Junctional tachycardia This term should only be used for focal tachycardias that originate from the AV nodal tissue directly, and are in fact rare in adult cardiology. Distinction fr om other forms of NCT is only possible at the electrophysi- ology (EP) study. RFA is high r isk as the AV may be damaged. B -blockers and \202 ecainide are effective. Further reading Blomstrom-Lundqvist C , Scheinman MM , Aliot EM , et al. ( 2003 ). ACC/AHA/ ESC guidelines for the management of patients with supraventricular arrhythmias . J Am Coll Cardiol 42 : 1493 \200\223 531 . JUNCTIONAL TACHYCARDIA 499 I aVR V1 V4 II aVL V2 V5 III avF V6 V3 II Fig. 10.8 Typical presenting ECG of AVNRT or AVRT. A narrow complex tachycardia without vis ible P waves. FP AVN SP Left side AP Fig. 10.9 Mechanism of AVNRT and AVRT. Both AVNRT and AVRT have re-entry mechanisms. Orthod romic AVRT via a left-sided accessory pathway (AP) (left). Activation from A to V is down t he atrioventricular node (AVN), then across the ventricular myocardium and back from V to A up the AP, thus completing the circuit. The ventricle therefore is an essential part of th e circuit. Antidromic AVRT (not shown) would activate in the opposite direction. Typical AV NRT (right) acti- vates from the atrium to the AVN via the slow pathway (SP) and from the A VN to the atrium via the fast pathway (FP), thus completing the circuit. The ventricle is a ctivated as a bystander via the bundle of His and is not an essential part of the circuit. Atypical AVNRT (not shown) activates in the opposite direction. 500 CHAPTER 10 Arrhythmias Atrial \201 brillation Atrial \201 brillation (AF) is the most common sustained cardiac arrhythmia, with a prevalence of 0.5 \200\2231 % in the general population but 10-fold gre ater in those aged over 65 years. It is an atrial arrhythmia where uniform acti- vation is replaced by chaos, such that co-ordinated contractile function is lost and the atria dilate . It is characterized by an ECG lacking any con- sistent P waves, and a rapid, irregular ve ntricular rate. Classi \201 cation Previously, many terms have been used to pre \201 x AF; however, an in ter- national consensus on nomenclature has now been reached. 1 This allows the correct sel ection of management options for patients. All episodes of AF lasting greater than 30 s sho uld be described as: \200 \201 rst detected or a recurrent episode \200 self-terminat ing or not self-terminating \200 symptomatic or asymptomatic . \200 paroxysmal (if self -terminating within 7 days) \200 persistent (if cardioverted to SR by any means or lasts > 7 days regardless of how it terminates) permanent (if cardioversion to SR is not possible or is not undertaken) \200 lone (in the absence of underlying structural heart disease), or idiopathic (in the absence of any disease). Causes AF is a common end-point for many forms of cardiac disease where atrial myocytes are damaged or subject to adverse stress generated by ischaemia, cyanosis, or elevated intraca vity or pericardial pressures. These changes alter the conduction properties of the myocard ium, facilitating \201 brillation (see Table 10.1 ). Table 10.1 Causes of atrial \201 brillation Common causes Potentially reversible causes Rare causes Hypertension \200 Left ventricular (LV) failure (any cause) \200 Coronary artery diseas e (CAD) \200 Mitral or tricuspid valve disease \200 Hypertrophic obstructive cardiomyop athy (HOCM) Alcohol binge \200 Pneumonia \200 Hyperthyroidism \200 Acute MI \200 Acute pericard itis \200 Myocarditis \200 Exacerbation of Congenital heart disease Autonomic \200\230vagal \200\231 overactivity Pericardial effusion \200 Cardiac metastases \200 Myocardial in \201 ltrative diseases (e.g. amyloid) \200 Atrial myxoma pulmonary disease \200 Pulmonary embolism \200 Cardiac surgery 1 Levy S, Camm AJ, Saksena S, et al. (2003). International consensus on nomenclature and cl assi \201 cation of atrial \201 brillation. J Cardiovasc Electrophysiol 14: 443 \200\223 5. ATRIAL FIBRILLATION 501 Symptoms and signs Palpitations, dyspnoea, fatigue, presyncope, syncope, and chest pain are common; however, 30 % of patients present with AF as an incidental \201 nding only. Ambu latory monitoring reveals that even patients with symp- tomatic paroxysmal AF have many asy mptomatic episodes. Physical \201 nd- ings are an irregular pulse (which if rapid will be faster at the apex than the wrist), variable intensity of the \201 rst heart sound, and absent \200\230a \200\231 waves in the JVP. 502 CHAPTER 10 Arrhythmias Atrial \201 brillation: investigations A reversible cause should be identi \201 ed early to allow appropriate treat- ment. The most important investigations are:1 \200 ECG : irr egular ventricular rate and absence of P waves. V rate depends on intact AV nodal function. In the presence of complete AV nodal block, a slow regular ventricular escape rhythm is pr esent. The