In contrast, the population of children, adolescents, and young adults has an overall annual risk of 1 per 100000, and there is somewhat a higher risk of SCD at the younger end of that age range.S2.2.2-41 An age- associated transition range, from the mid-20s to 35 to 40 years of age, is characterized by a steep increase in risk from that of the adolescent group to the middle- aged group, corresponding to the emergence of isch- emic heart disease. Although ischemic heart disease remains the most common underlying substrate associated with SCD, the incidence of ischemic heart disease-related SCD appears to be decreasing,S2.2.2-52 with various forms of cardiomyopathy associated with myocardial fibro- sis and LV hypertrophy increasing.S2.2.2-53 In addition, a trend over time has suggested that out-of-hospital cardiac arrest patients who are admitted alive to a hospital are becoming more likely to have high-risk clinical profiles, as opposed to manifest disease.S2.2.2-54 The younger population children, adolescents, and young adults is affected by a series of disorders that manifest earlier in life, including the genetic structural disorders and cardiac channelopathies, myocarditis, congenital heart disease, and other rare During the transition range, from the mid-20s to the mid-30s, causes of SCA and SCD in- clude a lower proportion of inherited diseases and in- creasing proportion of ischemic heart disease (>40% Despite the small progress that has been made in risk prediction of SCA and SCD, the greatest challenge is to identify the relatively small, high-risk subgroups con- cealed within the large general population who have no identified disease but are at risk of SCA as their first cardiac event (Figure 1).S2.2.2-50 3. MECHANISMS OF VA 3.1.


Although ischemic heart disease remains the most common underlying substrate associated with SCD, the incidence of ischemic heart disease-related SCD appears to be decreasing,S2.2.2-52 with various forms of cardiomyopathy associated with myocardial fibro- sis and LV hypertrophy increasing.S2.2.2-53 In addition, a trend over time has suggested that out-of-hospital cardiac arrest patients who are admitted alive to a hospital are becoming more likely to have high-risk clinical profiles, as opposed to manifest disease.S2.2.2-54 The younger population children, adolescents, and young adults is affected by a series of disorders that manifest earlier in life, including the genetic structural disorders and cardiac channelopathies, myocarditis, congenital heart disease, and other rare During the transition range, from the mid-20s to the mid-30s, causes of SCA and SCD in- clude a lower proportion of inherited diseases and in- creasing proportion of ischemic heart disease (>40% Despite the small progress that has been made in risk prediction of SCA and SCD, the greatest challenge is to identify the relatively small, high-risk subgroups con- cealed within the large general population who have no identified disease but are at risk of SCA as their first cardiac event (Figure 1).S2.2.2-50 3. MECHANISMS OF VA 3.1. Cellular Mechanisms and Substrates Mechanisms of VA include enhanced normal au- tomaticity, abnormal automaticity, triggered activ- ity induced by early or late afterdepolarizations, and Reentry requires a trigger to initiate the arrhythmia and a substrate to sustain it. The trig- ger may be a PVC, which may be due to automaticity. The substrate may be structural remodeling secondary to an underlying disease process, and often includes a scar secondary to a prior MI or surgical repair, or patchy fibrosis in the setting of cardiomyopathy or hypertrophy.


The substrate may be structural remodeling secondary to an underlying disease process, and often includes a scar secondary to a prior MI or surgical repair, or patchy fibrosis in the setting of cardiomyopathy or hypertrophy. Changes in ion channel or transporter function and/or expression and cell to cell coupling secondary to the underlying pathology may alter the initiation or propagation of the cardiac action poten- tial. The electrophysiological substrate is dynamically influenced by a variety of factors including cardiac metabolism, electrolytes, signaling pathways and au- tonomic effects. Enhanced automaticity or abnormal automaticity causing VA may arise from subordinate pacemaker cells in the His-Purkinje system or ventricu- lar myocardium. Normal automaticity results from phase 4 spontane- ous depolarization of the transmembrane action po- tential arising from a normal resting potential, reach- ing threshold and initiating an action potential.S3.4-1,S3.4-3 An initiating current (If ) is responsible for spontaneous phase 4 depolarization in the sinus node. The rate is determined by the integration of the maximum dia- stolic potential at the end of repolarization, the slope of phase 4 depolarization, and the threshold potential. In contrast, abnormal automaticity arises from a par- tially depolarized membrane potential that is usually close to the activation potential for calcium channels in the cell membrane.S3.4-1,S3.4-3 In the acute phase of an MI or during transient ischemia, increased extracellular potassium causes partial depolarization of the resting membrane potential creating injury currents between the infarcted/ischemic tissue and healthy myocardium. These injury currents may initiate spontaneous activity. In ischemia, abnormal automaticity may occur in both CLINICAL STATEMENTS AND GUIDELINES ventricular myocytes and Purkinje fibers, and may also enhance normal automaticity in Purkinje fibers in the ischemic zone. 3.3.


In ischemia, abnormal automaticity may occur in both CLINICAL STATEMENTS AND GUIDELINES ventricular myocytes and Purkinje fibers, and may also enhance normal automaticity in Purkinje fibers in the ischemic zone. 3.3. Triggered Activity Early afterdepolarizations occur during late phase 2 or early phase 3 of the action potential,S3.4-3 S3.4-5 usually in the setting of action potential prolongation due to an increase in inward currents (the late sodium cur- rent, the inward calcium current or the sodium cal- cium exchange current) or a decrease in repolarizing potassium currents. Under these conditions, early afterdepolarizations may be initiated when reacti- vation of the inward L-type calcium channel occurs before the membrane has returned to a more nega- tive potential than that required for calcium channel reactivation. Spontaneous calcium release from the sarcoplasmic reticulum may also result in activation of a depolarizing sodium/calcium exchange current. Early afterdepolarizations are the trigger for torsades de pointes VT associated with QT prolongation either induced by medications or other acquired factors or due to mutations of ion channels causing the long QT syndrome. In these cases, it is possible that the early afterdepolarization/triggered activity sequence is the trigger that culminates in polymorphic VT/VF. Delayed afterdepolarizations occur after complete membrane repolarization and develop under condi- tions of intracellular calcium overload. Factors con- tributing to elevated intracellular calcium load include tachycardia, catecholamines, hypokalemia, digoxin toxicity, cardiac hypertrophy, and HF.S3.4-6,S3.4-7 Elevated sarcoplasmic calcium content or increased sensitivity of the ryanodine receptor can initiate spontaneous calci- um release, which activates a transient inward current driven predominantly by the sodium calcium exchange current. If the membrane depolarization is sufficiently large, the inward sodium current is activated resulting in a triggered action potential.


If the membrane depolarization is sufficiently large, the inward sodium current is activated resulting in a triggered action potential. Delayed afterdepolar- izations are the underlying mechanism for VT in the setting of digoxin toxicity, catecholaminergic polymor- phic VT, and idiopathic outflow tract VA. Delayed af- terdepolarizations are also considered to be an impor- tant trigger of VA in the setting of HF. Purkinje cells are more susceptible to spontaneous sarcoplasmic re- ticulum calcium release than ventricular myocytes sug- gesting that delayed afterdepolarizations may be an important mechanism for some Purkinje fiber-related Reentry is the underlying mechanism for most sustained VA in the presence of structural heart Reentry may occur around a fixed anatomical obstacle, such as scar after an MI or surgically repaired congenital heart disease. In this setting, an excitable gap separates the excitation wave- front from its tail of refractoriness. The existence of structural reentrant substrates provide the rationale for VT ablation in scar-related VTs.S3.4-11,S3.4-12 Functional reentry around areas of functional block without anatomical obstacles can also occur. Two main models of functional reentry have been proposed.S3.4-2,S3.4-3 The leading circle model has a functionally refractory core and no excitable gap. Spiral wave reentry is driven by a rotor with a curved wavefront and wavetail pivoting around an excitable but unexcited core. There remains much debate about the precise mechanism(s) of VF (ro- tor versus multiple wavelet reentry). Both mechanisms may be operational in different phases of VF.S3.4-10 Phase 2 reentry may occur due to heterogeneity of ventricular repolarization. Electrotonic currents may flow from endocardial sites with longer action poten- tial durations to the epicardium with shorter action po- tential durations which can result in reexcitation when these sites have recovered from refractoriness.


Electrotonic currents may flow from endocardial sites with longer action poten- tial durations to the epicardium with shorter action po- tential durations which can result in reexcitation when these sites have recovered from refractoriness. This is believed to be one potential mechanism of VT/VF in and may also be operative dur- ing ischemia. 4. GENERAL EVALUATION OF PATIENTS WITH DOCUMENTED OR SUSPECTED VA 4.1. History and Physical Examination Recommendation for Syncope* Referenced studies that support the recommendation are summarized in Online Data Supplement 1. COR LOE Recommendation I B-NR Patients presenting with syncope for which VA is documented, or thought to be a likely cause, should be hospitalized for evaluation, monitoring, and management.S4.1-1 S4.1-4 *This section covers practices that are well accepted, and a new recommendation was determined to only be warranted for syncope. Synopsis VA can produce a wide spectrum of symptoms, and the severity of symptoms does not necessarily reflect the extent of structural heart disease or the potential risk of SCD. Symptoms of VA include palpitations, either skipped or extra beats or sustained palpitations, short- ness of breath, chest pain, dizziness, near syncope, and Palpitations may correlate with VA but are frequently reported during normal rhythm.S4.1-7 The differential diagnosis of exercise intolerance, chest pain, dyspnea, presyncope, and syncope includes VA but also includes other etiologies. Nonetheless, more dramatic CLINICAL STATEMENTS AND GUIDELINES symptoms, particularly in patients with known or dis- covered structural or electrical heart disease should prompt focused investigation for possible association with VA (Table 6). The elucidation of precipitating factors, such as exertional or emotional stress, concurrent medica- tions or illness, and alleviating factors is important.


The elucidation of precipitating factors, such as exertional or emotional stress, concurrent medica- tions or illness, and alleviating factors is important. The presence of a family history of SCD, ischemic heart disease, valvular heart disease, nonischemic cardiomyopathy (NICM), or HF raises concern for the presence of one of these disorders associated with VA. Obtaining a complete medication history is im- portant. Various antiarrhythmic and other medications can cause QT prolongation and torsades de pointes ; some medications can also induce Brugada type I electrocardiographic pat- tern and VF (www.brugadadrugs.org).S4.1-9,S4.1-10 Patients with bigeminy and trigeminy can present with effective bradycardia, an apical-radial pulse deficit and relative hypertension with a wide pulse pressure. Effective bradycardia from PVCs can result in inaccurate estimation of the heart rate. Although premature beats on auscultation of the heart can be detected, the physi- cal examination is focused largely on finding evidence of structural heart disease. Carotid bruits or diminished peripheral pulses may be indicators of atherosclerotic disease associated with ischemic heart disease. Jugular venous distention, rales, gallops, and peripheral edema provide evidence of HF. Auscultation may reveal cardiac murmurs consistent with valvular heart disease, such as aortic stenosis or mitral regurgitation, and may be as- sociated with HF and VA. A midsystolic click may indi- cate mitral valve prolapse that can be associated with Many VA are asymptomatic and detected only on an ECG or telemetry. Such cases highlight the need to search for evidence of underlying heart disease. Recommendation-Specific Supportive Text 1. Rapid, sustained VT may result in syncope sec- ondary to marked reduction in cardiac output, Table 6. Important Considerations in the Evaluation of Patients With Known or Suspected VA Component Assessment and Findings Relevant for VA and/or SCD Risk History 1.


