• PR interval. The PR interval (Fig. 12.1 and Box 12.1) is measured from the start of the P wave to the start of the QRS complex. It is the time taken for electrical activity beginning in the sinus node to pass through to the ventricles.

• ST segment. The ST segment begins at the end of the QRS complex and, together with the T wave, represents ventricular repolarization.

• QT interval. The QT interval is measured from the start of the QRS complex to the end of the T wave and divided by the square root of the R–R interval to correct for the heart rate. It is the time taken for ventricular depolarization and repolarization; if prolonged, it may predispose to ventricular arrhythmias.

• QRS. In the frontal plane, the mean QRS axis ranges from −30° to +100°. Hence, the normal QRS pattern is very variable in the limb leads. Left axis deviation is when the axis is more negative than −30° and right axis deviation is when the axis is more positive than +100°. Left axis deviation may be a normal variant or due to LV hypertrophy, left anterior hemiblock or inferior myocardial infarction. Right axis deviation may be a normal variant or due to right ventricular strain, left posterior hemiblock or lateral myocardial infarction.

Box 12.1 Normal ECG intervals

P wave duration	120 ms or less
PR interval	120–200 ms
QRS duration	100 ms or less
Corrected QT interval	440 ms or less in males
	460 ms or less in females

Action	Measurements	Note
Sinus rhythm	Basic intervals (PA, AH, His duration, HV, QRS and corrected QT)	Is there pre-excitation or evidence for slowed conduction?
Single ventricular extra-stimulus testing	Retrograde AV node effective refractory period (AVNERP)	Is there VA conduction? If so, is it via the AV node and decremental, or an accessory pathway?
Incremental ventricular pacing	Retrograde Wenckebach cycle length (WCL)
Single atrial extra-stimulus testing	Anterograde AVNERP	Is there AV conduction? If so, is it via the AV node and decremental, or an accessory pathway? Is there evidence for dual AV node physiology?
Incremental atrial pacing	Anterograde WCL
Arrhythmia induction pacing from the atrium	Atrial effective refractory period (AERP) Coupling interval(s) for arrhythmia induction	Extra-stimulus testing with 2 or more extra-stimuli, burst pacing and 2 or more premature beats during sinus rhythm
Wellen’s protocol	Ventricular effective refractory period (VERP) Coupling interval(s) for arrhythmia induction	Used to induce ventricular tachycardia. Ventricular extra-stimulus testing with up to 3 extra-stimuli

Pathophysiology of arrhythmias

• Normal electrical activation. The heart contains specialized conduction tissue that can generate rhythmic electrical pulses spontaneously. This is due to cyclical variations in the permeability of cell membranes to potassium, sodium and calcium ions. The activity of the specialized conduction tissue is modulated by the autonomic nervous system. Electrical pulses are rapidly conducted to the mass of cardiac myocytes, producing the mechanical events of each cardiac cycle. Usually, the cells of the sinus node generate electrical pulses most rapidly and are the physiological pacemaker. Cardiac myocyte activation can be divided into four stages (Fig. 12.2). Abnormalities during any of these stages can result in both bradyarrhythmias and tachyarrhythmias.

• Enhanced automaticity. Any cardiac myocytes depolarizing faster than the sinus node can override it and cause arrhythmias. These foci of abnormal cells typically occur at the ostia of the caval or pulmonary veins, along the crista terminalis in the right atrium, within the coronary sinus, close to the AV node, around the insertions of both AV valves and within the ventricular outflow tracts.

• Triggered activity. Oscillations in the membrane potential during stage 3 or 4 of the action potential are called early and late after-depolarizations respectively. If they achieve the threshold potential, premature action potentials may be triggered, causing arrhythmias. Myocardial ischaemia, electrolyte disturbances, pacing, catecholamines and certain drugs are potential causes. Torsades de pointes from QT interval prolongation and arrhythmias due to digoxin toxicity are examples.

• Re-entry. This causes the majority of clinical tachyarrhythmias. It is due to the rotation of electrical activity around a region of conduction block that is either fixed, e.g. scar, or functional. The initiating event is usually an ectopic beat that is conducted around the region of conduction block in one direction only due to differences in conduction velocity and refractoriness. As long as the head of the rotating electrical wavefront meets excitable myocardium, a stable re-entry circuit is established.

• Suppressed automaticity and conduction block. If depolarization of the sinus node is slowed by either excessive vagal tone or drugs such as β-blockers, sinus bradycardia results. Bradyarrhythmias also occur if conduction through the AV node is slowed or blocked by excessive vagal tone, drugs or disease. Other parts of the specialized conduction system may assume the role of cardiac pacemaker, producing an escape rhythm.

Fig. 12.2 The cardiac myocyte action potential.

Mechanisms and diagnosis of bradyarrhythmias

Sinus node-dependent arrhythmias

These include sinus bradycardia and sinus pauses with or without an escape rhythm.

Sinus bradycardia

Sinus bradycardia is a heart rate of < 60 bpm during sinus rhythm, with every P wave associated with a QRS complex. The causes of sinus bradycardia can be:

• Cardiac, e.g. sinus node ischaemia/infarction, sinus node and atrial fibrosis, myocarditis and cardiomyopathies

• Systemic, e.g. hypothermia, hypothyroidism, cholestatic jaundice, raised intracranial pressure, carotid sinus hypersensitivity and vasovagal syncope. Drugs include β-blockers, calcium channel blockers, amiodarone, digoxin and disopyramide.

Treatment of sinus bradycardia involves identifying and excluding specific causes, if possible. Specific measures are summarized in Box 12.2.

Sinus pauses

Sinus pauses can be due to either sinus node exit block or sinus arrest. Exit block is when an electrical impulse generated within the sinus node fails to conduct into the atria. Sinus arrest is when the sinus node fails to generate electrical impulses. In either case there is an absent P wave on the ECG; if the pause is prolonged, an escape rhythm may occur.

Sick sinus syndrome

Sick sinus syndrome encompasses sinus bradycardia, sinus pauses, permanent atrial fibrillation with bradycardia and tachycardia-bradycardia syndrome. The latter is a failure of stable sinus rhythm to establish following termination of a tachycardia such as atrial fibrillation and flutter, focal atrial tachycardia, junctional tachycardia and AV node re-entry tachycardia. Many patients also exhibit AV conduction abnormalities and bundle branch blocks.

Atrio-ventricular node-dependent arrhythmias

First-degree AV block

This is when every atrial electrical impulse is conducted slowly to the ventricles. Hence, each P wave is associated with a QRS complex but the PR interval is > 200 ms.

Second-degree block

This is when one or more, but not all, atrial electrical impulses fail to conduct to the ventricles. This encompasses both physiological and pathological variations in AV node conduction. The normal AV node exhibits the property of decrementation, which prevents excessive ventricular rates. Hence, increasingly premature atrial electrical impulses either are conducted to the ventricles more slowly or are blocked. This is due to the refractory properties of the AV node and is associated with changes in the PR intervals.

• Wenckebach AV block (Mobitz type 1 block). This is a benign form of second-degree block in which the PR interval progressively lengthens until an atrial electrical impulse fails to conduct to the ventricles (Fig. 12.3). However, successive PR intervals change in smaller increments, producing a progressive decrease in the RR intervals. The longest RR interval during Wenckebach periodicity incorporates the non-conducted P wave. Anatomically, this usually occurs at the level of the AV node. Patients are usually just monitored. If symptomatic, give atropine 0.5 mg IV every 2 mins, maximum dose 0.04 mg/kg.

• Mobitz type 2 block. Atrial electrical impulses failing to reach the ventricles despite a normal PR interval usually indicate a pathological process and may be associated with bundle branch block. Anatomically, the block is usually at the infra-nodal level of the His bundle and the ratio of non-conducted to conducted P waves is variable. The risk of progression to heart block is greater than Wenckebach AV block, and cardiac pacing is usually indicated. Atropine is not used and may in fact worsen the block.

Fig. 12.3 Rhythm strip ECG showing Wenckebach AV block with progressive PR prolongation, as marked out by the arrows, followed by a non-conducted P wave.

Third-degree or complete block (AV dissociation)

This is when no atrial electrical impulses are conducted to the ventricles. Hence, there is a continuously changing relationship between the P waves and QRS complexes (Fig. 12.4). Usually, there is a regular escape rhythm that arises below the level of block. A narrow QRS complex (< 125 ms) escape rhythm is from the His bundle and more stable than a broad QRS complex (> 125 ms), ventricular escape rhythm.

• Causes of third-degree block include ischaemic heart disease (e.g. acute myocardial infarction), post-cardiac operations/ablation, congenital abnormalities, autoimmune rheumatic disorders (e.g. SLE, rheumatoid arthritis, systemic sclerosis), infiltrative disorders (e.g. amyloid, sarcoid), haemochromatosis, infections and drugs.

• Treatment depends on aetiology. Recent-onset narrow-complex AV block may respond to IV atropine 600 mcg boluses but temporary pacing may be required. Chronic block will require permanent (dual chamber) pacing (p. 410). Broad-complex AV block presenting with a slow (15–40 bpm) rhythm, dizziness and blackouts (Stokes–Adams, p. 385) is treated with temporary, followed by permanent, pacing, which reduces the mortality. As ventricular arrhythmias are not uncommon, an implantable cardioverter-defibrillator (ICD) may be required.

Fig. 12.4 Complete heart block. The P waves and QRS complexes are completely dissociated from each other, with different PP and RR intervals.

Bundle branch blocks and hemiblocks

These are due to delayed conduction within the His–Purkinje system, producing QRS complex durations > 120 ms. Causes include ischaemic heart disease, idiopathic fibrosis of the conduction system, cardiomyopathies, aortic stenosis, hypertensive heart disease, recurrent pulmonary emboli, cor pulmonale, congenital lesions, infective endocarditis and myotonic dystrophy.

• Left bundle branch block (LBBB). In LBBB depolarization of the left ventricle is delayed, giving a deep QS pattern in lead V1 and tall R waves in leads 1 and V6 (Fig. 12.5). This is usually associated with heart disease and causes a reverse split of the second heart sound. In some patients with poor LV function this can result in dyssynchronous ventricular contraction that requires biventricular pacing.

• Right bundle branch block (RBBB). In RBBB depolarization of the right ventricle is delayed, giving an RSR complex in lead V1 and deep S waves in leads 1 and V6. This may be a normal finding in 1% of young adults and in 5% of the elderly population.

• Hemiblock and bifascicular blocks. The left bundle has anterior and posterior divisions, also known as fascicles. Conduction block may also occur at this level, producing the hemiblocks. Left anterior hemiblock causes left axis deviation, and left posterior hemiblock causes right axis deviation. Either hemiblock together with an RBBB is called a bifascicular block. In this situation, conduction block within the remaining fascicle will produce complete heart block.

Fig. 12.5 Part of a 12-lead ECG showing typical left bundle branch block with a broad, negative QRS complex in lead V1.

Mechanisms and diagnosis of tachyarrhythmias

Atrial origin

Sinus node tachycardias

These are sinus rhythms with a heart rate > 100 bpm. Causes are cardiac or systemic. Cardiac causes include acute myocardial ischaemia, acute heart failure, sinus node re-entry or enhanced sinus node automaticity. Systemically, it is found normally in children, exercise and pregnancy. Anaemia, hypovolaemia, acute hypoxia, thyrotoxicosis, pyrexia, catecholamine excess and drugs also cause sinus tachycardia.

• Specific treatment is directed against the potential causes, together with rate-slowing drugs such as β-blockers and calcium channel blockers. Enhanced sinus node automaticity or sinus node re-entry may require catheter ablation with or without permanent pacemaker implantation.

Focal tachycardias

These are uncommon tachycardias, caused by atrial foci that exhibit enhanced automaticity, triggered activity or micro re-entry. Typical causes include myocardial infarction, myocarditis, digoxin toxicity, chronic lung diseases, alcohol, hypokalaemia and catecholamine release. Foci can occur anywhere within the atria and at the junctions with their respective veins. They are usually conducted to the ventricles with varying degrees of AV block. Automatic foci usually exhibit gradual acceleration and deceleration. They also cause incessant tachycardias with a subsequent tachycardia cardiomyopathy.

The morphology of the P waves during tachycardia is highly variable, depending on the site of the tachycardia focus. If the focus is close to the sinus node, typical P waves may be seen. P wave morphologies may give some indication as to the site of the tachycardia focus (Table 12.2).

• Treatment. Some focal atrial tachycardias respond to adenosine IV up to 0.25 mg/kg and are subsequently treated pharmacologically or by catheter ablation.

Table 12.2 P wave morphologies in different ECG leads for focal atrial tachycardias

Flutters

These are caused by atrial macro re-entry circuits that rotate around anatomical structures and scars. They are associated with a slightly increased risk of embolic stroke and may compromise ventricular filling causing breathlessness.

Typical atrial flutter usually, but not always, has negative sawtooth-like flutter waves in the inferior ECG leads and positive flutter waves in lead V1 (Fig. 12.6). Frequently, typical atrial flutter is conducted with a 2-to-1 AV block, giving a heart rate of 150 bpm. The re-entry circuit is well characterized, and the zone of slow conduction critical to sustaining the circuit is the cavo-tricuspid isthmus.

• Treatment. Patients should be given warfarin and either rate control with digoxin and β-blockers, or rhythm control. Some patients also benefit from DC cardioversion. Catheter ablation of the cavo-tricuspid isthmus can successfully terminate and prevent recurrence of typical atrial flutter with minimal risk in 95% of patients. It is used for all patients with recurrent or haemodynamically significant atrial flutter.

Fig. 12.6 Atrial flutter. Flutter waves are marked with an F with a frequency of 240/min. Every fourth flutter wave is transmitted to the ventricles with a ventricular rate of 60/min.

Atrial fibrillation (AF)

AF is the commonest arrhythmia globally, with a prevalence of 0.5–1% of the general population and 5–10% of the population over 65 years. It is characterized by rapid (300–600 bpm), irregularly irregular contractions of the atria. The 12-lead ECG shows no regular atrial activity (Fig. 12.7) and the ventricles beat in an irregularly irregular fashion at rates of up to 150–200 bpm. The mechanisms underlying AF are thought to be a combination of triggering atrial ectopics usually originating within the pulmonary veins, and progressive electrical changes within the atrial myocardium (remodelling) that allow it to be sustained. AF is a consequence of a wide range of pathologies but it can exist independently in a structurally normal heart (lone AF).