QRS will be broad if there is aberrant conduction; ST \200\223T-wave changes may be due to rapid rate, digoxin, or underlying cardiac disease. ECHO transoesophageal echocardiography (TOE) : for LV function, valve lesions, pericardi al effusion, and to exclude intracardiac thrombus prior to version to SR. LA size is an imp ortant predictor of likely future maintenance of SR. thyroid function : thyrotoxicosis may present as AF only. \200 CXR: cardiomegaly, pulmona ry oedema, intrathoracic precipitant, valve calci \201 cation (mitral stenosis (MS)). urea and electrolytes (U&Es) : hypokalaemia, renal impairment. \200 troponin or cardiac e nzymes: ?MI. Expect small rise after DC shock. Troponin may be elevated with any prolonged tachycardia without an acute coronary syndrome. drug levels : especially if taking digoxin. \200 arterial blood gasses (ABGs) : if hypoxi c, shocked or ?acidotic. \200 other investigations depend on suspected precipitant. Other investigations when the patient is stable 24-hour ambulatory monitor to assess heart- rate control and look for episodes of symptomatic bradycardia, exercise test (or other isch aemia stress test), coronary angiography, cardiac magnetic resonance. 1 Wyse DG , Waldo AL , DiMarco JP et al. ( 2002 ). A comparison of rate control and rhythm control in patients with atrial \201 brillation . N Engl J Med 347 : 1825 \200\223 33 . This page intentionally left blank 504 CHAPTER 10 Arrhythmias Atrial \201 brillation: management (see Fig 10.10) The most important aspects of AF manag ement are preventing stroke and controlling patients \200\231 symptoms, not restoration of SR. Limiting the ven- tricular rate by pharmacologically blocking the atrioventricular (AV) node ( rate control ) is safe and often effective. Currently available antiarrhythmic drug s (AADs) that maintain SR ( rhythm control ) are limited by their toxicity and ef \201 cac y, which explains why a strategy of rhythm control (electrical cardioversion and AADs) may be worse than rate control alone. 1 Non- pharmacological strategies (ablation) and new effe ctive, safer AADs for rhythm control may change this paradigm in the future. Fig. 10.10 sum marizes contemporary AF management. Emergency management If the patient is haemodynamically compromised, then urgent external D C cardioversion under general anesthesia or sedation is needed. This is rarely necessary, a nd rate control is usually suf \201 cient to control symptoms. If symptoms persist despite rate control, cardioversion can be attempted pharmacologically with \202 ecainide (2 mg/ kg, max 150 mg, infused via a peripheral line over 30 min) or if LV impairment is suspected , amiodarone (5 mg/kg, max 300 mg infused via a central line). Patients must be moni- tored throughout for possible ventricular arrhythmia and hypotension. If AF has been present for > 48 hours, cardioversion should be preceded by a TOE to exclude atrial thrombus . All pat ients should be warfarinized for at least 4 weeks post cardioversion. Rate control Drugs: The \201 rst-line agents are B -blockers or non-dihydropyridine calci um- channel antagonists (verapamil or diltiazem), which are effective during both exercise and rest. Digoxin is effective at rest only, and should be considered a second-line agent. Rate control can be assessed by a 24-hour Holter monitor ensuring heart rates; at rest thes e are <80 bpm, mean <100 bpm, during moderate exercise <120 bpm. Pace and ablate: See below. Rhythm control If symptoms are not improved by rate control alone, or a reversible cause of AF has been treated, then rhythm control should be attempted. The trials of rate vs. rhyth m control under-represent younger patients (<65 years old), so in this group an aggressive strategy of rhythm control may be warranted regardless of symptoms. For persistent AF, SR i s restored by DC cardiover- sion. AADs or non-pharmacological methods are usually needed to maintain sinus rhythm. Drugs: Flecainide, propafenone, sotalol, disopyramide, and quinidine are all more effective than placebo in maintaining SR. They all can lead to long QT-related VT/VF and are contrai ndicated in patients with structural heart disease. Amiodarone is the most effective drug; however, its use is limited by non-cardiac side-effects, and it is not tolerated by up to 2 5 % . If AV nodal 1 NICE 2006 guidelines for anticoagulation in AF. ATRIAL FIBRILLATION: MANAGEMENT 505 function and QT interval are normal, these drugs can safely be started out of hospital. QRS width and QT interval should be monitored on a weekly basis until a target maintenance dos e is reached. Catheter and surgical ablation: This is the most effective method of maintaining SR but car ries a small procedural risk (see b Catheter ablation of atrial \201 brillation, p. 568). Pacemakers: Various pacemaker strategies are useful in maintaining SR. Atrial pacing modes (AAI or DDD) are mandatory, as