation of ventricular arrhythmia in the long QT syndrome (p. 708) may be caused by this mechanism.

Re-entry (or circus movements) (Fig. 14.37c)

The mechanism of re-entry occurs when a ‘ring’ of cardiac tissue surrounds an inexcitable core (e.g. in a region of scarred myocardium). Tachycardia is initiated if an ectopic beat finds one limb refractory (α), resulting in unidirectional block, and the other limb excitable. Provided conduction through the excitable limb (β) is slow enough, the other limb (α) will have recovered and will allow retrograde activation to complete the re-entry loop. If the time to conduct around the ring is longer than the recovery times (refractory periods) of the tissue within the ring, circus movement will be maintained, producing a run of tachycardia. The majority of regular paroxysmal tachycardias are produced by this mechanism.

Sinus bradycardia

Sinus bradycardia is due to extrinsic factors influencing a relatively normal sinus node or due to intrinsic sinus node disease. The mechanism can be acute and reversible or chronic and degenerative. Common causes of sinus bradycardia include:

Neurally mediated syndromes

Neurally mediated syndromes are due to a reflex (called Bezold–Jarisch) that may result in both bradycardia (sinus bradycardia, sinus arrest and AV block) and reflex peripheral vasodilatation. These syndromes usually present as syncope or pre-syncope (dizzy spells).

Carotid sinus syndrome occurs in the elderly and mainly results in bradycardia. Syncope occurs (see p. 676).

Neurocardiogenic (vasovagal) syncope (syndrome) usually presents in young adults but may present for the first time in elderly patients (see p. 676). It results from a variety of situations (physical and emotional) that affect the autonomic nervous system. The efferent output may be predominantly bradycardic, predominantly vasodilatory or mixed.

Postural orthostatic tachycardia syndrome (POTS) is a sudden and significant increase in heart rate associated with normal or mildly reduced blood pressure produced by standing. The underlying mechanism is a failure of the peripheral vasculature to appropriately constrict in response to orthostatic stress, which is compensated by an excessive increase in heart rate.

Many medications, such as antihypertensives, tricyclic antidepressants and neuroleptics, can be the cause of syncope, particularly in the elderly. Careful dose titration and avoidance of combining two agents with potential to cause syncope help to prevent iatrogenic syncope.

Atrioventricular block

There are three forms:

First-degree AV block

This is simple prolongation of the PR interval to >0.22 s. Every atrial depolarization is followed by conduction to the ventricles but with delay (Fig. 14.38).

Figure 14.38 An ECG showing first-degree atrioventricular block with a prolonged PR interval. In this trace, coincidental ST depression is also present.

Second-degree AV block

This occurs when some P waves conduct and others do not. There are several forms (Fig. 14.39):

Mobitz I block (Wenckebach block phenomenon) is progressive PR interval prolongation until a P wave fails to conduct. The PR interval before the blocked P wave is much longer than the PR interval after the blocked P wave.

Mobitz II block occurs when a dropped QRS complex is not preceded by progressive PR interval prolongation. Usually the QRS complex is wide (>0.12 s).

2 : 1 or 3 : 1 (advanced) block occurs when every second or third P wave conducts to the ventricles. This form of second-degree block is neither Mobitz I nor II.

Figure 14.39 Three varieties of second-degree atrioventricular (AV) block. (a) Wenckebach (Mobitz type I) AV block. The PR interval gradually prolongs until the P wave does not conduct to the ventricles (arrows). (b) Mobitz type II AV block. The P waves that do not conduct to the ventricles (arrows) are not preceded by gradual PR interval prolongation. (c) Two P waves to each QRS complex. The PR interval prior to the dropped P wave is always the same. It is not possible to define this type of AV block as type I or type II Mobitz block and it is, therefore, a third variety of second-degree AV block (arrows show P waves).

Wenckebach AV block in general is due to block in the AV node, whereas Mobitz II block signifies block at an infra-nodal level such as the His bundle. The risk of progression to complete heart block is greater and the reliability of the resultant escape rhythm is less with Mobitz II block. Therefore pacing is usually indicated in Mobitz II block, whereas patients with Wenckebach AV block are usually monitored.

Acute myocardial infarction may produce second-degree heart block. In inferior myocardial infarction, close monitoring and transcutaneous temporary back-up pacing are all that is required. In anterior myocardial infarction, second-degree heart block is associated with a high risk of progression to complete heart block, and temporary pacing followed by permanent pacemaker implantation is usually indicated; 2 : 1 Heart block may either be due to block in the AV node or at an infra-nodal level. Management depends on the clinical setting in which it occurs.

Third-degree (complete) AV block

Complete heart block occurs when all atrial activity fails to conduct to the ventricles (Fig. 14.40). In patients with complete heart block the aetiology needs to be established (Table 14.7). In this situation life is maintained by a spontaneous escape rhythm.

Figure 14.40 Two examples of complete heart block. (a) Congenital complete heart block. The QRS complex is narrow (0.08 s) and the QRS rate is relatively rapid (52 b.p.m.). (b) Acquired complete heart block. The QRS complex is broad (0.13 s) and the QRS rate is relatively slow (38 b.p.m.).