Important Considerations in the Evaluation of Patients With Known or Suspected VA Component Assessment and Findings Relevant for VA and/or SCD Risk History 1. Symptoms/events related to arrhythmia: Palpitations, lightheadedness, syncope, dyspnea, chest pain, cardiac arrest Symptoms related to underlying heart disease: Dyspnea at rest or on exertion, orthopnea, paroxysmal nocturnal dyspnea, chest pain, edema 3. Precipitating factors: Exercise, emotional stress Known heart disease: Coronary, valvular (eg, mitral valve prolapse), congenital heart disease, other Risk factors for heart disease: Hypertension, diabetes mellitus, hyperlipidemia, and smoking Antiarrhythmic medications Other medications with potential for QT prolongation and torsades de pointes Medications with potential to provoke or aggravate VA Stimulants including cocaine and amphetamines Supplements including anabolic steroids Medication-medication interaction that could cause QT prolongation and torsades de pointes 7. Past medical history Thyroid disease Acute kidney injury, chronic kidney disease, or electrolyte abnormalities Stroke or embolic events Lung disease Epilepsy (arrhythmic syncope can be misdiagnosed as epilepsy) Alcohol or illicit drug use Use of over-the-counter medications that could cause QT prolongation and torsades de pointes Unexplained motor vehicle crashes Family History 1. SCD, SCA, or unexplained drowning in a first-degree relative SIDS or repetitive spontaneous pregnancy losses given their potential association with cardiac channelopathies 3. Heart disease IHD Cardiomyopathy: Hypertrophic, dilated, ARVC Congenital heart disease Cardiac channelopathies: Long QT, Brugada, Short QT, CPVT Arrhythmias Conduction disorders, pacemakers/ICDs Neuromuscular disease associated with cardiomyopathies Muscular dystrophy (Continued) Examination 1. Heart rate and regularity, blood pressure 2. Jugular venous pressure 4. Pulses and bruits 6. Sternotomy scars ARVC indicates arrhythmogenic right ventricular cardiomyopathy; CPVT, catecholaminergic polymorphic ventricular tachycardia; IHD, ischemic heart disease; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SIDS, sudden infant death syndrome; and VA, ventricular arrhythmia. Table 6.


Sternotomy scars ARVC indicates arrhythmogenic right ventricular cardiomyopathy; CPVT, catecholaminergic polymorphic ventricular tachycardia; IHD, ischemic heart disease; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SIDS, sudden infant death syndrome; and VA, ventricular arrhythmia. Table 6. Continued Component Assessment and Findings Relevant for VA and/or SCD Risk CLINICAL STATEMENTS AND GUIDELINES followed by spontaneous recovery if VT termi- nates, or SCA if VT persists and is not treated promptly. Syncope or SCA may be the first manifestation of structural or electrical heart and some SCA victims have preced- ing sentinel syncope episodes.S4.1-15 Syncope, or its forewarnings of dizziness, lightheadedness, or near-syncope, may constitute a risk factor for SCA and SCD.S4.1-2 The initial evaluation at any age focuses on detection or exclusion of heart disease. Syncope during exercise should prompt thorough evaluation to rule out cardiac causes. Cardiac evaluation with echocardiography, ambulatory monitoring, and exercise testing may be warranted depending on the clinical informa- Cardiac causes of syncope include sustained VT, high-grade atrioventricular block or severe sinus bradycardia or prolonged sinus pauses, supraventricular tachycardia (SVT), malfunction of pacemakers, VA from cardiac channelopathies or structural heart disease syn- dromes, such as hypertrophic cardiomyopathy (HCM) or congenital heart disease.S4.1-3,S4.1-4,S4.1-16 Cardiac channelopathies and HCM are particu- larly important to consider in adolescents and young adults. Arrhythmic causes of syncope are often associated with very short periods of pre- monitory symptoms, or palpitations, and known preexisting heart disease, especially a history of a low LVEF or HF.S4.1-1 Among nonarrhythmic car- diac causes, considerations should include myo- cardial ischemia, severe aortic stenosis, HCM, HF, and prosthetic valve malfunction, pulmonary embolism, medications, and illicit drug use.S4.1-3 4.2. Noninvasive Evaluation 4.2.1. 12-lead ECG and Exercise Testing Recommendations for 12-lead ECG and Exercise Testing Referenced studies that support the recommendations are summarized in Online Data Supplement 2.


12-lead ECG and Exercise Testing Recommendations for 12-lead ECG and Exercise Testing Referenced studies that support the recommendations are summarized in Online Data Supplement 2. COR LOE Recommendations I B-NR In patients with sustained, hemodynamically stable, wide complex tachycardia, a 12- lead ECG during tachycardia should be I B-NR In patients with VA symptoms associated with exertion, suspected ischemic heart disease, or catecholaminergic polymorphic ventricular tachycardia, exercise treadmill testing is useful to assess for exercise-induced I B-NR In patients with suspected or documented VA, a 12-lead ECG should be obtained in sinus rhythm to look for evidence of heart Recommendation-Specific Supportive Text 1. A 12-lead ECG during tachycardia is the first diagnostic test that should be done in any patient found to be in a stable wide QRS complex tachy- cardia on a monitor. VT is the diagnosis in most adults with wide complex tachycardia and under- lying structural heart disease.S4.2.1-3 Criteria that support a diagnosis of VT include AV dissocia- tion, a QRS complex >0.14 s, monophasic R wave in aVR, specific QRS morphologies (eg, positively or negatively concordant QRS complexes in the precordial leads), the absence of an RS complex in all precordial leads and an RS interval >100 ms in at least 1 precordial lead.S4.2.1-2 Exceptions occur, particularly in patients with advanced heart disease and with the use of certain anti- For patients with preexisting bundle branch block, comparison of the QRS morphology during sinus rhythm with that during wide complex tachycardia is often relevant. 2. For exertion-related arrhythmic symptoms, exer- cise in a monitored setting may reproduce the symptoms and/or the related arrhythmia, allow- ing for diagnosis. Exercise testing is particularly important when catecholaminergic polymorphic ventricular tachycardia is a possibility.


Exercise testing is particularly important when catecholaminergic polymorphic ventricular tachycardia is a possibility. However, exertion-related symptoms and findings may not be reliably reproducible with exercise testing, and long-term electrocardiographic monitoring with external or implantable recorders may be necessary. 3. A 12-lead ECG may indicate the presence of structural heart disease such as prior MI or chamber enlargement that would increase the likelihood that a patient s symptoms might be due to VA, or it may provide evidence of the underlying substrate for documented VA. An ECG may also reveal evidence of inherited arrhythmia disorders, such as long QT syn- drome, Brugada syndrome, and arrhythmogenic right ventricular cardiomyopathy. In patients with structural heart disease, QRS duration and the presence of conduction abnormalities pro- vide prognostic information.S4.2.1-7 S4.2.1-14 Data on the use of microvolt T wave alternans and the signal averaged ECG are inconclusive, as such these tests are not routinely used in clinical ; the one exception is the potential use of signal averaged ECG in patients with arrhythmogenic right ventricular cardiomy- opathy (see Section 7.3). CLINICAL STATEMENTS AND GUIDELINES 4.2.2. Ambulatory Electrocardiography Recommendation for Ambulatory Electrocardiography Referenced studies that support the recommendation are summarized in Online Data Supplements 3 and 4. COR LOE Recommendation I B-NR Ambulatory electrocardiographic monitoring is useful to evaluate whether symptoms, including palpitations, presyncope, or syncope, are caused by VA.S4.2.2-1 S4.2.2-4 Recommendation-Specific Supportive Text 1. Ambulatory electrocardiographic monitoring is often used to assess the effectiveness of treatments to sup- press arrhythmias, but more robust data are needed on the clinical use of this practice. Continuous or intermittent ambulatory electrocardiographic recording with a Holter monitor or an event recorder is helpful in diagnosing suspected arrhythmias, estab- lishing their frequency, relating them to symptoms, and assessing the response to therapy.


Continuous or intermittent ambulatory electrocardiographic recording with a Holter monitor or an event recorder is helpful in diagnosing suspected arrhythmias, estab- lishing their frequency, relating them to symptoms, and assessing the response to therapy. Although the yield of these tests is relatively low, VT is occasion- A 24-hour continuous Holter recording is appropriate when symptoms occur at least once a day or when quantitation of PVCs/NSVT is desired to assess possible VA-related depressed ventricular function. For sporadic symptoms, event or looping monitors are more appropriate because they can be activated over extended periods of time and increase diagnostic yield.S4.2.2-2,S4.2.2-3 Adhesive patch electrocardiographic monitors can record for weeks and allow for continuous short-term 1-lead monitoring and patient activation for symptoms. Studies have shown satisfactory patient compli- ance, and arrhythmia detection; however, with some monitors, detected arrhythmias are not dis- covered until the patch is returned for analysis.S4.2.2- Serial evaluations with exercise testing and/ or 24-hour ambulatory monitoring are also used to assess rhythm burden and response of VA to therapy. Notably, implantable monitors are covered in Section 4.2.3. Importantly, when the suspicion of VA in a patient is high, outpatient ambulatory monitoring is inappropriate as prompt diagnosis and prevention of VA are warranted. It is important to accurately cor- relate the symptoms with the arrhythmias detected by ambulatory ECG monitoring. 4.2.3. Implanted Cardiac Monitors Recommendation for Implanted Cardiac Monitors Referenced studies that support the recommendation are summarized in Online Data Supplement 5. COR LOE Recommendation IIa B-R In patients with sporadic symptoms (including syncope) suspected to be related to VA, implanted cardiac monitors can be Recommendation-Specific Supportive Text 1. Implanted cardiac monitors provide continu- ous rhythm monitoring and stored recordings of electrograms based on patient activation or pre- set parameters, allowing a prolonged monitor- ing period of a few years.


Implanted cardiac monitors provide continu- ous rhythm monitoring and stored recordings of electrograms based on patient activation or pre- set parameters, allowing a prolonged monitor- ing period of a few years. These devices require a minor invasive procedure with local anesthesia for implantation. In patients with sporadic symp- toms, including syncope, implantable recorders are useful in diagnosing serious tachyarrhythmias (including VA) and bradyarrhythmias.S4.2.3-2 S4.2.3-4 They are generally reserved for patients in whom other ambulatory monitoring is nonrevealing due to the infrequency of events. A 25% added yield in diagnosis has been described after an unreveal- ing external ambulatory monitor.S4.2.3-5 In a study of patients with syncope, the implantable moni- tor had a greater diagnostic yield than conven- tional testing with external monitoring, tilt table testing and electrophysiological study.S4.2.3-2 A systematic review in patients with syncope con- cluded that use of these devices provide a higher rate of diagnosis and a trend toward reduction in syncope relapse after diagnosis, as compared with conventional management.S4.2.3-3 A prospec- tive study of patients after MI, with LVEF <40%, demonstrated NSVT (>16 beats long) in 13%, VT (>30 s) in 3% and VF in 3% of patients.S4.2.3-1 It is important to accurately correlate the symptoms with the arrhythmias detected by implanted car- diac monitors. 4.2.4. Noninvasive Cardiac Imaging Recommendations for Noninvasive Cardiac Imaging Referenced studies that support the recommendations are summarized in Online Data Supplement 6.