they reduce the AF burden. \200 \200\230Vagal AF \200\231 is prevented by pacing. \200 SAN disease symptoms are improved by a \200\230block and p ace \200\231 regimen, i.e. rate-controlling drugs for AF and pacing for bradycardic episode s. \200 Algorithms to suppress atrial ectopy, or multisite atrial pacing, are not very effective strategies to prevent AF. Pace and ablate : this is a palliative strategy when symptoms continue because adequate rate or rhythm control is not possible with drugs or by other means such a s ablation. A pacemaker is implanted, and 6 weeks following this, iatrogenic irreversible c omplete heart block is induced with radiofrequency ablation. This can bring dramatic sympto m improvement; however, patients are rendered pacing dependent. SYMPTOMS SCREENING INCIDENTAL AF Ventricular rate control Underlying cause? Stroke risk? Disabling symptoms? Treat underlying cause Aspirin or nothing Restore SR Warfarin Fig. 10.10 Contemporary management of atrial \201 brillation. 506 CHAPTER 10 Arrhythmias Anticoagulation Warfarin (international normalized ratio (INR) > 2) reduces strokes in AF b y 60 % , regardless of underlying risk, and is the current standard by which other anticoag ulation strategies are judged. Unfortunately, not all eligible patients receive it. Problem s are that it can be subtherapeutic (INR too low) or cause bleeding complications (INR too high). Decisions on whether to use warfarin long term depend on the patients \200\231 overa ll stroke risk, and no distinction should be made between paroxysmal, persistent, or perman ent AF. The CHADS2 (Congestive heart failure, Hypertension, Age > 75, Diabetes mellitus, an d previous Stroke; see Table 10.2 ) score is a very simple stroke risk calculator (warfarin needed if score (cid:2) 2). More complex guidelines are available from the National Instit ute for Health and Clinical Excellence (NICE). 1 Therapeutic anticoagulation with warfarin is always needed for at least 4 weeks pre- (unless TOE performed) and 4 weeks post-cardiove rsion. Aspirin (75 \200\223300 mg) has been shown in a meta-analysis to reduce strokes in AF by 20 % ; however, it is not clear whether this bene \201 t is due to its effects on vascular d isease rather than thrombogenesis per se. It is inferior to warfarin. Aspirin + clopidogrel (75 mg + 75 mg) has a lower annual stroke rate than aspirin alone (2. 4 % vs. 3.2 % ), but is not as effective as warfarin, even though it carries the same risk of bleeding complications. It should not be considered an equivalent alternative to warfari n. New pharmacological agents: Direct thrombin inhibitors are currently under evaluation but n ot yet licensed. Dabigatran 150 mg bd has been shown to be more effective than warfarin, wi th the same incidence of bleeding complications. At 110 mg bd, it is equivalent to warfarin with less bleeding. Monitoring of INR is not needed. Likely problems are compliance (needs to be taken twice daily), reversal of anticoagulation in emergency, and cost. Left atrial appendage occlusion: Most strokes in AF are due to thrombus emerging from the L A appendage. A custom-made Nitinol mesh (Watchman ) can be delivered percutaneously via the femoral vein and a trans-septal puncture to the appendage. The mesh endothelializes ove r, occludes the appendage, and prevents it acting as a source of thrombus for strokes. Equi valence to warfarin has been demonstrated; however, there is a small procedural risk of str oke and tamponade. 1 NICE 2006 guidelines for anticoagulation in AF ATRIAL FIBRILLATION: MANAGEMENT 507 Table 10.2 CHADS2 scoring system to assess risk of stroke in AF a Condition Score C ongestive heart failure 1 H ypertension 1 A ge > 75 years 1 D iabetes 1 Previous S troke or transient ischaemic attack (TIA) 2 Patients with paroxysmal, persistent, or permanent AF with score \211 2 are at high risk of stroke and should receive warfarin (INR 2 \200\2233) unless there is a contraindication a Fuster V, Ryden LE, Asinger RW, et al (2001). ACC/AHA/ESC Guidelines for the Management o f Patients with Atrial Fibrillation. Circulation 104 : 2118 \200\22350. 508 CHAPTER 10 Arrhythmias Ventricular tachycardia This section deals with diagnosis and pharmacological management. M echanisms and ablation are discussed in detail in Chapter 11. The most important distinctio n is the presence of structural heart disease. Impaired LV function is the strongest predic tor of a poor prognosis. Normal heart VT (benign VT) Right ventricular out \202 ow tract (RVOT) tachycardia This is due to automatic \201 ring cells in the RVOT, giving a character- istic ECG pattern of L BBB with a strongly inferior axis (see Fig. 10.11 ). Paroxysms of palpitation are related t o exercise. The tachycardia is ade- nosine sensitive. Symptoms are usually well controlled by verapamil or B-blocker, but RFA is a successful curative option. Care must be taken to e