Table 14.7 Aetiology of complete heart block

Congenital Autoimmune (e.g. maternal SLE) Structural heart disease (e.g. transposition of the great vessels) Idiopathic fibrosis Lev’s disease (progressive fibrosis of distal His–Purkinje system in elderly patients) Lenegre’s disease (proximal His–Purkinje fibrosis in younger patients) Ischaemic heart disease Acute myocardial infarct Ischaemic cardiomyopathy Non-ischaemic heart disease Calcific aortic stenosis Idiopathic dilated cardiomyopathy Infiltrations (e.g. amyloidosis, sarcoidosis, neoplasia)

Cardiac surgery e.g. following aortic valve replacement, CABG, VSD repair Iatrogenic Radiofrequency AV node ablation and pacemaker implantation Drug-induced e.g. digoxin, beta-blockers, non-dihydropyridine calcium-channel blockers, amiodarone Infections Endocarditis Lyme disease Chagas’ disease Rheumatic autoimmune disease e.g. SLE, rheumatoid arthritis Neuromuscular diseases e.g. Duchenne muscular dystrophy

SLE, systemic lupus erythematosus; CABG, coronary artery bypass graft surgery; VSD, ventricular septal defect; AV, atrioventricular.

Narrow complex escape rhythm (<0.12 s QRS complex) implies that it originates in the His bundle and therefore that the region of block lies more proximally in the AV node. The escape rhythm occurs with an adequate rate (50–60 b.p.m.) and is relatively reliable.

Treatment depends on the aetiology. Recent-onset narrow-complex AV block due to transient causes may respond to intravenous atropine, but temporary pacing facilities should be available for the management of these patients. Chronic narrow-complex AV block requires permanent pacing (dual chamber, p. 695) if it is symptomatic or associated with heart disease. Pacing is also advocated for isolated, congenital AV block, even if asymptomatic.

Broad complex escape rhythm (>0.12 s) implies that the escape rhythm originates below the His bundle and therefore that the region of block lies more distally in the His-Purkinje system.

The resulting rhythm is slow (15–40 b.p.m.) and relatively unreliable. Dizziness and blackouts (Stokes–Adams attacks) often occur. In the elderly, it is usually caused by degenerative fibrosis and calcification of the distal conduction system (Lev’s disease). In younger individuals, a proximal progressive cardiac conduction disease due to the inflammatory process is known as Lenegre’s disease. Sodium channel abnormalities have been identified in both syndromes. Broad-complex AV block may also be caused by ischaemic heart disease, myocarditis or cardiomyopathy. Permanent pacemaker implantation (p. 695) is indicated, as pacing considerably reduces the mortality. Because ventricular arrhythmias are not uncommon, an implantable cardioverter-defibrillator (ICD) may be indicated in those with severe left ventricular dysfunction (>0.30 s).

Bundle branch block

The His bundle gives rise to the right and left bundle branches. The left bundle subdivides into the anterior and posterior divisions of the left bundle. Various conduction disturbances can occur.

Complete block of a bundle branch

This is associated with a wider QRS complex (≥0.12 s). The shape of the QRS depends on whether the right or the left bundle is blocked.

Right bundle branch block (Fig. 14.41a) produces late activation of the right ventricle. This is seen as deep S waves in leads I and V₆ and as a tall late R wave in lead V₁ (late activation moving towards right- and away from left-sided leads).

Figure 14.41 Right bundle branch block versus bifascicular block. (a) A 12-lead ECG showing right bundle branch block. Note an rsR′ pattern with the tall R′ in lead V₁–V₂ and the broad S waves in leads I and V₅–V₆. (b) Compare with an ECG showing bifascicular block. In addition to right bundle branch block, note left axis deviation and deep S waves in leads III and AVF typical for left anterior hemiblock.

Left bundle branch block (Fig. 14.42) produces the opposite – a deep S wave in lead V₁ and a tall late R wave in leads I and V₆. Because left bundle branch conduction is normally responsible for the initial ventricular activation, left bundle branch block also produces abnormal Q waves.

Figure 14.42 A 12-lead ECG showing left bundle branch block. The QRS duration is >0.12 s. Note the broad notched R waves with ST depression in leads I, AVL and V₆, and the broad QS waves in V₁–V₃.

Atrioventricular nodal re-entry tachycardia (AVNRT)

This tachycardia is twice as common in women. Clinically, the tachycardia often strikes suddenly without obvious provocation, but exertion, coffee, tea and alcohol may aggravate or induce the arrhythmia. An attack may stop spontaneously or may continue indefinitely until medical intervention.

In AVNRT, there are two functionally and anatomically different pathways predominantly within the AV node: one is characterized by a short effective refractory period and slow conduction, and the other has a longer effective refractory period and conducts faster. In sinus rhythm, the atrial impulse that depolarizes the ventricles usually conducts through the fast pathway. If the atrial impulse (e.g. an atrial premature beat) occurs early when the fast pathway is still refractory, the slow pathway takes over in propagating the atrial impulse to the ventricles. It then travels back through the fast pathway which has already recovered its excitability, thus initiating the most common ‘slow-fast’, or typical, AVNRT.

The rhythm is recognized on ECG by normal regular QRS complexes, usually at a rate of 140–240/minute (Fig. 14.43a). Sometimes the QRS complexes will show typical bundle branch block. P waves are either not visible or are seen immediately before or after the QRS complex because of simultaneous atrial and ventricular activation. Less commonly observed (5–10%) is tachycardia when the atrial impulse conducts anterogradely through the fast pathway and returns through the slow pathway, producing a long RP’ interval (‘fast-slow’, or long RP’ tachycardia).

Figure 14.43 Atrioventricular junctional tachycardia. (a) Atrioventricular nodal re-entry tachycardia. The QRS complexes are narrow and the P waves cannot be seen. (b) Atrioventricular re-entry tachycardia (Wolff–Parkinson–White syndrome, WPW). The tachycardia P waves (arrows) are clearly seen after narrow QRS complexes. (c) An electrocardiogram taken in a patient with WPW syndrome during sinus rhythm. Note the short PR interval and the δ wave (arrow). (d) Atrial fibrillation in the WPW syndrome. Note tachycardia with broad QRS complexes with fast and irregular ventricular rate.