Noninvasive Cardiac Imaging Recommendations for Noninvasive Cardiac Imaging Referenced studies that support the recommendations are summarized in Online Data Supplement 6. COR LOE Recommendations I B-NR In patients with known or suspected VA that may be associated with underlying structural heart disease or a risk of SCA, echocardiography is recommended for evaluation of cardiac structure and IIa C-EO In patients presenting with VA who are suspected of having structural heart disease, cardiac magnetic resonance imaging (MRI) or computed tomography (CT) can be useful to detect and characterize underlying structural heart disease. Recommendation-Specific Supportive Text 1. Assessment of global and regional myocardial function, valvular structure and function, along with assessment for adult congenital heart CLINICAL STATEMENTS AND GUIDELINES disease is required in patients with or at high risk for VA or SCD, including patients with cardiomy- opathy, HF, prior MI, family history of cardiomy- opathy or SCD, or an inherited structural heart disease associated with SCD. Echocardiography is the most readily available and commonly used LVEF is a strong, independent predictor of SCD and cardiovascular mortality and a determinant of eligibility for ICD implantation for primary prevention of SCD.S4.2.4-1 In SCD-HeFT (the Sudden Cardiac Death in Heart the benefit of the ICD was not dependent on the modality (ie, echocardiogra- phy, radionuclide angiography, or contrast angio- grams) by which the LVEF was assessed. In clinical practice, if cardiac CTS4.2.4-3 or cardiac MRI has been performed and provides sufficient evalua- tion, echocardiography may be unnecessary. This recommendation for imaging differs from that of the 2017 ACC/AHA/HRS syncope guidelineS4.2.4-4 that applies to patients who may not have VA. 2. VA or SCA can be an initial manifestation of isch- emic heart disease, cardiomyopathic processes, or myocarditis.


VA or SCA can be an initial manifestation of isch- emic heart disease, cardiomyopathic processes, or myocarditis. Cardiac CT and cardiac MRI allow for evaluation of structural heart disease and assess- ment of LV and RV function including quantification of LVEF, LV mass and volume, valvular structure and coronary anatomy including anomalous coronary origins. Cardiac MRI can be useful in the evaluation for myocardial scar and infiltrative processes evi- dent as late gadolinium enhancement.S4.2.4-5 S4.2.4-9 Cardiac MRI also provides high-quality assessment of LV and RV function, size, and degree of fibrosis and is particularly useful in arrhythmogenic right ventricular cardiomyopathy and HCM. Recommendation for Biomarkers Referenced studies that support the recommendation are summarized in Online Data Supplement 7. COR LOE Recommendation IIa B-NR In patients with structural heart disease, measurement of natriuretic peptides (BNP or N-terminal pro-BNP) can be useful by adding prognostic information to standard risk factors for predicting SCD or SCA.S4.2.5-1 S4.2.5-4 Recommendation-Specific Supportive Text 1. Elevated levels of natriuretic peptides B-type natri- uretic peptide (BNP) or N-terminal pro-BNP are associated with increased risk of SCA and appro- priate ICD therapies, even after adjustment of LVEF and other risk factors.S4.2.5-1 S4.2.5-4 These biomarkers are also predictive of nonsudden cardiovascular mortality and thus are not specific to SCD risk alone.


Elevated levels of natriuretic peptides B-type natri- uretic peptide (BNP) or N-terminal pro-BNP are associated with increased risk of SCA and appro- priate ICD therapies, even after adjustment of LVEF and other risk factors.S4.2.5-1 S4.2.5-4 These biomarkers are also predictive of nonsudden cardiovascular mortality and thus are not specific to SCD risk alone. Natriuretic peptides have also been evaluated for predicting SCD in the general population.S4.2.5-5,S4.2.5-6 In the Nurses Health Study, an elevated N-terminal pro-BNP was an independent risk marker for SCD in presumably healthy women.S4.2.5-5 In an older adult population, higher baseline levels of N-terminal pro-BNP were associated with SCD over a 16-year These biomarkers may also have a potential role in facilitating the identifica- tion of individuals at increased risk of SCD and VA in the general population, particularly in those at intermediate or high risk of ischemic heart disease, but further studies are needed. Use of biomark- ers has not been shown to be useful for selecting patients for ICDs. A study of 4431 patients found high-sensitivity troponin to be only weakly predic- tive of SCD.S4.2.5-7 However, there are no data on whether high-sensitivity troponin can improve the current SCD prediction algorithms. 4.2.6. Genetic Considerations in Arrhythmia Syndromes Recommendation for Genetic Counselling* COR LOE Recommendation I C-EO In patients and family members in whom genetic testing for risk stratification for SCA or SCD is recommended, genetic counseling is beneficial. *Please refer to section 7.9 for disease-specific recommendations. Synopsis The diagnosis of most inherited arrhythmia syndromes is based on clinical features and family history.


Synopsis The diagnosis of most inherited arrhythmia syndromes is based on clinical features and family history. The availability of genetic testing for inherited arrhyth- mia syndromes can: 1) provide opportunity to confirm a suspected clinical diagnosis and sometimes provide prognostic information for the proband and 2) offer cascade screening of potentially affected family mem- bers when a disease-causing mutation is identified in the proband. The yield of genetic testing varies by dis- ease. The verification of pathogenicity of suspected mutations is an evolving field, and exome sequencing has identified an increasing number of variants of un- certain significance in the general population.S4.2.6-1 S4.2.6-5 Genotyping can have therapeutic implications for some arrhythmogenic phenotypes such as long QT syn- drome and Fabry s disease,S4.2.6-6 S4.2.6-9 where a mono- genic pathogenic mutation has been clearly identi- fied, the risk to mutation positive individuals has been extensively studied, and effective therapy relevant to the mutation can be instituted. In other diseases, such as Brugada syndrome, the role of a clear mono- genic disease-causing mutation is less certain, and the genotype does not provide therapeutic or prognostic information for the proband.S4.2.6-5,S4.2.6-10 S4.2.6-12 In ar- rhythmogenic right ventricular cardiomyopathy, some CLINICAL STATEMENTS AND GUIDELINES desmosomal mutation positive individuals do not de- velop disease, indicating that additional mutations and environmental interactions likely influence the clinical development of disease.S4.2.6-13 S4.2.6-16 Importantly, the absence of an identified disease-causing genetic muta- tion does not exclude the presence of disease, and as such, ongoing monitoring and decision-making are done based on the clinical phenotype.


In other diseases, such as Brugada syndrome, the role of a clear mono- genic disease-causing mutation is less certain, and the genotype does not provide therapeutic or prognostic information for the proband.S4.2.6-5,S4.2.6-10 S4.2.6-12 In ar- rhythmogenic right ventricular cardiomyopathy, some CLINICAL STATEMENTS AND GUIDELINES desmosomal mutation positive individuals do not de- velop disease, indicating that additional mutations and environmental interactions likely influence the clinical development of disease.S4.2.6-13 S4.2.6-16 Importantly, the absence of an identified disease-causing genetic muta- tion does not exclude the presence of disease, and as such, ongoing monitoring and decision-making are done based on the clinical phenotype. Genotyping is frequent- ly most useful when a pathogenic mutation is identified in the proband, such that screening can be applied to relatives who are in a preclinical phase, allowing institu- tion of lifestyle changes, therapy, or ongoing monitoring for those who are gene mutation positive.S4.2.6-7 Refer to Section 7.9 for disease-specific recommendations. In young patients (<40 years of age) without structural heart disease who have unexplained cardiac arrest, unex- plained near drowning, or recurrent exertional syncope, genetic testing may be important to identify an inherited arrhythmia syndrome as a likely cause.S4.2.6-17 S4.2.6-23 Recommendation-Specific Supportive Text 1.


In young patients (<40 years of age) without structural heart disease who have unexplained cardiac arrest, unex- plained near drowning, or recurrent exertional syncope, genetic testing may be important to identify an inherited arrhythmia syndrome as a likely cause.S4.2.6-17 S4.2.6-23 Recommendation-Specific Supportive Text 1. The decision to proceed with genetic testing requires discussion regarding the clinical use of genetic information to be obtained for both the proband and family members, as well as consideration of the important psychological, financial, employment, disability, and life insurance implications of posi- Balancing privacy of health care information for the proband with the right to know for family members, and the ability to provide appropriate communication of information to all potentially affected family mem- bers can be challenging on many levels, including family dynamics, geographic proximity, and access to health care.S4.2.6-25 For these reasons, genetic counseling generally occurs before proceeding with genetic testing, and, from a patient s perspective, is optimally provided by genetic counselors, if avail- able, in collaboration with physicians.S4.2.6-26,S4.2.6-27 A combined approach of genetic counseling with medical guidance may appropriately balance the decision as to whether genetic testing would be beneficial on an individual basis. 4.3. Invasive Testing 4.3.1. Invasive Cardiac Imaging: Cardiac Catheterization or CT Angiography Recommendation for Invasive Imaging: Cardiac Catheterization COR LOE Recommendation I C-EO In patients who have recovered from unexplained SCA, CT or invasive coronary angiography is useful to confirm the presence or absence of ischemic heart disease and guide decisions for myocardial revascularization. Recommendation-Specific Supportive Text 1. Although randomized studies are unavailable, coronary angiography has an important role in establishing or excluding the presence of sig- nificant obstructive ischemic heart disease in patients with SCA or those with life-threatening Recurrent polymorphic VT or VF can be due to ongoing myocardial ischemia that resolves with coronary revascularization.


Although randomized studies are unavailable, coronary angiography has an important role in establishing or excluding the presence of sig- nificant obstructive ischemic heart disease in patients with SCA or those with life-threatening Recurrent polymorphic VT or VF can be due to ongoing myocardial ischemia that resolves with coronary revascularization. Presence of ST-elevation on preresuscitation or early postresuscitation ECG suggests ischemia and potential ACS warranting urgent angiography and ST-elevation can also result from coronary spasm or DC shocks. The absence of ST-elevation after cardiac arrest does not exclude obstructive or thrombotic coronary lesions. A cor- onary angiogram may not be warranted if a non- ischemic cause of SCA is established. Coronary and CT angiography also have an important role excluding the presence of anomalous origin of the coronary arteries that may cause SCD. 4.3.2. Electrophysiological Study for VA Recommendations for Electrophysiological Study References that support the recommendations are summarized in Online Data Supplements 8 and 9.


Electrophysiological Study for VA Recommendations for Electrophysiological Study References that support the recommendations are summarized in Online Data Supplements 8 and 9. COR LOE Recommendations IIa B-R In patients with ischemic cardiomyopathy, NICM, or adult congenital heart disease who have syncope or other VA symptoms and who do not meet indications for a primary prevention ICD, an electrophysiological study can be useful for assessing the risk of III: No Benefit B-R In patients who meet criteria for ICD implantation, an electrophysiological study for the sole reason of inducing VA is not indicated for risk stratification.S4.3.2-8 S4.3.2-11 III: No Benefit B-NR An electrophysiological study is not recommended for risk stratification for VA in the setting of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, or early Synopsis Electrophysiological study can be used to induce sus- tained VA in patients with known or suspected VA. With the advent of the ICD and its proven benefit in the pri- mary and secondary prevention of SCD, there are fewer indications for programmed stimulation to provoke VA. Patients with HF and LVEF 35% generally will have an indication for an ICD and specific induction of VT/VF before implantation is not necessary. Patients with LVEF >35% and unexplained syncope or near-syncope may benefit from an electrophysiological study to determine CLINICAL STATEMENTS AND GUIDELINES if VT/VF is the cause of symptoms and to guide further therapy. Induction of VT/VF is often attempted before catheter ablation of the arrhythmia substrate to guide the procedure and to determine the success of the in- tervention after ablation is performed. An electrophysi- ological study can be used to determine the mechanism of a wide complex tachycardia. See Sections 7.3, 7.4, electrophysiological study for specific disease states. Recommendation-Specific Supportive Text 1.


