Ventricular extrasystoles (Fig. 18-1A) can be due to automaticity or reentry (Chap. 52). PVCs can be a sign of increased sympathetic tone; myocardial ischemia; hypoxia; electrolyte abnormalities, particularly hypokalemia; or underlying heart disease. During myocardial ischemia or in association with other heart disease, PVCs can be a harbinger of sustained VT or VF. In patients with heart disease, a higher frequency of ectopy and complexity (couplets and nonsustained VT) are associated with more severe disease and, in those with heart failure, with increased mortality. However, suppression of these arrhythmias with antiarrhythmic drugs does not improve survival. In the absence of cardiac disease, PVCs and nonsustained VT generally have a benign prognosis. PVCs that occur at a bigeminal frequency may not generate sufficient cardiac output for a radial pulse and hence may register at rates half that of the heart rate (Fig. 18-1A). Very frequent PVCs can depress ventricular function (see below).
Evaluation and management
When encountered during acute illness or as a new finding, evaluation should focus on detection and correction of potential aggravating factors and causes, specifically myocardial ischemia, ventricular dysfunction, and electrolyte abnormalities, most commonly hypokalemia. Underlying heart disease should be defined.
The ECG characteristics of the arrhythmia are often suggestive of whether structural heart disease is present. PVCs with smooth uninterrupted contours and sharp QRS deflections suggest an ectopic focus in relatively normal myocardium, whereas broad notching and slurred QRS deflections suggest a diseased myocardial substrate. The most frequent site of origin for idiopathic ventricular arrhythmias is the right ventricular outflow tract, giving rise to PVCs or VT that have a left bundle branch block configuration, with an inferiorly directed frontal plane axis as discussed below (Fig. 18-2). However, QRS morphology alone is not reliable as an indicator of disease or subsequent risk. Nonsustained VT is usually monomorphic with rates less than 200 beats/min and typically lasts less than 8 beats (Fig. 18-2). Nonsustained VT that is very rapid, polymorphic, or with a first beat that occurs prior to the peak of the T wave (“short-coupled”) is uncommon and should prompt careful evaluation for underlying disease or genetic syndromes associated with sudden death.
A family history of sudden death should prompt evaluation for genetic syndromes associated with sudden death, including cardiomyopathy, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy (see below). Any abnormality on the 12-lead ECG warrants further evaluation (Fig. 18-6). Repolarization abnormalities are seen in a number of genetically determined syndromes associated with sudden death, including the long QT syndrome, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy (ARVC), and hypertrophic cardiomyopathy. An echocardiogram is often necessary to assess ventricular function, wall motion abnormalities, and valvular heart disease. Cardiac magnetic resonance (CMR) imaging is also useful for this purpose and for the detection of ventricular scarring that is the substrate for sustained VT (Fig. 18-5). Exercise stress testing should be performed in patients with effort-related symptoms and in those at risk for coronary artery disease.
Precordial chest leads V1–V3 showing typical abnormalities of arrhythmogenic right ventricular cardiomyopathy (ARVC) (A) and Brugada syndrome (B). In ARVC, there is T inversion and delayed ventricular activation manifest as epsilon waves (arrows). Panel B shows ST elevation in V1 and V2 typical of the Brugada syndrome. (Figures reproduced from F Marchlinski: The tachyarrhythmias. In Longo DL et al [eds]: Harrison’s Principles of Internal Medicine, 18th edition. New York, McGraw-Hill, 2012, pp 1878–1900.)
Idiopathic PVCs and nonsustained VT
For PVC and nonsustained VT in the absence of structural heart disease or a genetic sudden death syndrome, no specific therapy is needed unless the patient has significant symptoms or evidence that frequent PVCs are depressing ventricular function (see below). Reassurance that the arrhythmia is benign is often sufficient to allow the patient to cope with the symptoms, which will often wax and wane in frequency over years. Avoiding stimulants, such as caffeine, is helpful in some patients. If symptoms require treatment, β-adrenergic blockers and nondihydropyridine calcium channel blockers (verapamil and diltiazem) are sometimes helpful (see Table 17-3). If these fail, more potent antiarrhythmic drugs or catheter ablation can be considered. The antiarrhythmic agents flecainide, propafenone, mexiletine, and amiodarone can be effective, but the potential for side effects warrants careful consideration. Catheter ablation can be effective if the arrhythmia occurs with sufficient frequency or is readily provoked such that its origin can be identified for ablation in a similar manner to that for idiopathic monomorphic VT as discussed below. Benefit must be carefully weighed against the procedure-related risks (see below).
PVCs and nonsustained VT associated with acute coronary syndromes
During and early after acute myocardial infarction (MI), PVCs and nonsustained VT are common and can be an early manifestation of ischemia and a harbinger of subsequent VF. Treatment with β-adrenergic blockers and correction of hypokalemia and hypomagnesemia reduce the risk of VF. Routine administration of the antiarrhythmic drugs such as lidocaine has not been shown to reduce mortality and is not indicated for suppression of PVCs or asymptomatic nonsustained VT.
Following recovery from acute MI, frequent PVCs (typically >10 PVCs per hour), repetitive PVCs with couplets, and nonsustained VT are markers for depressed ventricular function and increased mortality, but routine antiarrhythmic drug therapy to suppress these arrhythmias is not warranted. Treatment with the sodium channel blocker flecainide increased mortality. Amiodarone therapy reduces sudden death, but does not improve total mortality. Therefore, amiodarone is an option for treatment of symptomatic arrhythmias in this population when the potential benefit outweighs its potential toxicities. β-Adrenergic blockers reduce sudden death but have limited effect on spontaneous arrhythmias.