Fig. 12.7 A 12-lead ECG showing atrial fibrillation. There are no P waves but in leads V1 and V2 there is a rapid undulation of the baseline between the QRS complexes, demonstrating the fibrillatory activity. The RR intervals are continuously changing, resulting in an irregularly irregular pulse that is characteristic.

Clinically, patients either are asymptomatic or complain of palpitations, breathlessness, dizziness and, less commonly, syncope. AF is a spectrum ranging from infrequent episodes (paroxysmal), to those requiring termination with drugs or DC cardioversion (persistent), to permanent AF.

Management of AF consists of either restoring rate and rhythm or, if this is not possible in the long term, controlling rate and preventing complications.

• Acute AF

• AF that is a complication of an acute illness, e.g. a respiratory infection or alcohol toxicity, often reverts to sinus rhythm when the infection/cause is treated and resolves.

• Acute symptomatic AF, if documented < 48-hour duration, can be treated with synchronized DC cardioversion following immediate heparinization. This is successful in over 75% of cases but can recur.

• If AF lasts for > 48 hours, patients should be anticoagulated with warfarin (INR 2–3) for 3 weeks prior to cardioversion. The anticoagulation should be continued after successful cardioversion for at least 4 weeks, or longer if there are high risk factors for strokes. Alternatively, a transoesophageal echocardiogram (TOE) can be performed to rule out thrombosis in the left atrial appendage, obviating the need for anticoagulation prior to DC shock.

• Chemical cardioversion can alternatively be achieved by using an IV infusion of flecainide 2 mg/kg over 30 mins, maximum dose 150 mg or amiodarone IV infusion via a central venous catheter, initially 5 mg/kg over 20–120 mins with ECG monitoring. Patients again should be warfarinized prior to treatment

• If cardioversion fails (or the AF recurs), give amiodarone 300 mg over 1 hour before a further attempt at cardioversion. A second dose of amiodarone can be administered if necessary. Biphasic waveforms for cardioversion require less energy and have a higher efficacy than monophasic waves. The aims are as follows.

• Chronic AF

• Maintain sinus rhythm following DC conversion with anti-arrhythmic drugs (class 1c, e.g. flecainide, propafenone; or class III, e.g. amiodarone, sotalol — see p. 411).

• Control rate with a combination of digoxin, β-blockers or verapamil or diltiazem. The heart rate should be between 60 and 80 bpm at rest. Anticoagulant therapy should be continued. Dabigatran 220 mg oral daily, a direct thrombin inhibitor, is now being used instead of the more traditional warfarin (p. 245) as monitoring is not required.

• If rate control is poor despite optimal medical therapy patients should be considered for AV node ablation and pacemaker implantation (‘ablate and pace strategy’) but will require lifelong anticoagulation therapy.

• Catheter ablation should be offered to patients who remain symptomatic despite drug therapy with two different agents.

• For paroxysmal AF the pulmonary veins are electrically isolated, thereby eliminating the triggers. Success rates are between 80 and 85%.

• In persistent AF additional linear ablation is undertaken to compartmentalize the left atrium (catheter maze). This aims to prevent the formation of multiple re-entry circuits that sustain the AF. The success rate for permanent AF is 60–70% after one procedure. The ablation is a complex procedure, usually requiring an advanced mapping system, which can last up to 4 or 5 hours. The main risks include cardiac tamponade (1%), stroke (1–2%) and pulmonary vein stenosis (1%). Patients with structurally abnormal hearts and those over 65 years have an increased risk for embolic strokes (up to 5% per year) and should be anticoagulated with warfarin or dabigatran, even after ablation.

Atrio-ventricular junction origin

Atrio-ventricular node re-entry tachycardia (AVNRT)

This is one of the commonest causes of a paroxysmal supraventricular tachycardia, occurring in up to 60% of cases. It is more frequently found in females and most patients have structurally normal hearts.

• Clinical features. Typical symptoms include palpitations, dizziness, neck pulsations, chest discomfort and a polyuria that follows the termination of an episode. Syncope may occur in patients with impaired ventricular function and following termination from tachycardia-induced sinus arrest. AVNRT usually has an abrupt onset and termination, and can last from seconds to days. Patients usually have two functional and anatomically different pathways within the AV node — a fast conducting pathway and a slow pathway. The slow pathway repolarizes faster than the fast pathway. During sinus rhythm, antegrade conduction usually occurs via the fast pathway. If an atrial impulse occurs early, e.g. a premature beat when the fast pathway is refractory, antegrade conduction proceeds via the slow pathway in propagating the atrial impulses to the ventricles. Not all patients with dual AV node physiology develop AVNRT.

• Investigations. AVNRT can only occur if a stable micro re-entrant circuit can be established within the AV node between the fast and slow pathways. Usually, an atrial premature beat initiates the tachycardia. Less frequently, the initiation is from a ventricular premature beat.

• In typical AVNRT, the antegrade limb of the circuit is the slow pathway, with retrograde conduction up the fast pathway. Consequently, the atria and ventricles are depolarized almost simultaneously. This produces a narrow complex tachycardia (QRS < 0.125 sec) with rates between 150 and 240 bpm. The P wave resulting from retrograde conduction up the fast pathway is usually fused with the QRS complex. Sometimes, its terminal portion may be seen as a small positive deflection at the end of the QRS complex in lead V1 (Fig. 12.8).

• In atypical AVNRT, the antegrade limb is the fast pathway. Hence, atrial depolarization follows that of the ventricles, producing a distinct retrograde P wave and a long RP tachycardia.

• Treatment. AVNRT can be terminated using vagal manœuvres, e.g. Valsalva manœuvre, and drugs, e.g. IV adenosine, calcium channel blockers, e.g. verapamil, and β-blockers, e.g. propranolol. Prophylaxis with calcium channel blockers and β-blockers, flecainide and propafenone is used, but symptomatic AVNRT should be referred for catheter ablation, which has a low complication rate and is curative in 95% of cases.

Fig. 12.8 Typical atrio-ventricular node re-entry tachycardia. The ECG shows a regular narrow-complex tachycardia with retrograde P waves that are fused with the QRS complexes and appear as small ‘pseudo-R waves’ in V1 and ‘pseudo-S waves’ in the inferior leads, as marked by the blue arrows. These deflections are absent in the sinus rhythm QRS complexes.

Junctional tachycardia

This is caused by an automatic focus in the AV node. The commonest cause of this is digoxin toxicity, which produces a tachycardia with a Wenckebach-type AV block. Other causes include acute myocardial infarction, cardiac surgery, chronic obstructive pulmonary disease, rheumatic fever and hypokalaemia. The ECG usually shows a narrow-complex tachycardia with retrograde P waves that may be fused with the QRS complex or occur either side of it.

• Treatment is directed at the underlying cause.

Accessory pathway-dependent tachycardias

Accessory pathways (APs) are myocardial bundles that electrically couple the atria and ventricles, at one or several points across the AV junction, in addition to the AV node and His–Purkinje system. Most APs do not exhibit decremental conduction and are therefore able to conduct rapidly between atria and ventricles. APs may conduct both antegradely and retrogradely, or only retrogradely. The former are seen in the Wolff–Parkinson–White syndrome and the latter are known as concealed APs. A rare form of AP is the atrio-fascicular or Mahaim connection between the right atrium and the right bundle branch. These APs usually conduct in the antegrade direction only and exhibit decrementation.

• Wolff–Parkinson–White syndrome (WPW) has a prevalence of 0.1–0.4% and typically presents during infancy or in the second and third decades. Antegrade conduction via the AP causes ventricular pre-excitation, characterized by a PR interval of < 0.12 secs and a slurred initiation to the QRS complex called a delta wave (Fig. 12.9). During sinus rhythm, the extent of pre-excitation is determined by the relative conductions through the AP and the AV node–His–Purkinje system. AP conductivity and location, as well as the effects of autonomic tone on AV nodal conduction, are significant factors. Several detailed ECG algorithms have been devised for identifying AP location. Orthodromic AV re-entry tachycardia (AVRT) is seen in 84% of cases of WPW, AF in 51%, antidromic AVRT in 10% and ventricular fibrillation in less than 1%.

• Orthodromic AVRT is usually initiated by a premature ventricular or atrial beat establishing the macro re-entry circuit shown in Fig. 12.10a. The 12-lead ECG shows regular, narrow QRS complexes with retrograde P waves (Fig. 12.10b). However, functional delay in one of the bundle branches can produce broad QRS complexes. Orthodromic AVRT usually terminates with block in the AV node, although any limb of the circuit may be responsible. This is also the re-entry circuit seen with concealed AP tachycardias.

• Antidromic AVRT has a re-entry circuit that is the reverse of that for orthodromic AVRT (Fig. 12.11a). The ventricles are fully pre-excited and the 12-lead ECG demonstrates regular, broad QRS complexes similar to those in ventricular tachycardia (Fig. 12.11b). Antidromic AVRT usually terminates with block in the AV node. Atrio-fascicular or Mahaim APs produce a characteristic antidromic AVRT with LBBB morphology and left axis deviation.

• Atrial fibrillation in WPW has the greatest risk of causing haemodynamic compromise and ventricular fibrillation. The initiation is thought to be secondary to orthodromic and conducted ventricular ectopics AVRT, and the 12-lead ECG demonstrates a variably pre-excited, rapid, irregularly irregular broad QRS complex tachycardia (Fig. 12.12). However, there may be occasional normal QRS complexes due to dominant anterograde conduction down the AV node–His–Purkinje system.

• Treatment. Haemodynamically unstable patients should be treated by DC cardioversion. Drug therapy is targeted at the AV node, accessory pathway or both (Box 12.3).

• Orthodromic AVRT is usually terminated with IV AV nodal-blocking drugs such as adenosine, verapamil or diltiazem. If this fails, IV procainamide is administered with BP monitoring (Fig. 12.13). Chronic drug prophylaxis can be with either AV node-blocking drugs or those affecting the accessory pathway.

• Antidromic AVRT and pre-excited AF are treated with procainamide as first-line therapy, since AV nodal-blocking drugs may accelerate the tachycardia and cause ventricular fibrillation. Chronic drug prophylaxis is usually with flecainide and propafenone, which suppress conduction via the AP and AV node. Alternative drugs include procainamide, quinidine and disopyramide. Amiodarone is used only if other drugs are ineffective, due to its potential side-effects.

Fig. 12.9 Wolff–Parkinson–White syndrome. The ECG shows sinus rhythm with pre-excitation, as demonstrated by a short PR interval (marked in V5 by the blue lines) and a slurred upstroke to the QRS complex or ‘delta wave’ (marked in V5 by blue arrows).

Fig. 12.10 (a) Orthodromic AV re-entry. This circuit involves four sequential anatomical components — the left (or right) atrium, the AV node and His–Purkinje system, the left (or right) ventricle and the accessory pathway. The ventricles are activated via the AV node and His–Purkinje system. The atria are activated retrogradely via the accessory pathway. RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle. (b) Orthodromic AV re-entry tachycardia. The ECG complex shows a regular narrow-complex tachycardia with no pre-excitation. There are retrograde P waves that are shown in leads III and aVF by the blue arrows.

Fig. 12.11 (a) Antidromic AV re-entry. This circuit has four sequential anatomical components — the left (or right) atrium, the AV node and His–Purkinje system, the left (or right) ventricle and the accessory pathway. The ventricles are pre-excited via the accessory pathway. The atria are activated retrogradely via the AV node. RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.(b) Antidromic AV re-entry tachycardia. The ECG shows a regular broad-complex tachycardia with full pre-excitation. There are delta waves in each QRS complex that are marked in leads V1 and V4 by the blue arrows.

Fig. 12.12 Atrial fibrillation in Wolff–Parkinson–White syndrome. Note tachycardia with broad QRS complexes and fast and irregular ventricular rate.

Fig. 12.13 Management strategy for tachycardias in Wolff–Parkinson–White syndrome. AAVRT, antidromic AV re-entry tachycardia; AF, atrial fibrillation; DCC, DC cardioversion; OAVRT, orthodromic AV re-entry tachycardia

(Modified from Dhinoja & Lambiase 2005, with permission).

All patients with symptomatic WPW should be assessed for curative catheter ablation of the AP. This can be performed safely and has a success rate of 95%.

Long RP tachycardias

This is a special group of supraventricular tachycardias whose RP interval is > 50% of the RR interval (Fig. 12.14). The possible causes include focal atrial tachycardia, atypical AVNRT and orthodromic AVRT.

• Atypical AVNRT involves antegrade conduction via the fast pathway and retrograde conduction over the slow pathway. The retrograde P waves are therefore clearly visible after their associated QRS complexes.

• Orthodromic AVRT, also known as permanent junctional reciprocating tachycardia (PJRT), a type of AVRT, usually involves a concealed posteroseptal accessory pathway. The latter usually conducts slowly and may have decremental properties. The tachycardia is often incessant, causing a tachycardia-mediated cardiomyopathy that resolves following successful ablation of the accessory pathway.

Fig. 12.14 Long RP tachycardia. The ECG shows a regular narrow-complex tachycardia. There is a long RP interval and the retrograde P waves are marked by the blue arrows in lead III. The cause in this patient was an atypical AVNRT.

Ventricular origin

Ventricular tachycardia (VT)

This tachyarrhythmia originates from the ventricles and is usually a broad-complex tachycardia (QRS > 140 msec) with rates between 150 and 200 bpm, which can cause haemodynamic compromise. In monomorphic VT the QRS complexes are identical, whereas they vary in polymorphic VT. There is frequently underlying heart disease, most commonly ischaemic heart disease with previous myocardial infarction. Other pathologies include cardiomyopathies, ion channel disorders and congenital heart disease. Rarely, VT occurs in structurally normal hearts.

Typical symptoms of VT include palpitations, chest pain, dizziness, syncope and breathlessness. In some patients the presentation is with sudden death.

• Monomorphic VT is usually a re-entrant tachyarrhythmia. It is initiated by a premature ventricular beat that establishes a macro re-entry circuit around a region of scarring. The re-entry wavefront may traverse the scar through several different channels, occasionally producing a variable RR interval. Table 12.3 shows the ECG features that distinguish VT from an aberrantly conducted supraventricular tachycardia (SVT) and a pre-excited tachycardia. Fig 12.15 shows the Resuscitation Council (UK) management for tachycardias in adults.