Atrioventricular reciprocating tachycardia (AVRT)

This large circuit comprises the AV node, the His bundle, the ventricle and an abnormal connection of myocardial fibres from the ventricle back to the atrium. It is called an accessory pathway or bypass tract and results from an incomplete separation of the atria and the ventricles during fetal development.

In contrast to AVNRT, this tachycardia is due to a macro-reentry circuit and each part of the circuit is activated sequentially. As a result atrial activation occurs after ventricular activation and the P wave is usually clearly seen between the QRS and T wave (Fig. 14.43b).

Accessory pathways are most commonly situated on the left but may occur anywhere around the AV groove. The most common accessory pathways, known as Kent bundles, are in the free wall or septum. In about 10% of cases multiple pathways occur. Mahaim fibres are atrio-fascicular or nodo-fascicular fibres entering the ventricular myocardium in the region of the right bundle branch. Accessory pathways that conduct from the ventricles to the atria only are not visible on the surface ECG during sinus rhythm and are therefore ‘concealed’. Accessory pathways that conduct bidirectionally usually are manifest on the surface ECG. If the accessory pathway conducts from the atrium to the ventricle during sinus rhythm, the electrical impulse can conduct quickly over this abnormal connection to depolarize part of the ventricles abnormally (pre-excitation). A pre-excited ECG is characterized by a short PR interval and a wide QRS complex that begins as a slurred part known as the δ wave (Fig. 14.43c). Patients with a history of palpitations and a pre-excited ECG have a syndrome known as Wolff–Parkinson–White (WPW) syndrome.

During AVRT the AV node and ventricles are activated normally (orthodromic AVRT), resulting usually in a narrow QRS complex. Less commonly, the tachycardia circuit can be reversed, with activation of the ventricles via the accessory pathway and atrial activation via retrograde conduction through the AV node (antidromic AVRT). This results in a broad complex tachycardia. These patients are also prone to atrial fibrillation.

During atrial fibrillation, the ventricles may be depolarized by impulses travelling over both the abnormal and the normal pathways. This results in pre-excited atrial fibrillation, a characteristic tachycardia that is characterized by irregularly irregular broad QRS complexes (Fig. 14.43d). If an accessory pathway has a short antegrade effective refractory period (<250 ms), it may conduct to the ventricles at an extremely high rate and may cause ventricular fibrillation. The incidence of sudden death is 0.15–0.39% per patient-year and it may be a first manifestation of the disease in younger individuals. Verapamil and digoxin may allow a higher rate of conduction over the abnormal pathway and precipitate ventricular fibrillation. Therefore, neither verapamil nor digoxin should be used to treat atrial fibrillation associated with the WPW syndrome.

Atrial fibrillation

This is a common arrhythmia, occurring in 1–2% of the general population and 5–10% of patients over 75 years of age. It also occurs, particularly in a paroxysmal form, in younger patients. Any condition resulting in raised atrial pressure, increased atrial muscle mass, atrial fibrosis, or inflammation and infiltration of the atrium, may cause atrial fibrillation. There are also many genetic and systemic causes of atrial fibrillation (Table 14.10).

Although rheumatic heart disease, alcohol intoxication and thyrotoxicosis are the ‘classic’ causes of atrial fibrillation, hypertension and heart failure are the most common causes. Hyperthyroidism may provoke atrial fibrillation, sometimes as virtually the only feature of the disease, and thyroid function tests are mandatory in any patient with unaccounted atrial fibrillation. Atrial fibrillation occurs in one-third of patients after cardiac surgery. It usually manifests during the first 4 days and is associated with increased morbidity and mortality, largely due to stroke and circulatory failure, a longer hospital stay, and later recurrences.

In some patients no cause can be found, and this group is labelled as ‘lone’ atrial fibrillation. The pathogenesis of ‘lone’, or ‘idiopathic’, atrial fibrillation is unknown but genetic predisposition or even specific genetically predetermined forms of the arrhythmia have been proposed. About 30–40% of those with AF, especially those who present at a young age, have at least one parent with AF and genes associated with the sodium channel, the potassium channel, gap junction proteins and right left isomerism) have been implicated. Gene defects linked to chromosomes 10, 6, 5 and 4 have been associated with familial AF.

Atrial fibrillation is maintained by continuous, rapid (300–600/min) activation of the atria by multiple meandering re-entry wavelets, often driven by rapidly depolarizing automatic foci, located predominantly within the pulmonary veins. The atria respond electrically at this rate but there is no coordinated mechanical action and only a proportion of the impulses are conducted to the ventricles. The ventricular response depends on the rate and regularity of atrial activity, particularly at the entry to the AV node, the refractory properties of the AV node itself, and the balance between sympathetic and parasympathetic tone.

Long-term management of atrial fibrillation

Two strategies are available:

Major randomized studies in patients predominantly over the age of 65 years (AFFIRM) or in patients with heart failure (AF-CHF) have shown that there is no net mortality or symptom benefit to be gained from one strategy compared with the other. Which strategy to adopt needs to be assessed for each individual patient. Factors to consider include the likelihood of maintaining sinus rhythm and the safety/tolerability of antiarrhythmic drugs in a particular patient.