For survivors of an acute MI, an ICD reduces mortality in certain high-risk groups: patients who have survived >40 days after the acute MI and have a left ventricular (LV) ejection fraction of ≤0.30 or who have an ejection fraction <0.35 and have symptomatic heart failure (functional class II or III); and patients >5 days after MI who have a reduced LV ejection fraction, nonsustained VT, and inducible sustained VT or VF on electrophysiologic testing. ICDs do not reduce mortality when routinely implanted soon after MI or in patients after recent coronary artery revascularization surgery.
PVCs and nonsustained vt associated with depressed ventricular function and heart failure
PVCs and nonsustained VT are common in patients with depressed ventricular function and heart failure and are markers for disease severity and increased mortality, but antiarrhythmic drug therapy to suppress these arrhythmias has not been shown to improve survival. Antiarrhythmic drugs whose major action is blockade of the cardiac sodium channel (flecainide, propafenone, mexiletine, quinidine, and disopyramide) are avoided in patients with structural heart disease because of a risk of proarrhythmia, negative inotropic effects, and increased mortality. Therapy with the potassium channel blockers, e.g., dofetilide, does not reduce mortality. Amiodarone suppresses ventricular ectopy and reduces sudden death but does not improve overall survival. ICDs are the major therapy to protect against sudden death in patients at high risk and are recommended for those with LV ejection fraction <0.35 and New York Heart Association class II and III heart failure, in whom they reduce mortality by 20%, from 36% to 29%, over 5 years.
Ventricular ectopy is associated with increased mortality in patients with hypertrophic cardiomyopathy (Chap. 27) or with congenital heart disease (Chap. 22) associated with right ventricular or LV dysfunction. In these patients, management is similar to that for patients with ventricular dysfunction. Pharmacologic suppression of the arrhythmia has not been shown to improve mortality. ICDs are indicated for patients considered at high risk for sudden cardiac death.
Pvc-induced ventricular dysfunction
Very frequent ventricular ectopy and repetitive nonsustained VT (Fig. 18-2) can depress ventricular function, possibly through an effect similar to chronic tachycardia or by inducing ventricular dyssynchrony. Depression of ventricular function rarely occurs unless PVCs account for more than 10–20% of total beats over a 24-h period. Often the PVCs are idiopathic and unifocal, most commonly originating from the LV papillary muscles or outflow tract regions where they can be targeted for ablation. The distinction between PVC-induced ventricular dysfunction as compared to a cardiomyopathic process causing ventricular dysfunction and arrhythmia is difficult and in some cases can be made only retrospectively by observing an improvement in ventricular function after the arrhythmia is suppressed with an antiarrhythmic drug, such as amiodarone, or by catheter ablation.
Three or more ventricular beats at a rate slower than 100 beats/min are termed idioventricular rhythm (Fig. 18-1C). Automaticity is the likely mechanism. Idioventricular rhythms are common during acute MI (Chap. 41) and may emerge during sinus bradycardia. Atropine may be administered to increase the sinus rates if the loss of atrioventricular synchrony leads to hemodynamic compromise. This rhythm is also common in patients with cardiomyopathies or sleep apnea. It can also be idiopathic, often emerging when the sinus rate slows during sleep. Therapy should target any underlying cause and correction of bradycardia. Specific therapy for asymptomatic idioventricular rhythm is not necessary.
Sustained monomorphic VT presents as a wide QRS tachycardia that has the same QRS configuration from beat to beat, indicating an identical sequence of ventricular depolarization for each beat (Fig. 18-3A). VT originates from a stable focus or reentry circuit. In structural heart disease, the substrate is often an area of patchy replacement fibrosis due to infarction, inflammation, or prior cardiac surgery that creates anatomical or functional reentry pathways (Fig. 18-5). Less commonly, VT is related to reentry or automaticity in a diseased Purkinje system. In the absence of structural heart disease, idiopathic VT can present as sustained monomorphic VTs that are due to focal automaticity or reentry involving a portion of the Purkinje system.
The clinical presentation can vary depending on the rate of the arrhythmia, underlying cardiac function, and autonomic adaptation in response to the arrhythmia. Whereas patients with normal cardiac function might tolerate rapid VTs, those with severe LV dysfunction often experience symptoms of hypotension, even if VT is not particularly fast. Monomorphic VT may deteriorate to VF, which may be the initial cardiac rhythm recorded at the time of resuscitation.
Sustained monomorphic VT has to be distinguished from other causes of uniform wide QRS tachycardia. These include supraventricular tachycardia with left or right bundle branch block aberrant conduction, supraventricular tachycardias conducted to the ventricles over an accessory pathway (Chap. 17), and rapid cardiac pacing in a patient with a pacemaker or defibrillator. In the presence of known heart disease, VT is the most likely diagnosis of a wide QRS tachycardia. Hemodynamic stability during the arrhythmia does not exclude VT. A number of ECG criteria have been evaluated. The presence of AV dissociation is usually a reliable marker for VT (Fig. 18-7), but P waves can be difficult to define. A P wave following each QRS does not exclude VT because 1:1 conduction from ventricle to atrium can occur. A monophasic R wave or Rs complex in AVR or concordance from V1 to V6 of monophasic R or S waves is also relatively specific for VT (Fig. 18-7). Other QRS morphology criteria have also been described, but all have limitations and are not very reliable in patients with severe heart disease. In patients with known bundle branch block, the same QRS morphology during tachycardia as during sinus rhythm suggests supraventricular tachycardia rather than VT, but is not absolutely reliable. An electrophysiologic study is sometimes required for definitive diagnosis. Rarely, noise and movement artifacts on telemetry recordings can simulate VT; prompt recognition can avoid unnecessary tests and interventions.