xclude arrhythmogenic right ventricular cardiomyopathy (ARVC) as the diagnosis, particularl y if the ECG or ECHO is not typical (see b p. 524). LVOT tachycardia (RBBB + inferior axis) is also recognized. Fascicular tachycardia Its mechanism is uncertain; however, activation emerges from the lef t posterior fascicle. ECG typically shows RBBB with superior axis (see Fig. 10.12 ). It is sensitive to IV verapamil (which normally slows then termi- nates it) but not adenosine. Sy mptoms are well controlled with oral vera- pamil but RFA offers a cure. NORMAL HEART VT (BENIGN VT) 509 Fig. 10.11 Intermittent RVOT tachycardia and sinus rhythm. During the tachycardia beats, no tice the LBBB appearance and the positivity in leads II, III and aVF, indicating an inferio r axis. Fig. 10.12 12-lead ECG of fascicular tachycardia suggested by broad-complex tachycardia wit h RBBB appearance and superior axis. 510 CHAPTER 10 Arrhythmias VT with impaired LV function Symptoms Palpitations, chest pain, presyncope, syncope, dyspno ea, pulmonary oedema, and sudden death can all occur. How well patients tolerate the arrhyt hmia depends on their LV function and the tachycardia rate. Etiology Any cause of impaired LV function can cause VT. Common causes are coronary artery disease, dilated cardiomyopathy, and HOCM. They are due to re-entry around areas of scarred or diseased myocardium. VT may rapidly deteriorate to VF and these patients die suddenly. General management It is essential to treat the underlying heart failure and cause (angiote nsin-converting enzyme inhibitors (ACE-Is, B -blockers, diuretics, nitrates, statins). This reduces not only symptoms, but also the incidence of arrhythmia. B -Blockers Long-term antiarrhythmic reduce arrhythmia and sudden cardiac death (SCD), but the impact o f other drugs is minimal and often harmful. Flecainide, propafenone, and sotalol all increa se mortality and should be avoided, except in patients with implantable cardiac de \201 br illators (ICDs) under supervision of an electrophysiologist. Amiodarone and mexiletine have a neutral impact on prognosis but may reduce the number of VT episodes in very symptomatic patients. RFA is only possible when VT is slow and haemodynamically well tolerated, theref ore limiting its use. treatment Preventing SCD ICDs have dramatically improved survival for these patients. This page intentionally left blank 512 CHAPTER 10 Arrhythmias Palpitations: general approach These are a patient \200\231s awareness of their own heart b eat, whether normal, too fast, too slow, or irregular. Causes (see Table 10.3) Palpitations is generally a benign condition, with most people pres enting to a cardiologist having ectopic beats only or no underlying arrhythmia at all. Palp itations caused by ventricular arrhythmia or bradycardia are unusual but require urgent inv estigation and treatment. Palpitations are commonly found in patients with anxiety or depre ssion. Table 10.3 Causes of palpitations Arrhythmia Sensing own heart rhythm Not related to heart Depression \200 Anxiety Normal \200 Hyperdynamic circulation Atrial or ventricular ectopic beats \200 AF paroxysmal or pregnancy \200 hyperthyroidism \200 anemia \200 fever persistent Other supraventricular tachycardia (SVT) Physiological tachycardia VT \200 Bradycardia; AV or sinus node disease exercise \200 anxiety \200 caffeine Evaluation \200 Elicit a careful description of the symptoms and ask the patient to tap o ut the rhythm on a desk. Missed beats, sudden thumps, symptoms lasting a few seconds sugges t atrial or ventricular ectopics; sudden onset/ offset with rapid heart beat suggest SVT; a nd irregularity suggests AF. \200 Beware associated syncope, near syncope, or chest pain; these suggest a more sinister cause \200\224 ventricular arrhythmia or bradycardia. \200 Carefully rev iew drugs for potential causes. What is the patient \200\231s caffeine and alcohol intake? Look for evidence of structural heart disease (previous MI, murmur, signs of heart failure, abnormal ECG); these make ventricular arrhythmia more likely. \200 Is the patient thyrotoxic? PALPITATIONS: GENERAL APPROACH 513 Investigations 12-lead ECG Look for tachycardia/bradycardia (see previously). Evidence of previous MI Blood tests FBC (anemia?), biochemistry, thyroid function Ca 2 + , Mg2 + (especially if on diuretics) B iochemical markers of cardiac injury ECHO Extremely helpful even if just to reassure the patient. Look for structural heart disease \200\224 old MI, dilated cardiomyopathy, hypertrophiv cardiomyopathy (HCM), etc. If normal, then the prognosis is very good regardless, of arrhythmia Ambulatory (Holter) monitoring Continuous recording of patient \200\231s cardiac rhythm for 24 hours, 48 hours, or 7 days. Correlate the symptom diary with rhythm. Ensure that an appropriate length of recording is used e.g. a 24-hour monitor is pointless if symptoms occur once a month! Event (loop) recorder Cardiac monitor that continually records heart rhythm on a loop of 5 \200\22310 minutes but stores in memory only when activated by the patient during symptoms or if a preset heart r ate is detected (e.g. > 160 bpm or <40 bpm). Can be carried or worn for 2 \200\2234 weeks Implantable If there are palpitations associated with syncope loop recorder (Reveal \204 ) \200 Exercise test If palpitations are precipitated by exertion or associated with chest pain Electrophysiology When a de \201 nitive diagnosis cannot be made by other means but tachyarrhythmia is stron gly suspected study Management If an arrhythmia is identi \201 ed, treat as described previously. In most peop le, either no abnormality or ectopic beats only will be discovered, and reas- surance can b e given. 514 CHAPTER 10 Arrhythmias Syncope: general approach Syncope is a transient loss of consciousness (blackout) due to a disorder of the circulation. It is a medical emergency as it may be the \201 rst manifes- tation of an undiagnosed life-threatening condition. Causes are listed in Table 10.4 and t hey should be distinguished from the much rarer neuro- logical causes of transient loss of consciousness, e.g. epilepsy. Evaluation A systematic process is needed to establish a cause, future risk, and the approp riate management. In 10 \200\22315 % , a cause will not be found. Patients should not be di scharged until a diagnosis has been established (Fig. 10.13 ). \200 A clear history is es sential, including a reliable witness account if available. Was there truly loss of consciousness? An \200\230aura \200\231, tongue biting, tonic \200\223clonic episodes, incontinence (fecal more speci \201 c than urinary), paral ysis, or a prolonged period of disorientation afterwards, all suggest epilepsy. An absent o r minimal prodrome, preceding palpitations or chest pain, and dramatic collapse suggest arr hythmia. A clear precipitating event, e.g. pain or emotion, the description of \200\230clo uding in \200\231 and realization of \200\230going to faint \200\231 suggest re \202 ex s yncope. Are symptoms postural? Carefully review medications for BP-lowering and QT-prolongi ng drugs. Examination may reveal important cardiac lesions. Check L + S BP. Investigations 12-lead ECG Presence of arrhythmia or heart block may reveal the diagnosis. Long QT, WPW, Brugada (afte r \202 ecainide infusion) are all rare causes but may be apparent. Q waves, absent R wave , T-wave abnormalities, BBB, left ventricular hypertrophy (LVH) all suggest underlying stru ctural heart disease. Exercise ECG is indicated for exercise- related symptoms or where isc haemia is suspected ECHO Identifying structural heart disease is the key to management of unexplained syncope. Poor LV function strongly predicts malignant arrhythmias and risk of SCD. Further investigations such as ischaemia stress testing, TOE, MR, coronary angiography, may be indicated to eluci date the diagnosis Carotid sinus massage Simple to perform and may be diagnostic in elderly patients. A profound bradycardia and asy stole may be induced. Avoid in known or suspected carotid vascular disease Ambulatory (Holter) monitoring 24-hour ECG recording has a very low yield for identifying arrhythmia. A negative tape has no value. For patients with poor LV function, VT cannot be excluded in this way. Modern dig ital recorders can store 2 weeks continuously, increasing the yield SYNCOPE: GENERAL APPROACH 515 Implantable For infrequent episodes (less than once a month). It is implanted under the left clavicle u nder local anesthetic and continually records heart rhythm on a loop of 5 \200\22310 minute s but stores in memory only when activated by the patient, e.g. after a syncopal episode loop recorder (Reveal \204 ) Head-up tilt testing When re \202 ex syncope is suspected, this is performed. Patients are strapped to the tabl e and tilted at 60 \200\22380 degrees for 45 min, then if there are no symptoms, provocatio n can be given with glyceryl trinitrate (GTN) or isoprenaline. This will precipitate syncop e in 95 % of sensitive patients. Continuous beat-to-beat cardiac and BP monitoring allows p recise identi \201 cation of whether a heart-rate rise or fall precedes the BP drop Electrophysio logical Useful for the undiagnosed but strongly suspected arrhythmia. Failure to induce VT does ind icate a lower but not absent risk of future events, and therefore is of little value in det ermining the risk of sudden death and who should have an ICD study Table 10.4 Principle causes of transient loss of consciousness Cardiovascular (=syncope) Re \202 ex syncope (due to neurally mediated relexes) has various names: vasovagal ( \200 \230simple faint \200\231), neurocardiogenic syncope, carotid sinus syncope, situation-rela ted (micturition, cough, swallow), etc. Arrhythmia : bradycardia (AV or SA nodal disease), VT, VF, torsades de pointes (long