Anticoagulation

This is indicated in patients with atrial fibrillation related to rheumatic mitral stenosis or in the presence of a mechanical prosthetic heart valve. A scoring system known as CHADS₂ is used as the first step to determine the need for anticoagulation. CHADS₂ is an acronym standing for Congestive heart failure, Hypertension, Age ≥75, Diabetes mellitus and previous Stroke or TIA. Each factor scores 1 except previous stroke or TIA which scores 2. A total score of 2 implies that oral anticoagulation is needed. When the score is <2 the CHADS₂VASc scoring system should be applied. CHADS₂VASc adds Vascular disease (aorta, coronary or peripheral arteries), Age 65–74, and female Sex category. Each factor scores 1 except previous Age >75 and stroke or TIA which score 2. A CHADS₂VASc score of 2 requires oral anticoagulation and a score of 1 merits consideration for oral anticoagulation or aspirin. A score of 0 should not require any antithrombotic prophylaxis.

When oral anticoagulation is required either warfarin (dose adjusted to maintain an INR between 2.0 and 3.0) or dabigatran 150 mg two times daily (or 110 mg two times daily in elderly patients (>75 years), those with moderate renal impairment (creatinine clearance: 30 to 50 mL/min) or those taking P-glycoprotein inhibitors such as amiodarone and verapamil) can be considered. Other new oral anticoagulants, such as apixaban and rivaroxaban, are now also being used.

Atrial flutter

Atrial flutter is often associated with atrial fibrillation and often requires a similar initial therapeutic approach. Atrial flutter is usually an organized atrial rhythm with an atrial rate typically between 250 and 350 b.p.m. Typical, or isthmus-dependent, atrial flutter involves a macro re-entrant right atrial circuit around the tricuspid annulus. The wavefront circulates down the lateral wall of the right atrium, through the Eustachian ridge between the tricuspid annulus and the inferior vena cava, and up the interatrial septum, giving rise to the most frequent pattern, referred to as counter-clockwise flutter. Re-entry can also occur in the opposite direction (clockwise or reverse flutter).

The ECG shows regular sawtooth-like atrial flutter waves (F waves) between QRS complexes (Fig. 14.44c). In typical counter-clockwise atrial flutter, the F waves are negative in the inferior leads and positive in leads V₁ and V₂. In clockwise atrial flutter, the deflection of the F waves is the opposite. If F waves are not clearly visible, it is worth trying to reveal them by slowing AV conduction by carotid sinus massage or by the administration of AV nodal blocking drugs such as adenosine or verapamil.

Symptoms are largely related to the degree of AV block. Most often, every second flutter beat conducts, giving a ventricular rate of 150 b.p.m. Occasionally, every beat conducts, producing a heart rate of 300 b.p.m. More often, especially when patients are receiving treatment, AV conduction block reduces the heart rate to approximately 75 b.p.m.

Atrial tachycardia

This is an uncommon arrhythmia. Its prevalence is believed to be <1% in patients with arrhythmias. It is usually associated with structural heart disease but in many cases it is referred to as idiopathic. Macro re-entrant tachycardia often occurs after surgery for congenital heart disease. Atrial tachycardia with block is often a result of digitalis poisoning.

The mechanisms of atrial tachycardia are attributed to enhanced automaticity, triggered activity or intra-atrial reentry. Atrial re-entry tachycardia is usually relatively slow (125–150 b.p.m.) and can be initiated and terminated by atrial premature beats. The P′P′ intervals are regular. The PR interval depends on the rate of tachycardia and is longer than in sinus rhythm at the same rate.

Automatic tachycardia usually presents with higher rates (125–250 b.p.m.) and is often characterized by a progressive increase in the atrial rate with onset of the tachycardia (‘warm-up’) and progressive decrease prior to termination (‘cool-down’). Atrial tachycardia is typically caused by a focus which is frequently located along the crista terminalis in the right atrium, adjacent to a pulmonary vein in the left atrium, or around one of the atrial appendages. Automatic atrial tachycardia may also present as an incessant variety leading to tachycardia-induced cardiomyopathy. Short runs of atrial tachycardia may provoke more sustained episodes of atrial fibrillation.

Figure 14.44b demonstrates an atrial tachycardia at an atrial rate of 150/minute. The P waves are abnormally shaped and occur in front of the QRS complexes. Carotid sinus massage may increase AV block during tachycardia, thereby facilitating the diagnosis, but does not usually terminate the arrhythmia. Treatment options include cardioversion, antiarrhythmic drug therapy to maintain sinus rhythm, AV nodal slowing agents to control rate and, in selected cases, radiofrequency catheter ablation.

Atrial ectopic beats

These often cause no symptoms, although they may be sensed as an irregularity or heaviness of the heart beat. On the ECG they appear as early and abnormal P waves, and are usually, but not always, followed by normal QRS complexes (Fig. 14.44a). Treatment is not normally required unless the ectopic beats provoke more significant arrhythmias, when beta-blockers may be effective.

The Brugada syndrome

This inheritable condition accounts for part of a group of patients with idiopathic ventricular fibrillation who have no evidence of causative structural cardiac disease. It is more common in young male adults and in South-east Asia. The diagnosis is made by identifying the classic ECG changes that may be present spontaneously or be provoked by the administration of a class I antiarrhythmic (flecainide or ajmaline): right bundle branch block with coved ST elevation in leads V₁–V₃ (Fig. 14.46). Atrial fibrillation may occur.

Figure 14.46 The Brugada ECG. ST elevation in V₁–V₃ with right bundle branch block.

In 20% of cases it is a monogenic inheritable condition associated with loss of sodium channel function due to a mutation in the SCN5A gene. Recently other mutations in the SCN1B gene, glycerol-3-phosphate dehydrogenase-1-like gene (GPD1LL-type) and genes related to calcium channel subunits CACNA1C and CACNB2 have also been implicated in the genesis of this syndrome. It can present with sudden death during sleep, resuscitated cardiac arrest and syncope, or the patient may be asymptomatic and diagnosed incidentally or during familial assessment. There is a high risk of sudden death, particularly in the symptomatic patient or those with spontaneous ECG changes. The only successful treatment is an ICD. Beta-blockade is not helpful and may be harmful in this syndrome.