Algorithm for differentiation of ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberration. AV, atrioventricular.
When LV function is depressed or there is evidence of structural myocardial disease, scar-related reentry is the most likely diagnosis. Scars are suggested by pathologic Q waves on the ECG, segmental left or right ventricular wall motion abnormalities on echocardiogram or nuclear imaging, and areas of delayed gadolinium enhancement during MRI (Fig. 18-5).
Initial management follows Advanced Cardiac Life Support (ACLS) guidelines. If hypotension, impaired consciousness, or pulmonary edema is present, QRS synchronous electrical cardioversion should be performed, ideally after sedation if the patient is conscious. For stable tachycardia, a trial of adenosine is reasonable, as this may clarify a supraventricular tachycardia with aberrancy (Chap. 17). Intravenous amiodarone is the drug of choice if heart disease is present. Following restoration of sinus rhythm, hospitalization and evaluation to define underlying heart disease are required. Assessment of cardiac biomarkers for evidence of MI is appropriate, but acute MI is rarely a cause of sustained monomorphic VT, and elevations in troponin or creatine kinase (CK)-MB are more likely to indicate myocardial damage that is secondary to hypotension and ischemia from the VT. Subsequent management is determined by the underlying heart disease and frequency of VT. If VT recurs frequently or is incessant, administration of antiarrhythmic medications or catheter ablation may be required to restore stability. More commonly, sustained monomorphic VT occurs as an isolated episode, but with a risk of recurrence. ICDs are usually considered for VT associated with structural heart disease.
Sustained monomorphic VT in specific diseases
Patients who present with sustained VT associated with coronary artery disease typically have a history of prior large MI and present years after the acute infarct with a remodeled ventricle and markedly depressed LV function. Even when there is biomarker evidence of acute MI, a preexisting scar from previous MI should be suspected as the cause of the VT. Infarct scars provide a durable substrate for sustained VT, and up to 70% of patients have a recurrence of the arrhythmia within 2 years. Scar-related reentry is not dependent on recurrent acute myocardial ischemia, so coronary revascularization cannot be anticipated to prevent recurrent VT, even when it may be appropriate for other indications. Depressed ventricular function, which is a risk factor for sudden death, is usually present. Implantation of an ICD is warranted for most patients provided that there is a reasonable expectation of survival with acceptable functional status for the next year after recovery from the VT episode. ICDs reduce annual mortality from 12.3% to 8.8% and lower arrhythmic deaths by 50% in patients with hemodynamically significant sustained VT or a history of cardiac arrest compared with pharmacologic therapy. Chronic amiodarone therapy may be considered for patients who are not candidates for or who decline ICD placement.
Following ICD implantation, patients remain at risk for heart failure, recurrent ischemic events, and recurrent VT, with a 5-year mortality that exceeds 30%. Attention to therapies with survival benefit, including β-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, and statins, is important. Patients with frequent symptomatic recurrences of VT require antiarrhythmic drug therapy or catheter ablation.
Nonischemic dilated cardiomyopathy
Sustained monomorphic VT associated with nonischemic cardiomyopathy is usually due to scar-related reentry. The etiology of scar is often unclear, but progressive replacement fibrosis is the likely cause. On cardiac MRI, scars are detectable as areas of delayed gadolinium enhancement and are more often intramural or subepicardial in location as compared with patients with prior MI. Scars that cause VT are often located adjacent to a valve annulus and can occur in either ventricle. Any cardiomyopathic process can cause scars and VT, but cardiac sarcoidosis and Chagas’ disease (Chap. 33) are particularly associated with monomorphic VT (Table 18-2). An ICD is usually indicated with additional drugs or ablation for control of recurrent VT.