QT syn drome), WPW, SVT (rare) Postural hypotension : elderly, antihypertensive or heart-failure drugs Mechanical problems : severe valvular stenosis, HOCM, PE, pulmonary hypertension, aortic di ssection Neurological Epilepsy, vertebrobasilar ischaemia, migraine Psychogenic Fictitious, hysteria, panic disorders Other Hypoglycaemia, hyperventilation, hypoxia 516 CHAPTER 10 Arrhythmias Syncope Initial evaluation by history, examination, ECG, carotid sinus massage, L+S BP Definite cause found? Yes No Treat appropriately Unexplained syncope Yes No Cardiac structural disease? (evaluate with ECHO if necessary) At risk of ventricular arrhythmia refer to cardiologist for evaluation Episodes rare, and low risk? No Yes Test for neurally mediated syncope. If negative and symptoms persist consider invasive EP t esting and implantable loop recorder Discharge, investigate if symptoms recur Fig. 10.13 Guidelines for evaluation of the syncopal patient. Adapted from: Guidelines on m anagement (diagnosis and treatment) of syncope. European Heart Journal 2001; 22 , 1256 \200 \2231306. SYNCOPE: MANAGEMENT 517 Syncope: management Where a speci \201 c cause or precipitation is identi \201 ed, this s hould be treated or avoided (e.g. pacing for heart block), See speci \201 c chapters. Othe r points to note follow. Structural heart disease Patients with syncope and poor LV function need referral to a card iologist for consideration of ICD prescription, as there is a risk of sudden death Neurally mediated \200\230re \202 ex \200\231 syncope Treating re \202 ex syncope is a c hallenge. Lifestyle advice on avoiding pre- cipitating events (such as prolonged standing) and good hydration may be suf \201 cient. The use of pacemakers (dual chamber with speci \201 c rate- drop-detection algorithms) remains controversial. Asystole or severe bradycard ia detected spontaneously by an implantable loop recorder is a more appropriate indication than when induced by tilt testing. Drugs tried include \202 udrocortisone (to expand intr avascular volume), paroxetine (may interfere with the autonomic re \202 ex arc centrally), B -blockers (to block LV stretch receptors), and midodrine (A-adrenoreceptor agonist); how ever, a signi \201 cant evidence base is lacking. Driving 1 , The Driver and Vehicle Licen sing Agency (DVLA) has set \201 ve diagnostic categories of syncope to evaluate \201 tn ess to drive, ranging from no restric- tions following a vasovagal episode, 6-month license revoke for high risk or unknown cardiovascular cases, and 12 months following a seizure ev ent. 1 DVLA current medical standards of \201 tness to drive Y www.dvla.gov.uk. 518 CHAPTER 10 Arrhythmias Inherited arrhythmia syndromes This group of uncommon diseases attracts a great deal of pub lic interest because of sudden deaths that occur in otherwise healthy and unsuspecting youn g people. The care of patients and affected families has developed into a multidisciplinary subspecialty, involving cardiologists, geneticists, and pathologists. There is an overlap with inherited disorders of heart muscle, e.g. HCM. This section focuses on those condition s with a primary electrical problem, predominantly genetic disorders of the ion channel. Long QT syndrome Long QT syndrome (LQTS) is an autosomal dominant condition charac- terized by a prolonged QT interval on the surface ECG that predisposes to ventricular arrhythmias, syncope, and SCD. The disease may present in fetal life, although genetically affected ind ividuals may remain asymptomatic lifelong. It is estimated that LQTS affects \210 1:2500 o f the population. At a molecular level, genetically encoded mutations in either sodium or p otas- sium ion channels lead to a prolongation of ventricular repolarization and hence QT p rolongation. Over the last 15 years, the genes encoding both potassium and sodium channels have been identi \201 ed, enabling a better understanding of the transition from genetic a nd molecular anomalies to cardiac phenotype Cellular pathology The initial phase (phase 0) of the cardiac action potential (AP) is dete rmined by cellular depolarization via rapid sodium in \202 ux ( I Na ), whereas potassium ef \202 ux governs repolarization, further divided into the slow ( I ks ) and rapid ( I kr ) components of the delayed recti \201 er current, which determine phase 2 and 3 of cardi omyocyte repolarization respectively. Potassium channel mutations lead to a loss of channel function and hence directly delay repolarization and restoration of the resting myocyte vo ltage through a slowed K + ef \202 ux. Mutations in either the slow or rapid component of the delayed recti \201 er current lead to LQTS. Conversely, gain-of-function muta- tions w ithin the sodium channel facilitate a persistent late, slow I Na and thereby prolongation o f depolarization and delayed repolarization. The net effect of either excessive I Na or red uced I k is