See Sections 7.3, 7.4, electrophysiological study for specific disease states. Recommendation-Specific Supportive Text 1. A study of electrophysiological testing in patients with symptomatic NICM found inducible VT/VF in 28% of patients which was associated with a higher rate of ICD events during follow-up.S4.3.2-17 In a prospective cohort of 180 patients with isch- emic or NICM and syncope, induction of VT or VF at electrophysiological study correlated with car- diac mortality only in patients with ischemic heart disease. In patients with NICM, cardiac mortality correlated with LVEF but not with inducibility on 2. In patients who meet criteria for ICD implanta- tion (ie, HF and LVEF 35%), data do not sup- port the routine use of electrophysiological study solely for risk stratification, as such patients have been shown to derive survival benefit from the An electrophysiological study may be helpful, however, in selected patients suspected to have preexcitation or supraventricular arrhythmias as the cause of symptoms or wide complex tachycardias that warrant definitive diagnosis and management. SVT leading to VT/VF or aberrantly conducted SVT may also be suspected in younger patients or those with a preserved LVEF. Induction of SVT and ablation may then be curative, with no need for an ICD. In such cases, failure to induce VT/VF after elimination of the substrate for SVT would be expected. 3. Risk stratification for channelopathies is generally made on the basis of symptoms, the ECG,S4.3.2-13, exercise treadmill testing,S4.3.2-25 S4.3.2-27 and the results of genetic testing.S4.3.2-28 S4.3.2-32 The electrophysiological study (ie, programmed ventricular stimulation) does not have prognostic value for risk stratification in patients with these 5. THERAPIES FOR TREATMENT OR PREVENTION OF VA 5.1.


Risk stratification for channelopathies is generally made on the basis of symptoms, the ECG,S4.3.2-13, exercise treadmill testing,S4.3.2-25 S4.3.2-27 and the results of genetic testing.S4.3.2-28 S4.3.2-32 The electrophysiological study (ie, programmed ventricular stimulation) does not have prognostic value for risk stratification in patients with these 5. THERAPIES FOR TREATMENT OR PREVENTION OF VA 5.1. Medication Therapy With the exception of beta blockers (eg, metoprolol succinate, carvedilol), there is no evidence from RCTs that antiarrhythmic medications for VA improve survival when given for the primary or secondary prevention of SCD. However, the use of these medications is essential in some patients to control arrhythmias and improve symptoms. Medication use for VA is discussed, and any recommendations are listed, in subsequent sec- tions. Further, medication-induced proarrhythmia is ad- dressed in Section 10.7. Antiarrhythmic medications are often categorized by the Vaughan Williams 4-level schema (class I: fast sodium channel blockers; class II: beta blockers; class III: repolarization potassium current blockers; class IV: nondihydropyridines calcium channel blockers).S5.1.5.2-1 This system does not address the complexities in antiar- rhythmic medications, since nearly every agent has mul- tiple effects. Table 7 shows uses, electrophysiological effects, pharmacological effects, and common adverse effects of antiarrhythmic medications. 5.1.1. Medications With Prominent Sodium Channel Blockade Except in specific circumstances, sodium channel block- ers (Vaughn-Williams class I agents) have a limited role in the prevention of VT/SCD; this is based on a lack of survival benefit and increased mortality observed dur- ing chronic therapy in patients with ischemic heart dis- ease (see Section 10.7).


Medications With Prominent Sodium Channel Blockade Except in specific circumstances, sodium channel block- ers (Vaughn-Williams class I agents) have a limited role in the prevention of VT/SCD; this is based on a lack of survival benefit and increased mortality observed dur- ing chronic therapy in patients with ischemic heart dis- ease (see Section 10.7). Specific circumstances where sodium channel blockers have been used to treat VT/ SCA include: intravenous lidocaine for patients with re- fractory VT/cardiac arrest (especially witnessed)S5.1.5.2-3 ; oral mexiletine for congenital long QT syndromeS5.1.5.2-4 ; quinidine for patients with Brugada syndrome; and fle- cainide for patients with catecholaminergic polymor- phic ventricular tachycardia.S5.1.5.2-5 These medications could also be used in ICD patients with drug- and abla- tion-refractory VT. One newer medication of potential benefit, based on very limited data, is ranolazine. This medication, developed and FDA-approved as an antianginal agent, provides relatively specific late sodium channel current blockade in addition to less potent blockade of the phase 3 repolarizing potassium current; that is, the rap- id delayed rectifier potassium current; IKr. The potential for clinical antiarrhythmic efficacy is supported by basic studies and experimental models.S5.1.5.2-6 Clinical data are scant. In a study of 12 patients, ranolazine reduced ICD shocks in otherwise medication-resistant VT/VF in 11 In MERLIN TIMI-36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36), ranolazine did not reduce SCD but did reduce VT in the first few days after a non-ST-segment In 1 RCT, high-risk ICD patients with ischemic or NICM were randomly assigned to ra- nolazine 1000 mg twice a day versus placebo.S5.1.5.2-9 High risk was defined as: 1) having a primary prevention CLINICAL STATEMENTS AND GUIDELINES Table 7.


In a study of 12 patients, ranolazine reduced ICD shocks in otherwise medication-resistant VT/VF in 11 In MERLIN TIMI-36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36), ranolazine did not reduce SCD but did reduce VT in the first few days after a non-ST-segment In 1 RCT, high-risk ICD patients with ischemic or NICM were randomly assigned to ra- nolazine 1000 mg twice a day versus placebo.S5.1.5.2-9 High risk was defined as: 1) having a primary prevention CLINICAL STATEMENTS AND GUIDELINES Table 7. Pharmacological Characteristics of Available Antiarrhythmic Medications for Treating VA Antiarrhythmic Medication (Class) and Dose Uses in VA/SCA Target Electrophysiological Effects Pharmacological Characteristics Common Adverse Effects Acebutolol PO 200 1200 mg daily or up to 600 mg bid VT, PVCs Beta 1, Mild intrinsic sympathomimetic activity Sinus rate slowed AV nodal refractoriness increased Active metabolite t1/2 : pProlonged with renal impairment) Metab: H Excr: F 60%, U 40% Cardiac: Bradycardia, hypotension, HF, AVB Other: Dizziness, fatigue, anxiety, impotence, hyper/ hypoesthesia Amiodarone (III) IV: 300 mg bolus for VF/pulseless VT arrest; 150-mg bolus for stable VT; 1 mg/min x 6 h, then 0.5 mg/min x 18 h PO: 400 mg* q 8 to 12 h for 1 2 wk, then 300 400 mg daily; reduce dose to 200 mg daily if possible VT, VF, PVC, INa , ICa , IKr , IKs , Ito , Beta receptor, Alpha receptor receptor Sinus rate slowed QRS prolonged QTc prolonged AV nodal refractoriness increased; increased DFT : 26 107 d Metab: H Excr: F Cardiac: Hypotension, bradycardia, AVB, TdP, slows VT below programmed ICD detection rate, increases defibrillation threshold Other: Corneal microdeposits, thyroid abnormalities, ataxia, nausea, emesis, constipation, photosensitivity, skin discoloration, ataxia, dizziness, peripheral neuropathy, tremor, hepatitis, cirrhosis, pulmonary fibrosis or pneumonitis Atenolol (II) PO: 25 100 mg qd or bid VT, PVC, ARVC, LQTS Beta 1 Sinus rate slowed AV nodal refractoriness increased : 6 7 h (prolonged with renal impairment) Metab: H Excr: F 50%, U 40% Cardiac: Bradycardia, hypotension, HF, AVB Other: Dizziness, fatigue, depression, impotence Bisoprolol (II) PO: 2.5 10 mg once daily VT, PVC Beta 1 receptor Sinus rate slowed AV nodal refractoriness increased : 9 12 h Metab: H Excr: U Cardiac: Chest pain, bradycardia, AVB Other: Fatigue, insomnia, diarrhea Carvedilol (II) PO: 3.125 25 mg q VT, PVC Beta 1 and 2 receptors, Alpha Sinus rate slowed AV nodal refractoriness increased : 7 10 h Metab: H Excr: F Cardiac: Bradycardia, hypotension, AVB, edema, syncope Other: Hyperglycemia, dizziness, fatigue, diarrhea Diltiazem (IV) IV: 5 10 mg qd: 15 30 min Extended release: PO: VT specifically RVOT, idiopathic LVT ICa-L Sinus rate slowed PR prolonged AV nodal conduction slowed : Injection 2 5 h, immediate release 4.5 12 h, extended release 12 h, and severe hepatic impairment 14 16 h Metab: H Excr: U Cardiac: Hypotension, edema, HF, AVB, bradycardia, exacerbation of HFrEF Other: Headache, rash, constipation Esmolol (II) IV: 0.5 mg/kg bolus, VT Beta 1 receptor Sinus rate slowed AV nodal refractoriness increased : 9 min Metab: RBC esterases Excr: U Cardiac: Bradycardia, hypotension, HF, AVB Other: Dizziness, nausea Flecainide (IC) PO: 50 200 mg q 12 h VT, PVC (in the absence of structural heart disease).


Has a role in treating patients with CPVT INa , IKr , IKur PR prolonged QRS prolonged; increased DFT : 7 22 h Metab: H Excr: U Cardiac: Sinus node dysfunction, AVB, drug-induced Brugada syndrome, monomorphic VT in patients with a myocardial scar, exacerbation of HFrEF Other: Dizziness, tremor, vision disturbance, dyspnea, nausea Lidocaine (IB) IV: 1 mg/kg bolus, 1 3 mg/min 1 1.5 mg/kg. Repeat 0.5 0.75 mg/kg bolus every 5 10 min (max cumulative dose 3 mg/kg). Maintenance infusion is 1 4 mg/min although one could start at 0.5 mg/min VT, VF INa No marked effect on most intervals; QTc can slightly shorten terminal 90 120 min.


Maintenance infusion is 1 4 mg/min although one could start at 0.5 mg/min VT, VF INa No marked effect on most intervals; QTc can slightly shorten terminal 90 120 min. Prolonged in HF, liver disease, shock, severe renal disease Metab: H Excr: U Cardiac: Bradycardia, hemodynamic collapse, AVB, sinus arrest Other: Delirium, psychosis, seizure, nausea, tinnitus, dyspnea, bronchospasm (Continued) CLINICAL STATEMENTS AND GUIDELINES Metoprolol (II) IV: 5 mg q 5 min up to PO: 25 100 mg Extended release qd or q 12 h VT, PVC Beta 1 receptor Sinus rate slowed AV nodal refractoriness increased : 3 4 h Metab: H Excr: U Cardiac: Bradycardia, hypotension, AVB Other: Dizziness, fatigue, diarrhea, depression, dyspnea Mexiletine (IB) PO: 150 300 mg q 8 h or q 12 h T, VF, PVC, has a role in patients INa No marked effect on most intervals; QTc can slightly shorten : 10 14 h Metab: H Excr: U Cardiac: HF, AVB Other: Lightheaded, tremor, ataxia, paresthesias, nausea, blood dyscrasias Nadolol (II) PO: 40 320 mg daily VT, PVC, LQTS, CPVT Beta 1 and 2 receptors Sinus rate slowed AV nodal refractoriness increased : 20 24 h Metab: none Excr: U Cardiac: Bradycardia, hypotension, HF, AVB Other: Edema, dizziness, cold extremities, bronchospasm Procainamide (IA) IV: loading dose 10 17 mg/kg at 20 50 mg/ min Maintenance dose: 1 4 mg/min PO (SR preparation): 500 1250 mg q 6 h VT INa , IKr QRS prolonged QTc prolonged; increased DFT Metab: H : 2 5 h; NAPA 6 8 h prolonged in renal dysfunction.