• Bundle branch re-entry VT (BBR VT) is a re-entrant tachyarrhythmia in which the circuit involves the His bundle, both bundle branches and interventricular septal myocardium. As with other macro re-entry circuits, a zone of slow conduction is necessary to sustain the tachycardia. This is the LBB in the common form of BBR VT, which is the retrograde limb and gives an LBBB pattern on the ECG. However, since antegrade conduction is via the His–Purkinje system, the QRS complexes are similar to those for an SVT with aberrant conduction. There is usually underlying heart disease, particularly dilated cardiomyopathy.

• Idiopathic VT occurs in structurally normal hearts and can arise from either ventricle. Patients usually present with palpitations or syncope and the prognosis is good. The QRS duration is relatively short at 0.13–0.16 secs and VT may be misdiagnosed as SVT with aberrant conduction.

• The left ventricular type (also known as fascicular VT) is a re-entrant arrhythmia that responds to verapamil. The 12-lead ECG shows an RBBB monomorphic VT with left axis deviation.

• The right ventricular type, which is adenosine-sensitive, usually originates from the right ventricular outflow tract and is thought to be caused by triggered activity; it may, however, also arise from the LV outflow tract and aortic cusps. The 12-lead ECG usually shows LBBB with an inferior axis.

Table 12.3 ECG features distinguishing ventricular tachycardia from supraventricular tachycardia with aberrant conduction

ECG criterion	VT	SVT with aberrant conduction
AV relationship	Usually dissociated	Usually associated
Capture and fusion beats	Present	Absent
QRS duration	> 140 msec with RBBB morphology > 160 msec with LBBB morphology	≤ 140 msec ≤ 160 msec
Mean frontal plane axis	−90 to ±180°	Similar to sinus rhythm
QRS transition across chest leads	Usually positive or negative concordance, i.e. no transition	Similar to sinus rhythm

LBBB/RBBB, left/right bundle branch block.

Fig. 12.15 Adult tachycardia algorithm (with pulse).

(Reproduced with permission from the Resuscitation Council (http://www.resus.org.uk/siteindex.htm.)

•Investigations

• Patients should have transthoracic echocardiography.

• Some require further investigations with contrast echocardiography, cardiac MR scan, ajmaline testing and signal-averaged ECG.

• Certain patients may benefit from further risk stratification by VT stimulation testing. This especially applies to people with ischaemic heart disease and Brugada syndrome.

• Idiopathic and bundle branch re-entry VTs are referred for electrophysiology studies and possible curative ablation.

•Treatment

• Haemodynamically compromising VT requires immediate DC cardioversion.

• Drug therapy is usually with β-blockers and amiodarone.

• Fascicular VT is especially sensitive to verapamil.

• All patients with impaired LV function should also have optimal heart failure drug therapy (p. 419).

• Most other patients with symptomatic VT should have an ICD fitted (p. 410).

The only treatments to improve prognosis are β-blockers and ICDs. N.B. In patients with LV impairment, flecainide and propafenone increase mortality and should not be used.

Ventricular fibrillation (VF)

This is a cardiac arrest rhythm requiring immediate electrical defibrillation. There are advanced life support treatment algorithms that should be applied (p. 705). The underlying causes are similar to those of VT; the commonest is ischaemic heart disease with previous or acute myocardial infarction. The ECG shows disorganized electrical activity (Fig. 12.16) that is usually sustained. Unless there is an obvious reversible cause, such as acute myocardial ischaemia, all patients require ICD implantation.

Fig. 12.16 Ventricular fibrillation. Four beats of sinus rhythm are followed by a ventricular ectopic beat that initiates ventricular fibrillation. The ST segment during sinus rhythm is elevated owing to acute myocardial infarction in this case.

Sudden cardiac death

Sudden cardiac death (SCD) is defined as a sudden collapse within the first hour after onset of symptoms. The majority of patients become unconscious within seconds to minutes. This is sometimes preceded by chest pains, palpitations, breathlessness or generalized weakness.

In the USA, the incidence of SCD is 0.1–0.2% per year and SCD is responsible for 300 000 deaths annually. Around 50% of the 700 000 deaths per year from coronary heart disease are due to SCD (American Heart Association 2003, Heart and Stroke Statistical Update).

Ion channel disorders

Brugada syndrome

This is an inherited cause of idiopathic VF. It is commonest in young males from South-East Asia and classically presents with sudden death during sleep. Other symptoms include dizziness and syncope; some patients remain asymptomatic. In 20% of cases there is a sodium channel mutation (SCN5A) that causes characteristic coved ST segment elevation in ECG leads V1–V3. These changes either are present at baseline or may be provoked by drugs such as flecainide or ajmaline. In the absence of symptoms or documented ventricular arrhythmias, the presence of ECG changes is not associated with an increased risk of SCD. Patients with syncope or documented ventricular arrhythmias usually require ICD implantation, which improves prognosis.

Long QT syndrome (LQTS)

This is another cause of potentially lethal ventricular arrhythmias in structurally normal hearts and presents with sudden death or syncope. It is characterized by prolongation of the QT interval > 440 msec due to abnormal myocardial repolarization. The underlying causes may be ion channel mutations, certain drugs and electrolyte disturbances. The prevalence is around 1 in 4000, although it is probably under-diagnosed.

Two major forms of inherited LQTS have been described. They are the Romano–Ward and Jervell–Lange–Nielson (JLN) syndromes, which have ion channel mutations. These mutations affect currents generated by sodium or potassium ions. QT prolongation is the result of overloading cells with positive ions during repolarization. They each cause variations in T wave morphology. Some have a normal corrected QT interval (15%) but QT interval prolongation during exercise testing at faster heart rates. Ventricular arrhythmias are usually caused by adrenergic stimuli such as exercise, emotion and loud noises.

The classical VT in LQTS is torsades de pointes. This is a polymorphic VT in which the amplitude of the QRS complexes constantly changes around the isoelectric line (Fig. 12.17). This causes palpitations or syncope. Most episodes are self-terminating but SCD results from degeneration into VF.

• Management. All patients should undergo echocardiography to exclude any structural abnormality. Secondary causes of QT prolongation from drugs and electrolyte abnormalities should also be excluded (Box 12.4). All patients with confirmed congenital LQTs and family members should undergo genetic screening; mutations are only found in 50%. VT stimulation testing does not appear to be useful for risk stratification.

• Inherited LQTS. The mainstay of treatment is β–blockers and ICD implantation, as well as avoiding competitive sports. Adrenergic effects on the heart may be further reduced by left cervico-thoracic sympathectomy.

• Acquired LQTS. This is treated by stopping causative drugs and correcting electrolyte disturbances. IV magnesium sulphate 8 mmol over 10–15 min is effective at terminating torsades de pointes. Temporary pacing may also prevent bradycardia and VT.

Fig. 12.17 Supraventricular rhythm with a long QT 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.

Cardiomyopathies

SCD is uncommon in hypertrophic cardiomyopathy but is the commonest cause of SCD in young adults (p. 408).

Drug therapy

Anti-arrhythmic drugs are commonly used and work by affecting different components of the cardiac action potential. Consequently, they may precipitate arrhythmias and depress cardiac contractility. The Vaughan Williams classification describes them according to the effect on the action potential (Table 12.4). The use of individual drugs has been outlined in previous sections.

Table 12.4 The Vaughan Williams classification of anti-arrhythmic drugs

Device therapy

Pacing

Pacemakers are commonly used in the treatment of symptomatic bradycardias. Symptoms include syncope, dizziness, breathlessness and reduced exercise capacity. Pacemakers can be either temporary or permanent systems. All pacing systems usually consist of a transvenous endocardial pacing wire and a pacing generator.

• Temporary systems usually require a single pacing wire that is introduced aseptically via the internal jugular, subclavian or femoral veins and positioned within the right ventricle. The pacing generator is an external box. These systems should be left in situ for the least time possible, as there is a significant risk of infection.

• Permanent systems can have up to three wires that are usually introduced via the cephalic and/or subclavian veins. They can be positioned within the right atrium, right ventricle and, if indicated, tributaries of the coronary sinus for LV pacing. The pacing generator is a small box containing the pacing/sensing circuitry and a lithium iodine battery that lasts from 4 to 10 years. The system implant requires minor surgery to the pectoral region under local anaesthesia.

• Nomenclature. The basic function of a pacing system is described by a three-letter code that is recognized internationally. The first letter refers to the chamber(s) being paced, the second to the chamber(s) being sensed; the third describes the response to sensing (Table 12.5). Commonly used pacing modes include VVI, DDD and DDI.

• Indications. Symptomatic bradycardias can be caused by pathology within the specialized cardiac conduction system. The indications for permanent pacing are summarized in Box 12.5. Emergency temporary pacing is indicated in all haemodynamically unstable patients.

Table 12.5 International pacemaker nomenclature

I Chamber paced	II Chamber sensed	III Response to sensing
O: None	O: None	O: None
A: Atrium	A: Atrium	T: Triggered
V: Ventricle	V: Ventricle	I: Inhibited
D: Dual (A and V)	D: Dual (A and V)	D: Dual (T and I)

DDD and VVI are most commonly used.

Box 12.5 Indications for pacing

• Sinus node disease (tachycardia-bradycardia syndrome)

• Post-anterior myocardial infarction

– Mobitz type 2 block

– Complete (third-degree) block

– Transient Mobitz type 2 or complete block with bundle branch block

– Temporary pacing wire if new bifascicular block (right bundle branch block + left anterior or posterior hemiblock)

• Post-inferior myocardial infarction

– Persistent, symptomatic bradycardia (rare)

– Temporary pacing wire if bradycardia-induced hypotension (unresponsive to atropine), ventricular tachycardia or heart failure

• Sustained pause-dependent ventricular tachycardia

• Some high-risk congenital long QT syndrome patients

Ventricular mechanical dyssynchrony causes uncoordinated contraction of the different LV segments, thereby compromising ventricular function. This is often present in patients with a QRS duration of at least 130 ms and LBBB.

• Complications

• Pacemaker syndrome. This is seen in patients with VVI pacemakers whose AV nodes conduct retrogradely to the atria. Consequently, every ventricular paced beat causes atrial contraction against a closed AV valve. This leads to dizziness, breathlessness, syncope, fullness in the neck and pounding sensations or fullness in the head. Reducing the pacing rate or implanting an atrial pacing wire restores AV synchrony and relieves symptoms.

• Pacemaker-mediated tachycardia. This is seen with dual chamber pacing modes (VDD, DDD) when a ventricular paced beat is conducted retrogradely to the atria and is sensed by the atrial wire, triggering ventricular pacing again. This can be resolved by extending the post-ventricular atrial refractory period (PVARP) to prevent sensing of the retrograde P wave. Alternatively, the device could be reprogrammed to DDI mode, thereby preventing the ventricular pacing in response to the retrograde P wave.

• Atrial tachycardias. Any atrial tachycardia (commonly atrial flutter or fibrillation) can cause rapid ventricular pacing and consequent palpitations, dizziness, breathless or syncope. This is resolved by programming the pacemaker to switch pacing mode to VVI above a certain atrial rate or reprogramming to DDI mode (p. 412). Treatment (drugs and/or ablation) should be instituted for the atrial tachycardia.

Biventricular (cardiac resynchronization) pacing

This technique of pacing has been used in patients with severe heart failure to improve symptoms. It is offered to patients with New York Heart Association class 3 or 4 symptoms despite optimal medical therapy, an LV ejection fraction of 35% or less, an LV end-diastolic diameter of at least 55 mm and significant ventricular dyssynchrony.

Implantable cardioverter-defibrillators (ICDs)

These are specialized pacing devices that retain all of the functions of a standard pacemaker but, in addition, have the capacity to recognize and treat ventricular arrhythmias (VT, VF). The treatment modalities include ventricular burst pacing at rates exceeding the VT rate (anti-tachycardia pacing, ATP) and shocks (up to 41 J).

The devices consist of endocardial pacing wires as for a standard pacemaker, except for the right ventricular wire. This has one or two shocking coils in addition to the pacing and sensing component. One coil is always inside the right ventricle, with the second in the superior vena cava, although the latter is not mandatory. As with standard pacemakers, ICDs can be single chamber (right ventricle), dual chamber (right atrium and ventricle) and biventricular (for cardiac resynchronization therapy). The ICD generator is larger but still easily implanted in the pectoral region like a standard pacemaker. In addition to the pacing/sensing circuitry there is a lithium silver vanadium oxide battery and capacitors to store charge for the shocks.

ICDs are implanted for both primary and secondary prevention of SCD and are the most effective treatment available at present. The indications are summarized in Box 12.6.

Inappropriate therapies and device failure

Atrial tachycardias may result in inappropriate anti-tachycardia pacing or shocks. The most common problems are due to rapidly conducted AF or atrial flutter. If the ventricular rate encroaches into either the VT or VF therapy zones, the ICD will deliver therapy and may restore sinus rhythm. This problem is prevented by starting an anti-arrhythmic drug such as sotalol or amiodarone to prevent the atrial tachycardia, or by using AV nodal-blocking drugs to prevent excessive ventricular rates. Furthermore, the ICD may be reprogrammed to activate the atrial tachycardia discriminators. Some patients may require an electrophysiology study with a view to ablating the atrial tachycardia.

In some patients, the ICD over-senses the ventricular activity, giving an erroneously fast ventricular rate that may cause inappropriate therapies. This can be due to high T wave voltages, atrial activity, skeletal muscle activity (myopotentials) and noise from electrical appliances, e.g. lead fractures or a loose set screw securing the shocking lead to the generator. Over-sensing of the T wave or atrial activity may be resolved by decreasing the ventricular lead’s sensitivity without compromising VF detection. Alternatively, the shocking lead would require repositioning or replacement if fractured.

If the shocking lead becomes displaced or there is excessive fibrosis at the tip compromising electrical contact, the ventricular sensing will be compromised (under-sensing). The most serious consequence is a failure to detect VT or VF so that no therapy is delivered. This problem will usually necessitate a lead revision procedure.

Electrical storm

This is arbitrarily defined as at least three separate episodes of VT or VF within a 24-hour period requiring ICD therapy. Patients usually present with multiple anti-tachycardia pacing (ATP) episodes and/or shocks, which are painful and psychologically distressing.