to prolong the positive charge within the cell and cellular repolarization, whi ch manifests on the surface ECG as prolongation of the QT interval. QT prolongation and the associated after-depolarizations during critical periods in ventricular repolarization cre ate a short \200\223long \200\223short appearance on the ECG ulti- mately, and may precipit ate torsades de pointes (Fig. 10.15 ), a polymor- phic VT that is the hallmark arrhythmia o f QT prolongation. Congenital LQTS: clinical features Congenital LQTS was initially subdivided into two eponym ous syndromes; autosomal dominant Romano \200\223Ward syndrome, and the much rarer autosoma l recessive Jervell \200\223Lange \200\223Nielsen syndrome, which is associated with sensor ineural deafness and a severe cardiac phenotype. This clas- si \201 cation has now been su perseded by different LQTS subtypes based on LONG QT SYNDROME 519 the associated genetic and channel mutation (see Table 10.5 ). Long QT1 is classically asso ciated with syncope or cardiac arrest (due to ventricular arrhythmias) during exercise, par ticularly swimming, whereas in long QT2, symptoms relate to sudden emotional or auditory st imuli, especially if sud- denly waking from sleep. Women with long QT2 experience an increa sed frequency of symptoms in the \201 rst 9 months post-partum. Conversely, symptoms in l ong QT3 are typical at lower heart rates during sleep and rest, and although the frequency of symptoms is lower, the rate of sudden death is much higher. Symptoms of LQTS are misdiag nosed as epilepsy, vasovagal syncope, or breath-holding attacks, with potentially fatal con - sequences. Acquired LQTS (see Table 10.5 ) QT prolongation may result from cranial trauma, severe hypo thermia, elec- trolyte disturbance, bradycardia, and numerous pharmacological agents. These features may precipitate ECG changes and symptoms in patients with latent congenital LQTS. All patients with the congenital form of the disease should be given a list of drugs that must be actively avoided ( Y www.azcert.org ). Investigation and risk strati \201 cation The diagnosis of LQTS is based on the clinical h istory and ECG. The QT interval should be measured in lead II or V 5 and should be correcte d for heart rate according to Bazzet \200\231s formula; QTc = QT/ \210\232(RR)(see Fig. 10. 14 ). Risk strati \201 cation is based on age, sex, QT interval, recent symptoms, and gene tic diagnosis . RR interval Tangent T P U Lead II or V5 Baseline QRS QTc = QT / \210\232RR (sec) QT Fig. 10.14 QT interval is measured in lead II or V 5 from the point of the \201 rst sharp de \202 ection away from the baseline of the QRS interval to the end of the T wave, de \201 ned as the intersection of the baseline and a tangent drawn to the steepest slope of t he last limb of the T wave. Reproduced with permission from Postema et al . (2008). Heart R hythm 5 : 1015 \200\22318. 520 CHAPTER 10 Arrhythmias Long QT syndrome, continued Table 10.5 Characteristics of currently identi \201 ed congenital LQTS Effect of mutation Clinical features LQTS Mutation Ion current a I ks Loss of function Exercise-related syncope I KVLQT1 (CW11) I kr Loss of function Syncope related to sudden emotional or auditory stress II HERG (CW7) I Na Gain of function Symptoms at rest rather than when excited. Young age and usually presents as sudden death III SCN5A (CW3) IV Ankyrin-B (CW4) See below Loss of function \200\224 V KCNE1 (CW21) I ks Loss of function \200\224 I kr Loss of function \200\224 VI KCNE2 (CW21) a Potassium currents ( I k ) are repolarizing and the sodium currents ( I Na ) depolarizing . The ankyrin-B gene codes not for an ion channel but for a cellular structural protein tha t binds sodium ion channels (Splawski I, Shen J, Timothy KW, et al. (2000). Spectrum of mut ations in Long-QT syndrome genes. Circulation 102: 1178 \200\22385.) Common causes of acquired LQTS Drugs *2 \200 Antiarrhythmics : quinidine, procainamide, d isopyramide, \202 ecainide, propafenone, sotalol, ibutilide, dofetilide, amiodarone (rare ) \200 Antimicrobials : erythromycin, clarithromycin, trimethoprim, ketoconazole, itraconazole, chloroquine Antihistamines : terfenadine \200 Other drugs : amitriptyline, \202 uvoxamine, chlorpro mazine, domperidone, cisapride, glibenclamide. Electrolyte imbalance \200 Hypokalaemia, hypomagnesaemia, hypocalcaemia. Severe bradycard ia \200 Complete heart block, sino atrial node disease, hypothyroidism, hypothermia. Note this is not a comprehensive list and LQTS is the commonest single reason for new drugs being withdrawn. When a patient is known to be at risk from LQTS or there is concern that interaction may occur with other QT-prolonging drugs, all drugs and potential interactions. LONG QT SYNDROME, CONTINUED 521 Fig. 10.15 Torsades de pointes. A continuous tracing from three leads of a patient monitore d on CCU. The \201 rst complex is a sinus beat followed