TABLE 18-2VENTRICULAR ARRHYTHMIAS ASSOCIATED WITH DIFFERENT FORMS OF HEART DISEASE ||Download (.pdf) TABLE 18-2 VENTRICULAR ARRHYTHMIAS ASSOCIATED WITH DIFFERENT FORMS OF HEART DISEASE
I. Idiopathic VT without structural heart disease
A. Outflow tract origin
1. RV outflow tract: left bundle branch block pattern with inferior axis (tall QRS in inferior leads) and late transition in the precordial leads
2. LV outflow tract: prominent R in V1 with inferior axis
B. Left posterior fascicular VT
1. Right bundle branch block pattern with left axis deviation (most common)
II. Ischemic cardiomyopathy
A. Monomorphic VT is common with prior large myocardial infarction
B. Polymorphic VT and VF should prompt ischemia evaluation
III. Nonischemic cardiomyopathy
A. Polymorphic VT and VF more common but fibrotic scars can cause monomorphic VT especially with sarcoidosis and Chagas’ disease
IV. Arrhythmogenic right ventricular cardiomyopathy
A. Monomorphic VT usually of right ventricular origin (left bundle branch morphology)
B. Polymorphic VT and VF can occur independently or through degeneration of monomorphic VT
V. Repaired tetralogy of Fallot
A. Monomorphic VT of right ventricular origin (usually left bundle branch morphology)
VI. Hypertrophic cardiomyopathy
A. Polymorphic VT or ventricular fibrillation
B. Less commonly, monomorphic VT associated with myocardial scars
VIII. Genetic arrhythmia syndromes
A. Long QT syndrome: torsade de pointes VT
B. Brugada syndrome: VF
C. Catecholaminergic polymorphic VT: polymorphic VT or bidirectional VT
D. Short QT syndrome: ventricular fibrillation
E. Early repolarization syndrome: polymorphic VT or VF
ARVC (Chap. 27) is a rare genetic disorder most commonly due to mutations in genes encoding for cardiac desmosomal proteins. Approximately 50% have a familial transmission with autosomal dominant inheritance. A less common, autosomal recessive form is associated with cardiocutaneous syndromes that include Naxos disease and Carvajal syndrome. Patients typically present between the second and fifth decade with palpitations, syncope, or cardiac arrest owing to sustained monomorphic VT, although polymorphic VT can also occur. Fibrosis and fibro-fatty replacement most commonly involve the right ventricular myocardium and provide the substrate for reentrant VT that usually has a left bundle branch block–like configuration, consistent with the right ventricular origin. The sinus rhythm ECG suggests the disease in more than 85% of patients, most often showing T-wave inversions in V1–V3 (Fig. 18-6). Delayed activation of the right ventricle may cause a widened QRS (≥110 ms) in the right precordial leads and a prolonged S-wave upstroke in those leads, and occasionally a deflection at the end of the QRS known as an epsilon wave (Fig. 18-6). Cardiac imaging may show right ventricular enlargement or areas of abnormal motion or reveal areas of scar on CMR imaging with gadolinium. The monomorphic VT of early ARVC can sometimes be difficult to differentiate from idiopathic right ventricular outflow tract VT.
LV involvement can occur and occasionally precede manifest right ventricular disease. Heart failure is rare except in late stages, and survival to advanced age can be anticipated provided that VT can be controlled. An ICD is recommended. When VT is exercise-induced, it may respond to β-adrenergic blockers and limiting exercise. Sotalol, amiodarone, and catheter ablation have been used to reduce recurrences. Ablation targets are often located in the subepicardium of the RV.
VT occurs in 3–14% of patients late after repair of tetralogy of Fallot (Chap. 22) and contributes to a 2% per decade risk of sudden death. Monomorphic VT is due to reentry around areas of surgically created scar in the RV (Table 18-2). Factors associated with VT risk include age >5 years at the time of repair, high-grade ventricular ectopy, inducible VT on an electrophysiologic study, abnormal right ventricular hemodynamics, and sinus rhythm QRS duration >180 ms. An ICD is usually warranted for patients who have a spontaneous episode of VT, but criteria for a prophylactic ICD in other patients have not been established. Catheter ablation is used to control recurrent episodes.
Reentry through the Purkinje system occurs in approximately 5% of patients with monomorphic VT in the presence of structural heart disease. The reentry circuit typically revolves retrograde via the left bundle and anterograde down the right bundle, thereby producing VT that has a left bundle branch block configuration. Catheter ablation of the right bundle branch abolishes this VT. Bundle branch reentry is usually associated with severe underlying heart disease. Other scar-related VTs are often present and often require additional therapy or ICD implantation.
Idiopathic monomorphic VT
Idiopathic VT in patients without structural heart disease usually presents with palpitations, lightheadedness, and occasionally syncope, often provoked by sympathetic stimulation during exercise or emotional upset. The QRS morphology of the arrhythmia suggests the diagnosis (see below). The sinus rhythm ECG is normal. Cardiac imaging shows normal ventricular function and no evidence of ventricular scar. Occasionally a patient with structural heart disease is found to have concomitant idiopathic VT, unrelated to the structural disease. Sudden death is rare.
Outflow tract VTs originate from a focus, usually with features consistent with triggered automaticity. The arrhythmia may present with sustained VT, nonsustained VT, or PVCs often provoked by exercise or emotional upset. Repeated bursts of nonsustained VTs, which may occur incessantly, are known as repetitive monomorphic VTs and can cause tachycardia-induced cardiomyopathy with depressed ventricular function that recovers after suppression of the arrhythmia (Fig. 18-2). Most originate in the right ventricular outflow tract, which gives rise to VT that has a left bundle branch block configuration in V1 and an axis that is directed inferiorly, with tall R waves in leads II, III, and AVF (Fig. 18-2). Idiopathic VT can also arise in the LV outflow tract or in sleeves of myocardium that extend along the aortic root. LV origin is suspected when lead V1 or V2 has prominent R waves. Although this typical outflow tract QRS morphology favors idiopathic VT, some cardiomyopathies, notably ARVC, can cause PVCs or VT from this region. Excluding these diseases is an initial focus of evaluation.
LV intrafascicular VT presents with sustained VT that has a right bundle branch block–like configuration. It is often exercise-induced and occurs more often in men than women. The mechanism is reentry in or near the septal ramifications of the LV Purkinje system. This VT can be terminated by intravenous administration of verapamil.
Management of idiopathic VT
Treatment is required for symptoms or when frequent or incessant arrhythmias depress ventricular function. β-Adrenergic blockers are first-line therapy. Nondihydropyridine calcium channel blockers (diltiazem and verapamil) are sometimes effective. Catheter ablation is warranted for severe symptoms or when beta blockers or calcium channel blockers are not effective or not desired. Efficacy and risks of catheter ablation vary with the specific site of origin of the VT, being most favorable for arrhythmias originating in the right ventricular outflow tract.
LV fascicular VT can be terminated by intravenous administration of verapamil, although chronic therapy with oral verapamil is not always effective. Catheter ablation is recommended if β-adrenergic blockers or calcium channel blockers are ineffective or not desired.