Typical precipitants are listed in Box 12.7. Not infrequently, there is no obvious cause. The ICD is studied to confirm VT/VF and exclude atrial tachycardias. The treatment of storms is to identify and correct the precipitant and to provide symptomatic relief. If patients are receiving multiple shocks, they should be sedated and given opiates. If the VT can be treated by ATP rather than shocks, the ICD should be reprogrammed appropriately. Patients with a monomorphic VT should also be considered for catheter ablation. The mainstay of drug therapy is β-blockade, which may be IV initially, together with amiodarone or mexiletene. In Brugada syndrome, these drugs may exacerbate the storm and should be avoided if possible. Instead, patients should be started on an isoprenaline infusion, and class Ia drugs such as quinidine have been shown to be effective. If electrical storms fail to abate despite all treatment, general anaesthesia and intra-aortic balloon counterpulsation therapy may be effective.

Box 12.7 Causes of electrical storm

• Electrolyte disturbances — usually from heart failure medications

• Thyrotoxicosis — if already on amiodarone

• Acute heart failure

• Fever

• Acute myocardial ischaemia

• Atrial tachycardia

• Idiopathic

Appropriate therapies

If patients are repeatedly receiving therapy from the ICD, particularly shocks, the device programming and medications should be reviewed. Recently, there have been reports demonstrating that ATP is very effective for termination of fast VT, where previously a shock would have been delivered. All patients should be assessed for acute heart failure and treated appropriately. As the heart failure progresses, many patients develop slower VTs that may fall outside the VT therapy zone. These are difficult problems to treat, since patients may already be on optimal medical therapy and ICD reprogramming may lead to inappropriate therapy for sinus tachycardia. Catheter ablation of VT may be considered but remains a high-risk procedure in these patients.

Heart failure

Heart failure results from any structural or functional cardiac disorder that impairs the ability of the heart to function as a ‘pump’ to support the physiological functions of the body. Its incidence increases with age, rising to > 10% in 65-year-olds. Mortality is 50% 5 years after the diagnosis, despite current therapy.

Pathophysiology

• Systolic dysfunction arises from a reduction in the number of functioning myocytes, a reduction in the function of each myocyte or an increase in the demand, e.g. anaemia, where an increase in cardiac output is required. It can also arise from or lead to ventricular dilatation and remodelling, e.g. following acute myocardial injury.

• Impaired myocardial relaxation leads to increased diastolic pressure and wall stress.

• This increase leads to neurohormonal activation of the renin–angiotensin–aldosterone axis causing sodium and water retention.

• B-type natriuretic peptide is released in response to atrial stretch, again causing salt and water retention.

• Aldosterone also causes an increase in interstitial fibrosis, reducing the ability of the ventricle to relax.

• Activation of the sympathetic system causes tachycardia, increased myocardial oxygen demand and increased peripheral vascular resistance.

• Microvascular constriction occurs due to endothelin-related vasoconstriction.

• In valvular disease, regurgitant valves lead to unnecessary repeated ejection of blood from the heart and stenosed valves demand an increased force of contraction to eject the same volume of blood.

• In hypertension, increased wall stress is a stimulus to myocyte hypertrophy and thus ventricular hypertrophy. Hypertrophied ventricles relax poorly and contribute to the diastolic component of heart failure.

Clinical syndromes of heart failure

Symptoms depend on how rapidly the heart decompensates, the age and co-morbidities of the patient, and the aetiology of the failure.

• Acute heart failure (acute pulmonary oedema or cardiogenic shock, p. 443). This is usually seen after an acute myocardial infarction, a rupture of the interventricular septum or an acute valvular regurgitation.

• Chronic heart failure develops more insidiously and is often punctuated by episodes of acute heart failure.

• Left heart failure is caused by ischaemic heart disease (IHD) (commonest), systemic hypertension, mitral and aortic valve disease, and cardiomyopathies.

• Right heart failure occurs with left heart failure, chronic lung disease (cor pulmonale), pulmonary embolism (PE), pulmonary hypertension, right to left shunts, isolated right ventricular cardiomyopathy and mitral valve disease with pulmonary hypertension.

Symptoms of heart failure

(See New York Heart Association classification, Table 12.6.)

• Fatigue.

• Exertional dyspnoea.

• Orthopnoea.

• Paroxysmal nocturnal dyspnoea (PND).

Table 12.6 New York Heart Association (NYHA) classification of heart failure with therapy

Diagnosis

• ECG. When a patient presents with symptoms suggestive of heart failure, a normal 12-lead ECG excludes almost all cases of heart failure. It has a sensitivity of around 90% and a positive predictive value of 20–30%.

• CXR. The cardio-thoracic ratio is increased; signs of pulmonary venous congestion, fluid overload or pleural effusions are present.

• Natriuretic peptides. A normal serum B-type natriuretic peptide (BNP) and NT-pro BNP in combination with a normal ECG excludes the vast majority of cases of heart failure. A serum BNP < 100 pg/mL excludes heart failure as a cause of breathlessness, while > 500 pg/mL makes heart failure very likely.

• Other blood tests. These include U&E, calcium, fasting blood glucose, liver biochemistry, fasting lipid profile, FBC, thyroid function tests, ESR and CRP, auto-antibodies, iron studies, selenium level, serum amyloid and viral screen (Coxsackie, enterovirus, HIV).

• Transthoracic echocardiography (TTE). Two-dimensional and Doppler echocardiography are the diagnostic and quantitative tests of choice in suspected heart failure.

• Ventricular function can be measured in a variety of ways from the simple inner dimensions of the ventricles to the ejection fraction, relaxation, ventricular wall thickness and systolic thickening. An ejection fraction of < 0.45 is good evidence of systolic dysfunction.

• Stress echocardiography is useful to detect ischaemia as a cause of reversible heart failure. It assesses the viability of dysfunctional myocardium; dobutamine infusion identifies the contractile reserve in stunned or hibernating myocardium (p. 424).

• Nuclear cardiology. Radionuclide angiography (RNA) provides accurate measurements of left (and to a lesser extent, right) ventricular function, cardiac volumes and regional wall motion.

• Single photon-emission computed tomography (SPECT) can be used at rest or during stress (e.g. dobutamine infusion) with different radionuclides (e.g. ²⁰thallium or ^99mtechnetium) to detect ischaemia.

• Positron emission tomography (PET) uses a marker of metabolism (¹⁸FDG) and combines this with a measure of perfusion. It can detect glycolytic activity and therefore distinguishes viable, non-perfused muscle from non-viable, non-perfused muscle. It helps detect the reversibility of cardiac damage, in particular if revascularization may improve cardiac function by reawakening hibernating myocardium.

• Cardiac MRI (CMR) allows accurate measurements of cardiac volumes, wall thickness and LV mass. The use of dobutamine (for contractile reserve) or gadolinium (for delayed enhancement) helps assess viability of myocardium.

• Cardiac catheterization is used for the diagnosis of IHD (and suitability for revascularization). Measurement of pulmonary artery pressure, left atrial (wedge) pressure and LV end-diastolic pressure can be made.

• Holter (24-hour ambulatory ECG) monitoring excludes the presence of asymptomatic non-sustained ventricular tachycardia where ejection fraction is < 35% and the patient does not have symptoms of heart failure at rest. If VT is present, there is evidence to support the insertion of an ICD.

Management

Lifestyle

Patients and their family should be counselled and education given on healthy lifestyles, including weight/obesity control, exercise and diet.

• Smoking. The patient should stop.

• Exercise. Exertional breathlessness is not solely related to the lack of cardiac reserve but also to the lung function and skeletal muscle function of the patient. Patients should join cardiac rehabilitation programmes when their heart failure is stable. Bed rest is recommended for a short time because of its effect on reducing renin–angiotensin activation, when in acute heart failure.

• Diet. A healthy diet should be recommended to everyone. Salt intake should be reduced, with the patient avoiding foods rich in salt, and not adding salt during cooking or at the table. Fluid restriction is only necessary in severe heart failure. Alcohol acts as a diuretic but its effect on the myocardium is generally deleterious, with the possibility of developing alcoholic cardiomyopathy.

• Weight loss. Losing weight reduces disability by increasing mobility for the same effort. The direct cardiac effects include reduced systemic vascular resistance.

Pharmacological (Tables 12.6 and 12.7)

• Diuretics

• Loop diuretics. These are effective for fluid retention. In general, the principle is to use the minimum effective dose. Where more diuresis is required, increases in doses can later be accompanied by another class of diuretic (thiazide or metolazone) or a twice-daily dose. The diuresis lasts several hours (≥ 6) and the drugs are best taken in the morning to avoid nocturia.

Table 12.7 Drugs available for the treatment of heart failure

	Starting dose (daily)	Maximum dose (daily)
Loop diuretics
Furosemide	20–40 mg	250–500 mg
Bumetanide	0.5–1 mg	5–10 mg
Torasemide	5.0 mg	40 mg
Thiazide diuretics
Bendroflumethiazide	2.5 mg	10 mg
Chlortalidone	25 mg	200 mg
Metolazone	2.5 mg	10 mg
Angiotensin-converting enzyme (ACE) inhibitors
Captopril	6.25 mg 3 times daily	50 mg 3 times daily
Enalapril	2.5 mg	10–20 mg twice daily
Lisinopril	2.5–5.0 mg	30–35 mg
Perindopril	2 mg	4 mg
Ramipril	1.25 mg	10 mg
Angiotensin II receptor antagonists (ARBs)
Candesartan	4 mg	32 mg
Valsartan	20 mg twice daily	160 mg twice daily
Beta-adrenoreceptor blocking drugs
Carvedilol	3.125 mg twice daily	25-50 mg twice daily
Bisoprolol	1.25 mg	10 mg
Nebivolol	1.25 mg	10 mg
Aldosterone antagonists
Spironolactone	12.5–25 mg	50–200 mg
Eplerenone	25 mg	50 mg
Cardiac glycoside
Digoxin	Loading dose: 375–1500 mcg in divided doses over 24 hours	Maintenance dose: 62.5–500 mcg once daily with serum concentration ≥ 6 hrs post-dose of ≤ 2 ng/mL

Side-effects include hypotension, hyponatraemia, hypokalaemia and hypomagnesaemia (both of the latter can lead to QTc prolongation), renal impairment, hyperuricaemia and worsening control of diabetes mellitus.

• Thiazides. With the exception of metolazone, these diuretics are not as effective as loop diuretics in producing a diuresis. However, they act synergistically in combination with loop diuretics and are therefore useful where further diuresis is required despite adequate doses of these drugs.

Side-effects are similar, with hyponatraemia, hypokalaemia, hypomagnesaemia, hyperuricaemia and worsening control of diabetes mellitus.

• ACE inhibitors. These improve prognosis in terms of both mortality and reduced hospitalizations, as well as improving symptoms.

• Initiating ACE inhibitors is a priority for any patient with heart failure but monitoring of serum U&E is essential before and after initiation of treatment and 5–7 days after every increase in dose. Deterioration in renal biochemistry is likely if there is underlying renal impairment but the benefits of ACE inhibition in these circumstances are likely to be greater, provided acute kidney injury can be avoided.

• If creatinine rises to more than 50% of the baseline or to more than 200 µmol/L, stop all other nephrotoxic drugs and reduce the dose of ACE inhibitor. This may be an indicator of the presence of renal artery stenosis (p. 346). If the rise is more than 100% of baseline creatinine or above 350 µmol/L, stop the ACE inhibitor.

• A rise in serum potassium is common and is made worse by the concomitant use of potassium-sparing diuretics. Stop the ACE inhibitor when the serum K⁺ is ≥ 6.0 mmol/L; a serum potassium ≥ 6.5 needs urgent treatment (p. 711).

• When starting, use a small dose to allow for the possibility of a hypotensive response. Doses can then be doubled at 2-weekly intervals until a target dose is reached or adverse side-effects occur. If symptomatic hypotension supervenes, reduce the dose to the previous step. Other drugs that cause hypotension should be stopped to allow the maximum tolerated dose of ACE inhibitor.

• ACE inhibitors also increase the levels of bradykinin; this may help to explain a beneficial effect of these drugs over angiotensin receptor blockers, which are more specific for renin–angiotensin. Unfortunately, it also explains the increased incidence of dry cough (15%) in patients receiving ACE inhibitors, which is bradykinin-mediated.

• ACE inhibitors are the most effective drugs for heart failure and should always be prescribed if possible.

• Angiotensin receptor blockers (ARBs). These offer a theoretical advantage over ACE inhibitors because they do not increase the bradykinin levels, as seen with ACE inhibitors, so there is no troublesome cough. As there is no additional benefit over ACE inhibitors, ARBs are only recommended as a substitute to ACE inhibitors when cough is intolerable.

• Beta-adrenoreceptor blockers (β-blockers). Large RCTs have found benefit in patients treated with these drugs, including a decrease in mortality and hospitalization. There are no data to recommend one drug over the other and their clinical use is similar. Trials have used them as additional drugs to baseline diuretics and ACE inhibitors; the best results are seen in those with NYHA class III–IV symptoms. Start at a low dose and titrate upwards. Patients may experience transient fatigue, increased fluid retention and hypotension, with symptomatic improvement only occurring after several weeks. Dose titration may be aided by increased diuretic use if fluid retention is a problem. Bradycardia may be due to heart block, and a 12-lead ECG before and after initiating therapy will reveal any AV blockade. First-degree heart block need not preclude the use of β-blockers but in higher degrees of heart block, β-blockers are not usually used.

• Aldosterone antagonists

• Spironolactone. The addition of a low (sub-diuretic) 25 mg dose of spironolactone to ACE inhibitors, diuretics and β-blockers in cases of NYHA III–IV heart failure reduces mortality due to sudden death and due to heart failure. There is a significant risk of hyperkalaemia and renal dysfunction with this combination and monitoring is essential, starting before administration and continuing 5–7 days after commencing the drug. The trial evidence is based on a population with baseline creatinine ≤ 250 µmol/L, and if serum K⁺ rises to a threshold of 5.5 mmol/L, the dose should be halved and stopped if it goes over this.

Side-effects other than hyperkalaemia include gynaecomastia, which may be painful in up to 10% of patients taking the drug.

• Eplerenone This is a more selective aldosterone receptor antagonist, which avoids the side-effect of gynaecomastia seen with spironolactone. It has been shown to be effective in patients with an ejection fraction ≤ 0.4 post myocardial infarction, with clinical signs of pulmonary congestion or radiographic evidence of this. It has not been shown to be effective in chronic heart failure or heart failure due to non-infarction-related causes.