Long QT syndrome

This describes an ECG where the ventricular repolarization (QT interval) is greatly prolonged. The causes of long QT syndrome are listed in Table 14.12.

Table 14.12 Causes of long QT syndrome

Congenital long QT syndrome

Two major syndromes have been described, which may (Jervell and Lange–Nielsen syndrome) or may not (Romano–Ward syndrome) be associated with congenital deafness.

The molecular biology of the congenital long QT syndromes has been shown to be heterogeneous. It is usually a monogenic disorder and has been associated with mutations in cardiac potassium and sodium channel genes (Table 14.13). The different genes involved appear to correlate with different phenotypes (Fig. 14.47b) that can exhibit such variable penetrance that carriers may have completely normal ECGs. There are three major subtypes: LQT1 in which the arrhythmia is usually provoked by exercise, particularly swimming; LQT2 with provocation associated with emotion and acoustic stimuli; and LQT3 where the arrhythmias occur during rest or when asleep. It is likely that identification of the mutation involved will not only improve diagnostic accuracy, particularly with cascade screening in affected families, but also guide future therapy for the congenital long QT syndrome.

Table 14.13 Single gene mutations responsible for congenital long QT syndrome

Figure 14.47 Prolonged QT. (a) An ECG demonstrating a supraventricular rhythm with a long QT (LQT) interval giving way to atypical ventricular tachycardia (torsades de pointes). The tachycardia is short-lived and is followed by a brief period of idioventricular rhythm. (b) Further three examples of a prolonged QT interval corresponding to three different types of LQT.

Short QT syndrome

Five types have been described caused by genetic abnormalities leading to faster repolarization. Ventricular arrhythmias and sudden death may occur and an ICD is the best treatment.

Normal heart ventricular tachycardia

Monomorphic ventricular tachycardia in patients with structurally normal hearts (idiopathic VT) is usually a benign condition with an excellent long-term prognosis. Occasionally, it is incessant (so called Galavardin’s tachycardia) and if untreated may lead to cardiomyopathy.

Normal heart VT either arises from a focus in the right ventricular outflow tract or in the left ventricular septum. Treatment of symptoms is usually with beta-blockers. There is a special form of verapamil-sensitive tachycardia that responds well to non-dihydropyridine calcium antagonists. In symptomatic patients, radiofrequency catheter ablation is highly effective, resulting in a cure in >90% cases. It is sometimes difficult to distinguish arrhythmogenic right ventricular hypertrophy (p. 770) from this seemingly benign disorder.

Non-sustained ventricular tachycardia

Non-sustained ventricular tachycardia (NSVT) is defined as ventricular tachycardia that is ≥5 consecutive beats but lasts <30 s (Fig. 14.48d). NSVT can be found in 6% of patients with normal hearts and usually does not require treatment. NSVT is documented in up to 60–80% of patients with heart disease. There is insufficient evidence on prognosis, but an ICD has been shown to improve survival of patients with particularly poor left ventricular function (ejection fraction ≤30%) by preventing arrhythmic death. Antiarrhythmic suppression of NSVT is not usually advocated but beta-blockers may improve quality-of-life in symptomatic individuals.

Figure 14.48 Varieties of ventricular ectopic activity. (a) Two ventricular ectopic beats of different morphology (multimorphological). (b) Two ventricular premature beats (VPBs) occurring one after the other (a pair or couplet of VPBs). (c) Frequently repetitive ventricular ectopic activity of a single morphology. (d) Brief run of ventricular tachycardia (non-sustained ventricular tachycardia) that follows previous ectopic activity.

Ventricular premature beats

These may be uncomfortable, especially when frequent. The patient complains of extra beats, missed beats or heavy beats because it may be the premature beat, the post-ectopic pause or the next sinus beat that is noticed by the patient. The pulse is irregular owing to the premature beats. Some early beats may not be felt at the wrist. When a premature beat occurs regularly after every normal beat, ‘pulsus bigeminus’ may occur. If premature ventricular beats are highly symptomatic, treatment with beta-blockade may be helpful. If the ectopics are very frequent left ventricular dysfunction may develop, and if the ectopics stem from a single focus, especially when in the right ventricle, catheter ablation can be very effective.

These premature beats (Fig. 14.48a–c) have a broad (>0.12 s) and bizarre QRS complex because they arise from an abnormal (ectopic) site in the ventricular myocardium. Following a premature beat there is usually a complete compensatory pause because the AV node or ventricle is refractory to the next sinus impulse. Early ‘R-on-T’ ventricular premature beats (occurring simultaneously with the upstroke or peak of the T wave of the previous beat) may induce ventricular fibrillation in patients with heart disease, particularly in patients following myocardial infarction.

Ventricular premature beats are usually treated only if symptomatic. Usually simple measures such as reassurance and beta-blocker therapy are all that is required.

Venous return (preload)

In the intact heart, myocardial failure leads to a reduction of the volume of blood ejected with each heart beat and an increase in the volume of blood remaining after systole. This increased diastolic volume stretches the myocardial fibres and, as Starling’s law of the heart (p. 671) would suggest, myocardial contraction is restored. However, the failing myocardium results in depression of the ventricular function curve (cardiac output plotted against the ventricular diastolic volume) (Fig. 16.6, p. 871).