Prolonged in HF, liver disease, shock, severe renal disease Metab: H Excr: U Cardiac: Bradycardia, hemodynamic collapse, AVB, sinus arrest Other: Delirium, psychosis, seizure, nausea, tinnitus, dyspnea, bronchospasm (Continued) CLINICAL STATEMENTS AND GUIDELINES Metoprolol (II) IV: 5 mg q 5 min up to PO: 25 100 mg Extended release qd or q 12 h VT, PVC Beta 1 receptor Sinus rate slowed AV nodal refractoriness increased : 3 4 h Metab: H Excr: U Cardiac: Bradycardia, hypotension, AVB Other: Dizziness, fatigue, diarrhea, depression, dyspnea Mexiletine (IB) PO: 150 300 mg q 8 h or q 12 h T, VF, PVC, has a role in patients INa No marked effect on most intervals; QTc can slightly shorten : 10 14 h Metab: H Excr: U Cardiac: HF, AVB Other: Lightheaded, tremor, ataxia, paresthesias, nausea, blood dyscrasias Nadolol (II) PO: 40 320 mg daily VT, PVC, LQTS, CPVT Beta 1 and 2 receptors Sinus rate slowed AV nodal refractoriness increased : 20 24 h Metab: none Excr: U Cardiac: Bradycardia, hypotension, HF, AVB Other: Edema, dizziness, cold extremities, bronchospasm Procainamide (IA) IV: loading dose 10 17 mg/kg at 20 50 mg/ min Maintenance dose: 1 4 mg/min PO (SR preparation): 500 1250 mg q 6 h VT INa , IKr QRS prolonged QTc prolonged; increased DFT Metab: H : 2 5 h; NAPA 6 8 h prolonged in renal dysfunction. Anephric: proc 11 h and NAPA Excr: U Cardiac: TdP; AVB, hypotension and exacerbation of HFrEF Other: Lupus symptoms, diarrhea, nausea, blood dyscrasias Propafenone (IC) PO: Immediate release 150 300 mg q 8 h Extended release 225 425 mg q 12 h VT, PVC (in the absence of structural heart disease) INa , IKr , IKur , Beta receptor, Alpha receptor PR prolonged QRS prolonged; increased DFT : 2 10 h or 10 32 h : extensive h; poor metabolizers 10 32 h. Metab: H Excr: U Cardiac: HF, AVB, drug-induced Brugada syndrome Other: Dizziness, fatigue, nausea, diarrhea, xerostomia, tremor, blurred vision Propranolol (II) IV: 1 3 mg q 5 min to a total of 5 mg PO: Immediate release 10 40 mg q 6 h; Extended release 60 160 mg q 12 h VT, PVC, LQTS Beta 1 and 2 receptors, INa Sinus rate slowed AV nodal refractoriness increased : Immediate release Extended release 8 10 h Metab: H Excr: U Cardiac: Bradycardia, hypotension, HF, AVB Other: Sleep disorder, dizziness, nightmares, hyperglycemia, diarrhea, bronchospasm Quinidine (IA) PO: sulfate salt 200 600 mg q 6 h to q 12 h gluconate salt 324 648 mg q 8 h to q 12 h IV: loading dose: 800 mg in 50 mL infused at T, VF, (including short QT syndrome, Brugada) INa , Ito , IKr , M, Alpha receptor QRS prolonged QTc prolonged; increased DFT : 6 8 h longer in HF, liver cirrhosis, and with older age Metab: H Excr: U Cardiac: Syncope, TdP, AVB Other: Dizziness, diarrhea, nausea, esophagitis, emesis, tinnitus, blurred vision, rash, weakness, tremor; blood dyscrasias Ranolazine (not classified) PO: 500 1000 mg q VT INa , IKr Sinus rate slowed Tc prolonged : 7 h Metab: H Excr: U 75%, F 25% Cardiac: Bradycardia, hypotension Other: Headache, dizziness, syncope, nausea, dyspnea Sotalol (III) IV: 75 mg q 12 h PO: 80 120 mg q 12 h, may increase dose every 3 d; max 320 mg/d VT, VF, PVC IKr , Beta 1 and 2 receptor Sinus rate slowed QTc prolonged AV nodal refractoriness increased; decreased DFT : 12 h Metab: none Excr: U Cardiac: Bradycardia, hypotension, HF, syncope, TdP Other: Fatigue, dizziness, weakness, dyspnea, bronchitis, depression, nausea, diarrhea Table 7.


Continued Antiarrhythmic Medication (Class) and Dose Uses in VA/SCA Target Electrophysiological Effects Pharmacological Characteristics Common Adverse Effects (Continued) CLINICAL STATEMENTS AND GUIDELINES ICD without a history of documented VT/VF and with one of the following conditions: BUN 26 mg/dL, QRS >120 msec, atrial fibrillation, or NSVT or >500 VPBs on 24-hour Holter recording; 2) having a primary preven- tion ICD with a history of documented VT/VF appropri- ately treated with ICD therapy or untreated NSVT; or 3) having a secondary prevention ICD after documented VT/VF or cardiac arrest. Ranolazine did not significantly reduce the primary endpoint of VT/VF requiring appro- priate ICD therapy or death. In a prespecified secondary analysis, ranolazine was associated with a significant reduction in VT events treated with anti-tachycardia 5.1.2.


In a prespecified secondary analysis, ranolazine was associated with a significant reduction in VT events treated with anti-tachycardia 5.1.2. Beta Blockers Because of their excellent safety profile and effec- tiveness in treating VA and reducing the risk of SCD, beta blockers are often first-line antiarrhythmic Their antiarrhythmic efficacy is related to the effects of adrenergic-receptor blockade on sympathetically mediated triggering mechanisms, slowing of the sinus rate, and possibly inhibition of ex- cess calcium release by the ryanodine receptor.S5.1.5.2-12 Beta blockers reduce all-cause mortality and SCD in patients with HF with reduced EF (HFrEF).S5.1.5.2-13 S5.1.5.2-15 Although beta blockers have long been proven to re- duce mortality after MI,S5.1.5.2-16 registry data confirm that early beta blocker use in patients with MI and risk factors for shock (>70 years of age, symptoms <12 hours [ST-elevation MI patients], systolic blood pres- sure <120 mm Hg, and heart rate >110 beat/min on presentation) is associated with an increased risk of shock or death.S5.1.5.2-17 In the setting of polymorphic VT after MI, beta blockers reduce mortality.S5.1.5.2-18 Beta blockers suppress VA in some patients with structurally When used in combination with membrane-stabilizing antiarrhythmic medications, beta blockers can enhance antiarrhythmic efficacy.S5.1.5.2-20 Beta blockers (eg, nadolol, propranolol) are also first- line therapy for some cardiac channelopathies (eg, long QT syndrome, catecholaminergic polymorphic ventricu- lar tachycardia). 5.1.3. Amiodarone and Sotalol Amiodarone possesses a wide spectrum of actions that include blockade of beta receptors and sodium, calci- um and potassium currents (ie, a multichannel blocker). Its overall long-term effect on survival is controversial, with most studies showing no clear advantage over placebo.


Its overall long-term effect on survival is controversial, with most studies showing no clear advantage over placebo. A few studies and a meta-analysis of several large studies have shown a reduction in SCD using ami- odarone in patients with LV dysfunction due to prior MI and NICM,S5.1.5.2-21 S5.1.5.2-23 but SCD-HeFT showed no survival benefit from amiodarone compared with A secondary analysis of the SCD-HeFT showed increased risk of mortality with amiodarone in patients with New York Heart Association (NYHA) class A systematic review of the litera- ture in high-risk patients (LVEF <40%, with or without coronary disease), concluded that, for primary preven- tion, amiodarone, compared with no treatment or pla- cebo, decreased the risk of SCD (Risk ratio: 0.76; 95% CI: 0.66 0.88) and all-cause mortality (Risk ratio: 0.88; 95% CI: 0.78 1.00), but the quality of the supporting evidence was very low.S5.1.5.2-26 For secondary prevention of SCD, the same systematic review identified neither risk nor benefit with amiodarone.S5.1.5.2-26 Compared with beta-blocker therapy and other antiarrhythmic medications (including sotalol), amiodarone appears to reduce the risk of SCD and all-cause mortality.S5.1.5.2-26 Intravenous amiodarone has a role in reducing recur- rent VF/VF during resuscitation.S5.1.5.2-3,S5.1.5.2-27 S5.1.5.2-29 Chronic administration of amiodarone is associated with complex medication interactions and a host of adverse effects involving the lung, liver, thyroid, skin, and nervous system.


A few studies and a meta-analysis of several large studies have shown a reduction in SCD using ami- odarone in patients with LV dysfunction due to prior MI and NICM,S5.1.5.2-21 S5.1.5.2-23 but SCD-HeFT showed no survival benefit from amiodarone compared with A secondary analysis of the SCD-HeFT showed increased risk of mortality with amiodarone in patients with New York Heart Association (NYHA) class A systematic review of the litera- ture in high-risk patients (LVEF <40%, with or without coronary disease), concluded that, for primary preven- tion, amiodarone, compared with no treatment or pla- cebo, decreased the risk of SCD (Risk ratio: 0.76; 95% CI: 0.66 0.88) and all-cause mortality (Risk ratio: 0.88; 95% CI: 0.78 1.00), but the quality of the supporting evidence was very low.S5.1.5.2-26 For secondary prevention of SCD, the same systematic review identified neither risk nor benefit with amiodarone.S5.1.5.2-26 Compared with beta-blocker therapy and other antiarrhythmic medications (including sotalol), amiodarone appears to reduce the risk of SCD and all-cause mortality.S5.1.5.2-26 Intravenous amiodarone has a role in reducing recur- rent VF/VF during resuscitation.S5.1.5.2-3,S5.1.5.2-27 S5.1.5.2-29 Chronic administration of amiodarone is associated with complex medication interactions and a host of adverse effects involving the lung, liver, thyroid, skin, and nervous system. As a general rule, the longer the therapy and the higher dose of amiodarone, the great- er the likelihood of adverse effects that will require Verapamil (IV) IV: 2.5 5 mg q 15 30 min Sustained release PO: VT (specifically RVOT, verapamil- sensitive idiopathic LVT) ICa-L Sinus rate slowed PR prolonged AV nodal conduction slowed : 3 7 h Metab: H Excr: U Cardiac: Hypotension, edema, HF, AVB, bradycardia, exacerbation of HFrEF Other: Headache, rash, gingival hyperplasia, constipation, dyspepsia *Although up to 800 mg every 8 h might be used, higher doses of amiodarone are associated with a higher risk of adverse events.