• Digoxin. Digoxin has a positive inotropic effect and has been shown to improve symptoms of heart failure and to reduce the frequency of hospital admission due to heart failure, but it has no effect on mortality. In addition to this, its negative chronotropic effect and potential nephrotoxic effects may prevent adequate therapy with other, more effective drugs. Digoxin is therefore mainly used in patients who require rate control for AF where β-blockade does not produce the desired rate reduction at rest. It is also used in treatment-resistant cases. The risk of toxicity increases with hypokalaemia and pre-existing renal dysfunction. There are numerous potential drug interactions and the manifestations of toxicity include anorexia and fatigue. These may lead on to AV block, VT, atrial tachycardia and accelerated junctional rhythm associated with AF. Chronic use is also associated with gynaecomastia and down-sloping ST segment depression on ECG. Co-prescription with maximal therapy with ACE inhibitors, β-adrenergic blockers, diuretics and spironolactone has been studied and may offer additional benefits in patients with NYHA class III–IV heart failure.

Side-effects are hypotension, hyperkalaemia and renal impairment similar to those seen with ACE inhibitors.

• Warfarin. Although there is an excess of thromboembolic events in the heart failure population, risk stratification is difficult and the risks of warfarinization over a lifetime of heart failure is significant. In the presence of AF or a prior thromboembolic event and heart failure, long-term anticoagulation is beneficial. In addition, in the acute stages of ventricular thrombus or aneurysm, anticoagulation is indicated. There is little evidence otherwise to support its continuation and most protocols recommend cessation after 6 months’ therapy.

• Vasodilators. Owing to the superiority of ACE inhibitors and ARBs, nitrates should only be used when the former classes are contraindicated. However, when used at a relatively high dose, they are effective in reducing mortality due to heart failure. Oral nitrates in combination with conventional therapy for heart failure can sometimes be helpful in symptomatic relief of breathlessness. Examples include isosorbide mononitrate 20–40 mg 3 times daily.

• Aspirin. Aspirin 75 mg is recommended where atherosclerotic disease and heart failure coexist.

• Statins. These are used in patients with ischaemic heart disease.

• Ivabradine. This inhibits the I_F channels in the sino-atrial node. It slows the heart rate and may be beneficial in heart failure.

• Drugs to avoid or stop:

• Calcium channel blockers, such as diltiazem and verapamil, are negatively inotropic and promote fluid retention; they should be avoided if possible.

• Alpha-adrenergic blockers similarly showed a lack of benefit in heart failure and may lead to an excess of heart failure in patients treated for hypertension.

• Class I anti-arrhythmic drugs have been shown to increase the incidence of life-threatening arrhythmia in heart failure and also lower BP; they should be avoided.

• NSAIDs, including COX-II inhibitors, promote fluid retention and have been shown to increase the incidence of cardiac events.

• Positive inotropes, such as dobutamine, have been used in acute exacerbations of heart failure in order to support a low BP and increase cardiac output at the cost of increasing cardiac oxygen consumption and ventricular arrhythmia. They are therefore not recommended for routine use and should only be given if a more definitive treatment is awaited (e.g. reperfusion therapy) or if there is a clear exacerbation of heart failure.

Devices

The drug treatment of each patient should be optimized and all reversible ischaemia managed by revascularization.

• Cardiac resynchronization therapy (CRT) (biventricular pacing). An LBBB causes an interventricular conduction delay. This ‘block’ allows the septum to contract along with the right ventricle and the left ventricle, then contract as the septum is relaxing. This causes loss of a major contribution to ventricular function. To overcome this, pacing is required (p. 410).

• ICDs. Combining CRT with an ICD improves survival by preventing sudden death due to ventricular arrhythmia (p. 405).

• Ventricular assist devices. These are reserved for patients on maximal medical therapy but with severe intractable symptoms and awaiting transplant. These devices have a high incidence of infective and thrombotic side-effects but can provide some patients with support. They obviate the need for a transplant in some patients with reversible cardiomyopathies (e.g. peripartum cardiomyopathy and viral myocarditis).

• Heart transplantation. This is the treatment of choice for younger patients with severe intractable heart failure and a life expectancy of < 6 months. The median survival of recipients is 9 years. However, the demanding nature of follow-up and limited number of donors have meant that stringent selection criteria are applied to recipients in order to ensure the most effective use of the organs available to the people most likely to benefit. Absolute contraindications include life-threatening medical conditions likely to cause death within 5 years, age over 60 years, a history of non-concordance with drug therapy and severe mental ill health.

Diastolic heart failure

The prevalence of this is unclear because of differing criteria for diagnosis and thus there is a lack of definitive trials showing a mortality benefit of any drug. The uncontentious criteria are symptoms of congestive heart failure and evidence of abnormal LV relaxation, filling, diastolic distensibility or diastolic stiffness with normal LV function on echocardiography. Diastolic heart failure has an estimated annual mortality of 5–8%. The cause and associated conditions, such as hypertension, ischaemia or diabetes or any other cause of LV hypertrophy, should be ascertained. Fluid retention may respond to cautious use of diuretics but high diastolic filling pressures are needed to maintain filling in stiff ventricles.

Acute heart failure

Acute heart failure (AHF) occurs with the rapid onset of symptoms and signs of heart failure secondary to abnormal cardiac function, causing elevated cardiac filling pressures. This leads to severe dyspnoea as fluid accumulates in the interstitial and alveolar spaces of the lung (pulmonary oedema). AHF has a poor prognosis, with a 60-day mortality rate of nearly 10% and a rate of death or rehospitalization of 35% within 60 days. In patients with acute pulmonary oedema the in-hospital mortality rate is 12% and by 12 months this rises to 30%. Poor prognostic indicators include a high (≥ 16 mmHg) pulmonary capillary wedge pressure (PCWP), low serum sodium concentration, increased LV end-diastolic dimension on echo and low oxygen consumption.

The aetiology of AHF is similar to chronic heart failure.

• Patients with ischaemic heart disease present with an acute coronary syndrome or develop a complication of a myocardial infarct, e.g. papillary muscle rupture or ventricular septal defect requiring surgical intervention.

• Patients with valvular heart disease also present with AHF due to valvular regurgitation in endocarditis or prosthetic valve thrombosis. A thoracic aortic dissection may produce severe aortic regurgitation.

• Patients with hypertension present with episodes of flash pulmonary oedema despite preserved LV systolic function.

• In both acute and chronic kidney disease fluid overload and a reduced renal excretion will produce pulmonary oedema.

• Atrial fibrillation is frequently associated with AHF and may require emergency cardioversion.

Several clinical syndromes of AHF can be defined (Table 12.8). In a clinical environment both the Killip score (based on a cardio-respiratory clinical assessment) and the Forrester classification (based on right heart catheterization findings) are used to provide therapeutic and prognostic information.

Table 12.8 Clinical presentation of acute heart failure

Range of presentations	Signs and symptoms	Criteria
Mild acute decompensated heart failure	Mild signs and symptoms of AHF	Does not fulfil criteria for cardiogenic shock, pulmonary oedema or hypertensive crisis
Hypertensive acute heart failure	Signs and symptoms of heart failure are accompanied by high BP	High BP, CXR evidence of pulmonary oedema, relatively preserved LV function
Pulmonary oedema	Severe respiratory distress, with basal lung crackles and orthopnoea	O₂ saturation < 90% on room air prior to treatment and CXR evidence of pulmonary oedema
Cardiogenic shock	Low BP, tachycardia, cool peripheries, pulmonary oedema, oliguria and/or altered mental state	Systolic BP < 90 mmHg, reduction of MAP (> 30 mmHg) ± oliguria (< 0.5 mL/kg/hour), pulse rate > 90 bpm
High-output failure	High heart rate with warm peripheries, pulmonary congestion, and sometimes low BP as in septic shock	High cardiac output, warm peripheries, tachycardia and pulmonary congestion
Right heart failure	Raised JVP, hepatomegaly, peripheral oedema, ascites and hypotension

MAP, mean arterial pressure.

(Adapted from Nieminen et al 2005)

Pathophysiology

The pathophysiology of AHF is similar to that of chronic heart failure with activation of the renin–angiotensin–aldosterone axis and sympathetic nervous system. In addition, prolonged ischaemia (e.g. in acute coronary syndromes) results in myocardial stunning that exacerbates myocardial dysfunction but may respond to inotropic support. If myocardial ischaemia persists, the myocardium may exhibit hibernation (persistently impaired function due to reduced coronary blood flow), which may recover with successful revascularization.

Diagnosis

• CXR. This is required to confirm the presence of pulmonary oedema. Typically, there will be distended upper lobe pulmonary veins with septal lines and diffuse shadowing in a perihilar distribution. The cardio-thoracic ratio will be increased if there is pre-existing heart failure. Other causes of breathlessness may be apparent on the CXR.

• ECG. This is needed to assess cardiac rhythm, potential acute coronary syndromes, myocarditis, cardiomyopathy, evidence of LV hypertrophy or RV strain.

• TTE. TTE in patients without a prior diagnosis of cardiac disease assesses valve function, chamber size and function, and pulmonary arterial pressures.

• Routine blood tests. These include FBC, U&E, glucose, LFTs, troponin and/or creatine kinase (CK-MB). Measure ABGs if there is severe heart failure, and D-dimer if there is a high suspicion of PE and no history suggestive of sepsis.

• Plasma BNP. Levels > 100 pg/mL indicates heart failure.

• Cardiac catheterization. Contrast given during angiography exerts an additional fluid load and may worsen acute heart failure, but cardiogenic shock and AHF secondary to acute coronary syndromes can be improved by emergency revascularization; this can be facilitated by intra-aortic balloon pump (IABP) support if necessary.

Treatment

The goals of treatment in a patient with AHF include:

• short-term benefits:

• the immediate relief of symptoms

• stabilization of haemodynamics

• long-term benefits:

• reduction in length of hospital stay and hospital readmissions

• reduction in mortality from heart failure.

Patients with AHF should be managed in a high-care area with regular measurements of temperature, heart rate and BP, and cardiac monitoring. All patients require prophylactic anticoagulation with low molecular weight heparin (LMWH), e.g. enoxaparin 1 mg/kg SC daily or an antithrombin, e.g. dabigatram 220 mg daily.

Patients with haemodynamic compromise may require arterial lines (invasive BP monitoring and ABGs), central venous cannulation (IV medication, inotropic support, monitoring of CVP) and pulmonary artery cannulation (calculation of cardiac output/index/peripheral vasoconstriction/pulmonary wedge pressure).

• Initial therapy (Box 12.8) includes oxygen, diuretics and vasodilator therapy (Table 12.9) if the BP is maintained (systolic > 85 mmHg).

• Inotropic support (Table 12.10) with dobutamine, phosphodiesterase inhibitors or levosimendan (or nesiritide in the USA) can be added in patients who do not respond to the initial therapy (Fig. 12.18).

• Patients with profound hypotension may require inotropes and vasopressors to improve the haemodynamic status and alleviate symptoms but these agents have not been shown to improve mortality.

• Further therapy with non-invasive ventilation — CPAP/NIPPV (p. 542) — may be needed to improve oxygen saturation and reduction in the work of breathing. Mechanistic therapy may also be required (see below).

• New therapies include relaxin, a naturally occurring hormone, which has been used with success in heart failure.

Box 12.8 Treatment of acute heart failure

• Oxygen 60% via face mask

• Diuretic, e.g. furosemide 20–50 mg by slow IV injection, venodilates with reduction in preload and reduction in pulmonary congestion

• Morphine 5–10 mg IV (depending on size of patient), with an antiemetic, e.g. metoclopramide 10 mg IV, relieves anxiety and causes systemic vasodilatation

• Glyceryl trinitrate IV infusion 10–200 mcg/min venodilates and reduces preload

Table 12.9 Indications and dosing of IV vasodilators in acute heart failure

Table 12.10 Dosing of positive inotropic agents in acute heart failure

	Bolus	Infusion rate
Dobutamine	No	2–20 mcg/kg/min (β+)
Dopamine	No	< 3 mcg/kg/min: renal effect (δ+) 3–5 mcg/kg/min: inotropic (β+) > 5 mcg/kg/min: (β+), vasopressor (α+)
Milrinone	25–75 mcg/kg over 10–20 mins	0.375–0.75 mcg/kg/min
Enoximone	0.25–0.75 mg/kg	1.25–7.5 mcg/kg/min
Levosimendan*	12 mcg/kg over 10 mins (optional)^†	0.1 mcg/kg/min, which can be decreased to 0.05 or increased to 0.2 mcg/kg/min
Noradrenaline (norepinephrine)	No	0.2–1.0 mcg/kg/min
Adrenaline (epinephrine)	Bolus: 1 mg can be given IV during resuscitation, repeated every 3–5 mins	0.05–0.5 mcg/kg/min

* This agent also has vasodilator properties.

^† In hypotensive patients (systolic BP < 100 mmHg) initiation of therapy without a bolus is recommended.

(Dickstein et al 2008, with permission)

Fig. 12.18 Algorithm for the management of acute heart failure with systolic dysfunction.ACEI, angiotensin-converting enzyme inhibitor; BNP, brain natriuretic peptide; CPAP, continuous positive airway pressure; NTG, nitroglycerine (glyceryl trinitrate); PDEI, phosphodiesterase inhibitor; SBP, systolic blood pressure

(Nieminen et al 2005, with permission).

Mechanical assist devices

Mechanical assist devices can be used in patients failing 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 as a bridge to cardiac surgery including transplantation.

Ventricular assist devices (VADs)

VADs are mechanical devices that replace or help the failing ventricles in delivering blood around the body. The left ventricular assist device (LVAD) receives blood from the left ventricle and delivers it to the aorta; the 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 who are not candidates for transplantation). The main problems with VADs include thromboembolism, bleeding, infection and device malfunction.

Coronary Artery Disease

Epidemiology

Cardiovascular disease (CVD) is the leading cause of death in many parts of the world.

Approximately 50% of CVD deaths are from coronary artery disease (CAD). CAD is the most common cause of death in men under the age of 75 and the second most common cause of death in women under the age of 75.

Risk factors

Several risk factors for developing CAD have been well established, through numerous large epidemiological studies. These can be divided into non-modifiable and modifiable risk factors.

• Non-modifiable risk factors

• Age. This is a major risk factor for atherosclerosis. While fatty streaks can be found in teenagers, the volume of atheromatous plaques increases with age, and thus the risk of CAD. Using intravascular ultrasonography (IVUS) plaques are detectable in one-third of healthy people aged 20–29 who have no evidence of CAD on angiography.