Mild myocardial depression is not associated with a reduction in cardiac output because it is maintained by an increase in venous pressure (and hence diastolic volume). However, the proportion of blood ejected with each heart beat (ejection fraction) is reduced early in heart failure. Sinus tachycardia also ensures that any reduction of stroke volume is compensated for by the increase in heart rate; cardiac output (stroke volume × heart rate) is therefore maintained.

When there is more severe myocardial dysfunction, cardiac output can be maintained only by a large increase in venous pressure and/or marked sinus tachycardia. The increased venous pressure contributes to the development of dyspnoea, owing to the accumulation of interstitial and alveolar fluid, and to the occurrence of hepatic enlargement, ascites and dependent oedema, due to increased systemic venous pressure. However, the cardiac output at rest may not be much depressed, but myocardial and haemodynamic reserve is so compromised that a normal increase in cardiac output cannot be produced by exercise.

In very severe heart failure, the cardiac output at rest is depressed, despite high venous pressures. The inadequate cardiac output is redistributed to maintain perfusion of vital organs, such as the heart, brain and kidneys, at the expense of the skin and muscle.

Outflow resistance (afterload) (see Fig. 14.5)

This is the load or resistance against which the ventricle contracts. It is formed by:

An increase in afterload decreases the cardiac output. This results in a further increase of end-diastolic volume and dilatation of the ventricle itself, which further exacerbates the problem of afterload. This is expressed by Laplace’s law: the tension of the myocardium (T) is proportional to the intraventricular pressure (P) multiplied by the radius of the ventricular chamber (R): i.e. T ∝ PR.

Myocardial contractility (inotropic state)

The state of the myocardium also influences performance. The sympathetic nervous system is activated in heart failure via baroreceptors as an early compensatory mechanism, which provides inotropic support and maintains cardiac output. Chronic sympathetic activation, however, has deleterious effects by further increasing neurohormonal activation and myocyte apoptosis. This is compensated by a downregulation of β-receptors. Increased contractility (positive inotropism) can result from increased sympathetic drive, and this is a normal part of the Frank–Starling relationship (Fig. 14.5, p. 672). Conversely, myocardial depressants (e.g. hypoxia) decrease myocardial contractility (negative inotropism).

Neurohormonal and sympathetic system activation: salt and water retention

The increase in venous pressure that occurs when the ventricles fail leads to retention of salt and water and their accumulation in the interstitium, producing many of the physical signs of heart failure. Reduced cardiac output also leads to diminished renal perfusion, activating the renin-angiotensin system and enhancing salt and water retention (Fig. 12.5, p. 566), which further increases venous pressure (Fig. 14.51). The retention of sodium is in part compensated by the action of circulating atrial natriuretic peptides and antidiuretic hormone (see p. 650).

Figure 14.51 The compensatory physiological response to heart failure. Chronic activation of the renin-angiotensin and adrenergic systems results in a ‘vicious cycle’ of cardiac deterioration that further exacerbates the physiological response.

The interaction of haemodynamic and neurohumoral factors in the progression of heart failure remains unclear. Increased ventricular wall stress promotes ventricular dilatation and further worsens contractile efficiency. In addition, prolonged activation of the sympathetic nervous and renin-angiotensin-aldosterone systems exerts direct toxic effects on myocardial cells.

Myocardial remodelling in heart failure

Left ventricular remodelling is a process of progressive alteration of ventricular size, shape and function owing to the influence of mechanical, neurohormonal and possibly genetic factors in several clinical conditions, including myocardial infarction, cardiomyopathy, hypertension and valvular heart disease. Its hallmarks include hypertrophy, loss of myocytes and increased interstitial fibrosis. Remodelling continues for months after the initial insult, and the eventual change in the shape of the ventricle becomes responsible for significant impairment of overall function of the heart as a pump (Fig. 14.52a). In cardiomyopathy, the process of progressive ventricular dilatation or hypertrophy occurs without ischaemic myocardial injury or infarction (Fig. 14.52b).

Figure 14.52 Ventricular remodelling in (a) ischaemic (MI) and (b) non-ischaemic heart failure, e.g. in cardiomyopathy.

Abnormal calcium homeostasis

Calcium ion flux within myocytes plays a pivotal role in the regulation of contractile function. Excitation of the myocyte cell membrane causes the rapid entry of calcium into myocytes from the extracellular space via calcium channels. This triggers the release of intracellular calcium from the sarcoplasmic reticulum and initiates contraction (see Fig. 14.3, p. 670). Relaxation results from the uptake and storage of calcium by the sarcoplasmic reticulum (see Fig. 14.9, p. 674) controlled by changes in nitric oxide. In heart failure, there is a prolongation of the calcium current in association with prolongation of contraction and relaxation.

Apoptosis

Apoptosis (or ‘programmed cell death’) of myocytes has been demonstrated in animal models of ischaemic reperfusion, rapid ventricular pacing, mechanical stretch and pressure overload. Apoptosis is associated with irreversible congestive heart failure, and the spiral of ventricular dysfunction, characteristic of heart failure, results from the initiation of apoptosis by cytokines, free radicals and other triggers.

Natriuretic peptides (ANP, BNP and C-type)

Atrial natriuretic peptide (ANP) is released from atrial myocytes in response to stretch. ANP induces diuresis, natriuresis, vasodilatation and suppression of the renin-angiotensin system. Levels of circulating ANP are increased in congestive cardiac failure and correlate with functional class, prognosis and haemodynamic state. The renal response to ANP is attenuated in heart failure, probably secondarily to reduced renal perfusion, receptor downregulation, increased peptide breakdown, renal sympathetic activation and excessive renin-angiotensin activity.