Sustained polymorphic VT can be seen with any form of structural heart disease (Table 18-2). However, unlike sustained monomorphic VT, polymorphic VT does not always indicate a structural abnormality or focus of automaticity. Reentry with continually changing reentrant paths, spiral wave reentry, and multiple automatic foci are potential mechanisms (Chap. 52). Sustained polymorphic VT usually degenerates into VF. Polymorphic VT is typically seen in association with acute MI or myocardial ischemia, ventricular hypertrophy, and a number of genetic mutations that affect cardiac ion channels (Table 18-3).
TABLE 18-3CAUSES OF QT PROLONGATION AND TORSADE DE POINTES VENTRICULAR TACHYCARDIA ||Download (.pdf) TABLE 18-3 CAUSES OF QT PROLONGATION AND TORSADE DE POINTES VENTRICULAR TACHYCARDIA
1. Congenital long QT syndromes (see text for details)
Long QT syndrome type 1: Reduced repolarizing current IKs due to mutation in KCNQ1 gene
Long QT syndrome type 2: Reduced repolarizing current IKr due to mutation in KCNH2 gene
Long QT syndrome type 3: Delayed inactivation of the INa due to mutations in SCN5A gene
Others: Several other types of long QT syndromes have been described; long QT types 1, 2, and 3 account for 80–90% of cases
2. Acquired prolongation of QT interval
Class IA: Quinidine, disopyramide, procainamide
Class III: Sotalol, amiodarone (QT prolongation common but torsade ventricular tachycardia is rare), ibutilide, dofetilide, almokalant
Macrolides: Erythromycin, clarithromycin, azithromycin
Fluoroquinolones: Levofloxacin, moxifloxacin, gatifloxacin
Antifungals: Ketoconazole, itraconazole
Haloperidol, phenothiazines, thioridazine, trifluoperazine, sertindole, zimelidine, ziprasidone
Tricyclic and tetracyclic antidepressants
Antihistamines (histamine 1-receptor antagonists)
Terfenadine, astemizole, diphenhydramine, hydroxyzine
Cholinergic antagonists: Cisapride, organophosphates
Citrate (massive blood transfusions)
Fluoxetine (in conjunction with other drugs that prolong QT)
Myocardial ischemia and infarction
Liquid protein diets
Gastroplasty and ileojejunal bypass
Polymorphic VT associated with acute MI/myocardial ischEMIA
Acute MI or ischemia is a common cause of polymorphic VT and should be the initial consideration in management. Approximately 10% of patients with acute MI develop VT that degenerates to VF, related to reentry through the infarct border zone. The risk is greatest in the first hour of acute MI. Following resuscitation as per the ACLS guidelines, management is as for acute MI (Chap. 41). β-Adrenergic blockers, correction of electrolyte abnormalities, and prompt myocardial reperfusion are required. Repeated episodes of polymorphic VT suggest ongoing myocardial ischemia and warrant assessment of adequacy of myocardial reperfusion. Polymorphic VT and VF that occur within the first 48 h of acute MI are associated with greater in-hospital mortality, but those who survive past hospital discharge are not at increased risk for arrhythmic sudden death. Long-term therapy for postinfarct ventricular arrhythmia is determined by residual LV function, with an ICD being indicated for persistent severe LV dysfunction (LV ejection fraction <0.35).
Repolarization abnormalities and genetic arrhythmia syndromes
Abnormal prolongation of the QT interval is associated with the polymorphic VT Torsade de Pointes (Fig. 18-8). The VT often has a characteristic initiation sequence of a premature ventricular beat that induces a pause, followed by a sinus beat that has a longer QT interval and interruption of the T wave by the PVC that is the first beat of the polymorphic VT. This characteristic initiation is termed “pause-dependent” (Fig. 18-8). Causes of QT prolongation include electrolyte abnormalities, bradycardia, and a number of medications that block repolarizing potassium currents, notably the antiarrhythmic drugs sotalol, dofetilide, and ibutilide, but also a number of other medications used for noncardiac diseases, including erythromycin, pentamidine, haloperidol, phenothiazines, and methadone (Table 18-3). Individual susceptibility may be related to genetic polymorphisms or mutations that influence repolarization.
Electrocardiogram (ECG) of a patient with prolonged QT and episodes of torsade de pointes ventricular tachycardia (VT). A. Twelve-lead ECG showing a heart rate of 54, anterior wall T inversion, and QT interval of 600 ms. The corrected QT interval (QTc) is 585 ms. B. Telemetry ECG tracing with digital pulse waveform demonstrating bursts of torsade de pointes VT. The initiating sequence of the VT is characteristic, with a PVC inducing a pause followed by a sinus beat that had a longer QT and interruption of the T wave by a PVC that is the first beat of VT. The VT is self-terminating in this case.
Patients typically present with near-syncope, syncope, or cardiac arrest. Sustained episodes degenerate to VF requiring defibrillation. PVCs and nonsustained VT often precede episodes of sustained VT. Intravenous administration of 1–2 g of magnesium sulphate usually suppresses recurrent episodes. If magnesium alone is ineffective, increasing heart rate with isoproterenol infusion or pacing, to a rate of 100–120 beats/min as required to suppress PVCs, usually suppresses VT recurrences. These maneuvers allow time for correction of associated electrolyte disturbance (hypokalemia and hypocalcemia) and bradycardia and removal of any causative drugs (Table 18-3). Drug interactions that elevate levels of the offending agent are often a precipitating factor. Patients who experience a polymorphic VT induced by QT prolongation should be considered to have a susceptibility to the arrhythmia and should avoid all future exposure to medications known to prolong the QT interval.