As a general rule, the longer the therapy and the higher dose of amiodarone, the great- er the likelihood of adverse effects that will require Verapamil (IV) IV: 2.5 5 mg q 15 30 min Sustained release PO: VT (specifically RVOT, verapamil- sensitive idiopathic LVT) ICa-L Sinus rate slowed PR prolonged AV nodal conduction slowed : 3 7 h Metab: H Excr: U Cardiac: Hypotension, edema, HF, AVB, bradycardia, exacerbation of HFrEF Other: Headache, rash, gingival hyperplasia, constipation, dyspepsia *Although up to 800 mg every 8 h might be used, higher doses of amiodarone are associated with a higher risk of adverse events. Modified from Shleifer JW, Alpha indicates alpha-adrenergic receptor; ARVC, arrhythmogenic right ventricular cardiomyopathy; AV, atrioventricular; AVB, atrioventricular block; Beta, beta- adrenergic receptor; HF, heart failure; CPVT, catecholaminergic polymorphic ventricular tachycardia; DFT, defibrillation threshold; F, feces; H, hepatic; ICa , L-type calcium channel current; IK1 , inward rectifier potassium channel; IKACh , muscarinic receptor-gated potassium channel; IKATP , adenosine-activated potassium channel; IKr , rapid delayed rectifier potassium current; IKs , slow delayed rectifier potassium current; IKur , ultra-rapid delayed rectifier potassium current; INa , fast inward sodium current; Ito , transient outward potassium current; LQTS, long QT syndrome; LVT, left ventricular tachycardia; M, muscarinic; Metab, metabolism; NAPA, n-acetyl procainamide; PVC, premature ventricular complex; QTc, corrected QT interval; t1/2 , half-life; RVOT, right ventricular outflow tract; T3, triiodothyronine; TdP, torsades de pointes; U, urine; VT, ventricular tachycardia; and VF, ventricular fibrillation. Table 7. Continued Antiarrhythmic Medication (Class) and Dose Uses in VA/SCA Target Electrophysiological Effects Pharmacological Characteristics Common Adverse Effects CLINICAL STATEMENTS AND GUIDELINES discontinuance of the medication.S5.1.5.2-26 For this rea- son, chronic treatment of young patients with amioda- rone should be reserved as a bridge to more definitive treatment options such as catheter ablation.


Continued Antiarrhythmic Medication (Class) and Dose Uses in VA/SCA Target Electrophysiological Effects Pharmacological Characteristics Common Adverse Effects CLINICAL STATEMENTS AND GUIDELINES discontinuance of the medication.S5.1.5.2-26 For this rea- son, chronic treatment of young patients with amioda- rone should be reserved as a bridge to more definitive treatment options such as catheter ablation. Baseline evaluation of patients may include ECG, liver function tests, thyroid function tests, chest x-ray, and pulmo- nary function tests (including diffusing capacity of the lungs for carbon monoxide). Monitoring for toxicity generally includes periodic history and physical exami- nation, as well as evaluation of the ECG, chest x-ray, and thyroid, liver, and lung function. High-resolution chest CT is generally reserved for suspected pulmonary Although sotalol has some efficacy in suppressing VA, it has significant proarrhythmic effects and has not been shown to improve survival.S5.1.5.2-31 D-sotalol was shown in the SWORD (Survival With Oral d-Sotalol) trial to increase the risk of death in patients with heart Unlike amiodarone and many other an- tiarrhythmic agents, sotalol appears to reduce the de- Also, sotalol may lead to HF decompensation, and so its use in patients with an LVEF <20% is generally avoided. 5.1.4. Calcium Channel Blockers For the treatment of most VA, nondihydropyridines cal- cium channel blockers have no role. In fact, intravenous verapamil given for sustained VT has been associated with hemodynamic collapse, especially in patients with For patients with a structural- ly normal hearts, verapamil or diltiazem can suppress some outflow tract origin.S5.1.5.2-35 S5.1.5.2-39 Oral and in- travenous verapamil are effective in treating idiopathic interfascicular reentrant LVT.S5.1.5.2-38 Calcium channel bloickers should not be given to patients with VT in the settin of HFrEF. 5.1.5.


In fact, intravenous verapamil given for sustained VT has been associated with hemodynamic collapse, especially in patients with For patients with a structural- ly normal hearts, verapamil or diltiazem can suppress some outflow tract origin.S5.1.5.2-35 S5.1.5.2-39 Oral and in- travenous verapamil are effective in treating idiopathic interfascicular reentrant LVT.S5.1.5.2-38 Calcium channel bloickers should not be given to patients with VT in the settin of HFrEF. 5.1.5. Nonantiarrhythmic Medications and Therapies Administration of potassium and magnesium has been proposed as helpful adjuncts in the prevention Hypokalemia and hypomagne- semia are common consequences of diuretic therapy in HF, both have been associated with VA during an and can increase the risk of torsades de pointes in patients on medications or with conditions known to prolong the QT interval.S5.1.5.2-43 In fact, in patients with torsades de pointes, intravenous magnesium is first-line therapy.S5.1.5.2-44 In patients who are deficient in both magnesium and potassium, mag- nesium should be repleted to facilitate replacement of In the case of potassium, some recommend keeping the potassium level between 4.5 mmol/L and 5 mmol/L to prevent VA and A large observational study of pa- tients with an acute MI found that the lowest rates of death were seen in patients with serum potassium concentrations between 3.5 mmol/L and <4.5 mmol/ Interestingly, the rates of VA did not rise unless the potassium was <3 mmol/L or 5 mmol/L. Likewise, a large randomized, double-blind trial of intravenous magnesium in the post-MI period demonstrated no It remains quite rea- sonable to monitor potassium and magnesium during aggressive diuresis and in the post-MI period.


Likewise, a large randomized, double-blind trial of intravenous magnesium in the post-MI period demonstrated no It remains quite rea- sonable to monitor potassium and magnesium during aggressive diuresis and in the post-MI period. 5.1.5.2. n-3 Fatty Acids and Lipids Both n-3 poly-unsaturated fatty acids and statin therapies may have a role in the prevention of SCD, thought to be due to a stabilization of the bilipid myo- cyte membrane involved in maintaining electrolyte Early data were promising regarding the effects of n-3 polyunsaturated fatty acids on the reduction of cardiovascular events and SCD. In 2006, a large meta- analysis of 19 observational and RCTs demonstrated a significant association between the consumption of n-3 polyunsaturated fatty acids and prevention of The randomized GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto)-Prevenzione trial in people with recent MI, found that fish oil 1 g/d reduced mortality, due to fewer SCD.S5.1.5.2-51 However, subsequent RCTs have not replicated these benefits and have shown n-3 polyunsaturated fatty acids to be Because studies showed a consistent lack of harm from n-3 polyunsaturated fatty acids, patients can be reassured of their safety. Longer- term data will hopefully clarify the conflicting results. In contrast, statin medications clearly reduce mor- tality and appear to reduce the risk of SCD related to ischemic heart disease.S5.1.5.2-57 The predominant mecha- nism remains uncertain. Prevention of coronary plaque rupture or a direct cardioprotective effect reducing VA has been suggested.


Prevention of coronary plaque rupture or a direct cardioprotective effect reducing VA has been suggested. Experimental ischemia/reperfu- sion models demonstrate a cardioprotective effect of statins, and a large observational analysis observed this effect in humans.S5.1.5.2-42,S5.1.5.2-56 S5.1.5.2-58 This was ex- plored further in HF in several secondary analyses of patients on statins in ICD prevention trials, including the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy), SCD-HeFT, AVID (Antiarrhythmics versus Implantable and DEFINITE (DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation) trials that showed less SCD risk among the patients However, this general effect in HF was not confirmed in 2 prospective RCTs of rosuvastatin in HF; the CORONA (Controlled Rosu- vastatin Multinational Trial in Heart Failure) and GISSI- HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure).S5.1.5.2-63,S5.1.5.2-64 It appears that the beneficial effects of statins are con- CLINICAL STATEMENTS AND GUIDELINES fined to the population with or at risk for atheroscle- rotic cardiovascular disease and/or ischemia, and not HF generally. 5.2. Preventing SCD With HF Medications Recommendation for Pharmacological Prevention of SCD References that support the recommendation are summarized in Online Data Supplement 10. COR LOE Recommendation I A In patients with HFrEF (LVEF 40%), treatment with a beta blocker, a mineralocorticoid receptor antagonist and either an angiotensin-converting enzyme inhibitor, an angiotensin-receptor blocker, or an angiotensin receptor-neprilysin inhibitor is recommended to reduce SCD and all-cause Recommendation-Specific Supportive Text 1. For patients with HF and depressed LV func- tion, appropriate medical therapy is important to reduce SCD. These therapies have various beneficial effects on arrhythmia mechanisms. Beta blockers reduce myocardial oxygen demand and electrical excitability, and counter arrhyth- mogenic effects of sympathetic stimulation.


Beta blockers reduce myocardial oxygen demand and electrical excitability, and counter arrhyth- mogenic effects of sympathetic stimulation. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers decrease preload and afterload, decreasing myocardial oxygen demand, blocking the formation of angioten- sin II, and slowing the progression of ventricular remodeling and fibrosis. Mineralocorticoid recep- tor antagonists limit potassium loss, decrease fibrosis, and increase the myocardial uptake of RCTs in patients with HFrEF have consistently demonstrated that chronic therapy with beta blockers reduces all-cause mortality, VA, and Three beta blockers (ie, biso- prolol, carvedilol, sustained-release metoprolol suc- cinate) have been proven to reduce mortality in patients with current or prior symptoms of HFrEF without beta-blocker contraindications. Angiotensin- converting enzyme inhibition also reduces mortality Angiotensin-receptor blockers added to angiotensin-converting enzyme inhibitor showed additional benefit to angiotensin-converting enzyme inhibitors in someS5.2-10 but not other RCTs.S5.2-8,S5.2-11 Therapy with the mineralocorticoid-receptor antago- nists, spironolactone and eplerenone, have also dem- onstrated reductions in both all-cause mortality and Recent studies of the angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) versus angiotensin-converting enzyme inhibitor demonstrated a reduction in SCD and cardiac mortality.S5.2-14 5.3. Defibrillators for Treatment of VA and SCD See Sections 7, 10.2, 10.3, 10.8, and 10.9. Defibrillation is highly effective in terminating life- threatening VA. This therapy can be delivered by a transvenous ICD, a subcutaneous implantable cardio- verter-defibrillator, a wearable cardioverter-defibrillator or an external defibrillator. These devices monitor the heart rhythm continuously and deliver therapy in re- sponse to a tachycardia that meets preprogrammed detection rates and arrhythmia duration. The vast ma- jority of transvenous ICDs are implanted in the subcla- vicular area under fluoroscopy guidance. subcutaneous implantable cardioverter-defibrillators are implanted in the left side of the chest over the sixth rib between the left midaxillary and left anterior axillary lines.


subcutaneous implantable cardioverter-defibrillators are implanted in the left side of the chest over the sixth rib between the left midaxillary and left anterior axillary lines. ICDs with epicardial sensing and pacing leads are still being im- planted in some patients especially those with certain forms of congenital heart disease. The transvenous ICD has been in clinical use for >3 decades, and robust data from high-quality RCTs support its use in various patient populations includ- ing survivors of cardiac arrest, patients with VT and structural heart disease, and patients with significant LV dysfunction. 5.4. Catheter Ablation 5.4.1. General Considerations Catheter ablation is an important treatment option for patients with VA when antiarrhythmic medications are ineffective, not tolerated, or not desired by the patient. Monomorphic VA usually have an origin or substrate that can be targeted for ablation. Ablation is an op- tion for selected patients with polymorphic VT/VF only if an initiating PVC focus or substrate can be identified. The ablation strategy, risks and outcomes are related to the mechanism and location of the VA. Most VA origi- nate close to the subendocardium and are approached through a transvenous (for the right ventricle) or trans- aortic/transeptal (for the left ventricle) catheterization. Some diseases give rise to VA from the subepicardium, which may be approached by epicardial mapping and ablation. Pericardial access is usually achieved by a per- cutaneous subxiphoid puncture. The catheter ablation procedure usually involves attempts to induce VT by programmed electrical stimulation to confirm the di- agnosis and guide ablation. Problems limiting success include inability to induce an arrhythmia for mapping (common with idiopathic VA), or origin of the arrhyth- mia from an inaccessible location in the myocardium (common in some cardiomyopathies). CLINICAL STATEMENTS AND GUIDELINES 5.4.2. VA in Patients With No Apparent Structural Heart Disease See Section 8.