by two ectopics. There is then a long pause (2 s) followed by another sinus beat. 522 CHAPTER 10 Arrhythmias Long QT syndrome: management Torsades de pointes (TDP) usually terminates spontaneously, al though it may degenerate to VF. A prolonged episode causing cardiovascular compro- mise nee ds immediate DC cardioversion. For recurrent bursts or following a cardiac arrest, use IV m agnesium bolus and infusion, followed by urgent temporary pacing (at rate 90 \200\223110/mi n) if necessary. Acquired LQTS The underlying cause should be identi \201 ed and reversed. Stop offending d rugs. Give Mg 2 + before getting blood results. K + can be checked rapidly with a blood gas analyzer, replace if less than 4 mmol/L, and aim to achieve high normal levels. An isopren aline infusion can be commenced while waiting to pace. Long-term treatment is not usually n ecessary; however, a permanent pacemaker is required if non-reversible heart block was the cause. Congenital As most events are triggered by sudden increases of sympathetic activity, treatm ent is aimed at preventing this. Beta-blockade is the mainstay and is especially effective in LQT1, although less so in LQT3. Patients should avoid precipitating symptoms. Cardiac pa cing is useful to alleviate the B-blocker- induced bradycardia, and, where pauses have been identi \201 ed, to precipitate symptoms (LQT3). ICDs should only be used with careful con sideration, i.e. for patients at high risk of SCD or where a resuscitated cardiac arrest wa s the \201 rst event. ICDs prevent SCD but not TDP, and recurrent distressing shocks for non-sustained episodes can ruin a patient \200\231s life. Careful patient selection, concom itant use of B -blockers, and shrewd device programming minimizes inappropriate therapies. In resistant cases, or where ICD is contraindicated, left cardiac sympathectomy may be high ly effective. Asymptomatic patients Once a diagnosis of LQTS has been made, screening should be offered t o all family members. Screening (clinical and/or genetic) of affected fami- lies reveals pa tients with LQTS who have never had symptoms and may have normal QT intervals. All patients must be carefully evaluated and the risk determined on an individualized basis. Most patie nts do not die from LQTS but all are at risk (13 % incidence of fatal events over a lifetim e if untreated). A balance must be struck between lifelong treatment with side-effects and the specter of sudden death. Further reading Priori SG , Schwartz PJ , Napolitano C , et al ( 2003 ). Risk strati \201 cation in the long-QT syndrome . N Engl J Med 348 : 1866 \200\223 74 . This page intentionally left blank 524 CHAPTER 10 Arrhythmias Arrhythmogenic right ventricular cardiomyopathy (ARVC) ARVC is an autosomal dominant disord er characterized by \201 brofatty in \201 ltration of ventricular myocardium, which clas sically affects the right ventricle but may also show biventricular involvement. ARVC predo mi- nantly relates to genetically encoded abnormalities in the desomsome, a transmembrane a ssembly of proteins involved in interceullular adhesion and communication. The disease is p rogressive and may be notoriously dif \201 cult to diagnose in its early phases. Diagnosis is made according to international criteria based on electrocardiography, echocardiography , cardiac MR, and histology (see Table 10.6 ). Ventricular arrhythmia typically show a left bundle morphology that is indicative of a righ t ventricular origin, often relating to areas of scar within ventricular myocardium. In sin us rhythm, the ECG may show a broadened QRS and T-wave inversion in leads V 1 \200\223V 3 , and epsilon waves indicating late ventricular activation. The predominant risk is arrhyth mia, although a small proportion of patients progress to heart failure requiring transplant ation. Drug management includes B -blockers, sotalol, amiodarone, and class 1 agents in those with preserved LV function, although as they have limited potential in preventing SCD, an ICD i s warranted in high-risk cases. VT ablation may be acutely successful, but due to continual disease progression, the rate of recurrence is high. Genetic analysis for mutations in the \201 ve major desmosomal proteins should be performed in those with clinical or familial evidence of the disease. ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 525 Table 10.6 Diagnostic criteria for arrhythmogenic right ventricular tachycardia International Task Force Criteria 1994 a Modi \201 ed Task Force Criteria 2002 b Major Minor Con \201 rmed case of familial ARVC in \201 rst-degree relative, plus one of: Mild RV dilatation and reduction of EF Mild RV dilatation and reduction of EF Structural abnormalities Severe RV dilatation and reduction of ejection fraction (EF) Localized RV aneurysms Regional RV hypokinesia Regional RV hypokinesia Mild RV segmental dilatation Severe RV segmental dilatation