Congenital long QT syndrome
The congenital long QT syndrome (LQTS) is caused by mutations in genes coding for cardiac ion channels responsible for ventricular repolarization. The corrected QT (QTc) is typically prolonged to greater than 440 ms in men and 460 ms in women. Symptoms are due to Torsade de Pointes VT (Fig. 18-8). Several forms of congenital LQTS have been identified, but three groups of mutations that lead to LQTS type 1 (LQTS-1), LQTS type 2 (LQTS-2), or LQTS type 3 (LQTS-3) account for 90% of cases. The most frequently encountered mutations, LQTS1 and LQTS2, are due to abnormalities of potassium channels, but mutations affecting the sodium channel (LQTS3) and calcium channels have also been described (Table 18-3).
Patients often present with syncope or cardiac arrest, usually during childhood. In LQTS-1, episodes tend to occur during exertion, particularly swimming. In LQTS-2, sudden auditory stimuli or emotional upset predispose to events. In LQTS-3, sudden death during sleep is a notable feature. Asymptomatic patients may be discovered in the course of family screening or on a routine ECG. Genotyping can be helpful for family screening and to provide reassurance regarding the diagnosis. Correlations of genotype with risk and response to therapy are beginning to emerge. In most patients with LQTS-1 or LQTS-2, adequate doses of beta blocker therapy (the nonselective agents nadolol or propranolol) are sufficient protection from arrhythmia episodes. Markers of increased risk include QTc interval exceeding 0.5 s, female gender, and a history of syncope or cardiac arrest. Recurrent syncope despite beta blocker therapy or a high-risk profile merits consideration of an ICD. Avoidance of QT-prolonging drugs is critical for all patients with LQTS, including those who are genotype positive but have normal QT intervals.
Short QT syndrome is very rare compared to LQTS. The QTc is shorter than 0.36 s, and usually less than 0.3 s. The genetic abnormality causes a gain of function of the potassium channel (I Kr) or reduced inward depolarizing currents. The abnormality is associated with atrial fibrillation, polymorphic VT, and sudden death.
Brugada syndrome is a rare syndrome characterized by >0.2 mV of ST-segment elevation with a coved ST segment and negative T wave in more than one anterior precordial lead (V1–V3) (Fig. 18-6) and episodes of syncope or cardiac arrest due to polymorphic VT in the absence of structural heart disease. Cardiac arrest may occur during sleep or be provoked by febrile illness. Males are more commonly affected than females. Mutations involving cardiac sodium channels are identified in approximately 25% of cases. Distinction from patients with similar ST elevation owing to LV hypertrophy, pericarditis, myocardial ischemia or MI hyperkalemia, hypothermia, right bundle branch block, and ARVC is often difficult. Furthermore, the characteristic ST-segment elevation can wax and wane over time and may become pronounced during acute illness and fever. Administration of the sodium channel blocking drug flecainide, ajmaline, or procainamide can augment or unmask ST elevation in affected individuals. An ICD is indicated for individuals who have had unexplained syncope or been resuscitated from cardiac arrest. Quinidine has been used successfully to suppress frequent episodes of VT.
Early repolarization syndrome
Patients resuscitated from VF who have no structural heart disease or other identified abnormality have a higher prevalence of J-point elevation with notching in the terminal QRS. A family history of sudden death is present in some patients, suggesting a potential genetic basis. J-point elevation is also seen in some patients with the Brugada syndrome and associated with a higher risk of arrhythmias. An ICD is recommended for those who have had prior cardiac arrest. It should be noted that J-point elevation is commonly seen as a normal variant, and in the absence of specific symptoms, the clinical relevance is not known.
Catecholaminergic polymorphic VT
This rare familial syndrome is due to mutations in the cardiac ryanodine receptor and, less commonly, the sarcoplasmic calcium binding protein, calsequestin 2. These mutations result in abnormal sarcoplasmic calcium handling and polymorphic ventricular arrhythmias that resemble those seen with digitalis toxicity. The VT is polymorphic or has a characteristic alternating QRS morphology termed bidirectional VT. Patients usually present during childhood with exercise- or emotion-induced palpitations, syncope, or cardiac arrest. β-Adrenergic blockers (e.g., nadolol and propranolol) and an ICD are recommended. Verapamil, flecainide, or surgical left cardiac sympathetic denervation reduces or prevents recurrent VT in some patients.
Hypertrophic cardiomyopathy (HCM)
HCM is the most common genetic cardiovascular disorder, occurring in 1 in 500 individuals, and is a prominent cause of sudden death before the age of 35 years (Chap. 27). Sudden death can be due to polymorphic VT/VF. Rarely, sustained monomorphic VT occurs related to areas of ventricular scar. Risk factors include young age, nonsustained VT, failure of blood pressure to increase during exercise, recent (within 6 months) syncope, ventricular wall thickness >3 cm, and possibly the severity of LV outflow obstruction. An ICD is generally indicated for high-risk patients, but the specific risk profile warranting an ICD continues to be debated. Surgical myectomy, performed to relieve outflow obstruction, has been associated with a sudden death rate of less than 1% per year. The reported annual rate of sustained VT or sudden death after transcoronary ethanol septal ablation done to relieve outflow obstruction has been reported to range between 1 and 5%.