VA in Patients With No Apparent Structural Heart Disease See Section 8. VA that are not associated with underlying structur- al heart disease or a genetic arrhythmia syndrome are commonly referred to as idiopathic. Most idiopathic VA are monomorphic and based on a focal mecha- nism of triggered activity or abnormal automaticity; a few are due to reentry. For patients who are symp- tomatic, and in whom antiarrhythmic medications are ineffective, not tolerated, or not desired by the patient, catheter ablation is a treatment option. The ablation strategy is to identify the site of origin mani- fested by the earliest site of electrical activation, or when this is not practical, by pace mapping. Catheter ablation of idiopathic VA is usually accomplished with endocardial catheterization, though an epicardial ap- proach through the coronary venous circulation or a subxiphoid pericardial puncture may occasionally be required. Ablation failure for idiopathic VA is often due to inability to provoke the arrhythmia to allow mapping in the electrophysiological laboratory or ori- gin from an inaccessible region. 5.4.3. Scar-Related VT See Section 8. For most patients with structural heart disease, sustained monomorphic VT is due to reentry through regions of surviving myocardial fibers associated with areas of fibrous scar. The ablation strategy for these re- entry circuits is to identify and eliminate channels of surviving myocardium within the scar that are often as- sociated with slow conduction facilitating reentry. For most VTs that are related to prior MI, the substrate is on the subendocardial surface of the left ventricle. In NICM, the reentrant circuits are more variable in loca- tion, often involve the epicardial surface of either ven- tricle and frequently extending into the midmyocar- dium where ablation may be difficult to achieve from either surface.


In NICM, the reentrant circuits are more variable in loca- tion, often involve the epicardial surface of either ven- tricle and frequently extending into the midmyocar- dium where ablation may be difficult to achieve from either surface. In tetralogy of Fallot specific reentry paths have been defined.S5.4.3-1 Electroanatomical map- ping that helps clarify the relation of electrophysiologi- cal abnormalities to cardiac anatomy is commonly em- ployed. Areas of scar can be appreciated as regions of relatively low electrogram voltage. For scar-related VTs, hemodynamic intolerance often limits mapping during VT. Ablation is then often guided by substrate mapping, in which areas of scar and potential reentry circuit sub- strate are delineated in electroanatomic maps based on electrocardiographic and pacing characteristics as- sessed during hemodynamically stable sinus or paced rhythm. Catheter ablation of scar-related VT requires an advanced level of experience by the operator, electro- physiological laboratory staff, and anesthesiologists as well as availability of surgical back-up and specialized mapping, imaging, and ablation equipment.S5.4.3-2,S5.4.3-3 5.5. Surgery and Revascularization Procedures in Patients With Ischemic Heart Disease Recommendations for Surgery and Revascularization Procedures in Patients With Ischemic Heart Disease References that support the recommendations are summarized in Online Data Supplement 11. COR LOE Recommendations I B-NR Patients with sustained VA and survivors of SCA should be evaluated for ischemic heart disease, and should be revascularized as I C-EO In patients with anomalous origin of a coronary artery suspected to be the cause of SCA, repair or revascularization is recommended. Recommendation-Specific Supportive Text 1. Myocardial ischemia is a cause of sustained poly- morphic VT/VF, and revascularization is an effec- tive treatment to prevent myocardial ischemia.


Myocardial ischemia is a cause of sustained poly- morphic VT/VF, and revascularization is an effec- tive treatment to prevent myocardial ischemia. For patients with life-threatening VA, observa- tional studies show that patients undergoing coronary artery bypass graft (CABG) had substan- tially better survival after accounting for other The risk of SCD appears compara- ble for patients with complex ischemic heart disease For patients with low LVEF and ischemic heart disease amenable to CABG, the risk of SCD is lower with CABG than medical therapy.S5.5-2,S5.5-7 Observational studies show an association between a lower likelihood of death with revascularization for survivors of SCA and CABGS5.5-3 Revascularization alone is usually insufficient to prevent recurrence of sustained monomorphic VT; further evaluation for inducible VT is generally con- sidered if ventricular function is depressed and/or scar is present. 2. Anomalous aortic origin of the coronary arter- ies is detected in approximately 1% of patients undergoing routine coronary angiography, and <0.2% of children and adolescents under- Although ischemic heart disease is detected in as many as 24% to 55% of SCD cases in young patients <35 years anomalous aortic origin of the coronary arteries is an important cause of SCD in the young, reported in 10% to 17% of patients included in postmortem studies.S5.5-10,S5.5-11 Anomalous origin of the coronary arteries can be identified by echocardiography, invasive coronary angiography, CT angiography or cardiac MRI. In patients with SCA or life-threatening VA presumed CLINICAL STATEMENTS AND GUIDELINES related to ischemia caused by anomalous origin of a coronary artery, repair or revascularization is performed to alleviate ischemia and reduce the recurrence of VA.S5.5-6,S5.5-7,S5.5-12 S5.5-14 5.5.1. Surgery for Arrhythmia Management Recommendation for Surgery for Arrhythmia Management References that support the recommendation are summarized in Online Data Supplement 12.


Surgery for Arrhythmia Management Recommendation for Surgery for Arrhythmia Management References that support the recommendation are summarized in Online Data Supplement 12. COR LOE Recommendation IIb C-LD In patients with monomorphic VT refractory to antiarrhythmic medications and attempts at catheter ablation, surgical ablation may be Recommendation-Specific Supportive Text 1. Cardiac surgery as a standalone procedure for VT is rarely performed, but has a role in some highly symptomatic patients, when antiarrhyth- mic medications and catheter ablation fails or are not possible, particularly if the failure of abla- tion is due to an arrhythmia arising from an area that is inaccessible to catheter ablation, such as deep in the myocardium, beneath epicardial fat, or near the coronary arteries. Surgical ablation of tachycardia can also be performed at the time of other cardiac surgical interventions, such as dur- ing surgical resection of large aneurysms due to prior MI in which the border zone is often a sub- strate for VT, or placement of an LV assist device The procedure requires detailed characterization of the arrhythmia usually with preoperative imaging and mapping, therefore, surgical ablation is best undertaken at tertiary referral centers and with collaboration between experienced surgeons and electrophysiologists. 5.6. Autonomic Modulation Recommendations for Autonomic Modulation References that support the recommendations are summarized in Online Data Supplements 13 and 14. COR LOE Recommendations IIa C-LD In patients with symptomatic, non life- threatening VA, treatment with a beta blocker is reasonable.S5.6-1 IIb C-LD In patients with VT/VF storm in whom a beta blocker, other antiarrhythmic medications, and catheter ablation are ineffective, not tolerated, or not possible, cardiac sympathetic denervation may be Synopsis Sympathetic activation is proarrhythmic and parasym- pathetic activation is generally antiarrhythmic in VT/VF. Modulating the autonomic nervous system for the pur- pose of preventing arrhythmias is an emerging thera- peutic modality.


Modulating the autonomic nervous system for the pur- pose of preventing arrhythmias is an emerging thera- peutic modality. For the prevention of VA, autonomic modulation can be done either through interruption of sympathetic outflow to the heart, pharmacological beta blockade, or through stimulation of the parasym- pathetic pathway (eg, vagal nerve stimulators, spinal cord stimulators). Although autonomic modulation has proven efficacy for certain conditions such as long QT syndrome and catecholaminergic polymorphic ventricu- lar tachycardia (see Section 7.9), evidence is limited for its applicability to the broader group of VA, but studies are ongoing. Currently, there are limited data on the role of vagal nerve stimulators and spinal cord stimula- tors for the prevention of VA/SCD in humans, and thus no formal recommendation could be supported.S5.6-5 Recommendation-Specific Supportive Text 1. Many patients with non life-threatening VA require only reassurance, but others have symp- toms that warrant therapy. A small RCT of patients with symptomatic VA demonstrated a significant reduction in the arrhythmic burden 2. VT/VF storm causes significant morbidity and is associated with increased mortality. For VT/ VF storm refractory to treatment (medications, catheter ablation), cardiac sympathetic denerva- tion has been shown in several small, observa- to reduce the arrhythmia burden. This has been shown for left or bilateral cardiac sympathetic denervation, and it has been suggested that bilateral cardiac sympathetic denervation may be superior.S5.6-3 Although data are limited, the significant morbid- ity and limited options in these patients make car- diac sympathetic denervation a reasonable option in selected patients. 6. Acute Management of Specific VA Recommendations for Management of Cardiac Arrest References that support the recommendations are summarized in Online Data Supplements 15 and 16.


Acute Management of Specific VA Recommendations for Management of Cardiac Arrest References that support the recommendations are summarized in Online Data Supplements 15 and 16. COR LOE Recommendations I A CPR should be performed in patients in cardiac arrest according to published basic and advanced cardiovascular life support I A In patients with hemodynamically unstable VA that persist or recur after a maximal energy shock, intravenous amiodarone should be administered to attempt to achieve a stable rhythm after further CLINICAL STATEMENTS AND GUIDELINES I A Patients presenting with VA with hemodynamic instability should undergo direct current cardioversion.S6-1 S6-3 I B-NR In patients with polymorphic VT or VF with ST-elevation MI, angiography with emergency revascularization is recommended.S6-7 S6-10 I C-EO Patients with a wide-QRS tachycardia should be presumed to have VT if the diagnosis is unclear.


COR LOE Recommendations I A CPR should be performed in patients in cardiac arrest according to published basic and advanced cardiovascular life support I A In patients with hemodynamically unstable VA that persist or recur after a maximal energy shock, intravenous amiodarone should be administered to attempt to achieve a stable rhythm after further CLINICAL STATEMENTS AND GUIDELINES I A Patients presenting with VA with hemodynamic instability should undergo direct current cardioversion.S6-1 S6-3 I B-NR In patients with polymorphic VT or VF with ST-elevation MI, angiography with emergency revascularization is recommended.S6-7 S6-10 I C-EO Patients with a wide-QRS tachycardia should be presumed to have VT if the diagnosis is unclear. IIa A In patients with hemodynamically stable VT, administration of intravenous procainamide can be useful to attempt to IIa B-R In patients with a witnessed cardiac arrest due to VF or polymorphic VT that is unresponsive to CPR, defibrillation, and vasopressor therapy, intravenous lidocaine can be beneficial.S6-1,S6-4,S6-5,S6-14,S6-15 IIa B-R In patients with polymorphic VT due to myocardial ischemia, intravenous beta blockers can be useful.S6-16,S6-17 IIa B-NR In patients with a recent MI who have VT/VF that repeatedly recurs despite direct current cardioversion and antiarrhythmic medications (VT/VF storm), an intravenous beta blocker can be useful.S6-17,S6-18 IIb A In patients in cardiac arrest, administration of epinephrine (1 mg every 3 to 5 minutes) during CPR may be reasonable.S6-1,S6-19 S6-24 IIb B-R In patients with hemodynamically stable VT, administration of intravenous amiodarone or sotalol may be considered to attempt to III: No Benefit A In patients with cardiac arrest, administration of high-dose epinephrine (>1 mg boluses) compared with standard doses is not III: No Benefit A In patients with refractory VF not related to torsades de pointes, administration of intravenous magnesium is not beneficial.S6- III: Harm B-R In patients with suspected AMI, prophylactic administration of lidocaine or high-dose amiodarone for the prevention of VT is III: Harm C-LD In patients with a wide QRS complex tachycardia of unknown origin, calcium channel blockers (eg, verapamil and diltiazem) are potentially harmful.S6-30,S6-31 Recommendation-Specific Supportive Text 1.