• Gender. Pre-menopausal women have a lower incidence of CAD than age-matched men. After the menopause the incidence of CAD in women approaches that of men, suggesting a potential protective role of oestrogen. However, there is no evidence that hormone replacement therapy reduces the risk and isolated oestrogen replacement can increase cardiovascular events.

• Family history. The genetics of CAD are complex and polygenic. Having a first-degree relative who has developed CAD before the age of 50 in men and 55 years in women is an accepted risk factor for CAD.

• Modifiable risk factors

• Cigarette smoking. Both smokers and those exposed to environmental smoke (passive smoking) are at an increased risk of CAD. Smoking acts synergistically with other risk factors. It is probably the most significant modifiable factor. The risk from smoking declines to almost normal after 10 years of abstention.

• Diabetes. Type 1 and type 2 diabetes, an abnormal glucose tolerance test or a raised fasting glucose, are associated with an increased risk of CAD.

• Metabolic syndrome. This consists of visceral obesity, dyslipidaemia, hyperglycaemia, insulin resistance and hypertension.

• Dyslipidaemia. Raised levels of low-density lipoprotein (LDL) and reduced levels of high-density lipoprotein (HDL) are well-established risk factors. In addition, elevated triglyceride levels are an independent risk factor.

• Hypertension. The level of hypertension (both systolic and diastolic) is associated with a linear increased risk of CAD. Hypertension is often asymptomatic and therefore clinically ‘silent’. It should be measured regularly in patients above 55 years.

• Obesity. The body mass index (BMI) is used to measure obesity and the risk of CAD is correlated with an increasing BMI. Patients should aim for a BMI of < 25. There has been an increasing recognition that central obesity (due to visceral fat) is a risk factor for CAD. Central obesity is detected by a high waist to hip ratio and this is probably a more reliable marker of obesity than BMI.

• Physical activity. Lack of physical activity is now an established risk factor for CAD and a contributor to other risk factors, e.g. obesity and diabetes. Regular physical exercise (30 mins exercise of moderate intensity 5 or more days per week) protects against the development of CAD.

• Alcohol. A high intake of alcohol is associated with an increased risk of CAD. Moderate alcohol intake (2–4 U/day) may be associated with a reduced risk of CAD.

• C-reactive protein (CRP). There is evidence that a raised CRP is a risk factor, although there has been recent controversy. The exact mechanisms have not been fully elucidated. The high-sensitivity CRP (hs-CRP) assay has been shown to be useful in refining the level of risk in those already known to be at an increased risk of CAD.

• Coagulation factors. Factor VII polymorphisms, high serum fibrinogen and raised homocysteine levels have all been shown to be independent risk factors for CAD.

• Diets. Diets low in fresh fruit and vegetables, as well as low polyunsaturated fatty acids, are associated with increased risks.

Definitions and spectrum of disease

CAD causes a spectrum of disease from atherosclerotic plaques not limiting flow, to fibrotic, organized, flow-limiting atherosclerotic plaques.

• Chronic stable angina is due to flow-limiting lesions that restrict coronary blood flow.

• Acute coronary syndromes (ACS) occur when a plaque ruptures and a thrombus forms, which may result in myocardial necrosis (myocardial infarction). In order to diagnose an acute, evolving or recent myocardial infarction (MI), one of the following criteria must be fulfilled:

• a typical rise and/or fall in markers of myocardial necrosis (preferably troponin) above the 99th centile of the upper limit of normal (p. 431) with at least one of the following:

a) ischaemic symptoms

b) development of pathological Q waves on the ECG

c) ECG changes indicative of new ischaemia (new ST–T changes or LBBB)

d) other imaging showing new loss of viable myocardium or new regional wall motion abnormality.

• abnormal findings on ECG of an acute MI

• For the definition of an MI following percutaneous coronary intervention (PCI) a cutoff of 3 times the 99th centile of the upper limit of normal is used.

This definition of MI is based on the European Society of Cardiology (ECS) and American College of Cardiology consensus statement from 2007. As a result, many more patients are now diagnosed as having had an MI, especially those who have had intervention.

• STEMI, NSTEMI and unstable angina (UA). MI is classified according to the ECG changes as either ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI). This dictates subsequent management. UA differs from NSTEMI, in that there is no elevation in the serum markers. However, initially NSTEMI and UA may be indistinguishable; increased markers of necrosis may not be detectable for hours, as ischaemia needs to be severe enough in NSTEMI to cause sufficient myocardial damage to produce measurable quantities of markers, e.g. troponins, creatine kinase (CK-MB).The new highly sensitive troponin assays have changed the above definitions and more patients are being diagnosed as having an M1.

Clinical features

• Ischaemic cardiac chest pain (angina) is most often described as a heavy central chest pain that classically radiates to the arm(s), neck and/or jaw.

• Angina may be atypical in nature (e.g. epigastric pain with inferior ischaemia) or may be asymptomatic, e.g. in diabetics. In diabetics shortness of breath on exertion may well be due to myocardial ischaemia.

• Unprovoked angina at rest lasting more than 20 mins or crescendo angina is typical of an ACS.

• The pain in ACS is often associated with autonomic symptoms (nausea, vomiting and sweating).

• The symptoms of gastro-oesophageal reflux may be indistinguishable from ischaemic pain.

• Examination may reveal no abnormalities but it is essential to rule out cardiac failure, cardiac dysfunction and other coexisting diagnoses.

Investigations

Twelve-lead ECG

This must be performed in any patient with suspected CAD.

• A baseline ECG is always helpful but it may be normal or only show minor changes.

• ECGs should be repeated every 10–15 mins in any patients with suspected ACS or if pain worsens or recurs.

• A right-sided lead (V₂R) should be recorded in patients with suspected right-sided infarcts.

Biochemical serum markers of myocardial damage

• Troponins. Troponins are the most commonly used markers of myocardial necrosis.

• Either cardiac-specific troponin T or I is used; both are highly specific and sensitive for cardiac damage. They rise ~3–12 hours after an MI, peak at 24–48 hours and gradually decrease over a week. The new troponin assays are much quicker and more sensitive but some specificity is lost.

• In patients with suspected ACS troponin should be measured on admission and 12 hours afterwards.

• A raised troponin is a marker of myocardial ischaemia, of which there are many other causes (e.g. massive PE) and the troponin value should be used in conjunction with other findings to make a clinical diagnosis.

• Troponins are useful for predicting prognosis (the increase in level is directly proportional to the risk of cardiac death), stratifying risk (p. 440) and guiding further management in ACS.

•Creatine kinase (CK-MB)

• CK-MB is the proportion of the total CK released from the myocardium and therefore a marker of myocardial injury. It rises 3–12 hours after an MI, peaks around 24 hours and rapidly returns to normal in 48–72 hours.

• CK-MB is less sensitive and specific than cardiac troponins and therefore tends not to be used as a first-line marker of myocardial damage.

• CK-MB is often used for the diagnosis of MI caused by PCI.

• Other markers. Serum myoglobin rises early (2 hours) after an MI but is not cardiac-specific as it is also raised in end-stage renal disease. Heart-fatty acid binding protein (H-FABP) is another early marker of myocardial damage.

Imaging

• Coronary angiography. This is the gold standard for assessing the coronary arteries and identifying atherosclerotic lesions. Elective angiography is a very safe procedure with a combined risk of death, MI or stroke of < 0.1%. Indications include patients with a positive exercise test with angina, all NSTEMI ACS, patients who have had an MI revascularization with a positive stress test and those who have survived a sudden cardiac arrest. The timing will depend on the clinical scenario. Angiography allows identification of lesions that need revascularization (percutaneous or bypass graft surgery) and provides useful prognostic information.

• Additional tools. Additional tools, including IVUS and/or pressure wire, can be of great use in assessing functional implications and identifying the need for revascularization of coronary lesions.

• Transthoracic Echocardiography TTE. This is a non-invasive test and allows a full assessment of ventricular and valve structure and function. It also permits the identification of regional wall motion abnormalities due to myocardial ischaemia. Exercise or pharmacological (usually dobutamine) stress echo is useful and safe for the diagnosis and assessment of CAD. It highlights areas of ischaemia that are producing abnormal wall movement.

• CT. Electron beam CT (EBCT) scanners and 64 multi-detector CT (MDCT) can produce thin axial slices of the heart. The calcium score (i.e. the assessment of the degree of coronary calcification) can be calculated. This is of some prognostic use. A calcium score of ‘0’ gives a 0.3% chance of having CAD whilst with a score of > 400, the chance of CAD is 61–90%. CT coronary angiography (CTCA) is used for diagnostic coronary angiography and involves the injection of an iodinated contrast agent. It has 85% sensitivity with 90% specificity. It is especially useful in defining coronary anomalies and is also valuable in excluding other causes of chest pain, e.g. aortic dissection, PE.

• Cardiovascular magnetic resonance (CMR). CMR can be used as a ‘one-step’ approach for assessing CAD. It is used for the assessment of ischaemia in patients with suspected coronary disease and to assess myocardial viability prior to revascularization in patients with impaired cardiac function.

• Coronary artery anatomy and stenoses can be identified with ultra-fast breath-hold or respiratory-gated sequences; at present this is predominantly a research tool.

• Left ventricular function and wall motion abnormalities are detected with cine imaging performed at rest and during dobutamine-induced stress (stress echocardiogram).

• Myocardial perfusion is assessed with gadolinium and first-pass imaging. Ischaemia is demonstrated with adenosine for coronary vasodilatation.

• Myocardial viability is determined by using gadolinium and ‘delayed enhancement’ images.

• Nuclear imaging. Radionucleotide myocardial perfusion imaging is useful for the diagnosis and functional assessment of CAD. Single photon emission computed tomography (SPECT) involves the injection of an isotope of either ^99mtechnetium-tetrofosmin or ²⁰¹thallium. Perfusion images are then obtained at rest and peak stress (exercise or pharmacological); comparison of these images in different views allows the identification of areas of ischaemia.

• In patients with known CAD this technique can be used to assess the haemodynamic impact of known stenosis and thus guide revascularization.

• It also provides useful prognostic information in these patients, as a normal scan is associated with a very low risk of coronary events.

Management of acute coronary syndromes

Classification of ACS

When assessing any patient with a suspected ACS, remember ‘time is muscle’; these patients must be seen as a priority.

On the basis of history, examination and 12-lead ECG, patients can immediately be split into two groups to dictate subsequent management:

• ST elevation (STEMI) or new-onset LBBB (Figs 12.19 and 12.20). These patients need immediate reperfusion, preferably by PCI. However, if this is not available or a long delay is envisaged, then prompt thrombolytic therapy should be given.

• Non-ST elevation (NSTEMI). These patients are risk-stratified and referred for PCI according to this risk.

Fig. 12.19 An acute anterolateral myocardial infarction shown by a 12-lead ECG. Note the ST segment elevation in leads I, aVL and V2–V6. The T wave is inverted in leads I, aVL and V3–V6. Pathological Q waves are seen in leads V2–V6.

Fig. 12.20 An acute inferior wall myocardial infarction shown by a 12-lead ECG. Note the raised ST segment and Q waves in the inferior leads (III, III and aVF). The additional T wave inversion in V4 and V5 probably represents anterior wall ischaemia.

The diagnosis of STEMI, NSTEMI or troponin-negative ACS (unstable angina) becomes apparent when the troponin result becomes available. However, waiting for troponin results should never delay initial management, which is based on clinical findings and ECG (i.e. STEMI or NSTEMI). Sensitive and fast troponin assays are becoming more available.

Immediate medical management in A&E (Table 12.11)

All hospitals are expected to have a rapid triage for chest pain to ensure that all suspected ACS patients are seen without delay. There should be a multi-disciplinary team approach with defined guidelines (see Emergencies in medicine, Fig. 20.10). With all ACS patients:

• IV access should be gained and bloods sent for cardiac markers, biochemistry, lipid profile, FBC and clotting profile.

• Oxygen is no longer recommended (2008 British Thoracic Society guidelines), unless the patient is hypoxaemic.

• Aspirin 300 mg chewed, then 75–150 mg daily, should be given.

• Sublingual glyceryl trinitrate (GTN) 0.3–1 mg should be given for pain relief, repeated as necessary (provided BP is not compromised). This can be followed by an IV infusion of 1–10 mg/hour, which is titrated to pain whilst aiming to keep systolic BP > 100 mmHg.

• IV diamorphine (2.5–5 mg) or morphine 10 mg is used as analgesia, with metoclopramide 10 mg as an antiemetic.

• If there is ongoing or continuous recurrent ischaemia IV β-blockade with metoprolol is given in 5 mg boluses (up to a total of 15 mg), provided the patient is not in cardiogenic shock and/or hypotensive, and that there are no contraindications (e.g. asthma).

• Patients with a STEMI ideally should start β-blockers on the first day, provided they are definitely haemodynamically stable. If there is any doubt, wait until they are stable, to avoid the possibility of cardiac shock developing.

• All ACS patients should be transferred to a coronary care unit (CCU) for continuous monitoring and further specialist care.

• Patients with ACS should have clopidogrel 600 mg loading dose, unless PCI is not being considered, in which case the loading dose should be 300 mg; thereafter 75 mg daily is given in addition to aspirin. It has been shown to reduce mortality and the occurrence of major vascular events without an increase in the risk of bleeding in STEMI ACS. Prasugrel is an alternative.

• N.B. Proton pump inhibitors, particularly omeprazole, have now been shown not to reduce the antiplatelet effect of clopidogrel as they are inhibitors of cytochrome p450 (CYP2C19).

• In addition, urgent reperfusion (see below) is needed.