Genetic dilated cardiomyopathies
Genetic dilated cardiomyopathies account for 30–40% of cases of nonischemic dilated cardiomyopathies. Some are associated with muscular dystrophy. Autosomal dominant, recessive, X-linked, and mitochondrial inheritance patterns are recognized. Mutations in genes coding for structural proteins of the nuclear lamina (lamin A and C) and the SCN5A gene are particularly associated with conduction system disease and ventricular arrhythmias. Patients can experience polymorphic VT and cardiac arrest or develop areas of scar causing sustained monomorphic VT. ICDs are recommended for those who have had a sustained VT or are at high risk due to significantly depressed ventricular function (LV ejection fraction of ≤0.35 and associated with heart failure) or a malignant family history of sudden death.
VF is characterized by disordered electrical ventricular activation without identifiable QRS complexes (Fig. 18-3E). Spiral wave reentry and multiple circulating reentry wavefronts are possible mechanisms. Sustained polymorphic or monomorphic VT that degenerates to VF is a common cause of out-of-hospital cardiac arrest. Treatment follows ACLS guidelines with defibrillation to restore sinus rhythm. If resuscitation is successful, further evaluation is performed to identify and treat underlying heart disease and potential causes of the arrhythmia, including the possibility that monomorphic or polymorphic VT could have initiated VF. If a transient reversible cause such as acute MI is not identified, therapy to reduce the risk of sudden death with an ICD is often warranted. Chronic amiodarone therapy may be considered for individuals who are not ICD candidates.
Incessant VT and electrical storm
VT is incessant when it continues to recur shortly after electrical, pharmacologic, or spontaneous conversion to sinus rhythm. “VT storm” or “electrical storm” refers to three or more separate episodes of VT within 24 h, most commonly encountered in patients with ICDs. Slow incessant VT is sometimes asymptomatic, but can cause heart failure or tachycardia-induced cardiomyopathy. More commonly, these presentations are life-threatening and require emergent therapy. Measures to reduce sympathetic tone, including β-adrenergic blockade, sedation, and general anesthesia, have been used effectively. Intravenous administration of amiodarone and lidocaine can be effective for suppression. Urgent catheter ablation can be lifesaving.
TREATMENT Ventricular Arrhythmias ANTIARRHYTHMIC DRUGS
Use of antiarrhythmic drugs is based on consideration of the risks and potential benefit for the individual patient. The potential to increase the frequency of VT or cause a new VT, an undesirable effect known as “proarrhythmia,” is a potential risk. Many drugs have multiple effects, often blocking more than one channel. Drug doses, metabolism, and adverse effects are summarized in Chap. 18. β-Adrenergic Blockers
Many ventricular arrhythmias are sensitive to sympathetic stimulation, and β-adrenergic stimulation also diminishes the electrophysiologic effects of many antiarrhythmic drugs. The safety of β-blocking agents makes them the first choice of therapy for most ventricular arrhythmias. They are particularly useful for exercise-induced arrhythmias and idiopathic arrhythmias, but have limited efficacy for most arrhythmias associated with heart disease. Bradyarrhythmias are the major cardiac toxicity. Calcium Channel Blockers
The nondihydropyridine calcium channel blockers diltiazem and verapamil can be effective for some idiopathic VTs. The risk of proarrhythmia is low, but they have negative inotropic and vasodilatory effects that can aggravate hypotension. Sodium Channel-Blocking Agents
Drugs whose major effect is mediated through sodium channel blockade include mexiletine, quinidine, disopyramide, flecainide, and propafenone, which are available for chronic oral therapy (Table 18-3). Lidocaine, quinidine, and procainamide are available as intravenous formulations. Quinidine, disopyramide, and procainamide also have potassium channel-blocking effects that prolong the QT interval. These agents have potential proarrhythmic effects and, with the possible exception of quinidine, also have negative inotropic effects that may contribute to increased mortality observed in patients with prior MI. Long-term therapy is generally avoided in patients with structural heart disease but may be used to reduce symptomatic arrhythmias in patients with ICDs. Potassium Channel-Blocking Agents
Sotalol and dofetilide block the delayed rectifier potassium channel IKr, thereby prolonging the QT interval. Sotalol also has nonselective β-adrenergic blocking activity. It has a modest effect on reducing ICD shocks due to ventricular and atrial arrhythmias. Proarrhythmia with Torsade de Pointes due to QT prolongation occurs in 3–5% of patients. Both sotalol and dofetilide are excreted via the kidneys, necessitating dose adjustment or avoidance in renal insufficiency. These drugs must be avoided in patients with other risk factors for Torsade de Pointes, including QT prolongation, hypokalemia, and significant bradycardia. Amiodarone and Dronedarone
Amiodarone, which blocks multiple cardiac ionic currents and has sympatholytic activity, suppresses a variety of ventricular arrhythmias. It is administered intravenously for life-threatening arrhythmias. During chronic oral therapy, electrophysiologic effects develop over several days. It is more effective than sotalol in reducing ICD shocks and is the preferred drug for ventricular arrhythmias in patients with heart disease who are not candidates for an ICD. Bradyarrhythmias are the major cardiac adverse effect. Ventricular proarrhythmia can occur, but Torsade de Pointes VT is rare. Noncardiac toxicities are a major problem and contribute to drug discontinuation in approximately a third of patients during long-term therapy. Pneumonitis or pulmonary fibrosis occurs in approximately 1% of patients. Photosensitivity is common, and neuropathy and ocular toxicity can occur. Systematic monitoring is recommended during chronic therapy, including assessment for thyroid and liver toxicity every 6 months and lung toxicity with a chest radiograph and/or determination of lung diffusing capacity annually. Dronedarone has structural similarities to amiodarone but without the iodine moiety. Efficacy for ventricular arrhythmias is poor, and it increases mortality in patients with heart failure. IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS
ICDs are highly effective for termination of VT and VF and also provide bradycardia pacing. ICDs decrease mortality in patients at risk for sudden death due to structural heart diseases. In all cases, ICDs are recommended only if there is also expectation for survival of at least a year with acceptable functional capacity. The exception is in cases of patients with end-stage heart disease who are awaiting cardiac transplantation outside the hospital, or who have left bundle branch block QRS prolongation such that they are likely to have improvement in ventricular function with cardiac resynchronization therapy from a biventricular ICD.