IIa A In patients with hemodynamically stable VT, administration of intravenous procainamide can be useful to attempt to IIa B-R In patients with a witnessed cardiac arrest due to VF or polymorphic VT that is unresponsive to CPR, defibrillation, and vasopressor therapy, intravenous lidocaine can be beneficial.S6-1,S6-4,S6-5,S6-14,S6-15 IIa B-R In patients with polymorphic VT due to myocardial ischemia, intravenous beta blockers can be useful.S6-16,S6-17 IIa B-NR In patients with a recent MI who have VT/VF that repeatedly recurs despite direct current cardioversion and antiarrhythmic medications (VT/VF storm), an intravenous beta blocker can be useful.S6-17,S6-18 IIb A In patients in cardiac arrest, administration of epinephrine (1 mg every 3 to 5 minutes) during CPR may be reasonable.S6-1,S6-19 S6-24 IIb B-R In patients with hemodynamically stable VT, administration of intravenous amiodarone or sotalol may be considered to attempt to III: No Benefit A In patients with cardiac arrest, administration of high-dose epinephrine (>1 mg boluses) compared with standard doses is not III: No Benefit A In patients with refractory VF not related to torsades de pointes, administration of intravenous magnesium is not beneficial.S6- III: Harm B-R In patients with suspected AMI, prophylactic administration of lidocaine or high-dose amiodarone for the prevention of VT is III: Harm C-LD In patients with a wide QRS complex tachycardia of unknown origin, calcium channel blockers (eg, verapamil and diltiazem) are potentially harmful.S6-30,S6-31 Recommendation-Specific Supportive Text 1. The most common electrical mechanisms for car- diac arrest are VF and pulseless VT, but substan- tial numbers of cardiac arrests begin as severe bradyarrhythmias or asystole. Survival is better for patients presenting with VT or VF than for those with bradyarrhythmic or asystolic mechanisms.S6-32 Rapid arrival of paramedical personnel is the major determinant of survival.


Survival is better for patients presenting with VT or VF than for those with bradyarrhythmic or asystolic mechanisms.S6-32 Rapid arrival of paramedical personnel is the major determinant of survival. A number of strat- egies for responding to unexpected cardiac arrest, including rapid defibrillation and initiation of CPR for a witnessed cardiac arrest, have improved sur- vival probabilities for cardiac arrest victims.S6-2,S6-3 Nonetheless, the absolute number and propor- tion of survivors remain low, except in unique circumstances where there is an extraordinarily rapid response time to victims in VF or VT such as in monitored intensive care units, where sur- vival is >90%.S6-33 S6-36 Survival decreases rapidly after the initial 2 minutes from the onset of car- diac arrest, so that by 4 to 5 minutes, survival may be 25%, and by 10 minutes it is 0%.S6-33,S6-35,S6-36 Advanced life support activities, other than those directly related to cardioversion and defibrillation for control of tachyarrhythmias, have led to the generation of comprehensive protocols to guide responders. These AHA documents cover the broad expanse of clinical circumstances and con- siderations of mechanisms.S6-1,S6-37 2.


These AHA documents cover the broad expanse of clinical circumstances and con- siderations of mechanisms.S6-1,S6-37 2. Paramedic administration of amiodarone after at least 3 failed shocks and administration of epi- nephrine improved hospital admission rates when compared with placeboS6-6 or 1.5 mg/kg lido- in RCTs in adults with out-of-hospital cardiac arrest due to refractory VF or polymorphic VT, although survival to hospital discharge and survival with favorable neurologic outcome were not improved with amiodarone or lidocaine.S6-5 However, in the subset of patients with witnessed cardiac arrest due to initial shock-refractory VF or pulseless VT, survival to hospital discharge after amiodarone administration was higher than with The administration of procainamide in out-of-hospital cardiac arrest due to VF or pulse- less VT has been associated with more shocks, more pharmacologic interventions, longer resus- citation times, and lower survival.S6-38 3. VA with hemodynamic instability, including VF and pulseless monomorphic or polymorphic VT, causes loss of consciousness and leads to death if untreated. A short time to direct current car- dioversion is the major determinant of sur- vival, and defibrillation should be performed as quickly as possible. CPR is used until a perfusing rhythm is restored. If defibrillation is unsuccess- ful in returning spontaneous circulation, respond- ers follow advanced cardiovascular life support 4.


If defibrillation is unsuccess- ful in returning spontaneous circulation, respond- ers follow advanced cardiovascular life support 4. Quickly identifying and treating patients with out-of-hospital cardiac arrest related to acute cor- onary occlusion is associated with improved sur- vival and better functional recovery.S6-37 Coronary occlusion as a cause of cardiac arrest is not reli- ably predicted by clinical and electrocardiographic Recommendations for Management of Cardiac Arrest (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES and emergency coronary angiogra- phy should be considered (rather than later in the hospital stay or not at all) for unstable patients with a suspected cardiac etiology regardless of whether the patient is comatose or awake.S6-9,S6-39 In 1 observational study of patients resuscitated from SCA who did not have ST elevation and had angiography, one third were found to have a cul- prit lesion and coronary intervention appeared to be associated with a greater likelihood of favor- able neurologic outcome.S6-10 5. The initial management of any tachycardia should proceedaccordingtopublishedAHAadvancedcar- diovascular life support guidelines.S6-40 Immediate cardioversion should be performed for hemody- namic instability at presentation or if it develops subsequently. An ECG should be obtained for sta- ble rhythms. Wide-complex tachycardias, defined by a QRS duration 0.12 s,S6-37 can be due to VT, SVT with aberrancy, preexcited tachycardia, or a paced rhythm such as pacemaker-mediated tachycardia. An irregular wide-complex tachycar- dia may be AF with aberrancy, preexcited AF (ie, AF using an accessory pathway for anterograde conduction), atrial flutter, or VT.S6-37 A diagnosis should be established, and consultation with an arrhythmia expert considered.S6-37 6.


An irregular wide-complex tachycar- dia may be AF with aberrancy, preexcited AF (ie, AF using an accessory pathway for anterograde conduction), atrial flutter, or VT.S6-37 A diagnosis should be established, and consultation with an arrhythmia expert considered.S6-37 6. In 1 study, amiodarone was more effective than lidocaine in terminating incessant VT with improved survival at 24 hours.S6-26 For patients with recurrent, stable VT not in the setting of an AMI, intravenous procainamide has been shown to be superior to lidocaine for terminat- ing the arrhythmia.S6-11 One randomized trial of 62 patients found procainamide superior to amio- darone for termination of stable VT.S6-13 Adverse events, including hypotension were more com- mon with amiodarone, but the difference was not statistically significant. Procainamide and its metabolite n-acetylprocainamide have potassium channel blocking properties that may prolong the QT interval. In patients who already have QT pro- longation, administration of procainamide may further prolong the QT interval and lead to tors- ades de pointes.S6-11,S6-12,S6-26 7. Intravenous lidocaine is an alternative antiar- rhythmic medication of long-standing and widespread familiarity. Compared with no antiarrhythmic medication, lidocaine did not consistently increase a return of spontaneous circulation after defibrillation and was not asso- ciated with improvement in survival to hospital In prospective, blinded, RCTs, lidocaine was less effective than amiodarone in improving hospital admission rates after out-of- hospital cardiac arrest due to shock-refractory VF or polymorphic VT; but there were no differences between the 2 medications in survival to hospital However, in the subset of patients with witnessed SCA due to initial shock- refractory VF or pulseless VT, a subgroup analysis showed that survival to hospital discharge with lidocaine was better than with placebo.S6-5,S6-42 8.


Compared with no antiarrhythmic medication, lidocaine did not consistently increase a return of spontaneous circulation after defibrillation and was not asso- ciated with improvement in survival to hospital In prospective, blinded, RCTs, lidocaine was less effective than amiodarone in improving hospital admission rates after out-of- hospital cardiac arrest due to shock-refractory VF or polymorphic VT; but there were no differences between the 2 medications in survival to hospital However, in the subset of patients with witnessed SCA due to initial shock- refractory VF or pulseless VT, a subgroup analysis showed that survival to hospital discharge with lidocaine was better than with placebo.S6-5,S6-42 8. In a large meta-analysis of antiarrhythmic medi- cations in the setting of AMI, beta blockers were associated with a significant reduction Beta blockers can be effective in suppressing recurrent VF in patients with recent MI, with an associated improvement in 9. In patients with recurrent VT/VF (VT/VF storm) in the setting of a recent MI that is refractory to ami- odarone and/or lidocaine and repeated cardiover- sion, administration of a beta blocker has been shown to improve survival at 1 week. For those who did not survive, mortality was mostly due to recurrent VF. Survival at 1 year was also better in those treated with a beta blocker.S6-17,S6-18 Other measures to reduce sympathetic tone including sedation and general anesthesia are also often used. 10. Epinephrine produces beneficial effects in patients during cardiac arrest, primarily because of its alpha-adrenergic (ie, vasoconstrictor) effects.S6-1 These alpha-adrenergic effects can increase coronary and cerebral perfusion pressure during CPR.


Epinephrine produces beneficial effects in patients during cardiac arrest, primarily because of its alpha-adrenergic (ie, vasoconstrictor) effects.S6-1 These alpha-adrenergic effects can increase coronary and cerebral perfusion pressure during CPR. The value and safety of the beta-adrenergic effects of epinephrine are controversial because they may increase myocardial work and reduce One trial assessed short-term and longer-term outcomes when com- paring standard-dose epinephrine to placebo.S6-23 Standard-dose epinephrine was defined as 1 mg given intravenously or intraosseously every 3 to 5 minutes. For both survival to discharge and sur- vival to discharge with good neurologic outcome, there was no benefit with standard-dose epi- nephrine; however, the study was underpowered for analysis of either of these outcomes. There was, nevertheless, improved survival to hospital admission and improved return of spontaneous circulation with the use of standard-dose epi- nephrine. A number of trials have compared out- comes of standard-dose epinephrine with those of high-dose epinephrine. These trials did not demonstrate any benefit for high-dose epineph- rine over standard-dose epinephrine in relation to survival to discharge with a good neurologic recovery, survival to discharge, or survival to hos- 11. Amiodarone was more effective than lidocaine in terminating incessant VT with improved survival CLINICAL STATEMENTS AND GUIDELINES For patients with recurrent, sta- ble VT not in the setting of an AMI, intravenous procainamide has been shown to be superior to lidocaine for terminating the arrhythmia.S6-11 One RCT in 62 patients found procainamide superior to amiodarone for termination of stable VT.S6-13 Adverse events, including hypotension, were more common with amiodarone, but the differ- ence was not statistically signficant. Procainamide and its metabolite n-acetylprocainamide have potassium channel blocking properties that may prolong the QT interval.