Table 12.11 Pharmacological therapy in acute coronary syndromes

Drug	Dose	Notes
Antiplatelet
Aspirin	150–300 mg chewable or soluble aspirin, then 75–100 mg oral daily	Caution if active peptic ulceration
Clopidogrel	300 mg oral loading dose, then 75 mg oral daily	Caution — increased risk of bleeding, avoid if CABG planned
Prasugrel	60 mg loading dose then 10 mg if >60 kg or 5 mg if <60 kg daily	Used in combination with aspirin
Anti-thrombin
Heparin	5000 U IV bolus, then 0.25 U/kg/hour	Measure anticoagulant effect with APTT at 6 hours
Low molecular weight heparins	e.g. Enoxaparin 1 mg/kg SC twice daily
Fondaparinux	2.5 mg SC once daily
Bivalirudin	750 mcg/kg IV bolus, then 0.75 mg/kg/hour
Glycoprotein IIB/IIIA inhibitors
Abciximab	0.25 mg/kg IV bolus, then 0.125 mcg/kg/min up to 10 mcg/min IV × 12 hours	Indicated if coronary intervention likely within 24 hours
Eptifibatide	180 mcg/kg IV bolus, then 2 mcg/kg/min IV × 72 hours	Indicated in high-risk patients managed without coronary intervention or during PCI
Tirofiban	0.4 mcg/kg/min for 30 mins, then 0.1 mcg/kg/min × 48–108 hours	Indicated in high-risk patients managed without coronary intervention or during PCI
Analgesia
Diamorphine or morphine	2.5–5.0 mg IV10 mg IV	Prescribe with antiemetic, e.g. metoclopramide 10 mg IV
Myocardial energy consumption reduction
Atenolol	5 mg IV, repeated after 15 mins, then 25–50 mg oral daily	Avoid in asthma, heart failure, hypotension, bradyarrhythmias
Metoprolol	5 mg IV, repeated to a maximum of 15 mg, then 25–50 mg orally twice daily. In STEMI, wait 48 hours	Avoid in asthma, heart failure, hypotension, bradyarrhythmias
Coronary vasodilatation
Glyceryl trinitrate	2–10 mg/hour IV/buccal/sublingual	Maintain systolic BP > 90 mmHg
Plaque stabilization/ventricular remodelling
HMG-CoA reductase inhibitors (statins)
Simvastatin Pravastatin Atorvastatin	20–40 mg oral 20–40 mg oral 80 mg oral	Combine with dietary advice and modification
ACE inhibitors
Ramipril Lisinopril	2.5–10 mg oral 5–10 mg oral	Monitor renal function

APTT, activated partial thromboplastin time; CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction.

Reperfusion in STEMI ACS

Percutaneous coronary intervention (PCI)

PCI (if available on site or within 90 mins) is the treatment of choice in STEMI ACS. It should be used as soon as possible but within 90 mins of the patient arriving at hospital. It improves vessel patency and clinical outcome compared to thrombolytic therapy.

• Pre-procedure use of a glycoprotein (GP) IIb/IIIa inhibitor, e.g. abciximab, improves the outcome further; if nothing else, the bolus should always be given prior to angiography.

• Successful primary PCI for STEMI requires a dedicated service to be running within a hospital with a ‘door to balloon’ time of < 90 mins.

• Primary PCI should always be the first choice for patients with cardiogenic shock. However, it must be carried out within 24 hours or there is little benefit.

• Drug-eluting stents: coated stents lined with substances, e.g. sirolimus or paclitaxel, significantly reduce the incidence of coronary artery re-stenosis but late-stent thrombosis may be increased. Prolonged dual antiplatelet therapy (aspirin and clopidogrel) is therefore required with these stents for 1 year. Bare metal stents are currently used in STEMI, but there is increasing evidence that drug-eluting stents may confer a survival benefit.

Thrombolytic therapy

This still forms the mainstay of treatment of STEMI ACS in many countries. A ‘door to needle’ time of < 30 mins should be the minimum goal.

• There is clear benefit from thrombolysis for up to 12 hours after symptom onset. After 12 hours patients should be referred for PCI, as there is no clear benefit from thrombolysis in this group.

• Thrombolytic therapy should be administered to STEMI patients (PCI not being available) if they have:

• no contraindications, e.g. history of a stroke, gastrointestinal bleeding, trauma, anticoagulant therapy

• symptom onset within the last 12 hours and either

• ≥ 1 mm (0.1 mV) ST elevation in at least two contiguous precordial leads or at least two adjacent limb leads or

• new-onset LBBB.

• There is no good evidence to support the use of thrombolysis in patients with ST depression

• Rescue PCI is being performed (within 12 hours) in patients who fail to reperfuse.

Thrombolytic agents (Table 12.12)

• Alteplase (tPA), reteplase and tenecteplase all achieve faster reperfusion than streptokinase but need to be followed with a 24–48 hour-infusion of IV heparin therapy.

• However, there is evidence that 4–8 days on LMWH results in a reduction in reinfarction and mortality rates, irrespective of the thrombolytic agent given.

• Streptokinase should not be given to a patient who has had streptokinase previously because of the risk of anaphylaxis and/or immune tolerance. Apart from its low cost, there is little to favour streptokinase as a first-choice thrombolytic agent.

• Pre-hospital thrombolysis can be given to patients with STEMI by trained paramedics.

• For anterior MI there is evidence that alteplase is superior to streptokinase.

• Reteplase and tenecteplase are often favoured due to their ease of administration (bolus doses, as opposed to infusions that have to be made up for alteplase or streptokinase).

Table 12.12 Fibrinolytic regimes for ST elevation myocardial infarction (STEMI)

	Initial treatment (route is IV for all)	Need for heparin
Streptokinase	1.5 million U in 100 mL of 5% dextrose or 0.9% saline infusion over 30–60 mins	No
Alteplase (tPA)	0.15 mg bolus 0.75 mg/kg infusion over 30 mins then 0.5 mg/kg infusion over 60 mins Total dose must be < 100 mg	24–48 hours (or 4–8 days with LMWH), e.g. enoxaparin 1 mg/kg SC twice daily
Reteplase (rPA)	10 U bolus + 10 U bolus (30 mins apart)	24–48 hours (or LMWH as above)
Tenecteplase (TNK-tPA)	30 mg single bolus if < 60 kg 35 mg single bolus if 60 to < 70 kg 40 mg single bolus if 70 to < 80 kg 55 mg single bolus if 80 to < 90 kg 50 mg single bolus if ≥ 90 kg	24–48 hours (or LMWH as above)

LMWH, low molecular weight heparin.

If, after 60–90 mins, the ST elevation and/or pain have not resolved (or have recurred), the patient should be discussed immediately with a cardiologist, who should advise transfer with a view to rescue PCI (provided the patient is stable enough to transfer); if this is not possible, further thrombolytic therapy may be given.

It is not standard practice to use combined fibrinolytic regimes (e.g. reduced-dose thrombolysis and glycoprotein IIb/IIIa inhibitors). Although there is some evidence that they may reduce reinfarction, there is no benefit in terms of mortality reduction.

Patients can be transferred to CCU and given fibrinolysis, provided there is no delay. Otherwise, fibrinolysis should be started in A&E in a monitored bed. The transfer of a patient should never delay initiation of thrombolytic therapy.

After appropriate reperfusion therapy (either PCI or fibrinolysis), the patient should be monitored and managed on CCU.

NSTEMI ACS

• The ESC guidelines recommend that NSTEMI ACS patients undergoing immediate PCI receive either an LMWH (usually enoxaparin 1 mg/kg SC twice daily) or bivalirudin (a thrombin-specific anticoagulant) IV bolus 0.75 mg/kg; the actual clotting time (ACT) should be checked 5 mins after this, and if < 225, a second bolus of 0.3 mg/kg should be given (provided glomerular filtration rate (GFR) is > 30 mL/min), followed by an infusion of 1.75 mg/kg/hour.

• In patients not undergoing immediate PCI, the ESC guidelines now recommend the pure factor Xa inhibitors; fondaparinux 2.5 mg SC once daily should be used as the first-choice anticoagulant, as it is at least as effective as LMWH and is associated with fewer adverse bleeding episodes. If fondaparinux is not available, then an LMWH (usually enoxaparin 1 mg/kg SC twice daily) may be used.

Risk stratification, GP IIb/IIIa antagonists and revascularization in NSTEMI ACS

Patients with a NSTEMI ACS who have severe ongoing ischaemia (continuing chest pain and ischaemic ECG changes), haemodynamic instability or major arrhythmias, despite full medical therapy (as outlined earlier), are at very high risk and need immediate referral for angiography and PCI. These patients should be discussed with a cardiologist, who will often advise starting a GP IIb/IIIa antagonist, e.g. abciximab IV 250 mg/kg over 1 min, then IV infusion 125 ng/kg/min 10–60 mins before PCI; this is usually continued for 12 hours post PCI. For patients not going immediately to the laboratory for PCI, either tirofiban or eptifibatide given as infusions is usually the IIb/IIIa antagonist of choice (see below for dose schemes).

All other patients must be ‘risk-stratified’ using the results of their serum troponin level 12 hours post admission. There is a clear increase in risk of mortality with increasing troponin levels. Either the TIMI (Table 12.13) or the GRACE risk score can be used. A TIMI score of > 4 (or a GRACE risk score of > 140) is classified as high-risk.

• Low-risk patients. Patients who have no troponin rise 12 hours post admission, remain pain free and have minor or no ECG changes can be considered as low-risk. In this group SC LMWH and GTN infusions should be discontinued, and patients should be fully mobilized and have a pre-discharge exercise stress test. Patients with ischaemia at a very low workload should be discussed with a cardiologist prior to discharge, as they usually need either an early outpatient angiogram or possible retention for further assessment. All other patients can be managed as outpatients.

Table 12.13a TIMI risk score in acute coronary syndrome (NSTEMI/UA)

Risk factor	Score
Age > 65	1
≥ 3 risk factors for CAD	1
Known CAD (stenosis > 50%)	1
Aspirin use in last 7 days	1
Recent (≤ 24 hours) severe angina	1
Raised cardiac markers	1
ST deviation ≥ 0.5 mm	1
Elevated cardiac markers (CK-MB or troponin)	1

CAD, coronary artery disease; CK-MB, creatine kinase; NSTEMI, non-ST elevation myocardial infarction; UA, unstable angina.

Table 12.13b Risk of cardiac events (%) by 14 days in TIMI IIb

Total score	Death or MI (%)	Death, MI or urgent revascularization (%)
0/1	3	4.75
2	3	8.3
3	5	13.2
4	7	19.9
5	12	26.2
6/7	19	40.9

•Intermediate- and high-risk patients

• Angiography should be performed in all of this group, with a view to PCI. Provided patients are stable, this can be done after 48 hours of admission (whilst they are still inpatients).

• Treatment with a GP IIb/IIIa antagonist is beneficial in this group, with the benefit being greatest in diabetics with NSTEMI.

• Generally, abciximab is used if PCI is planned within 24 hours; otherwise use either tirofiban IV infusion 400 ng/kg/min for 30 mins, then 100 ng/kg/min for at least 48 hours (continue during and for 12–24 hours after PCI; max. duration 108 hours) or eptifibatide IV injection 180 mcg/kg, then IV infusion 2 mcg/kg/min for 72 hours (up to 96 hours if PCI is performed during treatment). GP IIb/IIIa antagonists can be safely co-prescribed with enoxaparin (an LMWH) and clopidogrel.

• Patients with refractory ischaemia (ongoing chest pain and/or persistent ischaemic ECG changes), despite full medical therapy, should be sent for urgent PCI after being started on a IIb/IIIa antagonist (e.g. abciximab).

• In the stable group of patients (pain-free and no ongoing dynamic ischaemic ECG changes), the decision as to whether GP IIb/IIIa antagonists should be started immediately and kept running until the time of angiography depends on local policies and should be discussed with a cardiologist. Evidence suggests that all patients having PCI benefit from IIb/IIIa antagonists. If the patient is not already on a GP IIb/IIIa antagonist, one is usually started in the catheter laboratory, just prior to the procedure, and continued for 12–24 hours afterwards.

• There is no benefit in the use of GP IIb/IIIa antagonists in patients who are going to be treated with medical therapy only and/or are not candidates for angiography.

Other therapies used in ACS

• Glucose-insulin-potassium (GIK) infusions. These are not given routinely but there is some evidence that they are beneficial in some ACS patients.

• IV magnesium. There is no evidence that routine use of this is of any benefit in ACS patients.

Secondary prevention and medical treatment

• Lifestyle advice and rehabilitation should ensure that all patients:

• stop smoking and be referred to a smoking cessation clinic if necessary

• start a low-cholesterol diet

• lose weight (with the aim of reaching their optimal weight)

• follow an appropriate exercise programme to improve their physical fitness.

• Education and advice regarding when patients can resume various activities (e.g. work, driving and sexual intercourse) should also be provided. Specialist cardiac rehabilitation nurses usually do this and offer a rehabilitation course. All diabetics should be referred to a clinic/diabetic nurse to ensure that their diabetes is kept under adequate control.

Pharmacological treatment

All ACS patients should be prescribed (and be discharged on) all of the following medications:

• Aspirin. Dosage is 75 mg once daily.

• ACE inhibitors. There is good evidence that all ACS patients benefit from an ACE inhibitor and that those with LV dysfunction benefit the most. An ACE inhibitor should be prescribed at the earliest safe opportunity (within the first 24 hours if possible) in all patients, provided they are not hypotensive and/or do not have significant renal dysfunction. Start with a low dose (e.g. ramipril 2.5 mg in the evening) and gradually titrate the dose upwards, aiming for the target dose (e.g. ramipril 10 mg once daily). Angiotensin II receptor antagonists (ARBs, e.g. valsartan) 160 mg twice daily is used in patients intolerant of ACE inhibitors.

• Beta-blockers. These reduce heart rate and thus myocardial oxygen demand, and should be given to all ACS patients once they are haemodynamically stable (provided there are no contraindications). Aim for a resting heart rate of < 60 bpm with either atenolol 25–100 mg once daily or metoprolol 25–100 mg 3 times daily.

• Statins (HMG-CoA reductase inhibitors). All patients should be started on a statin within the first 24 hours of hospital admission, irrespective of their lipid profile, e.g. atorvastatin 80 mg daily (p. 617). There is increasing evidence that, in addition to their beneficial lipid-lowering effect, statins also have other beneficial effects in ACS, such as a plaque stabilization. In the first 10 days intensive treatment aims for an LDL-C of < 1.8 mmol/L (70 mg/dL). After this, the dose may be lowered to aim for an LDL-C of < 3 mmol/L (114 mg/dL). After discharge from hospital, patients should be continued indefinitely on their statins; generally, the lower the cholesterol, the better the outcome. A serum cholesterol of < 5 mmol/L (190 mg/dL) (LDL-C < 3 mmol/L (114 mg/dL)) or a reduction by 30%, whichever is greater, should be achieved.

Full fasting lipid profiles should be obtained in all patients with CAD, to include LDL-C, HDL-C and triglycerides. Diet must be modified (p. 617), as this will improve the lipid profile in addition to medical therapy, e.g. bezafibrate 200 mg 3 times daily, used in addition to a statin in patients with a low HDL-C. Patients who have any of the following will need further assessment, treatment and family screening, if necessary, in the lipid clinic:

• no response to statin therapy

• a markedly elevated LDL-C

• a markedly elevated serum triglyceride

• an unusual lipid profile.