ICDs can often terminate monomorphic VT by a burst of rapid pacing faster than the VT, known as antitachycardia pacing (ATP) (Fig. 18-9A). If ATP fails or is not a programmed treatment, as is often the case for rapid VT or VF, a shock is delivered (Fig. 18-9B). Shocks are painful if the patient is conscious. The most common ICD complication is the delivery of unnecessary therapy (either ATP or shocks) in response to a rapid supraventricular tachycardia or electrical noise as a result of an ICD lead fracture. Interrogation of the ICD, which can be performed remotely and communicated via Internet, is critical after an ICD shock to determine the arrhythmia diagnosis and exclude an unnecessary therapy. Device infection occurs in approximately 1% of patients.
Despite prompt termination of VT or VF by an ICD, the occurrence of these arrhythmias predicts subsequent increased mortality and risk of heart failure. Occurrence of VT or VF should therefore prompt assessment for potential causes including worsening heart failure, electrolyte abnormalities, and ischemia. Repeated shocks, even if appropriate, often induce posttraumatic stress disorder. Antiarrhythmic drugs mostly in the form of amiodarone or catheter ablation are often required for suppression of recurrent arrhythmias. Antiarrhythmic drug therapy can alter the VT rate and the energy required for defibrillation, thereby necessitating programming changes in the ICD’s algorithms for detection and therapy. CATHETER ABLATION FOR VT
Catheter ablation is performed by guiding an electrode catheter to the arrhythmia origin and producing a thermal injury with radiofrequency current. The size and location of the arrhythmia substrate determine the ease and likely effectiveness of the procedure, as well as potential complications. The most common complications, which occur in <5% of patients, are related to vascular access, including bleeding, femoral hematomas, arteriovenous fistulae, and pseudoaneurysms.
Catheter ablation is a reasonable first-line therapy for many patients with symptomatic idiopathic VTs. Success rates for those originating from a focus in the right ventricular outflow tract are in the range of 80–90% but lower for idiopathic VTs arising in less common locations such as from the LV outflow tract or aortic root, along the atrioventricular valve annuli, and from the papillary muscles. Failure of ablation is often due to inability to induce the arrhythmia for precise localization or because the origin of the VT is from a site that is inaccessible or in close proximity to a coronary artery. Complications are infrequent but can include perforation with cardiac tamponade, atrioventricular block due to injury to the conduction system, and coronary artery injury for foci in proximity to a coronary vessel.
In patients with scar-related VT due to prior infarction or cardiomyopathy, ablation targets abnormal regions in the scar. Because these scars often contain multiple reentry circuits over relatively large regions, extensive areas of ablation are required, and these areas are often identified as regions of low voltage displayed on anatomic reconstructions of the ventricle (Fig. 18-5). If the circuits are not confined to the subendocardial scar, epicardial mapping and ablation can be performed via a subxiphoid pericardial puncture, similar to a pericardiocentesis. Epicardial mapping and ablation are often required for VTs due to nonischemic cardiomyopathy, but also have potentially greater risks of bleeding, coronary injury, and postprocedure pericarditis, which is usually transient. For drug-refractory VT due to prior MI, ablation abolishes VT in approximately half of patients and reduces the frequency of VT in an additional 20%. More than one procedure is necessary in up to 30% of patients. Ablation can be lifesaving for patients with very frequent or incessant VT. Procedure-related mortality is in the range of 3%, with most mortality due to continued uncontrollable VT when the procedure fails. In nonischemic heart disease, the arrhythmia substrate locations are more variable and outcomes are less well defined.
Catheter ablation can also be lifesaving for rare patients with recurrent polymorphic VT and VF that is repeatedly initiated by a uniform PVC. The initiating ectopic beat often originates from the Purkinje system or the right ventricular outflow tract and can be targeted for ablation.
When antiarrhythmic drug therapy and catheter ablation fail or are not options, surgical cryoablation, often combined with aneurysmectomy, can be effective therapy for recurrent VT due to prior MI and has also been used successfully in a few patients with nonischemic heart disease. Few centers now maintain the expertise for this therapy. Injection of absolute ethanol into the coronary arterial blood supply of the arrhythmia substrate has also been used for ablation in a small number of patients who have failed catheter ablation and drugs.
Implantable cardioverter-defibrillator (ICD) and therapies for ventricular arrhythmias. A. A monomorphic ventricular tachycardia (VT) is terminated by a burst of pacing impulses at a rate faster than VT (antitachycardia pacing). B. A rapid VT is converted with a high-voltage shock (arrow). The chest x-ray in panel C shows the components of an ICD capable of biventricular pacing. ICD generator in the subcutaneous tissue of the left upper chest, pacing leads in the right atrium and the left ventricular (LV) branch of the coronary sinus (LV lead), and a pacing/defibrillating lead in the right ventricle (RV lead) are shown.