Brain natriuretic peptide (BNP) (so called because it was first discovered in brain) is predominantly secreted by the ventricles, and has an action similar to that of ANP but greater diagnostic and prognostic value (p. 943).

C-type peptide, which is limited to vascular endothelium and the central nervous system, has similar effects to those of ANP and BNP.

The therapeutic benefits of the natriuretic peptides have been investigated in two ways:

Endothelial function in heart failure

The endothelium has a central role in the regulation of vasomotor tone. In patients with heart failure, endothelium-dependent vasodilatation in peripheral blood vessels is impaired and may be one mechanism of exercise limitation. The cause of abnormal endothelial responsiveness relates to abnormal release of both nitric oxide and vasoconstrictor substances, such as endothelin (ET). The activity of nitric oxide, a potent vasodilator, is blunted in heart failure. ET secretion from a variety of tissues is stimulated by many factors, including hypoxia, catecholamines and angiotensin II. The plasma concentration of ET is elevated in patients with heart failure, and levels correlate with the severity of haemodynamic disturbance. The major source of circulating ET in heart failure is the pulmonary vascular bed.

ET has many actions that potentially contribute to the pathophysiology of heart failure: vasoconstriction, sympathetic stimulation, renin-angiotensin system activation and left ventricular hypertrophy. Acute intravenous administration of endothelin antagonists improves haemodynamic abnormalities in patients with congestive cardiac failure, and oral endothelin antagonists are being developed. Plasma concentrations of some cytokines, in particular TNF, are increased in patients with heart failure.

Antidiuretic hormone (vasopressin)

Antidiuretic hormone (ADH) is raised in severe chronic heart failure, particularly in patients on diuretic treatment. High ADH concentration precipitates hyponatraemia which is an ominous prognostic indicator.

Multidisciplinary team approach

Heart failure care should be delivered by a multidisciplinary team with an integrated approach across the healthcare community. The use of multiple biomarkers, e.g. troponins and CRP, is of prognostic value. The multidisciplinary team should involve specialist healthcare professionals: heart failure nurse, dietitian, pharmacist, occupational therapist, physiotherapist and palliative care adviser.

Understanding the information needs of patients and carers is vital. Good communication is essential for best clinical management, which should include advice on anxiety, depression and ‘end-of-life’ issues.

Diuretics

These act by promoting the renal excretion of salt and water by blocking tubular reabsorption of sodium and chloride (p. 644). Loop diuretics (e.g. furosemide and bumetanide) and thiazide diuretics (e.g. bendroflumethiazide, hydrochlorothiazide) should be given in patients with fluid overload. Although diuretics provide symptomatic relief of dyspnoea and improve exercise tolerance, there is limited evidence that they affect survival. In severe heart failure patients, the combination of a loop and thiazide diuretic may be required. Serum electrolytes and renal function must be monitored regularly (risk of hypokalaemia and hypomagnesaemia).

Beta-blockers

Beta-blockers have been shown to improve functional status and reduce cardiovascular morbidity and mortality in patients with heart failure. Several trials (CIBIS, CIBIS II, MERIT-HF, COMET, SENOIRS) have assessed the effects of beta-blockers in varying degrees of heart failure. Bisoprolol and carvedilol reduce mortality in any grade of heart failure.

Nebivolol is used in the treatment of stable mild–moderate heart failure in patients over 70 years old.

In patients with heart failure, only evidence-based beta-blockers from successful trials should be used. In patients with significant heart failure, beta-blockers are started at a low dose and gradually increased.

Cardiac glycosides

Digoxin is a cardiac glycoside that is indicated in patients in atrial fibrillation with heart failure. It is used as add-on therapy in symptomatic heart failure patients already receiving ACEI and beta-blockers. The DIG study demonstrated that digoxin reduced hospital admissions in patients with heart failure.

Vasodilators and nitrates

The combination of hydralazine and nitrates reduces afterload and pre-load and is used in patients intolerant of ACEI or ARA. The Veterans Administration Cooperative Study demonstrated that the combination of hydralazine (with nitrates) improved survival in patients with chronic heart failure. The A-HeFT trial showed that the same combination reduced mortality and hospitalization for heart failure in black patients with heart failure.

Inotropic and vasopressor agents

Intravenous inotropes and vasopressor agents (see Table 14.25) are used in patients with chronic heart failure who are not responding to oral medication. Although they produce haemodynamic improvements they have not been shown to improve long-term mortality when compared with placebo.

Other medications

In hospital, all patients require prophylactic anticoagulation. Heart failure is associated with a four-fold increase in the risk of a stroke. Oral anticoagulants are recommended in patients with atrial fibrillation and in patients with sinus rhythm with a history of thromboembolism, left ventricular thrombus or aneurysm. In patients with known ischaemic heart disease antiplatelet therapy (aspirin, clopidogrel) and statin therapy should be continued. Arrhythmias are frequent in heart failure and are implicated in sudden death. Although treatment of complex ventricular arrhythmias might be expected to improve survival, there is no evidence to support this and it may increase mortality. In the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT), amiodarone showed no benefit compared to placebo in patients with impaired left ventricular function and mild-moderate heart failure (whereas an ICD reduced mortality by 23% compared to placebo). Patients with heart failure and symptomatic ventricular arrhythmias should be assessed for suitability for an ICD.

Ivabradine, which inhibits the I_F channels in the sincatrial node, slows the heart rate and in the SHIFT study was associated with a reduction in cardiovascular mortality and hospital admission for worsening heart failure in patients in sinus rhythm with chronic heart failure and left ventricular dysfunction (LVEF ≤35%) when compared to placebo.