In addition to the four agents listed above, all ACS patients who have had an MI (STEMI or NSTEMI) should be given:

• Clopidogrel. In patients with a STEMI, clopidogrel should be continued at 75 mg orally once daily for at least 4 weeks (COMMIT trial). However, there may be a benefit with longer-term treatment (CURE trial) and the ESC guidelines recommend use of clopidogrel for 12 months. In NSTEMI clopidogrel 75 mg once daily should be continued, in addition to aspirin, for at least 12 months.

• Prasugrel. This drug (10 mg daily) is being used instead of clopidogrel; it has a more rapid action and greater platelet inhibition.

The following may also be of use in ACS patients:

• Oral nitrates. These can be used if additional anti-anginal medications are needed. They do not improve prognosis.

• Calcium channel blockers. These can be used as an alternative agent in patients who cannot tolerate β-blockers and need anti-anginal therapy. Non-dihydropyridine calcium antagonists are used, e.g. diltiazem 60 mg 3 times daily, up to max. dose of 360 mg daily, or verapamil slow-release 120–480 mg daily. Avoid short-acting calcium antagonists, e.g. nifedipine, as they may increase mortality.

The following should be given in particular circumstances:

• Oral anticoagulants. There is no proven benefit for warfarin therapy in post-MI patients unless they have specific indications. The absolute cardiac indications for warfarin include atrial fibrillation, LV dysfunction with a documented embolic event, LV aneurysm and documented LV thrombus. Relative cardiac indications include severe LV dysfunction and an extensive anterior wall motion abnormality. Oral anti-thrombin agents, e.g. dabigatran may well replace warfarin.

• Eplerenone. 25 mg once daily, an aldosterone antagonist, should be given to all who have post-M1 heart failure.

Pre-discharge risk stratification and follow-up

All STEMI patients who have received successful fibrinolysis should proceed to a coronary angiogram. Those with a low risk, or if coronary angiography is not immediately available, should have a submaximal (modified Bruce) pre-discharge exercise test for risk stratification or an early outpatient (usually 6 weeks post discharge) symptom-limited (full Bruce) exercise test. Alternative non-invasive imaging (e.g. dobutamine stress echocardiography) should be used when exercise testing is contraindicated. Patients who have had successful PCI do not need routine exercise tests prior to discharge. Exercise testing is now less often performed, being replaced by a functional imaging study.

All ACS patients should be seen 4–6 weeks post discharge in the outpatient clinic to ensure that they are receiving appropriate secondary prevention, to up-titrate drug doses as necessary, to review symptoms and investigations, and to assess any need for further investigation and/or revascularization.

Management of complications of ACS

Refractory ischaemia

Any patient who develops recurrent ischaemia should be on or restarted on full medical therapy (heparin, nitrate and β-blocker) and moved to a monitored bed on CCU. If, despite full medical therapy, patients continue to have refractory ischaemia, they need urgent PCI.

Cardiogenic shock

Cardiogenic shock is associated with a very high mortality (70–80%). It is defined as an inadequate circulation (due to reduced cardiac output and hypotension) to meet the peripheral metabolic needs (usually manifested by oliguria or anuria and/or mental status changes). It is characterized by a low systolic pressure (usually < 90 mmHg) and adequate or high central filling pressure (pulmonary capillary wedge pressure ≥ 12 mmHg).

• Correctable causes for hypotension (inadequate filling, drugs (notably nitrate infusions), arrhythmias and electrolyte disturbances) need to be excluded.

• Patients need continuous invasive monitoring and high-dependency nursing care (at least a level 2 critical care bed).

• Central venous and arterial lines should be inserted. A pulmonary artery catheter is only occasionally necessary.

• Urgent bedside echo is essential to assess ventricular function and rule out other structural causes of hypotension.

• Serial ECGs should be performed.

• Give oxygen via a face mask (35–55%).

• Aim for a pulmonary wedge (filling) pressure of > 15 mmHg. If the patient remains hypotensive despite an adequate filling pressure, start dobutamine 5–10 mcg/kg and titrate this to aim for a systolic pressure of at least 90 mmHg.

• Patients with cardiogenic shock often require intra-aortic balloon pumping (IABP) urgently if they do not respond to dopamine therapy.

Patients with cardiogenic shock as a result of ischaemia need urgent angiography and percutaneous revascularization. This must be done urgently (N.B. Referring patients after 24 hours is too late!). Thrombolytic therapy should only be given when PCI is not available. Patients with cardiogenic shock due to other mechanical causes (e.g. ventricular septal defect) require surgery.

Right ventricular infarction

The treatment of cardiogenic shock due to right ventricular infarction is quite different from that due to LV infarction. Patients with RV infarction are dependent on high filling pressures and IV fluid loading is needed to optimize cardiac output. Avoid vasodilator drugs if possible.

Mechanical complications post MI

• Mitral regurgitation. Acute mitral regurgitation can be due to either papillary muscle ischaemia/rupture or mitral annulus dilatation. Papillary muscle ischaemia/rupture usually presents as acute haemodynamic deterioration with acute pulmonary oedema. On auscultation a pan-systolic murmur may be present. An echocardiogram will confirm the diagnosis and allows a full anatomical and functional assessment. Supportive therapy is required, including insertion of an IABP as a bridge to urgent mechanical therapy (PCI for ischaemic papillary dysfunction and valve replacement for papillary rupture).

• Ventricular septal defect (VSD). This usually occurs within the first 24 hours post thrombolysis and in patients who have not received thrombolysis either on day 1 or days 3–5. VSDs usually present with acute pulmonary oedema and haemodynamic deterioration; chest pain may be a feature. There is usually a loud pan-systolic murmur on examination. An echocardiogram shows the size and location of the defect. Supportive therapy is required, including insertion of an IABP as a bridge to surgical repair.

• Free wall rupture. This usually presents as either a cardiac arrest or acute haemodynamic compromise. Patients very rarely survive the initial insult. If they do, then pericardiocentesis (to relieve tamponade) and IABP insertion may act as a bridge to surgical repair, which is the only definitive treatment.

Heart failure

This is a poor prognostic feature post MI. Acute heart failure should be followed up and treated by the heart failure team (p. 419). An echocardiogram allows assessment of ventricular function and identification of other potentially treatable contributing causes (e.g. VSD). Any reversible causes, such as arrhythmia, ischaemia and drug therapy, need treatment. Any patients with an ejection fraction of < 35% is at high risk of SCD and must be discussed with a cardiologist (ideally, an electrophysiologist) prior to discharge, as they will benefit from insertion of an ICD, which can detect and treat dangerous ventricular arrhythmias.

Arrhythmias and bradycardias

Any arrhythmia that results in haemodynamic compromise needs urgent aggressive therapy; DC cardioversion should be used if necessary. Any contributing factors to an arrhythmia should be treated if possible (e.g. electrolyte disturbances). Reperfusion arrhythmias, such as ventricular ectopics, non-sustained ventricular tachycardia and accelerated idioventricular rhythm, are common and do not routinely need treatment.

• Supraventricular tachycardias (SVT). AF is common post MI and occurs in up to 20% of patients. Cardioversion is possible but relapse is frequent. Rate control with digoxin, β-blockers and prevention of thrombotic complications with warfarin are often required. Other SVTs should be treated (p. 403).

• Ventricular tachycardia (VT)

• Non-sustained VT (three or more beats of VT, <30 secs in total) is common in the first 24 hours post MI and carries no adverse risk or need for treatment. If non-sustained VT occurs later than 24 hours post MI it carries a risk and should be treated (p. 406).

• Sustained VT occurring in post-MI patients is associated with an increased mortality. It must be treated with urgent synchronized DC cardioversion if there is haemodynamic compromise; this should be followed by prophylactic drug therapy (p. 406). If the patient is initially stable, an IV β-blocker may be tried but this should be discussed with an electrophysiologist first.

• Recurrent VT in patients who have had revascularization needs further investigation by an electrophysiologist with possible insertion of an implantable defibrillator.

• Bradycardias and heart block. These are common post MI, especially with an inferior MI. If sinus bradycardia is associated with hypotension, it can be treated with IV atropine 0.3–0.5 mg up to a total of 1.5–2.0 mg.

• First-degree heart block requires no treatment.

• Type I second-degree heart block needs no treatment unless there is haemodynamic compromise, in which case atropine should be used first, and failing this, pacing.

• Type II second-degree (Mobitz II) and third-degree (complete) heart block need pacing if there is haemodynamic compromise or a broad escape rhythm.

If the patient is haemodynamically stable, then close monitoring on CCU is appropriate. In patients with an inferior STEMI, reperfusion should not be delayed, unless the patient is haemodynamically compromised, as heart block usually resolves with successful reperfusion. If pacing is required, then temporary transvenous pacing is used. However, those with persistent Mobitz II or complete AV block after 10 days are likely to need a permanent pacemaker inserted; this is usually the case with anterior infarcts.

Pericarditis and Dressler’s syndrome

• Pericarditis is common post MI; it is necessary to rule out ischaemia before making the diagnosis. Treatment is with high-dose aspirin 600 mg every 4 hours. There is no good evidence to support the use of oral steroids. Patients on oral anticoagulants may develop haemorrhagic effusions that necessitate drainage.

• Dressler’s syndrome is a form of autoimmune pericarditis that occurs 2–10 weeks post infarct. Treatment is with high-dose aspirin 600 mg every 4 hours.

• NSAIDs are best avoided in patients up to 4 weeks post MI, as they may impair infarct healing; after this they can be used.

Management of chronic stable angina

Risk stratification and investigation

These patients are usually referred to a rapid-access chest pain clinic or an outpatient clinic; they may occasionally present in A&E. Based on age, sex, history and a 12 lead ECG, a diagnosis of angina can be made, and the patient treated for angina. An exercise ECG is now not recommended (NICE guidelines) if the likelihood of coronary artery disease (CAD) is more than 90%. If there is doubt, CT calcium scoring (p. 432) can be helpful. If the score is 1-400, CT coronary angiography should be performed. If the angiogram shows CAD, treat as angina; if there is doubt perform functional tests. These tests include myocardial perfusion scintigraphy with single photon emission computed tomography (MAS with SPECT), stress echocardiography or contrast enhanced MR, depending on availability of the tests. Exercise ECGs are still being performed.

ECG exercise test

This is useful in patients with suspected chronic stable angina for risk stratification. It is however being superseded in many hospitals by non invasive imaging (see above).

• In properly selected patients it has a 75% specificity and 68% sensitivity.

• A Bruce or modified Bruce protocol is used. The patient walks on a treadmill with increasing speed and incline; BP, heart rate symptoms and ECG are monitored during and after the test. A positive test is indicated by an inability to exercise > 2 mins, new ST depressions of > 1 mm in multiple leads, hypotension, heart failure or sustained ventricular arrhythmias, and a post-exercise interval of > 5 mins for ischaemic ST changes to return to normal.

• Patients with suspected ACS should not be subjected to exercise testing, e.g. an acute MI in the previous 2 days or unstable angina.

• Other contraindications include severe aortic stenosis, severe heart failure, acute PE, pericarditis, myocarditis, aortic dissection, physical immobility and a pacemaker.

• Exercise testing is not as helpful in young and middle-aged women or patients with LBBB, and alternative non-invasive investigations, e.g. stress echocardiography, should be used.

If an exercise ECG is contraindicated, then an alternative form of non-invasive imaging should be used, e.g. radionucleotide myocardial perfusion imaging or stress echocardiography.

Coronary angiography

If patients have a positive exercise test, coronary angiography is helpful in the following conditions:

• severe stable angina (i.e. marked limitation of ordinary activity, e.g. climbing one flight of stairs at a normal pace), especially if symptoms are inadequately responding to medical therapy

• chronic stable angina (i.e. slight or no limitation of ordinary activity) and a history of MI or ischaemia at a low workload

• chronic stable angina in patients with bundle branch block with readily inducible ischaemia demonstrated by non-invasive imaging

• patients with stable angina being considered for major vascular surgery

• patients with serious ventricular arrhythmias, e.g. survivors of cardiac arrest

• patients who have been revascularized (PCI or coronary artery bypass graft (CABG)) with recurrent angina

• when it is essential to establish a diagnosis for occupational reasons.

Revascularization

• Left main stem stenosis or proximal triple vessel disease. These patients are generally referred for CABG surgery first. If they are not fit for surgery (e.g. due to severe co-morbidity) or refuse it, then PCI is the second choice. There is a proven benefit in terms of reduced mortality and MI rate from revascularization in patients with either of these patterns of disease.

• Other patterns of disease. These patients should be referred for PCI. Revascularization in this group of patients is an excellent treatment for symptomatic angina but provides no benefit in terms of either mortality or reduced MI rate. Diabetic patients with multi-vessel disease tend to do better with surgery than with PCI.

Secondary prevention and medical treatment

All patients should follow lifestyle advice (p. 441) and should be on aspirin 75 mg, a statin, an ACE inhibitor and a β-blocker (p. 441). All should be given a GTN spray to use as required. In addition, the following may be used as second-line anti-anginal treatments:

• Nitrates. Long-acting nitrates provide good symptomatic relief (e.g. isosorbide mononitrate up to 120 mg daily, in divided doses). Slow-release GTN patches are also available. Tolerance can be a problem with nitrates.

• Calcium channel blockers. Due to its rate-slowing properties diltiazem 60 mg daily up to total maximum dose of 360 mg can be used when β-blockers are contraindicated. It should only be co-prescribed with a β-blocker under close supervision. In patients on a β-blocker who need additional anti-anginal therapy, a dihydropyridine group such as long-acting nifedipine, e.g. 30–90 mg daily, or amlodipine 5–10 mg daily can be used, as these do not slow the heart rate.

• Nicorandil. This is good at relieving angina and has been shown to provide a reduced event rate in clinical trials. Give 10–30 mg orally × 2 daily.

• Ivabradine. This is an I_f channel inhibitor that reduces heart rate and has been developed as an anti-anginal drug. The usual dose is 2.5–7.5 mg orally twice daily. Reversible visual symptoms are reported at the higher dose. Ivabradine should not be co-prescribed with β-blockers or diltiazem.

• Ranolazine. This drug interacts with sodium channels but can cause QT interval prolongation. It is used if other drugs do not help.

• Eplerenone. This aldosterone antagonist is given 25 mg/day to patients post MI with clinical evidence of heart failure and reduced ejection fraction (monitor serum K⁺ levels).