Revascularization

While coronary artery disease is the most common cause of heart failure, the role of revascularization in patients with heart failure is unclear. Patients with angina and left ventricular dysfunction have a higher mortality from surgery (10–20%), but have the most to gain in terms of improved symptoms and prognosis. Factors that must be considered before recommending surgery include age, symptoms and evidence for reversible myocardial ischaemia.

Hibernating myocardium and myocardial stunning

‘Hibernating’ myocardium can be defined as reversible left ventricular dysfunction due to chronic coronary artery disease that responds positively to inotropic stress and indicates the presence of viable heart muscle that may recover after revascularization. It is due to reduced myocardial perfusion, which is just sufficient to maintain viability of the heart muscle. Myocardial hibernation results from repetitive episodes of cardiac stunning that occur, e.g. with repeated exercise in a patient with coronary artery disease.

Myocardial stunning is reversible ventricular dysfunction that persists following an episode of ischaemia when the blood flow has returned to normal, i.e. there is a mismatch between flow and function.

The prevalence of hibernating myocardium in patients with coronary artery disease can be estimated from the frequency of improvement in regional abnormalities in wall motion after revascularization and is estimated to be 33% of such patients. Techniques to try to identify hibernating myocardium include stress echocardiography, nuclear imaging techniques, cardiovascular magnetic resonance and positron emission tomography.

The clinical relevance of the hibernating and stunned myocardium is that ventricular dysfunction due to these mechanisms may be wrongly ascribed to myocardial necrosis and scarring which seems untreatable, whereas reversible hibernating and stunning respond to coronary revascularization.

Biventricular pacemaker or implantable cardioverter-defibrillator

Pacemakers (Fig. 14.55) are indicated in patients with sinoatrial disease and atrioventricular conduction block. Pacemakers are also valuable in patients without AV block but with prolonged PR intervals, left bundle branch block and severe mitral regurgitation. In patients with heart failure and left bundle branch block and NYHA class III heart failure (MUSTIC study) biventricular pacing was more beneficial than conventional right ventricular pacing. The results showed an improvement in symptoms and exercise tolerance. The effect on prognosis is being addressed by an ongoing trial (CARE HF).

Figure 14.55 Implanted biventricular pacing with ICD device.

Biventricular pacing can also be used in patients not responding to therapy in the following situations:

New guidelines recommend advanced pacing technologies should be used for cardiac resynchronization therapy (CRT) in selected patients with heart failure. Atrio-biventricular pacing has been shown to improve symptoms and reduce admission to hospital in patients with left bundle branch block and heart failure with poor LV function. The use of combined implantable defibrillators and atrio-biventricular pacemakers for patients with heart failure is likely to increase. One large trial (COMPANION) shows 21% reduction in all-cause mortality and all-cause admissions to hospital in the groups receiving biventricular pacing. ICD therapy in patients with NYHA (classes I and II, see Table 14.19) has shown a reduction in mortality compared with placebo and amiodarone.

Cardiac transplantation

Cardiac transplantation has become the treatment of choice for younger patients with severe intractable heart failure, whose life expectancy is <6 months. With careful recipient selection, the expected 1-year survival for patients following transplantation is over 90%, and is 75% at 5 years. Irrespective of survival, quality of life is dramatically improved for the majority of patients. The availability of heart transplantation is limited.

Heart allografts do not function normally. Cardiac denervation results in a high resting heart rate, loss of diurnal blood pressure variation and impaired renin-angiotensin-aldosterone regulation. Some patients develop a ‘stiff heart’ syndrome, caused by rejection, denervation and ischaemic injury during organ harvest and implantation. Transplantation of an inappropriately small donor heart can also result in elevated right and left heart pressure.

The complications of heart transplantation are summarized in Table 14.22. Many (infection, malignancy, hypertension and hyperlipidaemia) are related to immunosuppression. Allograft coronary atherosclerosis is the major cause of long-term graft failure and is present in 30–50% of patients at 5 years. It is due to a ‘vascular’ rejection process in conjunction with hypertension and hyperlipidaemia.

Table 14.22 Complications of cardiac transplantation

There are specific contraindications to cardiac transplantation (Table 14.23); notably, high pulmonary vascular resistance is an absolute contraindication. Several options to transplantation are available: cardiomyoplasty (augmentation of left ventricular contraction by wrapping a latissimus dorsi muscle flap around the ventricle) and the Batista procedure (surgical ventricular size reduction and remodelling the geometry of the left ventricle). Both procedures have a high mortality and limited evidence of substantial benefit in the medium term.

Table 14.23 Contraindications for cardiac transplantation

Mechanical assist devices

Mechanical assist devices can be used in patients who fail to respond to standard medical therapy but in whom there is either transient myocardial dysfunction with likelihood of recovery (e.g. post anterior myocardial infarction treated with coronary angioplasty) or a bridge is needed to cardiac surgery, including transplantation.

Ventricular assist devices (VAD) (Fig. 14.57) Ventricular assist devices are mechanical devices that replace or help the failing ventricles in delivering blood around the body. A left ventricular assist device (LVAD) receives blood from the left ventricle and delivers it to the aorta; a right ventricular assist device (RVAD) receives blood from the right ventricle and delivers it to the pulmonary artery. The devices can be extracorporeal (suitable for short-term support) or intracorporeal (suitable for long-term support as a bridge to transplantation or as destination therapy in patients with end-stage heart failure not candidates for transplantation). The main problems with VADs include thromboembolism, bleeding, infection and device malfunction.

Figure 14.57 Left ventricular assist device.

(From Moser DK, Riegel B. Cardiac Nursing. Philadelphia: Saunders; 2007: 981, with permission of Elsevier.)